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Carcinoma-Associated Fibroblasts

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https://www.readbyqxmd.com/read/28921304/expression-and-purification-of-an-fgf9-fusion-protein-in-e-coli-and-the-effects-of-the-fgf9-subfamily-on-human-hepatocellular-carcinoma-cell-proliferation-and-migration
#1
Shen Wang, Haipeng Lin, Tiantian Zhao, Sisi Huang, David G Fernig, Nuo Xu, Fenfang Wu, Mi Zhou, Chao Jiang, Haishan Tian
Fibroblast growth factor (FGF) 9 has oncogenic activity and plays an important role in the development of ovarian, lung, prostate, and gastric cancers. In the present study, with the aim of reducing the cost of utilizing growth factors in cancer research, a simple and efficient method for the preparation of recombinant human (rh)FGF9 in Escherichia coli was established. The rhFGF9 fusion protein (6 × His-TEV-rhFGF9) and the native protein released by tobacco etch virus (TEV) protease were obtained using a Ni-NTA system, with > 95% purity...
September 18, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28912898/inhibition-of-bone-marrow-derived-mesenchymal-stem-cells-homing-towards-triple-negative-breast-cancer-microenvironment-using-an-anti-pdgfr%C3%AE-aptamer
#2
Simona Camorani, Billy Samuel Hill, Raffaela Fontanella, Adelaide Greco, Matteo Gramanzini, Luigi Auletta, Sara Gargiulo, Sandra Albanese, Enrico Lucarelli, Laura Cerchia, Antonella Zannetti
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are shown to participate in tumor progression by establishing a favorable tumor microenvironment (TME) that promote metastasis through a cytokine networks. However, the mechanism of homing and recruitment of BM-MSCs into tumors and their potential role in malignant tissue progression is poorly understood and controversial. Here we show that BM-MSCs increase aggressiveness of triple-negative breast cancer (TNBC) cell lines evaluated as capability to migrate, invade and acquire stemness markers...
2017: Theranostics
https://www.readbyqxmd.com/read/28912872/preclinical-trial-of-the-multi-targeted-lenvatinib-in-combination-with-cellular-immunotherapy-for-treatment-of-renal-cell-carcinoma
#3
Chengkuan Cai, Jingyuan Tang, Baixin Shen, Liucheng Ding, Yunpeng Shao, Zhengsen Chen, Yinchao Ma, Haoliang Xue, Zhongqing Wei
Lenvatinib is an oral, multi-targeted tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor β, RET and KIT. Cellular immunotherapy has the potential to be a highly targeted treatment, with low toxicity to normal tissues and a high capacity to eradicate tumor tissue. The present study assessed the safety, maximum tolerated dose (MTD) and preliminary antitumor activity of lenvatinib and cellular immunotherapy in a murine model of renal cell carcinoma (RCC)...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28911071/prediction-of-pathological-response-to-neoadjuvant-treatment-in-rectal-cancer-with-a-two-protein-immunohistochemical-score-derived-from-stromal-gene-profiling
#4
S Gonçalves-Ribeiro, R Sanz-Pamplona, A Vidal, X Sanjuan, N Guillen Díaz-Maroto, A Soriano, J Guardiola, N Albert, M Martínez-Villacampa, I López, C Santos, J Serra-Musach, R Salazar, G Capellà, A Villanueva, D G Molleví
Background: Preoperative chemoradiotherapy followed by surgical mesorectal resection is the standard of care for locally advanced rectal carcinomas. Yet, predicting that patients will respond to treatment remains an unmet clinical challenge. Experimental design: Using laser-capture microdissection we isolated RNA from stroma and tumour glands from prospective pre-treatment samples (n = 15). Transcriptomic profiles were obtained hybridising PrimeView Affymetrix arrays...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28903357/intratumoral-acidosis-fosters-cancer-induced-bone-pain-through-the-activation-of-the-mesenchymal-tumor-associated-stroma-in-bone-metastasis-from-breast-carcinoma
#5
Gemma Di Pompo, Silvia Lemma, Lorenzo Canti, Nadia Rucci, Marco Ponzetti, Costantino Errani, Davide Maria Donati, Shonagh Russell, Robert Gillies, Tokuhiro Chano, Nicola Baldini, Sofia Avnet
Cancer-induced bone pain (CIBP) is common in patients with bone metastases (BM), significantly impairing quality of life. The current treatments for CIBP are limited since they are often ineffective. Local acidosis derived from glycolytic carcinoma and tumor-induced osteolysis is only barely explored cause of pain. We found that breast carcinoma cells that prefer bone as a metastatic site have very high extracellular proton efflux and expression of pumps/ion transporters associated with acid-base balance (MCT4, CA9, and V-ATPase)...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901303/role-of-collagen-triple-helix-repeat-containing-1-in-tumor-and-inflammatory-diseases
#6
REVIEW
Qian Wu, Qingrui Yang, Hongsheng Sun
Initially, collagen triple helix repeat containing-1 (CTHRC1) is expressed mainly in adventitial fibroblasts and neointimal smooth muscle cells of balloon-injured vessels, and increases cell migration, promotes tissue repair in response to injury. A variety of studies demonstrated that over-expression of CTHRC1 in solid tumors results in enhancement of migration and invasion of tumor cells, and is associated with decreased overall survival and disease-free survival. CTHRC1 expression is elevated in hepatitis B virus-infected patients and highly correlated with hepatocellular carcinoma progression as well...
