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Ioannis Karampinis, Elena Joas, Anna Dreyer, Ulrich Ronellenfitsch, Jens Jakob, Peter Hohenberger, Kai Nowak
INTRODUCTION: Neovascularisation is a critical step in the progression of malignant tumors. Circulating endothelial progenitor cells (cEPC) have been proposed as surrogate markers of vasculogenesis in malignancies. In this project, we studied the impact of tumor-specific therapy on cEPC and associated angiogenic factors in patients with soft tissue tumors. MATERIALS AND METHODS: Fifty-three patients with soft tissue tumors (25 soft tissue sarcomas, 19 GIST, 9 desmoids) and 15 healthy controls were included...
April 2018: European Journal of Surgical Oncology
Marianne Yardley, Thor Ueland, Pål Aukrust, Annika Michelsen, Elisabeth Bjørkelund, Lars Gullestad, Kari Nytrøen
Background: The present study explored and compared the immediate responses in markers of inflammation and angiogenesis in maintenance heart transplant (HTx) recipients before, during and after sessions of high-intensity interval training (HIT) versus moderate-intensity continuous training (MICT). The study aimed to explain some of the trigger mechanisms behind HIT in HTx recipients. Methods: This cross-over study included 14 HTx patients (mean±SD age: 53±13 years; time since HTx, 3±2 years)...
2017: Open Heart
Kaci A Bohn, Chris E Adkins, Mohamed I Nounou, Paul R Lockman
For metastases in the central nervous system, angiogenesis enhances metastatic potential and promotes progression. Primary factors which drive vessel growth are vascular endothelial growth factor (VEGF) and angiopoietin-2. Preclinical models show inhibition of either factor reduces metastases spread and inhibits growth. This work sets out to answer two questions in a preclinical mouse model. First, whether the combined inhibition of VEGF and angiopoietin-2, reduces passive permeability and limits drug uptake into brain metastases; and second, whether this inhibition reduces metastases burden in brain...
2017: Frontiers in Pharmacology
Tomer Shlamkovich, Lidan Aharon, William A Barton, Niv Papo
In many human cancers, the receptor tyrosine kinase (RTK) Tie2 plays important roles in mediating proliferation, survival, migration and angiogenesis. Thus, molecules that could potently inhibit activation of the Tie2 receptor would have a significant impact on cancer therapy. Nevertheless, attempts to develop Tie2-targeted inhibitors have met with little success, and there is currently no FDA-approved therapeutic selectively targeting Tie2. We used a combinatorial protein engineering approach to develop a new generation of angiopoietin (Ang)2-derived Tie2 antagonists as potential cancer therapeutics and as tools to study angiogenesis...
May 16, 2017: Oncotarget
Jae-Ho Jeong, KwangSoo Kim, Daejin Lim, Kun-Hee Kim, Hyung-Seok Kim, Sungsu Lee, Joo-Hye Song, Byoung-Gon Moon, Hyon E Choy, Sang Chul Park
Inflammaging is defined as low-grade, chronic, systemic inflammation in aging, in the absence of overt infection. Age-associated deterioration of gastrointestinal function could be ascribed to the inflammaging, although evidence is yet to emerge. Here we show that microvessels in aging mouse intestine were progressively deprived of supportive structures, microvessel-associated pericytes and adherens junction protein vascular endothelial (VE)-cadherin, and became leaky. This alteration was ascribed to up-regulation of angiopoetin-2 in microvascular endothelial cells...
January 3, 2017: Scientific Reports
Payal Shah, Navina Lueschen, Amin Ardestani, Jose Oberholzer, Johan Olerud, Per-Ola Carlsson, Kathrin Maedler
AIMS: Changes in the islet vasculature have been implicated in the regulation of β-cell survival and function during the progression to type 2 diabetes (T2D). Failure of the β-cell to compensate for the increased insulin demand in obesity eventually leads to diabetes; as a result of the complex interplay of genetic and environmental factors (e.g. ongoing inflammation within the islets) and impaired vascular function. The Angiopoietin/Tie (Ang/Tie) angiogenic system maintains vasculature and is closely related to organ inflammation and angiogenesis...
2016: PloS One
Oleh Andrukhov, Anja C Gemperli, Yan Tang, Nadia Howald, Michel Dard, Frank Falkensammer, Andreas Moritz, Xiaohui Rausch-Fan
OBJECTIVES: Enamel matrix derivative (EMD) is an effective biomaterial for periodontal tissue regeneration and might stimulate angiogenesis. In order to clarify mechanisms underlying its biological activity, we separated two EMD fractions with different molecular weight protein components and investigated their effects on human umbilical vein endothelial cells (HUVECs) in vitro. METHODS: Fraction Low-Molecular Weight (LMW) included proteins with a molecular weight (M...
