Xylosylated Detoxification of the Rice Flavonoid Phytoalexin Sakuranetin by the Rice Sheath Blight Fungus Rhizoctonia solani.

Sakuranetin (1) is a rice flavanone-type phytoalexin. We have already reported that the metabolites from the detoxification of 1 by Pyriculariaoryzae are naringenin (2) and sternbin. In this study, we investigated whether the rice sheath blight fungus Rhizoctoniasolani, another major rice pathogen, can detoxify 1. The extract of R. solani suspension culture containing 1 was analyzed by LC-MS to identify the metabolites of 1. Three putative metabolites of 1 were detected in the extract from the R. solani suspension culture 12 h after the addition of 1, and they were identified as 2, sakuranetin-4'-O-ß-d-xylopyranoside (3), and naringenin-7-O-ß-d-xylopyranoside (4) by NMR, LC-MS/MS, and GC-MS analyses. The accumulation of 2, 3, and 4 reached their maximum levels 9-12 h after the addition of 1, whereas the content of 1 decreased to almost zero within 9 h. The antifungal activities of 3 and 4 against R. solani were negligible, and 2 showed weaker antifungal activity than 1. We concluded that 2, 3, and 4 are metabolites from the detoxification of 1 by R. solani. Xylosylation is a rare and efficient detoxification method for phytoalexins.

Identification of Sternbin and Naringenin as Detoxified Metabolites from the Rice Flavanone Phytoalexin Sakuranetin by Pyricularia oryzae.

Sakuranetin (1) is a flavanone phytoalexin that has been reported to play an important role in disease resistance in rice plants. The rice blast fungus Pyricularia oryzae (syn. Magnaporthe oryzae) has been reported to metabolize 1 to lower its antifungal activity. Here, two flavanones, sternbin (2) and naringenin (3), were identified as metabolites of 1 in P. oryzae suspension culture by liquid chromatography tandem mass spectrometry (LC/MS/MS). The inhibition of 1, 2, and 3 on P. oryzae mycelial growth were 45%, 19%, and 19%, respectively, at a concentration of 100 µm. Thus, 2 and 3 are detoxified metabolites of 1 by P. oryzae.

Inhibition of Aurora-B function increases formation of multinucleated cells in p53 gene deficient cells and enhances anti-tumor effect of temozolomide in human glioma cells.

Cell division is an elemental process, and mainly consists of chromosome segregation and subsequent cytokinesis. Some errors in this process have the possibility of leading to carcinogenesis. Aurora-B is known as a chromosomal passenger protein that regulates cell division. In our previous studies of giant cell glioblastoma, we reported that multinucleated giant cells resulted from aberrations in cytokinesis with intact nuclear division occurring in the early mitotic phase, probably due to Aurora-B dysfunction. In this study, as we determined p53 gene mutation occurring in multinucleated giant cell glioblastoma, we investigated the role of Aurora-B in formation of multinucleated cells in human neoplasm cells with various p53 statuses as well as cytotoxity of glioma cells to temozolomide (TMZ), a common oral alkylating agent used in the treatment of gliomas. The inhibition of Aurora-B function by small-interfering (si)RNA led to an increase in the number of multinucleated cells and the ratios of G2/M phase in p53-mutant and p53-null cells, but not in p53-wild cells or the cells transduced adenovirally with wild-p53. The combination of TMZ and Aurora-B-siRNA remarkably inhibited the cell viability of TMZ-resistant glioma cells. Accordingly, our results suggested that Aurora-B dysfunction increases in the appearance of multinucleated cells in p53 gene deficient cells, and TMZ treatment in combination with the inhibition of Aurora-B function may become a potential therapy against p53 gene deficient and chemotherapeutic-resistant human gliomas.

Stereotactic radiosurgery for vestibular schwannomas: analysis of 317 patients followed more than 5 years.

OBJECTIVE: Many investigators have reported successful treatment of vestibular schwannomas with gamma knife radiosurgery (GKRS). However, long-term outcomes should be evaluated before concluding that GKRS is truly safe and effective for the treatment of vestibular schwannomas. METHODS: Between May 1991 and December 1998, 346 consecutive patients (excluding those presenting with neurofibromatosis Type 2) were treated with GKRS. Of these, 317 patients were assessed. Twenty-nine patients were lost to follow-up within 5 years. RESULTS: The median follow-up period was 7.8 years. Of 301 patients who underwent serial follow-up imaging, two (1%) experienced complete remission, 184 (61%) experienced partial remission, 93 (31%) had stable tumors, and 22 (7%) experienced treatment failure. The actuarial 5- or 10-year progression-free survival (PFS) rate was 93 and 92%, respectively. Tumors less than 15 cm3 in volume (10-yr PFS, 96%; P < 0.001) or which did not compress the brainstem and deviate the fourth ventricle (10-yr PFS, 97%; P = 0.008) resulted in significantly better PFS rates. Failure of treatment usually occurred within 3 years. When the tumor was treated with a marginal dose of 13 Gy or less, the hearing preservation rate was 68%, transient facial palsy developed at a rate of 1%, and facial numbness developed at a rate of 2%. CONCLUSION: GKRS proved to be a safe and effective treatment for patients followed longer than 5 years who presented with tumors with a volume of less than 15 cm3 and who did not have significant fourth ventricle deviation. Good functional outcomes were observed in this group of patients.