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https://www.readbyqxmd.com/read/28231386/evaluating-the-effectiveness-of-rna-in-situ-hybridization-for-detecting-lung-adenocarcinoma-with-anaplastic-lymphoma-kinase-rearrangement
#1
Naoki Nakajima, Akihiko Yoshizawa, Kyoko Kondo, Mariyo Rokutan-Kurata, Masahiro Hirata, Ayako Furuhata, Shinji Sumiyoshi, Makoto Sonobe, Toshi Menju, Masanobu Momose, Masakazu Fujimoto, Hiroshi Date, Hironori Haga
AIMS: An easy and rapid assay for detecting mRNA in formalin-fixed paraffin-embedded samples (RNA-in situ hybridization; RNA-ISH) has been reported recently. We investigated the diagnostic accuracy of RNA-ISH for detecting lung adenocarcinoma (LA) with anaplastic lymphoma kinase (ALK) gene rearrangement. METHODS AND RESULTS: We tested ALK RNA-ISH on 11 resected LAs for which ALK fusion was confirmed by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH)...
February 23, 2017: Histopathology
https://www.readbyqxmd.com/read/28228224/-clinical-advanced-in-early-stage-alk-positive-non-small-cell-lung-cancer-patients
#2
Qiongqiong Gao, Xiangli Jiang, Chun Huang
Lung cancer is the leading cause of cancer death in China. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases, with the majority of the cases diagnosed at the advanced stage. Molecular targeted therapy is becoming the focus attention for advanced NSCLC. Echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene (EML4-ALK) is among the most common molecular targets of NSCLC; its specific small-molecule tyrosine kinase inhibitors (TKIs) are approved for use in advanced NSCLC cases of ALK-positive...
February 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28218040/comprehensive-profiling-and-quantitation-of-oncogenic-mutations-in-non-small-cell-lung-carcinoma-using-single-molecule-amplification-and-re-sequencing-technology
#3
Jian Shi, Meng Yuan, Zhan-Dong Wang, Xiao-Li Xu, Lei Hong, Shenglin Sun
The carcinogenesis of non-small cell lung carcinoma has been found to associate with activating and resistant mutations in the tyrosine kinase domain of specific oncogenes. Here, we assessed the type, frequency, and abundance of epithelial growth factor receptor, KRAS, BRAF, and ALK mutations in 154 non-small cell lung carcinoma specimens using single-molecule amplification and re-sequencing technology. We found that epithelial growth factor receptor mutations were the most prevalent (44.2%), followed by KRAS (18...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28217366/crizotinib-inhibits-hyperpolarization-activated-cyclic-nucleotide-gated-channel-4-activity
#4
Zhushan Zhang, Tai-Qin Huang, Igor Nepliouev, Hengtao Zhang, Adam S Barnett, Paul B Rosenberg, Sai-Hong I Ou, Jonathan A Stiber
BACKGROUND: Sinus bradycardia is frequently observed in patients treated with crizotinib, a receptor tyrosine kinase inhibitor used for the treatment of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). We investigated whether crizotinib could influence heart rate (HR) through direct cardiac effects. METHODS: The direct effect of crizotinib on HR was studied using ECG analysis of Langendorff-perfused mouse hearts. The whole-cell patch clamp technique was used to measure the effects of crizotinib on the hyperpolarization-activated funny current, If, in mouse sinoatrial node cells (SANCs) and hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) activity in HEK-293 cells stably expressing human HCN4...
2017: Cardiooncology
https://www.readbyqxmd.com/read/28214087/targeting-the-pd-1-pd-l1-axis-in-non-small-cell-lung-cancer
#5
REVIEW
Rajiv Kumar, Dearbhaile Collins, Saoirse Dolly, Fiona McDonald, Mary E R O'Brien, Timothy A Yap
The last decade has witnessed rapid advances in the discovery and development of immune checkpoint inhibitors in cancer medicine, particularly drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). The proven antitumor efficacy coupled with low rates of drug-related toxicities observed, albeit idiosyncratic, with these novel immunotherapeutics have led to the registration of multiple PD-1 and PD-L1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, in second-line advanced NSCLC, whereas durvalumab and avelumab are in late-phase clinical testing...
