In a hospital based case-control study, 272 subjects (136 cases and 136 normal healthy individuals) were included. Scraped exfoliated cytosmears were collected. The objective was to detect the cytological atypias and to investigate their diagnostic importance in multi-stage human oral carcinogenesis. In the present study, ten types of cytological atypias were detected from different oral sites. Based on the pattern of keratinisation and morphological peculiarities, these are named as (1) Keratinized spindle cell (KSC) (2) Keratinized tadpole cell (KTC), (3) Keratinized strap (Antischkow) cell (KSC-A), (4) Large keratinized fibre cell (LKFC), (5) Small keratinized fibre cell (SKFC), (6) Large keratinized round cell (LKRC), (7) Small keratinized round cell (SKRC), (8) Micronucleated cell (MNC), (9) Plump keratinized squamous cell (PKSC) and (10) Non-keratinized malignant squamous cell (NMSC). Except NMSC- which was observed to be non-keratinized and poorly differentiated, all other cells were keratinized and appear to be either well differentiated or moderately differentiated. Nuclear Cytoplasmic (N/C) ratios in these atypias were observed to be in increasing trend from PKCS (1:27.9 in male and 1:28.9 in female)) to NMSC (1:1 in both sexes). Diagnostic tests also indicated that the Sensitivity was 83.5%, Specificity was 100%, positive predictive value (PPV) was 100%, negative predictive value (NPV) was 30% and the accuracy was found to be 84.6%. Genesis of such diagnostic cytological atypia indicates a sign of cellular alteration and index of oral carcinogenesis. Therefore, the detected pleomorphic atypical may be considered as ideal candidates for diagnosis, grading and early detection of human oral neoplasms.

Keywords : Cytosmear, pleomorphism, atipias, carcinogenesis, oral neoplasm

Background & objective: Bisphenol A (BPA) is an estrogen analogue; one of the xenoestrogens that has crawled into our lives over last 3 decades via plastic water containers (pet bottles, water cans, baby feeding bottle etc), food and beverage cans, the jar caps, water and milk pouches, toys, thermal paper rolls, dental implants, medical equipment and has now been affecting us in multifarious ways by acting through ERs in many signaling pathways. Thus it is involved in the pathogenesis of different endocrine disorders including female and male infertility, precocious puberty, hormone dependent tumours such as breast and prostate cancer and several fertility disorders including polycystic ovarian syndrome (PCOS); the estrogenic effects being cited maximum.

Material and methods: With the objective to study BPA leaching from different plastic containers different water samples were collected for which underground water (from tube well) which was presumed to be the purest form and devoid of BPA leaching from any source and samples from new and scratched pet bottles, new and scratched baby feeding bottle, water pouch, water heated in plastic bowl in a microwave oven, hot water poured in BPA-free plastic container and an ordinary polythene bag were assayed for BPA by HPLC with PDA detector.

Result: Taking tube-well water sample as control, the water samples from new pet bottle, scratched pet bottle, water pouch, new pet bottle exposed to sunlight for 2 months, BPA free plastic container, new and used baby feeding bottle and hot water poured into an ordinary polythene carry bag showed increase in BPA content which had statistical significances as 0.58, 0.001, 0.001, 0.001, 0.55, 0.8, 0.0056, 0.000001 respectively.

Conclusion: With the rising incidence of cancer and especially female breast cancer, BPA leaching into commonly used water sources may turn out as a strong risk factor. Government should take bold steps towards quality control measures for such water containers and enforce ban on hot food and beverage carriage in recycled poly bags altogether.

Compared to the timeline of surgery the subspecialty of Head and Neck Reconstruction is young and only a few decades old. In the early eighties, the options of reconstruction were borrowed from management of war injuries, using complicated, multistage procedures, using tube pedicled flaps, regional pedicle flaps or even extracorporeal fasciocutaneous flaps. Reconstructions were often done as a secondary procedure, which resulted in compromised functions and aesthesis. A better understanding of the cutaneous and skeletal vasculature, opened the era of pedicled myocutaneous and fasciocutaneous flaps. The true revolution in head and neck reconstruction was brought in with microsurgical reconstructions. Initial focus was in achieving wound closure, ignoring aesthesis, function, and donor site morbidities. Presently the focus is on achieving aesthesis, function and in minimising donor site morbidities. The authors will present the development and progress in soft tissue Head and Neck reconstruction experienced in the past three decades. At Tata Medical Center since its inception in 2012, 2400 patients of head and neck cancer was operated of which microsurgical reconstructions have been undertaken in over 370 patients. Though conventional free flaps, such as Radial artery forearm, Anterolateral thigh are the backbone of soft tissue reconstruction, there have been dynamic changes in the approach in combining flaps to address the multi-dimensional component of each defect. Personal philosophies of the author in reconstructing soft tissue reconstructions will be presented. To mention TWO areas of work, that will be presented – A. The three dimensional nature of post resection defects in the Head and neck are difficult to address using conventional free flaps. Perforator based flaps with multiple components are closer in achieving these goals. Designing multiple islanded flaps based on perforator, provides chimeric tissues, addressing these three dimensional defects. Where adequate perforators are unavailable to design Chimeric flaps, combined flaps, from different territories may be fabricated by anastomosing perforators. B. Complex defects often require two or more flaps .Using two different donor sites, increases morbidity, increases operating time and stretches the manpower resources of the surgical team. The authors strongly believe that the donor site is a weak link in any reconstruction and hence limits the harvest to a single donor site. Combining ALT and Antero medial thigh flaps, making a single ALT flap into two based on its perforator anatomy, or using the proximal peroneal perforator flap combined with a fibula osteocutaneous flap addresses most soft tissue reconstructions. C. Soft tissue free flaps such as Lateral arm as well as SCIP( Superficial circumflex artery flap) will also be discussed. The author will walk through the present understanding in Head and Neck reconstruction, with a focus on 3 dimensional planning, using image guided planning, 3d printing ,perforator concept in designing multiple tissue components, and functional restoration using functioning muscle transfers in tongue and cheek reconstruction to provide animation, otherwise the so called FOURTH dimension.

Locoregionally recurrent head and neck cancer remains a therapeutic challenge for all domains of oncology ; surgical, radiation and medical . The recurrence rates of patients treated with surgery and post op chemoradiation range from 17-52% with similar rates in patients treated with definitive chemoradiation. The treatment for resectable disease is surgery providing long term control rates as high as 45% .However in patients who are operated for recurrent disease further recurrence rates are as high as 60 % from some institutional series. Reirradiation with or without concurrent chemotherapy plays an important role in this setting as well as in patients who are inoperable at presentation. SBRT is an emerging modality of reirradiation that is associated with equal control rates compared to conventionally fractionated reirradiation with lesser toxicities. There is however a need for further elucidation of optimal patient selection criteria as well as an understanding of the need of the higher technical demands of the technique.

Multiple myeloma (MM) is the most common primary bone malignancy. It accounts for 10% of all the hematological malignancies diagnosed in USA. More commonly seen in African Americans than in white persons. Median age at diagnosis 68 yrs in male and 70 yrs in female. ⅓ to ⅔rd of patients present with bone pain. Vertebra, skull, ribs, sternum, proximal humeri, and femora bones are involved most frequently. Bone lesions occur due to Uncoupling of balance between osteoclastic and osteoblastic activity. IL-1β, IL-6, TNF-a, and MIP-1a all activate osteoclastic activity. Among these cytokines IL6 cytokine is important. It belongs to cytokine superfamily which includes leukemia inhibitory factor, oncostatin M, ciliary neurotrophic factor and IL11. In normal person it is secreted mainly by TH2 cells, monocytes, macrophages, activated B cells and endothelial cells. It has a synergistic action with IL1,TNFα and produces acute phase response, B cell proliferation and differentiation, immunoglobulin production and hematopoiesis. This cytokine is not only responsible for proliferation of MM cells but also produces destruction of bone. Contrary to it IL4, cytokine, secreted by TH2 cells have been found to be decreased in myeloma. In normal person IL4 produces proliferation of TH2 cell, B Cells, mast cell, eosinophil and isotype switching to IgE production. Hence we can conclude that MM shows elevated IL6 and decreased IL4. In future treatment with antiIL6 and recombinant IL4 can be tried to treat MM Patients.

In this paper, dual-phase-lag bio heat transfer model subjected to Fourier and non-Fourier boundary conditions for bi-layer tissues has been solved using finite element Legendre wavelet Galerkin method (FELWGM) during magnetic fluid hyperthermia. FELWGM localizes small scale variation of solution and fast switching of functional bases. It has been observed that moderate hyperthermia temperature range (41–46 °C) can be better achieved in spherical symmetric coordinate system and treatment method will be independent of the Fourier and non-Fourier boundary conditions used. The effect of phase-lag times has been observed only in tumor region. FCC FePt magnetic Nano-particle produces more effective treatment with respect to other magnetic Nano-particles. The effect of variability of magnetic heat source parameters (magnetic induction, frequency, diameter of magnetic Nano-particles, volume fractional of magnetic Nano-particles and ligand layer thickness) has been investigated. The physical property of these parameters has been described in detail during magnetic fluid hyperthermia (MFH) treatment and also discussed the clinical application of MFH in Oncology.

Presently there is no effective molecularly targeted treatment strategy available for metastatic castration resistant prostate cancer. The current research strongly suggests for identification of potential molecular targets and global molecular signaling map in the context of human prostate tumorigenesis and its progression. Currently, prostate cancer is the second leading cause of cancer in India and in 2016, more than 1.5 million new cases of prostate cancer has been detected in India, which is expected to reach nearly 3 million within 2020. Additionally, WHO (World Health Organization) warns that cancer (including prostate cancer) will become epidemic in India, which is the principal motivation for this current research. By an extensive manual curation of the published biomedical literature, we have recently developed HPCHM, a comprehensive database that depicts the first systems level molecular representation of human prostate cancer associated signaling and events, particularly at classical cancer hallmark level. These cancer hallmark capabilities, which is believed to be the fundamental organizing principle of human cancer, centrally drives and influences every aspect of prostate cancer development, from its initiation to pathogenesis. In this presentation, I will summarize our concept and attempt towards the fundamental conceptualization of cancer systems medicine and its application for hallmarks based systems level mechanistic exploration of human prostate cancer. Particularly it will cover most of the prostate cancer related pathogenic processes including inflammation, angiogenesis, immune deregulation, tumor microenvironment, chemo/radiation resistance, castration resistance, epithelial mesenchymal transition (EMT), cell invasion and bone metastasis.

Background/objective: HCC is a multistep process starting from chronic hepatitis that progress through cirrhosis to HCC. MicroRNA expression level was found to be deregulated in HCC. To find out whether the expression level of miR-34a and miR-183 was deregulated in HCC compared to controls without HCC.

Methods: Real time quantitative PCR was done to find out the miRNA expression level in terms of Ct value followed by statistical analysis.

Results: Over-expression of miR-183 and under-expression of miR-34a in HCC was detected. All changes in expression level of miR-34a and miR-183 were found to be due to HCC compared to controls without HCC. So both miR-34a and miR-183 were suitable to differentiate HCC from Cirrhosis and chronic hepatitis with an efficient diagnostic power of sensitivity, specificity and expression level. But they might not have any role in patients' survival.

Conclusion: miR-34a and miR-183 might be considered as potential markers of HCC screening molecule in addition to other approved panel of marker. Our study warrants further expression level study.

Abbreviations: HCC- Hepatocellular Carcinoma, LC- Liver Cirrhosis, miR- micro RNA, RT PCR- Real time Polymerase Chain Reaction, Ct -Threshold cycle

In elderly patients with glioblastomas, many questions remain unresolved, including the optimal fractionation schedule for radiotherapy, the role of temozolomide as monotherapy, and the most appropriate definition of “elderly” for clinical decision-making in this setting. Based on successful phase III trials, 60 Gy involved-field radiotherapy in 30 fractions over 6 weeks [Standard radiation therapy (RT)] with concurrent and adjuvant temozolomide is currently the standard of care. In this disease, age and Karnofsky Performance Status (KPS) are the most important prognostic factors. For elderly patients, clinical trials comparing standard RT with radiotherapy abbreviated to 40 Gy in 15 fractions over 3 weeks demonstrated similar outcomes, indicating shortened radiotherapy may be an appropriate option for elderly patients. There is also evidence that temozolomide alone may be more effective than radiotherapy alone for elderly patients with methylation of the O6-methylguanine–DNA methyltransferase (MGMT) gene promoter region. Although the incidence of MGMT promoter methylation is not age-dependent, extensive data are lacking with respect to the benefit of adding temozolomide to short-course radiotherapy in elderly patients with glioblastoma and its dependence on status regarding MGMT promoter methylation in tumors (MGMT status).In elderly still many unanswered questions like Can we do away with RT altogether for patients with MGMT methylation? or Can we combine TMZ with other hypofractionated regimens such as 34 Gy/10 or 25 Gy/5 fractions? Undoubtedly, further trials will be needed to answer these questions and guide our practice.

The concept of recognizable oral potentially malignant disorders has arisen following a number of salient clinicopathological observations and the realization that numerous histopathological and biomolecular tissue changes are common to both cancers and their potentially-malignant counterparts. Oral leukoplakia and oral-submucous-fibrosis are the most common oral-mucosal diseases of the potentially malignant spectrum having high prevalence in Indian population with significant malignant transformation rates. Being chiefly habit associated, these can be promptly treated. Leukoplakia is characterized by impairment of epithelial differentiation program. Although multifactorial, tobacco has been commonly implicated in its pathogenesis. Cofactors affecting prognosis include association with Candida, HPV; Parameters like Loss-of-heterozygosity(LOH), aneuploidy, mutation in tumor-suppressor-genes(TSG‟s), expression of tissue markers, and upregulation of cyclinD1, Matrix-metalloproteinases(MMP‟s), telomerase activities reflect oncogenic potential. Oral submucous fibrosis is a chronic progressive disorder with juxta-epithelial fibrosis as hallmark of the disease. Originally an idiopathic condition, its etiopathogenesis today is multifarious. Arecanut (alkaloids,copper,polyphenols), micronutrient deficiencies, autoimmunity, equilibrium shift amongst inflammatory cytokines, cell-cycle alterations , inactivation of oncosuppressor-genes, activation of angiogenic factors contribute to the development, progression and carcinogenesis in varying capacities. Addressing the above mechanisms will help in preventing progression of disease, risk stratification, delivering targeted therapy and improving overall prognosis.

Potentially malignant disorders (PMD) of oral mucosa, with risk of conversion to oral squamous cell carcinoma (OSCC) are described in the literature as “pre-cancer”, “precursor lesions”, “premalignant”, “intraepithelial neoplasia” and “potentially malignant”. The term PMD was defined by the WHO as the risk of malignancy being present in a lesion or condition either during the initial diagnosis or in future date. Oral cancer incidence is highest in India and approx 90-95% oral cancer cases belong to OSCC group. The scale of PMD and oral cancer varies from place to place within the country. PMDs like leukoplakia, OSMF, erythroplakia, lichen planus and solar elastosis are commonly seen in India and carry increased risk of malignant transformation. Early identification of such PMDs is very important to prevent conversion to OSCC. Due to increase in Tobacco habits, dietary factors, environmental exposures and genetic factors, the incidence of PMDs is on the rise thus increasing the burden of OSCC. As patients from many primary health centres and district hospitals are referred to SCB Dental College and Hospital, a tertiary care centre, the study was planned to evaluate the prevalence of PMDs and malignant lesions. Routine patients attending the department of Oral Medicine & Radiology, SCB Dental College and Hospital, for a period of 5 years from 2012-2017 were included in the study. The study revealed leukoplakia constituted the highest number among the PMDs and OSCC was the most prevalent oral malignancy.

Introduction: Uterine stromal neoplasm has always been a challenge to the pathologists for their non-specific clinical features, often indistinct gross features, overlapping histological features, and unpredicted immunohistochemical expression.This study was conducted to analyse the salient clinical morphologic & immunohistochemical characteristics of these tumors.

Materials & methods: All histopathologically proven cases of endometrial stromal neoplasm at the department of Pathology over a period of 5 years were retrieved..the clinical morphological features were analysed.

Results: We encountered 12 cases of endometrial stromal neoplasia. The spectrum included 3 cases of ESN, 5 cases of low grade ESS & 3 cases of high grade carcinosarcoma with a case of undifferentiated sarcoma . The mean age of presentation of carcinosarcomas (61 years) were a decade later as compared to ESS (46 years) & ESN (47 years). The ESN occurred in young adults . case of UUS at 26yrs. Menorrhagia with polypoid masses in the uterus . The age group of ESS-LG was perimenopausal with one case of intramural firm uterine mass. CD10 & SMA in 2 cases of LG-ESS showed positivity. The UUS showed positivity for vimentin, INI-1 & Ki 67 (50%).

Conclusion: Evaluation of morphology with additional immunohistochemical analysis will lead to a conclusive diagnosis.

Key words: Endometrial stromal neoplasm, Carcinosarcoma, Undifferentiated uterine sarcoma

Background: Lactoferrin (Lf), an iron binding ~80 kDa glycoprotein is a well characterized multifunctional protein found to be present in mammalian milk and in most exocrine secretions. Besides Lf‟s important physiological roles in the process of iron homeostasis, iron transportation and sequestration, it is well known for its properties such as antimicrobial, anti-viral anti-inflammatory and immunomodulatory functions

Objectives: Main objective of the study was to develop, characterize and see the bio-distribution of iron saturated lactoferrin protein loaded novel ceramic nanocarriers to deliver orally in Giardia lamblia infected, colon, breast and prostate cancer mice.

