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https://www.readbyqxmd.com/read/28821955/targeted-next-generation-sequencing-for-analyzing-the-genetic-alterations-in-atypical-adenomatous-hyperplasia-and-adenocarcinoma-in-situ
#1
Xuan Xu, Na Li, Ruiying Zhao, Lei Zhu, Jinchen Shao, Jie Zhang
PURPOSE: Atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS) have been defined as preinvasive pulmonary adenocarcinoma lesions according to the 2015 World Health Organization lung adenocarcinoma classification. We aimed to search for the most common gene mutations in patients with AAH and AIS and investigate the distinctions between the two groups at the molecular level. METHODS: We performed targeted next-generation sequencing on 18 cases with AAH and 28 cases with AIS to screen for mutations with the Ion Torrent Oncomine Solid Tumor DNA panel...
August 18, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28821506/crizotinib-has-antitumor-activity-in-alk-positive-alcl-and-imt
#2
(no author information available yet)
Crizotinib has an overall response rate of 90% in ALCL and 86% in IMT at the recommended phase II dose.
August 18, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28820968/reduced-activin-receptor-like-kinase-1-activity-promotes-cardiac-fibrosis-in-heart-failure
#3
Kevin J Morine, Xiaoying Qiao, Vikram Paruchuri, Mark J Aronovitz, Emily E Mackey, Lyanne Buiten, Jonathan Levine, Keshan Ughreja, Prerna Nepali, Robert M Blanton, S Paul Oh, Richard H Karas, Navin K Kapur
INTRODUCTION: Activin receptor-like kinase 1 (ALK1) mediates signaling via the transforming growth factor beta-1 (TGFβ1), a pro-fibrogenic cytokine. No studies have defined a role for ALK1 in heart failure. HYPOTHESIS: We tested the hypothesis that reduced ALK1 expression promotes maladaptive cardiac remodeling in heart failure. METHODS AND RESULTS: In patients with advanced heart failure referred for left ventricular (LV) assist device implantation, LV Alk1 mRNA and protein levels were lower than control LV obtained from patients without heart failure...
July 18, 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/28820294/k-deficiency-caused-defects-in-renal-tubular-cell-proliferation-oxidative-stress-response-tissue-repair-and-tight-junction-integrity-but-enhanced-energy-production-proteasome-function-and-cellular-k-uptake
#4
Chompunoot Kapincharanon, Visith Thongboonkerd
Hypokalemia is a common electrolyte disorder in hospitalized patients and those with chronic diseases and is associated with renal tubular injury. Our recent expression proteomics study revealed changes in levels of several proteins in renal tubular cells during K(+) deficiency. However, functional significance and mechanisms underlying such changes remained unclear. The present study, thus, aimed to investigate functional changes of renal tubular cells induced by K(+) deficiency. MDCK cells were maintained in normal-K(+) (ANK; [K(+)] = 5...
August 18, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28818606/recent-advances-in-targeting-ros1-in-lung-cancer
#5
REVIEW
Jessica J Lin, Alice T Shaw
ROS1 is a validated therapeutic target in non-small cell lung cancer (NSCLC). In a phase I study, the multi-targeted MET/ALK/ROS1 inhibitor crizotinib demonstrated remarkable efficacy in ROS1-rearranged NSCLCs, and consequently gained approval by the United States Food and Drug Administration as well as the European Medicines Agency in 2016. However, similar to other oncogene-driven lung cancers, ROS1-rearranged lung cancers treated with crizotinib eventually acquire resistance, leading to disease relapse. Novel ROS1 inhibitors and therapeutic strategies are therefore needed...
August 14, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28816991/a-case-report-of-tracheal-inflammatory-myofibroblastic-tumor-in-a-34-week-pregnant-woman-misdiagnosed-with-asthma
#6
Xiaochen Li, Juan Li, Xiaoling Rao, Qilin Ao, Xiaopei Cao, Yali Huang, Shengding Zhang, Xiaoyu Fang, Xiansheng Liu, Min Xie
RATIONALE: Inflammatory myofibroblastic tumor (IMT) is an uncommon neoplastic entity with a tendency of local recurrence and a low risk of distant metastasis. Involvement of trachea is extremely rare. PATIENT CONCERNS: A 34-week pregnant woman previously diagnosed with asthma for 2 months was admitted with persistent wheezing and hemoptysis. A computed tomography scan and bronchoscopy revealed a gigantic polyp in the trachea. DIAGNOSES: Tracheal inflammatory myofibroblastic tumor...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28811082/correlation-between-molecular-analysis-diagnosis-according-to-the-2015-who-classification-of-unresected-lung-tumours-and-ttf1-expression-in-small-biopsies-and-cytology-specimens-from-344-non-small-cell-lung-carcinoma-patients
#7
Prudence A Russell, Toni-Maree Rogers, Benjamin Solomon, Naveed Alam, Stephen A Barnett, Vivek Rathi, Richard A Williams, Gavin M Wright, Matthew Conron
We investigated correlations between diagnosis according to the 2015 World Health Organization (WHO) classification of unresected lung tumours, molecular analysis and TTF1 expression in small biopsy and cytology specimens from 344 non-small cell lung carcinoma (NSCLC) patients. One case failed testing for EGFR, KRAS and ALK abnormalities and six had insufficient tumour for ALK testing. Overall mutation rate in 343 cases was 48% for the genes tested, with 19% EGFR, 33% KRAS and 4% BRAF mutations, and 5% ALK rearrangements detected...
