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

The hypothesis that low body iron stores are protective against cancer whereas high body stores promote tumor occurrence was examined in the 1-methyl-1-nitrosourea (MNU)-induced experimental model for breast cancer. Twenty-one-day-old female Sprague-Dawley rats were randomized into one of three experimental groups and fed a formulation of AIN-76A diet modified to be low in iron (2 p.p.m.), or the same diet supplemented with an adequate (120 p.p.m.) or excess (1200 p.p.m.) amount of iron provided as FeSO4.7H2O. Rats were maintained on their respective diets throughout the experiment which was terminated 32 weeks post carcinogen administration. Rats were injected i.p. with either 25 mg MNU/kg body wt or the saline-solvent in which MNU was dissolved at 50 days of age. In the first 14 weeks, dietary iron deficiency resulted in a low hematocrit and a decrease in weight gain. The appearance of mammary tumors was markedly suppressed in this group compared to those given an adequate or excess level of iron. It has been reported in the literature that reduction in weight gain due to food restriction at a period immediately after carcinogen administration severely inhibits the subsequent development of tumors. Thus the low tumor incidence in the iron-deficient rats during this time frame could be attributed to the combined effects of low hematocrit and depressed weight gain. For the period between week 14 and week 32, the hematocrit in the iron-deficient animals was maintained at a normal level, and the body wt of these rats was comparable to that of the controls given an adequate level of iron. The rate of tumor appearance in the iron-deficient group during the second half of the experiment was similar to that of the iron-adequate group in the first half of the experiment. In other words, it appeared that once hematocrit and body wt gain were restored to normal in the iron-deficient animals, tumor incidence was only minimally affected by low dietary iron. In the second half of the experiment, the tumor incidence in the adequate iron group seemed to have plateaued, whereas it continued to rise in the excess iron group. Thus excess iron appears to be more prominent than iron deficiency in modification of mammary carcinogenesis, especially when the confounding effects of low hematocrit and reduced weight gain are taken into consideration in the latter case.
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PMID:Effect of dietary iron deficiency or excess on the induction of mammary carcinogenesis by 1-methyl-1-nitrosourea. 198 69

We studied the mode of iron transport and storage in a human breast cancer cell line (HT-24) in comparison with a breast epithelial cell line (HBL-100). It was found that HT-24 cells incorporated over 18 h more 59Fe as compared to HBL-100 (24 vs. 16%). Yet, the number of surface transferrin-binding sites was less in cancer cells (6.2 x 10(5)) than in epithelial cells (8 x 10(5)). Moreover, the transferrin receptors in cancer cells were less affected by iron overloading as compared with epithelial cells. Following immunoprecipitation of isoferritins with specific monoclonal antibodies (MoAbs), it was found that the quantity of de novo synthesized normal ferritin immunoprecipitated with CM-G-8 MoAb was similar in both cancer and epithelial cells. However, the amount of 59Fe incorporated into the protein was significantly higher in HBL-100 cells. In contrast, HT-24 cells synthesized a high amount of placental-like isoferritin (PLF) immunoprecipitated with CM-H-9 MoAb which was significantly higher (p less than 0.001) than in epithelial cells. This isoferritin was characterized by its low iron incorporation. It is noteworthy that the ratio of PLF to normal ferritin was 2:1 in cancer cells and 0.7:1 in epithelial cells, indicating that PLF is a major type of isoferritin synthesized by HT-24 breast cancer cells. Furthermore, a significant amount of PLF was expressed on the surface of cancer cells as compared to epithelial cells. The results of this study suggest that iron supply and distribution in breast neoplastic cells are not controlled similarly to normal cells.
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PMID:Comparison of transferrin receptors, iron content and isoferritin profile in normal and malignant human breast cell lines. 204 66

