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Background: Cancer is growing concern for every country. Reliable data is a source to define the magnitude of the problem, which then helps to plan for necessary action. This epidemiological study involves the collection and analysis of hospital registry data to assess the quantum of the problem of cancer over a five-year period from 2012-16 and to plan priority action. Materials and Methods: Hospital-based data for five years from 2012-2016 was retrieved from the department of radiotherapy at M. P. Shah Government Medical College, Jamnagar, Gujarat, India, and analysed to define the magnitude of the problem. All data was studied using Microsoft Excel 2016. Results: A total of 7355 patients were registered between 2012 and 2016, out of which 62 percent were male. Cancers of the cervix and uterus were discernibly less common in the Saurashtra region and accounted for only 12.37% of all cancers in females. Lung cancer was the leading cancer as a single site in males (24.13% of all cancers in males) and breast cancer in females (37.36% of all cancers in females). Head and neck cancer, all sites clubbed, was most common in males (42%). Jamnagar taluka represented around 50% of all cases at the study center. Conclusion: Tobacco-related cancers were most common in the male population, and stringent implementation of a national tobacco control program is the most appropriate measure to curtail incidences and hence mortality in this male population. Nonmodifiable risk factors like gender-related cancer were more common in the female population, and resource-appropriate screening is a suitable option for these diseases. A population-based cancer registry is required to further define the pattern pertinently, or an epidemiological study is required to find causes of the noticeably lower incidence of cancer of the cervix. [ABSTRACT FROM AUTHOR]

Aim: In this study, efficacy of collapsed cone algorithm-generated intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) were evaluated for treatment of thoracic esophageal cancer. Materials and Methods: Ten previously treated patients with VMAT were considered for evaluation. The planning parameters were evaluated in terms of max dose, mean dose, Homogeneity Index, Conformity Index for planning target volume, and organ at risk doses. Total monitor unit, treatment time, and gamma passing index were also reported. Results: The target dose coverage of the VMAT and IMRT plans achieved the clinical dosimetric criteria for all ten patients in the evaluation. Under the condition of equivalent target dose distribution, the VMAT plan's Conformity Index, monitor unit, treatment time, and gamma passing index rate were superior than in the IMRT plan, and the result was statistically significant. Conclusion: Collapsed cone algorithm-based VMAT can have a more effective and better approach for esophageal cancer than IMRT. [ABSTRACT FROM AUTHOR]

Purpose: To explore the feasibility and efficacy of interstitial brachytherapy application for nonresectable and chemo-resistant malignant liver and lung lesions. Materials and Methods: Percutaneous high-dose-rate interstitial brachytherapy (HDR ISBT) was applied in nine lesions of seven middle-aged patients with advanced carcinoma (five patients with liver lesion and two patients with lung lesion). All patients were surgically ineligible. All patients had already received systemic chemotherapy. Under computed tomography (CT) guidance (for lung lesion) or ultrasonography (USG) guidance (for liver lesion), a single stainless steel brachytherapy needle was inserted percutaneously in patients with lesion size ≤4 centimeter (cm) and multiple needles were inserted in patients of lesion size >4cm. A single dose of 15 Gy to 20 Gy with HDR ISBT was prescribed at the periphery of the lesion. The needles were removed just after treatment. Patients were kept under observation for 24 h after treatment. Results: The median size of the lesion was 6.5 cm. In all the cases of liver lesion, more than 75% shrinkage of tumor volume in follow-up at 6 mo was observed. It was more than 50% for lung lesion. None of the patients had developed significant complications as on the median follow up period of 15 mo (ranges 3–27 mo). Conclusions: Percutaneous CT-guided high-dose-rate interstitial brachytherapy is a minimally invasive, safe, and feasible treatment option with minimal complication for inoperable, chemo resistant, advanced cancers with encouraging treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: Urinary bladder cancer (UBC) is a disease quite common in developed countries; however, its incidence is increasing in developing countries as well. The diagnosis of UBC is generally based on a number of methods, of which urinary cytology is a very commonly used one. But it is not very reliable. Therefore many new markers and methods are being investigated to make non-invasive diagnosis of UBC easy and reliable. Objective: This study was carried out to find the usefulness of microRNA (miRNA)-10a as a diagnostic and prognostic marker in non-muscle-invasive urinary bladder carcinoma. Material and Method: Twenty patients with UBC were taken as cases with 20 controls. Urine cytological examination was done, as well as histopathological examination of tumor tissue of cases. Urinary miRNA-10a estimation of both the cases and controls were done. Result and Conclusion: It was found that miRNA-10a is significantly high in urine of patients with UBC. Its value also significantly correlated with the grade and stage of the tumor. Hence it can be concluded that urinary miRNA-10a is a potential candidate in the diagnosis and prognosis of UBC. [ABSTRACT FROM AUTHOR]

Objective: To evaluate efficacy and late toxicity of intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) in definitive management of head-and-neck cancers.Methods: In this prospective interventional study, histological proven squamous cell carcinoma of oropharynx, hypopharynx, or larynx with stage T1-3 N0-3 M0 who were not candidates for concurrent chemotherapy were treated with IMRT-SIB with radical intent. Doses prescribed for IMRT-SIB to meet the clinical needs of nodal volumes were either SIB-66 schedule 66 Gray (Gy) prescribed to high risk (HR) planned target volume (PTV), 60 (Gy) to intermediate risk (IR) PTV and 54 Gy to low risk (LR) PTV in 30 fractions or SIB-70 schedule 70 Gy to PTV-HR, 59.4 Gy to PTV-IR and 56 Gy to PTV-LR in 33 fractions.Result: Forty-five patients were included. Forty-two patients were treated with SIB-66 schedule and three patients with SIB-70 schedule. The median follow-up period was 21 (6-68) months. There was residual disease in three patients. Recurrence was observed in 24 patients. Most recurrences were in HR volume (n = 19) and three patients had distant failure. Estimated 2-year locoregional control, disease-free survival, and overall survival were 55.55%, 49.7%, and 51.1%, respectively. Grade 3 late skin toxicity, subcutaneous fibrosis, and xerostomia were observed in three patients.Conclusions: Efficacy and late toxicity of IMRT-SIB observed in our study suggest it as a suitable treatment option for patients who are not fit for chemoradiation. [ABSTRACT FROM AUTHOR]

Background: Oral cancer is a major health concern in the Indian subcontinent, where it ranks among the top three types of cancer in the country. Tobacco and its products have been implicated as a major etiologic factor behind cancers. It is believed that tobacco is an epidemic in itself taking the death toll to 7 million globally. In India alone, mortality because of tobacco is more than 1.3 million. Dentists are the first to notice any change in the oral cavity or come across any suspicious looking oral lesion and therefore are instrumental in primary prevention and care. Methods: The present study data are of the patients enrolled in a Tobacco Cessation Center(TCC) at a Dental College in Meerut in Meerut from May 2012 (since its inception) to March 2020. The following methods of counseling were carried out: group counseling, interactive sessions, audio--visual aids, and individual counseling sessions. Self-training for oral cavity examination was also given after every group counseling session. Behavioral counseling and pharmacological intervention were given as per Fagerström Test for Nicotine Dependence (FTND) score. At the end of 1 year, patients who quit were graded into 0, 1, and 2, with 0 for those who failed to quit, 1 for those who did completely quit, and 2 for those who reduced their habit by more than 50%. Results: The quit rate achieved was 57.6% (complete responders -43.2% and partial responders 14.4%). The relapse reported was 1.8%. Conclusion: A Tobacco cessation Center set up in a Dental College could be of great help in the primary prevention of oral cancer and can bring a drastic increase in quit rates. Proper counseling skills once nurtured in young under-graduates can boost the tobacco-free India campaign. [ABSTRACT FROM AUTHOR]