Results: In our study, we developed the nanoformulation of a novel alginate enclosed, chitosan coated Fe-bLf loaded ceramic nanocarriers (ACSC NCs). Uptakes of these NCs in vitro in human intestinal epithelial CaCo2 cells were analyzed, by measuring the endocytosis and transcytosis. The results show the NCs was having size range of 200nm with spherical morphology. SDS PAGE followed by western blotting, using specific antibodies against bLf confirms the structural integrity of the protein after the nano formulation. Confocal microscopy and flow cytometry qualitatively and quantitatively determines the internalization of rhodamine labeled NCs, upon treating them on to CaCo2 cells. In this study was carried out with the aim to investigate anti-parasitic activities of Fe bLf loaded ACSC NCs in cell based assays and in mice models of Giardia lamblia, a common parasite of children. Initially the experiments were carried out with native Australian bovine lactoferrin (bLf, ~15% saturated with iron). The efficacy of this protein was compared with other forms of Lf: Fe-Lf (100% saturated with iron), Apo-Lf (unsaturated with iron) using different concentrations in comparison to anti-parasitic drug, Metronidazole. The two forms of bovine lactoferrin (bLf)- apo & native forms showed microbicidal effect on the parasites in vitro and killing was concentration dependent. Apo-bLf showed more inhibitory activity against trophozoites of G. lamblia than native bLf after 12 hrs of incubation with the drug. When the effectiveness of bLf was tested in comparison with metronidazole (40 mM), bLf was found to be more effective in killing the parasites. Fe-bLf loaded ACSC NCs significantly reduced parasitic load in Giardia lamblia infected Balb/c mice. Fe bLf increased the average weight of the spleens of Giardia lamblia infected mice by 15%, accompanied by a major increase in the numbers of particular leukocyte subsets in the spleen. CD4+, CD8+, NK, IFN-+-expressing and dendritic cell numbers in the spleen were significantly (P<0.001) increased compared to corresponding cell numbers for mice maintained on the control diet. Fe-bLf loaded ACSC NCs bound to the intestinal epithelium and was preferentially taken up within Peyer‟s patches. It increased the production of Th1, Th2 and Th17 cytokines within the intestines, including TNF, IFN- -18, nitric oxide as well as IL17. Importantly, it restored both red and white peripheral blood cell numbers depleted by antiparasitic chemotherapy, potentially fortifying the mice against Giardia infections. In summary, Fe-bLf loaded ACSC NCs is a potent natural adjuvant and fortifying agent for augmenting antiparasitic chemotherapy, but needs to be saturated with iron and administered orally in Fe-bLf loaded ACSC NCs to be effective. Bio-distribution of ACSC NCs was determined my MRI, CT and confirmed by other imaging techniques. Taken together, our results are highly encouraging for the development of nanotherapeutic strategies for anti-parasitic infections.

Conclusions: Taken together, our results are highly encouraging for the development of nanotherapeutic strategies and drug delivery to provide more potent and targeted therapeutic, for gut infections. Fe-bLf loaded ACSC NCs were observed to be more effective as an antimicrobial agent. Our findings also demonstrate the potential future benefits of using these treatments as an alternative biotherapeutic approach for the increasing problem caused by OA, RA and other cartilage related irregularities.

Abstract : Lemur tyrosine kinase-3 (LMTK3) is a group of serine/threonine/tyrosine kinases that are found to be novel target for Estrogen receptor alpha positive breast cancer. In this study, LMTK3 domain is modelled and high throughput virtual screening studies were performed to identify potent LMTK3 inhibitors. Also, proteomic studies involving the interaction, stabilization and post translational modifications need to be investigated.

Methods: LMTK3 domain structure was predicted using molecular modelling and validated to check the presence of characteristic architecture of Protein kinases. Molecular dynamics and Principal component Analysis results showed the stability, overall motion and rigidity of LMTK3 in conformational space. In order to understand the binding mechanism of LMTK3 with ATP molecular docking studies were done. Further to investigate the binding cavity and critical residues involved in LMTK3, docking and molecular dynamics simulation studies were performed. Virtual screening and docking of compounds from ZINC and NCI database were performed using Glide module of Schrodinger.

Results and Discussion: Binding site information was obtained from the blind docking approach of ATP with LMTK3 and Tyr185 and Asp284 were identified as key residues involved in ATP binding. Moreover, by high throughput virtual screening of lead compounds on LMTK3, the inhibition was favored with appropriate hydrogen bonds and hydrophobic interactions with critical residues Tyr185 and Asp284 in target site of ATP-binding in the case of selected docked complexes. From virtual screening results, NCI26194, NCI160054, ZINC04670539, ZINC05607079 and ZINC04344028 were identified and further experimental investigations are required to validate these compounds as potent LMTK3 inhibitors.

Introduction : Head and neck cancers are among the 10 most common cancers globally and are the most common cancers in developing countries, especially in Southeast Asia. In India, it accounts for one fourth of male cancers and one tenth of female cancers. Airway obstruction is one of the major morbidities caused by these tumours. Prompt relief of the obstruction would not just save lives but also makes delivery of definitive treatment more effective. The severity of symptoms depends upon the site of obstruction, degree of obstruction and also other physiological factors. Here, we attempted to analyse the correlation between the degree of obstruction at the level of larynx with outcome of the patients in terms of tracheostomy rates and completion of definitive treatment without tracheostomy.

Materials and methods: All patients diagnosed to have primary cancers of head and neck (includes oropharynx, hypopharynx and larynx) who were treated with radiotherapy between the year January 2009 – June 2017 were included in the study. Area of the narrowest airway was measured on simulation CT. All the patients who had radiologically significant airway narrowing were analysed in terms of tracheostomy rates.

Results: Out of 377 head and neck cancer patients which were treated, radiologically significant narrowing of laryngeal airway was observed in 179 patients. 53 patients of them required tracheostomy. Laryngeal airway narrowing could be classified into low, intermediate, high and highest risk for tracheostomy with corresponding tracheostomy rates of 5.8%, 23.5%, 41.6% and 80% respectively.

Conclusions: All highest risk patients will require prophylactic tracheostomy where as high risk patients may benefit from tracheostomy. Intermediate risk patients can be considered depending upon other factors like age and comorbidities.

Introduction : Malignant spindle cell tumors of the larynx are rare, of which the most common are spindle cell squamous carcinomas (SCSCs). Sarcomas are extremely infrequent in the larynx. Composite tumors, further, are quite unheard of except for rare case reports. We present here a case of a spindle cell malignancy in an elderly male, which posed a diagnostic difficulty due to its unique morphological and immunohistochemical features. The tumor was superficial, polypoidal with proliferation of malignant spindle cells and abundant mitoses under an ulcerated epithelium. Occasional squamous cell rests with keratin pearls were present. Cells were strongly immunoreactive for vimentin, smooth muscle actin and sparse cells were p63 positive. Desmin was negative. The dilemma in diagnosis was of a SCSC with smooth muscle differentiation against a composite tumor. The tumor also turned out to be positive for Epstein Barr Virus latent membrane protein-1 (EBV-LMP1), establishing a noteworthy association.

Keywords: Laryngeal malignancy, spindle cells, leiomyosarcoma, squamous cell carcinoma

Key messages: Spindle cell malignancies of the larynx can be a carcinoma, sarcoma or extremely rarely, composite tumors. Knowledge of the entities is important as treatment strategies and prognosis differ.

Axillary Lymph Node Dissection (ALND) is considered the standard management of axilla in invasive breast cancer. Not only does it provide good local control but also provides pathological information about involvement of the axillary nodes which is essential for adjuvant treatment. However, the complications of ALND like lymphedema and restricted shoulder mobility led to replacement of ALND by SLNB in clinical node negative breast cancer. In those patients who are SLNB positive, Axillary radiotherapy is now an attractive option both in terms of Overall Survival (OS) and Disease Free Survival (DFS). The other features like axillary recurrence, local recurrence and distant recurrence have been seen to be similar both in ALND as well as ART in various studies. The earliest study which compared ALND versus ART directly was a phase III RCT NSABP B04. Long term follow up after 25 years showed no difference in DFS and OS. The contribution of axillary radiation on reducing the local recurrence rates was easily observed in the NSABP B04 in which there was no systemic therapy effect. Veronesi et al observed low axillary recurrence in cN0 patients who received who received wide local excision and radiotherapy. Frank J. et al also showed that in cN0 patients who were treated with breast conservation and radiotherapy, axillary recurrence rate was significantly low. These studies suggest that axillary radiation is a safe choice in patients who are clinically node negative. Besides, ALND leads to harmful complications like lymphedema and shoulder mobility restriction. The more recent AMAROS Trial also confirms that the type of axillary management (ALND versus ART) in patients with positive sentinel node does not have an effect on survival. Besides, axillary radiotherapy is associated with significantly less morbidity. Therefore, Axillary Radiotherapy is a valid treatment option with less morbidity than axillary lymph node dissection in cN0 but pN+ patients. However, patients with cN+, a multimodality approach including surgery followed by postoperative radiation provides the best local control and survival rates.

Aims: In this study we introduce selected CTCs markers (VEGF, VEGFR, EGF and EGFR) utility in monitoring and rational selection of gynecological cancers cases (cervical, endometrial and ovarian) and their association with clinical parameters along with brief notes how they can help to elucidate the treatment outcomes.

Methods: Expressions measured by flow cytometric methods as previously described by Iannone et al (2005). Briefly, the MNCs form 2 ml blood sample were harvested, fixed in 1% paraformaldehyde and permeabilised. Cells were incubated at 37 °C for 2 h with primary antibodies which followed by incubation with FITC-labeled secondary antibody for 60 min. Quantitative changes in expression of markers were analyzed as mean fluorescence intensity (MFI) at FL1-H (Log) axis using BD-LSR cytometer.

Results: The cases with low expression level as well as positivity of selected CTCs markers mRNA were also showing low micro vessel density (MVD) count and most of them were from lower histopathological stage of disease (p<0.05). Increased positivity and expression intensity of selected markers were found associated with higher FIGO stages and MVD counts (p<0.05). Follow-up study suggest that the high expression intensity of selected CTC markers resulted in poor response to treatments (p<0.05).

Discussion: Pretreatment expression pattern of these selected CTC markers in gynecological cancer cases will be helpful in diagnosis of cases having potential of angiogenesis and metastasis. A change in expression pattern of above markers will provide a prognostic factor for indication of advanced disease.

Background: Translation of underlying individual genomic heterogeneity in cancer into precision medicine practice requires annotated cancer biorepositories. An overview of experience and outcomes of Mayo Clinic Cancer Center Genito-Urinary (GU) liquid biobank established since 2009 is presented.

Methods: An institutional ethics approved prospective liquid biorepository was established in 09/2009 for advanced GU cancer patients visiting Mayo Clinic. Informed consent approved collection of 29.5 ml blood/urine was performed serially on enrolled patients and clinical annotation was obtained during follow up including previous, current and future treatments and their outcomes. All specimens were processed using a uniform protocol in which extraction of germline DNA from buffy coats; serum for proteomics; platelet poor and platelet rich plasma (in citrate and EDTA anticoagulants) for microRNA and cell free DNA extractions; and extraction of PAXgene RNA/DNA from whole blood was performed. Processing was done within 45 minutes of sample acquisition and storage in -80C freezers with no freeze-thaw cycles.

Results: Between 9/2009 and 01/2015, 535 advanced stage prostate cancer patients in hormone sensitive and castrate resistant stage; 250 advanced kidney cancer patients; 110 testicular cancer patients were enrolled and 1550 collections were performed serially. This generated >60,000 plasma/serum/DNA/RNA aliquots. Nucleic acids (DNA/RNA) from buffy coats and whole blood of 500- 1000 ng volume each were also extracted. Cell free DNA for somatic mutational and copy number analysis; single nucleotide profiling from germline DNA; RNA expression profiling from whole blood and microRNA analysis in plasma has been performed from this cohort along with proteomics using tandem mass spectrometry. By 2017, this has resulted in >35 publications; 5 patents; multiple national grant awards and enhanced precision cancer care.

Several approaches are applied to identify risk of developing cancer in different ethnic and racial groups. One of the approaches is epigenetics that facilitates cancer control throughout the cancer core continuum. To understand current progress and trends in the inclusion of epigenetics in cancer epidemiology, we evaluated the published literature and the National Cancer Institute (NCI) supported research grant awards in this field to identify trends in epigenetics research. We present a summary of the epidemiological studies in NCI‟s grant portfolio and in the scientific literature published irrespective of support from NCI. Biomarkers identified in the analysis might be useful in risk prediction of different cancers. Breast cancer was the most frequently studied cancer type in grants and publications. Blood cells and tumor tissue were the most commonly used biospecimens in these studies, although buccal cells, cervical cells, sputum, and stool samples also were used. DNA methylation profiling was the focus of the majority of studies, but several studies also measured microRNA profiles. We illustrate here the current status of epidemiologic studies that are evaluating epigenetic changes in large populations. Some research needs include developing improved strategies for epigenetic data analysis and interpretation; determining the stability of epigenetic marks in repeated biospecimen samples from the same people over time; and studies that examine the relationship between epigenetic marks in germline DNA and tumor DNA. While there are limitations to the broad application of epigenomics to epidemiology research, there are situations where this type of research is appropriate and it should be considered. Furthermore, approval of five epigenetic drugs for cancer treatment raised our hope of treating cancer with these drugs either using alone or in combination with conventional anticancer drugs. The current status of ongoing clinical trial will be discussed.

Pre-existing BCR-ABL kinase domain mutation leads to Imatinib resistance. Retrospective analysis of 50 patients of Imatinib resistance was done in GCRI, from January 2014 until May 2014. Allele Specific Oligonucleotide –Polymerase Chain Reaction (ASO-PCR) was performed on Genomic DNA of peripheral blood mononuclear cells (PBMCs). 47( 94%) were in Chronic phase, 2(4%) in accelerated phase, 1 (2%) in blastic crisis. Median duration of Imatinib was 48 months. 43/50 had one or more than 1 mutation, T315I mutation in 5 (10%) patients, M351T in 32% (16/50) & F311L in 8. We report M351T as the most common detected mutation 32% followed F311L 16% as against T351I , frequently reported. These mutations may be pre-existing and may have preceded T351I , which is acquired later.

Key words: Imatinib resistance, Pre-existing mutations, BCR-ABL Kinase Domain mutation, M351T mutation.

Cervical cancer is the third most common cancer worldwide, with 80% of cancer deaths occurring in lower middle income countries(LMIC). Exfoliativecervicovaginal cytology has been regarded as the gold standard for cervical cancer screening programs. Limitations are incorrect and inadequate sampling with upto 20% of harvested cells being transferred on the slide leading to a reduction in the sensitivity of the test. Fluid sampling techniques with automation are associated with a reduction in the incidence of inadequate cervical smears. Manual Liquid Based Cytology (MLBC) is a cost effective technique that enables cells to be suspended in a monolayer,improve detection of precursor lesions and specimen adequacy with ancillary techniques which are cell block with immunocytochemistry(IHC)and HPV testing. Cell blocks with IHC can be prepared from all types of cytological specimens. Current HPV tests are able to detect the presence of viral markers by with polymerase chain reaction which when combined with Pap smears can achieve nearly 100% sensitivity. Visual inspection tests with 3%-5% acetic acid (VIA) and/or Lugol‟s iodine (VILI) appear to be a satisfactory alternative screening approach to cytology. In developed countries recent advances , updates and scientific insights are done for HPV screening ,testing and management .In LMIC at the present time, three methods can potentially be used as triage test: (1) Visual methods (VIA/VILLI) (2) Cytology; and (3) Molecular testing with the choice of test essentially depends on the available health resources.

Key words : Imatinib resistance, Pre-existing mutations, BCR-ABL Kinase Domain mutation, M351T mutation.

Background: Post mastectomy radiotherapy (PMRT) reduces loco-regional recurrence (LRR) and improves overall survival.There is international consensus to recommend PMRT for patients with tumour size more than 5 cm, tumour invasion of the skin, pectoral muscle or chest wall and patients with > 4 positive lymph nodes. However, the role of PMRT for patients with T1 , T2 disease with 1–3 positive LN is still controversial. The side effects of radiotherapy and its associated morbidity have to be considered in the risk benefit ratio, thus difficult to arrive at consensus in early breast cancer.

Methods: 101 patients treated between 2012 to 2015 were studied retrospectively, The inclusion criteria for this analysis were:(1) Female patients with unilateral breast cancer and no distant metastasis at initial diagnosis who underwent mastectomy and axillary lymph node dissection; (2) postoperative pathology indicated T1–2 and 1–3 positive axillary lymph nodes (T1–2N1M0) disease, at least 10 lymph nodes removed by axillary dissection; (3) complete surgical resection of the tumor and negative margins; (4) complete estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor family 2 (Her2) status; (5) No neoadjuvant chemotherapy was administered before surgery and endocrine therapy was performed based on the hormone receptor status. In order to study the research questions, we formulated hypotheses as follows,1. Radiotherapy does not have any impact on recurrence post mastectomy.2. There is no influence of Peri nodal extension on recurrence. The above hypotheses were tested using chi- square test.

Results: Recurrences were obtained in 9 amongst radiotherapy and without radiotherapy in 16.When chi square was applied ,the value was highly significant.Hence our hypothesis was rejected. Also in case of PNE with recurrence and radiotherapy,8 had PNE with radiotherapy and recurrence and 27 had no recurrence, p value was 0.013% hence highly significant.

Conclusions: Radiotherapy should be strongly considered in patients with 1-3 nodes post mastectomy as it decreases the chances of recurrence.

India is one of the high incidence zones in head & neck cancer. In india, the most common head & neck cancers are those of oral cavity and pharynx. Infact, mouth and pharynx cancers are third most common cancer in males and fourth most common in females in the developing countries. There are chances of good loco-regional control with anatomical and functional preservation in head and neck cancers. There is role of single modality ( surgery or rt ) in stage I / II disease. There is role of combined modality in stage III / IV disease – combined modality [surgery + RT (in most patients), chemotherapy + RT in selected patients] There is always role of multidisciplinary management including radiation oncologists, surgical oncologists, medical oncologists, radiologists, medical physicists, radiotherapy technologists, dentists / prosthodontics , speech and swallowing therapists, physical medicine & rehabilitation and social services in the management of head and neck cancers. There are a lot of early reactions like mucositis, dermatitis , increasing hoarseness, dysphagia, laryngeal edema. there are late reactions like late reactions xerostomia, laryngeal edema, subcutaneous fibrosis, pharyngeal stricture, osteoradionecrosis. The general management of stomatitis include gargles and hygiene analgesics and antiinflammatory, local anesthetics, local application gels, nasogastric feeding, gaps in treatment till stomatitis decreases,parenteral feeding. There is evidence suggesting effectiveness of commonly used mouthwashes for the prevention of chemotherapy and radiotherapy induced oral mucositis. Thus it is important to use validated tools to regularly assess oral pain & hygiene.There is important role of dental professionals: vital before initiation of therapy as well as throughout treatment & follow up.The technique of Radiotherapy also determines the course of early and late reactions and thus conformal therapies have come up in a big way.There is now documented role Benzydamine gargles: anti-inflammatory with analgesic, anesthetic & anti-microbial properties reduces frequency & severity of ulcerative lesions.Lot of research papers prove role of other agents like Amifostine, Pilocarpine etc.Palliation of acute oral pain: most important component of patient care.

Radical Radiotherapy has been established as one of the standard of care treatment option in the management of localised and locally advanced prostate cancer. Conventional radiotherapy involves prolonged treatment lasting nearly 8 weeks. Unlike other tumours the alpha/beta ratio for prostate cancer is considered to be as low as 1.5 raising the possibility of superior outcomes with Hypofractionated Radiotherapy. Early trials of Hypofractionation have confirmed the feasibility of delivering relatively safe treatment. With the advent of advanced technology like IMRT and IGRT it is now possible to deliver precision radiotherapy and thus improve the treatment outcomes. A review of all randomised trials will be presented.

