Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The CD34 antigen is expressed by 1% to 4% of human and baboon marrow cells, including virtually all hematopoietic progenitors detectable by in vitro assays. Previous work from our laboratory has shown that CD34+ marrow cells can engraft lethally irradiated baboons. Because the CD34 antigen has not been detected on most solid tumors, positive selection of CD34+ cells may be used to provide marrow cells capable of engraftment, but depleted of tumor cells. In seven patients with stage IV breast cancer and two patients with stage IV neuroblastoma, 2.5 to 17.5 x 10(9) marrow cells were separated by immunoadsorption with the anti-CD34 antibody 12-8 and 50 to 260 x 10(6) positively selected cells were recovered that were 64 +/- 16% (range 35% to 92%) CD34+. The patients received 1.0 to 5.2 x 10(6) CD34-enriched cells/kg after marrow ablative therapy. Six patients engrafted, achieving granulocyte counts of greater than 500/mm3 at 34 +/- 10 (range 21 to 47) days and platelets counts of greater than 20,000/mm3 at 46 +/- 14 (range 28 to 66) days posttransplant. Five of these patients showed durable engraftment until the time of death 82 to 386 days posttransplant. One patient failed to sustain engraftment associated with metastatic marrow disease. Three patients died at days 14, 14, and 17 posttransplant, two of whom had evidence of early engraftment. These studies suggest that CD34+ marrow cells are capable of reconstituting hematopoiesis in humans.
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PMID:Engraftment after infusion of CD34+ marrow cells in patients with breast cancer or neuroblastoma. 170 96

Breast cancers treated with the antiestrogen tamoxifen invariably become resistant. To analyze the behavior of cell subpopulations within a tumor following tamoxifen treatment, we have used a new flow cytometry-based immunoassay and software that simultaneously quantitate PR levels and the DNA indices of ploidy and cell cycle stage in total cell populations or any subset thereof. The human breast cancer cell line T47D and its clonal derivatives were used as models of stage IV breast cancer, and growth and PR were measured as markers of antiestrogen responsiveness. We demonstrate and quantitate a remarkable heterogeneity in PR content and show the existence of distinct subpopulations with large differences in their PR levels and DNA indices, even among T47D sublines that are clonally derived. Following chronic tamoxifen treatment, an overall decrease in PR levels and growth masks an extensive heterogeneity in the response of cell subpopulations. PR levels decrease in some cells but increase in others; populations having a growth advantage expand while others contract. We find little evidence that cells, unaffected by the hormone, gain a growth advantage. Rather than exhibiting autonomy, we propose that under the influence of tamoxifen, tumors become remodeled as selected subpopulations emerge that are stimulated by the hormone, explaining the paradoxical recurrence of disease in patients undergoing endocrine therapy.
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PMID:Heterogeneity of progesterone receptor content and remodeling by tamoxifen characterize subpopulations of cultured human breast cancer cells: analysis by quantitative dual parameter flow cytometry. 173 47

The development of new and effective marker substances has optimized tumor-marker-guided follow-up programs to monitor generalization of disease and to assess the therapeutic outcome. Isoferritins of placental origin were first determined in the serum of patients with lymphoproliferative disease by way of the recently developed monoclonal antibody CMH-9. We have set up an Austro-Israeli working group and analysed 64 patients in terms of the sensitivity of placental ferritin (PLF) compared with the standard markers carcinoembryonic antigen (CEA) and mucinous-like cancer-associated antigen (MCA) in patients with metastatic breast cancer. We have additionally evaluated the importance of combined marker determination. Analysis of the data in view of site of metastatic spread yielded satisfying results both for PLF (sensitivity 70.4%) as well as MCA (sensitivity 76.9%) for visceral metastases; a combination of these two markers revealed a striking sensitivity of 88.4%, which, however, could not be improved by adding the third marker (CEA). With regard to non-visceral metastases, CEA and MCA were clearly superior.
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PMID:Placental isoferritin (PLF) in comparison with MCA and CEA in advanced breast cancer--first data from a pilot study. 177 47

