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https://read.qxmd.com/read/30781344/targeting-tumor-microenvironment-for-cancer-therapy
#1
REVIEW
Catarina Roma-Rodrigues, Rita Mendes, Pedro V Baptista, Alexandra R Fernandes
Cancer development is highly associated to the physiological state of the tumor microenvironment (TME). Despite the existing heterogeneity of tumors from the same or from different anatomical locations, common features can be found in the TME maturation of epithelial-derived tumors. Genetic alterations in tumor cells result in hyperplasia, uncontrolled growth, resistance to apoptosis, and metabolic shift towards anaerobic glycolysis (Warburg effect). These events create hypoxia, oxidative stress and acidosis within the TME triggering an adjustment of the extracellular matrix (ECM), a response from neighbor stromal cells (e...
February 15, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30775554/tumor-induced-osteomalacia
#2
REVIEW
Zinan Yin, Juan Du, Fan Yu, Weibo Xia
Tumor-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a rare paraneoplastic syndrome characterized by hypophosphatemia resulting from decreased tubular phosphate reabsorption, with a low or inappropriately normal level of active vitamin D. The culprit tumors of TIO could produce fibroblast growth factor 23 which plays a role in regulating renal Pi handling and 25-hydroxyvitamin D 1α-hydroxylase activity. Chronic hypophosphatemia could eventually lead to inadequate bone mineralization, presenting as osteomalacia...
December 2018: Osteoporosis and Sarcopenia
https://read.qxmd.com/read/30768574/desmoplasia-in-lymph-node-metastasis-of-pancreatic-adenocarcinoma-reveals-activation-of-cancer-associated-fibroblasts-pattern-and-t-helper-2-immune-cell-infiltration
#3
Eran Nizri, Shoshi Bar-David, Asaf Aizic, Neta Sternbach, Guy Lahat, Ido Wolf, Joseph Klausner
OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a peritumoral proliferation of fibroblasts and extracellular matrix production known as desmoplasia. We aimed to study desmoplasia in PDAC lymph node (LN) metastases. METHODS: We evaluated LNs from 66 patients with PDAC and LN metastases. We used immunohistochemistry and real-time polymerase chain reaction to phenotype the desmoplastic response. RESULTS: Desmoplasia was identified in 57% of patients with LN metastases (Des+)...
February 14, 2019: Pancreas
https://read.qxmd.com/read/30767087/autophagy-inhibition-with-chloroquine-reverts-paclitaxel-resistance-and-attenuates-metastatic-potential-in-human-nonsmall-lung-adenocarcinoma-a549-cells-via-ros-mediated-modulation-of-%C3%AE-catenin-pathway
#4
Satabdi Datta, Diptiman Choudhury, Amlan Das, Dipanwita Das Mukherjee, Moumita Dasgupta, Shreya Bandopadhyay, Gopal Chakrabarti
Paclitaxel is one of the most commonly used drugs for the treatment of nonsmall cell lung cancer (NSCLC). However acquired resistance to paclitaxel, epithelial to mesenchymal transition and cancer stem cell formation are the major obstacles for successful chemotherapy with this drug. Some of the major reasons behind chemoresistance development include increased ability of the cancer cells to survive under stress conditions by autophagy, increased expression of drug efflux pumps, tubulin mutations etc. In this study we found that inhibition of autophagy with chloroquine prevented development of paclitaxel resistance in A549 cells with time and potentiated the effect of paclitaxel by increased accumulation of superoxide-producing damaged mitochondria, with elevated ROS generation, it also increased the apoptotic rate and sub G0/ G1 phase arrest with time in A549 cells treated with paclitaxel and attenuated the metastatic potential and cancer stem cell population of the paclitaxel-resistant cells by ROS mediated modulation of the Wnt/β-catenin signaling pathway, thereby increasing paclitaxel sensitivity...
February 14, 2019: Apoptosis: An International Journal on Programmed Cell Death
https://read.qxmd.com/read/30759123/nuclear-position-relative-to-the-golgi-body-and-nuclear-orientation-are-differentially-responsive-indicators-of-cell-polarized-motility
#5
Megan E Brasch, Giuseppe Passucci, Anushree C Gulvady, Christopher E Turner, M Lisa Manning, James H Henderson
Cell motility is critical to biological processes from wound healing to cancer metastasis to embryonic development. The involvement of organelles in cell motility is well established, but the role of organelle positional reorganization in cell motility remains poorly understood. Here we present an automated image analysis technique for tracking the shape and motion of Golgi bodies and cell nuclei. We quantify the relationship between nuclear orientation and the orientation of the Golgi body relative to the nucleus before, during, and after exposure of mouse fibroblasts to a controlled change in cell substrate topography, from flat to wrinkles, designed to trigger polarized motility...
