Article
Medicine, Research & Experimental
Zehua Zhao, Tianming Li, Liping Sun, Yuan Yuan, Yanmei Zhu
Summary: This review summarizes the current knowledge of the role of cancer-associated fibroblasts (CAFs) in inducing drug resistance in tumor microenvironment. It emphasizes the importance of in-depth understanding of the cross-talk mechanisms between CAFs and cancer cells in guiding the development of new anticancer strategies.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Oncology
Richard A. O'Connor, Vishwani Chauhan, Layla Mathieson, Helen Titmarsh, Lilian Koppensteiner, Irene Young, Guilia Tagliavini, David A. Dorward, Sandrine Prost, Kevin Dhaliwal, William A. Wallace, Ahsan R. Akram
Summary: The success of immune checkpoint therapy suggests that tumor-reactive T cells can eliminate cancer cells but are constrained by immunosuppression. In the tumor micro-environment, cancer-associated fibroblasts (CAFs) play a significant role and interact bidirectionally with T cells. These interactions lead to the modulation of immune inhibitory factors and the promotion of an exhausted cytotoxic phenotype in T cells, highlighting the complexity of immune regulation in the tumor micro-environment.
Article
Cell Biology
Neus Bota-Rabassedas, Priyam Banerjee, Yichi Niu, Wenjian Cao, Jiayi Luo, Yuanxin Xi, Xiaochao Tan, Kuanwei Sheng, Young-Ho Ahn, Sieun Lee, Edwin Roger Parra, Jaime Rodriguez-Canales, Jacob Albritton, Michael Weiger, Xin Liu, Hou-Fu Guo, Jiang Yu, B. Leticia Rodriguez, Joshua J. A. Firestone, Barbara Mino, Chad J. Creighton, Luisa M. Solis, Pamela Villalobos, Maria Gabriela Raso, Daniel W. Sazer, Don L. Gibbons, William K. Russell, Gregory D. Longmore, Ignacio I. Wistuba, Jing Wang, Harold A. Chapman, Jordan S. Miller, Chenghang Zong, Jonathan M. Kurie
Summary: Cancer cells alter cancer-associated fibroblasts through specific secretory programs and repulsion processes, promoting cancer cell metastasis and sensitivity to pro-metastatic signals from fibroblasts.
Review
Biochemistry & Molecular Biology
Yu-Hsuan Hung, Li-Tzong Chen, Wen-Chun Hung
Summary: The microenvironment in tumors is complex and consists of different cell types and stromal proteins. The interactions between cancer cells, fibroblasts, and immune cells play a crucial role in promoting tumorigenesis. However, the multi-directional interplays between these cell types in vitro and in vivo are still not well understood. This review summarizes recent studies on the interaction of the Trinity members in the tumor microenvironment and proposes a functional network for their communication. The underlying mechanisms mediating these interplays are also discussed. Moreover, the correlations between the alterations in the distribution and functionality of these cell types under different circumstances are reviewed. Finally, the potential application of CD8(+) T cell-oriented therapy in the treatment of pancreatic cancer is highlighted.
Article
Oncology
Go Itoh, Kurara Takagane, Yuma Fukushi, Sei Kuriyama, Michinobu Umakoshi, Akiteru Goto, Kazuyoshi Yanagihara, Masakazu Yashiro, Masamitsu Tanaka
Summary: This study demonstrates a novel mechanism for expanding pro-tumor fibroblasts through the education of normal fibroblasts by cancer-associated fibroblasts (CAFs). The resulting CAF-educated fibroblasts (CEFs) generated reactive oxygen species and induced the expression of inflammatory cytokines and extracellular matrix proteins, influencing T-cell cytotoxic effects and tumor spreading. The upregulation of ASPN may play a key role in facilitating tumor dissemination and T-cell suppression.
MOLECULAR ONCOLOGY
(2022)
Article
Oncology
Weiyu Ge, Ming Yue, Ruirong Lin, Tianhao Zhou, Haiyan Xu, Yu Wang, Tiebo Mao, Shumin Li, Xiuqi Wu, Xiaofei Zhang, Yongchao Wang, Jingyu Ma, Yanling Wang, Shengbai Xue, Daiyuan Shentu, Jiujie Cui, Liwei Wang
Summary: Our study identified a novel metabolic cancer associated fibroblasts subset (meCAFs) enriched in pancreatic ductal adenocarcinoma (PDAC) and related to CD8+ T cells accumulation. The abundance of meCAFs was associated with poor prognosis but better immunotherapy responses in PDAC patients. We demonstrated that PLA2G2A+ meCAFs impede the antitumor immune function of CD8+ T cells and facilitate tumor immune escape in PDAC.
