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Chinmay R Surve, Camille L Duran, Xianjun Ye, Xiaoming Chen, Yu Lin, Allison S Harney, Yarong Wang, Ved P Sharma, E Richard Stanley, John C McAuliffe, David Entenberg, Maja H Oktay, John S Condeelis
Tumor cell intravasation is essential for metastatic dissemination, but its exact mechanism is incompletely understood. We have previously shown that in breast cancer, the direct and stable association of a tumor cell expressing Mena, a Tie2 hi /Vegf hi macrophage, and a vascular endothelial cell, creates an intravasation portal, called a "tumor microenvironment of metastasis" (TMEM) doorway, for tumor cell intravasation, leading to dissemination to distant sites. The density of TMEM doorways, also called TMEM doorway score, is a clinically validated prognostic marker of distant metastasis in breast cancer patients...
January 9, 2024: bioRxiv
#22
JOURNAL ARTICLE
Diana Cornelia Moisuc, Daniela Constantinescu, Mihai Vasile Marinca, Bogdan Gafton, Mariana Pavel-Tanasa, Petru Cianga
Colorectal cancer (CRC) ranks as second most common cause of cancer-related deaths. The CRC management considerably improved in recent years, especially due to biological therapies such as bevacizumab. The lack of predictive or prognostic biomarkers remains one of the major disadvantages of using bevacizumab in the CRC management. We performed a prospective study to analyze the prognostic and predictive roles of three potential serum biomarkers (Cyclophilin A (CypA), copeptin and Tie2) investigated by ELISA in 56 patients with metastatic CRC undergoing bevacizumab and chemotherapy between May 2019 and September 2021 at baseline and after one and six months of therapy...
January 16, 2024: Cancers
#23
JOURNAL ARTICLE
Kumboyono Kumboyono, Indah N Chomsy, Nadya N Shalshabilla, Hidayat Sujuti, Arie Srihardyastutie, Cholid T Tjahjono, Teuku Heriansyah, Titin A Wihastuti
INTRODUCTION: The main alkaloid component in cigarettes is nicotine. Cotinine, a metabolite of nicotine, is capable of causing dependence effects through endless mechanisms modulated by the ion channel nicotinic acetylcholine receptors nAChRs. Nicotine and cotinine can also cause damage to blood vessels through a chronic inflammatory process mediated by the Ligand-Tie2 Angiopoietin Receptor system. Hypoxic conditions that occur due to vascular inflammation cause a decrease in the concentration of nitric oxide (NO)...
2024: Tobacco Induced Diseases
#24
JOURNAL ARTICLE
Wancheng Lu, Zhijian Xiao, Hang Liao, Jianpeng Xie, Yihan Gao, Weichen Xiong, Qingye Zeng, Zhenhui Deng, Jiena Wu, Jinwei Chai, Xin Chen, Xueqing Xu
FS145, a protein containing a WGD motif, was previously described from the salivary transcriptome of the flea Xenopsylla cheopis. Nevertheless, its biological function and complete structure are still uncertain. Herein, FS145 was confirmed to adopt a common αββ structure with the WGD motif exposed on its surface and located right at the top of a loop composed of residues 72-81. Furthermore, FS145 dose-dependently inhibited the proliferation, adhesion, migration, and tube formation of HUVECs by not only binding to integrin αv β3 but also by subsequently inactivating the FAK/Src/MAPK pathway along with the reduction of the expression of MMP-2, MMP-9, VEGFA, bFGF, Ang2, Tie2, HIF-1α, and FAK...
January 9, 2024: International Journal of Biological Macromolecules
#25
JOURNAL ARTICLE
Jingkun Wu, Hongbin Wang, Naizhu Wang, Zai Wang, Qinghua Zhu
Hypertensive intracerebral hemorrhage (ICH) is a devastating condition, the molecular underpinnings of which remain not fully understood. By leveraging high-throughput transcriptome sequencing and network pharmacology analysis, this study unveils the significant role of the tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (TIE2) in ICH pathogenesis. Compared to controls, a conspicuous downregulation of TIE2 was observed in the cerebral blood vessels of hypertensive ICH mice. In vitro assays with human brain microvascular endothelial cells (HBMEC), HBEC-5i revealed that modulation of TIE2 expression significantly influences cellular proliferation, migration, and angiogenesis, mediated via the Rap1/MEK/ERK signaling pathway...
