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Non small cell lung cancer

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https://www.readbyqxmd.com/read/29470986/silencing-of-lncrna-hotair-decreases-drug-resistance-of-non-small-cell-lung-cancer-cells-by-inactivating-autophagy-via-suppressing-the-phosphorylation-of-ulk1
#1
Yan Yang, Caiyu Jiang, Yang Yang, Lu Guo, Jiang Huang, Xingren Liu, Chi Wu, Jun Zou
Drug resistance is an important factor leading to the recurrence and metastasis of Non-Small Cell Lung Cancer (NSCLC). Long non-coding RNAs (LncRNAs) play important roles in drug resistance of tumor cells. The aim of our study was to investigate the mechanism of LncRNA-HOTAIR in regulating drug resistance of NSCLC cells. Our data indicated that HOTAIR was overexpressed in NSCLC cell lines. Silencing of HOTAIR decreased cell proliferation and increased apoptosis of NSCLC cells (A549). Besides that, HOTAIR shRNA transfection suppressed drug resistance of A549 cells to Crizotinib by more effectively inhibiting cell viability and promoting apoptosis compared with HOTAIR scramble group...
February 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29470540/a-674563-a-putative-akt1-inhibitor-that-also-suppresses-cdk2-activity-inhibits-human-nsclc-cell-growth-more-effectively-than-the-pan-akt-inhibitor-mk-2206
#2
Paige M Chorner, Roger A Moorehead
AKT is a serine-threonine kinase implicated in tumorigenesis as a central regulator of cellular growth, proliferation, survival, and metabolism. Activated AKT is commonly overexpressed in non-small cell lung cancer (NSCLC) and accordingly AKT inhibitors are under clinical investigation for NSCLC treatment. Thus far, the AKT inhibitors being evaluated broadly target all three (1-3) AKT isoforms but recent evidence suggests opposing roles in lung tumorigenesis where loss of Akt1 inhibits while the loss of Akt2 enhances lung tumor development...
2018: PloS One
https://www.readbyqxmd.com/read/29470536/metastatic-site-as-a-predictor-of-nivolumab-efficacy-in-patients-with-advanced-non-small-cell-lung-cancer-a-retrospective-multicenter-trial
#3
Motohiro Tamiya, Akihiro Tamiya, Takako Inoue, Madoka Kimura, Kei Kunimasa, Kenji Nakahama, Yoshihiko Taniguchi, Takayuki Shiroyama, Shun-Ichi Isa, Kazumi Nishino, Toru Kumagai, Hidekazu Suzuki, Tomonori Hirashima, Shinji Atagi, Fumio Imamura
PURPOSE: To conduct a retrospective multicenter trial to determine the significance of metastatic site as a predictor of nivolumab efficacy in patients with advanced non-small cell lung cancer. METHODS: This study was conducted across three medical centers in Japan. We retrospectively reviewed all patients who commenced nivolumab treatment at these centers between December 17, 2015 and July 31, 2016. Clinical data were collected, including age, sex, smoking status, Eastern Cooperative Oncology Group performance status, and metastatic site (lymph nodes, liver, brain, bone, lungs [intrapulmonary metastasis], and malignant pleural effusion) at the time of commencing nivolumab treatment...
2018: PloS One
https://www.readbyqxmd.com/read/29468481/licarin-a-induces-cell-death-by-activation-of-autophagy-and-apoptosis-in-non-small-cell-lung-cancer-cells
#4
Uma Maheswari, Krishna Ghosh, Sudha Rani Sadras
Lung cancer has a relatively poor prognosis with a low survival rate and drugs that target other cell death mechanism like autophagy may help improving current therapeutic strategy. This study investigated the anti-proliferative effect of Licarin A (LCA) from Myristica fragrans in non-small cell lung cancer cell lines-A549, NCI-H23, NCI-H520 and NCI-H460. LCA inhibited proliferation of all the four cell lines in a dose and time dependent manner with minimum IC50 of 20.03 ± 3.12, 22.19 ± 1.37 µM in NCI-H23 and A549 cells respectively...
February 21, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29467960/a-liquid-biopsy-for-bronchopulmonary-lung-carcinoid-diagnosis
#5
Mark Kidd, Irvin M Modlin, Ignat Drozdov, Harry Aslanian, Lisa Bodei, Somer Matar, Kyung-Min Chung
No effective blood biomarker exists to detect and clinically manage bronchopulmonary (BP) neuroendocrine tumors (NET). We developed a blood-based 51 NET-specific transcript set for diagnosis and monitoring and evaluated clinical performance metrics. It accurately diagnosed the tumor and differentiated stable from progressive disease as determined by RECIST criteria. Gene expression was evaluated in: a) publicly available BPNET transcriptomes (GSE35679); b) two BPNET cell-lines; and c) BPNET tissue with paired blood ( n = 7)...
