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A systematic review of the effects and mechanisms of preoperative 5α-reductase inhibitors on intraoperative haemorrhage during surgery for benign prostatic hyperplasia 被引量:5
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作者 Huan-Tao Zong Xiao-Xia Peng +1 位作者 Chen-Chen Yang Yong Zhang 《Asian Journal of Andrology》 SCIE CAS CSCD 2011年第6期812-818,共7页
5α-reductase inhibitors (5α-RIs), including finasteride and dutasteride, are commonly used medical therapies for benign prostatic hyperplasia (BPH). Many studies reported that preoperative 5α-RI had impact on i... 5α-reductase inhibitors (5α-RIs), including finasteride and dutasteride, are commonly used medical therapies for benign prostatic hyperplasia (BPH). Many studies reported that preoperative 5α-RI had impact on intraoperative haemorrhage during surgery for BPH, but it was still in controversial. So, we conducted a systematic review of the effects and mechanisms of 5α-RIs on intraoperative bleeding for BPH. MEDLINE, EMBASE, the Cochrane Controlled Trail Register of Controlled Trials and the reference lists of retrieved studies were searched in the analysis. Sixteen publications involving 15 different randomized controlled trials (RCTs) and a total of 1156 patients were used in the analysis, including 10 RCTs for finasteride and five RCTs for dutasteride. We found that preoperative finasteride treatment decreases microvessel density (MVD) in resected prostate specimens. Total blood loss, blood loss per gram of resected prostate tissue and decreases in haemoglobin were all greatly reduced in the finasteride group as compared to controls. Dutasteride appeared to have no effect on bleeding. This meta-analysis shows that preoperative finasteride treatment could decrease intraoperative haemorrhage during surgery for BPH. Preoperative dutasteride had no effect on intraoperative haemorrhage, but further high-qualitv prospective studies are still needed to confirm this observation. 展开更多
关键词 5α-reductase inhibitor benign prostate hyperplasia HAEMORRHAGE META-ANALYSIS microvessel density
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The use of 5-alpha reductase inhibitors in the treatment of benign prostatic hyperplasia 被引量:13
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作者 Eric H.Kim John A.Brockman Gerald L.Andriole 《Asian Journal of Urology》 2018年第1期28-32,共5页
Benign prostatic hyperplasia(BPH)is characterized by an enlarged prostate,lower urinary tract symptoms(LUTS),and a decreased urinary flow rate.Common in older men,BPH is a progressive disease that can eventually lead ... Benign prostatic hyperplasia(BPH)is characterized by an enlarged prostate,lower urinary tract symptoms(LUTS),and a decreased urinary flow rate.Common in older men,BPH is a progressive disease that can eventually lead to complications including acute urinary retention(AUR)and the need for BPH-related surgery.Both normal and abnormal prostate growth is driven by the androgen dihydrotestosterone(DHT),which is formed from testosterone under the influence of 5-alpha reductase.Thus,5-alpha reductase inhibitors(5-ARIs)effectively reduce the serum and intraprostatic concentration of DHT,causing an involution of prostate tissue.Two 5-ARIs are currently available for the treatment of BPHdfinasteride and dutasteride.Both have been demonstrated to decrease prostate volume,improve LUTS and urinary flow rates,which ultimately reduces the risk of AUR and BPH-related surgery.Therefore,either alone or in combination with other BPH medications,5-ARIs are a mainstay of BPH management. 展开更多
关键词 Benign prostatic hyperplasia 5-alpha reductase inhibitors Lower urinary tract symptoms
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Medical therapy for clinical benign prostatic hyperplasia:α1 Antagonists,5α reductase inhibitors and their combination 被引量:4
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作者 Cheuk Fan Shum Weida Lau Chang Peng Colin Teo 《Asian Journal of Urology》 2017年第3期185-190,共6页
Medical therapy for clinical benign prostatic hyperplasia(BPH)has advanced significantly in the last 2 decades.Many new a1 antagonists and 5a reductase inhibitors(5ARi)are now commercially available.The practicing uro... Medical therapy for clinical benign prostatic hyperplasia(BPH)has advanced significantly in the last 2 decades.Many new a1 antagonists and 5a reductase inhibitors(5ARi)are now commercially available.The practicing urologist must decide on the most appropriate medication for his patients,taking into consideration various factors like efficacy,dosing regime,adverse effects,cost,patient’s socioeconomic background,expectations,drug availability and his own clinical experience.The use of combination therapy added further to the complexity in clinical judgment when prescribing.We highlight some of the key points in prescribing a1 antagonists,5ARi and their combination,based on our viewpoints and experience as urologists in an Asian clinical setting. 展开更多
