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https://www.readbyqxmd.com/read/28332433/the-cost-effectiveness-of-alectinib-in-anaplastic-lymphoma-kinase-positive-alk-advanced-nsclc-previously-treated-with-crizotinib
#1
J J Carlson, W Canestaro, A Ravelo, W Wong
Introduction Anaplastic lymphoma kinase (ALK) targeting drugs provide an important option for advanced non-small cell lung cancer patients with this distinct tumor type; however, there is considerable uncertainty as to which drug provides the optimal value after crizotinib treatment. This study estimated the cost-utility of alectinib vs ceritinib from a US payer perspective. Methods A cost-utility model was developed using partition survival methods and three health states: progression-free (PF), post-progression (PP), and death...
March 23, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28332225/molecular-dynamics-validation-of-crizotinib-resistance-to-alk-mutations-l1196m-and-g1269a-and-identification-of-specific-inhibitors
#2
Nagasundaram Nagarajan, Carlton Ranjith Wilson Alphonse, Prakash Vincent Samuel Gnana, Rajesh Kannan Rajaretinam
Anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients are mostly treated with ALK tyrosine kinase inhibitors (TKIs). Crizotinib is the first generation ALK inhibitor practiced as a primary chemo to combat cancer cells followed by second generation inhibitor ceritinib which are effective against crizotinib resistant ALK mutations. However, patients treated with these drugs invariably relapsed because of the development of new drug resistance mutations. In this study we explored the crizotinib resistance in the presence of ALK mutations L1196M and G1269A through molecular dynamics simulation studies...
March 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28332047/mechanisms-of-resistance-to-target-therapies-in-non-small-cell-lung-cancer
#3
Francesco Facchinetti, Claudia Proto, Roberta Minari, Marina Garassino, Marcello Tiseo
Targeted therapies are revolutionizing the treatment of advanced non-small cell lung cancer (NSCLC). The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements, has changed the treatment landscape while improving the prognosis of lung cancer patients. Inevitably, virtually all patients initially treated with targeted therapies develop resistance because of the emergence of an insensitive cellular population, selected by pharmacologic pressure. Diverse mechanisms of resistance, in particular to EGFR, ALK and ROS1 tyrosine-kinase inhibitors (TKIs), have now been discovered and may be classified in three different groups: (1) alterations in the target (such as EGFR T790M and ALK or ROS1 mutations); (2) activation of alternative pathways (i...
March 23, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28331757/inflammatory-myofibroblastic-tumor-of-the-breast-coexisting-with-pseudoangiomatous-stromal-hyperplasia
#4
Canan Kelten Talu, Yasemin Çakır, Ezgi Hacıhasanoğlu, Cem Leblebici, Şefika Aksoy, Mehmet Ali Nazlı
Inflammatory myofibroblastic tumors (IMTs) are uncommon breast lesions that consist of spindle cells accompanied by plasma cell-rich inflammatory infiltration, which may mimic breast cancer clinico-radiologically. A woman aged 38 years with a breast mass was referred to our general surgery clinic. The physical examination revealed a mass with irregular borders in the upper outer quadrant of the left breast. In mammography, the lesion was 15 mm in diameter with a spheric form and high density. Ultrasonographically, the mass was solid, heterogeneous, and hypoechoic with posterior enhancement...
October 2016: J Breast Health (2013)
https://www.readbyqxmd.com/read/28331184/the-long-non-coding-rna-linc01013-enhances-invasion-of-human-anaplastic-large-cell-lymphoma
#5
I-Hsiao Chung, Pei-Hsuan Lu, Yang-Hsiang Lin, Ming-Ming Tsai, Yun-Wen Lin, Chau-Ting Yeh, Kwang-Huei Lin
Anaplastic large-cell lymphoma (ALCL) is a rare type of highly malignant, non-Hodgkin lymphoma (NHL). Currently, only studies on the chimeric oncogene NPM-ALK have reported a link to ALCL progression. However, the specific molecular mechanisms underlying the invasion of ALCL are still unclear. Here, we sought to investigate differentially expressed, long non-coding RNAs (lncRNAs) in ALCL and their potential biological function. Our microarray analyses revealed that LINC01013, a novel non-coding RNA gene, was highly expressed in clinical specimens of ALCL and was significantly upregulated in invasive ALCL cell lines...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28330089/discovery-of-potential-alk-inhibitors-by-virtual-screening-approach
#6
Anish Kumar, V Shanthi, K Ramanathan
Crizotinib is an anticancer drug used for the treatment of non-small cell lung cancer. Evidences available suggest that there is a development of an acquired resistance against crizotinib action due to the emergence of several mutations in the ALK gene. It is therefore necessary to develop potent anti-cancer drugs for the treatment of crizotinib resistance non-small cell lung cancer types. In the present study, a novel class of lead molecule was identified using virtual screening, molecular docking and molecular dynamic approach...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28329531/skin-limited-relapse-of-systemic-anaplastic-large-cell-lymphoma
#7
Joshua A Farhadian, Vitaly Terushkin, Shane A Meehan, Craig Kornreich
Anaplastic large-cell lymphomas (ALCLs) are agroup of CD30-positive non-Hodgkin lymphomasthat are linked by common morphologic andimmunophenotypic features but have varyingclinical and genetic characteristics. The World HealthOrganization classification currently recognizes threesubtypes of ALCL: systemic anaplastic lymphomakinase-positive ALCL, systemic anaplastic lymphomakinase-negative (ALK-) ALCL, and primary cutaneousALCL. Here we present a 42-year-old man with ahistory of systemic ALK- ALCL, who was in remissionfor six months before relapsing with skin-limitedanaplastic large-cell lymphoma...
