Parathyroid hormone-related protein as a potential prostate cancer biomarker: Promoting prostate cancer progression through upregulation of c-Met expression.

Parathyroid hormone-related protein (PTHrP) plays a significant role in various tumor types, including prostate cancer. However, its specific role and underlying mechanisms in prostate cancer remain unclear. This study investigates the role of PTHrP and its interaction with the c-Met in prostate cancer. PTHrP was overexpressed and knocked down in prostate cancer cell lines to determine its effect on cell functions. Xenograft tumor models were employed to assess the impact of PTHrP overexpression on tumor growth. To delve into the interaction between PTHrP and c-Met, rescue experiments were conducted. Clinical data and tissue samples from prostate cancer patients were gathered and analyzed for PTHrP and c-Met expression. PTHrP overexpression in prostate cancer cells upregulates c-Met expression and augments cell functions. In contrast, PTHrP-knockdown diminishes c-Met expression and inhibits cell functions. In vivo experiments further demonstrated that PTHrP overexpression promoted tumor growth in xenograft models.Moreover, modulating c-Met expression in rescue experiments led to concurrent alterations in prostate cancer cell functions. Immunohistochemical analysis of clinical samples displayed a significant positive correlation between PTHrP and c-Met expression. Additionally, PTHrP expression correlated with clinical parameters like prostate-specific antigen (PSA) levels, tumor stage, lymph node involvement, distant metastasis, and Gleason score. PTHrP plays a crucial role in prostate cancer progression by upregulating c-Met expression. These insights point to PTHrP as a promising potential biomarker for prostate cancer.

Systematic review and meta-analysis of completely retroperitoneoscopic nephroureterectomy versus traditional retroperitoneoscopic nephroureterectomy in upper tract urothelial carcinoma.

BACKGROUND: This systematic review and meta-analysis aim to evaluate the efficacy and safety of completely retroperitoneoscopic nephroureterectomy (CRNU) for the treatment of upper urinary tract urothelial carcinoma (UTUC). METHODS: A systematic review of PubMed and Web of Science databases was conducted to identify trials comparing the outcomes of CRNU and other surgical procedures. A total of 6 case-control studies were selected for analysis. The efficacy and safety of CRNU were evaluated using mean difference or hazard ratio (HR) with 95% CIs, employing continuous or dichotomous method with a random or fixed-effect model. Meta-analysis was performed using STATA 11.0 software. RESULTS: The meta-analysis indicated that CRNU in subjects with UTUC was significantly associated with a shorter operation time (standardized mean difference, -1.36; 95% CI, -1.61 to -1.11, P < .001) and lower blood loss (standardized mean difference, -0.54; 95% CI, -0.77 to -0.31, P < .001) when compared to traditionally retroperitoneoscopic nephroureterectomy (TRNU). No significant difference was observed in the occurrence of grade I & II complications (HR, 1.04; 95% CI, 0.49-2.2, P = .915) and total complications (HR, 0.69; 95% CI, 0.38-1.27, P = .238) between CRNU and TRNU. CONCLUSION: The findings suggest that CRNU is an advanced surgical technique that is safe and effective for the treatment of UTUC. We recommend that CRNU be further employed for patients with UTUC. Further randomized, multicenter trials are needed to validate these results, given the limitations of this study.

Identify AGAP2 as prognostic biomarker in clear cell renal cell carcinoma based on bioinformatics and IHC staining.

