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Sinem Karaman, Harri Nurmi, Salli Antila, Kari Alitalo
The lymphatic vessels can be selectively stimulated to grow in adult mice, rats and pigs by application of viral vectors expressing the lymphangiogenic factors VEGF-C or VEGF-D. Vice versa, lymphangiogenesis in various pathological settings can be inhibited by the blocking of the VEGF-C/VEGFR3 interaction using a ligand-binding soluble form of VEGFR3. Furthermore, the recently discovered plasticity of meningeal and lacteal lymphatic vessels provides novel opportunities for their manipulation in disease. Adenoviral and adeno-associated viral vectors (AAVs) provide suitable tools for establishing short- and long-term gene expression, respectively and adenoviral vectors have already been used in clinical trials...
2018: Methods in Molecular Biology
Florian Baudin, Eric Benzenine, Anne-Sophie Mariet, Alain M Bron, Vincent Daien, Jean François Korobelnik, Catherine Quantin, Catherine Creuzot-Garcher
Importance: The number of patients affected by retinal diseases treated with intravitreal injections (IVTs) has resulted in a rapidly growing number of procedures. One of the worst complications after these injections is endophthalmitis. Objective: To evaluate the incidence of acute endophthalmitis after IVTs of corticosteroids or anti-vascular endothelial growth factor (anti-VEGF) agents. Design, Setting, and Participants: This population-based cohort study included patients undergoing IVTs from January 1, 2012, through December 31, 2015, in France...
September 13, 2018: JAMA Ophthalmology
L F Araujo, A D D Siena, J R Plaça, D B Brotto, I I Barros, B R Muys, C A O Biagi, K C Peronni, J F Sousa, G A Molfetta, L C West, A P West, A M Leopoldino, E M Espreafico, W A Silva
Mitochondria are central key players in cell metabolism, and mitochondrial DNA (mtDNA) instability has been linked to metabolic changes that contribute to tumorigenesis and to increased expression of pro-tumorigenic genes. Here, we use melanoma cell lines and metastatic melanoma tumors to evaluate the effect of mtDNA alterations and the expression of the mtDNA packaging factor, TFAM, on energetic metabolism and pro-tumorigenic nuclear gene expression changes. We report a positive correlation between mtDNA copy number, glucose consumption, and ATP production in melanoma cell lines...
September 21, 2018: Scientific Reports
Yudong Song, Cui Tang, Chunhua Yin
Given that vascular endothelial growth factor (VEGF) and placental growth factor (PIGF), over-expressed in breast cancer cells and M2-like tumor-associated macrophages (M2-TAMs) within tumor microenvironment (TME), work synergistically and independently in mediating tumor progression and immunosuppression, combinatorial immune-based approaches targeting them are expected to be a potent therapeutic modality for patients. Here, polyethylene glycol (PEG) and mannose doubly modified trimethyl chitosan (PEG = MT) along with citraconic anhydride grafted poly (allylamine hydrochloride) (PC)-based nanoparticles (NPs) (PEG = MT/PC NPs) with dual pH-responsiveness were developed to deliver VEGF siRNA (siVEGF)/PIGF siRNA (siPIGF) to both M2-TAMs and breast cancer cells for antitumor immunotherapy...
September 11, 2018: Biomaterials
Alexey Surov, Hans Jonas Meyer, Anne Kathrin Höhn, Osama Sabri, Sandra Purz
BACKGROUND: Our purpose was to evaluate associations of combined 18 F-FDG-PET and MRI parameters with histopathological features in head and neck squamous cell carcinoma (HNSCC). METHODS: Overall, 22 patients with HNSCC were acquired (10 with G1/2 tumors and 12 with G3 tumors).18 F-FDG-PET/CT and MRI was performed and maximum standardized uptake value (SUVmax ), total lesion glycolysis (TLG) and metabolic tumor volume (MTV) were estimated. Neck MRI was obtained on a 3 T scanner...
