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Targeted therapy lung cancer

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https://www.readbyqxmd.com/read/28927099/interleukin-6-identified-as-an-important-factor-in-hypoxia-and-aldehyde-dehydrogenase-based-gefitinib-adaptive-resistance-in-non-small-cell-lung-cancer-cells
#1
Shi-Min An, Hui-Min Lei, Xu-Ping Ding, Fan Sun, Chun Zhang, Ya-Bin Tang, Hong-Zhuan Chen, Ying Shen, Liang Zhu
Gefitinib resistance and relapse of the disease were the greatest challenges facing clinical therapy of non-small-cell lung cancer (NSCLC). Of note, regarding the hypoxia condition in solid tumor tissues in vivo, roles of hypoxia in gefitinib adaptive resistance and its association with lung cancer stem cells (LCSCs) have not been fully elucidated. In the present study, the role of hypoxia in gefitinib adaptive resistance and its association with aldehyde dehydrogenase (ALDH)-based LCSC gefitinib resistance were comparatively studied using RNA-sequencing (RNA-seq) technology...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926138/tnfaip8-regulates-hippo-pathway-through-interacting-with-lats1-to-promote-cell-proliferation-and-invasion-in-lung-cancer
#2
Yong Han, ZhongPing Tang, Yue Zhao, Qingchang Li, Enhua Wang
TNFAIP8 is associated with prognosis of several human malignancies. However, the molecular mechanism of TNFAIP8 in lung cancer remains unknown. In our study, we found TNFAIP8 could enhance TEAD luciferase activity and inhibits the activity of Hippo pathway. TNFAIP8 also increased cyclin D1, CDK6 and decreased p27 in lung cancer cells. In addition, TNFAIP8 increased total YAP protein and promoted nuclear localization of YAP. More importantly, YAP depletion blocked the role of TNFAIP8 on cell cycle-related proteins and TEAD luciferase activity, revealing that TNFAIP8 regulates Hippo pathway in a YAP-dependend manner...
September 19, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28925950/targeting-host-cell-surface-nucleolin-for-rsv-therapy-challenges-and-opportunities
#3
Peter Mastrangelo, Michael J Norris, Wenming Duan, Edward G Barrett, Theo J Moraes, Richard G Hegele
Nucleolin (NCL) has been reported as a cellular receptor for the human respiratory syncytial virus (RSV). We studied the effects of re-purposing AS1411, an anti-cancer compound that binds cell surface NCL, as a possible novel strategy for RSV therapy in vitro and in vivo. AS1411 was administered to RSV-infected cultures of non-polarized (HEp-2) and polarized (MDCK) epithelial cells and to virus-infected mice and cotton rats. Results of in vitro experiments showed that AS1411, used in micromolar concentrations, was associated with decreases in the number of virus-positive cells...
September 19, 2017: Vaccines
https://www.readbyqxmd.com/read/28924214/low-frequency-magnetic-fields-induce-autophagy-associated-cell-death-in-lung-cancer-through-mir-486-mediated-inhibition-of-akt-mtor-signaling-pathway
#4
Yujun Xu, Yizhong Wang, Anran Yao, Zhen Xu, Huan Dou, Sunan Shen, Yayi Hou, Tingting Wang
Low frequency magnetic fields (LF-MFs) can affect cell proliferation in a cell-type and intensity-dependent way. Previous study has reported the anti-tumor effect of LF-MFs in lung cancers. Our previous study also optimized the intensity and duration of LF-MFs to effectively inhibit the proliferation of lung cancer cells. However, the anti-tumor mechanism of LF-MFs remains unclear, which limit the clinical application of LF-MFs in anti-tumor therapy. Here, in a well-established Lewis Lung Cancer (LLC) mouse model, we found that LF-MFs inhibit tumor growth and induce an autophagic cell death in lung cancer...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923100/checkpoint-inhibitor-is-active-against-large-cell-neuroendocrine-carcinoma-with-high-tumor-mutation-burden
#5
Victoria E Wang, Anatoly Urisman, Lee Albacker, Siraj Ali, Vincent Miller, Rahul Aggarwal, David Jablons
BACKGROUND: Large cell neuroendocrine tumor (LCNEC) of the lung is a rare and aggressive tumor similar to small cell lung cancer (SCLC). Thus, it is often treated similarly to SCLC in the front-line setting with a platinum doublet. However, treatment for patients beyond the first line remains undefined. CASE PRESENTATION: We report the case of a patient with stage IB LCNEC (PD-L1 negative but positive for PD-L1 amplification and tumor mutation burden high) who progressed after adjuvant chemotherapy after surgery and subsequent therapy with an antibody drug conjugate targeting a neuroendocrine-specific cell surface marker but achieved a significant and durable response with pembrolizumab, a humanized IgG4 monoclonal anti-PD-1 antibody...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28922792/breathing-new-life-into-hypoxia-targeted-therapies-for-non-small-cell-lung-cancer
#6
Steven H Lin, Albert C Koong
No abstract text is available yet for this article.
