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https://www.readbyqxmd.com/read/28209610/the-tumor-microenvironment-at-a-turning-point-knowledge-gained-over-the-last-decade-and-challenges-and-opportunities-ahead-a-white-paper-from-the-nci-tme-network
#1
Yves A DeClerck, Kenneth J Pienta, Elisa C Woodhouse, Dinah S Singer, Suresh Mohla
Over the past 10 years, the Tumor Microenvironment Network (TMEN), supported by the NCI (Bethesda, MD), has promoted collaborative research with the explicit goal of fostering multi-institutional and transdisciplinary groups that are capable of addressing complex issues involving the tumor microenvironment. The main goal of the TMEN was to generate novel information about the dynamic complexity of tumor-host interactions in different organ systems with emphasis on using human tissues and supplemented by experimental models...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28209166/intra-tumor-heterogeneity-from-a-cancer-stem-cell-perspective
#2
REVIEW
Pramudita R Prasetyanti, Jan Paul Medema
Tumor heterogeneity represents an ongoing challenge in the field of cancer therapy. Heterogeneity is evident between cancers from different patients (inter-tumor heterogeneity) and within a single tumor (intra-tumor heterogeneity). The latter includes phenotypic diversity such as cell surface markers, (epi)genetic abnormality, growth rate, apoptosis and other hallmarks of cancer that eventually drive disease progression and treatment failure. Cancer stem cells (CSCs) have been put forward to be one of the determining factors that contribute to intra-tumor heterogeneity...
February 16, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28207184/an-im-penetrable-shield-how-the-tumor-microenvironment-protects-cancer-stem-cells
#3
Theresa Relation, Massimo Dominici, Edwin M Horwitz
Cancer stem cells (CSCs) are defined by their unlimited self-renewal ability and their capacity to initiate and maintain malignancy, traits that are not found in most cells that comprise the tumor. Although current cancer treatments successfully reduce tumor burden, the tumor will likely recur unless CSCs are effectively eradicated. This challenge is made greater by the protective impact of the tumor microenvironment (TME), consisting of infiltrating immune cells, endothelial cells, extracellular matrix, and signaling molecules...
February 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28197385/prognostic-and-predictive-aspects-of-the-tumor-immune-microenvironment-and-immune-checkpoints-in-malignant-pleural-mesothelioma
#4
Elly Marcq, Vasiliki Siozopoulou, Jorrit De Waele, Jonas van Audenaerde, Karen Zwaenepoel, Eva Santermans, Niel Hens, Patrick Pauwels, Jan P van Meerbeeck, Evelien L J Smits
Malignant pleural mesothelioma (MPM) is an aggressive cancer with a poor prognosis and an increasing incidence, for which novel therapeutic strategies are urgently required. Since the immune system has been described to play a presumed role in the protection against MPM, characterization of its tumor immune microenvironment (TME) and immune checkpoints can identify new immunotherapeutic targets and their predictive and/or prognostic value. To characterize the TME and the immune checkpoint expression profile, we performed immunohistochemistry (IHC) on formalin-fixed paraffin embedded (FFPE) tissue sections from 54 MPM patients (40 at time of diagnosis; 14 treated with chemotherapy)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197366/compensatory-upregulation-of-pd-1-lag-3-and-ctla-4-limits-the-efficacy-of-single-agent-checkpoint-blockade-in-metastatic-ovarian-cancer
#5
Ruea-Yea Huang, Ariel Francois, Aj Robert McGray, Anthony Miliotto, Kunle Odunsi
Tumor-associated or -infiltrating lymphocytes (TALs or TILs) co-express multiple immune inhibitory receptors that contribute to immune suppression in the ovarian tumor microenvironment (TME). Dual blockade of PD-1 along with LAG-3 or CTLA-4 has been shown to synergistically enhance T-cell effector function, resulting in a delay in murine ovarian tumor growth. However, the mechanisms underlying this synergy and the relative contribution of other inhibitory receptors to immune suppression in the ovarian TME are unknown...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28194687/fecal-incontinence-and-radiation-dose-on-anal-sphincter-in-patients-with-locally-advanced-rectal-cancer-larc-treated-with-preoperative-chemoradiotherapy-a-retrospective-single-institutional-study
#6
F Arias, C Eito, G Asín, I Mora, K Cambra, F Mañeru, B Ibáñez, L Arbea, A Viudez, I Hernández, J I Arrarás, M Errasti, M Barrado, M Campo, I Visus, S Flamarique, M A Ciga
BACKGROUND: The objective of the study is to determine the correlations among the variables of dose and the sphincter function (SF) in patients with locally advanced rectal cancer treated with preoperative capecitabine/radiotherapy followed by low anterior resection (LAR) + TME. METHODS: We retrospectively reviewed 92 consecutive patients with LARC treated at our center with LAR from 2006 and more than 2 years free from disease. We re-contoured the anal sphincters (AS) of patients with the help of the radiologist...
