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https://www.readbyqxmd.com/read/28914593/effects-of-local-administration-of-tiludronic-acid-on-experimental-periodontitis-in-diabetic-rats
#1
Nara L T Nunes, Michel R Messora, Luiz Fernando Oliveira, Mario Lisboa, Marina Costa Barcellos Garcia, Rodrigo O C C Rêgo, Arthur Belém Novaes, Sérgio Luís Scombatti de Souza, Edilson Ervolino, Flávia A C Furlaneto
BACKGROUND: Tiludronic acid (TIL) presents antiresorptive and anti-inflammatory properties and it has not been evaluated in the association periodontitis-diabetes mellitus (DM) to date. This study evaluated the effects of local administration of TIL on experimental periodontitis (EP) in rats with streptozotocin-induced DM. METHODS: Thirty-two animals (Rattus norvegicus, albinus, Wistar) were divided into groups DM/C (Control), DM/EP, DM/EP/TIL1 and DM/EP/TIL3. In groups EP, a ligature was placed around mandibular molars (MM)...
September 15, 2017: Journal of Periodontology
https://www.readbyqxmd.com/read/28850637/role-of-the-fc-region-in-the-vitreous-half-life-of-anti-vegf-drugs
#2
Kwangsic Joo, Sang Jun Park, Yewon Choi, Jung Eun Lee, Young Mi Na, Hye Kyoung Hong, Kyu Hyung Park, Ho Min Kim, Jae-Yong Chung, Se Joon Woo
Purpose: To identify the role of the fragment crystallizable (Fc) region in determining intraocular protein drug pharmacokinetics. Methods: We generated a new VEGF-Trap lacking the Fc region (FcfVEGF-Trap, MWt = 100 kDa) by replacing the Fc region of native VEGF-Trap (MWt = 145 kDa) with a dimerized coiled-coil domain. Forty-two rabbits were injected intravitreally with VEGF-Trap or FcfVEGF-Trap (n = 21 each) in one of the eyes, harvested at six time points (1 hour and 1, 2, 4, 14, and 30 days after injections)...
August 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28834531/maxillary-sinus-elevation-surgery-with-chronos-and-autogenous-bone-graft-immunohistochemical-assessment-of-runx2-vegf-trap-and-osteocalcin
#3
Rodrigo Dos Santos Pereira, Fernanda Brasil Boos, Luis Fernado Gorla, Idelmo Rangel Garcia, Roberta Okamoto, Eduardo Hochuli-Vieira
The purpose of this study was to evaluate a composite graft of ChronOS, a beta-tricalcium phosphate (β-TCP), mixed 1:1 with an autogenous bone graft in human maxillary sinus augmentation. A total of 12 maxillary sinuses were grafted with an autogenous bone graft (control group), and 9 maxillary sinuses were grafted with ChronOS mixed 1:1 with an autogenous bone graft (test group). After 6 months, biopsy samples were obtained concurrent to the placement of dental implants and were subjected to histomorphometric and immunohistochemical analyses for Runt-related transcription factor 2 (RUNX2), vascular endothelial growth factor (VEGF), tartrate-resistant acid phosphatase, and osteocalcin...
August 23, 2017: International Journal of Periodontics & Restorative Dentistry
https://www.readbyqxmd.com/read/28818671/incidence-and-risk-of-cardiotoxicity-in-cancer-patients-treated-with-targeted-therapies
#4
REVIEW
Matteo Santoni, Federico Guerra, Alessandro Conti, Alessandra Lucarelli, Silvia Rinaldi, Laura Belvederesi, Alessandro Capucci, Rossana Berardi
BACKGROUND: Cardiotoxicityis a serious side effect of molecularly targeted agents. The purpose of this study was to evaluate the incidence and Relative Risk (RR) of developing all-grade and high-grade cardiotoxicity in patients with solid tumors receiving targeted agents through a revised meta-analysis of available clinical trials. METHODS: The scientific literature regarding cardiotoxicity was extensively analyzed using MEDLINE, PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL)...
