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)

Cyclin D1/PRAD1 (bcl-1) is a recently discovered proto-oncogene that is overexpressed in mantle cell lymphomas and several other human tumors. In a previous study, the authors demonstrated expression of cyclin D1 in 15 of 15 cases of mantle cell lymphoma and 1 of 8 cases of B-chronic lymphocytic leukemia (B-CLL) using a polyclonal antibody and microwave enhanced immunohistochemical staining method on paraffin-embedded tissue sections. In this study, 107 additional B- and T-cell neoplasms were studied, including 47 cases of high grade lymphoma (33 diffuse large B-cell type, 9 Burkitt and Burkitt-like, 4 precursor T-lymphoblastic lymphoma, and 1 adult T-cell lymphoma/leukemia), 38 additional cases of low grade B-cell lymphoma (18 CLL, 15 hairy cell leukemia and 5 mantle cell lymphoma), and 22 plasmacytomas for expression of cyclin D1 using the same immunohistochemical staining technique. All cases of mantle cell lymphoma showed diffuse nuclear staining. No additional cases of CLL showed cyclin D1 expression. In contrast, 1 of 15 hairy cell leukemias and 1 of 22 plasmacytomas showed cyclin D1 staining. None of the high grade lymphomas demonstrated expression of cyclin D1 protein by immunostaining, including three cases of large B-cell lymphoma that coexpressed CD5. The authors conclude that cyclin D1 is expressed in all cases of mantle cell lymphoma, and only in very rare cases of B-CLL, hairy cell leukemia and plasmacytoma/myeloma. Cyclin D1 does not appear to play an important role in high grade lymphomas. In addition, most CD5 positive high grade B-cell lymphomas do not express cyclin D1, and are not likely to be derived from mantle cell lymphoma or other lymphomas with t(11;14).
 ...
PMID:Cyclin D1 expression in non-Hodgkin's lymphomas. Detection by immunohistochemistry. 754 Mar 62

Major interest in the analysis of mature plasma cell neoplasias of mice and humans has focused on identification of precursor cells that give rise to mature malignant plasma cells. Although several laboratories have recently suggested that such cells are present in the granulomas of pristane-treated mice and the bone marrow of some multiple myeloma patients, the in vivo cellular interactions required for their differentiation into mature plasma cell tumors remains unclear. Given the extensive interactions of peripheral T cells and normal B cells, we assessed the potential role of T cells in plasma-cell tumor development, by using a myc, raf-containing retrovirus, J3V1, to induce plasmacytomas in normal BALB/c mice, T-cell-deficient nude mice, and T-cell-reconstituted nude mice. The B-lineage tumors arising in normal BALB/c mice were uniformly mature plasmacytomas, most of which secreted immunoglobulin. In contrast, nude mice yielded predominantly non-immunoglobulin-secreting B-cell lymphomas with a phenotype characteristic of peripheral B cells. T-cell reconstitution of nude mice prior to tumor induction resulted in a shift from B-cell lymphomas to plasmacytomas. These results imply that transformation can occur prior to terminal differentiation of B cells and that such transformed cells can be driven to terminal differentiation by peripheral T cells. These findings further suggest that, in human multiple myeloma, the ability of T cells to influence the differentiation state of transformed B cells may provide a mechanism by which malignant plasma cells found in the bone marrow could arise from clonotypically related less-mature B cells found in both the bone marrow and periphery.
 ...
PMID:T cells induce terminal differentiation of transformed B cells to mature plasma cell tumors. 784 31

We have previously demonstrated the expression of shared idiotypes by the paraproteins from approximately one-quarter of patients with multiple myeloma (MM). We have now investigated whether similar cross-reactivity is expressed in the paraproteins of patients with monoclonal gammopathy of undetermined significance (MGUS), using a panel of 32 monoclonal antibodies (MAB) generated against follicular B cell lymphomas. The paraproteins from 76/409 (19%) patients with MGUS reacted with at least one of 23 different anti-idiotypic antibodies used in this study. 18 MABs demonstrated reactivity with more than one patient's paraprotein. Moreover, 10 MABs reacted frequently (with 5-22 paraproteins). Over half (41/76) of the reactive patients' paraproteins reacted with more than one MAB from this panel. This frequency of anti-idiotypic reactivity was similar to that of previously studied patients with myeloma, chronic lymphocytic leukaemia (CLL), and follicular B-cell lymphomas. There was no correlation between specific anti-idiotypic reactivity and the propensity to develop serious disease (MM, macroglobulinaemia, amyloidosis, or other lymphoproliferative disorders) in patients with MGUS. These results suggest that MGUS is derived from cells producing antibodies that are similar to those of other B-cell malignancies and that the pattern of idiotype expression is irrelevant to malignant potential.
 ...
PMID:Expression of shared idiotypes by paraproteins from patients with monoclonal gammopathy of undetermined significance. 798 12