In this study we have determined the plasmatic values of carcinoembryonic antigen (CEA) and mucinous like tumor associated antigen (MCA) in 20 women with metastatic breast cancer. CEA and MCA were determined by enzyme immunoassay technique. The results were analyzed by test r for the statement of statistical correlation. Since r was inferior to p 5% (r = 0.3255; p = 0.4438) the 2 parameters are not correlated and their biological expression must be considered independent.
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PMID:[Carcinoembryonic antigen (CEA) and mucinous-like tumor associated antigen (MAC). Statistic correlation in advanced breast carcinoma]. 178 86

Mitoxantrone (DHAD), an anthracenedione with antineoplastic properties similar to doxorubicin, was tested for therapeutic efficacy and for immunomodulating action on lymphocyte subsets in 16 metastatic breast cancer patients, 12 of whom had been previously treated with chemotherapy. DHAD was given intravenously at a dose of 14 mg/m2 every 21 days. To evaluate total T lymphocytes (CD3), T helper (CD4), and T suppressor/cytotoxic cells (CD8) and the CD4/CD8 ratio, venous blood samples were drawn before and after the first DHAD cycle. Moreover, in 8/16 patients, B lymphocytes (CD20), T suppressor cells (CD8+/CD57+), T cytotoxic cells (CD8+/CD57-), NK (CD16) and IL-2 receptor-expressing cells (CD25) were also measured at the same time. An objective tumor response was achieved in 5/16 (31%) patients and the response rate was significantly higher in patients pretreated with hormone therapy alone than in those pretreated with chemotherapy. No relation was found between clinical response and changes in the CD4/CD8 ratio. Neither the mean number nor the percentage of CD3, CDA and CD8 cells observed after DHAD were significantly different with respect to those seen before. In contrast, the mean number of T suppressor cells, B lymphocytes and CD25-positive cells was significantly lower after than before DHAD administration, whereas no difference was seen in NK cells. These results confirm in humans the immunomodulating properties of DHAD previously described in experimental conditions. However, the DHAD-induced changes in lymphocyte subsets do not seem to be related to the clinical response in breast cancer.
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PMID:Mitoxantrone as a single agent in pretreated metastatic breast cancer: effects on T lymphocyte subsets and their relation to clinical response. 186 50

Current research in the area of breast malignancies is focusing on identification of pathogenetic risk factors, chemoprevention, screening policies, local treatment modalities that minimize disfigurement, and improved adjuvant therapeutic and palliative systemic therapies. Although epidemiologic studies have produced contradictory results, oral contraceptive use before age 25 years and before 1st full-term pregnancy appears to increase the breast cancer risk. In need of thorough study is the safest form of estrogen replacement therapy in postmenopause. Screening programs aimed at early detection have been shown to reduce breast cancer mortality by 30% in women 50-69 years of age, but no preventive strategies have been identified for younger and older women. A trend toward breast-conserving primary therapy represents a major shift in this area. As long as the tumor is less than 4 cm in diameter and the resection margins are free of tumor, lumpectomy produces disease-free survival rates comparable to those obtained through total mastectomy. In node-positive patients, hormonal adjuvant systemic therapy is effective in postmenopausal women while chemotherapy is effective in premenopausal women. The data are insufficient to allow recommendations regarding adjuvant treatment of node-negative patients, whose overall survival rate is about 70%. In metastatic breast cancer, tamoxifen is the drug of choice for palliation. Prognostic factors currently under study include oncogene amplification, urokinase plasminogen activator level, expression of growth factors and growth factor receptors, proliferation parameters, mutations, and cathepsin D levels.
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PMID:Breast malignancy. 187 98

The composite methylene (chemical shift range 1.2-1.4 ppm) and methyl (0.8-0.9 ppm) resonances of the 1H NMR spectrum were analyzed in plasma samples from breast tumor patients, pregnant women, and healthy subjects. Using a 500 MHz NMR instrument operating at 25 degrees C, the peaks were analyzed for line width at half height and then averaged. A statistically significant difference (p less than 0.001) was found between the average (mean +/- SD) line width in the plasma samples from the 30 patients with metastatic breast cancer (34.1 +/- 5.0 Hz) and the controls matched for age and sex (38.7 +/- 4.4 Hz). In the 16 patients with localized breast cancer and the 16 with regional spread, the average line width was not different from that of matched controls. In 21 patients with benign tumor in the breast, the average line width was not different from that of matched controls. A difference in the average line width was found between 31 pregnant women in the third trimester (32.5 +/- 3.4 Hz) and their controls matched for age and sex (42.7 +/- 4.6 Hz) (p less than 0.001). The average line width was lower in the late (31.5 +/- 3.3) than in the early (34.5 +/- 2.5 Hz) part of the third trimester (p = 0.022). In 54 healthy male and 130 healthy female controls, line widths declined gradually with increasing age by decades, except in the fifth decade for the men and the sixth decade for the women.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Proton nuclear magnetic resonance spectroscopy measurements of methylene and methyl line widths in plasma: significant variations with extent of breast cancer, duration of pregnancy and aging. 191 Nov 2

