Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A hybridoma cell line that secretes monoclonal antibody, MAb-ER-Br-1-15-4-18 is established. The MAb is highly specific for estrogen receptor (ER) from human breast tumor cells. In order to raise the antibody, the ER was first isolated from human breast tumor. Mice were immunized with the partially purified ER and the fusion of the spleen cells from the mouse, showing the highest serum titer, with the cells of the NS-1 mouse myeloma line, produced hybrid cells which continuously secreted antibodies specific for ER. Three of the hybridoma cultures which tested strongly positive were cloned using limiting dilution method and one of the cell lines was selected for further study. The recovery of the MAb from the cell culture was done by ammonium sulfate precipitation followed by dialysis and then hydroxylapatite liquid chromatography using linear gradients. The purity of the antibody was checked by polyacrylamide gel electrophoresis. The MAb was isotyped and found to be IgG1. When checked against other antigens the MAb showed a minimal cross-reactivity to ER from rabbit uterus and none to ovalbumin or rat liver ferritin. Further experiments showed that the MAb recognized the ER bound to the hormone and ER in the nucleus of breast tumor cells.
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PMID:Production and characterization of a monoclonal antibody to partially purified estrogen receptor from human breast tumor. 292 8

A 65-kDa estrogen receptor (ER) protein has been demonstrated both by sucrose gradient analysis and by immunoblot, using anti-ER monoclonal antibodies (MAbs). Since the ER is denatured in many experimental situations, such as formaldehyde fixing of samples for histochemistry and electroimmunoblotting studies, in this work we used a denatured 60-70-kDa ER-rich protein preparation as antigen for mice immunization in order to raise anti-ER MAbs. That material was obtained by affinity purification on an allyl-estradiol matrix of the MCF-7 cytosolic ER, followed by further isolation and enrichment by PAGE. NS-1 myeloma cells and spleen lymphocytes from the immunized mice were fused, and resultant hybridoma colonies were screened by [125I]-estradiol-labelled nuclear ER immunoprecipitation. The isolated MAb, E476, shows a moderate ability to precipitate ER and reacts strongly with a 46-kDa antigen in Western blot assay. The 46-kDa antigen was not detectable in native cytosol but became reactive after 50% ammonium sulfate precipitation of cytosolic proteins. The 46-kDa antigen appeared concentrated in the NaSCN plus estradiol eluate of the affinity column used for cytosolic ER purification. Freshly prepared 60-70-kDa material from the preparative gel electrophoresis did not show any E476 reactivity. However, when the 60-70-kDa proteins were frozen, thawed and speed vacuum concentrated, the 46-kDa antigen became detectable. Storage increased the reactivity of the 60-70-kDa material with the E476 MAb. The 46-kDa antigen was present only in the ER positive cell lines, and was absent in all negative cell lines tested. The 46-kDa protein is also present in the ER positive human breast cancer specimens. We conclude that the 46-kDa protein identified with the E476 MAb in human breast cancer is probably a naturally occurring ER fragment.
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PMID:A 46-kDa antigen associated with estrogen receptor in human breast cancer. 338 60

Fusion of splenic lymphocytes from Lewis rats, immunized with affinity-purified estrogen receptor from the cytosol of MCF-7 human breast cancer cells, with two different mouse myeloma lines, has provided 13 monoclonal hybridoma lines secreting antiestrophilin antibodies, each of which (with one possible exception) recognizes a different antigenic determinant in the human receptor molecule. Of this library of monoclonal antibodies, some react with estrophilin from all sources tested, some react with mammalian but not avian receptors, whereas one preparation appears specific for estrophilin from primate sources. By proteolytic digestion under controlled conditions with mercury-deactivated papain, chymotrypsin, and trypsin, respectively, it is possible to remove sequentially the determinants recognized by one, two or three of the monoclonal antibodies, leaving the epitopes for the six remaining antibodies investigated on the steroid-binding portion of the receptor. The proteolytic fragment containing the epitope most readily removed (by mercuripapain) also contains the DNA-binding domain of the activated receptor molecule. Immunocytochemical staining, using the peroxidase procedure with various monoclonal antibody preparations, of frozen sections of human breast cancer tissue, fixed in ethanol or in picric acid-formaldehyde reagent, shows clearly that the majority of the native receptor, which appears in the cytosol after tissue homogenization, is actually localized within the nuclear compartment in the intact cell. The immunocytochemical technique also permits the identification of mixed populations of receptor-containing and non-containing cells in human breast cancers.
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PMID:Immunochemical studies of estrogen receptors. 620 Jul

