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https://www.readbyqxmd.com/read/29777777/mir-128-3p-directly-targets-vegfc-vegfr3-to-modulate-the-proliferation-of-lymphatic-endothelial-cells-through-ca-2-signaling
#1
Jie Zhou, Zhiyou He, Le Guo, Jizhang Zeng, Pengfei Liang, Licheng Ren, Minghua Zhang, Pihong Zhang, Xiaoyuan Huang
Lymphangiogenesis has been regarded as a physiological response to pathologic stimuli. The abnormal proliferation of lymphatic endothelial cell (LECs) and lymphangiogenesis is involved in the development of lymphatic disorders. Reportedly, VEGFC/VEGFR3 plays a key role in lymphangiogenesis; moreover, VEGFC/VEGFR3 exerts their cellular effects through activation of Ca2+ signaling in several cell types. Herein, we demonstrated that VEGFC significantly up-regulated LEC proliferation through VEGFR3; moreover, VEGFC/VEGFR3 induced Ca2+ signaling activation...
May 16, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29760193/expression-of-the-atypical-chemokine-receptor-ackr4-identifies-a-novel-population-of-intestinal-submucosal-fibroblasts-that-preferentially-expresses-endothelial-cell-regulators
#2
Carolyn A Thomson, Serge A van de Pavert, Michelle Stakenborg, Evelien Labeeuw, Gianluca Matteoli, Allan McI Mowat, Robert J B Nibbs
Atypical chemokine receptors (ACKRs) are expressed by discrete populations of stromal cells at specific anatomical locations where they control leukocyte migration by scavenging or transporting chemokines. ACKR4 is an atypical receptor for CCL19, CCL21, and CCL25. In skin, ACKR4 plays indispensable roles in regulating CCR7-dependent APC migration, and there is a paucity of migratory APCs in the skin-draining lymph nodes of Ackr4 -deficient mice under steady-state and inflammatory conditions. This is caused by loss of ACKR4-mediated CCL19/21 scavenging by keratinocytes and lymphatic endothelial cells...
May 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29753791/obstructive-lymphangitis-precedes-colitis-in-murine-norovirus-infected-stat1-deficient-mice
#3
Audrey Seamons, Piper M Treuting, Stacey Meeker, Charlie Hsu, Jisun Paik, Thea Brabb, Sabine S Escobar, Jonathan S Alexander, Aaron Ericsson, Jason G Smith, Lillian Maggio-Price
Murine norovirus (MNV) is an RNA virus that can prove lethal in mice with impaired innate immunity. We found that MNV-4 infection of Stat1-/- mice was not lethal, but produced a 100% penetrant, previously undescribed lymphatic phenotype characterized by chronic-active lymphangitis with hepatitis, splenitis, and chronic cecal and colonic inflammation. Lesion pathogenesis progressed from early ileal enteritis and regional dilated lymphatics to lymphangitis, granulomatous changes in the liver and spleen, and ultimately, typhlocolitis...
May 10, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29753018/ets-transcription-factor-etsrp-etv2-is-required-for-lymphangiogenesis-and-directly-regulates-vegfr3-flt4-expression
#4
Jennifer A Davis, Andrew L Koenig, Allison Lubert, Brendan Chestnut, Fang Liu, Sharina Palencia Desai, Tamara Winkler, Karolina Pociute, Kyunghee Choi, Saulius Sumanas
The molecular mechanisms initiating the formation of the lymphatic system, lymphangiogenesis, are still poorly understood. Here we have identified a novel role in lymphangiogenesis for an ETS transcription factor, Etv2/Etsrp, a known regulator of embryonic vascular development. Through the use of fully validated photoactivatable morpholinos we show that inducible Etv2 inhibition in zebrafish embryos at 1day post-fertilization (dpf) results in significant inhibition of lymphangiogenesis, while development of blood vessels is unaffected...
May 9, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29680577/cytokines-regulating-lymphangiogenesis
#5
REVIEW
Miguel Sáinz-Jaspeado, Lena Claesson-Welsh
Lymphatic vessels are established by differentiation of lymphendothelial progenitors during embryogenesis. Lymphangiogenesis, the formation of new lymphatic vessels from pre-existing ones is rare in the healthy adult but takes place during pathological conditions such as inflammation, tissue repair and tumor growth. Conditions of dysfunctional lymphatics exist after surgical interventions or in certain genetic diseases. A key lymphangiogenic stimulator is vascular endothelial growth factor-C (VEGFC) acting on VEGF receptor-3 (VEGFR3) expressed on lymphendothelial cells...