December 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28326957/alk-gene-copy-number-gain-and-immunohistochemical-expression-status-using-three-antibodies-in-neuroblastoma
#8
Eun Kyung Kim, Sewha Kim
Anaplastic lymphoma kinase ( ALK) gene aberrations-such as mutations, amplifications, and copy number gains-represent a major genetic predisposition to neuroblastoma (NB). This study aimed to evaluate the correlation between ALK gene copy number status, ALK protein expression, and clinicopathological parameters. We retrospectively retrieved 30 cases of poorly differentiated NB and constructed tissue microarrays (TMAs). ALK copy number changes were assessed by fluorescence in situ hybridization (FISH) assays, and ALK immunohistochemistry (IHC) testing was performed using three different antibodies (ALK1, D5F3, and 5A4 clones)...
March 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28321989/expansion-of-the-%C3%AF-oxidation-system-alkbgtl-of-pseudomonas-putida-gpo1-with-alkj-and-alkh-results-in-exclusive-mono-esterified-dicarboxylic-acid-production-in-e-%C3%A2-coli
#9
Youri M van Nuland, Fons A de Vogel, Gerrit Eggink, Ruud A Weusthuis
The AlkBGTL proteins coded on the alk operon from Pseudomonas putida GPo1 can selectively ω-oxidize ethyl esters of C6 to C10 fatty acids in whole-cell conversions with Escherichia coli. The major product in these conversions is the ω-alcohol. However, AlkB also has the capacity to overoxidize the substrate to the ω-aldehyde and ω-acid. In this study, we show that alcohol dehydrogenase AlkJ and aldehyde dehydrogenase AlkH are able to oxidize ω-alcohols and ω-aldehydes of esterified fatty acids respectively...
March 20, 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/28321814/immunotherapy-in-nsclc-a-promising-and-revolutionary-weapon
#10
Christian Rolfo, Christian Caglevic, Mariacarmela Santarpia, Antonio Araujo, Elisa Giovannetti, Carolina Diaz Gallardo, Patrick Pauwels, Mauricio Mahave
Lung cancer is the leader malignancy worldwide accounting 1.5 millions of deaths every year. In the United States the 5 year-overall survival is less than 20% for all the newly diagnosed patients. Cisplatin-based cytotoxic chemotherapy for unresectable or metastatic NSCLC patients in the first line of treatment, and docetaxel in the second line, have achieved positive results but with limited benefit in overall survival. Targeted therapies for EGFR and ALK mutant patients have showed better results when compared with chemotherapy, nevertheless most of patients will fail and need to be treated with chemotherapy if they still have a good performance status...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28321808/uncommon-features-of-surgically-resected-alk-positive-cavitary-lung-adenocarcinoma-a-case-report
#11
Shinkichi Takamori, Masafumi Yamaguchi, Kenichi Taguchi, Makoto Edagawa, Shinichiro Shimamatsu, Ryo Toyozawa, Kaname Nosaki, Fumihiko Hirai, Takashi Seto, Mitsuhiro Takenoyama, Yukito Ichinose
Some features found on chest computed tomography (CT), such as central tumor location, large pleural effusion, and the absence of a pleural tail, and a patient age of less than 60 years, have been suggested to be useful in predicting anaplastic lymphoma kinase (ALK) rearrangement in patients with non-small cell lung cancer (NSCLC).A 68-year-old female patient with a history of gynecological treatment was found to have a cavitary mass in the right lower lobe on an annual chest roentgenogram. The tumor was located in the peripheral area with a pleural tail showing no pleural effusion...
