Search results for "MIB"
showing 10 items of 193 documents
Network meta-analysis of randomized trials in multiple myeloma: efficacy and safety in relapsed/refractory patients.
2017
Despite major therapeutic advancements, multiple myeloma (MM) is still incurable and relapsed/refractory multiple myeloma (RRMM) remains a challenge; the rational choice of the most appropriate regimen in this setting is currently undefined. We performed a systematic review and 2 standard pairwise meta-analyses to evaluate the efficacy of regimens that have been directly compared with bortezomib or immunomodulatory imide drugs (IMiDs) in head-to-head clinical trials and a network meta-analysis (NMA) to determine the relevance of each regimen on the basis of all the available direct and indirect evidence. Sixteen trials were included in the pairwise meta-analyses, and 18 trials were included…
The coexistence of primary hyperparathyroidism and thyroid nodules: Should the preoperative work-up of the parathyroid and the thyroid diseases be sp…
2016
Introduction and objectives. Primary hyperparathyroidism (PHPT) can be found in concomitance with thyroid disease (TD) in a high frequency of cases. In this context the diagnostic exams for localizing the enlarged parathyroid(s) gland(s) could be less reliable or nonconclusive. Moreover, the thyroid carcinoma seems to be more frequent compared to that isolated thyroid desease and, therefore, carefully investigated. The main goal of the present study is to evaluate which diagnostic tool (US, MIBI) is more reliable for localizing the site of the PTH hypersecretion and to confirm if it is always advantageous a combination of both exams. Besides, we evaluated the incidence of thyroid carcinoma …
Lipid-Altering Efficacy of Ezetimibe/Simvastatin 10/20 mg Compared to Rosuvastatin 10 mg in High-Risk Patients with and without Type 2 Diabetes Melli…
2010
SUMMARY Aims: This post hoc analysis compared the effects of switching to ezetimibe/simvastatin 10/20 mg (EZE/SIMVA) or rosuvastatin 10 mg (ROSUVA) in uncontrolled high-risk hypercholesterolemic patients with/without type 2 diabetes mellitus (T2DM) despite statin monotherapy. Methods: Patients (n = 618) at high risk for coronary vascular disease with elevated LDL-C ≥100 and ≤190 mg/dL despite use of statins were randomized 1:1 to double-blind EZE/SIMVA 10/20 mg or ROSUVA 10 mg for 6 weeks. Patients were classified as having T2DM based on ≥1 of the following: diagnosis of T2DM, antidiabetic medication, or FPG ≥126 mg/dL. This analysis evaluated percent changes from baseline in lipids among p…
Clinical benefits of ezetimibe use: is absence of proof, proof of absence?
2012
Doggrell reviewed the evidence regarding the clinical benefits of ezetimibe in the July issue of Expert Opinion on Pharmacotherapy [1]. The author concludes that since clinical outcome data are sti...
Arginine Depletion in Combination with Canavanine Supplementation Induces Massive Cell Death in Myeloma Cells By Interfering with Their Protein Metab…
2018
Abstract Introduction Although the therapeutic armamentarium against multiple myeloma has tremendously increased in recent years, it still remains an incurable disease. A highly promising novel anti-tumoral treatment strategy is to target specific non-redundant metabolic achilles heels of individual cancer entities. The semi-essential amino acid arginine can be synthesized from citrulline in most physiological tissues due to expression of the rate-limiting enzyme argininosuccinate synthetase 1 (ASS1). Various tumor entities do not express ASS1, therefore depend on the exogenous availability of arginine and pharmacological approaches to systemically deplete arginine are in phase I-III clinic…
Apoptosis: a relevant tool for anticancer therapy.
2006
Apoptosis is a form of cell death that permits the removal of damaged, senescent or unwanted cells in multicellular organisms, without damage to the cellular microenvironment. Defective apoptosis represents a major causative factor in the development and progression of cancer. The majority of chemotherapeutic agents, as well as radiation, utilize the apoptotic pathway to induce cancer cell death. Resistance to standard chemotherapeutic strategies also seems to be due to alterations in the apoptotic pathway of cancer cells. Recent knowledge on apoptosis has provided the basis for novel targeted therapies that exploit apoptosis to treat cancer. These new target include those acting in the ext…
MYC and EGR1 synergize to trigger tumor cell death by controlling NOXA and BIM transcription upon treatment with the proteasome inhibitor bortezomib
2014
The c-MYC (MYC afterward) oncogene is well known for driving numerous oncogenic programs. However, MYC can also induce apoptosis and this function of MYC warrants further clarification. We report here that a clinically relevant proteasome inhibitor significantly increases MYC protein levels and that endogenous MYC is necessary for the induction of apoptosis. This kind of MYC-induced cell death is mediated by enhanced expression of the pro-apoptotic BCL2 family members NOXA and BIM. Quantitative promoter-scanning chromatin immunoprecipitations (qChIP) further revealed binding of MYC to the promoters of NOXA and BIM upon proteasome inhibition, correlating with increased transcription. Both pr…
Bortezomib Partially Improves Laminin α2 Chain–Deficient Muscular Dystrophy
2014
Congenital muscular dystrophy, caused by mutations in LAMA2 (the gene encoding laminin α2 chain), is a severe and incapacitating disease for which no therapy is yet available. We have recently demonstrated that proteasome activity is increased in laminin α2 chain-deficient muscle and that treatment with the nonpharmaceutical proteasome inhibitor MG-132 reduces muscle pathology in laminin α2 chain-deficient dy(3K)/dy(3K) mice. Here, we explore the use of the selective and therapeutic proteasome inhibitor bortezomib (currently used for treatment of relapsed multiple myeloma and mantle cell lymphoma) in dy(3K)/dy(3K) mice and in congenital muscular dystrophy type 1A muscle cells. Outcome measu…
Development of Novel Selective Peptidomimetics Containing a Boronic Acid Moiety, Targeting the 20S Proteasome as Anticancer Agents
2014
This paper describes the design, synthesis, and biological evaluation of peptidomimetic boronates as inhibitors of the 20S proteasome, a validated target in the treatment of multiple myeloma. The synthesized compounds showed a good inhibitory profile against the ChT-L activity of 20S proteasome. Compounds bearing a β-alanine residue at the P2 position were the most active, that is, 3-ethylphenylamino and 4-methoxyphenylamino (R)-1-{3-[4-(substituted)-2-oxopyridin-1(2H)-yl]propanamido}-3-methylbutylboronic acids (3 c and 3 d, respectively), and these derivatives showed inhibition constants (Ki ) of 17 and 20 nM, respectively. In addition, they co-inhibited post glutamyl peptide hydrolase act…
Optimization of peptidomimetic boronates bearing a P3 bicyclic scaffold as proteasome inhibitors
2014
Abstract A new series of pseudopeptide boronate proteasome inhibitors (2–3) was developed, through optimization of our previously described analogs of bortezomib, bearing a bicyclic 1,6-naphthyridin-5(6H)-one scaffold as P3 fragment (1). The biological evaluation on human 20S proteasome displayed a promising inhibition profile, especially for compounds bearing a P2 ethylene fragment, which exhibited Ki values in the nanomolar range for the ChT-L activity (e.g. 2a, Ki = 0.057 μM) and considerable selectivity for proteasome over bovine pancreatic α-chymotrypsin. Docking experiments into the yeast 20S proteasome revealed that the ligands are accommodated predominantly into the ChT-L site and t…