Lattice thermal conductivities of two SiO2_2 polymorphs by first-principles calculation and phonon Boltzmann transport equation

Lattice thermal conductivities of two SiO$_2$ polymorphs, i.e., $\alpha$-quartz (low) and $\alpha$-cristobalite (low), were studied using first-principles anharmonic phonon calculation and linearized phonon Boltzmann transport equation. Although $\alpha$-quartz and $\alpha$-cristobalite have similar phonon densities of states, phonon frequency dependencies of phonon group velocities and lifetimes are dissimilar, which results in largely different anisotropies of the lattice thermal conductivities. For $\alpha$-quartz and $\alpha$-cristobalite, distributions of the phonon lifetimes effective to determine the lattice thermal conductivities are well described by energy and momentum conservations of three phonon scatterings weighted by phonon occupation numbers and one parameter that represents the phonon-phonon interaction strengths

Expression and regulatory effects on cancer cell behavior of NELL1 and NELL2 in human renal cell carcinoma

We thank Professors Michael Rehli, Yoshiaki Ito, and Kristian Helin for gifting plasmids, Dr. Alasdair MacKenzie (University of Aberdeen) for helpful discussion, and Mr. Takashi Mizukami, Ms. Ryoko Tokuda, and Ms. Sanae Funaoka (Kanazawa University) for technical assistance.Peer reviewedPublisher PD

Reconsideration of progression to CRPC during androgen deprivation therapy

Androgen blockade-naïve prostate cancer (PCa) develops into CRPC during androgen deprivation therapy (ADT) by various genetic actions. The androgen-AR signaling axis plays a key role in this development. PCa cells mainly adapt themselves to the environment of lower androgen concentrations and change into androgen-hypersensitive cells or androgen-independent cells. Androgens of adrenal origin and their metabolites synthesized in the microenvironment in an intracrine/paracrine fashion act on surviving PCa cells and secrete prostate specific antigen (PSA). Total androgen deprivation (TAD) (castration, antiandrogen, and CYP17A1 inhibitor) can become an effective therapeutic strategy concerning the androgen signaling axis-related pathway. However, it is important to ascertain whether elevation of serum PSA results from AR activation or from an androgen-independent tumor volume effect. Then, clinicians can judge it adequately using the imaging studies such as CT or bone scan as well as PSA and bone metabolic markers, an approach which is necessary to judge which treatment is most suitable for the CRPC patients. This article is part of a Special Issue entitled \u27Essential role of DHEA\u27

前立腺癌再燃時に関与する遺伝子の同定と遺伝子治療

週齢SCID mouse背部皮下両側に前立腺癌細胞株LNCaP 1.O×10^6を50%matrigelとともにそれぞれinoculate。腫瘍が増大したmouseから一方の腫瘍を摘出し、subline化した(LN-Pre)。その後、mouseをcastrationし、そのうち再び増大した腫瘍を摘出し、新たなsublineを樹立(LN-REC0)。LN-REC0をcastrationしたSCID mouseにinoculate。増大した腫瘍を摘出し、低アンドロゲン環境下においても腫瘍増殖を認める新しい前立腺癌細胞株(LN-REC4)を樹立した。この細胞株を用いてin vitro, in vivoにおいて、増殖速度、細胞特性につき検討した。新しく樹立した細胞株LN-REC4はin vitroではアンドロゲン感受性を保持していた。しかし、in vivoにおいては、castrationしたmouseでは造腫瘍能、増殖速度とも親株LNCaP、LN-Preと比較して速く、再燃前立腺癌の良いモデルであると考えられた。 また、同時に前立腺癌の再燃に関与する遺伝子として、可能性のあるものをmedline等で調べたところ、Cyclooxygenase-2(COX-2)の関与が考えられた。このため、COX-2の発現に乏しいLNCaP細胞でCOX-2を強制発現させ、COX-2の機能を調べた。COX-2はLNCaP細胞の増殖をin vitro, in vivoにおいても促進した。また、血管新生に関与する遺伝子のう右VEGFの発現を亢進させていた。We inoculated LNCaP cells, androgen-sensitive human prostate cancer cells, onto 5-week aged scid mice subcutneously with 50 % matrigel. After tumor was increased visually, we castrated the mouse. First, tumor retarded for 2 weeks. Then it stated to enlarge. We sacrificed the mouse and took the tumor and subcultured. (LN-RECO). Next we inoculated the LN-RECO to the castrated mouse. Again we took the enlarged tumor and subcultured (LN-REC4).We characterized LN-REC4 cells. Although LN-REC4 cells were stimulated by androgen in vitro, the growth speed of those cells in the castrated mouse was faster than LNCaP cells, suggesting that LN-REC4 seemed to be a good model that reflect the relapse of prostate cancer.We also investigated the COX-2 gene since this gene seemed to be related with progression of prostate cancer. Overexpression of COX-2 gene in LNCaP cells induced cell proliferation in vitro and in vivo, and induced VEGF secretion.研究課題/領域番号:13671640, 研究期間(年度):2001–200

