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)

Paraoxon (E600) was conjugated to bovine serum albumin(BSA) or tachypleus tridentatus hemocyanin (TTH) by diazotization. Two hybridoma cell lines secreting monoclonal antibodies(McAb) against paraoxon have been established by fusing mouse myeloma cells and splenocytes from Balb/c mice immunized with E600-BSA. The chromosomes of the hybridoma cell 2B10 were analyzed. The immunoglobulin of the McAb was classified. The affinity and specificity of this antibody were determined. The hybridoma cells have fairly reserved the antibody-producing capacity after continuously growing or stored in liquid nitrogen for 10 weeks.
 ...
PMID:[Production and identification of anti-paraoxon monoclonal antibodies]. 1201 78

The major clinical manifestation of multiple myeloma results from osteolytic bone destruction. The only currently Food and Drug Administration-approved drug for the treatment of the bony complications of multiple myeloma is monthly intravenous pamidronate at a dose of 90 mg infused over 4 hours. Recent studies have shown the safety of 2-hour infusions. A randomized trial comparing pamidronate to placebo continued to show benefits throughout the 21-month trial. Although the duration of therapy has not been firmly determined, it is likely that discontinuation of this drug will be met by enhanced bone loss and an increased risk of bony complications for these patients. Thus, it is recommended that the drug be continued indefinitely. Support for this recommendation also comes from the reduced bone density observed in women with postmenopausal osteoporosis following the withdrawal of bisphosphonate treatment. Recent attempts to give higher doses, more frequent infusions (every 2 weeks or less), or more rapid infusions (1 hour or less) of pamidronate have occasionally been associated with albuminuria and azotemia. These modifications should therefore be avoided. Importantly, the drug can be safely administered at 90 mg monthly to patients with poor renal function. The use of pamidronate for myeloma patients without lytic bone involvement or with Durie-Salmon stages I or II disease has not been evaluated. However, it is recognized that most patients with earlier stages of disease or without lytic bone involvement also develop bony complications. There is no reason to believe that these patients would not benefit from monthly intravenous infusions of pamidronate. The potential antimyeloma effect of this agent is another reason to administer this drug in these types of patients. Thus, it is our practice to administer monthly pamidronate to myeloma patients regardless of stage or bone involvement. However, trials evaluating oral bisphosphonates have produced inconsistent clinical results, probably as a result of the erratic and scanty poor absorption as well as poor oral tolerability of these drugs. Although these oral agents may be useful in some patients, it is impossible to identify which myeloma patients will benefit from orally administered bisphosphonates. The more potent nitrogen-containing bisphosphonate zoledronic acid more effectively reverses hypercalcemia of malignancy than pamidronate, and it appears promising in reducing bone loss in cancer patients. However, its efficacy in preventing skeletal complications is still being evaluated. Many other types of new agents are in early clinical trials, but their efficacy remains unproven at the present time.
 ...
PMID:Bone disease in myeloma. 1205 27

Bendamustine hydrochloride is the active ingredient of Ribomustin (Ribosepharm GmbH, Munich, Germany). It was first synthesized in 1963 in the German Democratic Republic. Bendamustine is chemically related to the alkylating agent chlorambucil, with the benzene ring in the chlorambucil molecule replaced by a 1-methyl-benzimidazole moiety. The mechanisms of action of bendamustine have been under investigation since the early 1960s, and its first use was as a treatment for multiple myeloma in 1969. Bendamustine has three active moieties: an alkylating group, in common with the nitrogen mustard family; a benzimidazole ring, which may act as a purine analog; and a butyric acid side-chain. Bendamustine undergoes extensive first-pass metabolism. However, unmetabolized bendamustine accounts for about 45% of the total drug recovered in urine. The main transformation product is a cytotoxic hydroxy metabolite (beta-hydroxybendamustine). Bendamustine was originally synthesized with the intention of producing an antineoplastic agent with low toxicity and both alkylating and antimetabolic properties. However, it has been shown that, at least at high concentrations, it acts primarily as an alkylating agent. Based on the multiple actions and cell cycle effects of this agent, mechanism-based combination strategies have been suggested. The rationales behind bendamustine combination regimens and the importance of the sequence of administration of different drugs are explored.
 ...
PMID:Metabolism and mechanisms of action of bendamustine: rationales for combination therapies. 1217 Apr 25

