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Shear Stress AND Cancer

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https://www.readbyqxmd.com/read/28381539/transient-tissue-priming-via-rock-inhibition-uncouples-pancreatic-cancer-progression-sensitivity-to-chemotherapy-and-metastasis
#1
Claire Vennin, Venessa T Chin, Sean C Warren, Morghan C Lucas, David Herrmann, Astrid Magenau, Pauline Melenec, Stacey N Walters, Gonzalo Del Monte-Nieto, James R W Conway, Max Nobis, Amr H Allam, Rachael A McCloy, Nicola Currey, Mark Pinese, Alice Boulghourjian, Anaiis Zaratzian, Arne A S Adam, Celine Heu, Adnan M Nagrial, Angela Chou, Angela Steinmann, Alison Drury, Danielle Froio, Marc Giry-Laterriere, Nathanial L E Harris, Tri Phan, Rohit Jain, Wolfgang Weninger, Ewan J McGhee, Renee Whan, Amber L Johns, Jaswinder S Samra, Lorraine Chantrill, Anthony J Gill, Maija Kohonen-Corish, Richard P Harvey, Andrew V Biankin, T R Jeffry Evans, Kurt I Anderson, Shane T Grey, Christopher J Ormandy, David Gallego-Ortega, Yingxiao Wang, Michael S Samuel, Owen J Sansom, Andrew Burgess, Thomas R Cox, Jennifer P Morton, Marina Pajic, Paul Timpson
The emerging standard of care for patients with inoperable pancreatic cancer is a combination of cytotoxic drugs gemcitabine and Abraxane, but patient response remains moderate. Pancreatic cancer development and metastasis occur in complex settings, with reciprocal feedback from microenvironmental cues influencing both disease progression and drug response. Little is known about how sequential dual targeting of tumor tissue tension and vasculature before chemotherapy can affect tumor response. We used intravital imaging to assess how transient manipulation of the tumor tissue, or "priming," using the pharmaceutical Rho kinase inhibitor Fasudil affects response to chemotherapy...
April 5, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28329305/association-between-spousal-suicide-and-mental-physical-and-social-health-outcomes-a-longitudinal-and-nationwide-register-based-study
#2
Annette Erlangsen, Bo Runeson, James M Bolton, Holly C Wilcox, Julie L Forman, Jesper Krogh, M Katherine Shear, Merete Nordentoft, Yeates Conwell
Importance: Bereavement after spousal suicide has been linked to mental disorders; however, a comprehensive assessment of the effect of spousal suicide is needed. Objective: To determine whether bereavement after spousal suicide was linked to an excessive risk of mental, physical, and social health outcomes when compared with the general population and spouses bereaved by other manners. Design, Setting, and Participants: This nationwide, register-based cohort study conducted in Denmark of 6...
March 22, 2017: JAMA Psychiatry
https://www.readbyqxmd.com/read/28287578/modeling-ovarian-cancer-multicellular-spheroid-behavior-in-a-dynamic-3d-peritoneal-microdevice
#3
Shan-Shan Li, Carman K M Ip, Matthew Y H Tang, Samuel K H Sy, Susan Yung, Tak-Mao Chan, Mengsu Yang, Ho Cheung Shum, Alice S T Wong
Ovarian cancer is characterized by extensive peritoneal metastasis, with tumor spheres commonly found in the malignant ascites. This is associated with poor clinical outcomes and currently lacks effective treatment. Both the three-dimensional (3D) environment and the dynamic mechanical forces are very important factors in this metastatic cascade. However, traditional cell cultures fail to recapitulate this natural tumor microenvironment. Thus, in vivo-like models that can emulate the intraperitoneal environment are of obvious importance...
February 18, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28273493/influence-of-dynamic-flow-environment-on-nanoparticle-protein-corona-from-protein-patterns-to-uptake-in-cancer-cells
#4
Sara Palchetti, Daniela Pozzi, Anna Laura Capriotti, Giorgia La Barbera, Riccardo Zenezini Chiozzi, Luca Digiacomo, Giovanna Peruzzi, Giulio Caracciolo, Aldo Laganà
The fast growing use of nanoparticles (NPs) in biotechnology and biomedicine raises concerns about human health and the environment. When introduced in physiological milieus, NPs adsorb biomolecules (especially proteins) forming the so-called protein corona (PC). As it is the PC that mostly interacts with biological systems, it represents a major element of the NPs' biological identity with impact on nanotoxicology, nanosafety and targeted delivery of nanomedicines. To date, NP-protein interactions have been largely investigated in vitro, but this condition is far from mimicking the dynamic nature of physiological environments...
