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https://www.readbyqxmd.com/read/28050384/inflammatory-myofibroblastic-tumor-of-the-kidney-a-rare-renal-tumor
#1
Alvin Jose Pothadiyil, Suresh Bhat, Fredrick Paul, Jithesh Mampatta, Mahesh Srinivas
Inflammatory Myofibroblastic Tumour (IMT) or 'pseudotumour' of the kidney is a rare benign tumour of unknown aetiology affecting mostly young adults. A subset of IMT is neoplastic and harbours translocations of activin receptor-like kinase-1 (ALK-1) gene and can recur or rarely metastasize. Presentation varies from an incidentaloma to gross haematuria. Clinical examination and radiological investigations are usually inconclusive. Often, biopsy is inconclusive necessitating a management similar to that of Renal Cell Cancer (RCC)...
November 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28039177/differential-protein-stability-and-clinical-responses-of-eml4-alkfusion-variants-to-various-alk-inhibitors-in-advanced-alk-rearranged-non-small-cell-lung-cancer
#2
C G Woo, S Seo, S W Kim, S J Jang, K S Park, J Y Song, B Lee, M W Richards, R Bayliss, D H Lee, J Choi
BACKGROUND: Anaplastic lymphoma kinase (ALK) inhibition using crizotinib has become the standard of care in advanced ALK-rearranged non-small cell lung cancer (NSCLC), but the treatment outcomes and duration of response vary widely. Echinoderm microtubule-associated protein-like 4 (EML4)-ALK is the most common translocation, and the fusion variants show different sensitivity to crizotinib in vitro. However, there are only limited data on the specific EML4-ALK variants and clinical responses of patients to various ALK inhibitors...
December 29, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28024689/alk-testing-in-non-small-cell-lung-cancer-nsclc-immunohistochemistry-ihc-and-or-fluorescence-in-situ-hybridisation-fish-statement-of-the-germany-society-for-pathology-dgp-and-the-working-group-thoracic-oncology-aio-of-the-german-cancer-society-e-v-stellungnahme
#3
M von Laffert, P Schirmacher, A Warth, W Weichert, R Büttner, R M Huber, J Wolf, F Griesinger, M Dietel, Ch Grohé
The EML4-ALK pathway plays an important role in a significant subset of non-small cell lung cancer patients. Treatment options such as ALK tyrosine kinase inhibitors lead to improved progression free survival and overall survival. These therapeutic options are chosen on the basis of the identification of the underlying genetic signature of the EML-ALK translocation. Efficient and easily accessible testing tools are required to identify eligible patients in a timely fashion. While FISH techniques are commonly used to detect this translocation, the broad implementation of this type of ALK testing into routine diagnostics is not optimal due to technical, structural and financial reasons...
January 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/27988109/receptor-tyrosine-kinases-translocation-partners-in-hematopoietic-disorders
#4
REVIEW
Katelyn N Nelson, Malalage N Peiris, April N Meyer, Asma Siari, Daniel J Donoghue
Receptor tyrosine kinases (RTKs) activate various signaling pathways and regulate cellular proliferation, survival, migration, and angiogenesis. Malignant neoplasms often circumvent or subjugate these pathways by promoting RTK overactivation through mutation or chromosomal translocation. RTK translocations create a fusion protein containing a dimerizing partner fused to an RTK kinase domain, resulting in constitutive kinase domain activation, altered RTK cellular localization, upregulation of downstream signaling, and novel pathway activation...