Biophotonic techniques are being extensively used in clinical research for developing better patient healthcare treatment modalities through improved diagnosis, prognosis, and surveillance. Amongst them, vibrational spectroscopy has tremendous potential as the “molecular fingerprint” provided by it is a representative glimpse of the sample‟s biomolecular composition and anomalies if any. It can be effectively utilized to identify different pathologies. Fourier transform infrared (FTIR) spectroscopy is a vibrational spectroscopic technique which permits speedy, high-throughput nondestructive analysis of a wide range of sample types. Samples can range from biofluids [serum plasma/ urine/ saliva etc.], cells and tissues. FTIR peaks correspond directly to the vibration of a specific chemical bond/a particular functional group within the molecule. Thus, it provides direct information about the biochemical composition. It has been effectively used to characterize numerous types of cancers along with other diseases such as arthritis, diabetes, and scrapie. FTIR is used generally to produce absorbance spectra in the frequency region 600–4000 cm−1 which contain various sharp peaks and is beneficial for the identification of disease pattern. The region 950–1800 cm−1 is utilized to establish potential metabolic inconsistencies in samples as the variations in the carbohydrate, proteins (amino acid) and lipids are best reflected in this region. The peaks are identified taking the help of existing databases or published literature. Chemometrics based classification models are then developed using various supervised/unsupervised algorithms or a combination of methods like HCA and PLS-DA. It augments the sensitivity and specificity of the technique. The utility of FTIR spectroscopy as a metabolite profiling tool is achieving significance in the field of disease diagnostics as it can simultaneously analyze different metabolites like carbohydrates, amino acids, fatty acids, lipids, proteins and polysaccharides within a very short span of time.

Oral & maxillofacial region comprises of plethora of variants of tissue with unique features, thus this region involve different types of tumors with unique features with different cell of origin, sometimes it becomes difficult to diagnose such cases. This paper presents documentation of such rare cases reported in maxillofacial region with variant etiology and unique clinical, radiological and histopathological features . This will enhance awareness of clinicians for such rare tumors and will help in diagnosis and proper treatment planning.

Introduction: Testicular germ cell tumors (GCT) are the most common tumors in adolescents and young adults (20-30 years of age). GCTs are highly sensitive to chemotherapy and have excellent prognosis. There is paucity of data from India on GCT. The present study was conducted to assess the demographic features, clinical manifestations, pathology and outcomes of GCT patients treated at our centre.

Materials & Methods: Patients with testicular GCT above the age of 18 years, treated at our centre from 2001-2015 were included in the study, and the patients were censored on first of November 2017. Data was extracted retrospectively from the case records. Event Free Survival (EFS) and Overall Survival (OS) were calculated as per Kaplan Meier method. Variables were compared using log rank test.

Results: Data was available for 421 of 435 patients; who were treated during the study period. Among them, 128 patients had histological diagnosis of Seminoma (30%), and the rest 293 patients had Nonseminomatous germ cell tumor (NSGCT) (70%). Number of patients in IGCCCG good risk seminoma were 100 patients (78%), and intermediate risk seminoma were 28 (22%). Good risk NSGCT were 121 patients (41.3%), intermediate risk were 76 (25.9%), and poor risk were 96 (32.8%). Median age of the population was 31 years. Median follow up was 32.3 months (0.03-200 months). Three year OS for the whole cohort was 80.3%. Three year OS for seminoma was 91.4%, and of NSGCT was 75.3%. Three year OS for good risk seminoma was 94.2%, and intermediate risk seminoma was 80.9%. Three year OS for good risk NSGCT was 88.6%, intermediate risk NSGCT was 81.5%, and poor risk NSGCT was 52.3%. Factors predicting survival on univariate analysis were stage, IGCCCG risk, and compliance to treatment.

Conclusions: This is the largest data series from India on germ cell tumors. IGCCG good risk patients had excellent outcome. Poor risk patients had worse outcome. Majority of the patients presented with advanced disease.

The majority of cancer patients become malnourished during the course of their disease. Malnutrition is one of the most frequent complications of advanced cancer. Malnutrition deteriorates the efficiency of all kinds of oncologic interventions. As a consequence of it, treatment related toxicity increases, hospital stay is lengthened; chances of cure and survival as well as the quality of life of the patients worsen. Malnutrition and a loss of muscle mass are frequent in cancer patients and have a negative effect on clinical outcome. They may be driven by inadequate food intake, decreased physical activity and catabolic metabolic derangements. Nutritional status therefore influences all aspects of outcome of oncology care. In spite of this the use of medical nutritional therapy varies across health care providers but its application is far from being sufficient during active oncology interventions as well as rehabilitation and supportive care. It threatens not only the outcome and quality of life of cancer patients but also the success of oncologic treatments which often demand high input of human and financial resources. During recent years, many papers have addressed the incidence and causes of malnutrition in cancer patients, as well as its treatment with such measures as parenteral nutrition, nasogastric infusions, or appetite stimulants. In this review we present the basics of nutritional therapy including nutritional screening and evaluation, nutritional plan, the role of nutrition support teams, oral, enteral and parenteral nutrition, the use of different drugs and special nutrients and the follow-up of the patients. In cancer patients, oral nutrition is the preferred route of feeding since it is a significant part of the patient's daily routine and contributes to the patient's autonomy. It represents a privileged time to spend with family and friends, avoiding the tendency for isolation in these patients. The acknowledgement that the prescribed diet is individualized, adapted and adequate to individual needs empowers the patient with a feeling of control, and thus it is also a highly effective approach of psychological modulation. All these factors may potentially contribute to improve the patient's quality of life and may modulate treatment morbidity.

Keywords: Malnutrition, Cancer, Appetite, Palliative care, Nutrition assessment, Nutrition therapy, Enteral Nutrition, T Indo

In the present study, Beta-Sitosterol in Lawsonia methanolic leaf extract embedded in controlled release nanocomposite was prepared and evaluated for in vivo anticancer efficacy in Dimethyl hydrazine (DMH) induced colon cancer. In the present study, colon cancer was induced by s.c injection of DMH (20 mg/kg b.wt) for 15 weeks. The animals were divided into five groups as follows control, DMH alone, DMH and Beta Sitosterol nanocomposite (50mg/kg), DMH and Beta Sitosterol nanocomposite (100 mg/kg) and DMH and Standard Silymarin (100mg/kg) and the treatment was carried out for 15 weeks . At the end of the study period the blood was withdrawn and serum was separated for haematological, biochemical analysis and tumor markers. Further, the colonic tissue was removed for the estimation of antioxidants and histopathological analysis. The results of the study displays that DMH intoxication elicits altered haematological parameters (RBC,WBC and Hb), elevated lipid peroxidation and decreased antioxidants level (SOD, CAT, GPX, GST and GSH), elevated lipid profiles (cholesterol and triglycerides) , tumor markers (CEA and AFP) and altered colonic tissue histology. Meanwhile, treatment with Beta Sitosterol nanocomposites significantly restored the altered biochemical parameters in DMH induced colon cancer mediated by its anticancer efficacy. Further, Beta Sitosterol nanocomposite (100 mg/kg) showed marked efficacy.

Keywords: Nanocomposites, Herbal formulation, Henna, Beta Sitosterol, colon cancer, Dimethyl hydrazine, antioxidant, lipid peroxidation

Malignant melanoma originates from melanocytes or pigment cells. It accounts for only 2% in female genital tract with an incidence of only 1.6 cases per million females. Melanomas generally seen over the skin and mucous membranes. Superficial type of melanoma commonly seen in women and nodular type in men. Proper gynecological, histopathology and immunohistochemistry confirms the diagnosis of malignant melanoma of cervix. As patient usually present in advanced stage, and due to the aggressive behaviour of tumor the prognosis of malignant melanoma of cervix is poor.

Keywords: melanocytes, incidence, aggressive behaviour, advanced stage.

Purpose: To retrospectively evaluate the profile of functional neuroendocrine tumors referred for Gallium68-DOTA-NOC (somatostatin receptor) PET CT scan SSTR.

Method: Data of cases with clinical suspicion or biopsy proven neuroendocrine tumor was collected between Jan 2014 and May 2017. Subsequently those who had functional manifestations (ie hypertension in pheochromocytoma; hypoglycemia in insulinoma; gastric hypermotility in carcinoid; recurrence duodenal ulcers in gastrinoma) were evaluated. All procedures were performed using 1 to 2 millicuries of Gallium68- DOTA NOC (octreotide analogue) on nonfasting stomach. Images were acquired between 50 and 60 minutes using Siemens Biograph Horizon and GE Discovery 610 PET CT systems.

Result: 164 cases of SSTR PET scan were studies with following diagnosis- A. Nonfunctional NET B. Functional NET: Group A (n=129). 1. Neuroendocrine tumors (n= 82); 2. Medullary carcinoma of thyroid (n= 19); 3.Neuroblastoma (n=11); 4.Hypertension with no evidence of pheochromocytoma on SSTR (n=12); 5. Others (thymoma, dedifferentiated carcinoma of thyroid, opsoclonus myoclonus syndrome) (n=5); Group B (n=35): 1. Pheochromocytoma (n= 9); 2.Carcinoid (n=15); 3.Gastrinoma (n=3); 4.Insulinoma (n=8). Following were the results in various subcategories of functional NET 1.Pheochromocytoma –adrenal 6; extra adrenal 2 and negative one. 2.Carcinoid- lung 7, Gastric 2, duodenal 3, Appendicular 1, mediastinal 1, ileum 1. 3. Gastrinoma Pancreas 2, Duodenum 1. 4. Insulinoma six pancreatic positive; two negative. Following cases were histologically confirmed: Pheochromocytoma- adrenal 6/6; extra-adrenal 1/2 ; Carcinoid lung 7/7; Gastric 2/2; Duodenal 3/3; appendicular 1/1; mediastinal 1/1; ileal 1/1. Gastrinoma pancreas 1/ 2; duodenum 1/1; Insulinoma 3/6 pancreatic. (others were not operated for various reasons).

Conclusion: SSRT PET CT scan is gaining attention by practicing physicians for evaluation of various NET. Functional NET were diagnosed with high yield in selected patient group for diagnosis of respective tumors.

The recent research trends, shows many previous successes in the past years and which also pointed for many future related tasks for the women's health. The future will be very challenging. Nutrition deficiency affects both the body‟s immunological and non-immunological defenses. As a result, it increases the incidence, severity, and duration of common infectious diseases, such as Tuberculosis and autoimmune disorders. Deficiency of Iron is main cause for ill health in females. According to the WHO Global Burden of Disease report iron deficiency anemia ranks as second among leading causes of disability. This disease effects should causes serious obstacles to the health and socioeconomic development of nations. Considerably, as anemia is a contributing factor in 20 percent of all maternal deaths. The nutritional deficiency plays an important role in maternal mortality and child health. The nutritional deficiency not come in a day it comes over year by year, in which childhood, teenage and adolescent age is involved. Research has shown that the female with anemia like diseases have more risk of maternity and childbirth. They are prone to infection and transmission of diseases to their child too. In my research study it is found that junk food eating habits in adolescent females causes anemia like deficiency diseases, which later on responsible for so many illnesses in their body. It increases the virulence of infections, putting even healthy populations more at risk in the future. The role of obesity and poor diet quality in the development of chronic disease has long been recognized, where chronic disease rates are showing alarming increases. Good nutrition would be preventing not only diseases of deprivation, but also chronic diseases that afflict affluent and non-affluent populations alike. There is a need to awaken the young generation and make them aware about their futuristic outcomes.

Keywords: Key Words: Deficiency of Iron, nutritional deficiency, Anemia, morbidity and mortality.

There have been more than 500,000 new cases of cervical carcinoma diagnosed worldwide during 2014 alone. Most of the patients present with locally advanced disease, when local control becomes the main goal of the treatment. The standard treatment of such cases have traditionally been with external beam radiotherapy with concomitant chemotherapy followed be brachytherapy boost. BT boost improves overall survival and reduces local recurrence of disease. But, implementing and delivering an appropriate brachytherapy plan has several challenges. This is a technique that is sensitive to physician skills, requires intra cavitary insertion of applicators with added risks of anesthesia. Many patients are not suitable candidates for brachytherapy due to large residual disease, anatomical uncertainties or medical comorbid conditions, while others simply refuse due to concerns of invasiveness. Most important of all is the low availability of brachytherapy facilities in most Cancer Care centres, especially in countries like India. In 2012, only 25% of gynecologic cancer clinics used high-quality image-guided BT. In the era of newer methods of high dose, precise and conformal external beam radiotherapy, IMRT and SBRT provide viable options that appear as an alternative to the costly, logistically complex and invasive BT. But in spite of the advances in the form of IMRT and SBRT, brachytherapy remains irreplaceable due to its superior delivery method, enhanced dosimetry due to dwell time optimization and better accounting for the variations in target position precipitated by organ motion. Furthermore, it allows for delivery of a high dose to tumor, while maintaining a steep dose gradient to surrounding normal tissue, thus allowing better sparing of the adjacent bowel and bladder.

Introduction: Renal Involvement is common in Acute childhood leukemia. Objective: Prevalence of nephromegaly on ultrasound and its impact on outcome in children with acute leukemia.

Material and Methods: A Prospective observational study conducted in our department from September 2016 to August 2017.Recruited cases of established acute childhood leukemia , aged between 6m-18 years & those with parental consent. Excluded patients were patients already on chemotherapy and other causes of nephromegaly. A baseline Ultrasonography was done at the beginning and end of induction chemotherapy in patients with acute leukemia.

Results: 104 children were enrolled, 77 (84.5%) of ALL and 5(38.48%) of AML patients completed induction chemotherapy. Seven (7.6%) of ALL group of patients and 7 (53.84%) of AML patients expired during induction chemotherapy. Nephromegaly was found in 11.5% of our patients at presentation. NAH(Nephromegaly according to Height criteria) was found in 28.8% and NAA(Nephromegaly according to age criteria) in 11.5% of patients at presentation. In our study NAA resolved in 11(63.6%) ALL patients and in all AML patients. NAH resolved in 19 (76%) patients and all the AML patients. Mortality during induction chemotherapy was 13.3% in NAH group and 25% in NAA group.

Conclusion: In our study we tried to find the effect of nephromegaly on outcome after induction chemotherapy in acute childhood leukemia and found that there was less correlation of nephromegaly on outcome.

The technological advances like SRS and SBRT for cranial and extracranial radiosurgery has been a revolution in the field of radiation oncology. The Indian scenario might be little different keeping in mind the vast geographical area, the availability of technology and expertise and the overall cost of treatments. However, slowly the situation is changing with recent data coming up from Indian subcontinent. In this presentation we would like to highlight exclusive Indian data in this regard.

Introduction: Squamous carcinomas in the head and neck can manifest with variable morphologic features ranging from bland appearing verrucous carcinoma to sarcomatous spindle carcinoma, basaloid SCC and lymphoepithelial undifferentiated carcinoma.

In the present study, seven variants of SCC were encountered in one year. The patients were predominantly elderly males { 5/7] and the histomorphology was papillary SCC[ 2/7] affecting the pyriform fossa & vocal cord, basaloid SCC[ 2/7] affecting larynx & epiglottis and lymphoepithelial type SCC[ 1/7] affecting the vallecular. Verrucous SCC[ 1/7] and sarcomatoid spindle SCC [1/7] were observed in an older and young female respectively, in the lateral border of tongue.

Discussion: Variant squamous carcinomas pose morphologic challenges as verrucous type resembles verrucous hyperplasia, spindle type resembles sarcoma and papillary SCC mimics squamous papilloma. The biologic potential ranges from non- metastatic verrucous carcinoma, minimally metastatic papillary SCC to aggressive behavior of basaloid carcinoma, spindle carcinoma and lymphoepithelial undifferentiated carcinoma with invariable metastatic potential. Immunostaining with cytokeratin and P63 can help in the identification and typing of the aggressive variants.

Conclusion: It is important to identify the morphologic variants of squamous cell carcinomas in head and neck for risk stratification and tailoring of treatment options.

Key Words: Squamous- carcinoma- variants.

Allogeneic Blood Stem Cell Transplant is the cure for blood cancer. With very few registered blood stem cell donors available in India, the possibility of finding an unrelated genetic (HLA) match for an Indian anywhere in the world is very bleak. Motivated to create a viable registry of Indian donors, Mr. Raghu Rajagopal together with Dr. Nezih Cereb and Dr. Soo Young Yang of Histogenetics New York set up DATRI Blood Stem Cell Donors Registry in 2009. The age for registration is between 18 and 50 years. To register as a blood stem cell donor, a cotton swab is rubbed inside a person's cheek which is then tested for HLA typing. This HLA typing is stored in D'ATRI's database. Any person who is interested to enroll as a donor has to spend only 5 minutes to do a swab test and fill up a registration form and sign a consent form. The chance of getting a HLA matched donor for a patient is very rare (1 in 10,000). In case of a successful HLA match with a patient in future, the stem cells are collected from the donor through a painless outpatient procedure similar to blood donation called peripheral blood stem cell transplant. DATRI also ensures the safe transportation of the stem cells to the patient so that they can be injected into the patient‟s bloodstream. Till date DATRI has registered around 3,00,000 donors and has been able to facilitate 342 blood stem cell transplants.

Background : Despite radical surgery for esophageal carcinoma, a large number of patients experience recurrence. The aim of the current study is to evaluate the impact of various histo-pathological factors on patterns of recurrence and survival.

Material and Methods : The Present study was conducted at GCRI Ahmedabad between 2010 and 2016.The retrospective study analysed the outcome of 182 patients treated with surgery who met the inclusion criteria. Factors affecting the recurrence pattern and survival were analysed using Graph pad PRISM version 7.04, p value and hazard ratio were calculated using Log rank test.

Results : Out of 182 patients, 139(76.4%) were SCC and 43(23.6%) adenocarcinoma. 55 patients developed recurrences, 19 loco regional & 36 systemic recurrence. Variables associated with recurrences on univariate analysis were histology, PNI and ENE. LVI have no significant impact on DFS & OS. PNI had statistically significant impact on DFS (p= 0.017). ENE had statistically significant impact on OS (p= 0.0001). Histology & grade had statistically significant impact on DFS & OS.

Conclusions: Our study showed that recurrence is common Carcinoma esophagus. Systemic recurrence is more common than loco regional. Adenocarcinoma had significantly higher systemic recurrence than SCC. Poorly differentiated tumor has significantly less DFS and OS than well to moderately differentiated tumor. PNI is associated with decrease in DFS but no significant impact on OS. ENE was associated with decreased OS.

Keywords: SCC, adenocarcinoma, recurrence, prognostic factor, DFS, overall survival

PET scan followed by biopsy is the standard diagnosis for most types of cancers. In PET Scan, FDG (Fluorescent D Glucose), a glucose analogue is introduced in the body and its uptake location is identified by scanning. Cancer cells consume a lot of glucose and survive solely on it. Cancer has been linked to conditions of excessive energy intake like obesity, metabolic syndrome etc. Cancer has also been linked to lower anti oxidants, Vitamins and minerals in the body along with higher reactive oxygen species production. It has been found that certain foods and diet therapies show anti cancerous properties like anti-angiogenesis, anti proliferation, pro apoptosis. It is also confirmed that interchange of nucleus between normal cell and cancer cells do not have any effect on its cancerous nature. No genes or group of genes or mutations in them have specifically been identified yet to cause cancer of any type. The internal environment of the body including the hormonal status & growth factors like the amount of IGF-1 & VEGF influences the prognosis of the disease. The internal environment of the body can be changed with diet and lifestyle. This paper is aimed at looking at the deep physiology of cancer and impact of diet and lifestyle which is mostly neglected by the patients and the health experts resulting in serious implications. This paper will reflect about the importance and implications of diet and lifestyle on the body of a cancer patient and the disease itself with real life examples.