January 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29467933/determinants-of-variability-of-five-programmed-death-ligand-1-immunohistochemistry-assays-in-non-small-cell-lung-cancer-samples
#6
Ross A Soo, Joey Sze Yun Lim, Bernadette Reyna Asuncion, Zul Fazreen, Maria Cynthia Herrera, Mohd Feroz Mohd Omar, Nguyen Hoang Diem Phuong, Ju Ee Seet, Benhur Amanuel, Barry Iacopetta, David Byrne, Shona Hendry, Stephen Fox, Richie Soong
Programmed death ligand-1 (PD-L1) expression as determined by immunohistochemistry (IHC) is potentially predictive of clinical outcome. The aim of this study was to assess the concordance of reported PD-L1 IHC assays and investigate factors influencing variability. Consecutive sections from 20 non-small cell lung cancers (NSCLCs) comprising resection, core biopsy, cytology and pleural fluid samples underwent IHC with 5 different antibody/autostainer combinations: 22C3/Link48, 28-8/BOND-MAX, E1L3N/BOND-MAX, SP142/BenchMark and SP263/BenchMark...
January 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29467866/notch-signaling-and-non-small-cell-lung-cancer
#7
Bin Zou, Xue-Liang Zhou, Song-Qing Lai, Ji-Chun Liu
Lung cancer is the leading cause of cancer-associated mortality worldwide. Elucidation of the pathogenesis and biology of lung cancer is critical for the design of an effective treatment for patients. Non-small cell lung cancer (NSCLC) accounts for 80-85% of lung cancer cases. The abnormal expression of Notch signaling pathway members is a relatively frequent event in NSCLC. The Notch signaling pathway serves important roles in cell fate determination, proliferation, differentiation and apoptosis. Increasing evidence supports the association of Notch signaling dysregulation with various types of malignant tumor, including NSCLC...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29467863/detection-of-egfr-and-braf-mutations-by-competitive-allele-specific-taqman-polymerase-chain-reaction-in-lung-adenocarcinoma
#8
Yang Yang, Yi Meng, Hang Zhang, Xiaoyan Shen, Rutian Li, Lixia Yu, Baorui Liu, Lifeng Wang
Epithelial growth factor receptor (EGFR)-tyrosine kinase inhibitors are the standard first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) expressing sensitive EGFR-mutants. Other drugs target different driver mutants, including the serine/threonine-protein kinase B-raf (BRAF) inhibitor dabrafenib, which has exhibited promising efficacy for treating patients with metastatic BRAF-mutated NSCLC. Therefore, identifying patients carrying mutations that may be treated using targeted therapies is important...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29467859/fisetin-inhibits-the-growth-and-migration-in-the-a549-human-lung-cancer-cell-line-via-the-erk1-2-pathway
#9
Junjian Wang, Shaoxiang Huang
Lung cancer is the most prevalent malignant tumor type in the developed world and the discovery of novel anti-tumor drugs is a research hotspot. Fisetin, a naturally occurring flavonoid, has been reported to have anti-cancer effects in multiple tumor types. The present study found that fisetin inhibited the growth and migration of non-small cell lung cancer in vitro . MTT, wound-healing, cell-matrix adhesion and Transwell assays were performed and demonstrated that fisetin suppressed proliferation, migration, adhesion and invasion, respectively...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29467275/pharmacological-and-structural-characterizations-of-naquotinib-a-novel-third-generation-egfr-tyrosine-kinase-inhibitor-in-egfr-mutated-non-small-cell-lung-cancer
#10
Toshiyuki Hirano, Hiroyuki Yasuda, Junko Hamamoto, Shigenari Nukaga, Keita Masuzawa, Ichiro Kawada, Katsuhiko Naoki, Tatsuya Niimi, Shinya Mimasu, Hideki Sakagami, Kenzo Soejima, Tomoko Betsuyaku
Multiple epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) have been developed to effectively inhibit EGFR-derived signals in non-small cell lung cancer (NSCLC). In this study, we assessed the efficacy of EGFR-TKIs, including a novel third-generation inhibitor naquotinib (ASP8273), in clinically relevant EGFR mutations, including L858R, exon 19 deletion, L858R+T790M, exon 19 deletion+T790M with or without a C797S mutation, and several exon 20 insertion mutations. Using structural analyses, we also elucidated the mechanism of activation and sensitivity/resistance to EGFR-TKIs in EGFR exon 20 insertion mutations...
