MacroH2A1 downregulation enhances the stem-like properties of bladder cancer cells by transactivation of Lin28B.

The histone variant, macroH2A1, has an important role in embryonic stem cell differentiation and tumor progression in various types of tumors. However, the regulatory roles of macroH2A1 on bladder cancer progression have not been fully elucidated. Here, we show that macroH2A1 knockdown promotes stem-like properties of bladder cancer cells. The knockdown of macroH2A1 in bladder cancer cells increased tumorigenicity, radioresistance, degeneration of reactive oxygen species, increased sphere formation capability and an increase in the proportion of side populations. We found that macroH2A1 is required for the suppression of Lin28B identified as a novel downstream target of macroH2A1 in bladder cancer. Loss of macroH2A1 expression significantly correlated with the elevated levels of Lin28B expression and subsequently inhibited the mature let-7 microRNA expression. Furthermore, the stable overexpression of Lin28B enhances the several phenotypes, including tumorigenicity and sphere-forming ability, which are induced by macroH2A1 depletion. Importantly, Lin28B expression was regulated by macroH2A1-mediated reciprocal binding of p300 and EZH2/SUV39H1. Our results suggest that Lin28B/let-7 pathway is tightly regulated by macroH2A1 and its cofactors, and have a pivotal role in the bladder tumor progression and the regulation of stem-like characteristics of bladder cancer cells.

Influence of cyclic hydrostatic pressure on fibrocartilaginous metaplasia of achilles tendon fibroblasts.

The goal of this study was to demonstrate whether cyclically imposed hydrostatic pressure, compressive in nature, could induce fibrocartilaginous metaplasia in a purely tendinous cell source in vitro. The effect of short-duration cyclic hydrostatic pressure on tendon fibroblasts (tenocytes) expanded from rat Achilles tendon was studied. Total RNA was isolated either immediately after loading or 24 h later. The mRNA expression of tendon and cartilage specific markers - Collagen types I and II, Sox9, and Aggrecan was quantified by real-time reverse transcription polymerase chain reaction over multiple biological samples (n=6). For immediately isolated RNA samples, there were statistically significant increases in mRNA expression of Aggrecan and Collagen type II, while Collagen type I significantly decreased. Noticeably, for RNA samples isolated 24 h later, there were further increases in mRNA expression of Aggrecan and Collagen type II, whereas Collagen type I increased roughly three-fold relative to the non-loaded control. These findings support the hypothesis that cyclic hydrostatic pressurization can induce fibrocartilaginous metaplasia in tenocytes by upregulation of cartilaginous gene expression. Also, it was demonstrated that changes in mRNA expression as a result of single 2 h pressurization persist even up to 24 h.

Spontaneous acute tumor lysis syndrome with advanced gastric cancer.

Acute tumor lysis syndrome (TLS) occurs frequently in hematologic malignancies such as high-grade lymphomas and acute leukemia, which are rapidly proliferating and chemosensitive tumors. It occurs rarely in solid tumors and has never been reported in gastric adenocarcinoma. Typical biochemical findings of acute tumor lysis syndrome are hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia in patients with a malignancy. Rapid changes of these electrolytes may cause cardiac arrhythmia, seizure, acute renal failure and sudden death. Therefore, as soon as it is detected, it should be taken care of immediately. Until now almost all cases of TLS associated with solid tumor have developed after cytoreductive therapy in chemosensitive tumors. We report here a case of spontaneous acute tumor lysis in a patient of advanced gastric cancer with hepatic metastases and multiple lymphadenopathy. The biochemical finding of TLS improved with the management and tumor burden also showed slight response to the one cycled combination chemotherapy but the patient died of progressive pneumonia.

Expression of bFGF and VEGF in brain astrocytoma.

Neovascularization is an important factor in the prognosis of brain tumor and many angiogenetic factors have been evaluated for prognostic significance. Among them, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are known as potent angiogentic factors and mitogens. We evaluated seven cases of grade II brain astrocytoma. Four, group A, was diagnosed as anaplastic progression at their second operation, and three, group B, did not. Using monoclonal antibodies to bFGF and VEGF in paraffin embedded tissue from first operation, their immunoreactivity and differences between two groups were examined. The growth fractions of these tumor were also measured by Ki-67 monoclonal antibodies (MIB1). Immunostaining for bFGF in tumor cells were observed in both nuclei and cytoplasm, and for VEGF, mainly observed in the cytoplasm. Mean cell count number +/- standard deviation per high power field in each were as follows: 1) for bFGF, 20.08 +/- 6.38 in group A and 0.87 +/- 0.90 in group B (P < 0.01), 2) for VEGF, 43.75 +/- 17.09 in group A, and 0.8 +/- 1.06 in group B (P < 0.05) and 3) for the proliferation index with Ki-67 antibodies, 3.20 +/- 0.81 in group A and 0.77 +/- 1.03 in group B (P < 0.05). This data supports the assertion that angiogenetic factor such as bFGF and VEGF may contribute to progressive change of astrocytoma by tumor angiogenesis.