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https://www.readbyqxmd.com/read/28227912/a-hybrid-discrete-continuous-model-of-in-vitro-spheroid-tumor-growth-and-drug-response
#1
Giorgos Tzedakis, Evangelos Liapis, Eleftheria Tzamali, Giannis Zacharakis, Vangelis Sakkalis, Giorgos Tzedakis, Evangelos Liapis, Eleftheria Tzamali, Giannis Zacharakis, Vangelis Sakkalis, Giannis Zacharakis, Vangelis Sakkalis, Evangelos Liapis, Giorgos Tzedakis, Eleftheria Tzamali
Anti-cancer therapy efficacy in solid tumors mainly depends on drug transportation through the vasculature system and the extracellular matrix, on diffusion gradients and clonal heterogeneity within the tumor mass, as well as on the responses of the individual tumor cells to drugs and their interactions with each other and their local microenvironment. In this work, we develop a mathematical predictive model for tumor growth and drug response based on 3D spheroids experiments that possess several in vivo features of tumors and are considered better for drug screening...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28227433/microprinted-tumor-spheroids-enable-anti-cancer-drug-screening
#2
Pradip S Thakuri, Stephanie L Ham, Hossein Tavana, Pradip S Thakuri, Stephanie L Ham, Hossein Tavana, Stephanie L Ham, Hossein Tavana
Spheroids present a biologically relevant model of avascular tumors and a unique tool for discovery of anti-cancer drugs. Despite being used in research laboratories for several decades, spheroids are not routinely used for drug discovery primarily due to the difficulty of mass-producing uniformly-sized spheroids and intense labor involved in handling, drug treatment, and analyzing them. We overcome this barrier using a novel technology to robotically microprint spheroids in standard 384-well plates. An aqueous drop containing cancer cells is dispensed into a bath of a second, immiscible aqueous phase...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28223550/nadh-autofluorescence-a-new-metabolic-biomarker-for-cancer-stem-cells-identification-of-vitamin-c-and-cape-as-natural-products-targeting-stemness
#3
Gloria Bonuccelli, Ernestina Marianna De Francesco, Rianne de Boer, Herbert B Tanowitz, Michael P Lisanti
Here, we assembled a broad molecular "tool-kit" to interrogate the role of metabolic heterogeneity in the propagation of cancer stem-like cells (CSCs). First, we subjected MCF7 cells to "metabolic fractionation" by flow cytometry, using fluorescent mitochondrial probes to detect PCG1α activity, as well ROS and hydrogen-peroxide (H2O2) production; NADH levels were also monitored by auto-fluorescence. Then, the various cell populations were functionally assessed for "stem cell activity", using the mammosphere assay (3D-spheroids)...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28223538/tissue-transglutaminase-induces-epithelial-mesenchymal-transition-and-the-acquisition-of-stem-cell-like-characteristics-in-colorectal-cancer-cells
#4
Oluseyi Ayinde, Zhuo Wang, Martin Griffin
Human colon cancer cell lines (CRCs) RKO, SW480 and SW620 were investigated for TG2 involvement in tumour advancement and aggression. TG2 expression correlated with tumour advancement and expression of markers of epithelial-mesenchymal transition (EMT). The metastatic cell line SW620 showed high TG2 expression compared to the primary tumour cell lines SW480 and RKO and could form tumour spheroids under non- adherent conditions. TG2 manipulation in the CRCs by shRNA or TG2 transduction confirmed the relationship between TG2 and EMT...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28223521/nondestructive-nanostraw-intracellular-sampling-for-longitudinal-cell-monitoring
#5
Yuhong Cao, Martin Hjort, Haodong Chen, Fikri Birey, Sergio A Leal-Ortiz, Crystal M Han, Juan G Santiago, Sergiu P Paşca, Joseph C Wu, Nicholas A Melosh
Here, we report a method for time-resolved, longitudinal extraction and quantitative measurement of intracellular proteins and mRNA from a variety of cell types. Cytosolic contents were repeatedly sampled from the same cell or population of cells for more than 5 d through a cell-culture substrate, incorporating hollow 150-nm-diameter nanostraws (NS) within a defined sampling region. Once extracted, the cellular contents were analyzed with conventional methods, including fluorescence, enzymatic assays (ELISA), and quantitative real-time PCR...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28220831/the-distribution-of-the-apparent-diffusion-coefficient-as-an-indicator-of-the-response-to-chemotherapeutics-in-ovarian-tumour-xenografts
