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Cancer microenvironment

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https://www.readbyqxmd.com/read/28822888/apatinib-enhances-antitumour-activity-of-egfr-tkis-in-non-small-cell-lung-cancer-with-egfr-tki-resistance
#1
Fang Li, Tengjiao Zhu, Baoshan Cao, Jiadong Wang, Li Liang
BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)-rechallenged therapy for EGFR-mutant non-small cell lung cancer (NSCLC) patients who acquired resistance showed moderate efficacy. Considering the high interrelation between EGFR and vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) pathways, we firstly evaluated EGFR-TKI combined with apatinib (a highly selective VEGFR2 inhibitor) in EGFR-TKI-resistant model and patients...
August 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28822802/stromal-expression-of-activated-leukocyte-cell-adhesion-molecule-alcam-promotes-lung-tumor-growth-and-metastasis
#2
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/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/28819447/targeting-activated-platelets-a-unique-and-potentially-universal-approach-for-cancer-imaging
#7
May Lin Yap, James D McFadyen, Xiaowei Wang, Nicholas A Zia, Jan David Hohmann, Melanie Ziegler, Yu Yao, Alan Pham, Matthew Harris, Paul S Donnelly, P Mark Hogarth, Geoffrey A Pietersz, Bock Lim, Karlheinz Peter
Rationale The early detection of primary tumours and metastatic disease is vital for successful therapy and is contingent upon highly specific molecular markers and sensitive, non-invasive imaging techniques. We hypothesized that the accumulation of activated platelets within tumours is a general phenomenon and thus represents a novel means for the molecular imaging of cancer. Here we investigate a unique single chain antibody (scFv), which specifically targets activated platelets, as a novel biotechnological tool for molecular imaging of cancer...
2017: Theranostics
https://www.readbyqxmd.com/read/28819386/the-tumor-microenvironment-and-inflammatory-breast-cancer
#8
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
#9
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
#10
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
#11
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/28819116/silencing-of-tgf-%C3%AE-1-in-tumor-cells-impacts-mmp-9-in-tumor-microenvironment
#12
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
#13
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
#14
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/28818991/immune-modulation-therapy-and-imaging-workshop-report
#15
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
#16
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
#17
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
https://www.readbyqxmd.com/read/28817117/increased-tumor-infiltrating-cd45ra-ccr7-regulatory-t-cell-subset-with-immunosuppressive-properties-foster-gastric-cancer-progress
#18
Fang-Yuan Mao, Hui Kong, Yong-Liang Zhao, Liu-Sheng Peng, Weisan Chen, Jin-Yu Zhang, Ping Cheng, Ting-Ting Wang, Yi-Pin Lv, Yong-Sheng Teng, Xiao-Long Fu, Yu-Gang Liu, Xiao-Long Wu, Chuan-Jie Hao, Nan You, Ping Luo, Pei-Wu Yu, Quan-Ming Zou, Gang Guo, Yuan Zhuang
Regulatory T cells (Tregs) are major components of tumor-infiltrating immune cells with potent immunosuppressive properties in gastric cancer (GC) microenvironment. However, different subsets of the Tregs and their relevance to GC are unknown. Here, we found that patients with GC showed a significantly higher Tregs infiltration in tumors, and CD45RA(-)CCR7(-) Treg subset constituted most tumor-infiltrating Tregs. Tumor-infiltrating CD45RA(-)CCR7(-) Treg subset with an effector/memory phenotype accumulated in tumors and expressed low level of HLA-DR...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28816713/radiation-therapy-to-the-primary-in-metastatic-prostate-cancer-palliation-only-or-altering-tumor-biology
#19
Pierre Blanchard, Alberto Bossi, Karim Fizazi
PURPOSE OF REVIEW: Despite improvement in systemic treatment, the prognosis of men with de novo metastatic prostate cancer remains poor. Treating the local disease may not only reduce the occurrence of local urologic symptoms, but also slow the metastatic process, either by reducing the seeding from the primary tumor or by altering the microenvironment and thus minimizing the formation of new metastatic sites. RECENT FINDINGS: Retrospective and population-based studies have suggested that the addition of local treatment to systemic therapy may improve survival in this patient group...
August 14, 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/28816141/combined-radiation-therapy-and-immune-checkpoint-blockade-therapy-for-breast-cancer
#20
REVIEW
Zishuo I Hu, Alice Y Ho, Heather L McArthur
PURPOSE: Treatment with checkpoint inhibitors has shown durable responses in a number of solid tumors, including melanoma, lung, and renal cell carcinoma. However, most breast cancers are resistant to monotherapy with checkpoint inhibitors. Radiation therapy (RT) has been shown to have a number of immunostimulatory effects, including priming the immune system, recruiting immune cells to the tumor environment, and altering the immunosuppressive effects of the tumor microenvironment. RT therefore represents a promising adjuvant therapy to checkpoint blockade in breast cancer...
September 1, 2017: International Journal of Radiation Oncology, Biology, Physics
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