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Exosomes and lung

Tonje S Steigedal, Jimita Toraskar, Richard P Redvers, Marit Valla, Synnøve N Magnussen, Anna M Bofin, Signe Opdahl, Steinar Lundgren, Bedrich L Eckhardt, John M Lamar, Judy Doherty, Richard O Hynes, Robin L Anderson, Gunbjørg Svineng
Most cancer patients with solid tumors who succumb to their illness die of metastatic disease. While early detection and improved treatment have led to reduced mortality, even for those with metastatic cancer, some patients still respond poorly to treatment. Understanding the mechanisms of metastasis is important to improve prognostication, to stratify patients for treatment, and to identify new targets for therapy. We have shown previously that expression of nephronectin (NPNT) is correlated with metastatic propensity in breast cancer cell lines...
March 11, 2018: Neoplasia: An International Journal for Oncology Research
Elena Castellanos-Rizaldos, Dominik G Grimm, Vasisht Tadigotla, James Hurley, John Healy, Patricia L Neal, Mia Sher, Raajdeep Venkatesan, Chris Karlovich, Mitch Raponi, Anne K Krug, Mikkel Noerholm, Jihane Tannous, Bakhos A Tannous, Luis E Raez, Johan Skog
PURPOSE: About 60% of non-small cell lung cancer (NSCLC) patients develop resistance to targeted epidermal growth factor receptor (EGFR) inhibitor therapy through the EGFR T790M mutation. Patients with this mutation respond well to third generation tyrosine kinase inhibitors, but obtaining a tissue biopsy to confirm the mutation poses risks and is often not feasible. Liquid biopsies using circulating free tumor DNA (cfDNA) have emerged as a non-invasive option to detect the mutation, however sensitivity is low as many patients have too few detectable copies in circulation...
March 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Rie Kanaoka, Hisae Iinuma, Hitoshi Dejima, Takashi Sakai, Hirofumi Uehara, Noriyuki Matsutani, Masafumi Kawamura
OBJECTIVES: The aim of this study was to clarify the usefulness of plasma exosomal microRNA-451a (miR-451a) as a novel biomarker for the early prediction of recurrence and prognosis in non-small cell lung cancer (NSCLC) patients after curative resection. METHODS: Before surgery, plasma samples were collected and exosomal microRNA (miRNA) levels were evaluated. We first profiled specific exosomal miRNAs related to recurrence in 6 NSCLC patients with stage IA cancer by miRNA microarray...
March 13, 2018: Oncology
Xuming Sun, Lin Huang, Ru Zhang, Wei Xu, Jingyi Huang, Deepanjali D Gurav, Vadanasundari Vedarethinam, Ruoping Chen, Jiatao Lou, Qian Wang, Jingjing Wan, Kun Qian
Current metabolic analysis is far from ideal to engage clinics and needs rationally designed materials and device. Here we developed a novel plasmonic chip for clinical metabolic fingerprinting. We first constructed a series of chips with gold nanoshells on the surface through controlled particle synthesis, dip-coating, and gold sputtering for mass production. We integrated the optimized chip with microarrays for laboratory automation and micro-/nanoscaled experiments, which afforded direct high-performance metabolic fingerprinting by laser desorption/ionization mass spectrometry using 500 nL of various biofluids and exosomes...
February 28, 2018: ACS Central Science
Charitharth Vivek Lal, Nelida Olave, Colm Travers, Gabriel Rezonzew, Kalsang Dolma, Alexandra Simpson, Brian Halloran, Zubair Aghai, Pragnya Das, Nirmal Sharma, Xin Xu, Kristopher Genschmer, Derek Russell, Tomasz Szul, Nengjun Yi, J Edwin Blalock, Amit Gaggar, Vineet Bhandari, Namasivayam Ambalavanan
Premature infants are at high risk for developing bronchopulmonary dysplasia (BPD), characterized by chronic inflammation and inhibition of lung development, which we have recently identified as being modulated by microRNAs (miRNAs) and alterations in the airway microbiome. Exosomes and exosomal miRNAs may regulate cell differentiation and tissue and organ development. We discovered that tracheal aspirates from infants with severe BPD had increased numbers of, but smaller, exosomes compared with term controls...
