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Crizotinib

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https://www.readbyqxmd.com/read/28541041/self-assembled-zno-nanoparticle-capsules-for-carrying-and-delivering-isotretinoin-to-cancer-cells
#1
Wei Zhao, Ji-Shi Wei, Peng Zhang, Jie Chen, Ji-Lie Kong, Lian-Hua Sun, Huan-Ming Xiong, Helmuth Möhwald
ZnO@polymer core-shell nanoparticles are assembled into novel capsule shells with diameters of about 100 nm to load isotretinoin (ISO) with a capacity as high as 34.6 wt %. Although ISO, a widely used drug for acne treatment, by itself is not suitable for treating cancer because of its hydrophobicity, our ZnO-ISO composite showed much stronger anticancer activity. The improved cytotoxicity is ascribed to the synergistic effects of the ZnO@polymer and ISO, where the ZnO@polymer helps in the accumulation of ISO in cancer cells on the one hand, and on the other hand, ISO is released completely through ZnO decomposition under acidic conditions of cancer cells...
May 25, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28538401/atrial-fibrillation-was-changed-into-sinus-bradycardia-in-a-ros1-positive-advanced-lung-adenocarcinoma-patient-who-achieved-durable-response-to-crizotinib-a-case-report-and-literature-review
#2
Lan Liu, Jing Wu, Wei Zhao, Mei-Juan Huang
RATIONAL: The c-ros oncogene 1 receptor tyrosine kinase (ROS1)-rearrangements represent a new and rare genetic subtype of non-small-cell lung cancer. In recent years, the use of crizotinib in ROS1-rearranged lung cancer exhibits significant clinical efficacy. Crizotinib is generally well tolerated and the most frequent adverse events include visual disorders, gastrointestinal disturbances, cardiac, and endocrine abnormalities. From a cardiac perspective, crizotinib is associated with 2 main cardiac effects, QT interval prolongation and bradycardia...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28536155/brigatinib-approved-but-treatment-role-uncertain
#3
(no author information available yet)
The FDA has approved the ALK inhibitor brigatinib for patients with metastatic non-small cell lung cancer who cannot take crizotinib or whose disease worsened despite its use. The decision was based upon results of a phase II study that assessed two drug doses, with overall response rates of 45% and 56% respectively. The drug's effect on overall survival remains unclear, as does the optimal sequence of brigatinib and the three other ALK inhibitors.
May 23, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28535796/identification-of-eml4-alk-as-an-alternative-fusion-gene-in-epithelioid-inflammatory-myofibroblastic-sarcoma
#4
Quan Jiang, Han-Xing Tong, Ying-Yong Hou, Yong Zhang, Jing-Lei Li, Yu-Hong Zhou, Jing Xu, Jiong-Yuan Wang, Wei-Qi Lu
BACKGROUND: Known as solid tumors of intermediate malignant potential, most inflammatory myofibroblastic tumors (IMTs) are treatable as long as the tumor is en-bloc resected. However, in some cases, the tumors have recurred and grown rapidly after successful surgery. Some of these tumors were classified as an epithelioid inflammatory myofibroblastic sarcoma (EIMS). Most previously reported EIMSs have been caused by RANBP2-ALK fusion gene. We herein report an EIMS case caused by an EML4-ALK fusion gene...
May 23, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28534251/sequencing-of-alk-inhibitors-in-alk-non-small-cell-lung-cancer
#5
REVIEW
Shirish M Gadgeel
Major therapeutic advances have occurred over the last several years in the management of advanced ALK+ NSCLC patients. Crizotinib was the first agent approved for the management of ALK+ NSCLC patients after it demonstrated significantly greater clinical benefit compared to chemotherapy. Several next generation ALK inhibitors have demonstrated clinical benefit in patients with crizotinib refractory NSCLC patients including in the CNS. Based on available data, therapy with a next generation ALK inhibitor can be initiated following therapy with crizotinib without any assessment of the molecular mechanisms of resistance...
June 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28526734/brigatinib-achieves-whole-body-and-intracranial-responses
#6
(no author information available yet)
Brigatinib is tolerable and has antitumor activity in crizotinib-resistant ALK-positive NSCLC.
