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)

Thalidomide has immunomodulatory and anti-angiogenic properties which may underlie its activity in cancer. After its success in myeloma, it has been investigated in other plasma cell dyscrasias, myelodysplastic syndromes, gliomas, Kaposi's sarcoma, renal cell carcinoma, advanced breast cancer, and colon cancer. Thalidomide causes responses in 30-50% of myeloma patients as a single agent, and acts synergistically with corticosteroids and chemotherapy. Thalidomide results in the reduction or elimination of transfusion-dependence in some patients with myelodysplastic syndrome. Responses have also been seen in one-third of patients with Kaposi's sarcoma, in a small proportion of patients with renal cell carcinoma and high-grade glioma, and in some patients with colon cancer in combination with irinotecan. The drug is being investigated currently in a number of clinical trials for cancer. Drowsiness, constipation, and fatigue are common side effects, whereas peripheral neuropathy and skin rash are seen in one-third. A minority of patients experience bradycardia. Thrombotic phenomena are especially common when thalidomide is combined with chemotherapy. Adverse effects severe enough to necessitate cessation of therapy are seen in around 20% of patients. A therapeutic trial of thalidomide is essential in all patients with relapsed or refractory myeloma. In other cancers, the best way to use the drug is in the setting of clinical trials. In the absence of access to studies or alternative therapeutic options, thalidomide could be considered singly or in combination with standard therapy.
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PMID:Thalidomide in cancer. 1190 8

Kaposi sarcoma-associated herpesvirus (KSHV) has been associated with several diseases, but the association between KSHV and multiple myeloma (MM) remains controversial. To address this issue, we studied patients with MM for the presence of viral RNA transcripts as well as KSHV-specific cellular immune responses. Highly sensitive reverse transcription-polymerase chain reaction assays for detection of viral transcripts of KSHV open reading frame (ORF) 26, ORF72, and ORF74 did not detect viral gene transcripts in long-term cultures of bone marrow stromal cells from 23 patients with MM. Moreover, sensitive assays for KSHV ORF65-specific and ORF73-specific cytotoxic T-lymphocyte (CTL) activity that readily and routinely detect CTLs specific for ORF65 and ORF73 in patients positive for human immunodeficiency virus and KSHV did not show any specific responses in 16 patients with MM, despite the presence of positive Epstein-Barr virus-specific CTLs in all cases. These data therefore do not show a biologically important association between ongoing KSHV infection and MM.
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PMID:Absence of biologically important Kaposi sarcoma-associated herpesvirus gene products and virus-specific cellular immune responses in multiple myeloma. 1209 68

Recently, molecular evidence of the gamma herpesvirus, human herpesvirus 8 (HHV-8), was found in the nonmalignant bone marrow stromal cells of patients with multiple myeloma using a polymerase chain reaction (PCR)-based assay. Other investigators have been unable to confirm either the presence of HHV-8 using molecular techniques or serologic evidence of prior infection with HHV-8. In order to maximize the likelihood of detection of small quantities of the virus and minimize the risk of potential nucleic acid contamination, we used entire bone marrow biopsy core specimens for DNA extraction and amplification. These specimens included both malignant plasma cells and bone marrow stromal cells and were subjected to minimal manipulation prior to DNA extraction and PCR. We tested eight patients with various plasma cell dyscrasias and compared them to negative controls with non-Hodgkin's lymphoma using standard PCR assays utilizing the KS330(233)primers and probe for HHV-8. This assay is reproducibly positive in Kaposi's sarcoma tissue. We found no evidence of HHV-8 DNA in either the lymphoma controls or the samples from patients with the plasma cell dyscrasias using these methods. We conclude that HHV-8 is unlikely to play a major role in the pathogenesis of the plasma cell dyscrasias in the majority of patients with these diseases. This report adds to the body of evidence that HHV-8 is not associated with plasma cell dyscrasias like multiple myeloma.
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PMID:Human herpesvirus 8 genome is not found in whole bone marrow core biopsy specimens of patients with plasma cell dyscrasias. 1210 58

