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https://www.readbyqxmd.com/read/28635615/topography-on-a-subcellular-scale-modulates-cellular-adhesions-and-actin-stress-fiber-dynamics-in-tumor-associated-fibroblasts
#1
Mikheil Azatov, Xiaoyu Sun, Alexandra Suberi, John T Fourkas, Arpita Upadhyaya
Cells can sense and adapt to mechanical properties of their environment. The local geometry of the extracellular matrix, such as its topography, has been shown to modulate cell morphology, migration, and proliferation. Here we investigate the effect of micro/nanotopography on the morphology and cytoskeletal dynamics of human pancreatic tumor-associated fibroblast cells (TAFs). We use arrays of parallel nanoridges with variable spacings on a subcellular scale to investigate the response of TAFs to the topography of their environment...
June 21, 2017: Physical Biology
https://www.readbyqxmd.com/read/28624797/lymph-node-metastasis-and-the-physicochemical-micro-environment-of-pancreatic-ductal-adenocarcinoma-xenografts
#2
Lise Mari K Andersen, Catherine S Wegner, Trude G Simonsen, Ruixia Huang, Jon-Vidar Gaustad, Anette Hauge, Kanthi Galappathi, Einar K Rofstad
Pancreatic ductal adenocarcinoma (PDAC) patients develop lymph node metastases early and have a particularly poor prognosis. The poor prognosis has been shown to be associated with the physicochemical microenvironment of the tumor tissue, which is characterized by desmoplasia, abnormal microvasculature, extensive hypoxia, and highly elevated interstitial fluid pressure (IFP). In this study, we searched for associations between lymph node metastasis and features of the physicochemical microenvironment in an attempt to identify mechanisms leading to metastatic dissemination and growth...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28604162/intratumoral-infection-by-cmv-may-change-the-tumor-environment-by-directly-interacting-with-tumor-associated-macrophages-to-promote-cancer-immunity
#3
Dan A Erkes, Nicole A Wilski, Christopher M Snyder
Cytomegalovirus (CMV) is a herpesvirus that induces an extremely robust and sustained immune response. For this reason, CMV has been proposed as a vaccine vector to promote immunity to both pathogens and cancer. However, exploration of CMV as a vaccine vector is at an early stage and there are many questions. Using a mouse melanoma model, we recently found that a CMV-based vaccine induced large populations of melanoma-specific T cells, but was not effective at slowing tumor growth unless it was injected directly into the tumor...
June 12, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28595562/non-viral-delivery-systems-for-breast-cancer-gene-therapy
#4
Golnaz Vaseghi, Laleh Rafiee, Shaghayegh Haghjooy Javanmard
INTRODUCTION: The ever-evolving field of gene therapy promises several innovative treatments for cancer. Advances in genetic modification of tumor cells and micro environment have led to the development of more effective therapeutic strategies with fewer side effects. MATERIAL & METHODS: The development of effective delivery system challenges, remains. Non-viral vectors are interesting due to their bio-safety and their ability to transfer different types of nucleic acids...
June 6, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28534322/-value-of-functional-magnetic-resonance-imaging-in-predicting-outcomes-of-neoadjuvant-chemoradiotherapy-in-rectal-cancer
#5
Yishan Yu, Jinbo Yue, Jinming Yu
Rectal cancer is one of the common cancers which poses a threat to the health of mankind. In recent years. Multi-modality treatment strategies for locally advanced rectal cancer improve the treatment efficiency. Accurate prediction of the treatment response after the neoadjuvant chemoradiotherapy (CRT) can guide more suitable treatment strategy. MERCURY study proved the prognostic value of post-CRT standard morphologic MRI(T2-weighted) assessment of tumor regression grade(TRG), and MRI assessment of circumferential resection margin can guide the definitive surgery...
