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https://www.readbyqxmd.com/read/28745554/anaplastic-lymphoma-kinase-rearrangements-in-non-small-cell-lung-cancer-novel-applications-in-diagnostics-and-treatment
#1
Rodney E Shackelford, Junaid M Ansari, Eric X Wei, Jonathan S Alexander, James Cotelingam
The ALK gene, first identified as an anaplastic large cell lymphoma driver mutation, is dysregulated in nearly 20 different human malignancies, including 3-7% of non-small-cell lung cancers (NSCLC). In NSCLC, ALK commonly fuses with the EML4, forming a constitutively active tyrosine kinase that drives oncogenic progression. Recently, several ALK-inhibiting drugs have been developed that are more effective than standard chemotherapeutic regimens in treating advanced ALK-positive NSCLC. For this reason, molecular diagnostic testing for dysregulated ALK expression is a necessary part of identifying optimal NSCLC treatment options...
July 26, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28743163/alk-and-ros1-testing-on-lung-cancer-cytologic-samples-perspectives
#2
REVIEW
Pasquale Pisapia, Maria D Lozano, Elena Vigliar, Claudio Bellevicine, Francesco Pepe, Umberto Malapelle, Giancarlo Troncone
Cytologic sampling is the mainstay of diagnosing advanced lung cancer. Moreover, to select patients for personalized first-line or second-line treatment, epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) rearrangements are tested on cytologic preparations. Commercially available fluorescence in situ hybridization (FISH) and immunocytochemistry (ICC) assays have primarily been used for the identification of cells harboring ALK or ROS1 gene fusions on histologic rather than cytologic preparations...
July 25, 2017: Cancer
https://www.readbyqxmd.com/read/28742247/ventana-immunohistochemistry-assay-for-anaplastic-lymphoma-kinase-gene-rearrangement-detection-in-patients-with-non-small-cell-lung-cancer-a-meta-analysis
#3
Wang Zhiwei, Jiang Yuan, Yao Yihui, Hou Xin, Chen Jingtao, Shi Lei, Duan Yongjian
BACKGROUND: The aim of this study was to evaluate the diagnostic value of Ventana immunohistochemistry (IHC) assay for anaplastic lymphoma kinase (ALK) gene rearrangement screening in patients with non-small cell lung cancer (NSCLC). METHODS: Open published studies that reported the diagnostic performance of Ventana IHC assay for ALK gene rearrangement detection in NSCLC patients were extracted from PubMed, Embase, Google scholar, Wanfang, and China National Knowledge Infrastructure...
July 25, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28741662/molecular-breakdown-a-comprehensive-view-of-anaplastic-lymphoma-kinase-alk-rearranged-non-small-cell-lung-cancer
#4
Ka-Won Noh, Mi-Sook Lee, Seung Eun Lee, Ji-Young Song, Hyun-Tae Shin, Yu Jin Kim, Doo Yi Oh, Kyungsoo Jung, Minjung Sung, Mingi Kim, Sungbin An, Joungho Han, Young Mog Shim, Jae Ill Zo, Jhingook Kim, Woong-Yang Park, Se-Hoon Lee, Yoon-La Choi
Most anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancers (NSCLCs) show good clinical response to ALK inhibitors. However, some ALK-rearranged NSCLC patients show various primary responses with unknown reasons. Previous studies focused on the clinical aspects of ALK fusions in small cohorts, or were conducted in vitro and/or in vivo to investigate the function of ALK. One of the suggested theories describes how Echinoderm microtubule-associated protein-like 4 (EML4)-ALK variants play a role towards different sensitivities in ALK inhibitors...
July 25, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28740693/disease-flare-after-discontinuing-gefitinib-in-a-patient-with-lung-adenocarcinoma-and-concomitant-epithelial-growth-factor-receptor-mutation-and-anaplastic-lymphoma-kinase-translocation
#5
Eun Hye Park, Hwa Young Lee, Jin Woo Kim, Chang Dong Yeo
We report on a patient with lung adenocarcinoma and a concomitant epithelial growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation who developed a disease flare after discontinuing gefitinib. A 63-year-old woman with lung adenocarcinoma and a concomitant activating EGFR mutation and ALK translocation was treated with first-line gefitinib. After 4 months, she discontinued the gefitinib due to disease progression. She was admitted to the emergency room complaining of severe dyspnea and back pain 22 days after discontinuing gefitinib...