May 19, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28522754/met-exon-14-mutation-encodes-an-actionable-therapeutic-target-in-lung-adenocarcinoma
#7
Xinyuan Lu, Nir Peled, John Greer, Wei Wu, Peter Choi, Alice H Berger, Sergio Wong, Kuang-Yu Jen, Youngho Seo, Byron Hann, Angela Brooks, Matthew Meyerson, Eric A Collisson
Targeting somatically activated oncogenes has revolutionized the treatment of non-small cell lung cancer (NSCLC). Mutations in the gene mesenchymal-epithelial transition (MET) near the exon 14 splice sites are recurrent in lung adenocarcinoma and cause exon skipping (METΔ14). Here we analyzed 4,422 samples from 12 different malignancies to estimate the rate of said exon skipping. METΔ14 mutation and transcript were most common in lung adenocarcinoma. Endogenously expressed levels of METΔ14 transformed human epithelial lung cells in a Hepatocyte growth factor (HGF)-dependent manner...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28520527/open-label-multicenter-phase-ii-study-of-ceritinib-in-patients-with-non-small-cell-lung-cancer-harboring-ros1-rearrangement
#8
Sun Min Lim, Hye Ryun Kim, Jong-Seok Lee, Ki Hyeong Lee, Yun-Gyoo Lee, Young Joo Min, Eun Kyung Cho, Sung Sook Lee, Bong-Seog Kim, Moon Young Choi, Hyo Sup Shim, Jin-Haeng Chung, Yoon La Choi, Min Jeong Lee, Maria Kim, Joo-Hang Kim, Siraj M Ali, Myung-Ju Ahn, Byoung Chul Cho
Purpose ROS1 rearrangement is a distinct molecular subset of non-small-cell lung cancer (NSCLC). We investigated the efficacy and safety of ceritinib in patients with ROS1-rearranged NSCLC. Patients and Methods We enrolled 32 patients with advanced NSCLC who tested positive for ROS1 rearrangement by fluorescent in situ hybridization. Ceritinib 750 mg was administered once daily. The primary end point was objective response rate. The secondary end points were disease control rate; duration of response; progression-free survival; overall survival; toxicity; and concordance among fluorescent in situ hybridization, immunohistochemistry, and next-generation sequencing...
May 18, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28514730/circulating-micrornas-as-novel-biomarkers-of-alk-positive-nonsmall-cell-lung-cancer-and-predictors-of-response-to-crizotinib-therapy
#9
Liang-Liang Li, Li-Li Qu, Han-Jiang Fu, Xiao-Fei Zheng, Chuan-Hao Tang, Xiao-Yan Li, Jian Chen, Wei-Xia Wang, Shao-Xing Yang, Lin Wang, Guan-Hua Zhao, Pan-Pan Lv, Min Zhang, Yang-Yang Lei, Hai-Feng Qin, Hong Wang, Hong-Jun Gao, Xiao-Qing Liu
Circulating microRNAs are potential diagnostic and predictive biomarkers, but have not been investigated for patients with anaplastic lymphoma kinase (ALK)-positive lung cancer. In this exploratory study, we sought to identify potential plasma biomarkers for ALK-positive non-small cell lung cancer (NSCLC). A microRNA microarray was used to select ALK-related microRNAs in ALK-positive NSCLC (n = 3), ALK-negative NSCLC (n = 3), and healthy subjects (n = 3). Plasma levels of 21 microRNAs were differentially expressed for ALK-positive and ALK-negative NSCLC, including 14 down-regulated and 7 up-regulated microRNAs...
April 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28513466/non-small-cell-lung-cancer-mutations-targeted-and-combination-therapy
#10
Justyna Kutkowska, Irena Porębska, Andrzej Rapak
Year after year, a growing number of cases of non-small cell lung cancer (NSCLC), mostly caused by smoking, have been noted. Most patients die because of the late detection of cancer and tumor resistance to treatment with cytostatics. Treatment of patients with advanced NSCLC is impeded by the low sensitivity of the tumor to cytostatic agents and the co-existence of many diseases, which substrate is, like lung cancer, cigarette smoking. Along with the development of molecular biology, targeted therapy has started to be used, affecting specific signaling pathways involved in the processes of oncogenesis...
