Intestinal Cell News Volume 5.18 | May 24 2019

TOP STORY

Krt5⁺/Krt15⁺ Foregut Basal Progenitors Give Rise to Cyclooxygenase-2-Dependent Tumors in Response to Gastric Acid Stress

Researchers demonstrated the association of gastric acid stress with cyclooxygenase-2-dependent tumor formation originating from tumor-competent Krt5⁺/Krt15⁺ foregut basal progenitor cells. Their findings suggest that clinical management of microenvironmental stressor-mediated microscopic injury may be important in delaying tumor initiation from foregut basal progenitor cells expressing pre-existing tumorigenic mutation(s) and genetic alteration(s). [Nat Commun] Full Article

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Stem Cell Proliferation Is Kept in Check by the Chromatin Regulators Kismet/CHD7/CHD8 and Trr/MLL3/4

Investigators report that in Drosophila, the chromatin remodeler Kismet/CHD7/CHD8 limited intestinal stem cell number and proliferation without affecting differentiation. Stem-cell-specific whole-genome profiling of Kismet revealed its enrichment at transcriptionally active regions bound by RNA polymerase II and Brahma, its recruitment to the transcription start site of activated genes and developmental enhancers and its depletion from regions bound by Polycomb, Histone H1, and heterochromatin Protein 1. [Dev Cell] Full Article | Graphical Abstract

Aberrant Expression of Select piRNA-Pathway Genes Does Not Reactivate piRNA Silencing in Cancer Cells

The authors systematically investigated the potential reactivation of functional piRNA-silencing mechanisms in the aberrant context. While they observed expression of individual PIWI-interacting small RNA (piRNA)-pathway genes in cancer, they failed to detect the formation of functional piRNA-silencing complexes. [Proc Natl Acad Sci USA] Abstract

Combination of 5-Fluorouracil and Thymoquinone Targets Stem Cell Gene Signature in Colorectal Cancer Cells

Scientists designed and synthesized novel hybrid molecules linking 5-fluorouracil with the plant-derived compound thymoquinone and tested the potential of individual compounds and their combination to eliminate colorectal cancer stem cells. Both, Combi and SARB hybrid showed augmented cytotoxicity against colorectal cancer cells, but were non-toxic to organoids prepared from healthy murine small intestine. [Cell Death Dis] Full Article

A Short SOX9 Peptide Mimics SOX9 Tumor Suppressor Activity and Is Sufficient to Inhibit Colon Cancer Cell Growth

Researchers identified a short SOX9 sequence (S9pep) located at the hinge between the HMG DNA binding domain and the SOX-E central conserved domain that mimics SOX9 tumor suppressor properties. Doxycycline-induced S9pep expression in DLD-1 colorectal cancer (CRC) cells inhibited the growth potential of these cells, including CRC stem cells, restored cell-cell contact inhibition, and inhibited the activity of the oncogenic Wnt/β-catenin signaling pathway. [Mol Cancer Ther] Abstract

Effects of Copper Chelation on BRAF^V600E Positive Colon Carcinoma Cells

Investigators evaluated in vitro and in vivo the effects of copper depletion achieved by pharmacological treatment with tetrathiomolybdatein human colorectal cells bearing the BRAF^V600E mutation in comparison with BRAF wild type cells. They provided evidence that selective copper chelation differentially affected proliferation, survival and migration of colon cancer cells bearing the BRAF^V600E mutation compared to BRAF^wt acting via differential phosphorylation levels of ERK1/2. [Cancers] Full Article

Targeting of DDR1 with Antibody-Drug Conjugates Has Antitumor Effects in a Mouse Model of Colon Carcinoma

In vitro, T₄H₁₁-DM4 exhibited potent anti-proliferative activity with IC₅₀ values in the nanomolar range in a panel of colon cancer cell lines. In vivo, the antitumor efficacy of T₄H₁₁-DM4 was evaluated in three colon cancer cell lines expressing different levels of DDR1. [Mol Oncol] Abstract

Role of Pannexin-1 in the Cellular Uptake, Release and Hydrolysis of Anandamide by T84 Colon Cancer Cells

T84 colon cancer cells expressed Panx1 at the mRNA level, and released ATP in a manner that could be reduced by treatment with the Panx1 inhibitors carbenoxolone and mefloquine and the Panx1 substrate SR101. However, no significant effects of these compounds upon the uptake or hydrolysis of exogenously applied anandamide was seen. [Sci Rep] Full Article

Degradation of D-2-Hydroxyglutarate in the Presence of Isocitrate Dehydrogenase Mutations