Tumours with a plasmacytoid pattern taken from 32 dogs and four cats were examined for the presence of immunoglobulins, which would allow them to be designated as B-cell lymphomas. Within a total of 19 immunoglobulin-positive tumours, three types could be distinguished: extramedullary plasmacytoma (15), multiple myeloma (two) and immunocytoma (two). These tumours occurred in 18 of the dogs, and in one cat (extramedullary plasmacytoma). The characteristics of the immunoglobulin-producing tumours were investigated by light and electron-microscopy as well as by immunohistochemical methods. Seventeen of the 19 tumours expressed lambda-type light chains and one tumour kappa-type light chains. Heavy chains were also synthesized by five tumours.
 ...
PMID:Immunoglobulin-producing tumours in dogs and cats. 830 Sep 10

The generation of human antibodies derived from extranodal MALT type B-cell lymphomas allows to evaluate steps in their pathogenesis as well as to establish potential immunological therapies. Intraclonal diversity and the existence of bystander nonmalignant B-cells outline the need for reliable identification of the tumor immunoglobulin representing hybridomas. Human heterohybridomas were generated from five cases of MALT type B-cell lymphomas (4 low grade, one high grade) by the fusion of lymphoma B-cells with the murine myeloma cell line NSO and tested for isotype identity with the tumor. RT-PCR using VH Fr1/JH primers was performed with RNA of tumors and hybridomas that share the same isotype with the tumor. PCR-products were sequenced directly. In each case lymphomas were hybridized with a comparable fusion efficiency. DNA sequence analysis of the immunoglobulin heavy chain identified one or more hybridomas derived from the tumor. However some other hybridomas which share the same isotype with the tumor, may be different in their VH family or their sequence. Hybridomas can be used as a tool for the research on the MALT lymphoma immunoglobulin receptor. For the identification of tumor immunoglobulin, secreting hybridomas sequencing and the check of molecular identity is indispensable after isotype determination.
 ...
PMID:Receptor analysis of idiotype antibodies derived from MALT type B-cell lymphoma hybridomas. 926 3

Cytokines are regulatory molecules that are produced by a variety of cell types and are characterized by numerous biologic functions involved in the regulation of the immune system and hematopoiesis. This review summarizes the functions and regulation of cytokines in lymphomas and discusses the effect of a specific cytokine, interleukin-6 (IL-6), in B-cell lymphomas. IL-6 is a multipotent cytokine that can mediate the differentiation of B-cells into immunoglobulin-secreting cells, stimulate the autocrine or paracrine growth of myeloma cells, induce acute-phase proteins in liver cells, and may influence the pathogenesis of several diseases by autocrine or paracrine mechanisms. Patients with non-Hodgkin's lymphoma (NHL) have increased serum concentrations of IL-6; increased IL-6 levels can be associated with the presence of B-symptoms. Data presented in this review indicate that neoplastic cells from patients with NHL contained high concentrations of IL-6. Thus, elevated serum levels of IL-6 appear to originate from the lymphoma cells in patients with B-cell NHL, suggesting that the neoplastic cells may modulate the general status of patients with B-cell NHL. The inhibition or modification of the production of IL-6 in lymphoma cells may lead to a more effective control of the general status of patients with B-cell NHL.
 ...
PMID:Production and effects of interleukin-6 and other cytokines in patients with non-Hodgkin's lymphoma. 963 77

The ability to selectively target liposomal anticancer drugs via specific ligands against antigens expressed on malignant cells could improve the therapeutic effectiveness of the liposomal preparations as well as reduce adverse side effects associated with chemotherapy. Long-circulating formulations of liposomes containing lipid derivatives of poly(ethyleneglycol) [sterically stabilized liposomes (SLs)] have been described previously, and new techniques have recently been developed for coupling monoclonal antibodies (Abs) at the poly(ethyleneglycol) terminus of these liposomes. Ab-targeted SLs [immunoliposomes (SILs)] containing entrapped anticancer drugs are predicted to be useful in the treatment of hematological malignancies such as B-cell lymphomas or multiple myeloma, in which the target cells are present in the vasculature. The specific binding, in vitro cytotoxicity, and in vivo antineoplastic activity of doxorubicin (DXR) encapsulated in SILs coupled to monoclonal Ab anti-CD19 (SIL[anti-CD19]) were investigated against malignant B cells expressing CD19 surface antigens. Binding experiments with SIL[anti-CD19] resulted in a 3-fold higher association of the SILs with a human CD19+ B lymphoma cell line (Namalwa) in comparison with nontargeted SLs. Using flow cytometry, fluorescently labeled SIL[anti-CD19] bound to B cells with no recognition of T cells in a mixture of B cells and T cells in culture. Nontargeted SLs demonstrated significantly lower recognition of either B cells or T cells. Targeted DXR-SIL[anti-CD19] displayed a higher cytotoxicity to B cells relative to DXR entrapped in nontargeted SLs. Therapeutic experiments in severe combined immunodeficient mice implanted with Namalwa cells by the i.v. or i.p. routes resulted in significantly increased effectiveness of DXR-SIL[anti-CD19] compared to similar amounts of free DXR, DXR-SL (no Ab), or isotype-matched nonspecific Abs attached to DXR-SL. Single doses (3 mg/kg) of DXR-SIL[anti-CD19] administered i.v. resulted in a significantly improved therapeutic benefit, including some long-term survivors. From our results, we infer that targeted anti-CD19 liposomes containing the anticancer drug DXR may be selectively cytotoxic for B cells and may be useful in the selective elimination of circulating malignant B cells in vivo.
 ...
PMID:In vitro and in vivo targeting of immunoliposomal doxorubicin to human B-cell lymphoma. 969 62