September 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28807800/the-synergistic-effects-of-sr-and-si-bioactive-ions-on-osteogenesis-osteoclastogenesis-and-angiogenesis-for-osteoporotic-bone-regeneration
#5
Lixia Mao, Lunguo Xia, Jiang Chang, Jiaqiang Liu, Lingyong Jiang, Chengtie Wu, Bing Fang
Bioactive ions released from bioceramics play important roles in bone regeneration; however, it is unclear how each ionic composition in complex bioceramics exerts its specific effect on bone regeneration. The aim of this study is to elucidate the functional effects of Sr and Si ions in bioceramics on the regeneration of osteoporotic bone. A model bioceramic with Sr- and Si-containing components (SMS) was successfully fabricated and the effects of ionic products from SMS bioceramics on the osteogenic, osteoclastic and angiogenic differentiation of rBMSCs-OVX and RANKL-induced osteoclasts were investigated...
August 12, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28736316/early-actions-of-antivascular-endothelial-growth-factor-vascular-endothelial-growth-factor-receptor-drugs-on-angiogenic-blood-vessels
#6
Basel Sitohy, Sunghee Chang, Tracey E Sciuto, Elizabeth Masse, Mei Shen, Peter M Kang, Shou-Ching Jaminet, Laura E Benjamin, Rupal S Bhatt, Ann M Dvorak, Janice A Nagy, Harold F Dvorak
Tumors induce their heterogeneous vasculature by secreting vascular endothelial growth factor (VEGF)-A. Anti-VEGF/VEGF receptor (VEGFR) drugs may treat cancer, but the underlying mechanisms remain unclear. An adenovirus expressing VEGF-A (Ad-VEGF-A(164)) replicates the tumor vasculature in mice without tumor cells. Mother vessels (MVs) are the first angiogenic vessel type to form in tumors and after Ad-VEGF-A(164). Multiday treatments with a VEGF trap reverted MVs back to normal microvessels. We now show that, within hours, a single dose of several anti-VEGF drugs collapsed MVs to form glomeruloid microvascular proliferations (GMPs), accompanied by only modest endothelial cell death...
July 21, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28714916/targeting-of-tumor-neovasculature-with-grb-vegf121-a-novel-cytotoxic-fusion-protein
#7
REVIEW
Khalid A Mohamedali, Michael G Rosenblum
Angiogenesis is a critical process in numerous diseases, and intervention in neovascularization has therapeutic value in several disease settings, including ocular diseases, arthritis, and in tumor progression and metastatic spread. Various vascular targeting agents have been developed, including those that inhibit growth factor receptor tyrosine kinases, blocking antibodies that interfere with receptor signal transduction, and strategies that trap growth factor ligands. Limited anti-tumor efficacy studies have suggested that the targeted delivery of the human pro-apoptotic molecule Granzyme B to tumor cells has significant potential for cancer treatment...
July 17, 2017: Biomedicines
https://www.readbyqxmd.com/read/28655794/diffusion-mri-phenotypes-predict-overall-survival-benefitfrom-anti-vegf-monotherapy-in-recurrent-glioblastoma-converging-evidence-from-phase-ii-trials
#8
Benjamin M Ellingson, Elizabeth Gerstner, Marion Smits, Raymond Y Huang, Rivka R Colen, Lauren E Abrey, Dana T Aftab, Gisela M Schwab, Colin Hessel, Robert J Harris, Ararat Chakhoyan, Renske Gahrmann, Whitney B Pope, Kevin Leu, Catalina Raymond, Davis C Woodworth, John F de Groot, Patrick Y Wen, Tracy Batchelor, Martin J van den Bent, Timothy F Cloughesy
Anti-VEGF therapies remain controversial in the treatment of recurrent glioblastoma (GBM). In the current study we demonstrate that recurrent GBM patients with a specific diffusion MR imaging signature have an overall survival (OS) advantage when treated with cediranib, bevacizumab, cabozantinib, or aflibercept monotherapy at first or second recurrence. These findings were validated using a separate trial comparing bevacizumab with lomustine. <br /><br />Experimental Design: Patients with recurrent GBM and diffusion MRI from the monotherapy arms of 5 separate Phase II clinical trials were included: 1) cediranib (NCT00035656); 2) bevacizumab (BRAIN Trial, AVF3708g; NCT00345163); 3) cabozantinib (XL184-201; NCT00704288); 4) aflibercept (VEGF Trap; NCT00369590); and 5) bevacizumab or lomustine (BELOB; NTR1929)...
