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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
#1
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
#2
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/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
#3
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/28194436/real-time-genomic-profiling-of-histiocytoses-identifies-early-kinase-domain-braf-alterations-while-improving-treatment-outcomes
#4
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/28193280/functional-role-of-alk-related-signal-cascades-on-modulation-of-epithelial-mesenchymal-transition-and-apoptosis-in-uterine-carcinosarcoma
#5
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/28185914/therapeutic-strategies-and-mechanisms-of-drug-resistance-in-anaplastic-lymphoma-kinase-alk-rearranged-lung-cancer
#6
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
https://www.readbyqxmd.com/read/28183697/safety-and-antitumor-activity-of-the-multi-targeted-pan-trk-ros1-and-alk-inhibitor-entrectinib-rxdx-101-combined-results-from-two-phase-1-trials-alka-372-001-and-startrk-1
#7
Alexander Drilon, Salvatore Siena, Sai-Hong Ignatius Ou, Manish Patel, Myung Ju Ahn, Jeeyun Lee, Todd M Bauer, Anna F Farago, Jennifer J Wheler, Stephen V Liu, Robert Doebele, Laura Giannetta, Giulio Cerea, Giovanna Marrapese, Michele Schirru, Alessio Amatu, Katia Bencardino, Laura Palmeri, Andrea Sartore-Bianchi, Angelo Vanzulli, Sara Cresta, Silvia Damian, Matteo Duca, Elena Ardini, Gang Li, Jason Christiansen, Karey Kowalski, Ann Johnson, Rupal Patel, David Luo, Edna Chow-Maneval, Zachary Hornby, Pratik S Multani, Alice T Shaw, Filippo G De Braud
Entrectinib, a potent oral inhibitor of the tyrosine kinases TRKA/B/C, ROS1, and ALK, was evaluated in two Phase 1 studies in patients with advanced or metastatic solid tumors, including patients with active CNS disease. Here we summarize the overall safety and report the antitumor activity of entrectinib in a cohort of patients with tumors harboring NTRK1/2/3, ROS1, or ALK gene fusions, naïve to prior TKI treatment targeting the specific gene, and who were treated at doses that achieved therapeutic exposures consistent with the RP2D...
February 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28182271/optimizing-treatment-for-patients-with-alk-positive-lung-cancer
#8
Ibiayi Dagogo-Jack, Alice T Shaw, Gregory J Riely
In the nine years since the initial discovery of anaplastic lymphoma kinase (ALK) gene rearrangements in non-small cell lung cancer (NSCLC), there has been tremendous progress, culminating in an ever-expanding repertoire of agents that have activity in this disease. This review article provides an overview of currently approved ALK inhibitors, other ALK inhibitors in development, and commonly described mechanisms of resistance to ALK inhibitors. We also discuss emerging controversies in treatment of patients with ALK positive lung cancer, including the choice of first-line ALK inhibitor and the role of tyrosine kinase inhibitors in the treatment of central nervous system metastases...
February 9, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28181564/multiplexed-transcriptome-analysis-to-detect-alk-ros1-and-ret-rearrangements-in-lung-cancer
#9
Toni-Maree Rogers, Gisela Mir Arnau, Georgina L Ryland, Stephen Huang, Maruja E Lira, Yvette Emmanuel, Omar D Perez, Darryl Irwin, Andrew P Fellowes, Stephen Q Wong, Stephen B Fox
ALK, ROS1 and RET gene fusions are important predictive biomarkers for tyrosine kinase inhibitors in lung cancer. Currently, the gold standard method for gene fusion detection is Fluorescence In Situ Hybridization (FISH) and while highly sensitive and specific, it is also labour intensive, subjective in analysis, and unable to screen a large numbers of gene fusions. Recent developments in high-throughput transcriptome-based methods may provide a suitable alternative to FISH as they are compatible with multiplexing and diagnostic workflows...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28179901/biochemical-molecular-and-transcriptional-highlights-of-the-biosynthesis-of-an-effective-biosurfactant-produced-by-bacillus-safensis-pha3-a-petroleum-dwelling-bacteria
#10
Abdulsamie Hanano, Mouhnad Shaban, Ibrahem Almousally
Petroleum crude oil (PCO)-dwelling microorganisms have exceptional biological capabilities to tolerate the toxicity of petroleum contaminants and are therefore promising emulsifier and/or degraders of PCO. This study describes a set of PCO-inhabiting bacterial species, one of which, identified as Bacillus safensis PHA3, produces an efficient biosurfactant which was characterized as a glycolipid. Fourier transform infrared spectrometer, nuclear magnetic resonance, Thin layer chromatography, HPLC, and GC-MS analysis of the purified biosurfactant revealed that the extracted molecule under investigation is likely a mannolipid molecule with a hydrophilic part as mannose and a hydrophobic part as hexadecanoic acid (C16:0)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28178969/neuroblastoma-treatment-in-the-post-genomic-era
#11
REVIEW
Maria Rosaria Esposito, Sanja Aveic, Anke Seydel, Gian Paolo Tonini
Neuroblastoma is an embryonic malignancy of early childhood originating from neural crest cells and showing heterogeneous biological, morphological, genetic and clinical characteristics. The correct stratification of neuroblastoma patients within risk groups (low, intermediate, high and ultra-high) is critical for the adequate treatment of the patients.High-throughput technologies in the Omics disciplines are leading to significant insights into the molecular pathogenesis of neuroblastoma. Nonetheless, further study of Omics data is necessary to better characterise neuroblastoma tumour biology...
