Editorial Material
Oncology
James R. Goldenring
Summary: Intestinal-type gastric cancer can arise from precancerous metaplastic lineages, specifically from spasmolytic polypeptide-expressing metaplasia (SPEM) cells. A recent study identified an activating Kras(G12D) mutation in SPEM cells, which propagated into adenomatous and cancerous lesions, suggesting that SPEM lineages can serve as a direct precursor for dysplasia and intestinal-type gastric cancer.
JOURNAL OF PATHOLOGY
(2023)
Article
Biology
Miriam Jacome-Sosa, Zhi-Feng Miao, Vivek S. Peche, Edward F. Morris, Ramkumar Narendran, Kathryn M. Pietka, Dmitri Samovski, Hei-Yong G. Lo, Terri Pietka, Andrea Varro, Latisha Love-Gregory, James R. Goldenring, Ondrej Kuda, Eric R. Gamazon, Jason C. Mills, Nada A. Abumrad
Summary: Research on the gastric function of CD36 suggests that its absence leads to altered gland organization, increased fibronectin, and inflammatory signaling in gastric tissues in mice. Defective epithelial cell renewal and progenitor cell differentiation impairs mucosal repair, possibly due to altered lipid metabolism and fatty acid delivery. Low CD36 expression is associated with gastric diseases in humans, highlighting the importance of CD36 in gastric tissue repair.
COMMUNICATIONS BIOLOGY
(2021)
Article
Cell & Tissue Engineering
Jayati Chakrabarti, Martha Dua-Awereh, Michael Schumacher, Amy Engevik, Jennifer Hawkins, Michael A. Helmrath, Yana Zavros
Summary: Sonic Hedgehog (Shh) plays a crucial role in gastric epithelial regeneration by stimulating macrophage chemotaxis to the injured epithelium. Experimental evidence supports the hypothesis that Shh promotes macrophage migration through a Smo-dependent mechanism.
NPJ REGENERATIVE MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Spencer G. Willet, Nattapon Thanintorn, Helen McNeill, Sung-Ho Huh, David M. Ornitz, Won Jae Huh, Stella G. Hoft, Richard J. DiPaolo, Jason C. Mills
Summary: Acute and chronic gastric injury can lead to pyloric metaplasia, which is characterized by the death of parietal cells and the reprogramming of chief cells into proliferative, mucin-rich metaplasia cells. The transcription factor SOX9 has been identified as a potential regulator of mucous neck and metaplasia cell identity in the stomach. SOX9 is expressed in early gastric progenitors and mature mucous neck cells, and its misexpression can lead to an expansion of mucous gene expression in the gastric epithelium.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Immunology
Krystal D. Kao, Helmut Grasberger, Mohamad El-Zaatari
Summary: Gastric myeloid-derived suppressor cells (MDSCs) are a population that expands during gastric pre-neoplastic and neoplastic development. S100a8 is identified as a pan-specific marker for this population, and the subset S100a8(+)Cxcr2(+) plays a role in regulating gastric immunopathology and lipid peroxidation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Gastroenterology & Hepatology
Qiyue Chen, Kai Weng, Mi Lin, Ming Jiang, Yinshan Fang, Sanny S. W. Chung, Xiaobo Huang, Qing Zhong, Zhiyu Liu, Zening Huang, Jianxian Lin, Ping Li, Wael El-Rifai, Alexander Zaika, Haiyan Li, Anil K. Rustgi, Hiroshi Nakagawa, Julian A. Abrams, Timothy C. Wang, Chao Lu, Changming Huang, Jianwen Que
Summary: This study aimed to better target oncogenes to gastric stem cells and understand their behavior in the initial stages of gastric tumorigenesis. The results showed that SOX9 marks gastric stem cells that can self-renew and differentiate into all gastric epithelial cells. SOX9 modulates biased symmetric cell division in gastric stem cells, which is required for the malignant transformation. High levels of SOX9 are associated with recurrence and poor prognosis in gastric cancer.
