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https://www.readbyqxmd.com/read/29351359/cyr61-ccn1-regulates-sclerostin-levels-and-bone-maintenance
#1
Gexin Zhao, Bau-Lin Huang, Diana Rigueur, Weiguang Wang, Chimay Bhoot, Kemberly R Charles, Jongseung Baek, Subburaman Mohan, Jie Jiang, Karen M Lyons
CYR61/CCN1 is a matricellular protein that resides in the extracellular matrix, but serves regulatory rather than structural roles. CYR61/CCN1 is found in mineralized tissues and has been shown to influence bone healing in vivo and osteogenic differentiation in vitro. In this study we generated Cyr61 bone specific knockout mice to examine the physiological role of CYR61/CCN1 in bone development and maintenance in vivo. Extensive analysis of Cyr61 conditional knockout mice showed a significant decrease in both trabecular and cortical bone mass as compared to WT littermate...
January 19, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29350522/chemical-design-of-both-a-glutathione-sensitive-dimeric-drug-guest-and-a-glucose-derived-nanocarrier-host-to-achieve-enhanced-osteosarcoma-lung-metastatic-anticancer-selectivity
#2
Lu Su, Richen Li, Sarosh Khan, Ryan Clanton, Fuwu Zhang, Yen-Nan Lin, Yue Song, Hai Wang, Jingwei Fan, Soleil Hernandez, Andrew S Butters, Gamal Akabani, Ronan MacLoughlin, Justin Smolen, Karen L Wooley
Although nanomedicines have been pursued for nearly 20 years, fundamental chemical strategies that seek to optimize both the drug and drug carrier together in a concerted effort remain uncommon yet may be powerful. In this work, two block polymers and one dimeric prodrug molecule were designed to be coassembled into degradable, functional nanocarriers, where the chemistry of each component was defined to accomplish important tasks. The result is a poly(ethylene glycol) (PEG)-protected redox-responsive dimeric paclitaxel (diPTX)-loaded cationic poly(d-glucose carbonate) micelle (diPTX@CPGC)...
January 19, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29346731/direct-polymerization-of-the-arsenic-drug-penao-to-obtain-nanoparticles-with-high-thiol-reactivity-and-anti-cancer-efficiency
#3
Janina-Miriam Noy, Hongxu Lu, Philip Hogg, Jia-Lin Yang, Martina H Stenzel
PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid), which is a mitochondria inhibitor that reacts with adenine nucleotide translocator (ANT), is currently being trialed in patients with solid tumors. To increase the stability of the drug, the formation of nanoparticles has been proposed. Herein, the direct synthesis of polymeric micelles based on the anti-cancer drug PENAO is presented. PENAO is readily available for amidation reaction to form PENAO MA (4-(N-(S-penicillaminylacetyl) amino) phenylarsonous acid methacrylamide) which undergoes RAFT (reversible addition fragmentation chin transfer) polymerization with poly(polyethylene glycol methyl ether methacrylate) (PEGMA) as comonomer and poly(methylmethacrylate) (pMMA) as chain transfer agent, resulting in p(MMA)-b-p(PEG-co-PENAO) block copolymers with 3-15 wt...
January 18, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29345412/wnt5a-promotes-migration-and-invasion-of-human-osteosarcoma-cells-via-src-erk-mmp-14-pathway
#4
Xingwen Wang, Xin Zhao, Zhigang Yi, Bing Ma, Hong Wang, Yanchuan Pu, Jing Wang, Shuanke Wang
WNT5A, a representative ligand of activating several non-canonical Wnt signal pathways, plays significant roles in oncogenesis and tumor inhibition. It has been shown that the non-receptor tyrosine kinase SRC is required for WNT5A-induced invasion of osteosarcoma cells. However, the precise molecular mechanism underlying WNT5A/SRC-mediated osteosarcoma cells invasion remains poorly defined. The study was designed to explore the role of ERK1/2 in WNT5A/SRC-induced osteosarcoma cells invasion and the downstream target of the SRC/ERK1/2 signalings...
January 18, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29345189/microrna-19-contributes-to-the-malignant-phenotypes-of-osteosarcoma-in-vitro-by-targeting-pax6
#5
Qingbing Meng, Ming Dai, Xuejun Nie, Wensheng Zhang, Xingli Xu, Jian Li, Hongxin Mu, Xiaolan Liu, Ling Qin, Xiaoqi Zhu, Jun Yan, Minqian Zheng
This study was conducted to detect the expression of miR-19 and Pax6 (Paired box protein 6) in human osteosarcoma cells and the effects on biological characteristics of osteosarcoma cells. Quantitative real-time polymerase chain reaction was used to detect the expression of Pax6 and miR-19 in normal human osteoblasts (hFOB 1.19) and osteosarcoma cell lines (U2OS, Saos-2, and MG-63). Results showed that miR-19 was significantly upregulated in osteosarcoma cell lines compared with that in hFOB 1.19 cells, while the expression of Pax6 messenger RNA was significantly downregulated...