Review
Biochemistry & Molecular Biology
Anna Valeria Samarelli, Valentina Masciale, Beatrice Aramini, Georgina Pamela Colo, Roberto Tonelli, Alessandro Marchioni, Giulia Bruzzi, Filippo Gozzi, Dario Andrisani, Ivana Castaniere, Linda Manicardi, Antonio Moretti, Luca Tabbi, Giorgia Guaitoli, Stefania Cerri, Massimo Dominici, Enrico Clini
Summary: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease of unknown cause, potentially linked to smoking and environmental risk factors that may increase the risk of lung cancer. Common cellular and molecular mechanisms shared between IPF and lung cancer could lead to the identification of new therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Imke Stouten, Nadine van Montfoort, Lukas J. A. C. Hawinkels
Summary: The lack of response to therapy in pancreatic ductal adenocarcinoma (PDAC) patients has led to PDAC having a low survival rate. Immunotherapy has shown promise in other cancer types but is ineffective in PDAC due to its unique tumor microenvironment (TME) with low immune activity. Cancer-associated fibroblasts (CAFs) in the TME may play a role in the low immunotherapy response. Understanding the interactions between CAFs and immune cells in the TME could improve immunotherapy for PDAC and similar cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Arian Ansardamavandi, Mohammad Tafazzoli-Shadpour
Summary: The function of biological tissues is regulated at cellular level and is highly influenced by the physical microenvironment. In cancer, both chemical and physical signaling cascades play important roles in tumor growth and invasion, with cancer associated fibroblasts (CAFs) being crucial in this process. The interaction between cells and ECM, through mechanosensing pathways, defines the progression and invasion of cancer cells.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Oncology
Katherine E. Richards, Weikun Xiao, Reginald Hill
Summary: In this study, a novel mechanism was discovered in which exosomes derived from cancer-associated fibroblasts (CAFs) promote tumor proliferation and chemoresistance by suppressing the tumor suppressor PTEN. These findings provide insights into the potential use of exosome inhibitors as therapeutics to improve the effectiveness of chemotherapy.
Article
Cell Biology
Lei Xi, Meixi Peng, Shuiqing Liu, Yongcan Liu, Xueying Wan, Yixuan Hou, Yilu Qin, Liping Yang, Shanchun Chen, Huan Zeng, Yong Teng, Xiaojiang Cui, Manran Liu
Summary: Studies have shown that oxidized ATM phosphorylates BNIP3 to induce autophagosome accumulation and exosome release in breast CAFs. In addition, oxidized ATM phosphorylates ATP6V1G1, leading to lysosomal dysfunction and facilitating exosome release through fusion with multi-vesicular bodies. This process ultimately stimulates non-canonical NF-kappa B signaling and enhances the invasive abilities of recipient breast cancer cells.
JOURNAL OF EXTRACELLULAR VESICLES
(2021)
Article
Cell Biology
Brett H. Herzog, John M. Baer, Nicholas Borcherding, Natalie L. Kingston, Jad I. Belle, Brett L. Knolhoff, Graham D. Hogg, Faiz Ahmad, Liang- Kang, Jessica Petrone, Chieh-Yu Lin, Ramaswamy Govindan, David G. DeNardo
Summary: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related deaths. Fibrosis in NSCLC leads to reduced immune surveillance and poor responsiveness to immune checkpoint blockade. Fibrosis-induced alterations in dendritic cells and macrophage phenotypes contribute to immunosuppression. Targeting fibrosis through transforming growth factor-II receptor signaling overcomes immunotherapeutic resistance and enhances the efficacy of immune checkpoint blockade in the context of chemotherapy.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
XuKai Liu, JiZu Tang, LiQiang Peng, HaiBo Nie, YuanGuang Zhang, Pan Liu
Summary: Dysregulation of autophagy in cancer-associated fibroblasts has been shown to contribute to the malignant phenotypes of human tumors. This study investigated the role of CAFs autophagy in prostate cancer. Results demonstrated that CAFs had higher levels of autophagy compared to normal fibroblasts. Furthermore, inhibition of autophagy in CAFs suppressed the proliferation, migration, and invasion capabilities of PCa cells. Silencing of ATG5 in CAFs also inhibited fibroblast autophagy and suppressed malignant phenotypes of PCa cells. These findings suggest that CAFs play a promotive role in PCa through ATG5-dependent autophagy, providing a novel mechanism for PCa progression.
