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Cancer-associated fibroblasts

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https://www.readbyqxmd.com/read/29334123/cancer-associated-fibroblasts-tailored-tumor-microenvironment-of-therapy-resistance-in-gastrointestinal-cancers
#1
REVIEW
Yeqi Sun, Ruifen Wang, Meng Qiao, Yanchun Xu, Wenbin Guan, Lifeng Wang
Gastrointestinal cancers (GI) are a group of highly aggressive malignancies with heavy cancer-related mortalities. Even if continued development of therapy methods, therapy resistance has been a great obstruction for cancer treatment and thereby inevitably leads to depressed final mortality. Peritumoral cancer associated fibroblasts (CAFs), a versatile population assisting cancer cells to build a facilitated tumor microenvironment (TME), has been demonstrated exerting a promotion influence on cancer proliferation, migration, invasion, metastasis and also therapy resistance...
January 15, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29332341/association-of-the-combined-parameters-including-the-frequency-of-primary-cilia-cd8-tumor-infiltrating-lymphocytes-and-pd-1-expression-with-the-outcome-in-intestinal-cancer
#2
Josef Dvorak, Dimitar Hadzi Nikolov, Ladislav Dusek, Alzbeta Filipova, Igor Richter, David Buka, Ales Ryska, Jaroslav Mokry, Stanislav Filip, Bohuslav Melichar, Tomas Buchler, Jitka Abrahamova
PURPOSE: Primary cilium (PC) is considered to be a functional homologue of the immune synapse. Microtubule structures, PC of cancer associated fibroblasts and immune synapses between cytotoxic CD8+ tumor infiltrating lymphocytes (TILs) and cancer cells, are regularly found in varying amounts in the microenvironment of solid tumors. The purpose of this study was to find out the potential association and combined prognostic significance of the frequency of PC, PD-1 and CD8+ TILs in patients with intestinal cancer...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29331808/simultaneous-inhibition-of-hedgehog-signaling-and-tumor-proliferation-remodels-stroma-and-enhances-pancreatic-cancer-therapy
#3
Jun Zhao, Huamin Wang, Cheng-Hui Hsiao, Diana S-L Chow, Eugene J Koay, Yaan Kang, Xiaoxia Wen, Qian Huang, Ying Ma, James A Bankson, Stephen E Ullrich, Willem Overwijk, Anirban Maitra, David Piwnica-Worms, Jason B Fleming, Chun Li
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. It has an excessive desmoplastic stroma that can limit the intratumoral delivery of chemotherapy drugs, and protect tumor cells against radiotherapy. Therefore, both stromal and tumor compartments need to be addressed in order to effectively treat PDAC. We hereby co-deliver a sonic hedgehog inhibitor, cyclopamine (CPA), and a cytotoxic chemotherapy drug paclitaxel (PTX) with a polymeric micelle formulation (M-CPA/PTX). CPA can deplete the stroma-producing cancer-associated fibroblasts (CAFs), while PTX can inhibit tumor proliferation...
January 9, 2018: Biomaterials
https://www.readbyqxmd.com/read/29331323/regulation-of-inflammatory-factors-by-double-stranded-rna-receptors-in-breast-cancer-cells
#4
Amritha Venkatesh, Harika Nandigam, Maria Muccioli, Manindra Singh, Tiffany Loftus, Deana Lewis, Michelle Pate, Fabian Benencia
Malignant cells are not the only components of a tumor mass since other cells (e.g., fibroblasts, infiltrating leukocytes and endothelial cells) are also part of it. In combination with the extracellular matrix, all these cells constitute the tumor microenvironment. In the last decade the role of the tumor microenvironment in cancer progression has gained increased attention and prompted efforts directed to abrogate its deleterious effects on anti-cancer therapies. The immune system can detect and attack tumor cells, and tumor-infiltrating lymphocytes (particularly CD8 T cells) have been associated with improved survival or better response to therapies in colorectal, melanoma, breast, prostate and ovarian cancer patients among others...