April 19, 2018: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29679722/pulmonary-lymphatic-vessel-morphology-a-review
#6
REVIEW
E Weber, F Sozio, A Borghini, P Sestini, E Renzoni
Our understanding of lymphatic vessels has been advanced by the recent identification of relatively specific lymphatic endothelium markers, including Prox-1, VEGFR3, podoplanin and LYVE-1. The use of lymphatic markers has led to the observation that, contrary to previous assumptions, human lymphatic vessels extend deep inside the pulmonary lobule, either in association with bronchioles, intralobular arterioles or small pulmonary veins. Pulmonary lymphatic vessels may thus be classified into pleural, interlobular (in interlobular septa) and intralobular...
April 18, 2018: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/29666442/matrix-stiffness-controls-lymphatic-vessel-formation-through-regulation-of-a-gata2-dependent-transcriptional-program
#7
Maike Frye, Andrea Taddei, Cathrin Dierkes, Ines Martinez-Corral, Matthew Fielden, Henrik Ortsäter, Jan Kazenwadel, Dinis P Calado, Pia Ostergaard, Marjo Salminen, Liqun He, Natasha L Harvey, Friedemann Kiefer, Taija Mäkinen
Tissue and vessel wall stiffening alters endothelial cell properties and contributes to vascular dysfunction. However, whether extracellular matrix (ECM) stiffness impacts vascular development is not known. Here we show that matrix stiffness controls lymphatic vascular morphogenesis. Atomic force microscopy measurements in mouse embryos reveal that venous lymphatic endothelial cell (LEC) progenitors experience a decrease in substrate stiffness upon migration out of the cardinal vein, which induces a GATA2-dependent transcriptional program required to form the first lymphatic vessels...
April 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29656442/treatment-emergent-hypertension-and-efficacy-in-the-phase-3-study-of-e7080-lenvatinib-in-differentiated-cancer-of-the-thyroid-select
#8
Lori J Wirth, Makoto Tahara, Bruce Robinson, Sanjeev Francis, Marcia S Brose, Mouhammed Amir Habra, Kate Newbold, Naomi Kiyota, Corina E Dutcus, Elton Mathias, Matthew Guo, Steven I Sherman, Martin Schlumberger
BACKGROUND: Hypertension (HTN) is an established class effect of vascular endothelial growth factor receptor (VEGFR) inhibition. In the phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, HTN was the most frequent adverse event of lenvatinib, an inhibitor of VEGFR1, VEGFR2, VEGFR3, fibroblast growth factor receptor 1 (FGFR1), FGFR2, FGFR3, FGFR4, platelet-derived growth factor receptor α (PDGFRα), ret proto-oncogene (RET), and stem cell factor receptor (KIT)...
April 14, 2018: Cancer
https://www.readbyqxmd.com/read/29620526/vegf-c-promotes-the-development-of-lymphatics-in-bone-and-bone-loss
#9
Devon Hominick, Asitha Silva, Noor Khurana, Ying Liu, Paul C Dechow, Jian Q Feng, Bronislaw Pytowski, Joseph M Rutkowski, Kari Alitalo, Michael T Dellinger
Patients with Gorham-Stout disease (GSD) have lymphatic vessels in their bones and their bones gradually disappear. Here, we report that mice that overexpress VEGF-C in bone exhibit a phenotype that resembles GSD. To drive VEGF-C expression in bone, we generated Osx-tTA;TetO-Vegfc double-transgenic mice. In contrast to Osx-tTA mice, Osx-tTA;TetO-Vegfc mice developed lymphatics in their bones. We found that inhibition of VEGFR3, but not VEGFR2, prevented the formation of bone lymphatics in Osx-tTA;TetO-Vegfc mice...
April 5, 2018: ELife
https://www.readbyqxmd.com/read/29615616/heterogeneity-in-vegfr3-levels-drives-lymphatic-vessel-hyperplasia-through-cell-autonomous-and-non-cell-autonomous-mechanisms
#10
Yan Zhang, Maria H Ulvmar, Lukas Stanczuk, Ines Martinez-Corral, Maike Frye, Kari Alitalo, Taija Mäkinen
Incomplete delivery to the target cells is an obstacle for successful gene therapy approaches. Here we show unexpected effects of incomplete targeting, by demonstrating how heterogeneous inhibition of a growth promoting signaling pathway promotes tissue hyperplasia. We studied the function of the lymphangiogenic VEGFR3 receptor during embryonic and post-natal development. Inducible genetic deletion of Vegfr3 in lymphatic endothelial cells (LECs) leads to selection of non-targeted VEGFR3+ cells at vessel tips, indicating an indispensable cell-autonomous function in migrating tip cells...
