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Lisa Derosa, Mohamed Amine Bayar, Laurence Albiges, Gwénaël Le Teuff, Bernard Escudier
BACKGROUND: In patients with metastatic renal cell carcinoma (mRCC), the oncologic benefit of second-line treatment for high volume tumors or presence of more than five risk factors remain to be defined. Our aim was to develop and externally validate a new model most likely to correctly predict overall survival (OS) categories in second line. METHOD: mRCC patients treated within clinical trials at Gustave Roussy Cancer Campus (GRCC) formed the discovery set. Patients from two phase III trials from Pfizer database (PFIZERDB), AXIS (NCT00678392), and INTORSECT (NCT00474786), formed the external validation set...
February 9, 2019: Angiogenesis
Yunwei Shi, Xuchu Duan, Guangmin Xu, Xiaoning Wang, Guanyun Wei, Shikui Dong, Gangcai Xie, Dong Liu
MicroRNAs (miRNAs) are single-stranded small non-coding RNAs, generally 18-25 nucleotides in length, that act as repressors of gene expression. miRNAs are encoded by independent genes or processed from a variety of different RNA species. So far, there is no evidence showing that the ribosomal DNA-hosted microRNA is implicated in vertebrate development. Currently, we found a highly expressed small RNA hosted in ribosomal DNA was predicted as a novel miRNA, named miR-ntu1, in zebrafish endothelial cells by deep sequencing analysis...
January 17, 2019: Angiogenesis
Fen Tang, Michelle E LeBlanc, Weiwen Wang, Dan Liang, Ping Chen, Tsung-Han Chou, Hong Tian, Wei Li
Retinopathy of prematurity (ROP) with pathological retinal neovascularization is the most common cause of blindness in children. ROP is currently treated with laser therapy or cryotherapy, both of which may adversely affect the peripheral vision with limited efficacy. Owing to the susceptibility of the developing retina and vasculatures to pharmacological intervention, there is currently no approved drug therapy for ROP in preterm infants. Secretogranin III (Scg3) was recently discovered as a highly disease-restricted angiogenic factor, and a Scg3-neutralizing monoclonal antibody (mAb) was reported with high efficacy to alleviate oxygen-induced retinopathy (OIR) in mice, a surrogate model of ROP...
January 14, 2019: Angiogenesis
Boris Galjart, Pieter M H Nierop, Eric P van der Stok, Robert R J Coebergh van den Braak, Diederik J Höppener, Sofie Daelemans, Luc Y Dirix, Cornelis Verhoef, Peter B Vermeulen, Dirk J Grünhagen
BACKGROUND: In patients with resectable colorectal liver metastases (CRLM), distinct histopathological growth patterns (HGPs) develop at the interface between the tumour and surrounding tissue. The desmoplastic (d) HGP is characterised by angiogenesis and a peripheral fibrotic rim, whereas non-angiogenic HGPs co-opt endogenous sinusoidal hepatic vasculature. Evidence from previous studies has suggested that patients with dHGP in their CRLM have improved prognosis as compared to patients with non-desmoplastic HGPs...
January 12, 2019: Angiogenesis
Chikage Noishiki, Shinya Yuge, Koji Ando, Yuki Wakayama, Naoki Mochizuki, Rei Ogawa, Shigetomo Fukuhara
Angiogenesis, the growth of new blood vessels from pre-existing vessels, is critical for cutaneous wound healing. However, it remains elusive how endothelial cells (ECs) and pericytes (PCs) establish new blood vessels during cutaneous angiogenesis. We set up a live-imaging system to analyze cutaneous angiogenesis in adult zebrafish. First, we characterized basic structures of cutaneous vasculature. In normal skin tissues, ECs and PCs remained dormant to maintain quiescent blood vessels, whereas cutaneous injury immediately induced angiogenesis through the vascular endothelial growth factor signaling pathway...