September 18, 2018: Translational Oncology
Thibaud Mathis, Pauline Jardel, Olivier Loria, Benoit Delaunay, Anh-Minh Nguyen, Francesco Lanza, Carlo Mosci, Jean-Pierre Caujolle, Laurent Kodjikian, Juliette Thariat
The most frequent site of ocular metastasis is the choroid. The occurrence of choroidal metastases has increased steadily due to the longer survival of metastatic patients and the improvement of diagnostic tools. Fundoscopy, ultrasonography, and fluorescein angiography are now complemented by indocyanine green angiography and optical coherence tomography. Choroidal tumor biopsy may also confirm the metastatic nature of the tumor and help to determine the site of the primary malignancy. There is currently no consensus on the treatment strategy...
September 18, 2018: Progress in Retinal and Eye Research
Yu-Wei Han, Xiu-Juan Liu, Ying Zhao, Xiao-Ming Li
Vasogenic brain edema after subarachnoid hemorrhage (SAH) is an independent risk factor for death and poor prognosis. Disruption of the blood-brain barrier (BBB) is the main cause of vasogenic brain edema induced by SAH. Oleanolic acid (OA) is a natural pentacyclic triterpenoid with various biological functions. Previous studies have shown that prophylactic administration of OA could prevent the BBB disruption in autoimmune encephalomyelitis mice. In this context, we speculate that OA may play a neuroprotective role by protecting the integrity of the BBB and reducing vasogenic cerebral edema after SAH...
September 18, 2018: European Journal of Pharmacology
Pallabi Sengupta, Nilanjan Banerjee, Tanaya Roychowdhury, Anindya Dutta, Samit Chattopadhyay, Subhrangsu Chatterjee
c-MYC proto-oncogene harbours a transcription-inhibitory quadruplex-forming scaffold (Pu27) upstream P1 promoter providing anti-neoplastic therapeutic target. Previous reports showed the binding profile of human Cathelicidin peptide (LL37) and telomeric G-quadruplex. Here, we truncated the quadruplex-binding domain of LL37 to prepare a small library of peptides through site-specific amino acid substitution. We investigated the intracellular selectivity of peptides for Pu27 over other oncogenic quadruplexes and their role in c-MYC promoter repression by dual-luciferase assays...
September 17, 2018: Nucleic Acids Research
Yucang He, Xiaofang Yu, Zhuojie Chen, Liqun Li
Autologous fat transplantation is increasingly applied in plastic and reconstructive surgery. Stromal vascular fraction cells (SVFs) combined with angiogenic factors, such as VEGF (vascular endothelial growth factor A) and Ang-1 (angiogenin-1), can improve angiogenesis, which is a critical factor for graft survival. However, direct transplant with such a mixture is insufficient owing to the short half-life of angiogenic factors. In this study, we evaluated whether a double sustained release system of VEGF/ANG-1-PLGA (poly (lactic-co-glycolic acid)) microspheres plus SVFs can improve angiogenesis and graft survival after autologous fat transplantation...
September 21, 2018: Journal of Cellular Physiology
Dena H Jaffe, Wing Chan, Vladimir Bezlyak, Adrian Skelly
AIM: To determine the economic and humanistic burden of neovascular age-related macular degeneration (nAMD) in a cohort of patients treated with anti-VEGF in Europe and the US. PATIENTS & METHODS:  Seventy-nine respondents from the EU and 63 from the US with a self-reported diagnosis of nAMD and in current receipt of treatment, as reported in an international, general population survey, were compared with non-nAMD controls. RESULTS: Anti-VEGF-treated nAMD patients in the EU had a greater utilization of healthcare resources, poorer quality of life and greater overall activity impairment versus non-nAMD controls...
September 21, 2018: Journal of Comparative Effectiveness Research
Jordan Darden, Laura Beth Payne, Huaning Zhao, John C Chappell
Pericyte investment into new blood vessels is essential for vascular development such that mis-regulation within this phase of vessel formation can contribute to numerous pathologies including arteriovenous and cerebrovascular malformations. It is critical therefore to illuminate how angiogenic signaling pathways intersect to regulate pericyte migration and investment. Here, we disrupted vascular endothelial growth factor-A (VEGF-A) signaling in ex vivo and in vitro models of sprouting angiogenesis, and found pericyte coverage to be compromised during VEGF-A perturbations...
