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https://www.readbyqxmd.com/read/29050314/applicability-of-graded-prognostic-assessment-of-lung-cancer-using-molecular-markers-to-lung-adenocarcinoma-patients-with-brain-metastases
#1
Hongwei Li, Jianhong Lian, Songyan Han, Weili Wang, Haixia Jia, Jianzhong Cao, Xiaqin Zhang, Xin Song, Sufang Jia, Jiwei Ren, Weihua Yang, Yanfeng Xi, Shengmin Lan
Several scoring systems are available to estimate prognosis and assist in selecting treatment methods for non-small cell lung cancer (NSCLC) patients with brain metastasis, including recursive partitioning analysis (RPA), basic score for brain metastases (BS-BM), and diagnosis-specific graded prognostic assessment (DS-GPA). Lung-molGPA is an update of the DS-GPA that incorporates EGFR and/or ALK mutation status. The present study tested the applicability of these four indexes in 361 lung adenocarcinoma patients with brain metastasis...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29049466/breast-implant-associated-anaplastic-large-cell-lymphoma-a-systematic-review
#2
Ashley N Leberfinger, Brittany J Behar, Nicole C Williams, Kevin L Rakszawski, John D Potochny, Donald R Mackay, Dino J Ravnic
Importance: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), a rare peripheral T-cell lymphoma, is increasing in incidence. However, many practitioners who treat patients with breast cancer are not aware of this disease. Objectives: To assess how BIA-ALCL develops, its risk factors, diagnosis, and subsequent treatment and to disseminate information about this entity to the medical field. Evidence Review: A literature review was performed in an academic medical setting...
October 18, 2017: JAMA Surgery
https://www.readbyqxmd.com/read/29048652/activation-of-src-signaling-mediates-acquired-resistance-to-alk-inhibition-in-lung-cancer
#3
Ryohei Yoshida, Takaaki Sasaki, Yoshinori Minami, Yukiko Hibino, Shunsuke Okumura, Masatoshi Sado, Naoyuki Miyokawa, Satoshi Hayashi, Masahiro Kitada, Yoshinobu Ohsaki
Anaplastic lymphoma kinase (ALK) fusion oncogenes occur in approximately 3-5% of non-small cell lung cancer (NSCLC) cases. Various ALK inhibitors are in clinical use for the treatment of ALK-NSCLC, including the first generation ALK inhibitor, crizotinib, and recently the more highly potent alectinib and ceritinib. However, most tumors eventually become resistant to ALK specific inhibitors. To address the mechanisms underlying the development of ALK inhibitor resistance, we used iTRAQ quantitative mass spectrometry and phosphor-receptor tyrosine kinase arrays to investigate intracellular signaling alterations in ALK inhibitor resistant NSCLC cell lines...
September 28, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29046432/alk-is-a-therapeutic-target-for-lethal-sepsis
#4
Ling Zeng, Rui Kang, Shan Zhu, Xiao Wang, Lizhi Cao, Haichao Wang, Timothy R Billiar, Jianxin Jiang, Daolin Tang
Sepsis, a life-threatening organ dysfunction caused by infection, is a major public health concern with limited therapeutic options. We provide evidence to support a role for anaplastic lymphoma kinase (ALK), a tumor-associated receptor tyrosine kinase, in the regulation of innate immunity during lethal sepsis. The genetic disruption of ALK expression diminishes the stimulator of interferon genes (STING)-mediated host immune response to cyclic dinucleotides in monocytes and macrophages. Mechanistically, ALK directly interacts with epidermal growth factor receptor (EGFR) to trigger serine-threonine protein kinase AKT phosphorylation and activate interferon regulatory factor 3 (IRF3) and nuclear factor κB (NF-κB) signaling pathways, enabling STING-dependent rigorous inflammatory responses...
October 18, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29046324/etv6-ntrk3-and-strn-alk-kinases-fusions-are-recurrent-events-in-papillary-thyroid-cancer-of-adult-population
#5
André U Bastos, Ana Carolina de Jesus, Janete Maria Cerutti
OBJECTIVE: PTC-specific analysis identified novel fusions involving RET, BRAF, NTRK1, NTRK3, AGK and ALK genes in adults and pediatric PTC. Although many novel fusions are PTC-specific event and, therefore, are ideal for diagnosis purposes, validation across additional and larger cohorts is essential for introducing these potential diagnostic or prognostic biomarkers into the clinical practice. As most of the BRAF, NTRK3 and ALK fusions were initially found in pediatric PTC or in more aggressive thyroid carcinomas, and there is a great disparity across population, in this study, we screened a large set of adult sporadic PTC cases for the most prevalent kinases fusion lately described in the TCGA...
