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ゲノム病としての前立腺がん-内因性レトロウイルスとアンドロゲン調節領域-
Get PDF内因性レトロウイルス(endogenous retrovirus ; ERV)はTransposal element(TE)のひとつであり、ヒトゲノムの半分以上を占める。ERVはLTR(long terminal repeat)を特徴とし、このLTRの相同性によって再組換えが生じると考えられている。ERVは感染によって1)遺伝子調節領域のpromoter化2)エクソン化3)遺伝子末端のアデニール化などを惹起させ、本来のゲノムに影響を与える。昨年度では、前立腺癌に関与する遺伝子として、a)エストラジオールを産生する酵素CYP19(aromatase)、b)ACPP(酸性フォスファターゼ)c)テストステロンを産生する酵素HSD17B2の遺伝子をゲノムスクリニングで同定した。本年度は、本格的にa),b),c)の機能を解析した。前立腺がん培養細胞でアンドロゲン依存細胞(1)LNcaP,アンドロゲン非依存細胞(2)PC3、(3)DU145における発現を評価した。a)は(1)での発現は少なく、(2)前者で多く(3)後者では低かった。さらにb)では(1)、(2)、(3)の順に発現が高かった。c)は、(1)、(2)、(3)とも発現が低い。さらに、構造的な分析を行ったa)はHERV Iの感染により、CYP19のExon1をExonizationするので、前立腺がんゲノムで検証したところExon1の欠失していた例はなかった。b)はSINEの挿入によって発現の調節領域が付加されているので、この遺伝子内のSINEの欠失について検証したが認めなかった。さらに、c)はヒトERVであるMER67の挿入によって、Exon4が生じている。特にLTRの存在を、前立腺がんゲノムで検証したところ、LTR同士による相同再組換えによる欠失は認めなかった。本研究では、a),b),c)いずれも、ヒトERVの挿入によって、遺伝子が正常に機能できることが確認できたが、がんのマーカーとしての意義は少ない。研究課題/領域番号:20659248, 研究期間(年度):2008 – 2009出典：研究課題「ゲノム病としての前立腺がん-内因性レトロウイルスとアンドロゲン調節領域-」課題番号20659248
（KAKEN：科学研究費助成事業データベース（国立情報学研究所））
（https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-20659248/）を加工して作成金沢大学医学系research repor
Molecular evaluation of metastatic prostatic cancer and the study on enhancement of their effects treating for non-tratment and refractory prostatic cancer.
Get PDF1) 前立腺癌細胞の血行性微小播種の分子診断
前立腺癌細胞の分子マーカーとしてのPSAmRNAに対するPCRを行い,現在、患者のその後の臨床経過を詳細に観察している。
2) ARやestrogen receptor(ER)の発現増強を指標としてのこれらの発現誘導とその機序解明
4種類のヒト前立腺癌細胞株(LNCaP,PC-3,DU-145,TSUPr-l)に分化誘導作用を有する薬剤としてInterferon(IFN),5-azacytidine,all-trans retinoic acid(ATRA)を作用させ,細胞数と各種mRNAの発現についてRT-PCR法を用いて検討した.(1)IFNとATRAについては,増殖抑制効果は認められなかった.(2)5-azacytidineについてはすべての細胞株において濃度依存的に細胞増殖の抑制が認められた。
3) 2)の結果より、これらの分化誘導作用が細胞周期や転写系におけるプロモー夕に関与が示唆された。
細胞周期の制御を視点におき、癌抑制遺伝子であるp16のmRNAは,DU-145で強発現,LNCaPで弱発現を示したが,さらに、5-azacytidineの作用下では,本来発現のないTSUPr-1およびPC-3でも発現の誘導が観察され,これらの細胞株におけるpromoter regionの脱メチル化が示された.
5-azacytidineの曝露すなわちヒト前立腺癌細胞株において各種癌抑制遺伝子の脱メチル化を通して細胞増殖抑制作用を示す可能性が示唆された.
今後は,その他の細胞周期の制御に関わる遺伝子の発現を検討するとともに,増殖および分化の一つのマーカーとされるテロメラーゼ活性を測定し,増殖抑制機構の解明に尽力する予定である.1)Molecular evaluation of hematogenous micro-metastasis from prostatic cancer
Statistically we have selected patients according to their clinical stage, these patient had been preserved data such as PSA values, PSA mRNA from peripheral blood cells in advance. We are supposed to evaluate the relations between PSA value and the PSA expression using RT PCR.Now we are observing the clinical course these patients.
2)Induction of expression in androgen receptor (AR) and estrogen receptor (ER) for four prostatic cancer cell lines.
