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Tumor microenvironment

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https://www.readbyqxmd.com/read/27936345/targeting-integrin-linked-kinase-to-suppress-oncogenic-kras-signaling-in-pancreatic-cancer
#1
Po-Chen Chu, Samuel K Kulp, Tanios Bekaii-Saab, Ching-Shih Chen
Although oncogenic KRAS represents a therapeutically relevant target in pancreatic cancer, it is deemed "non-druggable" because of the intrinsic difficulty in designing direct inhibitors of KRAS. Our recent work demonstrated a KRAS-integrin-linked kinase (ILK) regulatory feedback loop that allows pancreatic cancer cells to regulate KRAS expression and to interact with the tumor microenvironment to promote aggressive phenotype. KRAS induces E2F1-mediated transcriptional activation of ILK expression, and ILK, in turn, controls KRAS expression via hnRNPA1, which binds and destabilizes the G-quadruplex in the KRAS promoter...
December 9, 2016: Small GTPases
https://www.readbyqxmd.com/read/27935862/targeting-of-interleukin-il-17a-inhibits-pdl1-expression-in-tumor-cells-and-induces-anticancer-immunity-in-an-estrogen-receptor-negative-murine-model-of-breast-cancer
#2
Yun-Feng Ma, Chen Chen, Dongqing Li, Min Liu, Zhuang-Wei Lv, Yanhong Ji, Jiru Xu
The expression of IL-17A and programmed death ligand 1 (PDL1) is increased in estrogen receptor-negative breast cancer. IL-17A promotes tumor cell survival and invasiveness and inhibits the antitumor immune response. The PDL1-PD1 (programmed death protein 1) signaling pathway promotes escape from immune surveillance in tumor cells. The pro-tumor properties of IL-17A and PDL1 in various cancers have been previously examined; however, the relationship and roles of IL-17A and PDL1 in ER-negative breast cancer have not been evaluated...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27935337/induction-of-interleukin-1%C3%AE-by-mouse-mammary-tumor-irradiation-promotes-triple-negative-breast-cancer-cells-invasion-and-metastasis-development
#3
Gina Bouchard, Hélène Therriault, Rachel Bujold, Caroline Saucier, Benoit Paquette
PURPOSE: Radiotherapy increases the level of inflammatory cytokines, some of which are known to promote metastasis. In a mouse model of triple negative breast cancer (TNBC), we determined whether irradiation of the mammary tumor increases the level of key cytokines and favors the development of lung metastases. MATERIAL AND METHODS: D2A1 TNBC cells were implanted in the mammary glands of a Balb/c mouse and then 7 days old tumors were irradiated (4x6 Gy). The cytokines IL-1β, IL-4, IL-6, IL-10, IL-17 and MIP-2 were quantified in plasma before, midway and after irradiation...
December 9, 2016: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/27935039/the-sabotaging-role-of-myeloid-cells-in-anti-angiogenic-therapy-coordination-of-angiogenesis-and-immune-suppression-by-hypoxia
#4
REVIEW
Chunyan Li, Tao Liu, Alexandr V Bazhin, Yuhui Yang
Tumor angiogenesis has become a promising target for anti-tumor therapy. Unfortunately, the somewhat inevitable occurrence of resistance has limited the efficacy of anti-angiogenic therapy. In addition to their well-established role in immune suppression, bone marrow-derived myeloid cells actively contribute to tumor angiogenesis. More importantly, myeloid cells constitute one of the major mechanisms of resistance to angiogenesis inhibition. As the most pervasive feature in tumor microenvironment, hypoxia is able to initiate both pro-angiogenic and immunosuppressive capacities of myeloid cells...
December 9, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27934883/preclinical-evaluation-of-radiation-and-systemic-rgd-targeted-adeno-associated-virus-phage-tnf-gene-therapy-in-a-mouse-model-of-spontaneously-metastatic-melanoma
#5
T J Quinn, N Healy, A Sara, E Maggi, C S Claros, R Kabarriti, L Scandiuzzi, L Liu, J Gorecka, A Adem, I Basu, Z Yuan, C Guha
The incidence of melanoma in the United States continues to rise, with metastatic lesions notoriously recalcitrant to therapy. There are limited effective treatment options available and a great need for more effective therapies that can be rapidly integrated in the clinic. In this study, we demonstrate that the combination of RGD-targeted adeno-associated virus phage (RGD-AAVP-TNF) with hypofractionated radiation therapy results in synergistic inhibition of primary syngeneic B16 melanoma in a C57 mouse model...
