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https://www.readbyqxmd.com/read/28822802/stromal-expression-of-activated-leukocyte-cell-adhesion-molecule-alcam-promotes-lung-tumor-growth-and-metastasis
#1
Ann-Helen Willrodt, Michal Beffinger, Martina Vranova, Darya Protsyuk, Katja Schuler, Maria Jadhav, Mathias Heikenwalder, Maries van den Broek, Lubor Borsig, Cornelia Halin Winter
Activated leukocyte cell adhesion molecule (ALCAM) is expressed on various cell types, including leukocytes, endothelial cells and certain tumor cells. While ALCAM expression on tumor cells has been linked with tumor invasion and metastatic spread, the contribution of ALCAM expressed in cells forming the tumor stroma to cancer progression has not been investigated. In this study, we made use of ALCAM-deficient (ALCAM(-/-)) mice to evaluate the role of ALCAM in lung tumor growth and metastasis. ALCAM(-/-) mice displayed an altered blood vascular network in the lung and the diaphragm, indicative of an angiogenesis defect...
August 16, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28822081/expression-profiling-of-the-map-kinase-phosphatase-family-reveals-a-role-for-dusp1-in-the-glioblastoma-stem-cell-niche
#2
Bradley N Mills, George P Albert, Marc W Halterman
The dual specificity phosphatases (DUSPs) constitute a family of stress-induced enzymes that provide feedback inhibition on mitogen-activated protein kinases (MAPKs) critical in key aspects of oncogenic signaling. While described in other tumor types, the landscape of DUSP mRNA expression in glioblastoma (GB) remains largely unexplored. Interrogation of the REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT) revealed induction (DUSP4, DUSP6), repression (DUSP2, DUSP7-9), or mixed (DUSP1, DUSP5, DUSP10, DUSP15) DUSP transcription of select DUSPs in bulk tumor specimens...
August 18, 2017: Cancer Microenvironment: Official Journal of the International Cancer Microenvironment Society
https://www.readbyqxmd.com/read/28822058/immune-dysfunction-in-non-hodgkin-lymphoma-avenues-for-new-immunotherapy-based-strategies
#3
REVIEW
Lorenzo Falchi
PURPOSE OF THIS REVIEW: The present review focuses on key aspects of non-Hodgkin lymphoma (NHL) evasion of immune surveillance and how these can be leveraged to devise effective immunotherapy strategies. RECENT FINDINGS: In recent years, significant progress has been made in the field of cancer immunotherapy. In particular, the remarkable clinical results of anti-programmed death (PD)-1/PD-ligand (L)1 antibodies are revolutionizing the treatment approach to multiple solid and hematologic tumors...
August 18, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28821904/developmentally-regulated-signaling-pathways-in-glioma-invasion
#4
REVIEW
Shwetal Mehta, Costanza Lo Cascio
Malignant gliomas are the most common, infiltrative, and lethal primary brain tumors affecting the adult population. The grim prognosis for this disease is due to a combination of the presence of highly invasive tumor cells that escape surgical resection and the presence of a population of therapy-resistant cancer stem cells found within these tumors. Several studies suggest that glioma cells have cleverly hijacked the normal developmental program of neural progenitor cells, including their transcriptional programs, to enhance gliomagenesis...
August 18, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28821192/could-the-pd-1-pathway-be-a-potential-target-for-treating-small-intestinal-adenocarcinoma
#5
Ramya Thota, Raul S Gonzalez, Jordan Berlin, Dana B Cardin, Chanjuan Shi
Objectives: The programmed death 1 (PD-1) pathway is upregulated in the immune microenvironment of many cancers. In this study, we examined the PD-1 pathway and the immune microenvironment of small intestinal adenocarcinomas by immunohistochemistry. Methods: From our department pathology archives we identified 42 small intestinal adenocarcinomas from between 2000 and 2015, with blocks available for IHC studies. Tumors were immunohistochemically stained for CD3, CD4, CD8, CD20, PD-1, and programmed death ligand 1 (PD-L1) expression...