Review
Biochemistry & Molecular Biology
Paulius Jonaitis, Limas Kupcinskas, Juozas Kupcinskas
Summary: Gastric cancer is a common cause of mortality worldwide, with intestinal metaplasia considered a key factor in its development. Recent research has identified various molecular alterations in intestinal metaplasia, some of which show strong associations with the disease and potential for prevention and treatment, though study homogeneity is a key limiting factor.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Xing-Jie Dai, Li-Juan Zhao, Long-Hua Yang, Ting Guo, Lei-Peng Xue, Hong-Mei Ren, Zhi-Li Yin, Xiao-Peng Xiong, Ying Zhou, Shi-Kun Ji, Hui-Min Liu, Hong-Min Liu, Ying Liu, Yi-Chao Zheng
Summary: In this study, the antipsychotic drug chlorpromazine was identified as an LSD1 inhibitor, and a series of chlorpromazine derivatives were synthesized. Among them, compound 3s showed the most potent inhibitory activity. Compound 3s inhibited LSD1 at the cellular level, downregulated PD-L1 expression in gastric cancer cells, and enhanced T-cell killing response. Animal studies confirmed that compound 3s can inhibit gastric cancer cell proliferation without significant toxicity in immunocompetent mice. These findings suggest that compound 3s may serve as a lead compound for further development to activate T-cell immunity in gastric cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Nutrition & Dietetics
Shaima Sirajudeen, Iltaf Shah, Sherif M. Karam, Asma Al Menhali
Summary: Vitamin D deficiency can result from insufficient light exposure or intake. This study investigated the biological effects of vitamin D deficiency on mouse gastric glands and found that the effects were influenced by the severity of deficiency. Unique gastric phenotypes were observed in mice with light-induced vitamin D deficiency compared to diet-induced deficiency.
Article
Immunology
Gaoming Wang, Ludi Yang, Yongkun Wang, Renhao Hu, Kehui Zhang, Taohua Guo, Bo Chen, Xiaohua Jiang, Ran Cui
Summary: This study characterized the immune microenvironment of gastric cancer (GC) and identified molecular subtypes that have distinct sensitivity to immunotherapy. An immune-related prognostic signature was established to predict treatment response and prognosis, providing new strategies for personalized treatment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell & Tissue Engineering
Ji-Hyun Lee, Somi Kim, Seungmin Han, Jimin Min, Brianna Caldwell, Aileen-Diane Bamford, Andreia Sofia Batista Rocha, JinYoung Park, Sieun Lee, Szu-Hsien Sam Wu, Heetak Lee, Juergen Fink, Sandra Pilat-Carotta, Jihoon Kim, Manon Josserand, Reka Szep-Bakonyi, Yohan An, Young Seok Ju, Anna Philpott, Benjamin D. Simons, Daniel E. Stange, Eunyoung Choi, Bon-Kyoung Koo, Jong Kyoung Kim
Summary: This study identified p57 as a molecular switch for maintaining the reserve stem cell state in chief cells of the stomach. p57 expression is constantly maintained in chief cells during homeostasis but rapidly diminishes after injury, leading to robust proliferation. Overexpression of p57 induces a long-term reserve stem cell state accompanied by altered niche requirements and a mature chief cell phenotype. However, constitutive expression of p57 impairs the injury response of chief cells.
Article
Pathology
Julio C. Poveda, Satyapal Chahar, Monica T. Garcia-Buitrago, Elizabeth A. Montgomery, Oliver G. McDonald
Summary: This study summarizes the histomorphology of well-differentiated gastric neuroendocrine tumors (gNETs) in patients with autoimmune metaplastic atrophic gastritis (AMAG). It found that most type 1 ECL-cell gNETs were low-grade and multifocal, but a significant proportion displayed unconventional morphologies. Unconventional gNETs grew within the mucosa and the background mucosa of patients with gNETs had already progressed to endstage metaplasia.
Article
Oncology
Omer An, Yangyang Song, Xinyu Ke, Jimmy Bok-Yan So, Raghav Sundar, Henry Yang, Sun Young Rha, Ming Hui Lee, Su Ting Tay, Xuewen Ong, Angie Lay Keng Tan, Matthew Chau Hsien Ng, Erwin Tantoso, Leilei Chen, Patrick Tan, Wei Peng Yong
Summary: This study introduces a novel A-to-I RNA editing signature as a prognostic and predictive biomarker in advanced gastric cancer, offering a new tool for improved patient stratification and response to therapy.
