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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone marrow dendritic cells (DC) from patients with multiple myeloma (MM) were recently reported to be infected with Kaposi's sarcoma-associated herpesvirus (KSHV). Because immunotherapy strategies using DC are very promising in this disease, we looked for KSHV DNA in clinical-grade DC generated in vitro from MM patients. Adherent apheresis cells from MM patients were maintained for 7 days in clinical-grade X-VIVO 15 culture medium supplemented with granulocyte-macrophage colony-stimulating factor, interleukin-4, or interleukin-13. Tumor necrosis factor alpha was added for the last 2 days. We obtained a cell population with a DC phenotype able to endocytose fluorescein isothiocyanate (FITC)-dextran and efficiently activate resting allogenic T lymphocytes. To detect KSHV DNA, we used polymerase chain reaction (PCR) followed by Southern blotting of PCR product with a sensitivity detecting a few copies of viral DNA. All the PCR were repeated in a blinded fashion three times, on 1 mug and 0.2 mug of genomic DNA, in two different laboratories. Clinical-grade DC from 10 (91%) of 11 patients were not infected with KSHV. The apheresis cells and the purified CD34(+) cells from the same patients were also negative. A very weak PCR band was detected with DC from one patient, but the initial apheresis cells were negative. The detection of KSHV infection in 1 (9%) of 11 MM patients probably represents background seroprevalence. It seems likely that functional and clinical-grade DC from MM patients can safely be used in clinical trials.
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PMID:Clinical-grade functional dendritic cells from patients with multiple myeloma are not infected with Kaposi's sarcoma-associated herpesvirus. 973 Oct 82

Seroepidemiology and polymerase chain reaction studies have strongly suggested that human herpesvirus type 8 (HHV-8) is associated with Kaposi's sarcoma, Castleman's disease, and body cavity-based lymphoma. The genome of HHV-8 harbors a viral analogue of the interleukin-6 (IL-6) gene. The amino acid sequence of the viral IL-6 (vIL-6) protein is 24.7% identical to human IL-6 (hIL-6). IL-6 as a B-cell growth and differentiation factor is known to play an essential role in the pathophysiology of B-cell tumors. Thus, it seems possible that virus-encoded IL-6 contributes to malignant growth of HHV-8-positive B-cell lymphatic tumors. We have tested a preparation of HHV-8-derived IL-6 for the ability to promote the proliferation of the human myeloma cell line INA-6, which is strictly dependent on exogenous IL-6 for growth and survival. Viral IL-6 significantly induced DNA synthesis of INA-6 cells, but required much more protein on a weight basis when compared with hIL-6 for maximal proliferation. The proliferative effect of vIL-6 was almost completely inhibited by a combination of anti-IL-6 receptor (IL-6R) and anti-gp130 antibodies or IL-6R superantagonist Sant7 and anti-gp130 antibodies. This report demonstrates that vIL-6 has proliferative activity on human cells and that the IL-6R and gp130 are involved in vIL-6 signaling in the myeloma cell line INA-6.
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PMID:Human herpesvirus type 8 interleukin-6 homologue is functionally active on human myeloma cells. 973 Oct 82

Since the discovery a decade ago that interleukin-6 is a growth factor for human multiple myeloma (MM) cells, great strides have been made in understanding the relationship of this cytokine to multiple myeloma. A plethora of studies on this topic has confirmed that interleukin-6 is a key growth and survival factor for myeloma cells, as well as a major morbidity factor for patients with MM. Their is strong evidence for both an autocrine (in MM cells) as well as a paracrine sources of interleukin-6 induction (from bone marrow stromal cells and osteoblast cells), with bone marrow stromal cells likely serving as the main center of production of interleukin-6 in patients with MM. Moreover, bone marrow stromal cells from patients with MM express viral interleukin-6, a functional homolog of human interleukin-6 that is produced by Kaposi's sarcoma-associated herpesvirus and may further enhance MM cell growth and survival. Soluble interleukin-6 receptor serum levels are elevated in patients with MM; soluble interleukin-6 receptor may amplify circulating interleukin-6 in patients with MM, and complex with interleukin-6, resulting in proliferation of MM cells that either express low or no detectable surface interleukin-6 receptor. Recent advances in our understanding of interleukin-6 signaling cascades mediating MM growth and survival, as well as its impact on cell cycle regulation in MM cells, may lead to therapeutics designed to interfere with these pathways. Finally, considerable progress has been made in identifying and developing agents including antibodies, biologic agents, hormones and drugs that interfere with the interleukin-6 signaling pathways and may therefore have a role in the treatment of MM.
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PMID:Interleukin-6 in multiple myeloma and related plasma cell dyscrasias. 951 2

Multiple myeloma results from an interplay between the monoclonal malignant plasma cells and supporting nonmalignant cells in the bone marrow. Recent studies suggest that the final transforming event in this B cell disorder occurs at a late stage of B cell differentiation based on the characteristics of the immunoglobulin genes expressed by the malignant clone as well as surface markers present on the tumor cells. Recently, an increasing pathogenic role in this malignancy by the nonmalignant cells in the bone marrow has been suggested by several studies. Specific infection of these supporting cells by the recently identified Kaposi's sarcoma-associated herpes virus (KSHV) suggests a novel mechanism by which this nonmalignant population may lead to the development of this B cell malignancy and support its growth.
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PMID:Multiple myeloma: the cells of origin--a two-way street. 951 71

