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https://www.readbyqxmd.com/read/29141888/lung-cancer-associated-pulmonary-hypertension-role-of-microenvironmental-inflammation-based-on-tumor-cell-immune-cell-cross-talk
#1
Soni Savai Pullamsetti, Baktybek Kojonazarov, Samantha Storn, Henning Gall, Ylia Salazar, Janine Wolf, Andreas Weigert, Nefertiti El-Nikhely, Hossein Ardeschir Ghofrani, Gabriele A Krombach, Ludger Fink, Stefan Gattenlöhner, Ulf R Rapp, Ralph Theo Schermuly, Friedrich Grimminger, Werner Seeger, Rajkumar Savai
Dyspnea is a frequent, devastating, and poorly understood symptom of advanced lung cancer. In our cohort, among 519 patients who underwent a computed tomography scan for the diagnosis of lung cancer, 250 had a mean pulmonary artery diameter of >28 mm, indicating pulmonary hypertension (PH). In human lung cancer tissue, we consistently observed increased vascular remodeling and perivascular inflammatory cell accumulation (macrophages/lymphocytes). Vascular remodeling, PH, and perivascular inflammatory cell accumulation were mimicked in three mouse models of lung cancer (LLC1, KRas(LA2) , and cRaf-BxB)...
November 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29134640/reduced-il-6-levels-and-tumor-associated-phospho-stat3-are-associated-with-reduced-tumor-development-in-a-mouse-model-of-lung-cancer-chemoprevention-with-myo-inositol
#2
Nese Unver, Oliver Delgado, Kirubel Zeleke, Amber Cumpian, Ximing Tang, Mauricio S Caetano, Hong Wang, Hiroyuki Katayama, Hua Yu, Eva Szabo, Ignacio Wistuba, Seyed Javad Moghaddam, Samir Hanash, Edwin J Ostrin
Several promising chemopreventive agents have for lung cancer emerged in preclinical models and in retrospective trials. These agents have been shown to modulate pathways altered in carcinogenesis and reduce markers of carcinogenesis in animal and cell culture models. Cancer-prone transgenic mice with oncogenic Kras expressed in the airway epithelium (Ccsp(Cre/+) ; Kras(LSL-G12D/+) ) were raised on diets compounded with myo-inositol. These animals form lung premalignant lesions in a stereotypical fashion over the ten weeks following weaning...
November 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29127023/interobserver-variation-among-pathologists-and-refinement-of-criteria-in-distinguishing-separate-primary-tumours-from-intrapulmonary-metastases-in-lung
#3
Andrew G Nicholson, Kathleen Torkko, Patrizia Viola, Edwina Duhig, Kim Geisinger, Alain C Borczuk, Kenzo Hiroshima, Ming S Tsao, Arne Warth, Sylvie Lantuejoul, Prudence A Russell, Erik Thunnissen, Alberto Marchevsky, Mari Mino-Kenudson, Mary Beth Beasley, Johan Botling, Sanja Dacic, Yasushi Yatabe, Masayuki Noguchi, William D Travis, Keith Kerr, Fred R Hirsch, Lucian R Chirieac, Ignacio I Wistuba, Andre Moreira, Jin-Haeng Chung, Teh Ying Chou, Lukas Bubendorf, Gang Chen, Giuseppe Pelosi, Claudia Poleri, Frank C Detterbeck, Wilbur A Franklin
Multiple tumor nodules (MTNs) are seen with increasing frequency in clinical practice. Based on the 2015 WHO classification of lung tumors, we assessed the reproducibility of the comprehensive histologic assessment (CHA) to distinguish second primary lung cancers (SPLC) from intrapulmonary metastases (IPM), looking for the most distinctive histological features. An international panel of lung pathologists reviewed a scanned sequential cohort of 126 tumors from 48 patients, recorded an agreed set of histologic features, including tumor typing and predominant pattern of adenocarcinoma, thereby opining whether the case was SPLC, IPM or a combination...
