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Gastroenterology & Hepatology
Andrea Costamagna, Dora Natalini, Maria del Pilar Camacho Leal, Matilde Simoni, Luca Gozzelino, Paola Cappello, Francesco Novelli, Chiara Ambrogio, Paola Defilippi, Emilia Turco, Elisa Giovannetti, Emilio Hirsch, Sara Cabodi, Miriam Martini
Summary: High expression of p130Cas is associated with higher histologic grade and poor prognosis in PDAC. Deletion of p130Cas inhibits acinar-derived tumorigenesis and progression by suppressing PI3K-AKT signaling. Targeting the PI3K pathway may be a rational therapeutic strategy for tumors with high expression of p130Cas.
Article
Cell Biology
Wang-jun Yang, Rong-chang Cao, Wang Xiao, Xiao-lou Zhang, Hao Xu, Meng Wang, Zhi-tao Zhou, Huo-ji Chen, Jia Xu, Xue-mei Chen, Jun-ling Zeng, Shu-ji Li, Min Luo, Yan-jiang Han, Xiao-bing Yang, Guo-dong Feng, Yu-heng Lu, Yuan-yuan Ni, Chan-gui Wu, Jun-jie Bai, Zi-qi Yuan, Jin Jin, Guo-wei Zhang
Summary: This study investigated the role of efferocytosis in chronic pancreatitis (CP) and its underlying mechanisms. The findings suggest that impaired efferocytosis and dysregulated phospholipid metabolism contribute to the development of CP. The acinar Atp8b1/LPC pathway, regulated by the transcription factor Bhlha15, plays a protective role in CP. These findings provide potential therapeutic targets for improving current CP therapies.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Isidoro Cobo, Sumit Paliwal, Cristina Bodas, Irene Felipe, Julia Melia-Aloma, Ariadna Torres, Jaime Martinez-Villarreal, Marina Malumbres, Fernando Garcia, Irene Millan, Natalia del Pozo, Joo-Cheol Park, Ray J. MacDonald, Javier Munoz, Raul Mendez, Francisco X. Real
Summary: NFIC is a transcription factor that regulates the function of pancreatic acinar cells and suppresses the development of pancreatic ductal adenocarcinoma. It controls the differentiation and physiological functions of pancreatic acinar cells by regulating the expression of acinar genes, including those involved in RNA and protein metabolism, as well as the genes involved in resolving endoplasmic reticulum stress. In pancreatic cancer, NFIC expression is down-regulated, leading to the formation of pre-neoplastic lesions driven by mutant KRAS.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, General & Internal
Li-Ping Sheng, Chao-Qun Han, Chi Nie, Tao Xu, Kun Zhang, Xuan-Ji Li, Xin-Ru Xie, Rong Lin, Zhen Ding
Summary: Novel biomarkers, exosomal microRNAs in the serum, have the potential for early diagnosis and treatment of chronic pancreatitis. Through bioinformatics analysis, differentially expressed Exo-miRNAs in the serum of CP patients were identified, as well as their target genes involved in the precursor of pancreatic cancer associated with CP.
Article
Cell & Tissue Engineering
Zhengyu Jiang, Feijing Wu, Pasquale Laise, Tanaka Takayuki, Fu Na, Woosook Kim, Hiroki Kobayashi, Wenju Chang, Ryota Takahashi, Giovanni Valenti, Masaki Sunagawa, Ruth A. White, Marina Macchini, Bernhard W. Renz, Moritz Middelhoff, Yoku Hayakawa, Zinaida A. Dubeykovskaya, Xiangtian Tan, Timothy H. Chu, Karan Nagar, Yagnesh Tailor, Bryana R. Belin, Akanksha Anand, Samuel Asfaha, Michael O. Finlayson, Alina C. Iuga, Andrea Califano, Timothy C. Wang
Summary: Although it was believed that adult pancreatic stem cells do not exist, it is now known that the acinar compartment contains progenitor cells, including tissue-repairing facultative progenitors. This study focuses on a pancreatic acinar population marked by the expression of trefoil factor 2 (Tff2). It is found that Tff2 defines a transit-amplifying progenitor population that contributes to normal homeostasis and protects against Kras-driven carcinogenesis.