January 7, 2024: Experimental Neurology
#26
JOURNAL ARTICLE
Stephanie J Hachey, Christopher J Hatch, Daniela Gaebler, Aneela Mocherla, Kevin Nee, Kai Kessenbrock, Christopher C W Hughes
Triple-negative breast cancer (TNBC) is highly aggressive with limited available treatments. Stromal cells in the tumor microenvironment (TME) are crucial in TNBC progression; however, understanding the molecular basis of stromal cell activation and tumor-stromal crosstalk in TNBC is limited. To investigate therapeutic targets in the TNBC stromal niche, we used an advanced human in vitro microphysiological system called the vascularized micro-tumor (VMT). Using single-cell RNA sequencing, we revealed that normal breast tissue stromal cells activate neoplastic signaling pathways in the TNBC TME...
January 5, 2024: Breast Cancer Research: BCR
#27
JOURNAL ARTICLE
Fei Hu, Kai Huang, Hanbo Zhang, Wenjie Hu, Songlin Tong, Hongming Xu
Random flaps are widely used in the treatment of injuries, tumors, congenital malformations, and other diseases. However, postoperative skin flaps are prone to ischemic necrosis, leading to surgical failure. Insulin-like growth factor- 1(IGF-1) belongs to the IGF family and exerts its growth-promoting effects in various tissues through autocrine or paracrine mechanisms. Its application in skin flaps and other traumatic diseases is relatively limited. Poly (lactic-co-glycolic acid) (PLGA) is a degradable high-molecular-weight organic compound commonly used in biomaterials...
January 2, 2024: European Journal of Pharmaceutical Sciences
#28
JOURNAL ARTICLE
Meichen Li, Jing Chen, Hui Yu, Baishen Zhang, Xue Hou, Honghua Jiang, Dan Xie, Likun Chen
BACKGROUND: Immunotherapy has shown intracranial efficacy in non-small cell lung cancer (NSCLC) patients with brain metastases. However, predictive biomarkers for intracranial response to immunotherapy are lacking. This post-hoc analysis aimed to explore the potential of immunological cytokines in cerebrospinal fluid (CSF) to predict intracranial tumor response to immunotherapy in patients with brain metastases. METHODS: Treatment-naive NSCLC patients with brain metastases who received camrelizumab plus chemotherapy were enrolled...
2024: Oncoimmunology
#29
REVIEW
Babak Saravi, Ulrich Goebel, Lars O Hassenzahl, Christian Jung, Sascha David, Aarne Feldheiser, Matthias Stopfkuchen-Evans, Jakob Wollborn
Capillary leak syndrome (CLS) represents a phenotype of increased fluid extravasation, resulting in intravascular hypovolemia, extravascular edema formation and ultimately hypoperfusion. While endothelial permeability is an evolutionary preserved physiological process needed to sustain life, excessive fluid leak-often caused by systemic inflammation-can have detrimental effects on patients' outcomes. This article delves into the current understanding of CLS pathophysiology, diagnosis and potential treatments...
December 20, 2023: Intensive Care Medicine Experimental
#30
RANDOMIZED CONTROLLED TRIAL
Kathy S Albain, Christina Yau, Emanuel F Petricoin, Denise M Wolf, Julie E Lang, A Jo Chien, Tufia Haddad, Andres Forero-Torres, Anne M Wallace, Henry Kaplan, Lajos Pusztai, David Euhus, Rita Nanda, Anthony D Elias, Amy S Clark, Constantine Godellas, Judy C Boughey, Claudine Isaacs, Debu Tripathy, Janice Lu, Rachel L Yung, Rosa I Gallagher, Julia D Wulfkuhle, Lamorna Brown-Swigart, Gregor Krings, Yunn Yi Chen, David A Potter, Erica Stringer-Reasor, Sarah Blair, Smita M Asare, Amy Wilson, Gillian L Hirst, Ruby Singhrao, Meredith Buxton, Julia L Clennell, Ashish Sanil, Scott Berry, Adam L Asare, Jeffrey B Matthews, Angela M DeMichele, Nola M Hylton, Michelle Melisko, Jane Perlmutter, Hope S Rugo, W Fraser Symmans, Laura J Van't Veer, Douglas Yee, Donald A Berry, Laura J Esserman
PURPOSE: The neutralizing peptibody trebananib prevents angiopoietin-1 and angiopoietin-2 from binding with Tie2 receptors, inhibiting angiogenesis and proliferation. Trebananib was combined with paclitaxel±trastuzumab in the I-SPY2 breast cancer trial. PATIENTS AND METHODS: I-SPY2, a phase II neoadjuvant trial, adaptively randomizes patients with high-risk, early-stage breast cancer to one of several experimental therapies or control based on receptor subtypes as defined by hormone receptor (HR) and HER2 status and MammaPrint risk (MP1, MP2)...
