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Glutathione transferase isoenzymes in cultured rat hepatocytes 总被引:1,自引:0,他引:1
Y Vandenberghe D Glaise D J Meyer A Guillouzo B Ketterer 《Biochemical pharmacology》1988,37(12):2482-2485
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目的 探讨经尿道汽化切除术在伴有膀胱出口梗阻的前列腺癌治疗中的应用价值.方法 伴膀胱出口梗阻(BOO)症状的前列腺癌(PCa)患者33例.对18例术前确诊经治疗后仍存在梗阻的PCa患者,手术以切除引起梗阻的癌组织,使尿路通畅为目的 .对15例术前未确诊患者按良性前列腺增生(BPH)切除,7例患者术中冷冻切片确诊PCa后,同时行睾丸切除术.8例患者术后病理确诊后再行睾丸切除术和(或)抗雄激素治疗.结果 33例患者手术均成功.术后暂时性尿失禁5例,肉跟血尿9例.27例患者随访10~36个月.死于PCa 8例,平均生存31个月.死于其他原因5例.术后3个月时血清前列腺特异性抗原(PSA)为(10.2±6.7)μg/L;剩余尿量平均(39.7±13.9)ml;国际前列腺症状评分(IPSS)为(8.7±1.6)分.各项指标与术前相比,差异均有统计学意义(P<0.05).结论 经尿道汽化切除术对伴有膀胱出口梗阻的前列腺癌有可靠的治疗作用,且在特定的情况下有协助诊断的作用. 相似文献
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Prostate cancer is the most prevalent cancer found in men above the age of fifty years and is frequently diagnosed in men between 45 and 89 years of age with a median age of 72 years. This work was undertaken to assess oxidative stress and anti oxidant status in patients with carcinoma of prostate. Glutathione (GSH), Malondialdehyde (MDA), Super Oxide Dismutase (SOD) levels in Erythrocytes and plasma Glutathione-S-Transferase (GST) levels were estimated in patients with carcinoma of prostate and compared to controls. It was observed that Erythrocyte GSH levels were significantly lower and Erythrocyte MDA & SOD levels were significantly higher in patients with carcinoma of prostate compared to controls. No significant change was observed in case of GST compared to controls. Oxidative stress may be involved in prostate cancer as evidenced by the higher MDA levels and lower GSH levels. The increased activity of antioxidant enzyme may be a compensatory regulation in response to oxidative stress. 相似文献
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目的探讨膀胱尿路上皮癌患者机体氧化应激变化及其与疾病严重程度的关系。方法膀胱癌组来自2009年6月至2011年6月我院收治的膀胱尿路上皮癌患者共159例,包括非肌层浸润性膀胱癌(Ta、T1)患者117例、肌层浸润性膀胱癌(T2以上)42例。选择同期健康体检人群120例作为正常对照组。分别检测各组血清维生素(Vit)C、VitE、超氧化物歧化酶(SOD)、谷胱苷肽过氧化物酶(GPx)、丙二醛(MDA)、总抗氧化活性(AOA)等。结果膀胱癌组血清VitC、VitE、SOD、GPx、AOA均明显低于正常对照组[(0.023±0.006)ms/L比(0.057±0.009)mg/L,(0.082±0.021)mg/L比(0.149±0.012)ms/L,(31±12)kU/L比(201±31)kU/L,(2136±436)U/L比(7674±922)U/L,(0.90±0.04)nmol/L比(1.67±0.29)nmo]/L,均P〈0.01];但MDA含量明显高于正常对照组[(12.6±4.2)ixmol/L比(3.1±0.9)μmol/L,P〈0.01]。