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Cancer-associated fibroblasts

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https://www.readbyqxmd.com/read/28088105/tectona-grandis-leaf-extract-free-and-associated-with-nanoemulsions-as-a-possible-photosensitizer-of-mouse-melanoma-b16-cell
#1
Cydia de Menezes Furtado, Fernando Sergio Escocio Drumond Viana de Faria, Ricardo Bentes Azevedo, Karen Py-Daniel, Ana Lygia Dos Santos Camara, Jaqueline Rodriguez da Silva, Everton de Holanda Oliveira, Anselmo Fortunato Ruiz Rodriguez, Igor Anatolievich Degterev
Over the past six years we have been studying extracts from tropical, specially Amazon, plants, to search for new sensitizers for photodynamic therapy of cancer and infectious diseases. Tectona grandis is a genus of tropical hardwood trees in the mint family, Lamiaceae. That is native to south and southeast Asia, but since the end of the 20th century is also gaining ground in the Amazon. The present work aims to evaluate the photodynamic potential of hydro-alcoholic extract from Tectona grandis LF leaves (TGE) and the same extract prepared as the oil-water nanoemulsion (TGE-NE) against melanoma B16 F10 cells...
January 5, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28087599/long-non-coding-rna-linc00092-acts-in-cancer-associated-fibroblasts-to-drive-glycolysis-and-progression-of-ovarian-cancer
#2
Linjie Zhao, Gaili Ji, Xiaobing Le, Chenlu Wang, Lian Xu, Min Feng, Yaguang Zhang, Huiliang Yang, Yu Xuan, Yanfei Yang, Lingzi Lei, Qilian Yang, Wayne Bond Lau, Bonnie Lau, Yi Chen, Xiangbing Deng, Shaohua Yao, Tao Yi, Xia Zhao, Yuquan Wei, Shengtao Zhou
The majority of patients with epithelial ovarian cancer are diagnosed at a late stage when peritoneal metastases exist, however, there is little knowledge of the metastatic process in this disease setting. In this study, we report the identification of the long non-coding RNA LINC00092 as a nodal driver of metastatic progression mediated by cancer-associated fibroblasts (CAF). Pro-metastatic properties of CAF in vitro and in vivo were found to associate with elevated expression of the chemokine CXCL14. In clinical specimens, elevated levels of CXCL14 in CAF also correlated with poor prognosis...
January 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28087332/exo-mfa-a-13c-metabolic-flux-analysis-to-dissect-tumor-microenvironment-secreted-exosome-contributions-towards-cancer-cell-metabolism
#3
Abhinav Achreja, Hongyun Zhao, Lifeng Yang, Tae Hyun Yun, Juan Marini, Deepak Nagrath
Dissecting the pleiotropic roles of tumor micro-environment (TME) on cancer progression has been brought to the foreground of research on cancer pathology. Extracellular vesicles such as exosomes, transport proteins, lipids, and nucleic acids, to mediate intercellular communication between TME components and have emerged as candidates for anti-cancer therapy. We previously reported that cancer-associated fibroblast (CAF) derived exosomes (CDEs) contain metabolites in their cargo that are utilized by cancer cells for central carbon metabolism and promote cancer growth...
January 10, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28077438/fibroblast-drug-scavenging-increases-intratumoural-gemcitabine-accumulation-in-murine-pancreas-cancer
#4
E Hessmann, M S Patzak, L Klein, N Chen, V Kari, I Ramu, T E Bapiro, K K Frese, A Gopinathan, F M Richards, D I Jodrell, C Verbeke, X Li, R Heuchel, J M Löhr, S A Johnsen, T M Gress, V Ellenrieder, A Neesse
OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry...
January 10, 2017: Gut
https://www.readbyqxmd.com/read/28077301/mir-124-down-regulation-is-critical-for-cancer-associated-fibroblasts-enhanced-tumor-growth-of-oral-carcinoma
#5
Xia Li, Qinqiao Fan, Jinyun Li, Jing Song, Yangcong Gu
Cancer associated fibroblasts (CAFs) are known to be involved in initiation, progression and metastasis of various cancers. However, the molecular mechanism of how CAFs affects the biological function of oral cancer (OC) has not been fully-addressed. In this study, we demonstrated that miR-124 was downregulated in oral CAFs and oral cancer cells (OCCs) when compared with matched normal fibroblasts (NFs). Hypermethylation in the promoter region of miR-124 genes was accounted for its downregulation. Interestingly, CAFs but not NFs exerted promotion effect on OCCs cell proliferation, migration and tumor growth in CAFs/NFs-OCCs co-culture...