July 2015: Dental Materials: Official Publication of the Academy of Dental Materials
Hsiu-Mei Chen, Chia-Hua Tsai, Wen-Chun Hung
Foretinib, a multiple kinase inhibitor undergoing clinical trials, could suppress the activity of hepatocyte growth factor (HGF) receptor c-MET and vascular endothelial growth factor receptor-2 (VEGFR-2). In addition, Foretinib may inhibit two critical lymphangiogenic signaling receptors VEGFR-3 and TIE-2. However, the effect of Foretinib on lymphatic endothelial cells (LECs) in vitro and lymphangiogenesis in vivo is still unknown. We found Foretinib decreased basal- and HGF-induced c-MET activity at low concentrations...
June 20, 2015: Oncotarget
O Coutelle, L M Schiffmann, M Liwschitz, M Brunold, V Goede, M Hallek, H Kashkar, U T Hacker
BACKGROUND: Effective vascular normalisation following vascular endothelial growth factor (VEGF) inhibition is associated with endothelial cell regression leaving empty basement membrane sleeves (BMS). These long-lived BMS permit the rapid regrowth of tumour vasculature upon treatment cessation and promote resistance to VEGF-targeting drugs. Previous attempts at removing BMS have failed. Angiopoietin-2 (Ang2) is a vascular destabilizing factor that antagonises normalisation. We hypothesised that Ang2 inhibition could permit vascular normalisation at significantly reduced doses of VEGF inhibition, avoiding excessive vessel regression and the formation of empty BMS...
February 3, 2015: British Journal of Cancer
Susan S Cohen, Bethany R Powers, Alexandra Lerch-Gaggl, Ru-Jeng Teng, Girija Ganesh Konduri
BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is associated with increased risk of neuro-developmental impairments. Whether relative fetal hypoxia during evolution of PPHN renders the fetal brain vulnerable to perinatal brain injury remains unclear. We hypothesized that in utero ductal constriction, which induces PPHN also impairs cerebral angiogenesis. METHODS: Fetal lambs with PPHN induced by prenatal ligation of the ductus arteriosus were compared to gestation matched twin controls...
November 2014: International Journal of Developmental Neuroscience
Elina Korpela, Darren Yohan, Lee Cl Chin, Anthony Kim, Xiaoyong Huang, Shachar Sade, Paul Van Slyke, Daniel J Dumont, Stanley K Liu
BACKGROUND: Most cancer patients are treated with radiotherapy, but the treatment can also damage the surrounding normal tissue. Acute skin damage from cancer radiotherapy diminishes patients' quality of life, yet effective biological interventions for this damage are lacking. Protecting microvascular endothelial cells from irradiation-induced perturbations is emerging as a targeted damage-reduction strategy. Since Angiopoetin-1 signaling through the Tie2 receptor on endothelial cells opposes microvascular perturbations in other disease contexts, we used a preclinical Angiopoietin-1 mimic called Vasculotide to investigate its effect on skin radiation toxicity using a preclinical model...
2014: BMC Cancer
Juergen Debus, Amir Abdollahi
Glioblastoma (GBM) is the most common malignant brain tumor. Radiotherapy post surgical resection remained the mainstay of the management of GBM for decades until the addition of temozolomide was shown to prolong the median overall survival (OS) by 2.5 months to 14.6 months in 2005. Infiltrative growth to surrounding normal brain tissue and cooption of vascular niches, peripheral microvasuclar hyperplasia, and central hypoxic regions with pseudopalisading necrosis are characteristics of GBM and are causally linked to their exceptional radio- and chemo-resistant phenotype...
2014: American Society of Clinical Oncology Educational Book
H M C Shantha Kumara, Elizabeth A Myers, Sonali A C Herath, Linda Njoh, Xiaohong Yan, Daniel Kirchoff, Nadav Dujovny, Richard L Whelan
BACKGROUND: Minimally invasive colorectal resection for cancer is associated with increased plasma levels of numerous proangiogenic proteins for 3 to 4 weeks postoperatively, and plasma from postoperative weeks 2 and 3 stimulates proangiogenic endothelial cell behavior in vitro. It is unknown if similar plasma changes occur after minimally invasive colorectal resection for benign pathology. OBJECTIVE: The aim of this study is to assess 1) plasma levels of angiopoetin-2, placental growth factor, and soluble vascular cell adhesion molecule-1 after minimally invasive colorectal resection for benign pathology and 2) postoperative plasma's effects on in vitro endothelial cell proliferation (branch point formation), migration, and invasion...