October 18, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29045518/negative-hyper-selection-of-metastatic-colorectal-cancer-patients-for-anti-egfr-monoclonal-antibodies-the-pressing-case-control-study
#6
C Cremolini, F Morano, R Moretto, R Berenato, E Tamborini, F Perrone, D Rossini, A Gloghini, A Busico, G Zucchelli, C Baratelli, E Tamburini, M Tampellini, E Sensi, G Fucà, C Volpi, M Milione, M Di Maio, G Fontanini, F De Braud, A Falcone, F Pietrantonio
Background: Refining the selection of metastatic colorectal cancer (mCRC) patients candidates for anti-EGFR monoclonal antibodies beyond RAS and BRAF testing is a challenge of precision oncology. Several uncommon genomic mechanisms of primary resistance, leading to activation of tyrosine kinase receptors other than EGFR or downstream signaling pathways, have been suggested by preclinical and retrospective studies. Patients and methods: We conducted this multicenter, prospective, case-control study to demonstrate the negative predictive impact of a panel of rare genomic alterations (PRESSING panel), including HER2/MET amplifications, ALK/ROS1/NTRK1-3/RET fusions, and HER2/PI3K/PTEN/AKT1 mutations...
September 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045514/exploratory-analysis-of-the-association-of-depth-of-response-and-survival-in-patients-with-metastatic-non-small-cell-lung-cancer-treated-with-a-targeted-therapy-or-immunotherapy
#7
C E McCoach, G M Blumenthal, L Zhang, A Myers, S Tang, R Sridhara, P Keegan, R Pazdur, R C Doebele, D Kazandjian
Background: Response Evaluation Criteria in Solid Tumors (RECIST) permits rapid evaluation of new therapeutic strategies in cancer. However, RECIST does not capture the heterogeneity of response in highly active therapies. Depth of tumor response may provide a more granular view of response. We explored the association between, depth of response (DepOR), with overall survival (OS) and progression free survival (PFS) for patients with NSCLC being treated with an ALK inhibitor (ALKi) or an anti-PD-1 antibody (Ab)...
August 2, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045271/rhabdomyosarcoma-cells-are-susceptible-to-cell-death-by-ldk378-alone-or-in-combination-with-sorafenib-independently-of-anaplastic-lymphoma-kinase-status
#8
Nadezda Dolgikh, Simone Fulda
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is often overexpressed in rhabdomyosarcoma (RMS). However, its oncogenic and functional role in RMS remains unclear. Therefore, we investigated the antitumor activity of LDK378 (ceritinib), a new second-generation ALK inhibitor approved for patients with ALK-positive non-small-cell lung cancers. Here, we report that LDK378 reduces cell viability and induces cell death in RMS cell lines at low micromolar IC50 concentrations irrespective of ALK expression levels or phosphorylation status...
November 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29044021/-asia-syndrome-breast-implant-and-still-s-disease
#9
Cristhian Armenteros, Andrea Odzak, Florencia Arcondo, Marcela De Dios Soler, Tatiana Sinigier, Marcelo Zylberman
Connective tissue diseases associated with silicone breast implants have been widely discussed. In the last decade, siliconosis has been included in the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) next to Gulf War syndrome, macrophage myofascitis and postvaccination phenomena. The ASIA syndrome may appear as lupus, rheumatoid arthritis, or more rarely, as adult Still's disease. We discuss the case of a patient with prolonged fever and clinical criteria for ASIA and Still's disease. The prostheses were resected and pathology showed absence of breast implant associated anaplastic lymphoma ALK (-)...