June 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28740365/spotlight-on-ceritinib-in-the-treatment-of-alk-nsclc-design-development-and-place-in-therapy
#6
REVIEW
Mariacarmela Santarpia, Maria Grazia Daffinà, Alessandro D'Aveni, Grazia Marabello, Alessia Liguori, Elisa Giovannetti, Niki Karachaliou, Maria Gonzalez Cao, Rafael Rosell, Giuseppe Altavilla
The identification of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) fusion gene in non-small cell lung cancer (NSCLC) has radically changed the treatment of a subset of patients harboring this oncogenic driver. Crizotinib was the first ALK tyrosine kinase inhibitor to receive fast approval and is currently indicated as the first-line therapy for advanced, ALK-positive NSCLC patients. However, despite crizotinib's efficacy, patients almost invariably progress, with the central nervous system being one of the most common sites of relapse...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28735509/diagnostic-utility-of-automated-surefish-dako-omnis-in-the-diagnosis-of-musculoskeletal-translocation-related-sarcomas
#7
Shintaro Sugita, Tomoyuki Aoyama, Yoshimasa Ito, Hiroko Asanuma, Taro Sugawara, Keiko Segawa, Yumika Ito, Noriaki Kikuchi, Mitsuhiro Tsujiwaki, Hiromi Fujita, Yusuke Ono, Tadashi Hasegawa
Fluorescence in situ hybridization (FISH) is an essential tool for genetic diagnosis in daily pathological work. Almost full automation of FISH can be achieved with the recently released automated SureFISH platform (Dako Omnis, Agilent Technologies, Santa Clara, CA, USA). Its utility has been reported in HER2 amplification of breast and gastric carcinoma and ALK-rearranged lung cancer. Here, we examined the utility of automated SureFISH for the identification of rearrangement signals in translocation-related sarcomas (TRSs), including 11 EWSR1-rearranged and 10 synovial sarcoma cases, compared with non-automated conventional FISH using the same specimens...
July 22, 2017: Pathology International
https://www.readbyqxmd.com/read/28735072/long-term-outcomes-of-adults-with-first-relapsed-refractory-systemic-anaplastic-large-cell-lymphoma-in-the%C3%A2-pre-brentuximab-vedotin-era-a-lysa-sfgm-tc-study
#8
Alexandre Morel, Josette Brière, Laurence Lamant, Michaël Loschi, Corinne Haioun, Richard Delarue, Olivier Tournilhac, Emmanuel Bachy, Anne Sonet, Sandy Amorim, Camille Laurent, Philippe Gaulard, Hervé Tilly, David Sibon
BACKGROUND: Long-term outcomes of adults with first-relapsed/refractory (R/R) systemic anaplastic large-cell lymphoma (ALCL) are not definitively established and should be evaluated. PATIENTS AND METHODS: We previously published the long-term outcomes of adults with ALCL initially treated with polychemotherapy in LYmphoma Study Association (LYSA) prospective clinical trials conducted during the pre-brentuximab vedotin era. Herein, we report the long-term outcomes of those patients after the first-relapsed/refractory (R/R) events...
July 20, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28733457/role-of-bone-morphogenetic-proteins-in-sprouting-angiogenesis-differential-bmp-receptor-dependent-signaling-pathways-balance-stalk-vs-tip-cell-competence
#9
Andreas Benn, Christian Hiepen, Marc Osterland, Christof Schütte, An Zwijsen, Petra Knaus
Before the onset of sprouting angiogenesis, the endothelium is prepatterned for the positioning of tip and stalk cells. Both cell identities are not static, as endothelial cells (ECs) constantly compete for the tip cell position in a dynamic fashion. Here, we show that both bone morphogenetic protein (BMP) 2 and BMP6 are proangiogenic in vitro and ex vivo and that the BMP type I receptors, activin receptor-like kinase (ALK)3 and ALK2, play crucial and distinct roles in this process. BMP2 activates the expression of tip cell-associated genes, such as DLL4 (delta-like ligand 4) and KDR (kinase insert domain receptor), and p38-heat shock protein 27 (HSP27)-dependent cell migration, thereby generating tip cell competence...
