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https://www.readbyqxmd.com/read/28097086/liver-x-receptor-agonist-t0901317-reverses-resistance-of-a549-human-lung-cancer-cells-to-egfr-tki-treatment
#1
Haixia Cao, Shaorong Yu, Dan Chen, Changwen Jing, Zhuo Wang, Rong Ma, Siwen Liu, Jie Ni, Jifeng Feng, Jianzhong Wu
Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is effective in lung cancer patients carrying sensitive EGFR mutations. In this study, we investigated if liver X receptor (LXR) agonist T0901317 could reverse the resistance of lung cancer cell lines A549 and H1650 to EGFR-TKI treatment. We found that T0901317 could make natural EGFR-TKI-resistant A549 human lung cancer cells sensitive to EGFR-TKI treatment and that this was dependent on LXRβ expression. However, T0901317 does not have a similar effect on another natural EGFR-TKI-resistant cell line H1650...
January 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28096935/practical-first-line-management-of-renal-cell-carcinoma-in-a-community-practice
#2
REVIEW
Henry Conter
Sunitinib is an oral receptor tyrosine kinase inhibitor (TKI) that targets signalling by vascular endothelial growth factor receptors (VEGFRs). The standard sunitinib dosing schedule for metastatic renal cell carcinoma (mRCC) is 50 mg for four weeks (28 days) of treatment, followed by a two-week (14-day) break from treatment (four/two schedule). However, this schedule is associated with toxicities that can limit the patient's health-related quality of life (HRQOL) and impede treatment compliance. Given the generally incurable nature of mRCC and the toxicity associated with therapy, treatment strategies should focus on achieving long-term response, preserving HRQOL, and minimizing treatment-related toxicity...
November 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28093244/novel-mutations-on-egfr-leu792-potentially-correlate-to-acquired-resistance-to-osimertinib-in-advanced-nsclc
#3
Kai Chen, Fei Zhou, Wenxiang Shen, Tao Jiang, Xue Wu, Xiaoling Tong, Yang W Shao, Songbing Qin, Caicun Zhou
Osimertinib is an irreversible third generation EGFR tyrosine kinase inhibitor (TKI) and has shown outstanding performances in treating EGFR T790M-positive advanced non-small cell lung cancer (NSCLC) patients, but acquired resistance is inevitable. EGFR C797S is the most notable resistance mechanism to this drug, but other EGFR mutations may also exist. In three lung adenocarcinoma patients resistant to osimertinib, we identified recurrent novel mutations at EGFR Leu792 codon by targeted next generation sequencing (NGS) of cell free DNA (cfDNA) from plasma or pleural effusion...
January 13, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28093061/polyphyllin-ii-restores-sensitization-of-the-resistance-of-pc-9-zd-cells-to-gefitinib-by-a-negative-regulation-of-the-pi3k-akt-mtor-signaling-pathway
#4
Ruzhen Zheng, Hao Jiang, Jinhui Li, Xinge Liu, Hongwei Xu
: EGFR tyrosine kinase inhibitors (TKIs) are widely used for advanced non-small cell lung cancer (NSCLC) patients with a sensitizing EGFR mutation and provide a promising treatment strategy. However, acquired resistance to EGFR-TKIs restrict their application. The mechanisms underlying acquired resistance to TKIs have been explored and Phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway plays a very important role in NSCLC development as well as EGFR-TKI resistance. Polyphyllin II(PP II) is the main steroidal saponin constituent which derives from the root of Paris polychylia...
December 13, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28089721/angiotensin-inhibitors-as-treatment-of-sunitinib-pazopanib-induced-hypertension-in%C3%A2-metastatic-renal-cell-carcinoma
#5
Patrick Penttilä, Juhana Rautiola, Tuija Poussa, Katriina Peltola, Petri Bono
BACKGROUND: Research suggests that baseline use of angiotensin system inhibitors (ASIs) improves outcome in patients with metastatic renal cell carcinoma (mRCC), but it remains unknown whether the type of antihypertensive medication used to initiate management at onset of treatment-induced hypertension (HTN) is associated with outcome. We evaluated the association of ASIs and outcome among patients with mRCC treated with first-line tyrosine kinase inhibitors (TKIs). PATIENTS AND METHODS: We identified 303 consecutive patients with mRCC who were treated with sunitinib or pazopanib in a single university hospital cancer center...