A biomarker is a measurable indicator used to distinguish precisely/objectively either normal biological state/pathological condition/response to a specific therapeutic intervention. The use of novel molecular biomarkers within evidence-based medicine may improve the diagnosis/treatment of disease, improve health outcomes, and reduce the disease's socio-economic impact. Presently cancer biomarkers are the backbone of therapy, with greater efficacy and better survival rates. Cancer biomarkers are extensively used to treat cancer and monitor the disease's progress, drug response, relapses, and drug resistance. The highest percent of all biomarkers explored are in the domain of cancer. Extensive research using various methods/tissues is carried out for identifying biomarkers for early detection, which has been mostly unsuccessful. The quantitative/qualitative detection of various biomarkers in different tissues should ideally be done in accordance with qualification rules laid down by the Early Detection Research Network (EDRN), Program for the Assessment of Clinical Cancer Tests (PACCT), and National Academy of Clinical Biochemistry. Many biomarkers are presently under investigation, but lacunae lie in the biomarker's sensitivity and specificity. An ideal biomarker should be quantifiable, reliable, of considerable high/low expression, correlate with the outcome progression, cost-effective, and consistent across gender and ethnic groups. Further, we also highlight that these biomarkers' application remains questionable in childhood malignancies due to the lack of reference values in the pediatric population. The development of a cancer biomarker stands very challenging due to its complexity and sensitivity/resistance to the therapy. In past decades, the cross-talks between molecular pathways have been targeted to study the nature of cancer. To generate sensitive and specific biomarkers representing the pathogenesis of specific cancer, predicting the treatment responses and outcomes would necessitate inclusion of multiple biomarkers. [ABSTRACT FROM AUTHOR]

Peripheral cemento-ossifying fibroma (PCOF) is a relatively rare tumor classified between fibro-osseous lesions. PCOF is an osteogenic neoplasm that ordinarily presents as an epulis-like growth with uncertain pathogenesis. It predominantly affects young adults, with peak prevalence between the first and second decades of life. We present here the case report of a 15-year-old girl, which was previously surgically excised twice and had recurred both the times. The disease duration was 2 years and a follow-up of 1-year was done. Clinical, radiographic, and histological characteristics are discussed with recommendations regarding the treatment is provided. [ABSTRACT FROM AUTHOR]

Background: The role of stromal microenvironment in growth, invasiveness, and metastatic potential of breast carcinoma (BC) is being recognized increasingly, both to predict prognosis and as potential therapeutic targets. The present study aimed to evaluate the correlation of angiogenesis, tumor-associated lymphocytes, and stromal CD10 expression with clinicopathologic parameters.Materials and Methods: This study included 100 consecutive cases of invasive BC undergoing modified radical mastectomy. Relevant clinical details, pathological grade, lymph nodal status, and clinical stage were noted. Paraffin-embedded sections were subjected to immunohistochemistry for CD34, CD20, CD45RO, and CD10. Microvessel density (MVD), tumor-associated lymphocytes, and stromal CD10 expression were estimated from these sections. Statistical analysis was done using nonparametric tests to correlate the clinic-pathologic features with each of these parameters.Results: MVD was found to be significantly higher in Grade III, node-positive cases, and higher stage breast cancers (P < 0.05). The number of T-lymphocytes was higher in node-positive cases, while B-lymphocytes were lower in number in higher grade tumors. CD10 expression showed a significant positive association with tumor grade, nodal status, and stage (P < 0.05 for each).Conclusion: This study demonstrates that changes in stromal microenvironment of BC such as MVD, tumor-associated lymphocytes, and stromal CD10 expression correlate with the clinicopathological parameters and hence may be exploited as prognostic markers or therapeutic targets, based on further larger studies. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to investigate the inhibitory role of second mitochondria determined activator of caspases mimetic on inhibitor of apoptosis proteins (IAPs) and regulation of caspases in nonsmall cell lung cancer cell line.Materials and Methods: Dimethyl sulfoxide and 3-(4, 5-dimethyl thizol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay was done to determine the IC50 of BV6 using NCI-H23 cell line. The levels of mRNA of X-linked IAP (XIAP), cellular IAP (cIAP-1), cIAP-2, caspase-6, and caspase-7 in H23 cell line were evaluated by a quantitative real-time polymerase chain reaction, while their protein expressions were tested using western blotting.Results: Two doses of BV6 dependently downregulated the expression of mRNA of XIAP (P = 0.002, P= 0.0003 vs. untreated), cIAP-1 (P = 0.05, P = 0.005 vs. untreated), and cIAP-2 (P = 0.001, P = 0.0002 vs. untreated), respectively, while the compound upregulated the mRNA expression of caspase-6 (P = 0.001, P < 0.0001 vs. untreated) and caspase-7 (P = 0.001, P = 0.0004 vs. untreated), respectively. Dose dependent of BV6 treatment significantly decreased the protein level of XIAP (P = 0.003, P = 0.007 vs. untreated), cIAP-1 (P = 0.02, P = 0.01 vs. untreated), and cIAP-2 (P = 0.008,P = 0.008 vs. untreated), respectively. However, the compound increased the protein level of caspase-6 and caspase-7 when compared to untreated control (P = 0.006,P = 0.001) and (P = 0.01, P = 0.001), respectively.Conclusions: The result showed that BV6 treatment reduced the level of mRNA of XIAP, cIAP-1, and cIAP-2 and increased the gene expression of caspase-6 and caspase-7 in NCI-H23 cell line. Therefore, the study revealed that BV6 could be used in future as additional therapeutics in lung cancer. [ABSTRACT FROM AUTHOR]

Aims: Nonsmall-cell lung carcinoma comprises 85% of lung malignancies and is usually associated with a poor prognosis due to diagnosis at advanced stages. Molecular diagnosis of computerized tomography (CT)-guided biopsy has the potential to identify subtypes of lung carcinoma like adenocarcinoma (AC) and squamous cell carcinoma (SCC) along with its molecular stratification. This approach will help predict the genetic signature of lung cancer in individual patients.Subjects and Methods: Histopathologically proved a CT-guided biopsy sample of lung cancer cases was used to screen for the expression of microRNA (miRNA) earlier quantitated in blood plasma. Primers against hsa-miR2114, hsa-miR2115, hsa-miR2116, hsa-miR2117, hsa-miR449c, and hsa-miR548q with control RNU6 were used to screen 30 AC, 30 SCC, 5 nonspecific granulomatous inflammation, and 8 control samples. Reverse transcription polymerase chain reaction (RT-PCR) data revealed expression of hsa-miR2114 and hsa-miR548q in AC as well as SCC.Results: RT-PCR data revealed that the expression of hsa-miR2116 and hsa-miR449c was found upregulated in AC while hsa-miR2117 was expressed in SCC cases. Bioinformatic analysis revealed that genes, where these miRNAs are located, were also upregulated while targets of these miRNAs were downregulated.Conclusions: miRNAs expression pattern in the CT-guided biopsy samples can be used as a potential tool to differentially diagnose lung cancer subtypes. The expression pattern of miRNAs matches very well in blood plasma and tissue samples, albeit levels were very low in the earlier case than later. This approach can also be used for screening mutations and other molecular markers in a personalized manner for the management of lung cancer patients. [ABSTRACT FROM AUTHOR]

Aim: This study intended to compare the dosimetric parameters using different definitions of prescription point A in high dose rate (HDR) brachytherapy of cervical cancer patients.Background: Manchester point A has been widely used for prescribing dose in brachytherapy. However, due to certain limitations of this point, a new definition of point A has been recommended by the American Brachytherapy Society (ABS).Materials and Methods: We retrospectively investigated 55 computed tomography-based plans of 20 cervical cancer patients treated with Ir-192-based intracavitary HDR brachytherapy. The dose of 7 Gy in 3 fractions each was prescribed to point A using revised Manchester definition of point A (AMAN) and ABS guideline definition (AABS). The effect of both definitions on various parameters including dose to point A and 90% of tumor volume (D90), dose received by 2cc volume of bladder, rectum and small bowel and treatment volume receiving 100% of prescription dose (V100) was analyzed.Results: Mean percentage difference of point AMAN dose and AABS dose with respect to prescription dose was 1.25% ± 1.43% and 1.21% ± 1.01%, respectively. Mean V100 was 80.4 ± 20.45cc and 88.47 ± 16.78cc for AMAN and AABS plans, respectively, while mean percentage difference between prescribed dose and D90 was found to be -37.90% ± 25.06% and -30.47% ± 25.50% respectively for both the definitions.Conclusion: Doses to both Manchester point A and ABS point A may be recorded during the transition period. However, ABS point A can be preferred over the Manchester point A as it conforms better with the desired dosimetric outcome and is found to be more static. [ABSTRACT FROM AUTHOR]

