Article
Oncology
George Sharbeen, Joshua A. McCarroll, Anouschka Akerman, Chantal Kopecky, Janet Youkhana, John Kokkinos, Jeff Holst, Cyrille Boyer, Mert Erkan, David Goldstein, Paul Timpson, Thomas R. Cox, Brooke A. Pereira, Jessica L. Chitty, Sigrid K. Fey, Arafath K. Najumudeen, Andrew D. Campbell, Owen J. Sansom, Rosa Mistica C. Ignacio, Stephanie Naim, Jie Liu, Nelson Russia, Julia Lee, Angela Chou, Amber Johns, Anthony J. Gill, Estrella Gonzales-Aloy, Val Gebski, Yi Fang Guan, Marina Pajic, Nigel Turner, Minoti Apte, Thomas P. Davis, Jennifer P. Morton, Koroush S. Haghighi, Jorjina Kasparian, Benjamin J. McLean, Yordanos F. Setargew, Phoebe A. Phillips
Summary: High expression of SLC7A11 in human PDAC tumor stroma, independently prognostic of poorer overall survival. The study demonstrates that PDAC-derived CAFs are highly dependent on SLC7A11 for cystine uptake and glutathione synthesis. Inhibition of SLC7A11 decreases CAF proliferation, reduces their resistance to oxidative stress, and inhibits their ability to support PDAC cell growth.
Article
Pathology
Hayley T. Morris, William R. Bamlet, Gina L. Razidlo, Laura M. Machesky
Summary: The expression of FSCN1 and EMT-TFs SLUG/SNAI2 and TWIST1 in pancreatic adenocarcinoma (PDAC) is associated with the development of the disease. High expression of FSCN1 is correlated with poorer survival. The expression of EMT-TFs is not associated with survival, but is correlated with FSCN1 expression.
PATHOLOGY RESEARCH AND PRACTICE
(2023)
Review
Cell Biology
Tianyi Zhang, Yanxian Ren, Pengfei Yang, Jufang Wang, Heng Zhou
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with a high deposition of extracellular matrix (ECM) and poor prognosis. ECM proteins derived from tumor cells reduce the effectiveness of conventional cancer treatment and contribute to tumor progression and metastasis. Cancer-associated fibroblasts (CAFs) in the ECM are promising targets for novel anti-tumor interventions.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Hong Hua Yan, Kyung Hee Jung, Ji Eun Lee, Mi Kwon Son, Zhenghuan Fang, Jung Hee Park, Soo Jung Kim, Ju Young Kim, Ju Han Lim, Soon-Sun Hong
Summary: The study revealed that ANGPTL4 plays a critical role in KRAS(G12D)-induced ADM, promoting its progression and influencing PDAC development by regulating periostin. The ANGPTL4/periostin axis is considered a potential therapeutic target for ADM-derived PDAC.
Article
Neurosciences
Milos Bogdanovic, Hila Asraf, Noa Gottesman, Israel Sekler, Elias Aizenman, Michal Hershfinkel
Summary: Tight regulation of neuronal Zn2+ is critical for physiological function. Multiple Zn2+ transporters, such as ZIP1 and ZIP3, are involved in the uptake and distribution of Zn2+. In this study, we found that the expression of ZIP1 and ZIP3 was developmentally regulated in mouse hippocampal neurons, with higher levels of expression in mature neurons. ZIP1 and ZIP3 were ubiquitously expressed on somas and most neuronal processes in cultured neurons, while in adult mouse hippocampal brain, ZIP1 was predominantly expressed in the CA3 stratum pyramidale, and ZIP3 primarily localized in the stratum lucidum. Silencing of ZIP1 or ZIP3 reduced Zn2+ uptake in vitro, and silencing of ZIP3 protected CA3 neurons from neurodegeneration following seizures in vivo. These findings suggest that distinct Zn2+ transporters play different roles in regulating Zn2+ accumulation and toxicity in different neuronal populations in the hippocampus.
JOURNAL OF NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Roman Bubin, Romans Uljanovs, Ilze Strumfa
Summary: The discovery of cancer stem cells (CSCs) in leukemia has led to active research on stemness in neoplastic tissues. CSCs are a subpopulation of malignant cells with unique properties, including a dedifferentiated state, self-renewal, pluripotency, resistance to therapy, epigenetic alterations, and higher tumorigenicity. CSCs have been confirmed in various malignancies, including pancreatic ductal adenocarcinoma, which has a poor prognosis. This review aims to summarize the current knowledge on the markers and molecular features of CSCs in pancreatic ductal adenocarcinoma and the therapeutic options for their elimination.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Liwei Cao, Chen Huang, Daniel Cui Zhou, Yingwei Hu, T. Mamie Lih, Sara R. Savage, Karsten Krug, David J. Clark, Michael Schnaubelt, Lijun Chen, Felipe da Veiga Leprevost, Rodrigo Vargas Eguez, Weiming Yang, Jianbo Pan, Bo Wen, Yongchao Dou, Wen Jiang, Yuxing Liao, Zhiao Shi, Nadezhda Terekhanova, Song Cao, Rita Jui-Hsien Lu, Yize Li, Ruiyang Liu, Houxiang Zhu, Peter Ronning, Yige Wu, Matthew A. Wyczalkowski, Hariharan Easwaran, Ludmila Danilova, Arvind Singh Mer, Seungyeul Yoo, Joshua M. Wang, Wenke Liu, Benjamin Haibe-Kains, Mathangi Thiagarajan, Scott D. Jewell, Galen Hostetter, Chelsea J. Newton, Qing Kay Li, Michael H. Roehr, David Fenyo, Pei Wang, Alexey Nesvizhskii, D. R. Mani, Gilbert S. Omenn, Emily S. Boja, Mehdi Mesri, Ana Robles, Henry Rodriguez, Oliver F. Bathe, Daniel W. Chan, Ralph H. Hruban, Li Ding, Bing Zhang, Hui Zhang
Summary: This study conducted comprehensive proteogenomic analysis of PDAC to understand the molecular alterations that drive oncogenesis. Multiple analyses were performed on tissues from patients, providing valuable resources for early detection and identification of therapeutic targets.
