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https://www.readbyqxmd.com/read/29137280/ppar%C3%AE-sumoylation-mediated-lipid-accumulation-in-lung-cancer
#1
Ai N H Phan, Vu T A Vo, Tuyen N M Hua, Min-Kyu Kim, Se-Young Jo, Jong-Whan Choi, Hyun-Won Kim, Jaekyoung Son, Young-Ah Suh, Yangsik Jeong
Metabolic reprogramming as a crucial emerging hallmark of cancer is critical for tumor cells to maintain cellular bioenergetics, biosynthesis and reduction/oxidation (REDOX) balance. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear hormone receptor regulating transcription of diverse gene sets involved in inflammation, metabolism, and suppressing tumor growth. Thiazolidinediones (TZDs), as selective PPARγ ligands, are insulin-sensitizing drugs widely prescribed for type 2 diabetic patients in the clinic...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136465/recent-progress-of-small-molecule-epidermal-growth-factor-receptor-egfr-inhibitors-against-c797s-resistance-in-non-small-cell-lung-cancer
#2
Lingfeng Chen, Weitao Fu, Lulu Zheng, Zhiguo Liu, Guang Liang
The epidermal growth factor receptor (EGFR) has been a particular interest for drug development for treatment of non-small-cell lung cancer (NSCLC). The current third-generation EGFR small-molecule inhibitors, especially osimertinib, are at the forefront clinically for treatment of patients with NSCLC. However, a high percentage of these treated patients developed a tertiary cystein797 to serine790 (C797S) mutation in the EGFR kinase domain. This C797S mutation is thought to induce resistance to all current irreversible EGFR TKIs...
November 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29135200/overview-of-silica-related-clusters-in-the-united-states-will-fracking-operations-become-the-next-cluster
#3
M Thomas Quail
Silicosis is the oldest know occupational pulmonary disease. It is a progressive disease and any level of exposure to respirable crystalline silica particles or dust has the potential to develop into silicosis. Silicosis is caused by silica particles or dust entering the lungs and damaging healthy lung tissue. The damage restricts the ability to breathe. Exposure to silica increases a worker’s risk of developing cancer or tuberculosis. This special report will provide background history of silicosis in the U...
January 2017: Journal of Environmental Health
https://www.readbyqxmd.com/read/29134637/ercc4-regulatory-variant-predict-grade-3-or-4-toxicities-in-patients-with-advanced-non-small-cell-lung-cancer-treated-by-platinum-based-therapy
#4
Ruoxin Zhang, Ming Jia, Yuan Xu, Danwen Qian, Mengyun Wang, Meiling Zhu, Menghong Sun, Jianhua Chang, Qingyi Wei
Platinum-based chemotherapy (PBC) in combination with the 3(rd) generation drugs is the first-line treatment for patients with advanced non-small cell lung cancer (NSCLC); however, the efficacy is severely hampered by grade 3-4 toxicities. Nucleotide excision repair (NER) pathway is the main mechanism of removing platinum-induced DNA adducts, contributing to the toxicity and outcome of PBC. We analyzed data from 710 Chinese NSCLC patients treated with PBC and assessed the associations of 25 potentially functional single nucleotide polymorphisms (SNPs) in eight NER core genes with overall, gastrointestinal and hematologic toxicities...
November 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29133313/site-specific-cancer-mortality-inequalities-by-employment-and-occupational-groups-a-cohort-study-among-belgian-adults-2001-2011
#5
Katrien Vanthomme, Laura Van den Borre, Hadewijch Vandenheede, Paulien Hagedoorn, Sylvie Gadeyne
OBJECTIVE: This study probes into site-specific cancer mortality inequalities by employment and occupational group among Belgians, adjusted for other indicators of socioeconomic (SE) position. DESIGN: This cohort study is based on record linkage between the Belgian censuses of 1991 and 2001 and register data on emigration and mortality for 01/10/2001 to 31/12/2011. SETTING: Belgium. PARTICIPANTS: The study population contains all Belgians within the economically active age (25-65 years) at the census of 1991...
