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)

The accurate diagnosis of mesothelioma remains difficult despite advances of diagnostic technique. And specific monoclonal antibody (McAb) against mesothelioma have not been reported. In an attempt to develop mesothelioma specific McAb(s), spleen cells from a mouse immunized with isolated tumor cells were fused to a drug resistant mouse myeloma cell lines. Over 200 hybridomas were assayed for their preferential reactivity with mesothelioma cell lines or mesothelioma tumor biopsy tissues. Two monoclonal antibodies 2A3 and 4E1 were identified that bound 6/7 of the mesotheliomas, tested, but did not bind to the majority, 11/13 (for 2A3) and 12/13 (for 4E1), of other lung tumor types. Based upon western blot analysis of one and two-dimensional gels and upon the distribution pattern of the antibody recognized molecule in mesotheliomas and non-mesothelioma lung tumors, 2A3 binds to the cell adhesion molecule CD44. While the specificity of 4E1 has not yet been unequivocally established it appears to recognize a variant form of the CD44 molecule.
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PMID:Generation of monoclonal antibodies that distinguish between mesotheliomas and other tumor of the lung. 753 37

CD44 variant isoforms (CD44v) are generated by alternative splicing of the nuclear RNA resulting in the expression of additional protein domains in the extracellular region of the CD44 standard molecule (CD44s). In multiple myeloma (MM), CD44 mediates binding of tumor cells to stroma and regulates interleukin-6 production. To evaluate the role of CD44v isoforms in MM, CD44v expression was analyzed by immunohistochemical staining of 64 bone marrow biopsies from 38 MM patients. Expression of variant isoforms containing the 9v domain was observed in 36% of cases and was associated with an advanced stage (P < .02; n = 61), a progressive disease (P < .001; n = 61), and a shorter overall survival (P < .02; n = 36). In contrast, 3v, 4v, 6v, or 10v isoforms were detected only in a small percentage of the patients. To analyze the exon composition in RNA-transcripts, reverse transcriptase polymerase chain reaction analyses followed by Southern hybridization with exon-specific probes were performed in fluorescence-activated cell sorted myeloma plasma cells. Tumors expressing the 9v domain showed complex, 9v-containing transcripts in combinations with the 3v, 7v, 8v, and 10v exons. Identical transcripts were detected in several myeloma cell lines and in a Ki-1 B-immunoblastic lymphoma. Similar to high-grade non-Hodgkin's lymphoma and gastric and renal cell carcinoma, overexpression of 9v-containing isoforms in MM is related to an unfavorable clinical presentation and represents a new prognostic parameter.
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PMID:Different CD44 splicing patterns define prognostic subgroups in multiple myeloma. 887 9

In a variety of human tumors, including high grade Non-Hodgkin's lymphoma (hgNHL), a linkage between expression of CD44 variant isoforms (CD44v) and tumor progression has been described. In search of an easily accessible diagnostic parameter, expression of CD44 standard (CD44s) and CD44 variant isoforms (exons v5, v6, v7 and v10) in peripheral blood lymphocytes (PBLs) of patients with hematological malignancies was evaluated by fluorescence activated cell scanning. The analysis of 30 blood samples of healthy donors and patients with non-malignant diseases and of 183 blood samples of patients with malignant hematological disorders revealed that only in patients with malignant disorders did a measurable proportion of PBLs express CD44 variant isoforms, mostly exons v5, v6, v7 and, less frequently, exon v10. Elevated levels of CD44v expression were noted in PBLs of patients with acute and chronic myeloid leukemia (AML: 16%, CML: 25%), Hodgkin's disease (HD: 17%), multiple myeloma (MM: 22%), polycythemia vera (PV: 33%), acute lymphoid leukemia (ALL: 23%) and, most frequently, in PBLs of patients with non-Hodgkin's lymphoma (NHL:54%). CD44v expression was not restricted to the malignant phenotype, but instead was also noted in T cells, B cells and monocytes, preferentially in a subpopulation of large cells. Furthermore, expression of CD44v in PBLs was not linked to the histological grading or clinical staging. There was, however, an inverse correlation with tumor progression, whereas response to therapy was frequently accompanied by upregulation of CD44v. Thus, expression of CD44v in the PBLs of patients with NHL mainly reflected immune responsiveness. Since NHL manifests itself primarily in lymphoid organs, its progression is difficult to follow. Monitoring of CD44v in PBLs could be used as an additional and convenient parameter for surveying the course of disease.
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PMID:Expression of CD44 variant isoforms in peripheral blood leukocytes in malignant lymphoma and leukemia: inverse correlation between expression and tumor progression. 896 Jan 9