Article
Oncology
Sheron Perera, Gun Ho Jang, Yifan Wang, Deirdre Kelly, Michael Allen, Amy Zhang, Robert E. Denroche, Anna Dodd, Stephanie Ramotar, Shawn Hutchinson, Mustapha Tehfe, Ravi Ramjeesingh, James Biagi, Bernard Lam, Julie Wilson, Sandra E. Fischer, George Zogopoulos, Faiyaz Notta, Steven Gallinger, Robert C. Grant, Jennifer J. Knox, Grainne M. O'Kane
Summary: In advanced PDAC, hENT1 mRNA expression predicts ORR and OS in patients receiving GnP, while no association was observed in patients receiving mFFX.
CLINICAL CANCER RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Nausika Betriu, Juan Bertran-Mas, Anna Andreeva, Carlos E. Semino
Summary: Syndecans, a subfamily of proteoglycans, play critical roles in various physiological processes and have implications in disease progression. Their interactions with other macromolecules contribute to normal cellular functions and disease pathogenesis.
Review
Oncology
Swathikan Chidambaram, Michal Kawka, Tamara M. H. Gall, David Cunningham, Long R. Jiao
Summary: Pancreatic ductal adenocarcinoma (PDAC) is the most common malignant pancreatic tumor, often originating from the ducts within the pancreas. This article summarizes the existing evidence on the progression of precancerous lesions to PDAC. Pancreatic intraepithelial lesions were found to be the most common precancerous lesion, leading to approximately 80% of PDAC cases. The lack of characterization of PDAC precursor cystic lesions may result in unnecessary surgeries for patients. Advances in molecular techniques may enable personalized management of pancreatic cancer in the future.
Review
Oncology
Eleonora Lai, Pina Ziranu, Dario Spanu, Marco Dubois, Andrea Pretta, Simona Tolu, Silvia Camera, Nicole Liscia, Stefano Mariani, Mara Persano, Marco Migliari, Clelia Donisi, Laura Demurtas, Valeria Pusceddu, Marco Puzzoni, Mario Scartozzi
Summary: Despite ongoing research, there is still insufficient data on BRCA1/2-mutant PDAC, and more understanding is needed on the specific landscape of PDAC with BRCA mutations.
BRITISH JOURNAL OF CANCER
(2021)
Article
Pathology
Koushik K. Das, Jeffrey W. Brown, Carlos Fernandez del-Castillo, Tiffany Huynh, Jason C. Mills, Yoko Matsuda, Kiron M. Das, Mari Mino-Kenudson
Summary: mAb Das-1 shows high specificity in distinguishing high-grade PanIN/PDAC from low-grade PanIN lesions, which may be helpful for pre-operative diagnosis and clinical risk stratification of PDAC.
Review
Gastroenterology & Hepatology
Adrien Grimont, Steven D. Leach, Rohit Chandwani
Summary: The pancreas contains a high level of cellular plasticity, which can alter cellular identity during injury, regeneration, and repair processes. The cell of origin of pancreatic cancer is difficult to determine, but research suggests that acinar cells may be the most likely origin of intraductal papillary neoplasms and pancreatic intraepithelial neoplasia, while both acinar and ductal cells can undergo malignant transformation into pancreatic ductal adenocarcinoma.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
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)
Article
Multidisciplinary Sciences
Stephano S. Mello, Brittany M. Flowers, Pawel K. Mazur, James J. Lee, Fabian Muelle, Sarah K. Denny, Sofia Ferreira, Kathryn Hanson, Seung K. Kim, William J. Greenleaf, Laura D. Wood, Laura D. Attardi
Summary: The majority of pancreatic ductal adenocarcinomas (PDACs) have TP53 mutations, highlighting the critical role of p53 in suppressing PDAC. This study shows that p53 suppresses PDAC by limiting acinar-to-ductal metaplasia (ADM) and suppressing PanIN cell proliferation. Furthermore, p53 dampens KRAS signaling in PanINs and regulates ECM remodeling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)