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)

When initiated the same day as dimethylbenzanthracene (DMBA) administration, daily treatment with 8 or 24 mug of the new antiestrogen RU 16117 (11alpha-methoxy ethinyl estradiol) completely prevented the appearance of mammary tumors in all animals up to the last time interval studied (130 days after DMBA administration). At daily doses of 0.5 and 2.0 mug of RU 16117, the tumor incidence was reduced to 78.6% and 40.0%, respectively. The levels of receptors for estradiol, progesterone, and prolactin in tumor tissue were reduced after treatment with 2.0 mug RU 16117 while the binding of growth hormone and insulin was not affected. While plasma LH levels were decreased after treatment with 8 or 24 mug RU 16117, plasma prolactin levels were slightly increased in animals receiving the highest dose of the antiestrogen. When RU 16117 was given at the daily dose of 24 mug for a period of 4 weeks, RU 16117 led to 65% reduction of the number of already established DMBA-induced mammary tumors. Not only the tumor number but also the tumor size was reduced by RU 16117 in a manner similar to that following ovariectomy. That the inhibitory effect of RU 16117 was not due to its low estrogenic activity is indicated by the absence of inhibitory effect of similar treatment with a range of doses (0.1-12.5 mug per day) of estradiol-17beta which cover the low estrogenic activity of the doses of RU 16117 used. Decreased levels of receptors for estradiol-17beta, progesterone, and prolactin were found in the tumors remaining after ovariectomy while treatment with the dose (24 mug) of RU 16117, efficient to inhibit tumor growth, has a similar inhibitory effect on the levels of estradiol-17beta and prolactin receptors. The present data indicate that the potent inhibitory effect of RU 16117 on the development and growth of DMBA-induced mammary tumors results from actions at both the hypothalamic-pituitary and tumor levels. The action at the peripheral level would be possibly secondary to a reduced sensitivity of the tissue to circulating hormones through lowering of hormone receptor concentrations.
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PMID:Potent inhibitory activity of a new antiestrogen, RU 16 117, on the development and growth of DMBA-induced rat mammary adenocarcinoma. 82 98

Endocrine regulation is altered with age. Changes in hormone secretory rates, patterns of secretion, and responses to physiologic and pharmacologic stimuli have been demonstrated. Target tissue sensitivity to hormones appears to be age related and to involve hormone receptor mechanisms, enzymatic responses, and carrier proteins. The aging process reflects changes in cellular structure and metabolism that decrease the function and efficiency of tissues. Structural changes occur with age and are characterized by a loss of elastic tissue, accumulation of highly crosslinked collagen, reduction in ground substance, and an increase in a cellular fluorescent pigment called lipofuscin. These changes decrease the pliability of tissues and alter membrane permeability. Modifications in protein synthesis and enzymatic systems may predispose the aged to autoimmune and neoplastic disease. Endocrine diseases are common in the aged and often may be atypical in their presentation. Cancer is common in the elderly and may be associated with endocrine manifestations because the tumor is producing hormones. Physicians must be aware of these syndromes so that a correct diagnosis can be established, treatment instituted, and the quality of life improved. Laboratory test results in the aged must be carefully interpreted because most aged patients are taking medications that interfere with endocrine tests and also the normal range for the elderly has not been clearly established. Abnormal laboratory diagnostic tests are common in the aged and do not always imply endocrine disease. No hormone can reverse the natural process of aging; however, hormones do regulate all metabolic functions and the neuroendocrine system plays a key role in all phases of growth, maturation, and aging.
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PMID:Physiology of aging: metabolic changes during the climacteric and menopausal periods. 83 75

Previous studies have indicated that hormone-responsive mammary tumors of GR mice are mixed populations of hormone-dependent and autonomous cells. We have now investigated whether these two cell types differ in susceptibility to cytostatic treatment. Experiments in which cyclophosphamide was injected in tumor-bearing mice did not reveal significant differences in percentage of inhibition between hormone-dependent, hormone-responsive, and hormone-independent tumors. Furthermore, the estrogen and progesterone receptor contents of the residual tumor masses after cyclophosphamide treatment were about the same as those of untreated tumors. When the cytostatically treated tumors were transplanted, the degree of hormone responsiveness of the transplants did not differ from that of transplants derived from untreated tumors, nor did their hormone receptor contents. These results indicate that the hormone-dependent and autonomous cells of GR mouse mammary tumors are inhibited to similar extents by cyclophosphamide. The possible significance of these results for combined endocrine therapy and chemotherapy is discussed.
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PMID:Effects of treatment with cyclophosphamide on hormone-dependent and hormone-independent tumor cells in transplanted GR mouse mammary tumors. 89 Jun 94

