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Isaac Nardi, Theresa Reno, Xinwei Yun, Terra Sztain, Jami Wang, Huifang Dai, Li Zheng, Jae Kim, Dan Raz
In the last decade, it has become clear that epigenetic changes act together with genetic mutations to promote virtually every stage of tumorigenesis and cancer progression. This knowledge has triggered searches for "epigenetic drugs" that can be developed into new cancer therapies. Here we report that triptolide reduced lung cancer incidence from 70% to 10% in a Fen1 E160D transgenic mouse model and effectively inhibited cancer growth and metastasis in A549 and H460 mouse xenografts. We found that triptolide induced lung cancer cell apoptosis that was associated with global epigenetic changes to histone 3 (H3)...
July 14, 2018: International Journal of Cancer. Journal International du Cancer
Jianzong Li, Yue Huang, Miaomiao Wu, Chuanfang Wu, Xin Li, Jinku Bao
Anaplastic lymphoma kinase (ALK) is considered as a validated molecular target in multiple malignancies, such as non-small cell lung cancer (NSCLC). However, the effectiveness of molecularly targeted therapies using ALK inhibitors is almost universally limited by drug resistance. Drug resistance to molecularly targeted therapies has now become a major obstacle to effective cancer treatment and personalized medicine. It is of particular importance to provide an improved understanding on the mechanisms of resistance of ALK inhibitors, thus rational new therapeutic strategies can be developed to combat resistance...
July 13, 2018: Scientific Reports
David S Ettinger, Dara L Aisner, Douglas E Wood, Wallace Akerley, Jessica Bauman, Joe Y Chang, Lucian R Chirieac, Thomas A D'Amico, Thomas J Dilling, Michael Dobelbower, Ramaswamy Govindan, Matthew A Gubens, Mark Hennon, Leora Horn, Rudy P Lackner, Michael Lanuti, Ticiana A Leal, Rogerio Lilenbaum, Jules Lin, Billy W Loo, Renato Martins, Gregory A Otterson, Sandip P Patel, Karen Reckamp, Gregory J Riely, Steven E Schild, Theresa A Shapiro, James Stevenson, Scott J Swanson, Kurt Tauer, Stephen C Yang, Kristina Gregory, Miranda Hughes
The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the targeted therapy and immunotherapy sections in the NCCN Guidelines. For the 2018 update, a new section on biomarkers was added.
July 2018: Journal of the National Comprehensive Cancer Network: JNCCN
Huan Tang, Yongguang Zhang, Dan Li, Suhong Fu, Minghai Tang, Li Wan, Kai Chen, Zhuowei Liu, Linlin Xue, Aihua Peng, Haoyu Ye, Lijuan Chen
EGFR T790 M accounts for 50% to 60% of cases of non-small-cell lung carcinoma (NSCLC) resistance to the first-generation EGFR tyrosine kinase inhibitors (TKIs). Hence, identifying novel compounds with activity against TKIs resistant is of great value. In this study, twenty honokiol and magnolol derivatives were isolated from the EtOH extract of Magnolia officinalis and the antiproliferative activity was evaluated on HCC827 (19del EGFR mutation), H1975 (L858 R/T790 M EGFR mutation), and H460 (KRAS mutation) cell lines...
June 27, 2018: European Journal of Medicinal Chemistry
Jimmy Ruiz, Antonius A Miller, Janet A Tooze, Sandrine Crane, William J Petty, Ajeet Gajra, Heidi D Klepin
BACKGROUND: Improved assessment strategies are needed to individualize treatment for adults of all ages receiving palliative chemotherapy for non-small cell lung cancer (NSCLC). Our aim was to evaluate the utility of the Fried Frailty Index (FFI) and a cancer-specific geriatric assessment (GA) to predict chemotherapy toxicity and overall survival (OS). METHODS: We conducted a multi-site pilot study of 50 patients with newly diagnosed advanced NSCLC, age ≥ 18 years...
