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)

Hormone deprivation may cause remission in women with advanced breast cancer. Occasionally this remission may last for 15 years. However, only 30% of women respond in this way. An essential 1st step in the response of hormone-sensitive tissues is binding of the hormone to a receptor protein in or on the target cell. For steroids, receptors have been found in the cytoplasm, while for polypeptide hormones, receptors seem to be on the surface of cell membranes. Between 40-85% of human breast cancers contain estrogen receptors. If estrogen receptors are present, 43-60% of patients have responded to endocrine therapy, whereas only 8% have responded if estrogen receptors were not present. Treatment with antiestrogens has achieved 16% response rates in patients in whom estrogen receptors were not present. Progesterone receptors have been detected in 57% of breast cancers, together with estrogen receptors in 49%. The significance of this finding is not apparent. The main peptide hormone implicated in promoting growth of breast cancers is thought to be prolactin. Growth hormone and human lactogen have also been implicated in promoting breast cancer. Receptors may be detected in human breast, prostate, endometrial, and other cancers and these preferentially bind estrogen, androgen, progesterone analogue, prolactin, growth hormone, or placental lactogen. The heterogeneity of human cancers is thus shown. Most remissions are short-lived and after relapse there is less chance for antihormonal therapy. To choose the best treatment at a given time the most hopeful prospect is that investigations may determine criteria for the study of the particular cancer in each patient.
 ...
PMID:Editorial: Hormone receptors and breast cancer. 17 60

Recent studies showed that both the pineal gland and the endogenous opioid system are involved in the modulation of the immune system and in the regulation of tumor growth. Moreover, a relationship between pineal and opioid system has been demonstrated. In order get an overall view of the psychoneuroendocrine interactions in cancer patients, the levels of melatonin, the most important pineal hormone, and of beta-endorphin have been measured on blood samples collected during the morning. The study was carried out on 54 patients, 42 healthy subjects, and in 34 patients having illnesses other than cancer. Breast cancer, lung carcinoma, and colorectum cancer were the three neoplasms detected in the patients investigated. Growth hormone (GH), somatomedin-C and prolactin (PRL) levels were also determined. beta-endorphin levels were found to be substantially within the normal range in patients with cancer, whereas those of melatonin were raised in several cases. The beta-endorphin/melatonin ratio was higher than 2 in normal subjects, in non-neoplastic patients and in most cancer patients without metastases, whereas this ratio was lower than 2 in almost all patients in a metastatic stage of the disease. Neither melatonin levels nor those of beta-endorphin appeared to be significantly correlated with GH, somatomedin-C, and PRL concentrations. The low beta-endorphin/melatonin ratio observed in metastatic patients suggests the presence of an unbalanced relation between the pineal and the opioid system in those subjects. Therefore, an anomalous relationship between pineal function and opioid activity might play a role in the clinical course of neoplastic disease.
 ...
PMID:A study on the relationship between the pineal gland and the opioid system in patients with cancer. Preliminary considerations. 296 35

Hypophysectomy was studied for its possible effects on cancer by alt eration of the endorcines at the New York Hospital-Cornell Medical Center beginning in 1953. The major effort has been the treatment of 850 cases of metastic breast cancer. In 80 patients with other types of metastatic cancer benefit was found only in 50 cases of prostatic cancer. Prolactin is mediated directly from the anterior pituitary to breast tissue where it aids and abets the growth of breast cancer; its secretion is largely dependent on the estrogen produced in ovaries and adrenals. In humans estrogen given after total hypophysectomy is found to be ineffective in altering metastases. Growth hormone is also produced in the anteriod lobe of the pituitary but its production is not dependent on an estrogen feed-back mechanism. If the primary cancer is dependent on the presence of prolactin, failures with hypophysectomy are explained the tumor having gained autonomy and being no longer so dependent. Contraindications to hypophysectomy include extensive pulmonary, liver, or brain metastases and any systemic disease that would preclude major surgery. Following a remission after oophorectomy, another remission with hypophysectomy may often be obtained. Neither the pathological type of a breast cancer nor the location of metastases alter the results. However the longer the interval between mastectomy and reactivation of the tumor, the more favorable the outlook. Maintenance substitution therapy following removal of the pituitary employs daily hydrocortisone, 17.5 mg orally, or equivalent steroid preparations. The mortality rate is 2% in the first 30 days after operation. In 88 patients evaluated 2 years after operation those who had received a remisssion lasting over 6 months survived nearly 5 times longer than those unbenefitted by the operation. The intracranial procedure is preferred. In cases of failure or when a remission terminates, male hormone therapy, chemotherapy, or radiation may have limited value.
 ...
PMID:Hypophysectomy for metastatic cancer. 466 60

