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Targeted therapy lung cancer

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https://www.readbyqxmd.com/read/28633205/advancing-the-science-of-myocardial-recovery-with-mechanical-circulatory-support-a-working-group-of-the-national-heart-lung-and-blood-institute
#1
EDITORIAL
Stavros G Drakos, Francis D Pagani, Martha S Lundberg, Timothy J Baldwin
The medical burden of heart failure (HF) has spurred interest in clinicians and scientists to develop therapies to restore the function of a failing heart. To advance this agenda, the National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group of experts from June 2 to 3, 2016, in Bethesda, Maryland, to develop NHLBI recommendations aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). MCS devices effectively reduce volume and pressure overload that drives the cycle of progressive myocardial dysfunction, thereby triggering structural and functional reverse remodeling...
July 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28631574/microrna-125a-5p-plays-a-role-as-a-tumor-suppressor-in-lung-carcinoma-cells-by-directly-targeting-stat3
#2
Lou Zhong, Siyuan Sun, Jiahai Shi, Fei Cao, Xiao Han, Zhong Chen
Increasing evidence supports that the dysregulation of microRNA expression plays an important role in the process of tumor occurrence and development. Studies have found that mir-125a-5p expression was downregulated in a variety of tumors, but the effects and mechanism of mir-125a-5p in lung cancer are still unclear. The aim of this study is to detect the expression of mir-125a-5p in lung cancer tissues and lung cancer cell lines and to explore the effects of mir-125a-5p on the biological characteristics of lung cancer cells; thus, this study aims to provide new methods and new strategies for the treatment of lung cancer...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28630215/mechanisms-of-primary-drug-resistance-in-fgfr1-amplified-lung-cancer
#3
Florian Malchers, Meryem Seda Ercanoglu, Daniel Schütte, Roberta Castiglione, Verena Tischler, Sebastian Michels, Ilona Dahmen, Johannes Brägelmann, Roopika Menon, Johannes M Heuckmann, Julie George, Sascha Ansén, Martin L Sos, Alex Soltermann, Martin Peifer, Jurgen Wolf, Reinhard Büttner, Roman K Thomas
<br />The 8p12-p11 locus is frequently amplified in squamous cell lung cancer (SQLC); the receptor tyrosine kinase fibroblast growth factor receptor 1 (FGFR1) being one of the most prominent targets of this amplification. Thus, small molecules inhibiting FGFRs have been employed to treat FGFR1-amplified SQLC. However, only about 11% of such FGFR1-amplified tumors respond to single agent FGFR inhibition and several tumors exhibited insufficient tumor shrinkage, compatible with the existence of drug-resistant tumor cells...
June 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28629461/cost-effectiveness-of-lung-cancer-screening-and-treatment-methods-a-systematic-review-of-systematic-reviews
#4
Farbod Ebadifard Azar, Saber Azami-Aghdash, Fatemeh Pournaghi-Azar, Alireza Mazdaki, Aziz Rezapour, Parvin Ebrahimi, Negar Yousefzadeh
BACKGROUND: Due to extensive literature in the field of lung cancer and their heterogeneous results, the aim of this study was to systematically review of systematic reviews studies which reviewed the cost-effectiveness of various lung cancer screening and treatment methods. METHODS: In this systematic review of systematic reviews study, required data were collected searching the following key words which selected from Mesh: "lung cancer", "lung oncology", "lung Carcinoma", "lung neoplasm", "lung tumors", "cost- effectiveness", "systematic review" and "Meta-analysis"...
June 19, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28628092/tissue-resident-memory-features-are-linked-to-the-magnitude-of-cytotoxic-t-cell-responses-in-human-lung-cancer
#5
Anusha-Preethi Ganesan, James Clarke, Oliver Wood, Eva M Garrido-Martin, Serena J Chee, Toby Mellows, Daniela Samaniego-Castruita, Divya Singh, Grégory Seumois, Aiman Alzetani, Edwin Woo, Peter S Friedmann, Emma V King, Gareth J Thomas, Tilman Sanchez-Elsner, Pandurangan Vijayanand, Christian H Ottensmeier
Therapies that boost the anti-tumor responses of cytotoxic T lymphocytes (CTLs) have shown promise; however, clinical responses to the immunotherapeutic agents currently available vary considerably, and the molecular basis of this is unclear. We performed transcriptomic profiling of tumor-infiltrating CTLs from treatment-naive patients with lung cancer to define the molecular features associated with the robustness of anti-tumor immune responses. We observed considerable heterogeneity in the expression of molecules associated with activation of the T cell antigen receptor (TCR) and of immunological-checkpoint molecules such as 4-1BB, PD-1 and TIM-3...
