Science et thérapie du cancer

By reviewing of previous studies, concentrating on recent systematic reviews and large prospective studies tries to give a clear picture with epidemiological evidence about the present scenario of cervical cancer control and HPV (Human Papilloma Virus) in India. Cervical cancer is the second most common cancer among women worldwide and most common malignancy in developing countries, particularly in India. It is unique among cancers in that it can largely be prevented through screening and removal of pre-cursor lesions. Nowadays, cervical screening for women is necessary because there are no signs and symptoms of cervical pre-cancers. The establishment of a prevention program is urgently required considering both screening and vaccination. But most women in India do not have access to effective screening programmes. It has been estimated that in India, even with a major effort to expand cytology services, it will not be possible to screen most of the population once in a lifetime in the near future. New HPV vaccines will also help prevent HPV infection and the pre-cancerous changes that lead to cervical cancer. The focus on identification and prevention of cervical cancer must be emphasized in a highly populated country like India to prevent its extensive blowout.

Ethyl carbamate (EC); urethane is a chemical carcinogen (IARC group 2A). It has been commonly found in the fermented food and beverages. EC induced cancerous lesion in different sites due to the formation of active metabolite; vinyl carbamate (VC). The current study aims to investigate the potential risk of cancerous lesions in small and repeated exposure of ethyl carbamate in BALB/C mice. Three groups of BALBL/C mice were treated for 120 days included untreated control; group treated with a single dose of urethane (1.5 g/kg B.w/i.p) at a day one; group treated with repeated doses, the first at a day one and a second at day sixty (1.5g/ kg B.w/i.p). Ethyl carbamate (EC) exposure showed sever changes of serum biochemical markers, apoptosis markers, inflammatory cytokines as well as lipid peroxide formation in lung homogenate, these changes were pronounced in repeated exposure to ethyl carbamate. In addition, histological examinations revealed that epithelial changes in pulmonary tissues were advanced in animals treated with repeated doses of ethyl carbamate. These findings indicate that repeated exposure to ethyl carbamate of fermented foods and beverages is an additional risk for lung cancer due to permanent mitochondrial dysfunction and increase the cellular mitotic activity.

Rituximab has been revolutionized and validated CD20 targeting monoclonal antibody. Although, it is widely used for lymphoma therapy and many patients have been benefited. However significant numbers of patients are refractory or developed resistance to current therapies due to low level of CD20 expression and/or availability on cells surface. Thus development of novel anti-CD20 mAbs with great cell killing ability and enhance CD20 levels on cell surface can potentially exploit lymphoma therapy. In this scenario, we are summarizing the recently developed mAbs against CD20 and compounds that have ability to induce CD20 expression at significant level. We also are providing information regarding combination strategy for use of radiation and anti-CD20 mAbs in vitro. However, it will need to be determined by rigorous at pre-clinical and clinic testing. We hope this review will be beneficial for current research in the area of immunotherapy or radio-immunotherapy.

Objective: Pancreatic cancer (PC) is a lethal disease with disappointing results from current treatment modalities, suggesting that novel therapeutic strategies are urgently needed. Since microRNAs (miRNAs) are important player in biology, the clinical utility of miRNAs for designing novel therapeutics is an active area of research. The objective of the present study was to examine differentially expressed miRNAs between normal and tumor tissues, and in plasma samples obtained from PC patients, chronic pancreatitis (CP) patients and healthy subjects (HC).

Material and methods: The miRNA expression profiling using formalin-fixed paraffin embedded (FFPE) tissues from normal and tumor specimens was accomplished using miRBase version 19 (LC Sciences, Houston, TX, USA). Quantitative real-time PCR (qRT-PCR) was subsequently performed in individual samples for 7 selected miRNAs. In addition, qRT-PCR was also performed for assessing the expression of 8 selected miRNAs in plasma samples.

Results: A significant difference in the expressions of miR-21, miR-205, miR-155, miR-31, miR-203, miR-214 and miR-129-2 were found in tumor tissue samples. Lower expression of miR-214 was found to be associated with better overall survival. We also observed differential expression of 8 miRNAs in plasma samples of CP and PC patients compared to HC. Interestingly, over expression of miR-21, and miR-31 was noted in both tumor tissues and in the plasma.

Conclusion: We found deregulated expression of miRNAs that could distinguish normal from PC in two different types of samples (tissues and plasma). Interestingly, lower expression of miR-214 was found to be associated with better overall survival. Although not statistically significant, we also observed higher expression of let-7a and lower expression of miR-508 to be associated with overall better survival. We conclude that our study nicely lays the foundation for detailed future investigations for assessing the role of these miRNAs in the pathology of pancreatic cancer.

Objective: Mucinous cystadenocarcinoma of appendix is a rare entity. To differentiated mucinous cystadenocarcinoma from mucinous cystadenoma is very challenging and depends on establishing the presence of malignant cells in the appendix wall. The invasion may be very difficult to assess in some cases, especially in early stages of the disease, which could have devastating prognostic effects on patients. Therefore, it is necessary to develop an ancillary test that can differentiate the mucinous cystadenocarcinoma from mucinous cystadenoma. So far, there is no report available about the role of differentially expressed miRNAs in the diagnosis of appendiceal mucinous cystadenocarcinoma.

Materials and Methods: Six confirmed mucinous appendiceal cystadenocarcinoma and twelve mucinous appendiceal cystadenoma cases were selected. The total RNAs were extracted from the formalin-fixed paraffinembedded specimen of these cases. The comprehensive miRNA microarray expression profiling from pooled aliquots of RNA samples from these two entities were analyzed to detect the differentially expressed miRNAs in mucinous cystadenocarcinoma. The best seven differentially expressed miRNAs were validated in individual cases by quantitative reverse transcriptase PCR (qRT-PCR).

Results: The microarray miRNA expression profiling analysis revealed 646 miRNAs that were differentially expressed in the mucinous cystadenocarcinoma. Among these differentially expressed miRNAs, the expression of 80 miRNAs showed statistical difference (p<0.01). The quantitative RT-PCR validated that the expression of miR-1, miR-4328 was significantly down regulated in mucinous cystadenocarcinoma compared to the mucinous cystadenoma (p<0.05). On the other hand, the expression of miR-200b, miR-200c, miR-451, miR-223 and miR-21 were significantly increased in mucinous cystadenocarcinoma (p<0.05).

Conclusion: The expression levels of miRNAs tested were significantly altered in the appendiceal mucinous cystadenocarcinoma samples compared to the mucinous cystadenoma. These data suggest that the miRNA expression in mucinous appendiceal neoplasm may help to supplement the morphological evaluation in distinguishing benign from malignant tumors.