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https://www.readbyqxmd.com/read/29143522/mmp-2-sensitive-ha-end-conjugated-poly-amidoamine-dendrimers-via-click-reaction-to-enhance-drug-penetration-into-solid-tumor
#1
Min Han, Ming-Yi Huang-Fu, Wang-Wei Guo, Ningning Guo, Jiejian Chen, Huina Liu, Zhiqi Xie, Mengting Lin, Qichun Wei, Jianqing Gao
Currently, the limited tumor penetration of nanoparticles remains a major challenge of cancer nanomedicine. Herein, we propose a size-shrinkable, drug delivery system based on a polysaccharide-modified dendrimer with tumor microenvironment responsiveness for the first time to our knowledge, which was formed by conjugating the terminal glucose of hyaluronic acid (HA) to the superficial amidogen of poly(amidoamine) (PAMAM), using a matrix metalloproteinase-2 (MMP-2)-cleavable peptide (PLGLAG) via click reaction...
November 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29141956/rapid-isolation-and-expansion-of-skin-derived-precursor-cells-from-human-primary-fibroblast-cultures
#2
Leithe Budel, Karima Djabali
Skin-derived precursor (SKP) cells have self-renewal and multipotent abilities and are found in the dermis. SKP cells have been isolated previously from pre-established dermal fibroblast cultures. In these procedures, long-term culture and low yield remain the crucial aspects requiring improvement. In this study, we exposed pre-established dermal fibroblasts to 30-min acid stress prior to isolating SKP cells (termed pH-SKP) and compared the yield to the previously published trypsin- and no-stress methods. Spheroid formation was confirmed and analyzed at days 3, 5 and 7...
November 15, 2017: Biology Open
https://www.readbyqxmd.com/read/29141914/proteotranscriptomics-reveal-signaling-networks-in-the-ovarian-cancer-microenvironment
#3
Thomas Worzfeld, Florian Finkernagel, Silke Reinartz, Anne Konzer, Till Adhikary, Andrea Nist, Thorsten Stiewe, Uwe Wagner, Mario Looso, Johannes Graumann, Rolf Müller
Ovarian cancer is characterized by early transcoelomic metastatic spread via the peritoneal fluid, where tumor cell spheroids (TU), tumor-associated T cells (TAT), and macrophages (TAM) create a unique microenvironment promoting cancer progression, chemoresistance and immuno-suppression. However, the underlying signaling mechanisms remain largely obscure.  To chart these signaling networks, we performed comprehensive proteomic and transcriptomic analyses of TU, TAT and TAM from ascites of ovarian cancer patients...
November 15, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29141026/in-depth-phenotypic-characterization-of-multicellular-tumor-spheroids-effects-of-5-fluorouracil
#4
Angélique Virgone-Carlotta, Manon Lemasson, Hichem C Mertani, Jean-Jacques Diaz, Sylvain Monnier, Thomas Dehoux, Hélène Delanoë-Ayari, Charlotte Rivière, Jean-Paul Rieu
MultiCellular Tumor Spheroids (MCTS), which mimic the 3-Dimensional (3D) organization of a tumor, are considered as better models than conventional cultures in 2-Dimensions (2D) to study cancer cell biology and to evaluate the response to chemotherapeutic drugs. A real time and quantitative follow-up of MCTS with simple and robust readouts to evaluate drug efficacy is still missing. Here, we evaluate the chemotherapeutic drug 5-Fluorouracil (5-FU) response on the growth and integrity of MCTS two days after treatment of MCTS and for three colorectal carcinoma cell lines with different cohesive properties (HT29, HCT116 and SW480)...
2017: PloS One
https://www.readbyqxmd.com/read/29139396/folic-acid-modified-pluronic-f127-coating-ag2s-quantum-dot-for-photoacoustic-imaging-of-tumor-cell-targeting
#5
Ruo-Yun Zhang, Zhao-Yang Wang, Xiao-Quan Yang, Yang Xuan, Kai Cheng, Cheng Li, Xian-Lin Song, Jie An, Xiao-Lin Hou, Yuan-Di Zhao
In this study, oil-soluble Ag2S quantum dot (QD) was synthesized through thermal decomposition of single-source precursor method, and Pluronic F127 (PF127), a triblock copolymer functionalized with folic acid (FA), was deposited on the surface of QD, then water-soluble PF127-FA@Ag2S nanoprobe with targeting ability was fabricated. The as-prepared PF127-FA@Ag2S exhibited spheroidal morphology and high dispersibility, with average diameters of 115 ± 20.7 nm (as observed by transmission electron microscopy). No obvious toxicity of PF127-FA@Ag2S nanoprobe was found in standard 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and colony-formation assay, indicating that decent biocompatibility and safety...
