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https://www.readbyqxmd.com/read/28329143/epidermal-growth-factor-receptor-mutations-are-linked-to-skip-n2-lymph-node-metastasis-in-resected-non-small-cell-lung-cancer-adenocarcinomas%C3%A2
#1
Francesco Guerrera, Stéphane Renaud, Fabrizio Tabbó, Anne-Claire Voegeli', Pier Luigi Filosso, Michèle Legrain, Monica Boita, Mickaël Schaeffer, Michèle Beau-Faller, Enrico Ruffini, Pierre-Emmanuel Falcoz, Giorgio Inghirami, Alberto Oliaro, Gilbert Massard
OBJECTIVES: The impact of skip N2 metastases (i.e. N2 lymph node metastases without N1) on survival in surgically resected non-small lung cancer remains an intriguing and rarely investigated topic. The goal of our study was to elucidate (i) skip N2 influence on overall survival (OS) and time to recurrence (TTR) in patients with resected lung adenocarcinoma and (ii) its link with epidermal growth factor receptor ( EGFR ) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutations...
December 15, 2016: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/28325631/new-concepts-of-personalized-therapy-in-salivary-gland-carcinomas
#2
REVIEW
Gunter Keller, Diana Steinmann, Alexander Quaas, Viktor Grünwald, Stefan Janssen, Kais Hussein
Salivary gland carcinomas are rare tumours and therapy strategies are less standardized than in lung, gastric or breast cancer. Therapy is based on surgery, but not all carcinomas are completely resectable, e.g. because carcinomas often show infiltration of nerves. For further therapy decision pathology is recommended, but evaluation of potential targets for personalized therapy is not part of the routine panel. Many salivary gland carcinomas can be resistant to radio- and/or chemotherapy, which limits therapeutic options...
March 18, 2017: Oral Oncology
https://www.readbyqxmd.com/read/28325254/egfr-inhibition-in-nsclc-new-findings%C3%A2-and-opened-questions
#3
REVIEW
Francesco Passiglia, Angela Listì, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Viviana Bazan, Antonio Russo
The targeted inhibition of epidermal growth factor receptor (EGFR) has represented a milestone in the treatment of lung cancer. Several studies convincingly and consistently demonstrated a significant superiority of EGFR-TKIs over standard platinum-chemotherapy in EGFR-mutated NSCLC patients, leading to the sequential approval of gefitinib, erlotinib and afatinib as new standard first-line clinical treatment. To date we are witnessing a second revolution in the management of EGFR-positive NSCLC thanks to the development of new treatment strategies aiming to overcome acquired resistance to TKIs and ultimately improve patients' outcomes...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28323756/tdf-associated-renal-tubular-dysfunction-non-invasive-assessment-of-mitochondrial-injury
#4
Ryan Samuels, Carla Roca Bayerri, John A Sayer, D Ashley Price, Brendan Ai Payne
OBJECTIVE: To determine whether TDF-associated renal tubular dysfunction is associated with evidence of mitochondrial injury in urine. DESIGN: Single centre cross-sectional observational study of HIV positive outpatients. METHODS: Biochemistry was performed on paired serum and urine samples. Mitochondrial DNA (mtDNA) was studied by real-time PCR and long-range PCR on cellular fractions of urine. RESULTS: 48 subjects were enrolled of whom half were TDF-treated...
March 18, 2017: AIDS
https://www.readbyqxmd.com/read/28323493/microparticles-containing-erlotinib-loaded-solid-lipid-nanoparticles-for-treatment-of-non-small-cell-lung-cancer
#5
Zahra Bakhtiary, Jaleh Barar, Ayuob Aghanejad, Amir Ata Saei, Elhameh Nemati, Jafar Ezzati Nazhad Dolatabadi, Yadollah Omidi
Non-small cell lung cancer (NSCLC) patients with sensitizing mutations in the exons 18-21 of the epithelial growth factor receptor (EGFR) geneshowincreased kinase activity of EGFR. Hence, tyrosine kinase inhibitors (TKIs) such as erlotinib (ETB) havecommonly been used as the second line therapeutic option in metastatic NSCLC. While the ETB is available as an oral dosage form, the local delivery of this TKI to the diseased cells of the lung may ameliorate its therapeutic impacts. In the current study, we report on the development of ETB-loaded solid lipid nanoparticle (SLN) based formulation of dry powder inhaler (ETB-SLN DPI)...
