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)

Thalidomide has several targets and mechanisms of action: a hypnosedative effect, several immunomodulatory properties with an effect on the production of TNF-alpha and the balance between the different lymphocyte subsets and an antiangiogenic action. Thalidomide has been used in several cutaneous inflammatory disorders (e.g., erythema nodosum leprosum in lepromatous leprosy, cutaneous lupus erythematosus and severe aphtosis), cancers (e.g., relapsed/refractory multiple myeloma, malignant melanoma and systemic signs in cancer) and inflammatory conditions (e.g., Crohn's disease and rheumatoid arthritis). Several side effects are associated with thalidomide. Some are major, such as teratogenicity, peripheral neuropathy and deep vein thrombosis. Somnolence and rash are frequently reported when thalidomide is used at higher doses as an anticarcinogenic agent and can lead to dose reduction or treatment discontinuation depending on severity. Minor side effects include abdominal pain and endocrine disturbances. To prevent the teratogenicity, use of thalidomide is strictly controlled in western countries with close adherence to a birth control programme. Close monitoring for early development of peripheral neuropathy is also recommended.
 ...
PMID:Thalidomide: an old drug with new clinical applications. 1468 Apr 61

The fusion of a murine B cell and a myeloma cell generates a hybridoma that produces monoclonal antibody (mAb). These murine mAb induce the HAMA (human anti-mouse antibodies) response. Murine mAb have been modified by genetic engineering, producing molecules with a higher proportion of human protein. At present, chimeric, humanized and fully human mAb are available. mAb block interactions between target molecules and their ligands or trigger the lyses of mAb-coated tumor cells. Numerous mAb have been developed using the recombinant DNA technology and several are available in the market. Trastuzumab, against HER2/neu, is useful in breast cancer; rituximab, against CD20 in B lymphocytes is useful in lymphoma; alemtuzumah, against CD52 is used in lymphoma and leukemia; daclizumab and basiliximab block the IL-2 receptor interaction and reduce acute rejection in kidney transplantation; abciximab, an antagonist of GPIIb/IIIa platelet receptor, is used in patients undergoing acute coronary syndromes. In autoimmunity diseases, blocking tumor necrosis factor by infliximab and adalimumab has demonstrated excellent results. Thus, infliximab is useful in the treatment of rheumatoid arthritis (RA), Crohn's disease and ulcerative colitis while adalimumab is the first fully human mAb available for RA. Infliximab and adalimumab reduce signs and symptoms in RA and they also interfere with progression of joint damage. Finally, the direct benefits of antagonist treatment can occur at the expense of a major adverse effect in some other biological function.
 ...
PMID:[New immunological weapons for medicine in the 21st Century: biological therapy based on the use of the latest generation monoclonal antibodies]. 1502 9

Renal involvement with amyloidosis is common but causes patient survival to be poor, rarely reaching 5 years. In this study, we retrospectively reviewed clinical and biological characteristics as well as treatments and outcomes of patients with renal amyloidosis followed for more than 5 years. Between 1975 and 2003, 485 patients were diagnosed with renal amyloidosis including only 12 patients who were followed more than 5 years. The six men and six women of mean age 42.4 years (range 18 to 66 years) displayed renal signs of lower limb edema in all cases; hypertension in four cases, proteinuria on urinalysis in all cases with microscopic hematuria in five cases. Biological tests showed nephrotic syndrome in 11 patients, normal renal function in nine patients, and renal failure in three patients whose mean creatinine was 481.6 micromol/L (range 294 to 726). The amyloidosis was AA type in 11 cases and non-AA in one case. An etiologic survey revealed spondylarthropathy in one patient, pulmonary tuberculosis in two patients, chronic bronchitis in three patients, hepatic hydatic cyst in one patient, Mediterranean familial fever in two patients, Crohn's disease in one patient, Hodgkin's lymphoma in one patient, and multiple myeloma in one patient. Specific treatment was initiated with colchicine in seven patients. At a 110-month mean follow-up (range 53 to 153 months), remission of nephrotic syndrome was observed in four cases, progression to chronic renal failure in two patients, and to end-stage renal failure in five cases (range 53 to 196 months), with stabilization of renal function in seven patients. In conclusion, primary amyloid disease should be optimally suppressed in patients with renal involvement. The role of this treatment in remission of renal amyloidosis is not well established. This efficacy of the treatment has been demonstrated in some patients with improved survival.
 ...
PMID:Renal amyloidosis followed more than 5 years: report of 12 cases. 1535 Apr 80

