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

This is a review of the most interesting studies on the possible role of sex and gut hormones in gastrointestinal (GI) carcinomas. Many experimental and some human studies suggest that sex and gut peptides may have a growth effect on normal or neoplastic gut cells. It may be possible in the future to develop strategies for patients with GI cancers that will be based upon hormonal manipulation in a manner similar to current strategies that are at present employed in the treatment of patients with breast cancer.
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PMID:[Possible role of sexual and gastrointestinal hormones on cancer of the digestive system]. 136 46

Studies of activity and all-cancer mortality have inconsistent findings and are difficult to interpret, largely because cancer refers not to one disease but to many distinct, site-specific diseases. However, mounting evidence suggests that physical activity may be associated with decreased mortality from and incidence of certain types of cancers. In 15 of 18 studies, higher levels of occupational and/or recreational activity were inversely related to colon cancer incidence and mortality. One major study found activity to be negatively related to occurrence of breast cancer, and conflicting findings exist regarding the association between activity and prostatic cancer. Given the consistency in the direction and magnitude of the findings regarding activity and colon cancer, the presence of appropriate temporal relationships between measured exposure and outcome, the suggestion of dose-response relationships and the existence of plausible biological mechanisms, including increased transit time and gut motility, the evidence supports the conclusion that activity is protective against colon cancer. Although that protective effect may be small, the attributable risk of colon cancer associated with inactivity may be quite high given the prevalence of inactivity in Western societies.
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PMID:Cancer and the protective effect of physical activity: the epidemiological evidence. 143 71

Down syndrome (DS) is a major cause of congenital heart and gut disease and mental retardation. DS individuals also have characteristic facies, hands, and dermatoglyphics, in addition to abnormalities of the immune system, an increased risk of leukemia, and an Alzheimer-like dementia. Although their molecular basis is unknown, recent work on patients with DS and partial duplications of chromosome 21 has suggested small chromosomal regions located in band q22 that are likely to contain the genes for some of these features. We now extend these analyses to define molecular markers for the congenital heart disease, the duodenal stenosis, and an "overlap" region for the facial and some of the skeletal features. We report the clinical, cytogenetic, and molecular analysis of two patients. The first is DUP21JS, who carries both a partial duplication of chromosome 21, including the region 21q21.1-q22.13, or proximal q22.2, and DS features including duodenal stenosis. Using quantitative Southern blot dosage analysis and 15 DNA sequences unique to chromosome 21, we have defined the molecular extent of the duplication. This includes the region defined by DNA sequences for APP (amyloid precursor protein), SOD1 (CuZn superoxide dismutase), D21S47, SF57, D21S17, D21S55, D21S3, and D21S15 and excludes the regions defined by DNA sequences for D21S16, D21S46, D21S1, D21S19, BCE I (breast cancer estrogen-inducible gene), D21S39, and D21S44. Using similar techniques, we have also defined the region duplicated in the second case occurring in a family carrying a translocation associated with DS and congenital heart disease. This region includes DNA sequences for D21S55 and D21S3 and excludes DNA sequences for D21S47 and D21S17.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Down syndrome: molecular mapping of the congenital heart disease and duodenal stenosis. 153 Nov 66