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.
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PMID:Risk of cancer among women with AIDS in New York City. 1218 15

Time trends in cancer incidence and mortality represent an essential tool for monitoring the changes in population lifestyle and in the environmental risks and the effectiveness of the health system on cancer control in a specific area. During 1985-1997 82 506 malignant tumours were diagnosed in the Tuscany Cancer Registry, central Italy (about 1 200 000 inhabitants) and 54 979 cancer deaths registered in the period 1985-1999 by the Regional Mortality Registry were analysed. A statistically significant decrease in incidence was evidenced for stomach and gallbladder in both sexes, and for oesophagus, larynx and lung among males. Significant increases were documented for melanomas of the skin, kidney and non-Hodgkin's lymphoma in both sexes for colon, prostate and Kaposi's sarcoma among males and for breast, thyroid and multiple myeloma among females. Mortality decreased significantly for stomach and thyroid in both sexes and for oral cavity and pharynx, oesophagus, rectum, larynx, lung, bone, prostate, testis and Hodgkin's disease among males and colon, gallbladder and breast among females. Mortality increased for soft tissue, brain and multiple myeloma. In conclusion, most of these data can be explained as the effect of the modifications that occurred in smoking habits between the sexes and as the consequence of the primary and secondary prevention activities that are ongoing in the area.
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PMID:Time trends in cancer incidence and mortality in central Italy. 1219 66

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.
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PMID:Unusual malignant tumours in patients with HIV infection. 1239 36

Thalidomide, administered as a sedative and antiemetic decades ago, was considered responsible for numerous devastating cases of birth defects and consequently was banned from markets worldwide. However, the drug remarkably has resurfaced with promise of immunomodulatory benefit in a wide array of immunologic disorders for which available treatments were limited. It is approved by the Food and Drug Administration for erythema nodosum leprosum (ENL). Although the relative paucity of leprosy and ENL worldwide may perceivably limit interest in and knowledge about thalidomide, increasing numbers of new and potential uses expand its applicability widely beyond ENL. Thalidomide, an inhibitor of tumor necrosis factor a, is the best known agent for short-term treatment of ENL skin manifestations, as well as postremission maintenance therapy to prevent recurrence. For this indication, it is effective as monotherapy and as part of combination therapy with corticosteroids. Studies of thalidomide in chronic graft-versus-host disease showed benefit in children and adults as treatment, but not as prophylaxis. The agent has been administered successfully for treatment of cachexia related to cancer, tuberculosis, and human immunodeficiency virus infection, although evidence of efficacy is inconclusive. Thalidomide monotherapy effectively induced objective response in trials in patients with both newly diagnosed and advanced or refractory multiple myeloma. Combination therapy with thalidomide and corticosteroids was also effective in these patients, as well as in treatment of aphthous and genital ulcers. Limited evidence supports the drug's benefit in treatment of Kaposi's sarcoma. Other thalidomide applications include Crohn's disease, rheumatoid arthritis, and multiple sclerosis. Somnolence, constipation, and rash were the most frequently cited adverse effects in studies, but thalidomide-induced neuropathy and idiopathic thromboembolism were critical causes for drug discontinuation. Thalidomide is still contraindicated in pregnant women, women of childbearing age, and sexually active men not using contraception. Clinicians should be conversant with thalidomide in ENL (its primary application) in the natural course of leprosy, as well as in the agent's other applications.
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PMID:Thalidomide for erythema nodosum leprosum and other applications. 1268 Apr 78

