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https://www.readbyqxmd.com/read/29161183/epitope-mapping-of-monoclonal-antibody-pmab-38-against-dog-podoplanin
#1
Yao-Wen Chang, Shinji Yamada, Mika K Kaneko, Yukinari Kato
Podoplanin (PDPN), a type I transmembrane sialoglycoprotein, is extensively expressed by normal lymphatic endothelial cells, renal podocytes, and pulmonary type I alveolar cells. Nevertheless, increased expression of PDPN in malignant tumors not only associates with poor prognosis but also facilitates hematogenous metastasis through interaction with C-type lectin-like receptor-2 presented on platelets, followed by PDPN-mediated platelet activation. We previously reported a novel PMab-38 antibody, an anti-dog PDPN (dPDPN) monoclonal antibody, which specifically recognizes PDPN in squamous cell carcinomas melanomas and cancer-associated fibroblasts in canine cancer tissues...
November 21, 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/29158066/the-potential-role-of-leptin-in-tumor-invasion-and-metastasis
#2
REVIEW
Amitabha Ray, Margot P Cleary
The adipocyte-released hormone-like cytokine/adipokine leptin behaves differently in obesity compared to its functions in the normal healthy state. In obese individuals, elevated leptin levels act as a pro-inflammatory adipokine and are associated with certain types of cancers. Further, a growing body of evidence suggests that higher circulating leptin concentrations and/or elevated expression of leptin receptors (Ob-R) in tumors may be poor prognostic factors. Although the underlying pathological mechanisms of leptin's association with poor prognosis are not clear, leptin can impact the tumor microenvironment in several ways...
November 11, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29157820/nymphaeol-c-a-prenylflavonoid-from-macaranga-tanarius-suppresses-the-expression-of-fibroblast-growth-factor-18
#3
Kazuki Yoshimura, Takahiro Hosoya, Misa Fujinami, Toshiro Ohta, Shigenori Kumazawa
BACKGROUND: Fibroblast growth factor 18 (FGF18) is one of the key factors in human signaling pathways and has been reported to be associated with the formation of various tissues. Additionally, FGF18 has been reported to maintain the telogen stage of the hair cycle, and its over-expression has also been observed in cancer cells. HYPOTHESIS/PURPOSE: We searched for natural compounds that inhibit the expression of FGF18 expression in vitro and evaluated their inhibitory mechanisms...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29156791/the-relationship-between-stromal-cell-derived-sparc-in-human-gastric-cancer-tissue-and-its-clinicopathologic-significance
#4
Yi Gao, Shui-Ping Yin, Xu-Shi Xie, Dan-Dan Xu, Wei-Dong Du
Background: We aimed to investigate the cellular source of secreted protein acidic and rich in cysteine (SPARC) in gastric cancer tissues and the relationship between SPARC expression and its prognostic significance. Methods: The expression of SPARC in 365 primary advanced gastric adenocarcinomas and 39 non-cancerous tissues was evaluated by immunohistochemical staining. Double-immunofluorescence staining was used to reveal the cellular source of SPARC in tumor tissues...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156523/cancer-associated-%C3%AF-broblasts-confer-cisplatin-resistance-of-tongue-cancer-via-autophagy-activation
#5
Juan-Kun Liao, Bin Zhou, Xiu-Mei Zhuang, Pei-Lin Zhuang, Da-Ming Zhang, Wei-Liang Chen
Cancer-associated fibroblasts (CAFs) play important roles in carcinogenesis and progression of tongue squamous cell carcinoma (TSCC). However, effect of CAFs on chemotherapy resistance of TSCC remains largely obscure. Here, we cultured the matched primary CAFs and normal fibroblasts (NFs) pairs and detected their roles in cisplatin sensitivity of TSCC, as well as autophagy-related protein LC3 and Beclin1 expressions. During exposure to cisplatin, TSCC with CAFs group exhibited significantly increased cell viability and IC50, but reduced apoptosis than that with NFs group...
November 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29153879/remodeling-the-tumor-microenvironment-with-emerging-nanotherapeutics
#6
REVIEW
Qin Chen, Guangxuan Liu, Shuo Liu, Hongyan Su, Yue Wang, Jingyu Li, Cong Luo
The tumor microenvironment (TME) has profound impacts on cancer progression and remodeling of the TME has emerged as a strategy to facilitate cancer therapy. Recently, great progress in TME modulation has been made, especially with the rapid developments in nanomedicine. In this review we outline the latest advances in remodeling of the TME based on nanotherapeutics. First, novel strategies developed to modulate the tumor extracellular matrix (ECM) are discussed, including disruption, mimicking, and intervening in tumor ECM fabrication...
