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zebrafish xenograft

Claudio Fenizia, Cinzia Bottino, Silvia Corbetta, Raffaella Fittipaldi, Pamela Floris, Germano Gaudenzi, Silvia Carra, Franco Cotelli, Giovanni Vitale, Giuseppina Caretti
SMYD3 is a methylase previously linked to cancer cell invasion and migration. Here we show that SMYD3 favors TGFβ-induced epithelial-mesenchymal transition (EMT) in mammary epithelial cells, promoting mesenchymal and EMT transcription factors expression. SMYD3 directly interacts with SMAD3 but it is unnecessary for SMAD2/3 phosphorylation and nuclear translocation. Conversely, SMYD3 is indispensable for SMAD3 direct association to EMT genes regulatory regions. Accordingly, SMYD3 knockdown or its pharmacological blockade with the BCI121 inhibitor dramatically reduce TGFβ-induced SMAD3 association to the chromatin...
December 14, 2018: Nucleic Acids Research
David Hill, Lanpeng Chen, Ewe Snaar-Jagalska, Bill Chaudhry
Cancer metastasis is the most important prognostic factor determining patient survival, but currently there are very few drugs or therapies that specifically inhibit the invasion and metastasis of cancer cells. Currently, human cancer metastasis is largely studied using transgenic and immunocompromised mouse xenograft models, which are useful for analysing end-point tumour growth but are unable to accurately and reliably monitor in vivo invasion, intravasation, extravasation or secondary tumour formation of human cancer cells...
2018: F1000Research
Qiong Wu, Kangdi Zheng, Xiaoting Huang, Li Li, Wenjie Mei
Tanshinone-IIA (Tan-IIA), a primary active component extracted from commonly used Chinese herbal, Salvia miltiorrhiza (Danshen), is considered as a potential inhibitor against tumor cell proliferation. However, the potential application of Tan-IIA is hindered by its poor water solubility and low bioavailability. In this work, an imidazole moiety was linked to the skeleton of Tan-IIA to enhance its antitumor activity. A series of Tan-IIA-based analogues TA01-TA12 were synthesized, and their inhibitory activities against the migration and invasion of MDA-MB-231 cells were investigated...
November 19, 2018: Journal of Medicinal Chemistry
Denver D Britto, Barbara Wyroba, Wenxuan Chen, Rhoswen A Lockwood, Khanh B Tran, Peter R Shepherd, Christopher J Hall, Kathryn E Crosier, Philip S Crosier, Jonathan W Astin
Tumour angiogenesis has long been a focus of anti-cancer therapy; however, anti-angiogenic cancer treatment strategies have had limited clinical success. Tumour-associated myeloid cells are believed to play a role in the resistance of cancer towards anti-angiogenesis therapy, but the mechanisms by which they do this are unclear. An embryonic zebrafish xenograft model has been developed to investigate the mechanisms of tumour angiogenesis and as an assay to screen anti-angiogenic compounds. In this study, we used cell ablation techniques to remove either macrophages or neutrophils and assessed their contribution towards zebrafish xenograft angiogenesis by quantitating levels of graft vascularisation...
November 29, 2018: Disease Models & Mechanisms
John T Gamble, Yuriyah Reed-Harris, Carrie L Barton, Jane La Du, Robert Tanguay, Juliet A Greenwood
Glioblastoma (GBM) is a deadly disease due to its ability to quickly invade and destroy brain tissue. Slowing or stopping GBM cell progression is crucial to help those inflicted with the disease. Our lab created an embryo-larval zebrafish xenograft model as a tool to study human GBM progression in an observable brain environment. The zebrafish brain is a dynamic and complex environment providing an optimal setting for studying GBM cell progression. Here we demonstrate the ability of our model to quantitate GBM proliferation, dispersal, blood vessel association, microtumor formation, and individual cell invasion by evaluating the importance of an extracellular matrix protein, laminin alpha 5 (lama5), on U251MG cell progression...
