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https://www.readbyqxmd.com/read/28344883/acquisition-of-tumor-cell-phenotypic-diversity-along-the-emt-spectrum-under-hypoxic-pressure-consequences-on-susceptibility-to-cell-mediated-cytotoxicity
#1
Stéphane Terry, Stéphanie Buart, Tuan Zea Tan, Gwendoline Gros, Muhammad Zaeem Noman, James B Lorens, Fathia Mami-Chouaib, Jean Paul Thiery, Salem Chouaib
Tumor escape to immunosurveillance and resistance to immune attacks present a major hurdle in cancer therapy, especially in the current era of new cancer immunotherapies. We report here that hypoxia, a hallmark of most solid tumors, orchestrates carcinoma cell heterogeneity through the induction of phenotypic diversity and the acquisition of distinct epithelial-mesenchymal transition (EMT) states. Using lung adenocarcinoma cells derived from a non-metastatic patient, we demonstrated that hypoxic stress induced phenotypic diversity along the EMT spectrum, with induction of EMT transcription factors (EMT-TFs) SNAI1, SNAI2, TWIST1, and ZEB2 in a hypoxia-inducible factor-1α (HIF1A)-dependent or -independent manner...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344662/nivolumab-in-renal-cell-carcinoma-latest-evidence-and-clinical-potential
#2
REVIEW
Camille Mazza, Bernard Escudier, Laurence Albiges
Similar to melanoma, renal cell carcinoma (RCC) has been historically considered as an immunogenic tumor, with interleukin 2 (IL-2) and interferon alpha (IFN-α) being the first approved treatments in the 1990s. However, these therapies were effective in only 10-20% of cases and were not well tolerated. Recently, new insights on the interaction between the immune system and tumor have identified the programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) pathway to be a key player in evading host immune responses...
March 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28344660/predictive-biomarkers-and-effectiveness-of-muc1-targeted-dendritic-cell-based-vaccine-in-patients-with-refractory-non-small-cell-lung-cancer
#3
Koji Teramoto, Yoshitomo Ozaki, Jun Hanaoka, Satoru Sawai, Noriaki Tezuka, Shozo Fujino, Yataro Daigo, Keiichi Kontani
BACKGROUND: The dendritic cell (DC)-based vaccine targeting the highly immunogenic tumor antigen, MUC1, has been promising for a cancer immunotherapy; however, predictive biomarkers for beneficial clinical responses of the vaccine remain to be determined. METHODS: DCs loaded with MUC1-derived peptide were subcutaneously administered to patients with MUC1-positive non-small cell lung cancer (NSCLC) that was refractory to standard anticancer therapies, every 2 weeks...
March 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28341226/lung-adenocarcinoma-and-squamous-cell-carcinoma-gene-expression-subtypes-demonstrate-significant-differences-in-tumor-immune-landscape
#4
Hawazin Faruki, Gregory M Mayhew, Jonathan S Serody, D Neil Hayes, Charles M Perou, Myla Lai-Goldman
INTRODUCTION: Molecular subtyping of lung Adenocarcinoma (AD) and lung Squamous Cell Carcinoma (SQ) reveal biologically diverse tumors that vary in their genomic and clinical attributes. METHODS: Using published immune cell signatures and several Lung AD and SQ gene expression datasets including The Cancer Genome Atlas (TCGA), immune response in relation to AD and SQ expression subtypes was examined. Expression of immune cell populations and other immune related genes including CD274 (PD-L1) was investigated in the tumor microenvironment relative to the expression subtypes of AD (Terminal Respiratory Unit (TRU), Proximal Proliferative (PP), and Proximal Inflammatory (PI)) and SQ subtypes (Primitive, Classical, Secretory, Basal)...
March 21, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28340578/abcb1-and-abcg2-drug-transporters-are-differentially-expressed-in-non-small-cell-lung-cancers-nsclc-and-expression-is-modified-by-cisplatin-treatment-via-altered-wnt-signaling
#5
M Vesel, J Rapp, D Feller, E Kiss, L Jaromi, M Meggyes, G Miskei, B Duga, G Smuk, T Laszlo, I Karner, J E Pongracz
BACKGROUND: Lung cancer (LC) is still the most common cause of cancer related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of all LC cases but is not a single entity. It is now accepted that, apart from the characteristic driver mutations, the unique molecular signatures of adeno- (AC) and squamous cell carcinomas (SCC), the two most common NSCLC subtypes should be taken into consideration for their management. Therapeutic interventions, however, frequently lead to chemotherapy resistance highlighting the need for in-depth analysis of regulatory mechanisms of multidrug resistance to increase therapeutic efficiency...