Like all drugs, combined oral contraceptives (COCs) have side effects that may be harmful or beneficial. During the last 20 years their adverse effects have been fully reported, but their benefits have been largely ignored. Most of the benefits of COCs result from the suppression of ovulation. This means that the advantages they confer are not dose-dependent, provided that ovarian activity is effectively suppressed. The most important health benefit of COCs worldwide is the effective prevention of pregnancy, which carries high risks in developing countries and has a mortality as high as 1 in 150 in Africa. The risk of ectopic pregnancy is reduced by 90% in COC-users compared with women using no contraception. The COC prevents the repeated proliferation of ovarian and endometrial tissue that takes place in the menstrual cycle, and it is therefore not surprising that it reduces the risk of ovarian and endometrial malignancy. What is surprising is that a relative risk of 0.6 for these cancers can be detected after only 12 months or less of COC use, and persists for at least 15 years after the COC is stopped. The COC reduces the incidence of benign breast disease, though not the types of disease linked with breast cancer. It considerably reduces the incidence of benign ovarian cysts, and this has been calculated to avoid 28 operations for functional ovarian cysts per 100,000 pill users every year. The risk of uterine fibroids is reduced by 17% with every five years of COC use. By thickening the cervical mucus, the COC reduces the risk of pelvic inflammatory disease by about 50%. By inhibiting growth and development of the endometrium it reduces the incidence of menorrhagia and consequently iron-deficiency anaemia, and it produces a 40% reduction in the frequency of dysmenorrhoea. Unlike the benefits of the COC, its risks appear to be to some extent dose-dependent. The first serious risk to be discovered was a three- to six-fold increase in venous thromboembolism, which is probably an oestrogen effect and disappears quickly when the COC is stopped. The COC doubles the risk of haemorrhagic stroke, this risk is related to smoking and hypertension, unlike the increased risk of thrombotic stroke. The risk of myocardial infarction is related to smoking and age, and COCs are contraindicated over the age of 35 in smokers though not necessarily in non-smokers. Much of this information, however, is based on studies involving older high-dose COCs. Risks may well be lower with modern COCs, but firm data are lacking.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Benefits and risks of oral contraceptives. 229 44

The purpose of this ongoing study is to determine whether thoracic radiotherapy for lung cancer produces an early increase in serum copper (Cu) concentration, an increase which might predict clinical outcome. Copper and iron concentrations were measured in serum obtained from nonsmall cell lung cancer patients at 0, 1, 2, 4, and 6 weeks after the start of radiotherapy. Control groups included patients irradiated for breast cancer (low dose of radiation to the lung), for endometrial, cervical or prostatic cancer (no dose to lung), and patients with congestive heart failure, pulmonary hypertension, chronic obstructive pulmonary disease (COPD), and cutaneous burns with or without smoke inhalation (no irradiation). Serum Cu concentration increased at least 10 micrograms/dl from the pretreatment level in approximately 75% of the adenocarcinoma and squamous cell lung cancer patients, but in only 1 of 4 undifferentiated lung cancer cases. In virtually all of these responders, serum Cu increased to a maximum at 2 weeks after the start of therapy, then plateaued or decreased slightly despite continuing irradiation. Within the subset of squamous cell lung cancers, there was a direct correlation between the degree of histologic differentiation and both baseline serum Cu concentration and the probability of an early increase therein. In contrast, only 33% of breast cancer patients and 15% of endometrial, cervical and prostate cancer patients exhibited an increase in serum Cu concentration at 2 weeks after the start of radiotherapy. Serum Cu concentration was within normal limits in virtually all patients with congestive heart failure, pulmonary hypertension, and COPD. Burn patients exhibited a significant reduction in serum Cu, although concomitant smoke inhalation increased serum Cu back to low-normal levels. Serum iron concentration did not change significantly in any category of patients. These data suggest that thoracic radiotherapy for well differentiated non-small cell lung cancer is accompanied by an early increase in serum Cu concentration. This increase is partly but not wholly related to lung dose in particular rather than tissue dose in general, and specifically reflects radiation-induced lung injury rather than pneumopathy in general. In lung cancer patients, the change in serum Cu concentration during the first 2 weeks of radiotherapy exhibits a sufficiently broad range (+60 to -13 micrograms/dl) to permit testing this parameter as a predictor of tumor response and pulmonary complications.
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PMID:Serum copper concentration as an index of clinical lung injury. 262 91

