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Bladder Tissue Microbiome Composition in Patients of Bladder Cancer or Benign Prostatic Hyperplasia and Related Human Beta Defensin Levels.

ABSTRACT: Balance between the microbiome associated with bladder mucosa and human beta defensin (HBD) levels in urine is a dynamic, sensitive and host-specific relationship. HBD1-possessing both antitumor and antibacterial activity-is produced constitutively, while the inducible production of antibacterial HBD2 and HBD3 is affected by bacteria. Elevated levels of HBD2 were shown to cause treatment failure in anticancer immunotherapy. Our aim was to assess the relationship between microbiome composition characteristic of tumor tissue, defensin expression and HBD levels measured in urine. Tissue samples for analyses were removed during transurethral resection from 55 bladder carcinoma and 12 prostatic hyperplasia patients. Microbiome analyses were carried out with 16S rRNS sequencing. Levels of HBD mRNA expression were measured with qPCR from the same samples, and urinary amounts of HBD1, 2 and 3 were detected with ELISA in these patients, in addition to 34 healthy volunteers. Mann-Whitney U test, Wilcoxon rank sum test (alpha diversity) and PERMANOVA analysis (beta diversity) were performed. Defensin-levels expressed in the tumor did not clearly determine the amount of defensin measurable in the urine. The antibacterial and antitumor defensin (HBD1) showed decreased levels in cancer patients, while others (HBD2 and 3) were considerably increased. Abundance of Staphylococcus, Corynebacterium and Oxyphotobacteria genera was significantly higher, the abundance of Faecalibacterium and Bacteroides genera were significantly lower in tumor samples compared to non-tumor samples. Bacteroides, Parabacteroides and Faecalibacterium abundance gradually decreased with the combined increase in HBD2 and HBD3. Higher Corynebacterium and Staphylococcus abundances were measured together with higher HBD2 and HBD3 urinary levels. Among other factors, defensins and microorganisms also affect the development, progression and treatment options for bladder cancer. To enhance the success of immunotherapies and to develop adjuvant antitumor therapies, it is important to gain insight into the interactions between defensins and the tumor-associated microbiome.

SUBMITTER: Mansour B

PROVIDER: S-EPMC9313236 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesOveractive bladder (OAB) symptoms are often encountered in patients after transurethral resection of the prostate (TUR-P) or transurethral incision of the prostate (TUI-P) for benign prostatic obstruction (BPO). Either antimuscarinics or β-3 agonist has been found effective in relieving OAB symptoms. However, urologists usually do not prescribe such medication immediately after TUR-P or TUI-P to avoid an increase in postvoid residual and risk of urinary tract infection. If OAB medication can be used and adverse events (AEs) can be reduced to minimum, patients' quality of life after bladder outlet obstruction surgery could be improved. This study compared the safety and efficacy between solifenacin and mirabegron in men undergoing TUR-P or TUI-P.Materials and methodsThis prospective, randomized trial compared the safety and efficacy of OAB medication on the reduction in Urgency Severity Score (USS), OAB Symptoms Score (OABSS), International Prostate Symptom Score, and urgency urinary incontinence episodes in men with BPO undergoing surgical intervention. All patients could void smoothly after catheter removal and were randomly received daily solifenacin 5 mg, mirabegron 50 mg, or no interventions for 4 weeks. At 2 and 4 weeks postoperatively, participants' OAB symptoms and AEs were evaluated.ResultsA total of 57 men were enrolled in this study with a mean age of 70.8 ± 6.1 years. At 2 weeks postoperatively, USS (1.56 ± 1.72 vs. 2.39 ± 1.72 vs. 2.26 ± 1.73, P < 0.011) and OABSS (5.33 ± 3.65 vs. 7.67 ± 4.19 vs. 8.58 ± 4.31, P < 0.000) were significantly reduced in patients taking solifenacin, mirabegron, or control, respectively. Two patients in the solifenacin group developed urinary retention. However, the changes of variables at 4 weeks postoperatively were insignificant among the three groups.ConclusionSolifenacin and mirabegron are two different drug classes both equally effective in treating immediate OAB symptoms after TUR-P or TUI-P. However, OAB symptoms could be relieved at 4 weeks without any medication. Considering AEs, β-3 agonist has a more favorable safety profile than antimuscarinics.

Project description:BackgroundMale lower urinary tract symptoms (LUTS) occur in more than half of men above 50 years of age. LUTS were traditionally attributed to benign prostatic hyperplasia (BPH) and therefore the clinical terminology often uses LUTS and BPH interchangeably. More recently, LUTS were also linked to fibrogenic and inflammatory processes. We tested whether osteopontin (OPN), a proinflammatory and profibrotic molecule, is increased in symptomatic BPH. We also tested whether prostate epithelial and stromal cells secrete OPN in response to proinflammatory stimuli and identified downstream targets of OPN in prostate stromal cells.MethodsImmunohistochemistry was performed on prostate sections obtained from the transition zone of patients who underwent surgery (Holmium laser enucleation of the prostate) to relieve LUTS (surgical BPH, S-BPH) or patients who underwent radical prostatectomy to remove low-grade prostate cancer (incidental BPH, I-BPH). Images of stained tissue sections were captured with a Nuance Multispectral Imaging System and histoscore, as a measure of OPN staining intensity, was determined with inForm software. OPN protein abundance was determined by Western blot analysis. The ability of prostate cells to secrete osteopontin in response to IL-1β and TGF-β1 was determined in stromal (BHPrS-1) and epithelial (NHPrE-1 and BHPrE-1) cells by enzyme-linked immunosorbent assay. Quantitative polymerase chain reaction was used to measure gene expression changes in these cells in response to OPN.ResultsOPN immunostaining and protein levels were more abundant in S-BPH than I-BPH. Staining was distributed across all cell types with the highest levels in epithelial cells. Multiple OPN protein variants were identified in immortalized prostate stromal and epithelial cells. TGF-β1 stimulated OPN secretion by NHPrE-1 cells and both IL-1β and TGF-β1 stimulated OPN secretion by BHPrS-1 cells. Interestingly, recombinant OPN increased the mRNA expression of CXCL1, CXCL2, CXCL8, PTGS2, and IL6 in BHPrS-1, but not in epithelial cell lines.ConclusionsOPN is more abundant in prostates of men with S-BPH compared to men with I-BPH. OPN secretion is stimulated by proinflammatory cytokines, and OPN acts directly on stromal cells to drive the synthesis of proinflammatory mRNAs. Pharmacological manipulation of prostatic OPN may have the potential to reduce LUTS by inhibiting both inflammatory and fibrotic pathways.

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Bladder Tissue Microbiome Composition in Patients of Bladder Cancer or Benign Prostatic Hyperplasia and Related Human Beta Defensin Levels.

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