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https://www.readbyqxmd.com/read/30113656/targeted-molecular-analysis-in-adrenocortical-carcinomas-a-strategy-towards-improved-personalized-prognostication
#1
Juliane Lippert, Silke Appenzeller, Raimunde Liang, Silviu Sbiera, Stefan Kircher, Barbara Altieri, Indrajit Nanda, Isabel Weigand, Andrea Gehrig, Sonja Steinhauer, Renzo J M Riemens, Andreas Rosenwald, Clemens R Müller, Matthias Kroiss, Simone Rost, Martin Fassnacht, Cristina L Ronchi
Context: Adrenocortical carcinoma (ACC) has a heterogeneous prognosis and current medical therapies have limited efficacy in its advanced stages. Genome-wide multi-omics-studies identified molecular patterns associated with clinical outcome. Objective: Here, we aimed at identifying a molecular signature useful for both personalized prognostic stratification and druggable targets, using methods applicable in clinical routine. Design: 117 tumor samples from 107 ACC patients were analyzed...
August 2, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/30113497/comparative-analysis-of-immune-checkpoint-inhibitors-and-chemotherapy-in-the-treatment-of-advanced-non-small-cell-lung-cancer-a-meta-analysis-of-randomized-controlled-trials
#2
Muhammad Khan, Jie Lin, Guixiang Liao, Yunhong Tian, Yingying Liang, Rong Li, Mengzhong Liu, Yawei Yuan
BACKGROUND: Recently, immune checkpoint inhibitors have shown survival advantage over chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). This meta-analysis was conducted to gather and analyze the available evidence (Evidence level I; Randomized Controlled Trials) comparing efficacy and safety of anti-programmed cell death-1 (PD1)/programmed cell death ligand 1 (PD-L1) therapies and chemotherapy in the treatment of advanced NSCLC. METHODS: A search strategy was devised to identify the randomized controlled trials (RCTs) using electronic databases of PubMed, Cochrane Library, and Web of Science...
August 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/30112342/patterns-of-epidermal-growth-factor-receptor-testing-across-111-tertiary-care-centers-in-india-result-of-a-questionnaire-based-survey
#3
Kumar Prabhash, Purvish M Parikh, Senthil J Rajappa, Vanita Noronha, Amit Joshi, Shyam Aggarwal, Shailesh Bondarde, Shekar Patil, Chirag Desai, Palanki Satya Dattatreya, Rajesh Naik, Sohit Anand, Raju Titus Chacko, Ghanshyam Biswas, Tarini P Sahoo, Deepak Dabkara, Vijay Patil, M V Chandrakant, Pratap K Das, Ashok K Vaid, Dinesh C Doval
Background: We conducted a survey of 111 medical oncologists across India to understand the current pattern of epidermal growth factor receptor (EGFR) mutation testing at their respective centers. Methods: Medical oncologists from 111 institutes across India were interviewed face to face using a structured questionnaire. They were divided into two groups - Group 1 with in-house EGFR testing and Group 2 who send samples to central/commercial laboratories outside their institutions...
July 2018: South Asian Journal of Cancer
https://www.readbyqxmd.com/read/30112177/treatment-response-to-osimertinib-in-a-patient-with-leptomeningeal-metastasis-from-lung-adenocarcinoma-following-failure-of-gefitinib-and-erlotinib-a-case-report
#4
Junjun Li, Xiaomei Liu, Caijun Yuan
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are effective in the treatment of advanced non-small-cell lung cancer (NSCLC) with leptomeningeal metastases (LM); however, a proportion of the patients with resistant tumors do not benefit from EGFR-TKI treatment. In the present study the case of a female patient with advanced lung adenocarcinoma harboring the EGFR L858R mutation (encoded in exon 21) who developed intracranial metastases following treatment with erlotinib after gefitinib failure is reported...
September 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/30111817/epithelial-mesenchymal-transition-emt-beyond-egfr-mutations-per-se-is-a-common-mechanism-for-acquired-resistance-to-egfr-tki
#5
Chien-Hui Weng, Li-Yu Chen, Yu-Chin Lin, Jin-Yuan Shih, Yun-Chieh Lin, Ruo-Yu Tseng, An-Chieh Chiu, Yu-Hsuan Yeh, Chi Liu, Yi-Ting Lin, Jim-Min Fang, Ching-Chow Chen
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is a major advance in treating NSCLC with EGFR-activating mutations. However, acquired resistance, due partially to secondary mutations limits their use. Here we report that NSCLC cells with acquired resistance to gefitinib or osimertinib (AZD9291) exhibit EMT features, with a decrease in E-cadherin, and increases in vimentin and stemness, without possessing any EGFR secondary mutations. Knockdown of E-cadherin in parental cells increased gefitinib resistance and stemness, while knockdown of vimentin in resistant cells resulted in opposite effects...
