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41.
HI Pass JS Donington P Wu P Rizzo M Nishimura R Kennedy M Carbone 《Canadian Metallurgical Quarterly》1998,116(5):854-859
BACKGROUND: A cohort (20%) of patients with mesothelioma will not have an exposure to asbestos. Recently, a DNA tumor virus (simian virus 40) has been shown to cause hamster mesotheliomas; we previously described simian virus 40-like DNA amino terminus sequences in 29 of 48 mesotheliomas. We analyzed an additional 42 mesotheliomas to determine (1) whether our initial observations were durable and (2) the extent to which the simian virus 40 genome is present in mesotheliomas. METHODS: Genomic DNA was extracted from snap frozen mesothelioma tumor samples and from the simian virus 40-induced hamster mesothelioma tumor H9A. Polymerase chain reaction primers were used to amplify various simian virus 40 large T-antigen regions including a 105-base pair amino terminus fragment, a 281-base pair carboxyl terminus fragment, and a 310-base pair fragment of the enhancer promoter region. Endonuclease digestions and Southern blotting were used to verify the expected product. RESULTS: Thirty of the 42 (71%) samples amplified T-antigen amino sequences, and specificity was verified by Southern hybridization. Sixteen of 42 samples (38%) amplified the appropriate size fragment for the carboxyl terminus, and digestion with BsaB1 matched that of H9A. Twenty-two of 42 samples (52%) amplified simian virus 40 regulatory sequences and Fok1 digestion matched that of the hamster control tumor. Sequence analysis (4 patients) revealed 100% homology with the regulatory region of simian virus 40 strain 776. CONCLUSIONS: These data suggest an association between the simian virus 40 virus and human mesothelioma that could be exploited for diagnostic/therapeutic options including early detection and potential vaccination strategies. 相似文献
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PURPOSE: To evaluate the 10-year outcome of patients with invasive (T2-3N0M0, staged according to the tumor, node, metastasis system) bladder cancer who responded completely to a combination of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) chemotherapy followed by bladder-sparing surgery. PATIENTS AND METHODS: Of 111 surgical candidates who received neoadjuvant MVAC, 60 (54%) achieved a complete clinical response (T0) on transurethral resection (TUR) of the primary tumor site. Of these, 28 requested follow-up with TUR alone, 15 had a partial cystectomy, and 17 elected a radical cystectomy. The patients were followed up for a median of 10 years (range, 8 to 13 years). RESULTS: Of 43 patients who had bladder-sparing surgery, 32 (74%) are alive, which includes 25 (58%) with an intact functioning bladder. Twenty-four patients (56%) developed bladder tumor recurrences from 5 to 96 months, which were invasive in 13 (30%) and superficial in 11 (26%). Thirteen patients required a salvage cystectomy, of whom 6 died, which includes 4 (9%) from a new invasive neoplasm. Of the 17 patients who had radical cystectomy, 11 (65%) are alive. CONCLUSION: The majority of patients with invasive bladder tumors who achieve T0 status after neoadjuvant MVAC chemotherapy preserve their bladders for up to 10 years with bladder-sparing surgery. The bladder remains at risk for new invasive tumors. Cystectomy salvages the majority, but not all, of relapsing patients. 相似文献
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LA Moulopoulos MA Dimopoulos D Weber L Fuller HI Libshitz R Alexanian 《Canadian Metallurgical Quarterly》1993,11(7):1311-1315
PURPOSE: To assess prospectively the role of magnetic resonance (MR) imaging in the staging of patients with a solitary bone plasmacytoma (SBP). PATIENTS AND METHODS: Twelve consecutive patients with an apparent SBP underwent MR imaging of both the primary tumor and the thoracic and lumbosacral spine to seek additional foci of marrow involvement that might have been undetected by standard skeletal survey. All patients received megavoltage irradiation (total dose, 40 Gy) to the primary lesion. RESULTS: MR imaging of the thoracic and lumbosacral spine showed additional foci of marrow replacement in four of 12 patients, with signal characteristics identical to those of the primary tumor. In all four patients, the abnormal protein persisted at greater than 50% of the pretreatment value following radiation treatment. In contrast, the myeloma protein disappeared or was reduced by greater than 50% in five of the six patients with secretory disease and without additional marrow abnormalities. One of four patients progressed to multiple myeloma 10 months after diagnosis with new lesions on conventional radiographs in the same areas as detected previously by MR imaging. CONCLUSION: Four of 12 patients considered to have a SBP by standard criteria may have been understaged, because MR imaging showed additional marrow abnormalities consistent with myeloma. MR imaging of the spine may contribute to the initial staging of SBP, especially since some patients may be cured with radiotherapy. 相似文献
