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Non small cell lung cancer

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https://www.readbyqxmd.com/read/28917258/stereotactic-body-radiotherapy-for-early-stage-lung-cancer-historical-developments-and-future-strategies
#1
Kevin L M Chua, Iris Sin, Kam W Fong, Melvin L K Chua, Hiroshi Onishi
The application of radiosurgery dose escalation extra-cranially in a moving target, surrounded by critical normal tissue, presents unique dosimetric and clinical challenges. Building on a strong foundation of robust technological advancements and well-planned clinical studies, lung stereotactic body radiotherapy (SBRT) has firmly established its place in the management of early stage non-small cell lung cancer (NSCLC). Nevertheless, favourable outcomes and long-term survival still evade a substantial proportion of patients, especially for central and larger peripheral lung tumours...
September 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28917254/stereotactic-radiotherapy-in-oligometastatic-cancer
#2
Thomas A C Kennedy, Mark T Corkum, Alexander V Louie
Oligometastatic cancer describes a disease state somewhere between localized and metastatic cancer. Proposed definitions of oligometastatic disease have typically used a cut-off of five or fewer sites of disease. Treatment of oligometastatic disease should have the goal of long-term local control, and in selected cases, disease remission. While several retrospective cohorts argue for surgical excision of limited metastases (metastasectomy) as the preferred treatment option for several clinical indications, limited randomized data exists for treating oligometastases...
September 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28916653/yap-suppresses-lung-squamous-cell-carcinoma-progression-via-deregulation-of-the-dnp63-gpx2-axis-and-ros-accumulation
#3
Hsinyi Huang, Wenjing Zhang, Yafang Pan, Yijun Gao, Lei Deng, Fuming Li, Fei Li, Xueyan Ma, Shenda Hou, Jing Xu, Peixue Li, Xiaoxun Li, Guohong Hu, Cheng Li, Haiquan Chen, Lei Zhang, Hongbin Ji
Lung squamous cell carcinoma (SCC), accounting for approximately 30% of non-small cell lung cancer, is often refractory to therapy. Screening a small molecule library, we identified digitoxin as a high potency compound for suppressing human lung SCC growth in vitro and in vivo. Mechanistic investigations revealed that digitoxin attenuated YAP phosphorylation and promoted YAP nuclear sequestration. YAP activation led to excessive accumulation of reactive oxygen species (ROS) by downregulating the antioxidant enzyme GPX2 in a manner related to p63 blockade...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28916621/-64-cu-labeled-repebody-molecules-for-imaging-of-epidermal-growth-factor-receptor-expressing-tumors
#4
Ayoung Pyo, Misun Yun, Hyeon-Sik Kim, Tae-Yoon Kim, Joong-Jae Lee, Jung Young Kim, Sunwoo Lee, Seong Young Kwon, Hee-Seung Bom, Hak-Sung Kim, Dong-Yeon Kim, Jung-Joon Min
The epidermal growth factor receptor (EGFR) is a member of the erbB family of receptors and is overexpressed in many tumor types. A repebody is a newly designed non-antibody protein scaffold for tumor targeting that contains leucine-rich repeat modules. In this study, three (64)Cu-labeled anti-EGFR repebodies with different chelators were synthesized, and their biological characteristics were assessed in cultured cells and tumor-bearing mice. Methods: Repebodies (rEgAs) were synthesized with the chelators p-SCN-Bn-NOTA, DOTA-NHS ester, or p-SCN-Bn-DTPA in 1...
September 15, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28916617/nivolumab-exposure-response-analyses-of-efficacy-and-safety-in-previously-treated-squamous-or-nonsquamous-non-small-cell-lung-cancer
#5
Yan Feng, Xiaoning Wang, Gaurav Bajaj, Shruti Agrawal, Akintunde Bello, Brian Lestini, Friedrich Graf Finckenstein, Jong-Soon Park, Amit Roy
Purpose: Nivolumab is a fully human IgG4 monoclonal antiprogrammed death-1 antibody with demonstrated efficacy, including durable responses and prolonged survival, in patients with previously treated, advanced non-small cell lung cancer (NSCLC). Exposure-response (E-R) analyses for efficacy and safety were conducted to inform the benefit-risk assessment of nivolumab in this patient population.Experimental Design: The analyses used clinical trial data from patients with squamous (n = 293) or nonsquamous (n = 354) NSCLC from four clinical trials who received nivolumab doses of 1 to 10 mg/kg every 2 weeks...