November 15, 2017: Nanotechnology
https://www.readbyqxmd.com/read/29138811/high-expression-of-mage-a9-contributes-to-stemness-and-malignancy-of-human-hepatocellular-carcinoma
#6
Youping Wei, Yanqin Wang, Jing Gong, Lihua Rao, Zhiwei Wu, Teng Nie, Dongling Shi, Liming Zhang
MAGE-A9, a well-characterized cancer testis antigen (CTA), belongs to a member of melanoma antigen gene (MAGE) family. In human malignancies, aberrant expression of MAGE genes correlated with poor clinical prognosis, increased tumor growth, metastases, and enrichment in stem cell populations of certain cancers. Cancer stem cells (CSCs) have been proposed to contribute to the major malignant phenotypes of liver cancer, including recurrence, metastasis and chemoresistance. However, expression and potential role of MAGE-A9 in liver cancer stem cells (LCSCs) still remain unclear...
November 9, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29138030/aspergillus-candidus-is-a-newly-recognized-source-of-sphaeropsidin-a-isolation-semi-synthetic-derivatization-and-anticancer-evaluation
#7
Yan Li, Robert Scott, Annie R Hooper, Geoffrey A Bartholomeusz, Alexander Kornienko, Gerald F Bills
This report details a search for alternative strains that produce the diterpenoid sphaeropsidin A (SphA) among A. candidus strains from the USDA Northern Regional Research Laboratories Culture Collection. We identified two strains that produced SphA using a limited set of test media. An initial scaled-up fermentation of NRRL 313 and isolation effort led to the procurement of sufficient quantities of SphA to prepare five semi-synthetic analogues (1-5) and evaluate their anticancer effects against glioblastoma cells D423 and Gli56 grown in 2D and 3D cultures...
November 4, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29133623/immu-140-a-novel-sn-38-antibody-drug-conjugate-targeting-hla-dr-mediates-dual-cytotoxic-effects-in-hematological-cancers-and-malignant-melanoma
#8
Thomas M Cardillo, Serengulam V Govindan, Maria B Zalath, Diane L Rossi, Yang Wang, Chien-Hsing Chang, David M Goldenberg
HLA-DR is a member of the MHC class II antigen family expressed on hematological and solid tumors.  Antibodies directed against HLA-DR have demonstrated some clinical success, but toxicities limited development.  IMMU-140 is an anti-HLA-DR antibody-drug conjugate comprised of the active metabolite of irinotecan, SN-38, conjugated to a humanized anti-HLA-DR IgG4 antibody (IMMU-114); the IgG4 naked antibody is devoid of immune functions. Our aim was to determine if SN-38, the metabolite of a drug not commonly used in hematopoietic cancers, would be effective and safe when targeted to HLA-DR-expressing tumors...
November 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29133622/ceritinib-enhances-the-efficacy-of-trametinib-in-braf-nras-wild-type-melanoma-cell-lines
#9
Daniel Verduzco, Brent M Kuenzi, Fumi Kinose, Vernon K Sondak, Zeynep Eroglu, Uwe Rix, Keiran S M Smalley
Targeted therapy options are currently lacking for the heterogeneous population of patients whose melanomas lack BRAF or NRAS mutations (~35% of cases). We undertook a chemical biology screen to identify potential novel drug targets for this understudied group of tumors. Screening a panel of 8 BRAF/NRAS-WT melanoma cell lines against 240 targeted drugs identified ceritinib and trametinib as potential hits with single agent activity. Ceritinib enhanced the efficacy of trametinib across the majority of the BRAF/NRAS-WT cell lines, and the combination showed increased cytotoxicity in both 3D spheroid culture and long-term colony formation experiments...
November 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29133100/physicochemical-properties-of-a-high-molecular-weight-levan-from-brenneria-sp-enid312
#10
Wei Xu, Qian Liu, Yuxiang Bai, Shuhuai Yu, Tao Zhang, Bo Jiang, Wanmeng Mu
A high molecular weight levan was produced by a novel levansucrase and some properties of this polymer were investigated. The levan exhibited a poroid microstructure as well as series of individual ellipsoidal or spheroidal particles. The weight-average molecular weight (M¯w) of the levan was determined to be 1.41×10(8)Da. In a 0.1% solution, the levan showed a mean diameter of 176nm, while in a 1% solution the diameter was 182nm. The decomposition temperature was determined to be 216.67°C, with an endothermic peak at 147...