The axonal surface glycoproteins neuronglia cell adhesion molecule (NgCAM) and axonin-1 promote cell-cell adhesion, neurite outgrowth and fasciculation, and are involved in growth cone guidance. A direct binding between NgCAM and axonin-1 has been demonstrated using isolated molecules conjugated to the surface of fluorescent microspheres. By expressing NgCAM and axonin-1 in myeloma cells and performing cell aggregation assays, we found that NgCAM and axonin-1 cannot bind when present on the surface of different cells. In contrast, the cocapping of axonin-1 upon antibody-induced capping of NgCAM on the surface of CV-1 cells coexpressing NgCAM and axonin-1 and the selective chemical cross-linking of the two molecules in low density cultures of dorsal root ganglia neurons indicated a specific and direct binding of axonin-1 and Ng-CAM in the plane of the same membrane. Suppression of the axonin-1 translation by antisense oligonucleotides prevented neurite outgrowth in dissociated dorsal root ganglia neurons cultured on an NgCAM substratum, indicating that neurite outgrowth on NgCAM substratum requires axonin-1. Based on these and previous results, which implicated NgCAM as the neuronal receptor involved in neurite outgrowth on NgCAM substratum, we concluded that neurite outgrowth on an NgCAM substratum depends on two essential interactions of growth cone NgCAM: a trans-interaction with substratum NgCAM and a cis-interaction with axonin-1 residing in the same growth cone membrane.
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PMID:Cell adhesion molecules NgCAM and axonin-1 form heterodimers in the neuronal membrane and cooperate in neurite outgrowth promotion. 897 25

L1 is a highly conserved cell adhesion molecule with complete homology of the cytoplasmic domain between the known mammalian protein sequences. Since the cytoplasmic domains of other adhesion molecules have been shown to influence adhesion, we have investigated the effects of deletion of the cytoplasmic domain on the ability of L1 to mediate homophilic adhesion. Full length L1 and a truncated L1, lacking 95% of the cytoplasmic domain, were expressed in myeloma cells. Independent stable transfectants were assayed for the ability to form aggregates. Myelomas expressing L1 lacking the cytoplasmic domain were able to form cell aggregates as well as the myelomas expressing full length L1. Cell aggregate formation was correlated with the level of L1 expression, and the aggregation could be blocked by anti-L1 Fabs. Similar results were obtained in adhesion assays of the myeloma cells to substrate-bound L1. These results indicate that the cytoplasmic domain of L1 is not required for homophilic interactions.
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PMID:The cytoplasmic domain of the cell adhesion molecule L1 is not required for homophilic adhesion. 906

CD44 variant isoforms (CD44v) have been shown to be important factors in adverse prognosis in hematological malignancies. To investigate whether CD44 expression is associated with malignant transformation in multiple myeloma, RNA and protein expression of CD44 standard (CD44s) and CD44v4, v6, v9, v10 containing isoforms was compared on bone marrow plasma cells from normal individuals and myeloma patients at different stages of disease. CD44s protein expression is strongly decreased on myeloma plasma cells and non-malignant B cells in affected bone marrow of myeloma patients, while no differences in CD44s expression were found between blood B cells from normal individuals and myeloma patients. CD44v isoforms were expressed on plasma cells in the majority of normal and myeloma samples analyzed. CD44v9 and v10 containing isoforms were differentially expressed on bone marrow plasma cells from normal individuals (predominantly CD44v9+v10+) and myeloma patients with stable (predominantly CD44v9-v10+) or progressive (predominantly CD44v9+v10- disease. Normal and myeloma plasma cells contained CD44 mRNA transcripts consisting of multiple CD44v exons. In addition, CD44v9 positive myeloma cells carried large CD44 transcripts. These results imply that detection of CD44v isoforms may be a valuable diagnostic tool for monitoring myeloma disease progression and response to treatment.
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PMID:CD44 isoforms distinguish between bone marrow plasma cells from normal individuals and patients with multiple myeloma at different stages of disease. 982 60

