Sarkar S.,Chittaranjan National Cancer Institute |
Alam N.,Chittaranjan National Cancer Institute |
Chakraborty J.,Chittaranjan National Cancer Institute |
Biswas J.,Chittaranjan National Cancer Institute |
And 3 more authors.
Medical Microbiology and Immunology | Year: 2017
Head and neck cancers constitute a multifactorial global disease burden and are associated with human papilloma virus (HPV) as a possible risk factor. The aim of the study is to understand the relationship between HPV and the development of head and neck lesions in Indian patients. To this end, frequency of HPV was assessed in relation to different demographic and etiological features and correlated with patient survival. The prevalence of HPV significantly increased from mild dysplastic lesions (43.6%) to head and neck squamous cell carcinoma (HNSCC) stage IV (68.5%) with HPV 16 being pre-dominant in both dysplasia (43.8%) and HNSCC (61.5%). Similar trend was observed in increasing grades of the tumour. In invasive lesions, patients aged below the median age of onset showed significantly higher occurrence of HPV than those above it. Patients harbouring HPV showed a significantly better survival irrespective of age of onset. Likewise, better survival was observed in tobacco habit negative/HPV-positive patients, and as reflected in both univariate and multivariate analysis. Majority of the HPV 16-positive samples showed moderate/high nuclear expression of HPV E6 and E7 proteins in tumours and respective basal layer of adjacent normal tissues. Thus, our data indicate that frequent HPV infection, along with tobacco habit, is a pre-requisite factor for the development of HNSCC of Indian patients but offers a better survival even during tobacco usage, implicating its diagnostic and prognostic importance. © 2017 Springer-Verlag Berlin Heidelberg
Mandal P.K.,Medical College |
Mondal S.K.,Medical College |
Roy S.,Saroj Gupta Cancer Center and Research Institute |
Adhikari A.,Medical College |
Sinha S.K.,Medical College
Journal of Cytology | Year: 2013
Background: Fine needle aspiration cytology (FNAC) is a rapid, cheap and reliable method for diagnosing any accessible lesion. However, there remains a group of malignant undifferentiated neoplasms, which can only be categorized with the help of immunocytochemistry (ICC). The categorization is important due to their vast difference in treatment and prognosis. Aim: To evaluate the effectiveness of ICC in categorizing the undifferentiated neoplasms diagnosed on routine FNAC smears. Materials and Methods: Thirty six cases of undifferentiated neoplasms were selected from a group of total 78 cytology cases of undifferentiated tumors from different sites like head and neck, lymph node, soft tissue etc. These were then subjected to a panel of ICC markers based on the clinical and cytomorphological features. Results: Of these, 21 were simple, ten were computerized tomography guided and five were ultrasound guided FNACs respectively. All the 78 cases were confirmed by histopathological examination and immunohistochemistry. Of the 36 cytological cases, final diagnosis correlated in 30 cases histologically. The six cases were incorrect either due to inadequate material on the smears (three cases) or false positive staining (three cases). Conclusions: Our study found that ICC is a sensitive and specific method for early and definitive diagnosis of undifferentiated neoplasms. However, selection of antibodies must be judicious to make it cost effective.
