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https://www.readbyqxmd.com/read/28929492/potent-antitumor-effect-of-tumor-microenvironment-targeted-oncolytic-adenovirus-against-desmoplastic-pancreatic-cancer
#1
Yan Li, JinWoo Hong, Joung-Eun Oh, A-Rum Yoon, Chae-Ok Yun
Pancreatic cancer is a leading cause of cancer-related death. Desmoplastic pancreatic tumors exhibit excessive extracellular matrix (ECM) and are thus highly resistant to anticancer therapeutics, since the ECM restricts drug penetration and dispersion. Here, we designed and generated two hypoxia-responsive and cancer-specific hybrid promoters, H(mT)E and H(E)mT. Transgene expression driven by each hybrid promoter was markedly higher under hypoxic conditions than normoxic conditions. Moreover, H(E)mT-driven transgene expression was highly cancer-specific and was superior to that of H(mT)E-driven expression...
September 20, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28915646/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#2
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 4(th) 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)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28880262/acceleration-of-pancreatic-tumorigenesis-under-immunosuppressive-microenvironment-induced-by-reg3g-overexpression
#3
Xiulan Liu, Zhongshi Zhou, Qi Cheng, Hongjie Wang, Hui Cao, Qianqian Xu, Yali Tuo, Li Jiang, You Zou, Hongyu Ren, Ming Xiang
Reg3g is a potential risk for pancreatic ductal adenocarcinoma (PDAC). We previously demonstrated that Reg3g promoted pancreatic carcinogenesis via a STAT3 signaling pathway in a murine model of chronic pancreatitis. Whether the immune response is involved in tumorigenesis induced by Reg3g remains unknown. In this study, Reg3g-regulated tumor immunity was evaluated in tumor-implanted murine models, immune cells, and tumor microenvironment. In mice that had been orthotopically or ectopically implanted with Panc02 cells, Reg3g overexpression increased EGFR and Ki67, diminished MHC-I and caspase-3 expression, and accelerated growth of tumors...
September 7, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28867243/a-mechanopharmacology-approach-to-overcome-chemoresistance-in-pancreatic-cancer
#4
Stefano Coppola, Ilaria Carnevale, Erik H J Danen, Godefridus J Peters, Thomas Schmidt, Yehuda G Assaraf, Elisa Giovannetti
Pancreatic ductal adenocarcinoma (PDAC) is a highly chemoresistant malignancy. This chemoresistant phenotype has been historically associated with genetic factors. Major biomedical research efforts were concentrated that resulted in the identification of subtypes characterized by specific genetic lesions and gene expression signatures that suggest important biological differences. However, to date, these distinct differences could not be exploited for therapeutic interventions. Apart from these genetic factors, desmoplasia and tumor microenvironment have been recognized as key contributors to PDAC chemoresistance...
March 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/28864770/retraction-abstract-408-acp-196-an-orally-bioavailable-covalent-selective-inhibitor-of-btk-modulates-the-innate-tumor-microenvironment-exhibits-antitumor-efficacy-and-enhances-gemcitabine-activity-in-pancreatic-cancer
#5
https://www.readbyqxmd.com/read/28855593/itga1-is-a-pre-malignant-biomarker-that-promotes-therapy-resistance-and-metastatic-potential-in-pancreatic-cancer
#6
Armen Gharibi, Sa La Kim, Justin Molnar, Daniel Brambilla, Yvess Adamian, Malachia Hoover, Julie Hong, Joy Lin, Laurelin Wolfenden, Jonathan A Kelber
Pancreatic ductal adenocarcinoma (PDAC) has single-digit 5-year survival rates at <7%. There is a dire need to improve pre-malignant detection methods and identify new therapeutic targets for abrogating PDAC progression. To this end, we mined our previously published pseudopodium-enriched (PDE) protein/phosphoprotein datasets to identify novel PDAC-specific biomarkers and/or therapeutic targets. We discovered that integrin alpha 1 (ITGA1) is frequently upregulated in pancreatic cancers and associated precursor lesions...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28854237/tumor-engraftment-in-patient-derived-xenografts-of-pancreatic-ductal-adenocarcinoma-is-associated-with-adverse-clinicopathological-features-and-poor-survival
#7
Ilaria Pergolini, Vicente Morales-Oyarvide, Mari Mino-Kenudson, Kim C Honselmann, Matthew W Rosenbaum, Sabikun Nahar, Marina Kem, Cristina R Ferrone, Keith D Lillemoe, Nabeel Bardeesy, David P Ryan, Sarah P Thayer, Andrew L Warshaw, Carlos Fernández-Del Castillo, Andrew S Liss
Patient-derived xenograft (PDX) tumors are powerful tools to study cancer biology. However, the ability of PDX tumors to model the biological and histological diversity of pancreatic ductal adenocarcinoma (PDAC) is not well known. In this study, we subcutaneously implanted 133 primary and metastatic PDAC tumors into immunodeficient mice. Fifty-seven tumors were successfully engrafted and even after extensive passaging, the histology of poorly-, moderately-, and well-differentiated tumors was maintained in the PDX models...
