Article
Medicine, Research & Experimental
Daphne N. Dorst, Esther M. M. Smeets, Christian Klein, Cathelijne Frielink, Daan Geijs, Marija Trajkovic-Arsic, Phyllis F. Y. Cheung, Martijn W. J. Stommel, Martin Gotthardt, Jens T. Siveke, Erik H. J. G. Aarntzen, Sanne A. M. van Lith
Summary: Patients with pancreatic ductal adenocarcinoma (PDAC) have a low 5-year survival rate of 9%. The dense tumor-supporting stroma, which is composed of cancer-associated fibroblasts, is a major factor limiting the efficacy of chemotherapy and immunotherapy. In this study, the feasibility of fibroblast activation protein (FAP)-targeted photodynamic therapy (tPDT) for treating PDAC was demonstrated in murine models.
MOLECULAR PHARMACEUTICS
(2023)
Review
Biochemistry & Molecular Biology
Tha Luong, Yuvasri Golivi, Ganji Purnachandra Nagaraju, Bassel F. El-Rayes
Summary: Cancer-associated fibroblasts (CAFs) are key components of the pancreatic tumor microenvironment (TME) and exhibit phenotypic and functional heterogeneity. They play a crucial role in promoting tumorigenesis and may also possess anti-tumor activity. The interaction between CAFs and infiltrated immune cells and mediators shapes the immunological state in the TME. Further research on the crosstalk between CAFs and the tumor immune environment may lead to new approaches for treating pancreatic ductal adenocarcinoma (PDAC).
CYTOKINE & GROWTH FACTOR REVIEWS
(2022)
Article
Oncology
Aimy Sebastian, Kelly A. Martin, Ivana Peran, Nicholas R. Hum, Nicole F. Leon, Beheshta Amiri, Stephen P. Wilson, Matthew A. Coleman, Elizabeth K. Wheeler, Stephen W. Byers, Gabriela G. Loots
Summary: The deficiency of Cdh11 significantly alters the tumor microenvironment in PDAC and contributes to enhanced anti-tumor immunity and increased survival.
FRONTIERS IN ONCOLOGY
(2023)
Review
Oncology
Raphael Peiffer, Yasmine Boumahd, Charlotte Gullo, Rebekah Crake, Elisabeth Letellier, Akeila Bellahcene, Olivier Peulen
Summary: Cancer-associated fibroblasts (CAFs) play a critical role in pancreatic cancer by influencing cancer cell metabolism through various mechanisms. CAF heterogeneity is characteristic of the pancreatic tumor microenvironment. Environmental changes in pH, oxygenation, and nutrient availability are heavily driven by stromal CAFs. The bidirectional crosstalk between CAFs and cancer cells promotes tumor aggressiveness and adaptation to external stress. This review summarizes the diversity of CAF subtypes, the metabolic crosstalk between CAFs and tumor cells, and the role of CAF-driven signaling, desmoplasia, and acidosis in cancer cell metabolism, highlighting potential therapeutic strategies.
Article
Oncology
Neel I. Nissen, Astrid Z. Johansen, Inna Chen, Julia S. Johansen, Rasmus S. Pedersen, Carsten P. Hansen, Morten A. Karsdal, Nicholas Willumsen
Summary: This study established an in vitro fibroblast model related to pancreatic ductal adenocarcinoma (PDAC) and used collagen biomarkers as a screening tool for anti-fibrotic drugs. The findings suggest that collagen biomarkers can quantify fibroblast activity in vitro and predict the survival rate in PDAC patients.
Review
Oncology
Ronnie Ren Jie Low, Wei Wen Lim, Paul M. Nguyen, Belinda Lee, Michael Christie, Antony W. Burgess, Peter Gibbs, Sean M. Grimmond, Frederic Hollande, Tracy L. Putoczki
Summary: PDO biobanks derived from PDAC patients have provided opportunities for developing new therapies and advancing our understanding of PDAC biology. Developing coculturing techniques for specific immune or stromal cell populations will help improve our understanding of the tumor microenvironment and its impact on treatment response.
