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https://www.readbyqxmd.com/read/28746017/tumor-evolution-heterogeneity-and-therapy-for-our-patients-with-advanced-cancer-how-far-have-we-come
#1
Wafik S El-Deiry, Barry Taylor, Joel W Neal
The clinical and molecular heterogeneity of various cancer types is well documented. In the era of precision oncology whereby molecular profiling of tumors is incorporated into clinical care, both intra- and intertumoral molecular and genetic heterogeneity have been described. Together, they impact patient treatment and outcomes. Host genetics and the tumor microenvironment impact on tumor evolution and heterogeneity through variations in immune cell infiltration, stromal variations, and selection pressures from hypoxia or nutrient stress, among others...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28745637/isolation-of-circulating-tumor-cells-in-an-orthotopic-mouse-model-of-colorectal-cancer
#2
Susan Kochall, May-Linn Thepkaysone, Sebastián A García, Alexander M Betzler, Jürgen Weitz, Christoph Reissfelder, Sebastian Schölch
Despite the advantages of easy applicability and cost-effectiveness, subcutaneous mouse models have severe limitations and do not accurately simulate tumor biology and tumor cell dissemination. Orthotopic mouse models have been introduced to overcome these limitations; however, such models are technically demanding, especially in hollow organs such as the large bowel. In order to produce uniform tumors which reliably grow and metastasize, standardized techniques of tumor cell preparation and injection are critical...
July 18, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28745625/a-protocol-for-multiple-gene-knockout-in-mouse-small-intestinal-organoids-using-a-crispr-concatemer
#3
Alessandra Merenda, Amanda Andersson-Rolf, Roxana C Mustata, Taibo Li, Hyunki Kim, Bon-Kyoung Koo
CRISPR/Cas9 technology has greatly improved the feasibility and speed of loss-of-function studies that are essential in understanding gene function. In higher eukaryotes, paralogous genes can mask a potential phenotype by compensating the loss of a gene, thus limiting the information that can be obtained from genetic studies relying on single gene knockouts. We have developed a novel, rapid cloning method for guide RNA (gRNA) concatemers in order to create multi-gene knockouts following a single round of transfection in mouse small intestinal organoids...
July 12, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28736348/pathological-progression-possible-origin-and-management-of-multiple-primary-intracranial-neuroendocrine-carcinomas-a-case-report
#4
Jingwei Cao, Wenzhe Xu, Zhenhui Du, Bin Sun, Feng Li, Yuguang Liu
BACKGROUND: Primary intracranial neuroendocrine carcinomas (NECs) are extremely rare malignant tumors with no previous reports of multiple ones in the literatures. CASE DESCRIPTION: The clinical presentation, preoperative and reexamined magnetic resonance imaging (MRI) findings, as well as the histopathological studies of a 56-year-old female subject with multiple intracranial NECs mimicking multiple intracranial meningiomas, who underwent three operations with left parietal craniotomy, right occipital parietal craniotomy, and left frontal craniotomy, separately and chronologically are presented in this article...
July 20, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28736217/high-content-screening-in-hpsc-neural-progenitors-identifies-drug-candidates-that-inhibit-zika-virus-infection-in-fetal-like-organoids-and-adult-brain
#5
Ting Zhou, Lei Tan, Gustav Y Cederquist, Yujie Fan, Brigham J Hartley, Suranjit Mukherjee, Mark Tomishima, Kristen J Brennand, Qisheng Zhang, Robert E Schwartz, Todd Evans, Lorenz Studer, Shuibing Chen
Zika virus (ZIKV) infects fetal and adult human brain and is associated with serious neurological complications. To date, no therapeutic treatment is available to treat ZIKV-infected patients. We performed a high-content chemical screen using human pluripotent stem cell-derived cortical neural progenitor cells (hNPCs) and found that hippeastrine hydrobromide (HH) and amodiaquine dihydrochloride dihydrate (AQ) can inhibit ZIKV infection in hNPCs. Further validation showed that HH also rescues ZIKV-induced growth and differentiation defects in hNPCs and human fetal-like forebrain organoids...