#6
Monique C Tourell, Ali Shokoohmand, Marietta Landgraf, Nina P Holzapfel, Patrina S P Poh, Daniela Loessner, Konstantin I Momot
Diffusion-weighted magnetic resonance imaging (DW-MRI) was used to evaluate the effects of single-agent and combination treatment regimens in a spheroid-based animal model of ovarian cancer. Ovarian tumour xenografts grown in non-obese diabetic/severe-combined-immunodeficiency (NOD/SCID) mice were treated with carboplatin or paclitaxel, or combination carboplatin/paclitaxel chemotherapy regimens. After 4 weeks of treatment, tumours were extracted and underwent DW-MRI, mechanical testing, immunohistochemical and gene expression analyses...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28218895/ferroelectric-glass-of-spheroidal-dipoles-with-impurities-polar-nanoregions-response-to-applied-electric-field-and-ergodicity-breakdown
#7
Akira Onuki, Kyohei Takae
Using molecular dynamics simulation, we study dipolar glass in crystals composed of slightly spheroidal, polar particles and spherical, apolar impurities between metal walls. We present physical pictures of ferroelectric glass, which have been observed in relaxors, mixed crystals (such as KCN$_x$KBr$_{1-x}$), and polymers. Our systems undergo a diffuse transition in a wide temperature range, where we visualize polar nanoregions (PNRs) surrounded by impurities. In our simulation, the impurities form clusters and their space distribution is heterogeneous...
February 20, 2017: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/28214855/fatty-acid-binding-protein-4-in-endometrial-epithelium-is-involved-in-embryonic-implantation
#8
Peng Wang, Qiuyuan Zhu, Huilian Peng, Mengkai Du, Minyue Dong, Hanzhi Wang
AIMS: To clarify the role of fatty acid-binding protein 4 (FABP4) of endometrial epithelial cell in the establishment and maintenance of pregnancy and the involvement in the pathogenesis of pregnancy loss. METHODS: The expression of FABP4 and uterine receptive factor (LIF, Integrin-β3 and Claudin 4) was determined by Western blotting or quantitative PCR. FABP4 siRNA was used to silence FABP4 while FABP4 inhibitor was used to inhibit the function of FABP4 in endometrial epithelial cell...
January 30, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28213554/hypoxia-selectively-enhances-integrin-receptor-expression-to-promote-metastasis
#9
Julia A Ju, Ines Godet, I Chae Ye, Jungmin Byun, Hasini Jayatilaka, Sun Joo Lee, Lisha Xiang, Debangshu Samanta, Meng Horng Lee, Pei-Hsun Wu, Denis Wirtz, Gregg L Semenza, Daniele M Gilkes
: Metastasis is the leading cause of breast cancer (BCa)mortality. Previous studies have implicated hypoxia-induced changes in the composition and stiffness of the extracellular matrix (ECM) in the metastatic process. Therefore, the contribution of potential ECM binding receptors in this process was explored. Using a bioinformatics approach the expression of all integrin receptor subunits, in two independent BCa patient data sets, were analyzed to determine if integrin status correlates with a validated hypoxiainducible gene signature...
February 17, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28212889/inhibition-of-proliferation-and-invasion-in-2d-and-3d-models-by-2-methoxyestradiol-in-human-melanoma-cells
#10
R R Massaro, F Faião-Flores, V W Rebecca, S Sandri, D K Alves-Fernandes, P C Pennacchi, K S M Smalley, S S Maria-Engler
Despite the recent advances in the clinical management of melanoma, there remains a need for new pharmacological approaches to treat this cancer. 2-methoxyestradiol (2ME) is a metabolite of estrogen that has shown anti-tumor effects in many cancer types. In this study we show that 2ME treatment leads to growth inhibition in melanoma cells, an effect associated with entry into senescence, decreased pRb and CyclinB1 expression, increased p21/Cip1 expression and G2/M cell cycle arrest. 2ME treatment also inhibits melanoma cell growth in colony formation assays, including cell lines with acquired resistance to BRAF and BRAF+MEK inhibitors...