Autologous bone marrow transplantation is a promising approach to the treatment of breast cancer but is at present limited to patients without bone marrow metastases. To eliminate malignant clonogenic breast cancer cells from normal human bone marrow, immunomagnetic separation has been combined with chemoseparation using 4-hydroperoxycyclophosphamide. Breast cancer cell lines have been mixed with a 10-fold excess of irradiated human bone marrow from normal donors. Mixtures have been incubated with a combination of five different monoclonal antibodies which bind to epithelial cell surface antigens of Mr 42,000, 55,000, 72,000, 200,000, and greater than 200,000. Antiglobulin coated microspheres which contained magnetite were added, and tumor cells were trapped in a magnetic field. Elimination of tumor cells from the decanted marrow was measured in a limiting dilution assay. Two treatments with antibody and microspheres permitted elimination of 2-4 logs of clonogenic breast cancer cells, depending upon the cell line studied. Similar treatment of nonirradiated normal marrow failed to affect levels of colony forming units-granulocyte-macrophage significantly. Use of immunomagnetic purging in combination with 4-hydroperoxycyclophosphamide eliminated up to 5 logs of tumor cells but reduced the recovery of colony forming units-granulocyte-macrophage. If prompt engraftment is observed following reinfusion of similarly treated marrow in phase I trials, these techniques should permit extension of autologous bone marrow transplantation to a larger population of breast cancer patients.
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PMID:Elimination of malignant clonogenic breast cancer cells from human bone marrow. 266 44

Transferrin (Tf), the major iron-binding protein in the plasma of vertebrate species is an essential growth factor for cells in serum-free media and appears to be involved in the regulation of growth and differentiation of human tissues. We report here that human breast cancer cells secrete a factor immunologically similar to Tf. The secretion of Tf by the hormone-responsive cell-line MCF-7 is stimulated by 17 beta-estradiol and reduced by the antiestrogen 4-hydroxy tamoxifen. These data suggest that Tf secreted by breast cancer cells may be an additional autocrine growth factor confering selective advantages to rapidly proliferating breast cancer cells and perhaps permit tumor cell growth in poorly vascularized areas.
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PMID:Secretion of transferrin by human breast cancer cells. 277 56

Bilateral breast tumors with a histologically scirrhous pattern were conclusively diagnosed as gastric carcinoma metastatic to the breast using mucosubstance histochemistry and electron microscopy. The majority of the carcinoma cells gave histochemically positive reactions for galactose oxidase-Schiff, stable class III con A, and high-iron diamine-alcian blue (HID-AB). Also electron microscopically, numerous HID-positive mucus droplets (sulfomucin) were seen in the carcinoma cells. These findings invalidated the possibility that the carcinomas were primary breast cancer. The practical applications of distinctive patterns of mucus secretion are discussed.
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PMID:Gastric carcinoma metastatic to the breast diagnosed by mucosubstance histochemistry and electron microscopy. 285 Dec 54

T-47D human breast cancer cells grown in culture medium containing low concentrations of fetal calf serum (FCS) proliferated very slowly, with an accumulation of cells in the G2 phase of the cell cycle, increased polyploid cells, and increased expression of transferrin receptors. Cell proliferation was stimulated by the addition of human transferrin or ammonium ferric citrate to the medium. Growth inhibition and accumulation of G2-phase cells could also be produced in T-47D cells grown in medium containing 10% FCS by the addition of the iron chelator, desferrioxamine. It is concluded that cellular deprivation of iron and/or transferrin is the major cause of reduced proliferation rates and G2-phase arrest which accompany the culture of these cells in medium supplemented with low concentrations of FCS.
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PMID:Cell cycle effects of iron depletion on T-47D human breast cancer cells. 299 33

