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21.
Monoclonal antibody PAb3 to c-erbB-2/neu protein was utilized in the immunoperoxidase staining of 86 human specimens from oral mucosa. These tissue specimens represented a spectrum from 7 normal to 9 simple hyperplasia, 15 mild dysplasia, 14 moderate dysplasia, 20 severe dysplasia and 21 squamous cell carcinoma. Our study indicated that as the cells acquire a more malignant phenotype, there was a progressive increase in neu expression. It also suggested that neu may be involved in the development of oral cancers and that its evaluation in the early stages may assist in the diagnosis and management of oral cancers. 相似文献
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本文采用Iodogen法将鼠抗人胃癌单克隆抗体RSF9(IgM)予以131I标记,研究RSF9在荷人胃癌裸鼠中的定位和显像能力。结果表明,RSF9在体内能特异性地与肿瘤组织结合,T/NT比值随时间延长逐渐升高,96hT/NT比值均大于2.5,瘤/血比值为2.69,肿瘤定位指数达5.18,SPECT得到清晰的肿瘤图像。RSF9具有良好的体内导向定位能力。IgM型单抗也可用于肿瘤显像。 相似文献
23.
Increased expression of certain glutathione S-transferase (GST) isoenzymes has frequently been associated with the development of resistance to alkylating agents and other classes of antineoplastic drugs in drug-selected cell lines. The question arises whether this phenomenon is causal or is a stress-induced response associated with drug resistance in these cell lines. We have constructed mammalian expression vectors containing the human GST mu and GST alpha 2 (Ha2) cDNAs and stably transfected them into the human breast cancer cell line MCF-7. Whereas the parental and pSV2neo-transfected cell lines display low GST activity, three individual transfected clones were identified in each group that expressed either GST mu or GST alpha 2. The range of GST activities was similar to those observed in cells selected for anticancer drug resistance. The GST mu specific activities were 56, 150, and 340 mlU/mg, compared with 10 mlU/mg of endogenous GST mu in control lines. Specific activities in GST alpha 2-transfected clones were 17, 28, and 52 mlU/mg, compared with no detectable alpha class GST in control lines. These clonal lines and the parental and pSV2neo-transfected control lines were tested for sensitivity to antineoplastic agents and other cytotoxic compounds. The clones with the highest activity in each group were 1.7-fold (GST alpha 2) to 2.1-fold (GST mu) resistant to the toxic effects of ethacrynic acid, a known substrate for GSTs. However, the GST-transfected cell lines were not resistant to doxorubicin, L-phenylalanine mustard, bis(2-chloroethyl)-1-nitrosourea, cisplatin, chlorambucil, or the GST substrates 1-chloro-2,4-dinitrobenzene or tert-butyl hydroperoxide. Thus, although L-phenylalanine mustard, bis(2-chloroethyl)-1-nitrosourea, chlorambucil, tert-butyl hydroperoxide, and 1-chloro-2,4-dinitrobenzene are known to be metabolized by glutathione-dependent GST-catalyzed reactions, there was no protection against any of these agents in MCF-7 cell lines overexpressing GST mu or GST alpha 2. We conclude that, at the levels of GST obtained in this transfection model system, overexpression of GST mu or GST alpha 2 is not by itself sufficient to confer resistance to these anticancer agents. These studies do not exclude the possibility that GST may be a marker of drug resistance or that other gene products not expressed in MCF-7 cells might cooperate with GST to confer drug resistance. 相似文献
24.
