Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rabbit polyclonal antibodies (pAb) were raised against a yeast ras-related protein YP20 and shown to be immunoreactive with human normal as well as altered Ha-ras and Ki-ras p21 gene products using immunoblotting and immunoprecipitation techniques. The p21 protein revealed by anti-YP20 antibodies comigrates with p21 protein detected by anti-p21 monoclonal antibody (Cetus Diagnostics). These pAbs were tested against a panel of human acetone-fixed tumor cell lines and malignant effusions and nonfixed fresh-frozen tissue sections obtained from cancer patients by the indirect immunofluorescence assay (IFA). Twelve of sixteen (75%) sarcoma and carcinoma cells lines and one fibroblast cell line were stained by the anti-YP20 pAb. The binding occurred most commonly in the cytoplasm. Six of eight fresh-frozen colon and breast cancer tissue sections were immunostained and normal sections from these organs or skin showed only low level of binding to the pAbs. Four of five malignant effusions were distinctively immunostained. These antibodies are suggested to serve as additional probes for assessing the expression of ras gene-related proteins in human malignancy.
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PMID:A yeast-derived ras-gene-related protein expressed in human tumor cells. I. Detection by polyclonal antibodies. 307 93

A retrospective cooperative study was undertaken to analyze the fate of 300 clinical Stage I and II breast cancer patients who were alive and apparently cured with both breasts preserved, 10 years following primary limited surgery with irradiation. All patients had been treated by tumor excision, with or without axillary dissection, followed by megavoltage radiation therapy. Follow-up ranged from 10.5 to 26 years, median 14.5 years. The overall actuarial survival (Kaplan-Meier) of the 300 "cured" patients was 86% at 15 years and 78% at 20 years, with 38.5% of deaths attributable to breast cancer. The actuarial probability of remaining free of metastatic disease was 91% at both 15 and 20 years, independent of age or clinical stage. Sixteen patients (5.3%) developed recurrent cancer in the treated breast beyond the tenth year, the actuarial probability of remaining free of breast recurrence being 94% and 90% at 15 and 20 years, respectively. Contralateral breast cancers developed during the second decade in 5 patients, with a cumulative risk of 6.5% at 20 years. Significant treatment-related problems appeared during the second decade in 5 patients, including one chest wall sarcoma; all of these patients had received at least 60 Gy to breast and regional nodal areas. A comparison of these results with those in the literature allowed the following conclusions to be drawn: (a) the risk of death, as well as breast cancer mortality during the second decade, are similar for both conservatively and radically treated patients with Stage I and II breast cancer; (b) the risk of contralateral breast cancer is not greater than that observed following primary radical surgery without radiation therapy; (c) ipsilateral breast "recurrences" continue to occur at about 1% per year during the second decade. Such late recurrences are highly operable and have a favorable prognosis; (d) late progression of treatment-related sequelae is uncommon. This analysis supports the continued use of breast-conserving surgery with radiation therapy in the treatment of Stage I and II breast cancer.
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PMID:The second ten years: long-term risks of breast conservation in early breast cancer. 311 88

The effect of preoperative intra-arterial infusion of mitomycin C, 5-fluorouracil (5-FU) and adriamycin (ADM) were studied in seven patients with locally advanced breast cancer, including five inflammatory carcinomas, and a patient with stromal sarcoma of the breast. Reducing rate of the primary tumor of more than 30% was observed in all cases, and remarkable degenerative changes of tumor cells were histologically noted in six out of eight surgical specimens. The tissue concentrations of 5-FU and ADM were also studied in five breast cancer patients. There was no correlation between the concentration of 5-FU or ADM and histological effect. In intra-arterial infusion, ADM seemed to have a high affinity to the regional lymphnode and breast tumor, compared to normal breast tissue and might also be applicable to the control of lymphnode metastasis. Three out of six cases which received radical mastectomy subsequently had recurrence except in the regional lymphnodes and the prognosis was unsatisfactory (5 year survival was 2/4). Other alternative or multi-disciplinary treatment seems to be necessary for improving the survival rate.
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PMID:[Preoperative intra-arterial infusion chemotherapy in locally advanced primary breast cancer-tissue concentrations of 5-fluorouracil and adriamycin, and the histological evaluation]. 314 Jul 32

