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https://www.readbyqxmd.com/read/29775809/transient-asymptomatic-pulmonary-opacities-during-osimertinib-treatment-and-its-clinical-implication
#1
Hansang Lee, Ho Yun Lee, Jong-Mu Sun, Se-Hoon Lee, Youjin Kim, Song Ee Park, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
INTRODUCTION: Osimertinib is an oral, potent, irreversible 3rd generation EGFR tyrosine kinase inhibitor (TKI) approved for the treatment of T790M positive non-small cell lung cancer (NSCLC) patients who failed 1st or 2nd generation EGFR TKIs. Interstitial lung disease (ILD) is a rare complication with osimertinib, occurring in 1-3%. Recently, relatively high incidence of transient asymptomatic pulmonary opacities (TAPOs) which are different from ILD has been described. However, its clinical implication has not been fully determined yet...
May 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29774795/prospective-evaluation-of-hypogonadism-in-male-metastatic-renal-cell-carcinoma-patients-treated-with-targeted-therapies
#2
Julie Bastin, Emilie Werbrouck, Annelies Verbiest, Kevin Punie, Oliver Bechter, Sherida Feng Woei-A-Jin, Pascal Wolter, Hans Wildiers, Evelyne Lerut, Herlinde Dumez, Brigitte Decallonne, Paul Clement, Dirk Vanderschueren, Maarten Albersen, Raymond Oyen, Patrick Schöffski, Benoit Beuselinck
Objectives To study the prevalence of hypogonadism in male patients with metastatic renal cell carcinoma (mRCC) starting with targeted therapies and the impact of the vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) sunitinib and pazopanib on the luteinizing hormone (LH)/testosterone (TT)-axis. Methods Male mRCC patients starting with targeted therapies were prospectively included in this study. TT- and LH-levels were sampled at start as well as during systemic therapy. Endpoints of the study were gonadal status (TT- and LH-levels) at start of targeted therapy and TT- and LH-evolution during targeted therapy...
May 18, 2018: Acta Clinica Belgica
https://www.readbyqxmd.com/read/29774100/differential-proteomic-profile-of-leukemic-cd34-progenitor-cells-from-chronic-myeloid-leukemia-patients
#3
Maria Rosaria Ricciardi, Valentina Salvestrini, Roberto Licchetta, Simone Mirabilii, Mattia Forcato, Gabriele Gugliotta, Simona Salati, Fausto Castagnetti, Gianantonio Rosti, Massimo Breccia, Giuliana Alimena, Rossella Manfredini, Silvio Bicciato, Roberto Massimo Lemoli, Agostino Tafuri
Chronic Myeloid Leukemia (CML) is a stem cell disease sustained by a rare population of quiescent cells which are to some extent resistant to tyrosine kinase inhibitors (TKIs). BCR-ABL oncogene activates multiple cross-talking signal transduction pathways (STP), such as RAS/MEK/ERK, PI3K/Akt, Wnt and STAT5, contributing to abnormal proliferation of clonal cells. From this perspective, the aim of this study was to analyze the expression and activation profile of STP involved in the mechanisms of cell proliferation/quiescence and survival of the progenitor CD34+ cells from chronic phase (CP) CML...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774010/efficacy-of-vandetanib-in-treating-locally-advanced-or-metastatic-medullary-thyroid-carcinoma-according-to-recist-criteria-a-systematic-review-and-meta-analysis
#4
Pierpaolo Trimboli, Marco Castellana, Camilla Virili, Francesco Giorgino, Luca Giovanella
Background: Vandetanib is the most largely used tyrosine kinase inhibitor (TKI) in patients with locally advanced and/or metastatic medullary thyroid cancer (MTC). Here, we conducted a systematic review on its efficacy and attempted to perform a meta-analysis adopting standardized RECIST criteria as end-points. Methods: The terms "medullary thyroid" and "protein kinase inhibitor" (then including all TKIs) were searched in PubMed, ClinicalTrials...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29766229/clinical-status-and-treatment-of-liver-metastasis-of-differentiated-thyroid-cancer-using-tyrosine-kinase-inhibitors
#5
Yoshiyuki Saito, Kiminori Sugino, Hiroshi Takami, Kenichi Matsuzu, Takashi Uruno, Keiko Ohkuwa, Wataru Kitagawa, Mitsuji Nagahama, Hirofumi Kawakubo, Koichi Ito, Yuko Kitagawa
BACKGROUND: Treatment of patients with liver metastasis of differentiated thyroid carcinoma (DTC) has not been sufficiently defined, because liver metastasis of DTC has been described mostly as case reports. Additionally, such patients are considered end-of-treatment responders. A relatively new approach using tyrosine kinase inhibitors (TKIs) may provide opportunities to manage systemic metastasis. This study aims to define the clinical features of DTC patients with liver metastasis and evaluate the benefits of TKIs...