July 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28732214/crispr-cas9-technology-based-xenograft-tumors-as-candidate-reference-materials-for-multiple-eml4-alk-rearrangements-testing
#10
Rongxue Peng, Rui Zhang, Guigao Lin, Xin Yang, Ziyang Li, Kuo Zhang, Jiawei Zhang, Jinming Li
The echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (ALK) receptor tyrosine kinase (EML4-ALK) rearrangement is an important biomarker that plays a pivotal role in therapeutic decision making for non-small-cell lung cancer (NSCLC) patients. Ensuring accuracy and reproducibility of EML4-ALK testing by fluorescence in situ hybridization, immunohistochemistry, RT-PCR, and next-generation sequencing requires reliable reference materials for monitoring assay sensitivity and specificity...
July 18, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28731868/inflammatory-myofibroblastic-tumors-of-the-female-genital-tract-are-under-recognized-a-low-threshold-for-alk-immunohistochemistry-is-required
#11
Justine L Pickett, Angela Chou, Juliana A Andrici, Adele Clarkson, Loretta Sioson, Amy Sheen, Jessica Reagh, Fedaa Najdawi, Yoomee Kim, Denise Riley, Jayne Maidens, David Nevell, Kirsten McIlroy, Susan Valmadre, Greg Gard, Russell Hogg, John Turchini, Gregory Robertson, Michael Friedlander, Anthony J Gill
Inflammatory myofibroblastic tumor (IMT) of the female genital tract is under-recognized. We investigated the prevalence of ALK-positive IMT in lesions previously diagnosed as gynecologic smooth muscle tumors. Immunohistochemistry (IHC) for ALK was performed on tissue microarrays of unselected tumors resected from 2009 to 2013. Three of 1176 (0.26%) "leiomyomas" and 1 of 44 (2.3%) "leiomyosarcomas" were ALK IHC positive, confirmed translocated by fluorescence in situ hybridization (FISH) and therefore more appropriately classified as IMT...
July 20, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28730760/targeted-therapy-with-anaplastic-lymphoma-kinase-inhibitors-in-non-small-cell-lung-cancer-even-with-brain-metastasis
#12
Bekir Muhammet Hacioglu, Osman Kostek, Bulent Erdogan, Sernaz Uzunoglu, Irfan Cicin
The incidence of brain metastases has increased as a result of improved systemic disease control and advances in imaging. Brain metastasis can occur approximately in 25-40% of the patients with non-small cell lung cancer (NSCLC) and it is a frequent cause of death. Stereotactic radiosurgery, whole-brain radiotherapy (WBRT) or surgical resection are the local treatment modalities for brain metastases which are feasible either alone, in combination, or as sequential treatments. Resistance to systemic therapy for brain metastasis poses significant clinical problems...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28730479/analysis-of-drug-resistance-using-kinome-wide-functional-screens
#13
Katherine R Singleton, Keith T Earley, Lynn E Heasley
The clinical success of tyrosine kinase inhibitors specific for BCR-ABL-, EGFR-, ALK-, and ROS1-driven cancers continues to spur the quest to match specific oncogene-defined tumor types with an appropriate molecularly targeted therapy. Unfortunately, responses to these agents are not durable with intrinsic or acquired resistance limiting benefit. Additionally, efforts to identify the appropriate targets of new drugs have focused on nonfunctional assays such as large-scale sequencing for somatic mutations or analysis of gene copy number...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28729021/ascend-8-a-randomized-phase-1-study-of-ceritinib-450-mg-or-600-mg-taken-with-a-low-fat-meal-versus-750-mg-in-fasted-state-in-patients-with-anaplastic-lymphoma-kinase-alk-rearranged-metastatic-non-small-cell-lung-cancer-nsclc
#14
Byoung Chul Cho, Dong-Wan Kim, Alessandra Bearz, Scott A Laurie, Mark McKeage, Gloria Borra, Keunchil Park, Sang-We Kim, Marwan Ghosn, Andrea Ardizzoni, Evaristo Maiello, Alastair Greystoke, Richard Yu, Karen Osborne, Wen Gu, Jeffrey W Scott, Vanessa Q Passos, Yvonne Y Lau, Anna Wrona
INTRODUCTION: Ceritinib 750 mg fasted is approved for treatment of anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC) patients previously treated with crizotinib. Part 1 of ASCEND-8 study determined whether administering ceritinib 450 mg or 600 mg with a low-fat meal may enhance gastrointestinal (GI) tolerability vs 750 mg fasted in ALK+ NSCLC patients while maintaining similar exposure. METHODS: ASCEND-8 is a multicenter, randomized, open-label, phase 1 study...
