Article
Chemistry, Medicinal
Yujia Bian, Diego Alem, Francisca Beato, Tara L. Hogenson, Xinrui Yang, Kun Jiang, Jianfeng Cai, Wen Wee Ma, Martin Fernandez-Zapico, Aik Choon Tan, Nicholas J. Lawrence, Jason B. Fleming, Yu Yuan, Hao Xie
Summary: This study developed novel SOS1 degraders and demonstrated SOS1 degradation as a feasible therapeutic strategy for KRAS-mutant CRC.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Maral Hajipour, Khatereh Mokhtari, Mohammad Mahdevar, Maryam Esmaeili, Maryam Peymani, Mohammad Hossein Nasr-Esfahani, Sepideh Mirzaei, Mehrdad Hasehmi, Kiavash Hushmandi, Kamran Ghaedi
Summary: This study identified lncRNAs affected by PPARγ activation through bioinformatics analysis and found that treatment with PIO significantly increased the expression levels of related genes and lncRNAs, providing a new strategy for understanding the function and activity of PPARγ in colon cancer.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Review
Oncology
G. Patelli, F. Tosi, A. Amatu, G. Mauri, A. Curaba, D. A. Patane, A. Pani, F. Scaglione, S. Siena, A. Sartore-Bianchi
Summary: RAS oncogene is commonly mutated in cancer, particularly in metastatic colorectal cancer (mCRC), leading to poor prognosis and resistance to certain treatments. Recent advancements in specific KRAS(G12C) inhibitors have renewed interest in targeting this biomarker. Direct KRAS(G12C) inhibition is emerging as a promising strategy in mCRC and other solid malignancies, showing potential for improved treatment efficacy in the future.
Article
Cell Biology
Jeeho Kim, Young Jin Jeon, Sung-Chul Lim, Joohyun Ryu, Jung-Hee Lee, In-Youb Chang, Ho Jin You
Summary: Ephexin1 is highly expressed in patient tissues of colorectal cancer (CRC) and lung cancer (LC), and plays a critical role in promoting tumorigenesis through the Ras-mediated signaling pathway. Phosphorylated Ephexin1 at Ser16 and Ser18 (pSer16/18) may serve as an effective therapeutic target for CRC and LC as it interacts with oncogenic K-Ras to promote downstream MAPK signaling.
CELL DEATH & DISEASE
(2021)
Article
Medicine, Research & Experimental
Xin Wang, Jian Wang, Jiahui Zhao, Hao Wang, Jing Chen, Jingjing Wu
Summary: This study reveals the role of HMGA2 in the recruitment and polarization of tumor-associated macrophages (TAMs) in colorectal cancer (CRC). The findings suggest that HMGA2 activates the transcription of STAT3 and induces the secretion of CCL2, leading to macrophage recruitment. The study also shows a positive association between HMGA2 expression in tumor cells and CD68 expression in the stroma, and patients with elevated CD68 expression have unfavorable overall survival.
Article
Multidisciplinary Sciences
Yan Huang, Dongzhi Yin, Lina Wu
Summary: Two distinct molecular subtypes of cuproptosis were identified in colorectal cancer, with subtype C1 associated with advanced clinical stage and worse overall survival. A predictive model was constructed and validated externally, showing higher survival rates in the low-risk group.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
John H. Strickler, Christel N. Rushing, Hope E. Uronis, Michael A. Morse, Donna Niedzwiecki, Gerard C. Blobe, Ashley N. Moyer, Emily Bolch, Renee Webb, Sherri Haley, Ace J. Hatch, Ivy P. Altomare, Gary B. Sherrill, David Z. Chang, James L. Wells, S. David Hsu, Jingquan Jia, S. Yousuf Zafar, Andrew B. Nixon, Herbert I. Hurwitz
Summary: The combination of cabozantinib and panitumumab has shown activity in patients with metastatic colorectal cancer, with dose modifications of cabozantinib improving tolerability. Further study is warranted to identify biomarkers for patient populations most likely to benefit.
Article
Oncology
Tobias Gutting, Veronika Hauber, Jens Pahl, Kay Klapproth, Wenyue Wu, Ioana Dobrota, Frank Herweck, Juliane Reichling, Laura Helm, Torsten Schroeder, Beifang Li, Philip Weidner, Tianzuo Zhan, Maximilian Eckardt, Johannes Betge, Sebastian Belle, Carsten Sticht, Timo Gaiser, Michael Boutros, Matthias P. A. Ebert, Adelheid Cerwenka, Elke Burgermeister
Summary: The study revealed that PPAR gamma agonists can upregulate PD-L1 expression in colorectal cancer, enhancing responsiveness to PD-L1 blocking antibodies and improving anti-tumoral responses. This suggests novel therapeutic strategies for CRC involving metabolic modifiers to enhance immune checkpoint antibody responses.
