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)

Cyclophosphamide and other alkylating agents suppress ovarian function in pre-menopausal women. However, endocrine details remain unknown regarding the influence of patients' age and obesity on CMF-induced hormonal changes. We studied changes in endocrine profile due to chemotherapy (CMF) in 70 pre-menopausal patients with axillary node positive, stage II and/or III breast carcinoma. Plasma levels of estrone (E1), estradiol (E2), androstenedione (A2), luteinizing hormone (LH), and prolactin (PRL) were determined on day 1 and 8 of each chemocycle for 12 cycles. After receiving therapy, 23% of the women continued to have regular menstrual cycles (non-amenorrheic group). In the remaining 77%, ovarian function was suppressed, as evidenced by the onset of amenorrhea within 0-11 months (amenorrheic group). The mean time to amenorrhea was 2.83 +/- 0.33 months (SE). The time required to develop amenorrhea inversely correlated to the patient's age. Both incidence of amenorrhea and time to amenorrhea remained unaffected by either patient's obesity or the timing of chemotherapy initiation in relation to menstrual cycle phase (progestational, follicular). Plasma hormone levels fluctuated widely in both groups during the first three chemocycles. During chemocycle months 4 to 10, in the amenorrheic group, plasma E1, E2, and P declined to their baseline levels with a concomitant rise in LH levels. At this time, E1, E2, and P levels were significantly lower in amenorrheics, despite menstrual cycle associated fluctuations in the non-amenorrheic group. Estrogens (E1 and E2) gradually declined further following the onset of amenorrhea in subsequent months. Further data analysis suggests that host age or obesity did not influence CMF-induced changes in the plasma endocrine profile.
Breast Cancer Res Treat 1992 Jan
PMID:Endocrine profile in breast cancer patients receiving chemotherapy. 155 88

Basal prolactin (PRL) and total lactogenic hormone (TLH) levels were measured using a new microbioassay (BA) and conventional immunoradiometric assay (IRMA) in patients with breast cancer and compared to an age-matched control group. No significant differences were found using the IRMA, but BA lactogenic levels were significantly elevated in breast cancer patients compared controls, leading to a markedly elevated BA/IRMA ratio for both PRL (2.7 vs 1.4, P less than 0.0001) and TLH (2.8 vs 1.4, P less than 0.0001) which was greatest for postmenopausal women. Using the mean +2 standard deviations as the upper limit of normal, there was no significant difference between breast cancer patients and controls for IRMA, but BA and BA/IRMA PRL levels were elevated in 42% and 61% of the patients, respectively. There was a weak negative correlation of BA and IRMA PRL with age for normals (r = -0.53 for both) but no correlation was evident for breast cancer patients (r = 0.06 and -0.13, respectively) implying a sustained absolute and relative bioactive hyperprolactinaemia at all ages. These results show increased lactogenic bioactivity in breast cancer and suggest that different forms of bioactive prolactin undetected by IRMA (or enhancing serum factors) are present in the sera of these patients.
 ...
PMID:Prolactin and total lactogenic hormone measured by microbioassay and immunoassay in breast cancer. 155 4

The rate of growth and spread of breast cancer varies considerably from patient to patient. An observational study was undertaken to identify possible associations between breast cancer growth characteristics and a wide variety of host factors, including demographic, anthropometric, hormonal and dietary variables in 91 patients with breast cancer. Increasing age was associated with favourable growth characteristics, while previous tonsillectomy was associated with adverse growth characteristics. There were no significant associations in anthropometric variables. For postmenopausal women, increasing bioavailability of oestradiol was associated with favourable growth characteristics, while increasing prolactin concentration was associated with adverse growth characteristics. Increasing consumption of sugar, fibre, fruit and vegetables and vitamins was associated with favourable growth characteristics. Consumption of fat (monounsaturated and saturated) was associated with adverse characteristics when adjustment was made for total energy intake. The host environment may play a role in the control of breast cancer growth. In particular, the associations with oestrogen and progesterone receptor status indicate that nutrients may be of value as biological response modifiers in patients having hormonal therapy. This requires further investigation to assess therapeutic potential.
 ...
PMID:Host factors and breast cancer growth characteristics. 162 87

