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Genome Wide Proteomics of ERBB2 and EGFR and Other Oncogenic Pathways in Inflammatory Breast Cancer
Zhang, Emma Yue,Cristofanilli, Massimo,Robertson, Fredika,Reuben, James M.,Mu, Zhaomei,Beavis, Ronald C.,Im, Hogune,Snyder, Michael,Hofree, Matan,Ideker, Trey,Omenn, Gilbert S.,Fanayan, Susan,Jeong, S American Chemical Society 2013 Journal of proteome research Vol.12 No.6
<P>In this study we selected three breast cancer cell lines (SKBR3, SUM149 and SUM190) with different oncogene expression levels involved in ERBB2 and EGFR signaling pathways as a model system for the evaluation of selective integration of subsets of transcriptomic and proteomic data. We assessed the oncogene status with reads per kilobase per million mapped reads (RPKM) values for ERBB2 (14.4, 400, and 300 for SUM149, SUM190, and SKBR3, respectively) and for EGFR (60.1, not detected, and 1.4 for the same 3 cell lines). We then used RNA-Seq data to identify those oncogenes with significant transcript levels in these cell lines (total 31) and interrogated the corresponding proteomics data sets for proteins with significant interaction values with these oncogenes. The number of observed interactors for each oncogene showed a significant range, e.g., 4.2% (JAK1) to 27.3% (MYC). The percentage is measured as a fraction of the total protein interactions in a given data set vs total interactors for that oncogene in STRING (Search Tool for the Retrieval of Interacting Genes/Proteins, version 9.0) and I2D (Interologous Interaction Database, version 1.95). This approach allowed us to focus on 4 main oncogenes, ERBB2, EGFR, MYC, and GRB2, for pathway analysis. We used bioinformatics sites GeneGo, PathwayCommons and NCI receptor signaling networks to identify pathways that contained the four main oncogenes and had good coverage in the transcriptomic and proteomic data sets as well as a significant number of oncogene interactors. The four pathways identified were ERBB signaling, EGFR1 signaling, integrin outside-in signaling, and validated targets of C-MYC transcriptional activation. The greater dynamic range of the RNA-Seq values allowed the use of transcript ratios to correlate observed protein values with the relative levels of the ERBB2 and EGFR transcripts in each of the four pathways. This provided us with potential proteomic signatures for the SUM149 and 190 cell lines, growth factor receptor-bound protein 7 (GRB7), Crk-like protein (CRKL) and Catenin delta-1 (CTNND1) for ERBB signaling; caveolin 1 (CAV1), plectin (PLEC) for EGFR signaling; filamin A (FLNA) and actinin alpha1 (ACTN1) (associated with high levels of EGFR transcript) for integrin signalings; branched chain amino-acid transaminase 1 (BCAT1), carbamoyl-phosphate synthetase (CAD), nucleolin (NCL) (high levels of EGFR transcript); transferrin receptor (TFRC), metadherin (MTDH) (high levels of ERBB2 transcript) for MYC signaling; S100-A2 protein (S100A2), caveolin 1 (CAV1), Serpin B5 (SERPINB5), stratifin (SFN), PYD and CARD domain containing (PYCARD), and EPH receptor A2 (EPHA2) for PI3K signaling, p53 subpathway. Future studies of inflammatory breast cancer (IBC), from which the cell lines were derived, will be used to explore the significance of these observations.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jprobs/2013/jprobs.2013.12.issue-6/pr4001527/production/images/medium/pr-2013-001527_0010.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/pr4001527'>ACS Electronic Supporting Info</A></P>
Whose Job Is It? Parents’ Perspectives on Volunteering to Help in New Zealand Kindergartens
Qilong Zhang,Louise Keown,Susan Farruggia 환태평양유아교육연구학회 2015 Asia-Pacific journal of research in early childhoo Vol.9 No.2
Volunteering to help is a traditional type of parental involvement in early childhood education. There have been concerns over the justification of teachers’ practice of leaving their work with parents, particularly for routine tasks such as washing and cleaning, however, little research has been conducted to scrutinize the practice and examine parents’ experiences with volunteering to help. Based on a sample of 25 parents from New Zealand public kindergartens, this study investigates parents ‘experiences with three types of volunteering to help at the kindergarten. Analysis of the semi-structured interview data has revealed enhancers (e.g., benefits for the child, justification of fundraising) and impediments (e.g., limited time, school commitment) to parent volunteering to help as well as the tensions in practice(e.g., relying on core parents, limited resource). The findings support the legitimacy of routine tasks and fundraising and highlight the importance of parent volunteering to help.
