Bulk and surface-sensitive high-resolution photoemission study of Mott-Hubbard systems SrVO3_3 and CaVO3_3

We study the electronic structure of Mott-Hubbard systems SrVO$_{3}$ and CaVO$_3$ with bulk and surface-sensitive high-resolution photoemission spectroscopy (PES), using a VUV laser, synchrotron radiation and a discharge lamp ($h\nu$ = 7 - 21 eV). A systematic suppression of the density of states (DOS) within $\sim$ 0.2 eV of the Fermi level ($E_F$) is found on decreasing photon energy i.e. on increasing bulk sensitivity. The coherent band in SrVO$_{3}$ and CaVO$_3$ is shown to consist of surface and bulk derived features, separated in energy. The stronger distortion on surface of CaVO$_{3}$ compared to SrVO$_{3}$ leads to higher surface metallicity in the coherent DOS at $E_F$, consistent with recent theory.Comment: 4 pages 5 figures (including 2 auxiliary figures); A complete analysis of the spectra based on the surface and bulk analysis shows in auxiliary figures Fig. A1 and A

Bisphosphonate induces apoptosis and inhibits pro-osteoclastic gene expression in prostate cancer cells

金沢大学医学部附属病院泌尿器科Aim: Bisphosphonates are well established for the management of cancer-induced skeletal complications. Recent studies suggest that bisphosphonates promote apoptosis of cancer cells as well as osteoclasts in bone metastatic sites. To determine the direct effects of bisphosphonate on prostate cancer, we examined the effects of minodronate on prostatic cancer cell growth and the expression of apoptosis-related proteins and osteoclastogenic factors. Methods: PC-3, DU145 and LNCaP cells were treated with amino-bisphosphonate minodronate. Then proliferation, apoptosis and expression of bcl-2, bax, poly (ADP)-ribose polymerase (PARP), caspase-3, receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinases-2 (MMP-2), and parathyroid hormone related protein (PTHrP) were assessed. Results: The proliferation of prostatic cancer cells was inhibited by minodronate. DNA fragmentation and TUNEL-positive nuclei were observed in minodronate-treated PC-3 cells. Minodronate decreased bcl-2 expression and induced bax expression, caspase-3 activity and degradation of PARP in DU145 and PC-3 cells. Minodronate decreased expression of RANKL, PTHrP and MMP-2 in PC-3 cells. Conclusions: Our results suggest that bisphosphonate not only promotes apoptosis directly but also decreases pro-osteoclastic gene expression in prostate cancer cells

The establishment of two paclitaxel-resistant prostate cancer cell lines and the mechanisms of paclitaxel resistance with two cell lines

BACKGROUND Although paclitaxel is used for hormone-resistant prostate cancer, relapse definitely occurs later. Details of the molecular mechanism responsible for paclitaxel- resistance remain unclear. METHODS We established paclitaxel-resistant cells, DU145-TxR and PC-3-TxR from parent DU145 and PC-3. To characterize these cells, we examined cross-resistance to other anticancer drugs. Expression of several potential genes that had been related to drug-resistance was compared with parent cells by RT-PCR and Western blotting. Methylation analysis of multiple drug resistance (MDR1) promoter was carried out using bisulfite-modified DNA from cell lines. Knockdown experiments using small interfering RNA (siRNA) were also performed to confirm responsibility of drug-resistance. Finally, cDNA microarray was performed to quantify gene expression in PC-3 and PC-3-TxR cells. RESULTS The IC 50 for paclitaxel in DU145-TxR and PC-3-TxR was 34.0- and 43.4-fold higher than that in both parent cells, respectively. Both cells showed cross-resistance to some drugs, but not to VP-16 and cisplatin. Methylation analysis revealed that methylated CpG sites of MDR1 promoter in DU145 and PC-3 cells were demethylated in DU145-TxR cells, but not in PC-3-TxR cells. Knockdown of P-glycoprotein (P-gp), which was up-regulated in resistant cells, by MDR-1 siRNA restored paclitaxel sensitivity in DU145-TxR but not in PC-3-TxR, indicating that up-regulation of P-gp was not always main cause of paclitaxel-resistance. Microarray analysis identified 201 (1.34%) up-regulated genes and 218 (1.45%) out of screened genes in PC-3-TxR. CONCLUSIONS Our data will provide molecular mechanisms of paclitaxel-resistance and be useful for screening target genes to diagnose paclitaxel sensitivity. Prostate 67: 955–967, 2007. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56002/1/20581_ftp.pd