January 4, 2019: Angiogenesis
Adeline Blandinières, Nicolas Gendron, Nour Bacha, Ivan Bièche, Richard Chocron, Hilario Nunes, Nathalie Nevo, Elisa Rossi, Bruno Crestani, Séverine Lecourt, Sylvie Chevret, Anna Lokajczyk, Virginie Mignon, Alexandre Kisaoglu, Karine Juvin, Sebastien Bertil, Dominique Valeyre, Audrey Cras, Pascale Gaussem, Dominique Israël-Biet, David M Smadja
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by obliteration of alveolar architecture, resulting in declining lung function and ultimately death. Pathogenic mechanisms involve a concomitant accumulation of scar tissue together with myofibroblasts activation and a strong abnormal vascular remodeling. Endothelial progenitor cells (ECFC subtype) have been investigated in several human lung diseases as a potential actor in IPF. We previously demonstrated that ECFCs are down-regulated in IPF in contrast to healthy controls...
January 3, 2019: Angiogenesis
Evgenii Boriushkin, Hui Zhang, Mitchell Becker, Janet Peachey, Mohammad A Shatat, Ralf H Adams, Anne Hamik
Angiogenesis is a multistep process that requires highly regulated endothelial cell (EC) behavior. The transcription factor Krüppel-like factor 4 (KLF4) is a critical regulator of several basic EC functions; we have recently shown that KLF4 disturbs pathological (tumor) angiogenesis by mediating the expression of members of VEGF and Notch signaling pathways. Notch signaling is central to orchestration of sprouting angiogenesis but little is known about the upstream regulation of Notch itself. To determine the role of KLF4 in normal (developmental) angiogenesis, we used a mouse retinal angiogenesis model...
January 3, 2019: Angiogenesis
Nicholas J Protopsaltis, Wei Liang, Eric Nudleman, Napoleone Ferrara
TH 17 cells play important yet complex roles in cancer development and progression. We previously reported that TH 17 cells and IL-17 mediate resistance to anti-VEGF therapy by inducing recruitment of immunosuppressive and proangiogenic myeloid cells to the tumor microenvironment. Here, we demonstrate that IL-22, a key effector cytokine expressed by TH 17 cells, directly acts on endothelial cells to promote tumor angiogenesis. IL-22 induces endothelial cell proliferation, survival, and chemotaxis in vitro and neovascularization in an ex vivo mouse choroid explant model...
December 11, 2018: Angiogenesis
Hua Zhang, Bo Jin, James E Faber
Vascular dysfunction contributes to the progression and severity of Alzheimer's disease (AD). Patients with AD also sustain larger infarctions after ischemic stroke; however, the responsible mechanisms are unknown. Pial collaterals are the primary source of protection in stroke. Unfortunately, natural aging and other vascular risk factors cause a decline in collateral number and diameter (rarefaction) and an increase in stroke severity. Herein, we tested the hypothesis that AD accelerates age-induced collateral rarefaction and examined potential underlying mechanisms...
December 5, 2018: Angiogenesis
Hee-Jun Na, Chung Eun Yeum, Han-Seop Kim, Jungwoon Lee, Jae Yun Kim, Yee Sook Cho
Testis-specific protein, Y-encoded like (TSPYL) family proteins (TSPYL1-6), which are members of the nucleosome assembly protein superfamily, have been determined to be involved in the regulation of various cellular functions. However, the potential role of TSPYL family proteins in endothelial cells (ECs) has not been determined. Here, we demonstrated that the expression of TSPYL5 is highly enriched in human ECs such as human umbilical vein endothelial cells (HUVECs) and human pluripotent stem cell-differentiated ECs (hPSC-ECs)...
