Association between interleukin-22 genetic polymorphisms and bladder cancer risk

OBJECTIVE:The cytokine interleukin-22 (IL-22), which is produced by T cells and natural killer cells, is associated with tumorigenesis and tumor progression in cancers. However, the role of IL-22 in bladder cancer has not been investigated.MATERIALS AND METHODS:A prospective hospital-based case-control study comprising 210 patients with pathologically proven bladder cancer and 210 age- and gender-matched healthy controls was conducted. The genotypes of 3 common polymorphisms (-429 C/T, +1046 T/A and +1995 A/C) of the IL-22 gene were determined with fluorogenic 5' exonuclease assays.RESULTS:Patients with bladder cancer had a significantly higher frequency of the IL-22 -429 TT genotype [odds ratio (OR)=2.04, 95% confidence interval (CI)=1.19, 3.49; p=0.009] and -429 T allele (OR=1.42, 95% CI=1.08, 1.87; p=0.01) than the healthy controls. These findings were still significant after a Bonferroni correction. When stratifying according to the stage of bladder cancer, we found that patients with superficial bladder cancer had a significantly lower frequency of the IL-22 -429 TT genotype (OR=0.48, 95% CI=0.23, 0.98; p=0.04). When stratifying according to the grade and histological type of bladder cancer, we found no statistical association. The IL-22 +1046 T/A and IL-22 +1995 A/C gene polymorphisms were not associated with the risk of bladder cancer.CONCLUSION:To the authors' knowledge, this is the first report documenting that the IL-22 -429 C/T gene polymorphism is associated with bladder cancer risk. Additional studies are required to confirm this finding

Antisense oligonucleotide targeting Livin induces apoptosis of human bladder cancer cell via a mechanism involving caspase 3

BACKGROUND AND AIM: in recent years, Livin, a new member of IAPs family, is found to be a key molecule in cancers. Researchers consider Livin may become a new target for tumor therapy; however, the role of it in bladder cancer is still unclear. The purpose of this article is to investigate Antisense Oligonucleotide (ASODN) of Livin on treating bladder cancer cell and underlying mechanisms. METHODS: Phosphorathioate modifying was used to synthesize antisense oligonucleotides targeting Livin, followed by transfection into human bladder cancer cell 5637. After transfection, Livin mRNA and protein level, cell proliferation and apoptosis changes, caspase3 level and its effect on human bladder cancer transplantable tumor in nude mice were measured. RESULT: results showed Livin ASODN effectively inhibited Livin expression and tumor cell proliferation, and these effects probably through enhanced caspase3 activity and apoptosis of tumor cells. In nude mice transplantable tumor model, Livin expressions were inhibited meanwhile caspase3 expression was increased. Tumor growth slowed down and apoptosis was enhanced. CONCLUSION: Our data suggest that Livin plays an important role in inhibiting apoptosis of bladder cancer cells. Livin ASODN may promote cell apoptosis, inhibit bladder cancer growth, and become one of the methods of gene therapy for bladder cancer

Impaired Delta Np63 Expression is Associated with Poor Tumor Development in Transitional Cell Carcinoma of the Bladder

The oncogenic isoform of the p63 protein, delta Np63 (ΔNp63), plays an important role in the pathogenesis of many epithelial carcinomas, and emerging evidences suggest that ΔNp63 is a promising drug target. However, the functions of ΔNp63 in transitional cell carcinoma of bladder (TCCB) are poorly defined. In this study, a ΔNp63 shRNA expression vector was transfected into TCCB cell line 5637 and cell cycling, cell proliferation and protein expression were assessed by flow cytometry and 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-dimethyl tetrazolium bromide (MTT) assay, and immunohistochemistry, respectively. The ΔNp63 shRNA expression vector was also injected into 5637 cell xenograft tumors in nude mice, and tumor size was measured, tumor tissue morphology was assessed by immunohistopathology and transmission electron microscopy. In the in vitro study, ΔNp63 shRNA transfection caused successful ΔNp63 gene silencing and resulted in significant arrest of cell cycling and cellular proliferation (p<0.05) as well as cyclin D1 expression. In the nude mouse xenograft model, ΔNp63 shRNA greatly inhibited tumor growth, induced tumor cell apoptosis (p<0.05) and resulted in cyclin D1 downregulation. Our data suggest that ΔNp63 may play an oncogenic role in TCCB progression through promoting cell survival and proliferation. Intratumoral administration of ΔNp63-specific shRNA suppressed tumor ΔNp63 expression and cellular proliferation while promoted tumor cellular apoptosis, and therefore inhibited tumor growth and improved survival of xenograft-bearing mice, which was not accompanied by significant signs of systemic toxicity