November 12, 2017: BMJ Open
https://www.readbyqxmd.com/read/29132432/ac-93253-iodide-a-novel-src-inhibitor-suppresses-nsclc-progression-by-modulating-multiple-src-related-signaling-pathways
#6
Yi-Hua Lai, Sih-Yin Lin, Yu-Shan Wu, Huei-Wen Chen, Jeremy J W Chen
BACKGROUND: The tyrosine kinase Src is involved in the progression of many cancers. Moreover, inhibiting Src activity has been shown to obstruct several signaling pathways regulated by the EGFR. Thus, Src is a valuable target molecule in drug development. The purpose of this study was to identify compounds that directly or indirectly modulate Src to suppress lung cancer cell growth and motility and to investigate the molecular mechanisms underlying the effects of these compounds. METHODS: Human non-small cell lung cancer (NSCLC) cell lines (PC9, PC9/gef, A549, and H1975) with different EGFR statuses were tested by cytotoxicity and proliferation assays after AC-93253 iodide treatment...
November 13, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29131934/methyl-dna-phosphate-adduct-formation-in-rats-treated-chronically-with-4-methylnitrosamino-1-3-pyridyl-1-butanone-and-enantiomers-of-its-metabolite-4-methylnitrosamino-1-3-pyridyl-1-butanol
#7
Bin Ma, Adam T Zarth, Erik S Carlson, Peter W Villalta, Pramod Upadhyaya, Irina Stepanov, Stephen S Hecht
The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a powerful lung carcinogen in animal models and is considered a causative factor for lung cancer in tobacco users. NNK is stereoselectively and reversibly metabolized to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which is also a lung carcinogen. Both NNK and NNAL undergo metabolic activation by α-hydroxylation on their methyl groups to form pyridyloxobutyl and pyridylhydroxybutyl DNA base and phosphate adducts, respectively...
November 13, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29131323/validity-and-usefulness-of-a-single-item-measure-of-patient-reported-bother-from-side-effects-of-cancer-therapy
#8
Timothy P Pearman, Jennifer L Beaumont, Daniel Mroczek, Mary O'Connor, David Cella
BACKGROUND: The improving efficacy of cancer treatment has resulted in an increasing array of treatment-related symptoms and associated burdens imposed on individuals undergoing aggressive treatment of their disease. Often, clinical trials compare therapies that have different types, and severities, of adverse effects. Whether rated by clinicians or patients themselves, it can be difficult to know which side effect profile is more disruptive or bothersome to patients. A simple summary index of bother can help to adjudicate the variability in adverse effects across treatments being compared with each other...
November 13, 2017: Cancer
https://www.readbyqxmd.com/read/29129514/a-green-multicomponent-synthesis-of-tocopherol-analogues-with-antiproliferative-activities
#9
Mariana Ingold, Rosina Dapueto, Sabina Victoria, Germán Galliusi, Carlos Batthyàny, Mariela Bollati-Fogolín, David Tejedor, Fernando García-Tellado, José M Padrón, Williams Porcal, Gloria V López
A one-pot efficient, practical and eco-friendly synthesis of tocopherol analogues has been developed using water or solvent free conditions via Passerini and Ugi multicomponent reactions. These reactions can be optimized using microwave irradiation or ultrasound as the energy source. Accordingly, a small library of 30 compounds was prepared for biological tests. The evaluation of the antiproliferative activity in the human solid tumor cell lines A549 (lung), HBL-100 (breast), HeLa (cervix), SW1573 (lung), T-47D (breast), and WiDr (colon) provided lead compounds with GI50 values between 1 and 5 μM...
November 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29125548/liquid-biopsy-and-therapeutic-targets-present-and-future-issues-in-thoracic-oncology
#10
REVIEW
Paul Hofman
The practice of liquid biopsy (LB) has revolutionized the care of patients with metastatic lung cancer. Many oncologists now use this approach in daily practice, applying precise procedures for the detection of activating or resistance mutations in EGFR. These tests are performed with plasma DNA and have been approved as companion diagnostic test for patients treated with tyrosine kinase inhibitors. ALK is another important target in lung cancer since it leads to treatment of patients who are positive for a rearrangement in ALK identified with tumor tissue...
November 10, 2017: Cancers
https://www.readbyqxmd.com/read/29124875/emerging-functions-of-the-egfr-in-cancer
#11
REVIEW
Sara Sigismund, Daniele Avanzato, Letizia Lanzetti
The physiological function of the Epidermal Growth Factor Receptor (EGFR) is to regulate epithelial tissue development and homeostasis. In pathological settings, mostly in lung and breast cancer and in glioblastoma, the EGFR is a driver of tumorigenesis. Inappropriate activation of the EGFR in cancer mainly results from amplification and point mutations at the genomic locus, but transcriptional upregulation or ligand overproduction due to autocrine/paracrine mechanisms have also been described. Moreover, the EGFR is increasingly recognized as a biomarker of resistance in tumors, since its amplification or secondary mutations have been found to arise under drug pressure...