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HI Ismail Y Hashimoto Y Kon K Okada WC Davis T Iwanaga 《Canadian Metallurgical Quarterly》1996,52(3):201-212
Mammary glands of pregnant, lactating and resting goats were studied by immunohistochemistry for lymphocyte subpopulations using a panel of monoclonal antibodies. All T lymphocyte subpopulations that may have a role in the immune response, CD2+, CD4+, CD8+ and gamma delta T cells and subsets, were present in the mammary gland and were noted to increase in number progressively during pregnancy, decrease significantly during lactation, and then moderately increase during the resting period. CD4+ cells, the predominant cell type in the mammary gland, were located mainly in the connective tissue, whereas CD2+, CD8+ and TcR1-N24+ cells were predominant in the intraepithelial areas. TcR1-N6+ cells were detected almost exclusively during pregnancy, being localized mainly in the connective tissue. Their proportion decreased markedly following parturition. Very few WC1-N3+ and -N4+ cells were detected in the mammary gland. It is suggested that the majority of gamma delta T lymphocytes in the mammary gland of the goat are CD2+ CD8+ WCl-, a distinctive subset from that of the WCl+ subset in peripheral blood. 相似文献
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Oxidation of catechol estrogens (CE) leads to the reactive electrophilic CE quinones. Reaction of CE-3,4-quinones with DNA has been implicated in tumor initiation. One pathway to prevent this reaction is conjugation of CE quinones with glutathione (GSH). Four CE, 4-hydroxy estrone (4-OHE1), 4-hydroxyestradiol (4-OHE2), 2-OHE1, and 2-OHE2, were conjugated with GSH after oxidation catalyzed by horseradish peroxidase (HRP), lactoperoxidase (LP), or rat liver microsomal cytochrome P450. This reaction is a free-radical chain autoxidation that produces very high yields of products. Six mono-GSH conjugates, 4-OHE1(E2)-2-SG, 2-OHE1(E2)-1-SG, and 2-OHE1(E2)-4-SG, and four di-GSH conjugates, 4-OHE1(E2)-1,2-bisSG and 2-OHE1(E2)-1,4-bisSG, were identified and quantified. These di-GSH conjugates were also obtained quantitatively from oxidation of mono-GSH conjugates by the same enzymes. HRP and LP gave very similar product profiles. Phenobarbital- and 3-methylcholanthrene-induced microsomes with either NADPH or cumene hydroperoxide as cofactor oxidized 4-OHE2 to form similar amounts of GSH conjugates. Enzymatic oxidation of 2-OHE1(E2) in the presence of GSH produced more 2-OHE1(E2)-4-SG than the 1-isomer. This contrasts with the direct reaction of E1(E2)-2,3-Q and GSH, in which the 1-isomer is formed more abundantly than the 4-isomer (Cao, K., Devanesan, P. D., Ramanathan, R., Gross, M. L., Rogan, E. G., and Cavalieri, E. L. (1998) Chem. Res. Toxicol. 11, 909-916). Competitive enzymatic oxidation of equimolar 4-OHE2 and 2-OHE2 in the presence of an equimolar amount of GSH yielded more 2-OHE2 conjugates than 4-OHE2 conjugates, despite E2-3,4-Q being more reactive with GSH than E2-2,3-Q. These results suggest that 2-OHE2 is a better substrate than 4-OHE2 in the catalytic oxidation to quinones, despite the greater reactivity of E2-3,4-Q, compared to E2-2,3-Q, with GSH. 相似文献
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The effect of mixidine fumarate on myocardial chronotropic responses to various stimulants was examined. Mixidine decreased elevated heart rate in the anesthetized dog to basal levels. It produced a dose-related decrease in heart rate elevated reflexly by aminophylline, by beta adrenergic stimulation induced by isoproterenol, by sympathetic nerve stimulation and by intravenous infusion of glucagon. Mixidine attenuated the increase in contractile force produced by sympathetic nerve stimulation but not that induced by isoproterenol. The compound antagonized the increase in rate of isolated guinea-pig atria induced by both isoproterenol and histamine. In the conscious dog, mixidine caused no decrease in resting heart rate, mean arterial pressure and cardiac output. It reduced atropine-induced sinus tachycardia as well as that induced by treadmill exercise. Experiments in the dog heart-lung preparation indicated that attenuation of an epinephrine-induced sinus tachycardia led to a decrease in myocardial oxygen consumption and an increase in myocardial efficiency. These studies suggest that mixidine fumarate induces an antichronotropic activity by a direct effect on the sinoatrial node and by attenuating sympathetic nervous system input to the heart. 相似文献
50.