Read by QxMD icon Read


Hideharu Kimura, Shingo Nishikawa, Hayato Koba, Taro Yoneda, Takashi Sone, Kazuo Kasahara
Epidermal growth factor receptor (EGFR) T790M mutation is associated with resistance to EGFR tyrosine kinase inhibitors' (EGFR-TKIs) in non-small cell lung cancer (NSCLC). The aims of this study are to develop a blood-based, non-invasive approach to detecting the EGFR T790M mutation in advanced NSCLC patients, using PointMan™ EGFR DNA Enrichment Kit which is a novel method for selective amplification of genotype specific sequences.Pairs of blood samples and tumor tissues were collected from NSCLC patients with an EGFR activating mutation and who were resistant to EGFR-TKI treatment...
2016: Advances in Experimental Medicine and Biology
Gianantonio Rosti, Fausto Castagnetti, Gabriele Gugliotta, Michele Baccarani
The therapeutic armamentarium for chronic myeloid leukaemia (CML) comprises mainly tyrosine kinase inhibitors (TKIs), with several agents available for frontline treatment, or for the treatment of disease resistance or intolerance to the first-choice or second-choice drug. The availability of different drugs is a major achievement, but means that choices must be made - which can be difficult and questionable at times. The most important end point considered in decision-making regarding treatment for any cancer is overall survival, but additional factors (such as age, prognostic category, safety, or the possibility of achieving treatment-free remission) should be considered when selecting an agent for frontline treatment...
October 18, 2016: Nature Reviews. Clinical Oncology
Jonas Leichsenring, Anna-Lena Volckmar, Nikolaus Magios, Cristiano Manuel Morais de Oliveira, Roland Penzel, Regine Brandt, Martina Kirchner, Farastuk Bozorgmehr, Michael Thomas, Peter Schirmacher, Arne Warth, Volker Endris, Albrecht Stenzinger
Patients with NSCLC harboring activating mutations in the EGFR benefit from targeted therapies. A synonymous polymorphism (rs1050171, p.Q787Q) was shown to be associated with improved overall survival (OS) in colorectal cancer patients. As data in NSCLC are limited, we retrospectively analyzed associations of p.Q787Q with clinicopathological parameters including clinical response and outcome in patients with lung adenocarcinoma (ADC) who received tyrosine kinase inhibitor (TKI) therapy. Of 642 ADC patients whose tumors were profiled by next generation sequencing, 102 (15...
October 17, 2016: Genes, Chromosomes & Cancer
Adriana Borriello, Ilaria Caldarelli, Debora Bencivenga, Emanuela Stampone, Silverio Perrotta, Adriana Oliva, Fulvio Della Ragione
The hope of selectively targeting cancer cells by therapy and eradicating definitively malignancies is based on the identification of pathways or metabolisms that clearly distinguish "normal" from "transformed" phenotypes. Some tyrosine kinase activities, specifically unregulated and potently activated in malignant cells, might represent important targets of therapy. Consequently, tyrosine kinase inhibitors (TKIs) might be thought as the "vanguard" of molecularly targeted therapy for human neoplasias. Imatinib and the successive generations of inhibitors of Bcr-Abl1 kinase, represent the major successful examples of TKI use in cancer treatment...
October 13, 2016: Oncotarget
Shaoyu Yang, Xueqin Chen, Yuelong Pan, Jiekai Yu, Xin Li, Shenglin Ma
The present study aimed to identify potential serum biomarkers for predicting the clinical outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‑TKIs). A total of 61 samples were collected and analyzed using the integrated approach of magnetic bead‑based weak cation exchange chromatography and matrix‑assisted laser desorption/ionization‑time of flight‑mass spectrometry. The Zhejiang University Protein Chip Data Analysis system was used to identify the protein spectra of patients that are resistant and sensitive to EGFR‑TKIs...
October 11, 2016: Molecular Medicine Reports
Magdalena Lukamowicz-Rajska, Christiane Mittmann, Michael Prummer, Qing Zhong, Jens Bedke, Jörg Hennenlotter, Arnulf Stenzl, Axel Mischo, Svenja Bihr, Manuela Schmidinger, Ursula Vogl, Iris Blume, Christoph Karlo, Peter Schraml, Holger Moch
A number of treatments targeting VEGF or mTOR pathways have been approved for metastatic clear cell Renal Cell Carcinoma (ccRCC), but the majority of patients show disease progression after first line therapy with a very low rate of complete or long-term responders. It has been shown that miRs may play a role in prediction of treatment response in various cancer types. The aim of our study was to identify a miR signature predictive for RCC patients' response to antiangiogenic tyrosine kinase inhibitor (TKI) treatment in the first line therapy...