Functional significance of the hepaCAM gene in bladder cancer

<p>Abstract</p> <p>Background</p> <p>The hepaCAM gene encodes a new immunoglobulin-like cell adhesion molecule, and its expression is suppressed in a variety of human cancers. Additionally, hepaCAM possesses properties often observed in tumor suppressor genes. However, the expression and biological function of hepaCAM has not been investigated in bladder cancer. Therefore we sought to examine hepaCAM expression and the relationship between its structure and function in human transitional cell carcinoma of bladder (TCCB).</p> <p>Materials and methods</p> <p>HepaCAM expression was evaluated in 28 normal and 34 TCCB bladder specimens and 2 TCCB cell lines using semi-quantitative RT-PCR. The wild-type hepaCAM and the extracellular domain-truncated mutant gene were transfected into the TCCB cell line T24, and the biological properties of both the wild-type gene and the domain-truncated mutant were then assessed.</p> <p>Results</p> <p>HepaCAM expression was down-regulated in 82% (28/34) of TCCB specimens and undetectable in the 2 TCCB cell lines tested. The localization of hepaCAM appeared to be dependent on cell density in T24 cells. In widely spread cells, hepaCAM accumulated on the perinuclear membrane and the cell surface protrusions, whereas in confluent cells, hepaCAM was predominantly localized at the sites of cell-cell contacts on the cell membrane. Functionally, hepaCAM expressed not only increased cell spreading, delayed cell detachment, enhanced wound healing and increased cell invasion; it also inhibited cell growth (P < 0.01). When the extracellular domain was deleted, the localization of hepaCAM was significantly altered, and it lost both its adhesive function and its influence on cell growth.</p> <p>Conclusions</p> <p>HepaCAM is involved in cell adhesion and growth control, and its expression is frequently silenced in TCCB. The extracellular domain of hepaCAM is essential to its physiological and biological functions.</p

Association between interleukin-22 genetic polymorphisms and bladder cancer risk

OBJECTIVE:The cytokine interleukin-22 (IL-22), which is produced by T cells and natural killer cells, is associated with tumorigenesis and tumor progression in cancers. However, the role of IL-22 in bladder cancer has not been investigated.MATERIALS AND METHODS:A prospective hospital-based case-control study comprising 210 patients with pathologically proven bladder cancer and 210 age- and gender-matched healthy controls was conducted. The genotypes of 3 common polymorphisms (-429 C/T, +1046 T/A and +1995 A/C) of the IL-22 gene were determined with fluorogenic 5' exonuclease assays.RESULTS:Patients with bladder cancer had a significantly higher frequency of the IL-22 -429 TT genotype [odds ratio (OR)=2.04, 95% confidence interval (CI)=1.19, 3.49; p=0.009] and -429 T allele (OR=1.42, 95% CI=1.08, 1.87; p=0.01) than the healthy controls. These findings were still significant after a Bonferroni correction. When stratifying according to the stage of bladder cancer, we found that patients with superficial bladder cancer had a significantly lower frequency of the IL-22 -429 TT genotype (OR=0.48, 95% CI=0.23, 0.98; p=0.04). When stratifying according to the grade and histological type of bladder cancer, we found no statistical association. The IL-22 +1046 T/A and IL-22 +1995 A/C gene polymorphisms were not associated with the risk of bladder cancer.CONCLUSION:To the authors' knowledge, this is the first report documenting that the IL-22 -429 C/T gene polymorphism is associated with bladder cancer risk. Additional studies are required to confirm this finding

In vitro and in vivo studies of pirarubicin-loaded SWNT for the treatment of bladder cancer