September 20, 2018: Angiogenesis
Scott M McClintic, Simon Gao, Jie Wang, Ahmed Hagag, Andreas K Lauer, Christina J Flaxel, Kavita Bhavsar, Thomas S Hwang, David Huang, Yali Jia, Steven T Bailey
Purpose: To use optical coherence tomography angiography (OCTA) derived quantitative metrics to assess the response of choroidal neovascularization to pro-re-nata (PRN) anti-endothelial growth factor (anti-VEGF) treatment in neovascular age-related macular degeneration (AMD). Design: Prospective longitudinal cohort study. Participants: Fourteen eyes from 14 study participants with treatment-naïve neovascular AMD were enrolled. Methods: Subjects were evaluated monthly and treated with intravitreal anti-VEGF agents under a PRN protocol for one year...
September 2018: Ophthalmology Retina
Changhao Chen, Wang He, Jian Huang, Bo Wang, Hui Li, Qingqing Cai, Feng Su, Junming Bi, Hongwei Liu, Bin Zhang, Ning Jiang, Guangzheng Zhong, Yue Zhao, Wen Dong, Tianxin Lin
Tumor-associated macrophages (TAMs) are the most abundant inflammatory infiltrates in the tumor microenvironment and contribute to lymph node (LN) metastasis. However, the precise mechanisms of TAMs-induced LN metastasis remain largely unknown. Herein, we identify a long noncoding RNA, termed Lymph Node Metastasis Associated Transcript 1 (LNMAT1), which is upregulated in LN-positive bladder cancer and associated with LN metastasis and prognosis. Through gain and loss of function approaches, we find that LNMAT1 promotes bladder cancer-associated lymphangiogenesis and lymphatic metastasis...
September 20, 2018: Nature Communications
Hongyao Hu, Le Li, Taihui Yu, Yanjun Li, Yanhong Tang
OBJECTIVE: Inflammation induced by muscle ischemia is involved in tissue repair and perfusion recovery in peripheral arterial disease (PAD) patients. Interleukin (IL)-22 is an inflammatory cytokine discovered in recent years and shows versatile functions; however, its role in PAD remains unknown. Here, we test whether IL-22 and its receptors are involved in angiogenesis in experimental PAD. METHODS AND RESULTS: Both IL-22 and its receptor-IL-22 receptor 1(IL-22R1) were upregulated in muscle and endothelial cells after ischemia...
September 17, 2018: Biochemical and Biophysical Research Communications
Kartik Angara, Thaiz F Borin, Mohammad H Rashid, Iryna Lebedyeva, Roxan Ara, Ping-Chang Lin, Asm Iskander, Roni J Bollag, Bhagelu R Achyut, Ali S Arbab
BACKGROUND: Glioblastoma (GBM) was shown to relapse faster and displayed therapeutic resistance to antiangiogenic therapies (AATs) through an alternative tumor cell-driven mechanism of neovascularization called vascular mimicry (VM). We identified highly upregulated interleukin 8 (IL-8)-CXCR2 axis in tumor cells in high-grade human glioma and AAT-treated orthotopic GBM tumors. METHODS: Human GBM tissue sections and tissue array were used to ascertain the clinical relevance of CXCR2-positive tumor cells in the formation of VM...
September 17, 2018: Neoplasia: An International Journal for Oncology Research
F Brennan Torstrick, Angela S P Lin, Daniel Potter, David L Safranski, Todd A Sulchek, Ken Gall, Robert E Guldberg
Polyether-ether-ketone (PEEK) is one of the most common materials used for load-bearing orthopaedic devices due to its radiolucency and favorable mechanical properties. However, current smooth-surfaced PEEK implants can lead to fibrous encapsulation and poor osseointegration. This study compared the in vitro and in vivo bone response to two smooth PEEK alternatives: porous PEEK and plasma-sprayed titanium coatings on PEEK. MC3T3 cells were grown on smooth PEEK, porous PEEK, and Ti-coated PEEK for 14 days and assayed for calcium content, osteocalcin, VEGF and ALP activity...