The authors describe uncommon combinations of multiple myeloma in three men aged 83, 63 and 55 years. In patient no. 1 both diseases--pernicious anaemia and multiple myeloma IgG-kappa were detected simultaneously. In patient no. 2 Crohn's disease preceded multiple myeloma IgA-lambda by more than 30 years. In patient no. 3 Gaucher's disease preceded multiple myeloma with paraproteinaemia IgA-lambda and IgG-kappa by more than 10 years. The diagnosis was facilitated by examination of the bone marrow, immunochemical examination of serum and urine and X-ray examination of the skeleton. In all patients the development of the myeloma had an adverse effect on the general course of the disease and despite treatment it soon proved fatal. In the discussion views on the possible causal associations between these diseases are discussed.
 ...
PMID:[Uncommon combination of multiple myeloma in three patients]. 1563 4

Etanercept is a commercially available pharmaceutical protein approved for treatment of rheumatoid arthritis, RA. Given subcutaneously, etanercept binds and inactivates soluble tumor necrosis factor-alpha, TNF. Etanercept has a good safety record and is of benefit in lowering pain, inflammation, and joint destruction in RA. RA is mediated by many factors, TNF among them. Malignant myeloma, MM, is a malignant clonal expansion of a post-germinal center B lymphocyte. Since TNF is a necessary growth factor for expansion and maintenance of MM cells, and etanercept binds soluble TNF and is of clinical benefit in RA, etanercept was tried experimentally in MM. Contrary to expectations, etanercept resulted in increased levels of TNF and possibly shortened survival. This paper presents an hypothesis of how this happened. There are two cognate receptors for TNF, termed R1 and R2 and two forms of TNF, soluble and transmembrane. Soluble TNF has greater affinity for TNF-R1 than for TNF-R2. Transmembrane TNF has equal affinity for the two receptors. Since TNF-R2 signaling tends to be more anti-apoptotic and activating of nuclear factor kappa B, NFkB, than is TNF-R1, and TNF-R1 tends to be more pro-apoptotic than is TNF-R2, by inactivating soluble TNF while leaving transmembrane TNF signaling relatively unchanged, etanercept changed the balance in TNF signaling from TNF-R1 towards TNF-R2 weighting. Anti-apoptosis and TNF synthesis would have been up-regulated by that shift. Early data indicates that the common generic antidepressant bupropion may ameliorate Crohn's disease course by down regulating TNF synthesis, maybe it will slow the course of MM as well.
 ...
PMID:Evidence of a mechanism by which etanercept increased TNF-alpha in multiple myeloma: new insights into the biology of TNF-alpha giving new treatment opportunities--the role of bupropion. 1596 26

Cytokines (interleukins, chemokines, and some growth factors) play an important role in cancer, metabolic disorders, autoimmune disorders and inflammatory diseases, such as rheumatoid arthritis, asthma, Crohn's disease, psoriasis, multiple sclerosis and asthma. Cytokine-based drugs and anticytokine therapies are an increasingly important class of drugs in the treatment and management of many diseases. Interferons are being used to treat viral diseases and cancers. Anti-tissue necrosis factor therapies, such as Enbrel (etanercept; Immunex Corp) and Remicade (infliximab; Centocor) have demonstrated clinical efficacy in rheumatoid arthritis and Crohn's disease. In addition, thalidomide (Celgene) is being used to treat erythema nodosum in leprosy, cancers (multiple myeloma and colon cancer) and autoimmune diseases. This conference focused on new developments in basic research, drug discovery and clinical development of cytokine-based drugs.
 ...
PMID:Cytokines as drug targets. 1601 67