Introduction: Variation of doses due to positional uncertainties of applicators based on orthogonal radiograph has been evaluated by several researchers. The present study has analyzed the various possibilities of special alterations of applicator placements in intracavitary brachytherapy (ICBT) and its impact on the dose to target volume, rectum, and bladder. An innovative approach has been suggested to quantify and utilize the special coordinates for reproducibility of applicator based on the pelvic bone landmark.Materials and Methods: A total of 27 fractions of 9 (n = 9) cancer cervix patients treated with external beam radiotherapy followed by ICBT have been evaluated retrospectively. The first fraction of each patient was planned as per the International Commission on Radiation Units and Measurements report 38 guidelines and was considered reference for consecutive fractions regarding dwell positions, dose to target volume, bladder, and rectum points. For each fraction, positioning of applicators regarding their spatial orientations with respect to pelvic bone landmarks and their correlation with dose to bladder and rectum was recorded and analyzed.Results: It was found that mean angulations between (1) the two applicator points with respect to tip of central tandem (α), (2) the two applicator points with junction point situated on the sacrum bone (β) and (3) the angle between the line joining applicator points and a point defined on pelvic bone (γ) is 62.20° ± 5.74°, 37.13° ± 5.64° and 105.51° ± 6.58°, respectively. Bladder dose increased with increment in α but decreased with increase of β and γ. Dose to rectum remained unaffected for γ. Mean distance from couch top to tip of central tandem and two ovoids is, respectively, 11.17 cm and 8.70 cm.Conclusion: Optimal plans even with orthogonal radiographs may be generated by verifying the application based on the parameters mentioned in the present study and computed tomography-based plans could be utilized more effectively instead of doing automatic or manual optimization. Whereever orthogonal radiograph based or template based ICBT practices is performed this study may create a dataset to have an optimal treatment plan even without three-dimensional images. [ABSTRACT FROM AUTHOR]

Immunotherapy is a treatment that uses specific components of a person's immune system to fight diseases. This is usually done by stimulating or assisting one's immune system is attacking the offending agent – for instance, in the case of cancer – the target of immunotherapy will be cancer cells. Some types of immunotherapy are also called biologic therapy or biotherapy. One of the fundamental challenges that a living cell encounters are to accurately copy its genetic material to daughter cells during every single cell cycle. When this process goes haywire, genomic instability ensues, and genetic alterations ranging from nucleotide changes to chromosomal translocations and aneuploidy occur. Genomic instability arising out of DNA structural changes (indels, rearrangements, etc.,) can give rise to mutations predisposing to cancer. Cancer prevention refers to actions taken to mitigate the risk of getting cancer. The past decade has encountered an explosive rate of development of anticancer therapy ranging from standard chemotherapy to novel targeted small molecules that are nearly cancer specific, thereby reducing collateral damage. However, a new class of emerging therapy aims to train the body's defense system to fight against cancer. Termed as "cancer immunotherapy" is the new approach that has gained worldwide acceptance. It includes using antibodies that bind to and inhibit the function of proteins expressed by cancer cells or engineering and boosting the person's own T lymphocytes to target cancer. In this review, we summarized the recent advances and developments in cancer immunotherapy along with their shortcoming and challenges. [ABSTRACT FROM AUTHOR]

Cancer male breast is not very common. It comprises <1% of all breast cancers. Primary sites of metastasis are bone, brain, lung, and liver. Endobronchial and tracheal metastasis is very rare. To the best of our information, this is the first case of male breast carcinoma with upfront tracheal and endobronchial metastasis which presented as Superior vena cava obstruction (SVCO), initially evaluated on the lines of metastatic nonsmall-cell lung cancer. A 60-year-old gentleman presented with shortness of breath and features of SVCO. On primary evaluation, he was thought to be a case of nonsmall-cell lung cancer. Later on, it was confirmed to be carcinoma male breast with endobronchial and tracheal metastasis, which was reconfirmed with biopsy. The case we came across had symptoms associated with endobronchial metastases from primary extrapulmonary tumor and which was later found out to be breast. Treatment options are very different from lung primary and thus, we should be aware of the unusual disease presentation. [ABSTRACT FROM AUTHOR]

Background: Relevance of aggressive treatment in advanced head neck squamous cell cancers(HNSCC) is debatable in view of expected poor outcome. Long treatment duration only adds up to the cost of treatment without any improvements in outcomes.Aims and Objectives: To assess the outcomes of hypofractionated "Christie" palliative radiotherapy regimen in advanced HNSCC.Materials and Methods: Patients of advanced HNSCC registered from June 2015 to June 2019 were treated by parallel pair field technique on Cobalt60 machine (Theatron 780E) to total dose of 50 Gray/16 fractions over 3.2 weeks. Toxicity was scored using Radiation Therapy Oncology Group (RTOG) criteria and response was evaluated as per WHO criteria.Results: Records of 110 patients of HNSCC with mean age of 56.19 years were analysed. Evaluation at 4-8 weeks after radiotherapy resulted in a complete response (CR) in 19.1%, partial response (PR) in 32.7%, stable disease (SD) in 29.1% and progressive disease (PD) in 3.6%, while 15.5% patients did not report for post treatment evaluation. Median progression free survival was 9.52 months (95% CI 5.9 - 13.1 months). The median overall survival was 12.7 ± 2.2 months (95% CI 8.2 - 17.2). Median time to progression after completion of radiotherapy was 84 days. Grade IV dermatitis and mucositis was encountered in 2.7% and 1.8% cases respectively, requiring hospitalization.Conclusion: Christie regimen for advanced HNSCC is a clinically viable option with acceptable outcomes in a resource constrained setting. [ABSTRACT FROM AUTHOR]

Xerostomia is a subjective symptom of dry mouth. It can occur as a part of the systemic disease, drug-induced side effect, or following therapeutic radiation therapy to the head-and-neck region. The primary complication faced by these xerostomic patients is the difficulty in retention of removable dentures. It is important to recognize that the prosthodontic management of these patients requires special attention and care. In an attempt to overcome the presence of xerostomia, several techniques of introducing reservoirs into the dentures containing salivary substitutes have been proposed. This case report presents a simplified approach for the construction of a reservoir in the maxillary denture, specifically in patients where other treatment modalities have failed. This technique provided excellent lubrication to oral tissues, hygienic for the patient, and utilized routine denture base material. [ABSTRACT FROM AUTHOR]

Introduction: More than 70% of lung cancer comprises nonsmall-cell lung carcinoma and is associated with poor survival outcome owing to late diagnosis. Identification of lung cancer in early stages when no clinical signs or symptoms are evident, can drastically improve the prognosis. To this end, we aimed to evaluate the changes occurring at tissue level by assessing the expression of six microRNAs (miRNAs) in lung adenocarcinoma (AC) and squamous cell carcinoma (SCC).Materials and Methods: Peripheral blood of histopathologically proven cases of lung AC and SCC was collected and processed for the isolation of miRNAs using commercially available kit. Primers against mir-2114, mir-2115, mir-2116, mir-2117, mir-449c, and mir-548q with loading control Caenorhabditis elegans were used. Screening was carried out in thirty cases of both AC and SCC, whereas twenty healthy controls were included.Results: Real-time polymerase chain reaction data revealed that the expression of mir-2114 and mir-449c in AC and mir-2115 in SCC was significantly upregulated. The expression of these miRNAs was also confirmed in lung AC cell line. The differential pattern of expression of these miRNAs can be used for precise diagnosis of lung carcinoma.Conclusions: We have used a noninvasive technique to identify the subtype of lung cancer based on molecular genetic signatures. The results suggest that through molecular profiling of miRNA, we can screen high-risk cases for cancer interception. [ABSTRACT FROM AUTHOR]