May 17, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28502721/met-exon-14-skipping-mutations-in-lung-adenocarcinoma-clinicopathologic-implications-and-prognostic-values
#11
Geun Dong Lee, Seung Eun Lee, Doo-Yi Oh, Dan-Bi Yu, Hae Min Jeong, Jooseok Kim, Sungyoul Hong, Hun Soon Jung, Ensel Oh, Ji-Young Song, Mi-Sook Lee, Mingi Kim, Kyungsoo Jung, Jhingook Kim, Young Kee Shin, Yoon-La Choi, Hyeong Ryul Kim
INTRODUCTION: Response to MET inhibitors in non-small cell lung cancer with MET exon 14 (METex14) skipping has fueled molecular screening efforts and search for optimal therapies. However, further work is needed to refine the clinicopathologic and prognostic implications of METex14 skipping METHODS: Among 795 East-Asian patients who underwent surgery for non-small cell lung cancer, we screened 45 patients with quintuple-negative (EGFR-/KRAS-/ALK-/ROS1-/RET-) lung adenocarcinomas using RT-PCR, and found 17 patients (37...
May 10, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28501140/alectinib-versus-crizotinib-in-patients-with-alk-positive-non-small-cell-lung-cancer-j-alex-an-open-label-randomised-phase-3-trial
#12
Toyoaki Hida, Hiroshi Nokihara, Masashi Kondo, Young Hak Kim, Koichi Azuma, Takashi Seto, Yuichi Takiguchi, Makoto Nishio, Hiroshige Yoshioka, Fumio Imamura, Katsuyuki Hotta, Satoshi Watanabe, Koichi Goto, Miyako Satouchi, Toshiyuki Kozuki, Takehito Shukuya, Kazuhiko Nakagawa, Tetsuya Mitsudomi, Nobuyuki Yamamoto, Takashi Asakawa, Ryoichi Asabe, Tomohiro Tanaka, Tomohide Tamura
BACKGROUND: Alectinib, a potent, highly selective, CNS-active inhibitor of anaplastic lymphoma kinase (ALK), showed promising efficacy and tolerability in the single-arm phase 1/2 AF-001JP trial in Japanese patients with ALK-positive non-small-cell lung cancer. Given those promising results, we did a phase 3 trial to directly compare the efficacy and safety of alectinib and crizotinib. METHODS: J-ALEX was a randomised, open-label, phase 3 trial that recruited ALK inhibitor-naive Japanese patients with ALK-positive non-small-cell lung cancer, who were chemotherapy-naive or had received one previous chemotherapy regimen, from 41 study sites in Japan...
May 10, 2017: Lancet
https://www.readbyqxmd.com/read/28501139/j-alex-alectinib-versus-crizotinib-in-alk-positive-lung-cancer
#13
Justin F Gainor, Alice T Shaw
No abstract text is available yet for this article.
May 10, 2017: Lancet
https://www.readbyqxmd.com/read/28499860/circulating-tumor-dna-identifies-egfr-co-amplification-as-a-mechanism-of-resistance-to-crizotinib-in-a-patient-with-advanced-met-amplified-lung-adenocarcinoma
#14
Ibiayi Dagogo-Jack, David Fabrizio, Jochen Lennerz, Alexa B Schrock, Lauren Young, Mari Mino-Kenudson, Subba R Digumarthy, Rebecca S Heist, Siraj M Ali, Vincent A Miller, Alice T Shaw
No abstract text is available yet for this article.
May 9, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28498406/crizotinib-a-met-inhibitor-prevents-peritoneal-dissemination-in-pancreatic-cancer
#15
Soichi Takiguchi, Kazuko Inoue, Kimihiko Matsusue, Masayuki Furukawa, Norihiro Teramoto, Haruo Iguchi
Peritoneal dissemination is a frequent occurrence in pancreatic cancer, which is associated with a poor prognosis. MET is associated with the progression of pancreatic cancer; therefore, we evaluated the effect of a MET inhibitor, crizotinib, on peritoneal dissemination of pancreatic cancer. Crizotinib inhibited the growth of 8 pancreatic cancer cell lines with the IC50 ranging from 1.4 to 4.3 µM. Invasion of the pancreatic cancer cell line Suit-2, was suppressed in vitro at a concentration of 1.0 µM, which is sufficient for the inhibition of MET phosphorylation...
May 11, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28497708/salivary-gland-secretory-carcinoma-with-high-grade-transformation-cdkn2a-b-loss-distant-metastasis-and-lack-of-sustained-response-to-crizotinib
#16
Nicole A Cipriani, Elizabeth A Blair, Joshua Finkle, Jennifer L Kraninger, Christopher M Straus, Victoria M Villaflor, Daniel Thomas Ginat
BACKGROUND: Salivary gland secretory carcinoma is usually a low-grade neoplasm. However, high-grade transformation can occur and has important implications for clinical outcome. METHODS: A patient presented with an enlarging buccal mass. Magnetic resonance imaging (MRI) showed a tumor with a biphasic appearance along the right parotid duct. Local excision and histopathologic examination confirmed the diagnosis of secretory carcinoma with high-grade transformation...
