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

A multicenter, randomized, controlled trial was conducted comparing active treatment with placebo in 227 patients with breast, colorectal, lung and other solid forms of cancer. Combination therapy, (CT) conventionally employed for the various types of tumor involved, was associated with MPA (117 patients) or placebo (110 patients). MPA was given orally as tablets, as a dose of 500 mg b.i.d. for 6 months. The results were, briefly, as follows: The incidence of leukopenia was significantly lower in the groups receiving MPA in patients with breast and colorectal cancer (P less than 0.02). Tumors of the lung and other solid forms showed no such difference. The incidence of thrombocytopenia was the same in all disease groups. Objective responses (CR + PR) were observed in 23/46 (50%) of breast cancer patients treated with CT + MPA, and in 13/47 (28%) of those given CT + placebo. The difference was significant (P less than 0.02). Subjective parameters also showed more improvement in the MPA group than in the patients given CT alone. No significant differences were found for the other types of tumor, but the numbers in this population were very limited. In a group of 45 patients, antithrombin III a (%), antithrombin III R: Ag (%), plasminogen (mg/dl), alpha-2 macroglobulin (%), factor VIII C (%), factor VIII R: Ag (%) and factor IX C (%) were determined. The most interesting post-treatment findings were an increase in anti-thrombin III (activity and antigen level) and in plasminogen. This suggests that MPA does not increase the risk of thrombosis, and might even, to some extent, impede tumor-induced thrombophilia.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Protective effect of high-dose medroxyprogesterone acetate (HD-MPA) on hematological toxicity induced by chemotherapy for advanced solid tumors: a multicentric controlled clinical trial. MPA-Hematology Italian Cooperative Group. 287 45

The relationship between proteinase-like peptidase activities and oestrogen receptor levels and status in breast cancer tissue homogenates from 61 patients with breast cancer has been evaluated. With Spearman's rank-order correlation analysis, significant positive correlations were observed between receptor levels and the activities of cathepsin-(B + L)-like, cathepsin-H-like, trypsin-like, plasminogen-activator-like and elastase-like peptidases. In addition, the activities of all but the latter enzyme were significantly higher in patients with receptor-rich tumours than in receptor-poor tumours, and this may have implications for future treatment regimens for patients with oestrogen-receptor-rich tumours. The findings reported are consistent with the suggestion that in breast cancer there may be an association between steroid receptors and proteolytic enzymes such that the release of these enzymes may be under hormonal control.
 ...
PMID:Proteinase-like peptidase activities and oestrogen receptor levels in breast cancer tissue. 292 Dec 76

The total plasminogen activator (PA) activity and the activities of urokinase type (uPA) and tissue type (tPA) plasminogen activators were measured in 43 primary human breast cancer homogenates. The majority of the PA activity was found in the 100,000 X g crude membrane pellets (log mean of 490 milli-IU/mg of protein, +1169, -346), and little PA activity was present in the cytosolic supernatant (log mean of 19 milli-IU/mg of protein, +168, -17). The activities of total PA and of each type of PA were compared to the estrogen receptor (ER) and epidermal growth factor receptor (EGFR) status of the tumors and to their histological grade. Total PA activity and uPA activity were not significantly different in any group of tumors stratified according to receptor status or tumor grade. Tissue type PA levels, however, were significantly lower in ER-negative compared with ER-positive tumors and in EGFR-positive compared with EGFR-negative tumors (P less than 0.01 and less than 0.05, respectively). The tPA activity was also related to grade, decreasing with worsening differentiation (P = 0.04). The ER-negative tumors were further stratified into EGFR-positive and -negative subgroups. Only the ER-negative tumors possessing EGFR had significantly lower tPA levels than the ER-positive tumors (P less than 0.01). Low tPA levels in breast cancers were, therefore, associated with ER negativity combined with EGFR positivity and may be an indication of poorer differentiation and prognosis.
 ...
PMID:Relationship of membrane-bound tissue type and urokinase type plasminogen activators in human breast cancers to estrogen and epidermal growth factor receptors. 314 Oct 47