Insulin-like growth factor I (IGF-I) is a potent breast cancer mitogen. Growth hormone (GH) up-regulates hepatic IGF-I gene expression and circulating IGF-I level. Tissue IGF bioactivity is influenced not only by circulating IGF-I and IGF-II levels but also by autocrine and paracrine production of these growth factors and by IGF binding proteins. There is considerable person-to-person variability in GH-IGF-I physiology. Both laboratory and epidemiological data are consistent with the hypothesis that the host GH-IGF-I axis influences breast cancer behavior, but such an effect has not been directly demonstrated. To determine whether breast cancer growth in an in vivo model is influenced by the host GH-IGF-I axis, we compared the growth of human MCF-7 breast cancer cells in control mice to that in mice homozygous for lit, a missense mutation resulting in loss of function of the pituitary GH-releasing hormone receptor and secondary suppression of GH and IGF-I. Breast cancer growth was significantly reduced in lit/lit animals compared to control hosts [tumor size (mean +/- SD) on day 39,444 +/- 82 versus 845 +/- 444 mm3, respectively; P < 0.001, Mann-Whitney U test]. These data demonstrate that in our model, host GH-IGF-I axis physiology plays a role in determining breast cancer behavior. The results a) suggest that patient-to-patient variability in GH-IGF-I physiology may contribute to the large variability between patients regarding breast cancer behavior, and b) motivate clinical trials of novel hormonal treatment strategies that target the GH-IGF-I axis.
 ...
PMID:Reduced growth of human breast cancer xenografts in hosts homozygous for the lit mutation. 860 94

Growth hormone (GH) is now believed to be the pituitary factor that is responsible for mammary ductal morphogenesis. Mammary development at puberty occurs because of synergy between GH and estrogen on formation of terminal end buds (TEBs). TEBs extend into the substance of the mammary gland fat pad, resulting in ductal morphogenesis. Ultimately, the whole mammary fat pad accommodates a complex network of ducts. IGF-I or des(1-3) IGF-I mimic the actions of GH on TEB formation in hypophysectomized, gonadectomized rats. Since GH stimulates IGF-I mRNA within the mammary gland synergistically, we hypothesize that IGF-I partially mediates actions of GH in mammary gland development. Studies in transgenic mice overexpressing IGF-I, des(1-3) IGF-I, or IGFBP-3 show that IGF-I causes ductal hypertrophy in the lactating mouse and prevention of post-lactational mammary gland involution. One of the mechanisms for this effect involves apoptosis. The potential role of GH or IGF-I in mammary carcinogenesis, and the applicability of animal studies to humans, are discussed.
Breast Cancer Res Treat 1998 Feb
PMID:Role of IGF-I in normal mammary development. 951 76

Perturbations of the insulin-like growth factor (IGF) axis, including the autocrine production of IGFs, IGF binding proteins (IGFBPs) and IGFBP proteases such as prostate specific antigen (PSA), and cathepsin D have been identified in prostate, lung and breast cancer cells and tissues. Serum IGFBP-3 levels have been found to be negatively correlated to the risk of cancer. Interestingly, IGFBP-3 is a potent inhibitor of IGF action and also mediates apoptosis via an IGF-independent mechanism. Recent case-control studies have found an approximately 10% increase in the serum levels of IGF-I in patients with prostate, breast and lung cancers, which are among the most frequently diagnosed cancers. While the studies indicate an association between serum IGF-I levels and cancer risk, causality has not been established. Thus, serum IGF-I level may actually be a confounding variable, serving as a marker for autocrine tissue IGF-I production. Growth hormone (GH) therapy raises both IGF-I and IGFBP-3 levels in serum. However, the role of GH in controlling prostate, breast and lung growth and carcinogenesis remains unclear from animal studies. Increased GH levels as seen in acromegaly have been associated with benign prostatic hyperplasia but not with prostate, breast or lung cancers, although colon cancer mortality may be increased. Should serum IGF-I levels be proven to play a causal role in the pathogenesis of cancer, interpreting the risk associated with therapies such as GH replacement must take into account both the duration of exposure and the risk magnitude associated with the degree of serum IGF-I elevation. Since GH-deficient patients often have a subnormal IGF-I serum level, which normalizes on therapy, their cancer risk on GH therapy probably does not increase substantially above that of the normal population. Until further research in the area dictates otherwise, ongoing surveillance and routine monitoring of IGF-I levels in GH recipients should become standard of care.
 ...
PMID:IGFs and human cancer: implications regarding the risk of growth hormone therapy. 1059 43

Pegvisomant is a mutated human growth hormone molecule, which binds to the growth hormone receptor. This binding, however, does not lead to signal transduction. Therefore, in high concentrations pegvisomant acts as a growth hormone receptor antagonist. In a short term study (3 months) pegvisomant was shown to be an effective treatment for acromegaly. On theoretical grounds decreasing the biological effects of growth hormone in patients with diabetes mellitus could have a favourable impact on the severity of the secondary complications associated with this disease. Animal models for diabetic retino- and nephropathy are in accordance with this concept. Human data are lacking but clinical studies investigating the effect of pegvisomant in diabetes mellitus are in preparation. Growth hormone, either directly or via its downstream effector insulin-like growth factor-I (IGF-I) has been implicated as an important factor in the growth of malignant tumours. Animal studies in which human colon and breast cancer models were used showed that pegvisomant can powerfully decrease tumour growth. Studies in cancer patients have not yet started.
 ...
PMID:[Growth hormone receptor antagonists: potential indications]. 1122 59