关键词 5αreductase inhibitors Adrenergicα1 receptor antagonists Drug therapy COMBINATION Prostatic hyperplasia
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Pre-Androgen Ablation Prostate Cancer Patients Who Bleed Do Well with 5 Alpha Reductase Inhibitors
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作者 Vitalis Obisike Ofuru Christopher Chinedu Obiorah 《Open Journal of Urology》 2018年第6期184-192,共9页
Background: Patients with gross haematuria are sometimes found to have prostate cancer after clinical evaluation. The treatment of such haematuria could be very challenging. Use of a 5 alpha reductase inhibitor like d... Background: Patients with gross haematuria are sometimes found to have prostate cancer after clinical evaluation. The treatment of such haematuria could be very challenging. Use of a 5 alpha reductase inhibitor like dutasteride has been found helpful in bleeding prostate cancer patients if they have not undergone hormonal manipulation before they developed haematuria. Patients and Method: 26 patients with gross haematuria of prostatic origin who had histologic confirmation of adenocarcinoma of the prostate but who have not had chemical or surgical castration were randomized to receive daily dutasteride in addition to vigorous saline irrigation and antibiotics on one arm and vigorous saline irrigation and antibiotics only as control on the other arm. The time taken before haematuria resolved and the amount of irrigation fluid used were noted. Statistical analysis was done using SPSS. Student’s t-test and Kaplan Meier survival analysis were used to test various variables at 0.5 significant levels. Results: Of the 26 patients 12(46.2%) received 0.5 mg oral dutasteride in addition to saline irrigation while 14 (53.8%) received saline irrigation only. Haematuria stopped in all of 12 (100%) patients on dutasteride arm but on 12 (85.7%) of the 14 patients on the control arm. It took significantly shorter time and lesser volume of irrigation fluid before haematuria resolved in those treated with dutasteride than in those on the control arm. Conclusion: Dutasteride is effective in the control of acute haematuria in pre-androgen ablation prostate cancer patients. 展开更多
关键词 PROSTATE Cancer BLEEDING 5-Alpha reductase inhibitors
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High performance thin layer chromatography as an effective tool for rapid screening of 5α-reductase inhibitors
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作者 Ruirong Zheng Mooseob Kim +1 位作者 Zhengtao Wang Li Yang 《Asian Journal of Traditional Medicines》 CAS 2021年第4期216-224,共9页
Benign prostatic hyperplasia(BPH)is a common disease in men,and is known to be related to 5α-reductase,which can affect steroid metabolism.Under the promotion of 5α-reductase,testosterone can be converted into dihyd... Benign prostatic hyperplasia(BPH)is a common disease in men,and is known to be related to 5α-reductase,which can affect steroid metabolism.Under the promotion of 5α-reductase,testosterone can be converted into dihydrotestosterone(DHT),and excessive DHT will cause related diseases.Since BPH seriously affects the quality of life of patients,it is essential to discover effective 5α-reductase inhibitors.In this study,the simple analytical method of high performance thin layer chromatography(HPTLC)was used to screen active compounds,and seven compounds with strong activity were screened out.This research will provide a reference for studying the material basis of drugs for the treatment of BPH. 展开更多
关键词 5α-reductase inhibitor benign prostatic hyperplasia HPTLC steroid hormones DIHYDROTESTOSTERONE
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Changes in aortic endothelium ultrastructure in male rats following castration, replacement with testosterone and administration of 50α-reductase inhibitor 被引量:14
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作者 Ying-Li Lu Lin Kuang +5 位作者 Hui Zhu Hui Wu Xue-Fang Wang Yu-Ping Pang Ning-Jian Wang Dan-Lu Yu 《Asian Journal of Andrology》 SCIE CAS CSCD 2007年第6期843-847,共5页
