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)

The binding of 125I-Tyr4 bombesin was investigated on plasma membranes of 8 human breast cancer cell lines and 2 long-term cultures of normal human breast epithelial cells. Scatchard plots were compatible with high-affinity, single-site class of receptors in 3 cell lines (KD of 0.75 x 10(-9) and 10(-9) M, Bmax of 0.75 x 10(-13) and 9.7 x 10(-13) M/mg protein in MDA-MB231 and in T47D cells, respectively) while no binding was observed in 5 other cell lines and normal epithelial cells. The neuropeptide and its structural analogues (natural or synthetic) inhibited the binding of 125I-Tyr4 bombesin in the following order of potency: gastrin-releasing peptide (GRP, EC50 = 1.7 x 10(-10) M) greater than BIM 26159 greater than bombesin, Tyr4 bombesin greater than BIM 26147 greater than litorin greater than neuromedin C. In contrast, 125I-Tyr4 bombesin binding was not displaced by neuromedin B, somatostatin, bradykinin and insulin. In agreement with our binding data, SDS-PAGE of the complex 125I-Tyr4 bombesin-receptor covalently linked by ethylene glycol-bis succinimidyl succinate (EGS) identified after autoradiography a single band with a molecular weight of 75,000, which disappeared in the presence of bombesin in excess. No transcription of either GRP or neuromedin B mRNA could be shown in tumor or normal cells. Exogenous gastrin-releasing peptide had no effect on growth of the cell lines when a serum-free medium was used, implicating that in breast cancer cell lines this receptor does not mediate growth but has a functional role.
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PMID:Characterization, in some human breast cancer cell lines, of gastrin-releasing peptide-like receptors which are absent in normal breast epithelial cells. 216 13

To appreciate the IGF1 sensitivity of breast tumors we detected IGF1-R with a biochemical assay (RRA). We then localized and quantified IGF1-R on frozen tissue sections by histo-autoradiographic analysis (HAA). In some cases, the IGF1 and IGF1-R mRNA expression were studied by Northern blot analysis. We also studied the IGF1 plasma concentration in primary breast cancers compared to controls. IGF1-R (RRA) were found in 87% (n = 297) of the breast cancers. The mean geometric value was 3.87% (specific binding as percentage of total radioactivity); we found a highly significant correlation between IGF1-R and ER on the one hand (P = 0.0001) and PgR on the other (P = 0.0001) (Spearman test). The presence of IGF1-R was associated with a better prognosis, either on relapse-free survival (actuarial analysis: P = 0.004; Cox analysis: P = 0.005) or overall survival (respectively P = 0.003; P = 0.005). The median duration of follow-up was 30 months. By Cox analysis IGF1-R was a better prognostic factor than ER and PgR. In a series of 77 cases of benign breast disease only 47% (36/77) were positive; the mean geometric level was 1.8%. The HAA IGF1-R quantification in 20 breast carcinomas and 12 cases of benign breast disease confirmed the RRA results and demonstrated that the labeling was localized on the epithelial component. In four breast cancers, we did not detect IGF1 mRNA; IGF1-R probe demonstrated two major mRNAs of 11 and 7 kB. Finally we found that IGF1 plasma level was higher in breast cancer patients than in healthy controls of the same age. These results show that IGF1 is implicated in breast cancer growth and suggest that anti-IGF1 treatment might be useful in human breast cancer: for this reason, we and others carried out a phase II clinical trial with somatostatin.
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PMID:Insulin-like growth factor 1 receptors (IGF1-R) and IGF1 in human breast tumors. 217 65

Sixteen post-menopausal patients with advanced breast cancer were treated with a long acting somatostatin analogue, SMS 201-995 (Sandostatin): 0.1 mg bid sub-cutaneously. The dose was chosen on the basis of efficiency in acromegaly treatment. SMS 201-995 activity was evaluated assaying Insulin Growth Factor 1 (IGF1) plasma concentration. A merely partial IGF1 decrease was noted. To be evaluable for response, patients had to be treated for at least 30 days. Among the 14 evaluable patients, we observed no response to SMS 201-995. However, we noted tumor stabilization in 3 patients after a 90 days treatment period. Side-effects were very mild. This first report on SMS 201-995 treatment of breast cancer suggests that further studies evaluating the effect of other modes of administration or drug association should be warranted.
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PMID:Effect of the long-acting somatostatin analogue SMS 201-995 (Sandostatin) in advanced breast cancer. 253 68