September 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28916341/design-synthesis-and-biological-evaluation-of-benzamide-and-phenyltetrazole-derivatives-with-amide-and-urea-linkers-as-bcrp-inhibitors
#6
Nehaben A Gujarati, Leli Zeng, Pranav Gupta, Zhe-Sheng Chen, Vijaya L Korlipara
Breast cancer resistant protein (BCRP/ABCG2), a 72kDa plasma membrane transporter protein is a member of ABC transporter superfamily. Increased expression of BCRP causes increased efflux and therefore, reduced intracellular accumulation of many unrelated chemotherapeutic agents leading to multidrug resistance (MDR). A series of 31 benzamide and phenyltetrazole derivatives with amide and urea linkers has been synthesized to serve as potential BCRP inhibitors in order to overcome BCRP-mediated MDR. The target derivatives were tested for their cytotoxicity and reversal effects in human non-small cell lung cancer cell line H460 and mitoxantrone resistant cell line H460/MX20 using the MTT assay...
September 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28916277/circulating-tumor-cell-as-a-biomarker-for-evaluating-allogenic-nk-cell-immunotherapy-on-stage-%C3%A2-non-small-cell-lung-cancer
#7
Mao Lin, Shu-Zhen Liang, Jian Shi, Li-Zhi Niu, Ji-Bing Chen, Ming-Jie Zhang, Ke-Cheng Xu
In this study, we determined the number of peripheral blood circulating tumor cells (CTCs) pre- and post-NK in patients with stage Ⅳ non- small cell lung cancer (NSCLC) as a reference for understanding the relevance of any changes to the efficacy of NK cells therapy. The patients were given one to three courses of immunotherapy.CTC numbers and CTC-related gene expression were measured in the peripheral blood of 31 patients with stage Ⅳ NSCLC at 1day before and 7 and 30 d after NK cells therapy using magnetic activated cell sorting (MACS) and fluorescence activated cell sorting (FACS) combined with real-time quantitative PCR (RT-qPCR)...
September 12, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28916198/treatment-outcome-and-quality-of-life-of-1239-patients-with-advanced-non-small-cell-lung-cancer-final-results-from-the-prospective-german-tlk-cohort-study
#8
Ulla von Verschuer, Roland Schnell, Hans Werner Tessen, Jochen Eggert, Adrian Binninger, Lisa Spring, Martina Jänicke, Norbert Marschner
OBJECTIVES: Real-life data on advanced non-small cell lung cancer (NSCLC) are centrally important to complement the results from clinical trials and to improve the standard of care. We present data on the choice of systemic first- and second-line treatment, number of treatment lines, survival and longitudinal data on health-related quality of life (HRQOL) of patients treated by medical oncologists in Germany. MATERIALS AND METHODS: 1239 patients with advanced NSCLC were recruited at start of first-line therapy into the prospective German clinical cohort study TLK (Tumour Registry Lung Cancer) by 107 sites between February 2010 and December 2013 and followed-up until January 2016...
August 22, 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28915900/a-randomized-phase-ii-study-to-assess-the-effect-of-adjuvant-immunotherapy-using-%C3%AE-galcer-pulsed-dendritic-cells-in-the-patients-with-completely-resected-stage-ii-iiia-non-small-cell-lung-cancer-study-protocol-for-a-randomized-controlled-trial
#9
Hideo Saka, Chiyoe Kitagawa, Yukito Ichinose, Mitsuhiro Takenoyama, Hidenori Ibata, Tatsuo Kato, Koji Takami, Motohiro Yamashita, Tadashi Maeda, Sadanori Takeo, Hitoshi Ueda, Kan Okabayashi, Seiji Nagashima, Tadayuki Oka, Hidenori Kouso, Seiichi Fukuyama, Kentaro Yoshimoto, Mototsugu Shimokawa, Akiko M Saito, Suminobu Ito
BACKGROUND: As the toxicity associated with the α-GalCer-pulsed dendritic cell (DC) therapy could be considered to be negligible, its addition to postoperative adjuvant chemotherapy would be expected to greatly improve the therapeutic effect, and could result in prolonged survival. The aim of the present study is to compare the therapeutic efficacy of alpha-galactosylceramide-pulsed DC therapy in patients who have undergone a complete resection of stage II-IIIA non-small-cell lung cancer (NSCLC) followed by postoperative adjuvant therapy with cisplatin plus vinorelbine, to that in patients who did not receive additional treatment (surgical resection plus postoperative adjuvant chemotherapy only)...