November 23, 2018: Angiogenesis
Haojie Dong, Chunhua Weng, Rongpan Bai, Jinghao Sheng, Xiangwei Gao, Ling Li, Zhengping Xu
The miR-200 family, consisting of miR-200a/b/c, miR-141, and miR-429, is well known to inhibit epithelial-to-mesenchymal transition (EMT) in cancer invasion and metastasis. Among the miR-200 family members, miR-200a/b/c and miR-429 have been reported to inhibit angiogenesis. However, the role of miR-141 in angiogenesis remains elusive, as contradicting results have been found in different cancer types and tumor models. Particularly, the effect of miR-141 in vascular endothelial cells has not been defined. In this study, we used several in vitro and in vivo models to demonstrate that miR-141 in endothelial cells inhibits angiogenesis...
November 21, 2018: Angiogenesis
Gregory Farber, Matthew M Parks, Nicole Lustgarten Guahmich, Yi Zhang, Sébastien Monette, Scott C Blanchard, Annarita Di Lorenzo, Carl P Blobel
The coronary vasculature is crucial for normal heart function, yet much remains to be learned about its development, especially the maturation of coronary arterial endothelium. Here, we show that endothelial inactivation of ADAM10, a key regulator of Notch signaling, leads to defects in coronary arterial differentiation, as evidenced by dysregulated genes related to Notch signaling and arterial identity. Moreover, transcriptome analysis indicated reduced EGFR signaling in A10ΔEC coronary endothelium. Further analysis revealed that A10ΔEC mice have enlarged dysfunctional hearts with abnormal myocardial compaction, and increased expression of venous and immature endothelium markers...
November 16, 2018: Angiogenesis
Moran Zarfati, Irit Avivi, Benjamin Brenner, Tami Katz, Anat Aharon
Bone marrow microenvironment is known to support angiogenesis, thus contributing to progression of multiple myeloma (MM). Bortezomib, a proteasome inhibitor (PI) widely used in MM treatment, has anti-angiogenic activity. Extracellular vesicles (EVs), shedding from cell surface, serve as mediators in cell-to-cell communication. We have hypothesized that MM cells (MMCs) treated with bortezomib generate EVs that could diminish angiogenesis, thus limiting MM progression. In the present study, EVs were obtained from MMCs (RPMI-8226), untreated (naïve) or pre-treated with bortezomib...
November 1, 2018: Angiogenesis
R Gianni-Barrera, A Butschkau, A Uccelli, A Certelli, P Valente, M Bartolomeo, E Groppa, M G Burger, R Hlushchuk, M Heberer, D J Schaefer, L Gürke, V Djonov, B Vollmar, A Banfi
VEGF induces normal or aberrant angiogenesis depending on its dose in the microenvironment around each producing cell in vivo. This transition depends on the balance between VEGF-induced endothelial stimulation and PDGF-BB-mediated pericyte recruitment, and co-expression of PDGF-BB normalizes aberrant angiogenesis despite high VEGF doses. We recently found that VEGF over-expression induces angiogenesis in skeletal muscle through an initial circumferential vascular enlargement followed by longitudinal splitting, rather than sprouting...
November 2018: Angiogenesis
Susan J Doh, Michael Yamakawa, Samuel M Santosa, Mario Montana, Kai Guo, Joseph R Sauer, Nicholas Curran, Kyu-Yeon Han, Charles Yu, Masatsugu Ema, Mark I Rosenblatt, Jin-Hong Chang, Dimitri T Azar
The study of lymphangiogenesis is an emerging science that has revealed the lymphatic system as a central player in many pathological conditions including cancer metastasis, lymphedema, and organ graft rejection. A thorough understanding of the mechanisms of lymphatic growth will play a key role in the development of therapeutic strategies against these conditions. Despite the known potential of this field, the study of lymphatics has historically lagged behind that of hemangiogenesis. Until recently, significant strides in lymphatic studies were impeded by a lack of lymphatic-specific markers and suitable experimental models compared to those of the more immediately visible blood vasculature...
