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https://www.readbyqxmd.com/read/28325895/simulation-assisted-design-of-microfluidic-sample-traps-for-optimal-trapping-and-culture-of-non-adherent-single-cells-tissues-and-spheroids
#1
Nassim Rousset, Frédéric Monet, Thomas Gervais
This work focuses on modelling design and operation of "microfluidic sample traps" (MSTs). MSTs regroup a widely used class of microdevices that incorporate wells, recesses or chambers adjacent to a channel to individually trap, culture and/or release submicroliter 3D tissue samples ranging from simple cell aggregates and spheroids, to ex vivo tissue samples and other submillimetre-scale tissue models. Numerous MST designs employing various trapping mechanisms have been proposed in the literature, spurring the development of 3D tissue models for drug discovery and personalized medicine...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28324660/single-and-combination-drug-screening-with-aqueous-biphasic-tumor-spheroids
#2
Pradip Shahi Thakuri, Hossein Tavana
Spheroids of cancer cells represent a physiologic model of solid tumors for cancer drug screening. Despite this known benefit, difficulties with generating large quantities of uniformly sized spheroids in standard plates, individually addressing spheroids with drug compounds, and quantitatively analyzing responses of cancer cells have hindered the use of spheroids in high-throughput screening applications. Recently, we addressed this challenge by using an aqueous two-phase system technology to generate a spheroid within an aqueous drop immersed in a second, immiscible aqueous phase...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28324645/three-dimensional-analysis-of-somatic-mitochondrial-dynamics-in-fission-deficient-injured-motor-neurons-using-fib-sem
#3
Hiromi Tamada, Sumiko Kiryu-Seo, Hiroki Hosokawa, Keisuke Ohta, Naotada Ishihara, Masatoshi Nomura, Katsuyoshi Mihara, Kei-Ichiro Nakamura, Hiroshi Kiyama
Mitochondria undergo morphological changes through fusion and fission for their quality control, which are vital for neuronal function. In this study, we examined three-dimensional morphologies of mitochondria in motor neurons under normal, nerve injured, and nerve injured plus fission-impaired conditions using the focused ion beam/scanning electron microscopy (FIB/SEM), because the FIB/SEM technology is a powerful tool to demonstrate both 3D images of whole organelle and the intra-organellar structure simultaneously...
March 21, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28322021/cytoprotective-and-antioxidant-effects-of-steen-solution-on-human-lung-spheroids-and-human-endothelial-cells
#4
Francesca Pagano, Cristina Nocella, Sebastiano Sciarretta, Luca Fianchini, Camilla Siciliano, Giorgio Mangino, Mohsen Ibrahim, Elena De Falco, Roberto Carnevale, Isotta Chimenti, Giacomo Frati
Respiratory diseases represent a major healthcare burden worldwide. Lung transplantation (LTx) is the gold-standard for end-stage patients, strongly limited by shortage of available/suitable donor lungs. Normothermic ex vivo lung perfusion (EVLP) has significantly increased the number of lungs suitable for transplantation. Steen solution is used for EVLP, but the mechanisms involved in its beneficial properties remain to be clarified. We investigated the effects of Steen solution in an in vitro protocol of cold starvation and normothermic recovery (CS/NR) on human lung spheroids, named pneumospheres (PSs), containing epithelial/basal cells, and on endothelial HUVEC cells...
March 20, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28320338/the-allosteric-akt-inhibitor-mk2206-shows-a-synergistic-interaction-with-chemotherapy-and-radiotherapy-in-glioblastoma-spheroid-cultures
#5
Ravi S Narayan, Carlos A Fedrigo, Eelke Brands, Rogier Dik, Lukas J A Stalpers, Brigitta G Baumert, Ben J Slotman, Bart A Westerman, Godefridus J Peters, Peter Sminia
BACKGROUND: Glioblastoma multiforme (GBM) is the most common, invasive and deadly primary type of malignant brain tumor. The Phosphatidylinositol-3-Kinase/AKT (PI3K/AKT) pathway is highly active in GBM and has been associated with increased survival and resistance to therapy. The aim of this study is to investigate the effects of AKT inhibition in combination with the current standard of care which consists of irradiation and temozolomide (TMZ) on human malignant glioma cells growing adherent and as multicellular spheroids in vitro...