September 15, 2017: Trials
https://www.readbyqxmd.com/read/28915714/the-efficacy-of-anti-pd-1-pd-l1-therapy-and-its-comparison-with-egfr-tkis-for-advanced-non-small-cell-lung-cancer
#10
REVIEW
Zhixin Sheng, Xu Zhu, Yanhua Sun, Yanxia Zhang
PURPOSE: To better understand the efficacy and safety of anti-PD-1/PD-L1 therapy (atezolizumab, pembrolizumab, nivolumab) in patients with previously treated advanced non-small-cell lung cancer (NSCLC). METHODS: The Cochrane Controlled Trial Register, Embase, Medline, and the Science Citation Index were searched for prospective published reports of atezolizumab, pembrolizumab, nivolumab in previously treated patients with advanced NSCLC. RESULTS: Finally, we identified 14 prospective published reports including four trials of atezolizumab covering 542 subjects, three trials of pembrolizumab covering 1566 subjects, seven trials of nivolumab covering 1678 subjects...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915708/targeting-metabolism-and-amp-activated-kinase-with-metformin-to-sensitize-non-small-cell-lung-cancer-nsclc-to-cytotoxic-therapy-translational-biology-and-rationale-for-current-clinical-trials
#11
REVIEW
Michael Troncone, Stephanie M Cargnelli, Linda A Villani, Naghmeh Isfahanian, Lindsay A Broadfield, Laura Zychla, Jim Wright, Gregory Pond, Gregory R Steinberg, Theodoros Tsakiridis
Lung cancer is the most fatal malignancy worldwide, in part, due to high resistance to cytotoxic therapy. There is need for effective chemo-radio-sensitizers in lung cancer. In recent years, we began to understand the modulation of metabolism in cancer and its importance in tumor progression and survival after cytotoxic therapy. The activity of biosynthetic pathways, driven by the Growth Factor Receptor/Ras/PI3k/Akt/mTOR pathway, is balanced by the energy stress sensor pathway of LKB1/AMPK/p53. AMPK responds both to metabolic and genotoxic stress...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915704/driver-genes-in-non-small-cell-lung-cancer-characteristics-detection-methods-and-targeted-therapies
#12
REVIEW
Qing-Ge Zhu, Shi-Ming Zhang, Xiao-Xiao Ding, Bing He, Hu-Qin Zhang
Lung cancer is one of the most common causes of cancer-related death in the world. The large number of lung cancer cases is non-small cell lung cancer (NSCLC), which approximately accounting for 75% of lung cancer. Over the past years, our comprehensive knowledge about the molecular biology of NSCLC has been rapidly enriching, which has promoted the discovery of driver genes in NSCLC and directed FDA-approved targeted therapies. Of course, the targeted therapies based on driver genes provide a more exact option for advanced non-small cell lung cancer, improving the survival rate of patients...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915692/biomarker-analysis-of-the-phase-3-torch-trial-for-first-line-erlotinib-versus-chemotherapy-in-advanced-non-small-cell-lung-cancer-patients
#13
Lucia Kim, Mauro Saieg, Massimo Di Maio, Ciro Gallo, Charles Butts, Fortunato Ciardiello, Ronald Feld, Dengxiao Cheng, Vittorio Gebbia, Marco Angelo Burgio, Yasmin Alam, Simona Signoriello, Antonio Rossi, Natasha Leighl, Paolo Maione, Alessandro Morabito, Geoffrey Liu, Ming-Sound Tsao, Francesco Perrone, Cesare Gridelli
BACKGROUND: The TORCH phase III trial compared the efficacy of first-line erlotinib followed by chemotherapy at progression (experimental arm) with the reverse sequence (standard arm) in unselected advanced non-small cell lung cancer (NSCLC) patients. Here we report biomarker analyses. METHODS: EGFR and KRAS mutation, expression of EGFR family members and of cMET and PTEN and EGFR and ABCG2 germline polymorphisms were tested on tumor tissue or blood samples to either confirm previously proposed predictive role or describe it in an explorative setting...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915686/evaluation-on-efficacy-and-safety-of-the-addition-of-x-knife-therapy-to-gefitinib-in-nsclc-patients-with-symptomatic-brain-metastases
#14
Linbo Cai, Xiaoguang Qiu, Haihong Yang, Mingyao Lai, Changguo Shan, Weiping Hong, Juan Li, Longhui Luo, Ping Zhang, Lichao Wang
BACKGROUND: Stereotactic radiosurgery (SRS) is a widely used therapy for brain metastases(BMs) in Non-small cell lung cancer(NSCLC). However, its role in symptomatic patients with EGFR mutation remains unclear. We have retrospectively reviewed the clinical data of patients with symptomatic BMs whom received SRS as a salvage approach and concurrent gifitinib therapy. METHODS: Seven patients with primary NSCLC, symptomatic BMs, and EGFR mutation were identified in a retrospective review of patients treated with SRS using X-knife at Guangdong 999 Brain Hospital between 1 January 2012 and 31 August 2014...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915678/meta-analysis-of-the-incidence-and-risks-of-interstitial-lung-disease-and-qtc-prolongation-in-non-small-cell-lung-cancer-patients-treated-with-alk-inhibitors