非肌层浸润性膀胱癌患者血清VitC、VitE、SOD、GPx均明显高于肌层浸润性膀胱癌[(0.027±0.014)mg/L比(0.012±0.005)ms/L,(0.095±0.019)ms/L比(0.046±0.007)ms/L,(37.1±10.9)kU/L比(14.9±2.7)kU/L,(2422±457)U/L比(1339±264)U/L,均P〈0.01];MDA含量低于肌层浸润性膀胱癌[(7.8±1.1)μmol/L比(25.8±3.6)μmol/L,P〈0.01];2组AOA差异无统计学意义(P〉0.05)。结论膀胱尿路上皮癌的发生发展与机体氧化应激有关,补充外源性抗氧化剂可能有助于膀胱尿路上皮癌的治疗和预防。 相似文献
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目的探讨急性尿潴留、尿路感染、慢性前列腺炎等合并症对良性前列腺增生(BPH)患者前列腺特异性抗原(PSA)的影响,评价总PSA(TPSA)与游离PSA(FPSA)/TPSA在BPH和前列腺癌鉴别诊断中的应用价值。方法对144例BPH以及前列腺癌患者进行PSA测定,其中前列腺癌组30例、BPH无合并症组43例、BPH有合并症组71例(合并急性尿潴留组23例、合并尿路感染组36例、合并慢性前列腺炎组12例),并对各组患者的血清TPSA及FPSA/TPSA比值的差异进行比较分析。结果前列腺癌组血清TPSA[(61.1±29.3)μg/L]明显高于BPH无合并症组[(2.8±0.6)μg/L]和BPH有合并症组[合并急性尿潴留组(5.1±2.6)μg/L,合并尿路感染组(6.7±2.0)μg/L,合并慢性前列腺炎组(8.1±5.3)μg/L],差异均有统计学意义(均P〈0.05),FPSA/TPSA比值[(0.14±0.02)μg/L]明显低于BPH无合并症组[(0.27±0.04)μg/L]和BPl4有合并症组[合并急性尿潴留组(0.26±0.06)μg/L),合并尿路感染组(0.25±0.05)μg/L,合并慢性前列腺炎组(0.23±0.07)μg/L,差异均有统计学意义(均P〈0.01);而有、无合并症的BPH各组之间上述指标差异均无统计学意义(均P〉0.05)。结论合并急性尿潴留、尿路感染、慢性前列腺炎的BPH患者的TPSA值比无合并症的BPH患者增高,但TPSA、FPSA/TPSA对BPH、前列腺癌仍有鉴别诊断价值。 相似文献
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Onehundred-and-thirteen patients with cancer of the urinary bladder (cases) were examined with respect to the frequency of
null genotypes of the polymorphic glutathione S-transferases GSTM1 and GSTT1. The allelic background in the German population
of the area was evaluated by analysing 170 newborns (controls). The frequency of GSTM1 and GSTT1 null genotypes in this population,
using methods based upon internal standard controlled polymerase chain reaction (PCR), was 0.54 and 0.18 respectively. An
elevated relative bladder cancer risk of GSTM1 null genotype carriers was indicated by comparison of this background with
the data of the bladder cancer cases (OR = 1.81; 95% CI [1.10, 2.98]; p = 0.019). The frequencies of the GSTT1 null genotype in the total group of bladder cancer cases versus controls did not differ
statistically. However, a significantly higher relative risk of bladder cancer for the GSTT1 null genotype was detected in
the cases-subgroup of non-smokers (OR = 3.84; 95% CI [1.21, 12.23]; p = 0.023). Thus, the GSTT1 null genotype might represent a minor risk factor for human bladder cancer which should be further
investigated.