January 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27960155/stimulation-of-suicidal-erythrocyte-death-by-ceritinib-treatment-of-human-erythrocytes
#5
Abdulla Al Mamun Bhuyan, Elena Signoretto, Rosi Bissinger, Florian Lang
BACKGROUND/AIMS: The anaplastic lymphoma kinase (ALK) inhibitor ceritinib is utilized for the treatment of ALK positive non-small cell lung carcinoma. Side effects of the drug include decrease of blood hemoglobin concentration. Possible causes of anemia include stimulation of suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling of eryptosis includes increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, ceramide, staurosporine sensitive protein kinase C, SB203580 sensitive p38 kinase, D4476 sensitive casein kinase 1, and zVAD sensitive caspases...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27910030/recurrent-cytogenetic-abnormalities-in-non-hodgkin-s-lymphoma-and-chronic-lymphocytic-leukemia
#6
Edmond S K Ma
Characteristic chromosomal translocations are found to be associated with subtypes of B-cell non-Hodgkin lymphoma (NHL), for example t(8;14)(q24;q32) and Burkitt lymphoma, t(14;18)(q32;q21) and follicular lymphoma, and t(11;14)(q13;q32) in mantle cell lymphoma. Only few recurrent cytogenetic aberrations have been identified in the T-cell NHL and the best known is the ALK gene translocation t(2;5)(p23;q35) in anaplastic large cell lymphoma. Since lymph node or other tissue is seldom submitted for conventional cytogenetics study, alternative approaches for translocation detection are polymerase chain reaction (PCR) or fluorescence in situ hybridization (FISH)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27879258/nucleophosmin-anaplastic-lymphoma-kinase-npm-alk-the-ultimate-oncogene-and-therapeutic-target
#7
Michael T Werner, Chen Zhao, Qian Zhang, Mariusz A Wasik
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase physiologically expressed by fetal neural cells. However, aberrantly expressed ALK is involved in the pathogenesis of diverse malignancies including distinct types of lymphoma, lung carcinoma, and neuroblastoma. The aberrant ALK expression in non-neural cells results from chromosomal translocations that create novel fusion proteins. These protein hybrids are comprised of the proximal part of a partner gene including its promoter region and the distal part of ALK including coding sequence for the entire kinase domain...
November 22, 2016: Blood
https://www.readbyqxmd.com/read/27877008/detection-of-alk-translocation-in-non-small-cell-lung-carcinoma-nsclc-and-its-clinicopathological-significance-using-the-ventana-immunohistochemical-staining-method-a-single-center-large-scale-investigation-of-1-504-chinese-han-patients
#8
Lin Yang, Yun Ling, Lei Guo, Di Ma, Xuemin Xue, Bingning Wang, Junling Li, Jianming Ying
OBJECTIVE: The novel fully automated immunohistochemistry (IHC) assay-Ventana anaplastic lymphoma kinase (ALK)-D5F3 for screening ALK rearrangements has been approved by China's Food and Drug Administration in 2013, our previous study disclosed a highly specificity and sensitivity nearly 100%, and its efficacy needs to be evaluated in a large cohort of primary lung adenocarcinoma patients, and to compare clinicopathological features with ALK (+) and ALK (-) lung adenocarcinoma. METHODS: A total of 1,504 consecutive surgical lung adenocarcinoma cases of Chinese Han population were collected and re-diagnosed according to the 2011 multidisciplinary classification of lung adenocarcinoma...
October 2016: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/27867615/current-evidence-in-support-of-the-second-generation-anaplastic-lymphoma-kinase-alk-tyrosine-kinase-inhibitor-alectinib-for-the-treatment-of-non-small-cell-lung-cancer-positive-for-alk-translocation
#9
EDITORIAL
https://www.readbyqxmd.com/read/27846861/intraosseous-inflammatory-myofibroblastic-tumor-of-the-mandible-with-a-novel-atic-alk-fusion-mutation-a-case-report
#10
Yoko Tateishi, Koji Okudela, Shigeo Kawai, Takehisa Suzuki, Shigeaki Umeda, Mai Matsumura, Mitomu Kioi, Kenichi Ohashi
BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare low-grade malignant neoplasm with a predilection for children and young adults, and typically arises in the lung, abdominopelvic region, and retroperitoneum. IMTs in the maxillofacial region are extreme rare. Approximately 50% of IMT harbor rearrangements of the anaplastic lymphoma kinase (ALK) gene at 2p23 with various fusion partners. CASE PRESENTATION: We herein report a case of intraosseous IMT of the mandible with a novel ATIC-ALK fusion...
November 15, 2016: Diagnostic Pathology
https://www.readbyqxmd.com/read/27776007/a-comparison-of-morphologic-and-molecular-features-of-braf-alk-and-ntrk1-fusion-spitzoid-neoplasms
#11
Sapna M Amin, Alexandra M Haugh, Christina Y Lee, Bin Zhang, Jeffrey A Bubley, Emily A Merkel, Anna Elisa Verzì, Pedram Gerami
Recent studies have identified translocations involving the kinase domains of ALK, NTRK1, BRAF, RET, and ROS in spitzoid neoplasms. Subsequent studies have also characterized morphologic features corresponding to ALK and NTRK1 translocations. In this study, we sought to further compare morphologic features across a range of 49 genetically defined spitzoid neoplasms with ALK, NTRK1, BRAF, or RET fusions to determine discriminating features. We also compared them with a group of 22 spitzoid neoplasms, which were confirmed to be negative for fusions in ALK, NTRK1, BRAF, and RET...