December 22, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28089594/epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-sensitive-exon-19-insertion-and-exon-20-insertion-in-patients-with-advanced-non-small-cell-lung-cancer
#6
Yen-Ting Lin, Yi-Nan Liu, Shang-Gin Wu, James Chih-Hsin Yang, Jin-Yuan Shih
BACKGROUND: The clinical responsiveness to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) patients with exon 19 insertion and the specific exon 20 insertion (A763_Y764 insFQEA) are still not well known. MATERIALS AND METHODS: We analyzed cancer specimens taken from NSCLC patients for EGFR mutations using RNA reverse transcription polymerase chain reaction or direct DNA sequencing. The clinical course and responsiveness to an EGFR TKI in patients with EGFR exon 19 insertion or exon 20 insertion (A763_Y764 insFQEA) were recorded...
December 28, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28089159/immunohistochemistry-for-egfr-mutation-detection-in-non-small-cell-lung-cancer
#7
Nina Turnšek Hitij, Izidor Kern, Aleksander Sadikov, Lea Knez, Karmen Stanič, Matjaž Zwitter, Tanja Cufer
INTRODUCTION: The sensitivity and specificity of immunohistochemistry (IHC) was compared with the standard polymerase chain reaction (PCR)-based method for detecting common activating epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC). Additionally, we evaluated predictive value of IHC EGFR mutation-positive status for EGFR tyrosine kinase inhibitor (TKI) treatment outcome and estimated cost-effectiveness for the upfront IHC testing. METHODS: The trial included 79 consecutive EGFR mutation-positive and 29 EGFR mutation-negative NSCLC cases diagnosed with reflex PCR-based testing...
December 2, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28088511/brief-report-egfr-l858m-l861q-cis-mutations-confer-selective-sensitivity-to-afatinib
#8
Jamie A Saxon, Lynette M Sholl, Pasi A Jänne
INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have been developed to treat patients with epidermal growth factor receptor (EGFR)-mutant lung cancers. However, the therapeutic efficacy of TKIs in patients with uncommon EGFR mutations remains unclear. METHODS: Next-generation sequencing was performed on a patient's lung adenocarcinoma tumor sample, revealing rare combined in cis (on the same allele) EGFR mutations. Stable Ba/F3 and NIH-3T3 cell lines harboring the mutations were established to investigate the effect of first, second, and third generation EGFR TKIs on cell proliferation by MTS assay and EGFR phosphorylation by Western blotting...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28088233/successful-recovery-from-a-subclavicular-ulcer-caused-by-lenvatinib-for-thyroid-cancer-a-case-report
#9
Morimasa Kitamura, Tomomasa Hayashi, Chiaki Suzuki, Shigeru Hirano, Ichiro Tateya, Yo Kishimoto, Koichi Omori
BACKGROUND: There are currently no effective therapeutic methods for locally recurrent, metastatic, or progressive radioactive iodine (RAI)-refractory differentiated thyroid cancer. However, multitargeted tyrosine kinase inhibitors (TKIs) such as lenvatinib or sorafenib have been approved for patients with RAI-refractory differentiated thyroid cancer as a second targeted therapy, and these agents can prolong patient survival. However, several cases have been reported that TKIs have caused fatal complications such as fistula formation or bleeding...
January 14, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28079885/mirna182-regulates-percentage-of-myeloid-and-erythroid-cells-in-chronic-myeloid-leukemia
#10
Deepak Arya, Sasikala P Sachithanandan, Cecil Ross, Dasaradhi Palakodeti, Shang Li, Sudhir Krishna
The deregulation of lineage control programs is often associated with the progression of haematological malignancies. The molecular regulators of lineage choices in the context of tyrosine kinase inhibitor (TKI) resistance remain poorly understood in chronic myeloid leukemia (CML). To find a potential molecular regulator contributing to lineage distribution and TKI resistance, we undertook an RNA-sequencing approach for identifying microRNAs (miRNAs). Following an unbiased screen, elevated miRNA182-5p levels were detected in Bcr-Abl-inhibited K562 cells (CML blast crisis cell line) and in a panel of CML patients...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28079142/the-prognostic-role-of-egfr-tkis-for-patients-with-advanced-non-small-cell-lung-cancer