PubMed | Chittaranjan National Cancer Institute, Medical College, North Bengal Medical College and Saroj Gupta Cancer Center and Research Institute
Type: Journal Article | Journal: Journal of cytology | Year: 2015
Percutaneous lung biopsy is now a common procedure in pulmonary medicine, and several different techniques are in use. The most common has been the use of a fine needle under computed tomography (CT) guidance combined with the trucut needle for histology.To evaluate the efficacy of fine needle aspiration cytology (FNAC) and immunocytochemistry in comparison with trucut biopsy and immunohistochemistry in patients with localized intrathoracic lesions suspicious for malignancy.Eighty patients with localized mass lesions in the lung on imaging (chest radiograph/CT) were selected for this study over a period of 1 year. FNAC was carried out by a 22 G spinal needle after localization of the mass in the CT scan followed by guided trucut biopsy. Immunocytochemistry and immunohistochemistry were performed as and when required.The mean age of our study population was 57.6 years and the M:F ratio was 4.2:1. Majority of the lesions were peripheral and in the right lung. Adenocarcinoma was most prevalent (49%), followed by squamous cell carcinoma and small cell carcinoma. Cyto-histopathological concordance was seen in 60 cases (75%). The highest rate of concordance was seen in small cell carcinoma (83.3%). The overall sensitivity of FNAC in distinguishing malignant lung lesions from benign lesions was 84.2% and the specificity was 100%. The sensitivity of cytology in diagnosing small cell carcinoma was 83.3% and of non-small cell carcinoma was 65.38%. Immunocytochemistry was carried out in 34 cases, all of which were followed by immunohistochemistry. Cyto-histopathological concordance was noted in 31 of these cases (91.2%). We used the standard panel of four markers (cytokeratin-7, thyroid transcription factor-1, p63 and CD56) for all selected cases.Cytology along with immunocytochemistry is highly effective in diagnosing and categorizing lung neoplasms, producing comparable results to trucut biopsy and immunohistochemistry.
Roy S.,Saroj Gupta Cancer Center and Research Institute |
Das I.,Saroj Gupta Cancer Center and Research Institute |
Nandi A.,Lane College |
Roy R.,Saroj Gupta Cancer Center and Research Institute
Indian Journal of Pathology and Microbiology | Year: 2015
Merkel cell carcinoma (MCC) is a highly aggressive neoplasm of skin with neuroendocrine differentiation. Primary MCC of the oral mucosa is exceedingly rare and even more unresponsive to therapy. A 15-year-old male presents with gradually increasing painless swelling in right side of the floor of mouth for 6 weeks. Computed tomography of head and neck region showed globular mass (4.6 cm × 1.7 cm) involving right side of the floor of mouth. Fine-needle aspiration from the upper deep cervical node suggested small round cell tumor. A trucut biopsy showed mass composed of trabeculae and nests of tumor cells with high N:C ratio, granular speckled chromatin, scanty to moderate amount of clear vacuolated cytoplasm. Cells were immunoreactive for cytokeratin-20, CD56, c-kit, CD99 and negative for p63, thyroid-transcription factor-1, CDX2, synaptophysin, neuron-specific enolase. Patient was started on chemotherapy with cyclophosphamide, doxorubicin and vincristine. The mass regressed in size and patient underwent wide local excision with pull-through approach. Patient is currently under combined chemoradiation regime and doing well.
Das Ghosh D.,Indian Statistical Institute |
Bhattacharjee B.,Indian Statistical Institute |
Bhattacharjee B.,University of Massachusetts Medical School |
Sen S.,National Institute of Biomedical Genomics |
And 5 more authors.
PLoS ONE | Year: 2012
This study was undertaken to decipher the interdependent roles of (i) methylation within E2 binding site I and II (E2BS-I/II) and replication origin (nt 7862) in the long control region (LCR), (ii) expression of viral oncogene E7, (iii) expression of the transcript (E7-E1∧E4) that encodes E2 repressor protein and (iv) viral load, in human papillomavirus 16 (HPV16) related cervical cancer (CaCx) pathogenesis. The results revealed over-representation (p<0.001) of methylation at nucleotide 58 of E2BS-I among E2-intact CaCx cases compared to E2-disrupted cases. Bisulphite sequencing of LCR revealed overrepresentation of methylation at nucleotide 58 or other CpGs in E2BS-I/II, among E2-intact cases than E2-disrupted cases and lack of methylation at replication origin in case of both. The viral transcript (E7-E1∧E4) that produces the repressor E2 was analyzed by APOT (amplification of papillomavirus oncogenic transcript)-coupled-quantitative-RT-PCR (of E7 and E4 genes) to distinguish episomal (pure or concomitant with integrated) from purely integrated viral genomes based on the ratio, E7 CT/E4 CT. Relative quantification based on comparative CT (theshold cycle) method revealed 75.087 folds higher E7 mRNA expression in episomal cases over purely integrated cases. Viral load and E2 gene copy numbers were negatively correlated with E7 CT (p = 0.007) and E2 CT (p<0.0001), respectively, each normalized with ACTB CT, among episomal cases only. The k-means clustering analysis considering E7 CT from APOT-coupled-quantitative-RT-PCR assay, in conjunction with viral load, revealed immense heterogeneity among the HPV16 positive CaCx cases portraying integrated viral genomes. The findings provide novel insights into HPV16 related CaCx pathogenesis and highlight that CaCx cases that harbour episomal HPV16 genomes with intact E2 are likely to be distinct biologically, from the purely integrated viral genomes in terms of host genes and/or pathways involved in cervical carcinogenesis. © 2012 Das Ghosh et al.
