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https://www.readbyqxmd.com/read/29443039/quantitative-measurement-of-%C3%AE-secretase-mediated-amyloid-precursor-protein-and-notch-cleavage-in-cell-based-luciferase-reporter-assay-platforms
#1
Bo-Jeng Wang, Pei-Yi Wu, Yun-Wen Chen, Yu-Tzu Chang, Noopur Bhore, Po-Fan Wu, Yung-Feng Liao
We have developed a pair of cell-based reporter gene assays to quantitatively measure γ-secretase cleavage of distinct substrates. This manuscript describes procedures that may be used to monitor γ-secretase-mediated cleavage of either APP-C99 or Notch, using a Gal4 promoter-driven firefly luciferase reporter system. These assays were established by stably co-transfecting HEK293 cells with the Gal4-driven luciferase reporter gene and either the Gal4/VP16-tagged C-terminal fragment of APP (APP-C99; CG cells), or the Gal4/VP16-tagged Notch-ΔE (NΔE; NG cells)...
January 25, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29440169/oncogenic-kinase-induced-pkm2-tyrosine-105-phosphorylation-converts-non-oncogenic-pkm2-to-a-tumor-promoter-and-induces-cancer-stem-like-cells
#2
Zhifen Zhou, Min Li, Lin Zhang, Hong Zhao, Özgür Şahin, Jing Chen, Jean J Zhao, Zhou Songyang, Dihua Yu
The role of pyruvate kinase M2 isoform (PKM2) in tumor progression has been controversial. Previous studies showed that PKM2 promoted tumor growth in xenograft models; however, depletion of PKM2 in the Brca1-loss-driven mammary tumor mouse model accelerates tumor formation. Since oncogenic kinases are frequently activated in tumors and PKM2 phosphorylation promotes tumor growth, we hypothesized that phosphorylation of PKM2 by activated kinases in tumor cells confers PKM2 oncogenic function, whereas non-phosphorylated PKM2 is non-oncogenic...
February 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29439832/factors-associated-with-positive-margins-in-women-undergoing-breast-conservation-surgery
#3
Brittany L Murphy, Judy C Boughey, Michael G Keeney, Amy E Glasgow, Jennifer M Racz, Gary L Keeney, Elizabeth B Habermann
OBJECTIVE: To identify factors predicting positive margins at lumpectomy prompting intraoperative reexcision in patients with breast cancer treated at a large referral center. PATIENTS AND METHODS: We reviewed all breast cancer lumpectomy cases managed at our institution from January 1, 2012, through December 31, 2013. Associations between rates of positive margin and patient and tumor factors were assessed using χ 2 tests and univariate and adjusted multivariate logistic regression, stratified by ductal carcinoma in situ (DCIS) or invasive cancer...
February 10, 2018: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/29438748/neuregulin-1-discovered-as-a-cleavage-target-for-the-hcv-ns3-4a-protease-by-a-microfluidic-membrane-protein-array
#4
Nika Schwartz, Michal Pellach, Yair Glick, Reuven Gil, Gahl Levy, Dorit Avrahami, Efrat Barbiro-Michaely, Yaakov Nahmias, Doron Gerber
The hepatitis C virus (HCV) non-structural protein 3 (NS3) is essential for HCV maturation. The NS3/4A protease is a target for several HCV treatments and is a well-known target for HCV drug discovery. The protein is membrane associated and thus probably interacts with other membrane proteins. However, the vast majority of known NS3 host partners are soluble proteins rather than membrane proteins, most likely due to lack of appropriate platforms for their discovery. Utilization of an integrated microfluidics platform enables analysis of membrane proteins in their native form...
February 10, 2018: New Biotechnology
https://www.readbyqxmd.com/read/29438113/morphologic-and-immunohistochemical-appraisal-of-primary-gastric-carcinomas
#5
Gunes Guner, Aynur Isik, Erdem Karabulut, Gokhan Gedikoglu, Cenk Sokmensuer, Aytekin Akyol
Gastric carcinoma management requires adjustments answering their genetic and morphologic heterogeneity. We aim to assess the expression and significance of a myriad of biomarkers (p53, MLH1, MSH2, PMS2, MSH6, Epstein-Barr encoding region-RNA, c-erbB2, E-cadherin, CEA, chromogranin, Ki-67, CDX2, presenilin-1, cathepsin E, MUC5AC, cyclin-dependent kinase 1) in 117 gastric carcinomas, which we have morphologically subclassified with a simple algorithm. Immunohistochemical stains were applied to 3 tissue microarrays of primary gastric carcinomas (n=117) obtained from resection specimens of untreated patients...