May 1, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28245569/pancreatic-cancer-induced-neutrophil-extracellular-traps-a-potential-contributor-to-cancer-associated-thrombosis
#5
Norbaini Abdol Razak, Omar Elaskalani, Pat Metharom
Pancreatic cancer (PaCa) is a highly metastatic cancer, and patients are at high risk of developing venous thromboembolism (VTE). Neutrophil extracellular traps (NETs) have been associated with cancer metastasis and cancer-associated thrombosis, but the ability of cancer to stimulate NET release is not known. The release of NETs has been shown to be a slow process and requires reactive oxygen species (ROS) production. Studies suggest that activated platelets are important mediators in the release. Here, we show that PaCa cells can stimulate the rapid release of NETs, independently of ROS production...
February 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28198106/in-vitro-microfluidic-models-of-tumor-microenvironment-to-screen-transport-of-drugs-and-nanoparticles
#6
REVIEW
Altug Ozcelikkale, Hye-Ran Moon, Michael Linnes, Bumsoo Han
Advances in nanotechnology have enabled numerous types of nanoparticles (NPs) to improve drug delivery to tumors. While many NP systems have been proposed, their clinical translation has been less than anticipated primarily due to failure of current preclinical evaluation techniques to adequately model the complex interactions between the NP and physiological barriers of tumor microenvironment. This review focuses on microfluidic tumor models for characterization of delivery efficacy and toxicity of cancer nanomedicine...
February 14, 2017: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/28197635/fluid-shear-stress-induces-cancer-stem-cell-like-phenotype-in-mcf7-breast-cancer-cell-line-without-inducing-epithelial-to-mesenchymal-transition
#7
Ursula L Triantafillu, Seungjo Park, Nikki L Klaassen, Andrew D Raddatz, Yonghyun Kim
Metastasis is the leading cause of cancer deaths due to the spread of cancer cells through the blood vessels and the subsequent formation of secondary tumors. Metastasizing cancer cells in the human vasculature are called circulating tumor cells (CTCs) and are characterized to express the epithelial cell adhesion molecule (EpCAM). They are further known to survive physiological fluid shear stress (FSS) conditions. However, the effect of FSS on CTC molecular phenotype, such as the epithelial to mesenchymal transition (EMT) and cancer stem cell (CSC) expression, has not been extensively studied...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28114946/permeability-across-a-novel-microfluidic-blood-tumor-barrier-model
#8
Tori B Terrell-Hall, Amanda G Ammer, Jessica I G Griffith, Paul R Lockman
BACKGROUND: The lack of translatable in vitro blood-tumor barrier (BTB) models creates challenges in the development of drugs to treat tumors of the CNS and our understanding of how the vascular changes at the BBB in the presence of a tumor. METHODS: In this study, we characterize a novel microfluidic model of the BTB (and BBB model as a reference) that incorporates flow and induces shear stress on endothelial cells. Cell lines utilized include human umbilical vein endothelial cells co-cultured with CTX-TNA2 rat astrocytes (BBB) or Met-1 metastatic murine breast cancer cells (BTB)...
January 23, 2017: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/28098159/fluid-shear-stress-activates-yap1-to-promote-cancer-cell-motility
#9
Hyun Jung Lee, Miguel F Diaz, Katherine M Price, Joyce A Ozuna, Songlin Zhang, Eva M Sevick-Muraca, John P Hagan, Pamela L Wenzel
Mechanical stress is pervasive in egress routes of malignancy, yet the intrinsic effects of force on tumour cells remain poorly understood. Here, we demonstrate that frictional force characteristic of flow in the lymphatics stimulates YAP1 to drive cancer cell migration; whereas intensities of fluid wall shear stress (WSS) typical of venous or arterial flow inhibit taxis. YAP1, but not TAZ, is strictly required for WSS-enhanced cell movement, as blockade of YAP1, TEAD1-4 or the YAP1-TEAD interaction reduces cellular velocity to levels observed without flow...
