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tumor stromal microenvironment

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https://www.readbyqxmd.com/read/28647610/the-jak-stat3-axis-a-comprehensive-drug-target-for-solid-malignancies
#1
REVIEW
Jennifer Huynh, Nima Etemadi, Frédéric Hollande, Matthias Ernst, Michael Buchert
Intercellular communication between tumor cells, immune cells and the stroma characterises the tumor microenvironment, which is instrumental for establishing the ecological niche that fosters tumor growth and metastasis. While tumor cell intrinsic STAT3 signaling provides a crucial axis to support cell proliferation and survival, it also regulates many activities of the non-transformed cells that collectively make up the tumor microenvironment. Accordingly, excessive activation of STAT3 is a hallmark of many malignancies, and often occurs in response to cytokines of the IL-6 and IL-10 families...
June 21, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28646022/nf1-hematopoietic-cells-accelerate-malignant-peripheral-nerve-sheath-tumor-development-without-altering-chemotherapy-response
#2
Rebecca D Dodd, Chang-Lung Lee, Tess Overton, Wesley Huang, William C Eward, Lixia Luo, Yan Ma, Davis R Ingram, Keila E Torres, Diana M Cardona, Alexander Lazar, David G Kirsch
Haploinsufficiency in the tumor suppressor NF1 contributes to the pathobiology of type 1 neurofibromatosis, but a related role has not been established in malignant peripheral nerve sheath tumors (MPNST) where NF1 mutations also occur. Patients with NF1-associated MPNST appear to have worse outcomes than patients with sporadic MPNST, but the mechanism underlying this correlation is not understood. To define the impact of stromal genetics on the biology of this malignancy, we developed unique mouse models that reflect the genetics of patient-associated MPNST...
June 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28640929/modulation-of-tumor-microenvironment-by-chemopreventive-natural-products
#3
REVIEW
Sin-Aye Park, Young-Joon Surh
The tumor microenvironment provides a niche in which cancer cells and their surrounding stromal cells reside and in which their interactions occur. The cross talk between cancer and stromal cells in the tumor microenvironment promotes many biological processes to support cancer cell growth, invasion, angiogenesis, and metastasis. Recently, not only cancer cells but also multiple types of surrounding stromal cells, including endothelial cells, immune cells, and fibroblasts in the tumor microenvironment, have been recognized to be attractive targets for reducing resistance to anticancer therapy and tumor recurrence...
June 22, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28639900/the-novel-cxcr4-antagonist-prx177561-reduces-tumor-cell-proliferation-and-accelerates-cancer-stem-cell-differentiation-in-glioblastoma-preclinical-models
#4
Giovanni Luca Gravina, Andrea Mancini, Alessandro Colapietro, Flora Vitale, Antonella Vetuschi, Simona Pompili, Giulia Rossi, Francesco Marampon, Peter J Richardson, Lee Patient, Lee Patient, Stephen Burbidge, Claudio Festuccia
Glioblastoma is the most frequent and the most lethal primary brain tumor among adults. Standard of care is the association of radiotherapy with concomitant or adjuvant temozolomide. However, to date, recurrence is inevitable. The CXCL12/CXCR4 pathway is upregulated in the glioblastoma tumor microenvironment regulating tumor cell proliferation, local invasion, angiogenesis, and the efficacy of radio-chemotherapy. In this study, we evaluated the effects of the novel CXCR4 antagonist, PRX177561, in preclinical models of glioblastoma...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28636979/exosomes-in-diagnosis-and-therapy-of-prostate-cancer
#5
REVIEW
Jun Pan, Meng Ding, Kai Xu, Chunhua Yang, Li-Jun Mao
Exosomes are small vesicular bodies released by a variety of cells. Exosomes contain miRNAs, mRNAs and proteins with the potential to regulate signaling pathways in recipient cells. Exosomes deliver nucleic acids and proteins to mediate the communication between cancer cells and stroma cells. In this review, we summarize recent progress in our understanding of the role of exosomes in prostate cancer. The tumorigenesis, metastasis and drug resistance of prostate cancer are associated with the cargos of exosomes such as miRNAs, lncRNAs and proteins...
