Review
Oncology
Linh-Huyen Truong, Siim Pauklin
Summary: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers with no effective treatment currently available. The complexity and dynamics of the tumor microenvironment (TME) play a crucial role in PDAC treatment resistance, emphasizing the need for a detailed understanding of the TME. Insights into the heterogeneous TME composition and interplay among its components are essential for developing more efficient therapeutic approaches for PDAC.
Article
Medicine, Research & Experimental
Yifan Liu, Yansha Sun, Peng Wang, Songling Li, Yiwei Dong, Min Zhou, Bizhi Shi, Hua Jiang, Ruixin Sun, Zonghai Li
Summary: In this study, the combined antitumor activity of FAP-targeted and CLDN18.2-targeted CAR-T cells against PDAC was explored. The results showed that prior infusion of FAP-targeted CAR-T cells could eliminate CAFs and enhance the anti-PDAC efficacy of subsequently infused CLDN18.2-targeted CAR-T cells. Moreover, FAP-targeted CAR-T cells could suppress the recruitment of MDSCs and promote the survival of CD8(+) T cells and CAR-T cells in tumor tissue.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Review
Cell Biology
Ester Pfeifer, Joy M. Burchell, Francesco Dazzi, Debashis Sarker, Richard Beatson
Summary: PDAC is associated with poor prognosis due to advanced stage at diagnosis and aggressive tumor biology. Efforts to target CAF, a predominant cell type in the tumor microenvironment, have shown disappointing results in clinical trials.
Review
Cell Biology
Martina Bedeschi, Noemi Marino, Elena Cavassi, Filippo Piccinini, Anna Tesei
Summary: Prostate cancer is a common cancer in European males and androgen deprivation therapy is the standard treatment. However, resistance to this therapy has led to cancer progression and long-term side effects. Studies have shown that cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment (TME) and targeting them could be a potential therapeutic approach to overcome therapy resistance in prostate cancer.
Review
Oncology
Mo Zhang, Zhixian Chen, Yan Wang, Hongbo Zhao, Yan Du
Summary: This review focuses on the important role of cancer-associated fibroblasts (CAFs) in the ovarian cancer tumor microenvironment. Different subtypes of CAFs have specific functions in tumor pathogenesis and can be potential treatment targets. Several clinical or preclinical trials have targeted CAFs to enhance ovarian cancer treatment outcomes.
Review
Oncology
Ryota Takahashi, Hideaki Ijichi, Mitsuhiro Fujishiro
Summary: Pancreatic cancer is highly lethal and understanding the role of nerves in the tumor microenvironment is crucial. Different types of nerves have been identified in the pancreatic cancer microenvironment and they play important roles in tumor biology. Neural signaling affects not only neural cells, but also tumor cells and immune cells, impacting tumor growth, inflammation, and anti-tumor immunity. Therefore, neural signaling in the pancreatic cancer microenvironment may serve as novel therapeutic targets. Modulating neural signaling could be a therapeutic strategy that targets the entire tumor microenvironment.
Review
Oncology
Kendelle J. Murphy, Cecilia R. Chambers, David Herrmann, Paul Timpson, Brooke A. Pereira
Summary: PDAC is a highly lethal solid malignancy with a low five-year survival rate of around 10%. The interactions between tumor and stromal or immune cells in the pancreatic tumor microenvironment play a critical role in both promoting and restraining the development and progression of PDAC. Understanding the role of the extracellular matrix and stromal cells like cancer-associated fibroblasts (CAFs) is vital for developing effective treatment strategies for this aggressive disease.
Review
Cell Biology
Deepshikha Mishra, Debabrata Banerjee
Summary: The cancer secretome is a collection of proteins released by cancer cells, which provides important information for cancer diagnosis and treatment. While previous studies have focused on the secretome of cancer cells, the contribution of stromal cells, particularly cancer-associated fibroblasts (CAFs), needs to be further explored. Investigating the secretome of CAFs can lead to the discovery of novel biomarkers and potential therapeutic targets, and enhance our understanding of personalized cancer treatment.
Review
Oncology
Tomohiko Shinkawa, Kenoki Ohuchida, Masafumi Nakamura
Summary: Stroma-targeting therapy in pancreatic ductal adenocarcinoma (PDAC) has been extensively studied, but no effective candidates have been found yet. Cancer-associated fibroblasts (CAFs) have been traditionally considered tumor-promoting, but recent studies suggest the existence of tumor-suppressive CAF subtypes. Single-cell RNA sequencing has revealed the heterogeneity within the tumor microenvironment of PDAC, including CAFs and tumor immunity. The clarification of this heterogeneity is urgently needed to develop effective therapeutic strategies for PDAC.
