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

A 38-year-old male was admitted in January 1984 due to lymphadenopathies with hyperimmunoglobulinemia with a serum IgG level of 2,872 mg/dl. Following this, he was observed as an outpatient in regard to lymphadenopathies of unknown origin. In 1989, after the fourth lymph node biopsy he was diagnosed as having idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia. At that time his serum IgG level was 8,090 mg/dl. The elevated serum interleukin-6 (IL-6) level, up to 21.1 pg/ml, was particularly interesting, because IL-6 is involved in the oncogenesis of plasmacytoma/myeloma. The patient also had thrombocytosis, hematuria, and a serum increased level of C reactive protein which seemed to be related to the effects of IL-6 i.e. thrombopoiesis, induction of the proliferation of mesenchymal cells, and induction of the production of acute phase proteins by hepatocytes, respectively. Even though he displayed no outward symptoms before and after treatment with prednisolone and melphalan, elevated immunoglobulin levels were still present.
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PMID:[Idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia with elevated level of serum interleukin-6]. 163 73

Interleukin-6, IL-6, is a pleiotropic cytokine which plays a central role in defense mechanisms, including the immune response, acute phase reaction and hematopoiesis. Abnormal expression of the IL-6 gene has been suggested to be involved in the pathogenesis of a variety of diseases, especially rheumatoid arthritis, Castleman's disease, mesangial proliferative glomerulonephritis, multiple myeloma and Kaposi's sarcoma. In the case of multiple myeloma and Kaposi's sarcoma, the existence of an IL-6-IL-6 receptor autocrine loop has been implicated in the oncogenesis process. On the other hand, IL-6 has a potent anti-tumor activity against certain types of tumors. This anti-tumor effect is mediated by in vivo induction of tumor specific cytotoxic T cells and in part by a growth inhibitory activity of IL-6.
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PMID:The evidence for interleukin-6 as an autocrine growth factor in malignancy. 164 91

Interleukin 6 (IL-6) is a multifunctional cytokine regulating immune response acute phase reaction and hematopoiesis. IL-6 plays a critical role in B cell differentiation to plasma cells and is a potent growth factor for plasmacytoma and myeloma. Abnormal production of IL-6 has been suggested to be involved in polyclonal plasma cell abnormalities and plasma cell neoplasias. The deregulated expression of the IL-6 gene in transgenic mice resulted in the generation of malignant plasmacytoma. Based on these findings, it could be considered that continuous IL-6 gene expression plays an essential role in a multistep oncogenesis of plasma cell neoplasias. The role of IL-6 and its receptor in the generation of plasma cell neoplasias and the mechanisms of the IL-6 gene expression and IL-6 receptor-mediated signal transduction are described.
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PMID:Interleukin 6 (IL-6) and its receptor: their role in plasma cell neoplasias. 206 19

Interleukin 6 (IL-6) was originally characterized as a B-cell differentiation factor, responsible for the terminal maturation of activated B cells to immunoglobulin producing cells. Recent works reveal that IL-6 has a wide variety of biological functions on various cells. In particular, IL-6 has been shown to augment the growth of freshly isolated human myeloma cells, and the myeloma cells constitutively produce IL-6 and express IL-6 receptors. Moreover, it has been shown that anti-IL-6 antibody can inhibit the in vitro growth of the myeloma cells. This is direct evidence that an autocrine loop is operating in freshly isolated myeloma cells, and that a constitutive production of IL-6 and activation of the IL-6 gene could be involved in the oncogenesis of human myeloma.
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PMID:Cytokines as autocrine growth factors in malignancies. 270 35

A c-Ha-ras oncogene, to a lesser extent the c-Ha-ras proto-oncogene, and the tumor promoter 12-O-tetradecanoylphorbol-13-acetate activate the inactive polyoma virus (Py) enhancer in a myeloma cell line and the partially active Py enhancer in NIH 3T3 fibroblasts, but have no effect on the active Py enhancer in LMTK- fibroblasts. In addition, c-Ha-ras can stimulate the inactive Py enhancer in embryonal carcinoma F9 cells. c-Ha-ras activation in embryonal carcinoma cells does not appear to involve reversal of "E1A-like" inhibition of the enhancer. We suggest that modulation of cellular enhancer activity could play a key role in tumorigenesis by oncogenes.
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PMID:The c-Ha-ras oncogene and a tumor promoter activate the polyoma virus enhancer. 302 48

Human B cell stimulatory factor 2 (BSF-2) was originally characterized and isolated as a T cell-derived factor that caused the terminal maturation of activated B cells to immunoglobulin-producing cells. Molecular cloning of the complementary DNA predicts that BSF-2 is a protein of relative molecular mass (Mr) 26,000 similar or identical to interferon beta 2, hybridoma plasmacytoma growth factor and hepatocyte stimulating factor. IL-6 has been proposed as a name for this molecule. It is now known that BSF-2 has a wide variety of biological functions and that its target cells are not restricted to normal B cells. Responses are also seen in T cells, plasmacytomas, hepatocytes, haematopoietic stem cells, fibroblasts and rat phoeochromocytoma, PC12 (Satoh, T. et al., manuscript in preparation). Of particular interest to this report is that human BSF-2 is a potent growth factor for murine plasmacytomas and hybridomas. This observation suggested to us that constitutive expression of BSF-2 or its receptor could be responsible for the generation of human myelomas. In this study we report that myeloma cells freshly isolated from patients produce BSF-2 and express its receptors. Moreover, anti-BSF-2 antibody inhibits the in vitro growth of myeloma cells. This is direct evidence that an autocrine loop is operating in oncogenesis of human myelomas.
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PMID:Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. 325 60