November 2018: Angiogenesis
Soheila Zeinali, Colette A Bichsel, Nina Hobi, Manuela Funke, Thomas M Marti, Ralph A Schmid, Olivier T Guenat, Thomas Geiser
Idiopathic pulmonary fibrosis is characterized by a progressive scarring and stiffening of the peripheral lung tissue that decreases lung function. Over the course of the disease, the lung microvasculature undergoes extensive remodeling. There is increased angiogenesis around fibrotic foci and an absence of microvessels within the foci. To elucidate how the anti-fibrotic drug nintedanib acts on vascular remodeling, we used an in vitro model of perfusable microvessels made with primary endothelial cells and primary lung fibroblasts in a microfluidic chip...
November 2018: Angiogenesis
Huichun Liang, Fei Ge, Yuhui Xu, Ji Xiao, Zhongmei Zhou, Rong Liu, Ceshi Chen
The sprouting of endothelial cells is the first step of tumor angiogenesis. Our previous study suggests that miR-153 suppresses breast tumor angiogenesis partially through targeting hypoxia-induced factor (HIF1α). In this study, we demonstrated that miR-153 also suppresses the migration and the tube formation of endothelial cells through directly targeting angiopoietin 1 (ANG1) in breast cancer cells. There was a negative correlation between miR-153 and ANG1 levels in breast cancer. miR-153 blocked the expression and secretion of ANG1 in breast cancer cells through binding to ANG1 mRNA...
November 2018: Angiogenesis
Devika Kir, Erica Schnettler, Shrey Modi, Sundaram Ramakrishnan
Non-coding RNAs are functional RNA molecules comprising the majority of human transcriptome. Only about 1.5% of the human genome is transcribed into messenger RNAs (mRNA) that are translated into proteins. Among the non-coding RNAs, miRNAs are extensively studied and miR targets in endothelial cells, perivascular cells, and angiogenic signaling are relatively well defined. MicroRNAs not only regulate transcripts in situ but also function as paracrine mediators in affecting angiogenesis at distant sites. Exosomal miRs are implicated in modulating endothelial cell function and angiogenesis...
November 2018: Angiogenesis
Duy T Dao, Lorenzo Anez-Bustillos, Jared Ourieff, Amy Pan, Paul D Mitchell, Hiroko Kishikawa, Gillian L Fell, Meredith A Baker, Randolph S Watnick, Hong Chen, Thomas E Hamilton, Michael S Rogers, Diane R Bielenberg, Mark Puder
Children with hypoplastic lung diseases, such as congenital diaphragmatic hernia, can require life support via extracorporeal membrane oxygenation and systemic anticoagulation, usually in the form of heparin. The role of heparin in angiogenesis and organ growth is inconclusive, with conflicting data reported in the literature. This study aimed to investigate the effects of heparin on lung growth in a model of compensatory lung growth (CLG). Compared to the absence of heparin, treatment with heparin decreased the vascular endothelial growth factor (VEGF)-mediated activation of VEGFR2 and mitogenic effect on human lung microvascular endothelial cells in vitro...
November 2018: Angiogenesis
Marchien G Dallinga, Bahar Yetkin-Arik, Richelle P Kayser, Ilse M C Vogels, Patrycja Nowak-Sliwinska, Arjan W Griffioen, Cornelis J F van Noorden, Ingeborg Klaassen, Reinier O Schlingemann
Tip cells, the leading cells of angiogenic sprouts, were identified in cultures of human umbilical vein endothelial cells (HUVECs) by using CD34 as a marker. Here, we show that tip cells are also present in primary human microvascular endothelial cells (hMVECs), a more relevant endothelial cell type for angiogenesis. By means of flow cytometry, immunocytochemistry, and qPCR, it is shown that endothelial cell cultures contain a dynamic population of CD34+ cells with many hallmarks of tip cells, including filopodia-like extensions, elevated mRNA levels of known tip cell genes, and responsiveness to stimulation with VEGF and inhibition by DLL4...
November 2018: Angiogenesis
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