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)

Predictive tests assisting in selection of breast cancer patients for endocrine therapy have been reviewed. Information gained from histologic sections, such as degree of the tumor differentiation, degree of elastosis, Barr-body count and the DNA content, are valuable predictors of prognosis and response to endocrine therapy. The length of time between mastectomy and recurrence of metastasis is an important factor in predicting response to ablative endocrine surgery. The presence of various enzymes in the tumor tissue, blood groups, immunologic competence, altered metabolism of tryptophan, urinary excretion of steroids and in vitro hormonal responsiveness of the tumor tissue have not been widely used as predictors of tumor response to endocrine therapy. The determination of hormone receptors in primary or metastatic breast tumors is at present the most reliable test in selecting breast cancer patients for endocrine therapy. Future developments in hormone receptor assay may provide a means of tailoring endocrine therapy to the individual patient.
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PMID:[Selection of patients with breast cancer with regard to endocrine therapy]. 19 40

Women with early breast cancer were given a loading dose of L-tryptophan after mastectomy and a comparison made between their excretion of metabolites of the kynurenine pathway and the rate of recurrence of the disease.
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PMID:Tryptophan metabolism and recurrence rates of patients with breast cancer after mastectomy. 124 77

Intracisternal A particles (IAPs) are retrovirus-like structures consistently observable in a variety of mouse tumor cells such as myeloma and hybridoma and in early embryonic cells derived from rodents but nothing is known of their infectivity. Mouse IAPs contain a gag-like protein, a reverse transcriptase and a polyadenylated RNA molecule (IAP RNA). DNA sequences complementary to IAP RNA (IAP genome) are interspersedly present in rodent such as mice, rats, Chinese hamsters and Syrian hamsters at several hundred to a thousand copies per haploid genome. Molecularly cloned IAP genomes from two species Mus and Syrian hamster were 6 to 8 kb in length with LTRs of about 0.4 kb long. The nucleotide sequence of the Syrian hamster IAP genome, H18, predicted a typical LTR-gag-prt-pol-env-LTR structure, although many stop codons were present in the region corresponding to env. The comparison of the deduced amino acid sequences of the pol region showed IAP (type A), mouse mammary tumor virus (MMTV) (type B), and squirrel monkey retrovirus (SMRV) (type D) genomes to be closely related. By using a DNA fragment encoding the pol region of the Syrian hamster IAP genome, human endogenous retroviruses termed HERV-K, were cloned from a fetal human liver gene library. Typical HERV-K genome was 9.5 kb in length having LTRs of about 1.0 kb. The HERV-K provirus could encode gag (666 codons), prt (334 codons), pol (937 codons), and env (618 codons) genes. HERV-K was shown to be closely related to types A, B and D retroviruses. The HERV-K genomes are present at about 50 copies per haploid human genome. In several human tumor cell lines, the HERV-K genome was expressed as 8.8 kb poly(A)+ RNA which appeared to be a full-size transcript of this genome. In the human breast cancer cell line T47D, stimulation of HERV-K genome expression was observed following female steroids treatment. In a detailed investigation on the organization of HERV-K proviruses in human genome, we found repetitive sequences homologous to the LTR region of the HERV-K genome. They were about 630 bp in length with an A rich tail at 3' end and found to be a SINE type nonviral retroposon. These elements were present at 4,000 to 5,000 copies per haploid human genome.
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PMID:Molecular biology of type A endogenous retrovirus. 171 Jun 82

A case-control study was performed to evaluate hormonal status in 154 female patients with bladder cancer and 213 healthy women. Cancer patients were characterized by shorter reproductive period and miscarriage, absence of gestation, endometrial and breast cancer and ovarian cysts in the past history. Evaluation of tryptophan metabolism in 131 male and 111 female patients with bladder cancer showed the occurrence of a carcinogenic metabolite--3-oxyanthranilic acid--in the urine to be higher in women. Blood hormone levels were measured in 55 female patients and 49 healthy women by radioimmunoassay. Decreased levels of progesterone and estradiol as well as of hormones potentiating their production (folitropin and lutropin) were the most frequent hormonal disorders encountered.
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PMID:[Endogenous risk factors for bladder neoplasms in women]. 184 51