Epidemiological studies of oral contraceptives pertaining to premenopausal women are briefly reviewed. Therapeutic considerations are noted. The clinical effects of aging and hormone replacement therapy are indicated in terms of metabolism, the endometrium, and bone mass. The pharmacological advantages and consequences of nonhormonal and hormonal contraception are explored. For aging women over 40, there is a need for relief of menopausal symptoms, contraception, and reduction of risks for atherosclerosis, hypertension, coronary heart disease, endometrial carcinoma, breast cancer, and osteoporosis. With the availability and use of low estrogen products, women over 40 can insure tissue support and prevent bone loss as long as the therapy is instituted within 3 years of the last menses. Over-40 women who drink and smoke should not use oral contraceptives. Sterilization does not satisfy longterm hormonal needs, and has other reported menstrual side effects. The dose and duration regimen of hormonal therapy must be carefully considered due to the effects on the endometrium., the coagulation system, the liver, lipids, and bone. Combination estrogen and progestogen is necessary, but consideration must be given to existing levels of endogenous hormones. Lipid patterns may change due to hormone replacement or as a result of aging and contribute to coronary heart disease. Hormone replacement can reverse the atherogenic pattern of increased low density lipoprotein levels and decreased high density lipoprotein levels; a chart gives the effects on lipids and coagulation from various estrogen or estrogen plus progestogen products. For the estrogen-deficient menopausal woman, high estrogen can decrease antithrombin III plasminogen and alpha-antitrypsin antigen levels. Lower dose progestogens are recommended. Studies of dose and effects on bone mass are reviewed and vaginal rings and transdermal steroid patches, triphasic formulations, and new progestational agents such as 19-nortestosterone derivatives are described. Newer low dose formulations are needed for the aging woman, as well as further research on what product best suits the variability of women aged 40-50
 ...
PMID:Contraception for the perimenopausal patient. 330 20

To understand the hormonal regulation of plasminogen activators (PAs) in human breast cancer, we have examined the hormonal regulation and properties of PAs in four human breast cancer cell lines that differ markedly in their estrogen receptor (ER) content: MCF-7 cells contain high levels of ER (approx 7 pmol/mg DNA) and their PA activity was increased 3-4-fold by physiological concentrations of estradiol; T47-D and ZR-75-1 cells contain lower levels of ER (0.9 and 2.1 pmol/mg DNA respectively) and their PA activity was also increased 3-4-fold by estradiol. In contrast, MDA-MB-231 cells, which do not contain ER, showed a high level of PA activity that was not modulated by estradiol. SDS-PAGE followed by zymography indicated that MCF-7 cells secreted tissue-type PA (t-PA), T47-D and ZR-75-1 cells secreted urokinase-type PA (u-PA), and MDA-MB-231 cells secreted both types of PAs. The types of PAs secreted by these cell lines did not change upon treatment with estradiol. Dose-response curves for the stimulation of MCF-7 PA activity by different estrogens showed an excellent correlation between affinities of the estrogens for ER and their potency in stimulating PA activity. With a clonal subline of MCF-7 cells, MCF-L, a soluble inhibitor of both t-PA and u-PA was secreted. Incubation of purified t-PA or u-PA with the serum-free conditioned medium from MCF-L cells resulted in a shift in the mobility of t-PA and u-PA in SDS-polyacrylamide gels to forms increased in molecular mass by about 50,000-70,000. The shifts in molecular mass could be prevented by the presence of the competitive inhibitor p-aminobenzamidine, indicating that the active sites of the PAs were involved in the formation of these complexes. Furthermore, co-cultivation, of RT4-D rat neuroblastoma cells, which exhibit high levels of t-PA activity, with MCF-L cells resulted in a marked decrease in the PA activity of the RT4-D cells. Our results were consistent with the following conclusions: t-PA, u-PA or both were secreted by human breast cancer cells. In the ER-containing cell lines, depending upon the specific cell line, t-PA or u-PA was stimulated by estrogens. The unstimulated levels of PA activity and the magnitude of PA stimulation by estrogens were not closely related to ER content.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Plasminogen activators in human breast cancer cell lines: hormonal regulation and properties. 338 80

The relation of in vitro properties to tumorigenicity was studied using eight sublines of the human breast cancer cell line MCF-7. Four of the eight were tumorigenic in estrogen-treated nude mice. The sublines differed for each of the in vitro properties measured, and no property correlated perfectly with tumorigenicity. Cytochalasin B-induced multinucleation was a property of all four tumorigenic sublines but of only one of the four nontumorigenic ones. Anchorage-independent growth and concanavalin A-mediated hemadsorption levels were higher in all sublines than reported levels for nontransformed fibroblasts and normal human or mouse mammary epithelial cells. The production of both plasminogen activator and a plasminogen-independent fibrinolytic activity showed no relationship to tumorigenicity but was higher in those sublines producing more invasive tumors. It appears that no one of these in vitro properties is sufficient to make a subline tumorigenic. Rather, the first three properties studied here and, perhaps, also production of plasminogen activator may each be necessary, but not sufficient, to make a subline tumorigenic. In addition, properties such as production of plasminogen activator and other proteases, while perhaps not essential to tumorigenicity, may confer characteristics, such as invasiveness, on the tumors produced by a given subline.
 ...
PMID:Relation of in vitro properties to tumorigenicity for a series of sublines of the human breast cancer cell line MCF-7. 377 50