Hybridoma cells have been produced by fusing SP2/O-Ag14 mouse myeloma cells with spleen cells from a mouse immunized with a purified preparation of estrogen receptor from calf uterus. The antibodies, all of the immunoglobulin G (IgG) class, interact with different forms of calf receptor as well as with rat and human receptors. The equilibrium dissociation constant of the antibody-receptor complex was measured in solid phase and in solution. With immobilized antibodies the Kd is 0.06 nM whereas in solution it is 0.5 nM. Only one antigenic determinant is present per molecule of receptor with the antibodies tested. The antibodies JS34/32 are able to form only a 1:1 complex with the 8S form of the receptor, whereas a 2:1 receptor-IgG complex is formed at low antibody concentration with the high-salt or nuclear form of receptor. The antibodies JS34/32 and JS28/32 prevent neither the nuclear uptake of the receptor nor the extraction of the translocated receptor from the nuclei.
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PMID:Monoclonal antibodies against estrogen receptor: interaction with different molecular forms and functions of the receptor. 715 74

Characterisation of murine hybridoma cell lines derived from the fusion of lymphocytes migrating from explant cultures of early, pregnancy-associated metrial glands (days 6-8 of gestation) to SP 2/0 cells, has been extended (van den Heuvel et al., J. Reprod. Immunol., 27 (1994) 13-36). These hybridomas have been grown in culture for over 2 years and are thought to represent the only immortalized lines of murine pregnancy-associated, uterine natural killer (uNK) cells. Previous studies had shown that these hybridomas, known as GWM cells, lack uNK cell surface markers, but share with uNK cells the expression of the lytic protein perforin and the ability to lyse YAC cells, a natural killer cell target (van den Heuvel et al., J. Reprod. Immunol., 27 (1994) 13-36). We report here, the evaluation of the transcription and expression of genes encoding the estrogen receptor (ER), the progesterone receptor (PR) and the interleukin 2 receptor complex (IL 2R alpha, beta and gamma) by uNK cells at day 8 of gestation and by GWM 1-2 cells and SP 2/0 cells. Our investigations indicate that expression of these genes divides day 8 uNK cells into subsets, with the predominant population being ER+, PR-, IL 2R alpha +, IL 2R beta + and IL 2R gamma +. Like day 8 uNK cells, most GWM 1-2 cells expressed all three chains of the IL 2R complex. In addition, GWM 1-2 cells expressed the ER but the PR was not detected on this cell line. Only the IL 2R alpha was detected on the SP 2/0 myeloma cell line. These studies further validate the use of GWM hybridomas as models for pregnancy-associated uNK cells.
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PMID:An analysis of the uterine lymphocyte-derived hybridoma cell line GWM 1-2 for expression of receptors for estrogen, progesterone and interleukin 2. 888 21

The skeleton is the most common organ to be affected by metastatic cancer, and tumors arising from the breast, prostate, thyroid, lung, and kidney possess a special propensity to spread to bone. Breast carcinoma, the most prevalent malignancy, causes the greatest morbidity. Of great clinical importance is the observation that metastatic bone disease may remain confined to the skeleton. In these patients, the decline in quality of life and eventual death is due almost entirely to skeletal complications and their subsequent treatment. Bone pain is the most common complication of metastatic bone disease, resulting from structural damage, periosteal irritation, and nerve entrapment. Recent evidence suggests that pain caused by bone metastasis may also be related to the rate of bone resorption. Hypercalcemia occurs in 5-10% of all patients with advanced cancer but is most common in patients with breast carcinoma, multiple myeloma, and squamous carcinomas of the lung and other primary sites. Pathologic fractures are a relatively late complication of bone involvement. The clinical courses of breast and prostate carcinoma are relatively long, with a median survival of 2-3 years. For patients with breast carcinoma, good prognostic factors for survival after the development of bone metastases are good histologic grade, positive estrogen receptor status, bone disease at initial presentation, a long disease free interval, and increasing age. In addition, patients with disease that remains confined to the skeleton have a better prognosis than those with subsequent visceral involvement. For patients with prostate carcinoma, adverse prognostic features include poor performance status, involvement of the appendicular skeleton and visceral involvement, whereas for patients with multiple myeloma, the levels of serum beta2-microglobulin and lactate dehydrogenase and the immunologic phenotype are the most important factors. These prognostic factors may be useful in planning the rational use of bisphosphonates in the treatment of advanced cancer.
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PMID:Skeletal complications of malignancy. 936 26