2019: PloS One
https://read.qxmd.com/read/30737978/enabled-homolog-shown-to-be-a-potential-biomarker-and-prognostic-indicator-for-breast-cancer-by-bioinformatics-analysis
#6
Qiang Li Li, Yan-Ling Su, Min Zeng, Wei-Xi Shen
BACKGROUND: Human enabled homolog (ENAH; also known as human ortholog of mammalian enabled, hMENA) is a member of the enabled/vasodilator-stimulated phosphor protein family that regulates fibroblast movement and nervous system development. The ENAH over-expression promotes breast cancer (BC) cell invasion and metastasis. METHODS: We studied ENAH mRNA expression in various tumors and normal tissues using the ONCOMINE database, and in an array of cancer cell lines using Cancer Cell Line Encyclopedia data...
January 30, 2019: Clinical and Investigative Medicine. Médecine Clinique et Experimentale
https://read.qxmd.com/read/30737838/clinical-significance-of-cancer-associated-fibroblasts-and-their-correlation-with-microvessel-and-lymphatic-vessel-density-in-lung-adenocarcinoma
#7
Ling Chen, Yue Qin, Tenglong Zhang, Ning Ding, Yi Chen, Zhe Zhang, Chengye Guo
BACKGROUND: To determine whether cancer-associated fibroblasts (CAFs) are associated with microvessel density (MVD) and lymphatic vessel density (LVD) in lung adenocarcinoma (ADC) or are not prognostic. METHODS: Ninety-three lung adenocarcinoma patients without adjuvant therapy between January 2010 and June 2011 were enrolled. CAFs, MVD, and LVD were identified by α-smooth muscle actin (α-SMA), CD34 and D2-40 staining via immunohistochemistry. Staining intensities were assessed and quantified...
February 8, 2019: Journal of Clinical Laboratory Analysis
https://read.qxmd.com/read/30736372/podoplanin-in-inflammation-and-cancer
#8
REVIEW
Miguel Quintanilla, Lucía Montero-Montero, Jaime Renart, Ester Martín-Villar
Podoplanin is a small cell-surface mucin-like glycoprotein that plays a crucial role in the development of the alveoli, heart, and lymphatic vascular system. Emerging evidence indicates that it is also involved in the control of mammary stem-cell activity and biogenesis of platelets in the bone marrow, and exerts an important function in the immune response. Podoplanin expression is upregulated in different cell types, including fibroblasts, macrophages, T helper cells, and epithelial cells, during inflammation and cancer, where it plays important roles...
February 6, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30723174/hypoxic-cancer-associated-fibroblasts-increase-ncbp2-as2-hiar-to-promote-endothelial-sprouting-through-enhanced-vegf-signaling
#9
Fernanda G Kugeratski, Samuel J Atkinson, Lisa J Neilson, Sergio Lilla, John R P Knight, Jens Serneels, Amelie Juin, Shehab Ismail, David M Bryant, Elke K Markert, Laura M Machesky, Massimiliano Mazzone, Owen J Sansom, Sara Zanivan
Intratumoral hypoxia causes the formation of dysfunctional blood vessels, which contribute to tumor metastasis and reduce the efficacy of therapeutic treatments. Blood vessels are embedded in the tumor stroma of which cancer-associated fibroblasts (CAFs) constitute a prominent cellular component. We found that hypoxic human mammary CAFs promoted angiogenesis in CAF-endothelial cell cocultures in vitro. Mass spectrometry-based proteomic analysis of the CAF secretome unraveled that hypoxic CAFs contributed to blood vessel abnormalities by altering their secretion of various pro- and anti-angiogenic factors...
February 5, 2019: Science Signaling
https://read.qxmd.com/read/30720165/mir-10b-suppresses-the-growth-and-metastasis-of-colorectal-cancer-cell-by-targeting-fgf13
#10
J-J Song, W Li
OBJECTIVE: MicroRNA (miRNA) plays important roles in the progression of different cancers. In this study, we investigated the precise role of miR-10b in the growth and metastasis of colorectal cancer (CRC) cell. PATIENTS AND METHODS: The levels of miR-10b in CRC cell lines were detected using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay. A series of functional assays, including cell proliferation, colony formation, wound healing and transwell invasion were conducted using miR-10b transfected cells...
January 2019: European Review for Medical and Pharmacological Sciences
https://read.qxmd.com/read/30720137/macc1-overexpression-in-carcinoma%C3%A2-associated-fibroblasts-induces-the-invasion-of-lung-adenocarcinoma-cells-via-paracrine-signaling
#11
Zhuoshi Li, Tao Guo, Lei Fang, Nan Li, Xiaochao Wang, Peng Wang, Shilei Zhao, Fengzhou Li, Yanwei Cui, Xin Shu, Lei Zhao, Jinxiu Li, Chundong Gu
Carcinoma‑associated fibroblasts (CAFs) are essential for initiating lung cancer cell invasion and metastasis. An elevated MACC1 expression has been implicated in the progression of lung adenocarcinoma. Hitherto, the role of MACC1 in lung adenocarcinoma‑derived CAFs remains unclear. In this study, CAFs isolated from the tissues of patients with lung adenocarcinoma expressed typical CAF markers (shown by immunohistochemical and immunofluorescence analysis) and exhibited enhanced migration and invasion abilities when co‑cultured with A549 cells in a microfluidic model...