January 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28072738/expression-quantitative-trait-loci-for-pi3k-akt-pathway
#6
Dongchan Ryu, Chaeyoung Lee
A genome-wide association study (GWAS) was conducted to identify expression quantitative trait loci (eQTLs) for the genes involved in phosphatidylinositol-3-kinase/v-akt murine thymoma viral oncogene homolog (PI3K/AKT) pathway.Data on mRNA expression of 341 genes in lymphoblastoid cell lines of 373 Europeans recruited by the 1000 Genomes Project using Illumina HiSeq2000 were utilized. We used their genotypes at 5,941,815 nucleotide variants obtained by Genome Analyzer II and SOLiD.The association analysis revealed 4166 nucleotide variants associated with expression of 85 genes (P < 5 × 10)...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28069875/15%C3%A2-methoxypuupehenol-induces-antitumor-effects-in-vitro-and-in-vivo-against-human-glioblastoma-and-breast-cancer-models
#7
Tyvette Hilliard, Gabriella Miklossy, Christopher Chock, Peibin Yue, Philip Williams, James Turkson
Studies with 15∝-methoxypuupehenol (15∝-MP), obtained from the extracts of Hyrtios sp., identified putative targets that are associated with its antitumor effects against human glioblastoma (GBM) and breast cancer. In the human GBM (U251MG) or breast cancer (MDA-MB-231) cells, treatment with 15∝-MP repressed pY705Stat3 (Signal Transducer and Activator of Transcription 3), pErk1/2 (extracellular signal-regulated kinase), pS147CyclinB1, pY507Alk (Anaplastic lymphoma kinase), and pY478ezrin levels, and induced pS10merlin, without inhibiting pJAK2 (Janus kinase) or pAkt induction...
January 9, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28068323/the-nogo-b-receptor-promotes-ras-plasma-membrane-localization-and-activation
#8
B Zhao, W Hu, S Kumar, P Gonyo, U Rana, Z Liu, B Wang, W Q Duong, Z Yang, C L Williams, Q R Miao
The localization of prenylated Ras at the plasma membrane promotes activation of Ras by receptor tyrosine kinases and stimulates oncogenic signaling by mutant Ras. The Nogo-B receptor (NgBR) is a transmembrane receptor that contains a conserved hydrophobic pocket. Here, we demonstrate that the NgBR promotes the membrane accumulation of Ras by directly binding prenylated Ras at the plasma membrane. We show that NgBR knockdown diminishes the membrane localization of Ras in multiple cell types. NgBR overexpression in NIH-3T3 fibroblasts increases membrane-associated Ras, induces the transformed phenotype in vitro, and promotes the formation of fibrosarcoma in nude mice...
January 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28060811/stromal-fibroblasts-from-the-interface-zone-of-triple-negative-breast-carcinomas-induced-epithelial-mesenchymal-transition-and-its-inhibition-by-emodin
#9
Hsiang-Chi Hsu, Liang-Chih Liu, Hao-Yu Wang, Chao-Ming Hung, Ying-Chao Lin, Chi-Tang Ho, Tzong-Der Way
"Triple negative breast cancer" (TNBC) is associated with a higher rate and earlier time of recurrence and worse prognosis after recurrence. In this study, we aimed to examine the crosstalk between fibroblasts and TNBC cells. The fibroblasts were isolated from TNBC patients' tissue in tumor burden zones, distal normal zones and interface zones. The fibroblasts were indicated as cancer-associated fibroblasts (CAFs), normal zone fibroblasts (NFs) and interface zone fibroblasts (INFs). Our study found that INFs grew significantly faster than NFs and CAFs in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28056982/different-clinical-significance-of-fgfr1-4-expression-between-diffuse-type-and-intestinal-type-gastric-cancer
#10
Mikito Inokuchi, Hideaki Murase, Sho Otsuki, Tatsuyuki Kawano, Kazuyuki Kojima
BACKGROUND: Receptor tyrosine kinases promote tumor progression in many cancers, although oncologic activation differs between diffuse-type gastric cancer (DGC) and intestinal-type gastric cancer (IGC). Fibroblast growth factor receptor (FGFR) is one RTK, and we previously reported the clinical significance of FGFR1, 2, 3, and 4 in gastric cancer. The aim of the present study was to reevaluate the clinical significance of FGFR1-4 expression separately in DGC and IGC. METHODS: Tumor samples, including 109 DGCs and 100 IGCs, were obtained from patients who underwent gastrectomy between 2003 and 2007 in our institution...
