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)

A number of agents targeting components of pathways and processes critical to neoplastic transformation and progression are ongoing clinical development. Notable successes include imatinib mesylate (STI571, Gleevec) in Chronic Myelogenous Leukemia (CML), and Gastrointestinal Stromal Tumors (GIST) and trastuzumab (Herceptin) in HER2 amplified breast carcinoma. More recently, gefitinib (ZD1839, Iressa) and bortezomib (PS-341, Velcade) have been approved for refractory nonsmall cell lung carcinoma (NSCLC) and multiple myeloma (MM), respectively. In addition, promising results from randomized studies of bevacizumab (Avastin) and cetuximab (IMC-225, Erbitux) have been reported and shortly may lead to their approval for the treatment of colorectal carcinoma (CRC). To what degree the success or failure of these agents has been due to target, the agent, the dose or the selection of patients is uncertain. Certainly, further evaluation of these factors is required to optimize the therapeutic impact of targeted agents and imaging modalities may play a vital role in this process. The purpose of this review is to summarize recent results from trials of selected targeted agents and to suggest roles imaging may play in the further development of these and other targeted agents.
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PMID:Recent advances of molecular targeted agents: opportunities for imaging. 1468 62

Accumulating data indicate translation plays a role in cancer biology, particularly its rate limiting stage of initiation. Despite this evolving recognition, the function and importance of specific translation initiation factors is unresolved. The eukaryotic translation initiation complex eIF4F consists of eIF4E and eIF4G at a 1:1 ratio. Although it is expected that they display interdependent functions, several publications suggest independent mechanisms. This study is the first to directly assess the relative contribution of eIF4F components to the expressed cellular proteome, transcription factors, microRNAs, and phenotype in a malignancy known for extensive protein synthesis-multiple myeloma (MM). Previously, we have shown that eIF4E/eIF4GI attenuation (siRNA/Avastin) deleteriously affected MM cells' fate and reduced levels of eIF4E/eIF4GI established targets. Here, we demonstrated that eIF4E/eIF4GI indeed have individual influences on cell proteome. We used an objective, high throughput assay of mRNA microarrays to examine the significance of eIF4E/eIF4GI silencing to several cellular facets such as transcription factors, microRNAs and phenotype. We showed different imprints for eIF4E and eIF4GI in all assayed aspects. These results promote our understanding of the relative contribution and importance of eIF4E and eIF4GI to the malignant phenotype and shed light on their function in eIF4F translation initiation complex.
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PMID:eIF4E and eIF4GI have distinct and differential imprints on multiple myeloma's proteome and signaling. 2571 31

Cancer patients have an increased risk of thrombosis. The development of cancer thrombosis is dependent on a number of factors including cancer type, stage, various biologic markers, and the use of central venous catheters. In addition, cancer treatment itself may increase thrombotic risk. Tamoxifen increases the risk of venous thromboembolism (VTE) by two- to sevenfold, while an impact on risk of arterial thrombosis is uncertain. Immunomodulatory imide drugs (IMiDs) such as thalidomide and lenalidomide increase the risk of VTE in patients with multiple myeloma (MM) by about 10-40% when given in combination with glucocorticoids or other chemotherapy agents; the risk of VTE in MM patients treated with IMiD-containing regimens necessitates that such patients receive thromboprophylaxis with aspirin, low-molecular-weight heparin, or warfarin. Among cytotoxic chemotherapy agents, cisplatin, and to a lesser extent fluorouracil, has been described in association with thrombosis. L-asparaginase in treatment of acute lymphoblastic leukemia is significantly associated with increased thrombosis particularly affecting the CNS, which may be due to acquired antithrombin deficiency; at some centers, plasma infusions or antithrombin replacement is used to mitigate this. Bevacizumab, an inhibitor of vascular endothelial growth factor, increases arterial and possibly venous thrombotic risk, although the literature is conflicting about the latter. Supportive care agents in cancer care, such as erythropoiesis-stimulating agents, granulocyte colony stimulating factor, and steroids, also have some impact on thrombosis. This review summarizes the mechanisms by which these and other therapies modulate thrombotic risks and how such risks may be managed.
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PMID:Thrombotic Risk from Chemotherapy and Other Cancer Therapies. 3131 82