2017: PloS One
https://www.readbyqxmd.com/read/28839967/yes-associated-protein-and-immunosuppressive-microenvironment-in-pancreatic-cancer-development-a-new-strategy-to-improve-immunotherapy-efficacy
#8
EDITORIAL
Rossana Berardi, Alessandro Bittoni
No abstract text is available yet for this article.
July 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28839168/drug-loaded-gingival-mesenchymal-stromal-cells-ginpa-mscs-inhibit-in-vitro-proliferation-of-oral-squamous-cell-carcinoma
#9
Valentina Coccè, Davide Farronato, Anna Teresa Brini, Carla Masia, Aldo Bruno Giannì, Giovanna Piovani, Francesca Sisto, Giulio Alessandri, Francesca Angiero, Augusto Pessina
Human mesenchymal stromal cells (MSCs) have been widely investigated both for regenerative medicine and their antinflammatory/immunomodulatory capacity. However, their ability to home pathological tissues suggested the development of strategies for using MSCs as carrier to deliver drug into tumor microenvironment. MSCs obtained from different tissues can be loaded in vitro with anti-cancer drugs by a simple procedures. In this report, we studied MSCs isolated and expanded from gingival papilla (GinPa-MSCs), by testing their ability to uptake and release three important anti-neoplastic drugs: Paclitaxel (PTX), Doxorubicin (DXR) and Gemcitabine (GCB)...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28838996/the-selective-tie2-inhibitor-rebastinib-blocks-recruitment-and-function-of-tie2hi-macrophages-in-breast-cancer-and-pancreatic-neuroendocrine-tumors
#10
Allison S Harney, George S Karagiannis, Jeanine Pignatelli, Bryan D Smith, Ece Kadioglu, Scott C Wise, Molly M Hood, Michael D Kaufman, Cynthia B Leary, Wei-Ping Lu, Gada Al-Ani, Xiaoming Chen, David Entenberg, Maja H Oktay, Yarong Wang, Lawrence Chun, Michele De Palma, Joan G Jones, Daniel L Flynn, John S Condeelis
Tumor-infiltrating myeloid cells promote tumor progression by mediating angiogenesis, tumor cell intravasation and metastasis, which can offset the effects of chemotherapy, radiation, and anti-angiogenic therapy. Here, we show that the kinase switch control inhibitor rebastinib inhibits Tie2, a tyrosine kinase receptor expressed on endothelial cells and pro-tumoral Tie2-expressing macrophages in mouse models of metastatic cancer. Rebastinib reduces tumor growth and metastasis in an orthotopic mouse model of metastatic mammary carcinoma through reduction of Tie2+ myeloid cell infiltration, anti-angiogenic effects, and blockade of tumor cell intravasation mediated by perivascular Tie2Hi/Vegf-AHi macrophages in the tumor microenvironment of metastasis (TMEM)...