August 15, 2018: Oncogene
https://www.readbyqxmd.com/read/30111420/-clinical-characteristic-of-triple-negative-essential-thrombocythaemia-patients-and-mutation-analysis-by-targeted-sequencing
#6
Man-Kai Ju, Rong-Feng Fu, Hui-Yuan Li, Xiao-Fan Liu, Feng Xue, Yun-Fei Chen, Yue-Ting Huang, Li-Yan Zhang, Ren-Chi Yang, Lei Zhang
BACKGROUND: Essential thrombocythemia is a subgroup of myeloproliferative neoplasms. Previous studies identified mutations of JAK2, CALR, and MPL that are closely related with the pathogenesis of myeloproliferative neoplasms. All these mutations contribute to the hyperactivation of JAK2/STAT pathway. However, a small proportion of essential thrombocythemia patients does not display such mutations. The pathogenesis of "triple-negative" form of essential thrombocythemia remains unknown...
August 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/30110953/assessment-of-the-mutational-status-of-nsclc-using-hypermetabolic-circulating-tumor-cells
#7
Matteo Turetta, Michela Bulfoni, Giulia Brisotto, Gianpiero Fasola, Andrea Zanello, Eva Biscontin, Laura Mariuzzi, Agostino Steffan, Carla Di Loreto, Daniela Cesselli, Fabio Del Ben
Molecular characterization is currently a key step in NSCLC therapy selection. Circulating tumor cells (CTC) are excellent candidates for downstream analysis, but technology is still lagging behind. In this work, we show that the mutational status of NSCLC can be assessed on hypermetabolic CTC, detected by their increased glucose uptake. We validated the method in 30 Stage IV NSCLC patients: peripheral blood samples were incubated with a fluorescent glucose analog (2-NBDG) and analyzed by flow cytometry. Cells with the highest glucose uptake were sorted out...
August 14, 2018: Cancers
https://www.readbyqxmd.com/read/30109777/efficacy-of-icotinib-in-advanced-lung-squamous-cell-carcinoma
#8
Shuai Liang, Yan Xu, Fenlai Tan, Lieming Ding, Yongbin Ma, Mengzhao Wang
BACKGROUND: There are controversial data supporting the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in patients with advanced lung squamous cell carcinoma (SCC). In this study, the efficacy of icotinib in unselected and EGFR-mutated patients with lung SCC was assessed. METHODS: We retrospectively analyzed the survival time of unselected advanced lung SCC patients treated with icotinib for at least 5 months between June 2013 and June 2016, and selected appropriate EGFR-mutated advanced lung ADC patients to have 1:1 ratio of propensity score matching with EGFR-mutated advanced lung SCC patients, and matching factors were age, sex, clinical stage, Karnofsky performance status (KPS), smoking history, EGFR mutation type, and treatment lines...
August 14, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/30108455/survival-analysis-in-caucasian-pulmonary-adenocarcinoma-patients-based-on-differential-targets-between-caucasian-and-asian-population
#9
Zheng Zhu, Zhigang Liang, Jichun Tong, Xiaoliang Mao, Yajun Yin, Lydia C Manor, Zhenya Shen
Ethnicity differences may contribute to the variety of overall survival in pulmonary adenocarcinoma, while the influence of ethnicity relevant somatic driver mutations (ERSDM) profile on Caucasian survival is not well investigated. In this study, we studied epidermal growth factor receptor (EGFR), tumor protein p53 (TP53), Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), and Serine/Threonine Kinase 11 (STK11) to construct the ERSDM profile. Those genes were selected as harboring somatic driver mutations with >10% prevalence and with different occurrence between Caucasian and Asian ethnicity...
July 2018: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/30108422/selection-of-luteolin-as-a-potential-antagonist-from-molecular-docking-analysis-of-egfr-mutant
#10
George Oche Ambrose, Olanrewaju John Afees, Nwufoh Chika Nwamaka, Nzikahyel Simon, Adebo Adeola Oluwaseun, Tosin Soyinka, Alakanse Suleiman Oluwaseun, Seyi Bankole
The life-threatening sides effect of the current EGFR mutant inhibitors (drugs) such as the eruption of rash which can be seen on the face, chest, back and even the trunk, diarrhea, nausea, vomiting, anorexia and stomatitis, necessitates the discovery of new potent and safe compounds as a chemo-therapeutic measure against lung cancer. Approximately about 10% of patients with Non-small cell lung cancer (NSCLC) in the US and about 35% in East Asia have tumor associated EGFR. These mutations occur within EGFR exon 18-21, which encodes a portion of the EGFR kinase domain and enables researchers to identify compounds that only recognizes and binds to the cancer cells...