January 5, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28056302/-expression-of-cd10-in-cancer-associated-fibroblasts-and-its-effect-on-initiation-and-progression-of-colorectal-carcinoma
#11
Y Zhu, J J Zheng, F Yang, Q Q Nie, Z L Zhu, H Deng
Objective: To study CD10 expression in cancer-associated fibroblasts (CAF) and related effect on colorectal cancer initiation and progression. Methods: A total of 226 surgical removed colorectal cancer specimens were collected with patient follow-up data. A panel of immunohistochemical markers(CD10, Ki-67, p53, cyclin D1 and β-catenin) were evaluated in carcinomas, adjacent adenomas and paired normal colorectal mucosa with correlation of clinicopathological parameters. Results: CD10 expression was not detected in the normal colorectal mucosa by immunohistochemistry...
December 8, 2016: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28055963/emetine-elicits-apoptosis-of-intractable-b-cell-lymphoma-cells-with-myc-rearrangement-through-inhibition-of-glycolytic-metabolism
#12
Tomohiro Aoki, Kazuyuki Shimada, Akihiko Sakamoto, Keiki Sugimoto, Takanobu Morishita, Yuki Kojima, Satoko Shimada, Seiichi Kato, Chisako Iriyama, Shunsuke Kuno, Yasuhiko Harada, Akihiro Tomita, Fumihiko Hayakawa, Hitoshi Kiyoi
Despite improved clinical outcomes of diffuse large B-cell lymphoma, a certain proportion of patients still develop a primary refractory disease. To overcome these lymphomas that are intractable to existing treatment strategies, the tumor microenvironment has been identified as a potential therapeutic target. Here we describe our search for effective drugs for primary refractory lymphoma cells with MYC rearrangement. Through the drug screening of 3,440 known compounds, we identified a unique compound, emetine...
December 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/28052029/arg-leu-tyr-glu-tetrapeptide-inhibits-tumor-progression-by-suppressing-angiogenesis-and-vascular-permeability-via-vegf-receptor-2-antagonism
#13
Yi-Yong Baek, Dong-Keon Lee, Joohwan Kim, Ji-Hee Kim, Wonjin Park, Taesam Kim, Sanghwa Han, Dooil Jeoung, Ji Chang You, Hansoo Lee, Moo-Ho Won, Kwon-Soo Ha, Young-Guen Kwon, Young-Myeong Kim
The tetrapeptide Arg-Leu-Tyr-Glu (RLYE) is known to inhibit vascular endothelial growth factor-A (VEGF-A)-induced angiogenesis in vitro. Herein, we examined its underlying mechanism and antitumor activity associated with vascular remodeling. RLYE inhibited VEGF-A-induced angiogenesis in a mouse model and suppressed VEGF-A-induced angiogenic signal cascades in human endothelial cells. However, RLYE showed no inhibitory effect on VEGF-A-induced proliferation and migration of multiple myeloma cells expressing VEGF receptor (VEGFR)-1, but not VEGFR-2...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/28052009/cancer-associated-fibroblasts-promote-an-immunosuppressive-microenvironment-through-the-induction-and-accumulation-of-protumoral-macrophages
#14
Hideyuki Takahashi, Koichi Sakakura, Takeshi Kudo, Minoru Toyoda, Kyoichi Kaira, Tetsunari Oyama, Kazuaki Chikamatsu
Stromal cells in the tumor microenvironment (TME) closely interact with tumor cells and affect tumor cell behavior in diverse manners. We herein investigated the mechanisms by which cancer-associated fibroblasts (CAFs) affect the functional polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC) in vitro and in human cancer samples. The expression of CD68, CD14, CD163, CD200R, CD206, HLA-G, CD80, and CD86 was higher in CD14-positive cells co-cultured with the culture supernatants of CAFs established from OSCC specimens (CAF-educated cells) than in control cells...
December 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/28045923/germline-genetic-variants-in-tek-angpt1-angpt2-mmp9-fgf2-and-vegfa-are-associated-with-pathologic-complete-response-to-bevacizumab-in-breast-cancer-patients
#15
Issam Makhoul, Valentina K Todorova, Eric R Siegel, Stephen W Erickson, Ishwori Dhakal, Vinay R Raj, Jeannette Y Lee, Mohammed S Orloff, Robert J Griffin, Ronda S Henry-Tillman, Suzanne Klimberg, Laura F Hutchins, Susan A Kadlubar
BACKGROUND: We previously reported improved pathologic complete response (pCR) in a prospective phase II study using neoadjuvant bevacizumab in combination with chemotherapy compared to chemotherapy alone in breast cancer patients (41% vs. 25%, p = 0.0291). In this study, we queried germline single-nucleotide polymorphisms (SNPs) in angiogenesis-related genes for their impact on pCR and overall survival (OS). METHODS: DNA for genotyping was available from 34 subjects who received bevacizumab in addition to chemotherapy and 29 subjects who did not...