Aim: To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into four groups: group A, normal rats... Aim: To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into four groups: group A, normal rats with sham castration; group B, castrated rats; group C, castrated rats given testosterone (T) undecanoate; and group D, intact rats treated with 5α-reductase inhibitor. After 10 weeks of treatment or castration, rats in different groups were killed and serum T, free T (FT) and dihydrotestosterone (DHT) were measured. The aortic endothelia were scanned under electron microcopy and the Vascular Endothelium Structure Score (VESS) was computed. Results: Serum T and FT concentrations of rats in group B were significantly lower than those of the other three groups (P 〈 0.01); DHT concentrations of group D rats were significantly decreased (P 〈 0.01 ) when compared with those of groups A and C. Rats in groups B and D rats (with low androgen levels) had obvious damage to their endothelial surfaces, which appeared crimpled, rough, adhesive and ruptured, and had high destruction of VESS. Conclusion: These results suggest that low concentrations of T and DHT are associated with ultrastructural damage of the aortic endothelia in male rats. 展开更多
关键词 ENDOTHELIUM ULTRASTRUCTURE TESTOSTERONE 5α-reductase inhibitor CASTRATION
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A novel thioredoxin reductase inhibitor inhibits cell growth and induces apoptosis in HL-60 and K562 cells 被引量:7
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作者 Zuo-fu PENG Lin-xiang LAN +4 位作者 Fang ZHAO Jing LI Qiang TAN Han-wei YIN Hui-hui ZENG 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2008年第1期16-21,共6页
Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone)ethane (BBSKE),a novel TrxR inhibitor,were investigat... Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone)ethane (BBSKE),a novel TrxR inhibitor,were investigated on human leu-kemia cell lines HL-60 and K562. BBSKE treatment induced cell growth inhibition and apoptosis in both cell lines. Apoptosis induced by BBSKE is through Bcl-2/Bax and caspase-3 pathways. Ehrlich's ascites carcinoma-bearing mice were used to inves-tigate the anti-tumor effect of BBSKE in vivo. Tumor-bearing mice treated with BBSKE showed an increase of life span with a comparable effect to cyclophosphamide (CTX). These results suggest a potential usage of BBSKE as a therapeutic agent against non-solid tumors. 展开更多
关键词 Thioredoxin reductase (TrxR) Novel TrxR inhibitor 1 2-[bis(1 2-benzisoselenazolone-3(2H)-ketone)]ethane(BBSKE) APOPTOSIS
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Screening of traditional Chinese medicine monomers as ribonucleotide reductase M2 inhibitors for tumor treatment 被引量:1
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作者 Ya-Ya Qin Song Feng +1 位作者 Xiao-Dong Zhang Bin Peng 《World Journal of Clinical Cases》 SCIE 2022年第31期11299-11312,共14页
BACKGROUND Ribonucleotide reductase(RR)is a key enzyme in tumor proliferation,especially its subunit-RRM2.Although there are multiple therapeutics for tumors,they all have certain limitations.Given their advantages,tr... BACKGROUND Ribonucleotide reductase(RR)is a key enzyme in tumor proliferation,especially its subunit-RRM2.Although there are multiple therapeutics for tumors,they all have certain limitations.Given their advantages,traditional Chinese medicine(TCM)monomers have become an important source of anti-tumor drugs.Therefore,screening and analysis of TCM monomers with RRM2 inhibition can provide a reference for further anti-tumor drug development.AIM To screen and analyze potential anti-tumor TCM monomers with a good binding capacity to RRM2.METHODS The Gene Expression Profiling Interactive Analysis database was used to analyze the level of RRM2 gene expression in normal and tumor tissues as well as RRM2's effect on the overall survival rate of tumor patients.TCM monomers that potentially act on RRM2 were screened via literature mining.Using AutoDock software,the screened monomers were docked with the RRM2 protein.RESULTS The expression of RRM2 mRNA in multiple tumor tissues was significantly higher than that in normal tissues,and it was negatively correlated with the overall survival rate of patients with the majority of tumor types.Through literature mining,we discovered that berberine,ursolic acid,gambogic acid,cinobufagin,quercetin,daphnetin,and osalmide have inhibitory effects on RRM2.The results of molecular docking identified that the above TCM monomers have a strong binding capacity with RRM2 protein,which mainly interacted through hydrogen bonds and hydrophobic force.The main binding sites were Arg330,Tyr323,Ser263,and Met350.CONCLUSION RRM2 is an important tumor therapeutic target.The TCM monomers screened have a good binding capacity with the RRM2 protein. 展开更多
关键词 Tumor Ribonucleotide reductase M2 inhibitor Traditional Chinese medicine MONOMER Molecular docking Literature mining