December 23, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28213819/conditional-knockout-of-activin-like-kinase-1-alk-1-leads-to-heart-failure-without-maladaptive-remodeling
#6
Kevin J Morine, Xiaoying Qiao, Vikram Paruchuri, Mark J Aronovitz, Emily E Mackey, Lyanne Buiten, Jonathan Levine, Keshan Ughreja, Prerna Nepali, Robert M Blanton, Richard H Karas, S Paul Oh, Navin K Kapur
Activin like kinase-1 (AlK-1) mediates signaling via the transforming growth factor beta (TGFβ) family of ligands. AlK-1 activity promotes endothelial proliferation and migration. Reduced AlK-1 activity is associated with arteriovenous malformations. No studies have examined the effect of global AlK-1 deletion on indices of cardiac remodeling. We hypothesized that reduced levels of AlK-1 promote maladaptive cardiac remodeling. To test this hypothesis, we employed AlK-1 conditional knockout mice (cKO) harboring the ROSA26-CreER knock-in allele, whereby a single dose of intraperitoneal tamoxifen triggered ubiquitous Cre recombinase-mediated excision of floxed AlK-1 alleles...
February 17, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28212996/analysis-of-a-panel-of-druggable-gene-mutations-and-of-alk-and-pd-l1-expression-in-a-series-of-thymic-epithelial-tumors-tets
#7
Marcello Tiseo, Angela Damato, Lucia Longo, Fausto Barbieri, Federica Bertolini, Alessandro Stefani, Mario Migaldi, Letizia Gnetti, Roberta Camisa, Paola Bordi, Sebastiano Buti, Giulio Rossi
INTRODUCTION: Thymic epithelial tumors (TETs) are rare neoplasms with different prognosis lacking consistent molecular alterations possibly leading to targeted therapy. We collected a consecutive series of TETs aimed at investigating the mutational status of druggable genes (EGFR, c-KIT, KRAS, BRAF, PDGFR-alpha and -beta, HER2 and c-MET) and the expression of ALK and PD-L1. PATIENTS AND METHODS: One hundred twelve consecutive cases of TETs and relative clinico-pathologic features were collected...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28212572/concurrent-gene-alterations-with-egfr-mutation-and-treatment-efficacy-of-egfr-tkis-in-chinese-patients-with-non-small-cell-lung-cancer
#8
Wentao Hu, Yahui Liu, Jian Chen
PURPOSE: We investigated the frequency of concurrent genes in EGFR-mutant non-small cell lung cancer patients and determined its value in predicting the efficacy of EGFR-TKIs treatment. METHODS: Three hundred and twenty patients, who harbored EGFR activating mutations and received EGFR-TKIs treatment, were examined for another eight genes including KRAS, NRAS, PIK3CA, BRAF, and HER2 mutations and ALK, ROS1, and RET fusion genes based on reverse transcription PCR...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212040/synthesis-and-speciation-dependent-properties-of-a-multimetallic-model-complex-of-nisod-that-exhibits-unique-hydrogen-bonding
#9
Ramsey A Steiner, Stephen P Dzul, Timothy L Stemmler, Todd C Harrop
The complex Na3[{Ni(II)(nmp)}3S3BTA(alk))] (1) (nmp(2-) = deprotonated form of N-(2-mercaptoethyl)picolinamide; H3S3BTA(alk) = N(1),N(3),N(5)-tris(2-mercaptoethyl)benzene-1,3,5-tricarboxamide, where H = dissociable protons), supported by the thiolate-benzenetricarboxamide scaffold (S3BTA(alk)), has been synthesized as a trimetallic model of nickel-containing superoxide dismutase (NiSOD). X-ray absorption spectroscopy (XAS) and (1)H NMR measurements on 1 indicate that the Ni(II) centers are square-planar with N2S2 coordination, and Ni-N and Ni-S distances of 1...
February 17, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28209747/pediatric-adolescent-and-young-adult-thyroid-carcinoma-harbors-frequent-and-diverse-targetable-genomic-alterations-including-kinase-fusions
#10
Pierre Vanden Borre, Alexa B Schrock, Peter M Anderson, John C Morris, Andreas M Heilmann, Oliver Holmes, Kai Wang, Adrienne Johnson, Steven G Waguespack, Sai-Hong Ignatius Ou, Saad Khan, Kar-Ming Fung, Philip J Stephens, Rachel L Erlich, Vincent A Miller, Jeffrey S Ross, Siraj M Ali
BACKGROUND: Thyroid carcinoma, which is rare in pediatric patients (age 0-18 years) but more common in adolescent and young adult (AYA) patients (age 15-39 years), carries the potential for morbidity and mortality. METHODS: Hybrid-capture-based comprehensive genomic profiling (CGP) was performed prospectively on 512 consecutively submitted thyroid carcinomas, including 58 from pediatric and AYA (PAYA) patients, to identify genomic alterations (GAs), including base substitutions, insertions/deletions, copy number alterations, and rearrangements...