Review
Immunology
Claudia Minici, Sabrina Testoni, Emanuel Della-Torre
Summary: Pancreatic adenocarcinoma is highly infiltrated by B lymphocytes, and their role in tumor development and progression has been overlooked. The interaction between B lymphocytes and neoplastic cells can have both stimulatory and inhibitory effects. Understanding the role of B lymphocytes in this lethal cancer is crucial for designing novel therapeutic strategies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Hideaki Ijichi
Summary: Understanding the tumor microenvironment is crucial for overcoming pancreatic ductal adenocarcinoma (PDAC). This article discusses various aspects of the microenvironment, including cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), immune microenvironment, metabolic properties, microbiome, neural signaling, and the effect of anesthetic drugs. The study found that the PDAC microenvironment is more complicated than expected, with heterogeneity and plasticity resulting from tumor-stromal interactions.
Review
Biochemistry & Molecular Biology
Utpreksha Vaish, Tejeshwar Jain, Abhi C. Are, Vikas Dudeja
Summary: PDAC is a major cause of cancer-related mortality in the western world, with CAFs playing a key role in the tumor microenvironment and being potential targets for therapy. However, there is significant heterogeneity in CAFs within PDAC, highlighting the importance of understanding and delineating this heterogeneity before targeting them for treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Nayela N. Chowdhury, Yi Yang, Ananya Dutta, Michelle Luo, Zimu Wei, Sara R. Abrahams, Alexey S. Revenko, Fenil Shah, Lindsey A. Miles, Robert J. Parmer, Bas de Laat, Alisa S. Wolberg, James P. Luyendyk, Melissa L. Fishel, Matthew J. Flick
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal metastatic disease associated with robust activation of the coagulation and fibrinolytic systems. Primary fibrinolytic protease plasminogen promotes PDAC tumor growth and metastatic potential through engaging plasminogen receptors on tumor cells.
MOLECULAR ONCOLOGY
(2024)
Article
Oncology
Ailin Wei, Huiling Zhao, Xue Cong, Linyao Wang, Yiyang Chen, Juxiang Gou, Ziyi Hu, Xiuying Hu, Yali Tian, Ka Li, Yufeng Deng, Haojiang Zuo, Mei Rosemary Fu
Summary: This study investigated the association between oral mycobiota and pancreatic ductal adenocarcinoma (PDAC). The findings suggest that PDAC patients have increased fungal abundance and decreased fungal diversity compared to healthy controls. Certain fungal species, such as Aspergillus and Cladosporium, showed high classification powers in distinguishing PDAC patients from healthy controls. The findings highlight the potential of using oral mycobiota as a biomarker for early detection and prevention of PDAC.
Review
Oncology
Zoe X. Malchiodi, Louis M. Weiner
Summary: This article discusses the interaction between natural killer (NK) cells and cancer-associated fibroblasts (CAFs) in pancreatic cancer, highlighting the importance of developing novel targeted therapies. Understanding and targeting this interplay may hold potential for improving immune response and survival in patients with pancreatic cancer.
Letter
Oncology
Xingyi Pan, Jiaojiao Zhou, Qian Xiao, Kenji Fujiwara, Mengwen Zhang, Guanglan Mo, Wei Gong, Lei Zheng
Summary: The study revealed that tumor cells from pancreatic ductal adenocarcinoma (PDAC) with liver or lung-specific metastatic potentials induce different methylation and metabolic gene expression in cancer-associated fibroblasts (CAFs), affecting CAF phenotypes. CAFs from liver metastasis showed a more homogeneous phenotype, while CAFs from lung metastasis maintained heterogeneity.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
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)
Review
Medicine, General & Internal
Natalia Michalak, Ewa Malecka-Wojciesko
Summary: This study summarizes the known modifiable risk factors for pancreatic ductal adenocarcinoma (PDAC) as well as recent reports. PDAC has a late diagnosis and poor prognosis, making accurate analysis of risk factors crucial. The incidence of PDAC is increasing, with the lowest five-year survival rate among all tumors. The impact of cigarette smoking, alcohol consumption, and chronic pancreatitis in increasing the risk of PDAC is continuously confirmed, while emerging reports focus on the influence of lifestyle factors and hepatotropic viruses.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Surgery
Alessandra L. Moore, Heather E. desJardins-Park, Bryan A. Duoto, Shamik Mascharak, Matthew P. Murphy, Dre M. Irizarry, Deshka S. Foster, Ruth E. Jones, Leandra A. Barnes, Clement D. Marshall, Ryan C. Ransom, Gerlinde Wernig, Michael T. Longaker
Article
Surgery
Michael S. Hu, Zeshaan N. Maan, Tripp Leavitt, Wan Xing Hong, Robert C. Rennert, Clement D. Marshall, Mimi R. Borrelli, Ted N. Zhu, Mikaela Esquivel, Andrew Zimmermann, Adrian McArdle, Michael T. Chung, Deshka S. Foster, Ruth Ellen Jones, Geoffrey C. Gurtner, Amato J. Giaccia, H. Peter Lorenz, Irving L. Weissman, Michael T. Longaker
Summary: The study shows that full thickness excisional wounds have the ability to inhibit tumor growth in vivo, with this effect being dose-dependent and influenced by the proximity between wounds and tumors. Additionally, the recruitment of circulating progenitor cells by healing wounds was significantly higher compared to growing tumors.