Article
Immunology
Yingying Lu, Baiqiang Li, Mei Wei, Qingtian Zhu, Lin Gao, Nan Ma, Xiaojie Ma, Qi Yang, Zhihui Tong, Guotao Lu, Weiqin Li
Summary: This study demonstrates the protective role of HDL and apoA-I in acute pancreatitis pathology, potentially driven by the inhibition of NLRP3 inflammasome signaling and acinar cell pyroptosis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Surgery
Rodrigo C. L. Edelmuth, Maria Cristina Riascos, Hala Al Asadi, Jacques A. Greenberg, Ileana C. Miranda, Haythem Najah, Carl V. Crawford, Felice H. Schnoll-Sussman, Brendan M. Finnerty, Thomas J. Fahey, Rasa Zarnegar
Summary: This study, using a rat model, found that administration of Vonoprazan can lead to morphological changes in the gastrointestinal tract, specifically causing alterations in certain cell types, such as PACM. The duration and dosage of Vonoprazan administration were shown to play a significant role in the development of PACM.
SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES
(2023)
Article
Oncology
Tiantian Jing, Xiaoli Xu, Chengsi Wu, Dianhui Wei, Lili Yuan, Yiwen Huang, Yizhen Liu, Boshi Wang
Summary: This study reveals the regulatory role of deubiquitinase POH1 in pancreatic ductal adenocarcinoma (PDAC) initiation and progression. POH1 stabilizes the MYC protein, promoting acinar-to-ductal metaplasia (ADM) and PDAC. Clinical evidence shows high expression of POH1 in PDAC samples and a correlation with poor prognosis. Targeting POH1 with a specific small-molecule inhibitor significantly reduces pancreatic tumor formation, offering a promising therapeutic strategy for PDAC treatment.
Article
Gastroenterology & Hepatology
Wenjie Ge, Algera Goga, Yuliang He, Pamuditha N. Silva, Christian Kurt Hirt, Karolin Herrmanns, Ilaria Guccini, Svenja Godbersen, Gerald Schwank, Markus Stoffel
Summary: miR-802 is a highly abundant and acinar-enriched pancreatic miRNA that is silenced during early stages of injury or oncogenic Kras(G12D)-induced transformation. Genetic ablation of mir-802 cooperates with Kras(G12D) by promoting ADM formation. miR-802 deficiency results in de-repression of the miR-802 targets Arhgef12, RhoA, and Sdc4, activation of RhoA, and induction of the downstream RhoA effectors ROCK1, LIMK1, COFILIN1, and EZRIN, thereby increasing F-actin rearrangement.
Article
Oncology
Francesca De Santis, Sandra L. Romero-Cordoba, Lorenzo Castagnoli, Tatiana Volpari, Simona Faraci, Giovanni Fuca, Elda Tagliabue, Filippo De Braud, Serenella M. Pupa, Massimo Di Nicola
Summary: This study investigates the activity and mechanisms of BCL6 in the CSC compartment of TNBC, mainly through Notch signaling, providing insights for the prospective design of combination treatment strategies targeting TNBC-associated biomarkers (such as BCL6) and molecules in developmentally conserved signaling pathways (such as Notch) to achieve long-lasting tumor control and improve patient outcomes.