Abbreviation: IGF-1 – Insulin like Growth Factor 1
VEGF – Vascular Endothelial Growth Factor

Keywords: Cancer Treatment, Diet, Food, Alternative Treatment

Objective - Cancers remain to be a heavy burden to human health and survival. Among oral salivary gland cancer, the clinical behavior of MEC (mucoepidermoid carcinoma) is largely unpredictable, ranging from indolent tumour growth to highly aggressive metastatic spread. Increased glycolysis is one of the hallmarks of cancer. This study aimed to analyze and compare the glucose transporter Glut-1 expression in MEC and MEC with GOC (Globulomaxillary cyst).

Method- Immunohistochemistry methodology applied using Glut-1 biomarker. Mucoepidermoid carcinoma and MEC with GOC cases were taken in this study to compare their aggressiveness. Normal mucosa as control group and RBCs were taken as the internal control group.

Result- All the data was statistically tabulated & we found increased expression of Glut-1 in MEC in comparison to normal mucosa. When we compared Glut-1 expression in both groups it was found that cystic variant showed less expression of Glut-1 in comparison to solid MEC but there is difference in Glut- 1 expression in the same group cases of MEC & MEC with GOC thus it is suggesting that GLUT1 is one of the molecular biomarkers that can provide information complementary to that which can be obtained from clinical and routine histopathological examination.

Conclusion- Increased Glut-1 expression shows the aggressiveness of different variant of MEC cases which should be emphasized among pathologists to contribute to consistent knowledge of clinical and biological tumor behavior in the oral cavity and result in more accurate treatment protocols by introducing neoadjuvant chemoradiotherapy.

Introduction - Second primary cancer is a new primary cancer that occurs in a person who has had cancer in the past as per National Cancer Institute.With the rapid pace of discoveries in tumor biology, innovative clinical trials and cutting edge technology, the overall survival of the patients has improved. The study attempted to analyze the pattern of presentation of second primary cancers reported to Regional Cancer Centre, India and to review the literature.

Objectives- The study design has set the following objectives:

1. Spectrum of second primary cancers reported to RCC, India.
2. Clinical characteristics of second primary cancers.
3. Clinical status of the patients.

Materials and Methods - A hospital based retrospective collection of data, among the patients that have been diagnosed with second de novo malignancy. The study was conducted over a 3 years period from 2013 to 2016.

Results - Over a period of 3 years total 26 cases of second primary cancers were observed. All the 26 cases were metachronous cancers. Among 26 patients, 12 (46.2%) were males and 14 (53.8%) were females. The most common age group 40-49 years. The median age at the time of primary cancer diagnosis was 46.5 years. The most common site of primary malignancy was breast (42.30%), followed by head and neck (30.77%), gynecological (11.54%), genitourinary (7.69%), CNS (3.85%) and hematological (3.85%) malignancies. The average time interval between appearance of primary and second primary cancers was 5.26 years. Among the second primary cancers, the most common site was gastrointestinal (30.77%),followed by gynecological (23.07%), head and neck (23.07%), lung (15.4%), and bone (7.69%) cancers.

Conclusion - The trend of incidence of second primary cancers are on the rise and not uncommon. Regular follow-up and thorough clinical evaluation is mandatory for early detection for these patients.

Introduction - Neuroendocrine tumors (NETs) are rare variety of neoplasms characterized by over expression of somatostatin receptors (SSTRs). Functional imaging like 68 Ga DOTANOC PET/CT plays a vital role in the initial evaluation and management of NETs. In this paper we evaluated the sensitivity, specificity of detecting primary, loco regional lymph nodes, distant metastasis, and its role in deciding therapy.

Methods- Between January 2015 to April 2017, a total of 42 patients underwent 68 Ga DOTANOC PET/CT whole body scan from (vertex to mid thigh) after injecting 1-2 mCi of radiotracer and the images were taken 45 minutes of tracer injection if necessary delayed images were taken. Out of 42 (19 males, 23 females; mean age, 58.25, Range 19 to 75 years) with histopathologically proven metastatic NETs and unknown primary site on conventional imaging and other laboratory tests. Histopathology (wherever available) or follow-up imaging taken as reference standard. Quantitative estimation of SSTR expression in the form of SUVmax of detected primary and metastatic sites calculated. Follow-up data was collected through careful survey of hospital medical records.

Results - Out of 42 patients (25-GI,14-GII,1-GIII and 2-unknown grade) , 41 patients show DOTANOC avidity of which 2 patients show simultaneous non FDG avid correspondent lesions on FDG PET/CT and the one patient (Grade -III) show DOTANOC non avid lesion on Ga-68 DOTANOC PET/CT. DOTANOC PET/CT scan identify primary sites in 29 patients (69.04%). Mean SUVmax of the detected primary sites was 27.1 with a range of (2.7-160.8).The wide range could be due to tumor heterogeneity (variability in receptor expression).Significant positive correlation was found between SUVmax of detected primary site and SUVmax of the histopathologically proven sites of metastasis (r=0.769 (n=19); P<0.0001). Based on the findings of the Ga-68 DOTANOC PET/CT scan, 9 out of 42 patients underwent surgery, 21 sandostatin, 10 peptide receptor radionuclide therapy and 2 chemotherapy. The sensitivity, specificity and accuracy for primary, 86.84% (95% CI: 71.9-95.6%), 100% (95% CI: 39.8-100%) and 88.1 % (95% CI: 75.1-94.8 %) for loco regional lymphadenopathy 94.73 % (95% CI: 73.9-99.8 %), 91.30 % (95% CI: 71.9-98.8 %), 95.45 (95% CI: 75.6-99.3) and for distant metastasis 100 % (95% CI: 84.6-100 %), 100% (95% CI: 83.1-100 %) and 100% (95% CI: 91.6-100 %) respectively.

Conclusion - Our findings indicate that Ga-68 DOTANOC PET/CT is a promising sensitive, specific and accurate initial modality in patients with metastatic NETs for detection of the primary site, smaller lesion and in guiding therapeutic decisions.

The practice of modern oncology is challenged by the growing age of target population (i.e. old age) and poor performance status thus, limiting the use of chemotherapy. The tolerability of various regimens in the young and elderly alike, translates into a great deciding factor for the choice of chemotherapy. The theranostic approach in nuclear medicine couples diagnostic imaging and therapy using the same molecule or at least very similar molecules which are either radiolabeled differently or given in different dosages. The detection of potential targets can help predict whether a patient will benefit from a particular treatment. Theranostics can be useful for estimating the potential response and eventual toxicity. They can also estimate potential responders interim to the completion of treatment. The oldest radioisotope in India used based on this theranostic approach is radioiodine( I131 ) with small doses for diagnosis and large doses for therapy for thyroid cancer and I-131 MIBG for diagnosis and therapy of Neuroblastoma. Newer development includes, a novel theranostic approach for diagnosis of recurrence in and selecting eligible patients for radionuclide therapy in castration resistant prostate cancer( Ga- 68 PSMA scan for diagnosis and Lu- 177 PSMA for therapy). For well differentiated and moderately differentiated NET (neuroendocrine tumours), Ga- 68 DOTA- SSTR PET-CT scans have served as a boon farting a lot better against FDG PET-CT scans in diagnosis and assessing response, restaging and for selecting patients especially inoperable metastatic NET for peptide receptor radionuclide therapy – PRRT (Lu-177 DOTATATE). PRRT having fared well against conventional somatostatin analogues (NETTER1 study) has given a promising option to NET patients. Recent developments with theranostic approach include Ga-68 pentixafor and Lu-177 pentixafor for multiple myeloma has paved way for more disciplined approach to quantify and treat the disease. A promising approach in patients with metastatic melanoma is the specific targeting of melanin. The newly developed theranostic agents include [123I]I-/[131I]I-BA52 and [18F]F-/[131I]F-ICF15002, which may play a considerable role in the future.

The main objective was to develop potential breast cancer marker from biological fluids like saliva which is reproducible, cost effective , non-invasive method and can be used for diagnosis and prognosis faithfully. In this horrible world of AIDS this method has an added advantage. Human saliva is a biological fluid of varying diagnostic potential with several advantages for disease diagnosis and prognosis, such as non-invasiveness, minimum cost and easy sample collection with minimum discomfort to the patient. Also handling of saliva during the diagnostic procedures is easier. In the present project proposal, we want to study and compare the findings in breast cancer and other types of cancer (other than breast cancer) and also to see its potential in early detection and Prognosis. Processing and analysis of this biological fluid is the most important criteria and tests could be easily conducted with saliva for early detection of the disease. While saliva is a source of easily accessible bodily fluid, there has been little effort to study its potential in cancer diagnosis . we have shown that the saliva of breast cancer patients express highly activated MMP-2 The findings increases the potential of salivary active MMP-2 to be a breast cancer marker ( our findings was accepted for presentation in Drug Delivery International Conference in Boston, USA this year August and Principal Investigator Prof Amitava Chatterjee was invited to present “Session Lecture” in this Conference, 22-25 August, 2016). The article was accepted for publication in Bentham Proceedings for International Conference. The main objective was to develop potential tumor marker from biological fluids which is reproducible, cost effective, non-invasive method and can be used for diagnosis and prognosis faithfully.

Mandible defines the contour and aesthetic appearance of the lower third of the face. It is essential for airway protection, proper occlusion, mastication, deglutition, and speech. Interruption in mandibular continuity produces both a cosmetic and functional deformity. Shape of the mandible is continuously changing with growth from birth to adulthood. In children there is low lying mandibular canal with small bony stock below the erupting tooth buds and size of the mandible, fibula and vessels are smaller in size leading to difficulty in fixation. These factors require attention for appropriate selection of reconstruction plate and fixation technique. Reconstruction of mandibular defects after trauma or tumor resection is one of the most challenging problems faced by reconstructive surgeons. Restoration of bony continuity alone is not considered the measure of success. Ideal mandible reconstruction should provide good contour, adequate alveolar height for dental rehabilitation to enable eating solid diet. Microvascular surgery has become the preferred method for mandible reconstruction. Whenever possible, immediate reconstruction at the time of segmental mandible resection will provide the best aesthetic and functional result. Four donor sites (fibula, iliac crest, radial forearm, and scapula) have become the primary sources of vascularized bone and soft tissue for the reconstruction. Fibula has multiple advantages, including bone length and thickness, donor site location permitting flap harvest simultaneously with tumor resection, and minimal donor site morbidity. The fibula flap is the first choice for mandible reconstruction. Dental rehabilitation with the use of prostheses and osseointegrated dental implants is an important part of the reconstructive process to optimize aesthetics and function. Soft tissue is preserved following resection of the benign tumour of the mandible, resulting in better aesthetic and functional reconstruction. Mandible reconstruction with vascularised fibula is preferred as it allows several osteotomies to be performed retaining vascularity of each segment for contouring and placement of one segment above the other (double barrel fibula flap) to increase the height for support of the lower lip and dental rehabilitation with dentures or osseointegrated implant. Double barrel reconstruction is essential for the teeth bearing segment of the mandible (body and symphysis). During excision for malignant tumours, in addition to part of the mandible there will be loss of soft tissue leading to poor aesthetic outcome even after adequate replacement. In oral cancer in addition to excision of the primary tumour and part of the mandible, neck node dissection is also required. Neck node dissection often results in hollowness in the submandibular region. Flexor hallucis muscle with the cutaneous and osseous component of the fibula flap can be used to fill the defect in the submandibular region resulting from lymph node clearance in cancer patients requiring mandible reconstruction. Flexor hallucis longus muscle harvested with free fibula flap gives satisfying results of submandibular region fullness in mandibulectomy with neck dissection patients. Mandible reconstruction with vascularised fibula flap is preferred as it provides a large amount of cortical bone and allows several osteotomies to be performed for better contouring, placement of one segment above the other to achieve adequate alveolar height. Skin and muscle can also be harvested with fibula flap for adequate replacement of soft tissue. Dental rehabilitation with prosthesis or implant is possible to improve the result.

Head and neck malignancy is a very common cancer among Indian males. This is attributable to common habit of chewing Tobacco, Gutkha, beetle and betel nuts etc. Presentation is usually at an advanced stage. Quite often surgery is ruled out due to advanced stage. Options for management left are Chemotherapy and Radiotherapy. Usually concurrent Chemo Radiotherapy is given. Head and neck region is very complex anatomically. The aim of giving Radiotherapy in such cancers is to achieve maximum local control with minimal toxicity to normal and vital structures. In the past parallel opposing conventional beams were used and there was considerable damage to vital structures. Now a days treatment is delivered with highly sophisticated linear Accelerators. Intensity Modulated and image guided treatment is given. Treatment is verified at regular intervals. if any discrepancy found replanning is done. With the newer technologies it is possible to deliver Biological effective Dose to tumour for better control while restricting the radiation dose to vital structures. Doses close to 70Gy are given in concurrent setting and 60-66 Gy in post-operative setting.

Breast Cancer is the no-1 cancer among women to day , both in the World and in India . This cancer is uncommon before the age of 20 .But the incidence increases with age .In Asean county an aggressive form ie; Triple negative Breast cancer is seen in high number .In India the pick incidence come one decade before the average world incidence. To day it is accepted that Ca Breast is a systemic disease, not confined to Breast only.

The traditional approach of removing breast for cure is no longer in practice by oncologists. Radical Mastectomy has been replaced with modified /simple mastectomy .Breast Conservation Surgery is recommended with a view to preserve it. Modern chemotherapy and Radiotherapy has contributed to its success. Oncologic cure has not been compromised, many times in advanced stage the purpose of surgery is limited to avoid fungiation, so a simple mastectomy is considered enough.

The other parameters that influence surgical decision and outcome are considered more relevant to day .These are hormonal status, human epithelial receptor status, proliferative index, genetic parameter(BRCA1,BRCA2) etc. All are not relevant to every patient, but it shapes the treatment decision to day. More over breast cancer treatment is not followed as a rule of thumb, but it is individualised.

In India the majority of breast cancer cases are treated by general surgeons and they refer the case to on co center after mastectomy, irrespective of stage of the disease.As a result, the overall outcome has not improved over ages.In my discussion I shall annalise the rational approach to breast cancer surgery as per different stages.My other friends will cover other modality of treatment . Most Breast Cancer patients need combined treatment for success.

Epithelial ovarian cancer is the most lethal of the gynecologic malignancies, largely due to delayed diagnosis in most patients. In the last 20 years or so, we have witnessed an unprecedented explosion in the number of new drugs approved for the treatment of ovarian cancer but only a few stimulating improvements in the diagnosis and treatment of cancer ovary. These include genetic testing in high grade serous carcinoma to use of HIPEC for advanced ovarian cancer and PIPAC for palliative surgery in recurrent peritoneal carcinomatosis. With shifted emphasis on no macroscopic disease from optimal cytoreduction there is renewed interest in the use of laser to vaporise carcinomatosis rather than excision. There is a fundamental difference between overall survival and cure and recent scientific developments though small, encourage an optimistic view. The introduction of Robotic surgery is adding to the precision of surgery. The aim of the presentation is to discuss recent knowledge about recommendations in ovarian cancer diagnosis and surgical care.

After careful studying of the local tradition and eating habits of people, inexpensive blenderized tube feeding formula consisting of foods with standard nutritional composition that meets the nutritional requirements of the children can be planned. As well by changing the proportion of the ingredients, it can be used for the adults. The enteral diets are formulated mainly with fresh foods and tested for their physical (homogeneity, stability, osmolality, pH, and flow rate) and chemical (moisture, ash, protein, lipids, energy, crude fiber, vitamin C, calcium, iron, magnesium, and zinc) characteristics. The cost was determined by surveying item prices in supermarkets and stores that specialize in nutritional support. The blenderized tube feeding formula was stable and homogeneous, and had slightly acidic pH, hypertonic osmolality, and flow rate comparable with gravity drip(20 per minute). Proximate composition analysis indicated appropriate levels of proteins, lipids, vitamin C, and zinc. The mean cost of 2000kcal of the standard blenderized tube feeding formula was Rs.7/- to Rs.8/- per 100gms., which is quite cheaper than the commercial enteral formulas. The planned diet can be an excellent choice for patients using blenderized tube feeding formulas as it consisted of habitual food items, had physical and nutritional quality, and was inexpensive.

Lifestyle is a way used by people, groups and nations depending on specific geographical, economic, political, cultural and religious text. Lifestyle is referred to the characteristics of inhabitants of a region in special time and place.In recent decades, life style is focussed as an important factor of health and segment of interest by researchers. According to the WHO, 60% of related factors to individual health and quality of life are correlated to lifestyle. Millions of people follow an unhealthy lifestyle. Hence, they encounter illness, disability and even death. Problems like metabolic diseases, joint and skeletal problems, cardio-vascular diseases, hypertension, overweight, violence and so on, can be caused by an unhealthy lifestyle. Making Decisions about the Foods We Eat affected our health. Many studies show that good nutrition lowers the risk for many diseases. Our food habits can bring on heart disease, stroke, some types of cancer, diabetes, and osteoporosis or help prevent them. The relationship of lifestyle and health should be highly considered. The presentations of unhealthy lifestyle includes Malnutrition, unhealthy diet, smoking, alcohol consumption, drug abuse, stress and so on which are dominant forms of Present days lifestyle. Consanguinity in some ethnicity is a dominant form of life style that it leads to the genetic disorders Besides, the lives of citizens face with new challenges. For instance, emerging new technologies within IT such as the internet and virtual communication networks, lead our world to a major challenge that threatens the physical and mental health of individuals. The challenge is the overuse and misuse of the technology,lack of physical activity, and poor health care seeking, in increased risks for mortality and morbidity is compelling. Understanding the pathways through which these various “unhealthy” behaviours affect health is complicated by the broader ecological context in which they occur. The complexity is further enhanced because behaviours do not occur in isolation and there is often a convergence of associations. As per the study conducted by researcher on the families of Indore City of Madhya Pradesh, sample constituting unmarried children between the age 0f 15-30 and their parents as well as grandparents focusing on structure, functions, core values and regulative norms among the members. It can be concluded that most of the youngsters favored having fast foods, having their personal gadgets, living their lives according to them For example, using the computer and other devices up to midnight, addiction to use mobile phone is related to depression symptoms and the patterns are all supported by their parents being at a busy schedule. Family is a fundamental social institution in society, the family, is considered the primary and most important agent of socialization. Therefore, lifestyle has a significant influence on physical and mental health of human beings. In order to develop and implement a meaningful behaviour change agenda we need to understand the complexity of behavioural factors and their dynamic interrelationships and how these collectively affect health. Diet is the greatest factor in lifestyle and has a direct and positive relation with health, continuous exercise along with a healthy diet, Exercise can also help reduce muscle pain, making it an ideal choice for people who feel limited by pain or mobility challenges sound sleep, normal sex relation are necessary for healthy life. Some studies stress on the relation of active lifestyle with happiness. Advanced technology facilitates the life of human beings. Leisure pastime is a sub factor of lifestyle. Neglecting leisure can bring negative consequences like people endanger their health.Making Decisions about the Way You Live based on beliefs, attitudes, and values. Personal behavior is affected by the information you learn at home and school, and from the radio, newspapers, and television An unhealthy family environment that includes any kind of abuse, whether physical, sexual, or psychological, can make it nearly impossible to achieve sound mental health. The aftereffects of abuse can linger for years, and some abuse victims experience post-traumatic stress disorder. If you're being abused, the first step is finding a way out. And if you have a history of abuse, don't deal with it alone. Seek treatment so you can move on with your life.