Article
Gastroenterology & Hepatology
Andrea T. Fisher, Ashley L. Titan, Deshka S. Foster, Patrick J. Worth, George A. Poultsides, Brendan C. Visser, Monica M. Dua, Jeffrey A. Norton
JOURNAL OF GASTROINTESTINAL SURGERY
(2020)
Article
Chemistry, Analytical
Michael Januszyk, Kellen Chen, Dominic Henn, Deshka S. Foster, Mimi R. Borrelli, Clark A. Bonham, Dharshan Sivaraj, Dhananjay Wagh, Michael T. Longaker, Derrick C. Wan, Geoffrey C. Gurtner
Article
Medicine, General & Internal
Stephen R. Knight, Catherine A. Shaw, Riinu Pius, Thomas M. Drake, Lisa Norman, Adesoji O. Ademuyiwa, Adewale O. Adisa, Maria-Lorena Aguilera-Arevalo, Sara W. Al-Saqqa, Ibrahim S. Al-Slaibi, Aneel Bhangu, Bruce M. Biccard, Peter Brocklehurst, Ainhoa Costas-Chavarri, Kathryn M. Chu, Anna J. Dare, Muhammed Elhadi, Cameron J. Fairfield, J. Edward Fitzgerald, Dhruv N. Ghosh, James Glasbey, Mark I. van Berge Henegouwen, J. C. Allen Ingabire, T. Peter Kingham, Marie Carmela M. Lapitan, Ismail Lawani, Bettina Lieske, Richard J. Lilford, Janet Martin, Kenneth A. Mclean, Rachel L. Moore, Dion Morton, Dmitri Nepogodiev, Faustin Ntirenganya, Francesco Pata, Thomas D. Pinkney, Ahmad U. Qureshi, Antonio Ramos-De la Medina, Aya M. Riad, Hosni Khairy Salem, Joana Simoes, Richard T. Spence, Neil J. Smart, Stephen Tabiri, Hannah S. Thomas, Thomas G. Weiser, Malcolm A. West, John Whitaker, Ewen M. Harrison
Summary: This study compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in low-income and middle-income countries, finding that patients in these countries presented with more advanced disease and had higher 30-day mortality rates, as well as more severe postoperative deaths caused by complications.
Article
Multidisciplinary Sciences
Shamik Mascharak, Heather E. DesJardins-Park, Michael F. Davitt, Michelle Griffin, Mimi R. Borrelli, Alessandra L. Moore, Kellen Chen, Bryan Duoto, Malini Chinta, Deshka S. Foster, Abra H. Shen, Michael Januszyk, Sun Hyung Kwon, Gerlinde Wernig, Derrick C. Wan, H. Peter Lorenz, Geoffrey C. Gurtner, Michael T. Longaker
Summary: This study identified a dermal ENF subpopulation that activates Engrailed-1 expression through mechanical tension, promoting skin tissue regeneration. Blocking mechanotransduction signaling can stimulate ENF-mediated wound regeneration, leading to recovery of skin appendages and mechanical strength.
Article
Oncology
Tammy Ju, Deshka Foster, Ashley Titan, Saleh Najjar, Gregory R. Bean, Kristen Ganjoo, Irene Wapnir
Summary: Radiation-induced breast angiosarcoma, also known as secondary angiosarcoma (SAS), is a rare entity with a high risk of metastatic recurrence. In this case study, intraoperative fluorescence-based skin angiography was used to guide surgical resection following a novel immunotherapy-based regimen for SAS, resulting in a complete pathological response.
