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)

To evaluate the risk of cancer among women with AIDS in New York City (NYC), we compared the cancer experience of AIDS-infected women in NYC with that of the general population of women in NYC by matching the population-based New York State Cancer Registry with the New York City AIDS Registry. A probabilistic algorithm was used to match names, birth dates, and, where available, Social Security numbers between 15,146 women with AIDS and 232,902 women with cancer. Standardized incidence ratios (SIR) were calculated as the ratio of observed to expected cancer cases in the population of NYC women matched for age, race, and calendar period of cancer diagnosis. Period-specific relative risks (RR) of cancer prevalence prior to AIDS, and incidence at or after AIDS were calculated to determine which cancers increased in proximity to an AIDS diagnosis, a surrogate marker of increasing immunodeficiency. Analysis was limited to women between the ages of 15 to 69 who were diagnosed with AIDS between 1981 and 1994. Among 15,146 women diagnosed with AIDS, we found 1,194 matches with the Cancer Registry. For cancers included in the 1993 AIDS case definition, the SIR was 178.49 for Kaposi's sarcoma, 48.97 for non-Hodgkin's lymphoma, and 9.20 for invasive cervical cancer. The overall SIR for all non-AIDS-defining cancers was 2.20. Among non-AIDS-defining cancers, elevated SIRs were found for cancers of the lung (7.95), esophagus (7.69), multiple myeloma (7.37), oral cavity and pharynx (6.55), Hodgkin's disease (5.65), leukemias (4.52), and rectal/anal cancers (3.23). Statistically significant increases in period-specific risks were found for all non-AIDS-defining cancers combined, but not for individual cancers. Dual screening by two registries and unknown behavioral factors complicate the ascertainment of cancer risk. Our results show significantly elevated risks for several non-AIDS-defining cancers; these results are consistent with other studies of cancers among persons with AIDS. Extension of the time period of analysis is required to test for the effects of new anti-viral treatments and their association with cancer development among HIV-infected women.
AIDS Public Policy J
PMID:Risk of cancer among women with AIDS in New York City. 1218 15

Plasma cell neoplasia occurs much less frequently than high-grade B-cell non-Hodgkins lymphoma in HIV-infected patients, but is nevertheless an AIDS-associated malignancy. In this report, we describe the fine-needle aspiration (FNA) findings of a mass in the left parotid region with plasmablastic features that occurred in a 41-yr-old HIV-infected homosexual man whom we diagnosed as having anaplastic myeloma. The patient had normochromic, normocytic anemia with a hematocrit of 21%, a white blood count of 2.2 x 10(9)/l with 76% neutrophils, and a CD4 count of 31%. He also had elevated levels of calcium (13.2 mg/dl), alkaline phosphatase (25,400 IU/l), blood urea nitrogen (2,600 mg/dl), and creatinine (2.5 mg/dl). Serum protein electrophoresis showed polyclonal hypergammaglobulinemia without any monoclonal component. A bone survey revealed multiple punched-out lytic lesions. FNA smears showed large plasmacytoid cells with eccentrically placed nuclei, prominent nucleoli, and moderate amounts of basophilic cytoplasm. By immunocytochemical staining, tumor cells were negative for CD19, CD20, and leukocyte-common antigen (LCA), but strongly positive for CD38 and kappa light chain. Anaplastic myeloma and plasmablastic lymphoma were considered in the differential diagnosis. Although the cytomorphologic and immunophenotypic findings of our case overlapped with those of plasmablastic lymphoma, the pattern of bone involvement with punched-out lytic lesions and absence of localization of the tumor to the mucosa of the oral cavity led us to a diagnosis of anaplastic myeloma. The patient initially received antiretroviral therapy followed by thalidomide and pulse dexamethasome therapy, but his response was poor. His HIV load increased, and his malignancy rapidly progressed with the development of multiple vertebral lesions, extraosseous extension, and eventually cord compression. He died of the disease less than 2 mo after presentation.
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PMID:Fine-needle aspiration cytology of a case of HIV-associated anaplastic myeloma. 1235 99