July 19, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28735502/regenerative-medicine-in-kidney-disease-where-we-stand-and-where-to-go
#6
REVIEW
Fernanda T Borges, Nestor Schor
The kidney is a complex organ with more than 20 types of specialized cells that play an important role in maintaining the body's homeostasis. The epithelial tubular cell is formed during embryonic development and has little proliferative capacity under physiological conditions, but after acute injury the kidney does have regenerative capacity. However, after repetitive or severe lesions, it may undergo a maladaptation process that predisposes it to chronic kidney injury. Regenerative medicine includes various repair and regeneration techniques, and these have gained increasing attention in the scientific literature...
July 22, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28734180/bottom-up-assembly-of-salivary-gland-microtissues-for-assessing-myoepithelial-cell-function
#7
Tugba Ozdemir, Padma Pradeepa Srinivasan, Daniel R Zakheim, Daniel A Harrington, Robert L Witt, Mary C Farach-Carson, Xinqiao Jia, Swati Pradhan-Bhatt
Myoepithelial cells are flat, stellate cells present in exocrine tissues including the salivary glands. While myoepithelial cells have been studied extensively in mammary and lacrimal gland tissues, less is known of the function of myoepithelial cells derived from human salivary glands. Several groups have isolated tumorigenic myoepithelial cells from cancer specimens, however, only one report has demonstrated isolation of normal human salivary myoepithelial cells needed for use in salivary gland tissue engineering applications...
July 14, 2017: Biomaterials
https://www.readbyqxmd.com/read/28732246/inspiration-from-heart-development-biomimetic-development-of-functional-human-cardiac-organoids
#8
Dylan J Richards, Robert C Coyle, Yu Tan, Jia Jia, Kerri Wong, Katelynn Toomer, Donald R Menick, Ying Mei
Recent progress in human organoids has provided 3D tissue systems to model human development, diseases, as well as develop cell delivery systems for regenerative therapies. While direct differentiation of human embryoid bodies holds great promise for cardiac organoid production, intramyocardial cell organization during heart development provides biological foundation to fabricate human cardiac organoids with defined cell types. Inspired by the intramyocardial organization events in coronary vasculogenesis, where a diverse, yet defined, mixture of cardiac cell types self-organizes into functional myocardium in the absence of blood flow, we have developed a defined method to produce scaffold-free human cardiac organoids that structurally and functionally resembled the lumenized vascular network in the developing myocardium, supported hiPSC-CM development and possessed fundamental cardiac tissue-level functions...
July 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/28724787/disrupted-apical-exocytosis-of-cargo-vesicles-causes-enteropathy-in-fhl5-patients-with-munc18-2-mutations
#9
Georg F Vogel, Jorik M van Rijn, Iris M Krainer, Andreas R Janecke, Carsten Posovzsky, Marta Cohen, Claire Searle, Prevost Jantchou, Johanna C Escher, Natalie Patey, Ernest Cutz, Thomas Müller, Sabine Middendorp, Michael W Hess, Lukas A Huber
Familial hemophagocytic lymphohistiocytosis 5 (FHL5) is an autosomal recessive disease caused by mutations in STXBP2, coding for Munc18-2, which is required for SNARE-mediated membrane fusion. FHL5 causes hematologic and gastrointestinal symptoms characterized by chronic enteropathy that is reminiscent of microvillus inclusion disease (MVID). However, the molecular pathophysiology of FHL5-associated diarrhea is poorly understood. Five FHL5 patients, including four previously unreported patients, were studied...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28720124/defining-the-role-of-lgr5-stem-cells-in-colorectal-cancer-from-basic-research-to-clinical-applications
#10
Masayuki Fujii, Toshiro Sato
Intestinal epithelium is structured by two distinct components: the villi and the crypts. The crypts harbor stem cells expressing Lgr5 and thus have been a representative model to study tissue stem cell functions. Recent advances in organoid technology and analytical modalities have enabled precise characterization of Lgr5(+) intestinal stem cells, providing insights into their roles in homeostasis and cancer.