May 15, 2018: World Journal of Surgery
https://www.readbyqxmd.com/read/29765525/clinical-characteristics-of-non-small-cell-lung-cancer-harboring-mutations-in-exon-20-of-egfr-or-her2
#6
Masayuki Takeda, Kazuko Sakai, Hidetoshi Hayashi, Kaoru Tanaka, Junko Tanizaki, Takayuki Takahama, Koji Haratani, Kazuto Nishio, Kazuhiko Nakagawa
Unlike common epidermal growth factor receptor gene ( EGFR ) mutations that confer sensitivity to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), mutations in exon 20 of either EGFR or the human EGFR2 gene ( HER2 ) are associated with insensitivity to EGFR-TKIs, with treatment options for patients with such mutations being limited. Clinical characteristics, outcome of EGFR-TKI or nivolumab treatment, and the presence of coexisting mutations were reviewed for NSCLC patients with exon-20 mutations of EGFR or HER2 as detected by routine application of an amplicon-based next-generation sequencing panel...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764505/xenograft-tumors-derived-from-malignant-pleural-effusion-of-the-patients-with-non-small-cell-lung-cancer-as-models-to-explore-drug-resistance
#7
Yunhua Xu, Feifei Zhang, Xiaoqing Pan, Guan Wang, Lei Zhu, Jie Zhang, Danyi Wen, Shun Lu
BACKGROUND: Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions show dramatic responses to specific tyrosine kinase inhibitors (TKIs); however, after 10-12 months, secondary mutations arise that confer resistance. We generated a murine xenograft model using patient-derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK- and EGFR-targeted TKIs crizotinib and osimertinib, respectively...
May 9, 2018: Cancer communications
https://www.readbyqxmd.com/read/29763936/synergistic-inhibition-of-thalidomide-and-icotinib-on-human-non-small-cell-lung-carcinomas-through-erk-and-akt-signaling
#8
Xiang Sun, Yang Xu, Yi Wang, Qian Chen, Liu Liu, Yangyi Bao
BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been widely used in the treatment of non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations. However, the survival of patients with EGFR-TKI administration is limited by the inevitable development of acquired drug resistance. Recently, multi-targeted drugs combination has been shown to be a promising strategy to improve the efficacy of EGFR-TKI treatment and enable the reduction of drug resistance in NSCLC...
May 15, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29762469/individualised-multimodal-treatment-strategies-for-anaplastic-and-poorly-differentiated-thyroid-cancer
#9
Sabine Wächter, Annette Wunderlich, Silvia Roth, Ioannis Mintziras, Elisabeth Maurer, Sebastian Hoffmann, Frederik A Verburg, Sebastian A Fellinger, Katharina Holzer, Detlef K Bartsch, Pietro Di Fazio
The prognosis of anaplastic (ATC) and poorly differentiated thyroid cancer (PDTC) is poor, due to their radioiodine refractoriness (RAI-R), high metastatic potential and current lack of effective treatment strategies. We aimed to examine the efficacy of the tyrosine kinase inhibitors (TKIs) sorafenib and selumetinib and the histone deacetylase inhibitor (HDACI) panobinostat in patient-derived tumor tissue (PDTT) of ATCs/PDTCs, the expression of sodium iodide symporter ( NIS ) and radioiodine up-take (RAI-U)...
May 15, 2018: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/29761660/feasibility-of-re-biopsy-and-egfr-mutation-analysis-in-patients-with-non-small-cell-lung-cancer
#10
Tae-Ok Kim, In-Jae Oh, Bo Gun Kho, Ha Young Park, Jin Sun Chang, Cheol-Kyu Park, Hong-Joon Shin, Jung-Hwan Lim, Yong-Soo Kwon, Yu-Il Kim, Sung-Chul Lim, Young-Chul Kim, Yoo-Duk Choi
BACKGROUND: In cases of EGFR-tyrosine kinase inhibitor (TKI) failure, re-biopsy may be useful to understand resistance mechanisms and guide further treatment decisions. However, performing re-biopsy is challenging because of several hurdles. We assessed the feasibility of re-biopsy in advanced non-small cell lung cancer (NSCLC) patients in real-world clinical practice. METHODS: We retrospectively reviewed the clinical and pathologic data of advanced NSCLC patients who experienced disease progression after previous treatment with EGFR-TKIs at a single tertiary hospital in Korea between January 2014 and December 2016...
