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https://www.readbyqxmd.com/read/28110331/distinct-benefit-of-overall-survival-between-patients-with-non-small-cell-lung-cancer-harboring-egfr-exon-19-deletion-and-exon-21-l858r-substitution
#1
Nobuyuki Koyama, Yasutaka Watanabe, Yuki Iwai, Rumi Kawamura, Chihiro Miwa, Yoshiaki Nagai, Koichi Hagiwara, Shinichiro Koyama
BACKGROUND: Exon 19 deletion (Del19) and exon 21 L858R substitution (L858R), which account for 90% of epidermal growth factor receptor (EGFR) mutations as common mutations, are associated with favorable outcomes with EGFR-tyrosine kinase inhibitors (TKIs) compared with other uncommon EGFR mutations in non-small-cell lung cancer (NSCLC). However, whether there are differences in overall survival (OS) between patients with these common EGFR mutations remains controversial. METHODS: The subjects studied were 74 NSCLC patients with common EGFR mutations treated with gefitinib or erlotinib...
January 21, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28110316/insensitivity-of-pi3k-akt-gsk3-signaling-in-peripheral-blood-mononuclear-cells-of-age-related-macular-degeneration-patients
#2
Liu Xunxian, Yao Zemin
Our recent studies with cultured retinal pigment epithelium cells suggested that overexpression of interleukin 17 receptor C (IL-17RC), a phenomenon observed in peripheral blood and chorioretinal tissues with age-related macular degeneration (AMD), was associated with altered activation of phosphatidylinositide 3-kinase (PI3K), Akt, and glycogen synthase kinase 3 (GSK3). We wondered whether or not altered PI3K, Akt, and GSK3 activities could be detected in peripheral blood mononuclear cells (PBMC) obtained from AMD patients...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28109974/incidences-and-outcomes-of-therapy-related-chronic-myeloid-leukemia-in-the-era-of-tyrosine-kinase-inhibitors-surveillance-of-the-cml-cooperative-study-group
#3
Noriyoshi Iriyama, Michihide Tokuhira, Tomoiku Takaku, Eriko Sato, Maho Ishikawa, Tomonori Nakazato, Kei-Ji Sugimoto, Hiroyuki Fujita, Isao Fujioka, Yoshihiro Hatta, Masahiro Kizaki, Norio Komatsu, Norio Asou, Tatsuya Kawaguchi
This study was performed to investigate the features and outcome of patients with therapy-related chronic myeloid leukemia (TR-CML) who were treated with tyrosine kinase inhibitors (TKIs). The analysis included 308 patients with CML in the chronic phase who were extracted from the CML Cooperative Study Group database. Of these patients, 11 (3.6%) were identified as having TR-CML. No differences in age, sex, white blood cell count, hemoglobin level, platelet count, or European Treatment and Outcome Study risk were observed between patients with TR-CML vs...
January 5, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28109944/synthesis-biological-evaluation-and-molecular-dynamics-md-simulation-studies-of-three-novel-f-18-labeled-and-focal-adhesion-kinase-fak-targeted-5-bromo-pyrimidines-as-radiotracers-for-tumor
#4
Yu Fang, Dawei Wang, Xingyu Xu, Jianping Liu, Aiqin Wu, Xiang Li, Qianqian Xue, Huan Wang, Hang Wang, Huabei Zhang
Focal adhesion kinase (FAK) is considered as an attractive target for oncology. A series of F-18 labeled 5-bromo-N(2)-(4-(2-fluoro-pegylated (FPEG))-3,5-dimethoxyphenyl)-N(4)-(4-methoxyphenyl)pyrimidine-2,4-diamine derivatives were prepared and evaluated as the FAK targeted radiotracers for the early diagnoses of tumor. For the study of the FAK targeted drug molecules, this was the first attempt to develop the tumor diagnostic imaging agents on the radiopharmaceutical level. They inhibited the activity of FAK with IC50 in the range of 91...
January 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28108801/phosphorylation-implications-in-cancer
#5
REVIEW
Vishakha Singh, Mahendra Ram, Rajesh Kumar, Raju Prasad, Birendra Kumar Roy, Kaushal Kumar Singh
Post translational modifications (PTMs) are involved in variety of cellular activities and phosphorylation is one of the most extensively studied PTM, which regulates a number of cellular functions like cell growth, differentiation, apoptosis and cell signaling in healthy condition. However, alterations in phosphorylation pathways result in serious outcomes in the form of diseases, especially cancer. Many signalling pathways including Tyrosine kinase, MAP kinase, Cadherin-catenin complex, Cyclin-dependent kinase etc...