Fas (APO-1/CD95) is a cell-surface receptor involved in cell death signaling. Germline mutations in the Fas gene have been associated with autoimmune lymphoproliferative syndrome, and somatic Fas mutations have been found in multiple myeloma. We have examined the entire coding region and all splice sites of the Fas gene in 150 cases of non-Hodgkin's lymphoma. Overall, mutations were identified in 16 of the tumors (11%). Missense mutations within the death domain of the receptor were associated with retention of the wild-type allele, indicating a dominant-negative mechanism, whereas missense mutations outside the death domain were associated with allelic loss. Fas mutations were identified in 3 (60%) MALT-type lymphomas, 9 (21%) diffuse large B-cell lymphomas, 2 (6%) follicle center cell lymphomas, 1 (50%) anaplastic large cell lymphoma, and 1 unusual case of B-cell chronic lymphocytic leukemia with a marked tropism for skin. Among the 16 patients with somatic Fas mutations, 15 showed extranodal disease at presentation, and 6 relapsed in extranodal areas. Ten of 13 evaluable patients showed features suggestive of autoreactive disease. Our data indicate that somatic disruption of Fas may play a role in the pathogenesis of some lymphomas, and suggest a link between Fas mutation, cancer and autoimmunity.
 ...
PMID:Somatic Fas mutations in non-Hodgkin's lymphoma: association with extranodal disease and autoimmunity. 978 34

Secular trends in the incidence of lymphoproliferative disorders on North and West Yorkshire and Humberside from 1985 to 94 were studied and changes in incidence by tumour subtype were analysed. Population-based data on the incidence of lymphoproliferative disorders were obtained from a specialist registry with a high level of ascertainment. Cases of chronic lymphocytic leukaemia and plasma cell myeloma were excluded and the remaining cases classified as Hodgkin's disease and non-Hodgkin's lymphoma (NHL). NHL were subdivided by site of origin and immunophenotype. Nodal B-cell lymphomas were further classified as diffuse large B-cell lymphoma, follicle centre lymphoma, mantle cell lymphoma and miscellaneous. During the study period there was a significant increase in total lymphoproliferative disorders with an average change of 2.5% per annum equivalent to 0.84/10,0000. Most of this increase was due to an increasing incidence of extranodal B-cell lymphomas and peripheral T-cell lymphomas. A numerically small but significant increase in diffuse large B-cell lymphomas was seen. There was no significant increase in other subtypes. The increased incidence of lymphomas in the area studied is mainly due to changes in two specific subgroups. There are several reasons why changes in extranodal B-cell lymphoma and peripheral T-cell lymphoma may have been particularly affected by changing diagnostic practices. Epidemiological studies of particular subtypes of lymphoproliferative disorder facilitate the identification of environmental factors involved in the pathogenesis of these tumours.
 ...
PMID:The changing incidence of lymphoproliferative disorders in Yorkshire. 980 76

The incidence and pattern of liver involvement in 127 liver specimens (2 biopsy and 125 autopsy specimens) from cases of acute myelogenous leukaemia (25), chronic myelogenous leukaemia (7), acute lymphatic leukaemia (5), chronic lymphatic leukaemia (9), multiple myeloma (25), low-grade non-Hodgkin's lymphoma (25), high-grade non-Hodgkin's lymphoma (24) and myeloproliferative diseases (7) were investigated histologically and immunohistochemically. Liver infiltration was found frequently in chronic leukaemia and myeloproliferative diseases (80-100%), acute leukaemia (60-70%) and non-Hodgkin's lymphoma (50-60%), but was significantly less common in multiple myeloma (32%) than in any of the other diagnostic groups. Hepatomegaly was found in over 50% of cases in all the diagnostic groups, but was not always associated with infiltration. Diffuse, non-destructive infiltration was most common: in acute myelogenous leukaemia, both the portal triads and sinusoids were usually involved; in chronic myelogenous leukaemia, multiple myeloma and myeloproliferative diseases, infiltration was mainly sinusoidal; and in lymphatic leukaemia and non-Hodgkin's lymphoma the portal triads were mainly involved. Nodular infiltration was seen in multiple myeloma and non-Hodgkin's lymphoma. The primary tumours and liver infiltrates generally exhibited the same immunophenotype, although reactivity with the antibody L26 (CD20) was only found in the primary lesion in many high-grade B-cell lymphomas. Thus, liver involvement is common in haematological malignancies, but the incidence and pattern of infiltration vary amongst the different types.
 ...
PMID:Incidence and pattern of liver involvement in haematological malignancies. 984 37


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>