3-Bromopyruvate (3BP) is a new, promising anticancer alkylating agent with several notable functions. In addition to inhibiting key glycolysis enzymes including hexokinase II and lactate dehydrogenase (LDH), 3BP also selectively inhibits mitochondrial oxidative phosphorylation, angiogenesis, and energy production in cancer cells. Moreover, 3BP induces hydrogen peroxide generation in cancer cells (oxidative stress effect) and competes with the LDH substrates pyruvate and lactate. There is only one published human clinical study showing that 3BP was effective in treating fibrolamellar hepatocellular carcinoma. LDH is a good measure for tumor evaluation and predicts the outcome of treatment better than the presence of a residual tumor mass. According to the Warburg effect, LDH is responsible for lactate synthesis, which facilitates cancer cell survival, progression, aggressiveness, metastasis, and angiogenesis. Lactate produced through LDH activity fuels aerobic cell populations inside tumors via metabolic symbiosis. In melanoma, the most deadly skin cancer, 3BP induced necrotic cell death in sensitive cells, whereas high glutathione (GSH) content made other melanoma cells resistant to 3BP. Concurrent use of a GSH depletor with 3BP killed resistant melanoma cells. Survival of melanoma patients was inversely associated with high serum LDH levels, which was reported to be highly predictive of melanoma treatment in randomized clinical trials. Here, we report a 28-year-old man presented with stage IV metastatic melanoma affecting the back, left pleura, and lung. The disease caused total destruction of the left lung and a high serum LDH level (4,283 U/L). After ethics committee approval and written patient consent, the patient received 3BP intravenous infusions (1-2.2 mg/kg), but the anticancer effect was minimal as indicated by a high serum LDH level. This may have been due to high tumor GSH content. On combining oral paracetamol, which depletes tumor GSH, with 3BP treatment, serum LDH level dropped maximally. Although a slow intravenous infusion of 3BP appeared to have minimal cytotoxicity, its anticancer efficacy via this delivery method was low. This was possibly due to high tumor GSH content, which was increased after concurrent use of the GSH depletor paracetamol. If the anticancer effectiveness of 3BP is less than expected, the combination with paracetamol may be needed to sensitize cancer cells to 3BP-induced effects.

Loss of erythropoietin-producing hepatocyte (Eph) B6 gene expression is associated with poor prognosis in neuroblastoma, melanoma and other tumors. The present study evaluated the expression of EphB6 receptor tyrosine kinase in normal and prostate cancer tissue using immunohistochemistry. The association between EphB6 expression, clinicopathological findings, proliferating-cell nuclear antigen (PCNA; another prognostic marker) and progression of prostate cancer was analyzed. Tissue microarray samples of normal prostatic tissue and prostate cancer tissue from 46 patients treated with radical prostatectomy for prostate cancer were included in this study. Polyclonal anti-EphB6 and monoclonal anti-PCNA antibodies were used to assess EphB6 and PCNA expression by immunohistochemistry. EphB6 was expressed in normal and prostate cancer tissue; however, its expression was significantly reduced in prostate cancer tissue compared with normal prostatic tissue (P<0.0001), in high volume (≥4 cm3) cancer compared with low volume (<4 cm3; P=0.015), and in pT3 stage compared with pT2 stage of the disease (P=0.0007). No correlation was observed between the expression of EphB6 and PCNA. Short biochemical progression-free survival was associated with low EphB6 protein expression (P=0.157). This study revealed that EphB6 may have a tumor suppressor effect in prostate cancer, at least during early stages of this disease. This provides new insight into the potential utility of EphB6 receptor as a diagnostic/prognostic marker for prostate cancer.

Many animal studies have reported an association between obesity and reduced iron storage. Systemic chronic inflammation induced by obesity and higher hepcidin levels has been suggested as a reason for the iron deficiency that occurs with obesity. Hepcidin is a master regulator of systemic iron homeostasis. Hepcidin is a peptide hormone, produced mainly from the liver. It inhibits intestinal iron absorption. The hepatic production of hepcidin is up-regulated by pro-inflammatory cytokines. An exercise is an effective approach for controlling obesity. Several studies showed that exercise reduced body weight. So this study hypothesized that regular exercises may be used as an adjuvant line in treating iron deficiency associated with obesity via reducing serum hepcidin. Materials and methods: 75 young male albino rats were categorized into 5 groups. Obesity was induced by high-fat diet (HFD) for 3 months in Group II, III, IV, and V. After 12 weeks, Rats of GIII and GV were injected once every 2 days with iron-III poly-maltose 50 ml/kg for 2 weeks. treadmill regular exercise was performed for 8 weeks for rats of GIV and GV. Measurement of body weight was done after 3 months of HFD and at the end of the experiment. Biochemical analysis was done for serum iron and serum hepcidin. Results: Measurement of body weight showed that exercise has a decreasing effect on body weight in obese rats. Exercise decreased serum hepcidin levels in obese rats and increased serum iron. Conclusion: Exercise decreases serum hepcidin level also improves the serum iron level in obese rats.Exercise, hepcidin, obesity, serum iron.