Article
Gastroenterology & Hepatology
Min Zhang, Shuofeng Hu, Min Min, Yanli Ni, Zheng Lu, Xiaotian Sun, Jiaqi Wu, Bing Liu, Xiaomin Ying, Yan Liu
Summary: This study utilized single-cell RNA sequencing to uncover molecular and cellular heterogeneity in gastric adenocarcinoma, identifying different cell subgroups with diverse differentiation degrees that may predict prognosis. Some subgroups corresponded to histopathological features, while others exhibited unique transcriptome profiles. Additionally, evidence was provided for potential transition from gastric chief cells into metaplasia expressing spasmolytic polypeptides.
Article
Oncology
Jihyun Kim, Charny Park, Kwang H. Kim, Eun Hye Kim, Hyunki Kim, Jong Kyu Woo, Je Kyung Seong, Ki Taek Nam, Yong Chan Lee, Soo Young Cho
Summary: Single-cell transcriptomic profiling offers insights into the behavior of gastric cancer cells, revealing the roles of intratumoral heterogeneity and different cellular lineages in carcinogenesis.
NPJ PRECISION ONCOLOGY
(2022)
Article
Gastroenterology & Hepatology
Vani Konda, Rhonda F. Souza, Kerry B. Dunbar, Jason C. Mills, Daniel S. Kim, Robert D. Odze, Stuart J. Spechler
Summary: This study aimed to characterize the early endoscopic and histologic features of radiofrequency ablation (RFA) wound healing in patients with Barrett's esophagus (BE). The results showed that squamous re-epithelialization of RFA wounds not only progressed through squamous cells extending from the proximal wound edge, but also through islands of squamous epithelium sprouting throughout the ablated segment. Additionally, subepithelial glandular structures associated with the squamous islands were found to increase post-RFA. Furthermore, subsquamous intestinal metaplasia (SSIM) was detected in biopsies of patients during the healing process. This study provides insights into the mechanisms of esophageal metaplasia and the healing of RFA wounds.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Cell Biology
Mahliyah Adkins-Threats, Jason C. Mills
Summary: Recent studies have discovered that adult organs recruit progenitor cells to regenerate tissues after injury using cell plasticity programs, and plasticity is more common than previously believed, even in homeostasis. This article focuses on the interplay between normal stem cell differentiation and plasticity in homeostasis and after injury, using the gastric epithelium as an example. It also examines the common features of regenerative programs and discusses how evolutionarily conserved plasticity programs can help us understand pathological processes.
CURRENT OPINION IN GENETICS & DEVELOPMENT
(2022)
Article
Clinical Neurology
Salma I. Patel, Wojciech Zareba, Bonnie LaFleur, Jean-Phillipe Couderc, Xiaojuan Xia, Raymond Woosley, Imran Y. Patel, Daniel Combs, Saif Mashaqi, Stuart F. Quan, Sairam Parthasarathy
Summary: Sleep-disordered breathing is associated with some measures of ventricular repolarization but does not modify the association between ventricular repolarization and overall mortality.
Letter
Dermatology
Bonnie LaFleur, Clara Curiel-Lewandrowski, Edgar Tapia, Joel Parker, Lisa White, H-H. Sherry Chow, Andrew P. South
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Pathology
Hideaki Mita, Hiroto Katoh, Daisuke Komura, Miwako Kakiuchi, Hiroyuki Abe, Hirofumi Rokutan, Koichi Yagi, Sachiyo Nomura, Tetsuo Ushiku, Yasuyuki Seto, Shumpei Ishikawa
Summary: In this study, immunohistochemical analysis of 342 gastric cancer cases revealed that approximately half of the samples showed aberrant expression of CDH11 in gastric cancer cells. The aberrant expression of CDH11 was statistically associated with bone metastasis, as well as liver and distant lymph node metastasis. Therefore, aberrant CDH11 expression in gastric cancer cells can serve as a predictive biomarker for distant metastasis.
PATHOLOGY RESEARCH AND PRACTICE
(2023)
Article
Geriatrics & Gerontology
Mladen Jergovic, Makiko Watanabe, Ruchika Bhat, Christopher P. Coplen, Sandip A. Sonar, Rachel Wong, Yvonne Castaneda, Lisa Davidson, Mrinalini Kala, Rachel C. Wilson, Homer L. Twigg, Kenneth Knox, Heidi E. Erickson, Craig C. Weinkauf, Christian Bime, Billie A. Bixby, Sairam Parthasarathy, Jarrod M. Mosier, Bonnie J. LaFleur, Deepta Bhattacharya, Janko Z. Nikolich
Summary: The severity of COVID-19 increases with age, and older adults have a higher mortality rate. Age-related immune pathobiology can be predicted by certain features in the blood. Older patients experience T-cell dysfunction, which may impair immune protection.
