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)

In our previous study we found that the ARH 77 human B lymphoblastoid cell line, originating from a patient with multiple myeloma, produced both human interferon-alpha (HuIFN-alpha) and HuIFN-beta after induction with Sendai virus. In order to examine whether IFN-alpha-producing ARH 77 cell clones can be separated from IFN-beta-producing ones, the ARH 77 line was cloned by the soft agar method. Twelve clones chosen at random were examined for IFN production and the antigenic types of IFN produced were determined. All examined clones simultaneously produced both HuIFN-alpha and HuIFN-beta, although the ratio of HuIFN-alpha to HuIFN-beta production was variable among the clones. This result suggests that one lymphoblastoid cell can produce both HuIFN-alpha and HuIFN-beta.
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PMID:The production of interferon-alpha and -beta by cloned human lymphoblastoid cells. Brief report. 631 31

Monoclonal antibody HBCA-12 obtained by hybridoma procedure after immunization with human mammary adenocarcinoma cell line MDA-MB-231 immunoprecipitated a cell surface sialoglycoprotein gp80 (apparent molecular weight 80 000) from MDA-MB-231 cells and a glycoprotein gp78 from human myeloma cell line ARH 77. A protein of a similar electrophoretic mobility was immunoprecipitated also from 35S-methionine metabolically radiolabeled human melanoma cell line VUP 1. The expression of the antigen recognized by HBCA-12 monoclonal antibody could be detected neither on PHA-induced nor on EBV-transformed peripheral blood mononuclear cells from healthy donors.
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PMID:Biochemical and histochemical characteristics of target antigen detected by monoclonal antibody HBCA-12 against a membrane component of human mammary carcinoma cell line. 652 96

Multiple myeloma is a plasma cell malignancy which is generally incurable in spite of a high initial response to chemotherapy. While animal models of myeloma are known, the recent developments of human xenografts in nude and SCID mice suggests a promising experimental model. The SCID model, in particular, holds promise because these animals readily accept hematopoietic and lymphoid transplantation and do not generally develop graft versus host reaction. We have developed two drug-resistant variants of the human multiple myeloma cell line ARH-77 by in vitro exposure to gradually increasing concentrations of doxorubicin (ARH-D60) or mitoxantrone (ARM-80). When injected into irradiated SCID mice, the ARH-D60 cell line grew in an orthotopic pattern with the development of osteolytic lesions. This is in contrast to the 8226/C1N human myeloma cell line which grows in a disseminated but nonorthotopic manner in the SCID mouse. Both the ARH-D60 and ARM-80 cell lines are resistant to doxorubicin and cross-resistant to mitoxantrone, vinca alkaloids, taxol and m-AMSA while maintaining sensitivity to antimetabolites and alkylating agents. Growth characteristics and cell cycle kinetics, including S-phase, were not altered in the resistant sublines. The ARH-D60 and ARM-80 cell lines both displayed a classic multidrug-resistance (MDR) phenotype which was partially reversed by the addition of verapamil. These two cell lines represent the first MDR human myeloma cell lines which have demonstrated an orthotopic growth pattern in the SCID mouse and thus may be of value in studying the pathophysiology of this disease.
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PMID:Development of an orthotopic SCID mouse-human tumor xenograft model displaying the multidrug-resistant phenotype. 854 75

We recently identified macrophage inflammatory protein 1-alpha (MIP-1alpha) as a factor produced by multiple myeloma (MM) cells that may be responsible for the bone destruction in MM (1). To investigate the role of MIP-1alpha in MM bone disease in vivo, the human MM-derived cell line ARH was stably transfected with an antisense construct to MIP-1alpha (AS-ARH) and tested for its capacity to induce MM bone disease in SCID mice. Human MIP-1alpha levels in marrow plasma from AS-ARH mice were markedly decreased compared with controls treated with ARH cells transfected with empty vector (EV-ARH). Mice treated with AS-ARH cells lived longer than controls and, unlike the controls, they showed no radiologically identifiable lytic lesions. Histomorphometric analysis demonstrated that osteoclasts (OCLs) per square millimeter of bone and OCLs per millimeter of bone surface of AS-ARH mice were significantly less than in EV-ARH mice, and the percentage of tumors per total bone area was also significantly decreased. AS-ARH cells demonstrated decreased adherence to marrow stromal cells, due to reduced expression of the alpha(5)beta(1) integrin and diminished homing capacity and survival. These data support an important role for MIP-1alpha in cell homing, survival, and bone destruction in MM.
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PMID:Antisense inhibition of macrophage inflammatory protein 1-alpha blocks bone destruction in a model of myeloma bone disease. 1174 67

Adoptive immunotherapy is a promising approach in the treatment of multiple myeloma. We have tested the identification, separation, and expansion of allogeneic myeloma-specific T cells in vitro. Irradiated myeloma cell line ARH 77 has been used to stimulate allogeneic CD4(+) and CD8(+) T lymphocytes. Activated myeloma-specific T cells that produced interferon-gamma were isolated using immunomagnetic beads and further expanded in vitro to numbers of up to 400 x 106 T cells. Specificity of the T lymphocytes was tested using a 5-(6-)carboxyfluoresceine diacetate succinimidyl ester (CFSE)-based cytotoxicity test. This study demonstrates the feasibility of identification and isolation of tumor-specific T cells from allogeneic donors that can be expanded in vitro to numbers useful for clinical applications.
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PMID:Isolation and expansion of allogeneic myeloma-specific interferon-gamma producing T cells for adoptive immunotherapy. 1701 95

Brain-derived neurotrophic factor (BDNF) was recently identified as a factor produced by multiple myeloma (MM) cells, which may contribute to bone resorption and disease progression in MM, though the molecular mechanism of this process is not well understood. The purpose of this study was to test the effect of BDNF on bone disease and growth of MM cells both in vitro and in vivo. Co- and triple-culture systems were implemented. The in vitro results demonstrate that BDNF augmented receptor activator of nuclear factor kappa B ligand (RANKL) expression in human bone marrow stromal cells, thus contributing to osteoclast formation. To further clarify the effect of BDNF on myeloma bone disease in vivo, ARH-77 cells were stably transfected with an antisense construct to BDNF (AS-ARH) or empty vector (EV-ARH) to test their capacity to induce MM bone disease in SCID-rab mice. Mice treated with AS-ARH cells were preserved, exhibited no radiologically identifiable lytic lesions and, unlike the controls treated with EV-ARH cells, lived longer and showed reduced tumor burden. Consistently, bones harboring AS-ARH cells showed marked reductions of RANKL expression and osteoclast density compared to the controls harboring EV-ARH cells. These results provide further support for the potential osteoclastogenic effects of BDNF, which may mediate stromal-MM cell interactions to upregulate RANKL secretion, in myeloma bone diseases.
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PMID:Inhibition of BDNF in multiple myeloma blocks osteoclastogenesis via down-regulated stroma-derived RANKL expression both in vitro and in vivo. 2307 4