August 24, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28813661/tissue-resident-macrophages-in-pancreatic-ductal-adenocarcinoma-originate-from-embryonic-hematopoiesis-and-promote-tumor-progression
#11
Yu Zhu, John M Herndon, Dorothy K Sojka, Ki-Wook Kim, Brett L Knolhoff, Chong Zuo, Darren R Cullinan, Jingqin Luo, Audrey R Bearden, Kory J Lavine, Wayne M Yokoyama, William G Hawkins, Ryan C Fields, Gwendalyn J Randolph, David G DeNardo
Tumor-associated macrophages (TAMs) are essential components of the cancer microenvironment and play critical roles in the regulation of tumor progression. Optimal therapeutic intervention requires in-depth understanding of the sources that sustain macrophages in malignant tissues. In this study, we investigated the ontogeny of TAMs in murine pancreatic ductal adenocarcinoma (PDAC) models. We identified both inflammatory monocytes and tissue-resident macrophages as sources of TAMs. Unexpectedly, significant portions of pancreas-resident macrophages originated from embryonic development and expanded through in situ proliferation during tumor progression...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28811976/long-lived-pancreatic-ductal-adenocarcinoma-slice-cultures-enable-precise-study-of-the-immune-microenvironment
#12
Xiuyun Jiang, Y David Seo, Jae Hyuck Chang, Andrew Coveler, Eslam N Nigjeh, Sheng Pan, Florencia Jalikis, Raymond S Yeung, Ian N Crispe, Venu G Pillarisetty
Pancreatic ductal adenocarcinoma (PDA) remains a deadly disease that is rarely cured, despite many recent successes with immunotherapy for other malignancies. As the human disease is heavily infiltrated by effector T cells, we postulated that accurately modeling the PDA immune microenvironment would allow us to study mechanisms of immunosuppression that could be overcome for therapeutic benefit. Using viable precision-cut slices from fresh PDA, we developed an organotypic culture system for this purpose. We confirmed that cultured slices maintain their baseline morphology, surface area, and microenvironment after at least 6 d in culture, and demonstrated slice survival by MTT assay and by immunohistochemistry staining with Ki-67 and cleaved-Caspase-3 antibodies...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811077/the-receptor-for-advanced-glycation-end-products-a-fuel-to-pancreatic-cancer
#13
REVIEW
Uzma Shahab, Mohd Kaleem Ahmad, Abbas Ali Mahdi, Mohd Waseem, Binish Arif, Moinuddin, Saheem Ahmad
The receptor for advanced glycation end products (RAGEs) was first illustrated in the year 1992. RAGE is a single-transmembrane and multi-ligand component of the immunoglobulin protein super family. The engagement of RAGE turns out to an establishment of numerous intracellular signalling mechanisms resulting in the progression and perpetuation of many types of cancer including, the pancreatic cancer. The present review primarily focuses on the multi-ligand activation of RAGEs leading to the downstream signalling cascade activation...
August 12, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28809532/transient-and-local-expression-of-chemokine-and-immune-checkpoint-traps-to-treat-pancreatic-cancer
#14
Lei Miao, Jingjing Li, Qi Liu, Richard Feng, Manisit Das, C Michael Lin, Tyler J Goodwin, Oleksandra Dorosheva, Rihe Liu, Leaf Huang
Pancreatic tumors are known to be resistant to immunotherapy due to the extensive immune suppressive tumor microenvironment (TME). We hypothesized that CXCL12 and PD-L1 are two key molecules controlling the immunosuppressive TME. Fusion proteins, called traps, designed to bind with these two molecules with high affinity (Kd = 4.1 and 0.22 nM, respectively) were manufactured and tested for specific binding with the targets. Plasmid DNA encoding for each trap was formulated in nanoparticles and intravenously injected to mice bearing orthotopic pancreatic cancer...