May 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28527736/the-effects-of-non-invasive-radiofrequency-electric-field-hyperthermia-on-biotransport-and-biodistribution-of-fluorescent-60-fullerene-derivative-in-a-murine-orthotopic-model-of-breast-adenocarcinoma
#6
Norman A Lapin, Martyna Krzykawska-Serda, Sean Dilliard, Yuri Mackeyev, Maciej Serda, Lon J Wilson, Steven A Curley, Stuart J Corr
The aim of this study is to understand the combined and differential biokinetic effects of radiofrequency (RF) electric-field hyperthermia as an adjunctive therapy to [60]fullerene nanoparticle-based drug delivery systems in targeting the micro-vasculature and micro-environments of breast cancer tumors. Intravital microscopy (IVM) is an ideal tool to provide the spatial and temporal resolution needed for quantification in this investigation. The water-soluble and fluorescent [60]fullerene derivative (C60-serPF) was designed to be an amphiphilic nanostructure, which is able to cross several biological membranes and accumulate in tumor tissues by passing through abnormally leaky tumor blood vessels...
May 17, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28525844/the-discovery-of-novel-potent-err-alpha-inverse-agonists-for-the-treatment-of-triple-negative-breast-cancer
#7
Yongli Du, Lianhua Song, Liudi Zhang, Hao Ling, Yanhui Zhang, Haifei Chen, Huijie Qi, Xiaojin Shi, Qunyi Li
The estrogen-related receptor α (ERRα) is an orphan receptor and a novel target for solid tumor therapy, conceivably through effects on the regulation of tumor cell energy metabolism associated with energy stress within solid tumor micro environments. Here we describe the discovery of novel potent inverse agonists of ERRα. In vitro, compound 11 potently inhibits ERRα's transcriptional activity by preventing endogenous PGC-1α and ERRα binding and suppresses the proliferation of different human cancer cell lines and the migration of breast cancer cells (MDA-MB-231)...
April 22, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28521819/linking-hypoxia-dna-damage-and-proliferation-in-multicellular-tumor-spheroids
#8
Stephen Riffle, Ram Naresh Pandey, Morgan Albert, Rashmi S Hegde
BACKGROUND: Multicellular Tumor Spheroids are frequently used to mimic the regionalization of proliferation and the hypoxic environment within avascular tumors. Here we exploit these features to study the activation of DNA damage repair pathways and their correlation to developing hypoxia. METHODS: Activation of DNA damage repair markers, proliferation, cell death, glycogen accumulation and developing hypoxia were investigated using immunofluorescence, immuno-histochemistry, EdU incorporation, Western blots, COMET assays, and pharmacological agents in A673 Ewing sarcoma spheroids and monolayer cultures...
May 18, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28479387/the-effects-of-tlr3-trif-and-traf3-snps-and-interactions-with-environmental-factors-on-type-2-diabetes-mellitus-and-vascular-complications-in-a-han-chinese-population
#9
Zixing Zhou, Chengli Zeng, Lihong Nie, Shiqi Huang, Congcong Guo, Di Xiao, Yajing Han, Xiaohong Ye, Meiling Ou, Chuican Huang, Xingguang Ye, Zihao Wen, Guang Yang, Chunxia Jing
Toll-like receptor 3 (TLR3) is involved in type I interferon-β (IFN-β) via TIR-domain-containing adapter-inducing interferon-β (TRIF) and Tumor necrosis factor receptor-associated factor 3 (TRAF3), culminating in inflammation and immunity reactions. TLR3 is implicated in insulin resistance and type 2 diabetes mellitus (T2DM). Eight SNPs of these genes were detected in 552 T2DM patients and 552 matched healthy control subjects. Gene-gene and gene-environment interactions and haplotype associations were also evaluated...
