Identification of Plausible Candidates in Prostate Cancer Using Integrated Machine Learning Approaches.

Background: Currently, prostate-specific antigen (PSA) is commonly used as a prostate cancer (PCa) biomarker. PSA is linked to some factors that frequently lead to erroneous positive results or even needless biopsies of elderly people. Objectives: In this pilot study, we undermined the potential genes and mutations from several databases and checked whether or not any putative prognostic biomarkers are central to the annotation. The aim of the study was to develop a risk prediction model that could help in clinical decision-making. Methods: An extensive literature review was conducted, and clinical parameters for related comorbidities, such as diabetes, obesity, as well as PCa, were collected. Such parameters were chosen with the understanding that variations in their threshold values could hasten the complicated process of carcinogenesis, more particularly PCa. The gathered data was converted to semi-binary data (-1, -0.5, 0, 0.5, and 1), on which machine learning (ML) methods were applied. First, we cross-checked various publicly available datasets, some published RNA-seq datasets, and our whole-exome sequencing data to find common role players in PCa, diabetes, and obesity. To narrow down their common interacting partners, interactome networks were analysed using GeneMANIA and visualised using Cytoscape, and later cBioportal was used (to compare expression level based on Z scored values) wherein various types of mutation w.r.t their expression and mRNA expression (RNA seq FPKM) plots are available. The GEPIA 2 tool was used to compare the expression of resulting similarities between the normal tissue and TCGA databases of PCa. Later, top-ranking genes were chosen to demonstrate striking clustering coefficients using the Cytoscape-cytoHubba module, and GEPIA 2 was applied again to ascertain survival plots. Results: Comparing various publicly available datasets, it was found that BLM is a frequent player in all three diseases, whereas comparing publicly available datasets, GWAS datasets, and published sequencing findings, SPFTPC and PPIMB were found to be the most common. With the assistance of GeneMANIA, TMPO and FOXP1 were found as common interacting partners, and they were also seen participating with BLM. Conclusion: A probabilistic machine learning model was achieved to identify key candidates between diabetes, obesity, and PCa. This, we believe, would herald precision scale modeling for easy prognosis.

A prospective longitudinal study to evaluate bone health, implication of FRAX tool and impact on quality of life (FACT-P) in advanced prostate cancer patients.

BACKGROUND: Androgen-deprivation therapy (ADT) as a treatment modality in advanced prostate cancer has deleterious effect on bone mineral density (BMD) and quality of life (QOL). Using FRAX (Fracture Risk Assessment) model, candidates at high risk of fractures can be predicted and appropriate treatment can be initiated at early step to prevent skeletal-related events. Objectives of the present study were to evaluate bone health, implication of FRAX tool in advanced prostate cancer and to see the impact of ADT and Bone-directed therapy (BDT) on FRAX and FACT-P QOL scores. MATERIAL & METHOD: We conducted a prospective longitudinal study of 83 localized and metastatic prostate cancer patients from March 2017 to Dec 2020. FRAX tool using BMD femoral neck (GE-Lunar) was used to compute the probability of 10-year Major osteoporotic fracture (MOF) and hip fracture risk %. Patients who received monthly Zolendronic acid with or without Vitamin-D/calcium supplementation were classified as BDT group. FRAX and FACT-P were measured at baseline and 12 months follow-up and compared between different therapeutic modalities to see the impact on clinical outcomes. RESULTS: Majority of patients had skeletal metastasis (78.3%) and high-grade disease at presentation. Secondary osteoporosis was the most commonly (82.05%) observed clinical risk factor (CRF) followed by smoking (19.23%). Hip fracture risk ≥3% accounted for larger proportion of patients than did MOF risk ≥20% (21.2% and 2.5%, respectively). Statistically significant reduction was observed in both MOF and hip fracture risk in BDT group, while worsening on ADT. ADT duration correlated positively with both MOF and hip fracture risk (R2=0.148, P<0.001 and R2=0.164, P<0.001, respectively). FRAX score accurately predict future fracture events in majority (80%) of high-risk patients. Statistically and clinically significant worsening in PWB, EWB, PCS, FACT-P Total, FACT-P TOI and FAPSI scores were observed in patients on ADT. Statistically and clinically significant improvement was noted in physical well-being in BDT group. However, other QOL domains and FACT-P total scores remained stable. CONCLUSIONS: ADT caused duration depended worsening of FRAX and FACT-P score in these patients while improvements of FRAX were seen on BDT. FRAX tool is advantageous in identifying the patients who require early intervention or therapy to decrease skeletal-related events.

Foreign body (kidney beans) in urinary bladder: An unusual case report.