Article
Medicine, General & Internal
Zeshaan N. Maan, Yuval Rinkevich, Janos Barrera, Kellen Chen, Dominic Henn, Deshka Foster, Clark Andrew Bonham, Jagannath Padmanabhan, Dharshan Sivaraj, Dominik Duscher, Michael Hu, Kelley Yan, Michael Januszyk, Michael T. Longaker, Irving L. Weissman, Geoffrey C. Gurtner
Summary: Hand injuries often lead to functional impairments, but fingertip regeneration is associated with hair follicle differentiation, Wnt, and hedgehog signaling pathways. Further research into these pathways may improve therapeutic outcomes for hand injuries in humans.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Oncology
Joseph D. Forrester, Deshka Foster, James M. Ford, Teri A. Longacre, Uri Ladabaum, Sara Fry, Jeffrey A. Norton
Summary: This study reports the long-term outcomes of total gastrectomy for patients with a family history of gastric cancer and CDH1 gene mutations that predispose to hereditary diffuse gastric cancer (HDGC). The results show that total gastrectomy is recommended for patients with inherited CDH1 mutations and the long-term quality of life following the surgery is acceptable.
Article
Oncology
Deshka S. Foster, Michael Januszyk, Daniel Delitto, Kathryn E. Yost, Michelle Griffin, Jason Guo, Nicholas Guardino, Andrea E. Delitto, Malini Chinta, Austin R. Burcham, Alan T. Nguyen, Khristian E. Bauer-Rowe, Ashley L. Titan, Ankit Salhotra, R. Ellen Jones, Oscar da Silva, Hunter G. Lindsay, Charlotte E. Berry, Kellen Chen, Dominic Henn, Shamik Mascharak, Heather E. Talbott, Alexia Kim, Fatemeh Nosrati, Dharshan Sivaraj, R. Chase Ransom, Michael Matthews, Anum Khan, Dhananjay Wagh, John Coller, Geoffrey C. Gurtner, Derrick C. Wan, Irene L. Wapnir, Howard Y. Chang, Jeffrey A. Norton, Michael T. Longaker
Summary: This study investigates the heterogeneity of cancer-associated fibroblasts (CAFs) using a comprehensive multiomics approach, identifying three superclusters of CAFs. The study finds that disrupting mechanical force or immune checkpoint inhibition therapy leads to changes in the distribution of CAF subpopulations and affects tumor growth. The results of this research are important for expanding our understanding of CAF biology, identifying regulatory pathways in CAF differentiation, and discovering therapeutic targets for tumor treatment.
Article
Biochemical Research Methods
Michael Januszyk, Michelle Griffin, Shamik Mascharak, Heather E. Talbott, Kellen Chen, Dominic Henn, Amanda F. Spielman, Jennifer B. L. Parker, Norah E. Liang, Asha Cotterell, Nicholas Guardino, Deshka S. Foster, Dhananjay Wagh, John Coller, Geoffrey C. Gurtner, Derrick C. Wan, Michael T. Longaker
Summary: This study presents a protocol using oligonucleotide barcoding for the tagging and pooling of multiple healing wound samples, reducing the cost of single cell RNA sequencing for large-scale studies. The protocol is applicable to multiple species, including mice, rats, pigs, and humans.
Meeting Abstract
Surgery
Jason L. Guo, Shamik Mascharak, Deshka S. Foster, Nicholas J. Guardino, Michelle Griffin, Elisabeth Miller, Shyam Raghavan, Teri A. Longacre, Jeffrey A. Norton, Michael T. Longaker
JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
(2022)
Meeting Abstract
Surgery
Khristian E. Bauer-Rowe, Michelle Griffin, Deshka Foster, Heather E. desJardins-Park, Shamik Mascharak, Jeffrey A. Norton, Jeong S. Hyun, Michael T. Longaker
JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
(2021)
Meeting Abstract
Surgery
Deshka S. Foster, Michael Januszyk, Kathryn E. Yost, Malini Chinta, Ashley L. Titan, Irene L. Wapnir, Geoffrey C. Gurtner, Howard Y. Chang, Jeffrey A. Norton, Michael T. Longaker
JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
(2021)