Paclitaxel is one of the best antineoplastic drugs found from nature in the past decades, which has been found effective against a wide spectrum of cancers including ovarian cancer, breast cancer, small and non small cell lung cancer, colon cancer, head and neck cancer, multiple myeloma, melanoma, and Kaposi's sarcoma. Like many other anticancer drugs, it has difficulties in clinical administration due to its poor solubility in water and most pharmaceutical reagents. In its current clinical application, an adjuvant called Cremophor EL has to be employed, which has been found to be responsible for many serious side effects. Nanoparticles of biodegradable polymers can provide an ideal solution to such an adjuvant problem and realize a controlled and targeted delivery of the drug with better efficacy and less side effects. With further development, such as particle size optimization and surface coating, nanoparticle formulation of paclitaxel can promote a new concept of chemotherapy to realize its full efficacy and to improve quality of life of the patients, which includes personalized chemotherapy, local chemotherapy, sustained chemotherapy, oral chemotherapy, chemotherapy across the blood-brain barrier, chemotherapy across the microcirculation barrier, etc. The present research proposes a novel formulation for fabrication of nanoparticles of poly(lactic-co-glycolic acid) (PLGA) by a modified solvent extraction/evaporation technique, in which natural emulsifiers, such as phospholipids, cholesterol and vitamin E TPGS are creatively applied to achieve high drug encapsulation efficiency, desired drug released kinetics, high cell uptake and high cytotoxicity. The nanoparticles composed of various recipes and manufactured under various conditions were characterized by laser light scattering (LLS) for size and size distribution, scanning electron microscopy (SEM) and atomic force microscopy (AFM) for morphological properties, X-ray photoelectron spectroscopy (XPS) and Fourier Transformation Infrared Spectroscopy (FTIR) for surface chemistry, zeta-potential for surface charge, and differential scanning calorimetry (DSC) for the thermogram properties. The drug encapsulation efficiency and the drug release kinetics under in vitro conditions were measured by high performance liquid chromatography (HPLC). It was found that these natural emulsifiers have great advantages for nanoparticle formulation of paclitaxel over the traditional macromolecular emulsifiers, such as polyvinyl alcohol (PVA). Nanoparticles of desired small size and narrow size distribution can be obtained. The drug encapsulation efficiency can be achieved as high as 100 %. The released kinetics can be made under control. The HT-29 cancer cell line experiment showed that after 24 hours of incubation, the cell mortality caused by the drug administered by such nanoparticle formulation could be more than 13 times higher than that caused by the free drug under similar conditions.
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PMID:Nanoparticles of biodegradable polymers for clinical administration of paclitaxel. 1496 22

Human herpesvirus 8 (HHV-8), also defined Kaposi's sarcoma (KS)-associated herpesvirus, was identified by Chang and colleagues in 1994 using purely molecular techniques, before any serological evidence or virus isolation in cell culture could be achieved. HHV-8 is unique among herpesviruses because its prevalence in the general population is low and because it possesses the richest weaponry of viral oncogenes and tumor-promoting factors ever described. Eleven HHV-8-specific genes are homologs of cellular genes, which were hijacked from the host during a long parallel evolution, and at least five of such genes show both in vitro and in vivo transforming ability. HHV-8 is the causative agent of KS, but it has also been associated with different hematologic malignancies, including primary effusion lymphoma (PEL), multicentric Castelman's disease (MCD), MCD-related immunoblastic/plasmablastic lymphoma and various atypical lymphoproliferative disorders. Although low-level silent infection was detected in bone marrow stromal cells from patients with multiple myeloma, a role of HHV-8 in this disease is unlikely. As seen with KS, the incidence of HHV-8-associated lymphoproliferative disorders is increased in the setting of human immunodeficiency virus infection.
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PMID:Human herpesvirus 8 (HHV-8/KSHV) and hematologic malignancies. 1512 45

Thalidomide, an oral agent with antiangiogenic and immunomodulatory properties, is being investigated extensively in the management of advanced cancer. Multiple studies with large numbers of patients have confirmed that this drug has significant activity in multiple myeloma. Some patients with myelofibrosis or myeodysplatic syndromes may reduce their need for transfusions after thalidomide treatment. The activity of thalidomide in solid tumors is less prominent. Studies in Kaposi's sarcoma, malignant melanoma, renal cell carcinoma and prostate cancer appear more promising especially when thalidomide is combined with biological agents or with chemotherapy. Limited activity was demonstrated in patients with glioma, while thalidomide appears to be inactive in patients with head and neck cancer, breast or ovarian cancer.
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PMID:Thalidomide in cancer medicine. 1527 53


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