November 10, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29123418/evaluating-the-cost-effectiveness-of-afatinib-after-platinum-based-therapy-for-the-treatment-of-squamous-non-small-cell-lung-cancer-in-france
#12
Maud Pignata, Christos Chouaid, Katell Le Lay, Laura Luciani, Ceilidh McConnachie, James Gordon, Stéphane Roze
Background and aims: Lung cancer has the highest mortality rate of all cancers worldwide. Non-small-cell lung cancer (NSCLC) accounts for 85% of all lung cancers and has an extremely poor prognosis. Afatinib is an irreversible ErbB family blocker designed to suppress cellular signaling and inhibit cellular growth and is approved in Europe after platinum-based therapy for squamous NSCLC. The objective of the present analysis was to evaluate the cost-effectiveness of afatinib after platinum-based therapy for squamous NSCLC in France...
2017: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/29121501/does-c-met-remain-a-rational-target-for-therapy-in-patients-with-egfr-tki-resistant-non-small-cell-lung-cancer
#13
REVIEW
Yi-Long Wu, Ross Andrew Soo, Giuseppe Locatelli, Uz Stammberger, Giorgio Scagliotti, Keunchil Park
Non-small cell lung cancer (NSCLC) inevitably develops resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. In 5-20% of cases, this can be attributed to aberrant c-Met activity, providing a clear rationale for the use of c-Met inhibitors in these patients. EGFR TKI-resistant tumors often remain sensitive to EGFR signaling, such that c-Met inhibitors are likely to be most effective when combined with continued EGFR TKI therapy. The phase III trials of the c-Met inhibitors onartuzumab and tivantinib, which failed to demonstrate significant benefit in patients with NSCLC but excluded patients with EGFR TKI-resistant disease, do not allow c-Met to be dismissed as a rational target in EGFR TKI-resistant NSCLC...
October 25, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29116596/antibody-drug-conjugates-for-the-treatment-of-solid-tumors-clinical-experience-and-latest-developments
#14
Aiko Nagayama, Leif W Ellisen, Bruce Chabner, Aditya Bardia
Antibody-drug conjugates (ADCs) are complex immunoconjugates designed to selectively deliver toxic small molecules preferentially to cancer cells. These immunoconjugates consist of a monoclonal antibody - directed to a tumor antigen - and a cytotoxic agent that is conjugated to the antibody via a molecular linker. Following the binding to a specific antigen on the surface of cancer cells, the conjugate is internalized and releases its cytotoxic payload to kill the malignant cell. ADCs that have gained regulatory approval from the US Food and Drug Administration (FDA) include brentuximab vedotin for CD30-positive Hodgkin's lymphoma and trastuzumab emtansine for human epidermal growth factor receptor 2 (HER2)-positive breast cancer...
November 8, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29113340/analgecine-enhances-the-anti-tumor-response-of-radiotherapy-by-increasing-apoptosis-and-cell-cycle-arrest-in-non-small-cell-lung-cancer
#15
Xue Chen, Xibing Zhuang, Qi Zhang, Youjun Luo, Sujuan Yuan, Tiankui Qiao
We investigated whether Analgecine treatment enhanced the antitumor response of radiotherapy in non-small cell lung cancer (NSCLC) cells. Lewis lung carcinoma (LLC) xenograft mice treated with Analgecine plus irradiation showed reduced tumor growth and increased survival. Tumor cell apoptosis was enhanced by Analgecine, based on TUNEL assays. It also increased plasma levels of pro-inflammatory cytokines (IL-6, IL-12, and IFN-γ) and decreased anti-inflammatory cytokines (TGFβ and IL-10), suggesting an enhanced immune response...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29111351/chemoprevention-with-isothiocyanates-from-bench-to-bedside
#16
Carsten Gründemann, Roman Huber
Intake of isothiocyanates (ITCs), naturally occurring as hydrolization products from glucosinolates (GLSs) in brassicaceae, has, in epidemiological studies, been weakly to moderately inversely correlated with the risk of colorectal cancer, prostate cancer and lung cancer. Numerous preclinical studies demonstrate chemopreventive mode of actions of ITCs, mainly related to a.) detoxification (induction of phase II enzymes), b.) anti-inflammatory properties by down-regulation of NFkappaB activity, c.) cyclin-mediated cell cycle arrest and d...
