Reversible inhibition of sperm under guidance as an intratubular and reversible contraception in female rats: An experimental study

Background: Reversible inhibition of sperm under guidance (“RISUG®”) is a promising intravasal male contraceptive. Objective: An exploratory study was conducted with a concept of non-invasive, transcervical, single-intervention and reversible contraception using RISUG® in females. Materials and Methods: In this experimental study, 60 adult Wistar albino female rats weighing 150-155 g, 3-4 months old were divided into four groups: group I: sham-operated control; group II: tubal occlusion with RISUG for 90 days; group III: tubal occlusion with RISUG® for 90 days and reversal with dimethyl sulphoxide and group IV: tubal occlusion with RISUG® for 90 days and reversal with 5% NaHCO3. Animals were subjected to bilateral fallopian tube occlusion with RISUG® and reversal with DMSO and NaHCO3. The estrous cycle, fertility and histology of fallopian tube were evaluated. Results: Group I showed 100% fertility during all mating schedules. Animals of experimental groups indicated positive mating, but 0% fertility was evident following 30, 60, and 90 days of tubal occlusion. However, after reversal, fertility steadily increased to normalcy in groups III (50% at 45 days, 80% at 105 days, 100% at 150 and 195 days) and IV (70% at 45 and 105 days, 100% at 150 and 195 days) animals. Group II illustrated disorganized inner cell linings and eosinated RISUG® implant-filled lumen. Reversal groups (III and IV) revealed complete restoration of cellular histo-architecture. Regular estrous cycle was noticed in all experimental groups. Conclusion: RISUG® is suitable for single intervention, intratubular, reversible contraception in female rats. Key words: Contraception, Fallopian tube, Tubal occlusion, RISUG®, Reversible

A partner monoclonal antibody to Moab 730 kills 100% of DU145 and PC3 androgen-independent cancer cells

A number of therapeutic options are available for patients with prostate carcinoma till the time that the tumour is hormone dependent. However, no fully effective therapy is available for the treatment of androgen-independent prostate carcinomas. Antibodies directed at epitopes unique to or overexpressed on the cancer cells could be of therapeutic utility. A monoclonal antibody (Moab) 2C4 has been generated, which binds with cells of two androgenin-dependent prostate cancers, DU145 and PC3, and does not bind to peripheral blood leukocytes (PBLs) of healthy donors. This antibody, along with the previously developed Moab 730, kills 100% of both DU145 and PC3 cells in the presence of complement and does not have a deleterious effect on PBLs of healthy males. The anti-tumour action of the two antibodies prevents the establishment of DU145 cell tumour in nude mice in vivo. Moab 2C4 in combination with 730 has potential for use as therapy for androgen-independent cancers

Heat shock protein 70-2 (HSP70-2) overexpression in breast cancer

Supplementary Methods, Supplementary table, Supplementary Figure Legends. (DOCX 41 kb

A Pilot Study on the Whole Exome Sequencing of Prostate Cancer in the Indian Phenotype Reveals Distinct Polymorphisms

Prostate cancer (PCa) is the third most common cancer among men in India, and no next-generation sequencing (NGS) studies have been attempted earlier. Recent advances in NGS have heralded the discovery of biomarkers from Caucasian/European and Chinese ancestry, but not much is known about the Indian phenotype/variant of PCa. In a pilot study using the whole exome sequencing of benign/PCa patients, we identified characteristic mutations specific to the Indian sub-population. We observed a large number of mutations in DNA repair genes, viz. helicases, TP53, and BRCA besides the variants of unknown significance with a possibly damaging rare variant (rs730881069/chr19:55154172C/TR136Q) in the TNNI3 gene that has been previously reported as a semi-conservative amino acid substitution. Our pilot study attempts to bring an understanding of PCa prognosis and recurrence for the Indian phenotype.</p

Sperm associated antigen 9 plays an important role in bladder transitional cell carcinoma.

