Review
Cardiac & Cardiovascular Systems
Jonathan Golledge, Shivshankar Thanigaimani, Janet T. Powell, Phil S. Tsao
Summary: Abdominal aortic aneurysm (AAA) causes a high number of deaths worldwide every year, but no drug therapy has been proven to effectively limit AAA growth in randomized controlled trials. Genome-wide association studies have identified potential drug targets, and treatments to reduce low-density lipoprotein cholesterol and smoking cessation are also being considered. However, previous placebo-controlled randomized trials have not shown convincing evidence of drug efficacy, mainly due to limitations such as small sample sizes and poor participant retention. Further large prospective studies on other targets are needed to address this issue.
EUROPEAN HEART JOURNAL
(2023)
Article
Hematology
Brian T. Steffen, James S. Pankow, Faye L. Norby, Pamela L. Lutsey, Ryan T. Demmer, Weihua Guan, Nathan Pankratz, Aixin Li, Guning Liu, Kunihiro Matsushita, Adrienne Tin, Weihong Tang
Summary: This study identified proteomic signatures and pathways related to 23 gene loci associated with abdominal aortic aneurysm (AAA). The results suggest that low levels of neogenin and kit ligand may be novel risk factors for AAA development.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Medicine, General & Internal
Tan Li, Bo Jiang, Yijun Wu, Jun Yang, Chunyan Ma, Yuan Yuan
Summary: This study investigated the correlation of single nucleotide polymorphisms (SNPs) in pri-miR-1-3p and mature miR-1-3p expression with postoperative mortality of abdominal aortic aneurysm (AAA) patients. The results showed that the variant genotypes of rs2155975 and rs4591246 were associated with increased all-cause mortality. Furthermore, low serum miR-1-3p levels before surgery were independently related to the incidents of all-cause death. This study demonstrated the importance of rs2155975 and rs4591246 polymorphisms and baseline serum miR-1-3p levels as promising markers to predict mortality among AAA patients following surgery.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Medicine, General & Internal
Petroula Nana, Konstantinos Dakis, Alexandros Brodis, Konstantinos Spanos, George Kouvelos
Summary: A systematic review examined the correlation of abdominal aortic aneurysm expansion rates with serum circulating biomarkers, identifying specific biomarkers potentially useful for individualized surveillance of patients with increased AAA growth rates. Various biomarkers, including D-dimers, LDL-C, HDL-C, and genetic factors, were found to be significantly associated with AAA growth rates, suggesting a potential role for serum biomarkers in patient monitoring.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Cardiac & Cardiovascular Systems
John Anagnostakos, Brajesh K. Lal
Summary: Abdominal aortic aneurysms (AAA) are common in older adults and can lead to serious morbidity and mortality if not treated promptly. The causes include trauma, infection, and inflammatory disorders, with risk factors such as smoking, advanced age, dyslipidemia, hypertension, and coronary artery disease. The pathophysiology involves arterial insult leading to inflammation and weakening of the arterial wall, requiring monitoring of size and growth rate to prevent rupture. Management options include controlling risk factors, surgical intervention based on risk assessment, and post-operative monitoring for complications. Advancements in technology have improved the diagnosis and treatment of AAA in recent years.
PROGRESS IN CARDIOVASCULAR DISEASES
(2021)
Article
Surgery
Sydney L. Olson, Annalise M. Panthofer, William Blackwelder, Michael L. Terrin, John A. Curci, B. Timothy Baxter, Fred A. Weaver, Jon S. Matsumura
Summary: This study examines the predictors of abdominal aortic aneurysm (AAA) volume growth and finds that baseline volume, tortuosity, maximum transverse diameter (MTD), current tobacco use, angiotensin II receptor blocker use, and history of diabetes mellitus are predictive of volume growth over time.
JOURNAL OF VASCULAR SURGERY
(2022)
Article
Cardiac & Cardiovascular Systems
Alexandra M. M. Filipkowski, Suman Kundu, Svetlana K. K. Eden, Charles W. W. Alcorn, Amy C. C. Justice, Kaku A. A. So-Armah, Hilary A. A. Tindle, Quinn S. S. Wells, Joshua A. A. Beckman, Matthew S. S. Freiberg, Aaron W. W. Aday
Summary: Compared with individuals without HIV infection, people with HIV do not have an increased risk of abdominal aortic aneurysm (AAA), but the risk of AAA is increased among HIV-infected individuals with low CD4+ T-cell counts or high HIV viral load.
