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https://www.readbyqxmd.com/read/28714960/bin1-reverses-pd-l1-mediated-immune-escape-by-inactivating-the-c-myc-and-egfr-mapk-signaling-pathways-in-non-small-cell-lung-cancer
#1
J Wang, Y Jia, S Zhao, X Zhang, X Wang, X Han, Y Wang, M Ma, J Shi, L Liu
Non-small cell lung cancer (NSCLC) is one of the most common and malignant carcinoma worldwide, and the incidence and mortality are increasing rapidly. Immunotherapy targeting programmed death 1/programmed death ligand 1 (PD-L1) signaling has shown prominent clinical effects in treating NSCLC; however, a poor understanding of the associated regulating molecular mechanisms of PD-L1 has become one of the biggest obstacles for further improving efficacy. Bridging integrator-1 (BIN1) can regulate numerous cancer-related molecules to exert multiple tumor-suppressing effects by either interacting or not interacting with c-MYC...
July 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28707199/radiation-induced-inflammatory-cascade-and-its-reverberating-crosstalks-as-potential-cause-of-post-radiotherapy-second-malignancies
#2
REVIEW
Sonia Gandhi, Sudhir Chandna
The disease-free survival following radiotherapy is often limited by the development of second/secondary cancers. This significant impediment to effective cancer treatment implicated even in the modern-day radiotherapy needs to be countered effectively. Critical analysis reveals that besides achieving effective tumor control, radiotherapy elicits certain cellular and systemic inflammatory events in tumor infiltrate, which remain relatively stable and tend to facilitate "in-field" or "out of field" oncogenesis in due course of time...
July 13, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28701895/decreased-serum-concentration-of-total-igg-is-related-to-tumor-progression-in-gastric-cancer-patients
#3
Hiroaki Saito, Kozo Miyatani, Yusuke Kono, Yuki Murakami, Hirohiko Kuroda, Tomoyuki Matsunaga, Yoji Fukumoto, Shuichi Takano, Tomohiro Osaki, Yoshiyuki Fujiwara
BACKGROUND: There is accumulating evidence that shows cell-mediated immunity regulated by T cells is impaired in cancer patients. Unfortunately, the mechanisms by which B cells participate in tumor immunity are only partially understood. METHODS: The serum concentration of Immunoglobulin G (IgG) was measured by Enzyme-Linked ImmunoSorbent Assay (ELISA) in patients with gastric cancer. Immunohistochemistry was also performed using the anti- cluster of differentiation (CD)134 antibody to evaluate the number of plasma cells in the tumor tissue...
June 2017: Yonago Acta Medica
https://www.readbyqxmd.com/read/28699895/a-role-for-brg1-in-the-regulation-of-genes-required-for-development-of-the-lymphatic-system
#4
Ajeet Pratap Singh, Julie Foley, Arpit Tandon, Dhiral Phadke, H Karimi Kinyamu, Trevor K Archer
Lymphatic vasculature is an important part of the cardiovascular system with multiple functions, including regulation of the return of interstitial fluid (lymph) to the bloodstream, immune responses, and fat absorption. Consequently, lymphatic vasculature defects are involved in many pathological processes, including tumor metastasis and lymphedema. BRG1 is an important player in the developmental window when the lymphatic system is initiated. In the current study, we used tamoxifen inducible Rosa26CreERT2-BRG1floxed/floxed mice that allowed temporal analysis of the impact of BRG1 inactivation in the embryo...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28691927/ubiquitination-of-tumor-suppressor-pml-regulates-prometastatic-and-immunosuppressive-tumor-microenvironment
#5
Ya-Ting Wang, Jocelyn Chen, Chou-Wei Chang, Jayu Jen, Tzu-Yu Huang, Chun-Ming Chen, Roger Shen, Suh-Yuen Liang, I-Cheng Cheng, Shuenn-Chen Yang, Wu-Wei Lai, Kuang-Hung Cheng, Tao-Shih Hsieh, Ming-Zong Lai, Hung-Chi Cheng, Yi-Ching Wang, Ruey-Hwa Chen
The tumor microenvironment plays an important role in tumor growth and metastasis. However, the mechanism by which tumor cells regulate the cell and non-cell constituents of surrounding stroma remains incompletely understood. Promyelocytic leukemia (PML) is a pleiotropic tumor suppressor, but its role in tumor microenvironment regulation is poorly characterized. PML is frequently downregulated in many cancer types, including lung cancer. Here, we identify a PML ubiquitination pathway that is mediated by WD repeat 4-containing cullin-RING ubiquitin ligase 4 (CRL4WDR4)...