Measurement of hepatitis B virus core-related antigen is valuable for identifying patients who are at low risk of lamivudine resistance

ArticleLIVER INTERNATIONAL. 26(1): 90-96 (2006)journal articl

Osteoblasts induce prostate cancer proliferation and PSA expression through interleukin-6-mediated activation of the androgen receptor

Prostate cancer (CaP) metastases selectively develop in bone as opposed to other sites through unknown mechanisms. Interleukin-6 (IL-6) is considered to contribute to CaP progression and is produced at high levels in osteoblasts. We hypothesized that osteoblast-derived IL-6 in the bone microenvironment contributes to the fertile soil for CaP growth. Accordingly, human CaP cells, LNCaP, C4-2B and VCaP, were treated with conditioned medium (CM) collected from human osteoblast-like HOBIT cells grown in androgen-depleted medium. We found that CM induced proliferation, prostate-specific antigen (PSA) protein and mRNA expression in a dose-dependent manner in these cell lines as determined by ELISA and real-time PCR, respectively. CM also activated the PSA promoter in these cells. Both HOBIT and primary osteoblast (POB) cells produced high levels of IL-6 measured by bioassay. LNCaP, C4-2B and VCaP cells expressed IL-6, but at much lower levels then the HOBIT and POB and they also expressed the IL-6 receptor mRNA, indicating they can respond to IL-6. Anti-IL-6 antibody added to HOBIT or POB CM dose-dependently inhibited the CM-induced cell proliferation and PSA expression in these CaP cell lines. HOBIT CM induced nuclear translocation of the AR and this was inhibited by anti-IL-6 antibody. Additionally, the antiandrogen bicalutamide inhibited HOBIT CM-induced cell proliferation. These results demonstrate that osteoblasts promote CaP growth through IL-6-mediated activation of the AR. Furthermore, these data underscore the importance of cross-talk between tumor and the bone microenvironment in the development of CaP bone metastases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42590/1/10585_2005_Article_56.pd

Down-regulation of E-cadherin enhances prostate cancer chemoresistance via Notch signaling

Abstract Background The chemoresistance of prostate cancer (PCa) is invariably associated with the aggressiveness and metastasis of this disease. New emerging evidence indicates that the epithelial-to-mesenchymal transition (EMT) may play pivotal roles in the development of chemoresistance and metastasis. As a hallmark of EMT, E-cadherin is suggested to be a key marker in the development of chemoresistance. However, the molecular mechanisms underlying PCa chemoresistance remain unclear. The current study aimed to explore the association between EMT and chemoresistance in PCa as well as whether changing the expression of E-cadherin would affect PCa chemoresistance. Methods Parental PC3 and DU145 cells and their chemoresistant PC3-TxR and DU145-TxR cells were analyzed. PC3-TxR and DU145-TxR cells were transfected with E-cadherin-expressing lentivirus to overexpress E-cadherin; PC3 and DU145 cells were transfected with small interfering RNA to silence E-cadherin. Changes of EMT phenotype-related markers and signaling pathways were assessed by Western blotting and quantitative real-time polymerase chain reaction. Tumor cell migration, invasion, and colony formation were then evaluated by wound healing, transwell, and colony formation assays, respectively. The drug sensitivity was evaluated using MTS assay. Results Chemoresistant PC3-TxR and DU145-TxR cells exhibited an invasive and metastatic phenotype that associated with EMT, including the down-regulation of E-cadherin and up-regulation of Vimentin, Snail, and N-cadherin, comparing with that of parental PC3 and DU145 cells. When E-cadherin was overexpressed in PC3-TxR and DU145-TxR cells, the expression of Vimentin and Claudin-1 was down-regulated, and tumor cell migration and invasion were inhibited. In particular, the sensitivity to paclitaxel was reactivated in E-cadherin-overexpressing PC3-TxR and DU145-TxR cells. When E-cadherin expression was silenced in parental PC3 and DU145 cells, the expression of Vimentin and Snail was up-regulated, and, particularly, the sensitivity to paclitaxel was decreased. Interestingly, Notch-1 expression was up-regulated in PC3-TxR and DU145-TxR cells, whereas the E-cadherin expression was down-regulated in these cells comparing with their parental cells. The use of γ-secretase inhibitor, a Notch signaling pathway inhibitor, significantly increased the sensitivity of chemoresistant cells to paclitaxel. Conclusion The down-regulation of E-cadherin enhances PCa chemoresistance via Notch signaling, and inhibiting the Notch signaling pathway may reverse PCa chemoresistance.https://deepblue.lib.umich.edu/bitstream/2027.42/136217/1/40880_2017_Article_203.pd