Review
Cardiac & Cardiovascular Systems
Jinping Lin, Shuwei Chen, Yuanyuan Yao, Min Yan
Summary: Abdominal aortic aneurysms (AAAs) are characterized by localized dilation of the abdominal aorta and can lead to serious consequences. Aortic rupture is the main complication and causes a significant number of deaths worldwide. Despite progress in research, there is still a lack of established methods to slow down aneurysm dilation, emphasizing the need for further studies.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Review
Cardiac & Cardiovascular Systems
Li Yin, Eric William Kent, Bowen Wang
Summary: Abdominal aortic aneurysm (AAA) is a common focal dilation of the aorta in the elderly population, which can lead to aneurysmal rupture with a mortality rate of around 80%. Despite increased screening efforts, there is currently no cure to halt the expansion of AAA, partly due to incomplete understanding of its pathogenesis. Animal models provide valuable insights into AAA pathophysiology, but no single experimental model fully captures the complexity of the disease.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Leander Gaarde Melin, Julie Husted Dall, Jes S. Lindholt, Lasse B. Steffensen, Hans Christian Beck, Sophie L. Elkrog, Pernille D. Clausen, Lars Melholt Rasmussen, Jane Stubbe
Summary: Supplementation of cycloastragenol can inhibit the progression of abdominal aortic aneurysm, possibly by reducing matrix metalloprotease-2 activity, preserving elastin, and reducing calcification.
Article
Biochemistry & Molecular Biology
Juri Lieberg, Anders Wanhainen, Aigar Ottas, Mare Vahi, Mihkel Zilmer, Ursel Soomets, Martin Bjorck, Jaak Kals
Summary: The study found that levels of certain amino acids and phosphatidylcholines were significantly lower in abdominal aortic aneurysm (AAA) patients compared to controls. However, there were no significant differences in metabolites distinguishing between patients with slow or fast growth of the AAA.
Article
Chemistry, Multidisciplinary
Yuanyuan Zhang, Tianxiao Liu, Zhiyong Deng, Wenqian Fang, Xian Zhang, Shuya Zhang, Minjie Wang, Songyuan Luo, Zhaojie Meng, Jing Liu, Galina K. Sukhova, Dazhu Li, Andrew N. J. McKenzie, Peter Libby, Guo-Ping Shi, Junli Guo
Summary: The development of abdominal aortic aneurysms (AAA) leads to an increase in the accumulation of lesion group-2 innate lymphoid cells (ILC2) and IL5 in the blood. Deficiency of ILC2 or induced depletion of ILC2 in mice results in accelerated AAA growth, increased lesion inflammation, and systemic IL5 and eosinophil (EOS) deficiency. Mechanistic studies reveal that ILC2 protect against AAA formation through the IL5 and EOS pathways. IL5 or ILC2 from wild-type (WT) mice induces EOS differentiation in bone marrow cells from ILC2-deficient mice, while IL5, IL13, and EOS or ILC2 from WT mice promote smooth muscle cell (SMC) proliferation and prevent SMC apoptosis. EOS from WT or IL5-deficient mice inhibits endothelial cell (EC) adhesion molecule expression, angiogenesis, dendritic cell differentiation, and Ly6C(hi) monocyte polarization. Reconstitution of WT EOS and ILC2 slows AAA growth in mice by increasing systemic EOS, while ILC2 indirectly contributes to AAA protection through the IL5 and EOS mechanism.
Review
Immunology
Zhen Yuan, Yi Lu, Jia Wei, Jiaqi Wu, Jin Yang, Zhejun Cai
Summary: Abdominal aortic aneurysms (AAAs) are local dilations of the infrarenal segment of aortas, with inflammation playing a central role in their development. In addition to inflammatory cells like T cells, macrophages, and neutrophils, special structures such as inflammasomes and neutrophil extracellular traps are investigated for their roles in aneurysm formation. Understanding the impacts and interactions of these inflammatory cells and structures is crucial for developing new screening and pharmacological interventions for AAA.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Medicinal
Ziyi Zhai, Xianjing Zhang, Yuchao Ding, Ziming Huang, Qian Li, Mingyue Zheng, Kenka Cho, Zhihui Dong, Weiguo Fu, Zaixing Chen, Baohong Jiang
Summary: Eugenol has potential therapeutic effects against abdominal aortic aneurysm (AAA) by inhibiting disease progression and protecting the integrity of the aortic structure. It exerts its effects by down-regulating the expressions of COX-2 and NF-kappa B.