February 16, 2017: Oncologist
https://www.readbyqxmd.com/read/28209203/crizotinib-associated-renal-cysts-carcs-incidence-and-patterns-of-evolution
#11
Laird B Cameron, Damian H S Jiang, Kate Moodie, Catherine Mitchell, Benjamin Solomon, Bimal Kumar Parameswaran
BACKGROUND: Novel therapeutic agents recently introduced for the treatment of cancer have several unusual side effects. An increased incidence of renal cystic lesions, often with features concerning for malignancy or infection, has been reported in patients with anaplastic lymphoma kinase (ALK) - rearranged advanced non-small cell lung cancer (NSCLC) treated with Crizotinib. Many of these lesions undergo spontaneous resolution despite developing complex features on imaging. We assess the incidence and patterns of evolution of Crizotinib Associated Renal Cysts [CARCs] at our institute and provide histopathology correlation of their benign nature...
February 16, 2017: Cancer Imaging: the Official Publication of the International Cancer Imaging Society
https://www.readbyqxmd.com/read/28203297/therapeutic-approach-to-treating-patients-with-braf-mutant-lung-cancer-latest-evidence-and-clinical-implications
#12
REVIEW
Adrianus J de Langen, Egbert F Smit
Lung adenocarcinoma is known for its high rate of somatic mutations and genomic rearrangements. The identification of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements that sensitize tumors to specific drugs has changed the therapeutic approach and prognosis in these molecularly-defined subgroups. Several other key genetic alterations have been identified, of which BRAF mutations are found in 4% of non-small cell lung cancer (NSCLC) cases. Targeted drugs against BRAF and downstream MEK were recently approved for the treatment of BRAF-positive melanoma and have entered clinical evaluation in NSCLC...
January 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28199742/genetic-analysis-and-clinicopathological-features-of-alk-rearranged-renal-cell-carcinoma-in-a-large-series-of-resected-chinese-renal-cell-carcinoma-patients-and-literature-review
#13
Wenjuan Yu, Yuewei Wang, Yanxia Jiang, Wei Zhang, Yujun Li
AIMS: Anaplastic lymphoma kinase (ALK)-rearranged renal cell carcinoma (RCC) is a rare subtype of RCC reported in recent years with 8 cases so far. The present study is focused on screening ALK-rearranged cases from a large cohort of RCCs in China to determine the frequency of ALK rearrangement and investigate the clinicopathological features and outcomes. METHODS AND RESULTS: Tissues from a total of 477 RCC patients in China were embedded into tissue microarrays for immunostaining...
February 15, 2017: Histopathology
https://www.readbyqxmd.com/read/28195686/diagnosis-of-anaplastic-lymphoma-kinase-rearrangement-in-cytological-samples-through-a-fluorescence-in-situ-hybridization-based-assay-cytological-smears-versus-cell-blocks
#14
Federica Zito Marino, Giulio Rossi, Matteo Brunelli, Maria Gabriella Malzone, Giuseppina Liguori, Giuseppe Bogina, Alessandro Morabito, Gaetano Rocco, Renato Franco, Gerardo Botti
Anaplastic lymphoma kinase (ALK) status analysis of lung cytological specimens should be successfully encouraged in routine practice because biopsy specimens are not always available. To date, the US Food and Drug Administration has approved both fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) as diagnostic tests for identifying ALK-positive patients eligible for treatment with crizotinib. Although ALK IHC is an optimal diagnostic tool, FISH becomes mandatory in equivocal cases. ALK FISH of paraffin-embedded tissue material is still the gold standard, whereas the cytological specimen assay has not yet been completely standardized...
