氟他胺的临床研究

氟他胺的临床研究中国医学科学院药物研究所（１０００５０）李丽，韩锐氟他胺（Ｆｌｕｔａｍｉｄｅ）是一种非类固醇类抗雄性激素药物。它的药理活性主要由羟化代谢产物２－羟化Ｆｌｕｔａｍｉｄｅ产生，动物研究证明Ｆｌｕｔａｍｉｄｅ的抗雄激素作用，主要影响雄激素依...     

限量饮食对黄曲霉素B_1-DNA加合物生成的影响

本实验用黄曲霉毒素Ｂ１（ＡｆｌａｔｏｘｉｎＢ１，ＡＦＢ１）作为致癌物代表，研究限量饮食（Ｆｏｏｄｒｅｓｔｒｉｃｔｉｏｎ，ＦＲ）对雄性Ｆ３４４大鼠和Ｂ６Ｃ３Ｆ１小鼠代谢活化ＡＦＢ１的影响。ＡＦＢ１－ＤＮＡ加合物（ＡＤＡ）作为ＡＦＢ１代谢活化的生物指标。结果显示ＦＲ降低大鼠和小鼠对ＡＦＢ１的代谢活化，ＡＤＡ的生成在大鼠和小鼠中分别减少４３％和３１％。ＡＤＡ的两种主要加合物的生成、分布和清除以及它们与ＡＦＢ１致癌作用的关系也作了讨论。     

限量饮食对黄曲霉素B1—DNA加成物生成的影响

本实验用黄曲霉霉素Ｂ１（ＡＦＢ１）作为致癌物代表，研究限量饮食（ＦＲ）对雄性Ｆ３４４大鼠和Ｂ６Ｃ３Ｆ１小鼠代谢活化ＡＦＢ１的影响。ＡＦＢ１－ＤＮＡ加合物（ＡＤＡ）作为ＡＦＢ１代谢活化的生物指标。结果显示ＦＲ降低大鼠和小鼠对ＡＦＢ１的代谢活化，ＡＤＡ的生成在大鼠和小鼠中分别减少４３％和３１％。ＡＤＡ的两种主要加合物的生成、分布和清除以及它们与ＡＦＢ１致癌作用的关系也作了讨论。     

单剂量黄曲霉毒素B1致大鼠肝癌作用的短期实验模型

本文报告单剂量黄曲霉毒素Ｂ１（ＡＦＢ１）致大鼠肝癌作用短期实验模型的研究。６周龄、雄性Ｗｉｓｔａｒ大鼠，经腹腔一次性注射不同剂量（０、０．５０、０．７５、１．００和１．５０ｍｇ／ｋｇ体重）的ＡＦＢ１，作为启动剂，两周后，饲以含０．０１５％的２－乙酰氨基芴（２－ＡＡＦ）饲料４周，实验第三周末，施行肝大部分切除术（ＰＨ）。所有动物于实验第６周处死，取肝组织作Ｇａｍｍａ－谷氨酰转肽酶（ＧＧＴ）化学染色，     

环氧乙烷对雄性大鼠生殖功能的影响

环氧乙烷对雄性大鼠生殖功能的影响钟先玖，周元陵，范卫（上海医科大学金山医院职防所）本文用器官重量、精子分析、性激素水平及生育力检测就环氧乙烷（ＥｔＯ）对雄鼠生殖功能的影响进行研究。Ｗｉｓｔａｒ雄性大鼠，静式吸入染毒，２ｈ／天，６天／周，连续染毒１３周...     

Flutamide治疗晚期乳腺癌

Flutamide(SCH-13521)2-甲基-氮[4’硝基-3三氟甲基苯]丙烯胺是酰替苯胺的衍生物。它是一种具有抗雄性素作用的非激素制剂。它可抑制靶细胞摄取雄激素,并阻止雄性索与靶细胞核结合。在成熟雄性大鼠,每天喂饲本品可使前列腺及精囊重量明显减轻。以本品治疗人类晚期前列腺癌,有效率达87.5％。除引起轻度男性乳腺发育及少数患者有轻度肝功能改变外,无其它副作用。近年来发现,绝经期前及绝经期后乳腺癌患者血清雄性素水平均较正常人高,因     

环氧乙烷对雄性大鼠精子形成的影响

环氧乙烷对雄性大鼠精子形成的影响钟先玖，范卫，周元陵（上海医科大学金山医院职防所）本文用光镜和电镜就环氧乙烷（ＥｔＯ）对精子形成的影响进行了研究，Ｗｉｓｔａｒ雄性大鼠，静式吸入染毒，浓度为０、５０、２００和４２０ｐｐｍ，２ｈ／日，６日／周，连续染毒１...     

