Common molecular changes in cancer cells are high carbon flux through the glycolytic pathway and overexpression of fatty acid synthase, a key lipogenic enzyme. Since glycerol 3-phosphate dehydrogenase creates a link between carbohydrates and the lipid metabolism, we have investigated the activity of glycerol 3-phosphate dehydrogenase and various lipogenic enzymes in human bladder cancer. The data presented in this paper indicate that glycerol 3-phosphate dehydrogenase activity in human bladder cancer is significantly higher compared to adjacent non-neoplastic tissue, serving as normal control bladder tissue. Increased glycerol 3-phosphate dehydrogenase activity is accompanied by increased enzyme activity, either directly (fatty acid synthase) or indirectly (through ATP-citrate lyase, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and citrate synthase) involved in fatty acid synthesis. Coordinated upregulation of glycerol 3-phosphate dehydrogenase and lipogenic enzymes activities in human bladder cancer suggests that glycerol 3-phosphate dehydrogenase supplies glycerol 3-phosphate for lipid biosynthesis.

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Bladder cancer is a common disease and a significant cause of death worldwide. There is thus great interest in identifying a diagnostic and prognostic biomarker, as well as gaining an understanding of the molecular basis of bladder cancer. Stearoyl-CoA desaturase 1 gene (SCD1) is highly overexpressed in many human cancers. However, the expression of SCD1 has not yet been investigated in patients with bladder cancer. Here, we document that (a) the SCD1 is highly overexpressed in human bladder cancer; (b) high expression of SCD1 is more frequently observed in the late stage of disease and patients with lymph node metastasis; (c) bladder cancer patients with a higher SCD1 mRNA level have a poorer survival rate than those with normal SCD1 expression. Overall, this is the first report to indicate an association between SCD1 mRNA level and clinical indicators of human bladder cancer. Our study has provided evidence supporting the potential role of SCD1 as a biomarker for human bladder cancer prognosis.

This study showed, to our knowledge for the first time, that orlistat exhibits significant antitumor activity against PANC-1 cells. This implies that orlistat analogs with good oral bioavailability may find application in pharmacotherapy of pancreatic cancer.

In the present study we correlate the p53 gene mutations in tumour tissue with urine sediment using a functional assay in yeast, and relate the p53 status to the outcome in a group of patients with transitional cell carcinoma of the bladder. The p53 mutations were found in three of 30 (10%) Ta/T1 tumour tissue samples and in two of 20 (10%) corresponding urine sediments. In the stage T2-T4 tumour p53 mutations were found in tumour tissues and urine sediments in 13 of 31 (42%) and in seven of 18 (39%) samples, respectively. In 80% (8/10) of cases, the p53 mutations found in tumour tissue were re-detected in urine sediment. Median follow-up was at 20 months. Disease recurred in 18 of the 61 patients (30%) with a median time of 5 months. In Ta/T1 tumours the frequency of recurrence was 37% (11/30) compared with 23% (7/31) of T2-T4 tumours. The 3-year overall survival (OS) was 82% (50/61). The p53 status was significantly associated with stage (P = 0.0077, two-sided Fisher's exact test), grade (P < 0.001) and lymph node involvement (P = 0.027). There was an association between the p53 mutations and shorter OS (P = 0.033; log-rank test); however in a multivariate analysis adjusted for stage, grade, lymph node status and age the p53 mutation was not an independent predictor of survival. There was no correlation of the p53 status with decreased disease-free survival (P = 0.8; log-rank test). The data presented indicate that the yeast functional assay is a useful method for p53 gene mutation analysis in tumour tissue and p53 mutation can be re-detected in urine sediment, but further validation of the assay in non-invasive screening for p53 mutations is needed.