Objective: The aim of good management for cancer survivors should not be limited to only clinical care, but rather it should also include best quality of life (QOL). The objective of this study was to find out various factors affecting QOL in cervical cancer patients so that by modifying these factors, the best QOL can be provided to them.Materials and Methods: This was a prospective cohort study conducted in the Department of Obstetrics and Gynaecology and Department of Radiotherapy, King George's Medical University (KGMU), Lucknow, from May 2015 to July 2016. The cases were selected from patients visiting the outpatient department or who were admitted to the Department of Obstetrics and Gynaecology and Department of Radiotherapy, KGMU. The data information was collected in the form of face-to-face interview using European Organization for Research and Treatment of Cancer general cancer QOL Score 30 (EORTC QLQ C-30) and EORTC QOL questionnaire cervical cancer module (QLQ CX-24) questionnaire.Results: QOL was assessed in 85 patients. Health-related QOL was separately studied in terms of overall general QOL and cancer cervix-specific QOL, and various factors affecting QOL were studied by multivariate analysis.Conclusion: Education, tobacco use, degree of differentiation of tumor, and size of tumor were the independent factors found to have statistically significant effect on QOL of cervical cancer survivors. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study to develop surface modified targeted moiety α-tocopherol (α-t) encapsulated with 5-fluorouracil (5-FU)-poly-D, L-lactic-co-glycolic acid nanoparticles (PLGA NPs) toward the anticancer activity against oral squamous cell carcinoma (OSCC).Materials and Methods: 5-FU was conjugated with the polymer, PLGA by ionic cross-linking and α-tocopherol use as a functionalized surface moiety. Characterization, drug entrapment efficiency, and in-vitro drug release system were optimized at different pH 7.4 and pH 4.5. The in-vitro cell was performed to optimize the anticancer activity through MTT assay and apoptotic staining assay was also performed by flow cytometry to evaluate the cellular apoptotic activity and cellular uptake.Results: The particle size was distributed within an average range of 145-162 nm, the polydispersity index values lie 0.16-0.30, and the surface charge was at the negative side, -17mV to -23mV. The in vitro drug release system showed more sympathetic situation at pH 7.4 as compared to pH 4.5, for targeted NPs, approximately 86% and 69%, respectively. The non-targeted 5-FU-PLGA NPs showed drug release of 83% and 64% at pH 7.4 and 4.5 subsequently. In vitro anticancer activity confirmed the intense inhibition by α-t-FU-PLGA NPs of 79.98% after 96 h treatment of SCC15 cells and confirmed the steady-state inhibition of 83.74% after 160 h incubation in comparison to 5-FU-PLGA NPs. Subsequently, the early apoptosis, 27.98%, and 16.45%, and late apoptosis, 47.29%, and 32.57%, suggested the higher apoptosis rate in targeted NPs against OSCC.Conclusions: The surface modified α-t-FU-PLGA NP was treated over SCC15 cells, and the oral cancer cells have shown the high intensity of cellular uptake, which confirmed that the target moiety has successfully invaded over the surface of cancer cells and shown advanced targeted delivery against OSCC. [ABSTRACT FROM AUTHOR]

Aims: The aim of this prospective study is to evaluate prognostic significance of tumor volume determined by three-dimensional (3D) ultrasound scan in uterine cervix cancer patients treated by radiotherapy.Patients and Methods: A total of 67 patients of Stage IB2-IIIB were studied and analyzed. Cervical tumor volume was determined by 3D ultrasound scan. Two groups were made on the basis of volume on ultrasound scan (Group 1 <40 cc = 36 and Group 2 >40 cc = 31). Both groups received external beam radiotherapy (EBRT) and intracavitary radiation therapy (ICRT). Cisplatin 40 mg/m 2 every week was given concurrently with external irradiation. Tumor volumes were taken by 3D USG every week during EBRT, after each fraction of ICRT, and after 8 weeks of completion of treatment. Primary end point was disease-free survival (DFS), and secondary endpoints were 5-year survival and toxicities.Results: After 2 months of completion of treatment, 1 out of 36 patients of Group A was having residual and 7 out of 31 of Group B were having residual diseases (P = 0.034). DFS and 5-year survival were significantly different in the groups (log rank test P = 0.0014, hazard ratio (HR) =2.3622 95% confidence interval (CI) 1.3090-4.2625 and P = 0.0421, HR = 1.9274 95% CI 0.9998-3.7156, respectively).Conclusions: Ultrasound is a cheap, simple, and useful in predicting the outcome of treatment and DFS based on the tumor volume. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to compare the delineation and treatment planning of 2 Phase based (end-expiration and end-inspiration) internal gross tumor volume (IGTV) with 10-phase based (four-dimensional [4D]) IGTV. Materials and Methods: Patients with lung tumors at different sites were selected for the study. The location of the tumor in Groups A, B, C were at the upper lobe (attached to the chest wall), middle lobe, and lower lobe, respectively. We contoured the GTV on each of the 10 respiratory phases of the 4D computed tomography (4DCT) data set. The combination of these GTVs produced the IGTV "All Phases." GTV was also generated on the extreme respiratory phases. The combination of these two GTVs produced IGTV "2 Phases." Treatment planning was done, and dose to organs at risks (OARs) were compared in both cases. Results: The average volume of IGTV "2 Phases" and IGTV "All Phases" for Group A were nearly same. However, for Group B and Group C, IGTV "2 Phases" were smaller than the IGTV "All Phases." Lung-GTV doses were less in "exp-insp" phases than in "4DCT" for Groups B, C, whereas it was same for "expiration-inspiration" and "4DCT" in Patient A. Conclusion: Patients with tumor upper lobe tumor have no difference in tumor coverage and OARs sparing in the 2 Phase and all phases but middle lobe and lower lobe have a greater excursion during respiration and hence greater all phases IGTV. [ABSTRACT FROM AUTHOR]

Background: Radiation stents made of Lipowitz metal or cerrobend alloy are commonly used to shield uninvolved tissues from electron beams used in therapeutic radiation treatment of head and neck cancers. However, studies investigating the efficacy of cerrobend shielding stent in patients with unilateral buccal carcinoma remain rare.Purpose: To evaluate the efficacy of cerrobend shielding stents in minimizing the potential adverse effects of radiation on oral tissues in buccal carcinoma patients.Materials and Methods: Twenty.eight participants were selected for the study based on predetermined inclusion criteria, out of which four participants were lost to follow-.up. Half of the remaining participants. (N = 12) were randomly given cerrobend shielding stent and the remaining 12 formed the control group. The effects of radiotherapy were evaluated by using Radiation Therapy Oncology Group. (RTOG) 0435 Head and Neck adverse effects grading tool. All participants were evaluated for xerostomia, mucositis, dysphagia, salivary changes, dysguesia, pain, trismus and radiation caries at baseline and 1 and 3. months post.radiotherapy.Results: All adverse effects were higher in control compared to study group, with post therapy difference for pain in swallowing, salivary changes, mucositis, dysphagia, dry mouth and caries being statistically significant.Conclusions: Cerrobend alloy can be used effectively as shielding stent to reduce the adverse effects associated with external beam radiation therapy in unilateral buccal carcinoma patients. [ABSTRACT FROM AUTHOR]