An increasing number of unique active new chemotherapeutic and biologic agents are currently available for clinical research studies. Nucleoside analogs in development for non-Hodgkin's lymphoma (NHL) include clofarabine, troxacitabine, and bendamustine, a hybrid of an alkylating nitrogen mustard group and a purine-like benzimidazole, with demonstrated activity in NHL. Drugs directed at the cell cycle include flavopiridol and UCN-01. The proteasome plays a pivotal role in cellular protein regulation and activation of NFkappaB, which maintains cell viability through the transcription of inhibitors of apoptosis. PS-341 is a specific, selective inhibitor of the 26S proteasome which induces apoptosis and has activity in cell types characterized by overexpression of Bcl-2. Response rates of 50%, including complete remissions, have been reported using this agent in patients with refractory multiple myeloma. Studies are ongoing in NHL and chronic lymphocytic leukemia. G3139, an antisense oligonucleotide, has shown promise in early studies. Rituximab has revolutionized the treatment of NHL. However, other active antibodies are now available, including alemtuzumab, epratuzumab, and Hu1D10. The radioimmunoconjugates (90)Y-ibritumomab tiuxetan and (131)I-tositumomab may also play an important role in the management of NHL. Future therapeutic strategies should involve rational combinations of new chemotherapy drugs, biologic agents, and antisense compounds to increase the cure rate in patients with lymphoma.
 ...
PMID:Hematologic malignancies: new developments and future treatments. 1217 Apr 31

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.
 ...
PMID:Fine-needle aspiration cytology of a case of HIV-associated anaplastic myeloma. 1235 99

Anti-resorptive bisphosphonates, such as pamidronate, are an effective treatment for osteolytic disease and hypercalcaemia in patients with multiple myeloma, but have also been shown to cause apoptosis of myeloma cell lines in vitro. In this study, we found that a single infusion of pamidronate, in 16 newly diagnosed patients with multiple myeloma, caused a marked increase in apoptosis of plasma cells in vivo in 10 patients and a minimal increase in four patients (P < 0.05). The nitrogen-containing bisphosphonates pamidronate and zoledronic acid also induced apoptosis of authentic, human bone marrow-derived plasma cells in vitro. Apoptosis of plasma cells in vitro was probably caused by inhibition of the mevalonate pathway and loss of prenylated small GTPases, as even low concentrations (>or= 1 micro mol/l) of zoledronic acid caused accumulation of unprenylated Rap1A in cultures of bone marrow mononuclear cells in vitro. GGTI-298, a specific inhibitor of geranylgeranyl transferase I, also induced apoptosis in human plasma cells in vitro, suggesting that geranylgeranylated proteins play a role in signalling pathways that prevent plasma cell death. Our results suggest that pamidronate may have direct and/or indirect anti-tumour effects in patients with multiple myeloma, which has important implications for the further development of the more potent nitrogen-containing bisphosphonates, such as zoledronic acid, in the treatment of myeloma.
 ...
PMID:Pamidronate causes apoptosis of plasma cells in vivo in patients with multiple myeloma. 1240 88

Six hybridoma cell lines secretion monoclonal antibodies(MAbs) against broad bean wilt virus(BBWV) were produced by fusing mouse myeloma cells(SP 2/0) with spleen cells from BAL B/c immunized by the BBWV particles. The hybridoma cell lines secreted MAbs stably after cultured in vitro for 3 months or stored in liquid nitrogen and then revived for several times. The titres of ascitic fluids of six MAbs ranged from 1:256,000 to 1:640,000 when measured by indirect ELISA. In agarose gel immunodiffusion test, it showed that the six MAbs represented the same isotype of murine antibodies, IgG1. Six MAbs could detect 4 tested BBWV isolates, but didn't crossreact with other 5 plant viruses. The result of Western blot showed that all the six MAbs can react with the 44.7 kD large coat protein subunit of BBWV. This is the first report of production of MAbs against BBWV.
 ...
PMID:[Production of monoclonal antibodies to broad bean wilt virus and application in virus detection]. 1254 40