February 21, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29467274/jak2-inhibitor-sar302503-abrogates-pd-l1-expression-and-targets-therapy-resistant-non-small-cell-lung-cancers
#11
Sean Pitroda, Melinda Stack, Gene-Fu Liu, Sui-Sui Song, Lucy Chen, Hua Liang, Akash D Parekh, Xiaona Huang, Paul B Roach, Mitchell C Posner, Ralph R Weichselbaum, Nikolai N Khodarev
Lung cancer is the leading cause of cancer deaths worldwide. Approximately 85% of all lung cancers are non-small-cell histology (NSCLC). Modern treatment strategies for NSCLC target driver oncogenes and immune checkpoints. However, less than fifteen percent of patients survive beyond five years. Here, we investigated the effects of SAR302503 (SAR), a selective JAK2 inhibitor, on NSCLC cell lines and tumors. We show that SAR is cytotoxic to NSCLC cells which exhibit resistance to genotoxic therapies, such as ionizing radiation, cisplatin, and etoposide...
February 21, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29467147/alectinib-for-advanced-alk-positive-non-small-cell-lung-cancer
#12
REVIEW
Ashley C Ly, Jacqueline L Olin, Morgan B Smith
PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, safety and tolerability, dosage and administration, and place in therapy of alectinib for treatment of patients with non-small-cell lung cancer (NSCLC) are reviewed. SUMMARY: In patients with NSCLC driven by mutations of ALK , the gene coding for anaplastic lymphoma kinase (ALK), treatment with the ALK inhibitor crizotinib has been found to provide median progression-free survival (PFS) of 10.9 months; however, therapeutic failures and tumor progression to brain metastases are common with crizotinib use, prompting research to find more potent and tolerable ALK inhibitors that target major oncogenic drivers of NSCLC...
February 21, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29466962/the-long-non-coding-rna-mycnos-01-regulates-mycn-protein-levels-and-affects-growth-of-mycn-amplified-rhabdomyosarcoma-and-neuroblastoma-cells
#13
Eleanor M O'Brien, Joanna L Selfe, Ana Sofia Martins, Zoë S Walters, Janet M Shipley
BACKGROUND: MYCN is amplified in small cell lung cancers and several pediatric tumors, including alveolar rhabdomyosarcomas and neuroblastomas. MYCN protein is known to play a key oncogenic role in both alveolar rhabdomyosarcomas and neuroblastomas. MYCN opposite strand (MYCNOS) is a gene located on the antisense strand to MYCN that encodes alternatively spliced transcripts, two of which (MYCNOS-01 and MYCNOS-02) are known to be expressed in neuroblastoma and small cell lung cancer with reciprocal regulation between MYCNOS-02 and MYCN reported for neuroblastomas...
February 21, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29466812/-non-small-cell-lung-cancer-development-of-parallel-mechanisms-of-resistance
#14
M Moeller, U Siebolts, C Wickenhauser, W Schuette
Acquired resistances to tyrosine kinase inhibitors in non-small cell lung cancer develop after 9 - 12 month. In 60 % of the cases these resistances arise because of a secondary EGFR-T790 M resistance mutation. This report is describing the case of a patient who developed parallel two different mechanisms of resistance: A T790 M resistance mutation and a transformation into a small cell neuroendocrine cancer. Under therapy with Osimertinib and chemotherapy with carboplatin and etoposide the tumor responsed partially...
February 21, 2018: Pneumologie
https://www.readbyqxmd.com/read/29466773/discovery-of-2-4-6-trisubstitued-pyrido-3-4-d-pyrimidine-derivatives-as-new-egfr-tkis
#15
Hao Zhang, Jin Wang, Ying Shen, Hui-Yan Wang, Wei-Ming Duan, Hong-Yi Zhao, Yuan-Yuan Hei, Minhang Xin, Yong-Xiao Cao, San-Qi Zhang
Targeting acquired drug resistance is the major challenge in the treatment of EGFR-driven non-small cell lung cancer (NSCLC). In this study, a novel class of compounds containing pyrido[3,4-d]pyrimidine scaffold was designed as new generation EGFR-TKIs to overcome this challenge. The most promising compound B30 inhibited HCC827 and H1975 cells growth with the IC50 values of 0.044 μM and 0.40 μM, respectively. Meanwhile, B30 displayed potent inhibitory activity against the EGFRL858R (IC50  = 1.1 nM) and EGFRL858R/T790M/C797S (IC50  = 7...