PHYTOTHERAPY RESEARCH
(2022)
Review
Medicine, General & Internal
Petroula Nana, Konstantinos Spanos, Konstantinos Dakis, Alexandros Brodis, George Kouvelos
Summary: This systematic review evaluates predictive imaging factors for AAA growth, with an emphasis on aneurysm diameter as the most studied factor associated with expansion and the main indication for intervention. The study highlights the importance of appropriate diagnostic modalities in identifying aneurysms with rapid growth and higher rupture risk. Future perspectives may include computed mathematical models for AAA growth prediction.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Dannielle D. Engle, Herve Tiriac, Keith D. Rivera, Arnaud Pommier, Sean Whalen, Tobiloba E. Oni, Brinda Alagesan, Eun Jung Lee, Melissa A. Yao, Matthew S. Lucito, Benjamin Spielman, Brandon Da Silva, Christina Schoepfer, Kevin Wright, Brianna Creighton, Lauren Afinowicz, Kenneth H. Yu, Robert Gruetzmann, Daniela Aust, Phyllis A. Gimotty, Katherine S. Pollard, Ralph H. Hruban, Michael G. Goggins, Christian Pilarsky, Youngkyu Park, Darryl J. Pappin, Michael A. Hollingsworth, David A. Tuveson
Review
Biochemistry & Molecular Biology
Maximilian Brunner, Zhiyuan Wu, Christian Krautz, Christian Pilarsky, Robert Gruetzmann, Georg F. Weber
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Review
Biochemistry & Molecular Biology
Bin Lan, Siyuan Zeng, Robert Gruetzmann, Christian Pilarsky
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Review
Biochemistry & Molecular Biology
Siyuan Zeng, Marina Poettler, Bin Lan, Robert Gruetzmann, Christian Pilarsky, Hai Yang
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Endocrinology & Metabolism
Hassan Mziaut, Georg Henniger, Katharina Ganss, Sebastian Hempel, Steffen Wolk, Johanna McChord, Kamal Chowdhury, Philippe Ravassard, Klaus-Peter Knoch, Christian Krautz, Juergen Weitz, Robert Gruetzmann, Christian Pilarsky, Michele Solimena, Stephan Kersting
MOLECULAR METABOLISM
(2020)
Article
Cell Biology
Holly Brunton, Giuseppina Caligiuri, Richard Cunningham, Rosie Upstill-Goddard, Ulla-Maja Bailey, Ian M. Garner, Craig Nourse, Stephan Dreyer, Marc Jones, Kim Moran-Jones, Derek W. Wright, Viola Paulus-Hock, Colin Nixon, Gemma Thomson, Nigel B. Jamieson, Grant A. McGregor, Lisa Evers, Colin J. McKay, Aditi Gulati, Rachel Brough, Ilirjana Bajrami, Stephen J. Pettitt, Michele L. Dziubinski, Simon T. Barry, Robert Gruetzmann, Robert Brown, Edward Curry, Marina Pajic, Elizabeth A. Musgrove, Gloria M. Petersen, Emma Shanks, Alan Ashworth, Howard C. Crawford, Diane M. Simeone, Fieke E. M. Froeling, Christopher J. Lord, Debabrata Mukhopadhyay, Christian Pilarsky, Sean E. Grimmond, Jennifer P. Morton, Owen J. Sansom, David K. Chang, Peter J. Bailey, Andrew Biankin
Article
Medicine, General & Internal
Melanie Langheinrich, Stefan Wirtz, Barbara Kneis, Matthias M. Gittler, Olaf Tyc, Robert Schierwagen, Maximilian Brunner, Christian Krautz, Georg F. Weber, Christian Pilarsky, Jonel Trebicka, Abbas Agaimy, Robert Grutzmann, Stephan Kersting
JOURNAL OF CLINICAL MEDICINE
(2020)
Article
Oncology
Ali Al-Fatlawi, Negin Malekian, Sebastian Garcia, Andreas Henschel, Ilwook Kim, Andreas Dahl, Beatrix Jahnke, Peter Bailey, Sarah Naomi Bolz, Anna R. Poetsch, Sandra Mahler, Robert Gruetzmann, Christian Pilarsky, Michael Schroeder
Summary: The study identified predictive RNA variants from blood samples of patients with pancreatic diseases, combining them with CA19-9 for deep learning to differentiate pancreatic cancer from chronic pancreatitis with high accuracy. This approach has the potential to greatly improve noninvasive clinical diagnosis and early treatment of pancreatic cancer.
Article
Oncology
Raphaela Schwappacher, Walburga Dieterich, Dejan Reljic, Christian Pilarsky, Debabrata Mukhopadhyay, David K. Chang, Andrew Biankin, Juergen Siebler, Hans J. Herrmann, Markus F. Neurath, Yurdagul Zopf
Summary: Exercise-induced cytokines in serum from advanced-stage pancreatic cancer patients inhibit cancer cell growth and migration, and induce cancer cell death. This study provides new insights into the cancer-protective function of exercise in pancreatic cancer and supports the use of sport therapies for cancer patients.
