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)

In 1989 we published a critical review of cancer epidemiology in petroleum workers, which included as a component of the review a meta-analysis by cancer site. Subsequently we have completed three additional reviews and meta-analyses on cell-type-specific leukemias (1995), multiple myeloma (1997), and non-Hodgkin's lymphoma (2000). The objective of the present investigation was to update our 1989 review and meta-analysis of nonlymphohematopoietic cancers in cohort studies of petroleum workers. Included in the present investigation were cohort studies of petroleum workers from the United States, the United Kingdom, Canada, Australia, Finland, Sweden, and Italy. Individual studies were reviewed with regard to specific cancer sites. For each cancer of interest, risk ratios from the individual studies were presented. In some studies, subcohort analyses stratified by exposure parameters such as length of employment, job category, and hire year were also reported. These subcohort or stratified analyses were reviewed and the results of these analyses were taken into consideration in our interpretation. In addition to the qualitative review of individual studies, a meta-analysis was performed to combine data from individual cohort studies of petroleum workers. The primary purpose of the meta-analysis was to provide a summary measure of risk for each cancer site. Based on a review and meta-analyses of cohort studies of more than 350,000 petroleum workers in the United States, the United Kingdom, Canada, Australia, Finland, Sweden, and Italy, we concluded that there was no increased mortality from digestive cancers (stomach, large intestine, liver, or pancreas), lung cancer, bladder cancer, kidney cancer, or brain cancer. The summary standardized mortality ratios for these cancer sites were all below unity. Significant increases of melanoma mortality were reported in some small groups of refinery workers in the United Kingdom and upstream operation workers in Canada, but no responsible agent(s) had been identified. The observed mortality from skin cancer in all other studies was similar to the expected. In particular, no significant increase of skin cancer mortality was reported in any of the U.S. studies. Elevated mortality from prostate cancer was noted in short-term workers at a U.S. refinery and in short-term workers employed in certain crafts at U.S. crude oil operations. However, the absence of an upward trend by length of employment in these workers argued against an association between exposure to petroleum products and prostate cancer. For all petroleum workers as a whole, mortality from prostate cancer was as expected.
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PMID:A critical review of cancer epidemiology in the petroleum industry, with a meta-analysis of a combined database of more than 350,000 workers. 1102 72

The breakthrough discovery of the anti-angiogenic effects of thalidomide gave impetus to a series of clinical trials in patients with solid tumors and hematologic malignancies. Thalidomide has been shown to block the activity of angiogenic substances like bFGF, VEGF and interleukin 6. This drug also down-regulates TNF alpha. Thalidomide has shown clinical antitumor activity in single-agent, phase II clinical trials in AIDS-related Kaposi sarcoma, glioma, multiple myeloma refractory to chemotherapy, and hormone-refractory prostate cancer. In contrast, thalidomide was inactive in breast, lung and kidney cancer. The dose-limiting toxicity of thalidomide is sedation. Other adverse effects include skin rash, constipation, dry mouth and liver function abnormalities, along with peripheral neuropathy and the drug's well-known teratogenic potential. The advantages of thalidomide include the convenience of the oral route of administration, the drug's toxicity profile--substantially milder than that of chemotherapy--and its low cost. The potential role of thalidomide in the treatment of human neoplasia will be confirmed by means of randomized clinical trials.
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PMID:[Thalidomide. Clinical trials in cancer]. 1118 34

To address concerns about the potential carcinogenicity of pacemakers, we launched the first epidemiologic study of cancer incidence among pacemaker recipients. A nationwide cohort of 16,357 pacemaker recipients in Denmark from 1982 through 1996 was identified. The Danish Cancer Registry was used to identify all incident cancers within the cohort, with almost 75,000 person-years of observation. The cohort had a slight excess of cancer overall (SIR = 1.19, 95% confidence interval [95% CI, 1.1-1.2]). This was largely caused by an elevated SIR for multiple myeloma among men (SIR = 1.78,95% CI, 1.1-2.8), which increased to 2.60 (95% CI, 0.9-5.7) 5-9 years after implantation, and to a similarly increased SIR for kidney cancer among women (SIR = 2.05, 95% CI, 1.3-3.0), which increased to 3.39 (95% CI, 1.6-6.2) after a latency period of 5-9 years. An excess of urinary bladder cancer was also seen after 10 years. No excess risk was observed for breast cancer or sarcomas, although the SIRs for sarcomas tended to increase over time, based on small numbers. Our results are largely reassuring but, as pacemakers become more common and are implanted at earlier ages and as survival following implantation improves, the excesses of bladder cancer, multiple myeloma among men, and kidney cancer among women with long-term followup warrant further investigation.
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PMID:Cancer risk among pacemaker recipients in Denmark, 1982-1996. 1262 86

