osteoprotegerin and Urinary-Bladder-Neoplasms

Topics: Anorexia Nervosa; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus; Enzyme-Linked Immunosorbent Assay; Female; Glycoproteins; Humans; Kidney Diseases; Male; Multiple Myeloma; Osteitis Deformans; Osteoprotegerin; Prostatic Neoplasms; Reagent Kits, Diagnostic; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Reference Values; Specimen Handling; Urinary Bladder Neoplasms

To investigate the expression of tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and osteoprotegerin (OPG) in bladder urothelial carcinomas (UCs) and assess possible interrelations with other regulators of TRAIL induced apoptosis (p65/NF-κB, p-ERK1/2, p-AKT) and FGFR3, as well as to elucidate their potential involvement in bladder tumourigenesis and determine their potential prognostic utility.. Paraffin embedded transurethral resection tissue from 128 patients with UC was immunostained for TRAIL and OPG as well as for p65/NF-κB, p-ERK1/2, p-AKT and FGFR3.. TRAIL and OPG were coexpressed in 96.6% of cases and positively interrelated. OPG expression was significantly different among histological grades, being higher in low-grade UCs and was inversely correlated with the presence of lymphovascular invasion (LVI). TRAIL also displayed an inverse relationship with histological grade, T-category and LVI. Both OPG and TRAIL expression were positively correlated with FGFR3 expression, the former relationship being marginal. Moreover, increased TRAIL expression was marginally correlated with lower NF-κB/p65 nuclear expression. Increased OPG expression adversely affected survival both in univariate and multivariate analysis.. OPG and TRAIL are frequently expressed and coexpressed in UCs, supporting the involvement of OPG in the resistance to TRAIL-driven apoptosis. Inhibition of NF-κB activation may also play a similar role, although less important. OPG emerged as an independent prognostic marker of adverse significance.

Topics: Aged; Apoptosis; Biomarkers, Tumor; Carcinoma, Transitional Cell; Cystotomy; Female; Greece; Humans; Male; Neoplasm Grading; Neoplasm Invasiveness; Osteoprotegerin; Prognosis; Survival Rate; TNF-Related Apoptosis-Inducing Ligand; Urinary Bladder Neoplasms

Sulforaphane, a well-characterised dietary isothiocyanate, has been demonstrated to be a potent anti-carcinogenic agent in numerous cancer models, including in bladder cancer cells. In the present study, sulforaphane up-regulated the expression of two Nrf2-dependent enzymes, glutathione transferase (GSTA1-1) and thioredoxin reductase (TR-1), and down-regulated cyclooxygenase 2 (COX-2) in human bladder cancer T24 cells. This action of sulforaphane was associated with the p38 MAPK activity. When a specific p38 MAPK inhibitor, SB202190, was used, both sulforaphane-induced up-regulation of GSTA1-1 and TR-1 and down-regulation of COX-2 were eliminated; in contrast, an activator of p38 MAPK, anisomycin, enhanced the effect of sulforaphane on modulation of GST, TR-1 and COX-2 expression. Moreover, it was established that anisomycin increased nuclear translocation of Nrf2, whereas SB202190 abrogated sulforaphane-induced Nrf2 translocation into the nucleus. In summary, these data suggest that p38 MAPK activation can regulate Nrf2-antioxidant response element (ARE)-driven enzymes and COX-2 expression, thereby facilitating the role of sulforaphane in cancer prevention. This study strongly supports the contention that p38 MAPK is a pivotal and efficient target of sulforaphane in the chemoprevention of bladder cancer.

Topics: Anticarcinogenic Agents; Blotting, Western; Cell Line, Tumor; Cyclooxygenase 2; Down-Regulation; Gene Expression; Glutathione Transferase; Humans; Isothiocyanates; NF-E2-Related Factor 2; Osteoprotegerin; p38 Mitogen-Activated Protein Kinases; Protein Transport; Response Elements; Reverse Transcriptase Polymerase Chain Reaction; Sulfoxides; Thiocyanates; Up-Regulation; Urinary Bladder Neoplasms

It is suggested that Scr-index for radiation-induced apoptosis in leukocytes in vitro be determined prior to combined therapy of urinary bladder cancer in order to estimate its efficacy. It was identified by studying leukocytes of peripheral blood from patients in whony white blood cells DNA level decreased after exposure to 2 Gy and 3-hr incubation at 37 degrees C. Values over 1.0 predicted relatively longer relapse-free survival. Scr-index of over 1.20 pointed to an insignificant decrease in leukocyte count during therapy. When it ranged 1.00-0.75, leukocyte count fell by approximately 25%; S(cr)-index below 0.55 indicated grade III blood poisoning.

Topics: Adult; Aged; Antineoplastic Agents; Biomarkers, Tumor; Chemotherapy, Adjuvant; Cystectomy; Disease-Free Survival; Female; Humans; Leukocyte Count; Leukopenia; Male; Mathematical Computing; Middle Aged; Neoplasm Invasiveness; Osteoprotegerin; Prognosis; Radiation-Sensitizing Agents; Radiotherapy, Adjuvant; Survival Analysis; Treatment Outcome; Urinary Bladder Neoplasms

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plays an important role in the process of lymphocyte-mediated cytotoxicity against malignant cells. Osteoprotegerin (OPG) is a soluble decoy receptor for TRAIL, and circulating OPG has been implicated in the protection of cells from TRAIL-mediated apoptosis. Thus, OPG may protect tumor cells from lymphocyte-mediated cytotoxicity and, as a result, contribute to tumor progression. In the current study, the authors investigated this hypothesis in patients with bladder carcinoma.. Serum OPG levels for 185 patients with bladder carcinoma were determined using an enzyme-linked immunosorbent assay. These levels then were assessed for potential correlations with various disease characteristics and outcome measures.. The mean serum OPG concentration in patients with bladder carcinoma was approximately 3 times greater than the mean concentration in healthy individuals, and among patients with bladder carcinoma, higher tumor stage and grade were found to be associated with increased serum OPG levels. Within the subpopulation of patients with superficial bladder carcinoma, after a follow-up period of 5 years, those who had low serum OPG levels tended to have a longer postoperative tumor-free interval compared with those who had high serum OPG levels. Furthermore, among patients with muscle-invasive bladder carcinoma, the 5-year disease-specific survival rate was greater for those who had low serum OPG levels than for those who had high serum OPG levels.. To the authors' knowledge, the current study is the first to demonstrate that serum OPG concentration is correlated with both tumor stage and tumor grade and that elevated serum OPG levels are predictive of early recurrence in patients with bladder carcinoma. These findings suggest that serum OPG concentration may have utility as a prognostic parameter in this setting.

Topics: Adult; Aged; Aged, 80 and over; Apoptosis; Apoptosis Regulatory Proteins; Biomarkers, Tumor; Carcinoma, Transitional Cell; Case-Control Studies; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Glycoproteins; Humans; Lung Neoplasms; Male; Membrane Glycoproteins; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Osteoprotegerin; Postoperative Care; Prognosis; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Survival Rate; TNF-Related Apoptosis-Inducing Ligand; Transfection; Tumor Necrosis Factor-alpha; Urinary Bladder Neoplasms