January 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28054593/high-shear-stresses-under-exercise-condition-destroy-circulating-tumor-cells-in-a-microfluidic-system
#10
Sagar Regmi, Afu Fu, Kathy Qian Luo
Circulating tumor cells (CTCs) are the primary targets of cancer treatment as they cause distal metastasis. However, how CTCs response to exercise-induced high shear stress is largely unknown. To study the effects of hemodynamic microenvironment on CTCs, we designed a microfluidic circulatory system that produces exercise relevant shear stresses. We explore the effects of shear stresses on breast cancer cells with different metastatic abilities, cancer cells of ovarian, lung and leukemic origin. Three major findings were obtained...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28029616/temporal-control-of-osteoblast-cell-growth-and-behavior-dictated-by-nanotopography-and-shear-stress
#11
Udesh Dhawan, Hsu-An Pan, Ying Hao Chu, Guewha S Huang, Po Chun Chen, Wen-Liang Chen
Biomaterial design involves assessment of cellular response to nanotopography parameters such as shape, dimension of nanotopography features. Here, the effect of nanotopography alongside the in vivo factor, shear stress, on osteoblast cell behavior, is reported. Tantalum oxide nanodots of 50 or 100 nm diameter were engineered using anodized aluminum oxide as a template. Bare tantalum nitride coated silicon substrates were taken as control (flat). MG63 (osteoblast) cells were seeded for 72 hours on flat, 50 or 100 nm nanodots and modulation in cell morphology, cell viability and expression of integrins was studied...
October 2016: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/27965040/hemodynamic-shear-stress-stimulates-migration-and-extravasation-of-tumor-cells-by-elevating-cellular-oxidative-level
#12
Shijun Ma, Afu Fu, Geraldine Giap Ying Chiew, Kathy Qian Luo
Cancer cells are shed into the blood stream and are exposed to hemodynamic shear stress during metastasis. It has been shown that shear stress can destroy circulating tumor cells (CTCs) both in vitro and in vivo. However, it remains unclear whether shear stress can modulate the properties and functions of tumor cells in a manner that might help CTCs to exit circulation. In this study, we established a microfluidic circulatory system to apply physiological fluid shear stress on breast cancer cells and demonstrated that an arterial level of shear stress significantly enhanced tumor cell migration in transwell and wound healing assays, and enhanced extravasation in a transendothelial assay...
March 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27935982/a-cost-effective-method-to-assemble-biomimetic-3d-cell-culture-platforms
#13
Sabreen Khalil, Nagwa El-Badri, Mohamed El-Mokhtaar, Saif Al-Mofty, Mohamed Farghaly, Radwa Ayman, Dina Habib, Noha Mousa
METHODS: We utilized the hAM to provide the biological and the three dimensional (3D) topographic components of the prototype. The 3D nano-roughness of the hAM was characterized using surface electron microscopy and surface image analysis (ImageJ and SurfaceJ). We developed additional macro-scale and micro-scale versions of the platform which provided additional shear stress factors to simulate the fluid dynamics of the in vivo extracellular fluids. RESULTS: Three models of varying complexities of the prototype were assembled...
2016: PloS One
https://www.readbyqxmd.com/read/27910892/dynamic-microenvironment-induces-phenotypic-plasticity-of-esophageal-cancer-cells-under-flow
#14
Gizem Calibasi Kocal, Sinan Güven, Kira Foygel, Aaron Goldman, Pu Chen, Shiladitya Sengupta, Ramasamy Paulmurugan, Yasemin Baskin, Utkan Demirci
Cancer microenvironment is a remarkably heterogeneous composition of cellular and non-cellular components, regulated by both external and intrinsic physical and chemical stimuli. Physical alterations driven by increased proliferation of neoplastic cells and angiogenesis in the cancer microenvironment result in the exposure of the cancer cells to elevated levels of flow-based shear stress. We developed a dynamic microfluidic cell culture platform utilizing eshopagael cancer cells as model cells to investigate the phenotypic changes of cancer cells upon exposure to fluid shear stress...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27794222/neovasculature-and-circulating-tumor-cells-dual-targeting-nanoparticles-for-the-treatment-of-the-highly-invasive-breast-cancer
#15
Jianhui Yao, Jingxian Feng, Xiaoling Gao, Dan Wei, Ting Kang, Qianqian Zhu, Tianze Jiang, Xunbin Wei, Jun Chen
Antiangiogenesis therapy has been served as a potent cancer treatment strategy for decades, yet disrupting neovasculature would provoke tumor cells into invasive growth and result in distal metastasis. The basic cause of cancer metastasis can be traced down to the presence of circulating tumor cells (CTCs) which detach from primary tumor site and act as 'seeds'. Epithelial cell adhesion molecule (EpCAM) is a potential biomarker for selective capture of epithelium-derived CTCs. Here, we integrated tumor neovessles-targetable ligands K237 peptide with Ep23 aptamer against EpCAM into a single drug-loaded nanoplatform using paclitaxel (PTX) as the model drug, aiming at damaging the primary tumor and neutralizing CTCs simultaneously to achieve a synergistic anti-tumor therapeutic effect...