Background: Arf GTPase-activating proteins are aberrantly expressed in a variety of tumors, but their role in clear cell renal cell carcinoma (ccRCC) was unclear. Exploring the biological role of Arf GAP with GTP binding protein like domain, Ankyrin repeat and PH domain 2 (AGAP2) in ccRCC could improve our understanding on the aggressiveness and immune relevance of ccRCC. Methods: The expression of AGAP2 was analyzed based on the Cancer Genome Atlas (TCGA) database and verified in ccRCC samples using immunohistochemistry. The association between AGAP2 and clinical cancer stages was explored by TCGA dataset and UALCAN. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to analyze the biological functions of AGAP2-related genes. Moreover, the relationship between AGAP2 and immune cell infiltration was investigated with TIME and TCGA dataset. Results: Compared to normal tissues, AGAP2 was upregulated in ccRCC tissues. Higher expression of AGAP2 was associated with clinical cancer stages, TNM stages, pathologic stages, and status. Prognostic analysis on AGAP2 showed that AGAP2 overexpression was associated with KIRC overall survival (OS) reduction (P = 0.019). However, higher expression of AGAP2 may improve the OS of CESC (P = 0.002), THYM (P = 0.006) and UCEC (P = 0.049). GO and KEGG analysis showed that AGAP2-related genes was related to T cell activation, immune activity and PD-L1 expression and PD-1 checkpoint pathway. Furthermore, our study showed that AGAP2 were significantly associated with T cells, Cytotoxic cells, Treg, Th1 cells, CD8 T cells, T helper cells. And AGAP2 expression level affected the abundance of immune cells infiltration. The infiltrating level of immune cells was different between the AGAP2 high-expression and low-expression groups. Conclusion: The expression of AGAP2 in ccRCC was higher than that in normal kidney tissues. It was significantly associated with clinical stage, poor prognosis, and immune cell infiltration. Therefore, AGAP2 may become an important component for ccRCC patients who receive precision cancer therapy and may be a promising prognostic biomarker.

Association between folic acid, homocysteine, vitamin B12 and erectile dysfunction-A cross-sectional study.

To evaluate the relationship between serum levels of folic acid (FA), homocysteine (HCY), vitamin B12 (B12) and erectile dysfunction (ED) and to explore their internal relationships. The study included 134 ED patients and 50 healthy controls. ED was assessed using IIEF-5 scores. ED group had lower median FA (6.08 versus 10.21; p < .001) and B12 (256.0 versus 337.5; p < .001) levels, and higher median HCY (11.4 versus 7.95; p < .001) levels, and these differences seemed to be more pronounced in the younger participants (age < 35 yr). FA decreased with the severity of ED (7.52 versus 6.15 versus 5.49 versus 3.97; p < .001), while HCY increased (10.35 versus 11.8 versus 12.9 versus 15; p < .001). Smoking and shift work were associated with lower FA levels. Multivariate analysis showed that serum FA and HCY revealed significant relation with ED. ROC analysis showed that FA ≤ 8.84 and HCY ≥ 10.35 were the best cut-off values for ED diagnosis. Both FA (r = -0.703, p < .001) and B12 (r = -0.576, p < .001) were negatively correlated with HCY. In conclusion, low FA levels and high HCY levels might be independent risk factors for ED. Low serum FA and B12 levels might co-cause high HCY levels and lead to ED.

A pan-cancer study of PD-1 and CTLA-4 as therapeutic targets.

BACKGROUND: Immunotherapy is a new and powerful weapon against tumors, represented by inhibitors of programmed death-1 (PD-1) and cytotoxic T lymphocyte-associated protein-4 (CTLA-4). This study aimed to determine the similarities and differences between PD-1 and CTLA-4 in 33 cancers in The Cancer Genome Atlas (TCGA) and the impact of subtypes of the immune environment on tumor production and treatment. METHODS: From the Xena browser, we downloaded TNM stage, immune subtypes, and tumor microenvironment scores for 33 tumors from TCGA. Expression of CTLA-4 and PD-1 in normal and tumor samples were compared for various tumors with normal tissue sample sizes greater than five. The relationship between expression and overall survival was investigated using one-way Cox analysis. The immune scores of 33 tumors were assessed using ESTIMATE prediction software to predict the degree of immune cell infiltration across tumors and calculate the correlation between PD-1 and CTLA-4 expression with the tumor microenvironment and tumor stem cells. We also examined the correlation between genes and drug sensitivity. RESULTS: PD-1 and CTLA-4 were highly expressed in breast invasive carcinoma (BRCA), cholangiocarcinoma (CHOL), esophageal carcinoma (ESCA), and kidney renal clear cell carcinoma (KIRC) (P<0.05), highly correlated with immune subtypes C2 (IFN-γ-dominant) and C6 (TGF-ß-dominant), and positively correlated with tumor microenvironmental immune scores (P<0.05). In renal clear cell carcinoma, PD-1 and CTLA-4 expression was positively correlated with clinical stage and microenvironmental score (r>0.7, P<0.05). CONCLUSIONS: The finding that PD1 and CTLA-4 are associated with the prognosis of most tumour patients and are closely related to the tumour microenvironment is of great value and provides a research direction for the screening of populations benefiting from immunotherapy.

Effect of Bariatric Surgery on Male Sexual Function: A Meta-Analysis and Systematic Review.