June 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28625639/longitudinal-monitoring-of-ctdna-egfr-mutation-burden-from-urine-correlates-with-patient-response-to-egfr-tkis-a-case-series
#6
Nishan Tchekmedyian, Raja Mudad, Fernando F Blanco, Victoria M Raymond, Jordan Garst, Mark G Erlander, Eric Haura, David Berz
Targetable, somatic EGFR mutations are highly prevalent in patients with non-small cell lung cancer (NSCLC), making them eligible for tyrosine kinase inhibitor (TKI) therapy. Circulating tumor DNA (ctDNA), isolated from blood or urine, has been demonstrated to reliably identify somatic tumor associated EGFR mutations, specifically in patients with inconclusive biopsy. When conventional imaging modalities are inconclusive, quantitative assessment of systemic ctDNA burden has the potential to assess therapeutic response...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28625637/a-randomized-phase-2-evaluation-of-the-chk1-inhibitor-ly2603618-administered-in-combination-with-pemetrexed-and-cisplatin-in-patients-with-advanced-nonsquamous-non-small-cell-lung-cancer
#7
Thomas Wehler, Michael Thomas, Christian Schumann, Joaquim Bosch-Barrera, Nuria Viñolas Segarra, Nicolas J Dickgreber, Klaus Dalhoff, Martin Sebastian, Jesus Corral Jaime, Miriam Alonso, Scott M Hynes, Ji Lin, Karla Hurt, Aimee Bence Lin, Emiliano Calvo, Luis Paz-Ares
This phase 2 portion of a phase 1/2 study examined the efficacy and safety of LY2603618, a selective checkpoint kinase 1 inhibitor, combined with pemetrexed and cisplatin (LY+Pem+Cis) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). This multicenter, randomized, controlled, open-label study (NCT01139775) enrolled patients with stage IV nonsquamous NSCLC and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized (2:1) to LY+Pem+Cis or pemetrexed and cisplatin (Pem+Cis)...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28625636/prognostic-impact-of-ttf-1-expression-in-patients-with-stage-iv-lung-adenocarcinomas
#8
Juliana B Schilsky, Ai Ni, Linda Ahn, Sutirtha Datta, William D Travis, Mark G Kris, Jamie E Chaft, Natasha Rekhtman, Matthew D Hellmann
OBJECTIVES: Thyroid transcription factor 1 (TTF-1) is routinely tested in the diagnostic evaluation of suspected lung cancers, is commonly expressed by lung adenocarcinomas, and may modulate lung cancer biology. We examined the role of TTF-1 as a predictive and prognostic marker in patients with advanced lung adenocarcinomas. MATERIALS AND METHODS: We analyzed clinical, pathologic, and molecular features, treatments received, and overall survival obtained from the medical records of 479 consecutive patients at a single site with stage IV lung adenocarcinomas and evaluable TTF-1 expression...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28625151/na-k-atpase-as-a-target-for-treatment-of-tissue-fibrosis
#9
Sergei N Orlov, Jenifer La, Larisa V Smolyaninova, Nickolai O Dulin
Myofibroblast activation is a critical process in the pathogenesis of tissue fibrosis accounting for 45% of all deaths. No effective therapies are available for the treatment of fibrotic diseases. We focus our mini-review on recent data showing that cardiotonic steroids (CTS) that are known as potent inhibitors of Na+,K+-ATPase affect myofibroblast differentiation in a cell type-specific manner. In cultured human lung fibroblasts (HLF), epithelial cells, and cancer-associated fibroblasts, CTS blocked myofibroblast differentiation triggered by profibrotic cytokine TGF-β...
June 19, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28624922/targeting-the-pd-1-pd-l1-immune-checkpoint-in-egfr-mutated-or-alk-translocated-non-small-cell-lung-cancer
#10
Olivier Bylicki, Nicolas Paleiron, Jacques Margery, Florian Guisier, Alain Vergnenegre, Gilles Robinet, Jean-Bernard Auliac, Radj Gervais, Christos Chouaid
Immune checkpoint inhibitors, notably antibodies targeting programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1), have modified the management of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). Several PD-1/PD-L1 inhibitors have been approved by health authorities for this indication and others are in clinical development. However, only a subset of patients truly benefits from these agents. For patients with mutated EGFR or translocated ALK NSCLC, for whom an immune checkpoint inhibitor can be prescribed after progression on tyrosine kinase inhibitors and chemotherapy, information is scarce and sometimes contradictory...