August 12, 2017: Pathology
https://www.readbyqxmd.com/read/28809478/ruthenium-ii-and-ruthenium-iii-complexes-of-p-benziporphyrin-merging-equatorial-and-axial-organometallic-coordination
#8
Aneta Idec, Miłosz Pawlicki, Lechosław Latos-Grażyński
A diamagnetic ruthenium(II) complex of 5,10,15,20-tetraphenyl-p-benziporphyrin [Ru(II)(p-BzP)(CO)Cl] was obtained via the insertion of ruthenium into p-benziporphyrin using triruthenium(0) dodecacarbonyl [Ru3(CO)12] as the metal source. The procedure applying dichloro(cycloocta-1,5-diene)ruthenium(II) (polymer, [Ru(COD)Cl2]n) afforded the paramagnetic six-coordinate ruthenium(III) p-benziporphyrin [Ru(III)(p-BzP)Cl2]. As shown by X-ray crystallography, the p-phenylene ring in both complexes is sharply tilted out of the N3 plane, as reflected by the respective N3 (pyrrole)-C6 (p-phenylene) dihedral angle [Ru(II)(p-BzP)(CO)Cl, 52...
August 15, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28808224/off-label-use-of-crizotinib-as-a-neoadjuvant-treatment-for-a-young-patient-when-conventional-chemotherapy-gave-no-benefits-in-stage-iiia-non-small-cell-lung-cancer
#9
Delphine Dumont, Pascal Dô, Delphine Lerouge, Gaëtane Planchard, Marc Riffet, Catherine Dubos-Arvis, Serge Danhier, Radj Gervais
BACKGROUND The treatment of locally advanced non-small cell lung cancer involves a combination of chemotherapy, surgery, and radiotherapy. Each case is discussed and the best strategy is chosen individually, following international guidelines. CASE REPORT A 37-year-old man was diagnosed with locally advanced broncho-pulmonary adenocarcinoma (stage IIIA). The disease was stable after 2 cycles of cisplatin plus Navelbine used as neoadjuvant therapy. FISH analysis revealed an ALK rearrangement. The patient then received unlicensed crizotinib as second-line neoadjuvant treatment, which led to an almost complete radiological and metabolic response...
August 15, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28806935/association-between-charlson-comorbidity-index-score-and-outcome-in-patients-with-stage-iiib-iv-non-small-cell-lung-cancer
#10
Lei Zhao, Lai-Han Leung, Jing Wang, Huihui Li, Juanjuan Che, Lian Liu, Xiaojun Yao, Bangwei Cao
BACKGROUND: This retrospective study investigated the association between the Charlson comorbidity index (CCI) score and the survival of patients with stage IIIB-IV (advanced, non-resectable) non-small cell lung cancer (NSCLC) who also did not have gene mutations in epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK). METHODS: The records of 165 patients (28-80 y, median 61 y) who met the above criteria and were admitted to Beijing Friendship Hospital Capital Medical University from 1 May 2010 to 1 October 2014were reviewed...
August 15, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28806414/alpha-tocopherol-attenuates-the-anti-tumor-activity-of-crizotinib-against-cells-transformed-by-npm-alk
#11
Yuki Uchihara, Fumihito Ueda, Kenji Tago, Yosuke Nakazawa, Tomoyuki Ohe, Tadahiko Mashino, Shigenobu Yokota, Tadashi Kasahara, Hiroomi Tamura, Megumi Funakoshi-Tago
Anaplastic large cell lymphomas (ALCL) are mainly characterized by harboring the fusion protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). The ALK inhibitor, crizotinib specifically induced apoptosis in Ba/F3 cells expressing NPM-ALK by inhibiting the activation of NPM-ALK and its downstream molecule, signal transducer and activator of transcription factor 3 (STAT3). We found that α-tocopherol, a major component of vitamin E, attenuated the effects of crizotinib independently of its anti-oxidant properties...