Plasminogen activator (ascites PA) was purified from the ascites of the patient with breast cancer using lysine-Sepharose, salting out, DEAE Sephadex A-50 and anti-urokinase (UK) Sepharose chromatography. The ascites PA was adsorbed on anti-UK Sepharose and its activity was neutralized by anti-UK IgG fraction. The molecular weights of the ascites PA proteins were 70,000, 32,000 and 25,000 daltons. The ascites PA activated plasminogen and showed amidolytic activity for S-2444. Zymograms of ascites PA showed that 70,000 and 32,000 daltons proteins had a PA activity. The ascites PA thus contained two types of PAs, one was similar to LMW-UK and the other was an UK type tissue PA.
 ...
PMID:Urokinase-type plasminogen activator in ascites obtained from the patient with mammary cancer. 404 Feb 79

In order to evaluate the efficacy of an anticoagulant treatment in neoplasia, we have looked for the existence and the possible role of hemostatic unbalance in patients affected by limited and uncomplicated thyroid and breast cancer by examining hemostasis in 25 patients. Our data allowed us to evidentiate an accelerated and increased fibrinoformation associated with the presence of plasminogen's activation inhibitor which overlaps the increased plasminogen's activators. We evidentiated also an increase of platelet functions in vitro and of their activation in vivo. These findings support the hypothesis of a possible role played by hemostasis alterations in the pathogenesis of thromboembolic complications, cancer growth and/or metastatization, and justify prophylactic and therapeutic anticoagulation.
 ...
PMID:Hemostatic disorders in 25 patients with limited and uncomplicated thyroid and breast cancer: prophylactic and therapeutic considerations. 624 45

Plasminogen activators (PAs), a family of proteases active in blood coagulation, may play an important role in cancer. Indeed, blood coagulation disorders, such as altered fibrinogen and fibrin metabolism and increased incidence of vascular thrombosis, are common in patients with advanced malignant disease. Different types of human tumors are known to contain high levels of PA. The isoelectric focusing patterns of the PAs present in tumors and plasma from patients with breast cancer were compared with those of purified human urokinase and melanoma tissue PA. The pattern of isoelectric molecular forms of PA active at pH 8 showed two groups of several bands: in plasma from tumor-bearing patients and controls, these groups were in the pl ranges of 6.6 to 6.8 and 8.0 to 8.5; in mammary adenocarcinoma tissue, the ranges were 6.8 to 7.9 and 9.0 to 9.4. These patterns were different from those obtained with purified markers; the latter were 5.8 to 9.4 and 5.9 to 7.6 for purified human urokinase and melanoma plasminogen tissue activator, respectively. PA activity in tumor-bearing patients was very high in malignant tissue and, on the contrary, very decreased in plasma; this latter decrease was correlated with the presence of metastases in the axillary lymph nodes. These results suggest that the high PA activity in the tumor tissue might participate in the destruction of the peritumoral tissue, thus allowing its invasion by tumor cells, whereas the low activity of PA in the plasma might increase plasma fibrin, reflecting thus an early disorder in blood coagulation which would enhance the formation of metastases.
 ...
PMID:Relationship between multiple forms of plasminogen activator in human breast tumors and plasma and the presence of metastases in lymph nodes. 653 66

In the MCF7 human breast cancer cell line, estradiol stimulates the synthesis of a 52 K secretory glycoprotein and has been reported to increase the plasminogen activator (PA) activity in the culture medium. Since one PA isozyme has a molecular weight close to 52 000 daltons under denaturing conditions, we asked whether the 52 K protein was a PA. The PA activity released in serum-free conditioned medium was evaluated by the increase in [125I]casein digestion observed in the presence of plasminogen. The 52 K protein was estimated by analysing the released proteins on SDS-polyacrylamide gel electrophoresis. When the conditioned medium was chromatographed on concanavalin A-Sepharose, the 52 K protein was retained on the gel, but not the PA. The two proteins also appeared different on the basis of their competing efficiency in a radioimmunoassay developed to quantify the 52 K protein. An antiserum against human urokinase failed to immunoprecipitate the 52 K protein. Under our culture conditions estradiol increased 52 K, but not PA, production. These results clearly indicate that the estradiol-regulated 52 K protein is not a plasminogen activator.
 ...
PMID:The estrogen-regulated 52 K protein adn plasminogen activators released by MCF7 cells are different. 653 16


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>