Treatment of ZR-75-1 human breast cancer cells with oestrogen has no direct effect on the expression of a transfected MMTV-LTR but enhances its inducibility in response to glucocorticoid treatment. This effect which can be produced with both oestradiol and diethylstilbestrol is specific to induction of the MMTV-LTR, no effect of the treatment on expression driven by the RSV-LTR being observed. The effect can be observed in cells pre-treated with oestrogen prior to removal of DNA and glucocorticoid addition but not in cells where oestrogen is added after removal of the DNA. The possible mechanisms of these effects and their relationship to the induction of oestrogen-responsive genes by this hormone are discussed.
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PMID:Oestrogen enhances the responsiveness of the MMTV-LTR to glucocorticoid in ZR-75-1 human breast cancer cells. 217 Jul 63

RU486 induced the binding to a palindromic progestin responsive element (PRE) in vitro of homo- and heterodimers of the human progesterone receptor (hPR) isoforms A and B, present in T47D breast cancer cells or in HeLa cells transiently expressing the recombinant proteins. The resulting complexes were indistinguishable from those induced with the agonist R5020 with respect to specificity, affinity and stability. Ligand exposure was a necessary prerequisite to observe PR/PRE complexes. Antagonist-induced complexes migrated more rapidly during electrophoresis than agonist-induced ones, and no 'mixed' PR/RU486-PR/R5020 complexes were observed, suggesting that the dimerization interfaces of agonist- and antagonist-bound molecules are non-compatible. The analysis of a series of deletion mutants and chimeric receptors revealed the presence of two transcription activation functions (TAFs), located in the N-terminal region A/B (TAF-1) and the hormone binding domain (TAF-2). In the presence of agonists, both TAFs were active in HeLa cells. In the presence of RU486 TAF-2 was inactive, while TAF-1 within the hPR form B/RU486 complex activated transcription from a reporter gene containing a single palindromic PRE. We consider this to be the most convincing evidence that the receptor/RU486-complex does in fact bind to PREs in vivo. No transcriptional activation was observed in the presence of RU486 from a reporter gene containing the complex MMTV-LTR PRE. In contrast to hPR form B, form A was not able to activate transcription from PRE/GRE-tk-CAT in the presence of RU486. In vivo competition between hPR/RU486 and either cPR/R5020 or the human glucocorticoid receptor/dexamethasone (hGR/Dex) complex further supported that hPR/RU486 bound in vivo to its cognate responsive element. Indeed, the observed inhibition of transcription was shown to be due to competition for the MMTV PRE, since no transcriptional interference by the hPR/RU486 was observed, and since no heterodimers were formed between hPR/RU486 and cPR/R5020 or hGR/Dex. That the ligand-free hPR, however, was unable to compete, demonstrated that ligand binding is the prerequisite for DNA binding of hPR in vivo.
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PMID:Agonistic and antagonistic activities of RU486 on the functions of the human progesterone receptor. 224 58

The precursor of cathepsin D, a lysosomal acidic protease, is secreted by human breast cancer cells, where its synthesis is specifically induced by estrogens and growth factors. In this study, we investigated the hormonal regulation of cathepsin D and its mRNA in uterine cells. In the Ishikawa endometrial cancer cell line, epidermal growth factor (EGF) increased the level of cathepsin D and its mRNA 2- to 3-fold. Although expression of the transiently transfected estrogen-responsive recombinant (Vit. tk. CAT) and the endogenous progesterone receptor was markedly increased by estradiol in Ishikawa cells, estradiol did not alter the level of cathepsin D or its mRNA. The progestin R5020 induced the expression of the LTR sp65 CAT, which contains the progesterone-responsive element of the MMTV but it too was without effect on cathepsin D. By contrast, the expression of cathepsin D gene, in normal rat uterus, was increased by R5020 but not by estradiol. We conclude that cathepsin D gene expression is regulated differently by sex steroid hormones in endometrial and breast cancer cell lines, whereas it is similarly induced by EGF in these cells.
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PMID:Differential regulation of cathepsin D by sex steroids in mammary cancer and uterine cells. 261 33