刺五加抗癌作用的实验研究

目的：为进一步探讨刺五加对实验性肝癌发的干预作用及可能机理。方法：４３只雄性大鼠被随机分成３组（１）正常对照组：喂普通饲料（２）３－ＭｅＤＡＢ组：喂含０．０６％３－ＭｅＤＡＢ饲料１０周（３）刺五加组,除致癌剂外另加入刺五加,历时２０周。实验过程中所有动物均自由进食及饮水。结果：刺五加组较３－ＭｅＤＡＢ组：Ｆ（１）外周血液及肝组织中ＰＡＩ－１含量明显减少。（２）肝细胞周期时相Ｇ０／Ｇ１比率增加,Ｓ期     

游离前列腺特异抗原及其与总前列腺特异抗原比值在前列腺癌诊断中的意义

近来有文献报道，对于前列腺癌诊断，血清游离前列腺特异抗原（ＦＰＳＡ）与总前列腺特异抗原（ＴＰＳＡ）比值（ＦＴＰＳＡ）优于单纯ＴＰＳＡ检测。我科收治６２例前列腺增生（ＢＰＨ）患者和４０例前列腺癌患者，年龄５９～８９岁。用放免法测定血清ＴＰＳＡ和ＦＰＳＡ，比较两组间ＴＰＳＡ、ＦＰＳＡ和ＦＴＰＳＡ的差异，并研究ＴＰＳＡ和ＦＰＳＡ间的相关性。ＢＰＨ和前列腺癌ＴＰＳＡ、ＦＰＳＡ以及ＦＴＰＳＡ比值见表１。相关性分析显示，前列腺癌组ＴＰＳＡ与ＦＰＳＡ之间有显著相关关系（相关系数ｒ＝０．４４，Ｐ＜０．０１…     

胰岛素样生长因子—1对肿瘤及宿主的代谢效应

本文报道在不同营养状态下胰岛素样生长因子－１（ＩＧＦ－１）对肿瘤及宿主蛋白质代谢的影响，Ｓｐｒａｇｕｅ－Ｄａｗｌｅｙ大鼠皮下接种Ｗａｌｋｅｒ２５６癌肉瘤细胞后分组予以禁食或静脉高营养（ｔｏｔａｌｐａｒｅｎｔｅｒａｌｎｕｔｒｉｔｉｏｎ，ＴＰＮ），分别观察外源性ＩＧＦ－１短期应用对肿瘤及宿主蛋白质代谢的改变，结果表明，在禁食状态下，小剂量的外源性ＩＧＦ－１对荷瘤宿主蛋白质代谢无明显影响，而肿瘤蛋白质合     

Development of androgen-independent carcinomas from androgen-dependent preneoplastic lesions in the male accessory sex organs of rats treated with 3,2'-dimethyl-4-aminobiphenyl and testosterone propionate.

Two kinds of cancer can be induced in rat male accessory sex organs, one a non-invasive carcinoma arising in the ventral lobe and the other an invasive lesion which develops in the dorsolateral and anterior lobe as well as the seminal vesicles. In the present study, one group of male rats were given biweekly s.c. injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB) for 20 weeks for induction of non-invasive carcinomas and the other group received DMAB with 40-week testosterone propionate for induction of invasive carcinomas. Half of the animals in each group were then subjected to bilateral orchiectomy at week 41 to remove testicular androgen, in order to examine the androgen dependence of both types of carcinomas as well as precancerous lesions. Animals were killed at weeks 41, 46 and 60. All parts of the prostate complex showed involution and significant weight reduction after castration, with a complete disappearance of atypical hyperplasias and carcinomas of the ventral prostate. However, in spite of suppression of development of atypical hyperplasias in the anterior prostate and seminal vesicles, the incidence of invasive carcinomas was not changed. Normal epithelial cells and atypical hyperplasias of all parts of the prostate and seminal vesicles and carcinomas of the ventral prostate were immunohistochemically positive for nuclear androgen receptor, while invasive carcinomas that developed in either castrated or non-castrated animals were negative. These findings suggest that in the ventral prostate, both precancerous and cancerous lesions are androgen-dependent, but in the anterior and seminal vesicles, cancerous lesions (invasive carcinomas) are androgen-independent while precancerous lesions are hormone-dependent.     