INTRODUCTION: Obesity is a worldwide public health issue with serious psychological and social impacts. Erectile dysfunction is also a common clinical condition, and obesity is one of its main risk factors. OBJECTIVE: The objective of this study was to systematically evaluate the effect of bariatric surgery on male sexual function. METHODS: A systematical research was carried out in Medline via PubMed, EMBASE, Cochrane Library, and Web of Science up to March 16, 2019, to identify published articles related to bariatric surgery and male sexual function in men. Two reviewers screened literature, extracted data, and assessed the quality of included studies. I2 index was applied to estimate the heterogeneity. All analyses were done using RevMan5.3 and Stata14. RESULTS: A total of 12 studies involving 420 participants were included. Analysis showed that bariatric surgery significantly reduced body mass index in morbidly obese patients (mean difference [MD] = -13.73; 95% CI -17.23 to -10.22; P < .00001). From 10 studies that reported the International Index of Erectile Function (IIEF) score, bariatric surgery led to a significant increase in IIEF-total score (MD = 8.2; 95% CI = 5.52-10.88; P < .00001), and erectile function score (MD = 3.76; 95% CI = 2.34-5.19; P < .00001), sexual desire (MD = 0.93; 95% CI = 0.55-1.32; P < .00001), sexual intercourse satisfaction (MD = 1.73; 95% CI = 0.43-3.03; P < .01), and total satisfaction (MD = 1.28; 95% CI = 0.56-2.00; P = .0005) were also significantly improved. However, bariatric surgery did not affect orgasm function (MD = 0.26; 95% CI = -0.15 to 0.68; P = .21). Three studies that reported the IIEF-5 score also showed a significant improvement of erectile function (MD = 5.45; 95% CI = 3.38-7.52; P < .00001). CONCLUSIONS: Bariatric surgery could improve the erectile function, sexual desire, sexual intercourse satisfaction, and total satisfaction in morbidly obese men. Due to limited data on body mass index and hormone levels, our meta-analysis had some limitations. More clinical studies are needed to further explore the relationship between bariatric surgery and male sexual function. Xu J, Wu Q, Zhang Y, et al. Effect of Bariatric Surgery on Male Sexual Function: A Meta-Analysis and Systematic Review. Sex Med 2019;7:270-281.

Influence of curcumin on HOTAIR-mediated migration of human renal cell carcinoma cells.

BACKGROUND: This study investigated the influence of curcumin on HOX transcript antisense RNA (HOTAIR)- mediated migration of cultured renal cell carcinoma (RCC) cells. MATERIALS AND METHODS: Five RCC cell lines (769-P, 769-P-vector, 769-P-HOTAIR, 786-0, and Kert-3 ) were maintained in vitro. The expression of HOTAIR mRNA was determined by quantitative real-time PCR and cell migration was measured by transwell migration assay. The effects of different concentrations of curcumin (0 to 80 µmol/L) on cell proliferation was determined by the CCK-8 assay and influence of non-toxic levels (0 to 10 µM) on the migration of RCC cells was also determined. RESULTS: Comparison of the 5 cell lines indicated a correlation between HOTAIR mRNA expression and cell migration. In particular, the migration of 769-P-HOTAIR cells was significantly higher than that of 769-P-vector cells. Curcumin at 2.5-10 µM had no evident toxicity against RCC cells, but inhibited cell migration in a concentration-dependent manner. CONCLUSIONS: HOTAIR expression is correlated with the migration of RCC cells, and HOTAIR may be involved in the curcumin-induced inhibition of RCC metastasis.

Chemomodulatory efficacy of lycopene on antioxidant enzymes and carcinogen-induced cutaneum carcinoma in mice.

Oxidative stress has been implicated in various pathological processes, including skin tumourigenesis. Cutaneum carcinoma is commonly responsible for considerable morbidity and mortality, and treatments have not progressed substantially in recent years. Alternative strategies, such as chemoprevention, are being considered. In this study, we investigated the chemomodulatory potential of lycopene against 9,10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative stress and skin carcinogenesis in female ICR mice. Pretreatment with lycopene at various doses significantly delayed tumour formation and growth. These treatments markedly reduced the tumour incidence and tumour volume. Moreover, lycopene inhibited the formation of reactive oxygen species and malondialdehyde, prevented the loss of glutathione, and affected the activities of a battery of oxidant enzymes in the skin of mice. Furthermore, mice that were administered lycopene exhibited higher levels of translocation of nuclear-factor-erythroid-2-related factor 2 into the nucleus compared with the vehicle-treated and model mice. Collectively, these results indicated that lycopene exerts a protective effect against DMBA/TPA-induced cutaneum carcinoma through antioxidant defence.