We proposed a method to reduce the volume of normal tissues irradiated by low doses in patients receiving CSI with RapidArc (RA) using Avoidance-Sector technique (RA+AS) and to compare its dosimetric implications with RA using full-arc (RA+FA) and 3D conformal technique (3DCRT). Four patients of CSI were retrospectively planned with 3DCRT, RA+FA, and RA+AS. Conformity-Index (CI), Homogeneity-Index (HI), and Paddick Gradient-Index (GI) were calculated. Quantitative evaluation was done using DVH analysis for PTVs and OARs. When compared with 3DCRT, GI, CI, and HI were favorable to RA based techniques. In comparison with 3DCRT the doses to OARs were lower with RA+AS with the difference being statistically significant in most instances. RA+AS significantly decreases the dose to OARs and their volumes receiving low doses in comparison with RA+FA and 3DCRT. [ABSTRACT FROM AUTHOR]

In developing countries, diagnosis of breast carcinoma is still made on fine-needle aspiration cytology (FNAC). For the resource-poor settings, FNAC is cheaper, less invasive and can sample different areas of the lesion compared with core needle biopsy. The role of breast FNA is usually limited to just categorize the lesion as benign or malignant. Prognostic information from cytomorphology, conveyed to the clinician depends upon the cytopathologist's way of formatting the report. PubMed-based literature search collated the information from articles describing the architectural and cytological features studied on breast aspiration smears. This review focuses on cytomorphological features and the different grading systems with their strengths, short-comings, and practical applicability. Eight worldwide articles proposing new methods of grading the cytological smears from breast cancers were published between 1980 and 2006. All the grading methods were developed for the most common type of breast cancer, that is, infiltrating duct carcinoma (not otherwise specified) type, and most of the workers used Papanicolaou-stained smears for the purpose of grading. Moreover, if interpreted carefully FNAC smears can convey information on most of the histological features. Hence, in developing countries, the focus should be on extracting the maximum information from cytological smears, so that a more precise "surgical pathology" type diagnosis can be given, instead of merely reporting as benign or malignant. Among all the discussed grading systems, we suggest grading system by Howell would be most appropriate and closest to the accepted histologic grading system as it applies Scarff-Bloom-Richardson histological grading system with modifications on FNA smears. We recommend it to be followed by all cytopathologists, in order to bring uniformity in the reporting of breast FNAs for grading the malignant lesions. [ABSTRACT FROM AUTHOR]

Coexistence of tuberculosis (TB) and palatal malignancy is a rare phenomenon and it has never been reported. Here, we present a case of hard palate carcinoma with TB in a 60-year-old male patient who was successfully managed by three pronged approaches by combining antitubercular therapy with chemotherapy and radiotherapy. [ABSTRACT FROM AUTHOR]

Background: To study the long term results of two phase II concurrent chemoradiotherapy protocols and conduct pooled data analysis with special emphasis on nodal density. Materials and Methods: In the period from April 2001 to May 2003, phase II Mitomycin C (MMC) and late chemo-intensification (LCI) protocols were started in the same institute, enrolling 69 and 74 patients respectively. Long term results for these individual trials are reported along with pooled data analysis. Results: Median follow-up time for whole group, MMC protocol and LCI protocol was 43.8 months (SD±19.8), 55 months (SD ±18.5) and 47.5 months (SD ±20.9) respectively. LRFS, DFS and OS at five years for whole group was 59.4, 43.5 and 47.1% respectively, for MMC protocol was 59.9, 45.5 and 49.5% respectively and for LCI, protocol was 53.6%, 41.5% and 44.4% respectively. Subgroup analysis revealed that MMC protocol was more effective than LCI protocol in terms of DFS and OS in patients with hypo dense nodes while opposite was true for Isodense nodes. Multivariate analysis revealed nodal density as an independent variable that had an impact on treatment outcome. Risk of death in patients with hypo dense nodes was 2.91 times that of Isodense nodes. Conclusions: Innovative and pragmatic approach is required to address locally advanced head neck cancer. Long term results for MMC and LCI protocols are encouraging. Integrating the basic concepts of these protocols may help develop new protocols, which will facilitate the search for the optimal solution. [ABSTRACT FROM AUTHOR]

Background: Cell regulatory G2/M phase proteins are the key regulators of mitosis and have been reported with abnormal expressions in various malignancies. Aim: To determine the expressions of these proteins in neoplastic uterine cervix tissue. Materials and Methods: This study evaluates the G2/M phase regulatory protein expression of Cyclin B1, Aurora-B, Pololike kinase 1 (PLK1) and LIM kinase1 (LIMK1) in tissues of 25 normal (control), 16 dysplastic (dysplasia) and 34 neoplastic (cancer) patients of uterine cervix. The expressions of different proteins were obtained by using Western Blot technique. Statistical Analysis: One way analysis of variance (ANOVA), Pearson correlation, Kaplan-Meier and other tests are used for analysis. Results and Conclusion: The level of expression of LIMK1 in cervical cancer patients was found to be significantly higher (P <0.01) than both the controls and dysplasia. The expression of Aurora B and PLK1 in cervical cancer patients was also found to be significantly higher (P <0.05) than controls but it did not differ with dysplasia. However, the expression of Cyclin B1 was similar among cervical cancer patients, dysplasia and controls (P>0.05). The expression of all the above proteins showed significant (P<0.01) and inverse relation with the survival of cancer patients. Among the selected candidate proteins, it was LIMK1 that showed the most positive correlation with the aggressiveness of the disease and negative correlation (r= -0.64; P<0.01) with the survival of patients. [ABSTRACT FROM AUTHOR]

Surface epithelial tumors of the ovary comprise over fourth of the ovarian neoplasms. Serous adenofibromas are lesser known variants of serous surface epithelial tumors. Though these tumors have a benign fate, yet they can be misinterpreted clinically and radiologically due to their borderline or malignant gross morphological as well as clinical presentation. The cell of origin of surface epithelial tumors of the ovary is histological debated; however, it is now ascertained to have origins from the ovarian cortical and surface lining. Adenofibromas are known to progress in an indolent manner with metachronous behavior for years. The present case is of an ovarian serous adenofibroma in a young female masquerading as peritoneal carcinomatosis. [ABSTRACT FROM AUTHOR]

Malignant transformation in a mature cystic teratoma (MCT) is rare occurring in 1.8% out of 8000 cases of MCT. The most common histological types are squamous cell carcinoma (SCC) followed by adenocarcinoma and melanoma. Clinically, these tumors are usually asymptomatic but may be discovered accidentally during gynecologic examination due to mass effect. We present cytology and histology correlation of a rare case of SCC arising in a dermoid cyst with metastasis to sigmoid. [ABSTRACT FROM AUTHOR]

Aggressive angiomyxoma is a rare mesenchymal neoplasm that typically affects females of reproductive age. It involves preferentially pelvic and perineal regions and was first described by Steeper and Rosai in 1983. Peak age of incidence for this tumor is in the fourth decade with very few cases reported in young girls. We present a case of this rare tumor in a 13-year-old female. [ABSTRACT FROM AUTHOR]