June 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28630212/a-pilot-study-of-stereotactic-body-radiation-therapy-combined-with-cytoreductive-nephrectomy-for-metastatic-renal-cell-carcinoma
#6
Anurag K Singh, Timothy B Winslow, Mohammad Habiby Kermany, Vincent Goritz, Lilia Heit, Austin Miller, Nicholas C Hoffend, Leighton C Stein, Lalith Kumaraswamy, Graham W Warren, Wiam Bshara, Kunle Odunsi, Junko Matsuzaki, Scott I Abrams, Thomas Schwaab, Jason B Muhitch
<p>While stereotactic body radiation therapy (SBRT) can reduce tumor volumes in metastatic renal cell carcinoma (mRCC) patients, little is known regarding the immunomodulatory effects of high-dose radiation in the tumor microenvironment. The main objectives of this pilot study were to assess the safety and feasibility of nephrectomy following SBRT treatment of mRCC patients and analyze the immunological impact of high-dose radiation.</p> <br /><br />Experimental Design: Human RCC cell lines were irradiated and evaluated for immunomodulation...
June 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28629450/interaction-with-adipocyte-stromal-cells-induces-breast-cancer-malignancy-via-s100a7-upregulation-in-breast-cancer-microenvironment
#7
Minako Sakurai, Yasuhiro Miki, Kiyoshi Takagi, Takashi Suzuki, Takanori Ishida, Noriaki Ohuchi, Hironobu Sasano
BACKGROUND: Breast adipocytes play important roles in both the development and function of mammary epithelial cells. Therefore, carcinoma-adipose stromal cell (ASC) interactions have been considered pivotal in supporting tumor growth in breast cancer. In addition, it has been demonstrated that the biological features of cancer-associated adipocytes differ from those of normal ASCs. Therefore, we investigated an interaction between ASCs and carcinoma cell lines to identify genes associated with ASC invasion of carcinoma cells...
June 19, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28627679/exosomes-new-players-in-cancer-review
#8
Wei Guo, Yibo Gao, Ning Li, Fei Shao, Chunni Wang, Pan Wang, Zhenlin Yang, Renda Li, Jie He
The past decade has witnessed an exponential increase in research on exosomes. For many years considered to be extracellular debris, exosomes are now considered important mediators in intercellular communication. The capability of exosomes to transfer proteins, DNA, mRNA, as well as non-coding RNAs has made them an attractive focus of research into the pathogenesis of different diseases, including cancer. Increasing evidence suggests that tumor cells release a large sum of exosomes, which may not only influence proximal tumor cells and stromal cells in local microenvironment, but also can exert systemic effects when participating in blood circulation...
June 13, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28618932/intimate-cross-talk-between-cancer-cells-and-the-tumor-microenvironment-of-b-cell-lymphomas-the-key-role-of-exosomes
#9
REVIEW
Biyu Xu, Ting Wang
B-cell lymphomas are composed of tumor cells and the tumor microenvironment, which is conventionally thought to be composed of a mixture of stromal cells, blood vessels, immune cells, and non-cell components, such as extracellular matrix, cytokines, and chemokines. Exosomes, small endocytically derived vesicles that have been proved to be present in a variety of tumor niches and involved in mediating cell signaling networks, are increasingly regarded as important components of tumor microenvironment. In this review, we first focus on the biogenesis, biodistribution, transportation, and other general characteristics of exosomes and then highlight the vital roles of exosomes in lymphomagenesis and disease progression, particularly from the perspective of immune dysfunction, virus infection, and therapeutic resistance mechanisms...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28615524/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#10
Jonas R M Van Audenaerde, Jorrit De Waele, Elly Marcq, Jinthe Van Loenhout, Eva Lion, Johan M J Van den Bergh, Ralf Jesenofsky, Atsushi Masamune, Geert Roeyen, Patrick Pauwels, Filip Lardon, Marc Peeters, Evelien L J Smits
Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer-related death in Western countries with a 5-year survival rate below 5%. One of the hallmarks of this cancer is the strong desmoplastic reaction within the tumor microenvironment (TME), orchestrated by activated pancreatic stellate cells (PSC). This results in a functional and mechanical shield which causes resistance to conventional therapies. Aiming to overcome this resistance by tackling the stromal shield, we assessed for the first time the capacity of IL-15 stimulated natural killer (NK) cells to kill PSC and pancreatic cancer cells (PCC)...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28614653/microfluidics-enabled-bottom-up-engineering-of-3d-vascularized-tumor-for-drug-discovery
#11
Pranay Agarwal, Hai Wang, Mingrui Sun, Jiangsheng Xu, Shuting Zhao, Zhenguo Liu, Keith J Gooch, Yi Zhao, Xiongbin Lu, Xiaoming He
Development of high-fidelity 3D models to recapitulate the tumor microenvironment is essential for studying tumor biology and screening anticancer drugs. Here we report a method to engineer the 3D microenvironment of human tumor, by encapsulating cancer cells in the core of microcapsules with a hydrogel shell for miniaturized 3D culture to obtain avascular microtumors first. The microtumors are then used as the building blocks for assembling with endothelial cells and other stromal cells to create macroscale 3D vascularized tumor...