The contribution of lipid peroxidation to the killing of human breast cancer cells by gamma-linolenate (GLA) was examined. Other fatty acids of different cytotoxic potential containing 2, 4, 5, and 6 double bonds were also tested for comparison. It was found that the cytotoxic potential varied with the ability of the fatty acids to stimulate the production of superoxide radicals. Neither hydrogen peroxide nor hydroxy radicals are significantly involved in cell killing. As nonspecific indicators of lipid peroxidation, measurements of the loss of unsaturated fatty acid in the phospholipids together with the generation of hydroperoxide breakdown products were done with the use of the thiobarbituric acid test. The results of these experiments showed that the effectiveness of a given fatty acid in killing cancer cells correlated with the intracellular thiobarbituric acid-reactive material (TBARM) content: GLA and arachidonate with 3 and 4 double bonds generated the most TBARM and were the most cytotoxic fatty acids, whereas docosahexaenoate with 6 double bonds was the least effective either in raising TBARM or in killing the malignant cells. Iron and copper accelerated the rate of cell death, whereas antioxidants such as vitamin E and butylated hydroxyanisole inhibited the effect of GLA dose dependently. Indomethacin, an inhibitor of endoperoxide formation, did not reduce either cell kill or TBARM amounts. In contrast, the addition of vitamin E acetate to the cancer cell cultures challenged with eicosapentaenoate reduced both cell killing and TBARM content. These results suggest that the effectiveness of a given fatty acid in killing cancer cells correlated with the extent of lipid peroxidation of the added fatty acid in the cells.
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PMID:Polyunsaturated fatty acid-induced cytotoxicity against tumor cells and its relationship to lipid peroxidation. 334 10

The structure/activity relationships for inhibition of aromatase and cholesterol side-chain cleavage enzyme (CSCC) by aminoglutethimide and some of its analogues are reviewed. Although more effective against aromatase than CSCC, aminoglutethimide markedly inhibits both enzymes. Optimal competitive antagonism of aromatase is obtained with a free amino or basic group at the 4' position of the phenyl ring substituent. This is important because two major metabolites of aminoglutethimide where the amino group is conjugated have low or no inhibitory effect on aromatase. Relocation of the free amino group to the nitrogen atom of the piperidinedione ring enhances CSCC inhibition. The piperidinedione ring is not essential for inhibitory activity, several 4'-aminophenyl pyrrolidinediones being as potent as aminoglutethimide for aromatase but less effective against CSCC. In this series 3-(4'-aminophenyl)-pyrrolidine-2,5-dione is a selective aromatase inhibitor. Inactivity of 4'-aminophenyl derivatives of imidazolidinedione and pyrimidinetrione indicate that the 4'-aminophenyl moiety alone is insufficient for antagonist activity against aromatase. Replacement of the aminophenyl group by the stronger basic 4-pyridyl moiety in aminoglutethimide yields a selective aromatase inhibitor. The structure/activity data suggest that there is a critical distance between the basic centre and the dione moiety for effective aromatase inhibition. Aminoglutethimide and its analogues possessing a free basic centre elicit a Type II difference spectrum with various cytochrome P-450 isozymes. The spectrally-determined binding affinity correlates with inhibitory activity of these compounds and indicates binding of the amino group to the iron centre of this haem enzyme. In reviewing the postulated mechanisms for the enzyme-mediated aromatisation of substrates it is seen that the initial oxidative attack is at the C-19 position of the steroid. It is proposed that two binding or association sites on the protohaem moiety of this P-450 enzyme (iron and propionic acid residues respectively) are required for the orientation of the substrate. Crystallographic evidence indicates there is a distance of about 6.3 A between the C-17 oxygen and the C-19 methyl of the aromatase substrates (these points interacting with the association sites). There is a similar distance between the basic function and the C-6 keto group for aminoglutethimide (and the C-5 keto group for the pyrrolidinediones). It is proposed that aminoglutethimide and its active analogues interact with aromatase at these binding sites competitively inhibiting the aromatisation of androstenedione and testosterone.
Breast Cancer Res Treat 1986
PMID:Pharmacology of aminoglutethimide: structure/activity relationships and receptor interactions. 375 30


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