Discovery platform for inhibitors of IgH gene enhancer activity.

Discovery platform for inhibitors of IgH gene enhancer activity. Cancer Biol Ther. 2018 Nov 27;:1-11 Authors: Dolloff NG Abstract Immunoglobulin heavy chain (IgH) translocations are common and early oncogenic events in B cell and plasma cell malignancies including B cell non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). IgH translocations bring oncogenes into close proximity with potent enhancer elements within the IgH locus, leading to oncogene up-regulation. As IgH enhancer activity is tightly controlled by B cell lineage-specific signaling and transcriptional networks, we hypothesized that IgH enhancers are potentially druggable targets/elements. To test this, we developed a molecular imaging-based high-throughput screening platform for discovering inhibitors of IgH enhancer-driven transcriptional activity. As proof of concept, we identified a low micromolar potency molecule (compound 30666) that inhibited immunoglobulin production by MM cells and blocked expression of an array of IgH translocation-induced oncogenes (CCND1, FGFR3/MMSET, and MYC) in MM and NHL cell lines. Prolonged exposure to 30666 significantly reduced the viability of IgH translocation-positive NHL and MM cells, but was less effective against cells lacking IgH translocations. Compound 30666 exhibited suitable pharmacological properties, including metabolic stability in liver microsomes and oral bioavailability in mice, and demonstrated preclinical anti-MM activity in a plasmac...
Source: Cancer Biology and Therapy - Category: Cancer & Oncology Authors: Tags: Cancer Biol Ther Source Type: research

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Publication date: Available online 19 October 2019Source: Practical Radiation OncologyAuthor(s): Barry S. Rosenstein
Source: Practical Radiation Oncology - Category: Cancer & Oncology Source Type: research
ConclusionThese findings suggest that targeted research and interventions are necessary to address the specific needs of rural lymphoma patients and survivors. To address the disparity in health outcomes within rural populations, health care professionals and investigators can utilize these data to engage rural patients in treatment decision-making and research planning.
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
ConclusionThe better prognosis in young patients is presumably due to their better physiological reserve and lower incidence of comorbidities. Efforts should be made in younger patients to diagnose early and treat aggressively.
Source: Cancer Epidemiology - Category: Cancer & Oncology Source Type: research
We examined racial differences in hospitalization outcomes; length of stay (LOS) in hospital, mortality in hospital, post-operative complications in patients who underwent hysterectomy and discharge disposition. Patients were matched on age at primary diagnosis, insurance status, residential region, and median income of residential area, modified Deyo comorbidity index, stage of disease and treatment. Categorical outcomes were analyzed by conditional logistic regression accounting for matched study design and odds ratios (95%CI) were reported. LOS was analyzed using t-test and beta estimate for difference in means was repo...
Source: Cancer Epidemiology - Category: Cancer & Oncology Source Type: research
Publication date: Available online 18 October 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Hui Deng, Weimin LiAbstractMonoacylglycerol lipase (MAGL) is a serine hydrolase that plays a crucial role catalysing the hydrolysis of monoglycerides into glycerol and fatty acids. It links the endocannabinoid and eicosanoid systems together by degradation of the abundant endocannabinoid 2-arachidaoylglycerol into arachidonic acid, the precursor of prostaglandins and other inflammatory mediators. MAGL inhibitors have been considered as important agents in many therapeutic fields, including anti-nociceptive, anxiolytic, anti-infl...
Source: Acta Pharmaceutica Sinica B - Category: Cancer & Oncology Source Type: research
Publication date: Available online 18 October 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Honggang Xiang, Jifa Zhang, Congcong Lin, Lan Zhang, Bo Liu, Liang OuyangAbstractAutophagy, defined as a scavenging process of protein aggregates and damaged organelles mediated by lysosomes, plays a significant role in the quality control of macromolecules and organelles. Since protein kinases are integral to the autophagy process, it is critically important to understand the role of kinases in autophagic regulation. At present, intervention of autophagic processes by small-molecule modulators targeting specific kinases has bec...
Source: Acta Pharmaceutica Sinica B - Category: Cancer & Oncology Source Type: research
This study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a cluster-dissociating therapeutic agent in vitro. Firstly, we found marked enrichment of αv integrin in collectively invading multicellular clusters in human OSCCs. Our study revealed that metastatic progression of OSCC was associated with augmented immunostaining of αv integrin in cancerous lesions. Following PEP06 treatment, cell clustering on fibronectin, migration, multicellular aggregation, anchorage-independent survival and colony formation of OSCC were significantly inhibited. Moreover, PEP06 suppres...
Source: Acta Pharmaceutica Sinica B - Category: Cancer & Oncology Source Type: research
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Source: Acta Pharmaceutica Sinica B - Category: Cancer & Oncology Source Type: research
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
AbstractPurposeThe identification of biomarkers characterizing the invasive potential of bladder cancer could enhance the clinical management of individual patients and therefore improve prognosis. The aim of this study was to define a miRNA panel in tumor tissues as well as in urinary extracellular vesicles (EVs) for discriminating muscle-invasive bladder cancer (MIBC) from non-muscle-invasive bladder cancer (NMIBC).MethodsmiRNA expression was analyzed in 24 formalin-fixed, paraffin-embedded (FFPE) tumor samples by microarray analysis and was further validated by qRT-PCR in 56 FFPE tumor samples as well as in 37 urinary E...
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
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