Intestinal Cell News Volume 5.10 | Mar 22 2019

TOP STORY

Repurposing the Selective Estrogen Receptor Modulator Bazedoxifene to Suppress Gastrointestinal Cancer Growth

Tumors of bazedoxifene-treated Apc-mutant mice retained excessive nuclear accumulation of β-catenin and aberrant WNT pathway activation. Likewise, bazedoxifene treatment of human colon cancer cells harboring mutant APC did not reduce aberrant canonical WNT signaling, but suppressed IL11-dependent STAT3 signaling. [EMBO Mol Med] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

Species-Specific Enhancement of Enterohemorrhagic E. coli Pathogenesis Mediated by Microbiome Metabolites

Researchers utilized organ-on-a-chip microfluidic culture technology to model damage of the human colonic epithelium induced by enterohemorrhagic E. coli infection, and showed that epithelial injury was greater when exposed to metabolites derived from the human gut microbiome compared to mouse. [Microbiome] Full Article | Press Release

Pt(IV) Bifunctional Prodrug Containing 2-(2-Propynyl)octanoato Axial Ligand: Induction of Immunogenic Cell Death on Colon Cancer

The Pt(IV) complexes showed comparable activity, of two orders of magnitude higher than reference drug oxaliplatin on three human and on one mouse colon cancer cell lines. In vivo experiments were carried out on immunocompetent BALB/c mice bearing the same syngeneic tumor. [J Med Chem] Abstract

TIAM1 Promotes Chemoresistance and Tumor Invasiveness in Colorectal Cancer

The authors established patient-derived cancer associated fibroblasts (CAFs) and tested whether the drug sensitivity of colorectal cancer (CRC) cell lines was altered with CAF-derived conditioned medium. High-TIAM1 expression correlated significantly with poor prognosis of CRC patients, and was overexpressed in patients who did not respond to chemotherapy. [Cell Death Dis] Full Article

Adaptation to HIF1α Deletion in Hypoxic Cancer Cells by Upregulation of GLUT14 and Creatine Metabolism

Researchers analyzed pathways that allow cells to survive hypoxic stress in the absence of HIF1α, using the HCT116 colon cancer cell line with deleted HIF1α versus control. Spheroids were used to provide a 3D model of metabolic gradients. [Mol Cancer Res] Abstract

miR-20a Inhibits Hypoxia-Induced Autophagy by Targeting ATG5/FIP200 in Colorectal Cancer

miR-20a inhibited the hypoxia-induced autophagic flux by targeting multiple key regulators of autophagy, including ATG5 and FIP200. Furthermore, by dual-luciferase assay investigators demonstrated that miR-20a directly targeted the 3′-untranslated region of ATG5 and FIP200, regulating their messenger RNA and protein levels. [Mol Carcinog] Abstract

Integrative Analysis of Paneth Cell Proteomic and Transcriptomic Data from Intestinal Organoids Reveals Functional Processes Dependent on Autophagy

Using 3D intestinal organoids enriched for Paneth cells, scientists compared the proteomic profiles of wild-type and autophagy-impaired organoids. They used an integrated computational approach combining protein-protein interaction networks, autophagy-targeted proteins and functional information to identify the mechanistic link between autophagy impairment and disrupted pathways. [Dis Model Mech] Full Article

Caveolin 1 Is Associated with Upregulated Claudin 2 in Necrotizing Enterocolitis

Experimental necrotizing enterocolitis (NEC) was induced in rats via hypoxia and bacteria-containing formula, and in Caco-2 cells by media inoculated with LPS. The expression of claudins was measured by gene and protein analysis. Experimental NEC in rat pups and Caco-2 cells had increased permeability compared to controls. Gene and protein expression of claudin 2 was increased in experimental NEC. [Sci Rep] Full Article

Inhibition of PGE₂/EP4 Receptor Signaling Enhances Oxaliplatin Efficacy in Resistant Colon Cancer Cells through Modulation of Oxidative Stress

PGE₂ levels were significantly elevated in oxaliplatin-resistant HT29 (OXR) cells compared to naïve parental HT29 cells. This increase was associated with elevated COX-2 and reduced 15-hydroxyprostaglandin dehydrogenase expression. RNAi knockdown of microsomal prostaglandin E synthase-1, the rate-limiting enzyme in PGE₂ synthesis, sensitized OXR cells to oxaliplatin. [Sci Rep] Full Article

Identification of Transmembrane Protein 237 as a Novel Interactor with the Intestinal Riboflavin Transporter-3 (RFVT-3): Role in Functionality and Cell Biology

The interaction between transmembrane protein 237 (TMEM237) with human RFVT-3 in human intestinal epithelial HuTu-80 cells was established by co-immunoprecipitation. Expressing TMEM237 in HuTu-80 cells led to a significant induction in riboflavin uptake, while its knockdown led to a significant reduction in uptake. [Am J Physiol Cell Physiol] Abstract

Intestinal Epithelial Tight Junction Barrier Regulation by Autophagy Related Protein ATG6/Beclin 1

In Caco-2 cells, beclin 1 was found to be co-immunoprecipitated with the tight junction (TJ) protein occludin and co-localized with occludin on the membrane. Treatment of Caco-2 cells with beclin 1 peptide reduced TJ barrier function. Activation of beclin 1 increased occludin endocytosis and reduced total occludin protein level. [Am J Physiol Cell Physiol] Abstract

Avenanthramide A Induces Cellular Senescence via miR-129-3p/Pirh2/p53 Signaling Pathway to Suppress Colon Cancer Growth

Avenanthramide A (AVN A) treatment triggered cellular senescence in human colon cancer cells, evidenced by enlarging cellular size, upregulating β-galactosidase activity, γ-H2AX positive staining and G1 phase arrest. Moreover, AVN A treatment significantly increased the expression of miR-129-3p, which markedly repressed the E3 ubiquitin ligase Pirh2 and other two targets IGF2BP3 and CDK6. [J Agric Food Chem] Abstract

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Immunotherapy in Colorectal Cancer: Rationale, Challenges and Potential

Investigators focus on new advances in expanding the efficacy of immunotherapy to early-stage colorectal cancer (CRC) and CRC that is mismatch-repair-proficient and has low microsatellite instability and discuss emerging approaches for targeting the immune microenvironment, which might complement immune checkpoint inhibition. [Nat Rev Gastroenterol Hepatol] Abstract

Bioengineering and Regeneration of Gastrointestinal Tissue: Where Are We Now and What Comes Next?

