Article
Pharmacology & Pharmacy
Jordan T. Jatko, Caitlin L. Darling, Michael P. Kellett, Lisa J. Bain
Summary: Exposure to arsenic significantly impacts intestinal stem cell differentiation and epithelial cell types, mainly through reductions in the Wnt-dependent pathway. While ISCs are not lost following arsenic exposure, specific Wnt-dependent progenitor cell formation and terminal differentiation in the small intestine are reduced.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)
Article
Cell Biology
Valeriya V. Zinina, Melanie Sauer, Lira Nigmatullina, Nastasja Kreim, Natalia Soshnikova
Summary: This study investigated the role of TCF7L1 in the embryonic and adult intestinal epithelium using conditional mouse mutants. The results showed that TCF7L1 prevents the precocious differentiation of embryonic intestinal epithelial progenitors towards enterocytes and ISCs. In addition, TCF7L1 is necessary for the differentiation of secretory epithelial progenitors along the tuft cell lineage and for the differentiation of enteroendocrine D- and L-cells in the anterior small intestine. The study concludes that TCF7L1-mediated repression of both Notch and WNT pathways is crucial for the correct differentiation of intestinal secretory progenitors.
Article
Multidisciplinary Sciences
Laura Sole, Teresa Lobo-Jarne, Daniel Alvarez-Villanueva, Josune Alonso-Maranon, Yolanda Guillen, Marta Guix, Irene Sangrador, Catalina Rozalen, Anna Vert, Antonio Barbachano, Joan Lop, Marta Salido, Beatriz Bellosillo, Raquel Garcia-Romero, Marta Garrido, Jessica Gonzalez, Maria Martinez-Iniesta, Erika Lopez-Arribillaga, Ramon Salazar, Clara Montagut, Ferran Torres, Mar Iglesias, Toni Celia-Terrassa, Alberto Munoz, Alberto Villanueva, Anna Bigas, Lluis Espinosa
Summary: This study reveals that sub-lethal dose of chemotherapy induces a quiescence-like phenotype and a YAP-dependent fetal-like intestinal stem cell state in wild-type p53 colorectal cancers, which is associated with higher metastatic activity and poor prognosis in patients.
NATURE COMMUNICATIONS
(2022)
Article
Agriculture, Dairy & Animal Science
Sara E. Cloft, Zehava Uni, Eric A. Wong
Summary: Mature small intestines have crypts populated by stem cells, which produce replacement cells for maintaining the absorptive villus surface area. The expression of stem cell markers Olfactomedin 4 (Olfm4) and Leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5) differed after hatching, with Olfm4 mRNA increasing and Lgr5 mRNA decreasing. Marker of proliferation Ki67 mRNA decreased post-hatch in the duodenum but was greatest in the ileum. The ontogeny of Olfm4, Lgr5, and Ki67 expressing cells shows that proliferation in the peri-hatch intestine changes from along the entire villi to being restricted within the crypts.
Article
Oncology
Shixin Chan, Rui Sun, Xucan Tu, Manyu Guo, Qianqian Yuan, Zhen Yu, Zhenglin Wang, Shaocheng Hong, Wei Han, Bingbing Zou, Zeng Li, Huabing Zhang, Wei Chen
Summary: The study demonstrates that rutaecarpine (RUT) can inhibit the proliferation and migration of colorectal cancer cells and induce cell apoptosis by inactivating NF-kappa B/STAT3 signaling pathway. This suggests the potential clinical application of RUT for the treatment of colorectal cancer.
Article
Medicine, Research & Experimental
Kai Aoki, Koki Yanazawa, Katsuyuki Tokinoya, Takehito Sugasawa, Takuji Suzuki, Yasuko Yoshida, Takuro Nakano, Naomi Omi, Yasushi Kawakami, Kazuhiro Takekoshi
Summary: Renalase expression is upregulated in fasting conditions and localized in the crypt. Overexpression of renalase protects intestinal cells from oxidative stress induced by H2O2, suggesting a potential protective role of renalase against oxidative stress. NF-kappa B p65 may play a role in regulating renalase expression in response to oxidative stress in the small intestine.