October 12, 2016: Oncotarget
Zofia Litwińska, Bogusław Machaliński
Chronic myeloid leukemia (CML) is a myeloproliferative disorder associated with clonal expansion of cancerous bone marrow stem cells. Tyrosine kinase inhibitors (TKIs) targeting Bcr-Abl oncoprotein are the first-line therapy for most CML patients, however, some are unresponsive to it or develop resistance. Recently, microRNAs (miRNAs) have been implicated in the progression of CML and the development of TKI resistance based on their important regulatory function in cell homeostasis. MicroRNAs are small noncoding RNAs that post-transcriptionally regulate gene expression...
October 13, 2016: Leukemia & Lymphoma
Shang-Gin Wu, Yih-Leong Chang, Chong-Jen Yu, Pan-Chyr Yang, Jin-Yuan Shih
To understand the impact of PIK3CA mutations on clinical characteristics and treatment response to epidermal growth factor tyrosine kinase inhibitors (EGFR TKIs) of lung adenocarcinoma, we examined PIK3CA and EGFR mutations in lung adenocarcinoma patients, and analyzed their clinical outcomes. Surgically excised tumor, bronchoscopy biopsy/brushing specimens and pleural effusions were prospectively collected from 1029 patients. PIK3CA and EGFR mutations were analyzed by RT-PCR and direct sequencing. In EGFR TKI-nave specimens, PIK3CA mutation rate was 1...
October 13, 2016: Scientific Reports
TaeHyung Kim, Marc S Tyndel, Hyeoung Joon Kim, Jae-Sook Ahn, Seung Hyun Choi, Hee Jeong Park, Yeo-Kyeoung Kim, Soo Young Kim, Jeffrey H Lipton, Zhaolei Zhang, Dennis Dong Hwan Kim
Somatic mutations commonly detected in a variety of myeloid neoplasms have not been systematically investigated in chronic myeloid leukemia (CML). We performed targeted deep sequencing on a total of 300 serial samples from 100 CML patients; thirty-seven patients carried mutations. Sixteen of these had evidence of mutations originating from preleukemic clones. Using unsupervised hierarchical clustering, we identified five distinct patterns of mutation dynamics arising following tyrosine kinase inhibitor (TKI) therapy...
October 12, 2016: Blood
Ayala Gover-Proaktor, Galit Granot, Saar Shapira, Oshrat Raz, Oren Pasvolsky, Arnon Nagler, Dorit L Lev, Aida Inbal, Ido Lubin, Pia Raanani, Avi Leader
Tyrosine kinase inhibitors (TKIs) have revolutionized the prognosis of chronic myeloid leukemia. With the advent of highly efficacious therapy, the focus has shifted toward managing TKI adverse effects, such as vascular adverse events (VAEs). We used an in vitro angiogenesis model to investigate the TKI-associated VAEs. Our data show that imatinib, nilotinib, and ponatinib reduce human umbilical vein endothelial cells (HUVECs) viability. Pharmacological concentrations of ponatinib induced apoptosis, reduced migration, inhibited tube formation of HUVECs, and had a negative effect on endothelial progenitor cell (EPC) function...
October 12, 2016: Leukemia & Lymphoma
Anna Cecília Dias Maciel Carneiro, Isadora Caixeta da Silveira, Arthur Silva Rezende, Bruna Raphaela Oliveira Silva, Virgínia Oliveira Crema
BACKGROUND: Oral squamous cell carcinoma is extremely invasive, this behavior is regulated by binding of extracellular molecules to the cell membrane receptors. The TKI-258 inhibits phosphorylation of FGFRs VEGFRs and PDGFRs. Our aim was to analyze the effect of TKI-258 treatment in cell movement by using SCC-4 cell line from human oral squamous cell carcinoma. METHODS: F-actin was stained with rhodamine phalloidin and confocal analysis was performed. The migration and invasion (membrane covered with Matrigel(TM) ) three-dimensional assays were performed, control and cells treated with TKI-258 that migrated through the membrane were counted after 24 h...
October 12, 2016: Journal of Oral Pathology & Medicine
Akira Kitanaka
The introduction of tyrosine kinase inhibitors (TKIs) has dramatically changed the management of patients with chronic myeloid leukemia (CML). Despite improved outcomes for most CML patients, disease progression from chronic phase (CP) to accelerated phase (AP) or blast phase (BP) occurs in 1-1.5% of cases per year with current TKI therapy. In addition, about 10-15% of newly diagnosed patients present in AP or BP. Even in the TKI era, the prognosis of patients with advanced-phase CML is not satisfactory. Although de novo AP patients who respond optimally to TKI have excellent outcomes, the prognosis of the remaining advanced-phase CML patients treated with TKI remains poor...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Naoto Takahashi
BCR-ABL tyrosine kinase inhibitor (TKI) has dramatically improved the prognosis of CML patients. Now, one of the most important factors with a marked effect on prognosis in CML patients is having a comorbidity. Recently, cardiovascular events (CVE) have been reported in some clinical trials as a late toxicity of TKI, which might be associated with off-target of TKI, ABL/ARG, PDGFR and VEGFR. Because TKI-associated CVE is one of the potentially lethal adverse events associated with TKI administration, hematologists must practice the "ABCDE steps" for CML patients treated with second generation TKI in collaboration with cardiologists...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Nader I Al-Dewik, Hisham M Morsi, Muthanna M Samara, Rola S Ghasoub, Cinquea C Gnanam, Subi K Bhaskaran, Abdulqadir J Nashwan, Rana M Al-Jurf, Mohamed A Ismail, Mohammed M AlSharshani, Ali A AlSayab, Tawfeg I Ben-Omran, Rani B Khatib, Mohamed A Yassin
BACKGROUND: Despite the revolutionary success of introducing tyrosine kinase inhibitors (TKIs), such as imatinib mesylate (IM), for treating chronic myeloid leukemia (CML), a substantial proportion of patients' treatments fail. AIM: This study investigates the correlation between patient adherence and failure of TKIs' treatment in a follow-up study. METHODS: This is a follow-up study of a new cohort of CML patients. Adherence to IM is assessed using the Medication Event Monitoring System (MEMS 6 TrackCap, AARDEX Ltd)...
