RESUMO
Gall bladder cancer (GBC) is becoming a very devastating form of hepatobiliary cancer in India. Every year new cases of GBC are quite high in India. Despite recent advanced multimodality treatment options, the survival of GBC patients is very low. If the disease is diagnosed at the advanced stage (with local nodal metastasis or distant metastasis) or surgical resection is inoperable, the prognosis of those patients is very poor. So, perspectives of targeted therapy are being taken. Targeted therapy includes hormone therapy, proteasome inhibitors, signal transduction and apoptosis inhibitors, angiogenesis inhibitors, and immunotherapeutic agents. One such signal transduction inhibitor is the specific short interfering RNA (siRNA) or short hairpin RNA (shRNA). For developing siRNA-mediated therapy shRNA, although several preclinical studies to evaluate the efficacy of these key molecules have been performed using gall bladder cells, many more clinical trials are required. To date, many such genes have been identified. This review will discuss the recently identified genes associated with GBC and those that have implications in its treatment by siRNA or shRNA.
RESUMO
Long non-coding RNA (lncRNA) have little or no coding potential. These transcripts are longer than 200 nucleotides. Since lncRNAs are master regulators of almost all biological processes, recent evidence proves that aberrantly expressed lncRNAs are pathogenic for oral squamous cell carcinoma (OSCC) and other diseases. LncRNAs influence chromatin modifications, transcriptional modifications, post-transcriptional modifications, genomic imprinting, cell proliferation, invasion, metastasis, and apoptosis. Consequently, they have an impact on the disease transformation, progression, and morbidity in OSCC. Therefore, circulating lncRNAs could be the potential cancer biomarker for the better clinical management (diagnosis, prognosis, and monitoring) of OSCC to provide advanced treatment strategies and clinical decisions. In this review, we report and discuss the recent understandings and perceptions of dysregulated lncRNAs with a focus on their clinical significance in OSCC-disease monitoring and treatment. Evidence clearly indicates that a specific lncRNA expression signature could act as an indicator for the early prediction of diagnosis and prognosis for the initiation, progression, recurrence, metastasis and other clinical prognostic-factors (overall survival, disease-free survival, etc.) in OSCC. The present review demonstrates the current knowledge that all potential lncRNA expression signatures are molecular biomarkers for the early prediction of prognosis in OSCC. Finally, the review provides information about the clinical significance, challenges and limitations of the clinical usage of circulating lncRNAs in a liquid biopsy method in early, pre-symptomatic, sub-clinical, accurate OSCC prognostication. More studies on lncRNA are required to unveil the biology of the inherent mechanisms involved in the process of the development of differential prognostic outcomes in OSCC.
RESUMO
The roles of gut microorganisms in cancer are diverse. Studies on metagenomics and bioinformatics have documented diverse microbial etiology in different tumors. Evidence supports that a commensal microbiome could provide a promising strategy to treat and prevent cancer through interference in several biologic processes, such as host cell survival and death, host immune function, inflammation, oncogenic signaling, and several hormone receptor signaling and detoxification pathways. The cumulative evidence recommends that metabolites of commensal gut microorganisms (e.g., short-chain fatty acids, omega-3 and -6 fatty acids) play an important role in cancer prevention, with a robust antiproliferative effect of omega-3 fatty acids. Intriguingly, the endocannabinoid system (omega-3 and -6 fatty acid-derived neurotransmitter of the body) shows diverse effects on cancer prevention and oncogenesis depending on the context of the tumor microenvironment. Thus, an interplay of gut microorganisms with their fatty acid metabolites and the endocannabinoid system play an important role in the development, progression, immunomodulation, and chemoresistance of cancer. In this review, we highlight aspects of the current knowledge of and interactions between the microbiome with fatty acids and the host endocannabinoid system. We also document their effect on host immunomodulation and chemoresistance, and discuss how these insights might translate into future development of microbiome-targeted therapeutic interventions.