Tumor regression is sometimes observed during glucocorticoid treatment of patients with breast cancer. The possibility of a direct tumor-growth-suppressing effect, mediated by steroid-hormone receptors, cannot be excluded. A 3H-dexamethasone-binding component in the cytoplasmatic fraction of human breast cancers was studied by agar-gel electrophoresis. Of 90 samples, 51% contained a significant amount of an apparent glucocorticoid receptor. In two specimens from metastases, in which a preexisting lymph node structure was almost completely replaced by tumor tissue, the glucocorticoid receptor character of the binding component was studied extensively. The component satisfied the steroid-hormone receptor criteria in being a high affinity (Kd approximately 4--9 X 10(9) M), low capacity binder. Competition studies with excess unlabelled steroids of different classes confirmed the specific glucocorticoid receptor character of the component. Both tumors contained also estrogen and androgen receptors and one contained an apparent progestin receptor.
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PMID:Demonstration of glucocorticoid receptors in human mammary carcinomas. 90 52

Miltefosine (hexadecylphosphocholine, HPC, CAS 58066-85-6) was investigated in transplanted primary methylnitrosourea-induced PYH mammary carcinoma of F344 rats. The therapy was performed in the 5th and 10th passage. At first HPC (113 mg/kg body weight) significantly reduced the median tumor volume, but a loss of activity was observed in the 10th passage. To explain the loss of sensitivity and to obtain information on the mechanism of action histology, cytoskeleton and hormone receptor content were investigated. The most important change was observed in the histopathology of the tumor. The initial tubular papillary adenocarcinoma was transformed into a malignant adenoacanthoma with epithelial structure. Vimentin as an endothelial marker of the cytoskeleton was equally expressed in all passages. Cytokeratin was weakly expressed in the earlier passages and intensively present in the late passages. The histopathological change from tubular adenocarcinoma to malignant adenoacanthoma might be caused by an overgrowth of the primary epithelial tumor cells or by a real transformation in the morphological characteristics of the tumor, which may occur during repeated transplantation.
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PMID:Effect of miltefosine on transplanted methylnitrosourea-induced mammary carcinoma growing in Fischer 344 rats. 128 10

The specimen excised for the mammographically detected lesion is somewhat unique and requires special consideration by the surgical pathologist. The biopsy, in most instances, contains no grossly visible lesion and is relatively large so that blocking in its entirety is not practical. The pathologist needs to establish that the radiological abnormality is contained in the biopsy and to this end specimen radiography is required. Established prognostic parameters for breast carcinoma, such as tumor size, histological type, grade and hormone receptor status are equally applicable in the non-palpable breast lesion but consideration should also be given to the identification of epithelial proliferations which have increased risk for subsequent carcinoma. In addition, the recognition of ductal carcinoma in situ in the biopsy indicates potential for widespread disease, and lobular carcinoma in situ, a less commonly detected lesion in mammography, is associated with multifocality and disease in the contra-lateral breast. Both lesions are also associated with increased risk of recurrence in the remaining breast tissue. Failure to observe the corresponding quantity of calcium seen in radiographs relates to the fact that calcium may occur, not only as calcium phosphate, but also as calcium oxalate, the latter not being stained by hematoxylin and eosin but readily detected by its birefringent nature in polarized light. Detailed correlation of serial thin slices of the specimen with radiographic features is largely an educational exercise but is the most time-consuming step in the examination of the non-palpable breast lesion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of the surgical pathologist in the examination of the non-palpable breast lesion. 128 67

The association of mammographic appearance with hormone receptor status was investigated in 397 patients with primary breast cancers. The mammographic appearance was classified as type 1, spiculated (n = 159); type 2, structural changes (density) (n = 102); type 3, calcifications (n = 30); type 4, circumscribed opacity (n = 65); and type 5, not visible on mammogram (n = 41). Univariate analysis showed a significant association with estrogen receptor (ER) status for age (less than 50 vs greater than or equal to 50 years), tumor TNM category (those in category 1 vs those in higher categories), and mammographic appearance; with progesterone receptor status, the association was significant only for age. Multivariate analysis adjusted for potential confounders confirmed a significant association between ER status and mammographic appearance (ER status was more likely with type 1 than with the other mammographic types), but the strength of the association was limited. The mammographic appearance of breast cancer is not a reliable method to predict hormone receptor status for clinical purposes.
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PMID:Breast cancer: reliability of mammographic appearance as a predictor of hormone receptor status. 131 Nov 18