2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28898237/nintedanib-selectively-inhibits-the-activation-and-tumour-promoting-effects-of-fibroblasts-from-lung-adenocarcinoma-patients
#7
M Gabasa, R Ikemori, F Hilberg, N Reguart, J Alcaraz
BACKGROUND: Nintedanib is a clinically approved multikinase receptor inhibitor to treat non-small cell lung cancer with adenocarcinoma (ADC) histology in combination with docetaxel, based on the clinical benefits reported on ADC but not on squamous cell carcinoma (SCC), which are the two most common histologic lung cancer subtypes. METHODS: We examined the potential role of tumour-associated fibroblasts (TAFs) in the differential effects of nintedanib in ADC and SCC...
September 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28892046/targeting-nuclear-receptors-in-cancer-associated-fibroblasts-as-concurrent-therapy-to-inhibit-development-of-chemoresistant-tumors
#8
J S K Chan, M K Sng, Z Q Teo, H C Chong, J S Twang, N S Tan
Most anticancer therapies to date focus on druggable features of tumor epithelia. Despite the increasing repertoire of treatment options, patient responses remain varied. Moreover, tumor resistance and relapse remain persistent clinical challenges. These observations imply an incomplete understanding of tumor heterogeneity. The tumor microenvironment is a major determinant of disease progression and therapy outcome. Cancer-associated fibroblasts (CAFs) are the dominant cell type within the reactive stroma of tumors...
September 11, 2017: Oncogene
https://www.readbyqxmd.com/read/28886304/the-roles-of-vasohibin-and-its-family-members-beyond-angiogenesis-modulators
#9
Hua Du, Jing Zhao, Ling Hai, Jing Wu, Hua Yi, Yonghong Shi
Vasohibin-1 is an intrinsic angiogenesis inhibitor, and is expressed in endothelial cells via induction by pro-angiogenesis factors. It is known to inhibit several processes of angiogenesis, with different mechanisms from extrinsic angiogenesis inhibitors. Vasohibin-2 is mainly expressed by mononuclear cells which have been mobilized from bone marrow. It not only promotes angiogenesis, but also modulates the releases of FGF-2 and VEGF, which are the two major inducers for vasohibin1. Hypoxic environment induces the expression of hypoxia-inducible Factor 1α with a result of VEGF release nearly in all tumor cell lines and tissues...
September 8, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28881637/cd147-functions-as-the-signaling-receptor-for-extracellular-divalent-copper-in-hepatocellular-carcinoma-cells
#10
Pengfei Ding, Xin Zhang, Shujuan Jin, Bo Duan, Pengxiang Chu, Yufei Zhang, Zhi-Nan Chen, Bin Xia, Fei Song
Elevated copper levels in tumor microenvironment are directly correlated to cancer progression in a variety of malignancies. Copper is required in angiogenesis, and promotes the proliferation and metastasis of cancer cells. However, the molecular mechanism of copper in promoting cancer progression remains elusive. Here we report that CD147 serves as a signaling receptor for extracellular Cu(2+) in hepatocellular carcinoma (HCC) cells. Cu(2+) binds to the extracellular membrane-proximal domain of CD147 and mediates its self-association...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881047/podoplanin-expression-in-cancer-associated-fibroblasts-predicts-unfavourable-prognosis-in-patients-with-pathological-stage-ia-lung-adenocarcinoma
#11
Yasuaki Kubouchi, Yohei Yurugi, Makoto Wakahara, Tomohiko Sakabe, Tomohiro Haruki, Kanae Nosaka, Ken Miwa, Kunio Araki, Yuji Taniguchi, Tatsushi Shiomi, Hiroshige Nakamura, Yoshihisa Umekita
AIMS: Podoplanin expression in cancer-associated fibroblasts (CAFs) has been proposed as an unfavourable indicator in squamous cell carcinoma of the lung, but little is known about its clinical significance in early-stage lung adenocarcinoma. We evaluated the prognostic impact of podoplanin expression in patients with pathological stage (p-stage) IA lung adenocarcinoma as categorized by the 8(th) edition of the tumour-node-metastasis classification for lung cancer. METHODS AND RESULTS: Immunohistochemical analyses using anti-podoplanin antibody were performed on resected specimens from 158 patients with p-stage IA lung adenocarcinoma...