Background: In neurooncology we deal with a variety of diagnoses like Glioma, ependymoma, medulloblastoma, pinealoblastoma, PNET, etc. The treatment of each of these cancers are different. Presently, the treatment is largely based on evidence from literature. During our discussion with patients we quote the results of standard studies. We forget for a moment that these results are from ideal conditions in fit patients enrolled in clinical trials. These results may not be reproducible in real world. Any institution will have enough number of patients of each diagnosis. We are not realising the power of data of our own patients. The main reason behind this is lack of computerisation and ignorance. Material and methods: With this idea in mind we joined hands with Indo US Cancer Knowledge Alliance (IUCKA) OHSL, IBM Watson (USA), and Prolitus Technologies to develop a database of our own neurooncology patients. Comuterization of data: Data is captured in well structured performas including history, physical examination, investigations, surgical details, histopathology report, special staining, adjuvant radiotherapy, adjuvant chemotherapy, status at follow up visits and so on. A powerful cognitive software is developed. The powerful database is going to look into whole collection in realtime and going to provide guidance for treatment based on the results from our own cases. Each patient entering into the database is going to guide a future patient if the index patient characteristics match to the patient. Suppose we have 500 cases of GBM in our database with reasonably good follow up. Once a new patient's case is entered into the system, the software is going to pull the information from similar patients in the system. This can predict the local control and survival for the index case which is going to get treated in our settings. We have also added some novel features to this software to make our day to day work easy. The software will also give rule based intelligent guidance for treatment. This means that we are blending the standard guidelines with the database. For example, once a GBM patient is entered into the system, it will suggest for surgery followed by concurrent chemo-radiation with the standard doses for RT and chemotherapy. The system will also advice the physician of the target volumes used for contouring. In a case of medulloblastoma it will suggest for craniospinal irradiation with doses, volumes, adjuvant and concurrent chemotherapy doses. The system will be able to send messages/emails for treatment visits or followups. The system can also identify the patients who are lost to followup . Once a patient comes to the hospital on a particular day, and patient puts his/her thumb on the thumb reader, the software can automatically redirect to the patients page displaying a short summary of the case and showing what the patient has come for on that day. Suppose patient has come for 4th cycle of adjuvant chemo, the system will ask to check for the blood results and to enter the weight. This will also ask whether the patient had any toxicities. If everything is fine, and once we put the weight in the particular field, the system will give the prescription for next cycle of chemotherapy to be taken as printout. The system can provide ready made data for publications at any point of time. The cloud based operation and offline access makes this even more attractive. Conclusion: Present day powerful computing tools can guide the treatment of an individual patient utilising the results of previous similar patients treated in the same environment. These results are more relevant than the literature ones. Computerization will also make our workflow very simplistic and help to avoid errors and saves the physician time in busy clinical settings. [ABSTRACT FROM AUTHOR]

Background: FAT1 gene is localized at chromosome 4q35.2 encoding a 506 KD a transmembrane protein and functions as oncogene and tumor suppressor depending on tissue types in human cancers. Our lab has identified an oncogenic role of FAT1 in glioblastoma.miR-221-3p/222-3p has been reported to have oncogenic role and targeting tumor suppressor (e.g. CDKN1B, PTEN, PUMA etc.) in many cancers along with glioblastoma multiform. miRNAs are noncoding RNA which are bound to the 3'UTR of target mRNA and repress their expression Here, we have elucidated the role of FAT1 gene in the regulation of miRNAs in glioma. Methodology: In order to delineate regulation of miRNA by FAT1 in glioma we used knockdown strategies followed by expression analysis by q-PCR. miRNA 221-3p/222-3p are isomiRs and acts as OncomiRs in human cancer. FAT1 specific siRNA and scramble siRNA were used in this study purchased from Invitrogen, USA. Glioma cell lines were maintained in Dulbecco's modified Eagle's Medium (DMEM) with 10% fetal calf serum (FCS). The Knockdown experiment were carried out in U87MG, U373, A172, T98, LN229 and GOSIII glioma cell lines. We have used Exiqon total RNA isolation kit to isolate miRNA and followed by preparing cDNA by using Exiqon cDNA synthesis kit. We have used LNA-primer (locked nucleic acid) to analyze the expression of miR-221/222-3p in glioma cell lines. We have done in-silico analysis to identify potential miRNA target molecules by using miRNA target prediction software (microrna.org, Diana-micro, Target Scan Human, and miRDB). GBM (Glioblastoma) tumor samplesv(n=18) were collected from Department of Neurosurgery/ Pathology of All India Institute of Medical Sciences, India. GBM tissue were collected in 1 ml of RNA-Later solution and incubated for 24 hours at 4°C. After removing RNA-Later solution the tumor tubes were immediately stored at -70°C till further use. For the control, normal human brain RNA were purchased commercially (Clonetech, USA). Results: We have observed increased expression of FAT1 and miRNA in different glioma cell lines (U87MG, U373MG, A172, LN229, T98G and GOS3). In order to validate the FAT1 and miRNA correlation we have used knockdown strategy in glioma cell lines. We have analyzed the expression of miRNA in glioma cell lines after FAT1 knockdown and compared with siControl. We have observed more than 80% FAT1 knockdown in U87MG, U373MG, A172, T98G and GOS3 and almost 70% FAT1 knockdown in LN229. We observed decreased expression of miR-221/222-3p after FAT1 knockdown in different glioma cell. We have done in-silico study to identify potential miRNA targets and found CDKN1B, TIMP, PDCD10, PUMA and PTEN molecules are the significant targets of miRNA. In order to validate these findings we have analyzed expression of PDCD10, PUMA and PTEN in FAT1 knockdown cells and compared with siControl cells. We observed increase expression PDCD10, PUMA and PTEN after FAT1 knockdown in glioma cell lines. Our observation suggests that FAT1 expression affects the miRNA and its target in glioma cell lines. In order to confirm our in-vitro observation and its clinical relevance, we have done correlation study in GBM tumors. GBM tumors (n=18) were collected and expression of FAT1, mRNA and its targets were analyzed by q-PCR. We have observed negative Pearson correlation of FAT1 with PDCD10 (correlation value -0.720), PTEN showed (correlation value -0.267) and PUMA (correlation value -0.218). In conclusion:- Taken together our in-vitro and GBM tumor data for the first time suggesting FAT1 to be a novel molecule regulating the expression of miRNA in GBM and FAT1 may emerge as a target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

INTRODUCTION Lung cancer is a very serious problem of the Indian subcontinent, especially in the lower socioeconomic subgroups. As per the ICMR [Indian Council Of Medical Research] registry of 2002 lung cancer is the 5th most common tumor overall and 2nd most common tumor in the males in India. It accounts for 6.9% of new cancer cases detected each year. CD133 is one of the bestcharacterized markers of CSCs in colorectal and pancreatic cancers however; its role in lung cancer needs further study. The tumorigenic cells in SCLC and NSCLC were first characterized as a rare population of undifferentiated cells expressing CD133, a marker of normal and CSCs of the hematopoietic, neural, endothelial and epithelial lineages. [18] AIM- To study the association of cancer stem cell marker CD133 with tumor grade and stage as well as smoking index, in lung carcinoma patients. MATERIAL AND METHODS-Biopsies from 55 fresh previously untreated lung cancer patients visiting the Pulmonary Medicine Department of Era's Lucknow Medical College and Hospital Lucknow [ELMC&H] & King George's Medical College and Hospital [KGMU], Lucknow were taken, after taking proper informed consent from them. Ethical clearance was taken from the institute. Complete history including the smoking index as well as the radiological profile was recorded. The biopsies were processed in Dept. of Pathology, into paraffin blocks, and stained by Haematoxylin and Eosin [Sigma] staining for histopathological diagnosis .Immunohistochemistry was done for detection of CSC marker CD 133[Daco]. CONCLUSION-On studying the association of the markers with the staging of the tumor we saw that the expression of CD133 was observed in 62.5% of Stage I, 90% of Stage II, 94.1% of Stage III and 100% of Stage IV cases. Statistically, there was a significant association between CD133 expression and stage of disease (p. [ABSTRACT FROM AUTHOR]