#11
Dan Zhao, Xuejing Chen, Na Qin, Dan Su, Lijuan Zhou, Quan Zhang, Xi Li, Xinyong Zhang, Mulan Jin, Jinghui Wang
Clinical trials have shown that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) did not improve the survival of patients with EGFR-mutated non-small cell lung cancer (NSCLC) because of the high crossover of treatments. Realistically, the role of EGFR-TKIs in NSCLC with mutated EGFR is not well known. We retrospectively analysed data from patients with recurrent or metastatic NSCLC. Clinical prognostic factors were identified by Cox proportional hazards modelling. Among 503 patients, the median overall survival (OS) for all of patients was 11...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28077790/flt3-activating-mutations-display-differential-sensitivity-to-multiple-tyrosine-kinase-inhibitors
#12
Bao Nguyen, Allen B Williams, David J Young, Hayley Ma, Li Li, Mark Levis, Patrick Brown, Donald Small
Fms-like tyrosine kinase-3 (FLT3) is a receptor tyrosine kinase that normally functions in hematopoietic cell survival, proliferation and differentiation. Constitutively activating mutations of FLT3 map predominately to the juxtamembrane domain (internal tandem duplications; ITD) or the activation loop (AL) of the kinase domain and are detected in about 1/3 of de novo acute myeloid leukemia (AML) patients. Small molecule tyrosine kinase inhibitors (TKI) effectively target FLT3/ITD mutations, but some activating mutations, particularly those on the AL, are relatively resistant to many FLT3 TKI...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28076323/clinical-outcome-of-tyrosine-kinase-inhibitors-alone-or-combined-with-radiotherapy-for-brain-metastases-from-epidermal-growth-factor-receptor-egfr-mutant-non-small-cell-lung-cancer-nsclc
#13
Qianqian Zhu, Yanan Sun, Yingying Cui, Ke Ye, Chengliang Yang, Daoke Yang, Jie Ma, Xiao Liu, Jinming Yu, Hong Ge
This study compared treatment outcomes between TKI monotherapy and TKI administration combined with brain radiotherapy (TKI + RT) in 133 non-small cell lung cancer (NSCLC) patients with brain metastasis (BM). We also evaluated the association of different epidermal growth factor receptor (EGFR) mutation subtypes with treatment outcome. To screen for potential variables affecting cranial progression free survival (PFS) and overall survival (OS), we performed univariate and multivariate analysis based on Cox proportional-hazards models...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28074067/expression-of-the-ctla-4-ligand-cd86-on-plasmacytoid-dendritic-cells-pdc-predicts-risk-of-disease-recurrence-after-treatment-discontinuation-in-cml
#14
C Schütz, S Inselmann, S Sausslele, C T Dietz, M C Müller, E Eigendorff, C A Brendel, S K Metzelder, T H Brümmendorf, C Waller, J Dengler, M E Goebeler, R Herbst, G Freunek, S Hanzel, T Illmer, Y Wang, T Lange, F Finkernagel, R Hehlmann, M Huber, A Neubauer, A Hochhaus, J Guilhot, F X Mahon, M Pfirrmann, A Burchert
It is unknown, why only a minority of chronic myeloid leukemia (CML) patients sustains treatment free remission (TFR) after discontinuation of tyrosine kinase inhibitor (TKI) therapy in deep molecular remission (MR). Here we studied, whether expression of the T-cell inhibitory receptor (CTLA-4)-ligand CD86 (B7.2) on plasmacytoid dendritic cells (pDC) affects relapse risk after TKI cessation. CML patients in MR displayed significantly higher CD86(+)pDC frequencies than normal donors (P<0·0024), whereas TFR patients had consistently low CD86(+)pDC (n=12)...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28073786/phase-1-study-of-twice-weekly-pulse-dose-and-daily-low-dose-erlotinib-as-initial-treatment-for-patients-with-egfr-mutant-lung-cancers
#15
H A Yu, C Sima, D Feldman, L L Liu, B Vaitheesvaran, J Cross, C M Rudin, M G Kris, W Pao, F Michor, G J Riely
BACKGROUND: Patients with EGFR-mutant lung cancers treated with EGFR tyrosine kinase inhibitors (TKIs) develop clinical resistance, most commonly with acquisition of EGFR T790M. Evolutionary modeling suggests that a schedule of twice weekly pulse and daily low-dose erlotinib may delay emergence of EGFR T790M. Pulse dose erlotinib has superior central nervous system (CNS) penetration and may result in superior CNS disease control. METHODS: We evaluated toxicity, pharmacokinetics, and efficacy of twice weekly pulse and daily low-dose erlotinib...