No association for Chinese HBV-related hepatocellular carcinoma susceptibility SNP in other East Asian populations.

published_or_final_versio

Prostate cancer stromal cells and LNCaP cells coordinately activate the androgen receptor through synthesis of testosterone and dihydrotestosterone from dehydroepiandrosterone

金沢大学附属病院泌尿器科金沢大学附属病院泌尿器科One of the mechanisms through which advanced prostate cancer (PCa) usually relapses after androgen deprivation therapy (ADT) is the adaptation to residual androgens in PCa tissue. It has been observed that androgen biosynthesis in PCa tissue plays an important role in this adaptation. In the present study, we investigated how stromal cells affect adrenal androgen dehydroepiandrosterone (DHEA) metabolism in androgen-sensitive PCa LNCaP cells. DHEA alone had little effect on prostate-specific antigen (PSA) promoter activity and the proliferation of LNCaP cells. However, the addition of prostate stromal cells or PCa-derived stromal cells (PCaSC) increased DHEA-induced PSA promoter activity via androgen receptor activation in the LNCaP cells. Moreover, PCaSC stimulated the proliferation of LNCaP cells under physiological concentrations of DHEA. Biosynthesis of testosterone or dihydrotestosterone from DHEA in stromal cells and LNCaP cells was involved in this stimulation of LNCaP cell proliferation. Androgen biosynthesis from DHEA depended upon the activity of various steroidogenic enzymes present in stromal cells. Finally, the dual 5a-reductase inhibitor dutasteride appears to function not only as a 5a-reductase inhibitor but also as a 3b-hydroxysteroid dehydrogenase inhibitor in LNCaP cells. Taken together, this coculture assay system provides new insights of coordinate androgen biosynthesis under the microenvironment of PCa cells before and after ADT, and offers a model system for the identification of important steroidogenic enzymes involved in PCa progression and for the development of the corresponding inhibitors of androgen biosynthesis. © 2009 Society for Endocrinology

Clinical outcome and virologic profiles of severe hepatitis B exacerbation due to YMDD mutations

Background/Aims: To study the outcome and the virologic profiles of severe hepatitis exacerbations due to YMDD mutants in lamivudine-treated patients. Methods: Eighteen lamivudine-treated patients with severe hepatitis exacerbations due to YMDD mutants were recruited. Laboratory and clinical parameters were monitored. Viral genotypes and YMDD mutations were determined. Results: None of the 18 patients had YMDD wild-type during exacerbations. Three (17%) and 15 (83%) patients had genotypes B and C, respectively. Elevated bilirubin levels and prolonged prothrombin time were found in 11 (61%) and six patients (33%) respectively. Three patients (17%) had adverse outcome with the development of ascites and/or encephalopathy. One of these patients required liver transplantation and one died. Both patients had evidence of cirrhosis before treatment and hepatitis B e antigen (HBeAg) seroreversion from anti-HBe positivity. The remaining 16 patients (89%) have no evidence of pre-existing cirrhosis. Thirty seven percent of patients had normal alanine aminotransferase levels at the last follow-up. The median HBV DNA level at the last follow-up was significantly lower than the pre-treatment level (P = 0.009). Conclusions: Though the majority of patients with severe hepatitis exacerbations due to YMDD mutants had uneventful course, early liver transplantation should be considered in patients with pre-existing cirrhosis and HBeAg seroreversion. © 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.postprin