chondroitin-sulfates and Kidney-Neoplasms

Glycosaminoglycans (GAGs) are heterogeneous, linear, highly charged, anionic polysaccharides consisting of repeating disaccharides units. GAGs have some biological significance in cancer progression (invasion and metastasis) and cell signaling. In different cancer types, GAGs undergo specific structural changes. In the present study, in depth investigation of changes in sulfation pattern and composition of GAGs, heparan sulfate (HS)/heparin (HP), chondroitin sulfate (CS)/dermatan sulfate and hyaluronan (HA) in normal renal tissue (NRT) and renal cell carcinoma tissue (RCCT) were evaluated. The statistical evaluation showed that alteration of the HS (HSNRT = 415.1 ± 115.3; HSRCCT = 277.5 ± 134.3), and CS (CSNRT = 35.3 ± 12.3; CSRCCT = 166.7 ± 108.8) amounts (in ng/mg dry tissue) were statistically significant (p < 0.05). Sulfation pattern in NRT and RCCT was evaluated to reveal disaccharide profiles. Statistical analyses showed that RCCT samples contain significantly increased amounts (in units of ng/mg dry tissue) of 4SCS (NRT = 25.7 ± 9.4; RCCT = 117.1 ± 73.9), SECS (NRT = 0.7 ± 0.3; RCCT = 4.7 ± 4.5), 6SCS (NRT = 6.1 ± 2.7; RCCT = 39.4 ± 34.7) and significantly decreased amounts (in units of ng/mg dry tissue) of NS6SHS (RCCT = 28.6 ± 6.5, RCCT = 10.2 ± 8.0), NS2SHS (RCCT = 44.2 ± 13.8; RCCT = 27.2 ± 15.0), NSHS (NRT = 68.4 ± 15.8; RCCT = 50.4 ± 21.2), 2S6SHS (NRT = 1.0 ± 0.4; RCCT = 0.4 ± 0.3), and 6SHS (NRT = 60.6 ± 17.5; RCCT = 24.9 ± 12.3). If these changes in GAGs are proven to be specific and sensitive, they may serve as potential biomarkers in RCC. Our findings are likely to help us to show the direction for further investigations to be able to bring different diagnostic and prognostic approaches in renal tumors.

Topics: Biomarkers, Tumor; Carcinoma, Renal Cell; Chondroitin Sulfates; Dermatan Sulfate; Heparitin Sulfate; Humans; Kidney Neoplasms

A better understanding of the molecular mechanisms of renal cell carcinogenesis could contribute to a decrease in the mortality rate of this disease. The aim of this study was to evaluate the glycosaminoglycans profile and heparanase expression in renal cell carcinoma. The study included 24 patients submitted to nephrectomy with confirmed pathological diagnosis of renal cell carcinoma. The majority of the samples (87.5%) were classified in the initial stage of renal cell carcinoma (clinical stages I and II). Heparanase messenger ribonucleic acid expression was evaluated by quantitative real-time reverse transcription polymerase chain reaction, and sulfated glycosaminoglycans were identified and quantified by agarose gel electrophoresis of renal cell carcinoma samples or non-neoplastic tissues obtained from the same patients (control group). The sulfated glycosaminoglycans and hyaluronic acid were analyzed in urine samples of the patients before and after surgery. The data showed a significant statistical increase in chondroitin sulfate, and a decrease in heparan sulfate and dermatan sulfate present in neoplastic tissues compared with non-neoplastic tissues. Higher heparanase messenger ribonucleic acid expression in the neoplastic tissues was also shown, compared with the non-neoplastic tissues. The urine glycosaminoglycans profile showed no significant difference between renal cell carcinoma and control samples. Extracellular matrix changes observed in the present study clarify that heparanase is possibly involved with heparan sulfate turnover, and that heparanase and the glycosaminoglycans can modulate initial events of renal cell carcinoma development.

Topics: Carcinoma, Renal Cell; Chondroitin Sulfates; Electrophoresis, Agar Gel; Glucuronidase; Glycosaminoglycans; Humans; Hyaluronic Acid; Kidney Neoplasms; Real-Time Polymerase Chain Reaction

Blood coagulation and fibrinolytic variables were measured in a peripheral vein in a study of 21 consecutive patients before and after angio-embolization of renal carcinoma. The first ten patients received conventional heparin, 5000 IU twice daily, and the following eleven a semi-synthetic heparin analogue (SSHA), 50 mg twice daily, for 5 days. The first injection was given 2 hours before embolization and the last injection at least 12 hours before the last blood sampling. Both groups showed increased levels of FPA on day 5-7, indicating that the anticoagulant influence had ceased. F VII levels decreased only in the SSHA group from embolization to day 3, but were increased in both groups on day 5-7. Levels of thrombin-antithrombin complexes (TAT) were significantly increased in the heparin group 2 hours after embolization, indicating that thrombin activity had been formed. The corresponding TAT level in the SSHA group was not significantly increased. The differences could possibly indicate a different mechanism of action on blood coagulation of SSHA as compared with heparin, with involvement of extrinsic pathway and maybe by-passing antithrombin III inhibition.

Topics: Aged; Anticoagulants; Blood Coagulation; Carcinoma, Renal Cell; Chondroitin Sulfates; Embolization, Therapeutic; Female; Heparin; Humans; Kidney Neoplasms; Male; Middle Aged; Renal Circulation

Twenty seven bladder tumors, three ureteral tumors and one renal pelvic tumor were studied by means of light microscopic histochemical methods for demonstration and identification of acid mucopolysaccharides. Alcian blue (pH 1.0), alcian blue (pH 2.5), periodic acid-Schiff (PAS) and aldehyde-fuchusin stainings were performed. These stainings showed that all tumor specimens contained acid mucopolysaccharides. For identifying individual acid mucopolysaccharides, enzyme digestion procedures were performed prior to staining with alcian blue. (streptomyces hyaluronidase, testicular hyaluronidase, chondroitinase ABC, chondroitinase AC, keratanase, heparinase, heparitinase.) According to these experiments, high-grade, and high-stage tumors contained large amounts of sulfated mucopolysaccharides. Squamous cell carcinomas of the bladder contained especially large amounts of chondroitin sulfate AC.

Topics: Aged; Alcian Blue; Carcinoma, Squamous Cell; Chondroitin Sulfates; Female; Glycosaminoglycans; Histocytochemistry; Humans; Kidney Neoplasms; Male; Middle Aged; Ureteral Neoplasms; Urinary Bladder Neoplasms