2018: Bioinformation
https://www.readbyqxmd.com/read/30108370/making-the-first-move-in-egfr-driven-or-alk-driven-nsclc-first-generation-or-next-generation-tki
#11
REVIEW
Gonzalo Recondo, Francesco Facchinetti, Ken A Olaussen, Benjamin Besse, Luc Friboulet
The traditional approach to the treatment of patients with advanced-stage non-small-cell lung carcinoma (NSCLC) harbouring ALK rearrangements or EGFR mutations has been the sequential administration of therapies (sequential treatment approach), in which patients first receive first-generation tyrosine-kinase inhibitors (TKIs), which are eventually replaced by next-generation TKIs and/or chemotherapy upon disease progression, in a decision optionally guided by tumour molecular profiling. In the past few years, this strategy has been challenged by clinical evidence showing improved progression-free survival, improved intracranial disease control and a generally favourable toxicity profile when next-generation EGFR and ALK TKIs are used in the first-line setting...
August 14, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/30107692/-clinical-value-of-droplet-digital-polymerase-chain-reaction-method-in-detecting-plasma-circulating-tumor-deoxyribonucleic-acid-epidermal-growth-factor-receptor-mutations-in-advanced-pulmonary-adenocarcinoma-patients
#12
L Ma, J L Lü, K Li, J H Wang, X J Yang, X Li, H Zhang, Q Zhang, N Qin, S C Zhang
Objective: To determine the clinical value of droplet digital polymerase chain reaction (ddPCR) method to detect plasma circulating tumor DNA (ctDNA) epidermal growth factor receptor (EGFR) mutations in advanced pulmonary adenocarcinoma. Methods: One hundred and thirty six patients with advanced pulmonary adenocarcinoma diagnosed in the Beijing Chest Hospital were collected from May 2015 to April 2017 for initial treatment. EGFR gene mutation in the plasma ctDNA was detected by both ddPCR and amplification refractory mutation system (ARMS) assays...
August 7, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/30107665/-lung-non-terminal-respiratory-unit-type-adenocarcinoma-a-clinicopathologic-study
#13
B Liu, N Wu, Q Shen, S S Shi, S S Zhang, Y Ru, Q Rao, X J Zhou
Objective: To evaluate the clinicopathologic characteristics of lung non-terminal respiratory unit (non-TRU) type adenocarcinoma. Methods: Seventy-two cases of lung non-TRU type adenocarcinoma that underwent complete resection and diagnosed at Departments of Pathology, Affiliated Suzhou Hospital of Nanjing Medical University and Nanjing General Hospital of the PLA from January 2005 to December 2016 were retrospectively studied. The histomorphological changes and precursor lesions were observed under microscope...
August 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/30107580/is-visible-aminolevulinic-acid-induced-fluorescence-an-independent-biomarker-for-prognosis-in-histologically-confirmed-world-health-organization-2016-low-grade-gliomas
#14
Mohammed Jaber, Christian Ewelt, Johannes Wölfer, Benjamin Brokinkel, Christian Thomas, Martin Hasselblatt, Oliver Grauer, Walter Stummer
BACKGROUND: Approximately 20% of low-grade gliomas (LGG) display visible protoporphyrin fluorescence during surgery after 5-aminolevulinic acid (5-ALA) administration. OBJECTIVE: To determine if fluorescence represents a prognostic marker in LGG. METHODS: Seventy-four consecutive patients with LGG (World Health Organization 2016) were operated on with 5-ALA. Fluorescent tissue was specifically biopsied. Tumor size, age, Karnofsky index, contrast-enhancement, fluorescence, and molecular factors (IDH1/IDH2-mutations, Ki67/MIB1 Index, 1p19q codeletions, ATRX, EGFR, p53 expression, and O6-methylguanine DNA methyltransferase promotor methylation), were related to progression-free survival (PFS), malignant transformation-free survival (MTFS) and overall survival (OS)...
August 9, 2018: Neurosurgery
https://www.readbyqxmd.com/read/30107372/clinical-impact-of-post-progression-survival-on-overall-survival-in-elderly-patients-with-non-small-cell-lung-cancer-harboring-sensitive-egfr-mutations-treated-with-first-line-egfr-tyrosine-kinase-inhibitors
#15
Hisao Imai, Yutaka Yamada, Tomohide Sugiyama, Hiroyuki Minemura, Kyoichi Kaira, Kenya Kanazawa, Takashi Kasai, Takayuki Kaburagi, Koichi Minato
BACKGROUND/AIMS: More than 50% of patients with lung cancer are aged > 65 years, and non-small-cell lung cancer (NSCLC) accounts for 85% of all cases of lung cancer among both elderly and adult patients. Subsequent therapies confound the capability to discern the effect of first-line chemotherapy on overall survival (OS). Therefore, using individual-level data, our study aimed to determine the relationships of progression-free survival (PFS) and post-progression survival (PPS) with OS after first-line epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment in elderly patients with NSCLC harboring sensitive EGFR mutations...
