Simvastatin up-regulates annexin A10 that can inhibit the proliferation, migration, and invasion in androgen-independent human prostate cancer cells

学位記番号：医博甲1599

THE INFLUENCES OF THE BUNT IMAGE UPON BALL MEETING BAT

In today’s baseball, a bunt is considered as an important tactic. Therefore the aim of this study was to define the kinematic characteristics of bunt comparing between experts and beginners. Five expert players and five healthy male students participated in this study. Subjects bunted 10 times. 3-D coordinate was determined by DLT METHOD. Using these variables, the variance of distance between the bat-head and forehead, and the variance of bat-angle were researched and analyzed by z-test (

Low-density lipoprotein receptors play an important role in the inhibition of prostate cancer cell proliferation by statins

AbstractBackgroundThere are some reports about the antitumor effects of statins in these days. Statins decrease the level of cholesterol in the blood by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Inhibition of this enzyme decreases intracellular cholesterol synthesis. Thus, the expression of low-density lipoprotein receptor (LDLr) is increased to import more cholesterol from the bloodstream. In this study, we assessed the effects of statins on the proliferation of prostate cancer cells, and studied the relationship between the expression of LDLr and the effects of statins.MethodsSimvastatin was used in the experiments. We studied the effect of simvastatin on PC-3 and LNCaP cell proliferation using the MTS assay, and evaluated the expression of LDLr after administration of simvastatin by quantitative polymerase chain reaction and Western blotting. Intracellular cholesterol levels in the prostate cancer cells were measured after administration of simvastatin. Furthermore, small interfering RNA (siRNA) was used to knockdown the gene expression of LDLr.ResultsIn PC-3 cells, simvastatin inhibited cell proliferation. In LNCaP cells, only a high concentration of simvastatin (100μM) inhibited cell proliferation. In LNCaP cells, the protein level of LDLr was increased by simvastatin. In PC-3 cells, the protein levels of LDLr were unregulated. In PC-3 cells, but not in LNCaP cells, intracellular cholesterol levels were significantly decreased by simvastatin. After knocking down LDLr expression by siRNA, intracellular cholesterol levels were decreased, and cell proliferation was inhibited by simvastatin in LNCaP cells.ConclusionSimvastatin inhibited prostate cancer cell growth by decreasing cellular cholesterol and could be more effective in androgen-independent prostate cancer, where there is loss of regulation of LDLr expression. LDLr was shown to play an important role in the statin-induced inhibition of prostate cancer cell proliferation. These results suggest that future studies evaluating the cholesterol-lowering effects of statin may lead to new approaches to the prevention and treatment of prostate cancer

Analysis of mTOR Inhibition-Involved Pathway in Ovarian Clear Cell Adenocarcinoma

This study was designed to clarify the mechanism of the mammalian target of rapamycin (mTOR)-hypoxia inducible factor-1 (HIF-1) pathway using the cultured cell strain derived from human ovarian clear cell adenocarcinoma (CCA). Everolimus (a derivative of rapamycin)-treated cells and non-treated cells did not show any difference in mTOR expression. But, phosphorylated-mTOR (p-mTOR) expression significantly decreased in the treated cells, and mTOR-related factors such as phosphorylated-4E-BP1 (p-4E-BP1), HIF-1α, and vascular endothelial growth factor (VEGF) in the downstream region of mTOR revealed a marked decrease in expression. The analysis of influences of the drug on the HIF-1α degradation system showed an increase in von-Hippel Lindau (VHL) expression in the treated cells. Increase of cleaved caspase-3, one of key factors involved in apoptosis, was also shown in the treated cells. In the next step, using nude mice implanted with RMG-1 cells, a decrease in tumor size was demonstrated in 4 of the 7 mice which were orally administered with everolimus. As a result, it was suggested that everolimus administration would be helpful as an anti-tumor therapy for CCA not only via down-regulation of p-mTOR but also degradation of HIF-1α by VHL and induction of apoptosis by cleaved caspase-3

Large-scale mapping observations of the CI(3P1-3P0) and CO(J=3-2) lines toward the Orion A molecular cloud

Large scale mapping observations of the 3P1-3P0 fine structure transition of atomic carbon (CI, 492 GHz) and the J=3-2 transition of CO (346 GHz) toward the Orion A molecular cloud have been carried out with the Mt. Fuji submillimeter-wave telescope. The observations cover 9 square degrees, and include the Orion nebula M42 and the L1641 dark cloud complex. The CI emission extends over almost the entire region of the Orion A cloud and is surprisingly similar to that of 13CO(J=1-0).The CO(J=3-2) emission shows a more featureless and extended distribution than CI.The CI/CO(J=3-2) integrated intensity ratio shows a spatial gradient running from the north (0.10) to the south (1.2) of the Orion A cloud, which we interpret as a consequence of the temperature gradient. On the other hand, the CI/13CO(J=1-0) intensity ratio shows no systematic gradient. We have found a good correlation between the CI and 13CO(J=1-0) intensities over the Orion A cloud. This result is discussed on the basis of photodissociation region models.Comment: Text file is 13 pages long, and 3 figure files (pdf format). NRO Report No. 508 (1999). University of Tokyo, Resceu 41/9

