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https://www.readbyqxmd.com/read/28919776/safety-pharmacokinetics-and-pharmacodynamics-of-oral-omaveloxolone-rta-408-a-synthetic-triterpenoid-in-a-first-in-human-trial-of-patients-with-advanced-solid-tumors
#1
Ben C Creelan, Dmitry I Gabrilovich, Jhanelle E Gray, Charles C Williams, Tawee Tanvetyanon, Eric B Haura, Jeffrey S Weber, Geoffrey T Gibney, Joseph Markowitz, Joel W Proksch, Scott A Reisman, Mark D McKee, Melanie P Chin, Colin J Meyer, Scott J Antonia
BACKGROUND: Omaveloxolone is a semisynthetic oleanane triterpenoid that potently activates Nrf2 with subsequent antioxidant function. We conducted a first-in-human Phase I clinical trial (NCT02029729) with the primary objectives to determine the appropriate dose for Phase II studies, characterize pharmacokinetic and pharmacodynamic parameters, and assess antitumor activity. METHODS: Omaveloxolone was administered orally once daily continuously in a 28-day cycle for patients with stage 4 relapsed/refractory melanoma or non-small cell lung cancer...
2017: OncoTargets and Therapy
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
#2
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/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
#3
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
https://www.readbyqxmd.com/read/28911086/large-scale-prospective-screening-of-egfr-mutations-in-the-blood-of-advanced-nsclc-patients-to-guide-treatment-decisions
#4
C Mayo-de-Las-Casas, N Jordana-Ariza, M Garzón-Ibañez, A Balada-Bel, J Bertrán-Alamillo, S Viteri-Ramírez, N Reguart, M A Muñoz-Quintana, P Lianes-Barragan, C Camps, E Jantús, J Remon-Massip, S Calabuig, D Aguiar, M L Gil, N Viñolas, A K Santos-Rodríguez, M Majem, B García-Peláez, S Villatoro, A Pérez-Rosado, J C Monasterio, E Ovalle, M J Catalán, R Campos, D Morales-Espinosa, A Martínez-Bueno, M González-Cao, X González, I Moya-Horno, A E Sosa, N Karachaliou, R Rosell, M A Molina-Vila
Background: In a significant percentage of advanced non-small-cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses. We prospectively analyzed if circulating-free DNA (cfDNA) purified from blood can be used as a surrogate in this setting to select patients for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Patients and methods: Blood samples were collected in 119 hospitals from 1138 advanced NSCLC patients at presentation (n = 1033) or at progression to EGFR-TKIs (n = 105) with no biopsy or insufficient tumor tissue...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28904885/the-clinical-utility-of-circulating-tumour-cells-in-patients-with-small-cell-lung-cancer
#5
REVIEW
Victoria Foy, Fabiola Fernandez-Gutierrez, Corinne Faivre-Finn, Caroline Dive, Fiona Blackhall
Small cell lung cancer (SCLC) accounts for 15% of lung cancer diagnosed worldwide. It is aggressive and characterised by early metastatic spread with rapid development of chemo resistance such that less than 5% of patients diagnosed survive 5 years. Surgery is rarely performed and failure to identify new effective treatments has been attributed in a large part to lack of good quality tumour biopsies available for translational research. Liquid biopsies provide a minimally invasive alternative to traditional tumour biopsy...
August 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28900080/-dynamics-of-line-1-retrotransposon-methylation-levels-in-circulating-dna-from-lung-cancer-patients-undergoing-antitumor-therapy
#6
A A Ponomaryova, N V Cherdyntseva, A A Bondar, A Y Dobrodeev, A A Zavyalov, S A Tuzikov, V V Vlassov, E L Choinzonov, P P Laktionov, E Y Rykova
Malignant cell transformation is accompanied with abnormal DNA methylation, such as the hypermethylation of certain gene promoters and hypomethylation of retrotransposons. In particular, the hypomethylation of the human-specific family of LINE-1 retrotransposons was observed in lung cancer tissues. It is also known that the circulating DNA (cirDNA) of blood plasma and cell-surface-bound circulating DNA (csb-cirDNA) of cancer patients accumulate tumor-specific aberrantly methylated DNA fragments, which are currently considered to be valuable cancer markers...