June 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28651842/sulodexide-prevents-activation-of-the-pla2-cox-2-vegf-inflammatory-pathway-in-human-retinal-endothelial-cells-by-blocking-the-effect-of-age-rage
#9
Giovanni Giurdanella, Francesca Lazzara, Nunzia Caporarello, Gabriella Lupo, Carmelina Daniela Anfuso, Chiara M Eandi, Gian Marco Leggio, Filippo Drago, Claudio Bucolo, Salvatore Salomone
Diabetic retinopathy is characterized by the breakdown of endothelial blood-retinal barrier. We tested the hypothesis that sulodexide (SDX), a highly purified glycosaminoglycan composed of 80% iduronylglycosaminoglycan sulfate and 20% dermatan sulfate, protects human retinal endothelial cells (HREC) from high glucose (HG)-induced damage, through the suppression of inflammatory ERK/cPLA2/COX-2/PGE2 pathway, by blocking the effect of advanced glycation end-products (AGEs). HREC were treated with HG (25mM) or AGEs (glycated-BSA, 2mg/ml) for 48h, with or without SDX (60μg/ml) or aflibercept (AFL, 40μg/ml), a VEGF-trap...
June 23, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28623721/macrophage-phenotypic-mechanomodulation-of-enhancing-bone-regeneration-by-superparamagnetic-scaffold-upon-magnetization
#10
Suisui Hao, Jie Meng, Yu Zhang, Jian Liu, Xin Nie, Fengxin Wu, Yanlian Yang, Chen Wang, Ning Gu, Haiyan Xu
Macrophages are involved in all phases of scaffold induced tissue regeneration, orchestrating the transition from an inflammatory to regenerative phenotype to guide all other cell types to complete the wound healing process when a tissue defect advances beyond the critical size. Therefore, harnessing macrophages by scaffolds is important for facilitating tissue regeneration in situ. In this work we utilized the superparamagnetic scaffold upon magnetization as a mechanostimulation platform to apply forces directly to macrophages grown in the scaffold, aiming to figure out whether the functions of macrophages related to bone tissue regeneration can be mechanomodulated and to elucidate the underlying mechanisms...
June 9, 2017: Biomaterials
https://www.readbyqxmd.com/read/28607469/pth-1-34-induced-differentiation-and-mineralization-of-mandibular-condylar-cartilage
#11
Mara Heather O' Brien, Eliane Hermes Dutra, Alexandro Lima, Ravindra Nanda, Sumit Yadav
Intermittent Parathyroid Hormone (I-PTH) is the only FDA approved anabolic drug therapy available for the treatment of osteoporosis in males and postmenopausal females. The effects of I-PTH on the chondrogenic lineage of the mandibular condylar cartilage (MCC) are not well understood. To investigate the role of I-PTH on the MCC and subchondral bone, we carried out our studies using 4 to 5 week old triple transgenic mice (Col1a1XCol2a1XCol10a1). The experimental group was injected with PTH (80 μg/kg) daily for 2 weeks, while control group was injected with saline...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28594896/zoledronate-suppressed-angiogenesis-and-osteogenesis-by-inhibiting-osteoclasts-formation-and-secretion-of-pdgf-bb
#12
Si-Yong Gao, Guang-Sen Zheng, Lin Wang, Yu-Jie Liang, Si-En Zhang, Xiao-Mei Lao, Kan Li, Gui-Qing Liao
PURPOSE: Bisphosphonates related osteonecrosis of jaw (BRONJ) is a severe complication of systemic BPs administration, the mechanism of which is still unclarified. Recently, platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts was reported to promote angiogenesis and osteogenesis. This study aimed to clarify whether bisphosphonates suppressed preosteoclasts releasing PDGF-BB, and whether the suppression harmed coupling of angiogenesis and osteogenesis, which could contribute to BRONJ manifestation...