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Aspects of Antithrombotic Effect of HMG-CoA Reductase Inhibitors 被引量:1
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作者 贺石林 《血栓与止血学》 2005年第1期3-4,共2页
Statins, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are widely used for the treatment of hypercholesteremia and have showed remarkable activity in preventing cardiovascular morbidity and mort... Statins, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are widely used for the treatment of hypercholesteremia and have showed remarkable activity in preventing cardiovascular morbidity and mortality. Recent studies demonstrated that statins have significant antithrombotic effect in addition to cholesterollowering action. Although the efficacy of statins for reducing cardiovascular events has historically been ascribed to their inhibitory activity on cholesterol synthesis, the degree of low-density lipoprotein cholesterol reduction by statins generally does not correlate with the magnitude of coronary risk reduction. 展开更多
关键词 抗血栓形成 还原酶抑制剂 预防 治疗
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Relation between Baseline Lipid Levels and Effectiveness of HMG-CoA Reductase Inhibitors in Patients with Hyperlipidemia
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作者 伍卫 周淑娴 +3 位作者 韦育林 张燕 王景峰 张旭明 《South China Journal of Cardiology》 CAS 2001年第1期13-16,共4页
Objective To evaluate whether the effects of HMG - CoA reductase inhibitors on patients with hyperlipidemia are closely related to baseline lipid levels. Methods The data analyzed originated from 3 separate multicente... Objective To evaluate whether the effects of HMG - CoA reductase inhibitors on patients with hyperlipidemia are closely related to baseline lipid levels. Methods The data analyzed originated from 3 separate multicenter clinical trials with similar designs during 1994 to 1999. 166 patients with mean age 58. 9±9. 2 years were involved in Simvastatin Clinical Trial with simvastatin 10 mg once daily for 8 weeks. 146 patients with mean age 57. 9±8. 7years were involved in Lovastatin Clinical Trial with lovastatin 20 mg once daily for 8 weeks. 105 patients with mean age 57. 8±9. 3 years were involved in Atorvastatin Clinical Trial with atorvastatin 10 mg once daily for 6 weeks. Baseline total cholesterol (TC) was more than 5. 98 mmol. L - 1, and baseline triglyceride (TG) was less than 4. 52 mmo. L - 1. The patients were grouped by baseline lipid levels. Results The higher the baseline TC, low density lipoprotein cholesterol (LDL - C) and TG levels were, the more effective the simvastatin, lovastatin, or atorvastatin was in reducing serum TC, LDL - C, and TG, respectively. A positive linear correlation was found between baseline values and effects of simvastatin, lovastatin, or atorvastatin in reducing serum TC, LDL - C, and TG, respectively. Conclusion The changes of reduction on serum lipid with HMG - CoA reductase inhibitors in patients with hyperlipidemia were influenced by baseline lipid levels. 展开更多
关键词 HMG - CoA reductase inhibitors Baseline lipid levels
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Differential expression of 5-alpha reductase sozymes in the prostate and its clinical implications 被引量:4
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作者 Kai Wang Dong-Dong Fan Song Jin Nian-Zeng Xing Yi-Nong Niu 《Asian Journal of Andrology》 SCIE CAS CSCD 2014年第2期274-279,I0010,共7页
The development of human benign or malignant prostatic diseases is closely associated with androgens, primarily testosterone (T) and dihydrotestosterone (DHT). T is converted to DHT by 5-alpha reductase (5-AR) i... The development of human benign or malignant prostatic diseases is closely associated with androgens, primarily testosterone (T) and dihydrotestosterone (DHT). T is converted to DHT by 5-alpha reductase (5-AR) isozymes. Differential expression of 5-AR isozymes is observed in both human benign and malignant prostatic tissues. 5-AR inhibitors (5-ARI) are commonly used for the treatment of benign prostatic hyperplasia (BPH) and were once promoted as chemopreventive agents for prostate cancer (PCa). This review discusses the role of the differential expression of 5-AR in the normal development of the human prostate and in the pathogenesis and progression of BPH and PCa. 展开更多
关键词 5-alpha reductase 5-alpha reductase inhibitor ANDROGEN benign prostatic hyperplasia PROSTATE prostate cancer
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Effects of phosphodiesterase 5 inhibitors on sperm parameters and fertilizing capacity 被引量:11