July 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28888924/mesothelin-specific-immune-responses-predict-survival-of-patients-with-brain-metastasis
#7
Liu Zhenjiang, Martin Rao, Xiaohua Luo, Elisabeth Sandberg, Jiri Bartek, Esther Schoutrop, Anna von Landenberg, Qingda Meng, Davide Valentini, Thomas Poiret, Georges Sinclair, Inti-Harvey Peredo, Ernest Dodoo, Markus Maeurer
BACKGROUND: Patients with advanced malignancies, e.g. lung cancer, ovarian cancer or melanoma, frequently present with brain metastases. Clinical presentation and disease progression of cancer is in part shaped by the interaction of the immune system with malignant cells. Antigen-targeted immune responses have been implicated in the prolonged survival of patients with cancer. This includes the tumor-associated antigen (TAA) mature mesothelin, a 40kDa cell surface-bound antigen that is overexpressed in several malignancies including lung ovarian and pancreatic cancer...
August 30, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28884371/egfr-t790m-mutation-testing-of-non-small-cell-lung-cancer-tissue-and-blood-samples-artificially-spiked-with-circulating-cell-free-tumor-dna-results-of-a-round-robin-trial
#8
Jana Fassunke, Michaela Angelika Ihle, Dido Lenze, Annika Lehmann, Michael Hummel, Claudia Vollbrecht, Roland Penzel, Anna-Lena Volckmar, Albrecht Stenzinger, Volker Endris, Andreas Jung, Ulrich Lehmann, Silke Zeugner, Gustavo Baretton, Hans Kreipe, Peter Schirmacher, Thomas Kirchner, Manfred Dietel, Reinhard Büttner, Sabine Merkelbach-Bruse
The European Commision (EC) recently approved osimertinib for the treatment of adult patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) harboring EGFR T790M mutations. Besides tissue-based testing, blood samples containing cell-free circulating tumor DNA (ctDNA) can be used to interrogate T790M status. Herein, we describe the conditions and results of a round robin trial (RRT) for T790M mutation testing in NSCLC tissue specimens and peripheral blood samples spiked with cell line DNA mimicking tumor-derived ctDNA...
September 8, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28855035/-retrospective-study-of-efficacy-in-bim-gene-polymorphism-on-first-line-egfr-tkis-treatment-for-advanced-lung-adenocarcinoma
#9
Kun Qian, Yi Zhang, Xiuyi Zhi
BACKGROUND: The aim of this study is to detect the BIM polymorphism in 85 formalin-fixed and parrffin-embedded (FFPE) and some blood samples of advanced lung adenocarcinoma patients and study the relativity betweenthe BIM polymorphism and tyrosine kinase inhibitor (TKI). The correlation between BIM detection of different types of specimens was discussed. METHODS: There were 85 patients who were diagnosed as advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) 19 or 21 exon mutation in thoracic surgery of Xuanwu Hospital from February 2013 to November 2014, all of who were received EGFR-TKI as first-line treatment in the study...
August 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28846180/synergistic-activity-of-sorafenib-and-betulinic-acid-against-clonogenic-activity-of-non-small-cell-lung-cancer-cells
#10
Justyna Kutkowska, Leon Strzadala, Andrzej Rapak
The highly selective multi-targeted agent - sorafenib - is an inhibitor of a number of intracellular signaling kinases with anti-proliferative, anti-angiogenic and pro-apoptotic effects in various types of tumors, including human non-small cell lung cancer (NSCLC). Betulin displays a broad spectrum of biological and pharmacological properties, including the anticancer and chemopreventive activity. Combination of drugs with different targets is a logical approach to overcome multilevel cross-stimulation among key signaling pathways in NSCLC progression...
August 28, 2017: Cancer Science
https://www.readbyqxmd.com/read/28843267/screening-for-circulating-tumour-cells-allows-early-detection-of-cancer-and-monitoring-of-treatment-effectiveness-an-observational-study
#11
Karin Ried, Peter Eng, Avni Sali
Background: Circulating-Tumour-Cells (CTC) provide a blood biomarker for early carcinogenesis, cancer progression and treatment effectiveness. An increase in CTCs is associated with cancer progression, a CTC decrease with cancer containment or remission. Several technologies have been developed to identify CTC, including the validated Isolation-by-Size-of-Epithelial-Tumour (ISET, Rarecells) technology, combining blood filtration and microscopy using standard histo-pathological criteria. Methods: This observational study compared CTC count to cancer status and cancer risk, by monitoring treatment effectiveness in cancer patients and by screening for CTC in asymptomatic patients with risk factors, including family history of cancer...