前立腺癌アンドロゲン応答性増殖・浸潤転移関連遺伝子の同定、および治療への応用

(1)アンドロゲン依存性LNCaP細胞からアンドロゲン非依存性株LN-REC4とLNCaP-SFを樹立した。 (2)castrationしたscid mouseの皮下に移植しても増殖が促進される理由のひとつに細胞からのVEGFの発現亢進による血管新生亢進が考えられた。 (3)DHTの有無で発現の変化する遺伝子をcDNA micro arrayを用いてそれぞれの細胞において同定した。LNCaP細胞とLNCAP-SF細胞で共にDHTにより発現が亢進する遺伝子・低下する遺伝子、LNCaP-SF細胞で発現が亢進するが、LNCaPで発現が変わらないか、逆に低下する遺伝子、LNCaP-SFで発現が低下し、LNCaPで発現が逆に亢進する遺伝子などが判明した。 (4)cDNA arrayの際に用いたRNAを使って再びRT-PCRにて発現の違いを確認し、artifactなのか本当にDHTで発現の変化した遺伝子なのか明らかにすることができ、さらにもう一度LNCaPとLNCaP-SFでDHTによる刺激を行い、RNA抽出、RT-PCRを行って再現性があるかどうかを確認した。 (5)cDNA microarrayでスクリーニングした遺伝子16,785genesのうちLNCaPで2倍以上発現の亢進している遺伝子は374genes,LNCaP-SFでは581genes。両細胞で発現の亢進している遺伝子は184genes認められた。また、LNCaPで2倍以上発現の減弱している遺伝子は623genes,LNCaP-SFでは388genesあった。このうち両細胞で発現の減弱している遺伝子は105genes認められた。また、LNCaPで発現が亢進し、LNCaP-SFで発現が減弱した遺伝子は22genesあり、その逆は1geneのみであった。1.We established androgen-independent prostate cancer cell lines, LN-REC4 and LNCaP-SF from LNCaP cells.2.These cells grew very well when they were inoculated in castrated scid mouse subcutaneously. One of this reason was speculated that increased VEGF secretion.3.We identified genes that were regulated by DHT by cDNA microarray analysis. (screened 16,785 genes).4.We confirmed that these genes were really regulated by DHT by RT-PCR.5.There were 374 and 581 genes in LNCaP and up-regulated by DHT and 623 and 388 genes down-regulated genes. 105 genes were down-regulated genes in both cell lines.研究課題/領域番号:17591669, 研究期間(年度):2005–2006出典：「前立腺癌アンドロゲン応答性増殖・浸潤転移関連遺伝子の同定、および治療への応用」研究成果報告書　課題番号17591669 (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)　　　本文データは著者版報告書より作

Androgen and prostate cancer: the role of primary androgen deprivation therapy in localized prostate cancer

