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Fausto Castagnetti, Francesco Di Raimondo, Antonio De Vivo, Antonio Spitaleri, Gabriele Gugliotta, Francesco Fabbiano, Isabella Capodanno, Donato Mannina, Marzia Salvucci, Agostino Antolino, Roberto Marasca, Maurizio Musso, Monica Crugnola, Stefana Impera, Elena Trabacchi, Caterina Musolino, Francesco Cavazzini, Giuseppe Mineo, Patrizia Tosi, Carmela Tomaselli, Michele Rizzo, Sergio Siragusa, Miriam Fogli, Riccardo Ragionieri, Alessandro Zironi, Simona Soverini, Giovanni Martinelli, Michele Cavo, Paolo Vigneri, Fabio Stagno, Gianantonio Rosti, Michele Baccarani
Chronic myeloid leukemia (CML) treatment is based on company-sponsored and academic trials testing different tyrosine kinase inhibitors (TKIs) as first-line therapy. These studies included patients selected according to many inclusion-exclusion criteria, particularly age and comorbidities, with specific treatment obligations. In daily clinical practice (real-life), inclusion-exclusion criteria do not exist and the treatment outcome does not only depend on the choice of first-line TKI, but also on second- and third-line TKIs...
October 22, 2016: American Journal of Hematology
Shuhang Wang, Yongping Song, Feifei Yan, Delong Liu
The tyrosine kinase inhibitors (TKI) of the epidermal growth factor receptor (EGFR) are becoming the first line of therapy for advanced non-small cell lung cancer (NSCLC). Acquired mutations in EGFR account for one of the major mechanisms of resistance to the TKIs. Three generations of EGFR TKIs have been used in clinical applications. AZD9291 (osimertinib; Tagrisso) is the first and only FDA approved third-generation EGFR TKI for T790M-positive advanced NSCLC patients. However, resistance to AZD9291 arises after 9-13 months of therapy...
October 21, 2016: Frontiers of Medicine
Elizabeth E Hjort, Weiqi Huang, Liping Hu, Elizabeth A Eklund
Icsbp/Irf8 is an interferon regulatory transcription factor that functions as a suppressor of myeloid leukemias. Consistent with this activity, Icsbp represses a set of genes encoding proteins that promote cell proliferation/survival. One such gene encodes Gas2, a calpain inhibitor. We previously found that increased Gas2-expression in Bcr-abl+ cells stabilized βcatenin; a Calpain substrate. This was of interest, because βcatenin contributes to disease progression in chronic myeloid leukemia (CML). Calpain has additional substrates implicated in leukemogenesis, including Stat5...
October 19, 2016: Oncotarget
Shuyang Yao, Xiuyi Zhi, Ruotian Wang, Kun Qian, Mu Hu, Yi Zhang
BACKGROUND: Epidermal growth factor receptor (EGFR) mutations occur in about 50% of Asian patients with non-small cell lung cancer (NSCLC). Patients with advanced NSCLC and EGFR mutations derive clinical benefit from treatment with EGFR-tyrosine kinase inhibitors (TKIs). This study assessed the efficacy and safety of adjuvant icotinib without chemotherapy in EGFR-mutated NSCLC patients undergoing resection of stage IB-IIIA. METHODS: Our retrospective study enrolled 20 patients treated with icotinib as adjuvant therapy...
September 2016: Thoracic Cancer
Vincent Yi-Fong Su, Chia-Jen Liu, Yuh-Min Chen, Teh-Ying Chou, Tzeng-Ji Chen, Sang-Hue Yen, Tzeon-Jye Chiou, Jin-Hwang Liu, Yu-Wen Hu
BACKGROUND: Currently, no large study addressing the relationship between lung cancer patients with different therapies and second primary malignancies (SPMs) is available. METHODS: Using the Taiwan National Health Insurance Research Database, we conducted a population-based cohort study. Patients with newly diagnosed lung cancer between 1997 and 2005 were enrolled and followed up until Dec. 31, 2011. The endpoint of the study was SPM occurrence. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of the study cohort to that of the general population...
October 20, 2016: Targeted Oncology
Yixiang Zhu, Puyuan Xing, Junling Li
Lung cancer is the deadliest cancer in the worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of lung tumor diagnoses. Squamous cell lung cancer (SQCLC) is a common pathological type, almost 20%-30% of NSCLC. Surgery, chemotherapy, and molecular targeted therapies are the mainstay of treatment for patients with SQCLC. But most patients are diagnosed at advanced stage so that they miss the chance of operation. While noteworthy outcomes have improved with adenocarcinoma of lung with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), a therapeutic plateau for advanced squamous cell lung cancer patients are still not solved...
October 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
Fang Cheng, Jing Wang, Jie Chen, Puyuan Xing, Junling Li
BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhinitors (EGFR-TKIs) inhibit tumor growth by affecting signal transduction, and are well tolerated. The aims of this study was to observe the effect of erlotinib in patients with squamous cell lung cancer. METHODS: The 34 patients with squamous cell lung cancer treated with erlotinib 150 mg orally once daily until disease progression or intolerable adverse reactions. RESULTS: The 7 patients were treated with erlotinib as first-line treatment, 6 patients as maintenance therapy (1 case withdrawal of severe toxicity), 9 patients second-line treatment, 5 patients as third-line and 7 patients as further-line therapy...