January 20, 2017: Protein Journal
https://www.readbyqxmd.com/read/28108609/visualization-and-quantification-of-browning-using-a-ucp1-2a-luciferase-knock-in-mouse-model
#6
Liufeng Mao, Baoming Nie, Tao Nie, Xiaoyan Hui, Xuefei Gao, Xiaoliang Lin, Xin Liu, Yong Xu, Xiaofeng Tang, Ran Yuan, Kuai Li, Peng Li, Ke Ding, Yu Wang, Aimin Xu, Jian Fei, Weiping Han, Pentao Liu, Lise Madsen, Karsten Kristiansen, Zhiguang Zhou, Sheng Ding, Donghai Wu
Both mammals and adult humans possess classic brown adipocytes and beige adipocytes, and the amount and activity of these adipocytes are considered key factors in combating obesity and its associated metabolic diseases. Uncoupling protein 1 (Ucp1) is the functional marker of both brown and beige adipocytes. To facilitate a reliable, easy, and sensitive measurement of Ucp1 expression both in vivo and in vitro, we generated a Ucp1-2A-luciferase knock-in mouse by deleting the stop codon for the mouse Ucp1 gene and replacing it with a 2A peptide...
February 2017: Diabetes
https://www.readbyqxmd.com/read/28108543/disease-characteristics-and-prognostic-implications-of-cell-surface-flt3-receptor-cd135-expression-in-pediatric-acute-myeloid-leukemia-a-report-from-the-children-s-oncology-group
#7
Katherine Tarlock, Todd A Alonzo, Michael R Loken, Robert B Gerbing, Rhonda E Ries, Richard Aplenc, Lillian Sung, Susana Raimondi, Betsy A Hirsch, Samir B Kahwash, Amy McKenney, E Anders Kolb, Alan S Gamis, Soheil Meshinchi
PURPOSE: The FLT3 cell-surface receptor tyrosine kinase (CD135) is expressed in a majority of both acute lymphoid leukemia (ALL) and myeloid leukemia (AML). However, the prognostic significance of CD135 expression in AML remains unclear. We therefore evaluated the association between FLT3 surface expression and disease characteristics and outcomes in pediatric patients with AML. EXPERIMENTAL DESIGN: We analyzed FLT3 receptor expression on AML blasts by multi-dimensional flow cytometry and its association with disease characteristics, clinical outcomes, and FLT3 transcript level in 367 children with AML treated on the Children's Oncology Group trial AAML0531...
January 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28108514/somatic-ephrin-receptor-mutations-are-associated-with-metastasis-in-primary-colorectal-cancer
#8
Lucy Mathot, Snehangshu Kundu, Viktor Ljungström, Jessica Svedlund, Lotte Moens, Tom Adlerteg, Elin Falk-Sörqvist, Verónica Rendo, Claudia Bellomo, Markus Mayrhofer, Carme Cortina, Magnus Sundström, Patrick Micke, Johan Botling, Anders Isaksson, Aristidis Moustakas, Eduard Batlle, Helgi Birgisson, Bengt Glimelius, Mats Nilsson, Tobias Sjöblom
The contribution of somatic mutations to metastasis of colorectal cancers (CRC) is currently unknown. To find mutations involved in the CRC metastatic process, we performed deep mutational analysis of 676 genes in 107 stages II-IV primary CRC, of which half had metastasized. The mutation prevalence in the ephrin (Eph) family of tyrosine kinase receptors was ten-fold higher in primary tumors of metastatic CRC than in non-metastatic cases and preferentially occurred in stage III and IV tumours. Mutational analyses in situ confirmed expression of mutant Eph receptors...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28108460/enhancer-remodeling-during-adaptive-bypass-to-mek-inhibition-is-attenuated-by-pharmacological-targeting-of-the-p-tefb-complex
#9
Jon S Zawistowski, Samantha M Bevill, Daniel R Goulet, Timothy J Stuhlmiller, Adriana S Beltran, Jose F Olivares-Quintero, Darshan Singh, Noah Sciaky, Joel S Parker, Naim U Rashid, Xin Chen, James S Duncan, Martin C Whittle, Steven P Angus, Sara Hanna Velarde, Brian T Golitz, Xiaping He, Charlene Santos, David B Darr, Kristalyn Gallagher, Lee M Graves, Charles M Perou, Lisa A Carey, H Shelton Earp, Gary L Johnson
Targeting the dysregulated BRaf-MEK-ERK pathway in cancer has increasingly emerged in clinical trial design. Despite clinical responses in specific cancers using inhibitors targeting BRaf and MEK, resistance develops often involving non-genomic adaptive bypass mechanisms. Inhibition of MEK1/2 by trametinib in triple negative breast cancer (TNBC) patients induced dramatic transcriptional responses, including upregulation of receptor tyrosine kinases (RTKs) comparing tumor samples before and after one week of treatment...