July 10, 2018: Journal of Geriatric Oncology
Janna Berg, Ann Rita Halvorsen, May-Bente Bengtson, Kristin A Taskén, Gunhild M Mælandsmo, Arne Yndestad, Bente Halvorsen, Odd Terje Brustugun, Pål Aukrust, Thor Ueland, Åslaug Helland
BACKGROUND: The development of both chronic obstructive pulmonary disease (COPD) and lung cancer (LC) is influenced by smoking related chronic pulmonary inflammation caused by an excessive innate immune response to smoke exposure. In addition, the smoking induced formation of covalent bonds between the carcinogens and DNA and the accumulation of permanent somatic mutations in critical genes are important in the carcinogenic processes, and can also induce inflammatory responses. How chronic inflammation is mirrored by serum markers in COPD and LC and if these markers reflect prognosis in patients with LC is, however, largely unknown...
July 13, 2018: BMC Cancer
Jeong Uk Lim, Chang Dong Yeo, Hye Seon Kang, Chan Kwon Park, Ju Sang Kim, Jin Woo Kim, Seung Joon Kim, Sang Haak Lee
INTRODUCTION: A combination of platelet and lymphocyte to monocyte ratio (LMR) (abbreviated as COP-LMR) has been recently evaluated as systemic inflammatory marker for prognostication in lung cancer. While previous study on COP-LMR has evaluated its prognostic value in NSCLC patients who underwent curative resections, the combination of these two markers has not been evaluated in advanced NSCLC yet. OBJECTIVES: In this study, we evaluated the prognostic value of COP-LMR in stage IV NSCLC with malignant pleural effusion under active anticancer treatment...
2018: PloS One
Timothy L McMurry, George J Stukenborg, Larry G Kessler, Graham A Colditz, Melisa L Wong, Amanda B Francescatti, David R Jones, Jessica R Schumacher, Caprice C Greenberg, George J Chang, David P Winchester, Daniel P McKellar, Benjamin D Kozower
OBJECTIVE: To evaluate whether an association exists between the intensity of surveillance following surgical resection for non-small cell lung cancer (NSCLC) and survival. BACKGROUND: Surveillance guidelines following surgical resection of NSCLC vary widely and are based on expert opinion and limited evidence. METHODS: A Special Study of the National Cancer Database randomly selected stage I to III NSCLC patients for data reabstraction. For patients diagnosed between 2006 and 2007 and followed for 5 years through 2012, registrars documented all postsurgical imaging with indication (routine surveillance, new symptoms), recurrence, new primary cancers, and survival, with 5-year follow-up...
July 12, 2018: Annals of Surgery
W Jeffrey Petty, James J Urbanic, Tamjeed Ahmed, Ryan Hughes, Beverly Levine, Kyle Rusthoven, Michael Papagikos, Jimmy R Ruiz, Brian E Lally, Michael Chan, Hollins Clark, Ralph B D'Agostino, A William Blackstock
PURPOSE: Recent data indicate consolidative radiation therapy (CRT) improves progression free survival (PFS) for patients with oligometastatic non-small cell lung cancer (NSCLC). Data regarding long term outcomes are limited. METHODS AND MATERIALS: In 2010, this prospective, multi-center, single arm, phase II trial was initiated and enrolled patients with oligometastatic NSCLC. Oligometastatic disease was defined as a maximum number of five metastatic lesions for all disease sites including no more than three active extracranial metastatic lesions...
July 9, 2018: International Journal of Radiation Oncology, Biology, Physics
Marcos Nieves Sedano, José Manuel Caro Teller, Carmen García Muñoz, Delia Fernandez Redondo, Santiago Ponce Aix, Miguel Menéndez Orenga, José Miguel Ferrari Piquero
PURPOSE: Erlotinib and gefitinib are both tyrosine kinase inhibitors (TKIs) approved for the treatment of non-small cell lung cancer (NSCLC). Although it is well known that the increase of gastric pH may decrease the solubility of TKIs, there is limited evidence about the clinical repercussion of this fact. The purpose of this study was to determine if the use of gastric acid suppressive therapy (As) concomitantly with TKIs has an adverse impact on progression-free survival (PFS) and to determine whether the type of drug used (proton pump inhibitors/PPIs or histamine-2 receptors antagonists (H2RAs) may influence it...