August 27, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28840770/predicting-tumor-hypoxia-in-non-small-cell-lung-cancer-by-combining-ct-fdg-pet-and-dynamic-contrast-enhanced-ct
#12
Aniek J G Even, Bart Reymen, Matthew D La Fontaine, Marco Das, Arthur Jochems, Felix M Mottaghy, José S A Belderbos, Dirk De Ruysscher, Philippe Lambin, Wouter van Elmpt
BACKGROUND: Most solid tumors contain inadequately oxygenated (i.e., hypoxic) regions, which tend to be more aggressive and treatment resistant. Hypoxia PET allows visualization of hypoxia and may enable treatment adaptation. However, hypoxia PET imaging is expensive, time-consuming and not widely available. We aimed to predict hypoxia levels in non-small cell lung cancer (NSCLC) using more easily available imaging modalities: FDG-PET/CT and dynamic contrast-enhanced CT (DCE-CT). MATERIAL AND METHODS: For 34 NSCLC patients, included in two clinical trials, hypoxia HX4-PET/CT, planning FDG-PET/CT and DCE-CT scans were acquired before radiotherapy...
August 25, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28839987/effect-of-huisheng-oral-solution-on-coagulation-function-in-perioperative-period-in-patients-with-primary-lung-cancer
#13
Xiaoguang Yang, Helin Zhang, Fanyi Kong, Guochen Wang, Qianyu Gu, Zheng Zhao, Tiezhi Li, Mingming Ren, Zuosheng Li, Yang Guo
BACKGROUND: The incidence of venous thromboembolism (VTE) is about 4-10% in lung cancer patients. Huisheng oral solution (HSOS) has been previously demonstrated to inhibit carageenan induced acute thrombosis in rats, reduce the incidence of thrombosis in the lungs and mesentery of tumor-bearing mice and inhibit tumor cell metastasis. The purpose of this study was to assess the anticoagulant effect of HSOS in lung cancer patients in the perioperative period. METHODS: This study was a multicenter, randomized, single-blind, blank-controlled clinical trial...
July 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28834230/renal-impairment-hampers-bisphosphonate-treatment-in-a-quarter-of-lung-cancer-patients-with-bone-metastasis
#14
Katalin Fábián, Rita Puskás, Tímea Kakuk, László Prés, Dorottya Fejes, Zsolt Szegedi, Lívia Rojkó, Zoltán Szállási, Balázs Döme, Orsolya Pipek, Judit Moldvay
Renal function impairment in lung cancer patients with bone metastases was investigated, as this can limit the application of bisphosphonates representing the gold standard in the management of such cases. Clinicopathological data of 570 lung cancer patients were retrospectively analysed for changes in renal function parameters. Co-morbidities included hypertension (50%), COPD (33%) and diabetes mellitus (15%). Statistical analysis was performed with Fisher's exact tests and a Cox proportional hazards model...
August 21, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28829813/clinical-validation-of-a-highly-sensitive-assay-to-detect-egfr-mutations-in-plasma-cell-free-dna-from-patients-with-advanced-lung-adenocarcinoma
#15
Yuping Li, Hanyan Xu, Shanshan Su, Junru Ye, Junjie Chen, Xuru Jin, Quan Lin, Dongqing Zhang, Caier Ye, Chengshui Chen
BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for noninvasive epidermal growth factor receptor (EGFR) mutations detection in lung cancer patients, but the existing methods have limitations in sensitivity or in availability. In this study, we evaluated the performance of a novel assay called ADx-SuperARMS in detecting EGFR mutations in plasma cell-free DNA from patients with advanced lung adenocarcinoma. METHODS: A total of 109 patients with metastatic advanced adenocarcinoma were recruited who provided both blood samples and matched tumor tissue samples...
