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https://www.readbyqxmd.com/read/27930702/a-survival-scoring-system-for-non-small-cell-lung-cancer-patients-with-de-novo-bone-metastases
#1
Yu-Mu Chen, Ying-Tang Fang, Chien-Hao Lai, Kun-Ming Rau, Cheng-Hua Huang, Huang-Chih Chang, Tung-Ying Chao, Chia-Cheng Tseng, Wen-Feng Fang, Chin-Chou Wang, Yung-Che Chen, Yu-Hsiu Chung, Yi-Hsi Wang, Mao-Chang Su, Shih-Feng Liu, Kuo-Tung Huang, Hung-Chen Chen, Ya-Chun Chang, Yu-Ping Chang, Meng-Chih Lin
In the pre-tyrosine kinase inhibitors (TKIs) era, non-small cell lung cancer (NSCLC) patients with de novo bone metastases had a worse prognosis than those without. However, whether epidermal growth factor receptor (EGFR)-TKIs affect the outcomes of EGFR mutant NSCLC patients with de novo bone metastases has not been well studied thus far. We retrospectively studied the effect of EGFR mutation status and first-line EGFR-TKIs on patient outcomes and created a survival scoring system for NSCLC patients with de novo bone metastases...
2016: PloS One
https://www.readbyqxmd.com/read/27929064/acquired-ras-or-egfr-mutations-and-duration-of-response-to-egfr-blockade-in-colorectal-cancer
#2
Beth O Van Emburgh, Sabrina Arena, Giulia Siravegna, Luca Lazzari, Giovanni Crisafulli, Giorgio Corti, Benedetta Mussolin, Federica Baldi, Michela Buscarino, Alice Bartolini, Emanuele Valtorta, Joana Vidal, Beatriz Bellosillo, Giovanni Germano, Filippo Pietrantonio, Agostino Ponzetti, Joan Albanell, Salvatore Siena, Andrea Sartore-Bianchi, Federica Di Nicolantonio, Clara Montagut, Alberto Bardelli
Blockade of the epidermal growth factor receptor (EGFR) with the monoclonal antibodies cetuximab or panitumumab is effective in a subset of colorectal cancers (CRCs), but the emergence of resistance limits the efficacy of these therapeutic agents. At relapse, the majority of patients develop RAS mutations, while a subset acquires EGFR extracellular domain (ECD) mutations. Here we find that patients who experience greater and longer responses to EGFR blockade preferentially develop EGFR ECD mutations, while RAS mutations emerge more frequently in patients with smaller tumour shrinkage and shorter progression-free survival...
December 8, 2016: Nature Communications
https://www.readbyqxmd.com/read/27928469/mechanisms-underlying-18-f-fluorodeoxyglucose-accumulation-in-colorectal-cancer
#3
REVIEW
Kenji Kawada, Masayoshi Iwamoto, Yoshiharu Sakai
Positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) is a diagnostic tool to evaluate metabolic activity by measuring accumulation of FDG, an analogue of glucose, and has been widely used for detecting small tumors, monitoring treatment response and predicting patients' prognosis in a variety of cancers. However, the molecular mechanism of FDG accumulation into tumors remains to be investigated. It is well-known that most cancers are metabolically active with elevated glucose metabolism, a phenomenon known as the Warburg effect...
November 28, 2016: World Journal of Radiology
https://www.readbyqxmd.com/read/27928026/azd3759-a-bbb-penetrating-egfr-inhibitor-for-the-treatment-of-egfr-mutant-nsclc-with-cns-metastases
#4
Zhenfan Yang, Qiuli Guo, Yingchun Wang, Kan Chen, Lin Zhang, Ziqiang Cheng, Yanping Xu, Xiaolu Yin, Yu Bai, Sarit Rabbie, Dong-Wan Kim, Myung-Ju Ahn, James Chih-Hsin Yang, Xiaolin Zhang
Non-small-cell lung cancer patients with activating mutations in epidermal growth factor receptor (EGFR) respond to EGFR tyrosine kinase inhibitor (TKI) treatment. Nevertheless, patients often develop central nervous system (CNS) metastases during treatment, even when their extracranial tumors are still under control. In the absence of effective options, much higher doses of EGFR TKIs have been attempted clinically, with the goal of achieving high enough drug concentrations within the CNS. Although limited tumor responses have been observed with this approach, the toxicities outside the CNS have been too high to tolerate...