October 21, 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27753543/stat3-targeted-treatment-with-silibinin-overcomes-the-acquired-resistance-to-crizotinib-in-alk-rearranged-lung-cancer
#12
Elisabet Cuyàs, Almudena Pérez-Sánchez, Vicente Micol, Javier A Menendez, Joaquim Bosch-Barrera
The signal transducer and activator of transcription 3 (STAT3) has been suggested to play a prominent role in mediating non-small-cell lung cancer (NSCLC) resistance to some tyrosine kinase inhibitor (TKI)-mediated therapies. Using a model of anaplastic lymphoma kinase gene (ALK)-translocated NSCLC with acquired resistance to the ALK TKI crizotinib, but lacking amplifications or mutations in the kinase domain of ALK, we herein present evidence that STAT3 activation is a novel mechanism of crizotinib resistance that involves the upregulation of immune escape and epithelial to mesenchymal transition (EMT) signaling pathways...
December 16, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27747151/a-long-term-survivor-of-non-small-cell-lung-cancer-harboring-concomitant-egfr-mutation-and-alk-translocation
#13
Fumio Imamura, Takako Inoue, Madoka Kimura, Kazumi Nishino, Toru Kumagai
In January 2003, a 55-year old, non-smoking woman visited our hospital to undergo treatment for T4N0M0 pulmonary adenocarcinoma of the left lung. Until death in October 2015, she received over 20 lines of treatment including a second line therapy with gefitinib, which showed long response. In March 2014, she noticed the left axillar lymph node swelling. Aspiration cytology of the lymph node revealed the presence of adenocarcinoma harboring EGFR exon 19 deletion (Ex19del) but not T790M. Concomitant ALK translocation of variant 1 was also detected...
2016: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/27713405/molecular-analysis-of-aggressive-renal-cell-carcinoma-with-unclassified-histology-reveals-distinct-subsets
#14
Ying-Bei Chen, Jianing Xu, Anders Jacobsen Skanderup, Yiyu Dong, A Rose Brannon, Lu Wang, Helen H Won, Patricia I Wang, Gouri J Nanjangud, Achim A Jungbluth, Wei Li, Virginia Ojeda, A Ari Hakimi, Martin H Voss, Nikolaus Schultz, Robert J Motzer, Paul Russo, Emily H Cheng, Filippo G Giancotti, William Lee, Michael F Berger, Satish K Tickoo, Victor E Reuter, James J Hsieh
Renal cell carcinomas with unclassified histology (uRCC) constitute a significant portion of aggressive non-clear cell renal cell carcinomas that have no standard therapy. The oncogenic drivers in these tumours are unknown. Here we perform a molecular analysis of 62 high-grade primary uRCC, incorporating targeted cancer gene sequencing, RNA sequencing, single-nucleotide polymorphism array, fluorescence in situ hybridization, immunohistochemistry and cell-based assays. We identify recurrent somatic mutations in 29 genes, including NF2 (18%), SETD2 (18%), BAP1 (13%), KMT2C (10%) and MTOR (8%)...
October 7, 2016: Nature Communications
https://www.readbyqxmd.com/read/27707887/overcoming-egfr-bypass-signal-induced-acquired-resistance-to-alk-tyrosine-kinase-inhibitors-in-alk-translocated-lung-cancer
#15
Masayoshi Miyawaki, Hiroyuki Yasuda, Tetsuo Tani, Junko Hamamoto, Daisuke Arai, Kota Ishioka, Keiko Ohgino, Shigenari Nukaga, Toshiyuki Hirano, Ichiro Kawada, Katsuhiko Naoki, Yuichiro Hayashi, Tomoko Betsuyaku, Kenzo Soejima
: Activation of the EGFR pathway is one of the mechanisms inducing acquired resistance to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) such as crizotinib and alectinib. Ceritinib is a highly selective ALK inhibitor and shows promising efficacy in non-small cell lung cancers (NSCLC) harboring the ALK gene rearrangement. However, the precise mechanism underlying acquired resistance to ceritinib is not well-defined. This study set out to clarify the mechanism in ALK-translocated lung cancer and to find the preclinical rationale overcoming EGFR pathway-induced acquired resistance to ALK-TKIs...