January 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29344886/identifying-genetic-dependencies-in-cancer-by-analyzing-sirna-screens-in-tumor-cell-line-panels
#6
James Campbell, Colm J Ryan, Christopher J Lord
Loss-of-function screening using RNA interference or CRISPR approaches can be used to identify genes that specific tumor cell lines depend upon for survival. By integrating the results from screens in multiple cell lines with molecular profiling data, it is possible to associate the dependence upon specific genes with particular molecular features (e.g., the mutation of a cancer driver gene, or transcriptional or proteomic signature). Here, using a panel of kinome-wide siRNA screens in osteosarcoma cell lines as an example, we describe a computational protocol for analyzing loss-of-function screens to identify genetic dependencies associated with particular molecular features...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29341215/microrna181c-inhibits-prostate-cancer-cell-growth-and-invasion-by-targeting-multiple-erk-signaling-pathway-components
#7
Zhengzheng Su, Mengni Zhang, Miao Xu, Xinglan Li, Junya Tan, Yunyi Xu, Xiuyi Pan, Ni Chen, Xueqin Chen, Qiao Zhou
BACKGROUND: The ERK signaling pathway is frequently deregulated in tumorigenesis, mostly by classical mechanisms such as gene mutation of its components (eg, RAS and RAF). However, whether and how multiple key components of ERK pathway are regulated by microRNAs are not clear. METHODS: We firstly predicted post-transcriptional regulation of multiple key components of the ERK signaling pathway by miR181c through bioinformatics analysis, and then confirmed the post-transcriptional regulation by dual luciferase reporter gene assays and Western blot analysis...
January 16, 2018: Prostate
https://www.readbyqxmd.com/read/29340095/tumoral-immune-infiltrate-if-pd-l1-expression-and-role-of-cd8-tia-1-lymphocytes-in-localized-osteosarcoma-patients-treated-within-protocol-isg-os1
#8
Emanuela Palmerini, Claudio Agostinelli, Piero Picci, Stefano Pileri, Teresa Marafioti, Pier-Luigi Lollini, Katia Scotlandi, Alessandra Longhi, Maria Serena Benassi, Stefano Ferrari
Background: We hypothesized that immune-infiltrates were associated with superior survival, and examined a primary osteosarcoma tissue microarrays (TMAs) to test this hypothesis. Methods: 129 patients (pts) with localized osteosarcoma treated within protocol ISG-OS1 were included in the study. Clinical characteristics, expression of CD8, CD3, FOXP3, CD20, CD68/CD163 (tumor associated macrophage, TAM), Tia-1 (cytotoxic T cell), CD303 (plasmacytoid dendritic cells: pDC), Arginase-1 (myeloid derived suppressor cells: MDSC), PD-1 on immune-cells (IC), and PD-L1 on tumoral cells (TC) and IC were analysed and correlated with outcome...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340064/antitumor-activity-of-resveratrol-against-human-osteosarcoma-cells-a-key-role-of-cx43-and-wnt-%C3%AE-catenin-signaling-pathway
#9
Da Xie, Gui-Zhou Zheng, Peng Xie, Qi-Hao Zhang, Fei-Xiang Lin, Bo Chang, Qin-Xiao Hu, Shi-Xin Du, Xue-Dong Li
Osteosarcoma is a high-grade bone sarcoma with strong invasive ability. However, treatment with traditional chemotherapeutic drugs is limited by low tolerability and side effects. Resveratrol has been reported previously to have selective antitumor effect on various tumor cells while little is known about its effects and underlying mechanism in osteosarcoma biology. In this study, we found that resveratrol inhibits proliferation and glycolysis, induces apoptosis and reduces the invasiveness of U2-OS cells in vitro...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339716/to-explore-the-mechanism-of-the-grm4-gene-in-osteosarcoma-by-rna-sequencing-and-bioinformatics-approach
#10
Yunguo Pang, Jinmin Zhao, Mitra Fowdur, Yun Liu, Hao Wu, Maolin He
BACKGROUND Glutamate metabotropic receptor 4 (GRM4) has been correlated with the pathogenesis of osteosarcoma. The objective of this study was to explore the underlying molecular mechanism of GRM4 in osteosarcoma. MATERIAL AND METHODS The expression levels of GRM4 in four human osteosarcoma cell lines and hFOB1.19 cells were examined by real-time quantitative PCR (RT-qPCR). The U2OS cells of the highest GRM4 expression were transfected with lentivirus-mediated small interfering RNA (siRNA). The differentially expressed genes (DEGs) after GRM4 gene silencing were screened through RNA sequencing, and analyzed by bioinformatics...
