Intestinal Cell News Volume 5.34 | Sep 13 2019

TOP STORY

Liquid versus Tissue Biopsy for Detecting Acquired Resistance and Tumor Heterogeneity in Gastrointestinal Cancers

In a prospective cohort of 42 patients with molecularly defined gastrointestinal cancers and acquired resistance to targeted therapy, direct comparison of postprogression cfDNA versus tumor biopsy revealed that cfDNA more frequently identified clinically relevant resistance alterations and multiple resistance mechanisms, detecting resistance alterations not found in the matched tumor biopsy in 78% of cases. [Nat Med] Abstract

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Metastatic Seeding of Human Colon Cancer Cell Clusters Expressing the Hybrid Epithelial/Mesenchymal State

Inhibition of E-cadherin or ZEB1 expression by shRNA notably prevented patient-derived xenograft-derived tumor organoids from colonizing the liver, when injected intrasplenically into mice, indicating E-cadherin and ZEB1 expressions to be required for their metastatic colonization. [Int J Cancer] Abstract

O-GlcNAcase Targets Pyruvate Kinase M2 to Regulate Tumor Growth

Researchers report that O-GlcNAcase (OGA) was upregulated in a wide range of human cancers and drove aerobic glycolysis and tumor growth by inhibiting pyruvate kinase M2 (PKM2). PKM2 was dynamically O-GlcNAcylated in response to changes in glucose availability. Under high glucose conditions, PKM2 was a target of OGA-associated acetyltransferase activity, which facilitated O-GlcNAcylation of PKM2 by O-GlcNAc transferase. [Oncogene] Abstract

CDCP1 Enhances Wnt Signaling in Colorectal Cancer Promoting Nuclear Localization of β-Catenin and E-Cadherin

The authors sought to identify CUB-domain containing protein 1 (CDCP1) regulated processes in colorectal cancer (CRC) using stem cell populations, enriched from primary cells and cell lines, in extensive in vitro and in vivo assays. These experiments, demonstrating that CDCP1 was functionally important in CRC tumor initiation, growth and metastasis, identified CDCP1 as a positive regulator of Wnt signaling. [Oncogene] Abstract

A Positive Feedback Loop of β-Catenin/CCR2 Axis Promotes Regorafenib Resistance in Colorectal Cancer

Scientists screened the expression of chemokine receptors and identified CC chemokine receptor 2 (CCR2) as a top upregulated gene in regorafenib-resistant cells. CCR2 silencing alleviated drug tolerance in regorafenib-resistant cells, while overexpression of CCR2 enhanced CRC cells resistance to regorafenib. [Cell Death Dis] Full Article

Long Noncoding RNA BFAL1 Mediates Enterotoxigenic Bacteroides fragilis-Related Carcinogenesis in Colorectal Cancer via the RHEB/mTOR Pathway

Enterotoxigenic Bacteroides fragilis (ETBF) is a well-known tumor-inducing bacterium in the human gut; however, its tumorigenic effect remains to be explored. Investigators revealed the mechanism by which a lncRNA participates in gut bacteria-induced carcinogenesis: B. fragilis-associated lncRNA1 (BFAL1) in CRC tissues mediated ETBF carcinogenesis. [Cell Death Dis] Full Article

CK7 and Consensus Molecular Subtypes as Major Prognosticators in V600EBRAF Mutated Metastatic Colorectal Cancer

Data and tissue specimens from 155 V600EBRAF mutated metastatic colon cancer patients treated at eight Italian Units of Oncology were collected. Specimens were analyzed by means of immunohistochemistry profiling performed on tissue microarrays. [Br J Cancer] Abstract

CircIFT80 Functions as a ceRNA of miR-1236-3p to Promote Colorectal Cancer Progression

Investigators compared the expression patterns of exosomal circRNAs between plasma of colorectal cancer (CRC) patients and healthy controls. They identified 448 significantly dysregulated exosomal circRNAs in CRC plasma. They focused on hsa_circ_0067835, which is located on chromosome 3 and derived from IFT80, and thus they named it circIFT80. [Mol Ther Nucleic Acids] Abstract

Multiplex Staining Depicts the Immune Infiltrate in Colitis-Induced Colon Cancer Model