Background: FAT1 is a transmembrane protein and function as an adhesion molecule. FAT1 gene is located on chromosome 4q35.2 encoding a 506KDa protein. The role of FAT1 in tumors is not fully characterized. Few reports suggest it behaves as a tumor suppressor and few reported it as oncogenic. Here in our study we are characterizing the role of FAT1 in primary brain tumors. There are studies showing altered expression of FAT1 in human gliomas with ~30% of them showing LOH at the FAT1 locus. TP53 is mutated in 50% of primary brain tumors. P53 being a transcription factor, regulates the expression of a number of target genes including regulating biological functions such as cell cycle arrest, apoptosis, senescence, differentiation and antiangiogenesis. Glioma is known to have hypoxic environment in its tumour core and hypoxic tumour micro environment and HIF1A is believed to play role in tumour progression . So, in this study we are analysing the interaction between FAT1, P53 and HIF1A in glioma progression. Methodology: In order to delineate molecular crosstalk among factors driving glioma progression, we used knockdown and overexpression strategies in glioma cell lines followed by expression analysis by Q-PCR, Immunofluorescence and Western Blot. Migratory potential of cells was assessed by Migration assay and invasion potential were assessed using Matrigel invasion assay and images were captured using Nikon fluorescence microscopy and confocal microscopy. For cell proliferation and viability assay MTT/ XTT were used. Cell cycle analysis was carried out using PI staining in Flow cytometry (BD canto FACS) Sample Collection: - Glial tumor samples were collected from Department of Neurosurgery/Pathology of All India Institute of Medical Sciences, India. Tissue were collected in 1 ml of RNA-Later solution and incubated for 24 hours at 4°C. After removing RNA-Later solution the tumor tubes were immediately stored at -70°C till further use. For the control, normal human brain RNA was purchased commercially. Transfection of cell lines: - 1) For Knockdown: Selection of target siRNA and corresponding control- We have been using commercially available siRNA (Invitrogen) for FAT1 knockdown in our lab. FAT1 and control siRNA Oligos are designed by Genscript siRNA construct builder software(http://www.genscript. com/siRNA_construct_builder.html). 2) FAT1_trunc (Truncated FAT1) transfection: plasmid containing truncated FAT1 gene in pcDNA vector 3.1 was used (gifted by Dr Timothy A Chan). Truncated FAT1 plasmid contains first two repeats of cadherins at N terminals and around 22 repeats of cadherins are removed retaining last few cadherin repeats along with intercellular region of FAT1 gene. The vectors is tested for its expression and also known to retain all its functions. Transfection is carried out for 48 hr. Empty vector PCDNA is used as control. Transfection was carried out after plating 40000 to 50000 cells in 6 well plates for U87MG cells line and 1.2-1.5 lakhs cells for GOS and U373 Cell lines. The total duration of transfection was 72 hr (excluding plating) for knockdown and 48 hr for overexpression experiments. Hypoxia exposure was given with 0.2% oxygen for 48 hr After transfection following experimental techniques were done • MTT/XTT assay - For Cell survival • Flow cytometry- For Apoptosis assay/cell cycle analysis • RNA isolation and lysate preparation- For pathway(s) analysis by Real-Time PCR and Western blotting. • Migration and invasion assay - BD Matrigel • ICC Results Hypoxic treatment exhibited a significant increase in expression levels (7 to 9-fold) of FAT1 in U87MG, U373MG and GOS3 glioma cell lines. On FAT1 Knockdown under severe hypoxia, P53 and HIF1A expression was decreased and on Fat1 Knockdown under normoxia the expression of p53 and HIF1A was increased. The downstream targets of P53 (Noxa, Puma, p21 and MDM2) and downstream targets of HIF1A (VEGF, Ca9, GLUT1 and PGK3) also showed similar trend as p53 and HIF1A. On western blot analysis, protein levels of HIF1A and p53 showed increased levels after FAT1 knockdown under normoxia and no significant change was observed under FAT1 Knockdown in hypoxia. Our array data showed differential gene expression on FAT1 after knockdown. We observed reduction in HIF1A expression after FAT1 Knockdown under hypoxia and increased p53 and HIF1A on FAT1 Knockdown under normoxia. Increased in FAT1 expression under hypoxia and reduction of HIF1A after FAT1 Knockdown seems to suggest a direct link of FAT1 and HIF1A. Further, on subjecting U87 MG (grade IV GBM cell line) to hypoxia, we observed the shift in subcellular localization of FAT1 from perinuclear and plasma membrane location to inside the nucleus on ICC experiments suggesting FAT1 itself act as a transcription factors or help other transcription factors to increase or decrease gene expression involved in hypoxia and tumour progression. On over expressing FAT1 trunc we observed increased p53 [removed]1.49 fold) in normoxia and 1.87 fold increase under hypoxia (0.2%O2). MDM2 (downstream target gene of p53) also increased after FAT1 over expression by 1.629 fold in normoxia and 1.42 in hypoxia. We also observed elevated HIF1A in U87 and GOS3 along with their downstream molecules. RNA was isolated from histopath positive glioma grade IV tumors samples and gene expression analysis was performed in 18 tumour samples. We observed in GBM patients samples a positive correlation between FAT1 expression and P53 (r2 0.723 p=0.0029) and positive correlation of p53 with HIF1A (r2 =0.620, p=0.0106) and correlation of FAT1 expression with HIF1A showed r2 0.44, p=0.063. The expressions correlating analysis for patient samples and qPCR analysis of glioma cell lines suggests an existence of an intermediary molecule connecting the HIF1A and p53 regulation by FAT1. We examined p300 a co transcription factor necessary for both p53 and HIF1A transcription activity. P300 is upregulated when FAT1 is knockdown under normoxic condition. Absence of FAT1 (knockdown) under normoxia in U87MG cell lines increased p53 (1.7fold) and HIF1A (1.5 fold) and also p300 (1.8 fold). Increase in P53 in FAT1 Knockdown under normoxia is due to C/EBP beta. C/EBP is a known transcription factor and has two binding site in p53 promotors and C/EBP beta expressions is increased on FAT1 knockdown under normoxia to 1.56 fold. HIF1A being onocogene should promotes proliferation/migration and invasion but in our study we observed decreased in migration and invasion (Matrigel assay) and decreased in proliferation (MTT/XTT cell proliferation assay) and increased in apoptosis (Annexin FITC and PI flowcytometry assay) and increased Sub G0 population (PI cell cycle assay) on Knock down of FAT1 in normoxia. Increased p53 and its downstream genes after FAT1 Knockdown activated p300/p53 combination over p300/HIF1A resulting in decreased oncogenicity in normoxia in absences of FAT1. On other hand after FAT1 over expressions we observed decreased p300 and decreased p53 and its downstream and increased migration/ invasion and viability. The cell viability was 74.61 % after FAT1 over expression compared to control under normoxia. In hypoxia, the cell viability was increased after FAT1 over [removed]91% compared to control). Migratory properties also showed significant increase in over expression sample (4.19 times) then mock control under normoxia. This observation points to the critical and important role of FAT1 in cell migration. In conclusion FAT1 plays an oncogenic role in glioma and HIF1A and p53 plays and important role. The exact mechanism involved in the oncogenesis by FAT1 is under study. [ABSTRACT FROM AUTHOR]

Background--Gall bladder cancer is endemic in Indo gangetic plain with patients usually presenting in advanced stages. However a significant number of cases are diagnosed Background--Gall bladder cancer is endemic in Indo Gangetic plain with patients usually presenting in advanced stages. However a significant number of cases are diagnosed incidentally. Fate of these patients is vastly different and there are no standard treatment guidelines for the same. We attempted to study these patients with an aim to understand this entity better. Methods: Records of all gall bladder cases registered in the department of radiotherapy between 2015 and 2016 were retrospectively analyzed. Of the 167 cases, 36 were incidentally diagnosed. Results: They were predominantly females (Male: Female =0.2:1) with mean age of 49.5 years(±10.1 SD, Range 25-66 years ) and 35% being <\=45 years. Baseline KPS ranged from 50-90, and mean baseline weight was 53kg (± 9.2SD, Range 35-74kg ). All patients presented with pain and underwent surgery because of associated cholelithiasis in 32 (89%). Post initial diagnosis, 67% of the cases underwent resurgery at our institute and surgeries performed were radical cholecystectomy in 18(50%), open simple cholecystectomy in 8 (21%), laparoscopic simple cholecystectomy in 4 (11%) and staging laparotomy in 6 (18%) patients. Consequently stage assessment was not possible in 33% cases, 36% were stage IV while remaining 31% were stage I-III. There were 9 (25%) N1 and 2 (5%) N2 patients. Metastases were found subsequently in 11 (31%) patients. Moderately differentiated adenocarcinoma was the most common histology in 19 (53%) patients. 15(42%) patients were lost to follow up after surgery, 2(5%) were kept under observation, 15(42%) received adjuvant chemotherapy and 4 (11%) received palliative chemotherapy. Platinum based doublet was the most common regimen used in 16 (45%) patients. For a median follow up of 07 months (0-28 months), there were 9 relapses, 5 (55%) were locoregional and 4 (45%) distant. The median overall survival was 24 months. Conclusions--incidentally diagnosed gall bladder cases tend to behave differently. However locoregional and distant relapses highlight the need for aggressive surgery along with effective systemic treatment in order to alter the fate of these patients. [ABSTRACT FROM AUTHOR]