The clinical charts of 2560 HIV-infected patients seen in our Unit between 01/89 and 08/01 were reviewed. All patients with a neoplasm were analysed to study the prevalence of tumours other than Kaposi's sarcoma (KS), non-Hodgkin's lymphoma (NHL) or cancer of the cervix. There were 43 unusual malignant tumours: 13 lung cancers, six leukaemias, six skin cancers, two carcinomas of the conjunctiva, two cancers of the penis, three of the anus, three of the larynx, one sarcoma of the ureter, one gastric carcinoid, one non-differentiated thyroid carcinoma, one non-differentiated prostate carcinoma, one cancer of the tongue, one cancer of the bladder, one adenocarcinoma of the rectum and one multiple IgM myeloma. Thirteen (43.3%) of the patients died, 10 (76.9%) from causes related to the tumour itself. These results suggest that HIV-infected patients have a higher prevalence of some neoplasms than the general population.
Int J STD AIDS 2002 Oct
PMID:Unusual malignant tumours in patients with HIV infection. 1239 36

AIDS-related primary effusion lymphoma (PEL) is an HIV-associated malignancy characterized by the ability of the tumor cells to specifically home in the serous body cavities. Here we used gene expression profile analysis (about 12 000 genes) to further define the phenotype of PEL and to investigate the lymphoma relationship to normal B cells and to other tumor subtypes, including non-Hodgkin lymphomas (NHLs) of immunocompetent hosts and AIDS-associated NHL (AIDS-NHL). The results showed that PEL displayed a common gene expression profile that is clearly distinct from all NHLs of immunocompetent hosts and AIDS-NHL subtypes and, in contrast to those, is not related to germinal center (GC) or memory B cells. The gene expression profile of PEL was defined as plasmablastic because it showed features of both immunoblasts identified by Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines and AIDS immunoblastic lymphoma, and plasma cells, as defined by multiple myeloma cell lines. Finally, our results identify a set of genes specifically expressed in PEL tumor cells. Their expression was validated at the protein level, suggesting their potential pathogenetic and clinical significance.
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PMID:Gene expression profile analysis of AIDS-related primary effusion lymphoma (PEL) suggests a plasmablastic derivation and identifies PEL-specific transcripts. 1253 89

Two common features in human immunodeficiency virus infection and acquired immunodeficiency syndrome, rheumatoid arthritis, and hematologic malignancies including multiple myeloma are elevated serum levels of beta(2)-microglobulin (beta(2)M) and activation or inhibition of the immune system. We hypothesized that beta(2)M at high concentrations may have a negative impact on the immune system. In this study, we examined the effects of beta(2)M on monocyte-derived dendritic cells (MoDCs). The addition of beta(2)M (more than 10 microg/mL) to the cultures reduced cell yield, inhibited the up-regulation of surface expression of human histocompatibility leukocyte antigen (HLA)-ABC, CD1a, and CD80, diminished their ability to activate T cells, and compromised generation of the type-1 T-cell response induced in allogeneic mixed-lymphocyte reaction. Compared with control MoDCs, beta(2)M-treated cells produced more interleukin-6 (IL-6), IL-8, and IL-10. beta(2)M-treated cells expressed significantly fewer surface CD83, HLA-ABC, costimulatory molecules, and adhesion molecules and were less potent at stimulating allospecific T cells after an additional 48-hour culture in the presence of tumor necrosis factor-alpha and IL-1beta. During cell culture, beta(2)M down-regulated the expression of phosphorylated mitogen-activated protein (MAP) kinases, extracellular signal-related kinase (ERK), and mitogen-induced extracellular kinase (MEK), inhibited nuclear factor-kappaB (NF-kappaB), and activated signal transducer and activator of transcription-3 (STAT3) in treated cells, all of which are involved in cell differentiation and proliferation. Thus, our study demonstrates that beta(2)M at high concentrations retards the generation of MoDCs, which may involve down-regulation of major histocompatibility complex class I molecules, inactivation of Raf/MEK/ERK cascade and NF-kappaB, and activation of STAT3, and it merits further study to elucidate the underlying mechanisms.
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PMID:Beta 2-microglobulin as a negative regulator of the immune system: high concentrations of the protein inhibit in vitro generation of functional dendritic cells. 1253 97