March 21, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28322512/clinicopathological-and-prognostic-features-of-surgically-resected-pathological-stage-i-lung-adenocarcinoma-harboring-epidermal-growth-factor-receptor-and-k-ras-mutation
#6
Kaoru Kaseda, Keisuke Asakura, Akio Kazama, Yukihiko Ozawa
BACKGROUND: This study aimed to evaluate mutations of the epidermal growth factor receptor (EGFR) and K-ras genes and their clinicopathological and prognostic features in patients with resected pathological stage I adenocarcinoma. METHODS: We examined 224 patients with surgically resected lung adenocarcinoma and analyzed the prognostic and predictive value of these mutations in 162 patients with pathological stage I adenocarcinoma. RESULTS: Mutations of the EGFR and K-ras genes were detected in 100 (44...
March 21, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28322191/met-gene-amplification-and-overexpression-in-chinese-non-small-cell-lung-cancer-patients-without-egfr-mutations
#7
Zhengbo Song, Xuzhou Wang, Yuhui Zheng, Haiyan Su, Yiping Zhang
BACKGROUND: The prevalence and clinical pathologic characteristics of MET amplification and overexpression in Chinese patients with non-small-cell lung cancer (NSCLC) remain unknown. In this multicenter study, we sought to reveal the frequency and clinical pathologic characteristics of MET amplification and to explore the predictive value of MET amplification and overexpression status in relation to survival in Chinese NSCLC patients. PATIENTS AND METHODS: MET amplification was detected by fluorescence in-situ hybridization in 791 patients with EGFR wild-type samples...
March 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28320414/epidermal-growth-factor-receptor-and-epididymis-invasion-as-prognostic-biomarkers-in-clinical-stage-i-testicular-germ-cell-tumours
#8
Miguel F Sanmamed, E Esteban, E Uriol, R Zarate, M Capelan, C Muriel, G Crespo, J P Berros, P Pardo-Coto, Q Perez, C Alvarez-Fernández, P Jiménez Fonseca, M Luque, A Astudillo
BACKGROUND: Inguinal orchiectomy is curative in 70-80% of clinical stage I testicular germ cell tumours (CS I TGCT). The identification of patients who are at low risk of relapse is critical to avoid unnecessary treatment. The aim of this study is to explore EGFR, hMLH-1/hMSH-2 and microsatellite instability (MSI) as potential prognostic factors of recurrence in CS I TGCT. METHODS: Fifty-six CS I TGCT patients who underwent inguinal orchiectomy were included in this study...
March 20, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28316074/a-comparison-of-alk-gene-rearrangement-and-alk-protein-expression-in-primary-lung-carcinoma-and-matched-metastasis
#9
Humberto E Trejo Bittar, Alyssa Luvison, Caitlyn Miller, Sanja Dacic
AIMS: The 2013 CAP/IASLC/AMP guideline for EGFR and ALK testing in lung carcinoma indicates that either the primary tumor or the metastasis is suitable for testing. The heterogeneity of gene mutations has been extensively studied, while similar reports on gene rearrangements are limited. The aim of this study was to determine if ALK status between primary tumor and matched metastasis differs. METHODS AND RESULTS: 15 ALK-FISH rearranged and 19 non-ALK-FISH rearranged adenocarcinomas were retrospectively collected based on availability of tissue from a matched metastatic site...
March 17, 2017: Histopathology
https://www.readbyqxmd.com/read/28315738/pulmonary-sarcomatoid-carcinomas-commonly-harbor-either-potentially-targetable-genomic-alterations-or-high-tumor-mutational-burden-as-observed-by-comprehensive-genomic-profiling
#10
Alexa B Schrock, Shuyu D Li, Garrett M Frampton, James Suh, Eduardo Braun, Ranee Mehra, Steven Buck, Jose A Bufill, Nir Peled, Nagla Abdel Karim, Cynthia Hsieh, Manuel Doria, James Knost, Rong Chen, Sai-Hong Ignatius Ou, Jeffrey S Ross, Philip J Stephens, Paul Fishkin, Vincent A Miller, Siraj M Ali, Balazs Halmos, Jane J Liu
BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is a high-grade non-small cell lung carcinoma (NSCLC) characterized by poor prognosis and resistance to chemotherapy. Development of targeted therapeutic strategies for PSC has been hampered due to limited and inconsistent molecular characterization. METHODS: Hybrid-capture based comprehensive genomic profiling (CGP) was performed on DNA from 15,867 FFPE NSCLCs including 125 PSCs (0.8%). Tumor mutational burden (TMB) was calculated from 1...
