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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
#1
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
#2
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/28911166/hormonal-and-growth-regulation-of-epithelial-and-stromal-cells-from-the-normal-and-malignant-endometrium-by-pigment-epithelium-derived-factor
#3
Julien Daubriac, Unnati M Pandya, Kuang-Tzu Huang, Savvas C Pavlides, Patricia Gama, Stephanie V Blank, Pratibha Shukla, Susan E Crawford, Leslie I Gold
We discovered that pigment epithelium-derived factor (PEDF)-null mice have endometrial hyperplasia, the precursor to human type I endometrial cancer (ECA), which is etiologically linked to unopposed estrogen (E2), suggesting that this potent antiangiogenic factor might contribute to dysregulated growth and the development of type I ECA. Treatment of both ECA cell lines and primary ECA cells with recombinant PEDF dose dependently decreased cellular proliferation via an autocrine mechanism by blocking cells in G1 and G2 phases of the cell cycle...
September 1, 2017: Endocrinology
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/28902355/establishment-of-two-ovarian-cancer-orthotopic-xenograft-mouse-models-for-in-vivo-imaging-a-comparative-study
#6
Jing Guo, Jing Cai, Yunxia Zhang, Yapei Zhu, Ping Yang, Zehua Wang
Orthotopic tumor animal models are optimal for preclinical research of novel therapeutic interventions. The aim of the present study was to compare two types of ovarian cancer orthotopic xenograft (OCOX) mouse models, i.e. cellular orthotopic injection (COI) and surgical orthotopic implantation (SOI), regarding xenograft formation rate, in vivo imaging, tumor growth and metastasis, and tumor microenvironment. The tumor formation and progression were monitored by bioluminescent in vivo imaging. Cell proliferation and migration abilities were detected by EdU and scratch assays, respectively...
October 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28901439/long-noncoding-rna%C3%A2-p21-modulates-cellular-senescence-via-the-wnt-%C3%AE-%C3%A2-catenin-signaling-pathway-in-mesenchymal-stem-cells
#7
Wenzheng Xia, Lei Zhuang, Xia Deng, Meng Hou
Mesenchymal stem cell (MSC)‑based therapies have demonstrated efficacy in animal models of cardiovascular diseases. However, MSCs decrease in quantity and quality with age, which reduces their capacity for damage repair. Long noncoding (lnc) RNAs regulate gene transcription and the fate of post‑transcriptional mRNA, affecting a broad range of age‑associated physiological and pathological conditions, including cardiovascular disease and cancer cell senescence. However, the functional role of lncRNAs in stem cell senescence remains largely unknown...
September 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28898237/nintedanib-selectively-inhibits-the-activation-and-tumour-promoting-effects-of-fibroblasts-from-lung-adenocarcinoma-patients
#8
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/28894697/the-potential-role-of-senescence-as-a-modulator-of-platelets-and-tumorigenesis
#9
Claudio A Valenzuela, Ricardo Quintanilla, Rodrigo Moore-Carrasco, Nelson E Brown
In addition to thrombus formation, alterations in platelet function are frequently observed in cancer patients. Importantly, both thrombus and tumor formation are influenced by age, although the mechanisms through which physiological aging modulates these processes remain poorly understood. In this context, the potential effects of senescent cells on platelet function represent pathophysiological mechanisms that deserve further exploration. Cellular senescence has traditionally been viewed as a barrier to tumorigenesis...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28894048/the-role-of-bile-acids-in-the-pathogenesis-of-bowel-diseases
#10
Magdalena Panek-Jeziorna, Agata Mulak
Bile acids not only play a cardinal role in the digestion and absorption of fat and fat-soluble vitamins, but also significantly affect gastrointestinal motor, sensory and secretory functions, intestinal barrier permeability and the regulation of the inflammatory response. The results of recent studies have revealed complex interactions between bile acids and the gut microbiota. In addition, bile acids also play a role of signaling molecules regulating the activity of lipid and glucose metabolic pathways, as well as a role of ligands for transcription factors...
August 24, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28893556/the-ilk-mmp9-mrtf-axis-is-crucial-for-endmt-differentiation-of-endothelial-cells-in-a-tumor-microenvironment
#11
Wojciech M Ciszewski, Katarzyna Sobierajska, Marta E Wawro, Wanda Klopocka, Natasza Chefczyńska, Angelika Muzyczuk, Kamil Siekacz, Agata Wujkowska, Jolanta Niewiarowska
Increasing evidence indicates that the tumor microenvironment is a critical factor supporting cancer progression, chemoresistance and metastasis. Recently, cancer-associated fibroblasts (CAFs) have been recognized as a crucial tumor stromal component promoting cancer growth and invasiveness via modulation of the extracellular matrix (ECM) structure, tumor metabolism and immune reprogramming. One of the main sources of CAFs are endothelial cells undergoing the endothelial-mesenchymal transition (EndMT). EndMT is mainly promoted by the Transforming Growth Factor-β (TGF-β) family secreted by tumor cells, though the role of particular members in EndMT regulation remains poorly understood...
