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151.
Qu CF Li Y Song YJ Rizvi SM Raja C Zhang D Samra J Smith R Perkins AC Apostolidis C Allen BJ 《British journal of cancer》2004,91(12):2086-2093
Control of micrometastatic pancreatic cancer remains a major objective in pancreatic cancer treatment. The overexpression of MUC1 mucin plays an important role in cancer metastasis. The aim of this study was to detect the expression of MUC1 in human primary tumour tissues and three pancreatic cancer cell lines (CAPAN-1, CFPAC-1 and PANC-1), and target MUC1-positive cancer cells in vitro using (213)Bi-C595 alpha-immunoconjugate (AIC). The expression of MUC1 on pancreatic tumour tissues and cancer cell lines was performed by immunohistochemistry and further confirmed by confocal microscope and flow cytometry analysis on the cell surface. Cytotoxicity of (213)Bi-C595 was tested by MTS assay. Apoptosis was documented using TUNEL assay. Overexpression of MUC1 was found in approximately 90% of tested tumour samples and the three pancreatic cancer cell lines. (213)Bi-C595 is specifically cytotoxic to pancreatic cancer cells in a concentration-dependent fashion. These results suggest that overexpression of MUC1 in pancreatic cancer is a useful target, and that the novel (213)Bi-C595 AIC selectively targets pancreatic cancer cells in vitro. (213)Bi-C595 may be a useful agent for the treatment of micrometastases or minimal residual disease (MRD) in pancreatic cancer patients with overexpression of MUC1 antigen. 相似文献
152.
Li Y Abbas Rizvi SM Blair nee Brown JM Cozzi PJ Qu CF Ow KT Tam PN Perkins AC Russell PJ Allen BJ 《International journal of radiation oncology, biology, physics》2004,60(3):896-908
PURPOSE: Control of metastatic prostate cancer (CaP) is an elusive objective. Some 30% of patients with clinically localized CaP will develop micrometastatic disease. Defining the expression of tumor-associated antigens on CaP will enable appropriate selection of therapeutic targets. METHODS AND MATERIALS: The expression of tumor-associated antigens on CaP cell lines (PC-3, DU 145, and LNCaP-LN3) was detected by immunohistochemistry and flow cytometry. Test and control alpha-conjugates were prepared using monoclonal antibodies, an inhibitor, plasminogen activator inhibitor type 2, that binds to the cell-membrane-bound protease, urokinase plasminogen activator, and a control protein labeled with (213)Bi using standard methods. These were used singly or together against three different CaP cell lines in vitro. The cytotoxicity of the alpha-conjugates was assessed using the [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] (MTS) assay. RESULTS: The PC-3 and DU 145 cancer cell lines expressed antigens that bind monoclonal antibodies BLCA-38 and #394 (mouse anti-human urokinase plasminogen activator B-chain) but not J591. The LNCaP-LN3 cells bound J591 but not #394 or BLCA-38. For the PC-3, DU 145, and LNCaP-LN3 cell lines, multiple-targeted alpha-therapy combining four alpha-conjugates (one-quarter doses of each) gave D(0) (37% cell survival) values of 15, 17, and 27 microCi/mL compared with those of the controls of 272, 289, and 281 microCi/mL, respectively. CONCLUSION: Metastatic prostate cancer-associated antigens recognized by multiple monoclonal antibodies are potential targets for alpha-therapy. Multiple-targeted alpha-therapy produced cytotoxicity specific to three CaP cell lines and may form the basis of treatment for micrometastatic CaP, overcoming the heterogeneity of expression of the targeted antigens. 相似文献
153.
Rizvi AA 《Annals of internal medicine》2004,141(3):243; author reply 243-243; author reply 244
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1. Changes in the activity of acetylcholinesterase (AChE) have been reported in diabetes mellitus that have been linked to certain brain defects. The erythrocyte membrane AChE is reported to be similar to AChE present in the brain. 2. Epicatechin, a member of a group of polyphenolic compounds collectively known as "catechins" that are present in tea and belong to the flavonoid family, has been reported to possess insulin-like activity. 3. In the present study, the in vitro effect of (-)epicatechin and/or insulin was tested on erythrocyte membrane AChE in normal and type 2 diabetic patients. The aim of the study was to test the efficacy of (-)epicatechin to mimic insulin in its effect on erythrocyte membrane AChE. 4. Acetylcholinesterase activity was significantly lower in type 2 diabetic patients than in normal controls and in vitro insulin treatment restored this activity to normal levels. Epicatechin (1 mmol/L) also caused an elevation in AChE activity in diabetic erythrocytes, an effect that was similar to the effect of insulin. 5. Epicatechin has a pronounced insulin-like effect on erythrocyte membrane-bound AChE in type 2 diabetic patients; however, the mechanism of action of epicatechin remains speculative. 相似文献
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An alpha-emitting immunoconjugate (AIC) against malignant melanoma was prepared from the radioisotope bismuth-213 and a melanoma monoclonal antibody, and was used to control the growth of subcutaneous melanoma in a nude mouse model. Activity tolerances were found to be 8 mCi/kg for intraperitoneal injection of the conjugate, and 10 mCi/kg for intralesional injections. Local targeted alpha therapy (TAT) via intralesional injections of activities in the range 12.5-200 microCi shows a very high level of inhibition of tumorigenesis and regression of tumours. Results show that isolated cancer cells and preangiogenic cell clusters can be eliminated by local TAT, and that intralesional injections of 100 microCi of AIC are sufficient to cause complete regression of melanomas with volumes up to 300 mm3 without any observed side effects. Systemic TAT was less effective, with all tumours experiencing growth delay and limited inhibition of tumour growth. These data provide the basis for clinical trials of TAT in recurrent subcutaneous melanoma. 相似文献
160.