Solar ultraviolet B (UV-B) radiation (280-320 nm) has been associated with reduced risk of cancer of the breast, colon, ovary, and prostate, as well as non-Hodgkin's lymphoma (NHL) through the production of vitamin D in papers extending back to 1980. Using data on the geographic distribution of cancer mortality rates in the US, another ten cancers have been added to the list for which UV-B/vitamin D is a risk reduction factor (Grant 2002b; submitted). These associations persist even after additional cancer risk and risk reduction factors such as smoking, urban or rural residence, Hispanic heritage, poverty, dietary factors, and use of nonsteroidal anti-inflammatory drugs are added to the analysis. As a further test of the protective role of UV-B radiation, an ecologic study of cancer mortality rates in Europe with UV-B radiation and dietary factors was conducted. Inverse correlations are found for UV-B radiation for a number of cancers, with those for bladder, breast, endometrial, ovarian, prostate, and renal cancer, and multiple myeloma and NHL having the strongest correlations in this and ongoing multicountry ecologic studies. These studies add further support for the role of UV-B radiation and vitamin D in reducing the risk of a large number of cancers.
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PMID:Ecologic studies of solar UV-B radiation and cancer mortality rates. 1289 36

We used the nationwide Swedish Family-Cancer Database to analyse the association of histology-specific brain tumours with other cancers in family members. Among 0-68-year-old offspring, 9414 patients with brain tumours were identified from 1961 to 2000, of whom, 3387 parents were diagnosed with any primary neoplasm. Astrocytoma, meningioma and neurinoma were the main histological types. Increased standardised incidence ratios (SIRs) were found for brain tumours in association with cancers at sites that are known features in recognised syndromes, such as haemangioblastoma and renal cancer in von Hippel-Lindau disease. In addition, an association between astrocytoma and melanoma was recognised. Among as yet unknown clustering, neurinoma was associated with testicular cancer and myeloma; meningioma was associated with cervical cancer; astrocytoma was associated with prostate cancer; ependymoma was associated with breast cancer. Although some of these may feature a true tumour cluster, they need to be confirmed in another setting.
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PMID:Association of brain tumours with other neoplasms in families. 1472 40

Interleukin (IL)-6 is a pleiotropic cytokine that has important roles in the regulation of the immune response, inflammation, and hematopoiesis. Disruption of IL-6 regulation might, however, affect the immune response and consequently induce immune-mediated inflammatory diseases such as rheumatoid arthritis, systemic juvenile idiopathic arthritis, Castleman disease, and Crohn's disease. Overproduction of IL-6 also contributes, through its roles as a growth factor or an antiapoptotic factor, to the development of malignant diseases such as multiple myeloma and renal cancer. Progress in the study of IL-6 has increased our understanding of the pathological roles of this cytokine in these diseases and provided key evidence that antagonizing its activities can be used as a therapeutic strategy. The application of molecular biology techniques to design monoclonal antibodies as therapeutic agents has made it possible to regulate the IL-6 signal to successfully treat diseases that have so far proved refractory to conventional therapies. Blocking IL-6 actions by use of a humanized antibody, tocilizumab, which targets the IL-6 receptor, has been proven to be therapeutically effective for rheumatoid arthritis, systemic juvenile idiopathic arthritis, Castleman disease and Crohn's disease. In this review, we discuss a paradigm of IL-6 from basic science to clinical use.
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PMID:Interleukin 6: from bench to bedside. 1707 1