January 30, 2019: International Journal of Oncology
https://read.qxmd.com/read/30720066/long-noncoding-rna-homeobox-a11-antisense-promotes-transforming-growth-factor-%C3%AE-1%C3%A2-induced-fibrogenesis-in-cardiac-fibroblasts
#12
Jiangting Wang, Xiaowei Liu, Qin Zhuang, Rongrong Pan, Linlin Zou, Zhenbo Cen, Lijiang Tang
Cardiac fibrosis is closely associated with various heart diseases and is an important pathological feature of cardiac remodeling. However, detailed mechanisms underlying cardiac fibrosis remain largely unknown. Long noncoding RNAs (lncRNAs) are reported to serve significant roles in the development of cardiac fibrosis. The present study aimed to identify the role of a novel lncRNA, homeobox A11 antisense (HOXA11‑AS), in cardiac fibrosis. Overexpression of HOXA11‑AS in mouse cardiac fibroblasts (CFs) increased the expression of transforming growth factor β1 (TGFβ1) and its downstream molecules, while knockdown of HOXA11‑AS inhibited the TGFβ1 signaling pathway...
January 24, 2019: Molecular Medicine Reports
https://read.qxmd.com/read/30719110/a-potential-novel-therapy-for-fgfr1-amplified-pancreatic-cancer-with-bone-metastasis-screened-by-next-generation-sequencing-and-a-patient-derived-xenograft-model
#13
Zhonghai Guan, Huanrong Lan, Dan Sun, Xuanwei Wang, Ketao Jin
Effective therapies are limited for pancreatic cancer, particularly for those with distant tumour metastases. Therefore, more individualised drug screening is urgently required. Next-generation sequencing (NGS) is a powerful tool to investigate the genomic landscape of patients and the mechanism of drug response, which may provide a broader vision for potential clinical drug screening. Patient-derived xenograft (PDX) models may have a significant advantage in predicting clinical treatment response. In our previous study, a PDX of pancreatic cancer bone metastasis was established, and NGS was conducted to investigate the molecular information...
February 2019: Oncology Letters
https://read.qxmd.com/read/30718260/plasminogen-activator-inhibitor-1-pai1-promotes-actin-cytoskeleton-reorganization-and-glycolytic-metabolism-in-triple-negative-breast-cancer
#14
Brock A Humphries, Johanna M Buschhaus, Yu-Chih Chen, Henry R Haley, Tonela Qyli, Benjamin Chiang, Nathan Shen, Shrila Rajendran, Alyssa Cutter, Yu-Heng Cheng, Yu-Ting Chen, Jason Cong, Phillip C Spinosa, Euisik Yoon, Kathryn E Luker, Gary D Luker
Migration and invasion of cancer cells constitute fundamental processes in tumor progression and metastasis. Migratory cancer cells commonly upregulate expression of plasminogen activator inhibitor 1 (PAI1), and PAI1 correlates with poor prognosis in breast cancer. However, mechanisms by which PAI1 promotes migration of cancer cells remain incompletely defined. Here we show that increased PAI1 drives rearrangement of the actin cytoskeleton, mitochondrial fragmentation, and glycolytic metabolism in triple negative breast cancer (TNBC) cells...
February 4, 2019: Molecular Cancer Research: MCR
https://read.qxmd.com/read/30710321/toll-like-receptor-4-and-matrix-metalloproteases-11-and-13-as-predictors-of-tumor-recurrence-and-survival-in-stage-ii-colorectal-cancer
#15
Noemi Eiro, Juan Francisco Carrión, Sandra Cid, Alejandro Andicoechea, José Luis García-Muñiz, Luis O González, Francisco J Vizoso
Current clinical-pathologic stratification factors do not allow clear identification of high-risk stage II colorectal cancer (CRC) patients. Therefore, the identification of additional prognostic markers is desirable. Toll-like receptor (TLR)-4 is activated during tumorigenesis and matrix metalloproteases (MMPs) are involved in invasion and metastasis. We aimed to evaluate the expression and clinical relevance of TLR4, MMP11 and MMP13 for patients with stage II CRC. Immunohistochemistry was used to study the expression of TLR4, MMP11 and MMP13 in 96 patients with stage II CRC...