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作者 F. Dimitriadis D. Giannakis +11 位作者 N. Pardalidis K. Zikopoulos E. Paraskevaidis N. Giotitsas V. Kalaboki P.Tsounapi D. Baltogiannis Georgiou M.Saito T.Watanabe I. Miyagawa N.Sofildtis 《Asian Journal of Andrology》 SCIE CAS CSCD 2008年第1期115-133,共19页
The aim of this review study is to elucidate the effects that phosphodiesterase 5 (PDE5) inhibitors exert on spermatozoa motility, capacitation process and on their ability to fertilize the oocyte. Second messenger ... The aim of this review study is to elucidate the effects that phosphodiesterase 5 (PDE5) inhibitors exert on spermatozoa motility, capacitation process and on their ability to fertilize the oocyte. Second messenger systems such as the cAMP/adenylate cyclase (AC) system and the cGMP/guanylate cyclase (GC) system appear to regulate sperm functions. Increased levels of intracytosolic cAMP result in an enhancement of sperm motility and viability. The stimulation of GC by low doses of nitric oxide (NO) leads to an improvement or maintenance of sperm motility, whereas higher concentrations have an adverse effect on sperm parameters. Several in vivo and in vitro studies have been carried out in order to examine whether PDE5 inhibitors affect positively or negatively sperm parameters and sperm fertilizing capacity. The results of these studies are controversial. Some of these studies demonstrate no significant effects of PDE5 inhibitors on the motility, viability, and morphology of spermatozoa collected from men that have been treated with PDE5 inhibitors. On the other hand, several studies demonstrate a positive effect of PDE5 inhibitors on sperm motility both in vivo and in vitro. In vitro studies of sildenafil citrate demonstrate a stimulatory effect on sperm motility with an increase in intracellular cAMP suggesting an inhibitory action of sildenafil citrate on a PDE isoform other than the PDE5. On the other hand, tadalafil's actions appear to be associated with the inhibitory effect of this compound on PDE11. In vivo studies in men treated with vardenafil in a daily basis demonstrated a significantly larger total number of spermatozoa per ejaculate, quantitative sperm motility, and qualitative sperm motility; it has been suggested that vardenafil administration enhances the secretory function of the prostate and subsequently increases the qualitative and quantitative motility of spermatozoa. The effect that PDE5 inhibitors exert on sperm parameters may lead to the improvement of the outcome of assisted reproductive technology (ART) programs. In the future PDE5 inhibitors might serve as adjunct therapeutical agents for the alleviation of male infertility. 展开更多
关键词 sperm fertilizing capacity phosphodiesterase 5 inhibitors SPERMATOZOA TESTIS male infertility
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Patterns of treatment with PDE5 inhibitors in the clinical practice in Italy: longitudinal data from the Erectile Dysfunction Observational Study 被引量:2
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作者 Ferdinando Fusco Riccardo Sicuteri +4 位作者 Andrea Rossi Stathis Kontodimas Jose Maria Haro Ciro Imbimbo 《Asian Journal of Andrology》 SCIE CAS CSCD 2009年第5期629-637,I0005,共10页
The Erectile Dysfunction Observational Study (EDOS) is a 6-months observational prospective multicentric study enrolling men with erectile dysfunction (ED) who asked, to be started on a treatment or to change a pr... The Erectile Dysfunction Observational Study (EDOS) is a 6-months observational prospective multicentric study enrolling men with erectile dysfunction (ED) who asked, to be started on a treatment or to change a previous treatment. Aims of the study were to analyse the pattern of treatment and compare the efficacy of treatments used. Patients were enrolled during a normal hospital visit and were prescribed a treatment for ED. They were asked at baseline and after 3 and 6 months, to answer a set of questions from the International Index of Erectile Function, Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) and Short Form of the Psychological and Interpersonal Relationships Scale questionnaires (SF-PAIRS). Clinicians were free to prescribe any therapy for ED available in the market, and to change therapy at any time during the study. Out of 1 338 patients, available for analysis at 6 months, 624 (47%) changed their treatment during the study and 714 (53%) continued with the drug prescribed at baseline. Patients assuming tadalafil had a significantly higher probability of maintaining the same treatment compared to sildenafil or vardenafil. There was no clinically significant difference in terms of efficacy, patient satisfaction, self-confidence and spontaneity between the different inhibitors of PDE5. The ‘time concerns' domain score of SF-PAIRS, was statistically better in patients assuming tadalafil. In conclusion sildenafil, vardenafil and tadalafil show similar efficacy in the clinical practice. However, patients receiving tadalafil display a lower risk to discontinue or change the treatment. 展开更多