Development of Androgen-independent Carcinomas from Androgen-dependent Preneoplastic Lesions in the Male Accessory Sex Organs of Rats Treated with 3,2'-Dimethyl-4-aminobiphenyl and Testosterone Propionate

Two kinds of cancer can be induced in rat male accessory sex organs, one a non-invasive carcinoma arising in the ventral lobe and the other an invasive lesion which develops in the dorsolateral and anterior lobe as well as the seminal vesicles. In the present study, one group of male rats were given biweekly s.c. injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB) for 20 weeks for induction of non-invasive carcinomas and the other group received DMAB with 40-week testosterone propionate for induction of invasive carcinomas. Half of the animals in each group were then subjected to bilateral orchiectomy at week 41 to remove testicular androgen, in order to examine the androgen dependence of both types of carcinomas as well as precancerous lesions. Animals were killed at weeks 41, 46 and 60. All parts of the prostate complex showed involution and significant weight reduction after castration, with a complete disappearance of atypical hyperplasias and carcinomas of the ventral prostate. However, in spite of suppression of development of atypical hyperplasias in the anterior prostate and seminal vesicles, the incidence of invasive carcinomas was not changed. Normal epithelial cells and atypical hyperplasias of all parts of the prostate and seminal vesicles and carcinomas of the ventral prostate were immunohistochemically positive for nuclear androgen receptor, while invasive carcinomas that developed in either castrated or non-castrated animals were negative. These findings suggest that in the ventral prostate, both precancerous and cancerous lesions are androgen-dependent, but in the anterior and seminal vesicles, cancerous lesions (invasive carcinomas) are androgen-independent while precancerous lesions are hormone-dependent.     

Chemoprevention of prostate carcinogenesis by DFMO and/or finasteride treatment in male Wistar rats

In the present study the chemopreventive activities of DFMO, the irreversible inhibitor of ornithine decarboxylase, and finasteride, the inhibitor of prostatic 5a-reductase, against the development of chemically induced prostate adenocarcinoma by methylnitrosourea/testosterone propionate in male Wistar rats were investigated. According to histological examination, oral administration of DFMO and finasteride, either alone or combined, for two months to MNU/TP-inoculated rats reduced the tumor incidence to 11.11%, 10% and 10%, respectively, compared to tumored controls (64.3%). DFMO and/or finasteride treatment resulted in significant reductions in the wet weight of the prostate gland and seminal vesicles and its ratio relative to the total body weight, as well as the levels of prostate total protein, DNA, RNA and DNA/RNA ratio, compared to tumored controls. However, the effect of the combined treatment was of no statistical significance compared to single DFMO or finasteride treatment, as demonstrated by the non-significant differences between the mean values of most of the studied parameters. The tumor chemopreventive activity and the prostate growth inhibitory effect of DFMO and finasteride were due to suppression of prostate polyamine synthesis. ANOVA test revealed that the relative weight of the prostate as well as blood and tissue polyamine levels could be used as significant endpoint biomarkers for DFMO and finasteride as cancer chemopreventive agents.     

Induction of invasive carcinomas in the accessory sex organs other than the ventral prostate of rats given 3,2'-dimethyl-4-aminobiphenyl and testosterone propionate

The promotion effects of testosterone propionate (TP) on prostate carcinogenesis were investigated in F344 rats given the prostatic carcinogen, 3,2'-dimethyl-4-aminobiphenyl (DMAB). One group of animals received s.c. DMAB injections at a dose of 50 mg/kg body weight at 2-week intervals for a total of 10 injections along with s.c. implantations of TP-containing Silastic tubes. A second experimental group of rats was given DMAB at the same dose and intervals but each injection of DMAB was combined with 3 prior consecutive daily 100-mg/kg body weight s.c. injections of TP. After cessation of carcinogen administration, animals in these two groups received TP implants from week 21 to the end of the experiment. All surviving animals were killed at week 56 and accessory sex gland tumor incidences were compared to those in DMAB alone and other appropriate control groups. The groups given TP plus DMAB and subsequent long term administration of TP developed lesions of the dorsolateral prostate, seminal vesicles, and coagulating glands which were all invasive adenocarcinomas. Incidences were 84.2% (16 of 19 rats) and 66.7% (12 of 18 rats), respectively. Macroscopic large tumors were induced in 13 animals among which 8 demonstrated metastasis to the abdominal cavity, liver, or lung. None of the control groups except for the group given TP injections plus DMAB had equivalent tumors. Development of carcinomas of the ventral prostate, which were all of in situ type, were not increased by subsequent treatment with TP. These data thus clearly showed that TP can exert strong enhancing effects on tumor development in the dorsolateral prostate, seminal vesicles, and coagulating glands but not in the ventral prostate.     

The effects of cholestyramine, colestipol, and ADR-132 on the rat prostate and dunning R-3327 adenocarcinoma

The effects of three compounds known to have hypocholesterolemic activity in several species were investigated on the rat prostate and the hormone-dependent R-3327 rat prostatic adenocarcinoma. Cholestyramine, colestipol, and ADR-132 are bile acid-sequestering anion exchange resins which were fed to separate groups of adult male Copenhagen X Fischer (F1) hybrid rats in doses of 0.25%, 1.00%, and 2.00% of diet. The results indicate that serum cholesterol levels in tumor-bearing rats and controls fed these compounds for 29 days were not reduced. The body and organ weights as well as the histological features of the prostate gland, seminal vesicles, and the R-3327 tumor were unaffected by these agents.     