April 3, 2018: Nature Communications
https://www.readbyqxmd.com/read/29577907/possible-role-of-ginsenoside-rb1-in-skin-wound-healing-via-regulating-senescent-skin-dermal-fibroblast
#11
Jingang Hou, Sunchang Kim
Cellular senescence suppresses cancer by inducing irreversible cell growth arrest. Nevertheless, senescent cells is proposed as causal link with aging and aging-related pathologies. The physiological beneficial functions of senescent cells are still of paucity. Here we show that senescent human dermal fibroblast accelerates keratinocytes scratch wound healing and stimulates differentiation of fibroblast. Using oxidative stress (100 μM H2 O2 exposure for 1 h) induction, we successfully triggered fibroblast senescence and developed senescence associated secretory phenotype (SASP)...
March 22, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29550364/mir-126-is-a-conserved-modulator-of-lymphatic-development
#12
Zacharias Kontarakis, Andrea Rossi, Sophie Ramas, Michael T Dellinger, Didier Y R Stainier
Organ homeostasis relies upon cellular and molecular processes that restore tissue structure and function in a timely fashion. Lymphatic vessels help maintain fluid equilibrium by returning interstitial fluid that evades venous uptake back to the circulation. Despite its important role in tissue homeostasis, cancer metastasis, and close developmental origins with the blood vasculature, the number of molecular players known to control lymphatic system development is relatively low. Here we show, using genetic approaches in zebrafish and mice, that the endothelial specific microRNA mir-126, previously implicated in vascular integrity, regulates lymphatic development...
March 14, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29517103/lenvatinib-exhibits-antineoplastic-activity-in-anaplastic-thyroid-cancer-in-vitro-and-in-vivo
#13
Silvia Martina Ferrari, Guido Bocci, Teresa Di Desidero, Giusy Elia, Ilaria Ruffilli, Francesca Ragusa, Paola Orlandi, Sabrina Rosaria Paparo, Armando Patrizio, Simona Piaggi, Concettina La Motta, Salvatore Ulisse, Enke Baldini, Gabriele Materazzi, Paolo Miccoli, Alessandro Antonelli, Poupak Fallahi
Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor (TKI) of VEGFR1-VEGFR3, FGFR1-FGFR4, PDGFRα, RET and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) signaling networks involved in tumor angiogenesis. We have evaluated the antitumor activity of lenvatinib in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C (undifferentiated thyroid cancer) and in an ATC-cell line (AF). The AF cell line was obtained from the primary ATC cultures and was the one that grew over 50 passages...
May 2018: Oncology Reports
https://www.readbyqxmd.com/read/29507684/tumor-microenvironment-promotes-prostate-cancer-cell-dissemination-via-the-akt-mtor-pathway
#14
Junlin Shi, Lihui Wang, Chunlin Zou, Yudui Xia, Siyuan Qin, Evan Keller, Atsushi Mizokami, Jian Zhang, Yi Lu
Metastasis causes high mortality in various malignancies, including prostate cancer (PCa). Accumulating data has suggested that cancer cells spread from the primary tumor to distant sites at early stage, which is characterized by disseminated tumor cells (DTCs). However, lack of direct evidence of partial localized PCa cells occurring epithelial-to-mesenchymal transition (EMT) and disseminating to distant sites (e.g bone marrow). In this study, we used luciferase labeled PCa cells to establish an EMT mouse model and to detect whether DTCs spread into the bone marrow...
February 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29468981/lenvatinib-in-the-therapy-of-aggressive-thyroid-cancer-state-of-the-art-and-new-perspectives-with-patents-recently-applied
#15
Silvia Martina Ferrari, Ilaria Ruffilli, Marco Centanni, Camilla Virili, Gabriele Materazzi, Magdalini Alexopoulou, Mario Miccoli, Alessandro Antonelli, Poupak Fallahi
BACKGROUND AND OBJECTIVE: Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptors (VEGFR1-VEGFR3), fibroblast growth factor receptors (FGFR1-FGFR4), platelet-derived growth factor receptor (PDGFR)α, rearranged during transfection (RET), and v-kit (KIT) signaling networks implicated in tumor angiogenesis. METHOD: Here we review the scientific literature about lenvatinib in the treatment of thyroid cancer...