PKM2 regulates hepatocellular carcinoma cell epithelial-mesenchymal transition and migration upon EGFR activation.

Pyruvate kinase isozyme type M2(PKM2) was first found in hepatocellular carcinoma(HCC), and its expression has been thought to correlate with prognosis. A large number of studies have demonstrated that epithelial-mesenchymal transition (EMT) is a crucial event in hepatocellular carcinoma (HCC) and associated metastasis, resulting in enhanced malignancy of HCC. However, the roles of PKM2 in HCC EMT and metastasis remain largely unknown. The present study aimed to determine the effects of PKM2 in EGF-induced HCC EMT and elucidate the molecular mechanisms in vitro. Our results showed that EGF promoted EMT in HCC cell lines as evidenced by altered morphology, expression of EMT-associated markers, and enhanced invasion capacity. Furthermore, the present study also revealed that nuclear translocation of PKM2, which is regulated by ERK pathway, regulated ß-catenin-TCF/LEF-1 transcriptional activity and associated EMT in HCC cell lines. These discoveries provide evidence of novel roles of PKM2 in the progression of HCC and potential therapeutic target for advanced cases.

Target expression of Staphylococcus enterotoxin A from an oncolytic adenovirus suppresses mouse bladder tumor growth and recruits CD3+ T cell.

We recently engineered an oncolytic adenovirus (PPE3-SEA) that expresses the superantigen, Staphylococcus enterotoxin A (SEA), and that has enhanced tumor specificity because the telomerase reverse transcriptase and hypoxia-inducible factor promoters regulate expression of E1A and E1B genes, respectively. Here, we evaluated the PPE3-SEA adenovirus anti-tumor activity against MB49 mouse bladder cancer cell proliferation in vitro and in vivo. PPE3-SEA infection of murine MB49 cells in vitro induced cytopathic effects, and significant expression of SEA mRNA and protein, as measured by RT-PCR and western blot, respectively. Subcutaneous MB29 bladder tumors were established in syngeneic C57BL/6 mice. After 10 days, tumors were injected with either oncolytic virus or PBS. Tumor dimensions were measured on days 1, 3, 5, 7, 9, and 11 post-treatment and tumor volumes were calculated. One of eight PPE3-SEA-treated mice had no tumor by day 9. PPE3-SEA treated group had significantly lower mean tumor volume beginning on day 5 post-treatment (p < 0.01), more fibrous tissue in the tumor, and increased presence of infiltrating CD3+ T cells than those of the control group. Gross appearance and histologic sections from the livers and kidneys of the PPE3-SEA-treated group were similar to those of the control group. In conclusion, oncolytic adenoviruses can provide a novel delivery vehicle for SEA to tumor sites, and PPE3-SEA warrants further study as a potential anti-tumor agent for bladder cancer.

The transurethral seminal vesiculoscopy in the diagnosis and treatment of the seminal vesicle disease.

To develop a transurethral endoscopy technique of the transurethral seminal vesiculoscopy to examine and treat seminal vesicle disease. A total of 61 patients with seminal vesicle disease were diagnosed and treated with the transurethral seminal vesiculoscopy through the distal seminal tracts and vesicles. 58 cases were successfully treated using transurethral seminal vesiculoscopy via the seminal vesicles. The operation took 25 ~ 85 min, with an average of (35.6) mins. In this group, seven cases were diagnosed as ejaculatory orifice cyst, 14 cases had blood clots in the seminal vesicles, and nine patients had stones in the seminal vesicles. All patients were treated properly. Follow-up occurred at 3 months, with two cases showing post-operative discomfort in perineal region. One patient had recurrence with seminal vesiculitis, which improved with treatment. Four infertile patients had a significant increase in sperm count and ejaculation volume and two of these patients were able to naturally inseminate within seven to 18 months post-surgery. This approach enables a new endoscopic technique with the transurethral seminal vesiculoscopy to diagnose and treat seminal vesicle disease through the normal anatomic pathway which can be easily performed with few post-operative complications.