May 4, 2017: Gene
https://www.readbyqxmd.com/read/28450700/sensitization-of-glioblastoma-tumor-micro-environment-to-chemo-and-immunotherapy-by-galectin-1-intranasal-knock-down-strategy
#10
Matthias Van Woensel, Thomas Mathivet, Nathalie Wauthoz, Rémi Rosière, Abhishek D Garg, Patrizia Agostinis, Véronique Mathieu, Robert Kiss, Florence Lefranc, Louis Boon, Jochen Belmans, Stefaan W Van Gool, Holger Gerhardt, Karim Amighi, Steven De Vleeschouwer
In this study, we evaluated the consequences of reducing Galectin-1 (Gal-1) in the tumor micro-environment (TME) of glioblastoma multiforme (GBM), via nose-to-brain transport. Gal-1 is overexpressed in GBM and drives chemo- and immunotherapy resistance. To promote nose-to-brain transport, we designed siRNA targeting Gal-1 (siGal-1) loaded chitosan nanoparticles that silence Gal-1 in the TME. Intranasal siGal-1 delivery induces a remarkable switch in the TME composition, with reduced myeloid suppressor cells and regulatory T cells, and increased CD4+ and CD8+ T cells...
April 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28444111/pattern-recognition-receptors-immune-targets-to-enhance-cancer-immunotherapy
#11
T Shekarian, S Valsesia-Wittmann, J Brody, M C Michallet, S Depil, C Caux, A Marabelle
Durable tumor responses and significant levels of disease control rates have been described in more than 20 advanced/metastatic cancer types with B7-family immune checkpoint-targeted anti-CTLA-4, anti-PD-1, and anti-PD-L1 monoclonal antibodies. These results and the recent approvals of ipilimumab, pembrolizumab, nivolumab and atezolizumab are currently revolutionizing the way we envision the future of cancer care. However these clinical benefits are not observed in all cancer types and in every patient. Therefore, our clinical challenge is to identify therapeutic strategies which could overcome the primary and secondary resistances to these novel cancer immunotherapies...
April 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28417928/potential-coagulation-factor-driven-pro-inflammatory-responses-in-ovarian-cancer-tissues-associated-with-insufficient-o%C3%A2-and-plasma-supply
#12
REVIEW
Shiro Koizume, Yohei Miyagi
Tissue factor (TF) is a cell surface receptor for coagulation factor VII (fVII). The TF-activated fVII (fVIIa) complex is an essential initiator of the extrinsic blood coagulation process. Interactions between cancer cells and immune cells via coagulation factors and adhesion molecules can promote progression of cancer, including epithelial ovarian cancer (EOC). This process is not necessarily advantageous, as tumor tissues generally undergo hypoxia due to aberrant vasculature, followed by reduced access to plasma components such as coagulation factors...
April 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28389020/seeds-in-the-liver
#13
REVIEW
Hongjie Ji, Yanrong Lu, Yujun Shi
The liver is a crucial organ for homeostasis and has a tremendous self-renewal and regenerative capacity. It has long been believed that the self-renewal and repair of the liver within a given physiological condition or its repopulation in chronic liver diseases, when hepatocyte proliferation is impaired, will primarily be conducted by the proliferating duct cells, termed "oval cells" or hepatic progenitor cells (HPCs). In addition, numerous studies have revealed that HPCs are the initial tumor cells of liver cancer under certain micro-environments...
May 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28302670/modelling-pulmonary-microthrombosis-coupled-to-metastasis-distinct-effects-of-thrombogenesis-on-tumorigenesis
#14
Colin E Evans, Asis Palazon, Jingwei Sim, Petros A Tyrakis, Alice Prodger, Xiao Lu, Saria Chan, Pär-Ola Bendahl, Mattias Belting, Love Von Euler, Helene Rundqvist, Randall S Johnson, Cristina Branco
Thrombosis can cause localized ischemia and tissue hypoxia, and both of these are linked to cancer metastasis. Vascular micro-occlusion can occur as a result of arrest of circulating tumour cells in small capillaries, giving rise to microthrombotic events that affect flow, creating localized hypoxic regions. To better understand the association between metastasis and thrombotic events, we generated an experimental strategy whereby we modelled the effect of microvascular occlusion in metastatic efficiency by using inert microbeads to obstruct lung microvasculature before, during and after intravenous tumour cell injection...