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28922791/targeting-hypoxia-to-improve-non-small-cell-lung-cancer-outcome
#7
Ahmed Salem, Marie-Claude Asselin, Bart Reymen, Alan Jackson, Philippe Lambin, Catharine M L West, James P B O'Connor, Corinne Faivre-Finn
Oxygen deprivation (hypoxia) in non-small cell lung cancer (NSCLC) is an important factor in treatment resistance and poor survival. Hypoxia is an attractive therapeutic target, particularly in the context of radiotherapy, which is delivered to more than half of NSCLC patients. However, NSCLC hypoxia-targeted therapy trials have not yet translated into patient benefit. Recently, early termination of promising evofosfamide and tarloxotinib bromide studies due to futility highlighted the need for a paradigm shift in our approach to avoid disappointments in future trials...
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28921309/lung-cancer-associated-brain-metastasis-molecular-mechanisms-and-therapeutic-options
#8
REVIEW
Meysam Yousefi, Tayyeb Bahrami, Arash Salmaninejad, Rahim Nosrati, Parisa Ghaffari, Seyed H Ghaffari
BACKGROUND: Lung cancer is the most common cause of cancer-related mortality in humans. There are several reasons for this high rate of mortality, including metastasis to several organs, especially the brain. In fact, lung cancer is responsible for approximately 50% of all brain metastases, which are very difficult to manage. Understanding the cellular and molecular mechanisms underlying lung cancer-associated brain metastasis brings up novel therapeutic promises with the hope to ameliorate the severity of the disease...
September 18, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28920712/maximized-nanodrug-loaded-mesenchymal-stem-cells-by-a-dual-drug-loaded-mode-for-the-systemic-treatment-of-metastatic-lung-cancer
#9
Sen Yao, Xuqian Li, Jingxuan Liu, Yuqing Sun, Zhuanhe Wang, Yanyan Jiang
Mesenchymal stem cells (MSCs), exhibiting tumor-tropic and migratory potential, can serve as cellular carriers to improve the effectiveness of anticancer agents. However, several challenges, such as the safety issue, the limited drug loading, the conservation of stemness and migration of MSCs, still remain in the MSC-based delivery system. In the present study, a novel nano-engineered MSC delivery system was established by loading doxorubicin (DOX)-polymer conjugates for the systemic treatment of pulmonary metastasis of breast cancer...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28919484/lung-cancer-epigenetics-from-knowledge-to-applications
#10
REVIEW
Michaël Duruisseaux, Manel Esteller
Lung cancer is the leading cause of cancer-related mortality worldwide. Advances in our understanding of the genomics of lung cancer have led to substantial progress in the treatment of specific molecular subsets. Immunotherapy also emerges as a major breakthrough in lung cancer treatment. However, challenges remain as a consensual approach for early lung cancer detection remains elusive while primary or secondary drug resistance eventually leads to treatment failure in all patients with advanced disease. Furthermore, a large portion of patients are still treated with conventional chemotherapy that is only modestly effective...