The prolactin receptor (PRLR) mediates the diverse effects of prolactin, which in the mammary gland include the development of lobuloalveolar structures and increased tumor cell proliferation. Treatment of mammary carcinoma cells with the differentiating agent sodium butyrate (NaB) is known to reduce PRLR binding activity and PRLR gene expression, however the mechanism which mediates these changes is unknown, prompting this investigation. Using MCF-7 human breast cancer cells, assay of the rate of PRLR gene transcription by the nuclear run-on technique indicated that 3 mM NaB reduced PRLR gene transcription by 50% after 3 h of treatment and that this effect was maintained for at least 24 h. The protein synthesis inhibitor cycloheximide failed to abrogate this effect, which indicated that NaB did not require continuing protein synthesis to reduce the rate of PRLR transcription. Measurement of PRLR mRNA stability, using Northern blot analysis at various times after the inhibition of transcription with actinomycin D, showed that NaB treatment did not alter PRLR mRNA half-life. These results indicate that NaB inhibits PRLR gene expression by a transcriptional mechanism that does not require continuing protein synthesis.
 ...
PMID:Transcriptional regulation of prolactin receptor gene expression by sodium butyrate in MCF-7 human breast cancer cells. 163 37

Prolactin receptor and oestrogen receptor are co-ordinately expressed in human breast cancer cell lines and in human breast tumour biopsies, leading to the suggestion that the expression of these receptors may be coupled. To examine this hypothesis, T-47D and MCF-7 human breast cancer cells were treated with sodium butyrate, a known modulator of oestrogen receptor levels, and the changes in oestrogen and prolactin receptor mRNA and binding activity were measured. In both cell lines treatment with 0.3-10 mM sodium butyrate resulted in a parallel decrease in prolactin and oestrogen receptor mRNA levels and binding activity. In T-47D cells, where the effect was transient, mRNA levels of both receptors recovered in parallel. These data indicated that oestrogen receptor and prolactin receptor gene expression is modulated in parallel by sodium butyrate and supported the hypothesis that the expression of these two receptors is coupled.
 ...
PMID:Coordinate regulation of oestrogen and prolactin receptor expression by sodium butyrate in human breast cancer cells. 173 81

In vivo studies have shown that the growth of the mammary gland is regulated by a complex synergistic interaction of protein, steroid and thyroid hormones, but it has proved difficult to fully reproduce these effects in vitro. It is becoming apparent that the hormones classically recognized as involved in mammary growth (oestrogen, progesterone, prolactin, GH, adrenal corticoids, triiodothyronine) bring about effects on epithelial cell proliferation at least in part through growth factors produced at distant sites (such as the liver) and also locally by mammary tissue, both parenchyma and stroma. Growth factor receptors can be demonstrated in mammary tissue. Receptor occupancy generates intracellular signals which enable cells to progress through the cell cycle, leading in ways still not understood to DNA synthesis and cell division. Within the mammary gland there probably exists a balance of stimulatory factors (such as IGFs and EGF/TGF-alpha) and inhibitory factors (such as TGF-beta). Interactions between epithelial and stromal cells, involving growth factors and the extracellular matrix, bring about pattern formation. Growth factors may also play some part in mammary differentiation and function, although the evidence here is less clear. Growth factors are also implemented in the failure of growth regulation which neoplastic transformation represents. Breast cancer cells can synthesize and secrete a variety of growth factors which may stimulate tumour growth through local autocrine/paracrine mechanisms. The oestrogen dependence of some breast cancers may involve oestrogen regulation of and interaction with growth factors, progression to hormone independence involving loss of this control. It is significant that the proteins which protooncogenes encode include growth factors and growth factor receptors. Much remains to be learnt about the nature and control of growth factors produced by and acting on the mammary gland. In breast cancer, this research offers the possibility of new methods of diagnosis and treatment.
 ...
PMID:The mammary gland. 175 17