March 15, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28315597/discovery-of-n-3-5-3-acrylamido-4-morpholine-4-carbonyl-phenyl-amino-1-methyl-6-oxo-1-6-dihydropyridin-3-yl-2-methylphenyl-4-tert-butyl-benzamide-chmfl-btk-01-as-a-highly-selective-irreversible-bruton-s-tyrosine-kinase-btk-inhibitor
#11
Qianmao Liang, Yongfei Chen, Kailin Yu, Cheng Chen, Shouxiang Zhang, Aoli Wang, Wei Wang, Hong Wu, Xiaochuan Liu, Beilei Wang, Li Wang, Zhenquan Hu, Wenchao Wang, Tao Ren, Shanchun Zhang, Qingsong Liu, Cai-Hong Yun, Jing Liu
Currently there are several irreversible BTK inhibitors targeting Cys481 residue under preclinical or clinical development. However, most of these inhibitors also targeted other kinases such as BMX, JAK3, and EGFR that bear the highly similar active cysteine residues. Through a structure-based drug design approach, we discovered a highly potent (IC50: 7 nM) irreversible BTK inhibitor compound 9 (CHMFL-BTK-01), which displayed a high selectivity profile in KINOMEscan (S score (35) = 0.00) among 468 kinases/mutants at the concentration of 1 μM...
March 2, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28314739/intratumorous-heterogeneity-for-ras-mutations-in-a-treatment-na%C3%A3-ve-colorectal-tumour
#12
Sebastian Lunke, Belinda Lee, Sevastjan Kranz, Peter Gibbs, Paul Waring, Michael Christie
Activating mutations in KRAS and NRAS genes in patients with colorectal cancer (CRC) are associated with a lack of response to treatment with anti-epidermal growth factor receptor (EGFR) therapies. Mutations in these genes are thought to be mutually exclusive, however reports have described CRCs with two activating rat sarcoma (RAS) mutations. This has fuelled discussion about whether these mutations are the result of intratumorous heterogeneity, or if they are co-occurring in the same cancer cell clone. We present a case of a colorectal tumour with three RAS mutations detected during routine diagnostic testing...
March 17, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28306520/assessment-of-real-time-pcr-method-for-detection-of-egfr-mutation-using-both-supernatant-and-cell-pellet-of-malignant-pleural-effusion-samples-from-non-small-cell-lung-cancer-patients
#13
Saeam Shin, Juwon Kim, Yoonjung Kim, Sun-Mi Cho, Kyung-A Lee
BACKGROUND: EGFR mutation is an emerging biomarker for treatment selection in non-small-cell lung cancer (NSCLC) patients. However, optimal mutation detection is hindered by complications associated with the biopsy procedure, tumor heterogeneity and limited sensitivity of test methodology. In this study, we evaluated the diagnostic utility of real-time PCR using malignant pleural effusion samples. METHODS: A total of 77 pleural fluid samples from 77 NSCLC patients were tested using the cobas EGFR mutation test (Roche Molecular Systems)...
March 17, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28306189/map4k4-is-a-novel-mapk-erk-pathway-regulator-required-for-lung-adenocarcinoma-maintenance
#14
Xuan Gao, Guangming Chen, Chenxi Gao, Dennis Han Zhang, Shih-Fan Kuan, Laura P Stabile, Guoxiang Liu, Jing Hu
About 76% of lung adenocarcinoma patients harbor activating mutations in the receptor tyrosine kinase (RTK)/RAS/RAF pathways, leading to aberrant activation of the MAPK pathways particularly the MAPK/ERK pathway. However, many lung adenocarcinomas lacking these genomic mutations also display significant MAPK pathway activation, suggesting that additional MAPK pathway alterations remain undetected. This study has identified serine/threonine kinase mitogen-activated protein 4 kinase 4 (MAP4K4) as a novel positive regulator of MAPK/ERK signaling in lung adenocarcinoma...
March 17, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28302223/-current-status-and-prospect-of-t790m-mutation-in-non-small-cell-lung-cancer
#15
Qin Yu, Da Jiang, Ying Li
Targeted therapy with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) is regarded as the main accepted first-line treatment on EGFR mutation in non-small cell lung cancer (NSCLC). Although targeted therapy for the first and two generation of TKIs may lead to longer progression-free survival (PFS) and better tolerance for patients, the long-term treatment will inevitably lead to drug resistance. Among them, more than 50% of acquired resistance is associated with T790M mutation. The latest guidelines from the National Comprehensive Cancer Network (NCCN) have been proposed that the three generation of TKI (Osimertinib) can be used in first-line TKI therapy progress with detecting T790M mutations in patients...
