ZFTA::RELA fusion in a distinct liposarcoma morphologically overlapping with chondroid lipoma.

Chondroid lipoma is a rare benign adipose tumor characterized by a recurrent ZFTA::MRTFB fusion. Herein, we report an unusual liposarcoma that partly exhibited overlapping features with those of chondroid lipoma and harbored a ZFTA::RELA fusion. A 59-year-old man presented with a shoulder mass that had existed for approximately 8 years and with increasing pain due to a pelvic mass. The 5.8-cm resected shoulder tumor partly consisted of nests and strands of variably lipogenic epithelioid cells within a hyalinized or focally chondromyxoid stroma, indistinguishable from chondroid lipoma. The histological pattern gradually transitioned to highly cellular, stroma-poor, diffuse sheets of cells with greater nuclear atypia and mitotic activity. Vascular invasion and necrosis were present. The metastatic pelvic tumor revealed a similar histology. Despite multimodal treatment, the patient developed multiple bone metastases and succumbed to the disease 14 months after presentation. Targeted RNA sequencing identified an in-frame ZFTA (exon 3)::RELA (exon 2) fusion, which was confirmed by reverse transcription-polymerase chain reaction, Sanger sequencing, and break-apart fluorescent in situ hybridization assays. The tumor showed a different histology from that of ependymoma, no brain involvement, and no match with any sarcoma types or ZFTA::RELA-positive ependymomas according to DNA methylation analysis. p65 and L1CAM were diffusely expressed, and a CDKN2A/B deletion was present. This is the first report of an extra-central nervous system tumor with a ZFTA::RELA fusion. The tumor partly displayed an overlapping histology with that of chondroid lipoma, suggesting that it may represent a hitherto undescribed malignant chondroid lipoma with an alternative ZFTA fusion.

OsDRE2 contributes to chitin-triggered response through its interaction with OsRLCK185.

The rice receptor-like cytoplasmic kinase 185 (OsRLCK185) interacts with the chitin receptor complex OsCERK1/CEBiP and positively regulates chitin-induced immune responses including MAP kinase activation, ROS production and defense gene expression. To elucidate the regulatory mechanisms of OsRLCK185-mediated immunity, we searched for interactors of OsRLCK185. OsDRE2a, rice homologs of the yeast Dre2 protein, were identified as novel interactors of OsRLCK185. OsDRE2a interacted with OsRLCK185 at plasma membrane. The conserved cysteine residues in CIAPIN1 domain of OsDRE2a were essential for tight interaction of OsRLCK185. OsDRE2a was phosphorylated by OsRLCK185. The expression of OsDRE2a and OsDRE2b was induced after chitin treatment. Reduction of OsDRE2a and OsDRE2b mRNA levels by RNA interference resulted in the decreased chitin-induced ROS production. Thus, it is likely that OsDRE2 regulates OsRLCK185-mediated immune responses.

Basic study on active changes in biological function of mouse liver graft in cold storage after low-dose x-irradiation.

We previously reported that low-dose X-irradiation alleviates ischemia-reperfusion injury such as mouse paw edema. In this study, we examined active changes in the biological function of mouse liver grafts in cold storage after low-dose X-irradiation. Mouse livers were sham-irradiated or were irradiated with 0.25, 0.5, 1.0, or 5.0 Gy of X-ray and stored for 4, 8, 24, or 48 h in preservation or saline solution. The results show that storage for 24 h in saline solution after 0.5 Gy irradiation significantly increased the activity of superoxide dismutase (SOD) and catalase. Following storage for 4, 8, or 48 h in preservation solution, lipid peroxide levels of the 0.5 Gy irradiated group were significantly lower than those of the sham irradiated group. Following storage for 24 h in preservation solution, the activity of SOD and catalase of the 1.0 Gy irradiated group were significantly higher than those of the sham irradiated group. Hepatocytes stored in saline solution were vacuolated. However, no vacuole formation was observed in hepatocytes stored in preservation solution. These findings suggest that low-dose irradiation significantly activates antioxidative functions of liver grafts. Moreover, the dose at which enhancement of antioxidative function occurs in livers stored in preservation solution, which contains glutathione, is significantly higher than that in saline solution.

No Different Sensitivity in Terms of Whole-Body Irradiation between Normal and Acatalasemic Mice.

To elucidate the radiosensitivity of an acatalasemic mouse, we examined the time and dose-dependency in the survival rates, the lymphocytes and the intestinal epithelial cells, and the antioxidant function after 3.0 to 12.0 Gy whole body irradiation. Results showed that no significant differences between acatalasemic mice and normal mice were observed in the survival rates and the histological changes in spleens and small intestine after each irradiation. The catalase activities in livers and spleens of acatalasemic mice were significantly lower than those of normal mice and the glutathione peroxidase activity in livers of acatalasemic mice was significantly higher than that of normal mice. At 10 days after 6.0 Gy irradiation, the catalase activities in livers of acatalasemic and normal mice and that in spleens of normal mice significantly decreased compared with no-irradiation control, and there were no differences between those catalase activities. The total glutathione content in acatalasemic mice was significantly higher than that in normal mice at 10 days after 6.0 Gy irradiation. These findings suggested that the radiosensitivity of acatalasemic mice in terms of whole body irradiation doesn't significantly differ from that of normal mice, probably due to compensated sufficient contents of glutathione peroxidase and total glutathione in acatalasemic mice.