March 24, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28340378/current-fda-approved-treatments-for-non-small-cell-lung-cancer-and-potential-biomarkers-for-its-detection
#6
REVIEW
Karla A Ruiz-Ceja, Yolanda I Chirino
BACKGROUND: Lung cancer is the leading worldwide cancer with almost 1.5 million deaths every year. Some drugs for lung cancer treatment have been available on the market for decades, but novel drugs have emerged promising better outcomes, especially for Non-Small Cell Lung Cancer (NSCLC), which represents 75% of lung cancer cases. However, how much do drugs have evolved for NSCLC treatment? Are they sharing the same mechanism of action? AIM: In this review we analyzed how the approved drugs by Federal Drug Agency for NSCLC have advanced in the last four decades identifying shared mechanism of action of medicines against NSCLC treatment and some of the potential biomarkers for early detection...
March 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28337291/cholecystokinin-attenuates-radiation-induced-lung-cancer-cell-apoptosis-by-modulating-p53-gene-transcription
#7
Yi Han, Chongyu Su, Daping Yu, Shijie Zhou, Xiaoyun Song, Shuku Liu, Ming Qin, Yunsong Li, Ning Xiao, Xiaoqing Cao, Kang Shi, Xu Cheng, Zhidong Liu
The deregulation of p53 in cancer cells is one of the important factors by which cancer cells escape from the immune surveillance. Cholecystokinin (CCK) has strong bioactivity in the regulation of a number of cell activities. This study tests a hypothesis that CCK interferes with p53 expression to affect the apoptotic process in lung cancer (tumor) cells. In this study, tumor-bearing mice and A549 cells (a tumor cell line) were irradiated. The expression of CCK and p53 in tumor cells was assessed with RT-qPCR and Western blotting...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28337225/bufei-huoxue-capsule-attenuates-pm2-5-induced-pulmonary-inflammation-in-mice
#8
Yue Jing, Hongchun Zhang, Zhe Cai, Yukun Zhao, Ye Wu, Xuan Zheng, Ying Liu, Yuying Qin, Mingjie Gu, Jin Jin
Atmospheric fine particulate matter 2.5 (PM 2.5) may carry many toxic substances on its surface and this may pose a public health threat. Epidemiological research indicates that cumulative ambient PM2.5 is correlated to morbidity and mortality due to pulmonary and cardiovascular diseases and cancer. Mitigating the toxic effects of PM2.5 is therefore highly desired. Bufei Huoxue (BFHX) capsules have been used in China to treat pulmonary heart disease (cor pulmonale). Thus, we assessed the effects of BFHX capsules on PM2...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28335643/prospects-and-progress-of-atezolizumab-in-non-small-cell-lung-cancer
#9
Johan Vansteenkiste, Els Wauters, Keunchil Park, Achim Rittmeyer, Alan Sandler, Alexander Spira
Immunotherapy has recently come to the forefront of oncology treatment as a potential means of combating cancer by restoring the body's adaptive cancer-immunity cycle. Atezolizumab is a monoclonal antibody agent that specifically targets programmed death ligand 1 (PD-L1), a key molecule in the cancer-immunity pathway, to block binding to its receptors PD-1 and B7.1. Areas covered: This review covers the role of atezolizumab in the treatment of non-small-cell lung cancer (NSCLC). Several studies have reported promising efficacy in this indication...
March 24, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28335260/a-label-free-microelectrode-array-based-on-one-step-synthesis-of-chitosan-multi-walled-carbon-nanotube-thionine-for-ultrasensitive-detection-of-carcinoembryonic-antigen
#10
Huiren Xu, Yang Wang, Li Wang, Yilin Song, Jinping Luo, Xinxia Cai
Carcinoembryonic antigen (CEA) has been an extensively used tumor marker responsible for clinical early diagnosis of cervical carcinomas, and pancreatic, colorectal, gastric and lung cancer. Combined with micro-electro mechanical system (MEMS) technology, it is important to develop a novel immune microelectrode array (MEA) not only for rapid analysis of serum samples, but also for cell detection in vitro and in vivo. In this work, we depict a simple approach to modify chitosan-multi-walled carbon nanotubes-thionine (CS-MWCNTs-THI) hybrid film through one-step electrochemical deposition and the CS-MWCNTs-THI hybrid films are successfully employed to immobilize anti-CEA for fabricating simple, label-free, and highly sensitive electro-chemical immune MEAs...