Article
Multidisciplinary Sciences
Kazuhiro Murakami, Yumi Terakado, Kikue Saito, Yoshie Jomen, Haruna Takeda, Masanobu Oshima, Nick Barker
Summary: Safe utilization of the regenerative potential of adult stem cells for clinical applications requires a comprehensive understanding of the regulatory mechanisms. Epithelial organoid cultures accurately mimic in vivo stem cell-driven epithelial renewal, offering a great ex vivo platform for studying key regulatory mechanisms. Through genome-scale CRISPR knockout screening, Alk, Bclaf3, and Prkra were identified as potential regulators of gastric epithelial differentiation and could suppress stemness/proliferation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Lubna M. Mehdawi, Souvik Ghatak, Payel Chakraborty, Anita Sjolander, Tommy Andersson
Summary: This study finds that WNT5A signaling inhibits colon cancer stemness and VEGFA expression by suppressing the expression of LGR5/RSPO3 and beta-catenin activity. This provides clues for developing new strategies to treat colon cancer.
Article
Engineering, Biomedical
JooHyun Jee, Jun-Hyeok Park, Jung Ho Im, Mi Sun Kim, Enoch Park, Taegyu Lim, Woo Hee Choi, Jee Hyun Kim, Woo Ram Kim, Ji Su Ko, Sang Yun Jeong, Seung Young Ko, Jung Il Lee, Kyung Jin Lee, Hyemi Jeon, Jae-Hwi Seo, Dong-Youn Hwang, Hyun Soo Shin, Jongman Yoo
Summary: Radiation proctitis is a collateral damage to healthy cells during radiation treatment of pelvic malignancies. The study showed that colon organoid-based regeneration could successfully treat this condition by engrafting onto the damaged rectal mucosa of irradiated mice, with Lgr5+ stem cells being pivotal to the process. These findings provide insights into the potential use of colon organoid-based regenerative therapy for radiation proctitis.
Article
Cell Biology
Hikaru Teramoto, Naohide Hirashima, Masahiko Tanaka
Summary: The study focuses on the roles of calcineurin (CN) in glial cells, particularly enteric glial cells (EGCs) in the small intestine. Knockout mice lacking CNB1 in glial cells show dysfunction and inflammation of the small intestine. The deficiency of CNB1 leads to reduced proliferation and increased apoptosis of EGCs, as well as abnormal expression and secretion of EGC-derived substances, contributing to dysfunction and inflammation of the small intestine.
Article
Biochemistry & Molecular Biology
Yusuke Kanda, Hirokazu Ohata, Toshiaki Miyazaki, Hiroaki Sakai, Yutaro Mori, Daisuke Shiokawa, Akira Yokoi, Takashi Owa, Atsushi Ochiai, Koji Okamoto
Summary: This study evaluated the sensitivity of colon cancer spheroids to E7386 and found that resistance to E7386 is associated with the activation of the NF-kappa B pathway. The combination of E7386 and NF-kappa B inhibitors may effectively inhibit proliferation in a subset of colon cancer cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Dovydas Sirvinskas, Omid Omrani, Jing Lu, Mahdi Rasa, Anna Krepelova, Lisa Adam, Sandra Kaeppel, Felix Sommer, Francesco Neri
Summary: We performed single-cell sequencing of aging mouse colonic epithelium and immune cells, and identified significant aging-associated changes in cell composition and signaling pathways. Our study provides new insights into the normal and age-associated states of the colon.
Article
Biochemistry & Molecular Biology
Jonas Wizenty, Stefanie Muellerke, Marina Kolesnichenko, Julian Heuberger, Manqiang Lin, Anne-Sophie Fischer, Hans-Joachim Mollenkopf, Hilmar Berger, Frank Tacke, Michael Sigal
Summary: Helicobacter pylori is a pathogen that causes chronic gastritis by colonizing the stomach. This study found that Rspo3 signaling through Lgr4 regulates the proliferation of stem cells and induces NF-kappa B activity in proliferating stem cells. The invasion of H. pylori leads to Lgr4-driven NF-kappa B activation, resulting in expansion of the gland base module and chemokine expression in stem cells, leading to gland hyperplasia and neutrophil recruitment.
Article
Gastroenterology & Hepatology
Lucas T. Jennelle, Christopher H. Dampier, Stephanie Tring, Steven Powell, Graham Casey
Summary: The study found that subjects with FAP had a significant increase in the number of LGR5+ stem cells in their colonic crypts, which may lead to an expanded proliferative zone more likely to develop mutations and contribute to accelerated adenoma development in FAP.
CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY
(2021)
Article
Biochemical Research Methods
Jing Wu, Yan Xu, Jiahong Yang, Xinyue Yu, Zhaodi Han, Linling Guo, Yin Huang, Yuxin Zhang
Summary: This study developed a novel LC-MS/MS method for quantification of 10 B vitamins in mouse colon tissue. The method was validated according to FDA guidelines and produced good results in terms of linearity, accuracy, precision, recovery, matrix effect, and stability. Application of the method revealed significant colon damage and accumulation of multiple B vitamins after doxorubicin treatment in mice with breast cancer.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2023)
Editorial Material
Surgery
Joseph C. Kong, Michael Flood, Robert G. Ramsay, Satish K. Warrier, Alexander Heriot
ANZ JOURNAL OF SURGERY
(2021)
Review
Gastroenterology & Hepatology
Michael P. Flood, Atandrila A. Das, Mikael L. Soucisse, Joseph Kong, Robert G. Ramsay, Michael Michael, Benjamin P. T. Loveday, Satish K. Warrier, Alexander G. Heriot
Summary: The addition of synchronous liver resection to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of resectable metastatic colorectal cancer did not increase perioperative major morbidity and mortality compared to cytoreduction and hyperthermic intraperitoneal chemotherapy alone. However, the presence of liver metastases was associated with inferior disease-free and overall survival. These findings support the continued practice of liver resection, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy in select patients with stage IV colorectal cancer.
DISEASES OF THE COLON & RECTUM
(2021)
Article
Biochemical Research Methods
Annalisa L. E. Carli, Shoukat Afshar-Sterle, Alin Rai, Haoyun Fang, Ryan O'Keefe, Janson Tse, Fleur M. Ferguson, Nathanael S. Gray, Matthias Ernst, David W. Greening, Michael Buchert
Summary: DCLK1 is a putative cancer stem cell marker that is associated with advanced disease and poor prognosis in malignant tumors, and has been shown to promote epithelial-to-mesenchymal transition. Additionally, DCLK1 influences the biogenesis of small extracellular vesicles, promoting cell migration and impacting signaling in gastric tumorigenesis.
Article
Oncology
Jennifer Huynh, David Baloyan, David Chisanga, Wei Shi, Megan O'Brien, Shoukat Afshar-Sterle, Mariah Alorro, Lokman Pang, David S. Williams, Adam C. Parslow, Pathum Thilakasiri, Moritz F. Eissmann, Louis Boon, Frederick Masson, Ashwini L. Chand, Matthias Ernst
Summary: IL11 is a member of the IL6 family of cytokines, and plays a role in regulating CD4+ T cell-mediated antitumor responses by suppressing the activity of host CD4(+) T cells in the tumor microenvironment. This suggests a potential immunomodulatory role for IL11 in colon cancer development that could be targeted for anticytokine-based therapy.
CANCER IMMUNOLOGY RESEARCH
(2021)
Editorial Material
Oncology
Michael Flood, Robert Ramsay, Alexander Heriot
ANNALS OF SURGICAL ONCOLOGY
(2022)
Article
Allergy
Veronika Kanderova, Tamara Svobodova, Simon Borna, Martina Fejtkova, Vendula Martinu, Jana Paderova, Michael Svaton, Jarmila Kralova, Eva Fronkova, Adam Klocperk, Stepanka Pruhova, Min Ae Lee-Kirsch, Ludmila Hornofova, Miroslav Koblizek, Petr Novak, Olga Zimmermannova, Zuzana Parackova, Anna Sediva, Tomas Kalina, Ales Janda, Jana Kayserova, Marcela Dvorakova, Milan Macek, Petr Pohunek, Petr Sedlacek, Ashleigh Poh, Matthias Ernst, Tomas Brdicka, Ondrej Hrusak, Jan Lebl
Summary: This article reports a new monogenic autoinflammatory disorder caused by a de novo activating mutation in the HCK gene, characterized by cutaneous vasculitis and chronic pulmonary inflammation. The study shows the aberrant functions of mutant HCK and the therapeutic efficacy of the Janus kinase 1/2 inhibitor Ruxolitinib in treating inflammatory lung disease.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Editorial Material
Oncology
Michael Flood, Vignesh Narasimhan, Kasmira Wilson, Wei Mou Lim, Robert Ramsay, Michael Michael, Alexander Heriot
ANNALS OF SURGICAL ONCOLOGY
(2022)
Article
Oncology
Michael P. Flood, Joseph C. Kong, Toan Pham, Peadar S. Waters, Mikael Soucisse, Robert Ramsay, Hui-Li Wong, Catherine Mitchell, Michael Michael, Jacob J. McCormick, Satish K. Warrier, Tim Akhurst, Alexander G. Heriot
Summary: The study aimed to assess the ability of preoperative PET in predicting the histological grade of pseudomyxoma peritonei (PMP). The results showed that preoperative PET had a positive correlation with high-grade PMP and acceptable sensitivity and specificity as a diagnostic tool. Therefore, PET should be considered a useful adjunct to predict the histological grade in the staging of PMP patients.