February 13, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28186976/32-phosphorus-selectively-delivered-by-listeria-to-pancreatic-cancer-demonstrates-a-strong-therapeutic-effect
#7
Dinesh Chandra, Benson Chellakkan Selvanesan, Ziqiang Yuan, Steven K Libutti, Wade Koba, Amanda Beck, Kun Zhu, Arturo Casadevall, Ekaterina Dadachova, Claudia Gravekamp
Our laboratory has developed a novel delivery platform using an attenuated non-toxic and non-pathogenic bacterium Listeria monocytogenes that infects tumor cells and selectively survives and multiplies in metastases and primary tumors with help of myeloid-derived suppressor cells (MDSC) and immune suppression in the tumor microenvironment (TME). 32P was efficiently incorporated into the Listeria bacteria by starvation of the bacteria in saline, and then cultured in phosphorus-free medium complemented with 32P as a nutrient...
February 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28184013/phosphatidylserine-sensing-by-tam-receptors-regulates-akt-dependent-chemoresistance-and-pd-l1-expression
#8
Canan Kasikara, Sushil Kumar, Stanley Kimani, Wen-I Tsou, Ke Geng, Viralkumar Davra, Ganapathy Sriram, Connor Devoe, Khanh-Quynh Nguyen, Anita Antes, Allen Krantz, Grzegorz Rymarczyk, Andrzej Wilczynski, Cyril Empig, Bruce D Freimark, Michael Gray, Kyle Schlunegger, Jeff Hutchins, Sergei V Kotenko, Raymond B Birge
: Tyro3, Axl and Mertk (collectively TAM receptors) are three homologous receptor tyrosine kinases (RTKs) that bind vitamin K-dependent endogenous ligands, Protein S (ProS) and Growth arrest specific factor 6 (Gas6), and act as bridging molecules to promote phosphatidylserine (PS)-mediated clearance of apoptotic cells (efferocytosis). TAM receptors are overexpressed in a vast array of tumor types, whereby the level of expression correlates with the tumor grade and the emergence of chemo- and radio-resistance to targeted therapeutics, but also have been implicated as inhibitory receptors on infiltrating myeloid-derived cells in the tumor microenvironment (TME) that can suppress host anti-tumor immunity...
February 9, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28179091/rectal-cancer-french-intergroup-clinical-practice-guidelines-for-diagnosis-treatments-and-follow-up-snfge-ffcd-gercor-unicancer-sfcd-sfed-sfro
#9
Jean-Pierre Gérard, Thierry André, Frédéric Bibeau, Thierry Conroy, Jean-Louis Legoux, Guillaume Portier, Jean-François Bosset, Guillaume Cadiot, Olivier Bouché, Laurent Bedenne
INTRODUCTION: This document is a summary of the French Intergroup guidelines regarding the management of rectal adenocarcinoma published in February 2016. METHOD: This collaborative work, under the auspices of most of the French medical societies involved in the management of rectal cancer, is based on the previous guidelines published in 2013. Recommendations are graded into 3 categories according to the level of evidence of data found in the literature. RESULTS: In agreement with the ESMO guidelines (2013), non-metastatic rectal cancers have been stratified in 4 risk groups according to endoscopy, MRI or endorectal-ultrasonography...
January 20, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28167218/tumor-regulation-of-the-tissue-environment-in-the-liver
#10
REVIEW
Tobias Eggert, Tim F Greten
The tumor microenvironment (TME) in the liver plays an important role in primary and metastatic liver tumor formation and tumor growth promotion. Cellular and non-cellular components of the TME significantly influence tumor development, growth, metastatic spread, anti-tumor immunity and response to tumor therapy. The cellular components of the TME in the liver not only consist of infiltrating immune cells, but also of liver-resident cells such as liver sinusoidal endothelial cells (LSEC) and hepatic stellate cells (HSC), which promote tumor growth by negatively regulating tumor-associated immune responses...
