HPV imprints in western India: The overlooked criteria for cancer profiling

Background: In India, HPV infection detection for cancer-typing has been largely evaded. Especially, data on prevalence of HPV types other than the highly prevalent HPV 16 and 18 are lacking, particularly from the western region. Thus, present study aimed to evaluate prevalence of HPV strains in three most prevailing cancers in India i.e. cervical, oral and oropharyngeal cancer. Materials & methods: DNA was isolated from tissue samples of 400 cervical cancer cases, 127 oral cancer cases and 75 oropharyngeal cancer cases and endpoint PCR was performed using degenerative primers MY 09/11, GP 5+/6+ and CP I/II. TS-PCR was conducted to detect HPV 16, 18, 31, 33, 45, 52, 58, 6 and 11. Results: Overall HPV infection was observed in 87% cases of cervical cancer, 12.5% of oral cancer and 26.7% of oropharyngeal cancer using degenerative primers. HPV 16 (72.5% in cervical cancer, 1.33% in oropharyngeal cancer), HPV 18 (14.8% in cervical cancer) and HPV 45 (2.3% in cervical cancer) were observed to be comparatively higher than the other HPV types. All the HPV types except HPV 11 were observed to be present in the studied cohort. HPV was also associated with younger age, well differentiated tumors with no lymph node metastasis. Conclusion: Prominent prevalence of HPV infection was noted in studied population. The study represents need of awareness for HPV screening at clinical set-ups which will lead to upgraded profiling of cancers and better disease management. Moreover, current study provides supportive data for initiation of HPV vaccination programs in India

Cysteamine Suppresses Invasion, Metastasis and Prolongs Survival by Inhibiting Matrix Metalloproteinases in a Mouse Model of Human Pancreatic Cancer

Background: Cysteamine, an anti-oxidant aminothiol, is the treatment of choice for nephropathic cystinosis, a rare lysosomal storage disease. Cysteamine is a chemo-sensitization and radioprotection agent and its antitumor effects have been investigated in various tumor cell lines and chemical induced carcinogenesis. Here, we investigated whether cysteamine has anti-tumor and anti-metastatic effects in transplantable human pancreatic cancer, an aggressive metastatic disease. Methodology/Principal Findings: Cysteamine’s anti-invasion effects were studied by matrigel invasion and cell migration assays in 10 pancreatic cancer cell lines. To study mechanism of action, we examined cell viability and matrix metalloproteinases (MMPs) activity in the cysteamine-treated cells. We also examined cysteamine’s anti-metastasis effect in two orthotopic murine models of human pancreatic cancer by measuring peritoneal metastasis and survival of animals. Cysteamine inhibited both migration and invasion of all ten pancreatic cancer cell lines at concentrations (,25 mM) that caused no toxicity to cells. It significantly decreased MMPs activity (IC50 38–460 mM) and zymographic gelatinase activity in a dose dependent manner in vitro and in vivo; while mRNA and protein levels of MMP-9, MMP-12 and MMP-14 were slightly increased using the highest cysteamine concentration. In vivo, cysteamine significantly decreased metastasis in two established pancreatic tumor models, although it did not affect the size of primary tumors. Additionally, cysteamin

Matrix Metalloproteinases and Their Inhibitors: Correlation with Invasion and Metastasis in Oral Cancer

Matrix metalloproteinases (MMPs) have been implicated in invasion and metastasis of various malignancies. The study evaluated a comprehensive profile of MMP-2 and MMP-9 and their inhibitors, tissue inhibitor of metalloproteinases-2 (TIMP-2) and tissue inhibitor of metalloproteinases-1 (TIMP-1), respectively in 50 controls and 75 patients with oral squamous cell carcinoma (OSCC). Blood samples from controls and patients as well as malignant and adjacent normal tissues from the patients were collected. The study examined pro, active and total forms of MMP-2 and MMP-9 using zymography. Enzyme-linked immunoassay (ELISA) and reverse transcription polymerase chain reaction were carried out to evaluate protein levels and mRNA expression; respectively, for the MMPs and TIMPs. Plasma pro, active and total MMP-2, MMP-9 as well as TIMP-1 and TIMP-2 levels were significantly higher in oral cancer patients as compared to the controls. mRNA expression of the MMPs and TIMPs was significantly higher in malignant tissues as compared to adjacent normal tissues. A significant positive correlation was observed between levels of proMMP-9 and active MMP-9 with differentiation, stage and infiltration. ProMMP-2 and active MMP-2 exhibited significant positive correlation with differentiation and lymph node involvement. The multivariate analysis of ELISA results revealed a significant positive correlation between MMP-2, TIMP-1 and TIMP-2 levels with lymph node involvement, stage and differentiation. The receiver operating characteristic curve (ROC) analysis showed that the levels of MMPs and TIMPs have significant discriminatory efficacy to differentiate between controls and patients. The results indicate that MMP-2, MMP-9, TIMP-1 and TIMP-2 have significant clinical usefulness for oral cancer patients. Zymographic analysis is a simple, cost effective, rapid and sensitive alternative assay