Growth hormone (GH) is used or is being evaluated for efficacy in treatment of short stature, aspects of aging, cardiac disorders, Crohn's disease, and short bowel syndrome. Therefore, we synthesized several stable growth hormone-releasing factor (GRF) analogues that could be therapeutically useful. One potent analog, [D-Ala(2),Aib(8, 18,)Ala(9, 15, 16, 22, 24-26,)Gab(27)]hGRF(1-27)NH(2) (GRF-6), with prolonged infusion caused severe diarrhea in monkeys; however, it had no side-effects in rats. Because GRF has similarity to VIP/PACAP and VIPomas cause diarrhea, this study investigated the ability of this and other GRF analogues to interact with the VIP/PACAP receptors. Rat VPAC(1)-R (rVPAC(1)-R), human VPAC(1)-R (hVPAC(1)-R), rVPAC(2)-R and hVPAC(2)-R stably transfected CHO and PANC 1 cells were made and T47D breast cancer cells containing native human VPAC(1)-R and AR4-2J cells containing PAC(1)-R were used. hGRF(1-29)NH(2) had low affinity for both rVPAC(1)-R and rVPAC(2)-R while VIP had a high affinity for both receptors. GRF-6 had a low affinity for both rVPAC(1)-R and rVPAC(2)-R and very low affinity for the rPAC(1)-R. VIP had a high affinity, whereas hGRF(1-29)NH(2) had a low affinity for both hVPAC(1)-R and hVPAC(2)-R. In contrast GRF-6, while having a low affinity for hVPAC(2)-R, had relatively higher affinity for the hVPAC(1)-R. In guinea pig pancreatic acini, all GRF analogues were full agonists at the VPAC(1)-R causing enzyme secretion. These results demonstrate that in contrast to native hGRF(1-29)NH(2,) GRF-6 has a relatively high affinity for the human VPAC(1)-R but not for the human VPAC(2)-R, rat VPAC(1)-R, rat VPAC(2)-R or rat PAC(1)-R. These results suggest that the substituted GRF analog, GRF-6, likely causes the diarrheal side-effects in monkeys by interacting with the VPAC(1)-R. Furthermore, they demonstrate significant species differences can exist for possible therapeutic peptide agonists of the VIP/PACAP/GRF receptor family and that it is essential that receptor affinity assessments be performed in human cells or from a closely related species.
 ...
PMID:GI side-effects of a possible therapeutic GRF analogue in monkeys are likely due to VIP receptor agonist activity. 1144 45

Growth hormone (GH) and prolactin (PRL) are anterior pituitary hormones that have multiple roles in growth and metabolism. Both hormones are important in mammary development and breast cancer. The epidermal growth factor (EGF) family of peptides and the receptors that they activate (the ErbB family) are also major players in mammary biology and pathophysiology. Recent studies in signal transduction have highlighted the interplay between signaling pathways referred to as crosstalk. In this review, cell biological and signaling studies related to crosstalk between GH and PRL and the ErbB family are discussed. In particular, the role of GH- and PRL-induced phosphorylation of ErbB receptors in regulating EGF responsiveness is highlighted with attention to potential pathophysiological relevance.
 ...
PMID:Mechanistic aspects of crosstalk between GH and PRL and ErbB receptor family signaling. 1823 42

Cytokines and growth factors are responsible for inducing the expression of suppressor of cytokine signaling (SOCS) and cytokine-inducible SH2 containing (CIS) proteins. SOCS and CIS proteins are negative regulators of the JAK/STAT pathway, and exert their physiological effects by suppressing the tyrosine kinase activity of cytokine receptors and inhibiting STAT activation. Growth hormone (GH) is considered as a true cytokine and its local production directly contributes to tumor progression. In an initial study, we have found that CIS expression is increased in human breast cancer in proliferative areas corresponding to high level of GH synthesis. The results of the study presented here confirm the presence of a negative feed back loop in MCF7 cells stably transfected with the hGH gene (MCF-hGH). Real-time PCR analysis showed that gene expression levels of CIS were increased by 80% in MCF-hGH cells as compared to control cell line. Similarly, we have found that the level of CIS gene expression is increased by 50% in primary cultures of human breast cancer, reinforcing the pathophysiological impact of CIS. We previously demonstrated that increasing levels of transfected CIS resulted in strong activation of the mitogen-activated protein (MAP) kinase pathway. Thus, CIS protein has been hypothesized as acting like an activator of the MAPK pathway and an inhibitor of the differentiated cells functions mediated through the JAK/STAT pathway. In the present study, we demonstrate the role of CIS protein in tumor progression in particular its positive effects on cell proliferation and colony formation.
 ...
PMID:Involvement of a JAK/STAT pathway inhibitor: cytokine inducible SH2 containing protein in breast cancer. 1849 55


1 2 Next >>