Hematopoietic malignancies have been shown to depend on cytokine growth factor autocrine/paracrine loops for growth and differentiation. This results in the constitutive activation of cytokine-mediated transcription factors like signal transducer and activators of transcription (STAT) 3 in non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Recent evidence demonstrates that cytokines also contribute to a drug-resistant phenotype in many tumor cell types. We hypothesized that inhibitors of the STAT3 pathway would sensitize drug-resistant and endogenous cytokine-dependent NHL and MM tumor cells to the cytotoxic effects of chemotherapeutic drugs. We examined an AIDS-related NHL cell line, 2F7, known to be dependent on interleukin (IL)-10 for survival and an MM cell line, U266, known to be dependent on IL-6 for survival. IL-10 and IL-6 signal the cells through the activation of Janus kinase (JAK)1 and JAK2, respectively. Thus, we investigated the effect of two chemical STAT3 pathway inhibitors, namely, piceatannol (JAK1/STAT3 inhibitor) and tyrphostin AG490 (JAK2/STAT3 inhibitor), on the tumor cells for sensitization to therapeutic drugs. We demonstrate by phosphoprotein immunoblotting analysis and electrophoretic mobility shift analysis that piceatannol and AG490 inhibit the constitutive activity of STAT3 in 2F7 and U266, respectively. Furthermore, piceatannol and AG490 sensitize 2F7 and U266 cells, respectively, to apoptosis by a range of therapeutic drugs including cisplatin, fludarabine, Adriamycin, and vinblastine. The specificity of the inhibitors was corroborated in experiments showing that piceatannol had no effect on U266 and, likewise, AG490 has no effect on 2F7. The sensitization observed by these inhibitors correlated with the inhibition of Bcl-2 expression in 2F7 and Bcl-xL expression in U266. Altogether, these results demonstrate that STAT3 pathway inhibitors are a novel class of chemotherapeutic sensitizing agents capable of reversing the drug-resistant phenotype of cytokine-dependent tumor cells.
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PMID:Inhibition of constitutive STAT3 activity sensitizes resistant non-Hodgkin's lymphoma and multiple myeloma to chemotherapeutic drug-mediated apoptosis. 1253 84

HIV-infected individuals have a high risk of developing non-Hodgkin lymphoma (NHL). In Europe, the prevalence of AIDS with a concurrent NHL diagnosis increased from 3.6% to 5.4% between 1994 and 2000. In population-based record linkages between cancer registries and AIDS registries in the USA, Italy, and Australia, the relative risks of NHL in people with AIDS ranged between 15 for low-grade and T-cell NHL and 400 for high-grade NHL. The corresponding relative risk of Hodgkin's disease was about 10, whereas the risks for multiple myeloma and leukaemias were in the range 2 to 5. Since the introduction of highly active antiretroviral therapy in the more developed countries (1996), most studies have suggested a decline in the incidence of some types of NHL, most notably the primary brain form. In studies from Africa, the risk of HIV-associated NHL is about ten times less than that in the more developed countries, but underascertainment and earlier death from other AIDS-related illnesses may explain the relative lack of HIV-associated lymphomas.
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PMID:Epidemiology of non-Hodgkin lymphomas and other haemolymphopoietic neoplasms in people with AIDS. 1257 53