September 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28892046/targeting-nuclear-receptors-in-cancer-associated-fibroblasts-as-concurrent-therapy-to-inhibit-development-of-chemoresistant-tumors
#12
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/28890895/isolation-of-fibroblast-activation-protein-specific-cancer-associated-fibroblasts
#13
Yingying Huang, Sufang Zhou, Yong Huang, Duo Zheng, Qiqi Mao, Jian He, Yiwei Wang, Dabing Xue, Xiaoling Lu, Nuo Yang, Yongxiang Zhao
The current study is to develop a gentle and efficient method for purification of fibroblast-activation protein positive (FAP(+)) cancer-associated fibroblasts (CAFs) from tumor tissues. Fresh tissues were isolated from BALB/c-Nude mice bearing human liver cancer cell line (HepG2), fully minced and separated into three parts, and digested with trypsin digestion and then treated with collagenase type IV once, twice, or thrice, respectively. Finally, the cells were purified by using FAP magnetic beads. The isolated CAFs were grown in culture medium and detected for the surface expression of fibroblast-activation protein (FAP)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28889950/exploring-metabolic-configurations-of-single-cells-within-complex-tissue-microenvironments
#14
Anne Miller, Csörsz Nagy, Bernhard Knapp, Johannes Laengle, Elisabeth Ponweiser, Marion Groeger, Philipp Starkl, Michael Bergmann, Oswald Wagner, Arvand Haschemi
Over the past years, plenty of evidence has emerged illustrating how metabolism supports many aspects of cellular function and how metabolic reprogramming can drive cell differentiation and fate. Here, we present a method to assess the metabolic configuration of single cells within their native tissue microenvironment via the visualization and quantification of multiple enzymatic activities measured at saturating substrate conditions combined with subsequent cell type identification. After careful validation of the approach and to demonstrate its potential, we assessed the intracellular metabolic configuration of different human immune cell populations in healthy and tumor colon tissue...
September 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28886304/the-roles-of-vasohibin-and-its-family-members-beyond-angiogenesis-modulators
#15
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/28883655/label-free-characterization-of-ultra-violet-radiation-induced-changes-in-skin-fibroblasts-with-raman-spectroscopy-and-quantitative-phase-microscopy
#16
S P Singh, Sungsam Kang, Jeon Woong Kang, Peter T C So, Ramanchandra Rao Dasari, Zahid Yaqoob, Ishan Barman
Minimizing morbidities and mortalities associated with skin cancers requires sustained research with the goal of obtaining fresh insights into disease onset and progression under specific stimuli, particularly the influence of ultraviolet rays. In the present study, label-free profiling of skin fibroblasts exposed to time-bound ultra-violet radiation has been performed using quantitative phase imaging and Raman spectroscopy. Statistically significant differences in quantifiable biophysical parameters, such as matter density and cell dry mass, were observed with phase imaging...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28883539/role-of-adipose-tissue-in-melanoma-cancer-microenvironment-and-progression
#17
E Zoico, E Darra, V Rizzatti, M Tebon, G Franceschetti, G Mazzali, A P Rossi, F Fantin, M Zamboni
BACKGROUND: An epidemiological association between excess weight and increased risk of cancer has been described in melanoma, for which the physiopathological mechanisms are still unknown. The study of tumor microenvironment and of the role of adipocytes in cancer development, progression and metastasis has recently received great interest. However, the role of peritumoral adipocytes has been characterized only in a few types of cancer and in melanoma it still remains to be defined. METHODS: We investigated the interactions between adipocytes and melanoma cells using an in vitro co-culture system...
September 8, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28881637/cd147-functions-as-the-signaling-receptor-for-extracellular-divalent-copper-in-hepatocellular-carcinoma-cells
#18
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/28881595/effects-of-increased-kindlin-2-expression-in-bladder-cancer-stromal-fibroblasts
#19
Jitao Wu, Cuicui Yu, Li Cai, Youyi Lu, Lei Jiang, Chu Liu, Yongwei Li, Fan Feng, Zhenli Gao, Zhe Zhu, Shengqiang Yu, Hejia Yuan, Yuanshan Cui
Kindlin-2 is a focal adhesion protein highly expressed in bladder cancer stromal fibroblasts. We investigated the prognostic significance of Kindlin-2 in bladder cancer stromal fibroblasts and evaluated the effects of Kindlin-2 on the malignant behaviors of tumor cells. Immunohistochemical staining of 203 paraffin-embedded bladder cancer tissues showed that Kindlin-2 expression correlated with advanced stage, high grade, and relapse of bladder cancer. Kaplan-Meier survival analysis demonstrated that patients exhibiting high Kindlin-2 expression had shorter survival times than those with low Kindlin-2 expression (p < 0...
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
#20
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
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