L-Histidinol, a protein synthesis inhibitor and structural analogue of L-histidine, has been demonstrated in chemotherapy-treated mice to be cytoprotective to normal stem cells but to enhance cytotoxicity to tumor cells. N,N-Diethyl-2-[4-(phenylmethyl) phenoxy]ethanamine.HCl (DPPE) is an antagonist of recently described microsomal and nuclear intracellular histamine receptors implicated in the mediation of proliferation and modulation of prostaglandin synthesis. DPPE is cytotoxic to tumor cells in vitro and cytoprotective to the gut in vivo. Noting the similar pharmacologic profiles for histidinol and DPPE and the structural resemblance between histidinol and histamine, we tested 1) whether binding to intracellular histamine receptors may be important to the action of histidinol, 2) whether there exists a differential effect of DPPE and histidinol on proliferating normal and transformed or malignant cells, and 3) whether DPPE, like histidinol, protects host cells from the effects of chemotherapy while augmenting tumor cell kill in vivo. It was observed that histidinol does compete at intracellular histamine receptors in isolated microsomes and nuclei, but with significantly lower affinity than DPPE. Nevertheless, for each agent, potency at intracellular histamine receptors correlates with potency to inhibit DNA and protein synthesis, without cytotoxicity, in normal mitogen-stimulated murine lymphocytes and to kill transformed mouse lymphocytes or MCF-7 human breast cancer cells. As demonstrated previously for histidinol (1-2 g/kg), DPPE (4 mg/kg) protected murine bone marrow progenitors from doxorubicin or fluorouracil, while doses of 4-50 mg/kg significantly enhanced the antitumor activity of doxorubicin and daunorubicin in murine models of early cancer. One postulate to explain the effects of intracellular histamine receptor ligands is that intracellular histamine mediates DNA and protein synthesis, possibly through a downward modulation of growth-inhibitory prostaglandin levels. Antagonism of the intracellular action of histamine at intracellular histamine receptors by DPPE or histidinol may result in differential perturbations of growth/eicosanoid metabolism in normal and malignant cells, thus forming the basis of a new approach to chemotherapy.
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PMID:Increased therapeutic index of antineoplastic drugs in combination with intracellular histamine antagonists. 188 59

Vitamin D3 (D2 is 22-ene,24-methyl D3) is a prehormone which is hydroxylated by mixed function mono-oxygenase NADPH-cytochrome P-450 ferredoxin/ferredoxin reductase systems in liver parenchyma and renal proximal tubular cells to 25-hydroxy, then 1,25-dihydroxyvitamin D, the active hormone. 1,25-dihydroxyvitamin D binds to a mainly intranuclear receptor in target cells [classically, bone, kidney and gut; now shown to be wider including parathyroid cells, endocrine cells generally and many cells of ectodermal (brain, skin) and mesodermal (blood forming cells, lymphnode cells) origin as well as tumour cells (breast, lymphoma, leukaemia)] and activates transcription for products such as calcium binding proteins, its own receptor protein, 24-hydroxylase and non-specific esterase which are active in calcium homeostasis and cell differentiation. Advanced methods for measuring components of the vitamin D endocrine system have been developed and involve column extractions, liquid chromatographic purifications (also HPLC) and protein and receptor binding assays as well as mass spectrometry. These have facilitated elucidation of vitamin D physiology (also in pregnancy and lactation) and of metabolic defects in classical, vitamin D resistant and renal rickets and osteomalacia, in sarcoidosis and in the possible involvement of the vitamin in cell differentiation, e.g. in myeloid leukaemia, and breast cancer.
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PMID:An emerging view of vitamin D. 224 81

Previous studies of the relationship between dietary fat and breast cancer have produced conflicting results and have provided no definitive evidence of a mechanistic link between fat and breast tumorigenesis. We conducted a study to compare postprandial levels of prolactin (Prl), a hormone suspected of promoting the growth of some human breast cancer, and several gut hormones, i.e., gastrin (Gs), vasoactive intestinal polypeptide (VIP), neurotensin (Nt), and cholecystokinin (CCK), following high- and low-fat isocaloric test meals. Data were obtained in the posttreatment period from 13 patients with breast cancer (nine stage I and four stage II), who were disease free clinically, and nine healthy controls. Subjects admitted to the research unit on 2 days were given the high-fat meal on day 1 and the low-fat meal on day 2. Blood samples were drawn before (i.e., fasting) and after test meal consumption. All hormone analyses were performed by radioimmunoassay. Results indicated a significant rise in postprandial Prl levels for stage II patients, but not for stage I patients or the controls. Postprandial Gs levels were also elevated, whereas VIP levels were markedly reduced in patients versus controls; these differences were most marked in stage II patients. No significant intergroup differences were noted in postprandial levels of Nt and CCK. Hormone levels of patients and controls did not differ between the test meal situations, which indicated that some other component of the test meals might have been responsible for altered Prl and Gs levels. The differences observed between the stage I and II patients indicated that diet may influence the aggressiveness of tumor behavior and development through alterations in postprandial hormone release.
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PMID:Postprandial levels of prolactin and gut hormones in breast cancer patients: association with stage of disease, but not dietary fat. 235 41