December 2017: Surgical Case Reports
https://www.readbyqxmd.com/read/28318251/molecular-simulation-studies-on-the-binding-selectivity-of-type-i-inhibitors-in-the-complexes-with-ros1-versus-alk
#12
Yuanxin Tian, Yonghuan Yu, Yudong Shen, Hua Wan, Shan Chang, Tingting Zhang, Shanhe Wan, Jiajie Zhang
ROS1 and ALK are promising targets of anti-cancer drugs for non small cell lung cancer. Since they have 49% amide acid sequence homology in the kinases domain and 77% identity at the ATP binding area, some ALK inhibitors also showed some significant responses for ROS1 in the clinical trial, such as the type-I binding inhibitor crizotinib and PF-06463922. As a newly therapeutic target, selective ROS1 inhibitor is relative rarely. Moreover, the molecular basis for the selectivity of ROS1 versus ALK still remains unclear...
March 20, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28316817/-n-4-dec-yloxy-2-oxido-benzyl-idene-3-hy-droxy-2-naphtho-hydrazidato-%C3%AE%C2%BA-3-n-o-o-di-methyl-tin-iv-crystal-structure-and-hirshfeld-surface-analysis
#13
Siti Nadiah Binti Mohd Rosely, Rusnah Syahila Duali Hussen, See Mun Lee, Nathan R Halcovitch, Mukesh M Jotani, Edward R T Tiekink
The title diorganotin compound, [Sn(CH3)2(C28H32N2O4)], features a distorted SnC2NO2 coordination geometry almost inter-mediate between ideal trigonal-bipyramidal and square-pyramidal. The dianionic Schiff base ligand coordinates in a tridentate fashion via two alkoxide O and hydrazinyl N atoms; an intra-molecular hy-droxy-O-H⋯N(hydrazin-yl) hydrogen bond is noted. The alk-oxy chain has an all-trans conformation, and to the first approximation, the mol-ecule has local mirror symmetry relating the two Sn-bound methyl groups...
March 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28316074/a-comparison-of-alk-gene-rearrangement-and-alk-protein-expression-in-primary-lung-carcinoma-and-matched-metastasis
#14
Humberto E Trejo Bittar, Alyssa Luvison, Caitlyn Miller, Sanja Dacic
AIMS: The 2013 CAP/IASLC/AMP guideline for EGFR and ALK testing in lung carcinoma indicates that either the primary tumor or the metastasis is suitable for testing. The heterogeneity of gene mutations has been extensively studied, while similar reports on gene rearrangements are limited. The aim of this study was to determine if ALK status between primary tumor and matched metastasis differs. METHODS AND RESULTS: 15 ALK-FISH rearranged and 19 non-ALK-FISH rearranged adenocarcinomas were retrospectively collected based on availability of tissue from a matched metastatic site...
March 17, 2017: Histopathology
https://www.readbyqxmd.com/read/28315448/scaffold-hopping-identifies-6-8-disubstituted-purines-as-novel-anaplastic-lymphoma-kinase-inhibitors
#15
Laura Schlütke, Markus Immer, Lutz Preu, Frank Totzke, Christoph Schächtele, Michael H G Kubbutat, Conrad Kunick
Rearrangements of anaplastic lymphoma kinase (ALK) are associated with several cancer diseases. Due to resistance development against existing ALK-inhibitors, new, structurally unrelated inhibitors are required. By a scaffold hopping strategy, 6,8-disubstituted purines were designed as analogues of similar ALK-inhibiting thieno[3,2-d]pyrimidines. While the new title compounds indeed inhibited ALK and several ALK mutants in submicromolar concentrations, they retained poor water solubility.
March 14, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28314727/transcriptomic-analyses-elucidate-adaptive-differences-of-closely-related-strains-of-p-aeruginosa-in-fuel
#16
Thusitha S Gunasekera, Loryn L Bowen, Carol E Zhou, Susan C Howard-Byerly, William S Foley, Richard C Striebich, Larry C Dugan, Oscar N Ruiz
Pseudomonas aeruginosa can utilize hydrocarbons, but different strains have varying degrees of adaptation despite their highly conserved genome. P. aeruginosa ATCC 33988 is highly adapted to hydrocarbons while strain PAO1, a human pathogen, is less-adapted and degrades jet fuel at a slower rate than does ATCC 33988. We investigated fuel specific transcriptomic differences between these strains in order to ascertain the underling mechanisms utilized by the adapted strain to proliferate in fuel. During growth in fuel, the genes related to alkane degradation, heat-shock response, membrane proteins, efflux pumps and several novel genes were upregulated in ATCC 33988...