February 3, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28159925/mirna-1246-induces-pro-inflammatory-responses-in-mesenchymal-stem-stromal-cells-by-regulating-pka-and-pp2a
#11
Alexander Bott, Nese Erdem, Shalom Lerrer, Agnes Hotz-Wagenblatt, Christian Breunig, Khalid Abnaof, Angelika Wörner, Heike Wilhelm, Ewald Münstermann, Adit Ben-Baruch, Stefan Wiemann
The tumor microenvironment (TME) has an impact on breast cancer progression by creating a pro-inflammatory milieu within the tumor. However, little is known about the roles of miRNAs in cells of the TME during this process. We identified six putative oncomiRs in a breast cancer dataset, all strongly correlating with poor overall patient survival. Out of the six candidates, miR-1246 was upregulated in aggressive breast cancer subtypes and expressed at highest levels in mesenchymal stem/stroma cells (MSCs). Functionally, miR-1246 led to a p65-dependent increase in transcription and release of pro-inflammatory mediators IL-6, CCL2 and CCL5 in MSCs, and increased NF-κB activity...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28143999/3d-hydrogel-based-microwell-arrays-as-a-tumor-microenvironment-model-to-study-breast-cancer-growth
#12
John Casey, Xiaoshan Yue, DungTrung Nguyen, Aylin Acun, Victoria Zellmer, Siyuan Zhang, Pinar Zorlutuna
The tumor microenvironment (TME) is distinctly heterogeneous and is involved in tumor growth, metastasis, and drug resistance. Mimicking this diverse microenvironment is essential for understanding tumor growth and metastasis. Despite the substantial scientific progress made with traditional cell culture methods, microfabricated three-dimensional (3D) cell cultures that can be precisely controlled to mimic the changes occur in the TME over tumor progression are necessary for simulating organ-specific TME in vitro...
February 1, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28137309/induction-of-metastasis-cancer-stem-cell-phenotype-and-oncogenic-metabolism-in-cancer-cells-by-ionizing-radiation
#13
REVIEW
Su Yeon Lee, Eui Kyong Jeong, Min Kyung Ju, Hyun Min Jeon, Min Young Kim, Cho Hee Kim, Hye Gyeong Park, Song Iy Han, Ho Sung Kang
Radiation therapy is one of the major tools of cancer treatment, and is widely used for a variety of malignant tumours. Radiotherapy causes DNA damage directly by ionization or indirectly via the generation of reactive oxygen species (ROS), thereby destroying cancer cells. However, ionizing radiation (IR) paradoxically promotes metastasis and invasion of cancer cells by inducing the epithelial-mesenchymal transition (EMT). Metastasis is a major obstacle to successful cancer therapy, and is closely linked to the rates of morbidity and mortality of many cancers...
January 30, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28132882/tumor-stroma-interaction-is-mediated-by-monocarboxylate-metabolism
#14
Brijesh B Patel, Ellen Ackerstaff, Inna S Serganova, John E Kerrigan, Ronald G Blasberg, Jason A Koutcher, Debabrata Banerjee
Human breast tumors contain significant amounts of stromal cells. There exists strong evidence that these stromal cells support cancer development and progression by altering various pathways (e.g. downregulation of tumor suppressor genes or autocrine signaling loops). Here, we suggest that stromal carcinoma-associated fibroblasts (CAFs), shown to be generated from bone marrow-derived mesenchymal stem cells, may (i) recycle tumor-derived lactate for their own energetic requirements, thereby sparing glucose for neighboring glycolytic tumor cells, and (ii) subsequently secrete surplus energetically and biosynthetically valuable metabolites of lactate oxidation, such as pyruvate, to support tumor growth...