November 7, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29118857/analysis-of-predictive-parameters-for-the-development-of-radiation-induced-pneumonitis
#4
Toru Yamagishi, Norio Kodaka, Yoshiyuki Kurose, Kayo Watanabe, Chihiro Nakano, Kumiko Kishimoto, Takeshi Oshio, Kumiko Niitsuma, Hiroto Matsuse
INTRODUCTION: Prevention and effective treatment of radiation-induced pneumonitis (RP) could facilitate greater use of radiation therapy (RT) for lung cancer. The purpose of this study was to determine clinical parameters useful for early prediction of RP. METHODS: Blood sampling, pulmonary function testing, chest computed tomography, and bronchoalveolar lavage (BAL) were performed in patients with pathologically confirmed lung cancer who had completed ≥60 Gy of RT, at baseline, shortly after RT, and at 1 month posttreatment...
October 2017: Annals of Thoracic Medicine
https://www.readbyqxmd.com/read/29111316/concentrations-of-sp-a-and-hsp70-are-associated-with-polarization-of-macrophages-in-pleural-effusions-of-non-small-cell-lung-cancer
#5
Mariusz Kaczmarek, Malgorzata Lagiedo, Agnieszka Masztalerz, Magdalena Kozlowska, Agata Nowicka, Beata Brajer, Halina Batura-Gabryel, Jan Sikora
Damage-associated molecular pattern (DAMP) molecules can initiate an immune response through Toll-like receptors (TLRs). DAMPs are released from cells as a response to the extracellular danger and can be by-products of tissue damage. In cancer microenvironment necrotic cells release debris which has potency to become DAMPs. Non-small cell lung cancer (NSCLC) is often accompanied by pleural effusion (PE), which contains a variety of DAMPs. Surfactant protein A (SP-A) and heat shock protein 70 (Hsp70) are important DAMPs in the respiratory tract...
October 27, 2017: Immunobiology
https://www.readbyqxmd.com/read/29110840/immunohistochemical-and-genetic-characteristics-of-lung-cancer-mimicking-organizing-pneumonia
#6
Tomohiro Ichikawa, Koichi Saruwatari, Sachiyo Mimaki, Masato Sugano, Keiju Aokage, Motohiro Kojima, Tomoyuki Hishida, Satoshi Fujii, Junji Yoshida, Takeshi Kuwata, Atsushi Ochiai, Kenji Suzuki, Masahiro Tsuboi, Koichi Goto, Katsuya Tsuchihara, Genichiro Ishii
INTRODUCTION: Lung cancer mimicking organizing pneumonia (LCOP) is a novel radiological entity of lung adenocarcinoma that could be misdiagnosed as inflammatory lesions. However, the characteristic biological and genetic features of LCOP are not fully clarified. MATERIALS AND METHODS: We used thin-section CT images to select cases of (LCOP) among surgically resected lung adenocarcinoma patients. We compared the clinicopathological characteristics and the immunophenotypes of LCOP (n=44) and other lepidic-predominant adenocarcinomas (non-LCOP, n=56)...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29098034/asa404-a-vascular-disrupting-agent-as-an-experimental-treatment-approach-for-brain-tumors
#7
Oliver Bähr, Stefanie Gross, Patrick N Harter, Elmar Kirches, Christian Mawrin, Joachim P Steinbach, Michel Mittelbronn
Malignant brain tumors, including gliomas, brain metastases and anaplastic meningiomas, are associated with poor prognosis, and represent an unmet medical need. ASA404 (DMXAA), a vascular disrupting agent, has demonstrated promising results in several preclinical tumor models and early phase clinical trials. However, two phase III trials in non-small cell lung cancer reported insufficient results. The aim of the present study was to determine the effects of ASA404 on brain tumors. The effects of ASA404 were evaluated in vitro and in vivo using subcutaneous, and orthotopical models for malignant glioma (U-87, LN-229, U-251, LN-308 and Tu-2449), brain metastasis (HT-29) and malignant meningioma (IOMM-Lee)...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29095622/novel-trem-1-inhibitors-attenuate-tumor-growth-and-prolong-survival-in-experimental-pancreatic-cancer
#8
Zu T Shen, Alexander B Sigalov
Pancreatic cancer (PC) is a highly lethal cancer with an urgent need to expand the limited treatment options for patients. Tumor-associated macrophages (TAMs) promote tumor aggressiveness and metastasis. High expression of triggering receptor expressed on myeloid cells 1 (TREM-1) on TAMs directly correlates with poor survival in patients with non-small cell lung cancer (NSCLC). We have previously hypothesized that blockade of TREM-1 could be a promising therapeutic strategy to treat cancer and shown that the novel, ligand-independent TREM-1 inhibitory peptides rationally designed using the signaling chain homooligomerization (SCHOOL) strategy suppress NSCLC growth in vivo...