Introducing a prognostic score for pretherapeutic assessment of seminal vesicle invasion in patients with clinically localized prostate cancer.

PURPOSE: To identify prostate cancer patients who will have the most likely benefit from sparing the seminal vesicles during 3D conformal radiation therapy. METHODS AND MATERIALS: From 1988 to 2001, 532 patients underwent radical prostatectomy for clinically localized prostate cancer. Primary endpoint was the pathological evidence of seminal vesicle invasion. Variables for univariate and multivariate analyses were age, prostate weight, clinical stage, PSA level, Gleason score, number and site of positive prostate sextant biopsies. Multivariate logistic regression with backward stepwise variable selection was used to identify a set of independent predictors of seminal vesicle invasion, and the variable selection procedure was validated by non-parametric bootstrap. RESULTS: Seminal vesicle invasion was reported in 14% of the cases. In univariate analysis, all variables except age and prostate weight were predictors of seminal vesicle invasion. In multivariate analysis, only the number of positive biopsies (P<0.0001), Gleason score (P<0.007) and PSA (P<0.0001) were predictors for seminal vesicles invasion. Based on the multivariate model, we were able to develop a prognostic score for seminal vesicle invasion, which allowed us to discriminate two patient groups: A group with low risk of seminal vesicles invasion (5.7%), and the second with a higher risk of seminal vesicles invasion (32.7%). CONCLUSIONS: Using the number of positive biopsies, Gleason score and PSA, it is possible to identify patients with low risk of seminal vesicles invasion. In this population, seminal vesicles might be excluded as a target volume in radiation therapy of prostate cancer.     

Imaging of primary leiomyosarcoma of the seminal vesicle

Leiomyosarcoma of the seminal vesicle is exceedingly rare. The ultrasound and CT findings in a recent case are described. These consist of a mass causing enlargement of the right seminal vesicle with involvement of the urinary bladder and prostate. The prostate gland was displaced inferiorly and to the left. Surgical resection and subsequent histology confirmed the diagnosis. The role of imaging in retrovesical masses is also discussed.     

Lesions of the prostate glands and seminal vesicles induced by N-methylnitrosourea in F344 rats pretreated with ethinyl estradiol

In an attempt to induce a high incidence of prostate carcinoma, N-methylnitrosourea (MNU), a multipotential carcinogen, was given during the period of cell proliferation of the prostate gland induced by administration of methyltestosterone (MT) to F344 rats pretreated with ethinyl estradiol (EE). Rats were given diet containing EE for 3 weeks and then diet containing 300 ppm of MT for 5 days. On the 3rd day of MT-treatment, they were given a single intravenous injection of 50 mg/kg body wt. of MNU. Control rats (group 4) were given vehicle only. After treatment with MT for 5 days, the rats were given basal diet (group 1), diet containing MT (group 2) or diet periodically containing EE (groups 3 and 4) until the end of the experiment (week 60). Carcinoma of the prostate was found only in 1 of 17 rats in group 3. Atypical hyperplasia of the prostate was found in 1 of 10 rats in group 1 and 3 of 17 rats in group 2. The incidences of atypical hyperplasia of the seminal vesicles in groups 1-3 were 0%, 41% and 29%, respectively. No tumor promoting effect of MT or EE was observed except promotion by MT on the development of atypical hyperplasia of the seminal vesicles.     

Radiotherapy for prostate cancer: should the seminal vesicles be considered target?

During radiotherapy for prostate cancer, the ability to predict occult seminal vesicle invasion is important since irradiation of the entire seminal vesicles necessitates enlarging the radiation fields beyond what is usually used to irradiate the prostate gland alone. We analyzed the records of 302 patients with clinical Stage T1 or T2 adenocarcinoma of the prostate treated with radical surgery at Duke University Medical Center between 1970 and 1983. Univariate and multivariate analyses were used to examine the relationship between the risk of occult seminal vesicle involvement (defined herein as histologic involvement of the seminal vesicles not detected by physical or radiologic examination) and the following factors: histologic grade, age, clinical stage, and preoperative acid phosphatase. Among 249 patients with complete information, increasing histologic grade (p < 0.001) and clinical stage (p < 0.04) were found to be the strongest predictors of occult seminal vesicle invasion. Conversely, seminal vesicle invasion was very unusual in well-differentiated T1-T2 tumors (6%). This low risk group represented 28% (70/249) of this patient population. There appears to be a substantial subset of patients with well differentiated T1 or T2 tumors who are at very low risk for occult seminal vesicle involvement and in whom the seminal vesicles can be excluded from the target volume. The reduction in target volume may reduce normal tissue reactions, facilitate dose escalation, and possibly increase local control rates.