Verma S.,CSIR - Central Electrochemical Research Institute |
Kesh K.,CSIR - Central Electrochemical Research Institute |
Gupta A.,Saroj Gupta Cancer Center and Research Institute |
Swarnakar S.,CSIR - Central Electrochemical Research Institute
Asian Pacific Journal of Cancer Prevention | Year: 2015
Matrix metalloproteinase (MMP) 9, a key member of multifunctional family of zinc dependent endopeptidases has been found to be upregulated during inflammation and in some cancers. MMPs cleave extracellular matrix (ECM) proteins and play critical roles in cellular apoptosis, angiogenesis, tumor growth and metastasis. Several genetic polymorphisms have been identified that show allele specific effects on MMP9 regulation and are associated with gastric cancer, the fourth most common malignancy in the world. Besides Helicobacter pylori infection, genetic predisposition is another documented risk factor for gastric carcinoma. The single nucleotide polymorphism (SNP) at position-1562C/T of MMP9 results in the modulation for binding of transcription factors to the MMP9 gene promoter and thereby causes differences in protein expression and enzymatic activity. MMP9 transcriptional regulation during gastric cancer development remains poorly known although several studies have demonstrated associations between MMP9-1562 C/T polymorphism with different diseases. Knowledge on mechanisms of MMP9 upregulation during gastric cancer may provide new paradigm in diagnostics and therapeutics.
PubMed | Institute of Nuclear Medicine and Allied Sciences, Saroj Gupta Cancer Center and Research Institute and Indian Institute of Technology Kharagpur
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2016
Amplification of PI3K-Akt pathway promotes radioresistance in various cancers including colorectal carcinoma. Local recurrence in colon cancer causes poor prognosis affecting overall survival of cancer-affected patient population. To avoid local recurrence, pre-operative or post-operative additional radiotherapy is given. However, main concern regarding radiotherapy is to increase the radiosensitivity of malignant cell without hampering the activities of normal cells. In this context, addition of two or more than two chemotherapeutic drugs as a radiosensitizer is a common practice in radiation biology. BI-69A11 earlier showed potential apoptosis-inducing effect in melanoma and colon carcinoma. Celecoxib showed anti-cancer effects in both COX-2 dependent and independent pathways and used to act as a radiosensitizing enhancer. Here, we suggest that the combination of BI-69A11 and celecoxib inhibits the phosphorylation of ataxia telangiectasia mutated (ATM) kinase and DNA-PK responsible for ionizing radiation (IR)-induced double-strand break (DSB) repair. Moreover, the combinatorial effect of BI-69A11 and celecoxib attenuates the IR-induced G2/M cell cycle arrest. Furthermore, this combination also impairs IR-induced activation of Akt and downstream targets of ATM. This might lead to induced activation of apoptotic pathway after triple therapy treatment modulating pro-apoptotic and anti-apoptotic proteins. This activation of apoptotic pathway also showed the interdependence of PUMA and BAD in triple combination-treated colon cancer cells in a p53 independent manner. This study reveals the therapeutic potential of the triple combination therapy in prevention of radioresistance. Besides, it also demonstrates the cytotoxic effects of triple combination therapy in colon cancer. This study shows utility and potential implication on safety of the patients undergoing radiation therapy.