June 2014: Diseases of the Colon and Rectum
Anastasia Efimenko, Nina Dzhoyashvili, Natalia Kalinina, Tatiana Kochegura, Renat Akchurin, Vsevolod Tkachuk, Yelena Parfyonova
Tissue regeneration is impaired in aged individuals. Adipose-derived mesenchymal stromal cells (ADSCs), a promising source for cell therapy, were shown to secrete various angiogenic factors and improve vascularization of ischemic tissues. We analyzed how patient age affected the angiogenic properties of ADSCs. ADSCs were isolated from subcutaneous fat tissue of patients with coronary artery disease (CAD; n = 64, 43-77 years old) and without CAD (n = 31, 2-82 years old). ADSC phenotype characterized by flow cytometry was CD90(+)/CD73(+)/CD105(+)/CD45(-)/CD31(-) for all samples, and these cells were capable of adipogenic and osteogenic differentiation...
January 2014: Stem Cells Translational Medicine
Christopher A Moxon, Ngawina V Chisala, Samuel C Wassmer, Terrie E Taylor, Karl B Seydel, Malcolm E Molyneux, Brian Faragher, Neil Kennedy, Cheng-Hock Toh, Alister G Craig, Robert S Heyderman
Endothelial dysregulation is central to the pathogenesis of acute Plasmodium falciparum infection. It has been assumed that this dysregulation resolves rapidly after treatment, but this return to normality has been neither demonstrated nor quantified. We therefore measured a panel of plasma endothelial markers acutely and in convalescence in Malawian children with uncomplicated or cerebral malaria. Evidence of persistent endothelial activation and inflammation, indicated by increased plasma levels of soluble intracellular adhesion molecule 1, angiopoetin 2, and C-reactive protein, were observed at 1 month follow-up visits...
February 15, 2014: Journal of Infectious Diseases
M V Strogov, S N Luneva, K I Novikov
The article deals with the results of study of level of growth factors in blood serum of patients with inherent and post-traumatic shortenings of limbs' bones. The detection in blood serum the level of epidermal growth factor insulin-like growth factor I and angiopoetins is proposed to monitor in given patients the reparative bone formation.
April 2013: Klinicheskaia Laboratornaia Diagnostika
Evgeny K Shevchenko, Pavel I Makarevich, Zoya I Tsokolaeva, Maria A Boldyreva, Veronika Yu Sysoeva, Vsevolod A Tkachuk, Yelena V Parfyonova
BACKGROUND: Modified cell-based angiogenic therapy has become a promising novel strategy for ischemic heart and limb diseases. Most studies focused on myoblast, endothelial cell progenitors or bone marrow mesenchymal stromal cells transplantation. Yet adipose-derived stromal cells (in contrast to bone marrow) are abundantly available and can be easily harvested during surgery or liposuction. Due to high paracrine activity and availability ADSCs appear to be a preferable cell type for cardiovascular therapy...
2013: Journal of Translational Medicine
Tadanori Mammoto, Amanda Jiang, Elisabeth Jiang, Akiko Mammoto
Development and regeneration of tissues and organs require precise coordination among endothelial, epithelial and mesenchymal morphogenesis. Angiogenesis plays key roles in normal development, wound healing, recovery from ischemic disease, and organ regeneration. It has been recognized that the combination of various angiogenic factors in an appropriate physiological ratio is critical for long-term functional blood vessel formation. Here we show that mouse soluble platelet-rich-plasma (PRP) extract, which includes abundant angiopoetin-1 (Ang1) and other angiogenic factors, stimulates endothelial cell growth, migration and differentiation in cultured human dermal microvascular endothelial cells in vitro and neonatal mouse retinal angiogenesis in vivo...
September 2013: Microvascular Research
Miklos Jaszberenyi, Andrew V Schally, Norman L Block, Marta Zarandi, Ren-Zhi Cai, Irving Vidaurre, Luca Szalontay, Arumugam R Jayakumar, Ferenc G Rick
Five-year survival of patients afflicted with glioblastoma multiforme (GBM) is rare, making this cancer one of the most feared malignancies. Previously, we reported that growth hormone-releasing hormone (GHRH) is a potent growth factor in cancers. The present work evaluated the effects of two antagonistic analogs of GHRH (MIA-604 and MIA-690) on the proliferation of U-87 MG GBM tumors, in vivo as well as in vitro. Both analogs were administered subcutaneously and dose-dependently inhibited the growth of tumors transplanted into nude mice (127 animals in seven groups)...
December 2013: Targeted Oncology
Sung-Whan Kim, Hong-Zhe Zhang, Chae-Eun Kim, Jong-Min Kim, Moo Hyun Kim
BACKGROUND: We previously reported that amniotic mesenchymal stem cells (AMMs) possess high angio-vasulogenic properties. In this study, we investigated the chemotactic abilities of AMMs for improved cardiac function and regenerative angiogenesis. METHODS: The expressions of chemotactic and angiogenic genes were determined by qRT-PCR. Myocardial infarction (MI) was induced in NOD/SCID mice and cells were directly transplanted into the border regions of ischemic heart tissue...
September 30, 2013: International Journal of Cardiology
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