2017: PloS One
https://www.readbyqxmd.com/read/28041973/prognostic-significance-of-stromal-grem1-expression-in-colorectal-cancer
#16
Bo Gun Jang, Hye Sung Kim, Weon Young Chang, Jeong Mo Bae, Hyeon Jeong Oh, Xianyu Wen, Seorin Jeong, Nam Yun Cho, Woo Ho Kim, Gyeong Hoon Kang
Cancer associated fibroblasts (CAFs) are the dominant cell population in the cancer stroma. Gremlin 1 (GREM1), an antagonist of the bone morphogenetic protein pathway, is expressed by CAFs in a variety of human cancers. However, its biological significance for cancer patients is largely unknown. We applied RNA in situ hybridization (ISH) to evaluate the prognostic value of stromal GREM1 expression in a large cohort of 670 colorectal cancers (CRCs). Overall GREM1 expression in CRCs was lower than that of the matched normal mucosa, and GREM1 expression had a strong positive correlation with BMI1 and inverse correlations with EPHB2 and OLFM4...
December 29, 2016: Human Pathology
https://www.readbyqxmd.com/read/28039358/stromal-senescence-by-prolonged-cdk4-6-inhibition-potentiates-tumor-growth
#17
Xiangnan Guan, Kyle M LaPak, Rebecca C Hennessey, Christina Y Yu, Reena Shakya, Jianying Zhang, Christin E Burd
: Senescent cells within the tumor microenvironment (TME) adopt a pro-inflammatory, senescence-associated secretory phenotype (SASP) that promotes cancer initiation, progression and therapeutic resistance. Here, exposure to Palbociclib (PD-0332991), a CDK4/6 inhibitor, induces senescence and a robust SASP in normal fibroblasts. Senescence caused by prolonged CDK4/6 inhibition is DNA damage-independent and associated with Mdm2 downregulation, whereas the SASP elicited by these cells is largely reliant upon NF-kappaB activation...
December 30, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28031367/barriers-to-infection-of-human-cells-by-feline-leukemia-virus-insights-into-resistance-to-zoonosis
#18
Anne Terry, Anna Kilbey, Asif Naseer, Laura S Levy, Shamim Ahmad, Ciorsdaidh Watts, Nancy Mackay, Ewan Cameron, Sam Wilson, James C Neil
: The human genome displays a rich fossil record of past gamma-retrovirus infections, yet no current epidemic is evident, despite environmental exposure to viruses that infect human cells in vitro. Feline leukemia viruses (FeLVs) rank high on this list, but domestic or workplace exposure has not been associated with detectable serological responses. Non-specific inactivation of gamma-retroviruses by serum factors appears insufficient to explain these observations. To investigate further we explored the susceptibility of primary and established human cell lines to FeLV-B, the most likely zoonotic variant...
December 28, 2016: Journal of Virology
https://www.readbyqxmd.com/read/28027646/protein-nanocage-mediated-fibroblast-activation-protein-targeted-photoimmunotherapy-to-enhance-cytotoxic-t-cell-infiltration-and-tumor-control
#19
Zipeng Zhen, Wei Tang, Mengzhe Wang, Shiyi Zhou, Hui Wang, Zhanhong Wu, Zhonglin Hao, Zibo Li, Lin Liu, Jin Xie
Carcinoma-associated fibroblasts (CAFs) are found in many types of cancer and play an important role in tumor growth and metastasis. Fibroblast-activation protein (FAP), which is overexpressed on the surface of CAFs, has been proposed as a universal tumor targeting antigen. However, recent studies show that FAP is also expressed on multipotent bone marrow stem cells. A systematic anti-FAP therapy may lead to severe side effects and even death. Hence, there is an urgent need of a therapy that can selectively kill CAFs without causing systemic toxicity...
January 4, 2017: Nano Letters
https://www.readbyqxmd.com/read/28027199/the-combination-of-resveratrol-and-high-fluence-light-emitting-diode-red-light-produces-synergistic-photobotanical-inhibition-of-fibroblast-proliferation-and-collagen-synthesis-a-novel-treatment-for-skin-fibrosis
#20
Andrew Mamalis, Jared Jagdeo
BACKGROUND: Skin fibrosis is a debilitating condition that significantly impacts patient quality of life. Ultraviolet phototherapy is currently used to treat several diseases featuring skin fibrosis. High-fluence light-emitting diode-generated red light (HF-LED-RL) does not cause DNA damage associated with skin cancer, and it is generally regarded as safe, portable, and cost-effective. Early clinical observations suggest that LED-generated light may possess antifibrotic effects, although these findings are largely unexplored...
January 2017: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
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