Basic study on biochemical mechanism of thoron and thermal therapy.

Exposure to water in hot springs containing thoron is thought to exercise beneficial effects on hypertension and diabetes mellitus. To put to a test this hypothesis we examined the time dependent changes in the levels of lipid peroxide, vasoactive- and diabetes associated substances in human blood in order to throw further light on the possible beneficial influence of thoron and thermal therapy on the mechanism of hypertension and diabetes mellitus. Every 2 days, nasal inhalation of vapor containing thoron was performed for 40 min. Blood samples were collected after each treatment at 1, 2, and 3 weeks after the first treatment. Results show that the treatment decreased the lipid peroxide levels. The finding suggests that the treatment contributes to the prevention of peroxidation reaction related to hypertension and diabetes mellitus. Moreover, the changes in vasoactive-associated substances indicate an increase in tissue perfusion, suggesting that the treatment plays a role in alleviating hypertension. The treatment decreased the total ketone body levels and the finding suggests that the treatment contributes to the prevention of diabetes mellitus related to the insulin deficiency.

Detection of in vivo genotoxicity of endogenously formed N-nitroso compounds and suppression by ascorbic acid, teas and fruit juices.

The genotoxicity of endogenously formed N-nitrosamines from secondary amines and sodium nitrite (NaNO(2)) was evaluated in multiple organs of mice, using comet assay. Groups of four male mice were orally given dimethylamine, proline, and morpholine simultaneously with NaNO(2). The stomach, colon, liver, kidney, urinary bladder, lung, brain, and bone marrow were sampled 3 and 24 h after these compounds had been ingested. Although secondary amines and the NaNO(2) tested did not yield DNA damage in any of the organs tested, DNA damage was observed mainly in the liver following simultaneous oral ingestion of these compounds. The administration within a 60 min interval also yielded hepatic DNA damage. It is considered that DNA damage induced in mouse organs with the coexistence of amines and nitrite in the acidic stomach is due to endogenously formed nitrosamines. Ascorbic acid reduced the liver DNA damage induced by morpholine and NaNO(2). Reductions in hepatic genotoxicity of endogenously formed N-nitrosomorpholine by tea polyphenols, such as catechins and theaflavins, and fresh apple, grape, and orange juices were more effective than was by ascorbic acid. In contrast with the antimutagenicity of ascorbic acid in the liver, ascorbic acid yielded stomach DNA damage in the presence of NaNO(2) (in the presence and absence of morpholine). Even if ascorbic acid acts as an antimutagen in the liver, nitric oxide (NO) formed from the reduction of NaNO(2) by ascorbic acid damaged stomach DNA.

Studies on possibility for alleviation of lifestyle diseases by low-dose irradiation or radon inhalation.

Our previous studies showed the possibility that activation of the antioxidative function alleviates various oxidative damages, which are related to lifestyle diseases. Results showed that, low-dose X-ray irradiation activated superoxide dismutase and inhibits oedema following ischaemia-reperfusion. To alleviate ischaemia-reperfusion injury with transplantation, the changes of the antioxidative function in liver graft using low-dose X-ray irradiation immediately after exenteration were examined. Results showed that liver grafts activate the antioxidative function as a result of irradiation. In addition, radon inhalation enhances the antioxidative function in some organs, and alleviates alcohol-induced oxidative damage of mouse liver. Moreover, in order to determine the most effective condition of radon inhalation, mice inhaled radon before or after carbon tetrachloride (CCl(4)) administration. Results showed that radon inhalation alleviates CCl(4)-induced hepatopathy, especially prior inhalation. It is highly possible that adequate activation of antioxidative functions induced by low-dose irradiation can contribute to preventing or reducing oxidative damages, which are related to lifestyle diseases.

Effects of KNK437 on heat-induced methylation of histone H3 in human oral squamous cell carcinoma cells.

PURPOSE: Methylation of H3 at lysine 4 (H3 Lys4) may be correlated with active gene trascription, whereas methylation of H3 at lysine 9 (H3 Lys9) may be linked to gene repression in murine cells and Schizosaccharomyces pombe. METHODS: Using Western blot analysis, heat-induced changes were studied in two human oral cancer cell lines, HSC4 (thermoresistant cells) and KB (thermosensitive cells). Histone H3 changes were studied; in particular for H3-Lys4 and H3-Lys9 methylation combined with KNK437. RESULTS: Heating of HSC4 cells at 45 degrees C for 20 min and KB cells for 3 min gradually increased H3-Lys4 and H3-Lys9 methylation. Treatment of both cells with 100 microM KNK437 before or after heat-treatment inhibited methylation of H3-Lys4, while methylation of H3 Lys9 remained unaffected. Use of KNK437 either before or after heat treatment inhibited the expression of HSP70. CONCLUSIONS: The findings suggest that heat-induced methylation of histone H3 may be correlated with the induction of HSPs by heating.