An Up-to-Date Anti-Cancer Treatment Strategy Focusing on HIF-1α Suppression: Its Application for Refractory Ovarian Cancer

Hypoxia inducible factor-1α (HIF-1α) predominantly determines the transcriptional activity of HIF-1, which induces the certain genetic expressions to participate in the proliferation and progression of the tumor. It is supposed that HIF-1α is also an extremely important factor in cancer treatment. Based on the results of our recent analyses using ovarian tumors, which indicated the close association of HIF-1α expression with the acquisition of malignancy and the characterization of histology, we further investigated the possibility of a new strategy of cancer therapy that targeted HIF-1α inhibition in the ovarian carcinoma. The cell line HUOCA-II, which originates from the refractory ovarian clear cell adenocarcinoma, was treated with rapamycin. The inhibitory effect of HIF-1α was analyzed by immunohistochemistry and western blotting. It was demonstrated that inhibition of HIF-1α and vascular endothelial growth factor (VEGF) expressions would lead to the down-regulation of tumor cell proliferation. Interestingly, there was little or no change in GLUT-1 expression by rapamycin administration. Thus, the inhibition of GLUT-1 may also be a key for the new strategy of cancer therapy as well as HIF-1α and VEGF

Alterations in Mucin Expression in Ovarian Mucinous Tumors: Immunohistochemical Analysis of MUC2, MUC5AC, MUC6, and CD10 Expression

The aim of this study was to evaluate the immunohistochemical expression of MUC2, MUC5AC, MUC6, and CD10 in ovarian mucinous adenoma (MA), mucinous borderline tumor (MB), and mucinous adenocarcinoma (MC), and to analyze the relationship between prognosis and these expressions. The expression of MUC2, MUC5AC, MUC6, and CD10 was evaluated by immunohistochemical analysis in 29 cases of MA, 29 cases of MB, and 26 cases of MC and scored based on the percentage of positive cells. Moreover, the ovarian mucinous tumors were classified into 4 phenotypes based on the staining patterns: intestinal, gastrointestinal, gastric, and unclassified patterns. The gastrointestinal pattern and the expression of MUC2 and CD10 increased from MA to MC. Conversely, the gastric pattern and MUC5AC expression decreased from MA to MC. Low MUC2 expression in MC was correlated with a better long-term survival rate. MUC2 expression in MC may be a useful predictor of the clinical outcome. The expression patterns of MUC2, MUC5AC, MUC6, and CD10 indicated that intestinal metaplasia may arise from the gastric-like epithelium in MA and that a close association exists between carcinogenesis and intestinal metaplasia in major ovarian mucinous tumors

A model relating transpiration for Japanese cedar and cypress plantations with stand structure

Previous studies have revealed that changes in forest structure due to management (e.g., thinning, aging, and clearcutting) could affect the forest water balance. However, there are unexplained variability in changes in the annual water balance with changing structure among different sites. This is the case even when analyzing data for specific species/regions. For a more advanced and process-based understanding of changes in the water balance with changing forest structure, we examined transpiration (E) observed using the sap-flux method for 14 Japanese cedar and cypress plantations with various structure (e.g., stem density and diameter) in Japan and surrounding areas and developed a model relating E with structural parameters. We expressed E using the simplified Penman–Monteith equation and modeled canopy conductance (G[c]) as a product of reference G[c] (G[cref]) when vapor pressure deficit is 1.0 kPa and functions expressing the responses of G[c] to meteorological factors. We determined G[cref] and parameters of the functions for the sites separately. E observed for the 14 sites was not reproduced well by the model when using mean values of G[cref] and the parameters among the sites. However, E observed for the sites was reproduced well when using G[cref] determined for each site and mean values of the parameters of the functions among the sites, similar to the case when using G[cref] and the parameters of the functions determined for each site. These results suggest that considering variations in G[cref] among the sites was important to reproduce variations in E, but considering variations in the parameters of the functions was not. Our analysis revealed that G[cref] linearly related with the sapwood area on a stand scale (A) and that Alinearly related with stem density (N) and powers of the mean stem diameter (d[m]). Thus, we proposed a model relating E with A (or N and d[m]), where G[cref] was calculated from A (or N and d[m]) and the parameters of the functions were assumed to be the mean values among the sites. This model estimates changes in Ewith changing structure from commonly available data (N and d[m]), and therefore helps improve our understanding of the underlying processes of the changes in the water balance for Japanese cedar and cypress plantations