L1 is a neural cell adhesion molecule (CAM) known to be important for normal neurological development. Despite being described as a neural CAM, we have documented L1 expression by antigen-presenting cells of myelomonocytic origin. Here we demonstrate that L1 can function as a costimulatory molecule in T cell activation. A monoclonal antibody that abrogates L1-L1 homophilic binding significantly reduced mixed leukocyte responses initiated by allogeneic L1+ dendritic cells. Autologous T cell activation in response to phytohemagglutinin was also inhibited by blockade of L1. In accordance with these results, transfection of human L1 into a murine myeloma cell line significantly increased the capacity of these cells to stimulate xenogeneic T cell responses. As a costimulatory ligand L1 could represent a novel target for immunotherapeutic intervention and may act as an important intermediary in neuroimmunological processes and disease.
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PMID:The human neural cell adhesion molecule L1 functions as a costimulatory molecule in T cell activation. 1074 12

Human bone marrow stroma (BST)-dependent myeloma sister cell lines MOLP-6 and MOLP-7 were established from the peripheral blood of a multiple myeloma (MM) patient with IgA kappa type MM (stage IIIB). The growth of the cell lines is constitutively dependent on BST cells; none of the cytokines tested nor the culture supernatant of the BST cells could support the growth. Both cell lines showed typical plasma cell morphology with abundant cytoplasm and one to four nuclei under Wright staining. The immunoprofiles of MOLP-6 and MOLP-7 correspond to that seen typically in primary MM cells: positive for cytoplasmic immunoglobulin (Ig) chains, a heavy and kappa light chains, CD9, CD28, CD40, CD44, CD45, CD56, and PCA-1; the cells were negative for surface Igs and various other B-cell, T-cell and myelomonocyte associated markers. Both cell lines also expressed adhesion molecules including HCAM (CD44), VLA-4 (CD49d/CD29), VLA-6 (CD49f/CD29), ICAM-1 (CD54), NCAM (CD56), LFA-3 (CD58) and L-selectin (CD62L). The doubling time of MOLP-6 and MOLP-7 was 48 and 168 hours, respectively. In addition to this growth characteristic, the maximum cell density of each cell line was obtained at 1.7 x 10(6) cells/ml and 9.7 x 10(5) cells/ml, respectively. The characteristics of each cell line may reflect intraclonal variation of the proliferative capacity. The MOLP-6 together with the MOLP-7 sister will be useful model systems for the investigation of the biology of myeloma.
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PMID:Human bone marrow stroma-dependent myeloma sister cell lines MOLP-6 and MOLP-7 derived from a patient with multiple myeloma. 1093 46