August 14, 2018: Chemotherapy
https://www.readbyqxmd.com/read/30107055/driver-mutations-of-young-lung-adenocarcinoma-patients-with-malignant-pleural-effusion
#16
Shang-Gin Wu, Yi-Nan Liu, Chong-Jen Yu, James Chih-Hsin Yang, Jin-Yuan Shih
Young lung cancer patients have several distinct characteristics. However, there are limited epidemiological data of genetic abnormalities in this population. We conducted a prospective cohort study to delineate the various oncogenic driver mutations of lung adenocarcinoma in young Asian patients. We consecutively collected malignant pleural effusions (MPEs) from lung adenocarcinoma patients. RNA was extracted from MPEs for mutation analysis by reverse transcription-polymerase chain reaction and direct sequencing...
August 14, 2018: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/30106368/chronic-tubulointerstitial-kidney-disease-in-untreated-adenine-phosphoribosyl-transferase-aprt-deficiency-a-case-report
#17
Benjamin Cochran, Tereza Kovačíková, Kateřina Hodaňová, Martina Živná, Aleš Hnízda, Angela G Niehaus, Alex Bonnecaze, Gowrie Balasubraminiam, Irene Ceballos-Picot, Amret Hawfield, Kendrah Kidd, Stanislav Kmoch, Anthony J Bleyer
Adenine phosphoribosyltransferase (APRT) deficiency (OMIM #614723) is a rare autosomal recessive defect in the purine salvage pathway that causes excessive production of 2,8-dihydroxyadenine, leading to nephrolithiasis and chronic kidney disease (CKD). This case report describes the natural history of CKD in untreated APRT deficiency. We describe a novel APRT mutation (chr16:88877985 G / C; c.195 C>/G; p.His54Asp) presenting with CKD without nephrolithiasis. The patient initially required dialysis, but kidney function improved with allopurinol...
August 14, 2018: Clinical Nephrology
https://www.readbyqxmd.com/read/30105645/the-role-of-targeted-agents-and-immunotherapy-in-older-patients-with-non-small-cell-lung-cancer
#18
REVIEW
Fabio Gomes, Rebecca Tay, Jaseela Chiramel, Raffaele Califano
Lung cancer is predominantly a disease of the elderly. This subgroup of patients poses many challenges and an appropriate geriatric assessment is crucial for treatment personalisation in order to reduce the risk of over- or under-treatment. Whilst cytotoxic chemotherapy has been the backbone of advanced non-small cell lung cancer (NSCLC) treatment for decades, the development of targeted agents for driver mutations such as EGFR, ALK, BRAF and ROS1 has changed the treatment paradigm and natural history of this disease...
August 14, 2018: Drugs & Aging
https://www.readbyqxmd.com/read/30105500/a-star-shaped-dna-probe-based-on-strand-displacement-for-universal-and-multiplexed-fluorometric-detection-of-genetic-variations
#19
Na Liu, Kai Xu, Liquan Liu, Xin Chen, Yufan Zou, Xianjin Xiao
A star-shaped fluorescent DNA probe (S-probe) is described that can recognize target DNA and discriminate it from interfering DNA via strand displacement including branch migration and toehold exchange. The artificially designed S-probe does not harm the strand displacement while it allows the fluorescently labelled strand and the quencher-labelled strand to be shared among different S-probes targeting different genetic variations. Generally, multiplexed detection of different MT/WT pairs requires different fluorophore-labelled and quencher-labelled strands...
August 13, 2018: Mikrochimica Acta
https://www.readbyqxmd.com/read/30105235/precision-oncology-in-liver-cancer
#20
REVIEW
Kevin M Sullivan, Heidi L Kenerson, Venu G Pillarisetty, Kimberly J Riehle, Raymond S Yeung
With the widespread adoption of molecular profiling in clinical oncology practice, many physicians are faced with making therapeutic decisions based upon isolated genomic alterations. For example, epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) are effective in EGFR-mutant non-small cell lung cancers (NSCLC) while anti-EGFR monoclonal antibodies are ineffective in Ras-mutant colorectal cancers. The matching of mutations with drugs aimed at their respective gene products represents the current state of "precision" oncology...
July 2018: Annals of Translational Medicine
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