February 14, 2017: Cancer
https://www.readbyqxmd.com/read/28194436/real-time-genomic-profiling-of-histiocytoses-identifies-early-kinase-domain-braf-alterations-while-improving-treatment-outcomes
#15
Lynn H Lee, Anjelika Gasilina, Jayeeta Roychoudhury, Jason Clark, Francis X McCormack, Joseph Pressey, Michael S Grimley, Robert Lorsbach, Siraj Ali, Mark Bailey, Philip Stephens, Jeffrey S Ross, Vincent A Miller, Nicolas N Nassar, Ashish R Kumar
Many patients with histiocytic disorders such as Langerhans cell histiocytosis (LCH) or Erdheim-Chester disease (ECD) have treatment-refractory disease or suffer recurrences. Recent findings of gene mutations in histiocytoses have generated options for targeted therapies. We sought to determine the utility of prospective sequencing of select genes to further characterize mutations and identify targeted therapies for patients with histiocytoses. Biopsies of 72 patients with a variety of histiocytoses underwent comprehensive genomic profiling with targeted DNA and RNA sequencing...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28193771/ceritinib-bests-chemo-for-untreated-alk-nsclc
#16
(no author information available yet)
Patients with ALK-positive non-small cell lung cancer may soon have a new first-line treatment option in ceritinib, which outperformed chemotherapy in a phase III study. However, toxicity issues remain a problem for ceritinib, and another next-generation ALK inhibitor, alectinib, is more likely to become the drug of choice for untreated patients.
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28193280/functional-role-of-alk-related-signal-cascades-on-modulation-of-epithelial-mesenchymal-transition-and-apoptosis-in-uterine-carcinosarcoma
#17
H Inoue, M Hashimura, M Akiya, R Chiba, M Saegusa
BACKGROUND: Anaplastic lymphoma kinase (ALK), which is a receptor tyrosine kinase, is essentially and transiently expressed in the developing nervous system. Recently, the deregulated expression of full-length ALK has been observed in some primary solid tumors, but little is known about its involvement in the tumorigenesis of uterine carcinosarcomas (UCSs). Here we examined the functional role of the ALK gene in UCSs. METHODS: Regulation and function of the ALK gene were assessed using two endometrial carcinoma cell lines...
February 14, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28191314/diagnosis-and-treatment-of-cd20-negative-b-cell-lymphomas
#18
REVIEW
Tasleem Katchi, Delong Liu
CD20 negative B cell non-Hodgkin lymphoma (NHL) is rare and accounts for approximately 1-2% of B cell lymphomas. CD20- negative NHL is frequently associated with extranodal involvement, atypical morphology, aggressive clinical behaviour, resistance to standard chemotherapy and poor prognosis. The most common types of these include plasmablastic lymphoma, primary effusion lymphoma, large B-cell lymphoma arising from HHV8-associated multicentric Castleman's disease, and ALK+ large B cell lymphoma. This review provides an overview of the diagnostic and treatment modalities for CD20 negative B cell NHL...
2017: Biomarker Research
https://www.readbyqxmd.com/read/28188721/pd-l1-over-expression-is-associated-with-a-poor-prognosis-in-asian-non-small-cell-lung-cancer-patients
#19
Haifeng Xia, Ji Shen, Fang Hu, Shaomu Chen, Haitao Huang, Yaozeng Xu, Haitao Ma
BACKGROUND: The prognostic role of programmed cell death-ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) remains controversial. This meta-analysis was conducted to clarify the association of PD-L1 with survival in NSCLC patients. METHODS: Relevant studies were collected from PubMed, Embase and Web of Science. Only studies in which PD-L1 expression was detected by immunohistochemical staining in NSCLC patients correlated with patient survival data were included...
February 7, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28185914/therapeutic-strategies-and-mechanisms-of-drug-resistance-in-anaplastic-lymphoma-kinase-alk-rearranged-lung-cancer
#20
REVIEW
Ryohei Katayama
Anaplastic lymphoma kinase (ALK) gene encoding the receptor tyrosine kinase ALK is expressed as a fusion gene in a variety of carcinomas. The expression of ALK is nearly undetectable in adults, and its activation is normally regulated by its ligands, FAM150A/B. However, ALK gene rearrangements result in different ALK fusion proteins that are constitutively expressed via the active promoter of fusion partner genes. ALK fusion proteins dimerize in a ligand-independent manner and lead to the dysregulation of cell proliferation via abnormal constitutive activation of ALK tyrosine kinase...
February 6, 2017: Pharmacology & Therapeutics
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