November 22, 2017: Immunobiology
https://www.readbyqxmd.com/read/29325937/histopathological-analysis-of-tamoxifen-on-epidural-fibrosis
#5
Yasar Ozturk, Ismail Bozkurt, Mesut Emre Yaman, Yahya Guvenc, Tolga Tolunay, Deniz Billur, Fatma Kubra Erbay, Salim Senturk, Gokhan Bozkurt
BACKGROUND: Epidural fibrosis is a challenging topic in spinal surgery. This phenomenon constitutes one of the the main reasons behind "post-laminectomy syndrome" or "failed-back surgery syndrome", which leads to persistent back and leg pain in association with compression and/or stretching the nerve root or the dura. The exact mechanism of action in epidural fibrosis is complex and remains uncertain. Excessive deposition of collagen, fibronectin, and dermatan sulfate known as "extracellular matrix", and decrease of tissue cellularity results in epidural fibrosis...
January 8, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29325547/paracrine-and-epigenetic-control-of-caf-induced-metastasis-the-role-of-hotair-stimulated-by-tgf-%C3%A3-1-secretion
#6
Yu Ren, Huan-Huan Jia, Yi-Qi Xu, Xuan Zhou, Xiao-Hui Zhao, Yun-Fei Wang, Xin Song, Zhi-Yan Zhu, Ting Sun, Yan Dou, Wei-Ping Tian, Xiu-Lan Zhao, Chun-Sheng Kang, Mei Mei
BACKGROUND: The communication between carcinoma associated fibroblasts (CAFs) and cancer cells facilitate tumor metastasis. In this study, we further underlying the epigenetic mechanisms of CAFs feed the cancer cells and the molecular mediators involved in these processes. METHODS: MCF-7 and MDA-MB-231 cells were treated with CAFs culture conditioned medium, respectively. Cytokine antibody array, enzyme-linked immunosorbent assay, western blotting and immunofluorescence were used to identify the key chemokines...
January 11, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29325523/fanconi-anemia-with-sun-sensitivity-caused-by-a-xeroderma-pigmentosum-associated-missense-mutation-in-xpf
#7
Isabell Popp, Maqsood Punekar, Nick Telford, Stavros Stivaros, Kate Chandler, Meenakshi Minnis, Anna Castleton, Claire Higham, Louise Hopewell, D Gareth Evans, Anja Raams, Arjan F Theil, Stefan Meyer, Detlev Schindler
BACKGROUND: Fanconi anemia (FA) is an inherited genomic instability disorder with congenital and developmental abnormalities, bone marrow failure and predisposition to cancer early in life, and cellular sensitivity to DNA interstrand crosslinks. CASE PRESENTATION: A fifty-one-year old female patient, initially diagnosed with FA in childhood on the basis of classic features and increased chromosomal breakage, and remarkable sun-sensitivity is described. She only ever had mild haematological abnormalities and no history of malignancy...
January 11, 2018: BMC Medical Genetics
https://www.readbyqxmd.com/read/29323185/biogenesis-of-podosome-rosettes-through-fission
#8
Szu-Lin Kuo, Chien-Lin Chen, Yi-Ru Pan, Wen-Tai Chiu, Hong-Chen Chen
Podosomes are dynamic actin-based membrane protrusions that are important for extracellular matrix degradation and invasive cell motility. Individual podosomes are often found to organize into large rosette-like structures in some types of cells, such as osteoclasts, endothelial cells, Src-transformed fibroblasts, and certain highly invasive cancer cells. In this study, we show that new podosome rosettes arise through one of two mechanisms; de novo assembly or fission of a pre-existing podosome rosette in Src-transformed fibroblasts...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29322415/laser-microdissection-of-cellular-compartments-for-expression-analyses-in-cancer-models
#9
Tae-Su Han, Masanobu Oshima
Cancer tissues are composed of various cell types including cancer cells, cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs) and endothelial cells. These surrounding stromal cells form the tumor microenvironment, partly through the inflammatory response, which plays an important role in the development and malignant progression of cancer. It is therefore important to examine the expression profiles and protein modifications of each cellular component independently to decipher the interaction between the tumor cells and the microenvironment...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29321666/are-there-multiple-cells-of-origin-of-merkel-cell-carcinoma
#10
REVIEW
J C Sunshine, N S Jahchan, J Sage, J Choi
Merkel cell carcinoma (MCC) is a rare but lethal cancer with the highest case-by-case fatality rate among all skin cancers. Eighty percent of cancers are associated with the Merkel cell polyomavirus (MCPyV). Twenty percent of MCCs are virus negative. Recent epidemiological data suggest that there are important, clinically relevant differences between these two subtypes of MCC. Recent studies in cancer genomics, mouse genetics, and virology experiments have transformed our understanding of MCC pathophysiology...