In this prospective follow-up study the prognostic value of the tumor prostacyclin/thromboxane ratio in human breast carcinoma was investigated. The stable degradation products of prostacyclin and thromboxane (6-keto-PGF1 alpha and TXB2, respectively), were measured by radio-immunoassay in homogenized primary tumours from 29 patients with primary non-metastatic breast cancer. The median follow-up was 43 months (range 24-58 months). Patients with recurrent disease or patients who died of breast cancer had a significantly higher 6-keto-PGF1 alpha/TXB2 ratio than the disease-free survivors (p = 0.018 and p = 0.047, respectively). There was no significant difference in the 6-keto-PGF1 alpha and TXB2 levels. These data indicate that the prostacyclin/thromboxane balance in the tumour might be a prognostic factor in breast cancer. Prostanoid may contribute to metastasis in breast cancer, but the problem is complex because the different prostaglandins have numerous actions that may produce both undesirable and desirable effects.
Tumour Biol 1991
PMID:Prostacyclin/thromboxane ratio in human breast cancer. 196 47

Since 1983, a series of experimental and clinical studies have been carried out on the possibility of enhancing the chemotherapy effectiveness in breast cancer by expanding the fraction of cycling cells. Theoretically estrogens should recruit breast cancer cells and this fact should result in a higher killing efficiency of antiproliferative drugs. Actually it has been clearly shown, by means of the thymidine labeling index and primer-dependent alpha-DNA polymerase assay, that low doses of diethylstilbesterol are able to increase the tumor proliferative activity of human breast cancer in vivo (estrogenic recruitment). Three randomized trials have been carried out (one in locally advanced and two in metastatic breast cancer) comparing conventional polychemotherapy vs chemotherapy with estrogenic recruitment. Only limited advantages have been observed in these trials. Searching for new modalities of kinetic manipulation of tumors, recombinant human growth hormone has been employed in a pilot study: the preliminary results indicate that it largely enhances tumor proliferative activity, suggesting the possibility of employing a growth factor system to increase chemosensitivity.
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PMID:In vivo manipulation of human breast cancer growth by estrogens and growth hormone: kinetic and clinical results. 198 Oct 14

Because leucovorin increases the antitumor activity of 5-fluorouracil (5-FU) in multiple tumor model systems, we performed a clinical trial to evaluate this combination in women who had received one or no prior chemotherapy regimens for metastatic breast cancer. Thirty-six women with measurable metastatic disease were treated with five consecutive days of i.v. leucovorin, 500 mg/m2/day infused over 30 min, followed 1 h later by i.v. bolus 5-FU, 375 mg/m2/day. Repeat cycles were planned at 4-week intervals. Tumor regression occurred in 10 of 36 patients (28%; 95% confidence interval, 14-45%) with a median time to disease progression (TTP) of 8.7 months (range 3.2-16.8 months) in the responding patients. The median TTP and survival for all patients were 3.0 and 12.4 months, respectively. Among 30 patients who had received prior 5-FU, tumor regressions were seen in seven (23%; 95% confidence interval 10-42%). The major dose-limiting toxicity in this study was mucositis, affecting 89% of the patients. Other toxicities were tolerable in the majority of patients. Although the role of leucovorin in breast cancer clinical practice remains undefined, the data from this trial support the hypothesis that leucovorin enhances the cytotoxic activity of 5-FU against human breast cancer.
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PMID:5-Fluorouracil plus leucovorin in women with metastatic breast cancer. A phase II study. 198 34


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