March 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28319891/time-and-cell-resolved-dynamics-of-redox-sensitive-nrf2-hif-and-nf-%C3%AE%C2%BAb-activities-in-3d-spheroids-enriched-for-cancer-stem-cells
#6
Anna P Kipp, Stefanie Deubel, Elias S J Arnér, Katarina Johansson
Cancer cells have an altered redox status, with changes in intracellular signaling pathways. The knowledge of how such processes are regulated in 3D spheroids, being well-established tumor models, is limited. To approach this question we stably transfected HCT116 cells with a pTRAF reporter that enabled time- and cell-resolved activity monitoring of three redox-regulated transcription factors Nrf2, HIF and NF-κB in spheroids enriched for cancer stem cells. At the first day of spheroid formation, these transcription factors were activated and thereafter became repressed...
March 10, 2017: Redox Biology
https://www.readbyqxmd.com/read/28319810/inhibitors-of-glut-slc2a-enhance-the-action-of-bcnu-and-temozolomide-against-high-grade-gliomas
#7
Alberto Azzalin, Giulia Nato, Elena Parmigiani, Francesca Garello, Annalisa Buffo, Lorenzo Magrassi
Glucose transport across glioblastoma membranes plays a crucial role in maintaining the enhanced glycolysis typical of high-grade gliomas and glioblastoma. We tested the ability of two inhibitors of the glucose transporters GLUT/SLC2A superfamily, indinavir (IDV) and ritonavir (RTV), and of one inhibitor of the Na/glucose antiporter type 2 (SGLT2/SLC5A2) superfamily, phlorizin (PHZ), in decreasing glucose consumption and cell proliferation of human and murine glioblastoma cells. We found in vitro that RTV, active on at least three different GLUT/SLC2A transporters, was more effective than IDV, a specific inhibitor of GLUT4/SLC2A4, both in decreasing glucose consumption and lactate production and in inhibiting growth of U87MG and Hu197 human glioblastoma cell lines and primary cultures of human glioblastoma...
March 17, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28319735/different-combinations-of-growth-factors-for-the-tenogenic-differentiation-of-bone-marrow-mesenchymal-stem-cells-in-monolayer-culture-and-in-fibrin-based-three-dimensional-constructs
#8
Marta Bottagisio, Silvia Lopa, Valentina Granata, Giuseppe Talò, Chiara Bazzocchi, Matteo Moretti, Arianna Barbara Lovati
Tendon injuries are severe burdens in clinics. The poor tendon healing is related to an ineffective response of resident cells and inadequate vascularization. Thanks to the high proliferation and multi-lineage differentiation capability, bone marrow-derived mesenchymal stem cells (BMSCs) are a promising cell source to support the tendon repair. To date, the association of various growth factors to induce the in vitro tenogenic differentiation of multipotent progenitor cells is poorly investigated. This study aimed to investigate the tenogenic differentiation of rabbit BMSCs by testing the combination of bone morphogenetic proteins (BMP-12 and 14) with transforming growth factor beta (TGF-β) and vascular endothelial growth factor (VEGF) both in 2D and 3D cultures within fibrin-based constructs...
March 16, 2017: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/28315430/oncolytic-adenovirus-expressing-relaxin-ydc002-enhances-therapeutic-efficacy-of-gemcitabine-against-pancreatic-cancer
#9
Kyung Hee Jung, Il-Kyu Choi, Hee-Seung Lee, Hong Hua Yan, Mi Kwon Son, Hyo Min Ahn, JinWoo Hong, Chae-Ok Yun, Soon-Sun Hong
Pancreatic cancer is a highly lethal disease for which limited therapeutic options are available. Pancreatic cancer exhibits a pronounced collagen-rich stromal reaction, which induces chemoresistance by inhibiting drug diffusion into the tumor. Complementary treatment with oncolytic virus such as an oncolytic adenovirus expressing relaxin (YDC002) is an innovative treatment option for combating chemoresistant pancreatic cancer. Here, we examined the ability of combined treatment with gemcitabine and YDC002, which degrades extracellular matrix (ECM), to efficiently treat chemoresistant and desmoplastic pancreatic cancer...