Article
Cell Biology
Juanjuan Dai, Yan He, Mingjie Jiang, Mengya Niu, Bin Li, Zengkai Wu, Jingpiao Bao, Li Wen, Xingpeng Wang, Guoyong Hu
Summary: This study revealed that Regenerating Family Member 4 (Reg4) plays a crucial role in pancreatic regeneration by regulating Notch activation, influencing acinar-to-ductal metaplasia and resolution of pancreatitis. Reg4 is identified as a new regulator and potential therapeutic target for pancreatic regeneration.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Louis Marstrand-Dauce, Diane Lorenzo, Anais Chassac, Pascal Nicole, Anne Couvelard, Cecile Haumaitre
Summary: Adult pancreatic acinar cells can undergo pancreatic acinar-to-ductal metaplasia (ADM), where differentiated acinar cells transform into duct-like cells. This process can lead to the development of pancreatic intraepithelial neoplasia (PanIN) and eventually pancreatic ductal adenocarcinoma (PDAC). Factors such as obesity, chronic inflammation, and genetic mutations contribute to the development of ADM and PanIN. Understanding the cellular and molecular mechanisms of ADM is crucial for developing new therapeutic strategies for pancreatitis and PDAC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Seema Parte, Rama Krishna Nimmakayala, Surinder K. Batra, Moorthy P. Ponnusamy
Summary: Pancreatic cancer is a deadly neoplastic malignancy with high mortality rates. Acinar to ductal cell metaplasia plays a crucial role in tumor initiation, making it important for understanding the pathogenesis and early diagnosis of pancreatic cancer.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Article
Gastroenterology & Hepatology
Jinhyuk Choi, Tae Gyu Oh, Hee-Won Jung, Kun-Young Park, Hyemi Shin, Taehee Jo, Du-Seock Kang, Dipanjan Chanda, Sujung Hong, Jina Kim, Hayoung Hwang, Moongi Ji, Minkyo Jung, Takashi Shoji, Ayami Matsushima, Pilhan Kim, Ji Young Mun, Man-Jeong Paik, Sung Jin Cho, In-Kyu Lee, David C. Whitcomb, Phil Greer, Brandon Blobner, Mark O. Goodarzi, Stephen J. Pandol, Jerome Rotter, Weiwei Fan, Sagar P. Bapat, Ye Zheng, Chris Liddle, Ruth T. Yu, Annette R. Atkins, Michael Downes, Eiji Yoshihara, Ronald M. Evans, Jae Myoung Suh
Summary: The phosphorylation of zinc finger protein and embryonic tumor cell locomotion coupling protein can regulate the migration ability of breast cancer cells.
Article
Gastroenterology & Hepatology
Michelle M. Cooley, Diana D. H. Thomas, Kali Deans, Yajing Peng, Aurelia Lugea, Stephen J. Pandol, Luigi Puglielli, Guy E. Groblewski
Summary: The study demonstrated that down-regulation of AT-1 during pancreatitis leads to chronic ER stress and pancreatic inflammation. Loss of AT-1 induces activation of unfolded protein response pathways and causes pancreatic disease characterized by intracellular trypsin accumulation, immune cell infiltration, and fibrosis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Endocrinology & Metabolism
Julia M. Assini, Erin E. Mulvihill, Amy C. Burke, Brian G. Sutherland, Dawn E. Telford, Sanjiv S. Chhoker, Cynthia G. Sawyez, Maria Drangova, Andrew C. Adams, Alexei Kharitonenkov, Christopher L. Pin, Murray W. Huff
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Genetics & Heredity
Paxton M. Moon, Silvia Penuela, Kevin Barr, Sami Khan, Christopher L. Pin, Ian Welch, Mukundan Attur, Steven B. Abramson, Dale W. Laird, Frank Beier
JOURNAL OF MOLECULAR MEDICINE-JMM
(2015)
Article
Cell Biology
Melissa A. Fenech, Caitlin M. Sullivan, Lucimar T. Ferreira, Rashid Mehmood, William A. Macdonald, Peter B. Stathopulos, Christopher L. Pin
JOURNAL OF CELLULAR PHYSIOLOGY
(2016)
Article
Cell Biology