Damage to the breast epithelium by chemical carcinogens as products of oxygen free radical release can lead to fibroblast proliferation, hyperplasia of epithelium, cellular atypia and breast cancer. Chemical carcinogens may accumulate in breast fluid in the non-lactating breast consequent to superoxide free radical production which occurs via the adenosine triphosphate (ATP) hypoxanthine pathway. This pathway is initiated by hypoxia of local tissue. Under hypoxic conditions ATP is broken down to form hypoxanthine. Hypoxanthine itself is broken down to produce xanthine and then uric acid. This results in the production of superoxide free radicals, the products of which are carcinogenic. The development of localized hypoxia, which is central to this hypothesis, is caused by acinal gland distention from fluid secreted by raised prolactin levels in the absence of oxytocin. Stimulation of the nipple in a non-lactating breast may raise plasma oxytocin and lower plasma prolactin levels. Contraction of the myoepithelial cells of the breast under the influence of oxytocin would relieve distention of the acinal glands and thus reduce hypoxia and the generation of lipid peroxidoses as products of free radical damage. The epidemiology of breast fibrosis and cancer support the notion that lack of nipple stimulation over time may be a significant variable. A review of this literature linked with current biochemical work on fibrosis and carcinogenesis suggest that draining the breasts of the products of superoxide free-radical release by the encouragement of regular nipple erections may prevent such breast disease.
 ...
PMID:Epidemiological and biochemical support for a theory on the cause and prevention of breast cancer. 180 62

The hormone dependency of the MCF-7 breast cancer cell line, while extensively tested in liquid culture, has not been previously evaluated under conditions of anchorage-independent growth in serum-free media. Using the soft agar clonogenic assay, we demonstrate that physiologically relevant concentrations of estradiol (E2), progesterone (Pg), and prolactin (PRL) similarly stimulated MCF-7 cell colony formation in the absence of serum. Addition of an anti-insulin-like growth factor-I (IGF-I) antibody inhibited E2- and Pg-stimulated growth, while PRL action was not affected. Similar results were obtained with an anti-IGF-I receptor antibody, except that its inhibitory effect on Pg-induced colony formation was modest and not statistically significant. Administration of either an anti-transforming growth factor-alpha (TGF-alpha) antibody or an anti-epidermal growth factor (EGF) receptor antibody similarly inhibited E2-stimulated MCF-7 cell growth in soft agar, while neither antibody influenced Pg or PRL effects. Addition of TGF-beta 1, -beta 2, -beta 3 similarly suppressed MCF-7 cell colony formation in a dose dependent manner to a degree comparable to that observed with 4-OH-tamoxifen (4-OH-T). Furthermore, the growth inhibitory effect of 4-OH-T was completely reversed by an anti-TGF-beta antibody. We conclude that IGFs and TGF-alpha are important mediators of E2-stimulated MCF-7 cell growth in soft agar. IGFs may also be playing a role in Pg action, while neither growth factor is involved in PRL-stimulated colony formation. Finally, TGF-beta appears to be an important mediator of antiestrogen-induced inhibition of tumor growth.
Breast Cancer Res Treat 1991 Dec
PMID:Growth factor involvement in the multihormonal regulation of MCF-7 breast cancer cell growth in soft agar. 181 68

Metabolic disorders induced by synthetic gestagens have been discussed under the aspect of single endocrine parameters or the carbohydrate or lipid metabolism. In order to obtain more complex information a prospective study of 26 patients was performed, who were treated with 1,000 mg medroxyprogesterone acetate (MPA) per day over a period of 5 weeks as a second-line therapy of breast cancer. Before treatment and afterwards once a week the serum concentrations of MPA, androstenedione, DHEA-S, cortisol, prolactin, insulin, c-peptide, glucose, cholesterol, triglycerides, phospholipids and the lipoprotein fractions (VLDL, IDL, LDL, HDL) were analyzed. Besides the reduction of the androgens and changes in the glucose regulation significant effects on the lipoprotein metabolism were observed, leading to the conclusion that under high-dose gestagen therapy very complex interactions of the endocrine and metabolic system occur.
 ...
PMID:[Plasma lipoprotein fractions in high-dose medroxyprogesterone acetate therapy in metastatic breast cancer]. 183 14

The comparison of blood levels of oestradiol, testosterone, prolactin, and sex-hormone binding globulin (SHBG) was made of 3250 rural Chinese and 300 British women, aged 35 to 64. To reduce the number of assays performed the blood samples were combined so as to form 390 and 30 pools, respectively. The Chinese had significantly less oestradiol and testosterone. Prolactin levels were similar in both races. SHBG was significantly lower in postmenopausal British women. In the Chinese women, testosterone was positively and prolactin negatively correlated with breast cancer mortality.
Breast Cancer Res Treat 1991 May
PMID:Serum hormone levels in British and rural Chinese females. 187 56


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