In our study, we evaluated an induction of AR and ER in AR-negative prostatic cell line (PC3, DU-145, TSUPr-1) and AR-positive cell line (LNCap) exposing agents such as interferon (INF), 5-azacytidine, all-trans retinoic acid (ATRA) which have an activity of potential cell differentiation.
(1)There are no effects suppressing cell proliferation any cell lines using INF and ATRA.On the other hand, there are some effect suppressing cell proliferation using 5-azacytidine in these four prostatic cancer cell lines every concentrations. This results suggested that this induction activity is depend on cell cycle or promoter of transcription mechanism.
(2)A cell cycle point of view, this system is related to p16 which is known to cancer suppressor gene. The p16 mRNA express high in DU145, low in LNCap. Furthermore TSUPr-1 and PC-3 which never express p16 protein in themselves induce the expression of p16 using 5-azacytidine.This means that the promoter region of these four prostatic cell line is demethylated. This result shows sate possibility that suppression of cell proliferation result in hypcmethylation exposing 5-azacytidine to prostatic cancer cell lines Next step we plan to evaluate the expression of genes which are related to controlling cell cycle, to demonstrate the telomerase activity as one of markers as proliferation and cell differentiation.研究課題/領域番号:09671618, 研究期間(年度):1997 – 1998出典：研究課題「前立腺癌転移の分子診断と未治療癌、再燃癌に対する治療効果増強に関する実験的研究 」課題番号09671618
（KAKEN：科学研究費助成事業データベース（国立情報学研究所））
（https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-09671618/096716181998kenkyu_seika_hokoku_gaiyo/）を加工して作成金沢大学医学部附属病院research repor
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Steroids metabolism and Cross-talk of steroid receptors in Prostatic cancer cells
Get PDF前立腺癌細胞株(LNCaP,PC-3,DU145)を用いたステロイド代謝について、各ステロイドを基質にした薄層クロマトグラフィーによる分析結果、副腎ステロイドが、とりわけDHEAがステロイドプールとして大きく関与していることを平成11年度に明らかにした。また、アンドロゲン依存性前立腺癌株においてアンドロステンジオンからDHEAにいたる経路が優位に代謝しており、非依存性癌ではその逆の代謝活性を認めた。これらの現象の一部はステロイド代謝系におけるグルクロン酸抱合及び硫酸抱合がホルモン依存性に関与している可能性を示唆した。その代謝酵素のひとつであるglucuronosyltransferaseの発現の相違について明らかにし、その関与の可能性を検証した。これらの現象を分子生物学的に検討した結果、前立腺癌細胞株LNCaPにおいてはグルクロン酸抱合を触媒するglucuronosyltransferaseが強く発現しており、PC3,DU145において少ないことを見出した。平成12年度は、LNCaPに対してglucuronosyltransferaseの選択的なanti-sense oligomaやアンチセンスDNAを作製導入し、その増殖活性が抑制されるかどうか検討した。anti-sense oligoma導入し前立腺癌細胞の増額やステロイド代謝について検討したが、有意差をみとめなかったが、アンチセンスDNA導入によって、増殖活性の増加を抑制することを証明した。したがって、in vitro系であるが前立腺癌におけるアンドロゲン依存性は、アンドロゲン除去機構の低下がみられた結果であると結論できたが、その機構について今後の課題となった。Adrenal androgens function as an androgen source within prostate and androgen target tissue. In this study, we compared the ability of three human prostatic cancer cell lines to metabolize the adrenal androgens, dehydroepiandrosterone (DHEA) and androstenedione in living cultured condition. Androgen-independent cell lines PC-3, DU145 and androgen-dependent cell line LNCaP were investigated. The effect of glucuronide and sulfate conjugates was also investigated. There is a strong tendency in PC-3 or DU145 to convert androstenedione to DHEA or DHEA-S reservoir. On the other hand, LNCaP is capable of converting DHEA into androstenedione and subsequently into dihydrotestosterone (DHT). Moreover, androgens were converted into a glucuronide conjugate in LNCaP, but not in PC-3 or DU145. As a result, the metabolism of the adrenal precursor shifted to androgen formation in LNCaP.This could be confirmed by means of reverse transcription-PCR of uridine diphospho-glucuronosyltransferase (UGT) 2B15. Kinetic properties of UGT activity in LNCaP revealed DHT to be a better substrate than testosterone for prostatic UGTs. In conclusion, our findings show that the adrenal precursor pool has the potential to contribute to the regulation of prostatic cells. Moreover, the presence of UGT activities in LNCaP may have a regulatory effect on the active androgen level in the intracellular environment.研究課題/領域番号:11671542, 研究期間(年度):1999-2000研究機関: 金沢大学医学部附属病院出典：「前立腺癌細胞におけるステロイド代謝及びレセプター間のクロストーグに関する研究」研究成果報告書 課題番号11671542
(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成9028313411671542research repor
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