December 2, 2018: Biochemical and Biophysical Research Communications
S Verykiou, M Alexander, N Edwards, R Plummer, B Chaudhry, P E Lovat, D S Hill
BACKGROUND: Patients with malignant melanoma often relapse following treatment with BRAF and/or MEK inhibitors (MEKi) due to development of drug resistance by melanoma subpopulations, mediated through induction of generic survival mechanisms. OBJECTIVES: The aim of this study was to establish the temporal pattern of CD271 regulation (a stem cell marker that mediates tumour aggressiveness) during development of resistance by melanoma to the MEKi trametinib, and to determine the association between development of resistance to trametinib and induction of pro-survival autophagy...
October 19, 2018: British Journal of Dermatology
Chung-I Yu, Chung-Yi Chen, Wangta Liu, Po-Chih Chang, Chiung-Wei Huang, Kuang-Fen Han, In-Pin Lin, Mei-Ying Lin, Chien-Hsing Lee
Presently, natural sources and herbs are being sought for the treatment of human oral squamous cell carcinoma (OSCC) in order to alleviate the side effects of chemotherapy. This study investigates the effect of sandensolide, a cembrane isolated from Sinularia flexibilis , to inhibit human OSCC cell growth with the aim of developing a new drug for the treatment of oral cancer. In vitro cultured human OSCC models (Ca9.22, SCC9 and HSC-3 cell lines) and oral normal cells (HGF-1), as well as a zebrafish xenograft model, were used to test the cytotoxicity of sandensolide (MTT assay), as well as to perform cell cycle analysis and Western blotting...
October 16, 2018: Marine Drugs
Fabiola Porta, Daniel Ehrsam, Claudia Lengerke, Henriette E Meyer Zu Schwabedissen
Cytotoxic compounds used to treat cancer are often associated with adverse events. The development of formulations activated by tumor-specific triggers would allow a reduction of systemic exposure while maintaining therapeutic concentrations in the tumor. One enzyme with proteolytic activity reported to be involved in tumor progression and assumed to be enhanced in the tumor environment is the matrixmetalloproteinase 9 (MMP-9). In our study, we aimed to develop surface modified PDMS-PMOXA polymersomes able to release their cytotoxic payload upon digestion by MMP-9...
October 1, 2018: Molecular Pharmaceutics
Margarita Parada-Kusz, Cristina Penaranda, Elliott J Hagedorn, Anne Clatworthy, Anil V Nair, Jonathan E Henninger, Christoph Ernst, Brian Li, Raquel Riquelme, Humberto Jijon, Eduardo J Villablanca, Leonard I Zon, Deborah Hung, Miguel L Allende
Xenografts of the hematopoietic system are extremely useful as disease models and for translational research. Zebrafish xenografts have been widely used to monitor blood cancer cell dissemination and homing due to the optical clarity of embryos and larvae, which allow unrestricted in vivo visualization of migratory events. Here, we have developed a xenotransplantation technique that transiently generates hundreds of hematopoietic tissue chimeric embryos by transplanting murine bone marrow cells into zebrafish blastulae...
September 28, 2018: Disease Models & Mechanisms
Joseph Mandelbaum, Ilya A Shestopalov, Rachel E Henderson, Nicole G Chau, Birgit Knoechel, Michael J Wick, Leonard I Zon
Pluripotent cells have been used to probe developmental pathways that are involved in genetic diseases and oncogenic events. To find new therapies that would target MYB -driven tumors, we developed a pluripotent zebrafish blastomere culture system. We performed a chemical genetic screen and identified retinoic acid agonists as suppressors of c-myb expression. Retinoic acid treatment also decreased c-myb gene expression in human leukemia cells. Translocations that drive overexpression of the oncogenic transcription factor MYB are molecular hallmarks of adenoid cystic carcinoma (ACC), a malignant salivary gland tumor with no effective therapy...