The authors cover the traditional aspect of using cells and scaffolds to replace parts of the tract. Several studies investigated different types of biomaterials and different types of cells. A more recent approach involved the use of gut-derived organoid units that can differentiate into all gut cell layers. [Expert Opin Biol Ther] Abstract

Visit our reviews page to see a complete list of reviews in the intestinal cell research field.

Alligator Bioscience: New Preclinical Data Demonstrate Strong Anti-Tumor Effects for the 4-1BB Antibody ATOR-1017

Alligator Bioscience announced that they will present preclinical data for the drug candidate ATOR-1017. The new data show that ATOR-1017, in an experimental model for colon cancer, displays potent anti-tumor effects. [Press release from Alligator Bioscience discussing research presented at the 4^th Annual Immuno-oncology Summit Europe, London] Press Release

Get an overview of intestinal organoids and their applications. Learn More

Gritstone Oncology Announces First Patient Dosed in a Clinical Study Evaluating Its Personalized Immunotherapy, GRANITE-001

The Phase I/II clinical study, referred to as GO-004, is evaluating GRANITE-001 in combination with immune checkpoint blockade for the treatment of patients with advanced solid tumors, including microsatellite stable colorectal cancer, gastroesophageal cancer, metastatic non-small cell lung cancer, and bladder cancer. [Gritstone Oncology, Inc.] Press Release

Aptevo Therapeutics Begins Phase I Clinical Trial of APVO210 a Novel Bispecific Antibody for the Treatment of Autoimmune and Inflammatory Diseases

Aptevo Therapeutics Inc. announced that it has commenced dosing in a Phase I clinical trial of APVO210, a novel bispecific antibody candidate built on Aptevo’s ADAPTIR^™ therapeutic protein platform which is being developed to treat autoimmune and inflammatory diseases. [Aptevo Therapeutics Inc.] Press Release

Vaxart Announces Initiation of Bivalent Norovirus Vaccine Phase Ib Clinical Trial

Vaxart, Inc. announced the initiation of a Phase Ib bivalent norovirus vaccine clinical trial. Norovirus is recognized as the leading cause of acute gastroenteritis in the United States. [Vaxart, Inc.] Press Release

BRAFTOVI^® (Encorafenib) in Combination with MEKTOVI^® (Binimetinib) and ERBITUX^® (Cetuximab) or Panitumumab Recommended by the National Comprehensive Cancer Network^® (NCCN) Guidelines as a Treatment Option for Patients with Advanced BRAF-Mutant Colorectal Cancer

Array BioPharma Inc. announced that the NCCN has updated their Clinical Practice Guidelines in Oncology for Colon and Rectal Cancer to include BRAFTOVI^® in combination with MEKTOVI^® and an anti-EGFR antibody as a Category 2a treatment for patients with BRAFV600E-mutant metastatic colorectal cancer, after failure of one or two prior lines of therapy for metastatic disease. [Array BioPharma Inc.] Press Release

Lack of Diversity in Genetic Datasets Is Risky for Treating Disease

Certain populations have been historically underrepresented in genome sequencing studies, but the NIH, private clinics, and 23andMe and other companies are trying to fix that. [The Scientist] Editorial

Chinese-American Scientist Societies Fear Racial Profiling

In a strongly worded letter published in Science, a group of Chinese-American scientists voice concern that recent proposals from the National Institutes of Health and FBI actions could lead to unjust targeting of ethnically Chinese scientists. [The Scientist] Editorial

Universities Spooked by Trump Order Tying Free Speech to Grants

US President Donald Trump is expected to issue an executive order on 21 March that would require universities to certify that they protect free speech or risk losing federal research funds. The order will apply to 12 research agencies, including the National Institutes of Health, the National Science Foundation, the Department of Energy and NASA, a White House official said. [Nature News] Editorial

NEW World Advanced Therapies and Regenerative Medicine Congress 2019
May 15-17, 2019
London, United Kingdom

Visit our events page to see a complete list of events in the community.

NEW Graduate Student Position – Breast & Colorectal Cancer Research (Dalhousie University)

NEW Postdoctoral Fellow – Inflammatory Bowel Disease Research (University of Toronto)

Postdoctoral Fellow – Functional Genomics & IBD (Wellcome Sanger Institute)

Research Group Leader – Intestinal Epithelial Barrier in Autoimmune Diseases (BioMed X Innovation Center)

Postdoctoral & Research Associate Positions – Biology of Intestinal & Colon Stem Cells & Gastrointestinal Cancer (Johns Hopkins University)

Postdoctoral Researcher Positions – Intestinal Epithelial Barrier in Autoimmune Diseases (BioMed X Innovation Center)

Faculty Position- General Gastroenterology (Oregon Health and Science University)

Assistant Professor – Basic and Translational Cancer Research (Texas Tech University Health Sciences Center)

Associate Professor – Oncology (University of California, Davis)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

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