Researchers optimized a protocol to sequentially stain formalin fixed paraffin embedded murine colon samples for CD3, CD8a, CD4, and CD4R5B0 antigens. With this approach they obtained a detailed lymphocyte profile, while preserving the morphological tissue context, generally lost with techniques like gene expression profiling or flow cytometry. [Sci Rep] Full Article

The Indole Compound MA-35 Attenuates Tumorigenesis in an Inflammation-Induced Colon Cancer Model

In the microscopic evaluation, MA-35 reduced inflammation and fibrosis in areas with dysplasia. Furthermore, the TNF-α mRNA level in the colon tended to be reduced, and the interleukin 6, TGF-β1 and fibronectin 1 mRNA levels in the colon were significantly reduced by MA-35. [Sci Rep] Full Article

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Microsatellite Instability and Immune Checkpoint Inhibitors: Toward Precision Medicine against Gastrointestinal and Hepatobiliary Cancers

The authors describe the molecular basis of the mismatch repair pathway, diagnostics of microsatellite instability (MSI) status, and the clinical importance of MSI status and the tumor mutation burden in developing therapeutic strategies against gastrointestinal and hepatobiliary malignancies. [J Gastroenterol] Abstract

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CytoDyn Announces FDA Clearance to Proceed with Phase II Study of Leronlimab (PRO 140) and Regorafenib as a Combination Therapy for Metastatic Colorectal Cancer

CytoDyn Inc. announced that the FDA has allowed a Phase II study to proceed for combination therapy of leronlimab and Regorafenib in patients with metastatic colorectal cancer. [CytoDyn Inc.] Press Release

Applied Molecular Transport Debuts with First Patient Dosed in Phase Ib Clinical Trial of AMT-101 in Adults with Ulcerative Colitis

Applied Molecular Transport (AMT) announced that the first patient has been dosed in the Phase 1b portion of a first-in-human clinical trial designed to evaluate the safety and tolerability of AMT-101, a novel oral gut-selective biologic fusion protein of interleukin 10for the treatment of adults with ulcerative colitis. [Applied Molecular Transport] Press Release

Science Under Maximum Pressure in Iran

Research scientists Shahin Akhondzadeh received a novel reason why a journal was unable to publish his work: his nationality. Akhondzadeh is Iranian and works at the Tehran University of Medical Science. And for the US-based journal and its publisher, that made him a persona non grata. [The Scientist] Editorial

Clubby and ‘Disturbing’ Citation Behavior by Researchers in Italy Has Surged

The rate at which scientists in Italy cite themselves and their compatriots is rising faster than in ten other developed countries, according to a new study. The surge in Italy’s clubby citation behavior is likely the result of a 2010 law requiring productivity standards for academic recruitment or promotion, the study authors say. [ScienceInsider] Editorial

EU Research Commissioner Named, but Lacks ‘Research’ in Her Title

Mariya Gabriel, a conservative politician from Bulgaria, is slated to become the next European research chief- although her job title, unlike that of her predecessors, doesn’t include the words “research” or “science.” Some researchers and science policy experts worry the new job title could signal a reduced standing for science within von der Leyen’s proposed executive branch for the European Union, made up of 26 commissioners. [ScienceMagazine] Editorial

NEW NF-kB, JAK-STAT & MAPK in Health, Disease & Therapy
October 7-11, 2019
Suzhou, China

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NEW Postdoctoral Researcher – Systems Biology of Cancer (Max Planck Institute for Molecular Genetics)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Research Technologist – Intestinal Stem Cell Biology (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Intestinal Graft-versus-Host-Disease (Medical College of Wisconsin)

Senior Researcher – Inflammatory Diseases (Genentech, Inc.)

Research Assistant – Pathophysiology of Enteroviruses (University of Cambridge)

Postdoctoral Researcher – Microbiome in IBD (GIGA-Medical Genomics Unit)

Postdoctoral Fellow – Quantifying Intra-tumour Heteregeneity with Multi-Omics Data (The Institute of Cancer Research)

Postdoctoral Fellow – Designer Probiotics (Massacheusetts General Hospital)

Postdoctoral Researchers – Microbiota in Neonatal Immunity and Imprinting (Institut Pasteur)

Principal Researcher – Systems Disease Biology (Boehringer Ingelheim)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

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