January 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29318551/analysis-of-invasive-activity-of-caf-spheroids-into-three-dimensional-3d-collagen-matrices
#11
María Ángeles Villaronga, Saúl Álvarez Teijeiro, Francisco Hermida-Prado, Marta Garzón-Arango, Victoria Sanz-Moreno, Juana María García-Pedrero
Tumor growth and progression is the result of a complex process controlled not only by malignant cancer cells but also by the surrounding tumor microenvironment (TME). Cancer associated fibroblasts (CAFs), the most abundant cellular component of TME, play an active role in tumor invasion and metastasis by promoting cancer cell invasion through cell-cell interactions and secretion of pro-invasive factors such as extracellular matrix (ECM)-degrading proteases. Due to their tumor-promoting activities, there is an emerging interest in investigating CAFs biology and its potential as drug targets for cancer therapies...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29317486/mutual-dependence-of-the-mrtf-srf-and-yap-tead-pathways-in-cancer-associated-fibroblasts-is-indirect-and-mediated-by-cytoskeletal-dynamics
#12
Charles T Foster, Francesco Gualdrini, Richard Treisman
Both the MRTF-SRF and the YAP-TEAD transcriptional regulatory networks respond to extracellular signals and mechanical stimuli. We show that the MRTF-SRF pathway is activated in cancer-associated fibroblasts (CAFs). The MRTFs are required in addition to the YAP pathway for CAF contractile and proinvasive properties. We compared MRTF-SRF and YAP-TEAD target gene sets and identified genes directly regulated by one pathway, the other, or both. Nevertheless, the two pathways exhibit mutual dependence. In CAFs, expression of direct MRTF-SRF genomic targets is also dependent on YAP-TEAD activity, and, conversely, YAP-TEAD target gene expression is also dependent on MRTF-SRF signaling...
January 9, 2018: Genes & Development
https://www.readbyqxmd.com/read/29314782/chemotherapy-induced-oral-mucositis-and-associated-infections-in-a-novel-organotypic-model
#13
Takanori Sobue, Martinna Bertolini, Angela Thompson, Douglas E Peterson, Patricia I Diaz, Anna Dongari-Bagtzoglou
Oral mucositis is a common side effect of cancer chemotherapy, with significant adverse impact on the delivery of anti-neoplastic treatment. There is lack of consensus regarding the role of oral commensal microorganisms in the initiation or progression of mucositis since relevant experimental models are non-existent. The goal of this study was to develop an in vitro mucosal injury model that mimics chemotherapy-induced mucositis, where the effect of oral commensals can be studied. A novel organotypic model of chemotherapy-induced mucositis was developed based on a human oral epithelial cell line and a fibroblast-embedded collagen matrix...
January 4, 2018: Molecular Oral Microbiology
https://www.readbyqxmd.com/read/29312628/mir-520f-promotes-cell-aggressiveness-by-regulating-fibroblast-growth-factor-16-in-hepatocellular-carcinoma
#14
Feng Feng Xu, Wen Feng Xie, Guo Qing Zha, Hong Wu Chen, Liang Deng
Cancer metastasis is a multistep cellular process, which has be confirmed one of mainly causes of cancer associated-death in hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) participate in tumorigenesis function as either tumor suppressor genes or oncogenes. In order to elaborate the critical miRNAs and their targets in HCC, we compared the differential expression of miRNA between HCC tissues and normal tissues. Microarray analysis revealed there were several significantly up-expression miRNAs in HCC, compared to normal solid tissue...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29311159/pd2-paf1-at-the-crossroads-of-the-cancer-network
#15
REVIEW
Saswati Karmakar, Parama Dey, Arokia P Vaz, Sukesh R Bhaumik, Moorthy P Ponnusamy, Surinder K Batra
Pancreatic differentiation 2 (PD2)/RNA polymerase II-associated factor 1 (PAF1) is the core subunit of the human PAF1 complex (PAF1C) that regulates the promoter-proximal pausing of RNA polymerase II as well as transcription elongation and mRNA processing and coordinates events in mRNA stability and quality control. As an integral part of its transcription-regulatory function, PD2/PAF1 plays a role in posttranslational histone covalent modifications as well as regulates expression of critical genes of the cell-cycle machinery...