June 14, 2017: ACS Nano
https://www.readbyqxmd.com/read/28608777/tumor-metabolism-in-the-microenvironment-of-nodal-metastasis-in-oral-squamous-cell-carcinoma
#12
Joseph Curry, Patrick Tassone, Kurren Gill, Madalina Tuluc, Voichita BarAd, Mehri Mollaee, Diana Whitaker-Menezes, Ulrich Rodeck, Adam Luginbuhl, David Cognetti, William Keane, Ubaldo Martinez-Outschoorn
Objective In many cancers, including head and neck squamous cell carcinoma (HNSCC), different regions within a tumor have different metabolic phenotypes. Transfer of metabolites between compartments promotes tumor growth and aggressive behavior. Metabolic compartmentalization in HNSCC nodal metastases has not been studied, nor has its impact on extracapsular extension or clinical outcomes been determined. Study Design Retrospective analysis based on immunohistochemistry staining. Setting Tertiary care center...
June 1, 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/28607806/significance-of-stromal-1-and-stromal-2-signatures-and-biologic-prognostic-model-in-diffuse-large-b-cell-lymphoma
#13
Asmaa Gaber Abdou, Nancy Asaad, Mona Kandil, Mohammed Shabaan, Asmaa Shams
OBJECTIVE: : Diffuse Large B Cell Lymphoma (DLBCL) is a heterogeneous group of tumors with different biological and clinical characteristics that have diverse clinical outcomes and response to therapy. Stromal-1 signature of tumor microenvironment of DLBCL represents extracellular matrix deposition and histiocytic infiltrate, whereas stromal-2 represents angiogenesis that could affect tumor progression. METHODS: : The aim of the present study is to assess the significance of stromal-1 signature using SPARC-1 and stromal-2 signature using CD31 expression and then finally to construct biologic prognostic model (BPM) in 60 cases of DLBCL via immunohistochemistry...
May 2017: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/28607804/mesenchymal-stromal-cells-role-in-tumor-microenvironment-involvement-of-signaling-pathways
#14
Armel Herve Nwabo Kamdje, Paul Takam Kamga, Richard Tagne Simo, Lorella Vecchio, Paul Faustin Seke Etet, Jean Marc Muller, Giulio Bassi, Erique Lukong, Raghuveera Kumar Goel, Jeremie Mbo Amvene, Mauro Krampera
Mesenchymal stromal cells (MSCs) are adult multipotent stem cells residing as pericytes in various tissues and organs where they can differentiate into specialized cells to replace dying cells and damaged tissues. These cells are commonly found at injury sites and in tumors that are known to behave like " wounds that do not heal." In this article, we discuss the mechanisms of MSCs in migrating, homing, and repairing injured tissues. We also review a number of reports showing that tumor microenvironment triggers plasticity mechanisms in MSCs to induce malignant neoplastic tissue formation, maintenance, and chemoresistance, as well as tumor growth...
May 2017: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/28586517/extracellular-vesicles-in-the-tumor-microenvironment-therapeutic-resistance-clinical-biomarkers-and-targeting-strategies
#15
REVIEW
L Han, J Xu, Q Xu, B Zhang, E W-F Lam, Y Sun
Numerous studies have proved that cell-nonautonomous regulation of neoplastic cells is a distinctive and essential characteristic of tumorigenesis. Two way communications between the tumor and the stroma, or within the tumor significantly influence disease progression and modify treatment responses. In the tumor microenvironment (TME), malignant cells utilize paracrine signaling initiated by adjacent stromal cells to acquire resistance against multiple types of anticancer therapies, wherein extracellular vesicles (EVs) substantially promote such events...
June 6, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28577085/endoplasmic-reticulum-stress-regulates-tumor-growth-and-anti-tumor-immunity-a-promising-opportunity-for-cancer-immunotherapy
#16
REVIEW
Eslam Mohamed, Yu Cao, Paulo C Rodriguez
The endoplasmic reticulum (ER) stress is a cellular process that occurs as a consequence of several stress circumstances, such as the accumulation of unfolded proteins in the lumen of the ER or distinct insults that disturb the ER normal function. Different conditions in the tumor microenvironment (TME), including hypoxia, nutrient deprivation, and the elevated production of reactive oxygen and nitrogen species destabilize the loading and dispatching of the newly synthesized proteins, triggering ER stress in cancer cells and tumor-infiltrating leukocytes...
