The Gujarat Cancer and Research Institute

Asarwa, India

The Gujarat Cancer and Research Institute

Asarwa, India
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Dave M.,Maharaja Krishnakumarsinhji Bhavnagar University | Daga A.,Saurashtra University | Rawal R.,The Gujarat Cancer and Research institute
International Journal of Pharmacy and Pharmaceutical Sciences | Year: 2015

Objective: AF9-MLL has been implicated in the pathogenesis of AML, New Therapeutic regimens are prerequisite for this category of hematological malignancy due to the poor prognosis. The experimental 3D structure of AF9-MLL is not available. Therefore, present study aims in developing the homology model and evaluating the best model through Energy Minimization and MD simulation. The structure further analyzed for functional Annotation. Methods: To the best of our knowledge, our study is novel in terms of predicting homology based 3D model of AF9-MLL leukemogenic fusion protein, facilitated by I-TASSER. The 3D modeled structure was subsequently optimized with MD simulation for 2 ns. Further stereo-chemical analysis and verification of the best structure so obtained were undertaken by different computational programs including PROCHECK, PROVE, Verify3D and ERRAT. Results: Homology model predicted from I-TASSER and refined by YASARA showed results with 86.5% residues in the most favorable region, 14.7% in the allowed region, 0.8% in the generously allowed region and 0.3% in the disallowed region. The RMSD between the modeled and the refined structure was found to be 2.37 Å. The results of ERRAT, Verify_3D, Prove and ProSA confirmed that the simulated model and energy minimized model is very good then the predicted raw model. The final structure was successfully submitted in Protein Model Database (PMDB) under ID: PM0080061. Conclusion: In this study, homology model was developed and Validated for MLL-AF9 using bio-informatics tools. These analyses validated that the simulated model is best, robust as well as reliable enough to be used for future study and the functional analysis shows the presence of CXXC domain. Eventually, these molecular and structural studies result in advancement of newer therapies. © 2015, International Journal of Pharmacy and Pharmaceutical Science. All rights reserved.

Patel S.,The Gujarat Cancer and Research Institute | Shah K.,The Gujarat Cancer and Research Institute | Mirza S.,The Gujarat Cancer and Research Institute | Daga A.,Saurashtra University | Rawal R.,The Gujarat Cancer and Research Institute
Current Stem Cell Research and Therapy | Year: 2015

Oral squamous cell carcinoma (OSCC) is amongst the most prevalent form of cancer worldwide with its predominance in the Indian subcontinent due to its etiological behavioral pattern of tobacco consumption. Late diagnosis, low therapeutic response and aggressive metastasis are the foremost confounders accountable for the poor 5 year survival rate of OSCC. These failures are attributed to the existence of “Cancer Stem cell (CSC)” subpopulation within the tumour environment. Quiescence, apoptotic evasion, resistance to DNA damage, abnormal expression of drug transporter pumps and in vivo tumorigenesis are the defining hallmarks of CSC phenotype. These CSCs have been distinguished from the tumor mass by determining the expression patterns of cell surface proteins, specific stemness markers and quantifying the cellular activities such as drug efflux & aldehyde dehydrogenase activity. Hence, it is necessary to understand the underlying mechanisms that regulate the CSC features in tumor development, metastasis and response to chemotherapy. Increasing evidence suggests that majority of malignant cells eventually undergoing Epithelial-Mesenchymal transition (EMT) share many biological characteristics with CSCs. Thus, this review encompasses the functional relevance of CSC and EMT markers in OSCC population with a hope to elucidate the fundamental mechanisms underlying cancer progression and to highlight the most relevant epigenetic mechanisms that contribute to the regulation of CSC features. We further aimed to explore the causal effects of nicotine, a major tobacco carcinogen, on epigenetic mechanisms regulating the OSCC CSCs and EMT markers which unravels the undisputable contribution of tobacco in oral carcinogenesis. © 2015 Bentham Science Publishers.

Bansal R.,The Gujarat Cancer and Research Institute
The Gulf journal of oncology | Year: 2012

Lipoadenoma of parathyroid gland is an unusual morphologic variant of parathyroid adenoma in which the glandular elements are associated with abundant mature adipose tissue. The lesion has also been reported as parathyroid lipohyperplasia, parathyroid hamartoma, and parathyroid adenoma with myxoid stroma. Most cases are functioning and are associated with hyperparathyroidism. Lipoadenoma of parathyroid gland are difficult to diagnose as a cause of hyperparathyroidism because of rarity of these lesions and overlap with normal parathyroid tissue on microscopic evaluation. Only few cases have been documented in the literature so far. The lesion may be overlooked by both surgeon and pathologists alike, if they are not aware of this specific clinicopathologic entity.