关键词 clinical practice ITALY phosphodiesterase type 5 inhibitors SILDENAFIL TADALAFIL VARDENAFIL
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Peptide Inhibitors of HIV-1 Virus Infection Based on Cullin-5 被引量:2
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作者 ZHU Ke-tong ZHANG Xi-zhen LOU Chao-ping GUO Bo DU Juan WANG Xiao-dan WU Yong-ge KONG Wei YU Xiang-hui 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 2008年第3期338-343,共6页
Virion infectivity factor(Vif) is one of the six accessory proteins of HIV-1 and is necessary for viral infectivity. Human Apolipoprotein B editing complex protein 3G(h-APOBEC3G) is a cytidine deaminase only expre... Virion infectivity factor(Vif) is one of the six accessory proteins of HIV-1 and is necessary for viral infectivity. Human Apolipoprotein B editing complex protein 3G(h-APOBEC3G) is a cytidine deaminase only expressed in "nonpermissive" cells and exhibits virus suppressive activity. With the aid of a Cullin-5 E3 ligase, Vif induces h-APOBEC3G degradation and with the destruction of this ligase, Vif is functionally inactive. Therefore, it is expected that blocking this E3 pathway would be a new therapeutic strategy against HIV-1 infection. In this article, the authors' took sequence alignment of the N-termini of Cullin-5 and three other members of the Cullin protein family, respectively. A set of small peptides has been synthesized based on the sequence comparison results and possible Vif-Cullin-5 interaction domains. Moreover, it has been demonstrated that several peptides can reduce virus infectivity in "nonpermissive" cells with a dose-responsive manner, but not in "permissive" cells. The results also indicate that the loss of viral infectivity may be because of the increase of APOBEC3G amount in the peptide-treated cells. It is concluded that peptides derived from Cullin-5 can block the APOBEC3G degradation induced by Vif and suppress HIV-1 infectivity. Therefore this study starts a novel strategy for the development of a new HIV-1 inhibitor. 展开更多
关键词 HIV-1 inhibitor PEPTIDE VIF Cullin-5 APOBEC3G
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Aldo-keto reductases:Role in cancer development and theranostics
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作者 SIDDAVARAM NAGINI PRATHAP REDDY KALLAMADI +1 位作者 KRANTHI KIRAN KISHORE TANAGALA GEEREDDY BHANUPRAKASH REDDY 《Oncology Research》 SCIE 2024年第8期1287-1308,共22页
Aldo-keto reductases(AKRs)are a superfamily of enzymes that play crucial roles in various cellular processes,including the metabolism of xenobiotics,steroids,and carbohydrates.A growing body of evidence has unveiled t... Aldo-keto reductases(AKRs)are a superfamily of enzymes that play crucial roles in various cellular processes,including the metabolism of xenobiotics,steroids,and carbohydrates.A growing body of evidence has unveiled the involvement of AKRs in the development and progression of various cancers.AKRs are aberrantly expressed in a wide range of malignant tumors.Dysregulated expression of AKRs enables the acquisition of hallmark traits of cancer by activating oncogenic signaling pathways and contributing to chemoresistance.AKRs have emerged as promising oncotherapeutic targets given their pivotal role in cancer development and progression.Inhibition of aldose reductase(AR),either alone or in combination with chemotherapeutic drugs,has evolved as a pragmatic therapeutic option for cancer.Several classes of synthetic aldo-keto reductase(AKR)inhibitors have been developed as potential anticancer agents,some of which have shown promise in clinical trials.Many AKR inhibitors from natural sources also exhibit anticancer effects.Small molecule inhibitors targeting specific AKR isoforms have shown promise in preclinical studies.These inhibitors disrupt the activation of oncogenic signaling by modulating transcription factors and kinases and sensitizing cancer cells to chemotherapy.In this review,we discuss the physiological functions of human AKRs,the aberrant expression of AKRs in malignancies,the involvement of AKRs in the acquisition of cancer hallmarks,and the role of AKRs in oncogenic signaling,and drug resistance.Finally,the potential of aldose reductase inhibitors(ARIs)as anticancer drugs is summarized. 展开更多
关键词 Aldo-keto reductases(AKRs) Aldo-keto reductase(AKR)inhibitors CANCER DRUG-RESISTANCE Xenobiotics