May 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Jie Yang, Yuan Zhang, Xiaoting Sun, Aaron M Gusdon, Nan Song, Linsong Chen, Gening Jiang, Yueye Huang
PURPOSE: This study aimed to investigate the prognostic value of different organs metastases in patients with non-small cell lung cancer (NSCLC) and its most common subtypes. METHODS: We identified 45,423 NSCLC cases (25,129 men and 20,294 women) between 2010 and 2013 with distant metastases, with complete clinical information obtained from the surveillance, epidemiology, and end results (SEER) database. RESULTS: Bone and liver were the most and the least common metastatic sites with rates of 37...
July 12, 2018: Journal of Cancer Research and Clinical Oncology
Kristina Buder-Bakhaya, Jessica C Hassel
Background: Immune checkpoint inhibition (ICI) with anti-CTLA-4 and/or anti-PD-1 antibodies is standard treatment for metastatic melanoma. Anti-PD-1 (pembrolizumab, nivolumab) and anti-PD-L1 antibodies (atezolizumab, durvalumab, and avelumab) have been approved for treatment of several other advanced malignancies, including non-small-cell lung cancer (NSCLC); renal cell, and urothelial carcinoma; head and neck cancer; gastric, hepatocellular, and Merkel-cell carcinoma; and classical Hodgkin lymphoma...
2018: Frontiers in Immunology
Weiguo Zhang, Bin Qiao, Junli Fan
We aimed to elucidate the roles and regulatory mechanism of miR-4443 in regulating the resistance of non-small cell lung cancer (NSCLC) cells to epirubicin (EPI). Fifty-four advanced NSCLC patients were classified as ''insensitive'' or ''sensitive'' according to patient's responses following EPI-based chemotherapy and then the expression of miR-4443 was determined. The EPI-resistant H1299 cells were collected and transfected with miR-4443 mimics, whereas parental H1299 cells were transfected with miR-4443 inhibitors...
July 1, 2018: Die Pharmazie
Xia-Wei Zhang, Wei Liu, Hong-Li Jiang, Bing Mao
Chinese herbal medicine (CHM) has been widely used in the treatment of advanced non-small-cell lung cancer (NSCLC), but their efficacy and safety remain controversial. We sought to comprehensively aggregate and evaluate the available evidence on the efficacy and safety of the combination treatment with CHM and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC patients. Our exhausted and systematical searching strategy yielded 64 related randomized controlled trials involving 4384 patients...
July 12, 2018: American Journal of Chinese Medicine
Jing Tu, Li Ting Song, Hong Lin Zhai, Juan Wang, Xiao Yun Zhang
As an attractive therapeutic target for non-small-cell lung cancer (NSCLC), anaplastic lymphoma kinase (ALK) has got increased attention, and the selectivity of ALK inhibitors is an enormous challenge. Recently, 2,4-Diarylaminopyrimidines with high inhibitory activity over InsR/IGF1R were reported as ALK inhibitors, which harboring phosphine oxide moiety. In this work, it is the first time to reveal that the incorporation of dimethylphosphine oxide moiety and the smaller active pocket of ALK is key factor in the selectivity of inhibitor 11q toward ALK over IGF1R/InsR...