Michelle Kim, Perri Deacon, Rommel G. Tirona, Richard B. Kim, Christopher L. Pin, Henriette E. Meyer zu Schwabedissen, Rennian Wang, Ute I. Schwarz
HISTOCHEMISTRY AND CELL BIOLOGY
(2017)
Article
Cell Biology
Elena N. Fazio, Claire C. Young, Jelena Toma, Michael Levy, Kurt R. Berger, Charis L. Johnson, Rashid Mehmood, Patrick Swan, Alphonse Chu, Sean P. Cregan, F. Jeffrey Dilworth, Christopher J. Howlett, Christopher L. Pin
MOLECULAR BIOLOGY OF THE CELL
(2017)
Article
Biochemistry & Molecular Biology
David L. Marks, Rachel L. Olson, Raul Urrutia, Daniel D. Billadeau, Nilotpal Roy, George A. Calin, Muller Fabbri, Marina Koutsioumpa, Dimitrios Iliopoulos, Tamas Ordog, Robert Huebert, Olga Sarmento, Adebowale O. Bamidele, William Faubion, Gwen L. Lomberk, Jens Siveke, Nita Ahuja, Juan Iovanna, Ryan A. Hlady, Keith Robertson, John Kisiel, Christopher L. Pin, Martin E. Fernandez-Zapico
Article
Endocrinology & Metabolism
Aijun Zhang, Douglas H. Sieglaff, Jean Philippe York, Ji Ho Suh, Stephen D. Ayers, Glenn E. Winnier, Alexei Kharitonenkov, Christopher Pin, Pumin Zhang, Paul Webb, Xuefeng Xia
JOURNAL OF ENDOCRINOLOGY
(2015)
Article
Chemistry, Medicinal
Lihai Yu, Nikola Despotovic, Michael S. Kovacs, Christopher L. Pin, Leonard G. Luyt
ACS MEDICINAL CHEMISTRY LETTERS
(2019)
Article
Gastroenterology & Hepatology
Yongde Luo, Yaying Yang, Muyun Liu, Dan Wang, Feng Wang, Yawei Bi, Juntao Ji, Suyun Li, Yan Liu, Rong Chen, Haojie Huang, Xiaojie Wang, Agnieszka K. Swidnicka-Siergiejko, Tobias Janowitz, Semir Beyaz, Guoqiang Wang, Sulan Xu, Agnieszka B. Bialkowska, Catherine K. Luo, Christoph L. Pin, Guang Liang, Xiongbin Lu, Maoxin Wu, Kenneth R. Shroyer, Robert A. Wolff, William Plunkett, Baoan Ji, Zhaoshen Li, Ellen Li, Xiaokun Li, Vincent W. Yang, Craig D. Logsdon, James L. Abbruzzese, Weiqin Lu
Article
Biochemistry & Molecular Biology
Melissa A. Fenech, McKenzie M. Carter, Peter B. Stathopulos, Christopher L. Pin
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2020)
Article
Gastroenterology & Hepatology
M. Teresa Borrello, Mickenzie B. Martin, Christopher L. Pin
Summary: Pancreatitis and pancreatic ductal adenocarcinoma are diseases involving genetic and environmental factors, and the unfolded protein response (UPR) plays a crucial role in the pancreas. Increased UPR activity is associated with acute injury and risk factors related to these diseases. Targeting the UPR can have significant implications for the treatment of pancreatitis and pancreatic cancer.
Article
Multidisciplinary Sciences
Moritz Binder, Ryan M. Carr, Terra L. Lasho, Christy M. Finke, Abhishek A. Mangaonkar, Christopher L. Pin, Kurt R. Berger, Amelia Mazzone, Sandeep Potluri, Tamas Ordog, Keith D. Robertson, David L. Marks, Martin E. Fernandez-Zapico, Alexandre Gaspar-Maia, Mrinal M. Patnaik
Summary: Mutations in the chromatin remodeler ASXL1 are associated with poor clinical outcome in chronic myelomonocytic leukemia (CMML). This study investigates the impact of these mutations on gene expression and chromatin remodeling, and reveals that ASXL1 mutations lead to abnormal chromatin dynamics, affecting gene expression and accessibility of key regulatory elements.
NATURE COMMUNICATIONS
(2022)
Article
Gastroenterology & Hepatology
Claire C. Young, Ryan M. Baker, Christopher J. Howlett, Todd Hryciw, Joshua E. Herman, Douglas Higgs, Richard Gibbons, Howard Crawford, Arthur Brown, Christopher L. Pin
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2019)
Article
Pharmacology & Pharmacy
Sarah J. Woolsey, Melanie D. Beaton, Sara E. Mansell, Matilde Leon-Ponte, Janice Yu, Christopher L. Pin, Paul C. Adams, Richard B. Kim, Rommel G. Tirona
MOLECULAR PHARMACOLOGY
(2016)