March 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28302219/-mucoepidermoid-carcinoma-of-the-lung-report-of-29-cases
#16
Jingjing Hou, Huijuan Wang, Guowei Zhang, Yanyang Huang, Zhiyong Ma
BACKGROUND: Pulmonary mucoepidermoid carcinoma (MEC) is an extremely rare pulmonary malignant tumor, its clinical features and conditions of prognosis is not entirely clear. The aim of this study is to discuss clinical features, diagnostic and therapeutic methods, and prognosis of pulmonary MEC. METHODS: We retrospectively studied 29 pulmonary MEC patients who diagnosed from January 2006 to December 2015 in Affiliated Hospital of Zhengzhou University. The clinical features, prognosis, diagnostic and therapeutic methods were analyzed...
March 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28302215/-altered-treg-and-il-1a-expression-in-the-immune-microenvironment-%C3%A2-of-lung-squamous-cell-cancer-after-egfr-blockade
#17
Haiyang He, Luyu Qi, Yiling Hou
BACKGROUND: Targeting the mutations and amplifications in the epidermal growth factor receptor (EGFR) gene has curative effects on cancers of the lung, oral cavity, and gastrointestinal system. However, a systemic immune inflammation is an adverse effect of this therapeutic strategy. In this study, we aimed to identify the possible changes in the tumor microenvironment that contribute to the anti-cancer activity of EGFR inhibition. METHODS: Squamous-cell cancers were induced by the syngeneic transplantation of either EGFR-null or wild-type mouse primary keratinocytes that had been transduced with an oncogenic H-ras retrovirus...
March 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28301925/retrospective-molecular-epidemiology-study-of-pd-l1-expression-in-patients-with-egfr-mutant-non-small-cell-lung-cancer
#18
Jong Ho Cho, Wei Zhou, Yoon-La Choi, Jong-Mu Sun, Hyejoo Choi, Tae-Eun Kim, Marisa Dolled-Filhart, Kenneth Emancipator, Mary Anne Rutkowski, Jhingook Kim
Purpose: Data are limited on PD-L1 expression in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Materials and Methods: We retrospectively evaluated the relationship between PD-L1 expression and recurrence-free (RFS) and overall survival in 319 patients with EGFR-mutant NSCLC who were treated at Samsung Medical Center from 2006 to 2014. Membranous PD-L1 expression on tumor cells was measured using the PD-L1 IHC 22C3 pharmDx antibody and reported as tumor proportion score (TPS)...
March 17, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28300714/biomarkers-and-immunotherapeutic-targets-in-glioblastoma
#19
REVIEW
Alice L Hung, Tomas Garzon-Muvdi, Michael Lim
Glioblastoma (GBM) is an aggressive central nervous system (CNS) cancer with poor prognosis despite maximal therapy. The recent advent of immunotherapy holds great promise for improving GBM survival and has already made great strides towards changing current management strategies. A diverse set of biomarkers has been implicated as immunotherapeutic targets and prognostic indicators in other cancers. Some of the more extensively studied examples include cytokines (IL-4, IL-13, and TGF-ß), checkpoint molecules (PD-1, CTLA-4, TIM-3, LAG-3, CD137, GITR, OX40), and growth/angiogenesis proteins (endoglin and EGFR)...
March 11, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28300553/neutrophil-elastase-inhibitor-sivelestat-ameliorates-gefitinib-naphthalene-induced-acute-pneumonitis-in-mice
#20
Hironori Mikumo, Toyoshi Yanagihara, Naoki Hamada, Eiji Harada, Saiko Ogata-Suetsugu, Chika Ikeda-Harada, Masako Arimura-Omori, Kunihiro Suzuki, Testuya Yokoyama, Yoichi Nakanishi
Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is an effective therapeutic agent for non-small cell lung cancer with EGFR mutations. It can cause severe acute pneumonitis in some patients. We previously demonstrated that mice with naphthalene-induced airway epithelial injury developed severe gefitinib-induced pneumonitis and that neutrophils played important roles in the development of the disease. This study aimed to investigate the effects of the neutrophil elastase inhibitor sivelestat on gefitinib-induced pneumonitis in mice...
March 12, 2017: Biochemical and Biophysical Research Communications
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