May 14, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29760799/hepatotoxicity-in-advanced-lung-adenocarcinoma-a-retrospective-study-of-2108-cases
#11
Jie Qian, Xueyan Zhang, Bo Zhang, Ping Gu, Lin Wang, Baohui Han
The study aimed to identify the risk factors and frequency of hepatotoxicity in patients with advanced lung adenocarcinoma. Liver function tests were documented in 2108 patients with advanced (IIIB/IV) lung adenocarcinoma at a single institution who received first line platinum-based doublet chemotherapy. Hepatotoxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Risk factors for hepatotoxicity were assessed using logistic regression analysis. Differences in hepatotoxicity between pemetrexed and non-pemetrexed regimens were evaluated after propensity score matching...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29758295/systematic-bioinformatic-approaches-reveal-novel-gene-expression-signatures-associated-with-acquired-resistance-to-egfr-targeted-therapy-in-lung-cancer
#12
Marjan Mojtabavi Naeini, Manoochehr Tavassoli, Kamran Ghaedi
OBJECTIVES: Human non-small cell lung cancer (NSCLC) that harbors activating mutations in epidermal growth factor receptor (EGFR) initially responds to treatment with EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib but eventually tumor cells acquire resistance. To date, several gene expression profiles have been reported in TKIs-resistant EGFR-mutant NSCLC. The objective of this study is to identify robust gene expression signatures, biological processes, and promising overcoming targets for TKIs-resistant EGFR-mutant NSCLC...
May 11, 2018: Gene
https://www.readbyqxmd.com/read/29755704/breastfeeding-in-patients-with-chronic-myeloid-leukaemia-case-series-with-measurements-of-drug-concentrations-in-maternal-milk-and-literature-review
#13
Ekaterina Chelysheva, Sergey Aleshin, Evgenia Polushkina, Roman Shmakov, Igor Shokhin, Ghermes Chilov, Anna Turkina
Breastfeeding in patients with chronic myeloid leukaemia (CML) during tyrosine kinase inhibitors (TKIs) therapy is not recommended but interruption of TKI treatment may cause the loss of remission. We studied the 3 cases of pregnancy and breastfeeding in women with CML and observed that stopping treatment without major molecular response may end in haematological relapse. The concentrations of nilotinib and imatinib in maternal milk were measured and nilotinib distribution in human breast milk was demonstrated for the first time...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29754184/discovery-of-a-potent-and-mutant-selective-egfr-inhibitor-that-overcomes-t790m-mediated-resistance-in-lung-cancer
#14
Dong Ha Kim, Yun Jung Choi, Seon Ye Kim, Jung-Eun Lee, Ki Jung Sung, Young Hoon Sung, Woo Sung Kim, Sung-Eun Kim, Hyung Chul Ryu, Jae Sun Kim, Lu Guangying, Chang-Min Choi, Jin Kyung Rho, Jae Cheol Lee
BACKGROUND: Despite remarkable activity in epidermal growth factor receptor (EGFR)-mutant lung cancer patients, the clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) is limited by the emergence of acquired resistance, which is mostly caused by a secondary T790M mutation. Fortunately, newly developed, mutant-selective EGFR-TKIs against T790M have been proven as an effective therapeutic approach although only osimertinib has received the FDA approval until now. OBJECTIVE: To determine the in vitro and in vivo efficacy of a new EGFR TKI, OBX1-012 in cells with mutant EGFR...
May 12, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29751136/anti-epidermal-growth-factor-vaccine-antibodies-enhance-the-efficacy-of-tyrosine-kinase-inhibitors-and-delay-the-emergence-of-resistance-in-egfr-mutant-lung-cancer-cells
#15
Jordi Codony-Servat, Silvia García-Roman, Miguel Ángel Molina-Vila, Jordi Bertran-Alamillo, Ana Giménez-Capitán, Santiago Viteri, Andrés F Cardona, Erik d'Hondt, Niki Karachaliou, Rafael Rosell
INTRODUCTION: Mutations in EGFR correlate with impaired response to immune checkpoint inhibitors and the development of novel immunotherapeutic approaches for EGFR mutant non-small cell lung cancer (NSCLC) is of particular interest. Immunization against EGF has demonstrated efficacy in a phase III trial including unselected NSCLC patients, but little was known about the mechanisms involved in the effects of the anti-EGF antibodies generated by vaccination (anti-EGF VacAbs) or their activity in tumor cells with EGFR mutations...