The VI International Workshop on Multiple Myeloma was organised by Professor Kenneth C Anderson, Dana Farber Cancer Institute, and held on June 14-18, 1997, in Boston, MA, USA. More than 500 participants from all over the world joined this workshop. Several subjects were introduced and one of the most exciting items of news was the identification of Kaposi's sarcoma-associated herpes virus in the bone marrow stromal cells of patients with MM. The aim of this overview is to give a glimpse of the subjects discussed and the statements made.
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PMID:Multiple myeloma: VI International Workshop, June 14-18, 1997, Boston, Massachusetts, USA. 964 23

In recent studies, the sequence of Kaposi's sarcoma-associated herpes virus (KSHV) or human herpes virus-8 (HHV-8) was detected in dendritic cells (DC) of patients with multiple myeloma (MM). A concern was raised whether there is an causal association between the viral infection and development of these tumors. In the present study, we have examined DC generated from blood adherent cells from 8 Swedish MM patients at different clinical stages and 2 patients with monoclonal gammopathy of undetermined significance. In addition, 6 myeloma cell lines and bone marrow cells from 2 MM patients were also studied. By polymerase chain reaction (PCR), including nested PCR, no virus DNA was demonstrable in the patients' DC or in myeloma cell lines or fresh bone marrow cells. Moreover, no antibody against KSHV was found in the serum of these 10 patients. Thus, our results indicate that blood-derived DC of MM patients in Sweden usually are not infected with KSHV/HHV-8. This study also suggests that KSHV/HHV-8 is not regularly associated with MM and consequently does not play a primary role in the pathogenesis of these tumors.
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PMID:Blood dendritic cells from myeloma patients are not infected with Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8). 965 37

We compared population-based incidence rates for classical Kaposi's sarcoma and multiple myeloma. Neither for men (Spearman's rank correlation coefficient (r) = 0.01, P = 0.97, 13 pairs) nor for women (r = 0.24, P = 0.42, 13 pairs) did the incidences of the two conditions correlate. This absence of correlation does not support the hypothesis that Kaposi's sarcoma and multiple myeloma share a common aetiology, such as HHV-8.
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PMID:Incidence rates of classical Kaposi's sarcoma and multiple myeloma do not correlate. 970 93

Kaposi's sarcoma and non-Hodgkin's lymphoma were among the earliest recognized manifestations of the acquired immunodeficiency syndrome (AIDS) epidemic. Excluding these two tumors, the overall risk of all other cancers in human immunodeficiency virus (HIV)-infected individuals is similar to that of the general population. However, varying levels of evidence link several additional neoplasms to HIV infection. The evidence is strongest for an association with Hodgkin's disease, with lower relative and absolute risks than for non-Hodgkin's lymphoma. Anogenital intraepithelial neoplasia also appears to be HIV associated, but increases of invasive disease are still uncertain for both cervical and anal cancers. Various studies have suggested associations with testicular seminoma, multiple myeloma, oral cancer, and melanoma, but the data are inconsistent. Leiomyosarcoma and benign leiomyomas have increased in incidence in HIV-infected children but are unusual in HIV-infected adults. Conjunctival carcinoma is seen in HIV-infected individuals in sub-Saharan Africa but it is uncommon in Western countries. Most other cancers do not seem to have increased incidences in HIV infection. The etiologic mechanisms of HIV-related cancer likely differ among these diverse cancers and do not globally increase cancer risk.
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PMID:Association of non-acquired immunodeficiency syndrome-defining cancers with human immunodeficiency virus infection. 970 98

Kaposi's sarcoma-associated herpesvirus (KSHV) is suspected to play a role in the aetiology of multiple myeloma. Because of similarities in the pathophysiology of multiple myeloma and Waldenstrom's macroglobulinaemia (WM), we investigated DNA samples from 20 bone marrow biopsies with WM for the detection of KSHV by PCR (KS330/ORF26). We performed two rounds of amplification and found that only 1/20 of the DNA samples obtained from biopsies had a detectable KSHV sequence. The positive patient was also infected by the human immunodeficiency virus (HIV). Our data provide evidence that KSHV cannot be implicated in the pathogenesis of WM.
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PMID:Kaposi's sarcoma-associated herpesvirus (KSHV) in bone marrow biopsies of patients with Waldenstrom's macroglobulinaemia. 972 9

Kaposi's sarcoma-associated herpesvirus (KSHV) serologic assays were used to detect specific antibodies to KSHV lytic and latent antigens in 27 patients with multiple myeloma, 27 control patients with other cancers, and 50 random blood donors. Antibodies to KSHV recombinant minor capsid antigen orf65 were found in 81% of patients with multiple myeloma, 22% of control patients with other cancers, and 6% of the blood donors. Antibodies to KSHV latent nuclear antigens were found in 52% of patients with multiple myeloma, 26% of control patients with other cancers, and 2% of the blood donors. All of the 11 patients with progressive multiple myeloma were KSHV-seropositive. Antibodies to Epstein-Barr virus nuclear antigen 1 were present in 89% of patients with multiple myeloma, 93% of control patients with other cancers, and 88% of the blood donors. These data support the possible association of KSHV infection with multiple myeloma, particularly with progressive disease.
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PMID:Antibodies to Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in patients with multiple myeloma. 972 56


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