December 9, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27934877/overexpression-and-gene-amplification-of-pd-l1-in-cancer-cells-and-pd-l1-immune-cells-in-epstein-barr-virus-associated-gastric-cancer-the-prognostic-implications
#6
Ruri Saito, Hiroyuki Abe, Akiko Kunita, Hiroharu Yamashita, Yasuyuki Seto, Masashi Fukayama
Cancer cells use PD-L1 to evade antitumor immunity through interaction with programmed cell death protein 1 (PD-1) on T cells. Recent whole-genome sequence studies revealed frequent gene amplification of PD-L1 in Epstein-Barr virus-associated gastric cancer (EBVaGC). To investigate the significance of PD-L1 in cancer cells and their microenvironment in EBVaGC, we studied PD-L1 expression by analysis of the public database and immunohistochemistry with fluorescent in situ hybridization (FISH) of the PD-L1 gene...
December 9, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27934069/blood-brain-barrier-penetrating-albumin-nanoparticles-for-biomimetic-drug-delivery-via-albumin-binding-protein-pathways-for-antiglioma-therapy
#7
Tingting Lin, Pengfei Zhao, Yifan Jiang, Yisi Tang, Hongyue Jin, Zhenzhen Pan, Huining He, Victor C Yang, Yongzhuo Huang
Nutrient transporters have been explored for biomimetic delivery targeting the brain. The albumin-binding proteins (e.g., SPARC and gp60) are overexpressed in many tumors for transport of albumin as an amino acid and an energy source for fast-growing cancer cells. However, their application in brain delivery has rarely been investigated. In this work, SPARC and gp60 overexpression was found on glioma and tumor vessel endothelium; therefore, such pathways were explored for use in brain-targeting biomimetic delivery...
November 22, 2016: ACS Nano
https://www.readbyqxmd.com/read/27933846/enhanced-cellular-internalization-and-on-demand-intracellular-release-of-doxorubicin-by-stepwise-ph-reduction-responsive-nanoparticles
#8
Fang Li, Wei-Liang Chen, Ben-Gang You, Yang Liu, Shu-di Yang, Zhi-Qiang Yuan, Wen-Jing Zhu, Ji-Zhao Li, Chen-Xi Qu, Ye-Juan Zhou, Xiao-Feng Zhou, Chun Liu, Xue-Nong Zhang
The efficient delivery of antitumor agents to tumor sites faces numerous obstacles, such as poor cellular uptake and slow intracellular drug release. In this regard, smart nanoparticles (NPs) that respond to the unique microenvironment of tumor tissues have been widely used for drug delivery. In this study, novel charge-reversal and reduction-responsive histidine-grafted chitosan-lipoic acid NPs (HCSL-NPs) were selected for efficient therapy of breast cancer by enhancing cell internalization and intracellular pH- and reduction-triggered doxorubicin (DOX) release...
November 30, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27933753/mass-cytometry-of-follicular-lymphoma-tumors-reveals-intrinsic-heterogeneity-in-proteins-including-hla-dr-and-a-deficit-in-non-malignant-plasmablast-and-germinal-center-b-cell-populations
#9
Cara Ellen Wogsland, Allison Rae Greenplate, Arne Kolstad, June Helen Myklebust, Jonathan Michael Irish, Kanutte Huse
BACKGROUND: Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma that has a risk of transformation to more aggressive lymphoma. Relatively little is known about the non-malignant B-cell and T-cell subset composition within the tumor microenvironment and whether altered phenotypes are associated with patterns of lymphoma B-cell heterogeneity. METHODS: Two mass cytometry (CyTOF) panels were designed to immunophenotype B and T cells in FL tumors. Populations of malignant B cells, non-malignant B cells, and T cells from each FL tumor were identified and their phenotypes compared to B and T cells from healthy human tonsillar tissue...