Article
Oncology
Shienny Sampurno, Timothy Chittleborough, Meara Dean, Michael Flood, Sandra Carpinteri, Sara Roth, Rosemary M. Millen, Helen Cain, Joseph C. H. Kong, John MacKay, Satish K. Warrier, Jacob McCormick, Jonathon G. Hiller, Alexander G. Heriot, Robert G. Ramsay, Andrew C. Lynch
Summary: This study compares the effects of different insufflation methods on patients undergoing colorectal cancer surgery and finds that dry-cold-carbon-dioxide insufflation leads to more peritoneal damage, inflammation, and hypothermia. The use of humidified-warm-CO2 insufflation can restore body temperature, reduce hospital stay, and protect peritoneal cells.
ANNALS OF SURGICAL ONCOLOGY
(2022)
Editorial Material
Oncology
Shienny Sampurno, Timothy Chittleborough, Meara Dean, Michael Flood, Sandra Carpinteri, Sara Roth, Rosemary M. Millen, Helen Cain, Joseph C. H. Kong, John MacKay, Satish K. Warrier, Jacob McCormick, Jonathon G. Hiller, Alexander G. Heriot, Robert G. Ramsay, Andrew C. Lynch
ANNALS OF SURGICAL ONCOLOGY
(2022)
Editorial Material
Oncology
Robert G. Ramsay, Michael Flood
Summary: Colorectal peritoneal metastases (CRPM) can develop resistance to oxaliplatin, a commonly used chemotherapy agent for hyperthermic intraperitoneal chemotherapy (HIPEC). However, genomic deletion or pharmacological inhibition of glutamate-cysteine ligase in CRPM tumors can effectively reduce the inactivation of oxaliplatin mediated by glutathione. These findings may reignite interest in combining HIPEC with cytoreductive surgery for the management of this previously considered incurable stage-IV disease.
BRITISH JOURNAL OF CANCER
(2022)
Article
Oncology
Michael P. Flood, Anshini Jain, Catherine Mitchell, Chelsee Hewitt, Robert Ramsay, Michael Michael, Alexander G. Heriot, Jeanne Tie
Summary: This study highlights the importance of molecular analysis in stratifying patients with colorectal peritoneal metastases. BRAF V600E mutation predicts poor outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and may help refine patient selection. Preoperative molecular analysis should be performed to determine prognosis and guide perioperative therapeutic options.
Article
Oncology
Robert Ramsay, Shienny Sampurno, Michael P. Flood, Andrew C. Lynch
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Marija Dinevska, Samuel S. Widodo, Liam Furst, Lucero Cuzcano, Yitong Fang, Stefano Mangiola, Paul J. Neeson, Phillip K. Darcy, Robert G. Ramsay, Ryan Hutchinson, Fabienne MacKay, Michael Christie, Stanley S. Stylli, Theo Mantamadiotis
Summary: Tumor microenvironment in malignant astrocytoma undergoes changes in cell composition, cell signaling activation, and extracellular matrix deposition during disease progression. Targeting the extracellular matrix and cell signaling activation will be critical in designing personalized therapy.
Review
Cell Biology
Robert G. Ramsay, Vicki Whitehall, Michael P. Flood
Summary: Adoption of organoid/tumoroid propagation of normal and malignant intestinal epithelia has provided unprecedented opportunities to compare cell growth factor and signaling dependencies. These 3D structures mimic tumors in terms of gene expression and offer deeper insights into the tumor microenvironment (TME). Manipulation of TME elements and evaluation of different therapies can be done using patient-derived tumor models.