July 18, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28717211/epithelial-cell-specific-raptor-is-required-for-initiation-of-type-2-mucosal-immunity-in-small-intestine
#11
Bola Aladegbami, Lauren Barron, James Bao, Jason Colasanti, Christopher R Erwin, Brad W Warner, Jun Guo
Intestinal tuft cells are one of 4 secretory cell linages in the small intestine and the source of IL-25, a critical initiator of the type 2 immune response to parasite infection. When Raptor, a critical scaffold protein for mammalian target of rapamycin complex 1 (mTORC1), was acutely deleted in intestinal epithelium via Tamoxifen injection in Tritrichomonas muris (Tm) infected mice, tuft cells, IL-25 in epithelium and IL-13 in the mesenchyme were significantly reduced, but Tm burden was not affected. When Tm infected mice were treated with rapamycin, DCLK1 and IL-25 expression in enterocytes and IL-13 expression in mesenchyme were diminished...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716722/dynamics-of-proliferative-and-quiescent-stem-cells-in-liver-homeostasis-and-injury
#12
Wanlu Cao, Kan Chen, Michiel Bolkestein, Yuebang Yin, Monique M A Verstegen, Marcel J C Bijvelds, Wenshi Wang, Nesrin Tuysuz, Derk Ten Berge, Dave Sprengers, Herold J Metselaar, Luc J W van der Laan, Jaap Kwekkeboom, Ron Smits, Maikel P Peppelenbosch, Qiuwei Pan
BACKGROUND & AIMS: Adult liver stem cells are usually maintained in a quiescent/slow cycling state. However, a proliferative population, marked by leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), was recently identified as an important liver stem cell population. We aimed to investigate the dynamics and functions of proliferative and quiescent stem cells in healthy and injured livers. METHODS: We studied LGR5-positive stem cells using diphtheria toxin receptor (DTR) and green fluorescent protein (GFP) knock-in mice...
July 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28716720/met-signaling-mediates-intestinal-crypt-villus-development-regeneration-and-adenoma-formation-and-is-promoted-by-stem-cell-cd44-isoforms
#13
Sander P J Joosten, Jurrit Zeilstra, Harmen van Andel, R Clinton Mijnals, Joost Zaunbrecher, Annet A M Duivenvoorden, Marc van de Wetering, Hans Clevers, Marcel Spaargaren, Steven T Pals
BACKGROUND & AIMS: Resistance of metastatic human colorectal cancer cells to drugs that block epidermal growth factor receptor (EGFR) signaling could be caused by aberrant activity of other receptor tyrosine kinases, activating overlapping signaling pathways. One of these receptor tyrosine kinases could be MET, the receptor for hepatocyte growth factor (HGF). We investigated how MET signaling, and its interaction with CD44 (a putative MET co-receptor regulated by Wnt signaling and highly expressed by intestinal stem cells [ISCs] and adenomas) affects intestinal homeostasis, regeneration, and adenoma formation in mini-gut organoids and mice...
July 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28713235/connecting-the-brain-to-itself-through-an-emulation
#14
Mijail D Serruya
Pilot clinical trials of human patients implanted with devices that can chronically record and stimulate ensembles of hundreds to thousands of individual neurons offer the possibility of expanding the substrate of cognition. Parallel trains of firing rate activity can be delivered in real-time to an array of intermediate external modules that in turn can trigger parallel trains of stimulation back into the brain. These modules may be built in software, VLSI firmware, or biological tissue as in vitro culture preparations or in vivo ectopic construct organoids...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28708059/a-tunable-refractive-index-matching-medium-for-live-imaging-cells-tissues-and-model-organisms
#15
Tobias Boothe, Lennart Hilbert, Michael Heide, Lea Berninger, Wieland B Huttner, Vasily Zaburdaev, Nadine L Vastenhouw, Eugene W Myers, David N Drechsel, Jochen C Rink
In light microscopy, refractive index mismatches between media and sample cause spherical aberrations that often limit penetration depth and resolution. Optical clearing techniques can alleviate these mismatches, but they are so far limited to fixed samples. We present Iodixanol as a non-toxic medium supplement that allows refractive index matching in live specimens and thus a substantial improvement of the live-imaging of primary cell cultures, planarians, zebrafish and human cerebral organoids.