March 8, 2018: JCI Insight
Hsiu-Kuan Lin, Hsi-Hui Lin, Yu-Wei Chiou, Ching-Lung Wu, Wen-Tai Chiu, Ming-Jer Tang
Caveolin-1 (Cav1) is down-regulated during MK4 (MDCK cells harbouring inducible Ha-RasV12 gene) transformation by Ha-RasV12 . Cav1 overexpression abrogates the Ha-RasV12 -driven transformation of MK4 cells; however, the targeted down-regulation of Cav1 is not sufficient to mimic this transformation. Cav1-silenced cells, including MK4/shCav1 cells and MDCK/shCav1 cells, showed an increased cell area and discontinuous junction-related proteins staining. Cellular and mechanical transformations were completed when MDCK/shCav1 cells were treated with medium conditioned by MK4 cells treated with IPTG (MK4+I-CM) but not with medium conditioned by MK4 cells...
March 4, 2018: Journal of Cellular and Molecular Medicine
Muthukumar Gunasekaran, Monal Sharma, Ramsey Hachem, Ross Bremner, Michael A Smith, Thalachallour Mohanakumar
Circulating exosomes containing donor HLA and lung-associated self-antigens (SAg) are thought to play an important role in allograft rejection after human lung transplantation. We characterized exosomes isolated from serum of 10 lung transplant recipients (LTxR) diagnosed with bronchiolitis obliterans syndrome (BOS) and compared them with exosomes isolated from serum of 10 stable LTxR. Lung-associated SAg (K-α-1-tubulin [Kα1T] and collagen V [Col-V]), MHC class II molecules, costimulatory molecules CD40, CD80, and CD86, and transcription factors class II MHC trans -activator, NF-κB, hypoxia-inducible factor 1-α, IL-1R-associated kinase 1, MyD88, and 20S proteasome were detected in exosomes from BOS, but not stable LTxR...
February 28, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
S N Tamkovich, N V Yunusova, A K Somov, G V Kakurina, E S Kolegova, E A Tugurova, P P Laktionov, I V Kondakova
To increase the sensitivity and specificity of the developed methods for diagnosis of oncological diseases using exosomes of blood, a stage of pre-selection of tumor exosomes from a common pool of circulating microvesicles is required. In the present work, universal proteins have been identified, their expression has been increased in the exosomes of patients with colorectal cancer, head and neck squamous cell carcinomas, and lung cancer. The use of antibodies against major exosomal proteins will further develop a simple and high-performance method of affinity isolation of tumor exosomes...
January 2018: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
Jianwei Gao, Xiangyu Qiu, Xinying Li, Hang Fan, Fang Zhang, Tangfeng Lv, Yong Song
Exosomes are membrane-bound, virus-size vesicles present in circulating blood. Tumor cells are avid producers of exosomes, which are thought to mimic molecular features of parent tumor cells. T-cell Immunoglobulin- and Mucin-domain-containing molecule 3 (Tim-3) is one of the next generation immune checkpoints and can be activated by its ligand Galectin-9, negatively regulating anti-tumor immune response. However, the characteristics of plasma exosomal Tim-3/Galectin-9 (Exo-T/G) in cancer remained unknown. Our study aimed to investigate the expression patterns and clinical value of plasma exosomal total protein (Exo-pro) and Exo-T/G in non-small cell lung caner (NSCLC)...
February 13, 2018: Biochemical and Biophysical Research Communications
José A Cañas, Beatriz Sastre, José M Rodrigo-Muñoz, Mar Fernández-Nieto, Pilar Barranco, Santiago Quirce, Joaquín Sastre, Victoria Del Pozo
BACKGROUND: Eosinophils, a central factor in asthma pathogenesis, have the ability to secrete exosomes. However, the precise role played by exosomes in the biological processes leading up to asthma has not been fully defined. OBJECTIVE: We hypothesised that exosomes released by eosinophils contribute to asthma pathogenesis by activating structural lung cells. METHODS: Eosinophils from asthmatic patients and healthy volunteers were purified from peripheral blood, and exosomes were isolated from eosinophils of asthmatic and healthy individuals...