July 17, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28726821/the-whole-genome-landscape-of-medulloblastoma-subtypes
#15
Paul A Northcott, Ivo Buchhalter, A Sorana Morrissy, Volker Hovestadt, Joachim Weischenfeldt, Tobias Ehrenberger, Susanne Gröbner, Maia Segura-Wang, Thomas Zichner, Vasilisa A Rudneva, Hans-Jörg Warnatz, Nikos Sidiropoulos, Aaron H Phillips, Steven Schumacher, Kortine Kleinheinz, Sebastian M Waszak, Serap Erkek, David T W Jones, Barbara C Worst, Marcel Kool, Marc Zapatka, Natalie Jäger, Lukas Chavez, Barbara Hutter, Matthias Bieg, Nagarajan Paramasivam, Michael Heinold, Zuguang Gu, Naveed Ishaque, Christina Jäger-Schmidt, Charles D Imbusch, Alke Jugold, Daniel Hübschmann, Thomas Risch, Vyacheslav Amstislavskiy, Francisco German Rodriguez Gonzalez, Ursula D Weber, Stephan Wolf, Giles W Robinson, Xin Zhou, Gang Wu, David Finkelstein, Yanling Liu, Florence M G Cavalli, Betty Luu, Vijay Ramaswamy, Xiaochong Wu, Jan Koster, Marina Ryzhova, Yoon-Jae Cho, Scott L Pomeroy, Christel Herold-Mende, Martin Schuhmann, Martin Ebinger, Linda M Liau, Jaume Mora, Roger E McLendon, Nada Jabado, Toshihiro Kumabe, Eric Chuah, Yussanne Ma, Richard A Moore, Andrew J Mungall, Karen L Mungall, Nina Thiessen, Kane Tse, Tina Wong, Steven J M Jones, Olaf Witt, Till Milde, Andreas Von Deimling, David Capper, Andrey Korshunov, Marie-Laure Yaspo, Richard Kriwacki, Amar Gajjar, Jinghui Zhang, Rameen Beroukhim, Ernest Fraenkel, Jan O Korbel, Benedikt Brors, Matthias Schlesner, Roland Eils, Marco A Marra, Stefan M Pfister, Michael D Taylor, Peter Lichter
Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets...