January 17, 2018: Medical Science Monitor Basic Research
https://www.readbyqxmd.com/read/29339189/magnetic-nanoparticles-modified-porous-scaffolds-for-bone-regeneration-and-photothermal-therapy-against-tumors
#11
Jia-Wei Lu, Fan Yang, Qin-Fei Ke, Xue-Tao Xie, Ya-Ping Guo
For effectively treating tumor related-bone defects, design and fabrication of multifunctional biomaterials still remain a great challenge. Herein, we firstly fabricated magnetic SrFe12O19 nanoparticles modified-mesoporous bioglass (BG)/chitosan (CS) porous scaffold (MBCS) with excellent bone regeneration and antitumor function. The as-produced magnetic field from MBCS promoted the expression levels of osteogenic-related genes (OCN, COL1, Runx2 and ALP) and the new bone regeneration by activated BMP-2/Smad/Runx2 pathway...
January 12, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29337282/comparative-proteome-analysis-of-monolayer-and-spheroid-culture-of-canine-osteosarcoma-cells
#12
Christiane Gebhard, Ingrid Miller, Karin Hummel, Martina Neschi Née Ondrovics, Sarah Schlosser, Ingrid Walter
Osteosarcoma is an aggressive bone tumor with high metastasis rate in the lungs and affects both humans and dogs in a similar way. Three-dimensional tumor cell cultures mimic the in vivo situation of micro-tumors and metastases and are therefore better experimental in vitro models than the often applied two-dimensional monolayer cultures. The aim of the present study was to perform comparative proteomics of standard monolayer cultures of canine osteosarcoma cells (D17) and three-dimensional spheroid cultures, to better characterize the 3D model before starting with experiments like migration assays...
January 11, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29334376/positively-selected-enhancer-elements-endow-osteosarcoma-cells-with-metastatic-competence
#13
James J Morrow, Ian Bayles, Alister P W Funnell, Tyler E Miller, Alina Saiakhova, Michael M Lizardo, Cynthia F Bartels, Maaike Y Kapteijn, Stevephen Hung, Arnulfo Mendoza, Gursimran Dhillon, Daniel R Chee, Jay T Myers, Frederick Allen, Marco Gambarotti, Alberto Righi, Analisa DiFeo, Brian P Rubin, Alex Y Huang, Paul S Meltzer, Lee J Helman, Piero Picci, Henri Versteeg, John Stamatoyannopolus, Chand Khanna, Peter C Scacheri
Metastasis results from a complex set of traits acquired by tumor cells, distinct from those necessary for tumorigenesis. Here, we investigate the contribution of enhancer elements to the metastatic phenotype of osteosarcoma. Through epigenomic profiling, we identify substantial differences in enhancer activity between primary and metastatic human tumors and between near isogenic pairs of highly lung metastatic and nonmetastatic osteosarcoma cell lines. We term these regions metastatic variant enhancer loci (Met-VELs)...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29333689/2d-black-phosphorus-reinforced-3d-printed-scaffolds-a-stepwise-countermeasure-for-osteosarcoma
#14
Bowen Yang, Junhui Yin, Yu Chen, Shanshan Pan, Heliang Yao, Youshui Gao, Jianlin Shi
With the ever-deeper understanding of nano-bio interactions and the development of fabrication methodologies of nanomaterials, various therapeutic platforms based on nanomaterials have been developed for next-generation oncological applications, such as osteosarcoma therapy. In this work, a black phosphorus (BP) reinforced 3D-printed scaffold is designed and prepared to provide a feasible countermeasure for the efficient localized treatment of osteosarcoma. The in situ phosphorus-driven, calcium-extracted biomineralization of the intra-scaffold BP nanosheets enables both photothermal ablation of osteosarcoma and the subsequent material-guided bone regeneration in physiological microenvironment, and in the meantime endows the scaffolds with unique physicochemical properties favoring the whole stepwise therapeutic process...