July 10, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28689639/regulation-of-inflammation-by-members-of-the-formyl-peptide-receptor-family
#6
REVIEW
Keqiang Chen, Zhiyao Bao, Wanghua Gong, Peng Tang, Teizo Yoshimura, Ji Ming Wang
Inflammation is associated with a variety of diseases. The hallmark of inflammation is leukocyte infiltration at disease sites in response to pathogen- or damage-associated chemotactic molecular patterns (PAMPs and MAMPs), which are recognized by a superfamily of seven transmembrane, Gi-protein-coupled receptors (GPCRs) on cell surface. Chemotactic GPCRs are composed of two major subfamilies: the classical GPCRs and chemokine GPCRs. Formyl-peptide receptors (FPRs) belong to the classical chemotactic GPCR subfamily with unique properties that are increasingly appreciated for their expression on diverse host cell types and the capacity to interact with a plethora of chemotactic PAMPs and MAMPs...
July 6, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28687750/5t4-specific-chimeric-antigen-receptor-modification-promotes-the-immune-efficacy-of-cytokine-induced-killer-cells-against-nasopharyngeal-carcinoma-stem-cell-like-cells
#7
Xueyang Guo, Hang Zheng, Weiren Luo, Qianbing Zhang, Jingxian Liu, Kaitai Yao
Relapse and metastasis of nasopharyngeal carcinoma (NPC) are presumably attributed to cancer stem cells (CSCs). In recent years, chimeric antigen receptor (CAR)-modified immune effector cells have been shown to have impressive antitumour efficacy. In this study, we aimed to identify appropriate tumour-associated antigens predominantly expressed on NPC stem cells (NPCSCs) and determine their suitability for CAR-engineered cytokine-induced killer (CIK) cell therapy against NPC. By investigating the expression patterns of potential target antigens (ROR1, 5T4 and CAIX) in NPC, we found that the oncofetal antigen 5T4 was predominately expressed in NPC cell lines and tissues but absent in non-cancerous nasopharyngeal tissues...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28686632/autophagy-dependent-regulation-of-tumor-metastasis-by-myeloid-cells
#8
Masahisa Jinushi, Tomoko Morita, Zhihang Xu, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Hideo Yagita, Yutaka Kawakami
Autophagy is a vital process controlling the lysosomal degradation of cellular organelles and thereby regulating tissue homeostasis in an environment-dependent fashion. Recent studies have unveiled the critical role of tumor cell-derived autophagy in regulating pro-tumor and anti-tumor processes depending on different stages and tumor microenvironments. However, the precise mechanism whereby autophagy regulates tumor progression remains largely unclear. Since myeloid cells contribute to tumor progression and metastasis, we evaluated the role of myeloid cell-specific autophagy in the regulation of tumor progression...
2017: PloS One
https://www.readbyqxmd.com/read/28685959/targeting-cholesterol-transport-in-circulating-melanoma-cells-to-inhibit-metastasis
#9
Yu-Chi Chen, Raghavendra Gowda, Raymond K Newswanger, Patrick Leibich, Barry Fell, Gerson Rosenberg, Gavin P Robertson
Despite recent break throughs in targeted- and immune-based therapies, rapid development of drug resistance remains a hurdle for the long-term treatment of melanoma patients. Targeting metastatically spreading circulating tumor cells (CTCs) may provide an additional approach to manage melanoma. This study investigates whether targeting cholesterol transport in melanoma CTCs can retard metastasis development. Nanolipolee-007, the liposomal form of leelamine, reduced melanoma metastasis in both a novel in vitro flow system mimicking the circulating system and in experimental as well as spontaneous animal metastasis models, irrespective of the BRAF mutational status of the CTCs...