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.
 ...
PMID:Interleukin 6: from bench to bedside. 1707 1

Natalizumab is a humanized monoclonal antibody that is produced in murine myeloma cells. It functions in the body as an antagonist of integrin heterodimers that contain the a4 integrin subunit. These heterodimers include a4b1 integrin and a4b7 integrin, which are expressed on the surface of most leukocytes. When natalizumab binds to the a4-subunit of the integrin, it prevents the a4-mediated adhesion of the leukocytes to their counter-receptor(s) (eg, vascular cell adhesion molecule-1 and mucosal addressin cell adhesion molecule-1), thus preventing transmigration of the leukocytes across the endothelium and into the inflamed parenchymal tissue. Clinical trials with natalizumab for the treatment of the relapsing forms of multiple sclerosis have found the drug is capable of delaying the accumulation of physical disability and reducing the frequency of clinical exacerbations. Clinical trials of natalizumab for the treatment of Crohn's disease have found the drug, alone or in combination with infliximab, is effective in improving clinical response and remission rates as well as health-related quality of life in patients with Crohn's disease who have not been able to achieve remission with infliximab therapy alone. Like all drugs, natalizumab is not without risks. The drug was temporarily withdrawn from the market because of 3 reported cases of progressive multifocal leukoencephalopathy. Subsequent evaluations determined that the risk of this severe, but rare, adverse reaction did not justify keeping the drug off the market. When natalizumab was reintroduced, however, a closed prescribing and distribution program (Tysabri Outreach Unified Commitment to Health [TOUCH]) was also introduced. This program requires all patients prescribed natalizumab to be enrolled in and to receive their medication through the TOUCH system. Any serious adverse reactions must be reported to the TOUCH and MedWatch systems.
 ...
PMID:Natalizumab: overview of its pharmacology and safety. 1739 28

Since 1964 only nine cases of multiple myeloma occurring in the setting of inflammatory bowel disease have been reported. Although this occurrence may be a mere unfortunate coincidence, there are sound pathophysiological reasons for such an event. The possibility that chronic inflammatory conditions, immunomodulator therapy, and infliximab can predispose to multiple myeloma and lymphoma is reviewed. We discuss in detail the only reported case of multiple myeloma arising in the setting of infliximab treatment for Crohn's disease. It is highly probable that infliximab therapy had a causal role in our patient developing multiple myeloma. The pathogenesis of multiple myeloma arising in the setting of infliximab therapy may be related to decreased apoptosis of plasma cell populations. Since it is possible that a causal association exists between infliximab therapy and multiple myeloma, additional screening measures may be required in patients with Crohn's disease on infliximab.
 ...
PMID:Review article: multiple myeloma and inflammatory bowel disease. 1771 42

Nuclear factor-kappaB (NF-kappaB) is responsible for the expression by regulating many genes for immune response, cell adhesion, differentiation, proliferation, angiogenesis and apoptosis. The function of NF-kappaB is inhibited by binding to NF-kappaB inhibitor (IkappaB), and imbalance of NF-kappaB and IkappaB has been associated with development of many diseases, including tumours. In this review, we focus on polymorphisms of the NFKB and NFKBI genes in relation to development of common inflammatory diseases including ulcerative colitis (UC), Crohn's disease (CD), rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, giant cell arthritis, type 1 diabetes, multiple sclerosis, celiac disease, and Parkinson's disease, as well as susceptibility of several cancers, such as oral squamous cell carcinoma, colorectal cancer (CRC), hepatocellular carcinoma, breast cancer and myeloma.
 ...
PMID:NFKB and NFKBI polymorphisms in relation to susceptibility of tumour and other diseases. 1770 19


<< Previous 1 2 3 4 5 Next >>