February 16, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29466052/long-noncoding-rna-snhg1-promotes-non-small-cell-lung-cancer-progression-by-up-regulating-mtdh-via-sponging-mir-145-5p
#16
Qingchun Lu, Shan Shan, Yanyan Li, Dongyi Zhu, Wenjing Jin, Tao Ren
Long noncoding RNAs participate in the progression and initiation of non-small cell lung cancer (NSCLC), although the mechanism remains unknown. The lncRNA identified as small nucleolar RNA host gene 1 ( SNHG1) is a novel lncRNA that is increased in multiple human cancers; however, the regulatory mechanism requires further investigation. In this study, we discovered that SNHG1 was markedly up-regulated in NSCLC tissues and cells and that SNHG1 silencing decreased tumor volumes. Moreover, we explored its regulatory mechanism and found that SNHG1 directly bound to microRNA (miRNA)-145-5p, isolating miR-145-5p from its target gene MTDH...
February 21, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29465823/differential-expression-of-various-clones-of-estrogen-receptor-in-cell-block-preparation-of-lung-adenocarcinoma
#17
Laleh Hakima, Kathie Schlesinger, Jaya Sunkara, Rouzan G Karabakhtsian
BACKGROUND: Women treated for breast cancer are at increased risk of developing pulmonary nodules which could represent new primary lung carcinomas or metastatic breast carcinoma. The FNA biopsy is frequently the first diagnostic choice in determining the primary site of the tumor. Estrogen receptor (ER) positivity in diagnostic tissue is generally used to favor breast over lung primary. However, the recent studies have shown a wide range of ER antibody cross reactivity with lung adenocarcinoma...
February 21, 2018: Diagnostic Cytopathology
https://www.readbyqxmd.com/read/29465809/idh2-is-a-novel-diagnostic-and-prognostic-serum-biomarker-for-non-small-cell-lung-cancer
#18
Jiang-Jiang Li, Ruilei Li, Wenxiang Wang, Baihua Zhang, Xin Song, Chunfang Zhang, Yang Gao, Qianjin Liao, Ya He, Shuo You, Zheqiong Tan, Xiangjian Luo, Yueshuo Li, Min Tang, Xinxian Weng, Wei Yi, Shifang Peng, Shaohui Liu, Ying Tan, Ann M Bode, Ya Cao
Lung cancer is the most common leading cause of cancer-related death worldwide. Late diagnosis contributes to a high mortality rate and poor survival of this cancer. In our previous study, we found that IDH2 polymorphism rs11540478 is a risk factor for lung cancer. Here, we examined IDH2 protein expression in culture medium in which two non-small-cell lung cancer (NSCLC) cell lines, H460 and A549, were growing. We found that the IDH2 protein was elevated in the culture supernatant fraction in a time and cell number-dependent manner...
February 21, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29465766/segmentectomy-versus-lobectomy-in-early-non-small-cell-lung-cancer-of-2-cm-or-less-in-size-a-population-based-study
#19
Mi Hyoung Moon, Young Kyu Moon, Seok Whan Moon
BACKGROUND AND OBJECTIVE: Standard surgical management for early stage lung cancer is lobectomy with mediastinal lymph node dissection. The feasibility of limited resection remains controversial; we retrospectively assessed lung cancer-specific survival (LCSS) and overall survival (OS) in early stage non-small cell lung cancer (NSCLC) to evaluate whether segmentectomy is comparable to standard lobectomy. METHODS: Patients with primary NSCLC of 20 mm or less who were diagnosed from 2000 to 2014 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database...
February 21, 2018: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/29464758/a-genomic-and-clinicopathologic-study-of-non-small-cell-lung-cancers-with-discordant-ros1-gene-status-by-fluorescent-in-situ-hybridization-and-immunohistochemical-analysis
#20
Jing Zhao, Xiaotong Chen, J Zheng, M Kong, B Wang, W Ding
BACKGROUND: ROS1 immunohistochemistry (IHC) using D4D6 antibody is a useful tool for screening patients with non-small cell lung cancer (NSCLC) slated for targeted therapy. Many studies and our data have identified cases that express the ROS1 protein strongly but are negative for ROS1 by fluorescent in situ hybridization (FISH). The present study investigated the driver mutation and clinicopathologic characteristics of 26 discordant cases (ROS1 IHC-positive but FISH-negative) to find new clues for distinguishing real ROS1-rearranged cases...
February 21, 2018: Histopathology
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