July 2, 2018: International Journal of Biological Macromolecules
Zhuo Gao, Ruiqi Liu, Na Ye, Chao Liu, Xiuli Li, Xiaodong Guo, Zhuoran Zhang, Xiaoxi Li, Yuanfei Yao, Xiaofeng Jiang
BACKGROUND/AIMS: Cell surface morphology plays pivotal roles in malignant progression and epithelial-mesenchymal transition (EMT). Previous research demonstrated that microvilli play a key role in cell migration of non-small cell lung cancer (NSCLC). In this study, we report that Forkhead box class O1 (FOXO1) is downregulated in human NSCLC and that silencing of FOXO1 is associated with the invasive stage of tumor progression. METHODS: The cell proliferation, migration, and invasion were characterized in vitro, and we tested the expression of the Epithelial-mesenchymal transition (EMT) marker by immunofluorescence staining and also identified the effect of FOXO1 on the microvilli by scanning electron microscopy (SEM)...
July 12, 2018: Cellular Physiology and Biochemistry
Wenju Liu, Xiaorong Sun, Yiqiang Qi, Xiufen Jia, Yong Huang, Ning Liu, Jinhu Chen, Shuanghu Yuan
OBJECTIVE: This study explored whether integrated texture parameter (ITP) of the fluorine-18-fluorodeoxyglucose PET (F-FDG PET) is a stratification factor for the survival of nonoperative patients with locally advanced non-small-cell lung cancer (LA-NSCLC). PATIENTS AND METHODS: Thirty-five patients with LA-NSCLC treated with chemoradiotherapy or radiotherapy were included in the retrospective study. Eight principal components (PCs) were extracted from 72 F-FDG PET texture features (TFs) using PC analysis...
August 2018: Nuclear Medicine Communications
M Alsharedi, H Bukamur, A Elhamdani
Epidermal growth factor receptor (EGFR) mutations, mostly seen in exon 19 or exon 21, are present in roughly 50% of patients with advanced non-small cell lung cancer (NSCLC) of Asian ethnicity compared with 12% in Caucasians. EGFR-mutated NSCLC patients have an increased sensitivity to EGFR tyrosine kinase inhibitors (TKIs), such as erlotinib, gefitinib or afatinib, showing superior response, progression-free survival and overall survival rates with EGFR-TKIs than with platinum doublet chemotherapy, which makes EGFR-TKIs the standard of care in this subgroup of NSCLC patients...
June 2018: Drugs of Today
Yichao Han, Hecheng Li
Lung cancer is the most frequently diagnosed cancer and the most common cause of cancer death globally, of which 85% is non-small cell lung cancer (NSCLC). Early detection of NSCLC is essential to identify potential individuals for radical cure. Although low-dose computed tomography (LDCT) is recommended as standard screening with a mortality reduction of 20%, it displays a high false positive rate that poses an issue of overdiagnosis. MicroRNAs (miRNAs) are a group of small non-coding RNAs acting as important regulators in post-transcriptional gene expression and have been studied for their extensive role as novel biomarkers in NSCLC...
May 2018: Journal of Thoracic Disease
Wen-Xian Wang, Chun-Wei Xu, Yan-Ping Chen, Wei Liu, Li-Hua Zhong, Fang-Fang Chen, Wu Zhuang, Yun-Jian Huang, Zhang-Zhou Huang, Rong-Rong Chen, Yan-Fang Guan, Xin Yi, Tang-Feng Lv, Wei-Feng Zhu, Jian-Ping Lu, Xiao-Jiang Wang, Yi Shi, Xian-Dong Lin, Gang Chen, Yong Song
Background: Advanced non-small cell lung cancer (NSCLC) patients who harbor anaplastic lymphoma kinase ( ALK ) rearrangement are sensitive to an ALK inhibitor (crizotinib), but not all ALK -positive patients benefit equally from crizotinib treatment. We analyze the impact of TP53 mutations on response to crizotinib in patients with ALK rearrangement NSCLC. Methods: Sixty-six ALK rearrangement NSCLC patients receiving crizotinib were analyzed. 21 cases were detected successfully by the next generation sequencing validation FFPE before crizotinib...
May 2018: Journal of Thoracic Disease
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