October 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
Xi Wu, Junling Li, Shulan Chen, Lei Yu, Boyan Yang
BACKGROUND: Adenosquamous carcinoma (ASC) is a rare subtype of lung cancer, it is mixed glandular and squamous cell carcinoma with a more aggressive behavior and poor prognosis than the other histologic subtypes. The aim of the study was to explore the clinicopathological characteristics and prognostic factors of ASC. METHODS: A total of 72 patients were enrolled. We investigated clinicalpathological features and prognostic factors retrospectively. RESULTS: The overall 72 ASC patients' median age was 34...
October 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
Jumpei Kashima, Yusuke Okuma, Maki Miwa, Yukio Hosomi
Brain metastases (BM) is one of the most crucial distant metastases in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. There is no consensus about which EGFR tyrosine kinase inhibitor (TKI) is most effective against BM in such patients. Here, we compared prognoses of patients with EGFR-TKI naïve EGFR-positive BM treated with erlotinib or gefitinib after BM diagnosis. Of 269 patients with NSCLC treated with EGFR-TKIs at a single institution, we reviewed medical records of 205 patients with documented EGFR mutations...
November 2016: Medical Oncology
Jing Yu, Yue Zhang, Lai-Han Leung, Lian Liu, Fan Yang, Xiaojun Yao
Monoclonal antibodies and small molecule tyrosine kinase inhibitors (TKIs) directed against the vascular endothelial growth factor (VEGF) or its receptors have been investigated in several studies for the treatment of advanced gastric cancer (GC). In the present study, we aimed to evaluate the efficacy and safety of angiogenesis inhibitors in advanced GC. We searched published randomized controlled trials (RCTs) comparing angiogenesis inhibitors with non-angiogenesis inhibitors for the treatment of GC. MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched...
October 18, 2016: Journal of Hematology & Oncology
Qiuyi Zhang, Xuchao Zhang, Honghong Yan, Benyuan Jiang, Chongrui Xu, Jinji Yang, Zhihong Chen, Jian Su, Yi-Long Wu, Qing Zhou
BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are remarkably effective for treating EGFR-mutant non-small cell lung cancer (NSCLC). However, the individual role of EGFR-TKIs in patients with brain metastasis (BM) arising from EGFR-mutant NSCLC remains unclear. METHODS: Patients with BM secondary to NSCLC and harboring EGFR-activating mutations were retrospectively screened. Patients who received gefitinib or erlotinib to control both extracranial lesions (ECLs) and intracranial lesions (ICLs) were eligible...
September 1, 2016: Thoracic Cancer
Ha Young Park, Hyung Joo Oh, Ki-Hyun Kim, Tae-Ok Kim, Cheol-Kyu Park, Hong-Jun Shin, Jung-Hwan Lim, Yong-Soo Kwon, In-Jae Oh, Yu-Il Kim, Sung-Chul Lim, Young-Chul Kim, Yoo-Duk Choi
BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutation is a reliable predictive factor for response to EGFR-tyrosine kinase inhibitors (TKIs). The quantified EGFR value may also predict response and survival within an EGFR mutated group. METHODS: We conducted a retrospective study of 836 lung cancer patients. The patient sample was divided into two groups based on the mean delta cycle threshold (∆Ct) value. EGFR mutation tests using peptide nucleic acid (PNA)-mediated clamping polymerase chain reaction (PCR) were performed...
September 1, 2016: Thoracic Cancer
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
Dominika Labochka, Barbara Moszczuk, Wojciech Kukwa, Cezary Szczylik, Anna M Czarnecka
Renal cell carcinoma (RCC) comprises 2‑3% of all malignant tumors in adults. Many studies have established the key roles of smoking, hypertension and other components of metabolic syndrome in the occurrence of RCC. Diabetes mellitus (DM), one of the main consequences of metabolic syndrome, appears much more often in patients with RCC. The prognosis for patients suffering from both diabetes and RCC is worse than for those with kidney cancer only. Diabetes is linked to higher rate of recurrence and a greater number of distant metastases...
October 17, 2016: International Journal of Molecular Medicine
Rajan P Dang, Daniel McFarland, Valerie H Le, Nadia Camille, Brett A Miles, Marita S Teng, Eric M Genden, Krzysztof J Misiukiewicz
Objectives. Invasion of differentiated thyroid cancer (DTC) into surrounding structures can lead to morbid procedures such as laryngectomy and tracheal resection. In these patients, there is a potential role for neoadjuvant therapy. Methods. We identified three studies involving the treatment of DTC with neoadjuvant chemotherapy: two from Slovenia and one from Japan. Results. These studies demonstrate that in selected situations, neoadjuvant chemotherapy can have a good response and allow for a more complete surgical resection, the treatment of DTC...
2016: International Journal of Surgical Oncology
Ye Xu, Chen Zhu, Wenliang Qian, Min Zheng
PURPOSE: Although many studies have explored clinicopathologic characteristics and prognosis of lung adenocarcinoma, a few literatures reported the mutational status of lung adenocarcinomas with lepidic pattern and whether there is difference between adenocarcinomas with pure lepidic component and lepidic predominant adenocarcinomas remain unknown. METHODS: One hundred and thirty-three patients including 92 adenocarcinomas with pure lepidic component and 41 lepidic predominant adenocarcinomas were subjected to the study...
October 13, 2016: Journal of Cancer Research and Clinical Oncology
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