July 7, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28680750/il-33-restricts-tumor-growth-and-inhibits-pulmonary-metastasis-in-melanoma-bearing-mice-through-eosinophils
#10
Valeria Lucarini, Giovanna Ziccheddu, Iole Macchia, Valentina La Sorsa, Francesca Peschiaroli, Carla Buccione, Antonella Sistigu, Massimo Sanchez, Sara Andreone, Maria Teresa D'Urso, Massimo Spada, Daniele Macchia, Claudia Afferni, Fabrizio Mattei, Giovanna Schiavoni
The alarmin IL-33 is an IL-1 family member that stimulates pleiotropic immune reactions depending on the target tissue and microenvironmental factors. In this study, we have investigated the role of IL-33/ST2 axis in antitumor response to melanoma. Injection of IL-33 in mice-bearing subcutaneous B16.F10 melanoma resulted in significant tumor growth delay. This effect was associated with intratumoral accumulation of CD8(+) T cells and eosinophils, decrease of immunosuppressive myeloid cells, and a mixed Th1/Th2 cytokine expression pattern with local and systemic activation of CD8(+) T and NK cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28680744/intratumoral-delivery-of-tumor-antigen-loaded-dc-and-tumor-primed-cd4-t-cells-combined-with-agonist-%C3%AE-gitr-mab-promotes-durable-cd8-t-cell-dependent-antitumor-immunity
#11
Zuqiang Liu, Xingxing Hao, Yi Zhang, Jiying Zhang, Cara D Carey, Louis D Falo, Walter J Storkus, Zhaoyang You
The progressive tumor microenvironment (TME) coordinately supports tumor cell expansion and metastasis, while it antagonizes the survival and (poly-)functionality of antitumor T effector cells. There remains a clear need to develop novel therapeutic strategies that can transform the TME into a pro-inflammatory niche that recruits and sustains protective immune cell populations. While intravenous treatment with tumor-primed CD4(+) T cells combined with intraperitoneal delivery of agonist anti-glucocorticoid-induced TNF receptor (α-GITR) mAb results in objective antitumor responses in murine early stage disease models, this approach is ineffective against more advanced tumors...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28666268/myeloid-specific-genetic-ablation-of-atp-binding-cassette-transporter-abca1-is-protective-against-cancer
#12
Maryam Zamanian-Daryoush, Daniel J Lindner, Joseph A DiDonato, Matthew Wagner, Jennifer Buffa, Patricia Rayman, John S Parks, Marit Westerterp, Alan R Tall, Stanley L Hazen
Increased circulating levels of apolipoprotein A-I (apoA-I), the major protein of high-density lipoprotein (HDL), by genetic manipulation or infusion, protects against melanoma growth and metastasis. Herein, we explored potential roles in melanoma tumorigenesis for host scavenger receptor class B, type 1 (SR-B1), and ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1), all mediators of apoA-I and HDL sterol and lipid transport function. In a syngeneic murine melanoma tumor model, B16F10, mice with global deletion of SR-B1 expression exhibited increased plasma HDL cholesterol (HDLc) levels and decreased tumor volume, indicating host SR-B1 does not directly contribute to HDL-associated anti-tumor activity...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28659795/exosomes-a-novel-strategy-for-treatment-and-prevention-of-diseases
#13
REVIEW
Jiaqi Wang, Xiaoyan Sun, Jiayu Zhao, Yang Yang, Xueting Cai, Jianguang Xu, Peng Cao
An "exosome" is a nanoscale membrane vesicle derived from cell endocytosis that functions as an important intercellular communication mediator regulating the exchange of proteins and genetic materials between donor and surrounding cells. Exosomes secreted by normal and cancer cells participate in tumor initiation, progression, invasion, and metastasis. Furthermore, immune cells and cancer cells exert a two-way bidirectional regulatory effect on tumor immunity by exchanging exosomes. Current studies on exosomes have further expanded their known functions in physiological and pathological processes...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28655998/exosomes-from-melatonin-treated-hepatocellularcarcinoma-cells-alter-the-immunosupression-status-through-stat3-pathway-in-macrophages
#14
Liang Cheng, Jiatao Liu, Qingqing Liu, Yu Liu, Lulu Fan, Fang Wang, Hanqing Yu, Yuhuan Li, Lijia Bu, Xiaoqiu Li, Wei Wei, Hua Wang, Guoping Sun