With the completion of the Human Genome project and Next generation rapid DNA sequencing based platforms, there has been a global phenomenon of Molecular medicine. In the last three decades, with the advent of high end technology and tools in Molecular Life sciences, there has been a transition from Blood/Serum/Sputum/Tissue, Protein based diagnostics to Nucleic Acid( DNA/RNA) based Diagnostics. It is imperative to understand the complexities of Genome based changes which are acquired and inherited. Genetic Disorders are mainly classified as inherited genetic dysfunctions and multiple of them lead to a syndrome. In a lifetime, a number of changes in the genome are acquired. These changes can be detected early or when they lead to dysfunction. Currently there are various platforms to detect these changes from single cell genomics to systemic approach, from in silico to molecular platforms. Predictive genomics may be useful information to prevent or delay the catastrophic events in our life and such changes are unique to each individual or group, therefore, it is the era of personalized or precision medicine. In the Indian context, we have to customize the arrays and platforms based on the unique diseases such as Head and neck- oral carcinoma to Thalassemia. In the area of Clinical cancer practice, the advent of targeted chemotherapeutics has paved way for companion molecular diagnostics approach in each of the disease condition to choose the right drug for the right target. The personalization approaches must be developed from Preconception counseling to Tumor DNA banking, or stem cell profiling and Cellular banking. The Next generation approach is a dynamic and evolving paradigm shift from general and routine approach to precise and specific approach with BIG data interpretomics involved in it. We are in the era of integrated and inclusive medicine where clinicians, Scientists and Patients are important stakeholders. The biggest challenge is to scale up the personalized approach as at one hand we have to tailor-make the therapy but on the other hand we have to reach the last man in the village. Therefore, the key is to integrate the digital platform with game changing approach of health care delivery tools in the era of silicon revolution. We are not far away from an era of Molecular Genomics being routinely practiced in every clinic and each patient have their personal Data with them to be used as per the clinical condition.

Background: Existing genomic tests for assessment of "risk of recurrence" in ER+ breast cancer patients are expensive and not validated for Indian patients. Breast cancer is a disease of pre-menopausal women in India/asia and are predominantly prescribed chemotherapy. We focused our efforts on developing a cost-effective predictive test which will: i) accurately estimate the "risk of recurrence" for ii) a broader (node - & +) set of pre- and post-menopausal Indian patients.

Methods: Using a retrospective training cohort of 300 node– and node patients, we developed "CanAssist-Breast" (CAB)- a morphometric Immunohistochemistry (IHC) based test comprising 5 biomarkers plus three clinical parameters (Tumor size, grade and node status) to arrive at a CAB Score. The risk stratification model was developed using SVM based machine learning technology and classifies patients into low- or high-risk for recurrence.

Results: We performed a prospectively designed retrospective clinical validation study on > 850 pre- and postmenopausal cases in India and worldwide (35% pre-menopausal, 65% Stage II) which shows NPV of 95%. The majority of patients called "low risk" had Stage 2, Grade 2/3 disease (clinically high risk), demonstrating that CAB reclassifies patients who would be considered high risk clinically. Further, CAB was also predictive of chemotherapy benefit and shown to be superior to prognostic tools such as IHC4, Ki67 or PREDICT. In a head-to-head pilot study with OncotypeDx, CAB has higher accuracy in predicting recurrences and has 80% concordance with Oncotype Dx on low-risk patients who do not recur.

Conclusions: We have developed and validated CAB- a cost-effective, CE marked and ISO-13485 accredited IHC based risk stratification test for ER+ early breast cancer patients. CanAssist-Breast is available for testing for patients in Asia.

Lung cancer is the leading cause of cancer-related deaths in India and globally. Tobacco smoking is the most important risk factor for lung cancer in both genders. According to Globocan report, lung cancer accounted for 17% of all cancers. There is definite increased tobacco consumption trend followed by rising trends of lung cancer mortality, especially in developing countries. The increase in tobacco smoking worldwide leads to increased incidence of lung cancer. The risk among continuous long term smokers is 10- to 20-fold in relation to the risk among never-smokers. In the remaining parts of the world tobacco epidemics is still evolving what brings rapid increase of the number of new lung cancer cases and deaths. Number of lung cancer deaths worldwide is expected to grow up to 3 million until 2035. The increase of the absolute number of lung cancer deaths in more developed countries is also caused mostly by population aging and in less developed countries predominantly by the evolving tobacco epidemic. Bidi smoking is a more prevalent form of smoked tobacco in India than cigarette smoking. Genetic susceptibility, age, air pollution, radon exposure, occupational exposures, gender, race, and pre-existing lung disease are important contributors and added to the effect of tobacco smoking. Diet rich in vegetables and fruits probably exerts a protective effect. High intake of meat, in particular fried red meat, increases the risk of lung cancer. Over the past 30 years, the distribution of histologic types of lung cancer has been changing from squamous cell carcinoma, which was formerly the predominant type, is decreasing, while adenocarcinoma has increased in both male and females over the country except few centre. Trend of adenocarcinoma incidence is increasing globally replaced squamous cell carcinoma (SqCC) as the most prevalent type. However, in several parts of North/North-East India, SqCC is still reported as the most common form of lung cancer. Different regions of India also vary substantially in relation to age, gender, histology, smoking profile, and disease stage distribution.

The lung cancer is broadly divided histologically into Non-small cell lung cancer (NSCLC ~85% of lung cancers) and Small cell lung cancer (SCLC~15% of lung cancers). Non-small cell lung cancer (NSCLC) is broadly classified into Adenocarcinoma and Squamous Cell Carcinoma. Reduction in NSCLC-NOS (non-small cell lung cancer- not otherwise specified) has led to apparent increase of adenocarcinoma and squamous cell carcinoma being more prevalent in many centres. Accurate histological NSCLC subtyping is necessary for optimal epidemiological assessment. Accuracy depends on the results with immunohistochemistry (IHC) or immunochemistry in small biopsy and cytology specimens. The detection of the genetic abnormalities like driver mutations, which drive carcinogenesis has changed the therapeutic approach to more of personalised or targeted therapy. Tumours are now being called according to their molecular profile which constitutes new molecular epidemiologic data. Established therapeutic targets are e.g. EGFR, ALK, ROS1, PD-1/PD-L1. However the emerging (e.g. MET, RET, NTRK), and elusive (e.g. TP53, KRAS, MYC) molecular targets are the future of epidemiology and management of lung cancer. Small Cell Lung Cancer is an aggressive neuroendocrine (NE) tumour derived from bronchial epithelial cells, SCLC (also known as oat-cell carcinoma) accounts for about 13–15% of lung cancer. It is so strongly correlated with a history of smoking, that the occurrence in a never smoker constitutes an anomaly.

Lung cancer is the most important cause of mortality in cancer patients in the whole world. Moreover these patients with lung cancer are often elderly, with comorbidities and unfit to receive chemotherapy. Non-small cell lung cancer is a heterogeneous disease due to the presence of driver mutations which are targetable. After the discovery of these druggable mutations the treatment of lung cancer has been revolutionized. Tyrosine kinase inhibitors like erlotinib, gefitinib, afatinib ,osimertinib and now immunotherapy has improved the survival in lung cancer up to 40 months. In the last couple of years the cornerstone for discovery in cancer therapeutics has been immunotherapy. Use of immunotherapy like nivolumab and pembrolizumab has proven to improve survival in lung cancer. Immunotherapy drugs like durvalumab are also offering better survival in stage III lung cancer patients after chemoradiotherapy. With these targeted treatment options available, personalized treatment of lung cancer patients is now possible.

The estimated loco-regional failure rates between 20-50% after multimodality therapies and approximately 30% for surgery followed by postoperative RT. Multi-disciplinary evaluation and decision making is always preferred. Patient selection is key for successful irradiation with respect to pre-existing comorbidities and organ dysfunction. All the risk factors and possible complications should be discussed in detail. For definitive cases doses >66Gy should be used whereas 54-60Gy is required in post-operative setting. Only patients with high-risk features found at histopathological examination of the resected specimen should be considered for postoperative reirradiation. Carefully observe the previous treatment details including spinal cord doses and dose distribution. Reirradiation results in Grade 3 or 4 late toxicities in 30-40% of the patients. Up to 5 -10% of patients may have treatment related mortality. The common late toxicities encountered are feeding tube dependence, strictures, aspiration pneumonia, osteoradionecrosis, carotid blowout, fistula, etc. Overall survival rates in the range of 40% to 50% at 2 years are achievable. Compared to salvage surgery alone, adjuvant reirradiation (with or without concomitant chemotherapy) improves LRC and DFS but has no effect on OS. Preferably IMRT with image guidance should be used. Reirradiation for recurrent and second primary tumors of the head and neck is now a reasonably safe and most accepted standard of treatment.

Reconstruction after cancer excision in head and neck region is always challenging. This is mainly because of the three dimensional nature of the defect and the thinness, pliability as well as the elasticity of the local tissue. Various local and loco-regional flaps are available as reconstructive options. Delto-pectoral flap, pectoralis major myocutaneous flap, forehead flap and fan flaps are amongst the commonly used ones for this region. Technological advancements have enabled reconstructive surgeons to bank on microvascular transfer of tissue from distant sites of the same individual. This has several advantages and convenient for the patients though there is a learning curve. Free transfer of radial artery forearm flap was first described in Chinese literature hence it is also known as Chinese flap. The flap gained enormous popularity because of its reliable anatomy, pliable skin, ease of elevation and long pedicle. Only disadvantage with this flap is poor esthetics of donor site and delayed healing of donor site if the tendons get exposed during harvest of flap. Meticulously performed these morbidities can be minimized. This flap can be made sensate, harvested with bone graft, and with reasonably large dimension of skin paddle. Its long vascular pedicle with saphenous vein provides comfort to the surgeon in terms of distance from the recipient vessels. This flap is an ideal option for reconstruction of buccal mucosa, tongue, cheek skin, proximal esophagus and reconstruction of many other anatomical structures. Free Radial artery forearm flap is also the hot pot for the beginners in the field of microsurgery due to the reasons mentioned. Hence this flap is a very useful tool for head and neck reconstruction.

Tumor microenvironment plays a critical role towards tumor progression. Immuno-suppressive factors derived from tumor microenvironment are known to inhibit anti-tumor responses of host cell immunity. Immuno-suppressive regulatory mechanisms extended from tumor site to secondary lymphoid organs are not fully understood. Implementation of counter suppressive responses by various immune modulators may be useful to investigate cell-signaling pathways associated with the immune regulatory suppressive mechanisms towards cancer progression. We have been working to dissect out the role of immune-regulatory T cells (Tregs) and immune-suppressive microenvironment associated with antitumor cytotoxic T cell (CTL) responses Moreover, we have found that a T helper type 1 (Th1) responses is partly beneficial towards anti-tumor CTL responses. Recently, we have proposed the complexity towards the manipulation of Tregs and antigen specific CTL-based tumor immunotherapy. Our current understanding towards the possible yet robust effector T cell responses associated to host Toll Like Receptor (TLRs) and Transient Receptor Potential (TRP) ion channels suggests possible implications towards the cellular and molecular role in tumor immunity. Research with cell lines, primary cells, animal model and also with the human blood samples from normal donors and patients are the prime components for such experimental studies. The current works are being supported by DBT, India; CSIR, India; DST-SERB, India; along with ILS and NISER Bhubaneswar, India research facility). Such understanding will be helpful towards designing immuno-therapeutic strategies for anticancer immunity.

Covalent recognition of ubiquitin (Ubs) and ubiquitin-like molecules (Ubls) play a significant role in protein function regulation and initiation of signaling. NEDD8 is an emerging molecule in the field of translational protein modification and regulation. A well-known substrate of NEDD8 is TP53 tumor suppressor protein. TP53 plays a critical role in inducing cell cycle arrest and apoptosis. Its loss or inactivation is a sine qua non of cancer. Consequently, therapies directed at restoring p53 function particularly its ability to induce apoptosis is a major focus of different cancer therapy including breast cancer and brain tumor. In this study, we studied the impact of NEDDylation on the activity of p53 and its activated form TP53-8D20D. Although NEDDylation of TP53 stabilizes it, but its effect on p53 transcriptional activity is not well understood and obscure. The present study elucidates that over expression of NEDDylated TP53 enhances apoptosis in breast cancer, thus suggesting that NEDDylated TP53 is active. Further, we report that Noxa is one of the crucial pro-apoptotic effectors of NEDDylated TP53-mediated apoptosis and NEDDylated TP53 induces the promoter activity of well known cell cycle regulator p21. Further study on the mechanism of activation of TP53 upon NEDDylation would help in establishment of new therapeutic targets for breast cancer treatment.

Prostate cancer is a common heterogeneous disease, especially in the developed world, and the prevalence is increasing in India. Moreover, there is an inheritable risk contributing appreciably to tumorigenesis. Most patients diagnosed in the post prostate-specific antigen era present with clinically localized disease, the majority of which do well regardless of treatment regimen undertaken. Current treatment strategies are based largely on anatomical and pathological parameters. In the recent past, several DNA sequencing studies of primary and advanced cancers have revealed recurrent patterns of genomic aberrations that expose mechanisms of resistance to available therapies and potential new drug targets. Suppression of androgen receptor (AR) signalling is the cornerstone of advanced prostate cancer treatment. Genomic aberrations of the androgen receptor or alternative splicing of its mRNA are increasingly recognised as biomarkers of resistance to AR-targeted therapies such as abiraterone or enzalutamide. Genomic aberrations of the PI3K–AKT axis, in particular affecting PTEN, are common in PCa, and compounds targeting different kinases in this pathway are showing promise in clinical trials. Both germline and somatic defects in DNA repair genes have been shown to sensitise some patients to therapy with PARP inhibition. In addition, abnormalities in mismatch-repair genes are associated with response to immune checkpoint inhibition in other solid tumours and present a tantalising therapeutic avenue to be pursued. Aberrations in CDK4/6–RB1 pathway genes occur in a subset of PCas, may associate with differential sensitivity to treatment, and are likely to have clinical implications beyond prognostication. Inhibitors of CDK4/6 are already being tested in prostate cancer clinical trials. Furthermore, deletions of RB1 are strongly associated with a neuroendocrine phenotype, a rare condition characterized by a non-AR-driven transcriptomic profile. Finally, aberrations in genes involved in regulating the chromatin structure are an emerging area of interest. Deletions of CHD1 are not infrequent in PCa and may associate with increased AR activity and genomic instability, and these tumours could benefit from DNA-damaging therapies. In this talk, I will be covering the evolution of grading of prostate cancer from the original Gleason system in the 1960-1970s to a more patient centric grading system proposed in 2013 from a group at Johns Hopkins Hospital, validated in 2014 by a large multi-institutional study, and subsequently accepted by the World Health Organization (WHO), College of American Pathology (CAP), and the AJCC TNM system. Also I will include: (1) historical background; (2) 2005 and 2014 International Society of Urological Pathology Grading Conferences; (3) Description of Gleason patterns; (4) new approaches to display Gleason grades; (5) grading variants and variations of acinar adenocarcinoma; (6) reporting rules for Gleason grading reporting secondary patterns of higher grade when present to a limited extent; (7) reporting secondary patterns of lower grade when present to a limited extent; (8) reporting percentage pattern 4; (9) general applications of the Gleason grading system; (10) needle biopsy with different cores showing different grades; (11) radical prostatectomy specimens with separate tumor nodules; (12) a new grading system for prostate cancer; (13) molecular pathology of prostate cancer. This would help summarizing how genomic discoveries in prostate cancer are changing the treatment landscape of advanced cancers, both by identifying biomarkers of resistance and by identifying vulnerabilities to be targeted. Advances in genomics have catalyzed changes in the landscape of urothelial carcinomas, especially reflected in the classification of high-grade tumors. While advanced stage in general is associated with poor outcome, there is a considerable heterogeneity in the clinical behavior among them. Recent studies have attempted to elucidate the profile of high-grade urothelial carcinomas, however, there is a paucity of data to support clinical use of molecular analysis. These are aggressive neoplasms with molecular heterogeneity culminating in variable biologic outcome of the disease. Molecular characterization, particularly in locally aggressive or metastatic setting ramifies actionable genomic alterations that can significantly impact the disease outcome, even in patients with refractory tumors. Molecular profiling of HGUC, particularly advanced or metastatic disease yields therapeutically actionable alterations such as FGFR3, ERBB2, and EGFR as seen by us and other multicentric studies, can significantly impact clinical management of patients with therapy refractory high-grade tumors. In this talk, I will be covering the genotype-phenotype correlation and variant histologies of high-grade urothelial carcinomas with an insight to prognosis and therapeutic decision-making.

The current classification of lymphoid neoplasms is based on clinical information, morphology, immunophenotype, and molecular genetic profiles. Despite technical and scientific progress, some aggressive B-cell lymphomas with features overlapping between two different types of lymphomas remain difficult to classify. The updated World Health Organization classification of Tumours of the Hematopoietic and Lymphoid Tissues has addressed this problem by creation of two new provisional categories of B-cell lymphomas, unclassifiable; one with features intermediate between diffuse large Bcell lymphoma and classical Hodgkin lymphoma and the second with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Also there are some other areas in lymphoma that needs special attention because of therapeutic and prognostic implications. In this talk, I will be discussing the following areas: 1. In situ lesions and follicular hyperplasia versus follicular lymphoma; 2. Hodgkin lymphoma; 3. Diagnosis of lymphoproliferative disorders with needle biopsies; 4. Small B Cell lymphoma and ancillary studies; 5. Gastrointestinal lymphoid proliferations and lymphomas; 6. An approach to large B-cell lymphomas, including double-hit and triple-hit lymphomas.