Article
Immunology
Isha Khanduri, Dipen M. Maru, Edwin R. Parra
Summary: The dominant polarization of the M2 macrophage subtype could drive new therapeutic approaches in patients with colorectal liver metastasis (CLM).
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Cell Biology
Loretta Laszlo, Anita Kurilla, Tamas Takacs, Gyongyi Kudlik, Kitti Koprivanacz, Laszlo Buday, Virag Vas
Summary: This review focuses on the special role of the most common mutated isoform of RAS, KRAS, in colorectal cancer (CRC), including its effects on cell signalling, research models, and processes related to CRC development. The article attempts to cover the diverse effects of KRAS mutations on age-related CRC development, as well as the driving forces behind the rising incidence of CRC in young adults.
Article
Oncology
Stefania Belli, Ada Pesapane, Alberto Servetto, Daniela Esposito, Fabiana Napolitano, Claudia Maria Ascione, Alessandra Allotta, Nicola Zambrano, Federica Zito Marino, Renato Franco, Teresa Troiani, Luigi Formisano, Roberto Bianco
Summary: This study suggests that p21-activated kinases (Paks) could be a therapeutic target for KRAS-mutated CRC. Genetic modulation or pharmacological inhibition of Paks can impair the proliferation of KRAS-mut CRC cells, but prolonged blockade of Paks leads to hyper-activation of the mTOR/p70S6K pathway. However, the addition of the mTOR inhibitor everolimus can prevent the growth of KRAS-mut CRC tumors and reverse the adaptive resistance to Paks targeting.
BRITISH JOURNAL OF CANCER
(2023)
Article
Environmental Sciences
Jiapeng Jie, Ling Ling, Yuguo Yi, Liang Tao, Xin Liao, Pingshi Gao, Qian Xu, Weigao Zhang, Yuxin Chen, Jianfa Zhang, Dan Weng
Summary: This study revealed that TBT can strongly activate PPAR gamma in human macrophages, leading to increased lipid accumulation and expression of lipid metabolism-related genes. The involvement of PPAR gamma in TBT-induced lipogenesis was confirmed by the down-regulation of effects in PPAR gamma-deficient macrophages. The findings suggest a potential mechanism for TBT-induced metabolism disturbance and obesity through targeting PPAR gamma.
ENVIRONMENTAL POLLUTION
(2021)
Article
Multidisciplinary Sciences
Roberta De Matteis, Magdalena B. Flak, Maria Gonzalez-Nunez, Shani Austin-Williams, Francesco Palmas, Romain A. Colas, Jesmond Dalli
Summary: Inflammation is linked to colorectal cancer, and aspirin mediates its immunomodulatory effects by increasing the concentration of aspirin-triggered specialized proresolving mediators (AT-SPM) and reducing the expression of programmed cell death protein-1. These findings reveal a central role for AT-SPM in regulating inflammation-associated colorectal cancer.
Article
Oncology
Micol Di Segni, Ilaria Virdia, Alessandra Verdina, Carla Azzurra Amoreo, Silvia Baldari, Gabriele Toietta, Maria Grazia Diodoro, Marcella Mottolese, Isabella Sperduti, Fabiola Moretti, Simonetta Buglioni, Silvia Soddu, Giuliana Di Rocco
Summary: This study investigated the expression of HIPK2 in colorectal cancer and its association with disease progression and mutational patterns. The results showed that the percentage of HIPK2-positive cells increased with tumor progression and was significantly correlated with tumor-stage and poorer prognosis. Additionally, high HIPK2 expression was found to be significantly associated with KRAS mutations but not with other cancer-related genes. Functional analysis revealed that activation of the RAS pathway, either through KRAS mutation or upstream receptor stimulation, increased HIPK2 expression. Depletion of HIPK2 impaired ERK phosphorylation and tumor growth in colorectal cancer cells with KRAS mutations.
MOLECULAR CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Jiuna Zhang, Xiaoyu Jiang, Jie Yin, Shiying Dou, Xiaoli Xie, Ting Liu, Yijun Wang, Shuling Wang, Xue Zhou, Dongxuan Zhang, Huiqing Jiang
Summary: RNF141 plays an oncogenic role in colorectal cancer by upregulating KRAS activity, which promotes tumor growth, cell proliferation, migration, and apoptosis by interacting with KRAS to induce its activation and enrichment on the plasma membrane.