November 15, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/29152128/modulation-of-cabozantinib-efficacy-by-the-prostate-tumor-microenvironment
#7
Manisha Tripathi, Srinivas Nandana, Sandrine Billet, Karen A Cavassani, Rajeev Mishra, Leland W K Chung, Edwin M Posadas, Neil A Bhowmick
The tumor microenvironment (TME) is increasingly recognized as the arbiter of metastatic progression and drug resistance in advanced prostate cancer (PCa). Cabozantinib is a potent tyrosine kinase inhibitor (TKI) with reported biological activity in the PCa epithelia, but failed to provide an overall survival benefit in phase 3 clinical trials. However, the promising biologic efficacy of the drug in early trials warranted a better understanding of the mechanism of action, with the goal of improving patient selection for TKI-based therapy such as cabozantinib...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152078/cd163-as-a-novel-target-gene-of-stat3-is-a-potential-therapeutic-target-for-gastric-cancer
#8
Zhenguo Cheng, Danhua Zhang, Baocheng Gong, Pengliang Wang, Funan Liu
CD163 is a member of the scavenger receptor cysteine-rich superfamily, and has been widely used to identify M2 type macrophage. However, the expression of CD163 in gastric cancer and its regulatory mechanism are still unclear. Here we show that CD163 is elevated in gastric cancer tissues. High expression of CD163 is a potential indicator to evaluate the status of tumor associated macrophages (TAMs), regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs) and cancer associated fibroblasts (Cafs)...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29141020/genomic-analysis-of-atypical-fibroxanthoma
#9
Kevin Lai, Catherine A Harwood, Karin J Purdie, Charlotte M Proby, Irene M Leigh, Namita Ravi, Thaddeus W Mully, Lionel Brooks, Priscilla M Sandoval, Michael D Rosenblum, Sarah T Arron
Atypical fibroxanthoma (AFX), is a rare type of skin cancer affecting older individuals with sun damaged skin. Since there is limited genomic information about AFX, our study seeks to improve the understanding of AFX through whole-exome and RNA sequencing of 8 matched tumor-normal samples. AFX is a highly mutated malignancy with recurrent mutations in a number of genes, including COL11A1, ERBB4, CSMD3, and FAT1. The majority of mutations identified were UV signature (C>T in dipyrimidines). We observed deletion of chromosomal segments on chr9p and chr13q, including tumor suppressor genes such as KANK1 and CDKN2A, but no gene fusions were found...
2017: PloS One
https://www.readbyqxmd.com/read/29137396/tgfbr-idh1-cav1-axis-promotes-tgf-%C3%AE-signalling-in-cancer-associated-fibroblast
#10
Xiaodan Hou, Jieying Zhang, Yongbin Wang, Wujun Xiong, Jun Mi
TGF-β signalling plays an important role in fibroblasts activation and tumour progression. Here, we report that the TGFBR-IDH1-Cav1 axis promotes TGF- β signalling in fibroblasts. Our data demonstrated that IDH1 was downregulated by TGF-β signalling in fibroblasts, and downregulation of IDH1 increased cellular concentration of α-ketoglutarate (α-KG) by accelerating glutamine metabolization. Interestingly, α-KG suppressed Cav1 expression through reducing the trimethylation of histone H3K4. Furthermore, Cav1 downregulation inhibited TGFBR protein degradation...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137358/tm4sf5-promotes-metastatic-behavior-of-cells-in-3d-extracellular-matrix-gels-by-reducing-dependency-on-environmental-cues
#11
Dae-Geun Song, Gyu-Ho Lee, Seo Hee Nam, Jin-Gyu Cheong, Doyoung Jeong, Seo-Jin Lee, Cheol-Ho Pan, Jae Woo Jung, Hye-Jin Kim, Jihye Ryu, Ji Eon Kim, Somi Kim, Chang Yun Cho, Min-Kyung Kang, Kyung-Min Lee, Jung Weon Lee
Transmembrane 4 L six family member 5 (TM4SF5) is highly expressed in hepatocellular carcinoma tissues and enhances migration in two-dimensional environments. Here, we investigated how TM4SF5 is involved in diverse pro-metastatic phenotypes in in vivo-like three-dimensional (3D) extracellular matrix gels. TM4SF5-positive cells aggressively formed invasive foci in 3D Matrigel, depending on TM4SF5-mediated signaling activity, cytoskeletal organization, and matrix metallopeptidase (MMP) 2-mediated extracellular remodeling, whereas TM4SF5-null cells did not...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137220/stromal-cyclin-d1-promotes-heterotypic-immune-signaling-and-breast-cancer-growth
#12