February 16, 2024: Clinical Cancer Research
#31
JOURNAL ARTICLE
Hazuki Soma, Daisuke Sakai, Yoshihiko Nakamura, Shota Tamagawa, Takayuki Warita, Jordy Schol, Erika Matsushita, Mitsuru Naiki, Masato Sato, Masahiko Watanabe
The angiopoietin-1 receptor (Tie2) marks specific nucleus pulposus (NP) progenitor cells, shows a rapid decline during aging and intervertebral disc degeneration, and has thus sparked interest in its utilization as a regenerative agent against disc degeneration. However, the challenge of maintaining and expanding these progenitor cells in vitro has been a significant hurdle. In this study, we investigated the potential of laminin-511 to sustain Tie2+ NP progenitor cells in vitro. We isolated cells from human NP tissue ( n = 5) and cultured them for 6 days on either standard (Non-coat) or iMatrix-511 (laminin-511 product)-coated (Lami-coat) dishes...
November 24, 2023: International Journal of Molecular Sciences
#32
JOURNAL ARTICLE
Y Zhang, S Lin, J Liu, Q Chen, J Kang, J Zhong, M Hu, M S Basabrain, Y Liang, C Yuan, C Zhang
Adding dental pulp stem cells (DPSCs) to vascular endothelial cell-formed vessel-like structures can increase the longevity of these vessel networks. DPSCs display pericyte-like cell functions and closely assemble endothelial cells (ECs). However, the mechanisms of DPSC-derived pericyte-like cells in stabilizing the vessel networks are not fully understood. In this study, we investigated the functions of E-DPSCs, which were DPSCs isolated from the direct coculture of human umbilical vein endothelial cells (HUVECs) and DPSCs, and T-DPSCs, which were DPSCs treated by transforming growth factor beta 1 (TGF-β1), in stabilizing blood vessels in vitro and in vivo...
December 6, 2023: Journal of Dental Research
#33
JOURNAL ARTICLE
Katrin Radloff, Birgitt Gutbier, Charlotte Maeve Dunne, Hanieh Moradian, Marko Schwestka, Manfred Gossen, Katharina Ahrens, Laura Kneller, Yadong Wang, Akanksha Moga, Leonidas Gkionis, Oliver Keil, Volker Fehring, Daniel Tondera, Klaus Giese, Ansgar Santel, Jörg Kaufmann, Martin Witzenrath
Dysfunction of endothelial cells (ECs) lining the inner surface of blood vessels are causative for a number of diseases. Hence, the ability to therapeutically modulate gene expression within ECs is of high therapeutic value in treating diseases such as those associated with lung edema. mRNAs formulated with lipid nanoparticles (LNPs) have emerged as a new drug modality to induce transient protein expression for modulating disease-relevant signal transduction pathways. In the study presented here, we tested the effect of a novel synthetic, nucleoside-modified mRNA encoding COMP-Ang1 (mRNA-76) formulated into a cationic LNP on attenuating inflammation-induced vascular leakage...
December 12, 2023: Molecular Therapy. Nucleic Acids
#34
JOURNAL ARTICLE
Peter Baluk, Keisuke Shirakura, Dietmar Vestweber, Donald M McDonald
Endothelial cells of mammalian blood vessels have multiple levels of heterogeneity along the vascular tree and among different organs. Further heterogeneity results from blood flow turbulence and variations in shear stress. In the aorta, vascular endothelial protein tyrosine phosphatase (VE-PTP), which dephosphorylates tyrosine kinase receptor Tie2 in the plasma membrane, undergoes downstream polarization and endocytosis in endothelial cells exposed to laminar flow and high shear stress. VE-PTP sequestration promotes Tie2 phosphorylation at tyrosine992 and endothelial barrier tightening...
November 30, 2023: Cell and Tissue Research
#35
JOURNAL ARTICLE
Ying Lin, Qifan Yang, Xiaoping Lin, Xianbao Liu, Yi Qian, Dilin Xu, Naifang Cao, Ximeng Han, Yanqing Zhu, Wangxing Hu, Xiaopeng He, Zhengyang Yu, Xiangmin Kong, Lianlian Zhu, Zhiwei Zhong, Kai Liu, Bin Zhou, Yidong Wang, Jinrong Peng, Wei Zhu, Jian'an Wang
BACKGROUND: A better understanding of the molecular mechanism of aortic valve development and bicuspid aortic valve (BAV) formation would significantly improve and optimize the therapeutic strategy for BAV treatment. Over the past decade, the genes involved in aortic valve development and BAV formation have been increasingly recognized. On the other hand, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) gene family members have been reported to be able to modulate cardiovascular development and diseases...