Review
Medicine, General & Internal
C. A. Bonfiglio, C. Weber, D. Atzler, E. Lutgens
Summary: Current therapies for cardiovascular disease primarily focus on lipid lowering and face residual risk. Inflammation, along with lipids, plays a significant role in atherosclerosis. Clinical trials targeting the interleukin-1 beta-inflammasome pathway have successfully reduced cardiovascular events but not overall CVD mortality. Novel and improved immunotherapeutics for CVD are eagerly anticipated.
QJM-AN INTERNATIONAL JOURNAL OF MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Virginia Egea, Remco Theodorus Adrianus Megens, Donato Santovito, Sarawuth Wantha, Richard Brandl, Wolfgang Siess, Sajjad Khani, Oliver Soehnlein, Alexander Bartelt, Christian Weber, Christian Ries
Summary: let-7f promotes hMSC tropism towards atheromas through the LL-37/FPR2 axis and demonstrates that hMSCs develop a potentially athero-protective signature upon contact with the human plaque environment.
CARDIOVASCULAR RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Laura A. Bosmans, Claudia M. van Tiel, Suzanne A. B. M. Aarts, Lisa Willemsen, Jeroen Baardman, Bram W. van Os, Myrthe den Toom, Linda Beckers, David J. Ahern, Johannes H. M. Levels, Aldo Jongejan, Perry D. Moerland, Sanne G. S. Verberk, Jan van den Bossche, Menno M. P. J. de Winther, Christian Weber, Dorothee Atzler, Claudia Monaco, Norbert Gerdes, Annelie Shami, Esther Lutgens
Summary: This study investigates the role of CD40 in atherosclerosis and shows that inhibiting CD40 signaling can reduce atherosclerosis. The researchers used myeloid-specific CD40-deficient mice and found that the absence of CD40 in myeloid cells reduces atherosclerosis and systemic inflammation by preventing pro-inflammatory macrophage polarization.
CARDIOVASCULAR RESEARCH
(2023)
Article
Hematology
Myrthe E. Reiche, Kikkie Poels, Laura A. Bosmans, Winnie G. Vos, Claudia M. van Tiel, Marion J. J. Gijbels, Suzanne A. B. M. Aarts, Myrthe den Toom, Linda Beckers, Christian Weber, Dorothee Atzler, Patrick C. N. Rensen, Sander Kooijman, Esther Lutgens
Summary: The CD40-CD40L dyad has an important role in chronic inflammatory diseases associated with aging. This study found that CD40 is also present on adipocytes. Deficiency of adipocyte CD40 leads to a decrease in bone marrow hematopoietic stem cells, increased T-cell activation, and elevated corticosterone levels, particularly with age. However, adipocyte CD40 deficiency also reduces atherosclerosis burden and ameliorates diet-induced obesity.
Article
Hematology
Christian Weber, Xavier Blanchet, Gregory Y. H. Lip
THROMBOSIS AND HAEMOSTASIS
(2023)
Editorial Material
Hematology
Gregory Y. H. Lip, Anne Rigby, Christian Weber
THROMBOSIS AND HAEMOSTASIS
(2023)
Review
Cell Biology
Sarajo K. Mohanta, Changjun Yin, Christian Weber, Andreas J. R. Habenicht
Summary: Two pairs of biological systems, namely the nervous and vascular systems, and the nervous and immune systems, have been defined as major participants in the regulation of physiological and pathological tissue reactions. The interactions between these systems have led to the concepts of neurovascular link and neuroimmunology. Recent studies on atherosclerosis have proposed the concept of neuroimmune cardiovascular interfaces (NICIs), which involve complex crosstalks between the nervous system, immune system, and cardiovascular system.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Emiel P. C. van der Vorst, Sanne L. Maas, Kosta Theodorou, Linsey J. F. Peters, Han Jin, Timo Rademakers, Marion J. Gijbels, Mat Rousch, Yvonne Jansen, Christian Weber, Michael Lehrke, Corinna Lebherz, Daniela Yildiz, Andreas Ludwig, Jacob F. Bentzon, Erik A. L. Biessen, Marjo M. P. C. Donners
Summary: This study demonstrates that endothelial ADAM10 plays a protective role in the development of murine atherosclerosis, primarily by limiting inflammation induced by oxidized low-density lipoprotein (oxLDL). The findings provide novel opportunities for treating atherosclerosis progression, but caution should be exercised when considering the use of ADAM10 inhibitors for therapy in other diseases.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Review
Cardiac & Cardiovascular Systems
Sarajo K. K. Mohanta, Changjun Yin, Christian Weber, Cristina Godinho-Silva, Henrique Veiga-Fernandes, Qian J. J. Xu, Rui B. B. Chang, Andreas J. R. Habenicht
Summary: The cardiovascular system is connected to the brain through complex axonal connections. Two distinct subcircuits, the artery-brain circuit and the heart-brain circuit, have recently been defined. The impact of the nervous system on the progression of cardiovascular disease is not well understood. This review explores the anatomy and inner workings of these subcircuits and discusses the possibility of a systemic cardiovascular brain circuit.