Timothy G Pestell, Xuanmao Jiao, Mukesh Kumar, Amy R Peck, Marco Prisco, Shengqiong Deng, Zhiping Li, Adam Ertel, Mathew C Casimiro, Xiaoming Ju, Agnese Di Rocco, Gabriele Di Sante, Sanjay Katiyar, Alison Shupp, Michael P Lisanti, Pooja Jain, Kongming Wu, Hallgeir Rui, Douglas C Hooper, Zuoren Yu, Aaron R Goldman, David W Speicher, Lisa Laury-Kleintop, Richard G Pestell
The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that drives cell autonomous cell cycle progression and proliferation. Herein we show cyclin D1 abundance is increased >30-fold in the stromal fibroblasts of patients with invasive breast cancer, associated with poor outcome. Cyclin D1 transformed hTERT human fibroblast to a cancer-associated fibroblast phenotype. Stromal fibroblast expression of cyclin D1 (cyclin D1(Stroma)) in vivo, enhanced breast epithelial cancer tumor growth, restrained apoptosis, and increased autophagy...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136508/cancer-associated-fibroblasts-neutralize-the-anti-tumor-effect-of-csf1-receptor-blockade-by-inducing-pmn-mdsc-infiltration-of-tumors
#13
Vinit Kumar, Laxminarasimha Donthireddy, Douglas Marvel, Thomas Condamine, Fang Wang, Sergio Lavilla-Alonso, Ayumi Hashimoto, Prashanthi Vonteddu, Reeti Behera, Marlee A Goins, Charles Mulligan, Brian Nam, Neil Hockstein, Fred Denstman, Shanti Shakamuri, David W Speicher, Ashani T Weeraratna, Timothy Chao, Robert H Vonderheide, Lucia R Languino, Peter Ordentlich, Qin Liu, Xiaowei Xu, Albert Lo, Ellen Puré, Chunsheng Zhang, Andrey Loboda, Manuel A Sepulveda, Linda A Snyder, Dmitry I Gabrilovich
Tumor-associated macrophages (TAM) contribute to all aspects of tumor progression. Use of CSF1R inhibitors to target TAM is therapeutically appealing, but has had very limited anti-tumor effects. Here, we have identified the mechanism that limited the effect of CSF1R targeted therapy. We demonstrated that carcinoma-associated fibroblasts (CAF) are major sources of chemokines that recruit granulocytes to tumors. CSF1 produced by tumor cells caused HDAC2-mediated downregulation of granulocyte-specific chemokine expression in CAF, which limited migration of these cells to tumors...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29136500/does-csf1r-blockade-turn-into-friendly-fire
#14
Tim F Greten
In this issue of Cancer Cell, Kumar et al. describe how CSF1R blockade induces not only an expected deprivation of tumor-associated macrophages, but also an accumulation of tumor-infiltrating polymorphonuclear mononuclear cells caused by Cxcl-1 released from cancer-associated fibroblasts.
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29135454/expression-of-a-novel-cnpy2-isoform-in-colorectal-cancer-and-its-association-with-oncologic-prognosis
#15
Jianhong Peng, Qingjian Ou, Jian Guo, Zhizhong Pan, Rongxin Zhang, Xiaojun Wu, Yujie Zhao, Yuxiang Deng, Caixia Li, Fulong Wang, Liren Li, Gong Chen, Zhenhai Lu, Peirong Ding, Desen Wan, Yujing Fang
Colorectal cancer (CRC) is a leading cause of cancer-related mortality. Recently, we identified a novel biomarker, canopy fibroblast growth factor signaling regulator 2 (CNPY2) isoform2, and subsequently investigated its expression and prognostic value in CRC patients. We initially generated CNPY2 isoform2 monoclonal antibodies and examined CNPY2 isoform2 expression in CRC cell lines and tissues using quantitative real-time polymerase chain reaction, western blot and immunohistochemistry analyses. We found that CNPY2 isoform2 expression significantly increased in tumor cell lines and tissues compared with that in normal colon epithelial cells and tumor-adjacent normal tissues...
November 13, 2017: Aging
https://www.readbyqxmd.com/read/29134439/treatment-related-survival-associations-of-claudin-2-expression-in-fibroblasts-of-colorectal-cancer
#16
Artur Mezheyeuski, Carina Strell, Ina Hrynchyk, Tormod Kyrre Guren, Anca Dragomir, Tatyana Doroshenko, Oksana Pashkova, Julia Gorgun, Kseniya Ruksha, Per Pfeiffer, Elin H Kure, Halfdan Sorbye, David Edler, Anna Martling, Bengt Glimelius, Arne Östman, Anna Portyanko
Claudin-2 is a trans-membrane protein-component of tight junctions in epithelial cells. Elevated claudin-2 expression has been reported in colorectal cancer (CRC). The aim of this study was to investigate the expression patterns of claudin-2 in human CRC samples and analyze its association with clinical characteristics and treatment outcome. TMAs of primary tumors from two cohorts of metastatic CRC (mCRC) were used. Claudin-2 IHC staining was evaluated in a semi-quantitative manner in different regions and cell types...