2017: PloS One
https://www.readbyqxmd.com/read/28524152/-vascular-endothelial-growth-factor-inhibitors-in-the-treatment-of-neovascular-age-related-macular-degeneration
#13
I N Dyakov, S K Zyryanov
Neovascular age-related macular degeneration (AMD) is the leading cause of vision loss in older patients. An important role in angiogenesis is played by regulatory mechanisms (an increase in the number of proliferating endothelial and stromal cells and morphological alterations in the vascular network) induced by factors from the vascular endothelial growth factor (VEGF) family. Since 2006, the key treatment of neovascular AMD includes agents that inhibit the activity of VEGF. This review covers the effectiveness and safety of the use of anti-VEGF agents in neovascular AMD patients...
2017: Vestnik Oftalmologii
https://www.readbyqxmd.com/read/28359053/platelets-as-a-novel-source-of-pro-inflammatory-chemokine-cxcl14
#14
Alexander Witte, Madhumita Chatterjee, Florian Lang, Meinrad Gawaz
OBJECTIVE: Platelets are a major source of chemokines. Here, we demonstrate for the first time that platelets express significant amounts of CXCL14 and disclose powerful effects of platelet-derived CXCL14 on monocyte and endothelial migration. METHODS: The expression of CXCL14 in platelets and in the supernatant of activated platelets was analysed by immunoblotting, ELISA, and flow cytometry. The effect of platelet-derived CXCL14 on monocyte migration was evaluated using a modified Boyden chamber...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28319320/the-endochondral-bone-protein-chm1-sustains-an-undifferentiated-invasive-phenotype-promoting-lung-metastasis-in-ewing-sarcoma
#15
Kristina von Heyking, Julia Calzada-Wack, Stefanie Göllner, Frauke Neff, Oxana Schmidt, Tim Hensel, David Schirmer, Annette Fasan, Irene Esposito, Carsten Müller-Tidow, Poul H Sorensen, Stefan Burdach, Günther H S Richter
Ewing sarcomas (ES) are highly malignant, osteolytic bone or soft tissue tumors, which are characterized by EWS-ETS translocations and early metastasis to lung and bone. In this study, we investigated the role of the BRICHOS chaperone domain-containing endochondral bone protein chondromodulin I (CHM1) in ES pathogenesis. CHM1 is significantly overexpressed in ES, and chromosome immunoprecipitation (ChIP) data demonstrate CHM1 to be directly bound by an EWS-ETS translocation, EWS-FLI1. Using RNA interference, we observed that CHM1 promoted chondrogenic differentiation capacity of ES cells but decreased the expression of osteolytic genes such as HIF1A, IL6, JAG1, and VEGF...
September 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28266351/biofabrication-of-a-co-culture-system-in-an-osteoid-like-hydrogel-matrix
#16
Tobias Zehnder, Aldo R Boccaccini, Rainer Detsch
Biofabrication aims to develop functional, biological constructs using automated processes (additive manufacturing, AM) involving different cell types and biomaterials (Groll  et al 2016  Biofabrication 13001 1-6). As bone tissue is based on the crosstalk between osteoblasts and osteoclasts at least, evaluating cell-cell and cell-material interactions is of interest to understand bone remodeling. There is increasing interest in the role of osteoclasts not only considering bone resorption, but also their influence on the proliferation, migration and differentiation of osteoblasts...