Osteoporosis is increasingly recognised in men. Low bone mass, risk factors for falling and factors causing fractures in women are likely to cause fractures in men. Bone mass is largely genetically determined, but environmental factors also contribute. Greater muscle strength and physical activity are associated with higher bone mass, while radial bone loss is greater in cigarette smokers or those with a moderate alcohol intake. Sex hormones have important effects on bone physiology. In men, there is no abrupt cessation of testicular function or 'andropause' comparable with the menopause in women; however, both total and free testosterone levels decline with age. A common secondary cause of osteoporosis in men is hypogonadism. There is increasing evidence that estrogens are important in skeletal maintenance in men as well as women. Peripheral aromatisation of androgens to estrogens occurs and osteoblast-like cells can aromatise androgens into estrogens. Human models exist for the effects of estrogens on the male skeleton. In men aged > 65 years, there is a positive association between bone mineral density (BMD) and greater serum estradiol levels at all skeletal sites and a negative association between BMD and testosterone at some sites. It is crucial to exclude pathological causes of osteoporosis, because 30 to 60% of men with vertebral fractures have another illness contributing to bone disease. Glucocorticoid excess (predominantly exogenous) is common. Gastrointestinal disease predisposes patients to bone disease as a result of intestinal malabsorption of calcium and colecalciferol (vitamin D). Hypercalciuria and nephrolithiasis, anticonvulsant drug use, thyrotoxicosis, immobilisation, liver and renal disease, multiple myeloma and systemic mastocytosis have all been associated with osteoporosis in men. It is possible that low-dose estrogen therapy or specific estrogen receptor-modulating drugs might increase BMD in men as well as in women. In the future, parathyroid hormone peptides may be an effective treatment for osteoporosis, particularly in patients in whom other treatments, such as bisphosphonates, have failed. Men with idiopathic osteoporosis have low circulating insulin-like growth factor-1 (IGF-1; somatomedin-1) concentrations, and IGF-1 administration to these men increases bone formation markers more than resorption markers. Studies of changes in BMD with IGF-1 treatment in osteoporotic men and women are underway. Osteoporosis in men will become an increasing worldwide public health problem over the next 20 years, so it is vital that safe and effective therapies for this disabling condition become available. Effective public health measures also need to be established and targeted to men at risk of developing the disease.
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PMID:Osteoporosis in men. New insights into aetiology, pathogenesis, prevention and management. 988 98

It has recently been reported that the human myeloma cell line U266 proceeds to undergo apoptosis after cultivation with the antiestrogen tamoxifen, thus raising the possibility that antiestrogens may be candidates for use in myeloma therapy. To obtain basic information on the effects of antiestrogens on myeloma cells, we investigated the mRNA expression levels of estrogen receptor (ER)-alpha, ER-beta, and coactivators and corepressors in nine human myeloma cell lines and compared them with those of seven human breast cancer cell lines including four ER-positive and three ER-negative lines. The alterations in cell growth and mRNA expression of the target genes of ER or those of cytokines in the myeloma lines by estradiol or antiestrogens (tamoxifen and toremifene) were also investigated. In addition, effects on membrane Fas expression, appearance of apoptosis, and cell cycle perturbation were analyzed. It was revealed that ER-beta and corepressors were dominantly expressed in myeloma cells, and antiestrogens induced growth inhibition through apoptosis mediated by a Fas-related pathway and G1 arrest of the cell cycle in myeloma cell lines.
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PMID:Estrogen receptors in human myeloma cells. 1072 10

Interleukin-6 (IL-6) is a multifunctional cytokine that plays important roles in the immune system, hematopoiesis, and acute phase reactions. Estrogens have significant roles in a variety of biological events, such as the development and maintenance of female reproductive organs, and bone and lipid metabolism. Previous studies demonstrated that estrogens suppress IL-6-induced osteoporosis and the growth of multiple myeloma cells by repressing IL-6 and IL-6 receptor gene expression. Here we present a novel mechanism for the inhibitory effect of estrogens on IL-6 function. IL-6-induced activation of signal transducer and activator of transcription 3 (STAT3) activity and STAT3-mediated gene expression were suppressed by 17beta-estradiol (E2) in breast cancer cells. E2-mediated inhibition of STAT3 activation was reversed by tamoxifen, an estrogen receptor (ER) antagonist. We provide evidence that the inhibitory action of ER on STAT3 activity was due to direct physical interactions between STAT3 and ER which represents a novel form of cross-talk between STAT3 and ER signaling pathways.
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PMID:Cross-talk between signal transducer and activator of transcription 3 and estrogen receptor signaling. 1111 55

A variety of cancers are associated with bone. Primary tumors can arise in bone, common cancers, such as those of breast and prostate origin, metastasize to bone, and multiple myeloma neoplastic disease affects bone profoundly. The cellular and molecular mechanisms underlying these pathological processes are increasingly being understood. The interaction of tumor cells with bone cells, osteoblasts and osteoclasts, and with the bone local environment is a new promising direction in research, which should help to develop new therapies. In this article we will relate the newest developments in the molecular research to the pathology of the tumor bone disease. Potential new targets for drugs, aimed specifically at tumor bone diseases, will be highlighted. Furthermore, we will describe the existing compounds that are either used in treatment or have a potential as therapeutic agents, such as bisphosphonates, Src inhibitors, and selective estrogen receptor modulators.
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PMID:Tumor bone diseases: molecular mechanisms and opportunities for novel treatments. 1267 61


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