October 22, 2016: Biomaterials
https://www.readbyqxmd.com/read/27773611/involvement-of-caveolin-1-in-low-shear-stress-induced-breast-cancer-cell-motility-and-adhesion-roles-of-fak-src-and-rock-p-mlc-pathways
#16
Niya Xiong, Shun Li, Kai Tang, Hongxia Bai, Yueting Peng, Hong Yang, Chunhui Wu, Yiyao Liu
Tumor cells translocating to distant sites are subjected to hemodynamic shear forces during their passage in the blood vessels. Low shear stress (LSS) plays a critical role in the regulation of various aspects of tumor cells functions, including motility and adhesion. Beyond its structural role, caveolin-1 (Cav-1), the important component of caveolae, represents a modulator of several cancer-associated functions as tumor progression and metastasis. However, the role of Cav-1 in regulating tumor cells response to shear stress remains poorly explored...
January 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27761800/investigation-of-biomimetic-shear-stress-on-cellular-uptake-and-mechanism-of-polystyrene-nanoparticles-in-various-cancer-cell-lines
#17
Taehee Kang, Chulhun Park, Beom-Jin Lee
Cancer cells in the tumor microenvironment are affected by fluid shear stress generated by blood flow in the vascular microenvironment and interstitial flows in the tumor microenvironment. Thus, we investigated how fluidic shear stress affects cellular uptake as well as the endocytosis mechanism of nanoparticles using a biomimetic microfluidic system that mimics the human dynamic environment. Positively charged amino-modified polystyrene nanoparticles (PSNs) at 100 μg/mL were delivered to cancer cells under static and biomimetic dynamic conditions (0...
December 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27660172/comparison-of-solid-and-fluid-constitutive-models-of-bone-marrow-during-trabecular-bone-compression
#18
Thomas A Metzger, Glen L Niebur
The mechanical environment and mechanobiology of bone marrow may play essential roles in bone adaptation, cancer metastasis, and immune cell regulation. However, the location of marrow within the trabecular pore space complicates experimental measurement of marrow mechanics. Computational models provide a means to assess the shear stress and pressure in the marrow during physiological loading, but they rely on accurate inputs for the marrow and the physics assumed for the interaction of bone and marrow. Elastic, viscoelastic, and fluid constitutive properties have all been reported from experimental measurements of marrow properties...
October 3, 2016: Journal of Biomechanics
https://www.readbyqxmd.com/read/27611979/probing-the-response-of-lung-tumor-cells-to-inflammatory-microvascular-endothelial-cells-on-fluidic-microdevice
#19
Hui Xu, Zhongyu Li, Yaqiong Guo, Xiaojun Peng, Jianhua Qin
The development of cancer depends on a complex tissue microenvironment for sustained growth, invasion, and metastasis. The extravasation of tumor cells is a critical event in tumor metastasis. However, the process and mechanism that underlie tumor cell extravasation remain unclear, which restricts the examination of many tumor processes and presents a formidable hurdle to drug development. To explore the initial steps by which lung tumor cells interact with the brain microvascular wall in the course of extravasation, we present a simple, inexpensive, and time-saving microfluidic device to mimic the inflammatory brain microvascular microenvironment and to investigate both the biochemical and mechanical causes of lung tumor cell rolling and adhesion on inflammatory endothelium to analyze the synergistic effects on tumor extravasation under fluidic shear stress conditions...
January 2017: Electrophoresis
https://www.readbyqxmd.com/read/27589843/tumor-vessel-normalization-after-aerobic-exercise-enhances-chemotherapeutic-efficacy
#20
Keri L Schadler, Nicholas J Thomas, Peter A Galie, Dong Ha Bhang, Kerry C Roby, Prince Addai, Jacob E Till, Kathleen Sturgeon, Alexander Zaslavsky, Christopher S Chen, Sandra Ryeom
Targeted therapies aimed at tumor vasculature are utilized in combination with chemotherapy to improve drug delivery and efficacy after tumor vascular normalization. Tumor vessels are highly disorganized with disrupted blood flow impeding drug delivery to cancer cells. Although pharmacologic anti-angiogenic therapy can remodel and normalize tumor vessels, there is a limited window of efficacy and these drugs are associated with severe side effects necessitating alternatives for vascular normalization. Recently, moderate aerobic exercise has been shown to induce vascular normalization in mouse models...
October 4, 2016: Oncotarget
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