To correlate the expression of neuro-endocrine (NE) markers with the presence of somatostatin receptors (SSR) in human breast cancer, a series of 100 cases was stained with the Grimelius silver procedure, by immunocytochemistry with specific NE markers (i.e., chromogranin A and B and synaptophysin) and by autoradiography for SSR. Nine cases were positive for at least one NE marker, while 4 cases were positive for all of them. SSR were detected in 17 cases, either with low (10 cases) or with high receptor density (7 cases). A highly significant correlation was established between the expression of NE markers and high SSR density. Our findings are additional evidence of the existence of a group of breast cancers showing morphological and cytochemical similarity with neuro-endocrine tumors present in other organs. The identification of this type of breast cancer is of biological and potential therapeutic interest.
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PMID:Correlative study on neuro-endocrine differentiation and presence of somatostatin receptors in breast carcinomas. 256 77

Three human breast cancer cell lines ZR-75-1, MDA-MB-436 and MCF-7 were found to contain respectively, 3.06, 2.69 and 1.86 fmol of somatostatin-like immunoreactivity (SLI) per 10(6) cells. Since SLI is undetectable in the passaging media it must, therefore, be synthesised by the cells. In the presence of fetal calf serum the cells were growth inhibited by addition of somatostatin or its long-lasting analogue, Sandostatin, but only after 3 days of continuous exposure. A 1-day exposure to either peptide had little or no effect on subsequent cell growth in peptide-free medium. Inhibition of cell proliferation is not due to cytotoxic effects of the dose used (500 ng ml-1, each) since both peptides caused short-term stimulation of growth in the absence of serum.
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PMID:Synthesis of somatostatin by breast cancer cells and their inhibition by exogenous somatostatin and sandostatin. 256 8

Binding capacities and apparent dissociation constants of receptors for [D-Trp6]-luteinizing hormone-releasing hormone [( D-Trp6]-LH-RH), somatostatin (SS-14), epidermal growth factor (EGF), and estrogen and progesterone were determined in 500 breast cancer specimens using multipoint assays. Specific binding sites greater than 10 fmol/mg cytosol protein for estrogen were found in 408 carcinomas (81.6%), and for progesterone in 340 specimens (68%). High affinity EGF receptors were present in membrane preparations from 335 samples (67%). In 260 of 500 samples (52%), two classes of [D-Trp6]-LH-RH membrane receptor sites were also detected, one class showing high affinity and low capacity, and the other class showing low affinity and high capacity; 178 biopsy samples (35.6%) exhibited binding sites for SS-14. Statistically significant inverse correlations were found between the binding capacities of estrogen and EGF receptors as well as between Bmax of progesterone and EGF receptors. Significant positive correlations were demonstrated between binding capacities of estrogen and progesterone and between Bmax of high affinity and low affinity binding sites of [D-Trp6]-LH-RH receptors. However, no correlation was found between the dissociation constants of different receptor sites in human breast cancer specimens. These results demonstrate that numerous human breast cancers, in addition to receptors for estrogen and progesterone, also show binding sites for EGF, [D-Trp6]-LH-RH and SS-14. The methods described herein permit a routine quantification of receptor sites for [D-Trp6]-LH-RH, SS-14, and EGF in membrane preparations of biopsy samples of breast cancer and can be used in conjunction with the determination of estrogen and progesterone receptors in nuclear-cytosolic extracts. The simultaneous measurements using a microanalytic approach allow the determination of peptide and steroid hormone receptors that might be involved in the response mechanisms of human breast cancer. It should be possible to correlate the levels of these receptors with clinical parameters to better identify endocrine-responsive neoplasms. This approach might be useful to guide a rational hormonal therapy in women with breast cancer.
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PMID:Characteristics and distribution of receptors for [D-TRP6]-luteinizing hormone-releasing hormone, somatostatin, epidermal growth factor, and sex steroids in 500 biopsy samples of human breast cancer. 256 34

Minced tumor fragments were xenografted into subcutaneous tissue of the lateral thoracic regions of young adult, virgin female nude mice to study the effects of somatostatin analog SMS 201-995 on growth of estrogen-dependent (MCF-7) and estrogen-independent (BT-20) human breast carcinomas. When tumors became palpable (6 to 10 days), mice were assigned randomly to receive either SMS (4 to 50 micrograms) or acetate buffer (0.2 ml) subcutaneously twice a day. For MCF-7, mean tumor volume was significantly lower on day 20 and days 30 through 50 in SMS-treated mice than in controls (p less than 0.05), and tumor doubling time was increased from 13.2 to 19.0 days. Calculated growth increment was significantly lower with SMS than with buffer treatment (1.1 +/- 0.1 vs 1.9 +/- 0.2) (p less than 0.001). For BT-20, mean tumor volume of SMS-treated mice was slightly, but not significantly, lower than that of controls; however, calculated growth increment was significantly lower for SMS treatment (3.2 +/- 0.3 vs 3.9 +/- 0.4) (p +/- 0.001), and tumor doubling time was increased from 4.0 to 5.8 days. For MCF-7, flow cytometric DNA analysis of tumor biopsy samples demonstrated a reduced G2 + M phase with SMS treatment. We conclude that SMS slows the growth of both MCF-7 and BT-20 human breast cancer xenografts in nude mice and that SMS may be clinically useful in the management of patients with breast carcinoma.
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PMID:Inhibition of growth of human breast carcinomas in vivo by somatostatin analog SMS 201-995: treatment of nude mouse xenografts. 256 69