Background--Gall bladder cancer is endemic in Indo gangetic plain with patients usually presenting in advanced stages. However a significant number of cases are diagnosed Background--Gall bladder cancer is endemic in Indo Gangetic plain with patients usually presenting in advanced stages. However a significant number of cases are diagnosed incidentally. Fate of these patients is vastly different and there are no standard treatment guidelines for the same. We attempted to study these patients with an aim to understand this entity better. Methods: Records of all gall bladder cases registered in the department of radiotherapy between 2015 and 2016 were retrospectively analyzed. Of the 167 cases, 36 were incidentally diagnosed. Results: They were predominantly females (Male: Female =0.2:1) with mean age of 49.5 years(±10.1 SD, Range 25-66 years ) and 35% being <\=45 years. Baseline KPS ranged from 50-90, and mean baseline weight was 53kg (± 9.2SD, Range 35-74kg ). All patients presented with pain and underwent surgery because of associated cholelithiasis in 32 (89%). Post initial diagnosis, 67% of the cases underwent resurgery at our institute and surgeries performed were radical cholecystectomy in 18(50%), open simple cholecystectomy in 8 (21%), laparoscopic simple cholecystectomy in 4 (11%) and staging laparotomy in 6 (18%) patients. Consequently stage assessment was not possible in 33% cases, 36% were stage IV while remaining 31% were stage I-III. There were 9 (25%) N1 and 2 (5%) N2 patients. Metastases were found subsequently in 11 (31%) patients. Moderately differentiated adenocarcinoma was the most common histology in 19 (53%) patients. 15(42%) patients were lost to follow up after surgery, 2(5%) were kept under observation, 15(42%) received adjuvant chemotherapy and 4 (11%) received palliative chemotherapy. Platinum based doublet was the most common regimen used in 16 (45%) patients. For a median follow up of 07 months (0-28 months), there were 9 relapses, 5 (55%) were locoregional and 4 (45%) distant. The median overall survival was 24 months. Conclusions--incidentally diagnosed gall bladder cases tend to behave differently. However locoregional and distant relapses highlight the need for aggressive surgery along with effective systemic treatment in order to alter the fate of these patients. [ABSTRACT FROM AUTHOR]

Introduction:Cervical carcinoma is the second most common malignancy in women worldwide. It is estimated that over a million women worldwide currently have cervical cancer. Worldwide, cervical cancer is both the fourth-most common cancer and the fourth-most common cause of death from cancer in women. In 2012, 528, 000 new cases of cervical cancer were diagnosed, and 266, 000 women died of the disease (GLOBOCAN 2012), nearly 90% of them in lowto middle-income class countries. Multifactorial causation, potential for prevention, and the sheer threat it poses make cervical cancer an important disease for in-depth studies, as has been attempted by this paper by studying the hypoxic marker. Recently, there has been increasing interest in the identification of biomarkers able to predict both response to treatment and survival. Aim: The aim of this study was to evaluate the association of hypoxic marker Carbonic anhydrase (CAIX) markers to predict the clinical outcome of patients with cervical carcinoma. Materials and methods:This study was conducted on biopsy proven previously untreated cases of cancer cervix who presented to the Department of Radiotherapy at King George's Medical University (KGMU), Lucknow, Uttar Pradesh, India. The study was a single institution, non-randomised, prospective study to evaluate carbonic anhydrase IX as a biomarker in cancer cervix patients undergoing radiotherapy. Sample size: Total 75 samples • 25 healthy control subjects (Age and sex matched) • 25 cancer cervix patients (duplicate samples i.e. baseline and follow up). Approximately 2 ml of blood was withdrawn before initiation of treatment and at the time of first follow up. Standard treatment was given as external beam radiotherapy (EBRT) with concurrent chemotherapy followed by intracavitary radiotherapy (ICRT). Blood samples was analysed for the level of CAIX..Statistical analyses was performed with the SPSS software package v13.0. Results: Pre-treatment high level of carbonic anhydrase IX correlated with poor treatment outcome. [ABSTRACT FROM AUTHOR]

Purpose: Prospective assessment of variation in quality-of-life (QoL) in locally advanced cancer esophagus patients receiving neoadjuvant chemotherapy (NACT) versus neoadjuvant chemoradiation (NACTRT). Methods: Patients randomly allocated to NACT and NACTRT arms were assessed using validated EORTC QLQ-C30 (ver 3) and EORTC QLQ-OES18 questionnaires in hindi delivered pre and post neoadjuvant treatment. Domains assessed were Global health status (QoL), Physical (PF) and Role functioning (RF), Nausea vomiting (NV), Fatigue (FA), Eating (OESEAT), Reflux (OESRFX) and Dysphagia (OESDYS). Results: 39 fit patients of mean age 54.6 (± 10.1 SD) years were treated with NACT (n=24) or NACTRT (n=15). Pretreatment baseline scores in both arms were comparable. Post neoadjuvant treatment, significant changes in QOL, PF, RF, OESRFX, OESDYS were documented in both arms. Post NACTRT, there was worsening of FA and NV while OESEAT scores failed to improve significantly. FI did not change with either treatment. Conclusion: Both NACT and NACTRT improved dysphagia, reflux and global QOL with consequent improvement in related domains. However, fatigue, nausea-vomitting and eating were adversely affected by the treatment intensification in chemoradiation arm. Longer follow up is required to assess sustained differences. TABLE: Domain Treatment arm Pretreatment Post neoadjuvant treatment Pre vs Post treatment significance QOL NACT 47.2 ± 6.3 77.0 ± 8.2 P< 0.05 NACTRT 45.5 ± 9.8 79.9 ± 6.8 P< 0.05 PF NACT 72.2 ± 15.5 83.3 ± 11.2 P< 0.05 NACTRT 75.1 ± 12.9 87.9 ± 11 P< 0.05 RF NACT 56.2 ± 15.3 36.1 ± 36.9 P< 0.05 NACTRT 58.9 ± 13.8 30 ± 34.6 P< 0.05 FA NACT 40.2 ± 13.8 34.7 ± 18.3 P= 0.4 NACTRT 39.9 ± 13.8 51.1 ± 17.2 P< 0.05 NV NACT 29.8 ± 24 20.8 ± 16.4 P= 0.06 NACTRT 19.9 ± 21 42.2 ± 29.4 P< 0.05 FI NACT 76.3 ± 18.3 72.2 ± 12.6 P= 0.5 NACTRT 64.4 ± 19.7 68.8 ± 8.6 P= 0.1 OESEAT NACT 41.3 ± 10.8 30.2 ± 6.8 P<0.05 NACTRT 37.7 ± 7.6 33.8 ± 9.6 P= 0.6 OESRFX NACT 19.4 ± 16.7 9.7 ± 15.4 P<0.05 NACTRT 28.8 ± 11 17.7 ± 17.1 P<0.05 OESDYS NACT 59.2 ± 22 75.4 ± 29.8 P<0.05 NACTRT 57 ± 24.4 68.1 ± 33.8 P<0.05 [ABSTRACT FROM AUTHOR]