Biochemical and biological studies have been carried out with 2-desamino-2-methylaminopterin (dmAMT), which inhibits tumor cell growth in culture but is only a weak inhibitor of dihydrofolate reductase (DHFR). Since it was possible that the species responsible for growth inhibition are polyglutamylated metabolites, the di-, tri-, and tetraglutamates of dmAMT were synthesized and tested as inhibitors of purified recombinant human DHFR, murine L1210 leukemia thymidylate synthase (TS), chicken liver glycinamide ribonucleotide formyltransferase (GARFT), and murine L1210 leukemia aminoimidazolecarboxamide ribonucleotide formyltransferase (AICARFT). The compounds with three and four gamma-glutamyl residues were found to bind two orders of magnitude better than dmAMT itself to DHFR, TS, and AICARFT, with 50% inhibitory concentration values in the 200 to 300 nM range against all three enzymes. In contrast, at a concentration of 10 microM, dmAMT polyglutamates had no appreciable effect on GARFT activity. These findings support the hypothesis that dmAMT requires intracellular polyglutamylation for activity and indicate that replacement of the 2-amino group by 2-methyl is as acceptable a structural modification in antifolates targeted against DHFR as it is in antifolates targeted against TS. In growth assays against methotrexate (MTX)-sensitive H35 rat hepatoma cells and MTX-resistant H35 sublines with a transport defect, dmAMT was highly cross-resistant with MTX, but not with the TS inhibitors N10-propargyl-5,8-dideazafolic acid and N-(5-[N-(3,4-dihydro-2-methyl-4-ox-oquinazolin-6-yl)-N- methylamino]thenoyl)-L-glutamic acid, implicating DHFR rather than TS as the principal target for dmAMT polyglutamates in intact cells. On the other hand, an H35 subline resistant to 2'-deoxy-5-fluorouridine by virtue of increased TS activity was highly cross-resistant to N10-propargyl-5,8-dideazafolic acid and not cross-resistant to MTX, but showed partial cross-resistance to dmAMT. Both thymidine and hypoxanthine were required to protect H35 cells treated with concentrations of dmAMT and MTX that inhibited growth by greater than 90% relative to unprotected controls. In contrast, N10-propargyl-5,8-dideazafolic acid and N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-yl)-N-methylamino] thenoyl)- L-glutamic acid required only thymidine for protection. Like MTX, therefore, dmAMT appears to inhibit purine as well as pyrimidine de novo synthesis, and its effect on cell growth probably reflects the ability of dmAMT polyglutamates to not only block dihydrofolate reduction but also interfere with other steps of folate metabolism, either directly or indirectly via alteration of reduced folate pools.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Biochemical and biological studies on 2-desamino-2-methylaminopterin, an antifolate the polyglutamates of which are more potent than the monoglutamate against three key enzymes of folate metabolism. 131 37

Between 1977 and 1986, 879 patients with Stage I and II breast cancer underwent excisional biopsy, axillary dissection, and radiation. Median follow-up was 61 months (range 2-159 months). The patients were divided into seven groups based on histologic subtype: (a) 368 patients with both infiltrating and intraductal ductal carcinoma, (b) 389 infiltrating ductal carcinoma, (c) 41 infiltrating lobular carcinoma, (d) 23 combined infiltrating ductal and lobular carcinoma, (e) 28 medullary carcinoma, (f) 12 colloid carcinomas, and (g) 18 tubular carcinomas. Significant differences in clinical T status, pathologic nodal involvement, administration of chemotherapy, estrogen receptor positivity, progesterone receptor positivity, and age were observed between some histologic subgroups. Tubular and colloid carcinomas were more likely to present with T1 lesions, hormone receptor positivity, and node negative status than the other histologic subtypes. Most medullary carcinomas were hormone receptor negative and were younger than 50 years old. Infiltrating lobular carcinoma patients were more frequently lymph node negative, older, node negative, and estrogen receptor positive compared to the other groups (except for tubular and colloid patients). Differences in the administration of chemotherapy primarily reflected differences in lymph node involvement. Location of the tumor in the breast and menopausal status did not correlate with histologic subtype. There were no significant differences in 5-year actuarial overall survival, cause-specific survival, or relapse-free survival between the histologic categories. In addition, patterns of first failure were not significantly different among the histologic groups in terms of local-only first failure, any local component of first failure, regional-only first failure, or any regional component of first failure. There was, however, a difference among the seven groups in distant metastasis-only at first failure with invasive ductal carcinomas having the highest rate. Despite this difference, histologic subtype had no impact on survival. The site of in-breast failure relative to the location of the original tumor was not significantly different between groups. The histologic subtype of invasive breast cancer is not an independent risk factor in predicting survival or pattern of failure. Conservative surgery and radiation therapy is effective treatment of ductal, lobular, medullary, colloid, and tubular invasive breast cancer.
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PMID:Outcome of conservative therapy for invasive breast cancer by histologic subtype. 132 87

Suspensions of fresh tumor-infiltrating lymphocytes (TIL) were prepared from 30 human breast ductal adenocarcinomas. To evaluate the phenotypic pattern of the isolated TIL, lymphocyte surface markers including CD19, CD3, CD4, CD8, CD16 and HLA-DR were examined by flow cytometry. Lymphocyte recovery ranged from 1.1% to 44%, independent of tumor size. TIL most often scored high for CD3+ with a varying number of CD4+ and CD8+ cells. Three samples out of 30 expressed up to 44% of CD19+ B cells, while CD3-CD16+ NK cells were rare. CD4 and CD8 expression was significantly different between the lymph node metastases group and the lymph node negative group (p < 0.01). 67% of the TIL with a CD4/CD8 ratio greater than 1 showed lymph node metastases. Furthermore, the CD4 expression of TIL and CD4/CD8 ratio correlated with tumor size (p < 0.01), but not with tumor differentiation and hormone receptor expression. Although there was considerable diversity of TIL among breast tumors, our data suggest that a high expression of CD4+ T cells may imply progression of the tumor, and an increased CD4/CD8 ratio of the TIL isolated from human breast adenocarcinoma may indicate development of metastases.
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PMID:Phenotypic analysis of tumor-infiltrating lymphocytes from human breast cancer. 133 79


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