First-in-Human Phase I Study of the Activin A Inhibitor, STM 434, in Patients with Granulosa Cell Ovarian Cancer and Other Advanced Solid Tumors.

CONCLUSIONS: While no direct antitumor efficacy was documented, potentially clinically meaningful dose-related metabolic effects, including treatment of cancer cachexia, were observed that support further exploration of Activin A inhibitors that limit BMP9 blockade. PMID: 31068369 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research

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Conclusion: Our study demonstrated that the aberrant expression of CDCA gene family members plays an indispensable role in tumorigenesis. PMID: 31955607 [PubMed - as supplied by publisher]
Source: Future Medicine: Biomarkers in Medicine - Category: Internal Medicine Tags: Biomark Med Source Type: research
Publication date: Available online 20 January 2020Source: Carbohydrate PolymersAuthor(s): Nadezhda E. Ustyuzhanina, Maria I. Bilan, Andrey S. Dmitrenok, Alexander S. Shashkov, Nora M.A. Ponce, Carlos A. Stortz, Nikolay E. Nifantiev, Anatolii I. UsovAbstractFucosylated chondroitin sulfate (FCS) HeSp was isolated from the Patagonian sea cucumber Hemioedema spectabilis. Ion-exchange chromatography was applied for purification of the FCS from the crude extract of sulfated polysaccharides. Analysis of monosaccharide and sulfate content of HeSp revealed the molar ratio of GlcA:GalNAc:Fuc:SO3Na as 1.15:1:1.1:3.9. Molecular weight...
Source: Carbohydrate Polymers - Category: Biomedical Science Source Type: research
Hereditary hemorrhagic telangiectasia (HHT), a genetic bleeding disorder leading to systemic arteriovenous malformations (AVMs), is caused by loss-of-function mutations in the ALK1/ENG/Smad1/5/8 pathway. Evidence suggests that HHT pathogenesis strongly relies on overactivated PI3K/Akt/mTOR and VEGFR2 pathways in endothelial cells (ECs). In the BMP9/10-immunoblocked (BMP9/10ib) neonatal mouse model of HHT, we report here that the mTOR inhibitor, sirolimus, and the receptor tyrosine kinase inhibitor, nintedanib, could synergistically fully block, but also reversed, retinal AVMs to avert retinal bleeding and anemia. Sirolimus...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Cancer immune evasion is achieved through multiple layers of immune tolerance mechanisms including immune editing, recruitment of tolerogenic immune cells, and secretion of immunosuppressive cytokines. Recent success with immune checkpoint inhibitors in cancer immunotherapy suggests a dysfunctional immune synapse as a pivotal tolerogenic mechanism. Tumor cells express immune synapse proteins to suppress the immune system, which is often modulated by epigenetic mechanisms. When the methylation status of key immune synapse genes was interrogated, we observed disproportionately hypermethylated costimulatory genes and hypometh...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Increased rates of locoregional recurrence are observed in patients with basal-like breast cancer (BC) despite the use of radiation therapy (RT); therefore, approaches that result in radiosensitization of basal-like BC are critically needed. Using patients’ tumor gene expression data from 4 independent data sets, we correlated gene expression with recurrence to find genes significantly correlated with early recurrence after RT. The highest-ranked gene, TTK, was most highly expressed in basal-like BC across multiple data sets. Inhibition of TTK by both genetic and pharmacologic methods enhanced radiosensitivity in mul...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Publication date: Available online 21 January 2020Source: Sensors and Actuators B: ChemicalAuthor(s): Ying Li, Pengchao Zhang, Tao Li, Rui Hu, Jiang Zhu, Ting He, Yunhuang Yang, Maili LiuAbstractCancer cells’ MMP9 activity plays vital roles in tumor development. Tumor cells are in an adhesion profile during cell-cell and cell-matrix interaction. However, it is challenging for current platforms (e.g., typical droplet systems) to measure MMP9 secreted by single cells in an adhesion profile and retrieve the cells of interest for downstream analysis. Herein, we report a single-cell protease sensor (SCPS) based on ‘...
Source: Sensors and Actuators B: Chemical - Category: Chemistry Source Type: research
In this study, protein-based nanoparticles were constructed with TRAIL and a dipeptide, diphenylalanine (FF), through molecular self-assembly. TRAIL-FF nanoparticles with sizes ranging from 60 nm to 500 nm could be prepared by controlling the concentration and the ratio of the two components. These nanoparticles could locate around the cytomembrane of MCF-7 cells due to the specific interaction between TRAIL and death receptors, thus transduce apoptotic signal. Therefore, the TRAIL-FF nanoparticles showed distinct killing effect on the cancer cells, such as MCF-7 and H460 cells, and the IC50 of the nanopartic...
Source: Colloids and Surfaces A: Physicochemical and Engineering Aspects - Category: Chemistry Source Type: research
Heparin has a non-predictable effect in the individual patient. The activated clotting time (ACT) is used to measure the level of anticoagulation after administration of heparin. To date, appropriate heparin dose protocols and corresponding therapeutic ACT values have not been established in non-cardiac arterial procedures (NCAP). The aim of this review was to study the use of ACT monitoring during NCAP, and whether an optimal ACT could be determined based on the fewest arterial thrombo-embolic complications (ATEC) and bleeding complications.
Source: Journal of Vascular Surgery - Category: Surgery Authors: Source Type: research
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Source: Anxiety, Stress and Coping - Category: Psychiatry & Psychology Authors: Source Type: research
This study aimed to determine the main single nucleotide polymorphisms that are associated with an increased or decreased risk of glioma development in healthy individuals. We conducted a systematic review of the articles published in English on the PUBMED database between January 2008 and December 2017. Our search resulted in a total of 743 articles; however, only 56 were included in this review. A total of 148 polymorphisms were found, which involved 64 different genes. The polymorphisms that were most associated with an increased risk of glioma development were polymorphic variants rs179782, rs13181, and rs3791679 of th...
Source: Cancer Investigation - Category: Cancer & Oncology Tags: Cancer Invest Source Type: research
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