September 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28820578/integrated-microfluidic-platform-with-multiple-functions-to-probe-the-tumor-endothelial-cell-interaction
#6
Ling Lin, Xuexia Lin, Luyao Lin, Qiang Feng, Takehiko Kitamori, Jin-Ming Lin, Jiashu Sun
Interaction between tumor and endothelial cells could affect tumor growth and progression, and induce drug resistance during cancer therapy. Investigation on tumor-endothelial cell interaction involves cell co-culture, protein detection, and analysis of drug metabolites, which are complicated and time-consuming. In this work, we present an integrated microfluidic device with three individual components (the cell co-culture component, the protein detection component, and the pre-treatment component for drug metabolites) to probe the interaction between tumor and endothelial cells...
August 18, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28820000/novel-combination-strategies-for-enhancing-efficacy-of-immune-checkpoint-inhibitors-in-the-treatment-of-metastatic-solid-malignancies
#7
Michael J Flynn, James M G Larkin
Immune-checkpoint inhibitor (ICPI) drugs, which include antibodies against CTLA-4, PD-1 and PD-L1, have been shown to induce durable complete responses in a proportion of patients with particular efficacy demonstrated in both the first line and refractory setting in advanced NSCLC and melanoma. However, these drugs remain effective only in a minority of unselected patients. Areas covered: This review will focus on mechanisms of resistance to ICPI and underline the importance of identification of novel predictive markers of responsiveness...
August 18, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28819426/central-role-of-cemip-in-tumorigenesis-and-its-potential-as-therapeutic-target
#8
REVIEW
Li Li, Lin-Hai Yan, Shwetha Manoj, Ying Li, Lu Lu
CEMIP (KIAA1199) was identified as migratory indicator protein which had been crudely studied in the last decade. Firstly its mutation site was reported to cause hearing loss due to the folding change of protein structure, meanwhile the over-expression of CEMIP referred to dreadful invasion and uncontrolled proliferation of tumor with distant metastasis, dedifferentiation, and limited survival opportunity of patients. Especially, over-expressed CEMIP also protected malignant tumor from strict microenvironment in hypoxia, low glucose and cracked barrier, leading to enhanced adaptability of tumor by stimulating the Wnt, EGFR, FGFR pathway...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819386/the-tumor-microenvironment-and-inflammatory-breast-cancer
#9
REVIEW
Aji Huang, Shousong Cao, Lili Tang
Inflammatory breast cancer (IBC) is a rare and very aggressive subtype of breast cancer with clinical manifestations similar to acute inflammation. The prognosis of IBC is still poor even though combination therapy with surgery, chemotherapy, and target therapy, mainly due to a lack of fully understanding of the cellular and molecular mechanisms of IBC pathogenesis and progression. In the present article, we have comprehensively reviewed the connection of the pathogenesis of IBC and inflammation, immune reaction and cancer, particularly focused on the role and mechanism of tumor microenvironment related to IBC formation, tumor cell proliferation, migration, invasion and metastasis as well as the clinical manifestations of IBC...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819379/hypoxia-inducible-factor-1-alpha-correlates-with-tumor-associated-macrophages-infiltration-influences-survival-of-gastric-cancer-patients
#10
Wei-Jie Zhang, Cheng Chen, Zhi-Hua Zhou, Shan-Ting Gao, Teong Jin Tee, Liu-Qing Yang, Yuan-Yuan Xu, Tao-Hong Pang, Xin-Yun Xu, Qi Sun, Min Feng, Hao Wang, Chun-Lei Lu, Guo-Zhong Wu, Sheng Wu, Wen-Xian Guan, Gui-Fang Xu
Background: Hypoxia was a common feature for accelerating tumor metastasis by both inducting epithelial-mesenchymal transition (EMT) of tumor cells and polarization of tumor-associated macrophages (TAMs). The association and roles between hypoxia, EMT and TAMs in the biological behavior of gastric cancer (GC) for the time being recurrence is unclear. Material and methods: hypoixa by expression of hypoxia-inducible factor-1 alpha (HIF-1α), polarized functional status of infiltrated TAMs by immunohistochemical staining of CD68 and CD163, and the expression of E-cadherin as EMT property had been evaluated in 236 patients consecutive with histologically confirmed GC...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819368/lack-of-breastfeeding-history-in-parous-women-with-inflammatory-breast-cancer-predicts-poor-disease-free-survival