Iproplatin [cis-dichlor-trans-dihydroxy-bis-isopropylamine platinum (CHIP, JM9)] is a new antineoplastic platinum analogue with an octahedral conformation. It has more water solubility than does cisplatin and was found to have less neurotoxicity and nephrotoxicity in experimental animals than cisplatin. Like cisplatin, it has been demonstrated to have a broad spectrum of activity in experimental tumor systems. A phase I study of iproplatin was conducted in 28 patients (12 with melanoma, 8 with sarcoma, 6 with breast cancer, and 2 with colon cancer). All patients had failed prior chemotherapy. Four consecutive doses of iproplatin were administered at weekly intervals followed by a rest period of two weeks for hematologic recovery (one course). One hundred forty-two weekly doses were administered with all patients except three receiving at least one full course. The weekly starting dose of 40 mg/m2 was increased to 120 mg/m2 given over 30 minutes without hydration. Myelosuppression predominantly thrombocytopenia, was the dose-limiting toxicity at weekly doses of greater than or equal to 95 mg/m2 per course. With iproplatin doses 75 mg/m2, 95 mg/m2, and 120 mg/m2, the lowest median granulocyte counts were 2.6 x 10(3)/mm3, 2.2 x 10(3)/mm3, and 1.8 x 10(3)/mm3, respectively. Similarly, at iproplatin doses of 75 mg/m2, 95 mg/m2, and 120 mg/m2, the lowest median platelet counts were 144 x 10(3)/mm3, 99 x 10(3)/mm3, and 31 x 10(3)/mm3, respectively. Mild to moderate nausea and vomiting were observed in the majority of patients. No significant neurotoxicity, nephrotoxicity, or ototoxicity was observed. Objective tumor regression was not observed in this study.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I study of weekly-administered iproplatin [cis-dichloro-trans-dihydroxy-bis-isopropylamine platin (chip, JM9)]. 322 43

Observations of cancer risk in irradiated human populations over time after exposure suggest that there are at least two, and perhaps more, very different patterns of temporal distribution of risk for radiation-induced cancer. The first, exemplified by bone sarcoma following therapeutic injection of 224Ra and chronic granulocytic leukemia in Japanese A-bomb survivors, is an early, wave-like pulse consisting of an increase in risk followed by a gradual decline back to baseline levels. The second, exemplified by breast cancer following a brief exposure to external gamma ray or X ray, and by lung cancer and stomach cancer in A-bomb survivors, is an increase in relative risk over about 10 years to a value which appears to remain constant over time thereafter. The first pattern suggests that tumor growth kinetics may play a central role in the temporal distribution of risk following exposure, while the second seems more consistent with multi-event models for carcinogenesis, in which radiation or some other cause of early events must be followed by one or more later events whose frequencies depend mainly on attained age. There are, however, other data that appear to conform to neither of the two models just mentioned. Influences of other cancer causes, like tobacco smoking, are potentially serious confounding factors in studies of induction period.
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PMID:Temporal distributions of risk for radiation-induced cancers. 331 74

Observation of one kindred with sarcoma, breast cancer and other neoplasms has led to the recognition of a familial cancer syndrome in young patients. To date, 24 affected families have been enrolled in the Cancer Family Registry of the National Cancer Institute, and 21 others have been reported in the literature. The major feature of the syndrome is an autosomal dominant pattern of breast cancers and sarcomas of bone and soft tissue at unusually early ages. Additional components of the syndrome appear to be brain tumors, leukemia, and adrenocortical carcinoma in children and adolescents. Family members are prone to develop multiple primary cancer. In addition to descriptive reports, the syndrome has been detected in segregation analysis of a consecutive series of children with soft tissue sarcomas; in studies of breast cancer among mothers of unselected children with sarcomas; and in prospective observation for new cancers in our previously reported families. Laboratory studies are in progress to seek the gene(s) associated with this syndrome of diverse cancers. Studies of this rare disorder may provide new insights into the pathogenesis of the 5 component tumors, particularly breast cancer, the commonest cancer among women in the United States and elsewhere.
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PMID:Keynote lecture. The familial syndrome of sarcomas and other neoplasms. 333 95

Previous research has shown that mothers of children with soft tissue sarcoma, osteosarcoma, and chondrosarcoma are at excess risk of developing breast cancer. The occurrence of malignant disease in the mothers of a population-based series of children with Ewing's sarcoma was investigated in order to determine whether these mothers were at excess risk of cancer and of breast cancer in particular. Sixty-one mothers were traced; there were two cases of breast cancer and two other registrable neoplasms. Risk of malignancy in the mothers was not in excess of expectation.
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PMID:Malignant disease in the mothers of children with Ewing's tumour. 335 41