A Spray-Processable, Low Bandgap, and Ambipolar Donor−Acceptor Conjugated Polymer
Steckler, Timothy T.,Zhang, Xuan,Hwang, Jungseek,Honeyager, Ryan,Ohira, Shino,Zhang, Xiao-Hong,Grant, Adrian,Ellinger, Stefan,Odom, Susan A.,Sweat, Daniel,Tanner, David B.,Rinzler, Andrew G.,Barlow, S American Chemical Society 2009 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.131 No.8
Ryan Urban,Justin Wong,Peter Lim,Susan Zhang,Ingrid Spadinger,Robert Olson,Francois Bachand,Clement Ho,Anna V. Tinker,Lovedeep Gondara,Sarah Nicole Hamilton 대한부인종양학회 2022 Journal of Gynecologic Oncology Vol.33 No.5
Objective: To evaluate gastrointestinal (GI) patient reported outcomes (PROs) in cervical cancer patients treated with definitive radiotherapy (RT), comparing 3D conformal RT (3DCRT) vs. intensity modulated/volumetric modulated arc therapy (IMRT/VMAT). Methods: An analysis of patients treated with definitive RT between 2015–2018 was performed. GI PROs were prospectively collected at baseline, during RT (acute), ≤12 weeks after RT (subacute), and >12 weeks after RT (late). GI PROs evaluated three symptom domains: bowel problems (BPs), bowel bother (BB), and abdominal problems (APs). Multiple linear regression analysis was performed to investigate associations between mean changes of symptom scores with clinical and dosimetric variables. Results: The cohort included 167 patients. A total of 100 (60%) patients were treated with IMRT/VMAT and 67 (40%) with 3DCRT. In the subacute phase, the mean change of symptom scores from baseline in 3DCRT vs. IMRT/VMAT were +0.9 vs. −1.15 (p=0.004) for BP, +2.18 vs. −0.10 (p=0.019) for BB, and +1.41 vs. −0.38 (p=0.021) for AP. Likewise, in the late phase, mean changes were +0.72 vs. −0.82 (p=0.014) for BP, +1.98 vs. −0.03 (p=0.008) for BB, and +1.29 vs. −0.31 (p<0.001) for AP. On multiple linear regression, use of 3DCRT vs. IMRT/VMAT was associated with greater mean changes in subacute BP (p=0.023) and late phase AP (p=0.019). A higher small bowel V50Gy was associated increased symptom scores in late AP (p=0.012). Conclusion: 3DCRT was associated with significantly greater worsening of GI PRO symptom scores in the subacute and late phase. These data support the ongoing use of IMRT/VMAT in routine practice
LaBonte, Melissa J.,Yang, Dongyun,Zhang, Wu,Wilson, Peter M.,Nagarwala, Yasir M.,Koch, Kevin M.,Briner, Colleen,Kaneko, Tomomi,Rha, Sun-Young,Gladkov, Oleg,Urba, Susan G.,Sakaeva, Dina,Pishvaian, Mich American Association for Cancer Research 2016 Molecular Cancer Therapeutics Vol.15 No.9
<P>An exploratory phase II biomarker-embedded trial (LPT109747; NCT00526669) designed to determine the association of lapatinib-induced fluoropyrimidine gene changes with efficacy of lapatinib plus capecitabine as first-line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma-independent of tumor HER2 status. Tumor biopsies obtained before and after 7- day lapatinib (1,250 mg) to analyze changes in gene expression, followed by a 14-day course of capecitabine (1,000 mg/m(2) twice daily, 14/21 days) plus lapatinib 1,250 mg daily. Blood samples were acquired for pharmacokinetic analysis. Primary clinical objectives were response rate (RR) and 5-month progression-free survival (PFS). Secondary objectives were overall survival (OS), PFS, time to response, duration of response, toxicity, and identification of associations between lapatinib pharmacokinetics and biomarker endpoints. Primary biomarker objectives were modulation of 5FU- pathway genes by lapatinib, effects of germline SNPs on treatment outcome, and trough steady-state plasma lapatinib concentrations. Sixty-eight patients were enrolled; (75% gastric cancer, 25% gastroesophageal junction). Twelve patients (17.9%) had confirmed partial response, 31 (46.3%) had stable disease, and 16 (23.9%) had progressive disease. Median PFS and OS were 3.3 and 6.3 months, respectively. Frequent adverse events included diarrhea (45%), decreased appetite (39%), nausea (36%), and fatigue (36%). Lapatinib induced no changes in gene expression from baseline and no significant associations were found for SNPs analyzed. Elevated baseline HER3 mRNA expression was associated with a higher RR (33% vs. 0%; P = 0.008). Lapatinib plus capecitabine was well tolerated, demonstrating modest antitumor activity in patients with advanced gastric cancer. The association of elevated HER3 and RR warrants further investigation as an important player for HER-targeted regimens in combination with capecitabine. (C)2016 AACR.</P>