February 16, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Ivana Bratić Hench, Jürgen Hench, Markus Tolnay
Examination of tumor molecular characteristics by liquid biopsy is likely to greatly influence personalized cancer patient management. Analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and tumor-derived exosomes, all collectively referred to as "liquid biopsies," are not only a modality to monitor treatment efficacy, disease progression, and emerging therapy resistance mechanisms, but they also assess tumor heterogeneity and evolution in real time. We review the literature concerning the examination of ctDNA and CTC in a diagnostic setting, evaluating their prognostic, predictive, and monitoring capabilities...
2018: Frontiers in Medicine
Yufeng Xie, Jie Wu, Aizhang Xu, Shahid Ahmeqd, Amer Sami, Rajni Chibbar, Andrew Freywald, Changyu Zheng, Jim Xiang
DNA vaccines composed of heterologous human HER2 and rat neu sequences induce stronger antibody response and protective antitumor immunity than either HER2 or neu DNA vaccines in transgenic mice. We previously developed HER2-specific exosome-targeted T-cell vaccine HER2-TEXO capable of stimulating HER2-specific CD8+ T-cell responses, but only leading to partial protective immunity in double-transgenic HLA-A2/HER2 mice with self-immune tolerance to HER2. Here, we constructed an adenoviral vector AdVHuRt expressing HuRt fusion protein composed of NH2-HER21-407 (Hu) and COOH-neu408-690 (Rt) fragments, and developed a heterologous human/rat HER2-specific exosome-targeted T-cell vaccine HuRt-TEXO using polyclonal CD4+ T-cells uptaking exosomes released by AdVHuRt-transfected dendritic cells...
February 5, 2018: Vaccine
Shaohua Cui, Zhuoan Cheng, Wenxin Qin, Liyan Jiang
In lung cancer and other malignancies, the so-called "liquid biopsy" is quickly moving into clinical practice. Its full potential has not yet been fully identified, but the "liquid biopsy" is no longer a promise but has become a reality that allows for better treatment selection and monitoring of lung cancer. This emerging field has significant potential to make up for the limitations of the traditional tissue-derived biomaterials. Exosomes are spherical nano-sized vesicles with a diameter of 40-100 nm and a density of 1...
February 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Yan Sun, Chunhui Huo, Zhi Qiao, Zhi Shang, Asad Uzzaman, Sha Liu, Xiaoteng Jiang, Liu-Yin Fan, Liyun Ji, Xin Guan, Cheng-Xi Cao, Hua Xiao
Extracellular vesicles (EVs) are cell-derived microparticles present in most body fluids, mainly including microvesicles and exosomes. EVs-harbored proteins have emerged as novel biomarkers for the diagnosis and prediction of different cancers. Herein, we successfully isolated microvesicles and exosomes from human saliva, which were further characterized comprehensively. Salivary EVs protein profiling in normal subjects and lung cancer patients was systematically compared through utilizing LC-MS/MS based label free quantification...
February 5, 2018: Journal of Proteome Research
Avijit Paul, Yakov Krelin, Tasleem Arif, Rina Jeger, Varda Shoshan-Barmatz
The mitochondrial pro-apoptotic protein SMAC/Diablo participates in apoptosis by negatively regulating IAPs and activating caspases, thus encouraging apoptosis. Unexpectedly, we found that SMAC/Diablo is overexpressed in cancer. This paradox was addressed here by silencing SMAC/Diablo expression using specific siRNA (si-hSMAC). In cancer cell lines and subcutaneous lung cancer xenografts in mice, such silencing reduced cell and tumor growth. Immunohistochemistry and electron microscopy of the si-hSMAC-treated residual tumor demonstrated morphological changes, including cell differentiation and reorganization into glandular/alveoli-like structures and elimination of lamellar bodies, surfactant-producing organs...