BACKGROUND: Majority of bladder cancer deaths are caused due to transitional cell carcinoma (TCC) which is the most prevalent and chemoresistant malignancy of urinary bladder. Therefore, we analyzed the role of Sperm associated antigen 9 (SPAG9) in bladder TCC. METHODOLOGY AND FINDINGS: We examined SPAG9 expression and humoral response in 125 bladder TCC patients. Four bladder cancer cell lines were assessed for SPAG9 expression. In addition, we investigated the effect of SPAG9 ablation on cellular proliferation, cell cycle, migration and invasion in UM-UC-3 bladder cancer cells by employing gene silencing approach. Our SPAG9 gene and protein expression analysis revealed SPAG9 expression in 81% of bladder TCC tissue specimens. High SPAG9 expression (>60% SPAG9 positive cells) was found to be significantly associated with superficial non-muscle invasive stage (P = 0.042) and low grade tumors (P = 0.002) suggesting SPAG9 putative role in early spread and tumorigenesis. Humoral response against SPAG9 was observed in 95% of patients found positive for SPAG9 expression. All four bladder cancer cell lines revealed SPAG9 expression. In addition, SPAG9 gene silencing in UM-UC-3 cells resulted in induction of G0-G1 arrest characterized by up-regulation of p16 and p21 and consequent down-regulation of cyclin E, cyclin D and cyclin B, CDK4 and CDK1. Further, SPAG9 gene silencing also resulted in reduction in cellular growth, and migration and invasion ability of cancer cells in vitro. CONCLUSIONS: Collectively, our data in clinical specimens indicated that SPAG9 is potential biomarker and therapeutic target for bladder TCC

Towards Understanding the Key Signature Pathways Associated from Differentially Expressed Gene Analysis in an Indian Prostate Cancer Cohort

Prostate cancer (PCa) is one of the most prevalent cancers among men in India. Although studies on PCa have dealt with genetics, genomics, and the environmental influence in the causality of PCa, not many studies employing the Next Generation Sequencing (NGS) approaches of PCa have been carried out. In our previous study, we identified some causal genes and mutations specific to Indian PCa using Whole Exome Sequencing (WES). In the recent past, with the help of different cancer consortiums such as The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC), along with differentially expressed genes (DEGs), many cancer-associated novel non-coding RNAs have been identified as biomarkers. In this work, we attempt to identify differentially expressed genes (DEGs) including long non-coding RNAs (lncRNAs) associated with signature pathways from an Indian PCa cohort using the RNA-sequencing (RNA-seq) approach. From a cohort of 60, we screened six patients who underwent prostatectomy; we performed whole transcriptome shotgun sequencing (WTSS)/RNA-sequencing to decipher the DEGs. We further normalized the read counts using fragments per kilobase of transcript per million mapped reads (FPKM) and analyzed the DEGs using a cohort of downstream regulatory tools, viz., GeneMANIA, Stringdb, Cytoscape-Cytohubba, and cbioportal, to map the inherent signatures associated with PCa. By comparing the RNA-seq data obtained from the pairs of normal and PCa tissue samples using our benchmarked in-house cuffdiff pipeline, we observed some important genes specific to PCa, such as STEAP2, APP, PMEPA1, PABPC1, NFE2L2, and HN1L, and some other important genes known to be involved in different cancer pathways, such as COL6A1, DOK5, STX6, BCAS1, BACE1, BACE2, LMOD1, SNX9, CTNND1, etc. We also identified a few novel lncRNAs such as LINC01440, SOX2OT, ENSG00000232855, ENSG00000287903, and ENST00000647843.1 that need to be characterized further. In comparison with publicly available datasets, we have identified characteristic DEGs and novel lncRNAs implicated in signature PCa pathways in an Indian PCa cohort which perhaps have not been reported. This has set a precedent for us to validate candidates further experimentally, and we firmly believe this will pave a way toward the discovery of biomarkers and the development of novel therapies