June 2, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28576522/pd-l1-expression-and-cd8-infiltration-shows-heterogeneity-in-juvenile-recurrent-respiratory-papillomatosis
#17
Tingyu Liu, Max Greenberg, Carissa Wentland, Brandon Sepe, Sarah Bowe, Gillian Diercks, Tiffany Huynh, Mari Mino-Kenudson, Richard Schlegel, David Kodack, Cyril Benes, Jeffrey Engelman, Christopher Hartnick
INTRODUCTION: Tumor immunotherapy have broadened therapeutic options for tumor treatment. The role of immune function in juvenile recurrent respiratory papillomatosis (JRRP) has not been investigated. Applying immunoblockade inhibitors as a novel disease treatment is unclear. Our study, for the first time, evaluates immune infiltration and immuno-suppressive molecule expression in JRRP. Our study provides insights in possibly treating this disease with tumor immunotherapies. We aimed to determine expression of programmed death-ligand 1 (PD-L1), a cancer escape protein, and presence of CD8+ T cell infiltration in tumor microenvironment...
April 2017: International Journal of Pediatric Otorhinolaryngology
https://www.readbyqxmd.com/read/28575019/clinicopathologic-significance-of-the-cxcl1-cxcr2-axis-in-the-tumor-microenvironment-of-gastric-carcinoma
#18
Hiroaki Kasashima, Masakazu Yashiro, Hirohisa Nakamae, Go Masuda, Haruhito Kinoshita, Tamami Morisaki, Tatsunari Fukuoka, Tsuyoshi Hasegawa, Takahiko Nakane, Masayuki Hino, Kosei Hirakawa, Masaichi Ohira
PURPOSE: It was reported that the chemokine (C-X-C motif) ligand 1 (CXCL1) from cancer cells stimulated the recruitment of bone marrow-derived mesenchymal cells (BM-MCs) into tumor stroma via chemokine (C-X-C motif) receptor 2 (CXCR2) signaling. We conducted this retrospective study to determine the clinicopathologic significance of the CXCL1-CXCR2 axis in human gastric cancer. METHODS: The correlations between the clinicopathological features of 270 primary gastric carcinomas and CXCL1 in cancer cells and CXCR2 in stromal cells were analyzed in immunohistochemical studies...
2017: PloS One
https://www.readbyqxmd.com/read/28567040/a-unique-cellular-and-molecular-microenvironment-is-present-in-tertiary-lymphoid-organs-of-patients-with-spontaneous-prostate-cancer-regression
#19
María de la Luz García-Hernández, Norma Ofelia Uribe-Uribe, Ricardo Espinosa-González, W Martin Kast, Shabaana A Khader, Javier Rangel-Moreno
OBJECTIVE: Multiple solid cancers contain tertiary lymphoid organs (TLO). However, it is unclear whether they promote tumor rejection, facilitate tumor evasion, or simply whether they are a byproduct of chronic inflammation. We hypothesize that although chronic inflammation induces TLO formation, the tumor milieu can modulate TLO organization and functions in prostate cancer. Therefore, our study seeks to elucidate the cellular and molecular signatures in unique prostatectomy specimens from evanescent carcinoma patients to identify markers of cancer regression, which could be harnessed to modulate local immunosuppression or potentially enhance TLO function...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28549596/emerging-roles-of-the-cxcl12-cxcr4-axis-in-pancreatic-cancer-progression-and-therapy
#20
REVIEW
Richard L Sleightholm, Beth K Neilsen, Jing Li, Maria M Steele, Rakesh K Singh, Michael A Hollingsworth, David Oupicky
Chemokine networks regulate a variety of cellular, physiological, and immune processes. These normal functions can become appropriated by cancer cells to facilitate a more hospitable niche for aberrant cells by enhancing growth, proliferation, and metastasis. This is especially true in pancreatic cancer, where chemokine signaling is a vital component in the development of the supportive tumor microenvironment and the signaling between the cancer cells and surrounding stromal cells. Although expression patterns vary among cancer types, the chemokine receptor CXCR4 has been implicated in nearly every major malignancy and plays a prominent role in pancreatic cancer development and progression...
May 23, 2017: Pharmacology & Therapeutics
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