#11
Shane R Stecklein, Jay P Reddy, Adam R Wolfe, Mirtha S Lopez, Tamer M Fouad, Bisrat G Debeb, Naoto T Ueno, Abenaa M Brewster, Wendy A Woodward
Purpose: Breastfeeding alters the breast microenvironment, and several lines of evidence suggest the breast microenvironment contributes to the clinical phenotype of inflammatory breast cancer. We investigated breastfeeding history as a modifier of locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) in parous women with inflammatory breast cancer. Methods: Parous women with inflammatory breast cancer were identified from a prospective registry at The University of Texas MD Anderson Cancer Center...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819364/the-crosstalk-between-ovarian-cancer-stem-cell-niche-and-the-tumor-microenvironment
#12
REVIEW
Manuel Varas-Godoy, Gregory Rice, Sebastián E Illanes
Ovarian cancer is one of the most important causes of cancer-related death among women in the world. Despite advances in ovarian cancer treatment, 70-80% of women who initially respond to therapy eventually relapse and die. There is evidence that a small population of cells within the tumors called cancer stem cells (CSCs) could be responsible for treatment failure due to their enhanced chemoresistance and tumorigenicity. These cells reside in a niche that maintains the principal properties of CSCs. These properties are associated with the capacity of CSCs to interact with different cells of the tumor microenvironment including mesenchymal stem cells, endothelial cells, immune cells, and fibroblasts, promoting cancer progression...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28819122/anti-inflammatory-drugs-suppress-ultrasound-mediated-mesenchymal-stromal-cell-tropism-to-kidneys
#13
Scott R Burks, Ben A Nguyen, Michele N Bresler, Matthew E Nagle, Saejeong J Kim, Joseph A Frank
Mesenchymal stromal cells (MSC) are potential renal therapeutics. Clinically, results are mixed partly because MSC tropism to kidneys is minimal following infusion. Ultrasound augmentation of the renal microenvironment is becoming increasingly-important in renal MSC therapies. We demonstrated pulsed-focused-ultrasound (pFUS) increases enhanced homing permeability and retention of MSC in mouse kidneys. Here, we characterized the temporal proteomic response to pFUS in mouse kidneys and its association with MSC tropism...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819116/silencing-of-tgf-%C3%AE-1-in-tumor-cells-impacts-mmp-9-in-tumor-microenvironment
#14
Lakisha D Moore-Smith, Tatyana Isayeva, Joo Hyoung Lee, Andra Frost, Selvarangan Ponnazhagan
Transforming growth factor (TGF)-β1 contributes to autocrine and paracrine functions in the tumor microenvironment (TME). The present study examined the effects of TGF-β1 crosstalk in TME and its role in mediating tumor formation and progression by targeted abrogation of TGF-β1 expression in metastatic cells in situ. Using species-specific primers, we found a significant increase in MMP-9 gene expression in the tumor-reactive stroma during late-stage metastasis in the lung. This effect was also confirmed in cancer-associated fibroblasts (CAFs) when co-cultured with the tumor cells...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819064/the-tumor-microenvironment-regulates-sensitivity-of-murine-lung-tumors-to-pd-1-pdl1-antibody-blockade
#15
Howard Y Li, Maria V McSharry, Bonnie Bullock, Teresa T Nguyen, Jeff Kwak, Joanna M Poczobutt, Trisha R Sippel, Lynn E Heasley, Mary C Weiser-Evans, Eric T Clambey, Raphael A Nemenoff
Immune checkpoint inhibitors targeting the interaction between programmed cell death-1 (PD-1) and its ligand PD-L1 induce tumor regression in a subset of non-small cell lung cancer patients. However, clinical response rates are less than 25%. Evaluation of combinations of immunotherapy with existing therapies requires appropriate pre-clinical animal models. In this study, murine lung cancer cells (CMT167 and LLC) were implanted either orthotopically in the lung or subcutaneously in--- syngeneic mice, and response to anti-PD-1/PD-L1 therapy was determined...