Beneficial effects of food restriction as well as elevated circulating adiponectin concentration on the cardiovascular system, lipid metabolism and non-insulin dependent diabetes have been reported. The present article indicates that the reduction in rat body and adipose tissue weight after long-term (1 month) food restriction (either 75% or 50% of ad libitum food intake) was accompanied by the increase in serum adiponectin concentration. The increase in serum adiponectin concentration is the result of the significant increase in white adipose tissue adiponectin gene expression. In contrast to long-term food restriction, short-term (3 days) food restriction (either 75% or 50% of ad libitum food intake) did not influence body and fat mass as well as serum adiponectin concentration and white adipose tissue adiponectin mRNA level. The obtained results suggest that long-term food restriction is necessary to increase in serum adiponectin concentration that could be beneficial, to prevent some disorders associated with low serum adiponectin concentration like obesity and obesity-related diseases.

Background/Aims: This study investigated the gene expression and DNA methylation of selected DNA repair genes (MBD4, TDG, MLH1, MLH3) and DNMT1 in human bladder cancer in the context of pathophysiological and prognostic significance. Methods: To determine the relationship between the gene expression pattern, global methylation and promoter methylation status, we performed real-time PCR to quantify the mRNA of selected genes in 50 samples of bladder cancer and adjacent non-cancerous tissue. The methylation status was analyzed by methylation-specific polymerase chain reaction (MSP) or digestion of genomic DNA with a methylation-sensitive restriction enzyme and PCR with gene-specific primers (MSRE-PCR). The global DNA methylation level was measured using the antibody-based 5-mC detection method. Results: The relative levels of mRNA for MBD4, MLH3, and MLH1 were decreased in 28% (14/50), 34% (17/50) and 36% (18/50) of tumor samples, respectively. The MBD4 mRNA expression was decreased in 46% of non-muscle invasive tumors (Ta/T1) compared with 11% found in muscle invasive tumors (T2-T4) (P<0.003). Analysis of mRNA expression for TDG did not show any significant differences between Ta/T1 and T2-T4 tumors. The frequency of increased DNMT1 mRNA expression was higher in T2-T4 (52%) comparing to Ta/T1 (16%). The overall methylation rates in tumor tissue were 18% for MBD4, 25% for MLH1 and there was no evidence of MLH3 promoter methylation. High grade tumors had significantly lower levels of global DNA methylation (P=0.04). There was a significant association between shorter survival and increased expression of DNMT1 mRNA (P=0.002), decreased expression of MLH1 mRNA (P=0.032) and the presence of MLH1 promoter methylation (P=0.006). Conclusion: This study highlights the importance of DNA repair pathways and provides the first evidence of the role of MBD4 and MLH3 in bladder cancer. In addition, our findings suggest that DNMT1 mRNA and MLH1 mRNA expression, as well as the status of MLH1 promoter methylation, are attractive prognostic markers in this pathology.

Corticosterone — product of 11-β-hydroxysteroid dehydrogenase type I (11βHSD1) stimulates adipocytes differentiation and activates lipogenic enzymes gene expression in white adipose tissue (WAT) of rats. The aim of the study was to examine the effect of chronic food restriction, often practised by obese individuals trying to lose body mass, on: a) 11βHSD1 gene expression, b) expression of genes associated with adipocyte differentiation (PPARg, SREBP-1, adiponectin), and c) expression of genes associated with lipogenesis in WAT of rats. Two-month old rats were divided into a control and a food restricted group obtaining 50% of food consumed by controls for 30 days. mRNA levels of studied genes in perirenal WAT were analysed by real-time PCR. 11βHSD1 and lipogenic enzymes activities were measured by radiometric conversion assay and by spectrophotometric assay respectively. Food restriction caused significant increase of 11βHSD1, PPARg, SREBP1, adiponectin and lipogenic enzymes mRNA levels in perirenal WAT. 11βHSD1 and some lipogenic enzymes activities were also increased by food restriction. The coordinated up-regulation of 11βHSD1, and genes associated with adipocyte differentiation and lipogenesis by food restriction suggests that such nutritional condition shifts WAT metabolism, that would permit this tissue to synthesize and accumulate triacylglycerols immediately after refeeding.