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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study describes the production of a synthetic hexapeptide (DTRPAP)-based anti-mucin (MUC-1) antibody, similar to those produced using either the intact mucin antigen or tumor extracts. This antibody was generated by immunization of rabbits with the synthetic peptide conjugated to bovine serum albumin as a carrier. Using both the ELISA and FACS analysis methods, we have shown that the antibody is reactive with human ovarian and breast cancer cells, but not with normal epithelial breast cells. This antibody is different from the previously reported anti-mucin HMFG-1, HMFG-2 and SM-3 monoclonal antibodies, since competitive experiments with the free synthetic peptide revealed only a 30% inhibition of HMFG-1 binding to the ovarian (OVCAR-3) cancer cells, as compared to 78% inhibition of the anti-synthetic peptide antibody. The peptide was non-inhibitory for HMFG-2, and induced a significant and reproducible stimulation of the SM-3 binding activity to the tumor cells.
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PMID:A short synthetic peptide (DTRPAP) induces anti-mucin (MUC-1) antibody, which is reactive with human ovarian and breast cancer cells. 992 71

It is known that steroids can induce cell surface receptor aggregation followed by activation of receptor and nonreceptor tyrosine kinases. It has been shown recently that 17beta-estradiol (E2) can stimulate the Src/p21ras/mitogen-activated protein kinase pathway in breast cancer cells, and this effect is supposed to mediate the E2-induced stimulation of breast cancer cell proliferation, possibly via activation of the c-fos and c-jun early genes or of genes involved in cell cycle control. Here we demonstrate the existence of an alternative mechanism of the cancer-promoting effect of E2. Human breast cancer cells (MCF-7) were exposed to the known proapoptotic agent vitamin E succinate (VES), added alone or together with different concentrations of E2. E2 conjugated with bovine serum albumin (E2-BSA), which cannot cross the plasma membrane of living cells, was also used in some experiments to assess whether E2 acted on the cell surface or at intracellular receptors. Apoptosis was analyzed by fluorescence-activated cell sorting after cell staining with propidium iodide and FITC-labeled annexin V. E2 showed a concentration-dependent stimulatory effect on spontaneous apoptosis but inhibited the VES-induced apoptosis. However, effects produced by the same molar concentrations of E2 were different when the hormone was free and when it was used in the form of the E2-BSA conjugate. The effects of E2 and E2-BSA were sensitive to genistein, a tyrosine kinase inhibitor. These data show that E2 modulates apoptosis of breast cancer cells, probably acting both at the cell surface and inside the cells. Tyrosine phosphorylation is involved in the signaling pathways mediating this E2 effect.
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PMID:Estradiol modulates breast cancer cell apoptosis: a novel nongenomic steroid action relevant to carcinogenesis. 1032 69

The formation of oestrone sulphate has been examined in MCF-7 (oestrogen receptor positive, ER+) and MDA-MB-231 (ER negative, ER-) breast cancer cells. Using intact cell monolayers and a physiological substrate concentration, progesterone (1 microM) and dexamethasone (1 microM) both increased oestrone sulphate formation in MCF-7 cells. In MDA-MB-231 cells, dexamethasone, but not progesterone, increased conjugate formation. A number of growth factors, cytokines and human serum albumin (HSA), which have previously been found to regulate oestrogen synthesis, were also examined for their ability to regulate oestrone sulphate formation. In MCF-7 cells epidermal growth factor, acidic and basic fibroblast growth factors, insulin-like growth factor-type I and insulin all stimulated oestrone sulphate formation. The cytokines, tumour necrosis factor alpha (TNFalpha) and interleukin-1beta also increased conjugate formation in the ER+ cells, as did HSA. In contrast, in MDA-MB-231 cells TNFalpha was without effect and HSA inhibited oestrone sulphate formation. The ability to modulate oestrone sulphate formation in ER+ cells may be an important mechanism to limit the availability of oestrogen to interact with the ER.
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PMID:The regulation of oestrone sulphate formation in breast cancer cells. 1036 10

Serum total, different isoforms of both alkaline and acid phosphatases, liver function enzymes, calcium, inorganic phosphate, heamatocrit, white blood cells and platelet counts were determined in 50 female patients suffering from breast cancer. The serum total alkaline and total acid phosphatases within the breast cancer group were variable with significant elevation of both enzymes compared with the corresponding control values. The activities of alanine and aspartate transferases were higher than the control values, while the decreases in serum albumin and heamatocrit were statistically significant. In the breast cancer patients, the increases in the activities of both heat and urea labile alkaline phosphatases were significant. Similarly, in the patients, the tartrate-labile acid phosphatases activity was significantly elevated while the difference in tartrate resistant activity was not significant. In 9 patients (18%), both total alkaline and acid phosphatases were excessively raised when compared with the control. The increased activities of urea-labile and heat-labile alkaline phosphatases as well as tartrate-resistant acid phosphatases are suggestive of increased activities of osteoclast and osteoblasts associated with bone metastasis. A possible diagnostic importance of this observation deserves further investigation, using monoclonal antibody techniques.
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PMID:Abnormal serum alkaline and acid phosphatase isoenzymes in female breast cancer patients. 1045 33