Investigators developed an LC-MS/MS-based enzyme activity assay that measured the temporal drop in substrate and compared this to the expression of D-2-hydroxyglutarate dehydrogenase (D2HDH) protein as measured by Western blot. Data clearly indicated that the maximum D-2-Hydroxyglutarate (D-2-HG) degradation rate by D2HDH was reached in vivo, as v_max was low in comparison to production of D-2-HG by mutant IDH1/2. [Sci Rep] Full Article

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Emerging Roles of C-Myc in Cancer Stem Cell-Related Signaling and Resistance to Cancer Chemotherapy: A Potential Therapeutic Target against Colorectal Cancer

The authors focus on the roles of c-Myc-related signaling in the regulation of cancer stem cells, chemotherapy resistance, and colorectal cancer organoids. They introduce the various types of c-Myc inhibitors and propose the possibility of c-Myc as a therapeutic target against colorectal cancer. [Int J Mol Sci] Full Article

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

Innovate Biopharmaceuticals Announces Presentation of Three Posters Focusing on the Molecular Biology and Pharmacology of Larazotide

Innovate Biopharmaceuticals, Inc. announced that larazotide acetate, a new class of medicine based on gut-restricted peptides which re-normalize the intestinal epithelial barrier and gut-liver axis, that three posters were presented. [Press release from Innovate Biopharmaceuticals, Inc. discussing research presented at 2019 Digestive Disease Week (DDW), San Diego] Press Release

Learn the basics of culturing mouse intestinal organoids with an instructional video series. Watch the Video Now

Parvus Therapeutics Enters into Worldwide Collaboration and License Agreement with Genentech to Develop Navacim™ Therapeutics for the Treatment of Autoimmune Diseases

Parvus Therapeutics has entered into a worldwide collaboration and license agreement with Genentech, a member of the Roche Group, to develop, manufacture, and commercialize novel Navacim™ therapeutics for the treatment of IBD, autoimmune liver diseases, and celiac disease. [Parvus Therapeutics] Press Release

Crinetics Pharmaceuticals Initiates Phase I Study of CRN01941 for the Treatment of Neuroendocrine Tumors

Crinetics Pharmaceuticals, Inc. announced the initiation of a Phase I, double-blind, randomized, placebo-controlled, single- and multiple-dose study to evaluate the safety, pharmacokinetics, and pharmacodynamics of CRN01941 in healthy volunteers. [Crinetics Pharmaceuticals, Inc.] Press Release

US FDA Approves GATTEX^® (Teduglutide) for Children 1 Year of Age and Older with Short Bowel Syndrome (SBS)

Takeda Pharmaceuticals, USA., Inc. announced that the FDA approved extending the indication of GATTEX^® for injection to pediatric patients one year of age and older with SBS who need additional nutrition or fluids from intravenous feeding. [Takeda Pharmaceuticals, USA, Inc. (PR Newswire Association LLC.)] Press Release

25^th Anniversary Gala Unites the Community and Raises Nearly $1.5 Million for Crohn’s and Colitis Canada

The sold-out Gala for Crohn’s and Colitis Canada, which took place at Vaughan’s Universal Eventspace on May 16, raised nearly $1.5 million to advance much-needed research and patient programs thanks to the philanthropic efforts of over 900 attendees. [Crohn’s and Colitis Canada] Press Release

Brazilian Scientists Strive to Turn Politicians into Allies

Brazil’s scientists are fighting back against President Jair Bolsonaro’s plans to slash funding for research and education programs. Researchers have joined with members of Brazil’s legislature, the National Congress, to highlight the strategic role that science, technology, and education play in the country’s economic and social development. [Nature News] Editorial

Taiwan Considers Double-Blind Peer Review for Grants

Taiwan’s science ministry is thinking of introducing double-blind peer review to assess research-grant proposals, a trend being adopted by some journals to eliminate bias. [Nature News] Editorial

NEW World Congress of Gastroenterology 2019
September 21-24, 2019
Istanbul, Turkey

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

NEW Postdoctoral Researcher – Genetics in IBD (Kennedy Institute of Rheumatology)

NEW Principle Investigator – Gut Physiology (Nestlé Research Center)

NEW Postdoctoral Researcher – Mucosal Immunology and Inflammation (Gilead Sciences, Inc.)

Postdoctoral Fellow – Intestinal Regenerative Medicine (Zhou Lab)

Postdoctoral Fellow – Intestinal and Pulmonary Stem Cell Biology (Stanford School of Medicine)

Postdoctoral Fellow – Functional Genomics of IBS (Wellcome Sanger Institute)

Postdoctoral Researcher – Intestinal Immunology (KU Leuven)

Postdoctoral Director – mRNA Treatment for Rare Diseases (Moderna)

Postdoctoral Researcher – Gastrointestinal Cancer & IBD (Case Western Reserve University)

Postdoctoral Position – Oesophago-Gastric Cancer Research (University of Cambridge)

Associate Professor – Oncology (University of California, Davis)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

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