January 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27686809/developments-for-personalized-medicine-of-lung-cancer-subtypes-mass-spectrometry-based-clinical-proteogenomic-analysis-of-oncogenic-mutations
#16
Toshihide Nishimura, Haruhiko Nakamura
Molecular therapies targeting lung cancers with mutated epidermal growth factor receptor (EGFR) by EGFR-tyrosin kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, changed the treatment system of lung cancer. It was revealed that drug efficacy differs by race (e.g., Caucasians vs. Asians) due to oncogenic driver mutations specific to each race, exemplified by gefitinib / erlotinib. The molecular target drugs for lung cancer with anaplastic lymphoma kinase (ALK) gene translocation (the fusion gene, EML4-ALK) was approved, and those targeting lung cancers addicted ROS1, RET, and HER2 have been under development...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27614248/combinational-analysis-of-fish-and-immunohistochemistry-reveals-rare-genomic-events%C3%A2-in-alk-fusion-patterns-in-nsclc-that-responds%C3%A2-to-crizotinib-treatment
#17
Wenbin Li, Jing Zhang, Lei Guo, Shannon Chuai, Ling Shan, Jianming Ying
INTRODUCTION: The purpose of this study was to explore the complicated rearrangement mechanisms underlying cases with atypical and negative anaplastic lymphoma receptor tyrosine kinase gene (ALK) fluorescence hybridization (FISH) and positive immunohistochemistry (IHC) results and to stress the importance of combinational assay of these two methods in current pathological diagnosis. METHODS: A total of 3128 NSCLCs were screened for ALK fusions through both FISH analysis and IHC assays with Ventana-D5F3 antibody...
January 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27597279/erlotinib-has-comparable-clinical-efficacy-to-chemotherapy-in-pretreated-patients-with-advanced-non-small-cell-lung-cancer-nsclc-a-propensity-adjusted-outcomes-research-based-study
#18
P Neumair, L Joos, R Warschkow, A Dutly, S Ess, F Hitz, M Früh, M Brutsche, F Baty, S Krähenbühl, T Cerny, M Joerger
OBJECTIVES: Controversy exists about the integration of erlotinib in patients with EGFR wildtype, advanced NSCLC. MATERIALS AND METHODS: We included patients with advanced NSCLC receiving at least two lines of palliative systemic treatment between January 2005 and December 2014 and not harbouring targetable driver mutations. Primary study endpoint was overall survival (OS), secondary endpoint progression-free survival (PFS). We used Kaplan-Meier statistics, multivariate Cox regression and Propensity score or Inverse Probability Weights (IPW) matching to compare clinical outcome between patients receiving erlotinib in second or further line and those receiving chemotherapy only...
October 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/27592306/nodal-signaling-modulates-the-expression-of-oct-4-via-nuclear-translocation-of-%C3%AE-catenin-in-lung-and-prostate-cancer-cells
#19
Yi-Fei Qi, Long Wu, Zi-Qian Li, Meng-Ling Wu, Hai-Fang Wang, Ka-Ying Chan, Lin-Lin Lu, Shao-Hui Cai, Hong-Sheng Wang, Jun Du
Nodal is a member of transforming growth factor beta (TGF-β) superfamily. Nodal promotes the self-renewal of human cancer stem cells (CSCs) and triggers carcinogenesis of human cancers via an autocrine manner through Smad2/3 pathway. In our study, generation of Nodal-overexpressed cancer cells was constructed, and the effect of Nodal on the stem cell marker Oct-4 was evaluated by overexpression or blocked Nodal/ALKs signaling pathway in non-small cell lung cancer cells A549 and prostate cancer cells PC3. Functionally, Nodal also increased the proliferation via the β-catenin nuclear translocation...
October 15, 2016: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27587193/-targeted-therapy-and-precision-medicine-more-than-just-words-in-the-treatment-of-lung-cancer
#20
D F Heigener, M Horn, M Reck
Between 10 and 15 % of non-small cell lung cancers (NSCLC) proliferate due to the presence of a so-called driver mutation. This molecular alteration allows the cancer to continue to proliferate and can be deliberately inhibited. In addition to mutations in the epidermal growth factor receptor gene (EGFR) and translocations between the echinoderm microtubule-associated protein-like 4 gene (EML 4) and the anaplastic lymphoma kinase gene (ALK), this applies to ROS1 gene translocations. For the former two alterations, many inhibitors are already available, whereas for ROS1 and other driving mutations the evidence is sparse due to the rare occurrence of these mutations in NSCLC...
December 2016: Der Internist
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