September 13, 2018: Biomaterials
Hyun-Dong Cho, Kwang-Deog Moon, Ki-Hun Park, Yong-Suk Lee, Kwon-Il Seo
Angiogenesis plays an important role in various pathological conditions such as cancer via excessive delivery of oxygen and nutrients. Recent studies have demonstrated that understanding the molecular basis of natural agents in angiogenesis is critical for the development of promising cancer therapeutics. In this study, auriculasin, an active component from Flemingia philippinensis, was found to exert strong anti-angiogenesis activity. Treatment with auriculasin suppressed proliferation of human umbilical vein endothelial cells (HUVECs) by modulating expression of Bcl-2, Bcl-XL , and vascular endothelial growth factor (VEGF)...
September 17, 2018: Food and Chemical Toxicology
Johanna Auriau, Clara Roujeau, Zakia Belaid Choucair, Atsuro Oishi, Carine Derviaux, Thomas Roux, Eric Trinquet, Olivier Hermine, Ralf Jockers, Julie Dam
Neuroplin 1 (NRP1), a transmembrane protein interacting with Vascular Endothelial Growth Factor VEGF-A165 (called here VEGF165) and the tyrosine kinase Receptor 2 (VEGFR2) promote angiogenesis and vascular homeostasis. In a pathophysiological context, several studies suggested that VEGFR2 and NRP1 mediate tumor development and progression. Given the involvement of the VEGF165 network in promoting tumor angiogenesis, NRP1, VEGFR2 and VEGF165 have been identified as targets for anti-angiogenic therapy. No binding assay exists to monitor specifically the binding of VEGF165 to the VEGFR2/NRP1 complex in intact cells...
September 17, 2018: Biochemical Pharmacology
Y Wang, L Wang, Z Wen, J Wang, Y Zhu, H Chen, H Li, J Han, J Xu, S Zhang, Z Hu, Y Song
SETTING: A high proportion of tuberculosis (TB) patients experience delayed wound healing after surgery, and the specific reasons for this phenomenon are not yet clear. OBJECTIVE: To analyse cytokine and growth factors at surgical sites to determine their contribution to delayed wound healing in patients with cervical lymph node TB (CLNT). DESIGN: We measured levels of interleukin (IL) 1β, IL-6, IL-10, IL-22, epidermal growth factor, fibroblast growth factor-2, interferon-gamma, tumour necrosis factor alpha and vascular endothelial growth factor A (VEGF-A) in cervical wound drainage fluid from 36 CLNT patients who underwent lymphadenectomy and in 24 thyroidectomy patients...
October 1, 2018: International Journal of Tuberculosis and Lung Disease
Shih-Chieh Ku, Pei-Shen Ho, Yu-Ting Tseng, Ta-Chuan Yeh, Shu-Li Cheng, Chih-Sung Liang
OBJECTIVE: Cellular, animal, and human epidemiological studies suggested that benzodiazepines increase the risk of cancer and cancer mortality. Obesity is also clearly linked to carcinogenesis. However, no human studies have examined benzodiazepine-associated carcinogenesis as assessed by changes in cancer biomarkers. METHODS: A total of 19 patients were recruited, and received a 6-week treatment of 0.5 mg lorazepam. The measured cancer biomarkers were angiopoietin-2 (ANG-2), soluble CD40 ligand, epidermal growth factor, endoglin, soluble Fas ligand (sFASL), heparin-binding EGF-like growth factor (HB-EGF), insulin-like growth factor binding protein, interleukin (IL)-6, IL-8, IL-18, plasminogen activator inhibitor (PLGF), placental growth factor, transforming growth factor (TGF)-α, tumor necrosis factor (TNF)-α, urokinase-type plasminogen (uPA), vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D...
September 2018: Psychiatry Investigation
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