December 9, 2016: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/27933314/tunneling-nanotubes-an-alternate-route-for-propagation-of-the-bystander-effect-following-oncolytic-viral-infection
#10
Justin Ady, Venugopal Thayanithy, Kelly Mojica, Phillip Wong, Joshua Carson, Prassanna Rao, Yuman Fong, Emil Lou
Tunneling nanotubes (TNTs) are ultrafine, filamentous actin-based cytoplasmic extensions which form spontaneously to connect cells at short and long-range distances. We have previously described long-range intercellular communication via TNTs connecting mesothelioma cells in vitro and demonstrated TNTs in intact tumors from patients with mesothelioma. Here, we investigate the ability of TNTs to mediate a viral thymidine kinase based bystander effect after oncolytic viral infection and administration of the nucleoside analog ganciclovir...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27933272/autophagy-dependent-secretion-contribution-to-tumor-progression
#11
REVIEW
Tom G Keulers, Marco B E Schaaf, Kasper M A Rouschop
Autophagy is best known as a lysosomal degradation and recycling pathway to maintain cellular homeostasis. During autophagy, cytoplasmic content is recognized and packed in autophagic vacuoles, or autophagosomes, and targeted for degradation. However, during the last years, it has become evident that the role of autophagy is not restricted to degradation alone but also mediates unconventional forms of secretion. Furthermore, cells with defects in autophagy apparently are able to reroute their cargo, like mitochondria, to the extracellular environment; effects that contribute to an array of pathologies...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27932417/molecular-pathways-the-necrosome-a-target-for-cancer-therapy
#12
Lena Seifert, George Miller
Necroptosis is a caspase 8-independent cell death that requires co-activation of receptor-interacting protein (RIP) 1 and RIP 3 kinases. The necrosome is a complex consisting of RIP1, RIP3 and Fas-associated protein with death domain (FADD) leading to activation of the pseudokinase mixed lineage kinase like (MLKL) followed by a rapid plasma membrane rupture and inflammatory response through the release of damage-associated molecular patterns (DAMPs) and cytokines. The necrosome has been shown to be relevant in multiple tumor types, including pancreatic adenocarcinoma, melanoma and several hematological malignancies...
December 8, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27931844/dendritic-cells-in-hematological-malignancies
#13
REVIEW
Domenico Galati, Gaetano Corazzelli, Rosaria De Filippi, Antonio Pinto
Dendritic cells (DCs) are bone-marrow-derived immune cells accounted for a crucial role in initiating and modulating the adaptive immune response and supporting the innate immune response independently from T cells. While functioning as the most effective antigen-presenting cells within the immune system, DCs can otherwise induce tolerance in central and peripheral lymphoid organs acting therefore as suppressors rather than stimulators of the immune response. Within mechanisms regulating antitumor immunity, DCs can capture antigens from viable or damaged tumor cells and present the processed peptides to T-cells to prompt the generation and maintenance of an effective tumor-specific T-cell response...
December 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27931833/hyperglycemia-tumorigenesis-and-chronic-inflammation
#14
REVIEW
Shu-Chun Chang, Wei-Chung Vivian Yang
Hyperglycemia is the most prominent sign that characterizes diabetes. Hyperglycemia favors malignant cell growth by providing energy to cancer cells. Clinical studies also showed an increased risk of diabetes being associated with different types of cancers. In addition, poorly regulated glucose metabolism in diabetic patients is often found with increased levels of chronic inflammatory markers, e.g., interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, and emerging evidence has highlighted activation of the immune response in the progression and development of cancer cells...
December 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27931798/differential-expression-of-low-density-lipoprotein-receptor-related-protein-1-lrp-1-and-matrix-metalloproteinase-9-mmp-9-in-prostate-gland-from-normal-to-malignant-lesions
#15
Mónica B Gilardoni, María M Remedi, Mabel Oviedo, Tristán Dellavedova, Juan P Sarría, Laura Racca, Mariana Dominguez, Claudia G Pellizas, Ana C Donadio
BACKGROUND: Metalloproteinases (MMPs) are relevant modulators of inflammation, tumor microenvironment, cancer invasion and metastasis. They can be regulated by the Low density lipoprotein Receptor-related Protein 1 (LRP-1), a receptor reported to mediate the clearance of lipoproteins, extracellular matrix (ECM) macromolecules and proteinases. The aim of this study was to evaluate the expression of LRP-1, MMP-2 and MMP-9 across various grades of prostatic diseases as benign prostatic hyperplasia (BPH), BPH plus prostatitis (BPH+P), high grade prostatic intraepithelial neoplasia (HGPIN) and prostate cancer (PCa)...