August 17, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28819027/combination-therapy-with-bispecific-antibodies-and-pd-1-blockade-enhances-the-antitumor-potency-of-t-cells
#16
Chien-Hsing Chang, Yang Wang, Rongxiu Li, Diane L Rossi, Donglin Liu, Edmund A Rossi, Thomas M Cardillo, David M Goldenberg
The DOCK-AND-LOCK (DNL®) method is a platform technology that combines recombinant engineering and site-specific conjugation to create multispecific, multivalent antibodies of defined composition with retained bioactivity. We have applied DNL® to generate a novel class of trivalent bispecific antibodies (bsAbs), each comprising an anti-CD3 scFv covalently conjugated to a stabilized dimer of different anti-tumor Fabs. Here we report the further characterization of two such constructs, (E1)-3s and (14)-3s, which activate T cells and target Trop-2- and CEACAM5-expressing cancer cells, respectively...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28819022/%C3%AE-adrenergic-signaling-in-mice-housed-at-standard-temperatures-suppresses-an-effector-phenotype-in-cd8-t-cells-and-undermines-checkpoint-inhibitor-therapy
#17
Mark J Bucsek, Guanxi Qiao, Cameron R MacDonald, Thejaswini Giridharan, Lauren Evans, Brian Niedzwecki, Haichao Liu, Kathleen M Kokolus, Jason W-L Eng, Michelle N Messmer, Kristopher Attwood, Scott I Abrams, Bonnie L Hylander, Elizabeth A Repasky
The immune context of tumors has significant prognostic value and is predictive of responsiveness to several forms of therapy, including immunotherapy. We report here that CD8(+) T cell frequency and functional orientation within the tumor microenvironment is regulated by β2-adrenergic receptor (β-AR) signaling in host immune cells. We used three strategies - physiologic (manipulation of ambient thermal environment), pharmacologic (β-blockers), and genetic (β2-adrenergic receptor knockout mice) to reduce adrenergic stress signaling in two widely studied preclinical mouse tumor models...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28818991/immune-modulation-therapy-and-imaging-workshop-report
#18
Anthony F Shields, Paula Jacobs, Mario Sznol, Michael M Graham, Ronald Germain, Lawrence Lum, Elaine Jaffee, Elisabeth G E de Vries, Sridhar Nimmagadda, Annick D Van den Abbeele, David Leung, Anna M Wu, Elad Sharon, Lalitha K Shankar
A workshop at the National Cancer Institute May 2, 2016 considered the current state of imaging in assessment of immunotherapy. Immunotherapy has shown some remarkable and prolonged responses in the treatment of tumors. However, responses are variable and frequently delayed, complicating the evaluation of new immunotherapy agents and customizing treatment for individual patients. Early anatomic imaging may show that a tumor has increased in size, but this could represent pseudoprogression. Based on imaging, clinicians must decide if they should stop, pause, or continue treatment...
August 17, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28818454/the-anti-tumor-effect-of-intravesical-administration-of-normal-urothelial-cells-on-bladder-cancer
#19
Chi-Ping Huang, Chi-Cheng Chen, Chih-Rong Shyr
BACKGROUND AIMS: Urothelial bladder cancer (UBC) is the second most common cancer of the genitourinary tract and for advanced forms of the disease it has a high mortality rate. There are no approved new molecularly targeted agents or chemotherapeutics for advanced UBC beyond cisplatin-based chemotherapy except the recently approved anti-programmed death ligand 1 (anti-PD-1/PD-L1) antibody. With complex genetic and epigenetic alterations in tumors, despite several druggable targets identified, to cure UBC is still a challenging unmet medical need...
August 14, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28817816/exosomes-derived-from-human-bone-marrow-mesenchymal-stem-cells-promote-tumor-growth-through-hedgehog-signaling-pathway
#20
Jin Qi, Yali Zhou, Zuoyi Jiao, Xu Wang, Yang Zhao, Yangbin Li, Huijuan Chen, Luxi Yang, Hongwen Zhu, Yumin Li
BACKGROUND/AIMS: Mesenchymal stem/stromal cells (MSCs) are known to home to sites of tumor microenvironments where they participate in the formation of the tumor microenvironment and to interplay with tumor cells. However, the potential functional effects of MSCs on tumor cell growth are controversial. Here, we, from the view of bone marrow MSC-derived exosomes, study the molecular mechanism of MSCs on the growth of human osteosarcoma and human gastric cancer cells. METHODS: MSCs derived from human bone marrow (hBMSCs) were isolated and cultured in complete DMEM/F12 supplemented with 10% exosome-depleted fetal bovine serum and 1% penicillin-streptomycin, cell culture supernatants containing exosomes were harvested and exosome purification was performed by ultracentrifugation...
August 16, 2017: Cellular Physiology and Biochemistry
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