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Incidence rate of prostate cancer in men treated for erectile dysfunction with phosphodiesterase type 5 inhibitors: retrospective analysis 被引量:2
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作者 Anthony H Chavez K Scott Coffield +1 位作者 M Hasan Rajab Chanhee Joe 《Asian Journal of Andrology》 SCIE CAS CSCD 2013年第2期246-248,I0008,共4页
The purpose of this study was to determine the incidence rate of prostate cancer among men with erectile dysfunction (ED) treated with phosphodiesterase type 5 inhibitors (PDE-5i) over a 7-year period vs. men with... The purpose of this study was to determine the incidence rate of prostate cancer among men with erectile dysfunction (ED) treated with phosphodiesterase type 5 inhibitors (PDE-5i) over a 7-year period vs. men with ED of the same age and with similar risk factors who were not treated with PDE-5i. In a retrospective review of electronic medical records and billing databases between the years 2000 and 2006, men with ED between the ages of 50 and 69 years and no history of prostate cancer prior to 2000 were identified. These individuals were divided into two groups: 2362 men who had treatment with PDE-5i, and 2612 men who did not have treatment. Demographic data in each group were compared. During the study period, 97 (4.1%) men with ED treated with PDE-5i were diagnosed with prostate cancer compared with 258 (9.9%) men with ED in the non-treated group (P〈00001). A higher percentage of African Americans were treated with PDE-5i vs. those who were not (10.5% vs. 7.1%; P〈O.O001). The PDE-5i group had lower documented diagnosis of elevated prostate-specific antigen (10.0% vs. 13.1%; P=-0.0008) and higher percentage of benign prostatic hyperplasia (38.4% vs. 35.1%; P=0.0149). Men with ED treated with PDE-5i tended to have less chance (adjusted odds ratio: 0.4; 95% confidence intervals: 0.3-0.5; P〈0.0001) of having prostate cancer. Our data suggest that men with ED treated with PDE-5i tended to have less of a chance of beine diaenosed with orostate cancer. Further research is warranted. 展开更多
关键词 erectile dysfunction (ED) phosphodiesterase 5 inhibitors (PDE-5i) prostate cancer prostatic neoplasms
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Cytochrome b5 reductase 2 suppresses tumor formation in nasopharyngeal carcinoma by attenuating angiogenesis 被引量:3
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作者 Huixin Ming Ying Lan +5 位作者 Feng He Xue Xiao Xiaoying Zhou Zhe Zhang Ping Li Guangwu Huang 《Chinese Journal of Cancer》 SCIE CAS CSCD 2015年第10期459-467,共9页
Background:Cytochrome b5 reductase 2(CYB5R2) is a potential tumor suppressor that inhibits cell proliferation and motility in nasopharyngeal carcinoma(NPC).Inactivation of CYB5R2 is associated with lymph node metastas... Background:Cytochrome b5 reductase 2(CYB5R2) is a potential tumor suppressor that inhibits cell proliferation and motility in nasopharyngeal carcinoma(NPC).Inactivation of CYB5R2 is associated with lymph node metastasis in NPC.This study aimed to explore the mechanisms contributing to the anti-neoplastic effects of CYB5R2.Methods:Polymerase chain reaction(PCR) assays were used to analyze the transcription of 84 genes known to be involved in representative cancer pathways in the NPC cell line HONE1.NPC cell lines CNE2 and HONE1 were transiently transfected with CYB5R2,and data was validated by real-time PCR.A chick chorioallantoic membrane(CAM)embryo model was implanted with CYB5R2-expressing CNE2 and HONE1 cells to evaluate the effect of CYB5R2 on angiogenesis.An immunohistochemical assay of the CAM model was used to analyze the protein expression of vascular endothelial growth factor(VEGF).Results:In CYB5R2-transfected NPC cells,PCR assays revealed up-regulated mRNA levels of Fas cell surface death receptor(FAS),FBJ murine osteosarcoma viral oncogene homolog(FOS),phosphoinositide-3-kinase regulatory subunit 1(PIK3R1),integrin beta 3(ITGB3),metastasis suppressor 1(MTSSl),interferon beta 1(IFNB1),and cyclin-dependent kinase inhibitor 2A(CDKN2A) and down-regulated levels of integrin beta 5(ITGB5),insulin-like growth factor 1(IGF1),TEK tyrosine kinase(TEK),transforming growth factor beta receptor 1(TGFBRl),and VEGF.The angiogenesis in the CAM model implanted with CYB5R2-transfected NPC cells was inhibited.Down-regulation of VEGF by CYB5R2 in NPC cells was confirmed by immunohistochemical staining in the CAM model.Conclusion:CYB5R2 up-regulates the expression of genes that negatively modulate angiogenesis in NPC cells and down-regulates the expression of VEGF to reduce angiogenesis,thereby suppressing tumor formation. 展开更多