January 26, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28123601/human-derived-normal-mesenchymal-stem-stromal-cells-in-anticancer-therapies
#15
REVIEW
Cheng Zhang, Shi-Jie Yang, Qin Wen, Jiang F Zhong, Xue-Lian Chen, Andres Stucky, Michael F Press, Xi Zhang
The tumor microenvironment (TME) not only plays a pivotal role during cancer progression and metastasis, but also has profound effects on therapeutic efficacy. Stromal cells of the TME are increasingly becoming a key consideration in the development of active anticancer therapeutics. However, dispute concerning the role of stromal cells to fight cancer continues because the use of mesenchymal stem/stromal cells (MSCs) as an anticancer agent is dependent on the specific MSCs subtype, in vitro or in vivo conditions, factors secreted by MSCs, types of cancer cell lines and interactions between MSCs, cancer cells and host immune cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28117423/interstitial-inorganic-phosphate-as-a-tumor-microenvironment-marker-for-tumor-progression
#16
Andrey A Bobko, Timothy D Eubank, Benoit Driesschaert, Ilirian Dhimitruka, Jason Evans, Rahman Mohammad, Elena E Tchekneva, Mikhail M Dikov, Valery V Khramtsov
Noninvasive in vivo assessment of chemical tumor microenvironment (TME) parameters such as oxygen (pO2), extracellular acidosis (pHe), and concentration of interstitial inorganic phosphate (Pi) may provide unique insights into biological processes in solid tumors. In this work, we employ a recently developed multifunctional trityl paramagnetic probe and electron paramagnetic resonance (EPR) technique for in vivo concurrent assessment of these TME parameters in various mouse models of cancer. While the data support the existence of hypoxic and acidic regions in TME, the most dramatic differences, about 2-fold higher concentrations in tumors vs...
January 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28115361/selective-reversible-inhibition-of-autophagy-in-hypoxic-breast-cancer-cells-promotes-pulmonary-metastasis
#17
Christopher M Dower, Neema Bhat, Edward W Wang, Hong-Gang Wang
Autophagy influences how cancer cells respond to nutrient deprivation and hypoxic stress, two hallmarks of the tumor microenvironment (TME). In this study, we explored the impact of autophagy on the pathophysiology of breast cancer cells using a novel hypoxia-dependent, reversible dominant-negative strategy to regulate autophagy at the cellular level within the TME. Suppression of autophagy via hypoxia-induced expression of the kinase-dead unc-51-like autophagy-activating kinase (ULK1) mutant K46N increased lung metastases in MDA-MB-231 xenograft mouse models...
February 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28114284/infiltrating-mast-cells-promote-renal-cell-carcinoma-angiogenesis-by-modulating-pi3k%C3%AE-akt%C3%AE-gsk3%C3%AE-%C3%AE-am-signaling
#18
Y Chen, C Li, H Xie, Y Fan, Z Yang, J Ma, D He, L Li
The recruitment of vascular endothelial cells from the tumor microenvironment (TME) to promote angiogenesis plays key roles in the progression of renal cell carcinoma (RCC). The potential impact of immune cells in the TME on RCC angiogenesis, however, remains unclear. Here, we found that recruitment of mast cells resulted in increased RCC angiogenesis in both in vitro cell lines and in vivo mouse models. Mechanistic analyses revealed that RCC recruited mast cells by modulating PI3KAKTGSK3βAM signaling...
January 23, 2017: Oncogene
https://www.readbyqxmd.com/read/28108623/tumor-induced-stromal-stat1-accelerates-breast-cancer-via-deregulating-tissue-homeostasis
#19
Victoria R Zellmer, Patricia M Schnepp, Sarah L Fracci, Xuejuan Tan, Erin N Howe, Siyuan Zhang
: The tumor microenvironment (TME) is a dynamic tissue space in which the tumor exists, plays a significant role in tumor initiation, and is a key contributor in cancer progression; however, little is known about tumor-induced changes in the adjacent tissue stroma. Herein, tumor-induced changes in the TME were explored at the morphological and molecular level to further understand cancer progression. Tumor-adjacent mammary glands (TAGs) displayed altered branching morphology, expansion of myofibroblasts, and increased mammosphere formation, broadly suggesting a tumor-induced field effect...
January 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28105369/potassium-channels-of-t-lymphocytes-take-center-stage-in-the-fight-against-cancer
#20
EDITORIAL
Laura Conforti
A recent study by Eil at al. published in Nature in September 2016 provides evidence that alterations of the K(+) homeostasis of tumor infiltrating lymphocytes (TILs) in necrotic areas of the tumor microenvironment (TME) suppress the function of effector T cells. Furthermore, they establish that overexpression of K(+) channels in T lymphocytes counterbalances this negative effect of the TME and restores the ability of TILs to function, ultimately leading to increased survival of tumor bearing mice. Thus, K(+) channels in T lymphocytes become interesting new targets for novel immunotherapies in cancer...
2017: Journal for Immunotherapy of Cancer
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