November 2, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29095595/matrix-metalloproteinase-cleavable-nanoparticles-for-tumor-microenvironment-and-tumor-cell-dual-targeting-drug-delivery
#9
Zhenliang Sun, Ruihong Li, Ji Sun, You Peng, Linlin Xiao, Xingxing Zhang, Yixin Xu, Man Wang
Matrix metalloproteinases (MMPs), mostly abundant in the tumor extracellular matrix (ECM), tumor cells, and tumor vasculatures, are closely correlated with tumor progression and metastasis. In this case, making use of MMPs was supposed to achieve site-specific drug delivery and a satisfactory tumor treatment effect. Herein, we rationally developed a novel tumor microenvironment and tumor cell dual-targeting nanoparticle by integrating a chemotherapeutic-loaded drug-loaded carrier and a versatile polypeptide-LinTT1-PVGLIG-TAT (LPT) which is composed of a multitargeting peptide-LinTT1 and a cell-penetrating peptide-TAT...
November 9, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29071196/trail-functionalized-gold-nanoparticles-selectively-trigger-apoptosis-in-polarized-macrophages
#10
Yen-Jang Huang, Shan-Hui Hsu
Tumor-associated macrophages (TAMs) have the same immunosuppressive effects as M2 macrophages in tumor progression and are correlated with poor-patient prognosis and survival in non-small cell lung cancer (NSCLC). Therefore, TAMs are the potential targets for cancer therapy. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of tumor necrosis factor superfamily and selectively induces cancer cell apoptosis, but not in most normal cells. Nanoparticles coated with multiple ligands can act as multivalent ligands that may actively crosslink cell surface receptors to affect downstream signals...
2017: Nanotheranostics
https://www.readbyqxmd.com/read/29055885/industrial-hog-farming-is-associated-with-altered-circulating-immunological-markers
#11
Jonathan N Hofmann, Meredith S Shiels, Melissa C Friesen, Troy J Kemp, Anil K Chaturvedi, Charles F Lynch, Christine G Parks, Ligia A Pinto, Allan Hildesheim, Michael C R Alavanja, Laura E Beane Freeman
OBJECTIVES: The previously observed inverse association between hog farming and risk of lung cancer in the Agricultural Health Study (AHS) has been attributed to endotoxin exposure, the levels of which are particularly high in industrial hog confinement facilities. We conducted an investigation to explore the potential biological mechanisms underlying this association, as well as other immunological changes associated with hog farming. METHODS: Serum immune marker levels were measured using a multiplexed bead-based assay in 61 active hog farmers and 61 controls matched on age, phlebotomy date and raising cattle...
October 21, 2017: Occupational and Environmental Medicine
https://www.readbyqxmd.com/read/29029603/the-pathophysiological-role-of-mitochondrial-oxidative-stress-in-lung-diseases
#12
REVIEW
Xiaojing Liu, Zhihong Chen
Mitochondria are critically involved in reactive oxygen species (ROS)-dependent lung diseases, such as lung fibrosis, asbestos, chronic airway diseases and lung cancer. Mitochondrial DNA (mtDNA) encodes mitochondrial proteins and is more sensitive to oxidants than nuclear DNA. Damage to mtDNA causes mitochondrial dysfunction, including electron transport chain impairment and mitochondrial membrane potential loss. Furthermore, damaged mtDNA also acts as a damage-associated molecular pattern (DAMP) that drives inflammatory and immune responses...