INTRODUCTION: Foreign body in urinary bladder has always been a topic of interest amongst the urologists and surgeon. Foreign body in lower urinary tract is not an unusual finding. Different types of foreign bodies has been retrieved from the lower urinary tract like for example, electric wire, safety pin, hairclip, intrauterine contraceptive device (IUCD), gauze pieces, battery, leech, hairballs and so on.This article presents an unusual case report of the presence of kidney beans in the bladder, self-inflicted by the patient in the middle of the night for the purpose of sexual gratification or autoerotism. A 25 years old male patient, chef by occupation, presented to the outpatient department with history of insertion of 4 kidney beans 3 days back through his penis during the act of masturbation. The patient had complaints of dysuria, one episode, next morning after the act, which was relieved thereafter. Patient came to us only for the purpose of removal of the kidney beans. Attempt was made to remove the beans by non-invasive method by cystoscopy but as the beans were soaked in urine they got swollen and forceps removal was not possible. Hence, the kidney beans were removed by an invasive method by a suprapubic incision. CONCLUSION: There has been many cases reported in literature about insertion of foreign bodies in bladder but presence of kidney beans in bladder is first of its kind as far as our knowledge is concerned.

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

BACKGROUND: Breast cancer is one of the leading cause of cancer-related deaths in women worldwide and increasing rapidly in developing countries. In the present study, we investigated the potential role and association of HSP70-2 with breast cancer. METHODS: HSP70-2 expression was examined in 154 tumor and 103 adjacent non-cancerous tissue (ANCT) specimens and breast cancer cell lines (MCF7, BT-474, SK-BR-3 and MDA-MB-231) by RT-PCR, quantitative-PCR, immunohistochemistry, Western blotting, flow cytometry and indirect immunofluorescence. Plasmid driven short hairpin RNA approach was employed to validate the role of HSP70-2 in cellular proliferation, senescence, migration, invasion and tumor growth. Further, we studied the effect of HSP70-2 protein ablation on signaling cascades involved in apoptosis, cell cycle and Epithelial-Mesenchymal-Transition both in culture as well as in-vivo human breast xenograft mouse model. RESULTS: HSP70-2 expression was detected in majority of breast cancer patients (83 %) irrespective of various histotypes, stages and grades. HSP70-2 expression was also observed in all breast cancer cells (BT-474, MCF7, MDA-MB-231 and SK-BR-3) used in this study. Depletion of HSP70-2 in MDA-MB-231 and MCF7 cells resulted in a significant reduction in cellular growth, motility, onset of apoptosis, senescence, cell cycle arrest as well as reduction of tumor growth in the xenograft model. At molecular level, down-regulation of HSP70-2 resulted in reduced expression of cyclins, cyclin dependent kinases, anti-apoptotic molecules and mesenchymal markers and enhanced expression of CDK inhibitors, caspases, pro-apoptotic molecules and epithelial markers. CONCLUSIONS: HSP70-2 is over expressed in breast cancer patients and was involved in malignant properties of breast cancer. This suggests HSP70-2 may be potential candidate molecule for development of better breast cancer treatment.

Heat shock protein 70-2 (HSP70-2) is a novel therapeutic target for colorectal cancer and is associated with tumor growth.

BACKGROUND: Colorectal cancer (CRC) is the third leading cause of cancer related deaths worldwide both in men and women. Our recent studies have indicated an association of heat shock protein 70-2 (HSP70-2) with bladder urothelial carcinoma. In the present study, we investigated the association of HSP70-2 with various malignant properties of colorectal cancer cells and clinic-pathological features of CRC in clinical specimens. METHODS: HSP70-2 mRNA and protein was investigated expression by RT-PCR, immunohistochemistry, immunofluorescence, flow cytometry and Western blotting in CRC clinical specimens and COLO205 and HCT116 cell lines. Plasmid-based gene silencing approach was employed to study the association of HSP70-2 with various malignant properties of COLO205 and HCT116 cells in in vitro and with tumor progression in in vivo COLO205 human xenograft mice model. RESULTS: HSP70-2 expression was detected in 78 % of CRC patients irrespective of various stages and grades by RT-PCR and IHC. Our analysis further revealed that HSP70-2 expression was detected in both COLO205 and HCT116 cell lines. Ablation of HSP70-2 expression resulted in reduced cellular growth, colony forming ability, migratory and invasive ability of CRC cells. In addition, ablation of HSP70-2 expression showed significant reduction in tumor growth in COLO205 human xenograft in in vivo mouse model. CONCLUSION: Collectively, our results indicate that HSP70-2 is associated with CRC clinical specimens. In addition, down regulation of HSP70-2 expression reduces cellular proliferation and tumor growth indicating that HSP70-2 may be a potential therapeutic target for CRC treatment.