Article
Cell Biology
Ujjwal Mukund Mahajan, Ahmed Alnatsha, Qi Li, Bettina Oehrle, Frank-Ulrich Weiss, Matthias Sendler, Marius Distler, Waldemar Uhl, Tim Fahlbusch, Elisabetta Goni, Georg Beyer, Ansgar Chromik, Markus Bahra, Fritz Klein, Christian Pilarsky, Robert Gruetzmann, Markus M. Lerch, Kirsten Lauber, Nicole Christiansen, Beate Kamlage, Ivonne Regel, Julia Mayerle
Summary: The study identified three metabolic PDAC subtypes associated with distinct complex lipid patterns through plasma metabolome analysis, revealing the heterogeneity of PDAC patients and laying the foundation for sphingolipid metabolism research in PDAC.
Article
Oncology
Bin Lan, Siyuan Zeng, Shuman Zhang, Xiaofan Ren, Yuming Xing, Isabella Kutschick, Susanne Pfeffer, Benjamin Frey, Nathalie Britzen-Laurent, Robert Gruetzmann, Nils Cordes, Christian Pilarsky
Summary: Pancreatic cancer is the fourth leading cause of cancer-related deaths in Western countries. Radiation therapy has not yielded satisfactory results in treating pancreatic cancer, and understanding radioresistance mechanisms and developing new therapeutic targets have become major challenges. In this study, the researchers used CRISPR-Cas9 screening and 3D cell culture to identify DYRK1A as a sensitive target for radiotherapy in pancreatic cancer. Furthermore, they showed that DYRK1A-targeted inhibitors could enhance the efficacy of radiotherapy. These findings support the use of CRISPR-Cas9 screening to identify novel therapeutic targets and develop strategies to improve radiotherapy efficacy in pancreatic cancer.
Article
Oncology
Hai Yang, Bin Liu, Dongxue Liu, Zhirong Yang, Shuman Zhang, Pengyan Xu, Yuming Xing, Isabella Kutschick, Susanne Pfeffer, Nathalie Britzen-Laurent, Robert Gruetzmann, Christian Pilarsky
Summary: Pancreatic cancer is a highly lethal cancer with limited treatment options. Chemotherapy, especially with gemcitabine, is the primary choice for patients; however, chemoresistance presents a significant challenge to its effectiveness. In this study, we used genome-wide CRISPR/Cas9 screening to identify DCK and CCNL1 as genes contributing to gemcitabine resistance in pancreatic cancer. Furthermore, we explored the mechanism of CCNL1-related resistance and found that the loss of CCNL1 activates the ERK/AKT/STAT3 pathway, leading to resistance to gemcitabine.
Review
Chemistry, Analytical
Yusong Wu, Yuqing Wang, Yanjun Lu, Xiaomei Luo, Yinghong Huang, Ting Xie, Christian Pilarsky, Yuanye Dang, Jianye Zhang
Summary: This review provides an overview of the conventional methods and microfluidic-based technologies for exosome separation, with a focus on the efficiency of exosome isolation by microfluidic devices. Additionally, advances in integrated microfluidics technologies for exosome separation and analysis are introduced.
Article
Oncology
Hang He, Shuman Zhang, Hai Yang, Pengyan Xu, Isabella Kutschick, Susanne Pfeffer, Nathalie Britzen-Laurent, Robert Gruetzmann, Deliang Fu, Christian Pilarsky
Summary: This study identified PCSK6 as a critical gene involved in liver metastasis in pancreatic cancer and investigated its biological functions and molecular mechanisms using CRISPR/Cas9 technology. It was found that inactivation of PCSK6 could efficiently suppress liver metastasis, suggesting its potential as a novel therapeutic target for liver metastasis in pancreatic cancer.
Article
Chemistry, Physical
Jonas Dinter, Ralf. P. P. Friedrich, Hai Yang, Christian Pilarsky, Harald Mangge, Marina Poettler, Christina Janko, Christoph Alexiou, Stefan Lyer
Summary: Pancreatic ductal adenocarcinoma is a difficult-to-treat cancer with poor long-term survival rates. In this study, a 3D cell culture model of human pancreatic ductal adenocarcinoma was used to investigate the potential use of superparamagnetic iron oxide nanoparticles (SPIONs) as a drug delivery system for the chemotherapeutic agent mitoxantrone (MTO). The results showed that MTO-loaded SPIONs induced cell death in tumor spheroids, with increased uptake in spheroids with a SMAD4 mutation. This suggests that MTO-loaded SPIONs could be a promising approach for treating pancreatic ductal adenocarcinomas.