October 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29023999/occupational-exposure-to-diesel-engine-exhaust-and-serum-cytokine-levels
#13
Yufei Dai, Dianzhi Ren, Bryan A Bassig, Roel Vermeulen, Wei Hu, Yong Niu, Huawei Duan, Meng Ye, Tao Meng, Jun Xu, Ping Bin, Meili Shen, Jufang Yang, Wei Fu, Kees Meliefste, Debra Silverman, Nathaniel Rothman, Qing Lan, Yuxin Zheng
The International Agency for Research on Cancer has classified diesel engine exhaust (DEE) as a human lung carcinogen. Given that inflammation is suspected to be an important underlying mechanism of lung carcinogenesis, we evaluated the relationship between DEE exposure and the inflammatory response using data from a cross-sectional molecular epidemiology study of 41 diesel engine testing workers and 46 unexposed controls. Repeated personal exposure measurements of PM2.5 and other DEE constituents were taken for the diesel engine testing workers before blood collection...
October 12, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29022575/gefitinib-inhibits-m2-like-polarization-of-tumor-associated-macrophages-in-lewis-lung-cancer-by-targeting-the-stat6-signaling-pathway
#14
Muhammad Tariq, Jie-Qiong Zhang, Gui-Kai Liang, Qiao-Jun He, Ling Ding, Bo Yang
M2-like polarized tumor-associated macrophages (TAMs) play a pivotal role in promoting cancer cell growth, invasion, metastasis and angiogenesis. The identification of M2-like TAMs during tumor progression is an attractive approach for cancer therapy. In this study, we investigated the relevance of macrophage polarization and the antitumor effect of gefitinib in Lewis Lung cancer (LLC) in vitro and in vivo. Gefitinib at a concentration below 2.5 μmol/L did not cause significant growth inhibition on LLC and RAW 264...
November 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28982587/engineering-macrophage-derived-exosomes-for-targeted-paclitaxel-delivery-to-pulmonary-metastases-in-vitro-and-in-vivo-evaluations
#15
Myung Soo Kim, Matthew J Haney, Yuling Zhao, Dongfen Yuan, Irina Deygen, Natalia L Klyachko, Alexander V Kabanov, Elena V Batrakova
Exosomes have recently emerged as a promising drug delivery system with low immunogenicity, high biocompatibility, and high efficacy of delivery. We demonstrated earlier that macrophage-derived exosomes (exo) loaded with a potent anticancer agent paclitaxel (PTX) represent a novel nanoformulation (exoPTX) that shows high anticancer efficacy in a mouse model of pulmonary metastases. We now report the manufacture of targeted exosome-based formulations with superior structure and therapeutic indices for systemic administration...
October 2, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28978138/il-33-blockade-suppresses-tumor-growth-of-human-lung-cancer-through-direct-and-indirect-pathways-in-a-preclinical-model
#16
Kailing Wang, Shan Shan, Zongjun Yang, Xia Gu, Yuanyuan Wang, Chunhong Wang, Tao Ren
Non-small-cell lung cancer (NSCLC) is the most common type in lung cancer, a leading cause of cancer-related death worldwide. Our previous study unraveled a pro-cancer function of IL-33 in fueling outgrowth and metastasis of human NSCLC cells. Herein, we determined that interfere with IL-33 activity was an effective strategy for limiting NSCLC tumor growth using a preclinical model with human NSCLC xenografts. IL-33 blockade efficiently inhibited tumor growth of NSCLC xenografts in immune-deficient mice. Mechanistically, IL-33 blockade suppressed outgrowth capacity of human NSCLC cells...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28966099/a-comparison-study-between-lycobetaine-loaded-nanoemulsion-and-liposome-using-nrgd-as-therapeutic-adjuvant-for-lung-cancer-therapy
#17
Tijia Chen, Ting Gong, Ting Zhao, Yao Fu, Zhirong Zhang, Tao Gong
To achieve tumor-selective drug delivery, various nanocarriers have been explored using either passive or active targeting strategies. Despite the great number of studies published annually in the field, only nanocarriers using approved excipients reach the clinical stage. In our study, two classic nanoscale formulations, nanoemulsion (NE) and liposome (Lipo) were selected for the encapsulation of lycobetaine (LBT). To improve the lipid solubility of LBT, oleic acid (OA) was used to complex (LBT-OA) with lycobetaine (LBT)...