January 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28108151/a-functional-genetic-screen-identifies-the-phosphoinositide-3-kinase-pathway-as-a-determinant-of-resistance-to-fibroblast-growth-factor-receptor-inhibitors-in-fgfr-mutant-urothelial-cell-carcinoma
#10
Liqin Wang, Tonći Šuštić, Rodrigo Leite de Oliveira, Cor Lieftink, Pasi Halonen, Marieke van de Ven, Roderick L Beijersbergen, Michel M van den Heuvel, René Bernards, Michiel S van der Heijden
Activating mutations and translocations of the FGFR3 gene are commonly seen in urothelial cell carcinoma (UCC) of the bladder and urinary tract. Several fibroblast growth factor receptor (FGFR) inhibitors are currently in clinical development and response rates appear promising for advanced UCC. A common problem with targeted therapeutics is intrinsic or acquired resistance of the cancer cells. To find potential drug targets that can act synergistically with FGFR inhibition, we performed a synthetic lethality screen for the FGFR inhibitor AZD4547 using a short hairpin RNA library targeting the human kinome in the UCC cell line RT112 (FGFR3-TACC3 translocation)...
January 17, 2017: European Urology
https://www.readbyqxmd.com/read/28107692/rna-binding-protein-msi2-positively-regulates-flt3-expression-in-myeloid-leukemia
#11
Ayuna Hattori, Daniel McSkimming, Natarajan Kannan, Takahiro Ito
FLT3 is frequently mutated and overexpressed in acute myelogenous leukemia (AML) and other hematologic malignancies. Although signaling events downstream of FLT3 receptor tyrosine kinase has been studied in depth, molecular mechanisms of how FLT3 expression is regulated at the post-transcriptional level in particular remain elusive. In this study, we investigated the roles of an RNA binding protein MSI2 as a regulator of FLT3 expression. MSI2 and FLT3 are significantly co-regulated in human AML and chronic myelogenous leukemia in blast crisis (BC-CML)...
January 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28107584/targeting-of-tumor-growth-and-angiogenesis-underlies-the-enhanced-antitumor-activity-of-lenvatinib-in-combination-with-everolimus
#12
Masahiro Matsuki, Yusuke Adachi, Yoichi Ozawa, Takayuki Kimura, Taisuke Hoshi, Kiyoshi Okamoto, Osamu Tohyama, Kaoru Mitsuhashi, Atsumi Yamaguchi, Junji Matsui, Yasuhiro Funahashi
The combination of lenvatinib-a multiple receptor tyrosine kinase (RTK) inhibitor-plus everolimus-a mammalian target of rapamycin (mTOR) inhibitor-significantly improved clinical outcomes versus everolimus monotherapy in a phase 2 clinical study of metastatic renal cell carcinoma (RCC). Here, we investigated potential mechanisms underlying the antitumor activity of the combination treatment in preclinical RCC models. Lenvatinib plus everolimus showed greater antitumor activity than either monotherapy in 3 human RCC xenograft mouse models (A-498, Caki-1, and Caki-2)...
January 20, 2017: Cancer Science
https://www.readbyqxmd.com/read/28107192/incidence-and-risk-of-infections-associated-with-egfr-tkis-in-advanced-non-small-cell-lung-cancer-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#13
Yingtian Wang, Mingzhen Wang, Qiaoxia Wang, Zhiying Geng, Mingxiang Sun
Currently, the overall incidence and risk of infections with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) patients remained undetermined. We searched Pubmed for related articles published from 1 January 1990 to 31 November 2015. Eligible studies included prospective randomized controlled trials (RCTs) evaluating therapy with or without EGFR-TKIs in patients with NSCLC. Data on infections were extracted. Pooled incidence, Peto odds ratio (Peto OR), and 95% confidence intervals (CIs) were calculated...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28105863/the-role-of-mtor-inhibition-as-second-line-therapy-in-metastatic-renal-carcinoma-clinical-evidence-and-current-challenges
#14
José Luis González-Larriba, Pablo Maroto, Ignacio Durán, Julio Lambea, Luis Flores, Daniel Castellano
Sequential treatment with targeted agents is the standard of care for patients with metastatic renal cell carcinoma (mRCC). Although first-line therapy with tyrosine kinase inhibitors (TKIs) is recommended for most patients, eventually all patients become resistant to them. Therefore, optimal selection of second-line therapy is crucial. Areas covered: We have reviewed the recent literature through pubmed search and recent congress presentations to briefly describe the clinical evidence for mTOR inhibition as a valid strategy in the treatment of mRCC after progression during anti-VEGFR therapy...