Article
Cell Biology
Jayashree Srinivasan, Anusha Vasudev, Carolyn Shasha, Hilary J. Selden, Encarnacion Perez Jr, Bonnie LaFleur, Shripad A. Sinari, Andreas Krueger, Ellen R. Richie, Lauren I. R. Ehrlich
Summary: Age-related thymus involution is caused by decreased T-cell production, which results in increased vulnerability to pathogens and reduced response to vaccines. Understanding the mechanisms of thymus involution can help develop strategies to restore T-cell production in older individuals. The number of early T-cell progenitors (ETPs) declines as early as 3 months of age in mice, indicating changes in thymic stromal niches and/or pre-thymic progenitors. The study also reveals a reduction in pre-thymic lymphoid progenitors in the bone marrow and blood, suggesting a decrease in the quality of the niches in the bone marrow and thymus. Notch signaling in both bone marrow lymphoid progenitors and ETPs diminishes, further contributing to the decline in ETPs. These findings demonstrate the importance of diminished lymphopoiesis and stromal support in the age-related thymus involution process.
Article
Genetics & Heredity
Yasushi Totoki, Mihoko Saito-Adachi, Yuichi Shiraishi, Daisuke Komura, Hiromi Nakamura, Akihiro Suzuki, Kenji Tatsuno, Hirofumi Rokutan, Natsuko Hama, Shogo Yamamoto, Hanako Ono, Yasuhito Arai, Fumie Hosoda, Hiroto Katoh, Kenichi Chiba, Naoko Iida, Genta Nagae, Hiroki Ueda, Chen Shihang, Shigeki Sekine, Hiroyuki Abe, Sachiyo Nomura, Tetsuya Matsuura, Eiji Sakai, Takashi Ohshima, Yasushi Rino, Khay Guan Yeoh, Jimmy So, Kaushal Sanghvi, Richie Soong, Akihiko Fukagawa, Shinichi Yachida, Mamoru Kato, Yasuyuki Seto, Tetsuo Ushiku, Atsushi Nakajima, Hitoshi Katai, Patrick Tan, Shumpei Ishikawa, Hiroyuki Aburatani, Tatsuhiro Shibata
Summary: A study on a cross-ancestry genomic and transcriptomic cohort of gastric cancer reveals significantly mutated genes and mutational signatures, some of which are specific to certain ancestries. The research involves the analysis of 1,335 cases and identifies 77 significantly mutated genes, including ARHGAP5 and TRIM49C. Subtype-specific drivers, such as PIGR and SOX9, are also identified, particularly enriched in the diffuse subtype of the disease. The findings also highlight the association of non-protein-truncating CDH1 mutations with sporadic diffuse-type cases and the link between alcohol consumption or metabolism and RHOA mutations in patients with East Asian ancestry. The study provides comprehensive insights into the molecular landscape of gastric cancer across various subtypes and ancestries.
Article
Oncology
Kentaro Minegishi, Yoh Dobashi, Teruhide Koyama, Yuko Ishibashi, Miki Furuya, Hiroyoshi Tsubochi, Yasukazu Ohmoto, Tomohiko Yasuda, Sachiyo Nomura
Summary: Trefoil factors (TFFs) have been found to be upregulated in various types of cancer, indicating their potential as biomarkers for screening. This study evaluated the clinical relevance of serum and urinary TFFs as biomarkers for lung cancer and their correlation with TFF expression levels in lung cancer tissue. The results showed that serum TFF levels were significantly higher in lung cancer patients, while urinary TFF levels were lower. Serum TFF1, TFF2, TFF3, and urinary TFF1, TFF3 showed the highest potential to discriminate between cancer and non-cancer samples. The findings suggest that serum and urinary TFF levels could serve as predictive biomarkers for lung cancer.