February 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28212490/vitamin-e-succinate-grafted-chitosan-oligosaccharide-rgd-conjugated-tpgs-mixed-micelles-loaded-with-paclitaxel-for-u87mg-tumor-therapy
#11
Yanzuo Chen, Shu Feng, Wenchao Liu, Zeting Yuan, Peihao Yin, Feng Gao
The poor therapeutic efficacy of hydrophobic chemotherapeutic drugs is an intrinsic limitation to successful chemotherapy. In the present study, a multi-task delivery system based on arginine-glycine-aspartic acid peptide (RGD) decorated vitamin E succinate (VES)-grafted-chitosan oligosaccharide (CSO)/RGD-conjugated D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS-RGD) mixed micelles (VeC/T-RGD MM) was first prepared for targeted delivery of paclitaxel (PTX), a hydrophobic anticancer drug, to improve the efficacy of U87MG tumor therapy...
February 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28210910/astrocyte-induced-reelin-expression-drives-proliferation-of-her2-breast-cancer-metastases
#12
Rahul Jandial, Cecilia Choy, Danielle M Levy, Mike Y Chen, Khairul I Ansari
Breast cancer metastasis to the brain develops after a clinical latency of years to even decades, suggesting that colonization of the brain is the most challenging step of the metastatic cascade. However, the underlying mechanisms used by breast cancer cells to successfully colonize the brain's microenvironment remain elusive. Reelin is an archetypal extracellular glycoprotein that regulates migration, proliferation, and lamination of neurons. It is epigenetically silenced in various cancers, and its expression in multiple myelomas is linked to poor patient survival...
February 17, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28209618/the-stat3-mirna-92-wnt-signaling-pathway-regulates-spheroid-formation-and-malignant-progression-in-ovarian-cancer
#13
Min-Wei Chen, Shu-Ting Yang, Ming-Hsien Chien, Kuo-Tai Hua, Chin-Jui Wu, Sheng-Mou Hsiao, Hao Lin, Michael Hsiao, Jen-Liang Su, Lin-Hung Wei
Ovarian cancer spheroids constitute a metastatic niche for transcoelomic spread that also engenders drug resistance. Spheroid-forming cells express active STAT3 signaling and display stem cell-like properties that may contribute to ovarian tumor progression. In this study, we show that STAT3 is hyperactivated in ovarian cancer spheroids and that STAT3 disruption in this setting is sufficient to relieve chemoresistance. In an NSG murine model of human ovarian cancer, STAT3 signaling regulated spheroid formation and self-renewal properties, whereas STAT3 attenuation reduced tumorigenicity...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28209486/vasodilator-stimulated-phosphoprotein-vasp-depletion-from-breast-cancer-mda-mb-231-cells-inhibits-tumor-spheroid-invasion-through-downregulation-of-migfilin-%C3%AE-catenin-and-urokinase-plasminogen-activator-upa
#14
Vasiliki Gkretsi, Andreas Stylianou, Triantafyllos Stylianopoulos
A hallmark of cancer cells is their ability to invade surrounding tissues and form metastases. Cell-extracellular matrix (ECM)-adhesion proteins are crucial in metastasis, connecting tumor ECM with actin cytoskeleton thus enabling cells to respond to mechanical cues. Vasodilator-stimulated phosphoprotein (VASP) is an actin-polymerization regulator which interacts with cell-ECM adhesion protein Migfilin, and regulates cell migration. We compared VASP expression in MCF-7 and MDA-MB-231 breast cancer (BC) cells and found that more invasive MDA-MB-231 cells overexpress VASP...
February 13, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28207963/nardilysin-promotes-hepatocellular-carcinoma-through-activation-of-signal-transducer-and-activator-of-transcription-3
#15
Yosuke Kasai, Kan Toriguchi, Etsuro Hatano, Kiyoto Nishi, Mikiko Ohno, Tomoaki Yoh, Keita Fukuyama, Takahiro Nishio, Masayuki Okuno, Keiko Iwaisako, Satoru Seo, Kojiro Taura, Masato Kurokawa, Makoto Kunichika, Shinji Uemoto, Eiichiro Nishi
Nardilysin (NRDC) is a metalloendopeptidase of the M16 family. We previously showed that NRDC activates inflammatory cytokine signaling, including interleukin-6-signal transducer and activator of transcription 3 (STAT3) signaling. NRDC has been implicated in the promotion of breast, gastric, and esophageal cancer, as well as the development of liver fibrosis. In this study, we investigated the role of NRDC in the promotion of hepatocellular carcinoma (HCC), both clinically and experimentally. We found that NRDC expression was up-regulated 3-fold in HCC tissue compared to the adjacent non-tumor liver tissue, which was confirmed by immunohistochemistry and western blotting...