Received: 2 May 1996 / Accepted: 16 July 1996 相似文献
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Piirilä P Wikman H Luukkonen R Kääriä K Rosenberg C Nordman H Norppa H Vainio H Hirvonen A 《Pharmacogenetics》2001,11(5):437-445
Diisocyanates are the most common low molecular weight chemicals to cause occupational asthma. However, only some 5-10% of exposed workers develop asthma, which suggests an underlying genetic susceptibility. Diisocyanates and their metabolites may be conjugated with glutathione by glutathione S-transferases (GSTs). We examined whether polymorphisms in the GSTM1, GSTM3, GSTP1 and GSTT1 genes modify allergic responses to diisocyanate exposure. The study population consisted of 182 diisocyanate exposed workers, 109 diagnosed with diisocyanate-induced asthma and 73 without asthma. Lack of the GSTM1 gene (null genotype) was associated with a 1.89-fold risk of diisocyanate-induced asthma [95% confidence interval (CI) 1.01-3.52]. Moreover, among the asthma patients, the GSTM1 null genotype was associated with lack of diisocyanate-specific immunoglobulin (Ig)E antibodies [odds ratio (OR) 0.18, 95% CI 0.05-0.61] and with late reaction in the specific bronchial provocation test (OR 2.82, 95% CI 1.15-6.88). Similarly, GSTM3 AA genotype was related to late reaction in the specific bronchial provocation test (OR 3.75, 95% CI 1.26-11.2). The GSTP1 Val/Val genotype, on the other hand, was related to high total IgE levels (OR 5.46, 95% CI 1.15-26.0). The most remarkable effect was seen for the combination of GSTM1 null and the GSTM3 AA genotype which was strongly associated with lack of diisocyanate-specific IgE antibodies (OR 0.09, 95% CI 0.01-0.73) and with late reaction in the bronchial provocation test (OR 11.0, 95% CI 2.19-55.3). The results suggest, for the first time, that the polymorphic GSTs, especially the mu class GSTs, play an important role in inception of ill effects related to occupational exposure to diisocyanates. 相似文献
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Cetin M Demirci D Unal A Altinbaş M Güven M Unlühizarci K 《Human & experimental toxicology》1999,18(3):137-140
To identify and describe the frequency and severity of hepatotoxicity in patients who received flutamide therapy for prostate cancer, 22 patients were treated with the combination of flutamide and goserilin or orchiectomy. After diagnosis and staging of prostate cancer, baseline results were obtained for a set of five liver function tests (LF Ts). Hepatotoxicity was assessed according to the WHO criteria. After initiation of flutamide therapy, LF Ts were performed at 4, 8 and 12 weeks and every 2 months thereafter. Severe hepatotoxicity appeared in two of 22 (9%) patients. Following the discontinuation of flutamide, one patient died due to acute liver failure. On the other patient an improvement of LF Ts occurred after cessation of flutamide. The observed severe hepatotoxicity in two of 22 (9%) patients occurred more frequent than is predicted in the literature. Patients treated with flutamide, having symptomatic or asymptomatic liver enzyme elevations, should be taken off therapy as soon as possible. 相似文献
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目的探讨膀胱癌患者手术前后尿脱落细胞端粒酶活性的临床意义。方法应用端粒重复序列扩增—微孔板杂交法对 2 4例膀胱癌患者术前尿、2 0例术后尿和 10例正常人尿进行定量端粒酶活性的检测。结果 2 4例膀胱癌患者术前自排尿端粒酶阳性率 83 3% (2 0 / 2 4 ) ,端粒酶活性OD值 0 4 4 8± 0 2 32 ;术后 2 0例膀胱癌患者自排尿端粒酶阳性率 10 0 % (2 / 2 0 ) ,端粒酶活性OD值0 2 16± 0 16 3;10例正常健康人的尿沉渣标本端粒酶活性检测均阴性 ,端粒酶阳性率为 0 0 % (0 /10 ) ,端粒酶活性OD值 0 0 84± 0 0 5 8;膀胱癌患者术前自排尿脱落细胞端粒酶阳性率和端粒酶活性OD值明显高于术后患者尿及正常人尿的端粒酶阳性率和OD值 (P <0 0 0 1)。结论检测尿标本中的端粒酶活性可以作为一种无创伤性的膀胱癌早期诊断和术后随访的指标之一 相似文献