Large dose extended field Radiation Therapy (RT) was successfully used as the only curative modality for Hodgkin's Lymphoma (HL) in the 1960s in the absence of multiagent chemotherapy, which resulted in irreversible late RT toxicities including second malignancies (SM) decades later. The more recently incorporated multiagent chemotherapy along with RT not only shown superior outcomes but also allowed RT dose and volume de-escalation. Subsequently, various multicenter randomized phaseIII studies also demonstrated equal efficacy of RT dose and volume de-escalation, which also resulted in significantly lesser late RT toxicities. Hence, short multiagent chemotherapy supplemented with miniRT constitutes an effective combined modality of treatment (CMT), especially in the early stages of HL.

Acute lymphoblastic leukemia (ALL) accounts for only 20% of adult leukemias but is the most common childhood acute leukemia, representing approximately 80% of cases. The most important prognostic indicators in ALL are age, white blood cell count at presentation, immunophenotype, minimal residual disease and karyotype. Cytogenetic abnormalities in ALL are associated with distinct immunological phenotypes and outcomes. We report the results of conventional karyotyping using standard G-banding technique in 290 patients with ALL diagnosed at our institute. ALL was more common in the pediatric age group and the most common phenotype was B-cell ALL. The most common findings detected in children were normal karyotype followed by hyperdiploidy and t(1;19), whereas in adults, it was normal karyotype followed by t(9;22). Apart from these commonly reported karyotypes, many other uncommon abnormalities were also encountered, such as previously unreported unique 3 way translocations with unknown clinical significance. Response assessment and survival outcomes in correlation to these karyotypes are to be analysed. This is the largest series on cytogenetic analysis in patients with ALL reported from India to the best of our knowledge.

Hypoxia is a pervasive feature of tumor microenvironment which trigger activation of the hypoxic response pathways through stabilization of HIFs (Hypoxia inducible factors). It is commonly involved in solid tumor biology including proliferation, glucose metabolism, angiogenesis, metastasis, and resistance to therapies. The overexpression of HIFs in solid tumors is associated with cellular adaptations to adverse microenvironment, aggressive cancer cell behaviors and eventually correlated with poor survival of patients. Endothelial cells (EC) and pericytes are two distinct types of cells in the blood vessel wall that help in neovasculature functions. Both the cells are primarily involved in tumor angiogenesis which leads to metastatic colonization to distant organs. Ang1 and Ang2 are expressed in pericyte and EC respectively under HIFs regulation. HIF2-α regulated Ang1 expression in hypoxic pericytes thereby inducing EC sprouting, migration and tube formation. Endothelial cells are regulated by HIF-1 α and HIF-2 α in response to hypoxia. HIF-2 α autonomously regulates expression of angiogenic factors such as fibronectin, integrins, endothelin B receptor, and Dll4 in endothelial cells, and helps in maintaining vessel integrity and tumour neovascularization. Tumors favor glycolysis for their survival and secret high amount of lactate in their niche. Lactate has proangiogenic roles and influences endothelial growth by stimulating IL8/NFkB signalling as well as increasing VEGF level. Endothelial AMPK, Akt, SIRT1 and Foxo1 modulate the utilisation of alternative energy substrates. Hypoxia induced HIF-1 α and lactate also activate the Notch signalling pathway which helps in tumor survival. In depth exploration of endothelial and pericyte metabolic changes, and interactions in response to hypoxia may give more insight into survival and therapeutic strategies to target tumour metabolism.

Raman spectroscopy an optical tool, has been envisaged and worked upon for oncological applications as early as the 1990s. The various studies undertaken till date have endeavoured to diagnose the disease at a pre-malignant state. To this end, several researchers have unravelled various biochemical signatures pertaining to oncogenesis and its prognosis. This is a concise analysis of the published results, their chief findings, and the multivariate statistical classification employed therein. It also extends to analyse the hurdles yet to overcome for the technique to reach the bedside. In the near future we would see the herald of this technique in routine diagnostic and surgical procedures.

A liquid biopsy, also known as fluid biopsy is the sampling and analysis of body fluids like blood, urine, saliva, CSF and pleural fluid for diagnosis and monitoring of diseases like cancer . It detects circulating tumour DNA (ct DNA) which is released into blood and fluids from apoptosis and necrosis of primary or metastatic tumour cells. From Sparsh Hospital, liquid biopsies were sent for nine lung cancer patients, two were positive for EGFR mutation. The genetic defects found in ct DNA like point mutations, chromosomal rearrangements and abnormal epigenetic patterns are identical to those found in the tumour source. This technique can also be used to detect fetal genetic disorders As early as seven weeks following conception by extraction of cell-free fetal DNA ( cff DNA). In case of heart attack, circulating endothelial cells (CECs) are sampled.

Hundred selected cases of cancer cervix belonging to Stage – III & IV were studied During the period from March 2014 to 2017 attending AHRCC, Cuttack. 80% cases belonging to Hindu community of low socio economic status maximum Cases were post menopausal in the age Group of 46 to 50 years. The lowest age of the patient is 39yr and highest Stage group is 58 yrs. Each patients after Cytomorphological and histopathological diagnosis of cancer cervix were subjected to a course of Radiotherapy. Which revealed cytoplasmic vacuolation, nuclear pyknosis, Kryorrhexis, Multinucleation ultimate disintegration of the cells etc. Most of the spontaneous chromosomal aberration were recorded in the chromosomal preparation obtained from the loose malignant cells of 50patients (stage – III invasive squamous cell cancer cervix) before Radiotherapy. Out of 3374 mitotic metaphase studied exhibited chromosomal aberration which includes gaps, breaks aneuploids, fragments of unknown origin, pyknosis, chromatic extraction, terminal fusion, translocation, stickiness and ring chromosome. Out of 100 patients, in 50patients of the study, the humoral immune response has been evaluated. The IgG levels in the patients before the treatment were found to be higher than the normal controls and this IgG levels increase after first treatment of Radiotherapy. Pre-treatment levels of IgA slightly higher then controls. Immunoglobulin levels of stage IV patients were comparatively higher than those of stage III patients. Probably there was a gradually increase in the levels of immunoglobulin with increase stage of the disease. Out of 100 patients, 87patients responded favourably to the Radiotherapy and 21 patients remain positive for Malignancy cells after full exposure of Radiotherapy. Presence of vacculated cell in the pretreatment smears and infiltration of histiocytes and Leukocytes during Radiotherapy can be considered as positive indices for Radio curability. The chromosomal data can be used as a parameter for diagnosis, prognosis and curability of this disease. The increase of IgG, IgA in the first exposure of Radiotherapy and then IgA levels at the end of the 2nd week are higher than those of control. After the end of 4thweeks of Radiotherapy, its level fluctuates. So immune factor also play a role during Radiotherapy is a parameter for the curability of the disease. The present piece of chromosomal study indicate that in cervical carcinoma patients have constitutional chromosomal aberration which include both stable and unstable aberrations. This study established that a considerable degree of structural and numerical chromosomal instability is associated with carcinoma cervix. So women should avoid being exposed to HPV, Don‟t smoke, women should get vaccinated . Certain types of sexual behavior increase risk of getting genital HPV infection. Such as unhealthy sanitation, having many partners as some cause of cervical cancer. Hence organization mass cytological programme women should regular pap smear during abnormal bleeding , the cancer cervix may be avoided.

Treatment of Breast cancer has undergone quite an improvisation in the last 20 years since the introduction of molecular biology, immunohistochemistry and availability of targeted therapy. We present our last 6 years’ experience in treating 862 Breast cancer patients in a single unit at a Regional cancer centre in India. Total of 862 breast cancer patients have been treated at our institute in a single surgical oncology unit from 2010 to 2016. Maximum incidence was observed in the age group 35-64 years (710/82.4%) and least in above 65 years (73/ 8.5%) with almost an equal number of patients coming from rural (51.9%) and urban (48.1%) population. Right sided breast cancer (56%) dominated compared to left (43.4) whereas 0.6% were bilateral. A higher incidence was noted amongst postmenopausal (54.2%) compared to premenopausal women (45.8%). Maximum patients were of Luminal A category (35%) with most of them presenting as Stage II (42.5%) and III (44.4%) disease. Triple Negative tumours contributed to significant 32.7% of the disease. 338 patients were given neoadjuvant chemotherapy before surgical management. 21 patients underwent Breast conservation surgery with Sentinel Lymph node biopsy done in 9 patients with 100% sentinel Lymph node identification rate while the rest underwent modified radical mastectomy. Adjuvant chemotherapy and Radiotherapy was Tad ministered to 437 and 702 patients respectively whereas 198 patients were given targeted therapy. Hormonal therapy was offered to 460 patients based upon their receptor status. In a developing country where health insurance cover and governmental policy is not available for the patients, it remains a challenge to offer the advanced management to all patients attending a regional cancer centre.

We have developed a new strategy to deliver anticancer drugs selectively into tumour cells by targeting sigma-2 receptors. Sigma-2 receptors are overexpressed in various tumour cells. The radiolabeledsigma-2 receptor ligand, [18F]ISO-1, provided high contrast images of solid tumours in cancer patients by the Positron Emission Tomography (PET). Sigma-2 ligands are rapidly internalized into cancer cells by endocytosis pathways and localize in multiple subcellular organelles such as lysosomes, mitochondria and the endoplasmic reticulum. These data suggest that sigma-2 receptor ligands are an excellent candidate for delivering anticancer drugs selectively to tumours. We conjugated a sigma-2 ligand, SW43, to a second mitochondria-derived activator of caspase (SMAC) mimetic drug. The resulting compound, SW III-123, successfully delivered the SMAC mimetic to ovarian cancer cells, suppressed tumour growth and improved mouse survival. Mechanistically, SW III-123 induced rapid degradation of inhibitor of apoptosis proteins (cIAP1 and cIAP2), accumulation of NF-dB-inducing kinase (NIK) and activation of caspase-8, -9 and -3. Tumour necrosis factor alpha (TNFα) antibody markedly blocked SW III-123-induced cell death and caspase-3 activity. The data suggest that SW III-123 activated NF-κBand apoptotic pathways. In conclusion, sigma-2 ligands are a promising tumour-targeting drug delivery agent. Sigma-2-conjugated SMC exemplifies a novel class of cancer chemotherapeutics.

Lung cancer is the most commonly diagnosed cancer in the United States and Europe and it is a major cause of cancer death. Surgical resection, when possible, offers the best chance of healing of NSCLC in selected patients and in early stage. In patients not candidates for surgery, chemotherapy and radiotherapy are mainly palliative. Cryoablation is a minimally invasive technique, highly innovative, which has only recently been used in the treatment of primary and secondary lung tumours. Cell death is obtained as a result of rapid freezing followed by slow thawing that causes necrosis of the target tissue. Cryoablation can be proposed with radical intent (curative) in cases of disease limited to the lung; individual tumours no larger than 5 cm or up to 5 multiple tumours confined to no larger than 3 cm each one. The advantages of cryoablation are due to very precise control of the treated area (display of the ice ball) sparing the surrounding healthy tissues. The major risks and complications of pulmonary cryoablation are those deriving from interventional treatment such as: local hematomas, pneumothorax, pulmonary bleeding caused by wrong placement of the cryoprobes and infections.

Cervical cancer remains one of the most common causes of cancer-related death among women in developing countries. Microtubules, being a validated anti-cancer drug target, prompted innovation of novel anti-mitotic chemotherapeutics which could overcome systemic toxicity related limitation of the clinically used anti-cancer drugs.

This study aims to explore the detailed anti-cancer mechanism of NMK-BH2, a novel bopindolol- hydrazide-hydrazine derivative based on indole scaffold. According to our data, the antiproliferative activity of NMK-BH2 was selective towards cervical cancer (HeLa) cells compared to normal cells, thus conferring therapeutic advantage of reduced host toxicity. NMK-BH2 caused G2/M arrest followed by mitochondria-mediated apoptosis through depolymerisation of cellular interphase and spindle microtubules. It also induced lethal autophagy, independent of apoptosis, contributing to enhanced cytotoxicity in HeLa cells. Characterisation of NMK-BH2 –tubulin interaction in cell-free system revealed that NMK-BH2 inhibited the microtubule assembly through strong and specific binding to tubulin at a single site, overlapping with colchicine-binding site on tubulin.

In conclusion, the present study suggests NMK-BH2 as an efficient and selective anti-cancer agent endowed with remarkable ability to target the cellular microtubule system, leading to apoptosis and autophagy-mediated cell death in HeLa cells and thus, inspires its establishment as a promising candidate for cervical cancer chemotherapy.

Bone metastases of breast cancer typically lead to a severe osteolysis resulting from unbalanced bone metabolism. On the other hand, the semi-metallic element gallium (Ga)is an inhibitor of bone resorption. Thus, using an established in vitro model associating conditioned medium from breast cancer cells with osteoclast precursor cells, we explored Ga activity on osteoclastogenic in an aggressive bone metastatic environment. We first observed that Ga dose-dependently inhibited osteoclast genesis induced by tumour cells medium. To mimic a more aggressive environment where pro-tumorigenic factors are released from bone matrix, metastatic breast tumour cells were stimulated with TGF-, a major cytokine involved in bone metastases development. In these circumstances, Ga still inhibited cancer cells medium-driven osteoclast genesis. Lastly, we evidenced that Ga directly and strongly impacted cancer cells proliferation/viability, as well as the expression of major osteolytic factors. This is the first time that antitumor properties of Ga have been specifically studied in the context of bone metastases. Our data strongly suggest that, through its action against the vicious cycle involving bone cells and tumour cells, Ga represents a relevant and promising candidate for a local delivery upon the resection of bone metastases from breast cancer.

This study is an attempt to obtain reliable data on the natural history of breast cancer growth. We analyse the opportunities for using classical mathematical models (exponential and logistic tumour growth models, Gompers and von Bertillon tumour growth models) to try to describe growth of the primary tumour and the secondary distant metastases of human breast cancer. The research aim is to improve predicting accuracy of breast cancer progression using an original mathematical model referred to Compass and corresponding software. We are interested in: 1) modelling the whole natural history of the primary tumour and the secondary distant metastases; 2) developing adequate and precise Compass which reflects relations between the primary tumour and the secondary distant metastases; 3) analysing the Compass scope of application; 4) implementing the model as a software tool.

The Compass is based on exponential tumour growth model and consists of a system of determinate nonlinear and linear equations; corresponds to TNM classification. It allows to calculate different growth periods of the primary tumour and the secondary distant metastases: 1) "non-visible period" for the primary tumour; 2) "non-visible period" for the secondary distant metastases; 3) "visible period" for the secondary distant metastases. The Compass is validated on clinical data of 10-years and 15-years survival depending on the tumour stage and diameter of the primary tumour (1. Engel J. et al. Eur J. Cancer. 2003; 39(12): 1794-1806; 2. Engel J. et al. Int. J. Radiate. Oncol. Biol. Phys. 2003; 55(5): 1186-1195; 3. Engel J. et al. Cancer Metastasis. 2012; 31(1-2): 235-246). The new predictive tool: 1) is a solid foundation to develop future studies of breast cancer growth models; 2) does not require any expensive diagnostic tests; 3) is the first predictor which makes forecast using only current patient data, the others are based on the additional statistical data.

The Compass model and predictive software: a) fit to clinical trials data; b) detect different growth periods of the primary tumour and the secondary distant metastases; c) make forecast of the period of the secondary distant metastases appearance; d) have higher average prediction accuracy than the other tools; e) can improve forecasts on survival of breast cancer and facilitate optimization of diagnostic tests.

The following are calculated by Compass: the number of doublings for «non-visible» and «visible» growth period of the secondary distant metastases; tumour volume doubling time (days) for «non-visible» and «visible» growth period of the secondary distant metastases.

The Compass enables, for the first time, to predict "whole natural history" of the primary tumour and the secondary distant metastases growth on each stage (pT1, pT2, pT3, pT4) relying only on the primary tumour sizes. Summarizing: a) Compass describes correctly the primary tumour growth of IA, IIA, IIB, IIIB (T1-4N0M0) stages without metastases in lymph nodes (N0); b) facilitates the understanding of the appearance period and inception of the secondary distant metastases.

We have analysed the dataset METABRIC to find reproducible genes to form linear and nonlinear models for survival prediction. We drew random half samples from the training data as bootstrap samples and applied the Cox Proportional Hazards Model to analyse the full training data and each half sample with the adjustment for the four clinical variables: age, ER, tumour size, and node. From the analysis of the full training data, we selected top 330 genes (top 1%). We selected 50 genes most reproducible in the analyses of the bootstrap samples with repetition rate greater than 0.36. The 50 selected genes include TFRC (one of 21 Oncotype DX genes) and other cancer genes such as PAWR, PKM2, STAT5Band ANGPT2. We used linear/nonlinear predictors to combine the expression of the selected genes. We used the validation data to examine the generalization performance of the predictors with adjustment for age, ER, tumour size, and node. The nonlinear model gave a signature with HR=1.7, CI:1.39-2.08 and P= 2.552e-07 better than the linear model. The METABRIC data analysis showed that the patients with high expression of STAT5Bhad better prognosis while those with high expression of TFRC had poor prognosis. The analysis of the tamoxifen treatment data showed that TFRC expression can be reduced by taking Tamoxifen without changing STAT5B. Our further understanding about these genes has clinical implications in breast cancer treatment.

Several hundred billion to a trillion cells die in the adult human body daily, and a considerable amount of fragmented cell-free nucleic acids (cfNAs) from dying cells are released into the circulation. Our research has shown that circulating cfNAs can freely enter into healthy cells, accumulate in their nuclei, trigger a DNA damage repair response (DDR) and integrate into host cell genomes by an unique mechanism http://www.ias.ac.in/article/fulltext/jbsc/040/01/0091-0111; http://f1000research.com/articles/4-924/v1). Similarly, at the tissue level, locally generated cfNAs from dead cells can be taken-up by healthy bystander cells to induce DDR that facilitates their integration into recipient cell genomes. Genomic integration of cfNAs leads to dsDNA breaks, inflammation, chromosomal instability, senescence and apoptosis of recipient cells. cfNAs from cancerous cells can cause oncogenic transformation of NIH3T3 cells which are tumorigenic in immune-deficient mice. These findings raise a new hypothesis of cancer metastasis which posits that metastasis arises from denovo oncogenic transformation of cells of target organs induced by cfNAs arising from apoptotic circulating tumour cells (CTCs). This hypothesis challenges the current dogma that metastasis are produced by growth of CTCs that are lodged in distant organs.