December 7, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27927060/new-data-on-clinical-decisions-in-nsclc-patients-with-uncommon-egfr-mutations
#5
Ting-Hui Wu, Emily Han-Chung Hsiue, Jih-Hsiang Lee, Chia-Chi Lin, James Chih-Hsin Yang
Non-small cell lung cancer patients harboring uncommon epidermal growth factor receptor (EGFR) mutations together account for approximately 10% of all EGFR mutations. The most common of which being G719X, S768I, L861Q, and exon 20 insertions. The clinical significance, particularly their response to EGFR tyrosine kinase inhibitors (TKIs) is largely unclear. Previous data is limited to a small fraction of patients in prospective studies and retrospective series. Recently, a combined analysis of patients with uncommon EGFR mutations in the Lux-Lung 2, Lux-Lung 3, Lux-Lung 6 trials provide new perspectives of uncommon EGFR mutations...
December 7, 2016: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/27926500/the-association-between-clinical-prognostic-factors-and-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-egfr-tki-efficacy-in-advanced-non-small-cell-lung-cancer-patients-a-retrospective-assessment-of-94-cases-with-egfr-mutations
#6
Jing-Hui Lin, Dong Lin, Ling Xu, Qiang Wang, Hui-Hua Hu, Hai-Peng Xu, Zhi-Yong He
OBJECTIVE: This study aimed to examine the association of clinical prognostic factors with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) efficacy in advanced non-small-cell lung cancer (NSCLC) patients. METHODS: The demographic and clinical characteristics of 94 patients with stage IV NSCLC were retrospectively reviewed, and the association between clinical factors and EGFR-TKIs efficacy was evaluated. RESULTS: Of the 94 stage IV NSCLC patients enrolled in this study, a 74...
December 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926478/bim-deletion-polymorphisms-in-hispanic-patients-with-non-small-cell-lung-cancer-carriers-of-egfr-mutations
#7
Andrés F Cardona, Leonardo Rojas, Beatriz Wills, Oscar Arrieta, Hernán Carranza, Carlos Vargas, Jorge Otero, Luis Corrales-Rodriguez, Claudio Martín, Noemí Reguart, Pilar Archila, July Rodríguez, Mauricio Cuello, Carlos Ortíz, Sandra Franco, Christian Rolfo, Rafael Rosell, On Behalf Of The CLICaP
BACKGROUND: Germline alterations in the proapoptotic protein Bcl-2-like 11 (BIM) can have a crucial role in diverse tumors. To determine the clinical utility of detecting BIM deletion polymorphisms (par4226 bp/ par363 bp) in EGFR positive non-small-cell lung cancer (NSCLC) we examined the outcomes of patients with and without BIM alterations. RESULTS: BIM deletion was present in 14 patients (15.7%). There were no significant differences between patients with and without BIM-del in clinical characteristics or EGFR mutation type; however, those with BIM-del had a worse overall response rate (ORR) to erlotinib (42...