2017: PloS One
https://www.readbyqxmd.com/read/28806116/systemic-therapy-for-stage-iv-non-small-cell-lung-cancer-american-society-of-clinical-oncology-clinical-practice-guideline-update
#12
Nasser Hanna, David Johnson, Sarah Temin, Sherman Baker, Julie Brahmer, Peter M Ellis, Giuseppe Giaccone, Paul J Hesketh, Ishmael Jaiyesimi, Natasha B Leighl, Gregory J Riely, Joan H Schiller, Bryan J Schneider, Thomas J Smith, Joan Tashbar, William A Biermann, Gregory Masters
Purpose Provide evidence-based recommendations updating the 2015 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC). Methods The ASCO NSCLC Expert Panel made recommendations based on a systematic review of randomized controlled trials from February 2014 to December 2016 plus the Cancer Care Ontario Program in Evidence-Based Care's update of a previous ASCO search. Results This guideline update reflects changes in evidence since the previous guideline update. Fourteen randomized controlled trials provide the evidence base; earlier phase trials also informed recommendation development...
August 14, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28805682/alk-in-non-small-cell-lung-cancer-nsclc-pathobiology-epidemiology-detection-from-tumor-tissue-and-algorithm-diagnosis-in-a-daily-practice
#13
REVIEW
Paul Hofman
Patients with advanced-stage non-small cell lung carcinoma (NSCLC) harboring an ALK rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. Several increasingly effective ALK inhibitors are now available for treatment of patients. However, despite an initial favorable response to treatment, in most cases relapse or progression occurs due to resistance mechanisms mainly caused by mutations in the tyrosine kinase domain of ALK. The detection of an ALK rearrangement is pivotal and can be done using different methods, which have variable sensitivity and specificity depending, in particular, on the quality and quantity of the patient's sample...
August 12, 2017: Cancers
https://www.readbyqxmd.com/read/28805673/alk-status-assessment-with-liquid-biopsies-of-lung-cancer-patients
#14
REVIEW
Paul Hofman
Patients with advanced stage non-small cell lung carcinoma (NSCLC) harboring an anaplastic lymphoma kinase ALK gene rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. However, while treatment is initially effective in most cases, relapse or progression occurs due to different resistance mechanisms including mutations in the tyrosine kinase domain of echinoderm microtubule-associated protein-like 4 (EML44)-ALK. The liquid biopsy concept has recently radically changed the clinical care of NSCLC patients, in particular for those harboring an epidermal growth factor receptor (EGFR) gene mutation...
August 12, 2017: Cancers
https://www.readbyqxmd.com/read/28803971/otp-an-automatized-system-for-managing-and-processing-ngs-data
#15
Eva Reisinger, Lena Genthner, Jules Kerssemakers, Philip Kensche, Stefan Borufka, Alke Jugold, Andreas Kling, Manuel Prinz, Ingrid Scholz, Gideon Zipprich, Roland Eils, Christian Lawerenz, Jürgen Eils
The One Touch Pipeline (OTP) is an automation platform managing Next-Generation Sequencing (NGS) data and calling bioinformatic pipelines for processing these data. OTP handles the complete digital process from import of raw sequence data via alignment of sequencing reads to identify genomic events in an automated and scalable way. Three major goals are pursued: firstly, reduction of human resources required for data management by introducing automated processes. Secondly, reduction of time until the sequences can be analyzed by bioinformatic experts, by executing all operations more reliably and quickly...
August 10, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28802494/toward-a-molecular-genetic-classification-of-spitzoid-neoplasms
#16
REVIEW
Michael T Tetzlaff, Alexandre Reuben, Steven D Billings, Victor G Prieto, Jonathan L Curry
The histopathologic spectrum of Spitzoid neoplasms includes Spitz nevi, atypical Spitz tumors, and Spitzoid melanomas. Advances in molecular genetics have evolved to the point that Spitzoid lesions can now be reasonably classified according to their distinctive molecular-genetic alterations: Spitzoid lesions with (1) 11p amplification and/or HRAS mutations; (2) isolated loss of 6q23 by fluorescence in situ hybridization (FISH); (3) homozygous deletion of 9p21 by FISH; (4) BAP1 loss and BRAFV600 E mutation; (5) translocations involving any of a number of different oncogenic kinase drivers, including ROS1, ALK, NTRK1, NTRK3, MET, BRAF, and RET; and (6) TERT promoter mutations...