February 8, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28174489/alk-gene-expression-status-in-pleural-effusion-predicts-tumor-responsiveness-to-crizotinib-in-chinese-patients-with-lung-adenocarcinoma
#12
Zheng Wang, Xiaonan Wu, Xiaohong Han, Gang Cheng, Xinlin Mu, Yuhui Zhang, Di Cui, Chang Liu, Dongge Liu, Yuankai Shi
OBJECTIVE: The relationship between anaplastic lymphoma kinase (ALK) expression in malignant pleural effusion (MPE) samples detected only by Ventana immunohistochemistry (IHC) ALK (D5F3) and the efficacy of ALK-tyrosine kinase inhibitor therapy is uncertain. METHODS: Ventana anti-ALK (D5F3) rabbit monoclonal primary antibody testing was performed on 313 cell blocks of MPE samples from Chinese patients with advanced lung adenocarcinoma, and fluorescence in situ hybridization (FISH) was used to verify the ALK gene status in Ventana IHC ALK (D5F3)-positive samples...
December 2016: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/28174383/-a-case-of-synchronous-double-cancer-of-the-lung-and-stomach-that-responded-to-cisplatin-and-s-1-combination-chemotherapy
#13
Tomohide Sugiyama, Takashi Kasai, Yoichi Nakamura, Yukari Kamiyama, Kiyoshi Mori
A 55-year-old man experienced weight loss, as noted by a physician who was examining him for hypertension. Upper gastrointestinal endoscopy revealed a tumor lesion with an ulcer on the posterior wall of the greater curvature. A biopsy confirmed the presence of an adenocarcinoma(HER2 negative), and demonstrated enlarged para-aortic lymph nodes. Thus, stage IV type 3 ulcer infiltration-type gastric cancer was diagnosed. Computed tomography was included in the examination, and demonstrated nodular shadows in the right lower lobe and enlarged mediastinal nodes, as well as bilateral multiple granular shadows...
January 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28167572/an-oncogenic-alk-fusion-and-an-rras-mutation-in-kras-mutation-negative-pancreatic-ductal-adenocarcinoma
#14
Yoko Shimada, Takashi Kohno, Hideki Ueno, Yoshinori Ino, Hideyuki Hayashi, Takashi Nakaoku, Yasunari Sakamoto, Shunsuke Kondo, Chigusa Morizane, Kazuaki Shimada, Takuji Okusaka, Nobuyoshi Hiraoka
PURPOSE: Oncogenic mutations in the KRAS gene are a well-known driver event, occurring in >95% of pancreatic cancers. The objective of this study was to identify driver oncogene aberrations in pancreatic cancers without the KRAS mutation. METHODS: Whole-exome and transcriptome sequencing was performed on four cases of KRAS mutation-negative pancreatic ductal adenocarcinoma, which were identified in a cohort of 100 cases. RESULTS: One case harbored an oncogenic DCTN1-ALK fusion...
February 6, 2017: Oncologist
https://www.readbyqxmd.com/read/28165669/non-invasive-ct-screening-for-pulmonary-arteriovenous-malformations-in-children-with-confirmed-hereditary-hemorrhagic-telangiectasia-results-from-two-pediatric-centers
#15
Nurcan Soysal, Mélanie Eyries, Suzanne Verlhac, Virginie Escabasse, Natascha Remus, Aline Tamalet, Jean-Yves Rioux, Stéphanie Franchi-Abella, Manuela Vasile, Sarah Robert, Céline Delestrain, Isabelle Hau, Hubert Ducou-Le Pointe, Florent Soubrier, Marie-France Carette, Ralph Epaud
BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder that is caused by mutations in mainly two genes, that is ENG, encoding endoglin (HHT1), or ACVRL1, encoding activin receptor-like kinase 1 (ALK-1/HHT2). HHT is characterized by recurrent epistaxis, mucocutaneous telangiectasia, and vascular visceral dysplasia responsible for visceral arteriovenous malformations (AVM). AIM: to report the experience of two university hospitals (Trousseau, Paris, and CHIC, Creteil) with screening children for HHT and pulmonary AVM (PAVM) using high resolution computed tomography (HRCT)...