Article
Medicine, Research & Experimental
Saeed Soleymanjahi, Valerie Blanc, Elizabeth A. Molitor, David M. Alvarado, Yan Xie, Vered Gazit, Jeffrey W. Brown, Kathleen Byrnes, Ta-Chiang Liu, Jason C. Mills, Matthew A. Ciorba, Deborah C. Rubin, Nicholas O. Davidson
Summary: RNA-binding protein 47 (RBM47) plays an important role in embryonic endoderm development, and this study found that it also has implications in adult intestine function. Knockout mice lacking Rbm47 showed increased cell proliferation and abnormal morphology in the intestine, while Rbm47-deficient mice were protected against colitis-associated cancer. The findings suggest that RBM47 is a cell-intrinsic modifier of intestinal growth, inflammatory, and tumorigenic pathways.
Article
Cell Biology
Yongji Zeng, Qing K. Li, Sujayita Roy, Jason C. Mills, Ramon U. Jin
Summary: Plasticity is an important property of the gastrointestinal tract and plays a role in both normal response to injury and cancer development. This study focuses on the development of gastric and esophageal cancers from intestinal metaplasia, and findings indicate that Barrett's esophagus exhibits incomplete intestinal metaplasia with concurrent expression of gastric and intestinal traits. Understanding the molecular pathways involved in the development of these cancers will lead to improved diagnostic and therapeutic approaches.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Gastroenterology & Hepatology
Spencer G. Willet, Nattapon Thanintorn, Helen McNeill, Sung-Ho Huh, David M. Ornitz, Won Jae Huh, Stella G. Hoft, Richard J. DiPaolo, Jason C. Mills
Summary: Acute and chronic gastric injury can lead to pyloric metaplasia, which is characterized by the death of parietal cells and the reprogramming of chief cells into proliferative, mucin-rich metaplasia cells. The transcription factor SOX9 has been identified as a potential regulator of mucous neck and metaplasia cell identity in the stomach. SOX9 is expressed in early gastric progenitors and mature mucous neck cells, and its misexpression can lead to an expansion of mucous gene expression in the gastric epithelium.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Gastroenterology & Hepatology
Long Long Cao, Heng Lu, Mohammed Soutto, Nadeem Bhat, Zheng Chen, Dunfa Peng, Ahmed Gomaa, Jia Bin Wang, Jian Wei Xie, Ping Li, Chao Hui Zheng, Sachiyo Nomura, Jashodeep Datta, Nipun Merchant, Zhi Bin Chen, Alejandro Villarino, Alexander Zaika, Chang Ming Huang, Wael El-Rifai
Summary: This study developed a classification method based on immune cell infiltration to classify GC and found that immune desert-type and excluded-type tumors are resistant to ICB therapy compared to immune-inflamed tumors. The study also identified the enrichment of epithelial-mesenchymal transition (EMT) signaling in immune desert-type GC, and showed that mesenchymal-like tumors in syngeneic mice exhibited T cell-exclusion and resistance to CTLA4 blockade.
Article
Surgery
Shinichiro Shiomi, Koichi Yagi, Ryohei Iwata, Shoh Yajima, Yasuhiro Okumura, Susumu Aikou, Hiroharu Yamashita, Sachiyo Nomura, Yasuyuki Seto
Summary: The study investigated the diagnostic utility of a newly established lymphatic flow mapping protocol for predicting lymph node metastasis in patients with esophageal or esophagogastric junction cancer. The results showed that this protocol potentially helps to predict lymph node metastasis intraoperatively in patients who did not undergo neoadjuvant chemotherapy.
SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES
(2023)
Article
Biochemistry & Molecular Biology
Yasuyoshi Sato, Hiroharu Yamashita, Yukari Kobayashi, Koji Nagaoka, Tetsuro Hisayoshi, Takuya Kawahara, Akihiro Kuroda, Noriyuki Saito, Ryohei Iwata, Yasuhiro Okumura, Koichi Yagi, Susumu Aiko, Sachiyo Nomura, Kazuhiro Kakimi, Yasuyuki Seto
Summary: We investigated the tumor immune response in gastric cancer patients receiving third-line nivolumab monotherapy to identify immune-related biomarkers for better patient selection. High T cell/Treg ratios and specific gene expression signatures show promise as potential biomarkers for treatment response, while the tumor-infiltrating immune response is compromised by prior treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)