Bone metastases are a common feature of a variety of solid tumors and are associated with substantial skeletal morbidity, including severe bone pain and pathologic fractures. Treatment with bisphosphonates, primarily pamidronate, is the current standard of care for patients with breast cancer and multiple myeloma who have predominantly osteolytic lesions. However, until recently no bisphosphonate had demonstrated efficacy in patients with osteoblastic lesions, which are common during the progression of prostate cancer and other solid tumors. Zoledronic acid, a potent, new-generation, nitrogen-containing bisphosphonate, has demonstrated significant benefits for patients with bone metastases resulting from a broad range of primary tumors, including multiple myeloma and breast, lung, kidney, and prostate cancers, and other solid tumors. Benefits include a decreased incidence of pathologic fractures and longer time to the first skeletal complication. Zoledronic acid is the first and only bisphosphonate to be proved effective in patients with all types of bone lesions, from osteolytic to osteoblastic, and therefore represents an important therapeutic advancement in the treatment of bone metastases.
 ...
PMID:Broad clinical activity of zoledronic acid in osteolytic to osteoblastic bone lesions in patients with a broad range of solid tumors. 1256 47

Advanced solid tumors are often aggressive and recurrent, and overall survival remains relatively poor despite contemporary therapeutic interventions. Bone metastases are common in these patients, and skeletal-related events, including bone pain, pathologic fractures, and potentially life-threatening hypercalcemia of malignancy, undermine the quality of patient survival. Bisphosphonates are widely used in the treatment of bone metastases associated with breast cancer and multiple myeloma, but have not been extensively investigated in the treatment of patients with solid tumors other than breast or prostate cancer. However, a new-generation nitrogen-containing bisphosphonate, zoledronic acid, has shown significant clinical benefits in indications in which other bisphosphonates have failed. In a phase III clinical trial in patients with bone metastases from solid tumors other than breast or prostate cancer, treatment with zoledronic acid (4 mg via 15-minute infusion) was well tolerated and significantly decreased the incidence of skeletal-related events and increased the time to first skeletal-related event compared with placebo-treated patients. This was the first demonstration of palliative efficacy for bisphosphonate therapy in patients with bone metastases from a wide variety of solid tumors.
 ...
PMID:Efficacy and safety of zoledronic acid in the treatment of bone metastases associated with lung cancer and other solid tumors. 1258 92

Circulating monocytes from multiple myeloma patients enrolled in a clinical study of anti-idiotype vaccination were labelled with clinical-grade anti-CD14 microbeads and positively selected with the CliniMACS instrument. Cells were then grown, according to good manufacturing practice guidelines, in fetal-calf-serum-free medium in cell culture bags and differentiated to dendritic cells (DC) with granulocyte-macrophage colony stimulating factor plus interleukin 4 (IL-4), followed by either tumour necrosis factor-alpha (TNF-alpha) or a cocktail of IL-1beta, IL-6, TNF-alpha and prostaglandin-E2. The CD14+ cell yield was increased from 17.6 +/- 6.5% to 93.8 +/- 6.3% (recovery 64.4 +/- 15.4%, viability > 97%). After cell culture, phenotypic analysis showed that 86.7 +/- 6.8% of the cells were DC: 2.27 +/- 0.9 x 108 DC/leukapheresis were obtained, which represented 20.7 +/- 4.6% of the initial number of CD14+ cells. Notably, the cytokine cocktail induced a significantly higher percentage and yield (28.6 +/- 3% of initial CD14+ cells) of DC than TNF-alpha alone, with secretion of larger amounts of IL-12, potent stimulatory activity on allogeneic T cells and efficient presentation of tumour idiotype to autologous T cells. Storage in liquid nitrogen did not modify the phenotype or functional characteristics of preloaded DC. The recovery of thawed, viable DC was 78 +/- 10%. Finally, interferon-alpha-2b was at least as efficient as IL-4 in inducing the differentiation of mature, functional DC from monocytes.
 ...
PMID:Generation of dendritic cells from CD14+ monocytes positively selected by immunomagnetic adsorption for multiple myeloma patients enrolled in a clinical trial of anti-idiotype vaccination. 1269 45


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>