November 10, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29133085/corrigendum-to-one-step-fabrication-of-hydrogel-microcapsules-with-hollow-core-for-assembly-and-cultivation-of-hepatocyte-spheroids-acta-biomater-50-2017-428-436
#11
Christian Siltanen, Michalitsa Diakatou, Jeremy Lowen, Amranul Haque, Ali Rahimian, Gulnaz Stybayeva, Alexander Revzin
No abstract text is available yet for this article.
November 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29132205/secretome-of-aggregated-embryonic-stem-cell-derived-mesenchymal-stem-cell-modulates-the-release-of-inflammatory-factors-in-lipopolysaccharide-induced-peripheral-blood-mononuclear-cells
#12
Nastaran Mohammadi Ghahhari, Faezeh Maghsood, Saeed Jahandideh, Majid Lotfinia, Shirin Lak, Behrooz Johari, Asaad Azarnezhad, Mehdi Kadivar
Background: Bone marrow mesenchymal stem cells (BM-MSCs) have emerged as a potential therapy for various inflammatory diseases. Because of some limitations, several recent studies have suggested the use of embryonic stem cell-derived MSCs (ESC-MSCs) as an alternative for BM-MSCs. Some of the therapeutic effects of the ESC-MSCs are related to the secretion of a broad array of cytokines and growth factors, known as secretome. Harnessing this secretome for therapeutic applications requires the optimization of production of secretary molecules...
November 14, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/29131587/cell-migration-and-bone-formation-from-mesenchymal-stem-cell-spheroids-in-alginate-hydrogels-are-regulated-by-adhesive-ligand-density
#13
Steve S Ho, Andrew T Keown, Bennett Addison, J Kent Leach
The adhesion and migration of cells entrapped in engineered materials is regulated by available adhesive ligands. Although mesenchymal stem cell (MSC) spheroids injected into damaged tissues promote repair, their transplantation in biomaterials which regulate cell migration from the aggregate may further enhance their therapeutic potential. Alginate hydrogels were modified with Arginine-Glycine-Aspartic acid (RGD) at increasing concentrations, and osteogenically induced human MSC spheroids were entrapped to assess cell migration, survival, and differentiation...
November 13, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29131185/refractive-index-measurement-of-suspended-cells-using-opposed-view-digital-holographic-microscopy
#14
Juanjuan Zheng, Peng Gao, Xiaopeng Shao, G Ulrich Nienhaus
Opposed-view digital holographic microscopy (OV-DHM) with autofocusing and out-of-focus background suppression was demonstrated and applied to measure the refractive index (RI) of suspended HeLa cells. In OV-DHM, a specimen is illuminated from two sides in a 4π-like configuration. The generated two opposite-view object waves, which have orthogonal polarization orientations, interfere with a common reference wave, and the generated holograms are recorded by a CMOS camera. The image plane of the sample was determined by finding the minimal variation between the two object waves...
November 10, 2017: Applied Optics
https://www.readbyqxmd.com/read/29131081/overexpression-of-the-transmembrane-protein-iqgap3-is-associated-with-poor-survival-of-patients-with-gastric-cancer
#15
Naohide Oue, Yuji Yamamoto, Takashi Oshima, Ryuichi Asai, Akira Ishikawa, Naohiro Uraoka, Naoya Sakamoto, Kazuhiro Sentani, Wataru Yasui
OBJECTIVE: Spheroid colony formation is a useful method of cancer stem cell (CSC) characterization. We previously showed that the IQ motif containing the GTPase-activating protein 3 gene (IQGAP3) is upregulated in spheroid body-forming gastric cancer (GC) cells compared with parental cells. We investigated IQGAP3 expression in GC. METHODS: IQGAP3 protein expression was analyzed by immunohistochemistry in 165 GC cases. RNA interference was used to inhibit IQGAP3 expression in GC cell lines...
November 1, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29130628/characterization-of-genetic-intratumor-heterogeneity-in-colorectal-cancer-and-matching-patient-derived-spheroid-cultures
#16
Sigrid Salling Árnadóttir, Maria Jeppesen, Philippe Lamy, Jesper Bertram Bramsen, Iver Nordentoft, Michael Knudsen, Søren Vang, Mogens Rørbaek Madsen, Ole Thastrup, Jacob Thastrup, Claus Lindbjerg Andersen
Patient-derived in vitro cultures of colorectal cancer (CRC) may help guide treatment strategies prior to patient treatment. However, most previous studies have been performed on a single biopsy per tumor. The purpose of this study was to analyze multiple spatially distinct biopsies from CRCs and see how well intratumor heterogeneity (ITH) was recapitulated in matching patient-derived spheroids. Three to five biopsies were collected from six CRC tumors. Each biopsy was split in two; one half was used for spheroid culturing, the other half was used for DNA and RNA purification...