February 6, 2017: Pediatric Pulmonology
https://www.readbyqxmd.com/read/28164089/met-hgf-pathway-activation-as-a-paradigm-of-resistance-to-targeted-therapies
#16
REVIEW
Brian Ko, Tianfang He, Shirish Gadgeel, Balazs Halmos
Resistance to targeted therapeutics is a key issue limiting the long-term utility of these medications in the management of molecularly selected subsets of cancer patients, including patients with non-small cell lung cancer harboring oncogenic alterations affecting EGFR, ALK and other genes. Bypass resistance mediated by activation of MET kinase has emerged as a frequent, validated and pivotal resistance mechanism in multiple types of cancers. Biochemical understanding is accumulating to explain the unique role of MET in such bypass pathways, providing alternate downstream activation opportunities and intricate interactions during epithelial-mesenchymal transitions...
January 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28163593/development-of-a-platform-for-breeding-by-design-of-cms-restorer-lines-based-on-an-sssl-library-in-rice-oryza-sativa-l
#17
Ziju Dai, Qing Lu, Xin Luan, Lian Ouyang, Jie Guo, Jiayan Liang, Haitao Zhu, Wenjuan Wang, Shaokui Wang, Ruizhen Zeng, Ziqiang Liu, Zemin Zhang, Xiaoyuan Zhu, Guiquan Zhang
Exploitation of the heterosis of hybrid rice has shown great success in the improvement of rice yields. However, few genotypes exhibit strong restoration ability as effective restorers of cytoplasmic male sterility (CMS) in the development of hybrid rice. In this study, we developed a platform for the breeding by design of CMS restorer lines based on a library of chromosomal single segment substitution lines (SSSLs) in the Huajingxian74 (HJX74) genetic background. The target genes for breeding by design, Rf3(4) and Rf4(4), which are associated with a strong restoration ability, and gs3, gw8, Wx(g1) and Alk, which are associated with good grain quality, were selected from the HJX74 SSSL library...
December 2016: Breeding Science
https://www.readbyqxmd.com/read/28153507/expression-of-p63-protein-in-anaplastic-large-cell-lymphoma-implications-for-genetic-subtyping
#18
Xueju Wang, Rebecca L Boddicker, Surendra Dasari, Jagmohan S Sidhu, Marshall E Kadin, William R Macon, Stephen M Ansell, Rhett P Ketterling, Karen L Rech, Andrew L Feldman
Anaplastic large cell lymphomas (ALCLs) are CD30-positive T-cell non-Hodgkin lymphomas that bear chromosomal rearrangements of the TP53 homologue, TP63, in a subset of cases that demonstrate aggressive clinical behavior. In the present study, we examined the relationship between p63 protein expression by immunohistochemistry and the results of fluorescence in situ hybridization (FISH) using TP63 probes in 116 ALCLs. We also determined the relative expression of full-length TAp63 and truncated ΔNp63 isoforms (e...
January 30, 2017: Human Pathology
https://www.readbyqxmd.com/read/28150468/ciliated-muconodular-papillary-tumor-of-the-lung-harboring-alk-gene-rearrangement-case-report-and-review-of-the-literature
#19
Yan Jin, Xuxia Shen, Lei Shen, Yihua Sun, Haiquan Chen, Yuan Li
Ciliated muconodular papillary tumor (CMPT) of the lung is an extremely rare peripheral tumor of the lung. The pathogenesis of CMPT is still unknown, and its nature as a benign tumor or reactive process is still open to discussion. Recent studies have identified BRAF, EGFR and AKT1 mutations in CMPT, which would support a true neoplastic process. Here for the first time, we report a case of morphologically typical CMPT harboring ALK gene rearrangement to further provide convincing evidence that CMPT is a neoplastic process rather than a reactive lesion...
February 2, 2017: Pathology International
https://www.readbyqxmd.com/read/28149754/non-small-cell-lung-cancer-nsclc-and-central-nervous-system-cns-metastases-role-of-tyrosine-kinase-inhibitors-tkis-and-evidence-in-favor-or-against-their-use-with-concurrent-cranial-radiotherapy
#20
REVIEW
Panagiota Economopoulou, Giannis Mountzios
Central nervous system (CNS) metastases, including brain metastases (BM) and leptomeningeal metastases (LM) represent a frequent complication of non-small cell lung cancer (NSCLC). Patients with BM comprise a heterogeneous group, with a median survival that ranges from 3 to 14 months. However, in the majority of patients, the occurrence of CNS metastases is usually accompanied by severe morbidity and substantial deterioration in quality of life. Local therapies, such as whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS) or surgical resection, either alone or as part of a multimodality treatment are available treatment strategies for BM and the choice of therapy varies depending on patient group and prognosis...
December 2016: Translational Lung Cancer Research
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