2017: Medicina
https://www.readbyqxmd.com/read/29042798/crizotinib-a-met-inhibitor-inhibits-growth-migration-and-invasion-of-breast-cancer-cells-in-vitro-and-synergizes-with-chemotherapeutic-agents
#10
Nehad M Ayoub, Kamal M Al-Shami, Mohammad A Alqudah, Nizar M Mhaidat
MET is a receptor tyrosine kinase known for its pleiotropic effects in tumorigenesis. Dysregulations of MET expression and/or signaling have been reported and determined to be associated with inferior outcomes in breast cancer patients rendering MET a versatile candidate for targeted therapeutic intervention. Crizotinib is a multi-targeted small-molecule kinase inhibitor for MET, ALK, and ROS1 kinases. This study evaluated the anti-proliferative, cytotoxic, anti-migratory, and anti-invasive effects of crizotinib in breast cancer cells in vitro...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29039585/identification-of-genome-variations-in-patients-with-lung-adenocarcinoma-using-whole-genome-re%C3%A2-sequencing
#11
Guiyuan Li, Yunqing Mei, Fan Yang, Shengming Yi, Lemin Wang
Lung adenocarcinoma is one of the types of non‑small cell lung carcinoma, which tends to be treated with surgical therapy rather than radiation therapy. It occurs in smokers and non‑smokers, and is the most common form of lung cancer among non‑smokers and women. Gene rearrangements, including ALK, ROS1 and RET, and gene mutations, including epidermal growth factor receptor (EGFR), HER2, Kristen rat sarcoma viral oncogene homolog, BRAF, phosphoinositide‑3‑kinase, catalytic, α polypeptide and MET, have been identified in lung adenocarcinoma, which enable targeted therapy in lung adenocarcinoma, for example erlotinib, gefitinib and afatinib, which are EGFR inhibitors...
October 17, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29036791/globo-h-expression-is-associated-with-driver-mutations-and-pd-l1-expressions-in-stage-i-non-small-cell-lung-cancer
#12
Ching-Yao Yang, Mong-Wei Lin, Yih-Leong Chang, Chen-Tu Wu
BACKGROUND: Globo H is a tumor-associated carbohydrate antigen exclusively expressed in cancer cells rather than normal tissue. Globo H has been found on many cancers of epithelial origins, and become an attractive target for cancer vaccine. OBJECTIVES: We aimed to study the expression of Globo H in non-small cell lung cancer (NSCLC) patients, and correlated its expression with common driver mutations, clinical outcomes, and status of immune checkpoint, programmed death-ligand 1 (PD-L1)...
September 29, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29035291/from-pathology-to-precision-medicine-in-anaplastic-large-cell-lymphoma-expressing-anaplastic-lymphoma-kinase-alk-alcl
#13
REVIEW
Michael T Werner, Qian Zhang, Mariusz A Wasik
Anaplastic large cell lymphoma expressing anaplastic lymphoma kinase (ALK+ ALCL) is a distinct subtype of non-Hodgkin lymphoma. In this review, we discuss the historical findings that led to its classification as a unique disease, despite its varied clinical presentation and histology. We discuss the molecular mechanisms underlying ALK+ ALCL pathology and the questions that remain in the field. Finally, we visit how decades of ALK+ ALCL research has yielded more precise drugs that hold promise for the future...
October 16, 2017: Cancers
https://www.readbyqxmd.com/read/29035132/hybrid-lipid-polymer-nanoparticles-for-pulmonary-delivery-of-sirna-development-and-fate-upon-in-vitro-deposition-on-the-human-epithelial-airway-barrier
#14
Ivana d'Angelo, Gabriella Costabile, Estelle Durantie, Paola Brocca, Valeria Rondelli, Annapina Russo, Giulia Russo, Agnese Miro, Fabiana Quaglia, Alke Petri-Fink, Barbara Rothen-Rutishauser, Francesca Ungaro
BACKGROUND: Nowadays, the downregulation of genes involved in the pathogenesis of severe lung diseases through local siRNA delivery appears an interesting therapeutic approach. In this study, we propose novel hybrid lipid-polymer nanoparticles (hNPs) consisting of poly(lactic-co-glycolic) acid (PLGA) and dipalmitoyl phosphatidylcholine (DPPC) as siRNA inhalation system. METHODS: A panel of DPPC/PLGA hNPs was prepared by emulsion/solvent diffusion and fully characterized...
October 16, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/29033318/an-alkynyl-fucose-halts-hepatoma-cell-migration-and-invasion-by-inhibiting-gdp-fucose-synthesizing-enzyme-fx-tsta3
#15
Yasuhiko Kizuka, Miyako Nakano, Yoshiki Yamaguchi, Kazuki Nakajima, Ritsuko Oka, Keiko Sato, Chien-Tai Ren, Tsui-Ling Hsu, Chi-Huey Wong, Naoyuki Taniguchi
Fucosylation is a glycan modification critically involved in cancer and inflammation. Although potent fucosylation inhibitors are useful for basic and clinical research, only a few inhibitors have been developed. Here, we focus on a fucose analog with an alkyne group, 6-alkynyl-fucose (6-Alk-Fuc), which is used widely as a detection probe for fucosylated glycans, but is also suggested for use as a fucosylation inhibitor. Our glycan analysis using lectin and mass spectrometry demonstrated that 6-Alk-Fuc is a potent and general inhibitor of cellular fucosylation, with much higher potency than the existing inhibitor, 2-fluoro-fucose (2-F-Fuc)...