September 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925186/up-regulation-of-transient-receptor-potential-melastatin-6-channel-expression-by-tumor-necrosis-factor-%C3%AE-in-the-presence-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor
#8
Chisa Furukawa, Naoko Fujii, Aya Manabe, Toshiyuki Matsunaga, Satoshi Endo, Hajime Hasegawa, Yoshinori Ito, Masahiko Yamaguchi, Yasuhiro Yamazaki, Akira Ikari
Anti-epidermal growth factor receptor (EGFR) drugs such as erlotinib and gefitinib cause a side effect of hypomagnesemia, but chemotherapy to treat this has not yet been developed. The transient receptor potential melastatin 6 (TRPM6) channel is involved in the reabsorption of Mg(2+) in the renal tubule. We reported previously that the expression of TRPM6 is up-regulated by epidermal growth factor (EGF) in renal tubular epithelial NRK-52E and HEK293 cells. EGF-induced elevation of TRPM6 expression was inhibited by erlotinib, gefitinib, and lapatinib...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27924500/mir-124-modulates-gefitinib-resistance-through-snai2-and-stat3-in-non-small-cell-lung-cancer
#9
Fa-Yong Hu, Xiao-Nian Cao, Qin-Zi Xu, Yu Deng, Sen-Yan Lai, Jing Ma, Jun-Bo Hu
Gefitinib is used as a first-line treatment for advanced non-small cell lung cancer (NSCLC). Unfortunately, most NSCLC patients inevitably develop gefitinib resistance during treatment. In addition to EGFR mutation status, the mechanisms involved are largely unknown. In this study, we showed that miR-124, a tumor suppressor, was significantly down-regulated in gefitinib-resistant NSCLC patients and cell lines compared with gefitinib-sensitive patients and cell lines. In addition, the miR-124 depletion induced gefitinib resistance, and miR-124 overexpression sensitized gefitinib-resistant cells to gefitinib...
December 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/27924059/an-open-label-phase-ii-study-evaluating-first-line-egfr-tyrosine-kinase-inhibitor-erlotinib-in-non-small-cell-lung-cancer-patients-with-tumors-showing-high-egfr-gene-copy-number
#10
Ewa Szutowicz-Zielińska, Krzysztof Konopa, Anna Kowalczyk, Małgorzata Suszko-Każarnowicz, Renata Duchnowska, Aleksandra Szczęsna, Magdalena Ratajska, Aleksander Sowa, Janusz Limon, Wojciech Biernat, Tomasz Burzykowski, Jacek Jassem, Rafał Dziadziuszko
BACKGROUND: First-line treatment with epidermal growth factor receptor (EGFR) inhibitors in NSCLC is effective in patients with activating EGFR mutations. The activity of erlotinib in patients harboring high EGFR gene copy number has been considered debatable. PATIENTS AND METHODS: A multicenter, open-label, single-arm phase II clinical trial was performed to test the efficacy of erlotinib in the first-line treatment of NSCLC patients harboring high EGFR gene copy number defined as ≥4 copies in ≥40% of cells...
December 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27923714/brief-report-acquired-braf-v600e-mutation-as-resistant-mechanism-after-treatment-with-osimertinib
#11
Chao-Chi Ho, Wei-Yu Liao, Chih-An Lin, Jin-Yuan Shih, Chong-Jen Yu, James Chih-Hsin Yang
INTRODUCTION: AZD9291 (osimertinib) is designed for acquired T790M mutation after first- and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been used. Some of the resistance mechanisms that present after osimertinib treatment, including a newly acquired EGFR C797S mutation, have been identified. It is unclear, however, whether the bypass pathway is also a resistant mechanism in patients after osimertinib treatment. METHODS: Cells from malignant pleural effusion were collected and cultured at the time of progression in a patient being treated with osimertinib...
December 3, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27923629/prognostic-value-of-rare-and-complex-mutations-in-egfr-and-serum-levels-of-soluble-egfr-and-its-ligands-in-iranian-non-small-cell-lung-carcinoma-patients
#12
Seyyed Mortaza Haghgoo, Adnan Khosravi, Esmaeil Mortaz, Mihan Pourabdollah Toutkaboni, Sharareh Seifi, Siamak Sabour, Abdolamir Allameh
BACKGROUND: A number of complex and rare mutations in epidermal growth factor receptor (EGFR) gene have been identified and the clinical implication of serum EGFR ligands has also been reported. However, the prognostic significance of these mutations and also the serum EGFR and its ligands in Non-Small Cell Lung Carcinoma (NSCLC) has remained a challenging issue. This study is aimed at finding the prognostic importance of EGFR rare mutations and serum EGFR, amphiregulin (AR), and TGF-α (Transforming Growth Factor-alpha) in NSCLC...