PubMed | Saroj Gupta Cancer Center and Research Institute
Type: Case Reports | Journal: Journal of cancer research and therapeutics | Year: 2016
Uveal melanoma is a cancer (melanoma) of the eye involving the iris, ciliary body, or choroid (collectively referred to as the uvea). The liver is a frequent site for metastasis in patients with uveal melanoma. The interval between the diagnosis of the uveal melanoma and the diagnosis of the metastatic lesion can vary. Despite therapy, the median survival of those with liver metastasis is 5-7 months. We report here a rare case of choroidal melanoma in a 45-year-old male smoker presented with liver metastasis within just 8 months after completion of initial treatments consists of enucleation of eye and 3 Dimensional conformal radiation therapy (3D-CRT). The metastasis is an incidental finding on imaging after having some vague symptoms. This type of very early metastasis after completing initial treatment is very rare and proves the aggressiveness of the disease.
PubMed | Indian Institute of Chemical Technology and Saroj Gupta Cancer Center and Research Institute
Type: Journal Article | Journal: PloS one | Year: 2014
Expression of matrix metalloproteinase-1 (MMP-1), an interstitial collagenase, plays a major role in cellular invasion during development of gastric cancer, a leading cause of death worldwide. A single-nucleotide polymorphism (SNP) -1607 1G/2G site of the MMP-1 gene promoter has been reported to alter transcription level. While the importances of other SNPs in the MMP-1 promoter have not yet been studied in gastric cancer, our aim was to investigate MMP-1 gene promoter polymorphisms and gastric cancer susceptibility in eastern Indian population. A total of 145 gastric cancer patients and 145 healthy controls were genotyped for MMP-1 -1607 1G/2G (rs1799750) by PCR-restriction fragment length polymorphism (RFLP), while MMP-1 -519 A/G (rs1144393), MMP-1 -422 T/A (rs475007), MMP-1 -340 T/C (rs514921) and MMP-1 -320 T/C (rs494379) were genotyped by DNA sequencing. A positive association was found with MMP-1 -422 T/A SNP that showed significant risk for regional lymph node metastasis (P=0.021, Odds ratio (OR)=3.044, Confidence intervals (CI)=1.187-7.807). In addition, we found a significant association with lower stomach tumor formation among gastric cancer patients for three adjacent polymorphisms near the transcriptional start sites of [MMP-1 -422 T/A (P=0.043, OR=2.182, CI=1.03-4.643), MMP-1 -340 T/C (P=0.075, OR=1.97, CI=0.94-4.158) and MMP-1 -320 T/C (P=0.034, OR=2.224, CI=1.064-40731)]. MMP-1 level in patients serum was correlated with MMP-1 promoter haplotypes conferring these three SNPs to evaluate the functional importance of these polymorphisms in lower stomach tumor formation and significant correlation was observed. Furthermore, MMP-1 -519 A/G polymorphism displayed poor cellular differentiation (P=0.024, OR=3.8, CI=1.69-8.56) attributing a higher risk of cancer progression. In conclusion, MMP-1 proximal promoter SNPs are associated with the risk of lower stomach tumor formation and node metastasis in eastern Indian population.
PubMed | Sri Aurobindo Seva Kendra, Saroj Gupta Cancer Center and Research Institute and National Institute of Biomedical Genomics
Type: Journal Article | Journal: Cellular oncology (Dordrecht) | Year: 2016
Previously, over-expression of the long noncoding RNA (lncRNA) HOTAIR has been found to be associated with the invasive and metastatic capacities of several epithelial cancers, including cervical cancer (CaCx). Here, we aimed at identifying functionally relevant genetic variants that may be employed to differentiate between clinically distinct CaCx subtypes, i.e., those exhibiting high HOTAIR levels and molecular signatures of metastasis and those lacking such signatures in the presence of low HOTAIR expression levels.Genomic DNA isolated from various cervical tissue samples (characterized by histopathology and HPV status) was used for HOTAIR amplicon sequencing, followed by validation of the findings by Sanger sequencing. The impact of the genetic variants found on the secondary structure of HOTAIR and the concomitant alterations in miRNA binding sites were determined through in silico analysis, followed by miRNA expression analysis by quantitative real-time PCR and confirmation of miRNA binding using a luciferase reporter assay.We found that rs2366152C was over-represented [OROur data indicate that rs2366152C not only has the potential to serve as a marker for singling out CaCx cases lacking metastatic molecular signatures, but also to explain the functional inactivation of HOTAIR in these cases, including the mechanism of its down-regulation.