September 19, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29030834/prognostic-impact-of-minimal-disseminated-disease-and-immune-response-to-npm-alk-in-japanese-children-with-alk-positive-anaplastic-large-cell-lymphoma
#16
Yuka Iijima-Yamashita, Tetsuya Mori, Atsuko Nakazawa, Reiji Fukano, Tetsuya Takimoto, Masahito Tsurusawa, Ryoji Kobayashi, Keizo Horibe
The prognostic impact of minimal disseminated disease (MDD) and anti-anaplastic lymphoma kinase (ALK) antibody titer in children with ALK-positive anaplastic large cell lymphoma (ALCL) was reported by an Italian/German group. Here, we examine their prognostic value in Japanese children with ALK-positive ALCL. We evaluated nucleophosmin (NPM)-ALK transcripts in 60 patients at diagnosis by RT-PCR and real-time PCR (qPCR). The antibody titer was assessed in 35 patients. Fifty-two percent were MDD positive by RT-PCR and 37% had more than 10 copies of NPM-ALK per 10(4) copies of ABL (10NCNs) by qPCR...
October 13, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29028122/atypical-alk-positive-spitz-tumors-with-9p21-homozygous-deletion-report-of-two-cases-and-review-of-the-literature
#17
Andrew J Rand, Wendy L Flejter, Christopher A Dowling, Linda M Brooke, Genevieve M Boland, Daniela Kroshinsky, Isaac R Rosenblum, Marier Hernandez-Perez, Julie D R Reimann
ALK rearrangements occur in up to 10% of spitzoid melanocytic neoplasms. No reported cases have shown homozygous deletion of 9p21 (CDKN2A) or gains of 6p25 (RREB1) or 11q13 (CCND1), which have been associated with aggressive clinical behavior. Here we report two unique cases. Case 1 occurred in a 9-year-old male with a 14-mm nodule on the anterior left thigh. Biopsy revealed an ALK-positive Spitz tumor containing an irregular nodule of densely packed melanocytes with increased mitoses and loss of p16 immunoreactivity...
October 13, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/29027617/zebrafish-as-a-model-to-study-neuroblastoma-development
#18
REVIEW
Mattie J Casey, Rodney A Stewart
Neuroblastoma is a pediatric solid tumor arising from embryonic neural crest progenitor cells that normally generate the peripheral sympathetic nervous system. As such, the location of neuroblastoma tumors is correlated with the distribution of major post-ganglionic clusters throughout the sympathetic chain, with the highest incidence in the adrenal medulla or lumbar sympathetic ganglia (~65%). Neuroblastoma is an enigmatic tumor that can spontaneously regress with minimal treatment or become highly metastatic and develop resistance to aggressive treatments, including radiation and high-dose chemotherapy...
October 13, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29027209/heterogeneous-distribution-of-alectinib-in-neuroblastoma-xenografts-revealed-by-matrix-assisted-laser-desorption-ionisation-mass-spectrometry-imaging-a-pilot-study
#19
Shoraku Ryu, Mitsuhiro Hayashi, Hiroaki Aikawa, Isamu Okamoto, Yasuhiro Fujiwara, Akinobu Hamada
BACKGROUND AND PURPOSE: The penetration of the anaplastic lymphoma kinase (ALK) inhibitor alectinib in neuroblastomas and the relationship between alectinib and ALK expression are unknown. The aim of this study was to perform a quantitative investigation of the inter- and intra-tumoural distribution of alectinib in different neuroblastoma xenograft models using matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI). EXPERIMENTAL APPROACH: The distribution of alectinib in NB1 (ALK amplification) and SK-N-FI (ALK wild-type) xenograft tissues was analysed using MALDI-MSI...
October 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29026208/targetable-fusions-of-the-frk-tyrosine-kinase-in-alk-negative-anaplastic-large-cell-lymphoma
#20
G Hu, S Dasari, Y W Asmann, P T Greipp, R A Knudson, H K Benson, Y Li, B W Eckloff, Jin Jen, B K Link, L Jiang, J S Sidhu, L E Wellik, T E Witzig, N N Bennani, J R Cerhan, R L Boddicker, A L Feldman
Leukemia accepted article preview online, 13 October 2017. doi:10.1038/leu.2017.309.
October 13, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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