The bone marrow puncture fluid of human multiple myeloma was inoculated subcutaneously in BALB/C/nu nude mice. After passage of the xenograft from nude mice in vitro, a murine malignant lymphosarcoma cell line was unexpectedly established, which was named NLB-SK. The murine NLB-SK cell line has been cultivated in vitro over 72 passages for 10 months. Repeated cryopreservation showed that the murine NLB-SK cell line revived satisfactorily. Based on cell biological characteristics the malignant transformation might be attributed to horizontal oncogenesis between human malignant tumor cells and nude mouse normal somatic cells.
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PMID:In vivo induction of malignant transformation of nude mouse B lymphocytes by a human multiple myeloma. 326 10

The major component of the core structure of avian sarcoma leukosis viruses is a 27 kD molecular weight polypeptide, p27. Spleen cells from mice immunized with the Schmidt-Ruppin strain of Rous sarcoma virus (RSV) were fused with mouse myeloma cells (SP2/0), and hybridoma cell lines producing monoclonal antibodies to p27 were isolated. The monoclonal antibodies were all of the IgG1 subclass with kappa light chains. These antibodies immunoprecipitated p27 and its precursor proteins from extracts of RSV-transformed cells. Reciprocal competitive binding experiments defined five nonoverlapping antigenic determinants within p27. The monoclonal antibodies also immunoprecipitated the transforming protein, p110gag-myc, from avian myelocytomatosis virus transformed cells. Their usefulness in studies of virion maturation and viral oncogenesis is discussed.
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PMID:Monoclonal antibodies specific for the virion polypeptide, p27, of avian retroviruses. 620 83

Continued monitoring of a family for new malignant tumors has revealed diverse immunological and neoplastic disorders during a 15-year period. In 1966, the proband developed lymphoma. In 1975, his antibody titers to Epstein-Barr virus (EBV) became elevated, and again, he developed a malignant lymphoma. He also had borderline hypo-immunoglobulin A, died of glioblastoma multiforme in 1977, and at autopsy, had adenomatous colonic polyps. His eldest brother has normal immunoglobulin levels, but developed immune thrombocytopenia in 1973 and had elevated EBV antibody titers in 1980. Another brother had hypo-immunoglobulin A, thymoma in 1965, and adenomas and adenocarcinoma of the colon. Two other brothers succumbed to glioblastoma in 1968 and 1969. The father of the proband had bronchiectasis in 1952, hypo-immunoglobulin M documented in 1972, and elevated EBV antibody titers 5 years preceding development of a malignant lymphoma. The latter contained 10 EBV genome equivalents/cell by EBV viral DNA/DNA reassociation kinetics analysis. The proband's grandmother had died of an immunoglobulin G-secreting myeloma in 1977, and his grandfather had borderline low immunoglobulin M, elevated EBV antibody titers, and hypopharyngeal carcinoma in 1980. Predisposition to oncogenesis in this family was probably inherited.
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PMID:Diverse familial malignant tumors and Epstein-Barr virus. 627 70

Spontaneously arising and chemically or virally induced tumors usually cannot be analyzed in the early stages of tumorigenesis. Growth characteristics of these tumors thus are not available and it is unknown whether their expansion at any stage is influenced by the immune system. We have developed the following strategy to evaluate possible deviations from exponential growth in initial stages when a tumor is not yet manifest and in order to overcome the two main objections against most experiments in tumor immunology: use of possibly selected transplantable tumors and high initial cell doses. BALB/c mice received 0.5 ml of Pristane intraperitoneally three times within 16 weeks. This treatment induces plasmacytomas in 58% of the animals within 1 year. Mice were bled twice a week beginning with the 5th week after the last injection and sera were stored. Guinea-pig anti-idiotypic antibodies were raised against the IgG myeloma protein of a plasmacytoma developing in mouse 6-15 and a radioimmunoassay was set up. Sera of mouse 6-15 were then tested in retrospect for appearance and increase of the myeloma idiotype Id 6-15. We followed this idiotype thus for 19 weeks from a concentration of about 10 micrograms/ml up to 3 mg/ml serum. Plasmacytoma 6-15 cell growth was calculated from the Id 6-15 levels. In early phases wave-like fluctuations were found, possibly due to varying ratios of secretor to total plasmacytoma 6-15 cells. This phase was followed by an exponential increase in secretor cell number. At no time was there evidence for anti-idiotypic auto-antibodies against Id 6-15. The data are discussed in connection with possibly early activation of cellular components of the immune system.
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PMID:Analysis of the growth characteristics of a primary BALB/c IgG plasmacytoma. 686 84


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