December 24, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
Ping Zhang, Hongxing Zhou, Kefeng Lu, Yunou Lu, Yan Wang, Tongbao Feng
Background: Breast cancer is the most common cancer in women worldwide. Cancer-secreted exosomes have recently been recognized as important mediators of intercellular communication. The aim of this study was to determine the role of exosomal long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in breast cancer progression. Materials and methods: Breast cancer specimens were obtained with informed consent from patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect MALAT1 expression, and cellular proliferation was measured using cell counting kit-8 (CCK-8) assay...
2018: OncoTargets and Therapy
Tadashi Maemura, Satoshi Fukuyama, Yukihiko Sugita, Tiago J S Lopes, Tomomi Nakao, Takeshi Noda, Yoshihiro Kawaoka
Exosomes regulate cell-cell communication by transferring functional proteins and RNAs between cells. Here, to clarify the function of exosomes during influenza virus infection, we characterized lung-derived exosomal microRNAs (miRNAs). Among the detected miRNAs, miR-483-3p was present at high levels in bronchoalveolar lavage fluid (BALF) exosomes during infection of mice with various strains of influenza virus, and miR-483-3p transfection potentiated gene expression of type I interferon and proinflammatory cytokine upon viral infection of MLE-12 cells...
January 24, 2018: Journal of Infectious Diseases
Tanyalak Parimon, Rena Brauer, Saundra Y Schlesinger, Ting Xie, Dianhua Jiang, Lingyin Ge, Ying Huang, Timothy Birkland, William C Parks, David Habiel, Cory Hogaboam, Sina A Gharib, Nan Deng, Zhenqui Liu, Peter Chen
Syndecan-1 is a transmembrane proteoglycan expressed prominently by lung epithelium and has pleiotropic functions such as regulating cell migration, proliferation, and survival. Loss of syndecan-1 expression by lung cancer cells is associated with higher-grade cancers and worse clinical prognosis. We evaluated the effect of syndecan-1 in various cell-based and animal models of lung cancer and found that lung tumorigenesis was moderated by syndecan-1. We also demonstrate that syndecan-1 (or lack thereof) altered the microRNA (miRNA) cargo carried within exosomes exported from lung cancer cells...
January 17, 2018: American Journal of Pathology
Jayoung Kim, Seung-Woo Hong, Seonghan Kim, Daejin Kim, Dae Young Hur, Dong-Hoon Jin, Bomi Kim, Yeong Seok Kim
Lung cancer is one of most common types of cancer worldwide. Lung cancer results in a death higher rate each year compared to colon, breast and prostate cancer combined. Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX‑2), an enzyme of which the expression is induced by various stimuli, such as inflammation. In addition, celecoxib triggers COX-2 loading on exosomes. Exosomes are small vesicles composed of a lipid bilayer membrane and are found in most biological fluids, such as blood breast milk and urine...
February 2018: International Journal of Oncology
Bartosz Szczesny, Michela Marcatti, Akbar Ahmad, Mauro Montalbano, Attila Brunyánszki, Sofia-Iris Bibli, Andreas Papapetropoulos, Csaba Szabo
This report identifies mitochondrial DNA (mtDNA) as a target and active mediator that links low-level oxidative stress to inflammatory response in pulmonary epithelial cells. Extrusion of mtDNA into the bronchoalveolar lavage fluid occurs as an early event in mice subjected to cigarette smoke injury, concomitantly with the depletion of mtDNA in the lung tissue. In cultured lung epithelial cells, prolonged, low-level oxidative stress damages the mtDNA, without any detectable damage to the nuclear DNA. In turn, cellular depletion of the mtDNA occurs, together with a transient remodeling of cellular bioenergetics and morphology - all without any detectable impairment in overall cell viability...
January 17, 2018: Scientific Reports
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