Dave H.,The Gujarat Cancer and Research Institute | Trivedi S.,The Gujarat Cancer and Research Institute | Shah M.,The Gujarat Cancer and Research Institute | Shukla S.,The Gujarat Cancer and Research Institute
Indian Journal of Experimental Biology | Year: 2011

Dual role of TGF-β signaling in breast tumorigenesis as an inhibitor in early stages and promoter in advanced stages has been well established and known as TGF-β switch. However, the biological mechanisms needs to be explored. Aim of the present study was to look for the usefulness of TGF-β2 as a predictive marker for breast cancer and to offer a better predictability to identify patients likely to benefit from antiTGF-β strategies. Circulatory as well as transcript levels of TGF- β2 were estimated from 118 pretherapeutic breast cancer patients using ELISA and q-PCR with ddCt method. Multifactorial analysis was performed to correlate the results to clinico-pathological prognosticators and Kaplan-Meier survival analysis with a median follow-up of 49 months was also evaluated. Circulating TGF-β2 was similar in control and breast cancer patients. TGF-β2 was significantly upregulated in advanced tumors compared to early tumors. An inverse correlation was observed between TGF-β2 protein and mRNA; nevertheless both exhibited significant correlations with clinico-pathological prognosticators. Higher expression of TGF-β2 mRNA was connected to an early relapse in advanced stage than early stage patients. It is the first report to evaluate circulatory and transcript levels exhibiting TGF-β switch and confirming the utility of TGF-β2 as an important predictive marker for breast cancer.

Mehta S.V.,The Gujarat Cancer and Research Institute | Shukla S.N.,The Gujarat Cancer and Research Institute | Vora H.H.,The Gujarat Cancer and Research Institute
Neoplasma | Year: 2013

Potential prognostic biomarkers in acute myeloid leukemia (AML) can be identified by understanding the cellular pathway and molecular changes underlying leukemogenesis. Deregulation of apoptosis is one of the important features of AML and to understand the molecular mechanism underlying apoptosis and its contribution to tumor progression, this study aimed to evaluate anti-apoptotic Bcl2 protein expression in AML and correlate with FLT3 parameters for their role in prognosis of disease. Bcl2 and FLT3 protein expression was quantified by flow cytometry on leukemic blasts in total 174 de novo AML, myelodysplastic syndrome (MDS) and aplastic anemia patients. FLT3 internal tandem duplication (ITD), Tyrosine kinase domain (TKD) point mutations and quantification of mRNA level was carried out using PCR and RT-PCR methods. The incidence of Bcl2 positivity was 71% in AML patients. Bcl2 positivity was significantly associated with CD34+ and CD117+ AML. Bcl2 positivity tended to be associated with reduced DFS while Bcl2 positivity with FLT3 protein positivity was significantly associated with reduced DFS. In multivariate analysis, Bcl2+ and combined Bcl2+/FLT3 protein+ along with high WBC count emerged as poor prognostic factors for reduced DFS and high blast count for predicting reduced OS. In MDS patients, the incidence of Bcl2 expression was high while in aplastic anemia patients, incidence of Bcl2 expression was low. Patients with Bcl2 and FLT3 protein positivity showed significantly reduced DFS suggesting parallel role of these proteins in imparting chemoresistance to the leukemic cells.

Dave H.,The Gujarat Cancer and Research Institute | Shah M.,The Gujarat Cancer and Research Institute | Trivedi S.,The Gujarat Cancer and Research Institute | Shukla S.,The Gujarat Cancer and Research Institute
International Journal of Biological Markers | Year: 2012

Transforming growth factor betas (TGF-βs) are multifunctional cytokines with a biphasic role in breast tumorigenesis, acting as tumor suppressors at early stages while stimulating tumor progression at later stages (TGF-β switch). Among the 3 human isoforms, TGF-β1 is known to be overexpressed in several tumor types including breast tumors. TGF-β signaling and"crosstalk" in the tumor microenvironment presents a unique challenge and an opportunity to develop novel therapies. We assessed circulating TGF-β1 levels by ELISA in blood samples from 117 previously untreated breast cancer patients in this prospective study to explore the TGF-β switch at the forefront. The levels were correlated with clinicopathological prognosticators like age, menopausal status, nodal status, histological type, histological grade, necrosis, stromal involvement, and survival. Higher mean preoperative serum TGF-β1 was observed in early-stage patients than controls (p=0.05) as revealed by receiver operating characteristic (ROC) analysis. Elevation of TGF-β1 was evident in patients with advanced-stage breast cancer compared with those having early-stage disease (p=0.0001). Prognosticators of an aggressive phenotype were associated with higher TGF-β1 levels, and higher levels thus announced the likelihood of relapse, marking the role of TGF-β1 as a tumor promoter and evidencing the existence of a TGF-β switch. Moreover, higher levels of TGF-β1 shortened the overall survival in breast cancer patients (p=0.010). The results indicate that circulating TGF-β1 may be used as a predictive and prognostic marker in breast carcinoma. © 2011 Wichtig Editore.