February 19, 2018: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/29447908/primary-lymphedema-and-other-lymphatic-anomalies-are-associated-with-22q11-2-deletion-syndrome
#16
Marta Unolt, Jessica Barry, Maria Cristina Digilio, Bruno Marino, Anne Bassett, Erwin Oechslin, David W Low, Jean B Belasco, Staci Kallish, Kathleen Sullivan, Elaine H Zackai, Donna M McDonald-McGinn
BACKGROUND: Lymphedema is an abnormal accumulation of interstitial fluid within the tissues. Primary lymphedema is caused by aberrant lymphangiogenesis and it has been historically classified based on age at presentation. Although most cases are sporadic, primary lymphedema may be familial or present in association with chromosomal abnormalities and syndromic disorders. To the best of our knowledge, primary lymphedema has never been described in patients with 22q11.2 deletion syndrome...
February 12, 2018: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/29409810/foxf2-deficiency-permits-basal-like-breast-cancer-cells-to-form-lymphangiogenic-mimicry-by-enhancing-the-response-of-vegf-c-vegfr3-signaling-pathway
#17
Qing-Shan Wang, Rui He, Fan Yang, Li-Juan Kang, Xiao-Qing Li, Li Fu, Baocun Sun, Yu-Mei Feng
Lymphatic metastasis is the main route of breast cancer metastasis. It is known that lymphangiogenesis facilitates lymphatic metastasis through vascular endothelial growth factor-C (VEGF-C)/VEGF receptor 3 (VEGFR3) pathway-linked interactions between the tumor and its microenvironment. Here, we report a novel mechanism of lymphatic metastasis by which aggressive basal-like breast cancer (BLBC) cells form lymphatic vessel-like structures that are identified by the positive expression of lymphatic endothelial cell markers lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), podoplanin, and VEGFR3, and termed as lymphangiogenic mimicry (LM), for the first time...
April 28, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29397483/glomerular-endothelial-cell-maturation-depends-on-adam10-a-key-regulator-of-notch-signaling
#18
Gregory Farber, Romulo Hurtado, Sarah Loh, Sébastien Monette, James Mtui, Raphael Kopan, Susan Quaggin, Catherine Meyer-Schwesinger, Doris Herzlinger, Rizaldy P Scott, Carl P Blobel
The principal function of glomeruli is to filter blood through a highly specialized filtration barrier consisting of a fenestrated endothelium, the glomerular basement membrane and podocyte foot processes. Previous studies have uncovered a crucial role of endothelial a disintegrin and metalloprotease 10 (ADAM10) and Notch signaling in the development of glomeruli, yet the resulting defects have not been further characterized nor understood in the context of kidney development. Here, we used several different experimental approaches to analyze the kidneys and glomeruli from mice lacking ADAM10 in endothelial cells (A10ΔEC mice)...
May 2018: Angiogenesis
https://www.readbyqxmd.com/read/29350326/oxyresveratrol-prevents-murine-h22-hepatocellular-carcinoma-growth-and-lymph-node-metastasis-via-inhibiting-tumor-angiogenesis-and-lymphangiogenesis
#19
Yuanqi Liu, Wei Ren, Yang Bai, Lihong Wan, Xiaodong Sun, Yin Liu, Wenbi Xiong, Yuan-Yuan Zhang, Liming Zhou
The purpose of this study was to investigate the effects and mechanisms of oxyresveratrol (Oxyres) on hepatocellular carcinoma (HCC) in vitro and in vivo. The MTT and Transwell assays were performed to investigate the effects of Oxyres on cell proliferation and migration of two HCC cell lines, QGY-7701 and SMMC-7721 cells. H22 cells were subcutaneously injected into hind foot pads of 70 male mice to establish a lymph node metastasis model. These mice were randomly divided into seven groups as follows, control group, HCC group, Oxyres 20 mg/kg group, Oxyres 40 mg/kg group, Oxyres 60 mg/kg group, Resveratrol (Res) group, and Adriamycin (ADM) group...
March 2018: Journal of Natural Medicines
https://www.readbyqxmd.com/read/29348629/the-suppressive-role-of-calcium-sensing-receptor-in-endometrial-cancer
#20
Xiaoyan Xin, Xianqin Zeng, Dilu Feng, Teng Hua, Shuangge Liu, Shuqi Chi, Qinghua Hu, Hongbo Wang
Studies have shown that calcium sensing receptor (CaSR) is involved in the progressions of several human cancers. However, the role of CaSR in endometrial cancer remains unknown. This study provides a preliminary analysis of the CaSR effect on endometrial cancer development. Ectopic CaSR expression by lentiviral transfection (CaSR-OV) in Ishikawa cells significantly increased intracellular calcium ([Ca2+ ]i ) levels and cell apoptosis. E-cadherin and β-catenin expression and complex formation at the membrane were increased in CaSR-OV Ishikawa cells relative to control Ishikawa cells (vector)...
January 18, 2018: Scientific Reports
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