December 3, 2016: Clinical Biochemistry
https://www.readbyqxmd.com/read/27923066/somatic-genomics-and-clinical-features-of-lung-adenocarcinoma-a-retrospective-study
#13
Jianxin Shi, Xing Hua, Bin Zhu, Sarangan Ravichandran, Mingyi Wang, Cu Nguyen, Seth A Brodie, Alessandro Palleschi, Marco Alloisio, Gianluca Pariscenti, Kristine Jones, Weiyin Zhou, Aaron J Bouk, Joseph Boland, Belynda Hicks, Adam Risch, Hunter Bennett, Brian T Luke, Lei Song, Jubao Duan, Pengyuan Liu, Takashi Kohno, Qingrong Chen, Daoud Meerzaman, Crystal Marconett, Ite Laird-Offringa, Ian Mills, Neil E Caporaso, Mitchell H Gail, Angela C Pesatori, Dario Consonni, Pier Alberto Bertazzi, Stephen J Chanock, Maria Teresa Landi
BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and has a high risk of distant metastasis at every disease stage. We aimed to characterize the genomic landscape of LUAD and identify mutation signatures associated with tumor progression. METHODS AND FINDINGS: We performed an integrative genomic analysis, incorporating whole exome sequencing (WES), determination of DNA copy number and DNA methylation, and transcriptome sequencing for 101 LUAD samples from the Environment And Genetics in Lung cancer Etiology (EAGLE) study...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27922739/tyrosine-kinase-aurora-kinase-and-leucine-aminopeptidase-as-attractive-drug-targets-in-anticancer-therapy-characterisation-of-their-inhibitors
#14
Joanna Ziemska, Jolanta Solecka
Cancers are the leading cause of deaths all over the world. Available anticancer agents used in clinics exhibit low therapeutic index and usually high toxicity. Wide spreading drug resistance of cancer cells induce a demanding need to search for new drug targets. Currently, many on-going studies on novel compounds with potent anticancer activity, high selectivity as well as new modes of action are conducted. In this work, we describe in details three enzyme groups, which are at present of extensive interest to medical researchers and pharmaceutical companies...
2016: Roczniki Państwowego Zakładu Higieny
https://www.readbyqxmd.com/read/27922678/a-novel-rapid-point-of-care-test-for-lung-cancer-patients-to-detect-epidermal-growth-factor-receptor-gene-mutations-by-using-real-time-droplet-pcr-and-fresh-liquid-cytology-specimens
#15
Shiho Asaka, Akihiko Yoshizawa, Kazuyuki Matsuda, Akemi Yamaguchi, Hiroshi Yamamoto, Takayuki Shiina, Rie Nakata, Kaoru Ogawa, Meng Zhang, Takayuki Honda
Epidermal growth factor receptor gene (EGFR) mutations are associated with response to tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). We developed a novel, rapid EGFR mutation assay using a real-time droplet-polymerase chain reaction machine (EGFR d-PCR assay). The purpose of this study was to validate the performance of the EGFR d-PCR assay using fresh liquid cytology specimens. We analyzed three major EGFR mutations (L858R in exon 21, E746_A750del in exon 19 and T790M in exon 20) in 80 fresh liquid cytology specimens of adenocarcinoma (ADC) or NSCLC-not otherwise specified (NOS) via the EGFR d-PCR assay and conventional real-time PCR assay using the therascreen® EGFR RGQ PCR kit (Therascreen assay)...