Melatonin is an indolamine synthesized from tryptophan in the pineal gland. It is regarded as "the epiphyseal hormone". Its antigonadotropic action has been demonstrated in animals, both in vitro and in vivo, together with its inhibitory effect on numerous endocrine functions and its anti-convulsive properties. Recently developed assay methods have made it possible to obtain clinical data, for the moment purely descriptive. Melatonin is present in several body fluids, such as urine, blood and cerebrospinal fluid. It is secreted in circadian cycles, with low concentrations during the day and high concentrations at night; sex has no influence on this pattern, but secretion is highest in the summer and winter and lowest in the spring and autumn. The part played by melatonin in the genesis of puberty is undetermined. Melatonin secretion appears to be mediated by the adrenergic system, since beta-blockers inhibit the nocturnal rise. However, contrary to what happens in animals, most beta-adrenergic stimulants do not increase melatonin concentrations. Abnormal concentrations or perturbations in the melatonin secretion rhythm have been demonstrated in such diseases as breast cancer, cirrhosis of the liver, Klinefelter's syndrome, Cushing's syndrome and haemochromatosis. Depressive syndromes are often associated with abnormal melatonin cycles. It has been suggested that melatonin could be used as a biological marker in cancer and psychiatric diseases, but its physiological function in man remains obscure.
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PMID:[Melatonin]. 293 8

The nutritional status of three groups of postmenopausal women (age 41-80 yrs) with advanced breast cancer was investigated with special reference to vitamin B6. The interference of hormonal treatment was studied with respect to the progestin megestrol acetate (Group MA, n = 14) and the antiestrogen tamoxifen (Group TAM, n = 15) compared with untreated patients (Group U, n = 11). Healthy postmenopausal women served as controls (Group C, n = 16). Nutritional status was judged from body mass index (BMI), vitamin and trace element status, hematology, and clinico-chemical parameters. Intake of nutrients was calculated from a food record. Hormonal status was studied by analysis of LH, FSH, and prolactin in plasma and of steroids and catecholamines and their metabolites in 24-hour urine. Compared with values for Group C, nutrient intake, hematology, clinico-chemical parameters, and 24-hour urinary excretion of catecholamines and their metabolites of patient groups (U, TAM, and MA) were not significantly different. The BMI of patients was significantly higher (by about 10%; 60% showed an overweight) than that of controls. With respect to fat-soluble vitamin status, significantly lower plasma levels of vitamin A (at least 40% lower, with deficient levels in more than 50% of the patients), D (40% lower), and E (20% lower) were found for Group U. However, water-soluble vitamin status of the four groups was fairly similar. A significantly higher excretion of xanthurenic acid in 24-hour urine, after an oral tryptophan load, was observed for Groups TAM and MA. This is most probably the result of hormonal treatment without affecting vitamin B6 status. Small, but significant, differences between groups were found for trace element status, especially with respect to lower plasma selenium of Group U (25% lower). LH, FSH, and prolactin in plasma and excretion of steroids in 24-hour urine showed levels that could be expected for controls and for untreated and hormonally treated patients. We concluded that the nutritional status of all patients is reasonably adequate. Hormonal treatment did not influence vitamin B6 status, although levels of vitamins A, D, and E and of selenium seem to be elevated.
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PMID:Investigations on the nutritional status of advanced breast cancer patients. The influence of long-term treatment with megestrol acetate or tamoxifen. 343 93

Plasma levels of total tryptophan were significantly lower in 51 patients with breast cancer than in 14 women with benign breast cancer following surgery and after 12 weeks. The urinary excretion of xanthurenic and 5-hydroxyindoleacetic acids were similar in patients with cancer and benign disease but the excretion of N'-methylnicotinamide (NMN) was significantly higher (P less than 0.001) in the cancer patients. It is suggested that the elevated urinary excretions of NMN is due to higher NAD activity reflecting elevated glycolysis through the Cori cycle.
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PMID:Tryptophan metabolism in patients with breast cancer. 403 62


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