September 14, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28918830/metformin-has-positive-therapeutic-effects-in-colon-cancer-and-lung-cancer
#11
DeAnna Henderson, Danielle Frieson, Jeffrey Zuber, Solomon S Solomon
BACKGROUND: Metformin (MF), a diabetic drug, has antineoplastic activity as adjuvant therapy for breast cancer and prostate cancer. MF is thought to work via inhibition of mammalian target of rapamycin and activation of p53 and liver kinase B1 via adenosine 5'-monophosphate-activated protein kinase. We investigated survival, recurrences and metastasis in patients with type 2 diabetes mellitus (DM2) along with colorectal cancer (CC) or lung cancer (LC) taking MF using the electronic medical record in Memphis Veterans Affairs Medical Center (colon, n = 202; lung, n = 180)...
September 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28917254/stereotactic-radiotherapy-in-oligometastatic-cancer
#12
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/28916526/monoclonal-antibodies-directed-against-cadherin-rgd-exhibit-therapeutic-activity-against-melanoma-and-colorectal-cancer-metastasis
#13
Ruben A Bartolomé, Carmen Aizpurua, Marta Jaén, Sofia Torres, Eva Calviño, Juan I Imbaud, J Ignacio Casal
PURPOSE: New targets are required for the control of advanced metastatic disease. We investigated the use of cadherin RGD motifs, which activate the α2β1integrin pathway, as targets for the development of therapeutic monoclonal antibodies (mAbs). EXPERIMENTAL DESIGN: CDH17 fragments and peptides were prepared and used for immunization and antibody development. Antibodies were tested for inhibition of β1 integrin and cell adhesion, proliferation and invasion assays using cell lines from different cancer types: colorectal, pancreatic, melanoma and breast cancer...
September 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
#14
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/28915716/implementation-and-utilization-of-the-molecular-tumor-board-to-guide-precision-medicine
#15
REVIEW
Shuko Harada, Rebecca Arend, Qian Dai, Jessica A Levesque, Thomas S Winokur, Rongjun Guo, Martin J Heslin, Lisle Nabell, L Burt Nabors, Nita A Limdi, Kevin A Roth, Edward E Partridge, Gene P Siegal, Eddy S Yang
BACKGROUND: With rapid advances in genomic medicine, the complexity of delivering precision medicine to oncology patients across a university health system demanded the creation of a Molecular Tumor Board (MTB) for patient selection and assessment of treatment options. The objective of this report is to analyze our progress to date and discuss the importance of the MTB in the implementation of personalized medicine. MATERIALS AND METHODS: Patients were reviewed in the MTB for appropriateness for comprehensive next generation sequencing (NGS) cancer gene set testing based on set criteria that were in place...
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
#16
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
#17
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/28915686/evaluation-on-efficacy-and-safety-of-the-addition-of-x-knife-therapy-to-gefitinib-in-nsclc-patients-with-symptomatic-brain-metastases
#18
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/28915640/marsdenia-tenacissima-extract-overcomes-axl-and-met-mediated-erlotinib-and-gefitinib-cross-resistance-in-non-small-cell-lung-cancer-cells
#19
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/28914637/signal-transducer-and-activator-of-transcription-gain-of-function-primary-immunodeficiency-immunodysregulation-disorders
#20
Filippo Consonni, Laura Dotta, Francesca Todaro, Donatella Vairo, Raffaele Badolato
PURPOSE OF REVIEW: To describe primary immunodeficiencies caused by gain-of-function (GOF) mutations of signal transducer and activator of transcription (STAT) genes, a group of genetically determined disorders characterized by susceptibility to infections and, in many cases, autoimmune manifestations. RECENT FINDINGS: GOF mutations affecting STAT1 result in increased STAT tyrosine phosphorylation and secondarily increased response to STAT1-signaling cytokines, such as interferons...
September 13, 2017: Current Opinion in Pediatrics
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