September 7, 2017: Histopathology
https://www.readbyqxmd.com/read/28869838/fgfr2-driven-signaling-counteracts-tamoxifen-effect-on-er%C3%AE-positive-breast-cancer-cells
#12
Lukasz Turczyk, Kamila Kitowska, Magdalena Mieszkowska, Kamil Mieczkowski, Dominika Czaplinska, Dominika Piasecka, Radzisław Kordek, Andrzej C Skladanowski, Piotr Potemski, Hanna M Romanska, Rafal Sadej
Signaling mediated by growth factors receptors has long been suggested as one of the key factors responsible for failure of endocrine treatment in breast cancer (BCa). Herein we present that in the presence of tamoxifen, FGFs (Fibroblast Growth Factors) promote BCa cell growth with the strongest effect being produced by FGF7. FGFR2 was identified as a mediator of FGF7 action and the FGFR2-induced signaling was found to underlie cancer-associated fibroblasts-dependent resistance to tamoxifen. FGF7/FGFR2-triggered pathway was shown to induce ER phosphorylation, ubiquitination and subsequent ER proteasomal degradation which counteracted tamoxifen-promoted ER stabilization...
August 31, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28865028/drebrin-at-junctional-plaques
#13
Wiebke K Ludwig-Peitsch
Adhesion, segregation, and cellular plasticity are regulated by actin filaments anchored at the plaques of adherens junctions, sites of mechanical stabilization, and interfaces of multiple signaling networks. Drebrins were originally identified in neuronal cells, but the isoform drebrin E was also detected at adherens junctions of a wide range of non-neuronal cells, including polarized epithelia, endothelia, and fibroblasts. Here the protein is enriched at actin filament bundles associated with junctional plaques...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28841878/the-role-of-lutheran-basal-cell-adhesion-molecule-in-human-bladder-carcinogenesis
#14
Hong-Yi Chang, Hsin-Mei Chang, Tsung-Jung Wu, Chang-Yao Chaing, Tzong-Shin Tzai, Hong-Lin Cheng, Giri Raghavaraju, Nan-Haw Chow, Hsiao-Sheng Liu
BACKGROUND: Lutheran/basal cell adhesion molecule (Lu/BCAM) is a membrane bound glycoprotein. This study was performed to investigate the role and downstream signaling pathway of Lu/BCAM in human bladder tumorigenesis. METHODS: Five human bladder cancer (E6, RT4, TSGH8301, TCCSUP and J82), one stable mouse fibroblast cell line (NIH-Lu) expressing Lu/BCAM transgene and sixty human uroepithelial carcinoma specimens were analyzed by real-time PCR, immunohistochemistry (IHC), immunofluorescence (IFA) staining, Western blotting and promoter luciferase assay for Lu/BCAM, respectively...
August 26, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28833123/telomere-length-variation-in-tumor-cells-and-cancer-associated-fibroblasts-potential-biomarker-for-hepatocellular-carcinoma
#15
Li-Jie Ma, Xiao-Ying Wang, Meng Duan, Long-Zi Liu, Jie-Yi Shi, Liang-Qing Dong, Liu-Xiao Yang, Zhi-Chao Wang, Zhen-Bin Ding, Ai-Wu Ke, Ya Cao, Xiao-Ming Zhang, Jian Zhou, Jia Fan, Qiang Gao
The role of telomere dysfunction and aberrant telomerase activities in hepatocellular carcinoma (HCC) has been overlooked for many years. This study aimed to delineate the variation and prognostic value of telomere length in HCC. Telomere-specific fluorescence in situ hybridization (FISH) and qPCR were used to evaluate telomere length in HCC cell lines, tumor tissues and isolated non-tumor cells within the tumor. Significant telomere attrition was found in tumor cells and cancer-associated fibroblasts (CAFs) compared to their normal counterparts, but not in intratumor leukocytes or bile duct epithelial cells...
August 21, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28831645/effects-of-cytokines-derived-from-cancer-associated-fibroblasts-on-androgen-synthetic-enzymes-in-estrogen-receptor-negative-breast-carcinoma
#16
Kyoko Kikuchi, Keely May McNamara, Yasuhiro Miki, Ju-Yeon Moon, Man Ho Choi, Fumiya Omata, Minako Sakurai, Yoshiaki Onodera, Yoshiaki Rai, Yasuyo Ohi, Yasuaki Sagara, Minoru Miyashita, Takanori Ishida, Noriaki Ohuchi, Hironobu Sasano
PURPOSE: The tumor microenvironment plays pivotal roles in promotion of many malignancies. Cancer-associated fibroblasts (CAFs) have been well-known to promote proliferation, angiogenesis, and metastasis but mechanistic understanding of tumor-stroma interactions is not yet complete. Recently, estrogen synthetic enzymes were reported to be upregulated by co-culture with stromal cells in ER positive breast carcinoma (BC) but effects of co-culture on androgen metabolism have not been extensively examined...