October 27, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29108919/egfr-immunohistochemistry-as-biomarker-for-antibody-based-therapy-of-squamous-nsclc-experience-from-the-first-ring-trial-of-the-german-quality-assurance-initiative-for-pathology-quip-%C3%A2
#17
Iver Petersen, Manfred Dietel, Wolf J Geilenkeuser, Masoud Mireskandari, Wilko Weichert, Katja Steiger, Andreas H Scheel, Reinhard Büttner, Peter Schirmacher, Arne Warth, Felix Lasitschka, Hans-Ulrich Schildhaus, Thomas Kirchner, Simone Reu, Hans Kreipe, Florian Länger, Markus Tiemann, Christoph Schulte, Korinna Jöhrens
BACKGROUND: EGFR and its downstream signaling pathway are important targets for cancer therapy. Recently, the monoclonal anti-EGFR antibody Necitumumab in combination with gemcitabine and cisplatin was approved (EMA/14106/2016) for first-line treatment of squamous non-small cell carcinoma (SqNSCLC). Eligibility was restricted to cases with positive EGFR expression. In this context, a ring trial of the Quality Assurance Initiative for Pathology (QuIP(®)) was launched to prepare the German pathology community for a reliable and reproducible, immunohistochemically based biomarker test...
September 28, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29108860/fibrosis-imaging-current-concepts-and-future-directions
#18
Maike Baues, Anshuman Dasgupta, Josef Ehling, Jai Prakash, Peter Boor, Frank Tacke, Fabian Kiessling, Twan Lammers
Fibrosis plays an important role in many different pathologies. It results from tissue injury, chronic inflammation, autoimmune reactions and genetic alterations, and it is characterized by the excessive deposition of extracellular matrix components. Biopsies are routinely employed for fibrosis diagnosis, but they suffer from several drawbacks, including their invasive nature, sampling variability and limited spatial information. To overcome these limitations, multiple different imaging tools and technologies have been evaluated over the years, including x-ray imaging, computed tomography (CT), ultrasound (US), magnetic resonance imaging (MRI), positron emission tomography (PET) and single-photon emission computed tomography (SPECT)...
November 3, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29108335/a-three-gene-immunohistochemical-panel-serves-as-an-adjunct-to-clinical-staging-of-patients-with-head-and-neck-cancer
#19
Chin-Ann J Ong, Nicholas B Shannon, Stefan Mueller, Sze Min Lek, Xuan Qiu, Fui Teen Chong, Ke Li, Kelvin K N Koh, Gerald C A Tay, Thakshayeni Skanthakumar, Jacqueline S G Hwang, Tony Kiat Hon Lim, Mei Kim Ang, Daniel S W Tan, Ngian-Chye Tan, Hiang Khoon Tan, Khee Chee Soo, N Gopalakrishna Iyer
Background: Current management of head and neck squamous cell carcinoma (HNSCC) depends on tumor staging. Despite refinements in clinical staging algorithms, outcomes remain unchanged for the last two decades. In this study, we set out to identify a small, clinically applicable molecular panel to aid prognostication of patients with HNSCC. Materials and Methods: Data from The Cancer Genome Atlas (TCGA) was used to derive copy number aberrations and expression changes to identify putative prognostic genes...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29107685/toxicity-and-structure-activity-relationship-sar-of-%C3%AE-%C3%AE-dehydroamino-acids-against-human-cancer-cell-lines
#20
Romeu A Videira, Paula B Andrade, Luís S Monteiro, Patrícia Valentão, Paula M T Ferreira, David M Pereira
A library of N-protected dehydroamino acids, namely dehydroalanine, dehydroaminobutyric acid and dehydrophenylalanine derivatives, was screened in three human cancer cell lines [(lung (A549), gastric (AGS) and neuroblastoma (SH-SY5Y)] in order to characterize their toxicological profile and identify new molecules with potential anticancer activity. Results showed N-protected dehydrophenylalanine and dehydroaminobutyric acid derivatives have no or low toxicity for all tested cell lines. The N-protected dehydroalanines exhibit significant toxic effects and the AGS and SH-SY5Y cells were significantly more vulnerable than A549 cells...
October 28, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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