February 12, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29437753/dynamic-changes-of-circulating-tumour-dna-in-surgical-lung-cancer-patients-protocol-for-a-prospective-observational-study
#6
Kezhong Chen, Heng Zhao, Fan Yang, Bengang Hui, Tianyang Wang, Lieu Tu Wang, Yanbin Shi, Jun Wang
INTRODUCTION: Circulating tumour DNA (ctDNA) has potential applications in cancer management. Most previous studies about ctDNA focused on advanced stage cancer patients. We have completed a clinical prospective study (NCT02645318) and showed the feasibility and clinical application of ctDNA detection in early stage non-small cell lung cancer (NSCLC) patients. The aim of this study is to investigate the elimination rate of ctDNA level after surgery. This is the first prospective study to evaluate the perioperative dynamic changes of ctDNA in surgical lung cancer patients...
February 6, 2018: BMJ Open
https://www.readbyqxmd.com/read/29437532/using-a-dihydrofolate-reductase-based-strategy-for-producing-the-biosimilar-version-of-pertuzumab-in-cho-s-cells
#7
Amin Ramezani, Abbas Ghaderi
Targeted therapy using monoclonal antibodies (mAbs) against epidermal growth factor receptor-2 (ErbB2) has been utilized for the treatment of breast cancer, recently. Pertuzumab, one of the anti-ErbB2 mAbs, was approved by FDA in 2012 for the treatment of metastatic breast cancer. The aim of this study was to produce biosimilar version of pertuzumab in Chinese hamster ovary (CHO)-S cell line, and compare its ErbB2-binding and biological activities, with commercial drug, Perjeta. To this end, a dihydrofolate reductase (DHFR)-based strategy was used to produce a CHO-S stable cell pool capable of producing high levels of pertuzumab...
February 13, 2018: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/29434871/mechanisms-for-dna-damaging-agent-induced-inactivation-of-erbb2-and-erbb3-via-the-erk-and-p38-signaling-pathways
#8
Chul Min Park, Yuki Kawasaki, Alaa Refaat, Hiroaki Sakurai
Cisplatin (CDDP) and doxorubicin (DOX) are chemotherapeutic drugs that trigger apoptosis by inducing DNA-damage. A previous study using breast cancer cells demonstrated the negative feedback modulation of the epidermal growth factor receptor (EGFR) and receptor tyrosine-protein kinase erbB-2 (ErbB2) via extracellular signal-regulated kinase (ERK)-mediated phosphorylation of conserved Thr-669 and Thr-677 residues, respectively, in the juxtamembrane domain. In addition, CDDP has been identified to cause negative feedback inhibition of activated EGFR in lung cancer cells...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29431801/integrated-dual-modality-microfluidic-sensor-for-biomarker-detection-using-lithographic-plasmonic-crystal
#9
Md Azahar Ali, Shawana Tabassum, Qiugu Wang, Yifei Wang, Ratnesh Kumar, Liang Dong
This paper reports an integrated dual-modality microfluidic sensor chip, consisting of a patterned periodic array of nanoposts coated with gold (Au) and graphene oxide (GO), to detect target biomarker molecules in a limited sample volume. The device generates both electrochemical and surface plasmon resonance (SPR) signals from a single sensing area of Au-GO nanoposts. The Au-GO nanoposts are functionalized with specific receptor molecules, serving as a spatially well-defined nanostructured working electrode for electrochemical sensing, as well as a nanostructured plasmonic crystal for SPR-based sensing via the excitation of surface plasmon polaritons...
February 12, 2018: Lab on a Chip
https://www.readbyqxmd.com/read/29430172/dysregulation-of-neuregulin-1-erbb-signaling-in-the-hippocampus-of-rats-after-administration-of-doxorubicin
#10
Dehua Liao, Yujin Guo, Daxiong Xiang, Ruili Dang, Pengfei Xu, Hualin Cai, Lizhi Cao, Pei Jiang
Objective: Long-term use of doxorubicin (Dox) can cause neurobiological side effects associated with depression, but the underlying mechanisms remain equivocal. While recent evidence has indicated that Neuregulin-1 (NRG1) and its ErbB receptors play an essential role in neural function, much is still unknown concerning the biological link between the NRG1/ErbB pathway and the Dox-induced neurotoxicity. Therefore, we examined the protein expression of NRG1 and ErbB receptors in the hippocampus of rats following Dox treatment...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29426804/escmid-study-group-for-infections-in-compromised-hosts-esgich-consensus-document-on-the-safety-of-targeted-and-biologic-therapies-an-infectious-diseases-perspective-cell-surface-receptors-and-associated-signaling-pathways
#11
REVIEW
J Aguilar-Company, M Fernández-Ruiz, R García-Campelo, A C Garrido-Castro, I Ruiz-Camps
BACKGROUND: The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biologic therapies. AIMS: To review, from an infectious diseases perspective, the safety profile of therapies targeting cell surface receptors and associated signaling pathways among cancer patients and to suggest preventive recommendations...