Sentinel node biopsy (SNB) in breast cancer is a promising surgical technique that avoids unnecessary axillary lymph node dissection. To optimize lymphatic mapping with radiopharmaceuticals, mammary lymphoscintigraphy with 30-50 MBq of technetium-99m-diethylenetriamine pentaacetic acid human serum albumin (99mTc-HSAD), technetium-99m-human serum albumin (99mTc-HSA), or technetium-99m-tin colloid (99mTc-TC) were investigated in 69 cases of primary breast cancer. Dynamic early images were obtained during the first 30 or 40 minutes, and static delayed images were obtained 6 hours after tracer injection. Hot spots as sentinel lymph nodes (SLNs) appeared in 51 of 69 cases (74%): in early images in 27 cases and in delayed images in 24 cases. SLNs were visualized more frequently in 23 of the 26 cases (88%) treated with 99mTc-HSAD and in 21 of the 24 cases (88%) treated with 99mTc-HSA than in only 7 of the 19 cases (37%) treated with 99mTc-TC. In 26 of the 51 cases, SLNs were identified as faint spots in delayed images. There was a significant difference in the first appearance of SLNs on the lymphoscintiscan between 43 cases of dense breast parenchyma and 26 cases of fatty breast parenchyma. These results suggest that 99mTc-HSAD or 99mTc-HSA is acceptable for lymphatic mapping, but in cases which have faint spots in delayed images or fatty breast parenchyma, gamma probe-guided SNB may result in failure or misleading false-negative SLNs.
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PMID:Mammary lymphoscintigraphy with various radiopharmaceuticals in breast cancer. 1058 2

A covalent conjugate (NR-LU-10/SA) was prepared between streptavidin (SA) and NR-LU-10, a mAb that binds an antigen expressed on the surface of most human carcinomas. NR-LU-10/SA was injected into nude mice bearing human tumor xenografts. Injection of biotinylated galactosyl-human serum albumin reduced the circulating levels of conjugate by 95%. Subsequent administration of (90)Y-1,4,7, 10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-biotin achieved peak uptake at the tumor within 2 hr while >80% of the radioactivity was eliminated in the urine. A single dose of 600-800 microCi of (90)Y-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-biotin produced cures in 10/10 mice with established (>200 mm(3)) s.c. human small cell lung or colon cancer xenografts and 8/10 cures in mice with human breast cancer xenografts without significant toxicity.
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PMID:Cure of human carcinoma xenografts by a single dose of pretargeted yttrium-90 with negligible toxicity. 1067 37

Sentinel node navigation surgery (SNNS) is a promising surgical technique to avoid unnecessary axillary lymph node dissection (ALND) in breast cancer. There are various choices regarding the site of injection of the vital blue dye or radiopharmaceuticals, the dose of radioactivity used, the interval between dye injection or lymphoscintiscan and SNNS, and various surgical procedures for SNNS in breast cancer. However, many investigators have reported that SNNS is feasible and reliable in histologically sentinel node-negative breast cancer. In our hospital, SNNS with indigocarmine began in January 1998. After a feasibility study of SNNS in 200 cases of early breast cancer, practical SNNS is being performed using indigocarmine and double-tracer technetium-99m-human serum albumin and technetium-99m-tin colloid. As of January 2000, the identification rate of sentinel lymph nodes was 97% and ALND was omitted in 57 (63%) of 90 cases examined. Clinical outcome, arm morbidity, and cost benefits should be evaluated in a randomized trial comparing SNNS to ALND. Nevertheless, SNNS in breast cancer will be necessary for surgical oncologists in the near future.
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PMID:[Sentinel node navigation surgery in breast cancer]. 1077 99