September 28, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28957436/is-serum-level-of-cc-chemokine-ligand-18-a-biomarker-for-the-prediction-of-radiation-induced-lung-toxicity-rilt
#18
Eleni Gkika, Werner Vach, Sonja Adebahr, Tanja Schimeck-Jasch, Anton Brenner, Thomas Baptist Brunner, Klaus Kaier, Antje Prasse, Joachim Müller-Quernheim, Anca-Ligia Grosu, Gernot Zissel, Ursula Nestle
The CC chemokine ligand 18 (CCL18) is produced by alveolar macrophages in patients with fibrosing lung disease and its concentration is increased in various fibrotic lung diseases. Furthermore CCL18 is elevated in several malignancies as it is produced by tumor associated macrophages. In this study we aimed to analyze the role of CCL18 as a prognostic biomarker for the development of early radiation induced lung toxicity (RILT), i.e. radiation pneumonitis after thoracic irradiation and its significance in the course of the disease...
2017: PloS One
https://www.readbyqxmd.com/read/28950145/determination-of-poor-prognostic-immune-features-of-tumour-microenvironment-in-non-smoking-patients-with-lung-adenocarcinoma
#19
Tomonari Kinoshita, Chie Kudo-Saito, Reiko Muramatsu, Tomonobu Fujita, Miyuki Saito, Haruna Nagumo, Toshiharu Sakurai, Shinobu Noji, Emi Takahata, Tomonori Yaguchi, Nobuo Tsukamoto, Yuichiro Hayashi, Kaoru Kaseda, Ikuo Kamiyama, Takashi Ohtsuka, Kenji Tomizawa, Masaki Shimoji, Tetsuya Mitsudomi, Hisao Asamura, Yutaka Kawakami
We have previously demonstrated that the prognostic significance of tumour-infiltrating CD8(+) T cells significantly differs according to histological type and patient smoking habits in non-small cell lung cancer (NSCLC). This work suggested that infiltrating CD8(+) T cells may not be activated sufficiently in the immunosuppressive microenvironment in non-smokers with adenocarcinoma. To understand the immunogenic microenvironment in NSCLC, we characterised immune cells comprehensively by performing an immunohistochemical evaluation using an alternative counting method and multicolour staining method (n = 234), and assessed immune-related gene expression by using genetic analytical approaches (n = 58)...
September 23, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28925793/sequential-administration-of-mva-based-vaccines-and-pd-1-pd-l1-blocking-antibodies-confers-measurable-benefits-on-tumor-growth-and-survival-preclinical-studies-with-mva-%C3%AE-gal-and-mva-muc1-tg4010-in-a-murine-tumor-model
#20
Christelle Remy-Ziller, Christine Thioudellet, Julie Hortelano, Murielle Gantzer, Virginie Nourtier, Marie-Christine Claudepierre, Benoit Sansas, Xavier Préville, Kaïdre Bendjama, Eric Quemeneur, Karola Rittner
TG4010, a Modified Vaccinia virus Ankara (MVA) expressing human mucin1 (MUC1) has demonstrated clinical benefit for patients suffering from advanced non-small cell lung cancer (NSCLC) in combination with chemotherapy. To support its development, preclinical experiments were performed with either TG4010 or β-galactosidase-encoding MVA vector (MVA-βgal) in mice presenting tumors in the lung. Tumor growth was obtained after intravenous injection of CT26 murine colon cancer cells, engineered to express either MUC1 or βgal...
September 19, 2017: Human Vaccines & Immunotherapeutics
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