January 15, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29333015/a-profile-of-pediatric-solid-tumors-a-single-institution-experience-in-kashmir
#15
Namita Sharma, Ayesha Ahmad, Gull M Bhat, Sheikh A Aziz, Mohammad Maqbool Lone, Nisar A Bhat
Aims: The purpose of this retroprospective study was to study the epidemiological characteristics and outcomes of children with solid tumors at our institution. Subjects and Methods: Three hundred and three pediatrics patients registered at Regional Cancer Centre (RCC), Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, Kashmir, between January 2008 and June 2014, were analyzed with regard to demographic status, presenting complaints, investigations, treatment, morbidity, and outcomes...
October 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29332359/novel-molecular-and-metabolic-aspects-in-osteosarcoma
#16
Evangelos Tsiambas, Panagiotis P Fotiades, Chrissa Sioka, Dimitrios Kotrotsios, Evangelia Gkika, Andreas Fotopoulos, Stylianos N Mastronikolis, Ilianna E Armata, Evangelos Giotakis, Vasileios Ragos
Osteosarcoma (OS) is the most frequent bone-forming malignancy in children and adolescents. Concerning its molecular landscape, there is no a direct relationship with a specific gene, but a combination of genetic events. A broad spectrum of activated oncogenes and downregulated suppressor genes has been already explored and considered crucial for its progressive pathogenesis. Mechanisms of gene deregulation include amplifications, point mutations, allelic losses and also epigenetic abnormalities such as aberrant promoter methylation...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29332356/%C3%AE-aescin-shows-potent-antiproliferative-activity-in-osteosarcoma-cells-by-inducing-autophagy-ros-generation-and-mitochondrial-membrane-potential-loss
#17
Zhao-Rui Liu, Li-Zhi Sun, Tang-Hong Jia, Dao-Fu Jia
PURPOSE: Osteosarcoma is one of the frequent bone tumor affecting mainly children and is associated with considerable mortality. The limited availability of anticancer drugs and less efficacious treatment options have led to poor survival rates of patients with osteosarcoma. Therefore, there is need to look for more viable treatment options and against this backdrop, natural products may prove handy. Therefore the aim of the present study was to evaluate the anticancer activity of a natural product of plant origin, β-aescin, against U2OS human osteosarcoma cells...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29330865/a-case-of-radiation-induced-osteosarcoma-of-the-skull-presenting-as-a-cutaneous-epidermotropic-tumour-with-a-short-latent-period
#18
E Rashidghamat, E Calonje
Radiation induced sarcoma is an unusual but well documented tumor. The frequency of radiation induced sarcoma of the head and neck region has been reported as 0.143%. In the literature the median interval between irradiation and development of sarcoma is 11 years. Cases of RIS with a short latent period i.e. less than four years are rare. We report a case of a 34 year-old female who developed an osteosarcoma of the scalp, over a previous craniotomy scar, three years after excision of a frontal anaplastic oligodendroglioma which had been followed by a course of 6 weeks radiotherapy (58 Gy) and 6 cycles of Temozolomide...
January 13, 2018: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/29330462/mir-143-3p-inhibits-the-proliferation-migration-and-invasion-in-osteosarcoma-by-targeting-fosl2
#19
Xiangran Sun, Guo Dai, Ling Yu, Qingzhu Hu, Jingteng Chen, Weichun Guo
Osteosarcoma (OS) is the most common type of primary malignant bone tumor and mainly occurs in children and adolescent. Because of its early migration and invasion, OS has a poor prognosis. It has been reported that mircoRNAs (miRNAs) play a crucial role in the occurrence and development of multiple tumors. In this study, we identified the aberrant-expression of miR-143-3p in osteosarcoma and examined the role of miR-143-3p in OS development. Further, we searched the miR-143-3p target gene and verified its accuracy by luciferase experiments...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330051/anti-tumor-effects-of-triptolide-on-angiogenesis-and-cell-apoptosis-in-osteosarcoma-cells-by-inducing-autophagy-via-repressing-wnt-%C3%AE-catenin-signaling
#20
Xugui Li, Qilin Lu, Wei Xie, Yang Wang, Guanqing Wang
Osteosarcoma is a common malignant bone tumor occurring in adolescents and children. The poor prognosis and low 5-year survival rate of osteosarcoma partly due to high metastasis of osteosarcoma. Triptolide (TPL), an extract from Tripterygium wilfordii, is widely used in cancer treatment. In our present study, we aimed to study the effect of TPL in osteosarcoma treatment and explore the associated regulation mechanism. Our study revealed that TPL inhibited angiogenesis by suppressing the expression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in dose dependent manner...
January 9, 2018: Biochemical and Biophysical Research Communications
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