June 18, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28624921/lung-adenocarcinoma-survival-in-egfr-mutated-african-caribbean-patients-a-multicenter-study-in-the-french-west-indies
#11
Nicolas Leduc, Vincent Atallah, Moustapha Agossou, Vincent Vinh-Hung, Mathieu Orre, Paul Sargos, Vincent Molinie
BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. Shorter survival has been repeatedly reported for patients of African ancestry. Multivariate analysis demonstrated that this gap could be a consequence of socio-economic disparities instead of genetic specificities. However, those results were obtained in a pre-targeted therapies era and the effect of tyrosine kinase inhibitors targeting EGFR are not known in this population. OBJECTIVE: In this French West Indies study, we report overall survival (OS) in a frequently mutated population treated for lung adenocarcinoma within an equal-access healthcare system...
June 18, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28624806/targeting-the-tumor-promoting-microenvironment-in-met-amplified-nsclc-cells-with-a-novel-inhibitor-of-pro-hgf-activation
#12
Benjamin Y Owusu, Shantasia Thomas, Phanindra Venukadasula, Zhenfu Han, James W Janetka, Robert A Galemmo, Lidija Klampfer
Targeted therapeutic agents, such as inhibitors of epithelial growth factor receptor (EGFR), have transformed the management of non-small cell lung cancer (NSCLC) patients. MET-amplified NSCLC cells display resistance to EGFR-targeting agents, but are addicted to MET signaling for survival and proliferation and are sensitive to MET inhibition. However, responsive cancer cells invariably develop resistance to MET-targeted treatment.The tumor microenvironment plays a major role in resistance to anticancer therapy...
May 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28624450/%C3%AE-elemene-inhibits-tumor-promoting-effect-of-m2-macrophages-in-lung-cancer
#13
Xiaomu Yu, Maoyi Xu, Na Li, Zongjuan Li, Hongye Li, Shujuan Shao, Kun Zou, Lijuan Zou
Macrophages in tumor are mostly M2-polarized and have been reported to promote tumorigenesis, which are also defined as tumor-associated macrophages (TAMs). β-elemene has therapeutic effects against several cancers, however, it remains unknown whether β-elemene could inhibit cancer by targeting TAMs. Herein, we examined the effect of β-elemene on macrophages to elucidate a novel mechanism of β-elemene in tumor therapy. We showed that the conditioned medium of M2 macrophages promoted lung cancer cells to migration, invasion and epithelial mesenchymal transition, which could be inhibited by β-elemene...
June 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28623259/microrna-34a-encapsulated-in-hyaluronic-acid-nanoparticles-induces-epigenetic-changes-with-altered-mitochondrial-bioenergetics-and-apoptosis-in-non-small-cell-lung-cancer-cells
#14
Malav Trivedi, Amit Singh, Meghna Talekar, Grishma Pawar, Parin Shah, Mansoor Amiji
Therapies targeting epigenetic changes for cancer treatment are in Phase I/II trials; however, all of these target only nuclear DNA. Emerging evidence suggests presence of methylation marks on mitochondrial DNA (mtDNA); but their contribution in cancer is unidentified. Expression of genes encoded on mtDNA are altered in cancer cells, along with increased glycolytic flux. Such glycolytic flux and elevated reactive oxygen species is supported by increased antioxidant; glutathione. MicroRNA-34a can translocate to mitochondria, mediate downstream apoptotic effects of tumor suppressor P53, and inhibit the antioxidant response element Nrf-2, resulting in depleted glutathione levels...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622690/exploiting-cancer-s-phenotypic-guise-against-itself-targeting-ectopically-expressed-peptide-g-protein-coupled-receptors-for-lung-cancer-therapy
#15
REVIEW
Mahjabin Khan, Tao Huang, Cheng-Yuan Lin, Jiang Wu, Bao-Min Fan, Zhao-Xiang Bian
Lung cancer, claiming millions of lives annually, has the highest mortality rate worldwide. This advocates the development of novel cancer therapies that are highly toxic for cancer cells but negligibly toxic for healthy cells. One of the effective treatments is targeting overexpressed surface receptors of cancer cells with receptor-specific drugs. The receptors-in-focus in the current review are the G-protein coupled receptors (GPCRs), which are often overexpressed in various types of tumors. The peptide subfamily of GPCRs is the pivot of the current article owing to the high affinity and specificity to and of their cognate peptide ligands, and the proven efficacy of peptide-based therapeutics...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28621369/transport-of-nanoparticles-across-pulmonary-surfactant-monolayer-a-molecular-dynamics-study
#16
Yan Xu, Li Deng, Hao Ren, Xianren Zhang, Fang Huang, Tongtao Yue
Pulmonary nanodrug delivery is an emerging concept, especially for targeted lung cancer therapy. Once inhaled, the nanoparticles (NPs) acting as drug carriers need to efficiently cross the pulmonary surfactant monolayer (PSM) of lung alveoli, which act as the first barrier for external particles entering the lung. Herein, by performing molecular dynamics simulations, we study how inhaled NPs interact with the PSM, particularly focusing on the transport of NPs with different properties across the PSM. While hydrophilic NPs translocate directly across the PSM, transport of hydrophobic NPs is achieved as the PSM wraps them...