February 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/28205649/comparative-studies-of-oxaliplatin-based-platinum-iv-complexes-in-different-in-vitro-and-in-vivo-tumor-models
#16
Simone Göschl, Ekaterina Schreiber-Brynzak, Verena Pichler, Klaudia Cseh, Petra Heffeter, Ute Jungwirth, Michael A Jakupec, Walter Berger, Bernhard K Keppler
Using platinum(iv) prodrugs of clinically established platinum(ii) compounds is a strategy to overcome side effects and acquired resistances. We studied four oxaliplatin-derived platinum(iv) complexes with varying axial ligands in various in vitro and in vivo settings. The ability to interfere with DNA (pUC19) in the presence and absence of a reducing agent (ascorbic acid) was investigated in cell-free experiments. Cytotoxicity was compared under normoxic and hypoxic conditions in monolayer cultures and multicellular spheroids of colon carcinoma cell lines...
February 16, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28205573/extracellular-protonation-modulates-cell-cell-interaction-mechanics-and-tissue-invasion-in-human-melanoma-cells
#17
Verena Hofschröer, Kevin Alexander Koch, Florian Timo Ludwig, Peter Friedl, Hans Oberleithner, Christian Stock, Albrecht Schwab
Detachment of cells from the primary tumour precedes metastatic progression by facilitating cell release into the tissue. Solid tumours exhibit altered pH homeostasis with extracellular acidification. In human melanoma, the Na(+)/H(+) exchanger NHE1 is an important modifier of the tumour nanoenvironment. Here we tested the modulation of cell-cell-adhesion by extracellular pH and NHE1. MV3 tumour spheroids embedded in a collagen matrix unravelled the efficacy of cell-cell contact loosening and 3D emigration into an environment mimicking physiological confinement...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203090/exploring-targeted-therapy-of-osteosarcoma-using-proteomics-data
#18
Parunya Chaiyawat, Jongkolnee Settakorn, Apiruk Sangsin, Pimpisa Teeyakasem, Jeerawan Klangjorhor, Aungsumalee Soongkhaw, Dumnoensun Pruksakorn
Despite multimodal therapeutic treatments of osteosarcoma (OS), some patients develop resistance to currently available regimens and eventually end up with recurrent or metastatic outcomes. Many attempts have been made to discover effective drugs for improving outcome; however, due to the heterogeneity of the disease, new therapeutic options have not yet been identified. This study aims to explore potential targeted therapy related to protein profiles of OS. In this review of proteomics studies, we extracted data on differentially expressed proteins (DEPs) from archived literature in PubMed and our in-house repository...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28202590/advances-in-multicellular-spheroids-formation
#19
REVIEW
X Cui, Y Hartanto, H Zhang
Three-dimensional multicellular spheroids (MCSs) have a complex architectural structure, dynamic cell-cell/cell-matrix interactions and bio-mimicking in vivo microenvironment. As a fundamental building block for tissue reconstruction, MCSs have emerged as a powerful tool to narrow down the gap between the in vitro and in vivo model. In this review paper, we discussed the structure and biology of MCSs and detailed fabricating methods. Among these methods, the approach in microfluidics with hydrogel support for MCS formation is promising because it allows essential cell-cell/cell-matrix interactions in a confined space...
February 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28202286/equatorial-wrinkles-in-the-human-lens-capsule
#20
H J Burd, G A Montenegro, L P Cortés, R I Barraquer, R Michael
Equatorial wrinkles, or crenations, have been previously observed around the equator in coronal images of the human ocular lens. However, wrinkles are typically not apparent when the lens is viewed from saggital directions. In the current paper, the existence and geometry of these wrinkles is shown to be consistent with a mechanical model of the isolated lens, in which the capsule is held in a state of residual tension by a spatially uniform internal pressure. The occurrence of equatorial wrinkles is therefore seen to be a mechanical consequence of the spheroidal shape of the lens capsule and an excess intralenticular pressure...
February 12, 2017: Experimental Eye Research
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