Intravenous immunoglobulins (IVIg) are therapeutic preparations of normal human IgG that have been used for more than 20 years for substitutive therapy in patients with primary antibody deficiencies. Recent studies pointed out the need to obtain normal residual levels of IgG (i.e. 8 g/L) in order to reduce the number and severity of bacterial infections in these patients. The IVIg are also prescribed for the substitutive therapy of secondary immunodeficiencies such as chronic lymphoid leukemia and multiple myeloma with hypogammaglobulinemia and severe and/or recurrent infections, and human immunodeficiency virus (HIV)-infected children with recurrent bacterial infections before the era of highly active antiretroviral agents. However, in the latter situation, no recent study has evaluated IVIg therapy in acquired immunodeficiency syndrome (AIDS) children receiving highly active antiretroviral agents (HAART), and the use of IVIg must probably be restricted to the currently rare clinical situation in Western Europe of children with AIDS who develop recurrent infections despite the administration of HAART and prophylactic cotrimoxazole. IVIg have also been reported to prevent infections, interstitial pneumonia and graft-vs. host disease during the first 90 days post-transplant in allogeneic bone-marrow transplant recipients. However, this result was not confirmed by two recent studies and IVIg therapy should probably only be proposed for a subgroup of bone-marrow allografted patients such as those with hypogammaglobulinemia and sepsis. With the exception of erythrovirus B19 infection with erythroblastopenia, no clear benefit of IVIg therapy has been reported for the curative management of other infectious diseases.
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PMID:Intravenous immunoglobulins in infectious diseases: where do we stand? 1284 45

CD28, which is expressed on most T cells, can provide a costimulatory signal during T cell activation. Although principally considered to be a T cell-associated molecule, CD28 has been seen to be expressed on mast cells and natural killer cells, as well as on plasma and myeloma cells, but not on cells representing earlier stages of B cell development. Here were report that CD28 was expressed on Epstein-Barr virus (EBV)-positive B lymphoblastoid and AIDS-associated non-Hodgkin's lymphoma cell lines. These cells also expressed the ligands for CD28, B7-1 and B7-2, but not CTLA-4. Furthermore, peripheral blood B cells infected with EBV ex vivo expressed CD28 after infection. Cross-linking with a stimulatory anti-CD28 antibody resulted in an increased expression of CD71 (transferrin receptor) or CD25 (interleukin-2 alpha receptor subunit). The addition of a blocking CTLA-4-Ig fusion protein, or antisense oligonucleotides for CD28, resulted in a decreased expression of these molecules. In 1 cell line, the addition of an anti-CD28 stimulatory antibody reduced Fas-induced apoptosis, and antisense oligonucleotide-induced inhibition of CD28 expression enhanced Fas-mediated apoptosis. Overall, these results suggest a role for CD28 and its ligands, B7-1 and B7-2, in homotypic interactions in EBV+ B cell lines, which may mediate cellular activation and/or viability.
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PMID:Expression and function of CD28 on Epstein-Barr virus-positive B cell lines and AIDS-associated non-Hodgkin's lymphoma cell lines. 1285 3

The spectrum of hematologic and immunologic abnormalities induced by HIV infection is broad. Although the incidence of HIV-associated B-cell neoplasms has increased, relatively few cases of multiple myeloma have been reported, and even fewer cases have detailed treatment outcome. The case of an HIV-infected man in whom multiple myeloma was diagnosed following progressive anemia and fatigue is described. The patient began treatment consisting of thalidomide, dexamethasone, and clarithromycin, which led to a rapid and dramatic antitumor response. He experienced modest regimen-related toxicities while retaining a normal CD4+ T-lymphocyte count and a nondetectable HIV viral load. The immunologic and antitumor effects of thalidomide in the context of multiple myeloma and HIV infection are also briefly reviewed. Given thalidomide's relatively favorable side-effect profile and purported immunologic benefit, further studies of this drug in the treatment of HIV-associated multiple myeloma should be pursued.
AIDS Read 2003 Aug
PMID:Thalidomide-based treatment for HIV-associated multiple myeloma: a case report. 1452 25


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