November 29, 2023: Circulation
#36
JOURNAL ARTICLE
Lu Jiang, Xiaohan Hu, Yajun Feng, Zhen Wang, Hanyun Tang, Qiang Lin, Yunyan Shen, Yun Zhu, Qinying Xu, Xiaozhong Li
BACKGROUND: Tie2, a functional angiopoietin receptor, is expressed in vascular endothelial cells and plays an important role in angiogenesis and vascular stability. This study aimed to evaluate the effects of an agonistic Tie2 signal on renal interstitial fibrosis (RIF) and elucidate the underlying mechanisms. METHODS: We established an in vivo mouse model of folic acid-induced nephropathy (FAN) and an in vitro model of lipopolysaccharide-stimulated endothelial cell injury, then an agonistic Tie2 monoclonal antibody (Tie2 mAb) was used to intervent these processes...
November 27, 2023: Pediatric Research
#37
JOURNAL ARTICLE
Irina V Kologrivova, Tatiana E Suslova, Olga A Koshelskaya, Elena S Kravchenko, Olga A Kharitonova, Ekaterina A Romanova, Alexandra I Vyrostkova, Alla A Boshchenko
The aim was to investigate the association of monocyte heterogeneity and presence of circulating endothelial cells with the severity of coronary atherosclerosis in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). We recruited 62 patients with CAD, including 22 patients with DM2. The severity of atherosclerosis was evaluated using Gensini Score. Numbers of classical (CD14++CD16-), intermediate (CD14++CD16+), and non-classical (CD14+CD16++) monocyte subsets; circulating endothelial progenitor cells; and the presence of circulating endothelial cells were evaluated...
October 27, 2023: Biomedicines
#38
JOURNAL ARTICLE
Ararat J Ablooglu, Abhishek Desai, Jin-San Yoo, Cheon Ho Park, Eun-Ah Lee, Bu Yeon Kim, Hyunsun Park, Young Ae Lee, Sang Ryeol Shim, Weon Sup Lee, Kirk M Druey
Vascular dysfunction resulting from endothelial hyperpermeability is a common and important feature of critical illness due to sepsis, trauma, and other conditions associated with acute systemic inflammation. Clarkson disease [monoclonal gammopathy-associated idiopathic systemic capillary leak syndrome (ISCLS)] is a rare, orphan disorder marked by spontaneous and recurrent episodes of hypotensive shock and peripheral edema due to widespread vascular leakage in peripheral tissues. Mortality from acute flares approaches 30% due to lack of effective therapies...
November 15, 2023: Science Advances
#39
JOURNAL ARTICLE
Anoek L I van Leeuwen, Elise Beijer, Roselique Ibelings, Nicole A M Dekker, Marjolein R A van der Steen, Joris J T H Roelofs, Matijs van Meurs, Grietje Molema, Charissa E van den Brom
BACKGROUND: The endothelial angiopoietin/Tie2 system is an important regulator of endothelial permeability and targeting Tie2 reduces hemorrhagic shock-induced organ edema in males. However, sexual dimorphism of the endothelium has not been taken into account. This study investigated whether there are sex-related differences in the endothelial angiopoietin/Tie2 system and edema formation. METHODS: Adult male and female heterozygous Tie2 knockout mice (Tie2+/-) and wild-type controls (Tie2+/+) were included (n = 9 per group)...
2023: PloS One
#40
JOURNAL ARTICLE
Hai Zhang, Rachita K Sumbria, Rudy Chang, Jiahong Sun, David H Cribbs, Todd C Holmes, Mark J Fisher, Xiangmin Xu
BACKGROUND: Cerebral microhemorrhages (CMH) are associated with stroke, cognitive decline, and normal aging. Our previous study shows that the interaction between oxidatively stressed red blood cells (RBC) and cerebral endothelium may underlie CMH development. However, the real-time examination of altered RBC-brain endothelial interactions in vivo, and their relationship with clearance of stalled RBC, microglial responses, and CMH development, has not been reported. METHODS: RBC were oxidatively stressed using tert-butylhydroperoxide (t-BHP), fluorescently labeled and injected into adult Tie2-GFP mice...
November 15, 2023: Journal of Neuroinflammation
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