CIRCULATION RESEARCH
(2023)
Review
Cardiac & Cardiovascular Systems
Christian Weber, Andreas J. R. Habenicht, Philipp von Hundelshausen
Summary: This review summarizes recent progress in the therapeutic targeting of inflammatory components in atherosclerosis. Novel strategies, such as interference with the CD40L-CD40 dyad and selective targeting of TRAFs, show potential in reducing atherosclerosis and plaque instability without immune side effects. Additionally, modulation of the chemokine system and disruption of the adventitial neuroimmune cardiovascular interfaces offer promising avenues for intervention beyond anti-inflammatory approaches.
EUROPEAN HEART JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Christine Krammer, Bishan Yang, Sabrina Reichl, Simon Besson-Girard, Hao Ji, Verena Bolini, Corinna Schulte, Heidi Noels, Kai Schlepckow, Georg Jocher, Georg Werner, Michael Willem, Omar El Bounkari, Aphrodite Kapurniotu, Ozgun Gokce, Christian Weber, Sarajo Mohanta, Jurgen Bernhagen
Summary: Atherosclerosis is a chronic inflammatory condition of our arteries and the underlying pathology of heart attacks and strokes. The role of the inflammatory cytokine MIF in the progression of atherosclerosis and its relationship with age and atherogenic cytokines are not fully understood.
Article
Cardiac & Cardiovascular Systems
Stephan Sachs, Anna Goetz, Brian Finan, Annette Feuchtinger, Richard D. DiMarchi, Yvonne Doering, Christian Weber, Matthias H. Tschoep, Timo D. Mueller, Susanna M. Hofmann
Summary: Long-acting acylated GIP analog (acyl-GIP) treatment can improve dyslipidemia and atherosclerosis independently of body weight loss. This treatment may improve dyslipidemia by directly modulating lipid metabolism in the inguinal fat depot.
CARDIOVASCULAR DIABETOLOGY
(2023)
Article
Multidisciplinary Sciences
Julian U. G. Wagner, Lukas S. Tombor, Pedro Felipe Malacarne, Lisa-Maria Kettenhausen, Josefine Panthel, Haris Kujundzic, Nivethitha Manickam, Katja Schmitz, Maria Cipca, Kathrin A. Stilz, Ariane Fischer, Marion Muhly-Reinholz, Wesley T. Abplanalp, David John, Sarajo K. Mohanta, Christian Weber, Andreas J. R. Habenicht, Giulia K. Buchmann, Stephan Angendohr, Ehsan Amin, Katharina Scherschel, Nikolaj Kloecker, Malte Kelm, Dominik Schuettler, Sebastian Clauss, Stefan Guenther, Thomas Boettger, Thomas Braun, Christian Baer, Minh-Duc Pham, Jaya Krishnan, Susanne Hille, Oliver J. Mueller, Tarik Bozoglu, Christian Kupatt, Eleonora Nardini, Selma Osmanagic-Myers, Christian Meyer, Andreas M. Zeiher, Ralf P. Brandes, Guillermo Luxan, Stefanie Dimmeler
Summary: Aging reduces nerve density in the heart and dysregulates vascular-derived neuroregulatory genes, leading to impaired cardiovascular health.
Article
Cell Biology
Simon Ebert, Lan Zang, Noor Ismail, Michael Otabil, Adrian Frohlich, Virginia Egea, Susann Acs, Mikkel Hoeberg, Marie-Luise Berres, Christian Weber, Jose M. A. Moreira, Christian Ries, Juergen Bernhagen, Omar El Bounkari
Summary: TIMP-1 interacts with CD74 to regulate vascular inflammation and atherosclerosis. TIMP-1 binding to CD74 promotes monocyte migration and vascular smooth muscle cell proliferation, playing a crucial role in vascular inflammation and atherosclerosis.
Article
Cell Biology
Sarajo K. Mohanta, Ting Sun, Shu Lu, Zhihua Wang, Xi Zhang, Changjun Yin, Christian Weber, Andreas J. R. Habenicht
Summary: The nervous, immune, and cardiovascular systems form a tissue network that regulate cardiovascular function. The different systems interact with each other, and further research may lead to new therapies for cardiovascular diseases.