Intravesical chemotherapy is an important part of the treatment for superficial bladder cancer. However, the response to it is limited and its side effects are extensive. Functional single-walled carbon nanotubes (SWNT) have shown promise for tumor-targeted accumulation and low toxicity. In the present study, we performed in vivo and in vitro investigations to determine whether SWNT-based drug delivery could induce high tumor depression in rat bladder cancer and could decrease the side effects of pirarubicin (tetrahydropyranyl-adriamycin, THP). We modified SWNT with phospholipid-branched polyethylene glycol and constructed an SWNT-THP conjugate via a cleavable ester bond. The cytotoxicity of SWNT-THP against the human bladder cancer cell line BIU-87 was evaluated in vitro. Rat bladder cancer in situ models constructed by N-methyl-N-nitrosourea intravesical installation (1 g/L, 2 mg/rat once every 2 weeks for 8 weeks) were used for in vivo evaluation of the cytotoxicity of SWNT and SWNT-THP. Specific side effects in the THP group including urinary frequency (N = 12), macroscopic hematuria (N = 1), and vomiting (N = 7) were identified; however, no side effects were observed with SWNT-THP treatment. Flow cytometry was used to assess the cytotoxicity in vitro and in vivo. Results showed that SWNT alone did not yield significant tumor depression compared to saline (1.74 ± 0.56 and 1.23 ± 0.42%) in vitro. SWNT-THP exhibited higher tumor depression than THP-saline in vitro (74.35 ± 2.56 and 51.24 ± 1.45%) and in vivo (52.46 ± 2.41 and 96.85 ± 0.85%). The present findings indicate that SWNT delivery of THP for the treatment of bladder cancer leads to minimal side effects without loss of therapeutic efficacy. Therefore, this nanotechnology may play a crucial role in the improvement of intravesical treatment of bladder cancer

Analysis of factors associated with delayed diagnosis and treatment of testicular torsion in 1005 cases from Chongqing city, China: a cross-sectional study

Abstract This study aimed to investigate the clinical and social factors of delayed treatment for testicular torsion (TT) and to explore the risk factors of testicular excision in China. The clinical data of 1005 patients with TT who were admitted to 48 medical institutions in Chongqing city (China) from January 2012 to December 2021 were retrospectively analyzed. It was revealed that the misdiagnosis rates of non-senior (junior and middle) grade doctors and senior doctors were 25.1% and 9.6%, respectively. The proportion of TT patients who received timely treatment (within 6 h after onset of symptoms) was 23.8%. The results of the multivariable logistic regression analysis indicated that absent cremasteric reflex was a protective factor for delayed surgery of more than 6 h from onset of symptoms to surgery. Misdiagnosis, consultation with a non-urologist as the first consultant doctor, absence blood flow in color Doppler ultrasound, negative high-riding testis findings, the presence of fever, and non-manual detorsion were identified as risk factors associated with delayed surgery (more than 6 h from the onset of symptoms) for TT. Furthermore, misdiagnosis, non-urologist first-consultant doctor, absent blood flow in DUS, non-manual detorsion, fever, degree of cord twisting > 180, and the initial diagnosis in tertiary hospitals were risk factors for orchidectomy. Having TT on the right side, and the presence of nausea and vomiting were identified as protective factors for orchidectomy. Technical training in the diagnosis and treatment of TT should be extended to primary hospitals and doctors to significantly improve their accuracy in managing this condition

Relationship between rumination and post-traumatic growth in mobile cabin hospital nurses: The mediating role of psychological resilience

Psychological resilience helps individuals to actively respond to various emergencies, but its mediating role between the rumination and post-traumatic growth (PTG) of nurses remains unknown. Our study aimed to explore the extent to which psychological resilience mediates the association between rumination and PTG among nurses working in mobile cabin hospitals. This cross-sectional survey was conducted on 449 medical team members working in mobile cabin hospitals to support the prevention and control of coronavirus disease 2019 in Shanghai, China in 2022. Pearson correlation analysis was applied to assess the correlation between rumination, psychological resilience, and PTG. Structural equation models were used to examine the mediating role of psychological resilience between rumination and PTG. Our study results showed that deliberate rumination directly promoted psychological resilience and PTG and had positive effects on PTG through the mediating effect of psychological resilience. Invasive rumination had no direct effect on PTG. However, it had a negative effect on PTG through the mediating effect of psychological resilience. Together the results of this study indicate that the mediating effect of psychological resilience was significant in the association of rumination and PTG among mobile cabin hospital nurses, with a higher individual psychological resilience level helping nurses to achieve PTG. Therefore, targeted interventions should be implemented to improve nurses’ psychological resilience and guide their rapid growth