Age and gender related changes in stereoselective pharmacokinetics and pharmacodynamics of verapamil and norverapamil. 总被引:2,自引:2,他引:0 下载免费PDF全文
S K Gupta L Atkinson T Tu J A Longstreth 《British journal of clinical pharmacology》1995,40(4):325-331
1. Pharmacokinetics and pharmacodynamics of R- and S-verapamil and R- and S-norverapamil were studied at steady state following administration of 180 mg verapamil delivered by a controlled-release gastrointestinal therapeutic system (COER-verapamil). 2. Of the 30 young (19 to 43 years) and 30 elderly subjects (65 to 80 years) enrolled, approximately half of each age group were women; all subjects were healthy and none were smokers. 3. Mean R- and S-verapamil and R- and S-norverapamil Cmax, Cmin, and AUC values for elderly subjects were 1.2 to 2.2 times greater than those for young subjects; these differences were statistically significant at P < 0.05. Median tmax values for young and elderly subjects were not significantly different for any enantiomer. The mean half-life values of R- and S-verapamil for elderly subjects were approximately 20 h compared with approximately 13 h for young subjects, respectively. The mean half-life values of R- and S-norverapamil for elderly subjects were approximately 31 h and 20 h, respectively, compared with approximately 19 h and 21 h for young subjects, respectively. 4. In both age groups, the mean plasma verapamil concentrations of each enantiomer were higher for women than for men at all time points. 5. Mean arterial pressure (MAP) had a significant correlation to R- (r2 = 0.86) and S-verapamil (r2 = 0.87) concentration values that was not influenced by either gender or age of the patient. Change in PR-interval also had a significant correlation to R- and S-verapamil concentration values. However, the sensitivity of the response to changes in R- and S-verapamil concentration values in elderly subjects was about 1/5 of that in younger subjects. 相似文献
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John Goffin Stefan Baral Dongsheng Tu Dora Nomikos Lesley Seymour 《Clinical cancer research》2005,11(16):5928-5934
PURPOSE: Tumor responses in early-phase trials are used to determine whether new agents warrant further study. Given that spontaneous regressions are observed in melanoma and renal cell carcinoma, this study assessed whether tumor responses, particularly in these two tumor types, predict for future regulatory drug approval. EXPERIMENTAL DESIGN: The literature was reviewed to assess tumor response rates to cytotoxic agents in phase I and II trials in the following solid tumors: melanoma, renal cell carcinoma, non-small-cell lung cancer, breast cancer, ovarian cancer, colorectal cancer, and other solid tumors. Response rates were categorized and the relationship of these categories to the end point of regulatory drug approval was determined. RESULTS: Fifty-eight drugs were assessed in 100 phase I trials, and 46 of these drugs were also studied in 499 phase II trials. Higher overall response rates in both phase I trials (P = 0.03) and phase II trials (P < 0.0001) were predictive of regulatory approval. However, response in melanoma or renal cell carcinoma was not predictive for either phase I or phase II studies. CONCLUSIONS: For cytotoxic agents, although overall objective response rates reliably predict subsequent marketing approval, isolated responses in melanoma and renal cell carcinoma are not predictive. 相似文献
28.
珊瑚型人工髋关节置换术的临床随访及松动原因的分析 总被引:5,自引:0,他引:5
自1983年至今应用珊瑚型人工髋关节置换术共54例60髋。其中人工全髋关节置换术34例40髋,人工股骨头置换术20例20髋。在54例60髋珊瑚型人工髋关节置换术中,有37髋随访6个月~13年,平均随访时间约7年,疗效满意率为85.1%,其中假体松动4例占14.8%,髋臼松动2例7.4%。假体松动原因是假体与股骨负重界面之间没有达到稳定接触,假体与髓腔形状不相匹配,修整髓腔松质骨时,髓腔扩大器应比假体小一号,避免假体与界面存留缝隙。对于髋臼发育不良的患者应避免髋关节旋转中心向外侧移位,应向内上方加深髋臼以减少水平移位距离,其次髋臼植骨加盖勿在负重区。 相似文献
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本文研究了26株P_c~r或O_x~r金黄色葡萄球菌的细胞结合青霉素酶。证实它们除有细胞外青霉素酶还具有细胞结合青霉素酶。金黄色葡萄球菌的总青霉素酶活力为22947~387743u/ml。细胞外青霉素酶活力为140~2130u/ml,占总酶含量的1%以下(菌株85051例外);大量青霉素酶是细胞结合的青霉素酶,活力为19937~382033u/ml。 相似文献