May 8, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29748023/cost-effectiveness-analysis-of-policy-options-on-first-line-treatments-for-advanced-non-small-cell-lung-cancer-in-thailand
#16
Chulaporn Limwattananon, Supon Limwattananon, Onanong Waleekhachonloet, Thananan Rattanachotphanit
OBJECTIVES: Tyrosine kinase inhibitors (TKIs) have shown to be better for progression-free survival than chemotherapy as the first-line treatment for advanced, non-small cell lung cancer (NSCLC), especially in patients with epidermal growth factor receptor mutation (EGFR M+). This study evaluates under the Thai health system context, cost-effectiveness of (A) the use of platinum doublets for all without EGFR testing, and (B) an EGFR test followed by TKIs or platinum doublets conditional on test results...
June 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29748021/egfr-tkis-plus-chemotherapy-demonstrated-superior-efficacy-than-egfr-tkis-alone-as-first-line-setting-in-advanced-nsclc-patients-with-egfr-mutation-and-bim-deletion-polymorphism
#17
Sangtian Liu, Yayi He, Tao Jiang, Shengxiang Ren, Fei Zhou, Chao Zhao, Xuefei Li, Jie Zhang, Chunxia Su, Xiaoxia Chen, Weijing Cai, Guanghui Gao, Wei Li, Fengying Wu, Jiayu Li, Jing Zhao, Qiong Hu, Mingchuan Zhao, Caicun Zhou, Fred R Hirsch
BACKGROUND: Non-small-cell lung cancer (NSCLC) patients with both epidermal growth factor receptor (EGFR) positive mutation and B-cell chronic lymphocytic leukemia/lymphoma-like 11 (BIM) deletion polymorphism had a poor clinical response to EGFR-tyrosine kinase inhibitors (TKIs). The current study aimed to investigate the clinical efficacy and tolerability of EGFR-TKIs plus chemotherapy versus EGFR-TKIs alone as first-line treatment in advanced NSCLC patients with EGFR mutations and BIM deletion polymorphism...
June 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29748019/long-term-survival-with-erlotinib-in-advanced-lung-adenocarcinoma-harboring-synchronous-egfr-g719s-and-kras-g12c-mutations
#18
Biagio Ricciuti, Sara Baglivo, Vienna Ludovini, Angelo Sidoni, Giulio Metro, Marta Brambilla, Annamaria Siggillino, Maria Sole Reda, Alberto Rebonato, Daniele Maiettini, Rita Chiari
Although epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS) mutations were thought to be mutually exclusive in patients with non-small cell lung cancer (NSCLC), the development of high sensitive large-scale mutation analysis, has increasingly shown that activating EGFR mutations occasionally coexist with other dominant genetic alterations. Herein, we discuss the case of a patient with advanced NSCLC harboring both the uncommon EGFR G719S and the KRAS G12C mutations, who was treated for 9 years with erlotinib achieving a long-term survival...
June 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29742077/philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-in-adults-current-treatments-and-future-perspectives
#19
Musa Yilmaz, Hagop Kantarjian, Farhad Ravandi-Kashani, Nicholas J Short, Elias Jabbour
Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) accounts for approximately one-fourth of cases of adult ALL. It typically presents with an aggressive clinical course, responds poorly to standard chemotherapy, and carries a high risk for relapse. The landscape of Ph+ ALL therapy has changed favorably since the development of tyrosine kinase inhibitors (TKIs). With the successful incorporation of TKIs into chemotherapy regimens, remissions occur more frequently and patients live longer...
March 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29741440/bosutinib-dasatinib-imatinib-nilotinib-and-ponatinib-differentially-affect-the-vascular-molecular-pathways-and-functionality-of-human-endothelial-cells
#20
Ayala Gover-Proaktor, Galit Granot, Metsada Pasmanik-Chor, Oren Pasvolsky, Saar Shapira, Oshrat Raz, Pia Raanani, Avi Leader
The tyrosine kinase inhibitors (TKIs), nilotinib, ponatinib, and dasatinib (but not bosutinib or imatinib), are associated with vascular adverse events (VAEs) in chronic myeloid leukemia (CML). Though the mechanism is inadequately understood, an effect on vascular cells has been suggested. We investigated the effect of imatinib, nilotinib, dasatinib, bosutinib, and ponatinib on tube formation, cell viability, and gene expression of human vascular endothelial cells (HUVECs). We found a distinct genetic profile in HUVECs treated with dasatinib, ponatinib, and nilotinib compared to bosutinib and imatinib, who resembled untreated samples...
May 9, 2018: Leukemia & Lymphoma
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