March 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28314117/three-dimensional-cell-cultures-in-drug-discovery-and-development
#10
Ye Fang, Richard M Eglen
The past decades have witnessed significant efforts toward the development of three-dimensional (3D) cell cultures as systems that better mimic in vivo physiology. Today, 3D cell cultures are emerging, not only as a new tool in early drug discovery but also as potential therapeutics to treat disease. In this review, we assess leading 3D cell culture technologies and their impact on drug discovery, including spheroids, organoids, scaffolds, hydrogels, organs-on-chips, and 3D bioprinting. We also discuss the implementation of these technologies in compound identification, screening, and development, ranging from disease modeling to assessment of efficacy and safety profiles...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28302668/sulphated-glycosaminoglycans-support-an-assortment-of-planarian-rhabdite-structures
#11
Matthew J Hayes
Planaria are soft-bodied, bilateral flatworms of the phylum Playhelminthes. They are covered in cilia and use ciliary-gliding to traverse the substratum while hunting. Their body surface is covered in a layer of viscous slime primarily derived from specialised secretory granules known as rhabdites. The slime must somehow stay associated with the surface of the animal in aqueous environments whilst also lubricating the interface of the animal and the surfaces over which the animal moves. The slime prevents damage to the animal's soft body and also contributes to adhesion to the substratum...
March 16, 2017: Biology Open
https://www.readbyqxmd.com/read/28302167/proton-nmr-characterization-of-intact-primary-and-metastatic-melanoma-cells-in-2d-3d-cultures
#12
Gokula Krishnan Ramachandran, Chen Hua Yeow
OBJECTIVE: To characterize the differences between the primary and metastatic melanoma cell lines grown in 2D cultures and 3D cultures. METHODS: Primary melanoma cells (WM115) and metastatic melanoma cells (WM266) extracted from a single donor was cultured in 2D as well as 3D cultures. These cells were characterized using proton NMR spectrometry, and the qualitative chemical shifts markers were identified and discussed. RESULTS: In monolayer culture (2D), we observed one qualitative chemical shift marker for primary melanoma cells...
March 16, 2017: Biological Research
https://www.readbyqxmd.com/read/28301591/in-vivo-and-ex-vivo-cetuximab-sensitivity-assay-using-three-dimensional-primary-culture-system-to-stratify-kras-mutant-colorectal-cancer
#13
Takahiro Tashiro, Hiroaki Okuyama, Hiroko Endo, Kenji Kawada, Yasuko Ashida, Masayuki Ohue, Yoshiharu Sakai, Masahiro Inoue
In clinic, cetuximab, an anti-EGFR antibody, improves treatment outcomes in colorectal cancer (CRC). KRAS-mutant CRC is generally resistant to cetuximab, although difference of the sensitivity among KRAS-mutants has not been studied in detail. We previously developed the cancer tissue-originated spheroid (CTOS) method, a primary culture method for cancer cells. We applied CTOS method to investigate whether ex vivo cetuximab sensitivity assays reflect the difference in sensitivity in the xenografts. Firstly, in vivo cetuximab treatment was performed with xenografts derived from 10 CTOS lines (3 KRAS-wildtype and 7 KRAS mutants)...
2017: PloS One
https://www.readbyqxmd.com/read/28298153/exploring-drug-dosing-regimens-in-vitro-using-real-time-3d-spheroid-tumor-growth-assays
#14
Madhu Lal-Nag, Lauren McGee, Steven A Titus, Kyle Brimacombe, Sam Michael, Gurusingham Sittampalam, Marc Ferrer
Two-dimensional monolayer cell proliferation assays for cancer drug discovery have made the implementation of large-scale screens feasible but only seem to reflect a simplified view that oncogenes or tumor suppressor genes are the genetic drivers of cancer cell proliferation. However, there is now increased evidence that the cellular and physiological context in which these oncogenic events occur play a key role in how they drive tumor growth in vivo and, therefore, in how tumors respond to drug treatments...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28297606/a-novel-cellular-spheroid-based-autophagy-screen-applying-live-fluorescence-microscopy-identifies-nonactin-as-a-strong-inducer-of-autophagosomal-turnover
#15
Francesco Pampaloni, Benjamin Mayer, Konstantin Kabat Vel-Job, Nariman Ansari, Katharina Hötte, Donat Kögel, Ernst H K Stelzer
Dysregulation of the basal autophagic flux has been linked to several pathological conditions, including neurodegenerative diseases and cancer. In addition, autophagy has profound effects on the response of tumor cells to therapy. Hence, the search for pharmacological modulators of autophagy is of great clinical relevance. We established a drug screening assay in which the autophagic flux is measured by recording the fluorescence emission of the tandem fusion protein mRFP-GFP-LC3 by dynamic live-cell imaging...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28297570/human-lung-spheroids-as-in-vitro-niches-of-lung-progenitor-cells-with-distinctive-paracrine-and-plasticity-properties