Review
Biotechnology & Applied Microbiology
James Mason, Daniel Ohlund
Summary: The tumor microenvironment plays a crucial role in cancer initiation and progression. Understanding the interactions between cancer cells and the various components of the tumor microenvironment is essential for developing effective treatment strategies. Co-culture models have been developed to study these interactions, providing insights into the role of the stroma and tumor-stromal interactions.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Woosol Chris Hong, Da Eun Lee, Hyeon Woong Kang, Myeong Jin Kim, Minsoo Kim, Ju Hyun Kim, Sungsoon Fang, Hyo Jung Kim, Joon Seong Park
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly form of pancreatic cancer and the role of CD74 in PDAC is not well understood. Silencing CD74 in the pancreatic cancer cell line Capan-1 led to reduced cell proliferation, migration, invasion, increased apoptosis, and decreased expression and secretion of S100A8 and S100A9. The study suggests that CD74 may serve as a potential diagnostic biomarker and therapeutic target for pancreatic cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Jin Yuan, Xiaoyang Li, Shengji Yu
Summary: Three-dimensional cancer organoids derived from self-organizing cancer stems faithfully mimic the structure, features, and genetic signatures of tumors. Co-culture models involving immune cells or fibroblasts provide a means to investigate the tumor microenvironment and molecular interactions, potentially benefiting cancer research and precision medicine. However, the lack of a complete tumor microenvironment remains a major limitation that needs to be addressed for further improvements.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Ryota Ando, Akihiro Sakai, Tadashi Iida, Kunio Kataoka, Yasuyuki Mizutani, Atsushi Enomoto
Summary: Recent research has shown that cancer-associated fibroblasts (CAFs) in pancreatic ductal adenocarcinoma (PDAC) have diverse states and plasticity, which can either suppress or promote cancer progression. These heterogeneous CAFs also affect the sensitivity of PDAC to anticancer therapeutics. Further studies are needed to understand the roles of CAFs in disease progression and to develop therapeutics that modulate the tumor microenvironment in PDAC.
Review
Biochemistry & Molecular Biology
Rita Rebelo, Cristina P. R. Xavier, Elisa Giovannetti, M. Helena Vasconcelos
Summary: Pancreatic stellate cells (PSCs) and cancer-associated fibroblasts (CAFs) play important roles in the pancreatic tumor microenvironment (TME) by modulating fibrosis. The dense stroma formed by these cells leads to immunosuppression and therapy resistance, contributing to the treatment failure in pancreatic ductal adenocarcinoma (PDAC). Understanding the heterogeneity of CAFs and their interaction with PDAC cells is crucial for developing effective therapies and biomarkers.
TRENDS IN MOLECULAR MEDICINE
(2023)
Article
Oncology
Koelina Ganguly, Ashu Shah, Pranita Atri, Sanchita Rauth, Moorthy P. Ponnusamy, Sushil Kumar, Surinder K. Batra
Summary: This review provides a comprehensive understanding of the interplay between chemokines and mucinome in the stromal modulation and immune suppression of pancreatic cancer. It highlights the need for future studies to decipher the complexities of chemokine-mediated control and its potential application in prognostication and stratification of pancreatic cancer patients for immunotherapy.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Surgery
Julian Michelotto, Joseph M. G. V. Gassner, Simon Moosburner, Vanessa Muth, Madhukar S. Patel, Markus Selzner, Johann Pratschke, Igor M. Sauer, Nathanael Raschzok
Summary: Ex vivo liver machine perfusion has been shown in prospective clinical studies to be a safe and feasible strategy for expanding the donor pool in both standard and extended criteria donors. Current research is focused on using ex vivo perfusion in extended criteria donors and declined organs.
LANGENBECKS ARCHIVES OF SURGERY
(2021)
Article
Medicine, General & Internal
Francesca Borlak, Anja Reutzel-Selke, Anja Schirmeier, Julia Gogolok, Ellen von Hoerschelmann, Igor M. Sauer, Johann Pratschke, Marcus Bahra, Rosa B. Schmuck
Summary: In pancreatobiliary tumors, there is a significant overexpression of key proteins in the Notch signaling pathway, although this does not have a significant impact on patient survival. Further studies are needed to determine the relevance of the Notch pathway for patient survival.
MEDICINA-LITHUANIA
(2021)
Article
Biochemical Research Methods
Nicolai Seiffert, Peter Tang, Eriselda Keshi, Anja Reutzel-Selke, Simon Moosburner, Hannah Everwien, Dag Wulsten, Hendrik Napierala, Johann Pratschke, Igor M. Sauer, Karl H. Hillebrandt, Benjamin Struecker
Summary: A refined decellularization process was used to create TEVG with retained ECM and mechanical quality, providing a platform for developing small-diameter TEVG. Isolation of ECFC from high cardiovascular risk group was successful and sufficient. Survival of diabetic ECFC depended on support from rMSC/hMSC under static conditions, with a limited survival time of 14 days post seeding.
JOURNAL OF BIOLOGICAL ENGINEERING
(2021)
Article
Oncology
Ellen Von Hoerschelmann, Christopher C. M. Neumann, Matthaus Felsenstein, Julia Gogolok, Anja Reutzel-Selke, Igor M. Sauer, Johann Pratschke, Marcus Bahra, Rosa B. Schmuck
Summary: CAFs play a crucial role in the migration of PDAC cells, enhancing their ability to migrate through paracrine effects. Compared to benign fibroblasts, CAFs exhibit higher migratory capacity, potentially making them a promising therapeutic target for treating PDAC.