MicroRNA (miR) deregulation is associated with colorectal cancer (CRC) development and recurrence; therefore, miRs may be reliable biomarkers for detecting early relapse postoperatively. Ten candidates were identified using miR arrays: miR-7, miR-31, miR-93, miR-141, miR-195, miR-375, miR-429, miR-494, miR-650, and let-7b. Substantial differences were observed in their expression levels between early relapsed and non-early relapsed CRC patients. Using a miR RTqPCR, we observed that expression levels of miR-93, miR-195, and let-7b were significantly decreased, whereas those of miR-7, miR-141 and miR-494 showed increases that were more significant in the CRC tissue samples from the early relapsed patients than the non-early relapsed patients. A panel of 6 miRs (miR-7, miR-93, miR-195, miR-141, miR-494, and let-7b), at a cut-off value of 2 deregulated miRs, distinguished early relapsed CRC from non-early relapsed CRC, with a sensitivity of 76.6% and a specificity of 71.4%. By combining this 6-miRs panel with 6 clinicopathologic factors, at a cut-off value of 4, distinguished early relapsed CRC from non-early relapsed CRC, with a sensitivity of 89.4% and a specificity of 88.9%.This study showed that the developed miR panel has the potential to improve predicting early relapse in CRC patients.

Prostate cancer is the most common malignancy and the second leading cause of cancer-related mortality among men in the United States. Although androgen-deprivation therapy (medical or surgical castration) is highly effective for advanced prostate cancer, the majority of patients eventually develop resistance and progress to castration-resistant prostate cancer (CRPC). Unfortunately, most cases of CRPC are currently incurable. The cause of castration resistance is still not completely known. Recent genetic mouse models and studies with cancer patients firmly demonstrated the critical roles of Hippo signalling in cancer development. Yes-associated protein, YAP, is an effector of the Hippo tumour suppressor pathway. The oncoprotein YAP has been implicated in promoting several types of tumour formation, such as liver and skin tumorigenesis and rhabdomyosarcoma. We found that YAP mRNA was upregulated in androgen-insensitive prostate cancer cells (LNCaP-C81 and LNCaP-C4-2) when compared to the androgen-sensitive LNCaP cells. YAP knockdown greatly reduced the migratory and invasive rates of LNCaP-C4-2 cells. Importantly, ectopic expression of YAP was sufficient to promote LNCaP cells from androgen-sensitive to androgen-insensitive in vitro and YAP conferred castration resistance in vivo. Deletion of MST1/2 (core tumour suppressors in the Hippo pathway) or YAP did not affect the prostate development. YAP activation or MST1/2 inactivation was not sufficient to promote prostate tumorigenesis.

Treatment of Breast cancer has undergone quite an improvisation in the last 20 years since the introduction of molecular biology, immunohistochemistry and availability of targeted therapy. We present our last 6 years’ experience in treating 862 Breast cancer patients in a single unit at a Regional cancer centre in India. Total of 862 breast cancer patients have been treated at our institute in a single surgical oncology unit from 2010 to 2016. Maximum incidence was observed in the age group 35- 64 years (710/82.4%) and least in above 65 years (73/ 8.5%) with almost an equal number of patients coming from rural (51.9%) and urban (48.1%) population. Right sided breast cancer (56%) dominated compared to left (43.4) whereas 0.6% were bilateral. A higher incidence was noted amongst postmenopausal (54.2%) compared to premenopausal women (45.8%). Maximum patients were of Luminal A category (35%) with most of them presenting as Stage II (42.5%) and III (44.4%) disease. Triple Negative tumours contributed to significant 32.7% of the disease. 338 patients were given neoadjuvant chemotherapy before surgical management. 21 patients underwent Breast conservation surgery with Sentinel Lymph node biopsy done in 9 patients with 100% sentinel Lymph node identification rate while the rest underwent modified radical mastectomy. Adjuvant chemotherapy and Radiotherapy was administered to 437 and 702 patients respectively whereas 198 patients were given targeted therapy. Hormonal therapy was offered to 460 patients based upon their receptor status. In a developing country where health insurance cover and governmental policy is not available for the patients, it remains a challenge to offer the advanced management to all patients attending a regional cancer centre.

Neuroblastoma is a paediatric tumour of the Sympatico adrenal lineage of the neural crest characterized by an extreme molecular and clinical heterogeneity, which is the main cause of the unsatisfactory response to standard multimodal therapy. The identification of new and selective biomarkers is crucial to fill the gaps about the biological and molecular mechanisms of neuroblastoma and to improve cancer therapies. This study identified a positive and promising correlation between Tropomodulin’s (Tmods) proteins and neuroblastoma. Tmods bind the pointed end of actin filaments, regulate polymerization and depolymerization processes, modifying actin cytoskeleton dynamic and influencing neuronal development processes. High expression levels of Tmods positively correlate with high survival probability neuroblastoma patients’. Functional studies on neuroblastoma cell lines demonstrated that Tmod 1 Knocking induced cell cycle arrest, cell proliferation arrest and a mature functional differentiation. Tmod 1 overexpression is responsible of particular cell morphology and biochemical changes, which direct cells towards a neuronal prognostic favourable differentiation profile. On the contrary, Tmod 1 downregulation caused the loss of mature cell differentiation for the development of neuroendocrine cell characteristics, delineating an aggressive and prognostic unfavourable tumor behaviour. This work indicates that Tmods can be the innovative and prognostic favourable biomarkers in high-risk neuroblastoma and contributes to understanding new biological mechanisms to improve personalized therapeutics opportunities.

Vitamin C has been shown to protect against oxidant injury at physiological concentrations and has been suggested as having both a preventative and therapeutic role in a number of pathologies when administered at pharmacological levels. In our clinic we treat cancer patients by high doses of vitamin C intravenously (15-75 grams) during 40 years. According to our data, there was positive response to IVC, which was demonstrated by measurements of inflammation (C- reactive protein) and inflammatory/angiogenesis cytokines. 174 cytokines with tumour markers were determined in cancer patients before and after a series of IVC treatments. The average levels (z-scores) for inflammatory and angiogenesis promoting cytokines, that were higher than averages for healthy controls, decreased over the course of treatment. A decrease in the level of inflammation correlated with the decrease in the levels of tumour markers. Clinical studies of chemotherapy with vitamin C demonstrated that IVC does not interfere with anti-tumour effects of chemotherapy. IVC may improve time to relapse, enhance reductions in tumour mass and improve survival in combination with chemotherapy. IVC treatment improves quality of life, physical function, and toxicities associated with chemotherapy. Our Phase I clinical study and other trials indicated that IVC can be administered safely with relatively few adverse effects.

Strategies to enhance an antigen specific immunity against cancer have been met with limited clinical success. We adopt a 2-tier protocol coupling active with passive immunization, allowing a prospective clinical evaluation of survival in 31 terminal cancer patients. Treatment commences with subcutaneous inoculation of whole cancer cell antigen followed by re-infusion of ex vivo expanded autologous T cells. Tumour-specific cytotoxic T cells were confirmed via Elispot and Real-time Cell Analysing (RTCA) Assay, and serum cytokines were also measured pre and post therapeutically. Statistical tests show tumour-specific T cell response is effectively invoked post treatment. Spearman correlation analysis determined significant association between higher post treatment cytotoxicity scores and longer survival duration in months(R=0.59, p=0.005). This result is mirrored by the Elispot count. Prospective controlled trials are needed to further clarify the role of cancer whole antigen immunization with adoptive cell therapy, but these encouraging preliminary observations suggest that this combination can induce more durable responses to immunotherapy.

Vitamin C has been shown to protect against oxidant injury at physiological concentrations and has been suggested as having both a preventative and therapeutic role in a number of pathologies when administered at pharmacological levels. In our clinic we treat cancer patients by high doses of vitamin C intravenously (15-75 grams) during 40 years. According to our data, there was positive response to IVC, which was demonstrated by measurements of inflammation (C- reactive protein) and inflammatory/angiogenesis cytokines. 174 cytokines with tumour markers were determined in cancer patients before and after a series of IVC treatments. The average levels (z-scores) for inflammatory and angiogenesis promoting cytokines, that were higher than averages for healthy controls, decreased over the course of treatment. A decrease in the level of inflammation correlated with the decrease in the levels of tumour markers. Clinical studies of chemotherapy with vitamin C demonstrated that IVC does not interfere with anti-tumour effects of chemotherapy. IVC may improve time to relapse, enhance reductions in tumour mass and improve survival in combination with chemotherapy. IVC treatment improves quality of life, physical function, and toxicities associated with chemotherapy. Our Phase I clinical study and other trials indicated that IVC can be administered safely with relatively few adverse effects.

Strategies to enhance an antigen specific immunity against cancer have been met with limited clinical success. We adopt a 2-tier protocol coupling active with passive immunization, allowing a prospective clinical evaluation of survival in 31 terminal cancer patients. Treatment commences with subcutaneous inoculation of whole cancer cell antigen followed by re-infusion of ex vivo expanded autologous T cells. Tumour-specific cytotoxic T cells were confirmed via Elispot and Real-time Cell Analysing (RTCA) Assay, and serum cytokines were also measured pre and post therapeutically. Statistical tests show tumour-specific T cell response is effectively invoked post treatment. Spearman correlation analysis determined significant association between higher post treatment cytotoxicity scores and longer survival duration in months(R=0.59, p=0.005). This result is mirrored by the Elispot count. Prospective controlled trials are needed to further clarify the role of cancer whole antigen immunization with adoptive cell therapy, but these encouraging preliminary observations suggest that this combination can induce more durable responses to immunotherapy.

Introduction: The protein kinase CK2(formerly Casein Kinase II) is implicated in tumorigenesis and transformation. However, the mechanisms of CK2activation and the role of CK2in breast cancer remains to be elucidated.

Methods: CK2activity, phosphorylation, and protein expression were determined in ER+ MCF-7 and T47D, and ER- MDA-MB-231 human breast cancer cell lines. The expression of the various genes involved in reactive oxygen species (ROS) metabolism and CK2in human breast cancer tissues were investigated using RT2 PCR array (Qiazen), and immunohistochemistry, respectively.

Results: Oestrogen increased CK2activity and phosphorylation in ER+, but not in ER- cell lines, which were inhibited by the antioxidant N-acetyl-L-cysteine (NAC). H2O2 enhanced CK2activity and phosphorylation. Estrogen increased ROS generation in ER+, but not in ER- cell lines through activation of p38 MAPK. The PCR array demonstrated that, among the 115 oxidative stress-related genes examined, 11.3% genes were downregulated and 2.6% genes were upregulated in ER+/PR+, 7.0% genes were downregulated in HER2+, and 6.1% genes were upregulated in triple negative breast cancer tissues, respectively. Nuclear CK2protein expression was observed in 100% (15/15), 100% (15/15) and 92% (12/13) of ER+/PR+, HER2+, and triple negative cancer tissues, respectively.

Conclusios: The data suggest that 1) estrogen activated protein kinase CK2via the induction of ROS/p38 pathway 2) there were no significant differences in the expression of oxidative stress-related gene and CK2a protein among the three different types of human breast cancer cells.

Four heart hormones, namely atrial natriuretic peptide (ANP), long-acting natriuretic peptide (LANP), vessel dilator and kaliuretic peptide reduce up to 97% of cancer cells in vitro. These four cardiac hormones eliminate up to 80 % of human pancreatic adenocarcinomas, 2/3rds of human breast cancers and up to 89% of human small cell lung cancers growing in athymic mice. ANP intravenously for 3 hours after “curative” lung surgery as an adjunct to surgery results in a two year relapse-free survival of 91% compared to 75% with surgery alone. Their anticancer mechanisms of action involve binding to receptors on the cancer cells followed by 95% inhibition of the conversion of inactive to active rat sarcoma-bound guanosine triphosphate (RAS)-mitogen –activated protein kinase kinases 1/2 (MEK 1/2 ) (98% inhibition)-extracellular signal-related kinases 1/2 (ERK1/2 ) (96 % inhibition) in cascade cancer cells. They are dual inhibitors of vascular endothelial growth factor (VEGF) and its VEGF2 receptor (up to 89% ) They also inhibit MAPK9 i.e. c-JUN-N-terminal kinase 2. One of the downstream targets of VEGF is B-catenin, which they inhibit up to 88%. These four peptide hormones inhibit the Wingless-related integration site (WNT) pathway 68% and WNT secreted-Frizzled protein is reduced by up to 84%. Signal transducer and activator of transcription 3 (STAT 3), a final “switch” that activates gene expression that leads to malignancy, is specifically decreased up to 88 % by these peptides as they do not affect STAT 1. There is cross –talk between the RAS-MEK 1/2-ERK 1/2 kinase cascade , VEGF, B-catenin, JNK, WNT, and STAT pathways and each of these pathways and their cross talk is inhibited by these peptide hormones. They enter the nucleus of cancer cells where they inhibit the proto-oncogenes c-Fos (up to 82 %) and c-Jun (up to 61%). Conclusion: These multiple kinase inhibitors have both adjunct and primary anticancer effect ANP is one of four hormones synthesized by the ANP prohormone gene.

Cancer is a disease that causes high mortality rates in Indonesia and has a tendency to increase. A wide variety of prevention and treatment of cancer has been done in Indonesia but there is no treatment that is really effective. Indonesia has a huge potential in natural resources, including plants that can be used as medicine. Piper retrofractum and Zingiberis officinale var. rubrum are plants which has anticancer activity in the active ingredient. By using the method of literature study, this paper focuses on assessing the activity and effectiveness of the combination of the active ingredient in Piper retrofractum and Zingiberis officinale var. rubrum that have a potential synergistic effects as anticancer in the appropriate dosage form. Curcumin can induces apoptosis of cancer cell and piperine as an antioxidant that inhibits the free radical chain oxidative so it can prevent the oxidative stress.

Optimization of the extraction of active ingredients piperine from Piper retrofractum and curcumin from Zingiberis officinale var. rubrum can be done by soxhlet extraction method with solvent ethanol 95%. Soxhlet method yields an efficient curcumin and piperine extraction, the efficiency of solvent and time. The extract that obtained from the extraction process should be standardized to ensure its quality so it implies safety and efficacy of dosage form produced. Effort to maximize the activity and effectiveness as an anticancer, extract can be made dosage form based on microencapsulation technology with variation concentration of core and coating agent using spray drying techniques. The formulation technology of the combination of Piper retrofractum and Zingiberis officinale var. rubrum based on microencapsulation is expected to provide a therapeutic effect that is secure, effective, and efficient against cancer.

Keywords : Curcumin, Microencapsulation, Piperine, Piper retrofractum, Zingiberis officinale var.rubrum

Recently, some authors reported that the Topoisomerase enzymes such as TOPO II is more expressed in aggressive subset of tumours (for example breast tumour that overexpresses HER- 2/neu). Based on these evidences recently our group has synthesized a new molecule, called SC4, which inhibits the TOPOII, reducing the proliferation and acts negatively on the cellular migration; furthermore, SC4 shown in vivo an antiproliferative effect and a reduction in the systemic toxic effects. We have tested SC4 on two cancer cell lines, that representing the principal "Big Killer" of the oncology: pancreatic cancer human cell (Mia-PaCa2) and triple negative breast cancer human cell (MDA.MB231). In vitro cytotoxic assays have demonstrated the ability of SC4 to inhibit cell proliferation. The MTT assay , FACs Colony Assay results support the inhibition of proliferation. Likewise, we performed two experimental in vivo to evaluate the SC4 inhibition activity on proliferation and migration, and to assess the degree of safety. Orthotopic cancer xenograft mouse models and in vivo models of secondary localization (Lung Colonization)confirm the anticancer activity. In conclusion SC4 inhibits proliferation and migration of human tumour cell lines by blocking the activity of TOPO II, and may be considered as a potent inhibitor of tumour growth and invasion in mouse model; for these reasons could be considered a valid prototype for the development of new antineoplastic therapies.

The immune system in cancer cells was revealed with the understanding that immunoglobulins expressed on the cancer surface play important roles in cancer immunology. RP215 monoclonal antibody generated in 1987 against ovarian cancer cell extract was shown to react specifically with a carbohydrate-associated epitope mainly found in the variable region of immunoglobulin heavy chains and expressed on the surface of almost all of cancer cells (designated in general as CA215). Since then, RP215 has become a unique probe to study mechanisms of action by which the cancer cells are affected by these immunoglobulins. Generally speaking, RP215 and anti-human immunoglobulins are equally effective in inducing apoptosis and complement-dependent cytotoxicity reactions to cultured cancer cells and reducing the volume of the implanted tumor in nude mouse animal models. Interaction studies were performed between isolate cancerous immunoglobulins and/or CA215 and human serum proteins, most of which exhibit either anti-cancer or pro-cancer properties. Therefore, it is hypothesized that cancerous immunoglobulins may function to interact with these human proteins for the growth/proliferation as well as protections of cultured cancer cells in human circulations. RP215 may be further developed as candidates of anti-cancer drugs to target most of cancer cells for immunotherapy of human cancer.

Breast cancer is the most common cancer in females all over the world with approximately one million new cases each year as well as one of second leading causes of death among females. In Pakistan, the most frequently diagnosed cancer among females is also breast cancer. Breast cancer is more common in Pakistani population as compared to the Western population. In Pakistan every year at-least 90,000 women suffer from breast cancer. One in every nine Pakistani women suffers from breast cancer which is one of the highest incidence rates in Asia. Recently, incidence of breast cancer is 21.5% among all and 45.9% among female patients, reported. Its incidence in Pakistan is 2.5 times higher than that in neighbouring countries like Iran and India. Key factors that play role in the development of breast carcinoma are the genetics and environment, the reproductive experience, the effect of endogenous and exogenous hormones in females, the change in immune status, host vulnerability and the biologic determinants of breast carcinoma. The present study is aimed to provide awareness about breast cancer as well as an updated knowledge about the prevalence, risk factors and disease knowledge of breast cancer in Pakistan.

Keywords: Breast cancer, incidence, prevalence, risk factors, Pakistan

Prostate cancer is the second most common cause of death from cancer in men of all ages. The three conventional treatment options include surgery, radiation and chemotherapy. In many cases, these treatments are used in combination. Increased resistance to current chemotherapies by prostate cancer calls for an urgent need to discover and develop new therapeutics that can slow the growth of cancer cells while having lesser side effects on patients. In an effort to discover new anticancer drugs from natural products, several Jamaican plants were screened for anticancer activity. The Jamaican Ball Moss (Tillandsia recurvata L.) was one such plant that exhibited potent activity against the prostate cancer cell lines in vitro and in vivo. To explore the mechanism of action of the plant material, a crude extract of Ball Moss was screened for interaction with over 450 kinases. The crude extract was active against 5 kinases (kd = 8-14 μg/ml), of which 4 are implicated in prostate cancer onset and proliferation. The kinases are; CSNK2A2, DRAK1, GAK and MEK5. Based on our scientific determination of the molecular target for this potent extract, our lab produced a nutraceutical (Alpha Prostate Formula) for the prevention and treatment of prostate cancer.

The high prevalence and incidence of breast cancer in Indonesia remains a disheartening issue, for it has turned out to be a threat for the quality of Indonesian women’s life. Let alone the fact that the patients and their families often lose interest in recognizing the issue of breast cancer, both benign and malignant. Besides, the problem faced by breast cancer patients in determining which kind of diagnosis or best therapy is still overlooked by the patients as well as their family members. This includes their indifference toward the patients’ nutrition during chemotherapy, which now thus must be taken into consideration.