August 28, 2017: ACS Nano
https://www.readbyqxmd.com/read/28798308/prognostic-value-of-programmed-cell-death-protein-1-expression-on-cd8-t-lymphocytes-in-pancreatic-cancer
#15
Tao Shen, Liangjing Zhou, Hua Shen, Chengfei Shi, Shengnan Jia, Guo Ping Ding, Liping Cao
Pancreatic cancer is one of the most aggressive malignancies and has a highly immunosuppressive tumour microenvironment. Immune checkpoint blockade has led to remarkable and durable objective responses in a number of malignancies and antibody-based strategies targeting programmed cell death protein 1 (PD-1) are showing promise where traditional modalities of surgery, radiotherapy, and chemotherapy have failed. In this study, we examined the clinical value of PD-1 protein expression by CD8+ peripheral T lymphocytes or tumour-infiltrating T lymphocytes (TILs) in pancreatic ductal adenocarcinoma (PDAC)...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794854/tgf-%C3%AE-in-pancreatic-cancer-initiation-and-progression-two-sides-of-the-same-coin
#16
REVIEW
Wei Shen, Guo-Qing Tao, Yu Zhang, Bing Cai, Jian Sun, Zhi-Qiang Tian
Pancreatic cancer is highly lethal malignant tumor with characterised rapid progression, invasiveness and resistance to radiochemotherapy. Transforming growth factor-β (TGF-β) signaling plays a dual role in both pro-tumorigenic and tumor suppressive of pancreatic cancer, depending on tumor stage and microenvironment. TGF-β signaling components alteration are common in pancreatic cancer, and its leading role in tumor formation and metastases has received increased attention. Many therapies have investigated to target TGF-β signaling in the preclinical and clinical setting...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28753978/seed-in-soil-pancreatic-cancer-influenced-by-tumor-microenvironment
#17
REVIEW
Huey-Jen Lin, Jiayuh Lin
Pancreatic ductal adenocarcinoma is a fatal malignancy with a five-year survival rate lower than 7%, and most patients dying within six months of diagnosis. The factors that contribute to the aggressiveness of the disease include, but are not limited to: late diagnosis, prompt metastasis to adjacent vital organs, poor response, and resistance to anticancer treatments. This malignancy is uniquely associated with desmoplastic stroma that accounts for 80% of tumor mass. Understanding the biology of stroma can aid the discovery of innovative strategies for eradicating this lethal cancer in the future...
July 21, 2017: Cancers
https://www.readbyqxmd.com/read/28750018/pancreatic-cancer-cell-fibroblast-co-culture-induces-m2-like-macrophages-that-influence-therapeutic-response-in-a-3d-model
#18
Janina Kuen, Diana Darowski, Tobias Kluge, Meher Majety
Pancreatic cancer (PC) remains one of the most challenging solid tumors to treat with a high unmet medical need as patients poorly respond to standard-of-care-therapies. Prominent desmoplastic reaction involving cancer-associated fibroblasts (CAFs) and the immune cells in the tumor microenvironment (TME) and their cross-talk play a significant role in tumor immune escape and progression. To identify the key cellular mechanisms induce an immunosuppressive tumor microenvironment, we established 3D co-culture model with pancreatic cancer cells, CAFs and monocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28705232/hypoxia-inducible-factor-2%C3%AE-promotes-tumor-progression-and-has-crosstalk-with-wnt-%C3%AE-catenin-signaling-in-pancreatic-cancer
#19
Qi Zhang, Yu Lou, Jingying Zhang, Qihan Fu, Tao Wei, Xu Sun, Qi Chen, Jiaqi Yang, Xueli Bai, Tingbo Liang
BACKGROUND: Pancreatic cancer is a devastating disease that is characterized by persistent hypoxia. The roles of hypoxia-inducible factor-2α (hif-2α) are different to those of hif-1α, although both are critical for tumor cells to adapt to the hypoxic microenvironment. However, unlike the well-studied hif-1α, the role of hif-2α in tumors, including pancreatic cancer, is poorly understood. METHODS: Herein, we used a mutated hif-2α (A530T) to figure out the problem that wild-type hif-2α is quickly degraded which limits the study of its function...
July 14, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28705007/pancreas-adenocarcinoma-novel-therapeutics
#20
Benjamin A Krantz, Kenneth H Yu, Eileen M O'Reilly
Pancreatic ductal adenocarcinoma (PDAC) is the third highest cause of cancer-related deaths in the US, and is projected to be second only to non-small cell lung cancer (NSCLC) by the 2020s. Current therapies have a modest impact on survival and median overall survival (mOS) across all stages of disease remains under a year. Over the last decade, however, great strides have been made in the understanding of PDAC pathobiology including the role of the tumor microenvironment (TME), DNA damage repair and mechanism of immunosuppression...
June 2017: Chinese Clinical Oncology
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