February 1, 2019: Pathology Oncology Research: POR
https://read.qxmd.com/read/30710055/heterotypic-caf-tumor-spheroids-promote-early-peritoneal-metastatis-of-ovarian-cancer
#16
Qinglei Gao, Zongyuan Yang, Sen Xu, Xiaoting Li, Xin Yang, Ping Jin, Yi Liu, Xiaoshui Zhou, Taoran Zhang, Cheng Gong, Xiao Wei, Dan Liu, Chaoyang Sun, Gang Chen, Junbo Hu, Li Meng, Jianfeng Zhou, Kenjiro Sawada, Robert Fruscio, Thomas W Grunt, Jörg Wischhusen, Víctor Manuel Vargas-Hernández, Bhavana Pothuri, Robert L Coleman
High-grade serous ovarian cancer (HGSOC) is hallmarked by early onset of peritoneal dissemination, which distinguishes it from low-grade serous ovarian cancer (LGSOC). Here, we describe the aggressive nature of HGSOC ascitic tumor cells (ATCs) characterized by integrin α5high (ITGA5high ) ATCs, which are prone to forming heterotypic spheroids with fibroblasts. We term these aggregates as metastatic units (MUs) in HGSOC for their advantageous metastatic capacity and active involvement in early peritoneal dissemination...
February 1, 2019: Journal of Experimental Medicine
https://read.qxmd.com/read/30709621/durotaxis-by-human-cancer-cells
#17
Brian J DuChez, Andrew D Doyle, Emilios K Dimitriadis, Kenneth M Yamada
Durotaxis is a type of directed cell migration in which cells respond to a gradient of extracellular stiffness. Using automated tracking of positional data for large sample sizes of single migrating cells, we investigated 1) whether cancer cells can undergo durotaxis; 2) whether cell durotactic efficiency varies depending on the regional compliance of stiffness gradients; 3) whether a specific cell migration parameter such as speed or time of migration correlates with durotaxis; and 4) whether Arp2/3, previously implicated in leading edge dynamics and migration, contributes to cancer cell durotaxis...
January 12, 2019: Biophysical Journal
https://read.qxmd.com/read/30707559/human-cancer-cell-membrane-coated-biomimetic-nanoparticles-reduce-fibroblast-mediated-invasion-and-metastasis-and-induce-t-cells
#18
Jiefu Jin, Balaji Krishnamachary, James Dion Barnett, Samit Chatterjee, Di Chang, Yelena Mironchik, Flonne Wildes, Elizabeth Jaffee, Sridhar Nimmagadda, Zaver M Bhujwalla
Biomimetic nanoparticles (NPs) combine the flexibility and reproducibility of synthetic materials with the functionality of biological materials. Here, we developed and characterized biomimetic poly (lactic-co-glycolic acid) (PLGA) NPs coated with human cancer cell membrane fractions (CCMFs) to form CCMF coated PLGA (CCMF-PLGA) NPs. We evaluated the ability of these CCMF-PLGA NPs to disrupt cancer cell-stromal cell interactions, and to induce an immune response. Western blot analysis verified the plasma membrane purity of CCMFs...
February 1, 2019: ACS Applied Materials & Interfaces
https://read.qxmd.com/read/30700832/isolation-and-characterization-of-patient-derived-cns-metastasis-associated-stromal-cell-lines
#19
Ben Yi Tew, Christophe Legendre, Gerald C Gooden, Kyle N Johnson, Rae Anne Martinez, Jeff Kiefer, Mark Bernstein, Jennifer Glen, Loren Butry, Aleksander Hinek, Steven A Toms, Bodour Salhia
The functional role of human derived stromal cells in the tumor microenviornment of CNS metastases (CM) remain understudied. The purpose of the current study was to isolate and characterize stromal cells of the tumor microenvironment in CM. Four different patient-derived cell lines (PDCs) of stromal and one PDC of tumorigenic origin were generated from breast or lung CM. PDCs were analyzed by DNA/RNA sequencing, DNA methylation profiling, and immunophenotypic assays. The stromal derived PDCs were termed CNS metastasis-associated stromal cells (cMASCs)...
January 30, 2019: Oncogene
https://read.qxmd.com/read/30698309/the-role-of-tenascin-c-and-twist1-in-gastric-cancer-cancer-progression-and-prognosis
#20
Wenbo Qi, Zhaoting Yang, Haoyue Li, Yan Cui, Yanhua Xuan
The aim of the present study was to identify the relation between Tenascin-C (TNC) and Twist1 and determine their clinical significance in gastric cancer (GC). We analyzed the expression of TNC and Twist1 in 159 GC samples and in 91 non-tumor samples using immunohistochemistry. In this study, TNC expression in stromal fibroblasts of GC was remarkably higher than non-tumor gastric lesions. The expression of TNC in GC stromal fibroblasts was significantly associated with pT stage, lymph node metastasis, distant metastasis...
February 2019: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
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