July 19, 2017: Nature
https://www.readbyqxmd.com/read/28723950/high-affinity-anti-tim-3-and-anti-kir-monoclonal-antibodies-cloned-from-healthy-human-individuals
#16
Stefan Ryser, Angeles Estellés, Edgar Tenorio, Lawrence M Kauvar, Mikhail L Gishizky
We report here the cloning of native high affinity anti-TIM-3 and anti-KIR IgG monoclonal antibodies (mAbs) from peripheral blood mononuclear cells (PBMC) of healthy human donors. The cells that express these mAbs are rare, present at a frequency of less than one per 105 memory B-cells. Using our proprietary multiplexed screening and cloning technology CellSpot™ we assessed the presence of memory B-cells reactive to foreign and endogenous disease-associated antigens within the same individual. When comparing the frequencies of antigen-specific memory B-cells analyzed in over 20 screening campaigns, we found a strong correlation of the presence of anti-TIM-3 memory B-cells with memory B-cells expressing mAbs against three disease-associated antigens: (i) bacterial DNABII proteins that are a marker for Gram negative and Gram positive bacterial infections, (ii) hemagglutinin (HA) of influenza virus and (iii) the extracellular domain of anaplastic lymphoma kinase (ALK)...
2017: PloS One
https://www.readbyqxmd.com/read/28722675/using-droplet-digital-pcr-to-analyze-mycn-and-alk-copy-number-in-plasma-from-patients-with-neuroblastoma
#17
Marco Lodrini, Annika Sprüssel, Kathy Astrahantseff, Daniela Tiburtius, Robert Konschak, Holger N Lode, Matthias Fischer, Ulrich Keilholz, Angelika Eggert, Hedwig E Deubzer
The invasive nature of surgical biopsies deters sequential application, and single biopsies often fail to reflect tumor dynamics, intratumor heterogeneity and drug sensitivities likely to change during tumor evolution and treatment. Implementing molecular characterization of cell-free neuroblastoma-derived DNA isolated from blood plasma could improve disease assessment for treatment selection and monitoring of patients with high-risk neuroblastoma. We established droplet digital PCR (ddPCR) protocols for MYCN and ALK copy number status in plasma from neuroblastoma patients...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28721808/molecular-tests-for-the-choice-of-cancer-therapy
#18
Anna P Sokolenko, Evgeny N Imyanitov
There are over a dozen of approved cancer drugs, whose administration is tailored to predictive laboratory tests. The examples include estrogen and progesterone receptor status determination for the use of endocrine therapy, HER2 assessment for the administration of HER2-targeting agents, EGFR and ALK gene testing for lung cancer treatment, BRAF analysis in melanoma, etc. While first predictive tests relied on relatively easy laboratory procedures, more recent developments require rather sophisticated assays...
July 19, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28721573/exposure-to-silver-nanoparticles-affects-viability-and-function-of-natural-killer-cells-mostly-via-the-release-of-ions
#19
Loretta Müller, Selina K Steiner, Laura Rodriguez-Lorenzo, Alke Petri-Fink, Barbara Rothen-Rutishauser, Philipp Latzin
Natural killer (NK) cells play a crucial role in linking innate and adaptive immune responses, especially during viral infections and tumor surveillance. They have two major effector functions: the killing of stressed/abnormal cells and the release of cytokines. Their activity is regulated via inhibitory and activating surface receptors. At the same time that the production and use of engineered nanoparticles is steadily increasing, the risk for exposure to silver nanoparticles (AgNPs) from consumer products or biomedical applications is growing...
July 18, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28721071/adverse-renal-effects-of-anaplastic-lymphoma-kinase-inhibitors-and-the-response-to-alectinib-of-an-alk-lung-cancer-patient-with-renal-dysfunction
#20
Midori Shimada, Minoru Fukuda, Masaaki Fukuda, Takeshi Kitazaki, Kohji Hashiguchi, Takaya Ikeda, Hiroyuki Yamaguchi, Katsumi Nakatomi, Kazuto Ashizawa, Hiroshi Mukae
A 62-year-old female patient with renal dysfunction and pulmonary adenocarcinoma developed postoperative recurrence and received carboplatin/pemetrexed and maintenance pemetrexed. As an anaplastic lymphoma kinase (ALK) gene translocation was identified, the therapy was changed to crizotinib. However, the patient's blood creatinine level increased, and her physical status worsened. Alectinib also induced exacerbation of renal dysfunction but was controlled by dose reduction of 140 mg twice daily for 2 weeks treatment and 2 weeks break were repeated, and exhibited a partial response for 16 months...
2017: OncoTargets and Therapy
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