May 11, 2017: Biofabrication
https://www.readbyqxmd.com/read/28262664/motor-neurons-control-blood-vessel-patterning-in-the-developing-spinal-cord
#17
Patricia Himmels, Isidora Paredes, Heike Adler, Andromachi Karakatsani, Robert Luck, Hugo H Marti, Olga Ermakova, Eugen Rempel, Esther T Stoeckli, Carmen Ruiz de Almodóvar
Formation of a precise vascular network within the central nervous system is of critical importance to assure delivery of oxygen and nutrients and for accurate functionality of neuronal networks. Vascularization of the spinal cord is a highly stereotypical process. However, the guidance cues controlling blood vessel patterning in this organ remain largely unknown. Here we describe a new neuro-vascular communication mechanism that controls vessel guidance in the developing spinal cord. We show that motor neuron columns remain avascular during a developmental time window, despite expressing high levels of the pro-angiogenic vascular endothelial growth factor (VEGF)...
March 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28133920/dual-targeting-of-vascular-endothelial-growth-factor-and-bone-morphogenetic-protein-9-10-impairs-tumor-growth-through-inhibition-of-angiogenesis
#18
Yuichi Akatsu, Yasuhiro Yoshimatsu, Taishi Tomizawa, Kazuki Takahashi, Akihiro Katsura, Kohei Miyazono, Tetsuro Watabe
Clinical development of anti-angiogenic agents has been a major landmark in cancer therapy for several types of cancers. Signals mediated by both vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)-9 and 10 have been implicated in tumor angiogenesis. However, previous studies have shown that targeting the individual signals was not sufficiently effective in retarding tumor growth in certain preclinical and clinical conditions. In the present study, we developed a novel decoy chimeric receptor that traps both VEGF and BMP-9/10...
January 2017: Cancer Science
https://www.readbyqxmd.com/read/28116649/phase-i-trial-of-aflibercept-vegf-trap-with-radiation-therapy-and-concomitant-and-adjuvant-temozolomide-in-patients-with-high-grade-gliomas
#19
Lakshmi Nayak, John de Groot, Jeffrey S Wefel, Timothy F Cloughesy, Frank Lieberman, Susan M Chang, Antonio Omuro, Jan Drappatz, Tracy T Batchelor, Lisa M DeAngelis, Mark R Gilbert, Kenneth D Aldape, Alfred W K Yung, Joy Fisher, Xiaobu Ye, Alice Chen, Stuart Grossman, Michael Prados, Patrick Y Wen
Anti-vascular endothelial growth factor (VEGF) therapy has shown promise in the treatment of high-grade gliomas (HGG). Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for VEGF-A, VEGF-B and placental growth factor, depleting circulating levels of these growth factors. The Adult Brain Tumor Consortium conducted a phase I trial of aflibercept and temozolomide (TMZ) in patients with newly diagnosed HGG with 2 dose levels and a 3+3 design. Three arms using aflibercept were examined; with radiation and concomitant temozolomide; with adjuvant temozolomide using the 5/28 regimen; and with adjuvant temozolomide using the 21/28 day regimen...
March 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28031424/the-dart-study-results-from-the-dose-escalation-and-expansion-cohorts-evaluating-the-combination-of-dalantercept-plus-axitinib-in-advanced-renal-cell-carcinoma
#20
Martin H Voss, Rupal S Bhatt, Elizabeth R Plimack, Brian I Rini, Robert S Alter, J Thaddeus Beck, Dawn Wilson, Xiaosha Zhang, Musa Mutyaba, Chad Glasser, Kenneth M Attie, Matthew L Sherman, Shuchi S Pandya, Michael B Atkins
Purpose: Activin receptor-like kinase 1 (ALK1) is a novel target in angiogenesis. Concurrent targeting of ALK1 and VEGF signaling results in augmented inhibition of tumor growth in renal cell carcinoma (RCC) xenograft models. Dalantercept is an ALK1-receptor fusion protein that acts as a ligand trap for bone morphogenetic proteins 9 and 10. The DART Study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of dalantercept plus axitinib in patients with advanced RCC and determined the optimal dose for further testing...
December 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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