A change in microsatellite instability caused by cisplatin-based chemotherapy of ovarian cancer

To clarify the mechanism of acquired CDDP resistance in ovarian cancer, we compared the microsatellite instability (MSI) by the amplification of 10 microsatellite loci and immunohistochemical detection of hMSH2 and hMLH1 expression between the primary resected tumours and the secondary resected residual tumours after 5 or 6 courses of CDDP-based chemotherapy in the 24 cases of ovarian cancer. Of the 24 primary resected tumours, 9 (37.5%) showed MSI (7 cases of MSI-L, 2 cases of MSI-H), while 15 (72.5%) were microsatellite stable tumours (MSS). The primary tumours also had MSI in the residual tumours after CDDP-based chemotherapy. However, all of the cases with MSS in the primary resected tumours exhibited MSI (2 cases were MSI-L, and 13 cases were MSI-H) in the residual tumours after CDDP-based chemotherapy (P< 0.001). Furthermore, 11 (73.3%) of these cases which changed from MSS to MSI also had a change in the expression of hMLH1 from positive to undetectable (P< 0.001). Our data suggest that tumour MSI changes during CDDP-based chemotherapy, and that the loss of hMLH1 expression is one of the factors that has the greatest effect on this transformation. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Inhibition of NOS- like activity in maize alters the expression of genes involved in H2O2 scavenging and glycine betaine biosynthesis

Nitric oxide synthase-like activity contributes to the production of nitric oxide in plants, which controls plant responses to stress. This study investigates if changes in ascorbate peroxidase enzymatic activity and glycine betaine content in response to inhibition of nitric oxide synthase-like activity are associated with transcriptional regulation by analyzing transcript levels of genes (betaine aldehyde dehydrogenase) involved in glycine betaine biosynthesis and those encoding antioxidant enzymes (ascorbate peroxidase and catalase) in leaves of maize seedlings treated with an inhibitor of nitric oxide synthase-like activity. In seedlings treated with a nitric oxide synthase inhibitor, transcript levels of betaine aldehyde dehydrogenase were decreased. In plants treated with the nitric oxide synthase inhibitor, the transcript levels of ascorbate peroxidase-encoding genes were down-regulated. We thus conclude that inhibition of nitric oxide synthase-like activity suppresses the expression of ascorbate peroxidase and betaine aldehyde dehydrogenase genes in maize leaves. Furthermore, catalase activity was suppressed in leaves of plants treated with nitric oxide synthase inhibitor; and this corresponded with the suppression of the expression of catalase genes. We further conclude that inhibition of nitric oxide synthase-like activity, which suppresses ascorbate peroxidase and catalase enzymatic activities, results in increased H2O2 content

Tpr, a large coiled coil protein whose amino terminus is involved in activation of oncogenic kinases, is localized to the cytoplasmic surface of the nuclear pore complex

Abstract. From a panel of monoclonal antibodies raised against fractions of rat liver nuclear envelopes (NEs), we have identified an antibody, RL30, which reacts with novel nuclear pore complex (NPC) antigens that are not O-glycosylated. By immunofluorescence staining of cultured cells, RL30 reacts exclusively with the NE in a punctate pattern that largely coincides with that of identified NPC proteins. RL30 labels only the cytoplasmic surface of the NPC in immunogold electron microscopy, predominantly in peripheral regions nearby the cytoplasmic ring. In immunoblots of isolated rat liver NEs and cultured rat cells, RL30 recognizes a 265-kD band, as well as a series of 175-265-kD bands in rat liver NEs that are likely to be proteolytic products of p265. Sequencing of peptide

Arthrodesis to L5 versus S1 in long instrumentation and fusion for degenerative lumbar scoliosis

There is a debate regarding the distal fusion level for degenerative lumbar scoliosis. Whether a healthy L5-S1 motion segment should be included or not in the fusion remains controversial. The purpose of this study was to determine the optimal indication for the fusion to the sacrum, and to compare the results of distal fusion to L5 versus the sacrum in the long instrumented fusion for degenerative lumbar scoliosis. A total of 45 patients who had undergone long instrumentation and fusion for degenerative lumbar scoliosis were evaluated with a minimum 2 year follow-up. Twenty-four patients (mean age 63.6) underwent fusion to L5 and 21 patients (mean age 65.6) underwent fusion to the sacrum. Supplemental interbody fusion was performed in 12 patients in the L5 group and eleven patients in the sacrum group. The number of levels fused was 6.08 segments (range 4–8) in the L5 group and 6.09 (range 4–9) in the sacrum group. Intraoperative blood loss (2,754 ml versus 2,938 ml) and operative time (220 min versus 229 min) were similar in both groups. The Cobb angle changed from 24.7° before surgery to 6.8° after surgery in the L5 group, and from 22.8° to 7.7° in the sacrum group without statistical difference. Correction of lumbar lordosis was statistically better in the sacrum group (P = 0.03). Less correction of lumbar lordosis in the L5 group seemed to be associated with subsequent advanced L5-S1 disc degeneration. The change of coronal and sagittal imbalance was not different in both groups. Subsequent advanced L5-S1 disc degeneration occurred in 58% of the patients in the L5 group. Symptomatic adjacent segment disease at L5-S1 developed in five patients. Interestingly, the development of adjacent segment disease was not related to the preoperative grade of disc degeneration, which proved minimal degeneration in the five patients. In the L5 group, there were nine patients of complications at L5-S1 segment, including adjacent segment disease at L5-S1 and loosening of L5 screws. Seven of the nine patients showed preoperative sagittal imbalance and/or lumbar hypolordosis, which might be risk factors of complications at L5-S1. For the patients with sagittal imbalance and lumbar hypolordosis, L5-S1 should be included in the fusion even if L5-S1 disc was minimal degeneration