We present a method for the determination of the phytoestrogens daidzein and genistein in plasma (serum). These weakly estrogenic isoflavones occur in soybeans and in smaller amounts in some other beans and plants. It has been suggested that they may afford protection against prostate and breast cancer. The method is based on time-resolved fluoroimmunoassay (TR-FIA) using a europium chelate as a label. After synthesis of 4'-O-carboxymethyl-daidzein and 4'-O-carboxymethyl-genistein the compounds are coupled to bovine serum albumin (BSA), then used as antigens to immunize rabbits. The tracers with the europium chelate are synthesized using the same 4'-O-derivative of the isoflavones. After enzymatic hydrolysis and ether extraction the immunoassay is carried out using the VICTOR 1420 multilabel counter (Wallac Oy, Turku, Finland). The antisera cross-reacted to some extent with some isoflavonoids but not with flavonoids. The cross-reactivity seems not to influence the results, which were highly specific for both compounds. The correlation coefficients between the TR-FIA methods and the reference method based on isotope dilution gas chromatography-mass spectrometry were high; r-values were about 0.95-0.99 depending on concentration. The intra-assay coefficients of variation (CV%) for daidzein and genistein at three different concentrations vary 3.2-4.5 and 3.2-4.1, respectively. The inter-assay CVs vary 5.0-6.3 and 4.5-5.3, respectively. The working ranges of the daidzein and genistein assays are 1.0-216 and 1.7-370 nmol/l, respectively. The plasma values (n = 80) of daidzein and genistein are very low in Finnish subjects (mean for daidzein, 3.8+/-6.8 and for genistein, 3.2+/-7.6 nmol/l; median value for daidzein 1.5 and for genistein 1.4 nmol/l).
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PMID:Time-resolved fluoroimmunoassay of plasma daidzein and genistein. 1080 84

HER2/neu oncogene encodes a 185 kDa trans-membrane protein which is overexpressed in 20-30% of breast and ovarian cancers and portends a poor prognosis. We have studied the targeting and therapy of this oncoprotein with 4D5, a murine monoclonal antibody which recognizes a distinct epitope on the extracelluar domain of HER2/neu. We conjugated the antibody with an active ester of the macrocyclic chelating agent DOTA, radiolabeled the conjugate with either (111)In or (90)Y, and studied the antibody distribution and therapy, respectively, in athymic mice bearing xenografts of MCF7/HER2/neu, a human breast cancer cell line transfected with the HER2/neu oncogene. For the biodistribution of (111)In-labeled DOTA-4D5, a high specificity of tumor localization (30% ID/g) was seen with a tumor-to-blood ratio of greater than 2 at 48 h postinjection. Compared to a previously published study with (125)I-labeled 4D5 in beige nude mice bearing NIH3T3/HER2/neu xenografts [De Santes et al. (1992) Cancer Res. 52, 1916-1923], (111)In-labeled 4D5 antibody gave superior antibody uptake in tumor (30% ID/g vs 17% ID/g at 48h). In the therapy study, treatment of the nude mice bearing MCF7/HER2/neu xenografts with 100 microCi (3 microg) of (90)Y-labeled DOTA-4D5 caused a 3-fold reduction of tumor growth compared to untreated controls (injected with human serum albumin) in 40 days. Treatment of animals with 100 microCi of nonspecific antibody (90)Y-labeled DOTA-Leu16 (3 microg) had no tumor growth inhibition. Treatment with unlabeled DOTA-4D5 (3 microg) had a slight effect on tumor growth compared to untreated controls. When analyzed at the level of single animals, no effect was seen in seven of nine animals; however, in two of the animals, tumor growth inhibition was observed. Although a cold antibody therapeutic effect was unexpected at this dose level (3 microg), it may be possible that in some animals that 3 microg of antibody of (90)Y-labeled DOTA-4D5 augmented tumor growth reduction. To further explore the effects of cold antibody treatment alone, animals were treated with 100 or 400 microg of unlabeled 4D5 administered in two doses. These animals showed a 1.7-1.8-fold reduction in tumor growth over 28 days, a result less than that obtained with RIT only.
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PMID:Biodistribution and radioimmunotherapy of human breast cancer xenografts with radiometal-labeled DOTA conjugated anti-HER2/neu antibody 4D5. 1082 48

Sentinel lymph node excision in breast cancer is a minimally invasive diagnostic procedure for accurate staging of the axilla and for avoiding unnecessary axillary dissection. In patients with palpable breast cancer we injected microcolloidal particles of human serum albumin labelled with technetium-99m the day before surgery. The sentinel node was detected intraoperatively with a handheld gammaprobe and then removed. Complete axillary dissection was performed and the nodes inspected by routine histological examination. The axillary lymph node status was correctly predicted by the sentinel node technique in 32 of 33 breast cancer patients. Two cases of micrometastases escaped routine histopathological detection but were identified by immunohistochemical analysis applying the antibody AE1/AE3 to pancytokeratins. Immunohistochemical examination of the sentinel node improves the diagnostic security of patients with breast carcinoma by detection of micrometastases.
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PMID:Detection of micrometastases in sentinel lymph nodes of the breast applying monoclonal antibodies AE1/AE3 to pancytokeratins. 1085 37


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