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Bladder cancer is a common genitourinary malignancy and carcinoma in situ (CIS) of the bladder exists as a potentially aggressive variant of the superficial form of the disease. Treatment must reflect the unpredictable nature of this disease entity. In 1976, the use of intravesical Bacillus Calmette-Guerin (BCG) was described for the management of early stage bladder cancer. A subsequent report demonstrated efficacy in a cohort of patients with CIS of the bladder. Since this time, intravesical BCG has been recognised as the initial therapy for CIS of the bladder. Although a 6-week treatment with intravesical BCG has been established as standard therapy in patients with CIS, there has been no consensus as to the subsequent treatment for patients in the setting of failure to initial management with BCG. In addition, a number of reports have demonstrated an increased potential of adverse effects after repeated treatment with intravesical BCG. A variety of alternative immunological and chemotherapeutic agents have been developed in response to the limitations of BCG for patients with refractory CIS of the bladder. At present, valrubicin remains the only agent that is approved by the US Food and Drug Administration for the specific indication of CIS of the bladder unresponsive to intravesical BCG. Although these agents appear promising, the most efficacious therapy remains to be determined. The specific treatment protocol for refractory CIS of the bladder remains elusive. It is ultimately the combined decision of the clinician and patient to determine which course of management is most beneficial. 相似文献
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E C Grose J H Richards R H Jaskot M G Ménache J A Graham W C Dauterman 《Toxicology》1987,44(2):171-179
A 2-h inhalation exposure to 4.6 mg Cd/m3 decreased pulmonary total glutathione peroxidase (GSH Px) activity and non-selenium peroxidase (GSH non-Se-Px) activity but had no effect on GSH selenium peroxidase (Se-Px) activity. Seventy-two hours after exposure there was an increase in total GSH Px and GSH Se-Px activity and a decrease in GSH non-Se-Px activity. Exposure to 0.44 mg Cd/m3 for 2 h caused no effect on GSH Se-Px at either 0 or 72 h post exposure, but total GSH Px and GSH non-Se-Px activities were decreased up to 72 h post exposure. Exposure to 4.6 mg Cd/m3 caused an increase in hepatic GSH Se-Px activity 72 h post exposure, but no other significant changes were observed in the liver. Changes in GSH non-Se-Px activity did not relate to changes in GSH transferase (Tr) activity. The data suggest that alterations in GSH Px activity by Cd2+ may be due to changes in GSH non-Se-Px activity and that changes in pulmonary GSH Tr and GSH non-Se-Px activities may not be as closely linked as in the liver. 相似文献
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《中国医药科学》2019,(20):35-37
目的探讨康复新液联合间苯三酚及帕瑞昔布治疗前列腺电切除术后膀胱痉挛的效果。方法选取2017年2月~2018年7月收治的前列腺电切除术后膀胱痉挛患者90例为研究对象,随机分为对照组与观察组,各45例,对照组接受间苯三酚联合帕瑞昔布治疗,观察组在对照组基础上加康复新液,比较两组治疗效果、膀胱功能。结果观察组治疗总有效率为97.78%,明显较对照组82.22%高,差异有统计学意义(P0.05);与治疗前比较,治疗后的痉挛次数、尿频次数、尿急次数均有下降,且观察组显著优于对照组,组间比较差异有统计学意义(P 0.05);治疗后,两组的膀胱过度活动症评分(OABSS)、膀胱状况感知量表(PPBC)、疼痛视觉模拟评分(VAS)均较治疗前显著降低,且观察组治疗后上述评分显著低于对照组,差异均有统计学意义(P 0.05)。结论康复新液联合间苯三酚及帕瑞昔布治疗前列腺电切除术后膀胱痉挛效果满意,能有效改善膀胱功能,值得推广。 相似文献
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F A Teulings G E Mulder-Kooy H A Peters W Fokkens B Van Der Werf-Messing 《Acta vitaminologica et enzymologica》1975,29(1-6):108-112
In comparison with healthy age- and sex-comparable subjects, a significantly higher concentration of unconjugated 3-hydroxyanthranilic acid was detected in the urine of untreated bladder and kidney carcinoma patients. Because of tryptophan metabolite 3-hydroxyanthranilic acid is suspected to be involved in the carcinogenesis of bladder tumours, it is of importance to know if the concentration will normalize to the level of the control group after curation of the tumours, indicating that the aberration was a result of the disease itself. The first results from a study in bladder carcinoma patients during the follow-up after curation of the tumours suggest a persistent increase in the urinary concentration of free 3-hydroxyanthranilic acid. 相似文献