March 17, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28303028/alectinib-ch5424802-antagonizes-abcb1-and-abcg2-mediated-multidrug-resistance-in-vitro-in-vivo-and-ex-vivo
#17
Ke Yang, Yifan Chen, Kenneth Kin Wah To, Fang Wang, Delan Li, Likun Chen, Liwu Fu
Alectinib, an inhibitor of anaplastic lymphoma kinase (ALK), was approved by the Food and Drug Administration (FDA) for the treatment of patients with ALK-positive non-small cell lung cancer (NSCLC). Here we investigated the reversal effect of alectinib on multidrug resistance (MDR) induced by ATP-binding cassette (ABC) transporters, which is the primary cause of chemotherapy failure. We provide the first evidence that alectinib increases the sensitivity of ABCB1- and ABCG2-overexpressing cells to chemotherapeutic agents in vitro and in vivo...
March 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28302170/identification-of-residues-important-for-the-activity-of-aldehyde-deformylating-oxygenase-through-investigation-into-the-structure-activity-relationship
#18
Qing Wang, Luyao Bao, Chenjun Jia, Mei Li, Jian-Jun Li, Xuefeng Lu
BACKGROUND: Aldehyde-deformylating oxygenase (ADO) is a key enzyme involved in the biosynthetic pathway of fatty alk(a/e)nes in cyanobacteria. However, cADO (cyanobacterial ADO) showed extreme low activity with the k cat value below 1 min(-1), which would limit its application in biofuel production. To identify the activity related key residues of cADO is urgently required. RESULTS: The amino acid residues which might affect cADO activity were identified based on the crystal structures and sequence alignment of cADOs, including the residues close to the di-iron center (Tyr39, Arg62, Gln110, Tyr122, Asp143 of cADO-1593), the protein surface (Trp 178 of cADO-1593), and those involved in two important hydrogen bonds (Gln49, Asn123 of cADO-1593, and Asp49, Asn123 of cADO-sll0208) and in the oligopeptide whose conformation changed in the absence of the di-iron center (Leu146, Asn149, Phe150 of cADO-1593, and Thr146, Leu148, Tyr150 of cADO-sll0208)...
March 16, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28299304/effects-of-phlebotomy-on-liver-enzymes-and-histology-of-patients-with-nonalcoholic-fatty-liver-disease
#19
Mahsa Khodadoostan, Maryam Zamanidoost, Ahmad Shavakhi, Hosein Sanei, Masood Shahbazi, Mehdi Ahmadian
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD), defined as excessive liver fat deposition and one of end-stage liver disease causes. Increased ferritin levels are associated with insulin resistance and a higher hepatic iron and fat content. Hyperferritinemia has been associated with severity of liver damage in NAFLD. The study aimed to evaluate the effects of phlebotomy on liver enzymes and histology in such patients. MATERIALS AND METHODS: Thirty-two eligible patients who had NAFLD and after 6 months of lifestyle modification still had NAFLD, and whose ferritin serum was above 250 mg/dl, were enrolled in this clinical trial study...
2017: Advanced Biomedical Research
https://www.readbyqxmd.com/read/28296581/three-year-follow-up-of-an-alectinib-phase-i-ii-study-in-alk-positive-non-small-cell-lung-cancer-af-001jp
#20
Tomohide Tamura, Katsuyuki Kiura, Takashi Seto, Kazuhiko Nakagawa, Makoto Maemondo, Akira Inoue, Toyoaki Hida, Hiroshige Yoshioka, Masao Harada, Yuichiro Ohe, Naoyuki Nogami, Haruyasu Murakami, Hiroshi Kuriki, Tadashi Shimada, Tomohiro Tanaka, Kengo Takeuchi, Makoto Nishio
Purpose Alectinib is an anaplastic lymphoma kinase (ALK) -specific kinase inhibitor that seems to be effective against non-small-cell lung cancer (NSCLC) with a variety of ALK mutations. The primary analysis of AF-001JP reported a promising overall response rate. To assess progression-free survival (PFS) and overall survival (OS), patients from the phase II part of AF-001JP were followed up for approximately 3 years. Patients and Methods Oral alectinib 300 mg was administered twice per day to patients with ALK inhibitor-naïve, ALK-positive NSCLC who had progressed after one or more regimens of previous chemotherapy...
March 15, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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