2017: PloS One
https://www.readbyqxmd.com/read/28818987/response-assessment-of-68-ga-dota-e-c-rgdfk-2-pet-ct-for-lung-adenocarcinoma-patients-treated-with-nintedanib-plus-docetaxel
#16
Oscar Arrieta, Francisco O Garcia-Perez, David Michel-Tello, Laura-Alejandra Ramirez-Tirado, Quetzali Pitalua-Cortes, Graciela Cruz-Rico, Eleazar-Omar Macedo-Perez, Andres F Cardona, Jaime de la Garza-Salazar
Nintedanib is an oral angiokinase inhibitor used as a second-line treatment for non-small-cell lung cancer (NSCLC). New radiotracers, such as (68)Ga-DOTA-E-[c(RGDfK)]2, that target αvβ3 integrin might impact the clinical practice as a non-invasive method for assessing angiogenesis inhibitors. Methods: From July 2014 through October 2015, 38 patients received second-line nintedanib plus docetaxel. All the patients underwent PET/CT with (68)Ga-DOTA-E-[c(RGDfK)]2 radiotracer and blood-sample tests to quantify angiogenesis factors (FGF, VEGF and PDGF-AB) prior to and after completing 2 therapy cycles...
August 17, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28813112/what-do-cochrane-systematic-reviews-say-about-the-clinical-effectiveness-of-screening-and-diagnostic-tests-for-cancer
#17
André Tito Pereira Bueno, Vladimir Lisboa Capelasso, Rafael Leite Pacheco, Carolina de Oliveira Cruz Latorraca, Tiago Biachi de Castria, Daniela Vianna Pachito, Rachel Riera
CONTEXT AND OBJECTIVE: The purpose of screening tests for cancer is to detect it at an early stage in order to increase the chances of treatment. However, their unrestrained use may lead to unnecessary examinations, overdiagnosis and higher costs. It is thus necessary to evaluate their clinical effects in terms of benefits and harm. DESIGN AND SETTING: Review of Cochrane systematic reviews, carried out in the Discipline of Evidence-Based Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo...
July 2017: São Paulo Medical Journal, Revista Paulista de Medicina
https://www.readbyqxmd.com/read/28793041/experimental-study-of-peripheral-blood-pro-surfactant-protein-b-for-screening-non-small-cell-lung-cancer
#18
Yong He, Zhenjie Jiang, Fengzhi Tong, Mingwu Li, Xingru Yin, Shixin Hu, Linlin Wang
Purpose: To evaluate the possibility of using peripheral-blood presurfactant protein B (Pro-SFTPB) for screening non-small cell lung cancer (NSCLC). Methods: A total of 873 healthy volunteers and 165 lung cancer patients hospitalized in the Fifth People's Hospital of Dalian were tested Pro-SFTPB once every half year from January 2014 to September 2015. The healthy volunteers were also conducted spiral computed tomography (CT) examination once every year. The data were then com-pared and statistically analyzed...
July 2017: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/28772286/prevalence-of-cancer-at-baseline-screening-in-the-national-cancer-institute-li-fraumeni-syndrome-cohort
#19
Phuong L Mai, Payal P Khincha, Jennifer T Loud, Rosamma M DeCastro, Renée C Bremer, June A Peters, Chia-Ying Liu, David A Bluemke, Ashkan A Malayeri, Sharon A Savage
Importance: Establishment of an optimal cancer surveillance program is important to reduce cancer-related morbidity and mortality in individuals with Li-Fraumeni syndrome, a rare, highly penetrant cancer predisposition syndrome. Objective: To determine the feasibility and efficacy of a comprehensive cancer screening regimen in Li-Fraumeni syndrome, using multiple radiologic techniques, including rapid whole-body magnetic resonance imaging (MRI) and laboratory measurements...
August 3, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28765402/monitoring-risk-factors-of-cardiovascular-disease-in-cancer-survivors
#20
Ambika Kapoor, Vineet Prakash, Mallika Sekhar, Diana M Greenfield, Matthew Hatton, Michael Ej Lean, Pankaj Sharma, Thang S Han
There exist published literature for cardiovascular disease (CVD) risk monitoring in cancer survivors but the extent of monitoring in clinical oncology practice is unknown. We performed an interactive survey at a Royal College of Physicians conference (11 November 2016) attended by practitioners with an interest in late effects of cancer treatment and supplemented the survey with an audit among 32 lung cancer survivors treated at St Peter's NHS Hospital in 2012-2016. Among the practitioners, 40% reported CVD risk monitoring performed at least annually, which is compatible with European Group for Blood and Marrow Transplantation Guidelines, but 31% indicated that monitoring was never performed...
July 2017: Clinical Medicine: Journal of the Royal College of Physicians of London
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