金沢大学医薬保健研究域医学系Background: The basic mechanisms and clinical efficacy of primary androgen deprivation therapy (PADT), especially combined androgen blockade (CAB) for localized or locally advanced prostate cancer (PCa) have been outlined. An important point relates to which patients are suitable candidates for PADT. Methods: A retrospective review of the efficacy of PADT in 628 patients with localized or locally advanced PCa treated with PADT at seven institutions in Japan was carried out. Results: It was found that more than 30% of low- or intermediate-risk localized PCa patients could have their disease controlled over the long-term by PADT alone. Short-term or intermittent PADT could not be recommended because of the possibility of character change in the cancer cells as a result of incomplete androgen ablation. Conclusion: Algorithms are proposed for the treatment of localized PCa not only in low- and intermediate-risk groups, but also in the high-risk group. Future research directions are indicated. © 2008 WPMH GmbH

Primary combined androgen blockade in localized disease and its mechanism

金沢大学医薬保健研究域医学系In spite of clinical practice guidelines such as NCI-PDQ - in which primary androgen deprivation therapy (PADT) is not recommended as the primary treatment for localized prostate cancer - many patients have been treated with PADT. One of the reasons is that urologists themselves permit patients\u27 desire because they know the effectiveness of PADT for some patients in their experiences. In this review we demonstrate basic mechanisms and the clinical efficacy of primary combined androgen blockade (PCAB) for localized or locally advanced prostate cancer. Then we discuss which patients are candidates for PCAB, and show that more than 30% of low- or intermediate-risk localized prostate cancers could be controlled in the long term with only PCAB. Short-term or intermittent PADT could not be recommended because of the possibilities of changing the character of the cancer cells by incomplete androgen ablation. We propose algorithms for the treatment of localized prostate cancer not only in low- and intermediate-risk groups but also in the high-risk group. © 2008

Severe Renal Hemorrhage in a Pregnant Woman Complicated with Antiphospholipid Syndrome: A Case Report

Antiphospholipid syndrome is a systemic autoimmune disease with thrombotic tendency. Consensus guidelines for pregnancy with antiphospholipid syndrome recommend low-dose aspirin combined with unfractionated or low-molecular-weight heparin because antiphospholipid syndrome causes habitual abortion. We report a 36-year-old pregnant woman diagnosed with antiphospholipid syndrome receiving anticoagulation treatment. The patient developed left abdominal pain and gross hematuria at week 20 of pregnancy. An initial diagnosis of left ureteral calculus was made. Subsequently abdominal-pelvic computed tomography was required for diagnosis because of the appearance of severe contralateral pain. Computed tomography revealed serious renal hemorrhage, and ureteral stent placement and pain control by patient-controlled analgesia were required. After treatment, continuance of pregnancy was possible and vaginal delivery was performed safely. This is the first case report of serious renal hemorrhage in a pregnant woman with antiphospholipid syndrome receiving anticoagulation treatment and is an instructive case for urological and obstetrical practitioners

Therapies for castration-resistant prostate cancer in a new era: The indication of vintage hormonal therapy, chemotherapy and the new medicines

When advanced prostate cancer recurred during hormonal therapy and became the castration-resistant prostate cancer, "vintage hormonal therapy," such as antiandrogen alternating therapy or estrogen-related hormonal therapy, was widely carried out in Japan until 2013. This vintage hormonal therapy controlled the progression of castration-resistant prostate cancer. When castration-resistant prostate cancer relapses during these therapies, chemotherapy using docetaxel has been carried out subsequently. Since new hormonal therapies using abiraterone acetate and enzalutamide, which improve the prognosis of castration-resistant prostate cancer, became available in Japan from 2014, therapeutic options for castration-resistant prostate cancer have increased. Furthermore, the improvement of the further prognosis is promising by using cabazitaxel for docetaxel-resistant castration-resistant prostate cancer and radium-223 for castration-resistant prostate cancer with bone metastasis. An increase in therapeutic options gives rise to many questions, including best timing to use them and the indication. Furthermore, physicians have to consider the treatment for the recurrence after having carried out chemotherapy. We want to argue the difference in hormonal therapy between Japan and Western countries, and problems when carrying out new treatments, and the importance of imaging in the present review article. © 2017 The Japanese Urological Association.Embargo Period 12 month