May 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28475456/brigatinib-in-patients-with-crizotinib-refractory-anaplastic-lymphoma-kinase-positive-non-small-cell-lung-cancer-a-randomized-multicenter-phase-ii-trial
#17
Dong-Wan Kim, Marcello Tiseo, Myung-Ju Ahn, Karen L Reckamp, Karin Holmskov Hansen, Sang-We Kim, Rudolf M Huber, Howard L West, Harry J M Groen, Maximilian J Hochmair, Natasha B Leighl, Scott N Gettinger, Corey J Langer, Luis G Paz-Ares Rodríguez, Egbert F Smit, Edward S Kim, William Reichmann, Frank G Haluska, David Kerstein, D Ross Camidge
Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression. We evaluated two regimens of brigatinib, an investigational next-generation ALK inhibitor, in crizotinib-refractory ALK-positive NSCLC. Patients and Methods Patients were stratified by brain metastases and best response to crizotinib. They were randomly assigned (1:1) to oral brigatinib 90 mg once daily (arm A) or 180 mg once daily with a 7-day lead-in at 90 mg (180 mg once daily [with lead-in]; arm B)...
May 5, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28474864/the-impact-of-met-inhibition-on-small-cell-lung-cancer-cells-exhibiting-aberrant-activation-of-the-hgf-met-pathway
#18
Hirokazu Taniguchi, Tadaaki Yamada, Shinji Takeuchi, Sachiko Arai, Koji Fukuda, Shuichi Sakamoto, Manabu Kawada, Hiroyuki Yamaguchi, Hiroshi Mukae, Seiji Yano
Small-cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers, and is characterized as being extremely aggressive, often displaying rapid tumor growth and multiple organ metastases. In addition, the clinical outcome of SCLC patients is poor due to early relapse and acquired resistance to standard chemotherapy treatments. Hence, novel therapeutic strategies for the treatment of SCLC are urgently required. Accordingly, several molecular targeted therapies were evaluated in SCLC; however, they failed to improve the clinical outcome...
May 5, 2017: Cancer Science
https://www.readbyqxmd.com/read/28469773/crizotinib-synergizes-with-cisplatin-in-preclinical-models-of-ovarian-cancer
#19
Xiao-Xiu Huang, Feng-Feng Xie, Li-Jiao Hou, Xiu-Xiu Chen, Rong-Ying Ou, Jiang-Tao Yu, Jian-Ge Qiu, Wen-Ji Zhang, Qi-Wei Jiang, Yang Yang, Di-Wei Zheng, Yao Chen, Jia-Rong Huang, Kun Wang, Meng-Ning Wei, Wen-Feng Li, Zhi Shi, Xiao-Jian Yan
Crizotinib, a small molecule inhibitor of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and c-MET (also called MET or hepatocyte growth factor receptor), has been approved by the Food and Drug Administration for the treatment of patients with advanced non-small cell lung cancer whose tumors have rearrangements in the ALK or ROS1 gene. However, the anticancer effect of crizotinib on ovarian cancer is still unclear. In this study, our data show that crizotinib can actively induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the decreasing phosphorylation of the downstream signaling effectors AKT and ERK in human ovarian cancer cells...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28465216/ros1-protein-tyrosine-kinase-inhibitors-in-the-treatment-of-ros1-fusion-protein-driven-non-small-cell-lung-cancers
#20
REVIEW
Robert Roskoski
ROS1 protein-tyrosine kinase fusion proteins are expressed in 1-2% of non-small cell lung cancers. The ROS1 fusion partners include CD74, CCDC6, EZR, FIG, KDELR2, LRIG3, MSN, SDC4, SLC34A2, TMEM106B, TMP3, and TPD52L1. Physiological ROS1 is closely related to the ALK, LTK, and insulin receptor protein-tyrosine kinases. ROS1 is a so-called orphan receptor because the identity of its activating ligand, if any, is unknown. The receptor is expressed during development, but little is expressed in adults and its physiological function is unknown...
April 30, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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