June 16, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28620581/third-generation-tyrosine-kinase-inhibitors-targeting-epidermal-growth-factor-receptor-mutations-in-non-small-cell-lung-cancer
#17
REVIEW
Tristan A Barnes, Grainne M O'Kane, Mark David Vincent, Natasha B Leighl
Sensitizing mutations in the epidermal growth factor receptor (EGFR) predict response to EGFR tyrosine kinase inhibitors (TKIs) and both first- and second-generation TKIs are available as first-line treatment options in patients with advanced EGFR-mutant non-small cell lung cancer. Eventual resistance develops with multiple mechanisms identifiable both upon repeat biopsy and in plasma circulating tumor DNA. The T790M gatekeeper mutation is responsible for almost 60% of cases. A number of third-generation TKIs are in clinical development, and osimertinib has been approved by the US Food and Drug Administration for the treatment of patients with EGFR T790M mutant lung cancer after failure of initial EGFR kinase therapy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28620571/leptomeningeal-carcinomatosis-in-recurrent-non-small-cell-lung-cancer-a-case-report-and-review-of-current-treatment-modalities
#18
Saqib Abbasi, Elias Moussaly, Jean P Atallah
Leptomeningeal carcinomatosis (LC) is an uncommon sequelae of non-small cell lung cancer. The treatment modalities for LC have historically been limited with an overall poor prognosis. This case report outlines a 76-year-old female who presented with recurrence of non-small cell lung cancer as LC. LC is difficult to treat, and options include radiation, chemotherapy (systemic and intrathecal), as well as targeted therapies. This case outlines a unique approach and reviews the current literature on the effectiveness of these options in non-small cell lung cancer...
May 12, 2017: Curēus
https://www.readbyqxmd.com/read/28620146/mitochondrial-asncmtrna-1-and-asncmtrna-2-as-potent-targets-to-inhibit-tumor-growth-and-metastasis-in-the-renca-murine-renal-adenocarcinoma-model
#19
Vincenzo Borgna, Jaime Villegas, Verónica A Burzio, Sebastián Belmar, Mariela Araya, Emanuel Jeldes, Lorena Lobos-González, Verónica Silva, Claudio Villota, Luciana Oliveira-Cruz, Constanza Lopez, Teresa Socias, Octavio Castillo, Luis O Burzio
Knockdown of antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptosis in several human and mouse tumor cell lines, but not normal cells, suggesting this approach for a selective therapy against different types of cancer. Here we show that in vitro knockdown of murine ASncmtRNAs induces apoptotic death of mouse renal adenocarcinoma RenCa cells, but not normal murine kidney epithelial cells. In a syngeneic subcutaneous RenCa model, treatment delayed and even reversed tumor growth. Since the subcutaneous model does not reflect the natural microenviroment of renal cancer, we used an orthotopic model of RenCa cells inoculated under the renal capsule...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28620130/circulating-microparticles-are-prognostic-biomarkers-in-advanced-non-small-cell-lung-cancer-patients
#20
Chin-Chou Wang, Chia-Cheng Tseng, Huang-Chih Chang, Kuo-Tung Huang, Wen-Feng Fang, Yu-Mu Chen, Cheng-Ta Yang, Chang-Chun Hsiao, Meng-Chih Lin, Chi-Kung Ho, Hon-Kan Yip
We investigated whether circulating microparticles (MPs) could serve as prognostic biomarkers in non-small cell lung cancer (NSCLC) patients. We enrolled 25 control subjects and 136 NSCLC patients categorized into disease-progression (DP, n=42) and disease-control (DC, n=94) groups. Flow cytometric analysis showed that levels of four types of circulating microparticles (EDAc-MPs, EDAp-MPs, PDAc-MPs and PDAp-MPs) were higher in the study patients than the control subjects (P < 0.04). DP patients showed poor initially performance status and more non-adenocarcinomas than DC patients...
June 6, 2017: Oncotarget
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