Amgen Sees Positive Results From Kyprolis Study

Amgen took a step forward in its efforts to make its Kyprolis cancer therapy a standard treatment for many multiple myeloma patients, saying the drug performed better than older rival Velcade in a study.
Source: WSJ.com: Health - Category: Pharmaceuticals Tags: PAID Source Type: news

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In this study, we investigated the effect of CUDC-907 on human pancreatic cancer cells in vitro and in vivo. Our results showed that CUDC-907 potently inhibited the proliferation of 9 pancreatic cancer cell lines in vitro with IC50 values ranging from 6.7 to 54.5 nM. Furthermore, we revealed the antitumor mechanism of CUDC-907 in Aspc-1, PANC-1, and Capan-1 pancreatic cancer cells: it suppressed the HDAC6 subunit, thus downregulating c-Myc protein levels, which was a mode of action distinct from the existing mechanisms. Consistently, the extraordinary antitumor activity of CUDC-907 accompanied by downregulation of c...
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research
The polyamine metabolic pathway has been considered a rational target for antineoplastic therapy since it was discovered that polyamines are absolute requirements for tumor initiation, growth, and, in some instances, survival. Although several promising preclinical studies have demonstrated the critical nature of polyamines for tumor growth, the clinical success of agents targeting polyamine metabolism have been lacking. In the accompanying article, Bianchi-Smiraglia et al. identify both a new target and new drug that inhibits polyamine biosynthesis, reduces intracellular polyamines, and inhibits the growth of several mode...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
This study identifies a previously unrecognized regulatory axis between AHR and polyamine metabolism and reveals CLF as an inhibitor of AHR and a potentially clinically relevant anti-MM agent.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Abstract Patients who experienced cardiovascular side effects during cancer therapy with carfilzomib for multiple myeloma had relapsed multiple myeloma, so have be previously treated with other cancer therapies. The present is a single center cohort study to evaluate early cardiovascular effects of administration of irreversible proteasome inhibitor carfilzomib in naïve patients. We included 24 patients and collected cardiovascular side effects, echocardiographic parameters and endothelial function at baseline and after 4 cycles. At early follow up we observed increase in blood arterial pressure values (mean ...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research
We describe recent observations with regard to functional exhaustion of iNKT and MAIT cells in MM pathology and discuss the potential application of checkpoint inhibition as an attractive target for prolonged activation of these immunomodulatory T cells in the treatment of MM.
Source: Molecular Immunology - Category: Allergy & Immunology Source Type: research
In this study, heptamer Smac peptide was fused to a well-known octaarginine cell-penetrating peptide for promoting its intracellular access. Both therapeutic Smac part and cell-penetrating octaarginine parts of the peptide sequence constrained in a cyclic structure so as to enhance the apoptosis-inducing potential of the SmacN7 peptide. Biological assays interestingly showed that cyclic peptides P4, P5 and P7 gave rise to a significant level of cytotoxicity and apoptosis mediated cell death in multiple myeloma tumor cells (MM) comparing to linear peptide. PMID: 30123940 [PubMed - as supplied by publisher]
Source: Amino Acids - Category: Biochemistry Authors: Tags: Amino Acids Source Type: research
AbstractThe inhibition of histone deacetylase (HDAC) has become a well-recognized target for cancer therapy. Until now only five HDAC inhibitors i.e., SAHA, romidepsin (FK-228), belinostat, chidamide, and panobinostat have been approved by FDA. The first four of them are being employed for the treatment of cutaneous T-cell lymphoma and last one is being used for the treatment of multiple myeloma. In the present study, structure and ligand-based computational approaches were selected to design novel histone deacetylase inhibitors. A ligand-based pharmacophore model was developed employing phase module that exhibited five si...
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research
Characterization of intratumoral heterogeneity is critical to cancer therapy, as the presence of phenotypically diverse cell populations commonly fuels relapse and resistance to treatment. Although genetic variation is a well-studied source of intratumoral heterogeneity, the functional impact of most genetic alterations remains unclear. Even less understood is the relative importance of other factors influencing heterogeneity, such as epigenetic state or tumor microenvironment. To investigate the relationship between genetic and transcriptional heterogeneity in a context of cancer progression, we devised a computational ap...
Source: Genome Research - Category: Genetics & Stem Cells Authors: Tags: METHOD Source Type: research
This study identified a previously unrecognized regulatory axis between AHR and polyamine metabolism and discovered clofazimine as an inhibitor of AHR and a potentially clinically-relevant anti-multiple myeloma agent.RNA-seq: human multiple myeloma MM1S and human normal fibroblasts WI38 cells -/+ CLF 2-4uM for 24hrs; -/+ shAHR
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Characterization of intratumoral heterogeneity is critical to cancer therapy, as the presence of phenotypically diverse cell populations commonly fuels relapse and resistance to treatment. Although genetic variation is a well-studied source of intratumoral heterogeneity, the functional impact of most genetic alterations remains unclear. Even less understood is the relative importance of other factors influencing heterogeneity, such as epigenetic state or tumor microenvironment. To investigate the relationship between genetic and transcriptional heterogeneity in a context of cancer progression, we devised a computational ap...
Source: Genome Research - Category: Genetics & Stem Cells Authors: Tags: METHOD Source Type: research
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