July 11, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28331343/silencing-trim59-inhibits-invasion-migration-and-epithelial-to-mesenchymal-transition-via-tgf-%C3%AE-smad2-3-signaling-pathway-in-bladder-cancer-cells
#11
Wei Chen, Kai Zhao, Chenkui Miao, Aiming Xu, Jianzhong Zhang, Jundong Zhu, Shifeng Su, Zengjun Wang
The evolutionarily conserved genes that encode the tripartite motif (TRIM) protein family are involved in various biological processes, including cellular immunity, inflammatory reaction, antiviral activity, and tumor progression. One member of this protein family, Trim59, has been reported as a novel biomarker for the occurrence and progression of multiple human carcinomas, such as lung cancer, gastric cancer, cervical cancer, and osteosarcoma. However, little is known about the relationship between Trim59 and bladder carcinogenesis...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28331303/soluble-common-gamma-chain-exacerbates-copd-progress-through-the-regulation-of-inflammatory-t-cell-response-in-mice
#12
Byunghyuk Lee, Eunhee Ko, Jiyeon Lee, Yuna Jo, Hyunju Hwang, Tae Sik Goh, Myungsoo Joo, Changwan Hong
Cigarette smoking (CS) is a major cause of considerable morbidity and mortality by inducing lung cancer and COPD. COPD, a smoking-related disorder, is closely related to the alteration of immune system and inflammatory processes that are specifically mediated by T cells. Soluble common gamma chain (sγc) has recently been identified as a critical regulator of the development and differentiation of T cells. We examined the effects of sγc in a cigarette smoke extract (CSE) mouse model. The sγc level in CSE mice serum is significantly downregulated, and the cellularity of lymph node (LN) is systemically reduced in the CSE group...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28325757/loss-of-cd73-prevents-accumulation-of-alternatively-activated-macrophages-and-the-formation-of-prefibrotic-macrophage-clusters-in-irradiated-lungs
#13
Simone de Leve, Florian Wirsdörfer, Federica Cappuccini, Alexandra Schütze, Alina V Meyer, Katharina Röck, Linda F Thompson, Jens W Fischer, Martin Stuschke, Verena Jendrossek
While radiotherapy is a mainstay for cancer therapy, pneumonitis and fibrosis constitute dose-limiting side effects of thorax and whole body irradiation. So far, the contribution of immune cells to disease progression is largely unknown. Here we studied the role of ecto-5'-nucelotidase (CD73)/adenosine-induced changes in the myeloid compartment in radiation-induced lung fibrosis. C57BL/6 wild-type or CD73(-/-) mice received a single dose of whole thorax irradiation (WTI, 15 Gy). Myeloid cells were characterized in flow cytometric, histologic, and immunohistochemical analyses as well as RNA analyses...
March 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28325292/sirna-encapsulated-hybrid-nanoparticles-target-mutant-k-ras-and-inhibit-metastatic-tumor-burden-in-a-mouse-model-of-lung-cancer
#14
Maryna Perepelyuk, Olubunmi Shoyele, Ruth Birbe, Chellappagounder Thangavel, Yi Liu, Robert B Den, Adam E Snook, Bo Lu, Sunday A Shoyele
There is an unmet need in the development of an effective therapy for mutant K-ras-expressing non-small-cell lung cancer (NSCLC). Although various small molecules have been evaluated, an effective therapy remains a dream. siRNAs have the potential to downregulate mutant K-ras both at the protein and mRNA levels. However, a safe and effective delivery of siRNAs to tumors remains a limitation to their translational application in the treatment of this highly debilitating disease. Here we developed a novel hybrid nanoparticle carrier for effective delivery of anti-mutant K-ras to NSCLC (AKSLHN)...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28322297/standardized-herbal-formula-pm014-inhibits-radiation-induced-pulmonary-inflammation-in-mice
#15
Jee-Youn Kim, Dasom Shin, Gihyun Lee, Jin-Mo Kim, Dongwook Kim, Yong-Min An, Byung Rok Yoo, Hanna Chang, Miran Kim, Jaeho Cho, Hyunsu Bae
Radiation therapy is widely used for thoracic cancers. However, it occasionally causes radiation-induced lung injuries, including pneumonitis and fibrosis. Chung-Sang-Bo-Ha-Tang (CSBHT) has been traditionally used to treat chronic pulmonary disease in Korea. PM014, a modified herbal formula derived from CSBHT, contains medicinal herbs of seven species. In our previous studies, PM014 exhibited anti-inflammatory effects in a chronic obstructive pulmonary disease model. In this study, we have evaluated the effects of PM014 on radiation-induced lung inflammation...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28321814/immunotherapy-in-nsclc-a-promising-and-revolutionary-weapon