February 6, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29423054/copy-number-profiles-of-paired-primary-and-metastatic-colorectal-cancers
#12
Futoshi Kawamata, Ann-Marie Patch, Katia Nones, Catherine Bond, Diane McKeone, Sally-Ann Pearson, Shigenori Homma, Cheng Liu, Lochlan Fennell, Troy Dumenil, Gunter Hartel, Nozomi Kobayasi, Hideki Yokoo, Moto Fukai, Hiroshi Nishihara, Toshiya Kamiyama, Matthew E Burge, Christos S Karapetis, Akinobu Taketomi, Barbara Leggett, Nicola Waddell, Vicki Whitehall
Liver metastasis is the major cause of death following a diagnosis of colorectal cancer (CRC). In this study, we compared the copy number profiles of paired primary and liver metastatic CRC to better understand how the genomic structure of primary CRC differs from the metastasis. Paired primary and metastatic tumors from 16 patients and their adjacent normal tissue samples were analyzed using single nucleotide polymorphism arrays. Genome-wide chromosomal copy number alterations were assessed, with particular attention to 188 genes known to be somatically altered in CRC and 24 genes that are clinically actionable in CRC...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29422515/notch-signaling-regulates-hey2-expression-in-a-spatiotemporal-dependent-manner-during-cardiac-morphogenesis-and-trabecular-specification
#13
Lianjie Miao, Jingjing Li, Jun Li, Xueying Tian, Yangyang Lu, Saiyang Hu, David Shieh, Ryan Kanai, Bo-Yang Zhou, Bin Zhou, Jiandong Liu, Anthony B Firulli, James F Martin, Harold Singer, Bin Zhou, Hongbo Xin, Mingfu Wu
Hey2 gene mutations in both humans and mice have been associated with multiple cardiac defects. However, the currently reported localization of Hey2 in the ventricular compact zone cannot explain the wide variety of cardiac defects. Furthermore, it was reported that, in contrast to other organs, Notch doesn't regulate Hey2 in the heart. To determine the expression pattern and the regulation of Hey2, we used novel methods including RNAscope and a Hey2 CreERT2 knockin line to precisely determine the spatiotemporal expression pattern and level of Hey2 during cardiac development...
February 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29420467/her-kinase-inhibition-in-patients-with-her2-and-her3-mutant-cancers
#14
David M Hyman, Sarina A Piha-Paul, Helen Won, Jordi Rodon, Cristina Saura, Geoffrey I Shapiro, Dejan Juric, David I Quinn, Victor Moreno, Bernard Doger, Ingrid A Mayer, Valentina Boni, Emiliano Calvo, Sherene Loi, Albert C Lockhart, Joseph P Erinjeri, Maurizio Scaltriti, Gary A Ulaner, Juber Patel, Jiabin Tang, Hannah Beer, S Duygu Selcuklu, Aphrothiti J Hanrahan, Nancy Bouvier, Myra Melcer, Rajmohan Murali, Alison M Schram, Lillian M Smyth, Komal Jhaveri, Bob T Li, Alexander Drilon, James J Harding, Gopa Iyer, Barry S Taylor, Michael F Berger, Richard E Cutler, Feng Xu, Anna Butturini, Lisa D Eli, Grace Mann, Cynthia Farrell, Alshad S Lalani, Richard P Bryce, Carlos L Arteaga, Funda Meric-Bernstam, José Baselga, David B Solit
Somatic mutations of ERBB2 and ERBB3 (which encode HER2 and HER3, respectively) are found in a wide range of cancers. Preclinical modelling suggests that a subset of these mutations lead to constitutive HER2 activation, but most remain biologically uncharacterized. Here we define the biological and therapeutic importance of known oncogenic HER2 and HER3 mutations and variants of unknown biological importance by conducting a multi-histology, genomically selected, 'basket' trial using the pan-HER kinase inhibitor neratinib (SUMMIT; clinicaltrials...
February 8, 2018: Nature
https://www.readbyqxmd.com/read/29416916/genotyping-and-mrna-profiling-reveal-actionable-molecular-targets-in-biliary-tract-cancers
#15
Kyriaki Papadopoulou, Samuel Murray, Kyriaki Manousou, Ioannis Tikas, Christos Dervenis, Joseph Sgouros, Dimitra Rontogianni, Sotirios Lakis, Mattheos Bobos, Christos Poulios, Stavroula Pervana, Georgios Lazaridis, George Fountzilas, Vassiliki Kotoula
Biliary tract cancer (BTC) represents a heterogeneous disease with dismal outcome. Herein, we examined genotype and angiogenesis features in BTC. We applied genotyping (Sanger, qPCR, 101-gene panel NGS), mRNA relative quantification methods, and β-catenin immunohistochemistry in 84 FFPE BTC (55 gallbladder [GBC], 14 intrahepatic [ICC], 15 extrahepatic [ECC] carcinomas). We identified 541 mutations in 68 (81%) tumors. Top mutated genes were CTNNB1 (36%); PTEN (33%); TP53 (31%); PIK3R1 (29%); PIK3CA (13%); BRCA2 and KRAS (12%); BRCA1 (11%)...