January 8, 2018: Cancer Research
https://www.readbyqxmd.com/read/29310782/the-biochemistry-and-immunohistochemistry-of-versican
#16
Stephen P Evanko, Christina K Chan, Pamela Y Johnson, Charles W Frevert, Thomas N Wight
Versican is a chondroitin sulfate proteoglycan found in the extracellular matrix that is important for changes in cell phenotype associated with development and disease. Versican has been shown to be involved in cardiovascular disorders, as well as lung disease and fibrosis, inflammatory bowel disease, cancer, and several other diseases that have an inflammatory component. Versican was first identified as a fibroblast proteoglycan and forms large multimolecular complexes with hyaluronan and other components of the provisional matrix during wound healing and inflammation...
2018: Methods in Cell Biology
https://www.readbyqxmd.com/read/29306747/heterocellular-3d-scaffolds-as-biomimetic-to-recapitulate-the-tumor-microenvironment-of-peritoneal-metastases-in%C3%A2-vitro-and-in%C3%A2-vivo
#17
Emiel De Jaeghere, Elly De Vlieghere, Jasper Van Hoorick, Sandra Van Vlierberghe, Glenn Wagemans, Leen Pieters, Elodie Melsens, Marleen Praet, Jo Van Dorpe, Matthieu N Boone, Rouba Ghobeira, Nathalie De Geyter, Marc Bracke, Christian Vanhove, Sara Neyt, Geert Berx, Bruno G De Geest, Peter Dubruel, Heidi Declercq, Wim Ceelen, Olivier De Wever
Peritoneal metastasis is a major cause of death and preclinical models are urgently needed to enhance therapeutic progress. This study reports on a hybrid hydrogel-polylactic acid (PLA) scaffold that mimics the architecture of peritoneal metastases at the qualitative, quantitative and spatial level. Porous PLA scaffolds with controllable pore size, geometry and surface properties are functionalized by type I collagen hydrogel. Co-seeding of cancer-associated fibroblasts (CAF) increases cancer cell adhesion, recovery and exponential growth by in situ heterocellular spheroid formation...
December 23, 2017: Biomaterials
https://www.readbyqxmd.com/read/29304760/regulation-of-pancreatic-stellate-cell-activation-by-notch3
#18
Haiyan Song, Yuxiang Zhang
BACKGROUND: Activated pancreatic stellate cells (PaSCs) are the key cellular source of cancer-associated fibroblasts in the pancreatic stroma of patients with pancreatic ductal adenocarcinoma (PDAC), however, the activation mechanism of PaSCs is not yet known. The Notch signaling pathway, components of which are expressed in stromal cells, is involved in the fibrosis of several organs, including the lung and liver. In the current study, we investigated whether Notch signal transduction is involved in PaSC activation in PDAC...
January 5, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29301607/force-mediated-proinvasive-matrix-remodeling-driven-by-tumor-associated-mesenchymal-stem-like-cells-in-glioblastoma
#19
Eun-Jung Lim, Yongjoon Suh, Seungmo Kim, Seok-Gu Kang, Su-Jae Lee
In carcinoma, cancer-associated fibroblasts participate in force-mediated extracellular matrix (ECM) remodeling, consequently leading to invasion of cancer cells. Likewise, the ECM remodeling actively occurs in glioblastoma (GBM) and the consequent microenvironmental stiffness is strongly linked to migration behavior of GBM cells. However, in GBM the stromal cells responsible for force-mediated ECM remodeling remain unidentified. We show that tumor-associated mesenchymal stem-like cells (tMSLCs) provide a proinvasive matrix condition in GBM by force-mediated ECM remodeling...
January 5, 2018: BMB Reports
https://www.readbyqxmd.com/read/29301364/immune-evasion-in-pancreatic-cancer-from-mechanisms-to-therapy
#20
REVIEW
Neus Martinez-Bosch, Judith Vinaixa, Pilar Navarro
Pancreatic ductal adenocarcinoma (PDA), the most frequent type of pancreatic cancer, remains one of the most challenging problems for the biomedical and clinical fields, with abysmal survival rates and poor therapy efficiency. Desmoplasia, which is abundant in PDA, can be blamed for much of the mechanisms behind poor drug performance, as it is the main source of the cytokines and chemokines that orchestrate rapid and silent tumor progression to allow tumor cells to be isolated into an extensive fibrotic reaction, which results in inefficient drug delivery...
January 3, 2018: Cancers
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