Clinical studies have demonstrated an altered pineal function in cancer patients. Owing to the documented antineoplastic activity of the pineal gland, these anomalies could have a prognostic significance. This study was carried out to monitor changes in blood levels of melatonin, the most important pineal hormone, in relation to the clinical response to chemotherapy in human neoplasms. The study included 42 cancer patients of both sexes (breast cancer, 10; lung cancer, 13; colon cancer, 11; soft tissue sarcoma, 4; testicular cancer, 1; Hodgkin's disease, 1; peritoneal mesothelioma, 2). Melatonin serum levels were measured by radioimmunoassay before and 28 days after each cycle of chemotherapy. The results showed that, irrespectively of the type of tumor and chemotherapeutic regimen, 12/16 patients (75%) whose melatonin markedly enhanced after chemotherapy had an objective regression. In contrast, 2/26 patients only (8%) whose melatonin did not enhance after chemotherapy had a clinical response. The percentage of objective responses was statistically significantly higher in patients with a chemotherapy-induced melatonin increase than in those with no melatonin increase (p less than 0.001). This study seems to demonstrate that melatonin determination can be used as a predictor of the objective response to chemotherapy in cancer patients. Moreover, it suggests that the antineoplastic effect of cytotoxic drugs may require participation of the pineal gland.
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PMID:Melatonin increase as predictor for tumor objective response to chemotherapy in advanced cancer patients. 340 Jan 24

Central pathology review for quality assurance in cooperative clinical cancer trials has been an accepted practice for over a decade. However, the actual value of such pathology review has never been statistically evaluated or the need defined in a comprehensive manner. Pathology exclusions in 35 completed and ongoing Eastern Cooperative Oncology Group (ECOG) trials were analyzed. Ineligibility rates ranged from 0% to 16.9%. The lowest ineligibility rates occurred in breast cancer, small cell and non-small cell lung cancer, squamous cell carcinoma of head and neck, and gastrointestinal carcinoma protocols. The highest rates occurred in rare cancers such as malignant thymoma, endocrine carcinomas, and in the sarcoma-mesothelioma area. Simulated prototypical trials involving an aggressive and an indolent cancer were examined to evaluate the precision with which treatment differences would be measured when pathologically ineligible cases were included. Analysis of these models indicated that in trials in which the pathology exclusion rate is greater than 10%, slide review is prudent. When the exclusion rate is 5% to 10%, the necessity for pathology confirmation depends on the scientific objective of the trial. If less than 5% pathology exclusions characterize a clinical trial, routine pathology review is not justified. Routine histopathologic review for quality assurance in cooperative groups is not always necessary and may be eliminated in studies of the more common cancers. The practical value of reallocating limited pathology resources for investigative studies in cooperative groups is significant.
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PMID:Statistical and empirical evaluation of histopathologic reviews for quality assurance in the Eastern Cooperative Oncology Group. 340 67

The limitations of the agar suspension culture method for primary culturing of human tumor cells prompted development of a monolayer system optimized for cell adhesion and growth. This method grew 83% of fresh human tumor cell biopsy specimens, cultured and not contaminated, from a heterogeneous group of 396 tumors including lung cancer (93 of 114, 82%); melanoma (54 of 72, 75%); sarcoma (46 of 59, 78%); breast cancer (35 of 39, 90%); ovarian cancer (16 of 21, 76%); and a miscellaneous group consisting of gastrointestinal, genitourinary, mesothelioma, and unknown primaries (78 of 91, 86%). Cell growth was characterized morphologically with Papanicolaoustained coverslip cultures and cytogenetically with Giemsastained metaphase spreads. Morphological features such as nuclear pleomorphism, chromatin condensation, basophilic cytoplasm, and melanin pigmentation were routinely seen. Aneuploid metaphases were seen in 90% of evaluable cultures, with 15 of 28 showing 70% or more aneuploid metaphases. Colony-forming efficiency ranged between 0.01 and 1% of viable tumor cells, with a median efficiency of 0.2%. This culture system uses a low inoculum of 25,000 viable cells per well which permitted chemosensitivity testing of nine drugs at four doses in duplicate from 2.2 X 10(6) viable tumor cells and radiation sensitivity testing at five doses in quadruplicate from 0.6 X 10(6) cells. Cultures were analyzed for survival by computerized image analysis of crystal violet-stained cells. Drug sensitivity studies showed variability in sensitivity and in survival curve shape with exponential cell killing for cisplatin, Adriamycin, and etoposide, and shouldered survival curves for 5-fluorouracil frequently seen. Radiation sensitivity studies also showed variability in both sensitivity and survival curve shape. Many cultures showed exponential cell killing, although others had shouldered survival curves. This method for growing cells from primary human biopsy specimens is more efficient than the agar culture method, enables easier and better biological analysis of the actual cells grown, and permits improved characterization of drug and radiation survival curves.
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PMID:Drug and radiation sensitivity measurements of successful primary monolayer culturing of human tumor cells using cell-adhesive matrix and supplemented medium. 348 78


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