#16
Christian Rolfo, Christian Caglevic, Mariacarmela Santarpia, Antonio Araujo, Elisa Giovannetti, Carolina Diaz Gallardo, Patrick Pauwels, Mauricio Mahave
Lung cancer is the leader malignancy worldwide accounting 1.5 millions of deaths every year. In the United States the 5 year-overall survival is less than 20% for all the newly diagnosed patients. Cisplatin-based cytotoxic chemotherapy for unresectable or metastatic NSCLC patients in the first line of treatment, and docetaxel in the second line, have achieved positive results but with limited benefit in overall survival. Targeted therapies for EGFR and ALK mutant patients have showed better results when compared with chemotherapy, nevertheless most of patients will fail and need to be treated with chemotherapy if they still have a good performance status...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28321811/interleukin-2-old-and-new-approaches-to-enhance-immune-therapeutic-efficacy
#17
Pooja Dhupkar, Nancy Gordon
Interleukin-2 (IL-2) is a very well-known cytokine that has been studied for the past 35 years. It plays a major role in the growth and proliferation of many immune cells such NK and T cells. It is an important immunotherapy cytokine for the treatment of various diseases including cancer. Systemic delivery of IL-2 has shown clinical benefit in renal cell carcinoma and melanoma patients. However, its use has been limited by the numerous toxicities encountered with the systemic delivery. Intravenous IL-2 causes the well-known "capillary leak syndrome," or the leakage of fluid from the circulatory system to the interstitial space resulting in hypotension (low blood pressure), edema, and dyspnea that can lead to circulatory shock and eventually cardiopulmonary collapse and multiple organ failure...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28319049/resisting-fatal-attraction-a-glioma-oncometabolite-prevents-cd8-t-cell-recruitment
#18
Liliana E Lucca, David A Hafler
Immunotherapy has emerged as a potent approach for treating aggressive cancers, such as non-small-cell lung tumors and metastatic melanoma. Clinical trials are now in progress for patients with malignant gliomas; however, a better understanding of how these tumors escape immune surveillance is required to enhance antitumor immune responses. With gliomas, the recruitment of CD8+ T cells to the tumor is impaired, in part preventing containment or elimination of the tumor. In this issue of the JCI, Kohanbash and colleagues present an elegant dissection of how gliomas exploit an enzymatic activity acquired through a common mutation to abrogate the migration of CD8+ T cells to the tumor...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28317087/imaging-and-clinicopathological-features-of-nivolumab-related-cholangitis-in-patients-with-non-small-cell-lung-cancer
#19
Hisato Kawakami, Junko Tanizaki, Kaoru Tanaka, Koji Haratani, Hidetoshi Hayashi, Masayuki Takeda, Ken Kamata, Mamoru Takenaka, Masatomo Kimura, Takaaki Chikugo, Takao Sato, Masatoshi Kudo, Akihiko Ito, Kazuhiko Nakagawa
Background Nivolumab demonstrates promising efficacy for the treatment of non-small cell lung cancer and other malignancies. The clinical benefit of nivolumab, however, may be hampered by specific immune-related adverse events (irAEs), and little is known regarding nivolumab-related cholangitis. Methods A computerized search of our clinical database identified 3 metastatic non-small cell lung cancer patients with nivolumab-related cholangitis. All patients were treated with intravenous nivolumab monotherapy (3...
March 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28315073/mechanisms-of-resistance-to-immune-checkpoint-antibodies
#20
Rodrigo N Ramos, Eliane Piaggio, Emanuela Romano
Immunotherapy using checkpoint inhibitors has changed the way we treat several aggressive cancers such as melanoma, non-small cell lung and head & neck cancers, among others, with durable responses achieved in the metastatic setting. However, unfortunately, the vast majority of patients do not respond to checkpoint inhibition therapy and a minority of patients, who do respond to treatment, develop secondary resistance and experience relapse by mechanisms still inadequately understood. Emerging evidence shows that alterations in multiple signaling pathways are involved in primary and/or secondary resistance to checkpoint inhibition...
March 18, 2017: Handbook of Experimental Pharmacology
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