October 1, 2018: Journal of Experimental Medicine
Qing-Hua Lin, Wei Qu, Jian Xu, Feng Feng, Ming-Fang He
Angiogenesis is a crucial process in the development of inflammatory diseases, including cancer, psoriasis and rheumatoid arthritis. Recently, several alkaloids from Picrasma quassioides had been screened for angiogenic activity in the zebrafish model, and the results indicated that 1-methoxycarbony-β-carboline (MCC) could effectively inhibit blood vessel formation. In this study, we further confirmed that MCC can inhibit, in a concentration-dependent manner, the viability, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro, as well as the regenerative vascular outgrowth of zebrafish caudal fin in vivo...
August 2018: Chinese Journal of Natural Medicines
He-Zhong Zhang, Chong-Yong Li, Jia-Qi Wu, Rui-Xue Wang, Ping Wei, Mei-Hui Liu, Ming-Fang He
BACKGROUND: Para-coumaric acid methyl ester (pCAME) is one of the bioactive components of Costus speciosus (Koen) Sm. (Zingiberaceae). This plant is traditionally used in Asia to treat catarrhal fevers, worms, dyspepsia, and skin diseases. PURPOSE: To investigate the anti-angiogenic activity of pCAME and its molecular mechanism of action. STUDY DESIGN: We investigated the anti-angiogenic activity of pCAME on human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish (Danio rerio) in vivo...
September 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Afu Fu, Yu Ming Peh, Weida Ngan, Na Wei, Kathy Qian Luo
Treating systemic metastases at the micrometastatic stage is a potential strategy to inhibit cancer metastasis. This study aims to establish an apoptosis sensor-based platform for rapid, effective, and noninvasive identification of drugs that can inhibit the proliferation of micrometastatic cancer cells. We stably transfected the plasmid DNA encoding the fluorescence resonance energy transfer-based caspase-3 sensor into highly metastatic melanoma B16F10 cells. The resulting B16F10-C3 cells were applied for screening of antiproliferative and proapoptotic drugs in two-dimensional (2D) monolayer, three-dimensional (3D) spheroids, and zebrafish xenotransplantation tumors...
November 2018: Biotechnology and Bioengineering
Hefei Zhang, Quan Zhang, Ge Gao, Xinjian Wang, Tiantian Wang, Zhitao Kong, Guoxiang Wang, Cuizhen Zhang, Yun Wang, Gang Peng
The mTOR signaling pathways regulate cell growth and are involved in multiple human diseases. Here, we identify UBTOR, a previously unannotated gene as a functional player in regulating cell growth and mTOR signaling. Reduction of UBTOR function in cultured hippocampal neurons and PC12 cells promotes neurite outgrowth. UBTOR depletion activates mTOR signaling and promotes cell growth, whilst UBTOR overexpression suppresses colony formation in cancer cell lines. Studies in cultured cells and zebrafish model show that UBTOR inhibits mTOR signaling by stabilizing the mTOR complex component DEPTOR, and ubtor gene disruption result in higher mTOR activity and aggravate HRAS(G12V) induced neoplasia in the zebrafish...
August 2018: PLoS Genetics
Ping Chen, Xiaoting Luo, Zhihui Che, Wenli Zhang, Fuchen Liu, Daisen Hou, Dongqin Yang, Jie Liu
BACKGROUND/AIMS: Regulator of cullins-1 (ROC1) is a pivotal component of cullin-RING E3 ubiquitin ligases, which help to regulate distinct cellular processes by governing the degradation of various substrates. Because the role of ROC1 in gastric cancer is largely uncharacterized, we investigated the relationship between ROC1 expression and the prognosis of gastric cancer patients and explored the biological function of ROC1 and its underlying mechanisms in gastric cancer. METHODS: Kaplan-Meier and multivariate Cox regression analyses were used to evaluate the correlation between the carcinogenesis of gastric cancer and ROC1...