Article
Pathology
Yi Zhao, Jiaqiang Sun, Yue Liang, Xuan Jiang, Xiaomin Tang, Yuxuan Sun, Chenyu Xu, Guanglun Wan, Jingwu Sun, Chunchen Pan
Summary: This study found that increased expression of ST2 on Tregs is associated with IL-33 signaling derived from CAFs in laryngeal cancer. The tumor microenvironment is the main source of IL-33, with fibroblasts being the primary producers. ST2-expressing Tregs exhibit enhanced proliferation and expression of immune-suppressive molecules. High expression of ST2 on Tregs, as well as the presence of IL-33-positive CAFs, is associated with worse survival outcomes in laryngeal cancer.
PATHOLOGY RESEARCH AND PRACTICE
(2022)
Article
Oncology
Jie Chen, Yan Wang, Weimin Zhang, Di Zhao, Lingyuan Zhang, Jing Zhang, Jiawen Fan, Qimin Zhan
Summary: The activation of CAFs by NOX5 facilitates tumor malignancy in ESCC by inducing a cytokine cascade that fuels the progression of tumor cells.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Steven J. Mileto, Thierry Jarde, Kevin O. Childress, Jaime L. Jensen, Ashleigh P. Rogers, Genevieve Kerr, Melanie L. Hutton, Michael J. Sheedlo, Sarah C. Bloch, John A. Shupe, Katja Horvay, Tracey Flores, Rebekah Engel, Simon Wilkins, Paul J. McMurrick, D. Borden Lacy, Helen E. Abud, Dena Lyras
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Review
Oncology
Christine Koulis, Raymond Yap, Rebekah Engel, Thierry Jarde, Simon Wilkins, Gemma Solon, Jeremy D. Shapiro, Helen Abud, Paul McMurrick
Correction
Neurosciences
David I. Finkelstein, Jessica L. Billings, Paul A. Adlard, Scott Ayton, Amelia Sedjahtera, Colin L. Masters, Simon Wilkins, David M. Shackleford, Susan A. Charman, Wojciech Bal, Izabela A. Zawisza, Ewa Kurowska, Andrew L. Gundlach, Sheri Ma, Ashley I. Bush, Dominic J. Hare, Philip A. Doble, Simon Crawford, Elisabeth C. L. Gautier, Jack Parsons, Penny Huggins, Kevin J. Barnham, Robert A. Cherny
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Surgery
Ali Riaz Baqar, Simon Wilkins, Wei Chun Wang, Karen Oliva, Suellyn Centauri, Raymond Yap, Paul McMurrick
Summary: This study aimed to compare the impact of extracorporeal side-to-side and end-to-side stapled anastomosis on outcomes after an oncological laparoscopic right hemicolectomy. The results showed that the type of stapling technique affected operative duration and postoperative ileus rates, but had no impact on lymph node yield or anastomotic leaks.
ANZ JOURNAL OF SURGERY
(2022)
Article
Gastroenterology & Hepatology
Rebekah M. Engel, Thierry Jarde, Karen Oliva, Genevieve Kerr, Wing Hei Chan, Sara Hlavca, David Nickless, Stuart K. Archer, Raymond Yap, Pravin Ranchod, Stephen Bell, Ann Niap, Christine Koulis, Ashley Chong, Simon Wilkins, Trevor C. Dale, Andrew J. Hollins, Paul J. McMurrick, Helen E. Abud
Summary: Patient-derived colorectal cancer organoids (PDCOs) have the potential utility in personalized cancer medicine, as they recapitulate key characteristics of the primary tumor and can be used as a powerful tool for cancer research.
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Surgery
Simon Wilkins, Raymond Yap, Shehara Mendis, Peter Carne, Paul J. McMurrick
Summary: Abdominoperineal resection (APR) of rectal cancer is associated with poorer outcomes than anterior resection. Extra-levator abdominoperineal excision (ELAPE) technique reduced intra-operative perforation (IOP) rates and circumferential resection margin (CRM) involvement, but increased wound complications. Studies suggest that sub-optimal surgical technique may be responsible for high CRM and IOP rates rather than the technique itself. ELAPE does not always have lower CRM involvement rates than APR and has higher morbidity. The impact of ELAPE on oncological outcomes is still uncertain.