关键词 CYTOCHROME b5 reductase 2 NASOPHARYNGEAL carcinoma CHICK embryo model ANGIOGENESIS
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ASSOCIATION OF PLASMA HOMOCYSTEINE LEVEL AND N^5, N^(10) -METHYLENETETRAHYDROFOLATE REDUCTASE GENE POLYMORPHISM WITH CEREBRAL INFARCTION 被引量:5
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作者 张颖冬 朱志刚 刘阳 《Chinese Medical Sciences Journal》 CAS CSCD 2002年第4期231-235,共5页
Objective. To investigate the relationship of plasma homocysteine (Hcy) level to stroke and genetic factor to elevated plasma Hcy level.Methods. The plasma Hcy level was measured by capillary electrophoresis- ultravio... Objective. To investigate the relationship of plasma homocysteine (Hcy) level to stroke and genetic factor to elevated plasma Hcy level.Methods. The plasma Hcy level was measured by capillary electrophoresis- ultraviolet detection and the gene polymorphism of N5, N10 - methylenetetrahydrofolate reductase (MTHFR) was studied with PCR - RFLP assay in 43 patients with cortical cerebral infarction and 42 healthy controls.Results. The plasma Hcy level of the patients ( 19. 3 + 6. 0 μ mol/L) was markedly higher than that of the controls (13.7 + 5.4 μ mol/L) ( t = 4. 16, P < 0. 001). There are 3 genotypes, C/C, C/T and T/T, about base - variation of MTHFR gene at locus 677. The plasma Hcy level of the subjects with T/T genotype was higher than that of subjects with other genotypes. However, the frequencies of each genotype and allele were not significantly different between the patients and the controls.Conclusions. The elevated plasma Hcy level is a risk factor for atherothrombotic cerebral infarction, and is related to the C→T mutation at locus 677 of MTHFR gene. 展开更多
关键词 HOMOCYSTEINE N5 N10-methylenetetrahydrofolate reductase cerebral infarction
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Evaluation and diagnostic testing of erectile dysfunction in the era of phosphodiesterase type 5 inhibitors 被引量:1
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作者 Kenneth Jacobsohn Run Wang 《Asian Journal of Andrology》 SCIE CAS CSCD 2007年第1期3-7,共5页
The diagnosis and treatment of erectile dysfunction has changed dramatically since the availability of safe and effective oral therapies. Unfortunately, not all men can be adequately treated in this way, and might req... The diagnosis and treatment of erectile dysfunction has changed dramatically since the availability of safe and effective oral therapies. Unfortunately, not all men can be adequately treated in this way, and might require more invasive testing to diagnose and treat the specific cause of their dysfunction. This review looks at the tests and strategies available for men who cannot be treated by oral therapy alone. 展开更多
关键词 erectile dysfunction TESTING TREATMENT DIAGNOSIS phosphodiesterase type 5 inhibitors
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Primary 4-3-oxosteroid 5β-reductase deficiency:Two cases in China 被引量:9
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作者 Jing Zhao Ling-Juan Fang +3 位作者 Kenneth DR Setchell Rui Chen Li-Ting Li Jian-She Wang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第47期7113-7117,共5页
Aldo-keto reductase 1D1(AKR1D1) deficiency,a rare but life-threatening form of bile acid deficiency,has not been previously described in China.Here,we describe the first two primary 4-3-oxosteroid 5β-reductase defici... Aldo-keto reductase 1D1(AKR1D1) deficiency,a rare but life-threatening form of bile acid deficiency,has not been previously described in China.Here,we describe the first two primary 4-3-oxosteroid 5β-reductase deficiency patients in China's Mainland diagnosed by fast atom bombardment-mass spectroscopy of urinary bile acids and confirmed by genetic analysis.A high proportion of atypical 3-oxo-4-bile acids in the urine indicated a deficiency in 4-3-oxosteroid 5β-reductase.All of the coding exons and adjacent intronic sequence of the AKR1D1 gene were sequenced using peripheral lymphocyte genomic DNA of two patients and one of the patient's parents.One patient exhibited compound heterozygous mutations:c.396C>A and c.722A>T,while the other was heterozygous for the mutation c.797G>A.Based on these mutations,a diagnosis of primary 4-3-oxosteroid 5β-reductase deficiency could be confirmed.With ursodeoxycholic acid treatment and fat-soluble vitamin supplements,liver function tests normalized rapidly,and the degree of hepatomegaly was markedly reduced in both patients. 展开更多
关键词 Primary 4-3-oxosteroid 5β-reductase gene CHOLESTASIS Bile acid therapy Aldo-keto reductase 1D1 Bile acid synthetic defects
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