August 22, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28814667/adrenergic-mediated-increases-in-inhba-drive-caf-phenotype-and-collagens
#17
Archana S Nagaraja, Robert L Dood, Guillermo Armaiz-Pena, Yu Kang, Sherry Y Wu, Julie K Allen, Nicholas B Jennings, Lingegowda S Mangala, Sunila Pradeep, Yasmin Lyons, Monika Haemmerle, Kshipra M Gharpure, Nouara C Sadaoui, Cristian Rodriguez-Aguayo, Cristina Ivan, Ying Wang, Keith Baggerly, Prahlad Ram, Gabriel Lopez-Berestein, Jinsong Liu, Samuel C Mok, Lorenzo Cohen, Susan K Lutgendorf, Steve W Cole, Anil K Sood
Adrenergic signaling is known to promote tumor growth and metastasis, but the effects on tumor stroma are not well understood. An unbiased bioinformatics approach analyzing tumor samples from patients with known biobehavioral profiles identified a prominent stromal signature associated with cancer-associated fibroblasts (CAFs) in those with a high biobehavioral risk profile (high Center for Epidemiologic Studies Depression Scale [CES-D] score and low social support). In several models of epithelial ovarian cancer, daily restraint stress resulted in significantly increased CAF activation and was abrogated by a nonspecific β-blocker...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28808378/rutamarin-an-active-constituent-from-ruta-angustifolia-pers-induced-apoptotic-cell-death-in-the-ht29-colon-adenocarcinoma-cell-line
#18
Shafinah Ahmad Suhaimi, Sok Lai Hong, Sri Nurestri Abdul Malek
BACKGROUND: Ruta angustifolia Pers. is a perennial herb that is cultivated worldwide, including Southeast Asia, for the treatment of various diseases as traditional medicine. OBJECTIVE: The purpose of the study was to identify an active principle of R. angustifolia and to investigate its effect on the HT29 cell death. MATERIALS AND METHODS: The methanol and fractionated extracts (hexane, chloroform, ethyl acetate, and water) of R. angustifolia Pers...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28807937/hnf1b-loss-exacerbates-the-development-of-chromophobe-renal-cell-carcinomas
#19
Mianen Sun, Pan Tong, Wen Kong, Baijun Dong, Yiran Huang, In Young Park, Lijun Zhou, Xian-De Liu, Zhiyong Ding, Xuesong Zhang, Shanshan Bai, Peter German, Reid Powell, Quan Wang, Xuefei Tong, Nizar M Tannir, Surena F Matin, W Kimryn Rathmell, Gregory N Fuller, Ian E McCutcheon, Cheryl Lyn Walker, Jing Wang, Eric Jonasch
Chromophobe renal cell carcinoma (ChRCC) is characterized by major changes in chromosomal copy number (CN). No model is available to precisely elucidate the molecular drivers of this tumor type. HNF1B is a master regulator of gene expression. Here we report that the transcription factor HNF1B is downregulated in the majority of ChRCC and that the magnitude of HNF1B loss is unique to ChRCC. We also observed a strong correlation between reduced HNF1B expression and aneuploidy in ChRCC patients. In murine embryonic fibroblasts or ACHN cells, HNF1B deficiency reduced expression of the spindle checkpoint proteins MAD2L1 and BUB1B, and the cell cycle checkpoint proteins RB1 and p27...
August 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28806666/doxorubicin-loaded-environmentally-friendly-carbon-dots-as-a-novel-drug-delivery-system-for-nucleus-targeted-cancer-therapy
#20
Yifang Yuan, Bin Guo, Liying Hao, Na Liu, Yunfeng Lin, Wushuang Guo, Xiaoguang Li, Bin Gu
Chemotherapy is widely applied against various kinds of carcinoma. Generally, chemotherapeutic agents, such as Doxorubicin (DOX), Paclitaxel (PTX), 5-Fluorouracil (5-FU), Methotrexate (MTX), and Vinblastine (VLB) are combined with a view to maximizing their efficacy. Unfortunately, chemotherapeutics are indiscriminate and also kill normal healthy cells, resulting in serious side effects. This non-productive and destructive distribution of chemotherapeutics is regarded as one of the largest problems associated with chemotherapy...
July 10, 2017: Colloids and Surfaces. B, Biointerfaces
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