Cancer cells may often support their own growth, survival, and drug resistance by autocrine/paracrine loops based on the production of different factors; results from us and others have shown that similar interleukin-6 (IL-6)-related loops are operative in multiple myeloma and prostate or renal cancer. Because this aspect has not been investigated in detail for hepatocellular carcinoma (HCC), we have examined it in HA22T/VGH cells. These differ from other primary liver cancer cell lines (that is, HepG2, HuH-6, and HuH-7) in that enzyme-linked immunosorbent assay (ELISA) showed the HA22T/VGH cells to secrete remarkable amounts of IL-6 (16.8 ng/10(6) cells/24 h); this production, due to constitutive activation of NF-kappaB, is inhibited by agents like curcumin and dehydroxymethylepoxyquinomicin (DHMEQ), which interfere with the transcription factor. Flow cytometry, ELISA, mRNA, and Western blotting analyses were performed to characterize the status of the IL-6 receptor in HA22T/VGH cells. Two transmembrane glycoproteins that form the functional IL-6 receptor have been identified: the ligand-binding gp80 and the signal-transducer gp130. Soluble forms of gp80 also trigger membrane gp130 signaling when complexed with IL-6, while soluble forms of gp130 inhibit the same process. Our results showed that HA22T/VGH cells express gp130 at their surface, but release only traces of its soluble form. For gp80, the cells produced the mRNAs of both its membrane and soluble form. However, in immunoblotting they exhibited a very faint content of the same subunit, which, in addition, was neither expressed at the cell surface nor secreted. In MTT assays, incubation with a neutralizing anti-IL-6 antibody for up to 7 days did not affect the growth of HA22T/VGH cells. Also, other specific anti-IL-6 approaches (siRNA or AODN) failed to produce this result. In conclusion, autostimulatory loops mediated by IL-6 are less likely to occur in HCC than in other kinds of cancer. However, since release of IL-6 is frequent in HCC, especially in its more advanced stages, the use of agents like curcumin or DHMEQ might be beneficial to counteract its adverse systemic effects (e.g., cachexia).
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PMID:Significance of autologous interleukin-6 production in the HA22T/VGH cell model of hepatocellular carcinoma. 1726 74

Material and methods. Between 1996 and 2002, a total of 21 patients were treated with intamedullary nailing for metastatic tumors (12 men and 9 women) without view of pathological fractures. Average patients age at operation was 68,9 (range 21-80). The primary origin of metastatic tumors was: renal cancer most common 6 times, breast cancer 5, lung cancer 4, prostate cancer 2, cervical cancer 1. We included 3 patients with lymphoma to clinical materials. The humerus was involved in 13 cases, femur 7, tibia 1 of metastatic tumors. <br /> Results. The time of patients life from the operation time depended on the type of neoplasm: breast - 5 months, kidney - 5 months, lung - 3 months, prostate - 16,5 months, myeloma - 16 months, uterus - 6 months. The mean was 7,5 months.<br /> Conclusions. The average postoperative survival period was 7,5 months. There were no embolism or thrombosis complications. All patients were given professional oncological advice and were treated palliatively.
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PMID:Locked nailing for metastatic disease of the long bones. 1803 25

Thalidomide has regained value in the multimodality treatment of leprosy, multiple myeloma, prostate, ovarian and renal cancer. Complications related to arterial and venous complications are well described. However, pulmonary complications remain relatively uncommon. The most common pulmonary side-effect reported is non-specific dyspnea. We report a patient with multiple myeloma, who developed an eosinophilic pneumonia, shortly after starting thalidomide. She had complete resolution of her symptoms and pulmonary infiltrates on discontinuation of the drug and treatment with corticosteroids. Physicians should be cognizant of this potential complication in patients receiving thalidomide who present with dyspnea and pulmonary infiltrates.
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PMID:Thalidomide-Related Eosinophilic Pneumonia: A case report and brief literature review. 1877 68

Bortezomib represents a new class of anti-cancer drugs, the proteasome inhibitors. We evaluated the in vitro activity of bortezomib with regard to tumour-type specificity and possible mechanisms of drug resistance in 115 samples of tumour cells from patients and in a cell-line panel, using the short-term fluorometric microculture cytotoxicity assay. Bortezomib generally showed dose-response curves with a steep slope. In patient cells, bortezomib was more active in haematological than in solid tumour samples. Myeloma and chronic myeloid leukaemia were the most sensitive tumour types although with great variability in drug response between the individual samples. Colorectal and kidney cancer samples were the least sensitive. In the cell-line panel, only small differences in response were seen between the different cell lines, and the proteasome inhibitors, lactacystin and MG 262, showed an activity pattern similar to that of bortezomib. The cell-line data suggest that resistance to bortezomib was not mediated by MRP-, PgP, GSH-; tubulin and topo II-associated MDR. Combination experiments indicated synergy between bortezomib and arsenic trioxide or irinotecan. The data support the current use of bortezomib but also points to its potential utility in other tumour types and in combination with cytotoxic drugs.
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PMID:In vitro activity of bortezomib in cultures of patient tumour cells--potential utility in haematological malignancies. 1901 12


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