September 2017: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/28800395/using-chemistry-to-target-neuroblastoma
#17
Jeanne N Hansen, Xingguo Li, Y George Zheng, Louis T Lotta, Abhishek Dedhe, Nina F Schor
Neuroblastoma is a cancer of the neural crest almost exclusively seen in childhood. While children with single, small primary tumors are often cured with surgery alone, the 65% of children with neuroblastoma whose disease has metastasized have less than a 50% chance of surviving five years after diagnosis. Innovative pharmacological strategies are critically needed for these children. Efforts to identify novel targets that afford ablation of neuroblastoma with minimal toxicity to normal tissues are underway...
August 11, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28797780/clinical-practice-recommendations-on-indication-and-timing-of-hematopoietic-cell-transplantation-in-mature-t-cell-and-nk-t-cell-lymphomas-an-international-collaborative-effort-on-behalf-of-the-guidelines-committee-of-the-american-society-for-blood-and-marrow
#18
Mohamed A Kharfan-Dabaja, Ambuj Kumar, Ernesto Ayala, Mehdi Hamadani, Peter Reimer, Christian Gisselbrecht, Francesco d'Amore, Esa Jantunen, Takashi Ishida, Ali Bazarbachi, Francine Foss, Ranjana Advani, Timothy S Fenske, Hillard M Lazarus, Jonathan W Friedberg, Mahmoud Aljurf, Lubomir Sokol, Kensei Tobinai, Eric Tse, Linda J Burns, Julio C Chavez, Nishitha M Reddy, Ritsuro Suzuki, Sairah Ahmed, Auayporn Nademanee, Mohamad Mohty, Ajay K Gopal, Michelle A Fanale, Barbara Pro, Alison J Moskowitz, Anna Sureda, Miguel Angel Perales, Paul A Carpenter, Bipin N Savani
Recognizing the significant biologic and clinical heterogeneity of mature T-cell and NK/T-cell lymphomas, the American Society for Blood and Marrow Transplantation invited experts to develop clinical practice recommendations related to the role of auto-HCT and allo-HCT for specific histologic subtypes. We used the GRADE methodology to assist in moving from evidence to decision-making and ultimately generating final recommendations. Auto-HCT in front-line consolidation is recommended in PTCL-NOS, AITL, ALCL-ALK negative, NK/T-cell (disseminated), EATL and hepatosplenic lymphomas...
August 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28795492/treatment-of-alk-rearranged-non-small-cell-lung-cancer-a-review-of-the-landscape-and-approach-to-emerging-patterns-of-treatment-resistance-in-the-australian-context
#19
M Itchins, P L Chia, S A Hayes, V M Howell, A J Gill, W A Cooper, T John, P Mitchell, M Millward, S J Clarke, B Solomon, N Pavlakis
Since the identification of anaplastic lymphoma kinase (ALK) gene rearrangements in non-small cell lung cancer (NSCLC) in 2005, the treatment of ALK-rearranged NSCLC (ALK+ NSCLC) has evolved at a rapid pace. This molecularly distinct subset of NSCLC has uniquely important biology, clinicopathologic features and mechanisms of drug resistance which impact on the choice of treatment for a patient with this disease. There are multiple ALK tyrosine kinase inhibitors now available in clinical practice with efficacy data continuing to emerge and guide the optimal treatment algorithm...
August 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28794371/successful-treatment-with-alectinib-for-choroidal-metastasis-in-anaplastic-lymphoma-kinase-rearranged-non-small-cell-lung-cancer
#20
Tomoko Funazo, Kyohei Morita, Naoya Ikegami, Chisato Konishi, Satoshi Nakao, Ryo Ariyasu, Masato Taki, Kazuhiko Nakagawa, Moon Hee Hwang, Chie Yoshimura, Toshiaki Wakayama, Yasuo Nishizaka
Choroidal metastasis is rare in cancer patients and it may cause visual disturbances that reduce their quality of life. In non-small cell lung cancer (NSCLC), targeted therapy against actionable driver mutations has gradually replaced radiotherapy as the treatment of choice for choroidal metastasis. Recently, there have been several case reports of choroidal metastasis in patients with anaplastic lymphoma kinase (ALK)-rearranged NSCLC. We herein report the case of a 40-year-old Japanese woman diagnosed with choroidal metastasis of an ALK-rearranged NSCLC who received alectinib as the first-line chemotherapy...
August 10, 2017: Internal Medicine
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