Environmental factors promote the development of and decrease survival from Breast Cancer. Prospective morphological and hormonal studies indicate biological markers for this disease are evident in premenopausal women. The majority of premenopausal patients are non-obese (Body Mass Index, BMI less than 25). Lean women have a greater proportion of estrogen receptor negative (ER-) tumours, which may grow faster and have a higher concentration of epithelial growth factor (EGF). We have reported that lean, BMI less than 23, versus obese, BMI greater than 28, women have a different gut-pancreatic peptide hormone response to meals and that differences in these peptide hormones occur between healthy and age weight matched premenopausal patients. We hypothesize that the diet peptide hormone control of food intake in lean women is associated with the development of mammary dysplasia, change in growth factor profile and steroid hormone metabolism.
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PMID:Leanness, peptide hormones and premenopausal breast cancer. 264 23

The trophic effect of gut hormones may have important clinical applications for treatment of gut and pancreatic cancers. We now have developed methods by which we can quantitate gut hormone receptors in normal and neoplastic gut mucosa and pancreas. Analysis of gut and pancreatic tumors for gut hormone receptors may thus allow us to select patients with these cancers who would respond to treatment with hormones, antihormones, or hormone ablation in a manner similar to current strategies that are employed successfully for treatment of patients with breast cancer.
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PMID:Effects of gastrointestinal peptides on gastrointestinal cancer growth. 269 52

Prostata cancer is one of the most dangerous tumours occurring in the older man. No general accepted therapy has existed up to now. In this study we were engaged on the pharmacokinetics of fosfestrol (Honvan) after oral administration. Its active principle is E-diethylstilbestrol (E-DES), the main metabolite. 250-1600 ng/ml E-DES are measurable after 60-110 min in the plasma of 11 patients suffering from metastatic prostata cancer who have been administered 360 mg fosfestrol orally. This range is equivalent to E-DES concentrations in plasma of 1-4 x 10(-6) mol/l. Thus that E-DES concentration range (5 x 10(-6) mol/l) is nearly attained for a short time to the concentration which hinders the mitosis of human breast cancer cells. Surprisingly similar but not higher concentration - time courses may be measured after a bolus infusion of 360 mg fosfestrol (lasting 45 min). Furthermore, E-DES-glucuronide, E-DES-sulphate and the mixed E-DES-glucuronide-sulphate could be observed in plasma after oral administration. In spite of the high sensitivity of the analytical method (limit of detection for fosfestrol 0.1 micrograms/ml and for E-DES and its mono-conjugates 2-5 ng/ml) neither fosfestrol nor E-DES-monophosphate are detectable in plasma due to the biotransformation of fosfestrol, which is already metabolized by the enzymes of the gut wall. Both phosphates only exist in plasma after intravenous infusion. Further investigations are linked with the question if phase II-conjugates of E-DES can eventually be prodrugs delivering E-DES by cleavage of the ester bonds.
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PMID:[Drug therapy of metastasizing prostate carcinoma with special reference to the bioavailability of fosfestrol after oral administration]. 305 34

The phenolic lignans enterolactone and enterodiol appear periodically in women's urine, dependent upon synthesis from plant-derived lignans by the intestinal microflora. The phytoestrogen equol is also present in women's urine, and is also derived from a vegetarian diet. Antiestrogenic or antiproliferative actions of these compounds have been postulated and related to the observation that there is a reduced incidence of breast cancer associated with diet. We evaluated the estrogenic and antiestrogenic activity of these compounds using four sensitive assays in tissue culture, including the use of human breast cancer cell lines T47D and MCF-7. Unexpectedly, we found that enterolactone and enterodiol, as well as equol, are weak estrogens, and that enterolactone and equol could stimulate the growth of estrogen-dependent breast cancer cell lines. We suggest that these environmental agents can promote the growth of breast cancer, particularly hormone-dependent metastases that may be located near the gut or in the mesenteries or liver, where the concentration of these intestinally produced compounds would be highest. Treatment with an antiestrogen such as tamoxifen blocks the estrogenic activity of these compounds. In the absence of treatment with an antiestrogen such as tamoxifen, hormonal therapy to block steroidal estrogen synthesis in a patient with breast cancer could conceivably be circumvented by a vegeterian diet rich in the precursors to estrogenic compounds such as enterolactone and equol.
Breast Cancer Res Treat 1987 Nov
PMID:Stimulation of breast cancer cells in vitro by the environmental estrogen enterolactone and the phytoestrogen equol. 342 25


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