2016: Clinical Medicine Insights. Oncology
Poe-Hirr Hsyu, Daniela Soriano Pignataro, Kyle Matschke
PURPOSE: Bosutinib is an oral, dual Src and Abl tyrosine kinase inhibitor (TKI) approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia resistant or intolerant to prior TKI therapy. Bosutinib is primarily metabolized by cytochrome P450 (CYP) 3A4, suggesting drug interaction potential with other CYP3A4 modulators. This open-label, randomized, 2-sequence, 2-period crossover study assessed the effect of single-dose aprepitant, a moderate CYP3A4 inhibitor, on the single-dose pharmacokinetic profile of oral bosutinib 500 mg...
October 7, 2016: European Journal of Clinical Pharmacology
Daisuke Yamada, Satoshi Watanabe, Kohichi Kawahara, Takehiko Maeda
Aberrant changes to several signaling pathways because of genetic mutations or increased cytokine production are critical for tumor cells to become malignant. Semaphorin 3A (SEMA3A) acts as a bivalent factor that suppresses or promotes tumor development in different pathological backgrounds. Previously, we showed that SEMA3A positively regulated the proliferative and glycolytic activities of mouse-derived Lewis lung carcinoma (LLC) cells. Plexins A1-A4 (PLXNA1-PLXNA4) are SEMA3A receptors; however, it is not known which subtype is critical for oncogenic SEMA3A signaling...
October 4, 2016: Biochemical and Biophysical Research Communications
Stephanie Bauer, Susan Buchanan, Irene Ryan
Several tyrosine kinase inhibitors (TKIs) are now approved for the treatment of chronic myeloid leukemia in chronic phase. The efficacy of these drugs has been repeatedly demonstrated, as has their tolerability in most patients. However, late and chronic toxicities become an important issue for many patients facing long-term TKI exposure. For patients on long-term imatinib, gastrointestinal events, fluid retention, muscle cramps, fatigue, and hepatotoxicity are among the most common and most clinically relevant adverse events (AEs)...
January 2016: Journal of the Advanced Practitioner in Oncology
Hongqing Zhuang, Jing Bai, Joe Y Chang, Zhiyong Yuan, Ping Wang
OBJECTIVE: To investigate the effects of mTOR inhibition on drug resistance in lung adenocarcinoma after combined radiation and erlotinib therapy. RESULTS: Combined radiation and erlotinib therapy produced clear radiosensitization effects both in vitro and in vivo; however, tumor cells remained drug resistant. Additionally, combined radiation and erlotinib therapy significantly increased p-AKT and p-P70 levels. After mTOR inhibition, the number of surviving cells significantly decreased compared with that before inhibition, and the in vivo growth curve was significantly reduced...
October 4, 2016: Oncotarget
Yaqiong Tian, Zengli Zhang, Liyun Miao, Zhimin Yang, Jie Yang, Yinhua Wang, Danwen Qian, Hourong Cai, Yongsheng Wang
Recently, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have revolutionized non-small cell lung cancer (NSCLC) treatment. However, resistance remains a major obstacle. Anexelekto (AXL) is a member of receptor tyrosine kinases (RTKs) and shares the same downstream signaling pathways with EGFR, such as PI3K/AKT and MAPK/ERK. AXL overexpression in resistant tumors has been implicated in many previous studies in vitro and in vivo. In this study, we further examined whether expression of AXL and its downstream targets increased in gefitinib-resistant PC9 cells (PC9GR)...
2016: Oncology Research
Shu Meng, Hongyan Wu, Jing Wang, Qiyuan Qiu
The proto-oncogene protein RET is a receptor tyrosine kinase that plays an important role in the development and progress of various human cancers. Currently, targeting RET with small-molecule tyrosine kinase inhibitors (TKIs) has been established as promising therapeutic strategy for thyroid carcinoma (TC). However, two gatekeeper mutations V804M and V804L in RET kinase domain have been frequently observed to cause drug resistance during the targeted therapy, largely limiting the application of reversible TKIs in TC...
October 2016: Molecular Informatics
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"