Immunosuppression is a significant factor in the progression of tumor invasion and metastasis. Melatonin, a well-known hormone, has certain cytotoxic and immune regulatory effects to inhibit tumor function. Exosomes are small membrane vesicles released by many kinds of cells, which contain different macromolecules, such as mRNAs and microRNAs (miRNAs), and proteins that can mediate communications between cells. Tumor-derived exosomes may cause immunosuppression, however, it is unknown whether melatonin can attenuate an immunosuppressive status by altering the function of tumor-derived exosomes...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28647610/the-jak-stat3-axis-a-comprehensive-drug-target-for-solid-malignancies
#15
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/28634284/co-administration-of-rankl-and-ctla4-antibodies-enhances-lymphocyte-mediated-anti-tumor-immunity-in-mice
#16
Elizabeth Ahern, Heidi Harjunpaa, Deborah Barkauskas, Stacey Allen, Kazuyoshi Takeda, Hideo Yagita, David Wyld, William C Dougall, Michele W L Teng, Mark J Smyth
Purpose: Novel partners for established immune checkpoint inhibitors in the treatment of cancer are needed to address the problems of primary and acquired resistance. The efficacy of combination RANKL and CTLA4 blockade in anti-tumor immunity has been suggested by recent case reports in melanoma. Here we provide a rationale for this combination in mouse models of cancer. <br />Experimental Design: The efficacy and mechanism of a combination of RANKL and CTLA4 blockade was examined by tumor infiltrating lymphocyte analysis, tumor growth and metastasis using a variety of neutralizing antibodies and gene-targeted mice...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28633645/generation-of-populations-of-antigen-specific-cytotoxic-t-cells-using-dcs-transfected-with-dna-construct-encoding-her2-neu-tumor-antigen-epitopes
#17
Maria Kuznetsova, Julia Lopatnikova, Julia Khantakova, Rinat Maksyutov, Amir Maksyutov, Sergey Sennikov
BACKGROUND: Recent fundamental and clinical studies have confirmed the effectiveness of utilizing the potential of the immune system to remove tumor cells disseminated in a patient's body. Cytotoxic T lymphocytes (CTLs) are considered the main effectors in cell-mediated antitumor immunity. Approaches based on antigen presentation to CTLs by dendritic cells (DCs) are currently being intensively studied, because DCs are more efficient in tumor antigen presentation to T cells through their initiation of strong specific antitumor immune responses than other types of antigen-presenting cells...
June 20, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28627679/exosomes-new-players-in-cancer-review
#18
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/28617999/adenosine-an-endogenous-mediator-in-the-pathogenesis-of-gynecological-cancer
#19
REVIEW
Amirhossein Bahreyni, Seyed Sattar Samani, Elnaz Ghorbani, Farzad Rahmani, Reza Khayami, Younes Toroghian, Reihane Behnam-Rassouli, Majid Khazaei, Mikhail Ryzhikov, Mohammad Reza Parizadeh, Malihe Hasanzadeh, Amir Avan, Seyed Mahdi Hassanian
Extracellular concentration of adenosine increases in the hypoxic tumor microenvironment. Adenosine signaling regulates apoptosis, angiogenesis, metastasis and immune suppression in cancer cells. Adenosine-induced cell responses depend upon different subtypes of adenosine receptors activation and type of cancer. Suppression of adenosine signaling via inhibition of adenosine receptors or adenosine generating enzymes including CD39 and CD73 on ovarian or cervical cancer cells is a potentially novel therapeutic approach for gynecological cancer patients...
June 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28611041/an-immunosuppressive-dendritic-cell-subset-accumulates-at-secondary-sites-and-promotes-metastasis-in-pancreatic-cancer
#20
Justin A Kenkel, William W Tseng, Matthew G Davidson, Lorna Tolentino, Okmi Choi, Nupur Bhattacharya, E Scott Seeley, Daniel Winer, Nathan E Reticker-Flynn, Edgar G Engleman
Pancreatic ductal adenocarcinoma (PDAC) after complete surgical resection is often followed by distant metastatic relapse for reasons that remain unclear. In this study, we investigated how the immune response at secondary sites affects tumor spread in murine models of metastatic PDAC. Early metastases were associated with dense networks of CD11b(+)CD11c(+)MHC-II(+)CD24(+)CD64(low)F4/80(low) dendritic cells (DC), which developed from monocytes in response to tumor-released GM-CSF. These cells uniquely expressed MGL2 and PD-L2 in the metastatic microenvironment and preferentially induced the expansion of T regulatory cells (Treg) in vitro and in vivo...
June 13, 2017: Cancer Research
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