In this pilot clinical trial conducted in 10 postmenopausal women with advanced breast cancer, we evaluated the endocrine effects and toxicity of combined somatostatin analog and dopaminergic therapy in the attempt to suppress both growth hormone (GH) and prolactin (PRL) secretion. The patients' mean age was 63 years (range: 54-77) and the average number of previous treatments was 4.8 +/- 2 (SD). All patients were treated with the somatostatin analog SMS 201-995 (100-200 micrograms s.c. in a.m. and h.s.) and bromocriptine (2.5 mg orally twice a day). During treatment, GH levels following provocative testing (either L-DOPA or insulin-induced hypoglycemia) were suppressed in 7/9 patients. Basal somatomedin-S (Sm-C) levels declined in 6/9 women. Both GH and Sm-C levels decreased in 4 patients, while in the remaining 5 only one of the two parameters was lowered on treatment. PRL secretion (during provocative TRH testing) was almost totally abolished in 8/9 patients. The treatment did not affect circulating levels of FSH, LH, E1, E2, E1-S, T4, T3RU, or cortisol. Seven patients experienced no side effects. Nausea occurred in 3, but was severe enough in only one to require discontinuation of therapy. One patient experienced disease stabilization consisting of less than 50% regression of skin nodules and pleural effusion, a decline in CEA titer, and an improved performance status lasting 7 months. We conclude that combined SMS 201-995 and bromocriptine therapy is safe and frequently suppresses GH and PRL secretion. Its role in the treatment of metastatic breast cancer should be tested in patients with less advanced disease.
Breast Cancer Res Treat 1989 Dec
PMID:Endocrine effects of combined somatostatin analog and bromocriptine therapy in women with advanced breast cancer. 257 6

BDF female mice inoculated with MXT mammary adenocarcinoma were treated for 30 days with microcapsules of the luteinizing hormone-releasing hormone (LH-RH) agonist D-Trp-6-LH-RH (releasing 25 micrograms/day for 30 days), microcapsules of the somatostatin agonist RC-160 (liberating 25 micrograms/day for one month), or the combination of these peptides. Bilateral surgical ovariectomy was performed in one group which served as an additional control. Tumor volume was measured weekly during the treatment period of 30 days. When tumor volume changes in the treated groups were compared to the corresponding changes in controls, the combination of D-Trp-6-LH-RH and RC-160 was the most effective in inhibiting tumor growth and approached the effect of surgical ovariectomy. At the conclusion of the experiment, tumor weights were also measured. All peptide analogs inhibited tumor weight by 42 to 63%. In the D-Trp-6-LH-RH treated group, ovarian weights and uterine weights decreased by 48% and 52%, respectively, as compared to controls. Histologically, the regressive changes in tumors caused by the treatment with RC-160, D-Trp-6-LH-RH and their combination were characterized by the coexistence of apoptosis (programmed cell death) and coagulation necrosis. The transition of apoptosis into coagulation necrosis was a common finding. The term 'apoptotic index' is proposed for the ratio of tumorous glands containing apoptotic cells. The apoptotic index was higher in the treated groups than in the control.
Breast Cancer Res Treat 1989 Dec
PMID:Growth inhibition of MXT mammary carcinoma by enhancing programmed cell death (apoptosis) with analogs of LH-RH and somatostatin. 257 7

The axillary lymph-node-status is the most important prognostic factor in breast cancer patients without distant metastases. The proportion of node positive axillae depends on the number of histologically documented nodes (at least 6 according to TNM recommendations). The prognostic significance of solitary micro-metastases and of metastases detected only by serial sectioning or by immunocytochemistry is not yet established. An important prerequisite for successful conserving breast-cancer treatment is patient selection. Selection leads to a high proportion of patients with favourable prognosis: primary tumors less than 3 cm in diameter, at least 2/3 without axillary lymph-node-metastases, at least 1/3 less than 50 years old. That means attribution of prognostically less favourable patients to mastectomy. Tumor diameter and grading are established prognostic parameters of the primary. The significance of grading is independent of the system used and also independent of the reproducibility by different investigators. Measurement of tumor cell ploidy, proliferation and of epidermal growth factor-receptor content may add to the safety of prognosis prediction. Steroid hormone receptor content, eventually also Somatostatin-receptor and Aromatase activity in the tumor tissue can influence the therapeutic decisions.
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PMID:[Pathologic-anatomic parameters for the prognosis of invasive breast cancer following amputation or saving the breast]. 266 53


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