This research aims at observing therapy needs in general, particularly that of nutrition of breast cancer patients during their chemotherapy and post-therapy period. This research is the result of qualitative data collected by case study on 17 breast cancer patients undergoing chemotherapy in Al-Ihsan Hospital, Bandung District and Hasnain Hospital, Bandung City. These patients have undergone an in-depth interview either on their own or accompanied by a family member. The result of the qualitative research is obtained through content analysis observation, showing a shallow understanding about therapy, both generally and specifically, regarding the importance of nutrition and the escalation of its amount on the patient and their families. In fact, one of the things that support the patient’s immune system during their chemotherapy is the sufficient condition of nutrition. Not only that, the result shows that cancer survivors claim they keep a balanced intake of nutrition during and after therapy. Therefore, it is necessary to make a formula about nutrition needs of breast cancer patients, in the preparatory, momentary, and pre-empting stage of chemotherapy.

Keywords: Nutrition therapy, breast cancer.

Introduction: Breast cancer is the most common malignancy in women, accounting for 29% of all female cancers. It accounts for < 1% of all cancer cases in men. In a population-based cancer registries in Gharbia, Egypt, breast cancer was the most frequent cancer among Egyptian females. Prognostic information for the individual patient is based on the analysis of biological markers in the primary tumour including (ER), (PR), (HER2) and Ki67, together with age, tumour size, histological grade and lymph node involvement. Molecular subtyping of breast cancer may provide additional prognostic information regarding patient outcome.

Objectives: To evaluate the prognostic effect of breast cancer subtypes on local relapse rates, distant metastases, and survival in women underwent breast conservative surgery for early stages breast cancer.

Material and Methods: Data of 100 patients affected by early stage breast cancer and treated with breast-conserving therapy were reviewed. Patients were grouped, based on the basis of receptor status and HER-2 status, patients were grouped, as: luminal A (ER + and/or PR+, Ki67 low and HER2-), luminal B (ER + and/or PR+, Ki67 high and/or HER2+), HER2-positive (ER-, PR- and HER2+) and triple negative (ER-, PR, HER2-). Distribution of variables among subtypes was evaluated with Pearson’s test. Survival rates were calculated with life tables; Cox regression stepwise method was used to identify predictive variables of survival.

Results: Median age was (range 18-50) and median follow up time of 40 months (range 36.83- 43.17).Breast cancer specific survival and distant metastases rates were different among breast cancer subtypes (both outcomes P= 0.001) , there was significant difference regarding local relapse rates (P=0.002 ). Axillary nodes status (P= 0.007), adjuvant therapy (P= <0.001) and breast cancer subtypes resulted prognostic factors of breast cancer specific survival; axillary node status (P= 0.007) and breast cancer subtypes had an impact on distant metastases.

Conclusions: In our study, breast cancer subtype seems a prognostic factor of breast cancer specific survival and distant metastases rates & of local relapse rate. Patients could be submitted to conservative surgery, if feasible, but considering the differences in survivals, patients with worse prognosis should receive more aggressive adjuvant treatment.

Increased consumption of refined carbohydrates, sugars, and saturated fats is accompanied by low intake of fruits and vegetables; this dietary pattern is involved in the etiology of different types of cancers, the global cause of morbidity and mortality in the Western countries and gulf region. Colorectal cancer, CRC, is among the primary preventive cancers if adequate intake of antioxidants was provided either by diet, and nutritional supplements. Our research group at Sultan Qaboos University has successfully identified phytonutrients- rich dietary bioactive agents (Date Pit Pomegranate Peel, Mushroom Extract, and Nabag Extract) which provide antioxidant protective effect against oxidative stress-induced CRC, using in-vivo experimental study models. Our results have shown a net subjective improvement in the CRC pathogenesis as evident by a marked decrease in tumour growth, increase in intra cellular glutathione level, and antioxidant enzymes-improved activities. It was concluded that the high intake of plant-based foods might be adopted as a dietary based intervention approach for the primary prevention of oxidative-stress mediated cancers, including CRC. The mechanism was thought to be by abrogating oxidative stress in carcinogenic cells.

Introduction: Environmental tobacco smoke (ETS) is the primary etiologic factor responsible for lung cancer. However, only 10–15 % of smokers develop lung cancer, suggesting a genetic role in modifying individual susceptibility to lung cancer. Antioxidant enzymes and genetic polymorphisms should be considered.

Aim: The present study aimed to evaluate the role of antioxidant enzyme activity and genetic polymorphisms in modifying the susceptibility to lung cancer among individuals exposed to ETS. Subjects and Methods: A total of 150 male subjects were divided into three groups: 50 lung cancer patients, 50 chronic smokers, and 50 passive smokers. Genotyping of microsomal epoxide hydrolase (mEH) exon 3 (Tyr113Hist) and exon 4 (Hist139Arg) polymorphisms were done by the polymerase chain reaction-restriction fragment length polymorphism technique. MnSOD (Val16Ala) polymorphism was detected by the real time-TaqMan assay. Erythrocyte MnSOD activity was measured spectrophotometrically.

Results: ETS-exposed individuals (both active and passive smokers) who carried the His allele of mEH exon3 have a 2.9-fold increased risk of lung cancer (odds ratio [OR] 2.9, P < 0.001). In addition, ETS-exposed carriers of the Arg allele of mEH exon 4 have a 2.1-fold increased risk of lung cancer (OR 2.1, P = 0.024). However, no association between the MnSOD Val16Ala polymorphism and lung cancer was detected among ETS-exposed individuals (OR 1.6, P = 0.147), although the lung cancer group had significantly lower MnSOD activity than the chronic or passive smoker groups (P = 0.03). Conclusions Exons 3 and 4 polymorphisms of the mEH gene may contribute to lung cancer susceptibility through disturbed antioxidant balance. However, this was not the case with the MnSOD Val16Ala single-nucleotid polymorphism. Antioxidant enzymes may modulate the influence of ETS exposure on lung cancer risk.

The aim of this study was to investigate VEGF expression in tumour tissue in patients with breast cancer in relation to stromal tissue and normal breast tissue in patients with benign breast disease, and in relation to circulating VEGF and IL-6 levels, preoperatively and postoperatively. Samples from 20 patients with breast cancer and 15 patients with benign breast disease were included. Immunohistochemical staining was used for determining VEGF expression in tissue samples. Measuring VEGF and IL-6 levels was conducted by ELISA.

Differences in VEGF expression between tumour and stroma were significant (p=0,007) and between tumour and normal breast tissue in benign disease patients (p=0,0001), and also between stromal and normal breast tissue (p=0,004). Circulating VEGF were significantly higher in serum from patients with breast cancer than in patients with benign breast disease pre- and post-operatively (p=0,023; p=0,019). VEGF levels were higher postoperatively in serum (p=0,009) and in seroma (p=0,0001). Circulating IL-6 were significantly higher in serum from patients with breast cancer than in patients with benign breast disease (p=0,023) postoperatively. IL-6 levels were higher postoperatively in serum (p=0,015) and seroma (p=0,0001). IL-6 levels were significantly higher in serum from patients with benign breast disease postoperatively (p=0,018). Statistically significant correlation between VEGF and IL-6 in seroma from patients with breast cancer was found (p=0,009). Results from present study suggest synergistic activity of VEGF and IL-6 in wound healing process after breast cancer surgery.

Expression can be disrupted either through genetic or epigenetic alterations. In cancer, over half of tumour suppressor genes are affected through methylation. It can also affect other important signal transduction pathways leading to altered receptor function, altered function of transcription factors, and disruption of normal cell–cell interaction. Aberrant methylation can occur at very early stage in cancer leading to malignancy, hypermethylated gene promoters hold great promise as tumour markers for early detection and their reversible nature provides an effective drug target for gene reactivation.

The Notch signalling pathway is one such developmental pathway governing cell fate decisions, differentiation, cell proliferation and apoptosis. Deregulated Notch signalling is found to have a prominent role in development of various cancers. Glioblastoma is most common primary brain tumour with very poor prognosis despite aggressive treatment regiments. Therefore, it is important to study genetic and epigenetic events leading to gliomagenesis and consequent aggressive phenotype to guide new treatment strategies.

The aim of this study was to detect Notch pathway genes potentially regulated by promoter methylation from human glioblastoma FFPE sections. Using methylation specific PCR, we identified Notch3 and JAG2 promoters as hypermethylated and Notch4 with both methylated and unmethylated promoter. Despite methylation, Notch3 showed robust gene expression suggesting its partial dependency on promoter methylation and presence of alternative regulatory mechanisms. However, low gene expression of JAG2 and absence of Notch4 gene expression suggest possibility of epigenetic silencing. This study provides gene expression and DNA methylation profiles of Notch pathway genes in glioblastoma. Epigenetic mechanisms can be used as markers that may guide treatment decisions.

Celastrol (CEL), a plant-derived triterpenoid, is a known inhibitor of Hsp90 and NF-κB activation pathways and has recently been suggested to be of therapeutic importance in various cancers. However, the molecular mechanisms of celastrol- mediated effects in lung cancer are not systematically studied. Moreover, it suffers from poor bioavailability and offsite toxicity issues. This study aims to study the effect of celastrol loaded into exosomes against two non-small cell-lung carcinoma (NSCLC) cell lines and explore the molecular mechanisms to determine the proteins governing the cellular responses. We observed that celastrol inhibited the proliferation of A549 and H1299 NSCLC cells in a time- and concentration- dependent manner as indexed by MTT assay. Mechanistically, CEL pre- of H1299 cells completely abrogated TNFα-induced NF-κB activation and upregulated the expression of ER-stress chaperones Grp 94, Grp78, and pPERK. These changes in ER-stress mediators were paralleled by an increase in apoptotic response as evidenced by higher annexin-V/PI positive cells evaluated by FACS and immunoblotting which showed upregulation of the ER stress specific proapoptotic transcription factor, GADD153/CHOP and alteration of Bax/Bcl2 levels. Exosomes loaded with CEL exhibited enhanced the anti-tumor efficacy compared to free CEL against lung cancer cell xenograft. CEL did not exhibit any gross or systemic toxicity in wild-type C57BL6 mice as determined by hematological and liver and kidney function test. Together, our data demonstrate the chemotherapeutic potential of celastrol in lung cancer and that exosomal formulation enhances its efficacy and reduces dose related toxicity.

Regulatory T cells (Tregs) are a specialized subpopulation of CD4+ T cells, which act to suppress the activation of other immune cells. Tregs are either naturally occurring or induced. Tregs have crucial role in induction of immune tolerance during infection, pregnancy, transplantation, autoimmunity and neoplasia’s. They are recently recognized as key component of the tumour microenvironment and important determinant of tumour progression; Tregsare implicated in both solid tumour and hematological malignancies. Thus manipulation of Tregs represents an emergingtherapeutic approach to cancer treatment.

The following items will be discussed:

• T regulatory Cells Types and function
• Tregs induction mechanisms
• Identification of Tregs
• Mechanisms underlying the role of Tregs in hematological malignancies
• Manipulation of Tregs as a targeted therapy in hematological alignancies

The Epstein-Barr virus (EBV) is a herpesvirus infecting more than 90% of the human population. The tropism of EBV for B lymphocytes is evidenced in its association with many lymphoproliferative disorders. Different types of EBV (EBV-1 and EBV-2), classified on the basis of EBNA-2 genotyping, have been reported in benign and malignant pathologies, but there is almost no information about their frequency in the Pakistani population. The aim of this study was to determine the frequency and distribution of EBNA-2-based EBV genotypes in lymphoma patients. Genomic DNA was extracted from formalin-fixed paraffin embedded (FFPE) tissue samples obtained from 73 EBVDNA- positive lymphoma patients. The β-globin gene was amplified to assess the presence and quality of cellular DNA from all samples. EBER-1 DNA was detected by PCR to confirm EBV presence in tissue samples. EBNA-1 mRNA relative quantification by quantitative PCR substantiated EBNA-1 mRNA overexpression in 52% of EBV-positive cases in comparison to an EBV-positive cell line control. EBNA-2 genotyping was done by nested polymerase chain reaction (PCR). Among typable samples, EBV-1 was present in 90.7%; EBV-2, in 9.3%. These results show that EBV-1 is the most prevalent type in the lymphoma population of Pakistan, similar to reports from other countries. This definition of EBV epidemiology in Pakistani lymphoma patients represents an important first step in using EBV for prognosis and monitoring treatment response in patients.

Keywords: Epstein - Barr virus; Genotyping; Non-Hodgkin Lymphoma; Hodgkin Lymphoma; EBER-1; EBNA-1;EBNA-2.

Neoplastic metastasis is a major route where tumour cells transfer from the primary tumour and colonize at other parts of our body to form secondary tumour. Cancer incidences are rising and novel anti-neoplastic compounds with new mechanism of actions are essential for preventing cancer related death. In the current examination, a novel series of pyridazine analogues 6a-m was synthesized and evaluated against metastatic neoplastic cells. Experimental data postulated that compound 6j has potential cytotoxic efficacy with prolonged activity against various cancer cells, including A549, HepG2, A498, CaSki and SiHa cells. Moreover, compound 6j arrests the A549 migration and invasions markedly by counteracting matrix metalloproteinase (MMP)-2 and MMP-9 expressions. Altogether, we concluded that compound 6j down regulates MMP-2 and MMP-9, thereby impairs metastatic cancer cell migration and invasions which can be translated into a potent anti-neoplastic agent.

Keywords: Pyridazine; Metastasis; Migration and invasion; MMPs; Cancer.

Introduction: The late effects of cancer treatment have gained a worldwide interest among hematologists, reproductive endocrinologists, oncologists, and all health care providers, and the protection against iatrogenic infertility caused by chemotherapy assumes a high priority.

Methods: Recent meta analyses of RCT's concluded that GnRHa cotreatment along chemotherapy significantly decreased POF rate. However, cyclic ovarian function is not equivalent to fertility [pregnancies].Therefore we evaluated the PR after exposure to gonadotoxic chemotherapy+ GnRHa vs controls. We have administered a monthly depot IM injection of GnRH-agonistic analogue to 300 young women exposed to gonadotoxic chemotherapy for malignant or non-malignant diseases, after informed consent, starting before chemotherapy for up to six months, in parallel to, and until the end of chemotherapy. These patients were compared to a control group of 200 patients of comparable age (14-40 years), who were similarly treated [chemotherapy without GnRH-a]. Neither the age, nor the diagnoses, or radiotherapy exposure differed between the two groups. The cumulative doses of each chemotherapeutic agent and the mean or median radiotherapy exposure did not differ between the groups. The patients who have not visited our clinic in the last 6 months were interviewed by phone to verify the data on pregnancies. The study was approved by the institutional RB ethics [Helsinki] committee.

Results: Less than 13% developed irreversible hypergonadotropic amenorrhea in the GnRHa co treatment group, vs 50% in controls The remaining patients resumed cyclic ovarian function, and 90 patients spontaneously conceived 178 times, and were delivered of 129 healthy neonates, in the GnRHa+ chemotherapy group. In the control group only 55 pregnancies were reported in 31 patients The age of the patients who spontaneously conceived, in the GnRHa group was 14-38 at chemotherapy compared to 14-30 y's in the control group. One patient, in the GnRHa group, spontaneously conceived three times and was delivered of three healthy neonates despite two stem cell transplantations [SCT], 11 years apart. Several patients spontaneously conceived up to six times. GnRH-a co treatment was beneficial not only against regular chemotherapy but also for lymphoma patients undergoing SCT in significantly decreasing the POF rate. The possible de-novo formation of follicles by the surviving germline stem-cells brings about a decrease in FSH concentration and return of regular cycles, ovulation, and even gestations. Most relevant to this equivocal and highly debatable issue, is a publication from one of the previous opponents to GnRH-a use for fertility preservation, reporting that the use of GnRH-a during chemotherapy has significantly increased the probability to conceive [OR= 12.87; P[0.001=. Furthermore, in keeping with our experience, two recent prospective RCT [NEJM, 2015 and JAMA 2016] have found significantly higher pregnancy rate and delivery rate, in addition to significantly higher cyclic ovarian function in the GnRHa+ chemotherapy group. In addition, they reported either similar or significantly higher survival rates of breast cancer patients in the GnRHa+ chemotherapy group vs. controls. Two recent expert committees have concluded that GnRHa cotreatment in parallel to chemotherapy is beneficial in minimizing POF rate and increasing pregnancy rate in survivors and recommended its use.

Conclusions: GnRHa cotreatment in parallel to chemotherapy is beneficial in minimizing POF rate and increasing pregnancy rate in survivors. Therefore, it should be offered to every young woman before gonadotoxic chemotherapy in addition to cryopreservation of embryos, ova, and ovarian tissue. Future endeavours may include Sphingosine-1-Phosphate as a novel means for fertility preservation, immunotherapy instead of chemotherapy, and in-vitro maturation [IVM] of primordial follicles from the cryopreserved ovarian tissues to mature metaphase-II fertilizable oocytes for IVF. This may completely omit the risk of reintroducing malignant cells while auto transplanting cryopreserved varian tissue.

Death Receptor 5 (DR5) is known to be an important anti-cancer drug target. TRAIL is a natural ligand of DR5, but its drug action is limited because of several factors. A few agonistic ligands were identified as TRAIL-DR5 axis modulators, which enhance the cellular apoptosis. Literature suggest that quinacrine (QC) acts as a DR5 agonistic ligand. However, the detailed mechanism explaining how QC interacts with TRAIL-DR5 axis has not been established. Also focused in vitro and in vivo experimental analysis to validate the hypothesis is not yet performed. In this work, extensive studies have been carried out using in silico analysis (molecular dynamics), in vitro analysis (cell based assays) and in vivo analysis (based on mice xenograft model), to delineate the mechanism of QC action in modulating the TRAIL-DR5 signalling. The MD simulations helped in identifying the important residues contributing to the formation of a QC-TRAIL-DR5 complex, which provide extra stability to it, consequently leading to the enhanced cellular apoptosis. QC caused a dose dependent increase of DR5 expression in cancer cells but not in normal breast epithelial cells, MCF-10A. QC showed a synergistic effect with TRAIL in causing cancer cell apoptosis. In DR5-KD MCF-10A-Tr (DR5 knocked down) cells, TRAIL+ QC failed to significantly increase the apoptosis but over expression of full length DR5 in DR5- silence cells induced apoptosis, further supporting DR5 as a drug target for QC. An increase in the release of reactive species (ROS and RNS) and activation of enzymes (FADD, CASPASES 3, 8, 9 and cytochrome-C) indicated the involvement of mitochondrial intrinsic pathway in TRAIL+QC mediated apoptosis. In vivo study pointed out that TRAIL+QC co-administration increases the expression of DR5 and reduce the tumor size in xenograft mice. This combined in silico, in vitro and in vivo analysis revealed that QC enhances the cellular apoptosis via the modulation of TRAIL-DR5 complexation and the mitochondrial intrinsic pathway.