December 2, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27922044/from-tumour-heterogeneity-to-advances-in-precision-treatment-of-colorectal-cancer
#16
REVIEW
Cornelis J A Punt, Miriam Koopman, Louis Vermeulen
In recent years, the high heterogeneity of colorectal cancer (CRC) has become evident. Hence, biomarkers need to be developed that enable the stratification of patients with CRC into different prognostic subgroups and in relation to response to therapies, according to the distinctive tumour biology. Currently, only RAS-mutation status is used routinely as a negative predictive marker to avoid treatment with anti-EGFR agents in patients with metastatic CRC, and mismatch-repair status can guide the use of adjuvant chemotherapy in patients with early stage colon cancer...
December 6, 2016: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/27921038/the-clinical-manifestation-and-management-of-autosomal-dominant-polycystic-kidney-disease-in-china
#17
REVIEW
Cheng Xue, Chen-Chen Zhou, Ming Wu, Chang-Lin Mei
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic hereditary kidney disease characterized by progressive enlargement of renal cysts. The incidence is 1-2‰ worldwide. Mutations in two genes (PKD1 and PKD2) cause ADPKD. Currently, there is no pharmaceutical treatment available for ADPKD patients in China. Summary: This review focused on advances in clinical manifestation, gene diagnosis, risk factors, and management of ADPKD in China. There is an age-dependent increase in total kidney volume (TKV) and decrease in renal function in Chinese ADPKD patients...
October 2016: Kidney Diseases
https://www.readbyqxmd.com/read/27920501/three-generations-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-developed-to-revolutionize-the-therapy-of-lung-cancer
#18
REVIEW
Haijun Zhang
Lung cancer, ~80%-85% of which is non-small-cell lung cancer (NSCLC), is the leading cause of cancer-related mortality worldwide. Sensitizing mutations in epidermal growth factor receptor (EGFR) gene (EGFRm(+)), such as exon 19 deletions and exon 21 L858R point mutations, are the most important drivers in NSCLC patients. In this respect, small-molecule EGFR tyrosine kinase inhibitors (TKIs) have been designed and developed, which launched the era of targeted, personalized and precise medicine for lung cancer...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27920137/oncogenic-met-as-an-effective-therapeutic-target-in-non-small-cell-lung-cancer-resistant-to-egfr-inhibitors-the-rise-of-the-phoenix
#19
Livio Trusolino
Anecdotal reports have shown that concomitant inhibition of EGFR and MET can be clinically effective in patients with non-small cell lung cancer carrying EGFR mutations and MET amplification, but large phase III trials in genetically unselected individuals have failed to confirm the benefit of this combination therapy. A new study corroborates the evidence that lung cancer susceptibility to EGFR and MET blockade is sustained by genetically based activation of both targets and identifies a mutation in MET that confers acquired resistance to standard MET inhibitors hitting the active kinase, yet is vulnerable to other MET-directed compounds with a different binding mode...
December 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27919997/lung-cancer-in-women-with-a-family-history-of-cancer-the-spanish-female-specific-database-world07
#20
Dolores Isla, Enriqueta Felip, Nuria Viñolas, Mariano Provencio, Margarita Majem, Angel Artal, Isabel Bover, Pilar Lianes, Ramón DE Las Peñas, Silvia Catot, Javier DE Castro, Ana Blasco, Josefa Terrasa, José Luis Gonzalez-Larriba, Oscar Juan, Manuel Dómine, Reyes Bernabe, Pilar Garrido
BACKGROUND: The WORLD07 project is a female-specific database to prospectively analyze the characteristics of Spanish women with lung cancer. PATIENTS AND METHODS: We analyzed and compared lung cancer features in women with and without a family history of cancer/lung cancer. RESULTS: Two thousand and sixty women were included: 876 had a family history of cancer (lung cancer, 34%) and 886 did not, with no significant differences between groups, except for smoking status (p=0...
December 2016: Anticancer Research
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