Hitherto conducted studies concerned with the problem of cytoadhesive molecules (CAM) dealt only in a very limited way with the problem of multiple myeloma (MM). The subject of the submitted paper was evaluation of the relationship of soluble forms of "vascular cell adhesive molecule-1" (sVCAM-1) and "intercellular cell adhesion molecule-1" (sICAM-1) in serum from the peripheral bloodstream (PBS) and serum from a bone marrow aspirate (BMA) with selected clinical and laboratory indicators of MM (beta 2-microglobulin, thymidine kinase, immunochemical type of MM, S-creatinine, S-monoclonal immunoglobulin, S-albumin, Hb, percentage ratio of plasmocytes in bone marrow, age, performance status, stage and substage of MM and activity of disease) and proliferation characteristics of myeloma plasmocytes. The authors analyzed two groups of patients with MM, a group of 64 examined in different stages of MM and a group of 39 examined when the diagnosis of MM was established (median age 63 and 64 years, male/female ratio 1.6 and 1.3:1). The sVCAM-1 and sICAM-1 levels were examined by the ELISA method. Elevated values of sVCAM-1 in PBS were recorded in both groups in 87.5% and 87% patients, medians of sVCAM-1 exceeded the upper range of normal values (714 ng/ml) almost twice (1180 and 1295 ng/ml) whereby median values in BMA (1347 and 1546 ng/ml) were always somewhat higher than in PBS. Elevated sICAM-1 values in PBS were found in 35 and 33% patients, median levels of sICAM-1 in PBS and in BMA did not exceed the upper normal range (691 ng/ml) and did not differ substantially (518 vs. 476 and 518 vs. 500 ng/ml). Correlation analysis (Pearson's correlation coefficient and Mann-Whitney's test, p0.05) revealed in both groups a significant relationship of both CAM assessed in PBS and BMA (sVCAM-1 p-0.0000 and p-0.012, sICAM-1 p-0.0000 and p-0.0011). No relationship was found between sVCAM-1 and s-ICAM-1 levels assessed in PBS and BMA with proliferation indexes of myeloma plasmocytes, i.e. values of the propidium-iodide index PI/CD38 and PI/B-B4 (CD138). In the whole group of 64 patients a relationship was found between sVCAM-1 in PBS and values of S-creatinine (p - 0.004), Hb (p - 0.033), S-albumin (p - 0.035), S-beta 2-microglobulin (S-B2M) (p - 0.0000) and S-thymidine kinase (S-TK)(p-0.0000), when evaluating BMA, a relationship with B2M (p -0.011). In the group of 39 patients examined when the diagnosis of MM was made a relationship was found of sVCAM-1 in PBS to S-B2M) (p - 0.0000), S-TK (p-0.0000) and to S-creatinine (p -0.005), in BMA there was only a relationship with B2M (p - 0.020). In the whole group of 64 patients there was no relationship between s-ICAM levels in PBS with any of the examined indicators, when evaluating BMA only a relationship with B2M (p - 0.038) and TK (p - 0.022). In the group of 39 patients examined during the diagnosis of MM a relationship was found of sICAM-1 only with B2M in BMA (p - 0.013). In the total group of 64 a relationship was found between sVCAM-1 in PBS with the patient's age (p - 0.032) and the substage of MM(p-0.024), in the group of 39 patients a relationship between sVCAM on PBS and the substage of MM (p -0.031). On analysis of sICAM-1 a relationship was found between levels in BMA only with the patient's age (p -0.015). From the investigation ensued that despite evidence of a number of correlations between sVCAM and sICAM-1 levels and clinical and laboratory indicators of MM no relationship was found which could be applied under conditions of clinical practice. Assessment of levels of different indicators in serum of bone marrow aspirate did not reveal any advantages over examination in peripheral blood serum.
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PMID:[Relation of the soluble cytoadhesion molecules VCAM-1 and ICAM-1 to selected clinical and laboratory indicators in multiple myeloma]. 1095 65

Mucin1 (MUCI) is a class of high molecular weight glycoproteins found in the cell membranes of human epithelial cells. Epithelial glycoprotein 40 (EGP40) is a homophilic cell-cell adhesion molecule and expressed on the surface of most simple epithelial cells and the majority of carcinomas. We analyzed the expression of MUC1 and EGP40 in human bone marrow (BM) and peripheral blood (PB) by reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry (ICC). Eight BM and 95 PB samples from healthy donors, 39 BM and 17 PB samples from patients with haematological malignancies and 45 BM samples from patients with breast cancer were analyzed. MUC1 mRNA and EGP40 mRNA and protein were detected in BM samples and PB samples from healthy donors and from patients with multiple myeloma (MM), non-Hodgkin's lymphoma (NHL) and chronic myelogenous leukaemia (CML). The positive cells showed erythroblast-like and plasmacell-like morphology by immunocytochemistry. The MUC1 and EGP40 nested PCR were positive in 83.3% (10/12) and in 100% (33/33) respectively of BM from patiens with breast cancer who had no evidence of distant metastases. It is concluded that MUC1 and EGP40 is expressed in haematopoietic tissues and haematological malignancies. Therefore, MUC1 and EGP40 expression as a marker for detection of breast cancer cells and micrometastatic epithelial cells in BM and PB is not specific using RT-PCR technique and immunocytochemistry.
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PMID:Evaluation of MUC1 and EGP40 in bone marrow and peripheral blood as a marker for occult breast cancer. 1120 3


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