November 24, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27931212/pdgf-aa-mediates-mesenchymal-stromal-cell-chemotaxis-to-the-head-and-neck-squamous-cell-carcinoma-tumor-microenvironment
#16
Tammara L Watts, Ruwen Cui, Peter Szaniszlo, Vicente A Resto, Don W Powell, Irina V Pinchuk
BACKGROUND: The robust desmoplasia associated with head and neck squamous cell carcinoma (HNSCC) suggests that the tumor microenvironment may be an important component in the pathophysiology of this cancer. Moreover, the high recurrence rate and poor clinical response to chemotherapy and radiation treatment further underscores that the non-cancerous cells of the microenvironment, such as mesenchymal stromal cells (MSCs), cancer associated fibroblasts (CAFs), and pericytes, may be important in the pathophysiology of HNSCC...
December 8, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27930920/indoleamine-2-3-dioxygenase-regulates-t-cell-activity-through-vav1-rac-pathway
#17
Runmei Li, Hui Li, Qian Sun, Liang Liu, Chen Zhang, Xiubao Ren
The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) suppresses T-cell responses and promotes immune tolerance in tumor resistance. A previous study determined that IDO inhibits Vav1 mRNA expression and the activation of Vav1 and its downstream targets in T cells in the guanine exchange factor (GEF)-independent pathway. The current study aims to determine whether IDO induces T-cell immunosuppression through Vav1/Rac signaling pathway, which is a GEF-dependent pathway. The correlation between Vav1 mRNA expressions in T cells of tumor infiltrating lymphocytes and the levels of IDO expression in lung cancer tissues from lung cancer patients was detected...
December 5, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27930550/role-of-immune-cells-in-pancreatic-cancer-from-bench-to-clinical-application-an-updated-review
#18
Jae Hyuck Chang, Yongjian Jiang, Venu G Pillarisetty
BACKGROUND: Pancreatic cancer (PC) remains difficult to treat, despite the recent advances in various anticancer therapies. Immuno-inflammatory response is considered to be a major risk factor for the development of PC in addition to a combination of genetic background and environmental factors. Although patients with PC exhibit evidence of systemic immune dysfunction, the PC microenvironment is replete with immune cells. METHODS: We searched PubMed for all relevant English language articles published up to March 2016...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27929537/upregulation-of-mir-205-under-hypoxia-promotes-epithelial-mesenchymal-transition-by-targeting-aspp2
#19
Xingwen Wang, Miao Yu, Kunming Zhao, Mengmeng He, Wenjie Ge, Yuhui Sun, Yihua Wang, Haizhu Sun, Ying Hu
The epithelial-mesenchymal transition (EMT) is one of the crucial procedures for cancer invasion and distal metastasis. Despite undergoing intensive studies, the mechanisms underlying EMT remain to be completely elucidated. Here, we identified that apoptosis-stimulating protein of p53-2 (ASPP2) is a novel target of MiR-205 in various cancers. Interestingly, the binding site of MiR-205 at the 3'-untranslated region of ASPP2 was highly conserved among different species. An inverse correlation between MiR-205 and ASPP2 was further observed in vivo in cervical cancers, suggesting MiR-205 may be an important physiological inhibitor of ASPP2...
December 8, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27929420/tumor-microenvironment-metabolism-a-new-checkpoint-for-anti-tumor-immunity
#20
REVIEW
Nicole E Scharping, Greg M Delgoffe
When a T cell infiltrates a tumor, it is subjected to a variety of immunosuppressive and regulatory signals in the microenvironment. However, it is becoming increasingly clear that due to the proliferative and energetically-deregulated nature of tumor cells, T cells also operate at a metabolic disadvantage. The nutrient dearth of the tumor microenvironment (TME) creates "metabolic checkpoints" upon infiltrating T cells, impacting their ability to survive, proliferate and function effectively. In this review, we summarize the basics of tumor cell and T cell metabolism and discuss recent advances elucidating the individual metabolic checkpoints exerted on T cells that drive their dysfunction in the TME...
December 6, 2016: Vaccines
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