May 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28287120/optimizing-non-invasive-radiofrequency-hyperthermia-treatment-for-improving-drug-delivery-in-4t1-mouse-breast-cancer-model
#15
Matthew J Ware, Martyna Krzykawska-Serda, Jason Chak-Shing Ho, Jared Newton, Sarah Suki, Justin Law, Lam Nguyen, Vazrik Keshishian, Maciej Serda, Kimberly Taylor, Steven A Curley, Stuart J Corr
Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28257435/idelalisib-and-caffeine-reduce-suppression-of-t-cell-responses-mediated-by-activated-chronic-lymphocytic-leukemia-cells
#16
Barry D Hock, Sean A MacPherson, Judith L McKenzie
Chronic lymphocytic leukemia (CLL) is associated with T cell dysfunction. Activated CLL cells are found within the lymphoid tumor micro-environment and overcoming immuno-suppression induced by these cells may improve anti-CLL immune responses. However, the mechanisms by which activated CLL cells inhibit T cell responses, and reagents targeting such mechanisms have not been identified. Here we demonstrate that the ability of in vitro activated CLL cells to suppress T cell proliferation is not reversed by the presence of ecto-nuclease inhibitors or blockade of IL-10, PD-1 and CTLA-4 pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28255126/-regulatory-effect-of-exosome-on-cell-apoptosis
#17
Xin Li, Zuocheng Yang
Exosome, a nano-grade biological membrane structure, is secreted by multiple cells, widely distributing in saliva, plasma, milk and other body fluid. It can directly and indirectly take part in the biological information transcription between the receptor cells and their micro-environment. Recent studies have demonstrated that exosomes play pivotal roles in the occurrence and development of viral infectious diseases, tumors and other cell apoptosis related diseases via regulating the apoptosis in various ways...
February 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28249898/defining-cancer-subpopulations-by-adaptive-strategies-rather-than-molecular-properties-provides-novel-insights-into-intratumoral-evolution
#18
Arig Ibrahim-Hashim, Mark Robertson-Tessi, Pedro M Enriquez-Navas, Mehdi Damaghi, Yoganand Balagurunathan, Jonathan W Wojtkowiak, Shonagh Russell, Kam Yoonseok, Mark C Lloyd, Marilyn M Bui, Joel S Brown, Alexander R A Anderson, Robert J Gillies, Robert A Gatenby
Ongoing intratumoral evolution is apparent in molecular variations among cancer cells from different regions of the same tumor, but genetic data alone provide little insight into environmental selection forces and cellular phenotypic adaptations that govern the underlying Darwinian dynamics. In three spontaneous murine cancers (prostate cancers in TRAMP and PTEN mice, pancreatic cancer in KPC mice), we identified two subpopulations with distinct niche construction adaptive strategies that remained stable in culture: (i) invasive cells that produce an acidic environment via upregulated aerobic glycolysis; and (ii) noninvasive cells that were angiogenic and metabolically near-normal...
May 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28219197/-down-regulation-of-mir-146b-5p-promotes-malignant-transformation-of-fusion-cells-after-co-culture-of-macrophages-with-glioma-stem-cells-in-vitro
#19
H H Cai, H Y Wang, H R Liu, Y J Sheng, D G Xi, Y P Xue, X L Dai, A D Wang, Q Huang, J Dong
Objective: To observe mutual interactions between macrophages(Mφ) and glioma stem cells (GSCs)in dual-color tracing model in vitro, to identify the biological characteristics of fusion cells in multiple levels, and to analysis the relevant molecular mechanisms. Methods: Red fluorescent protein(RFP) gene was stably transfected into human GSCs cell line SU4. Mφ cells were obtained from Balb/c nude mice with enhanced green fluorescent protein (EGFP) expression. Then two cells were co-cultured in dual-color tracing platform...
February 7, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28213330/drug-discovery-strategies-in-the-field-of-tumor-energy-metabolism-limitations-by-metabolic-flexibility-and-metabolic-resistance-to-chemotherapy
#20
REVIEW
N D Amoedo, E Obre, R Rossignol
The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro...
February 16, 2017: Biochimica et Biophysica Acta
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