#16
Isotta Chimenti, Francesca Pagano, Francesco Angelini, Camilla Siciliano, Giorgio Mangino, Vittorio Picchio, Elena De Falco, Mariangela Peruzzi, Roberto Carnevale, Mohsen Ibrahim, Giuseppe Biondi-Zoccai, Elisa Messina, Giacomo Frati
Basic and translational research on lung biology has discovered multiple progenitor cell types, specialized or facultative, responsible for turnover, renewal, and repair. Isolation of populations of resident lung progenitor cells (LPCs) has been described by multiple protocols, and some have been successfully applied to healthy human lung tissue. We aimed at understanding how different cell culture conditions may affect, in vitro, the phenotype of LPCs to create an ideal niche-like microenvironment. The influence of different substrates (i...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28294357/expression-of-factors-involved-in-dental-pulp-physiopathological-processes-by-nemotic-human-pulpal-fibroblasts
#17
J Le Clerc, S Tricot-Doleux, P Pellen-Mussi, M Pérard, S Jeanne, F Pérez
AIM: To investigate in human pulp fibroblasts (HDPF) the expression of factors involved in dental pulp physiopathological processes and in an experimental model of cell activation called nemosis, and to compare the behaviour of pulp cell activation with sound lung fibroblasts MRC5, employed as a reference model for nemosis. METHODOLOGY: Nemotic response was induced in 3-dimensional cultures of HDPF and lung fibroblasts. The expressions of molecules involved in physiological (alkaline phosphatase, type I collagen) and in inflammatory processes (IL-6, CXCL8, CCL20, COX-2) were studied using real-time PCR...
March 10, 2017: International Endodontic Journal
https://www.readbyqxmd.com/read/28294325/three-dimensional-culture-of-buffalo-granulosa-cells-in-hanging-drop-mimics-the-preovulatory-follicle-stage
#18
Monica Yadav, Himanshu Agrawal, Mamta Pandey, Dheer Singh, Suneel Kumar Onteru
Granulosa cell (GC) culture models mimicking the intrafollicular environment are limited. Such models have a great potential in reproductive toxicity studies. The buffalo, a monovulatory species like humans, could be a better model than polyovulatory rodents. Therefore, we targeted the development and characterization of three-dimensional (3D) culture systems for buffalo GCs. The GCs from small ovarian follicles (SF) maintained the CYP19 gene expression for 144 h in a 2D culture system. Hence, GCs from SF were cultured directly in 3D using hanging drop and Poly-{(2-hydroxyethyl methacrylate)} (polyHEMA) methods in the DMEM media containing 1ng/mL FSH and 10 ng/mL IGF-1 for 144 h...
March 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28293067/syndecan-1-acts-as-an-important-regulator-of-cxcl1-expression-and-cellular-interaction-of-human-endometrial-stromal-and-trophoblast-cells
#19
Dunja Maria Baston-Buest, Olga Altergot-Ahmad, Sarah Jean Pour, Jan-Steffen Krüssel, Udo Rudolf Markert, Tanja Natascha Fehm, Alexandra Petra Bielfeld
Successful implantation of the embryo into the human receptive endometrium is substantial for the establishment of a healthy pregnancy. This study focusses on the role of Syndecan-1 at the embryo-maternal interface, the multitasking coreceptor influencing ligand concentration, release and receptor presentation, and cellular morphology. CXC motif ligand 1, being involved in chemotaxis and angiogenesis during implantation, is of special interest as a ligand of Syndecan-1. Human endometrial stromal cells with and without Syndecan-1 knock-down were decidualized and treated with specific inhibitors to evaluate signaling pathways regulating CXC ligand 1 expression...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28290010/bayesian-calibration-validation-and-uncertainty-quantification-for-predictive-modelling-of-tumour-growth-a-tutorial
#20
Joe Collis, Anthony J Connor, Marcin Paczkowski, Pavitra Kannan, Joe Pitt-Francis, Helen M Byrne, Matthew E Hubbard
In this work, we present a pedagogical tumour growth example, in which we apply calibration and validation techniques to an uncertain, Gompertzian model of tumour spheroid growth. The key contribution of this article is the discussion and application of these methods (that are not commonly employed in the field of cancer modelling) in the context of a simple model, whose deterministic analogue is widely known within the community. In the course of the example, we calibrate the model against experimental data that are subject to measurement errors, and then validate the resulting uncertain model predictions...
March 13, 2017: Bulletin of Mathematical Biology
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