2018: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29416807/survival-and-time-to-initiation-of-adjuvant-chemotherapy-among-breast-cancer-patients-a-systematic-review-and-meta-analysis
#16
Qiao-Hui Zhan, Jian-Qin Fu, Fang-Meng Fu, Jie Zhang, Chuan Wang
The relationship between survival and time to the start of adjuvant chemotherapy (AC) among breast cancer patients is unclear. In order to illustrate the effect of delaying the initiation of AC on survival we have undertaken a systematic review and meta-analysis. We identified 12 available studies in the meta-analysis including 15 independent analytical groups. This meta-analysis showed that a 4-week delay before AC was associated with a significantly worse overall survival (OS)(HR=1.13; 95% confidence interval [CI], 1...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416677/identification-of-human-age-associated-gene-co-expressions-in-functional-modules-using-liquid-association
#17
Jialiang Yang, Yufang Qin, Tiantian Zhang, Fayou Wang, Lihong Peng, Lijuan Zhu, Dawei Yuan, Pan Gao, Jujuan Zhuang, Zhongyang Zhang, Jun Wang, Yun Fang
Aging is a major risk factor for age-related diseases such as certain cancers. In this study, we developed Age Associated Gene Co-expression Identifier (AAGCI), a liquid association based method to infer age-associated gene co-expressions at thousands of biological processes and pathways across 9 human tissues. Several hundred to thousands of gene pairs were inferred to be age co-expressed across different tissues, the genes involved in which are significantly enriched in functions like immunity, ATP binding, DNA damage, and many cancer pathways...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416660/foxm1-is-a-promising-candidate-target-in-the-treatment-of-breast-cancer
#18
Xiao-Feng Lu, De Zeng, Wei-Quan Liang, Chun-Fa Chen, Shu-Ming Sun, Hao-Yu Lin
Forkhead box protein M1(FoxM1) is a member of forkhead superfamily transcription factors. Emerging evidences have progressively contributed to our understanding on a central role of FoxM1 in human cancers. However, perspectives on the function of FoxM1 in breast cancer (BC) remain conflicting, and mostly were from basic research. Here, we explored the expression profile and prognostic values of FoxM1 based on analysis of pooled clinical datasets derived from online accessible databases, including ONCOMINE , Breast Cancer Gene-Expression Miner v4...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29410073/the-receptor-tyrosine-kinase-erbb4-is-expressed-in-skin-keratinocytes-and-influences-epidermal-proliferation
#19
Christine Hoesl, Jennifer M Röhrl, Marlon R Schneider, Maik Dahlhoff
BACKGROUND: The epidermal growth factor receptor (EGFR) and associated receptors ERBB2 and ERBB3 are important for skin development and homeostasis. To date, ERBB4 could not be unambiguously identified in the epidermis. The aim of this study was to analyze the ERBB-receptor family with a special focus on ERBB4 in vitro in human keratinocytes and in vivo in human and murine epidermis. METHODS: We compared the transcript levels of all ERBB-receptors and the seven EGFR-ligands in HaCaT and A431 cells...
January 30, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29409051/impact-of-genomic-alterations-on-lapatinib-treatment-outcome-and-cell-free-genomic-landscape-during-her2-therapy-in-her2-positive-gastric-cancer-patients
#20
S T Kim, K C Banks, E Pectasides, S Y Kim, K Kim, R B Lanman, A Talasaz, J An, M G Choi, J H Lee, T S Sohn, J M Bae, S Kim, S H Park, J O Park, Y S Park, H Y Lim, N K D Kim, W Park, H Lee, A J Bass, K Kim, W K Kang, J Lee
Background: To identify predictive markers for responders in lapatinib-treated patients and to demonstrate molecular changes during lapatinib treatment via cell-free genomics. Patients and Methods: We prospectively evaluated the efficacy of combining lapatinib with capecitabine and oxaliplatin as first line neoadjuvant therapy in patients with previously untreated, HER2-overexpressing advanced gastric cancer (AGC). A parallel biomarker study was conducted by simultaneously performing immunohistochemistry (IHC) and next-generation sequencing with tumor and blood samples...
February 2, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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