FRONTIERS IN SURGERY
(2022)
Article
Oncology
Hengkang Yan, Mary E. Vail, Linda Hii, Nancy Guo, Paul J. McMurrick, Karen Oliva, Simon Wilkins, Nayanendu Saha, Dimitar B. Nikolov, Fook-Thean Lee, Andrew M. Scott, Peter W. Janes
Summary: ADAM10 is a cell surface protein that can control functions during normal development and become deregulated in cancer cells. Researchers developed an antibody that can detect the active form of ADAM10 and successfully used it to kill tumor cells.
Article
Surgery
Anna Taylor, Simon Wilkins, Nicholas Gelber, Wei Chun Wang, Karen Oliva, Raymond Yap, Paul McMurrick, Pravin Ranchod
Summary: The aim of this study was to assess the efficacy of intravenous hyoscine butylbromide on the accuracy of MRI rectal cancer staging. The results showed that while IV hyoscine butylbromide improved the accuracy of T2 and T3 staged rectal cancer, it had no effect on T1 staged cancer or N-staging. Therefore, department protocols may need to be re-assessed regarding the prescription of these medications for MRI rectal cancer staging.
ANZ JOURNAL OF SURGERY
(2023)
Article
Surgery
Christine Georges, Raymond Yap, Stephen Bell, Keith Chip Farmer, Lauren C. L. Cohen, Simon Wilkins, Suellyn Centauri, Rebekah Engel, Karen Oliva, Paul J. McMurrick
Summary: This retrospective study evaluated the impact of four colorectal surgical procedures on patient-reported outcome measures. The study found that patients who underwent a right hemicolectomy had the best post-operative function and reduced symptoms, while patients who underwent an ultra-low anterior resection or an abdominoperineal resection had the worst outcomes.
ANZ JOURNAL OF SURGERY
(2023)
Review
Oncology
Rezav Amiri Khosroshahi, Mohammad Heidari Seyedmahalle, Sheida Zeraattalab-Motlagh, Laleh Fakhr, Simon Wilkins, Hamed Mohammadi
Summary: This study aimed to investigate the dose-dependent effects of omega-3 fatty acids supplementation on inflammatory factors in cancer patients. The results showed that daily intake of 1 g of omega-3 fatty acids (oral/enteral) significantly reduced IL-6 and TNF-alpha levels. Intake of 0.5 g/kg/day of omega-3 fatty acids (parenteral) also had a positive impact on TNF-alpha, but with low certainty of evidence.
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
(2023)
Article
Nutrition & Dietetics
Reza Amiri Khosroshahi, Hamed Mohammadi, Maryam Barkhordar, Sheida Zeraattalab-Motlagh, Hossein Imani, Amirabbas Rashidi, Erfan Sadeghi, Simon Wilkins, Seyed Asadollah Mousavi
Summary: This study compared nutritional screening tools for patients with leukemia before allo-HSCT and found that there was good agreement between GLIM and NRS-2002, fair agreement between GLIM and ESPEN, and fair agreement between NRS-2002 and ESPEN. There was moderate agreement among all the tools. NRS-2002 is an accepted tool for screening malnutrition and showed good agreement with GLIM in this study. Further research is needed to introduce a valid tool in the HSCT setting.
FRONTIERS IN NUTRITION
(2023)
Article
Gastroenterology & Hepatology
Raymond Yap, Simon Wilkins, Mohammad Asghari-Jafarabadi, Karen Oliva, Wei Chun Wang, Suellyn Centauri, Paul J. McMurrick
Summary: This study aims to investigate the postoperative outcomes of colorectal cancer surgery in patients aged 80 and over. The results demonstrate that surgical treatment of older patients is safe with acceptable survival rates. However, efforts are needed to reduce complications in older patients.
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
(2023)
Article
Surgery
J. Gemma Solon, Karen Oliva, K. Chip Farmer, Wei Wang, Simon Wilkins, Paul J. McMurrick
Summary: This study evaluated the rate of lymph node metastases in patients undergoing surgical resection for malignant polyps removed endoscopically and found that tumor location may be a useful predictive marker. However, further research with larger sample sizes is needed to confirm this finding.
ANZ JOURNAL OF SURGERY
(2021)