November 11, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29129665/intravasation-of-sw620-colon-cancer-cell-spheroids-through-the-blood-endothelial-barrier-is-inhibited-by-clinical-drugs-and-flavonoids-in-vitro
#17
Silvio Holzner, Stefan Brenner, Atanas Georgiev Atanasov, Daniel Senfter, Serena Stadler, Chi Huu Nguyen, Adryan Fristiohady, Daniela Milovanovic, Nicole Huttary, Sigurd Krieger, Zsuzsanna Bago-Horvath, Oliver de Wever, Ioannis Tentes, Ali Özmen, Walter Jäger, Helmut Dolznig, Verena Maria Dirsch, Robert Michael Mader, Liselotte Krenn, Georg Krupitza
Mechanisms how colorectal cancer (CRC) cells penetrate blood micro-vessel endothelia and metastasise is poorly understood. To study blood endothelial cell (BEC) barrier breaching by CRC emboli, an in vitro assay measuring BEC-free areas underneath SW620 cell spheroids, so called "circular chemorepellent induced defects" (CCIDs, appearing in consequence of endothelial retraction), was adapted and supported by Western blotting, EIA-, EROD- and luciferase reporter assays. Inhibition of ALOX12 or NF-κB in SW620 cells or BECs, respectively, caused attenuation of CCIDs...
November 10, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29128818/comparison-of-2d-and-3d-neural-induction-methods-for-the-generation-of-neural-progenitor-cells-from-human-induced-pluripotent-stem-cells
#18
Abinaya Chandrasekaran, Hasan X Avci, Anna Ochalek, Lone N Rösingh, Kinga Molnár, Lajos László, Tamás Bellák, Annamária Téglási, Krisztina Pesti, Arpad Mike, Phetcharat Phanthong, Orsolya Bíró, Vanessa Hall, Narisorn Kitiyanant, Karl-Heinz Krause, Julianna Kobolák, András Dinnyés
Neural progenitor cells (NPCs) from human induced pluripotent stem cells (hiPSCs) are frequently induced using 3D culture methodologies however, it is unknown whether spheroid-based (3D) neural induction is actually superior to monolayer (2D) neural induction. Our aim was to compare the efficiency of 2D induction with 3D induction method in their ability to generate NPCs, and subsequently neurons and astrocytes. Neural differentiation was analysed at the protein level qualitatively by immunocytochemistry and quantitatively by flow cytometry for NPC (SOX1, PAX6, NESTIN), neuronal (MAP2, TUBB3), cortical layer (TBR1, CUX1) and glial markers (SOX9, GFAP, AQP4)...
October 14, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29127321/metabolic-profiling-of-healthy-and-cancerous-tissues-in-2d-and-3d
#19
Shonagh Russell, Jonathan Wojtkowiak, Andy Neilson, Robert J Gillies
Metabolism is a compartmentalized process, and it is apparent in studying cancer that tumors, like normal tissues, demonstrate metabolic cooperation between different cell types. Metabolic profiling of cells in 2D culture systems often fails to reflect the metabolism occurring within tissues in vivo due to lack of other cell types and 3D interaction. We designed a tooling and methodology to metabolically profile and compare 2D cultures with cancer cell spheroids, and microtissue slices from tumors, and normal organs...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29125896/an-in-situ-dynamic-continuum-of-supramolecular-phosphoglycopeptides-enables-formation-of-3d-cell-spheroids
#20
Huaimin Wang, Junfeng Shi, Zhaoqianqi Feng, Rong Zhou, Shiyu Wang, Avital A Rodal, Bing Xu
Higher-order assemblies of proteins, with a structural and dynamic continuum, is a new paradigm in biology, but these insights have yet to be applied in designing biomaterials. Dynamic assemblies of supramolecular phosphoglycopeptides (sPGPs) transform a 2D cell sheet to 3D cell spheroids. A ligand-receptor interaction between a glycopeptide and a phosphopeptide produces sPGPs that form nanoparticles, which transform to nanofibrils upon partially enzymatic dephosphorylation. The assemblies form dynamically and hierarchically in situ on the cell surface, and interact with extracellular matrix molecules and effectively abolish contact inhibition of locomotion (CIL) of the cells...
November 10, 2017: Angewandte Chemie
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