ANTICANCER RESEARCH
(2021)
Correction
Engineering, Biomedical
Christoph Rueger, Markus A. Feufel, Simon Moosburner, Christopher ozbek, Johann Pratschke, Igor M. Sauer
INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY
(2021)
Article
Biochemical Research Methods
Eriselda Keshi, Peter Tang, Marie Weinhart, Hannah Everwien, Simon Moosburner, Nicolai Seiffert, Michael Lommel, Ulrich Kertzscher, Brigitta Globke, Anja Reutzel-Selke, Benjamin Struecker, Johann Pratschke, Igor Maximillian Sauer, Nils Haep, Karl Herbert Hillebrandt
Summary: This study demonstrates the effectiveness of surface modification of vascular grafts in enhancing their thromboresistance in an ex vivo whole blood perfusion system. It is the first study to expose engineered vascular grafts to human whole blood immediately after seeding, showing promising results in preventing thrombus formation and maintaining platelet counts.
JOURNAL OF BIOLOGICAL ENGINEERING
(2021)
Review
Oncology
Sandra Pavicevic, Sophie Reichelt, Deniz Uluk, Isabella Lurje, Cornelius Engelmann, Dominik P. Modest, Uwe Pelzer, Felix Krenzien, Nathanael Raschzok, Christian Benzing, Igor M. Sauer, Sebastian Stintzing, Frank Tacke, Wenzel Schoening, Moritz Schmelzle, Johann Pratschke, Georg Lurje
Summary: Cholangiocarcinoma is a rapidly increasing global malignancy of the biliary tract, often presenting with advanced or unresectable disease. Biomarkers obtained from patients' serum or tumor tissue could help guide therapy and identify those at higher risk of recurrence. Genetic aberrations in cholangiocarcinoma have also been linked with improved response to targeted therapies. This review provides an overview of prognostic and predictive biomarkers in cholangiocarcinoma.
Article
Medicine, General & Internal
Matthaus Felsenstein, Flora Lindhammer, Mathilde Feist, Karl Herbert Hillebrandt, Lea Timmermann, Christian Benzing, Brigitta Globke, Dario Zocholl, Mengwen Hu, Uli Fehrenbach, Bruno Valentin Sinn, Uwe Pelzer, Igor Maximillian Sauer, Johann Pratschke, Thomas Malinka
Summary: This study confirms the improvement in long-term survival of PDAC-resected cancer patients with Pn0, and highlights the significant impact of perineural invasion on the long-term survival of formally curative patients. These findings provide new insights into risk stratification and multimodal treatment strategies for pancreatic cancer patients.
JOURNAL OF CLINICAL MEDICINE
(2022)
Letter
Gastroenterology & Hepatology
Simon Moosburner, Igor M. Sauer, Bjoern Weiss, Johann Pratschke, Nathanael Raschzok
JOURNAL OF HEPATOLOGY
(2023)
Article
Cell & Tissue Engineering
Eriselda Keshi, Peter Tang, Tobias Lam, Simon Moosburner, Luna Haderer, Anja Reutzel-Selke, Lutz Kloke, Johann Pratschke, Igor Maximilian Sauer, Karl Herbert Hillebrandt
Summary: Islet transplantation for the treatment of type 1 diabetes has been unsuccessful in long-term follow-up. In this study, a proof-of-concept islet embedding structure (IES) was 3D printed using biocompatible ink. The IES consisted of a vascular system surrounding a central cavity for the islets. Preliminary experiments showed successful engraftment of human islets within the IES, highlighting the importance of co-culture and the islet niche.
TISSUE ENGINEERING PART C-METHODS
(2023)
Article
Oncology
Sebastian Knitter, Gregor Duwe, Anika Sophie Beierle, Sina Pesthy, Paul Viktor Ritschl, Karl Herbert Hillebrandt, Alexander Arnold, Thomas Malinka, Dominik Paul Modest, Marcus Bahra, Johann Pratschke, Igor Maximilian Sauer, Moritz Schmelzle, Andreas Andreou
Summary: This study investigated the protective effects of inhibiting vascular endothelial growth factor (VEGF) on the development of sinusoidal obstruction syndrome (SOS) in mice with colorectal liver metastases (CLM) undergoing oxaliplatin-based chemotherapy. The results showed that VEGF inhibition reduced the incidence of SOS, potentially through changes in the VEGF pathway. This suggests that inhibiting VEGF may help reduce complications after liver resection in CLM patients. Further clinical studies are needed to confirm these findings.
Article
Gastroenterology & Hepatology
Simon Moosburner, Igor M. Sauer, Frank Forster, Thomas Winklmann, Joseph Maria George Vernon Gassner, Paul V. Ritschl, Robert Ollinger, Johann Pratschke, Nathanael Raschzok
Summary: Strategies to reduce the incidence of early allograft dysfunction (EAD) are needed to control costs in liver transplantation, as our study found that EAD leads to significantly higher hospital costs primarily attributed to recipient health status.
HEPATOLOGY COMMUNICATIONS
(2021)