Shah K.,The Gujarat Cancer and Research Institute | Parikh S.,The Gujarat Cancer and Research Institute | Rawal R.,The Gujarat Cancer and Research Institute
Asian Pacific Journal of Cancer Prevention | Year: 2016

Chronic myeloid leukaemia (CML) is a clonal myeloproliferative hematopoietic stem cell disorder. Deregulated BCR-ABL fusion tyrosine kinase activity is the main cause of CML disease pathogenesis, making BCR-ABL an ideal target for inhibition. Current tyrosine kinase inhibitors (TKIs) designed to inhibit BCR-ABL oncoprotein activity, have completely transformed the prognosis of CML. Interruption of TKI treatment leads to minimal residual disease reside (MRD), thought to reside in TKI-insensitive leukaemia stem cells which remain a potential reservoir for disease relapse. This highlights the need to develop new therapeutic strategies for CML either as small molecule master TKIs or phytopharmaceuticals derived from nature to achieve chronic molecular remission. This review outlines the past, present and future therapeutic approaches for CML including coverage of relevant mechanisms, whether ABL dependent or independent, and epigenetic factors responsible for developing resistance against TKIs. Appearance of mutant clones along the course of therapy either pre-existing or induced due to therapy is still a challenge for the clinician. A proposed in-vitro model of generating colony forming units from CML stem cells derived from diagnostic samples seems to be achievable in the era of high throughput technology which can take care of single cell genomic profiling.

Singh R.D.,The Gujarat Cancer and Research Institute | Patel K.R.,The Gujarat Cancer and Research Institute | Patel P.S.,The Gujarat Cancer and Research Institute
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis | Year: 2016

Background and aim: p53 mutations are critical players in etiopathogenesis of oral cancer. Interestingly, they show differences in terms of type and codon specificity. These differences might be attributed to geographical variations in tobacco use. We aimed to analyze the frequency of p53 mutations in oral cancer patients from Gujarat, India and their effect on clinico-pathological features, local recurrence and survival. Material and methods: p53 mutation analysis was performed on 46 paired tissue samples (adjacent normal and primary malignant) using PCR-SSCP and sequencing. Results: Sequencing confirmed 51 p53 mutations in 46 paired tissues. Three novel mutations (frameshift deletion in exon 4; G > T transversion at codon 117 in exon 4 and G. >. A transition at codon 319 in exon 9) were identified. Distinct pattern of p53 mutations was observed: more common C. >. T transitions and recurring mutation sites at codon 90 and 116 in exon 4. Interestingly, the probability of developing recurrence was higher in small tumors (<4 cm) with p53 mutations and in cases with p53 mutations in both adjacent normal and malignant tissues. A significant low disease free survival and overall survival was observed in cases harboring truncating and transcriptionally non-active mutations. Conclusion: We report a very high frequency and a diverse pattern of p53 mutations in cases from this region. Interestingly, three distinct novel mutations in exons 4 and 9 were also observed. Analyzing p53 mutation status in tumor tissues at an early stage could serve as an important prognostic factor. © 2015 Elsevier B.V.

Singh R.,The Gujarat Cancer and Research Institute | Haridas N.,Pramukhswami Medical College | Shah F.,The Gujarat Cancer and Research Institute | Patel J.,The Gujarat Cancer and Research Institute | And 2 more authors.
Oral Diseases | Year: 2014

Polymorphic variability in the enzymes involved in biotransformation of tobacco-related pro-carcinogens plays an important role in modulating oral cancer susceptibility. CYP1A1*2A, CYP1A1*2C, GSTM1 and GSTT1 polymorphisms were determined in 122 oral carcinoma cases and 127 controls from Gujarat, West India using PCR-based methods. The results revealed that the polymorphic variants of CYP1A1 gene did not show association towards oral cancer risk. The GSTM1 and GSTT1 null genotypes were found to be over-represented in patients than controls, suggesting a moderate increase in risk of oral cancer. The oral cancer risk was significantly increased in the patients having either alone or concurrent deletion of GSTM1 and GSTT1. The results also suggested significant association between tobacco habits, especially chewing, variant genotypes of CYP1A1, GSTM1 and GSTT1 and oral cancer risk. Our data have provided evidence that GST polymorphism modified the susceptibility to oral cancer and individuals with variant genotypes of the three genes with tobacco habits are at significant risk of developing oral cancer. © 2013 John Wiley & Sons A/S.

PubMed | The Gujarat Cancer and Research Institute
Type: Journal Article | Journal: Journal of cancer research and therapeutics | Year: 2016

Oral cancer has become a grave problem in many parts of the globe with two.thirds of the cases occurring in developing countries. Chronic inflammation plays a prominent role in the development of oral cancer. The rationale for molecular targeted prevention of oral cancer is promising. Therefore, there are continued improvements to our understanding of the molecular connections between inflammation and oral cancer. The inflammatory mediators including nuclear factor kappa B, vascular endothelial growth factor, inflammatory cytokines, prostaglandin pathways, p53, reactive oxygen and nitrogen species, and microRNAs are major key players in the pathogenesis of oral cancer. Currently, visual cytology.based techniques and biopsy are used to detect dysplasia and early stage of oral squamous cell carcinoma. These approaches are limited in their ability to judge the severities of oral lesions and are useful only after the appearance of visual changes. Thus, traditional cytological and biopsy assays combined with testing of inflammatory biomarkers would be beneficial for the efficient early detection of oral dysplastic lesions and early stages of oral squamous cell carcinoma.

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