July 14, 2017: ELife
https://www.readbyqxmd.com/read/28707964/roles-of-diffusion-dynamics-in-stem-cell-signaling-and-three-dimensional-tissue-development
#16
Richard J McMurtrey
Recent advancements in the ability to construct three-dimensional (3D) tissues and organoids from stem cells and biomaterials have not only opened abundant new research avenues in disease modeling and regenerative medicine but also have ignited investigation into important aspects of molecular diffusion in 3D cellular architectures. This paper describes fundamental mechanics of diffusion with equations for modeling these dynamic processes under a variety of scenarios in 3D cellular tissue constructs. The effects of these diffusion processes and resultant concentration gradients are described in the context of the major molecular signaling pathways in stem cells that both mediate and are influenced by gas and nutrient concentrations, including how diffusion phenomena can affect stem cell state, cell differentiation, and metabolic states of the cell...
July 14, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28705002/preclinical-models-of-pancreatic-ductal-adenocarcinoma
#17
Benjamin D Krempley, Kenneth H Yu
Unlike many other cancers, pancreatic ductal adenocarcinoma (PDAC) has seen only incremental improvement in mortality despite significant advances in our understanding of the underlying biology. A primary obstacle to progress has been our inability to properly model PDAC in a preclinical setting. PDAC is difficult to study because of its genetic heterogeneity, intricate stromal microenvironment, and complex interplay with our immune system. Finding a model that properly accounts for all these criteria remains difficult...
June 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28702885/use-of-a-super-hydrophobic-microbioreactor-to-generate-and-boost-pancreatic-mini-organoids
#18
Tiziana A L Brevini, Elena F M Manzoni, Sergio Ledda, Fulvio Gandolfi
Cell remarkable ability to self-organize and rearrange in functional organoids has been greatly boosted by the recent advances in 3-D culture technologies and materials. This approach can be presently applied to model human organ development and function "in a dish" and to predict drug response in a patient specific fashion.Here we describe a protocol that allows for the derivation of functional pancreatic mini-organoids from skin biopsies. Cells are suspended in a drop of medium and encapsulated with hydrophobic polytetrafluoroethylene (PTFE) powder particles, to form microbioreactors defined as "Liquid Marbles," that stimulate cell coalescence and 3-D aggregation...
July 13, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28699415/a-scalable-approach-for-the-generation-of-human-pluripotent-stem-cell-derived-hepatic-organoids-with-sensitive-hepatotoxicity-features
#19
Malte Sgodda, Zhen Dai, Robert Zweigerdt, Amar D Sharma, Michael Ott, Tobias Cantz
The quest for physiologically-active human hepatocyte-like cells for in vitro research and drug screening is high. The recent progress in the field of pluripotent stem cell (PSC) - derived hepatic cells within the last decade brings those cells closer to applications in translational medicine. However, the classical two-dimensional (2D) cell culture systems are of limited use, because relevant cell-cell interactions based on cell polarity, which is a major prerequisite for proper hepatic cell metabolisms, are not provided...
July 12, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28697965/beyond-organoids-in-vitro-vasculogenesis-and-angiogenesis-using-cells-from-mammals-and-zebrafish
#20
REVIEW
Muhammad Ibrahim, Michael K Richardson
The ability to culture complex organs is currently an important goal in biomedical research. It is possible to grow organoids (3D organ-like structures) in vitro; however, a major limitation of organoids, and other 3D culture systems, is the lack of a vascular network. Protocols developed for establishing in vitro vascular networks typically use human or rodent cells. A major technical challenge is the culture of functional (perfused) networks. In this rapidly advancing field, some microfluidic devices are now getting close to the goal of an artificially perfused vascular network...
July 8, 2017: Reproductive Toxicology
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