#15
Liping Lin, Juanjuan Zhao, Ning Kong, Yan He, Jiazhu Hu, Fuxi Huang, Jianjun Han, Xiaolong Cao
BACKGROUND: To conduct a systematic review and meta-analysis to assess the overall incidence and risk of interstitial lung disease (ILD) and QTc prolongation associated with anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (-TKIs) in non-small-cell lung cancer (NSCLC) patients. RESULTS: A total of 1,770 patients from 8 clinical trials were included. The incidences of high-grade ILD and QTc prolongation was 2.5% (95% CI 1.7-3.6%), and 2.8% (95% CI 1.8-4...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915677/docetaxel-versus-docetaxel-plus-cisplatin-for-non-small-cell-lung-cancer-a-meta-analysis-of-randomized-clinical-trials
#16
Ang Li, Zhi-Jian Wei, Han Ding, Hao-Shuai Tang, Heng-Xing Zhou, Xue Yao, Shi-Qing Feng
OBJECTIVE: To compare the activity, efficacy and toxicity of docetaxel versus docetaxel plus cisplatin in patients with non-small-cell lung cancer. METHODS: A literature search was performed in the EMBASE, Medline, Cochrane Library, Web of Science, China National Knowledge Internet, Wan-fang databases. The trials that were found were then evaluated for eligibility. The Cochrane Collaboration's Review Manager software was used to perform the meta-analyses. RESULTS: Nine clinical trials including 1257 patients were included...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915650/microrna-107-5p-suppresses-non-small-cell-lung-cancer-by-directly-targeting-oncogene-epidermal-growth-factor-receptor
#17
Ping Wang, Xiaomin Liu, Yang Shao, Huimin Wang, Chen Liang, Baohui Han, Zhongliang Ma
MicroRNAs (miRNAs) are dysregulated in cancers, including human non-small cell lung cancer (NSCLC). The function of MicroRNA-107-5p (miR-107-5p) in NSCLC is not fully elucidated. Epidermal growth factor receptor (EGFR) is a cancer-driven gene in tumorigenesis. In this study, we found that miR-107-5p was significantly decreased in NSCLC tissues and NSCLC cell lines. Moreover, our results indicated that miR-107-5p could suppress cell proliferation, inhibit metastasis, impede cell cycle, and promote apoptosis via directly targeting EGFR...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915640/marsdenia-tenacissima-extract-overcomes-axl-and-met-mediated-erlotinib-and-gefitinib-cross-resistance-in-non-small-cell-lung-cancer-cells
#18
Shu-Yan Han, Wei Zhao, Hai-Bo Han, Hong Sun, Dong Xue, Yan-Na Jiao, Xi-Ran He, Shan-Tong Jiang, Ping-Ping Li
Tyrosine kinase inhibitors (TKIs) are an effective treatment strategy for non-small cell lung cancer (NSCLC) patients harboring mutations that result in constitutive activation of the epidermal growth factor receptor (EGFR). However, most patients eventually develop resistance to TKIs. This occurs due to additional EGFR mutations or the activation of bypass signaling pathways. In our previous work, we demonstrated that Marsdenia tenacissima extract (MTE) restored gefitinib sensitivity in resistant NSCLC cells with EGFR T790M or K-ras mutations...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915624/microwave-ablation-combined-with-egfr-tkis-versus-only-egfr-tkis-in-advanced-nsclc-patients-with-egfr-sensitive-mutations
#19
Zhigang Wei, Xin Ye, Xia Yang, Aimin Zheng, Guanghui Huang, Wenhong Li, Jiao Wang, Xiaoying Han, Min Meng, Yang Ni
We conducted this retrospective study to investigate whether microwave ablation (MWA) of primary tumor sites plus epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) could improve survival in advanced non small cell lung cancer (NSCLC) with EGFR mutations. MWA was conducted at the primary tumor sites, followed by EGFR-TKIs in the MWA plus EGFR-TKIs group. EGFR-TKIs were administered until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS) and objective response rate (ORR)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915609/polymorphisms-of-pri-mir-219-1-are-associated-with-the-susceptibility-and-prognosis-of-non-small-cell-lung-cancer-in-a-northeast-chinese-population
#20
Chang Zheng, Xuelian Li, Lingzi Xia, Xue Fang, Xiaowei Quan, Zhihua Yin, Yuxia Zhao, Baosen Zhou
Occurrence and development of non-small cell lung cancer (NSCLC) is a complex process affected both by gene and environment. Single nucleotide polymorphisms (SNPs) in microRNAs' (miRNAs) biogenesis influenced the expression of mature miRNAs, further had an impact on risk of NSCLC. Our study focused on the correlation between rs213210, rs421446 or rs107822 polymorphisms in pri-miR-219-1 and susceptibility or prognosis of NSCLC in Chinese. A case-control study of 405 new-diagnosis patients and 405 controls was performed...
August 22, 2017: Oncotarget
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