January 20, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28105602/ibrutinib-a-review-in-chronic-lymphocytic-leukaemia
#15
Emma D Deeks
Ibrutinib (Imbruvica(®)) is an oral irreversible inhibitor of Bruton's tyrosine kinase, a B-cell receptor (BCR) signalling kinase expressed by various haematopoietic cells, B-cell lymphomas and leukaemias. The drug is indicated for the treatment of certain haematological malignancies, including chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL), which are the focus of this review. In phase III CLL/SLL trials, ibrutinib monotherapy was more effective than chlorambucil in the first-line treatment of elderly patients (RESONATE-2) and more effective than ofatumumab in previously-treated adults (RESONATE)...
January 20, 2017: Drugs
https://www.readbyqxmd.com/read/28105557/the-anticancer-drug-sunitinib-promotes-autophagyand-protects-from-neurotoxicity-in-an-hiv-1-tat-model-of-neurodegeneration
#16
Jerel A Fields, Jeff Metcalf, Cassia Overk, Anthony Adame, Brian Spencer, Wolfgang Wrasidlo, Jazmin Florio, Edward Rockenstein, Johnny J He, Eliezer Masliah
Despite the success of antiretroviral therapies to control systemic HIV-1 infection, the prevalence of HIV-associated neurocognitive disorders (HANDs) has not decreased among aging patients with HIV. Autophagy pathway alterations, triggered by HIV-1 proteins including gp120, Tat, and Nef, might contribute to the neurodegenerative process in aging patients with HAND. Although no treatments are currently available to manage HAND, we have previously shown that sunitinib, an anticancer drug that blocks receptor tyrosine-kinase and cyclin kinase pathways, might be of interest...
January 19, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28105368/clinical-and-immunologic-correlates-of-response-to-pd-1-blockade-in-a-patient-with-metastatic-renal-medullary-carcinoma
#17
Kathryn E Beckermann, Pradeep C Jolly, Ju Y Kim, Jennifer Bordeaux, Igor Puzanov, W Kimryn Rathmell, Douglas B Johnson
BACKGROUND: Renal medullary carcinoma (RMC) is a rare kidney tumor that occurs in adolescent and young adults, typically in association with sickle cell trait. RMC exhibits rapid disease progression, frequent metastases at diagnosis, and dismal clinical outcomes. Currently available therapies, including cisplatin-based combination chemotherapy, multi-tyrosine kinase, and mTOR inhibitor strategies demonstrate either transient responses or minimal activity. Therefore, further molecular characterization and additional treatment strategies are urgently needed in this aggressive disease...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28105360/long-term-disease-stabilization-following-treatment-with-erlotinib-in-heavily-pretreated-patients-with-wild-type-epidermal-growth-factor-receptor-non-small-cell-lung-carcinoma-two-case-reports
#18
Minas Sakellakis, Angelos Koutras, Maria Pittaka, Efstathios Tsitsopoulos, Fotini Kalofonou, Haralabos P Kalofonos
Lung adenocarcinomas carrying epidermal growth factor receptor (EGFR) mutations have been identified as a unique group of entities that depend on EGFR for their proliferation and metastasis. The introduction of reversible EGFR tyrosine kinase inhibitors, such as erlotinib, has significantly affected the management of metastatic disease in this subset of patients. Interestingly, although erlotinib is highly effective in patients with EGFR mutations, it may occasionally prove useful, even in the absence of mutations...
December 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28105244/her2-overexpression-reverses-the-relative-resistance-of-egfr-mutant-h1975-cell-line-to-gefitinib
#19
Jing Xu, Li Shen, Bi-Cheng Zhang, Wen-Hong Xu, Shu-Qin Ruan, Chi Pan, Qi-Chun Wei
Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that has been demonstrated to be clinically useful for the treatment of patients with non-small cell lung cancer (NSCLC). However, ~50% of patients do not respond to EGFR TKI treatment through the emergence of mutations, such as T790M. Therefore, it is important to determine which patients are eligible for treatment with gefitinib. As a preferred dimerization partner for EGFR, the role of EGFR 2 (HER2) in mediating sensitivity to gefitinib is poorly understood...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105215/role-of-axl-expression-in-non-small-cell-lung-cancer
#20
Xiaohan Qu, Jinlu Liu, Xinwen Zhong, Xi Li, Qigang Zhang
The present study aimed to investigate the expression profile of AXL in non-small cell lung cancer (NSCLC) and its clinical significance. The current study included 257 NSCLC patients, tyrosine-protein kinase receptor UFO (AXL) expression in paired lung cancer and adjacent normal lung tissues of NSCLC patients were compared by immunohistochemistry, western blot analysis and quantitative polymerase chain reaction (qPCR). These methods were used to detect the expression of the AXL gene and protein in fresh tissues from 35 patients...
December 2016: Oncology Letters
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