October 25, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28073775/dasatinib-changes-immune-cell-profiles-concomitant-with-reduced-tumor-growth-in-several-murine-solid-tumor-models
#16
Can Hekim, Mette Ilander, Jun Yan, Erin Michaud, Richard Smykla, Markus Vähä-Koskela, Paula Savola, Siri Tähtinen, Leena Saikko, Akseli Hemminki, Panu E Kovanen, Kimmo Porkka, Francis Yf Lee, Satu Mustjoki
Dasatinib, a broad range tyrosine kinase inhibitor (TKI), induces rapid mobilization of lymphocytes and clonal expansion of cytotoxic cells in leukemia patients. Here, we investigated whether dasatinib could induce beneficial immunomodulatory effects in solid tumor models. The effects on tumor growth and on the immune system were studied in four different syngeneic mouse models (B16.OVA melanoma, 1956 sarcoma, MC38 colon, and 4T1 breast carcinoma). Both peripheral blood (PB) and tumor samples were immunophenotyped during treatment...
January 10, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28068944/the-acceleration-of-glucose-accumulation-in-renal-cell-carcinoma-assessed-by-fdg-pet-ct-demonstrated-acquisition-of-resistance-to-tyrosine-kinase-inhibitor-therapy
#17
Noboru Nakaigawa, Keiichi Kondo, Daiki Ueno, Kazuhiro Namura, Kazuhide Makiyama, Kazuki Kobayashi, Koichi Shioi, Ichiro Ikeda, Takeshi Kishida, Tomohiro Kaneta, Ryogo Minamimoto, Ukihide Tateishi, Tomio Inoue, Masahiro Yao
BACKGROUND: Tyrosine-kinase inhibitor (TKI) targeting angiogenesis improves the prognosis of patients with metastatic renal cell carcinoma (RCC), but its effect is temporary. In order to understand the mechanism by which RCC acquires resistance to TKI, we investigated the change of glucose accumulation in RCC by FDG PET/CT when they demonstrated progression disease (PD) against TKI. METHODS: We monitored the FDG accumulation in RCC of 38 patients treated with TKI by 162 PET/CT sequentially until they were judged to demonstrate PD...
January 9, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28068878/long-term-control-of-hypercortisolism-by-vandetanib-in-a-medullary-thyroid-carcinoma-with-a-somatic-ret-mutation
#18
Anne-Cécile Paepegaey, Beatrix Cochand-Priollet, Estelle Louiset, Pierre Olivier Sarfati, Marco Alifano, Nelly Burnichon, Marie Bienvenu-Perrard, Najiba Lahlou, Léopoldine Bricaire, Lionel Groussin
CONTEXT: Medullary thyroid carcinomas (MTCs) complicated by ectopic Cushing's syndrome have a poor prognosis, partially due to the difficulties to control hypercortisolism by adrenal blocking drugs. Recent reports (including the initial follow-up of this patient) have suggested that tyrosine kinase inhibitors (TKIs) may be a therapeutic option due to an antisecretory action on ACTH. However, there is a lack of long-term follow-up studies. CASE DESCRIPTION: We report the case of a 58 year-old man with a MTC-related Cushing's syndrome resistant to a combination of several anticortisolic drugs...
January 9, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28066597/the-impact-of-smoking-status-on-radiologic-tumor-progression-patterns-and-response-to-epidermal-growth-factor-receptor-egfr-tyrosine-kinase-inhibitors-in-lung-adenocarcinoma-with-activating-egfr-mutations
#19
Yoon Ki Cha, Ho Yun Lee, Myung-Ju Ahn, Keunchil Park, Jin Seok Ahn, Jong-Mu Sun, Yoon-La Choi, Kyung Soo Lee
BACKGROUND: The aim of this study was to evaluate the impact of smoking on the treatment outcome of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant lung adenocarcinoma, with consideration of other factors including radiologic tumor progression pattern according to patient smoking status. METHODS: A total of 224 patients with EGFR mutant lung adenocarcinomas that were treated with EGFR-TKIs were retrospectively reviewed...
November 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28061473/immunotherapy-incorporation-in-the-evolving-paradigm-of-renal-cancer-management-and-future-prospects
#20
Kenneth G Liu, Sorab Gupta, Sanjay Goel
Significant progress has been made in the management of renal cell carcinoma (RCC) during the last few decades. In early stage, localized disease, surgical resection remains the modality of choice, with no therapeutic interventions as options for post-operative therapy other than simple observation and clinical surveillance. However, treatment options in the advanced or metastatic setting are increasing at a dizzying pace, initially with cytokine therapy, then with the increased availability of targeted therapy including novel small-molecule inhibitors of receptor tyrosine kinases and monoclonal antibodies targeting novel proteins, establishing them as the current standard of care...
December 30, 2016: Oncotarget
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