2018: Cellular Physiology and Biochemistry
Vinay K Kartha, Khalid A Alamoud, Khikmet Sadykov, Bach-Cuc Nguyen, Fabrice Laroche, Hui Feng, Jina Lee, Sara I Pai, Xaralabos Varelas, Ann Marie Egloff, Jennifer E Snyder-Cappione, Anna C Belkina, Manish V Bais, Stefano Monti, Maria A Kukuruzinska
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy characterized by tumor heterogeneity, locoregional metastases, and resistance to existing treatments. Although a number of genomic and molecular alterations associated with HNSCC have been identified, they have had limited impact on the clinical management of this disease. To date, few targeted therapies are available for HNSCC, and only a small fraction of patients have benefited from these treatments...
July 20, 2018: Genome Medicine
Jin-Young Lee, Aloran Mazumder, Marc Diederich
In vitro and in vivo pre-clinical screening of novel therapeutic agents are an essential tool in cancer drug discovery. Although human cancer cell lines respond to therapeutic compounds in 2D (dimensional) monolayer cell cultures, 3D culture systems were developed to understand the efficacy of drugs in more physiologically relevant models. In recent years, a paradigm shift was observed in pre-clinical research to validate the potency of new molecules in 3D culture systems, more precisely mimicking the tumor microenvironment...
June 26, 2018: Journal of Visualized Experiments: JoVE
Wangdong Jin, Li Zhou, Bo Yan, Li Yan, Fucun Liu, Peijian Tong, Wenhua Yu, Xiaoqiao Dong, Li Xie, Jin Zhang, Yiqiao Xu, Chunqi Li, Qiang Yuan, Letian Shan, Thomas Efferth
Osteosarcoma becomes the second leading cause of cancer death in the younger population. Current outcomes of chemotherapy on osteosarcoma were unsatisfactory to date, demanding development of effective therapies. Tea is a commonly used beverage beneficial to human health. As a major component of tea, theabrownin has been reported to possess anti-cancer activity. To evaluate its anti-osteosarcoma effect, we established a xenograft model of zebrafish and employed U2OS cells for in vivo and in vitro assays. The animal data showed that TB significantly inhibited the tumour growth with stronger effect than that of chemotherapy...
September 2018: Journal of Cellular and Molecular Medicine
Giulia Fornabaio, Raymond L Barnhill, Claire Lugassy, Laurent A Bentolila, Nathalie Cassoux, Sergio Roman-Roman, Samar Alsafadi, Filippo Del Bene
Cutaneous melanoma is a highly aggressive cancer with a propensity for distant metastasis to various organs. In contrast, melanoma arising in pigmented uveal layers of the eye metastasizes mostly in the liver. The mechanisms of these metastases, which are ultimately resistant to therapy, are still unclear. Metastasis via intravascular dissemination of tumour cells is widely accepted as a central paradigm. However, we have previously described an alternative mode of tumour dissemination, extravascular migratory metastasis, based on clinical and experimental data...
July 11, 2018: Scientific Reports
Maomao Zhang, Julie S Di Martino, Robert L Bowman, Nathaniel R Campbell, Sanjeethan C Baksh, Theresa Simon-Vermot, Isabella S Kim, Pearce Haldeman, Chandrani Mondal, Vladimir Yong-Gonzales, Mohsen Abu-Akeel, Taha Merghoub, Drew R Jones, Xiphias Ge Zhu, Arshi Arora, Charlotte E Ariyan, Kivanç Birsoy, Jedd D Wolchok, Katherine S Panageas, Travis Hollmann, Jose Javier Bravo-Cordero, Richard M White
Advanced, metastatic melanomas frequently grow in subcutaneous tissues and portend a poor prognosis. Though subcutaneous tissues are largely composed of adipocytes, the mechanisms by which adipocytes influence melanoma are poorly understood. Using in vitro and in vivo models, we find that adipocytes increase proliferation and invasion of adjacent melanoma cells. Additionally, adipocytes directly transfer lipids to melanoma cells, which alters tumor cell metabolism. Adipocyte-derived lipids are transferred to melanoma cells through the FATP/SLC27A family of lipid transporters expressed on the tumor cell surface...
August 2018: Cancer Discovery
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