November 13, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29133591/chemokine-signaling-facilitates-early-stage-breast-cancer-survival-and-invasion-through-fibroblast-dependent-mechanisms
#17
Gage Brummer, Diana S Acevedo, Qingting Hu, Mike Portsche, Wei Fang, Min Yao, Brandon Zinda, Megan Myers, Nehemiah S Alvarez, Patrick Fields, Yan Hong, Fariba Behbod, Nikki Cheng
Ductal carcinoma in situ (DCIS) is the most common form of breast cancer, with 50,000 cases diagnosed every year in the United States. Over-treatment and under-treatment remain significant clinical challenges in patient care. Identifying key mechanisms associated with DCIS progression could uncover new biomarkers to better predict patient prognosis and improve guided treatment. Chemokines are small soluble molecules that regulate cellular homing through molecular gradients. CCL2-mediated recruitment of CCR2+ macrophages are a well-established mechanism for metastatic progression...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29122677/inducible-knockdown-of-procollagen-i-protects-mice-from-liver-fibrosis-and-leads-to-dysregulated-matrix-genes-and-attenuated-inflammation
#18
Olena Molokanova, Kai Schönig, Shih-Yen Weng, Xiaoyu Wang, Matthias Bros, Mustafa Diken, Svetlana Ohngemach, Morten Karsdal, Dennis Strand, Alexei Nikolaev, Leonid Eshkind, Detlef Schuppan
Organ fibrosis is characterized by a chronic wound-healing response, with excess deposition of extracellular matrix components. Here, collagen type I represents the most abundant scar component and a primary target for antifibrotic therapies. Liver fibrosis can progress to cirrhosis and primary liver cancer, which are the major causes of liver related morbidity and mortality. However, a (pro-)collagen type I specific therapy remains difficult and its therapeutic abrogation may incur unwanted side effects. We therefore designed tetracycline-regulated procollagen alpha1(I) short hairpin (sh)RNA expressing mice that permit a highly efficient inducible knockdown of the procollagen alpha1(I) gene in activated (myo-)fibroblasts, to study the effect of induced procollagen type I deficiency...
November 6, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29119969/tumor-targeting-efficacy-of-a-bf211-prodrug-through-hydrolysis-by-fibroblast-activation-protein-%C3%AE
#19
Xiao-Ping Chai, Guang-Long Sun, Yan-Fen Fang, Li-Hong Hu, Xuan Liu, Xiong-Wen Zhang
BF211, a bufalin (BF) derivative, exhibits stronger anti-cancer activity than BF but with potential cardiotoxicity. Fibroblast activation protein-α (FAPα) is a membrane-bound protease specifically expressed by carcinoma-associated fibroblasts, thus has been used for the selective delivery of anticancer agents. In this study, we used a FAPα-based prodrug strategy to synthesize a dipeptide (Z-Gly-Pro)-conjugated BF211 prodrug named BF211-03. BF211-03 was hydrolyzed by recombinant human FAPα (rhFAPα) and cleaved by homogenates of human colon cancer HCT-116 or human gastric cancer MGC-803 xenografts...
November 9, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29116739/gold-nanocluster-mediated-cellular-death-under-electromagnetic-radiation
#20
Anna Cifuentes-Rius, Angela Ivask, Shreya Das, Nuria Penya Auladell, Laura Fabregas, Nicholas L Fletcher, Zachary H Houston, Kristofer James Thurecht, Nicolas H Voelcker
Gold nanoclusters (Au NCs) have become a promising nanomaterial for cancer therapy due to their biocompatibility and fluorescent properties. In this study, the effect of ultrasmall protein-stabilized 2 nm Au NCs on six types of mammalian cells (fibroblasts, B-lymphocytes, glioblastoma, neuroblastoma, and two types of prostate cancer cells) under electromagnetic radiation is investigated. Cellular association of Au NCs in vitro is concentration-dependent and Au NCs have low intrinsic toxicity. However, when Au NC-incubated cells are exposed to 1 GHz electromagnetic field (microwave radiation, µW), cell viability significantly decreases thus demonstrating that Au NCs exhibit specific µW dependent cytotoxicity, likely resulting from localized heating...
November 8, 2017: ACS Applied Materials & Interfaces
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