Tehran University Medical Journal

Background: Aberrant pre-mRNA alternative splicing is a common event in cancer cells. Many abnormally spliced RNA variants have been observed in tumor cells and they can be used as biomarkers or therapeutic targets in new drug design. Increasing our knowledge in understanding the mechanisms of alternative pre-mRNA splicing for cancer-related genes and determination of cancer specific isoforms are important for the development of new strategies in cancer therapy. The aim of this study was isoforms identification and expression of PIK3CA, FGFR3 and FGFR1 genes in bladder cancer by RNA Sequencing and Real-Time PCR.
Methods: This cross-sectional study was conducted at Urology Research Center of Sina Hospital, Tehran University of Medical Sciences, Tehran, from September 2014 to October 2016. Paired tumor and adjacent normal tissues samples were obtained from 30 bladder cancer subjects. Total RNAs were extracted from bladder tumor and normal tissues. Quantitative and qualitative examinations have been done. After quality control, fragmentation of RNAs and cDNA library construction, next-generation RNA sequencing was performed. Resulting raw data were analyzed with different bioinformatics software. Differential expression was confirmed by Real-Time PCR.

Conclusion: RNA sequencing make possible to do the accurate assessment of transcript abundance and identification of different isoforms resulted from aberrant pre-mRNA alternative splicing, which is a crucial process for the maturation of transcripts of multi-exon genes. Regarding the differences in isoforms expression in tumor and normal tissues of bladder cancer, they have potential to be used as biomarkers and sensitive targets for cancer therapy.

Cancer immunotherapy refers to any intervention that leverages the immune system to eliminate a malignancy. Successful cancer immunotherapies generate an anti-cancer response that is systemic, specific, and durable and overcome to the primary limitations of traditional cancer treatment modalities. In this review paper, the effective methods in immune system to treat cancer, such as immunosuppression in tumor microenvironment (TME), cancer vaccines and T cell adaptive therapy are mentioned. Engineered T cells can use for destruction of the different cancer tissues to diagnose tumor surface antigens. Promotion in culture of T cell methods and their engineering with retroviral vectors that carry T cell receptors or chimeric antigen receptors (CAR) by co-stimulator domains, provide opportunity to treat tumor by T cells. The tumors with high genome mutation, such as lung and melanoma, have severe environmental mutagenesis that is induced by ultra violet light in melanoma and Tobacco in lung cancers. Expression of tumor specific receptors is increased by engineered T cells. The neo-antigens conduct the intensity of intra tumor T cell response. The present of CD8+ in tumor site with more mutation is higher and the mutation load is showed strong relation with the clinical response. In addition to the successful approaches to cancer immunotherapy, the other combination and molecular therapies by nanomaterials are listed. Nanomaterials as efficient modulators and diverse vaccine have been developed in the treatment of cancer. In recent cancer vaccine development has been on subunit vaccines that contain purified tumor antigens or antigenic epitopes as an antigen source. However, soluble bolus-based subunit vaccines typically induce weak cytotoxic T lymphocyte responses which limit their utility for cancer. To overcome this, nanoscale colloids can be used to promote more efficient antigen presentation by acting as phagocytic substrates. Nanomaterials are showed co-suppression and immunization in tumor microenvironment by multiple additive functions in preclinical models. In this manner, they exhibited good prospects because of the good results in overcoming the limitations of current therapies. In this review paper is tried to provide new prospect for therapies and hope it creates highest efficacy and lowest side effects for the treatment of patients in the near future.