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Prostate cancer is the most prevalent cancer found in men above the age of fifty years and is frequently diagnosed in men between 45 and 89 years of age with a median age of 72 years. This work was undertaken to assess oxidative stress and antioxidant status in patients with carcinoma of prostate. Erythrocyte ascorbic acid and plasma vitamin E levels were estimated in patients with carcinoma of prostate and compared to controls. It was observed that there was a significant decrease in Erythrocyte ascorbic acid and plasma vitamin E levels in patients with carcinoma of prostate compared to controls. The decrease in the levels of antioxidant vitamins may be due to the increased turnover for preventing the oxidative damage in these patients. 相似文献
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Dichloroacetic acid (DCA) is a drinking water contaminant, a therapeutic agent, and a rodent carcinogen. Glutathione transferase zeta (GSTZ1-1) catalyzes the biotransformation of a range of alpha-haloalkanoates and the cis-trans isomerization of maleylacetoacetate. GSTZ1-1 catalyzes the bioactivation of fluorine-lacking dihaloacetates to S-(alpha-halocarboxymethyl)glutathione, a reactive intermediate that covalently modifies and inactivates the enzyme or is hydrolyzed to glyoxylate. The purpose of this study was to examine the GSTZ1-1-catalyzed bioactivation of DCA, including the reaction of DCA-derived glyoxylate with amino acid nucleophiles and the characterization of the structures and kinetics of adduct formation by LC/MS. The binding of [1-(14)C]DCA-derived label to bovine serum albumin required both GSTZ1-1 and GSH, whereas the binding to dialyzed rat liver cytosolic protein was increased in the presence of GSH. Studies with model peptides (antiflammin-2 and IL-8 inhibitor) indicated that glyoxylate, rather than S-(alpha-chlorocarboxymethyl)glutathione, was the reactive species that modified amino acid nucleophiles. Both addition (+74 Da) and addition-elimination (+56 Da) adducts of glyoxylic acid were observed. Addition adducts (+74 Da) could not be characterized completely by mass spectrometry, whereas addition-elimination adducts (+56 Da) were characterized as 2-carboxy-4-imidazolidinones. 2-Carboxy-4-imidazolidinones were formed by the rapid equilibrium reaction of glyoxylate with the N-terminal amino group of antiflammin-2 to give an intermediate carbinolamine (K(eq) = 0.63 mM(-1)), which slowly eliminated water to give an intermediate imine (k(2) = 0.067 hour(-1)), which rapidly cyclized to give the 2-carboxy-4-imidazolidinone. Glucose 6-phosphate dehydrogenase was inactivated partially by glyoxylate when reactants were reduced with sodium borodeuteride, which may indicate that glyoxylate reacts with selective lysine epsilon-amino groups. The results of the present study demonstrate that GSTZ1-1 catalyzes the bioactivation of DCA to the reactive metabolite glyoxylate. The reaction of glyoxylate with cellular macromolecules may be associated with the multiorgan toxicity of DCA. 相似文献
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Glutathione transferase T1 and M1 genotype polymorphism in the normal population of Shanghai 总被引:8,自引:0,他引:8
Jianhua Shen Goufang Lin Wuxing Yuan Jingwei Tan Hermann M. Bolt Ricarda Thier 《Archives of toxicology》1998,72(7):456-458
Glutathione transferases are known to be important enzymes in the metabolism of xenobiotics. In humans genetic polymorphisms
have been reported for the hGSTM1 and hGSTT1 genes leading to individual differences in susceptibility towards toxic effects,
such as cancer. This study describes the distribution of the two polymorphisms of hGSTT1 and hGSTM1 in the normal Chinese
population of Shanghai. Out of 219 healthy individuals having been genotyped for GSTT1 and GSTM1, 108 (49%) were identified
to be homozygously deficient for the GSTT1 gene and 107 (49%) for the GSTM1 gene.
Received: 26 January 1998 / Accepted: 8 April 1998 相似文献
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目的探讨前列腺电切+内镜引导下耻骨上膀胱造瘘口取石的临床疗效。方法2001年4月~2007年6月应用前列腺电切+内镜引导下耻骨上膀胱造瘘口取石法治疗前列腺增生症合饼膀胱结石患者51例。结果51例病人均排尿通畅,取尽结石。结论经尿道前列腺电切+内镜引导下耻骨上膀胱穿刺造瘘口取石,操作简单,安全有效,尤其适用于前列腺增生症合饼多发性结石患者。 相似文献