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- 저자 : Alan Balch (검색결과 2 건)
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Balch, Curt,Naegeli, Kaleb,Nam, Seungyoon,Ballard, Brett,Hyslop, Alan,Melki, Christina,Reilly, Elizabeth,Hur, Man-Wook,Nephew, Kenneth P Landes Bioscience 2012 Cancer Biology & Therapy Vol.13 No.8
<P>Previously, we demonstrated potent antineoplastic activity of a distinctive histone deacetylase inhibitor (HDACI), AR42, against chemoresistant CP70 ovarian cancer cells in vitro and in vivo. Here, in follow-up to that work, we explored AR42 global mechanisms-of-action by examining drug-associated, genome-wide microRNA and mRNA expression profiles, which differed from those of the well-studied HDACI vorinostat. Expression of microRNA genes in negative correlation with their 'target' coding gene (mRNA) transcripts, and transcription factor genes with expression positively correlated with coding genes having their cognate binding sites, were identified and subjected to gene ontology analyses. Those evaluations showed AR42 gene expression patterns to negatively correlate with Wnt signaling (> 18-fold induction of SFRP1), the epithelial-to-mesenchymal transition (40% decreased ATF1), and cell cycle progression (33-fold increased 14-3-3σ). By contrast, AR42 transcriptome alterations correlated positively with extrinsic ('death receptor') apoptosis (> 2.3-fold upregulated DAPK) and favorable ovarian cancer histopathology and prognosis. Inhibition of Wnt signaling was experimentally validated by: (1) > 2.6-fold reduced Wnt reporter activity; and (2) 36% reduction in nuclear, activated β-catenin. Likely AR42 induction of multiple (type I or type II autophagic) cell death cascades was further supported by 57% decreased reliance upon reactive oxygen, increased mitochondrial membrane disruption, and caspase independence, as compared with vorinostat. Taken together, we demonstrate distinct antineoplastic pathway alterations, in aggressive ovarian cancer cells, following treatment with a promising HDACI, AR42. These combined computational and experimental approaches may also represent a straightforward means for mechanistic studies of other promising antineoplastics, and/or the identification of agents that may complement epigenetic therapies.</P>
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Financial toxicity in patients with gynecologic malignancies: a cross sectional study
Burak Zeybek,Emily Webster,Natalia Pogosian,Joan Tymon-Rosario,Alan Balch,Gary Altwerger,Mitchell Clark,Gulden Menderes,Gloria Huang,Masoud Azodi,Elena S. Ratner,Peter E. Schwartz,Alessandro D. Santin 대한부인종양학회 2021 Journal of Gynecologic Oncology Vol.32 No.6
Objective: To evaluate financial toxicity and assess its risk factors among patients with gynecologic cancers. Methods: This is a cross sectional study that included 2 survey tools, as well as patient demographics, disease characteristics, and treatment regimen. Financial toxicity is measured by validated Comprehensive Score for Financial Toxicity (COST) tool. Participants were also asked to complete a 55-question-survey on attitudes and perspectives surrounding cost of care. Descriptive statistics was used to report patient demographics. Spearman's rank correlation was calculated to assess the relation between financial toxicity and patient/ disease related variables. Graphpad Prism Software Version 8.0 was used for analyses. Results: A total of 50 patients with various gynecologic malignancies were enrolled. Median COST score was 20.5 (range, 1–33). Sixty-five percent of the patients reported being in debt due to their cancer care and 4% filed bankruptcy. Correlation analysis showed that COST score was correlated with age (r=−0.3, p=0.028), malignancy type (r=0.3, p=0.039) and income (r=0.3, p=0.047). Ovarian cancer patients had significantly less financial toxicity (median COST score=23) when compared to patients with other gynecologic malignancies (median COST score=17, p=0.043). When scores were dichotomized into low (score ≥22) and high toxicity (score <22), 58% (29/50) of the patients were noted to have high financial toxicity. Enrollment to a clinical trial did not significantly alleviate financial burden. Conclusion: Financial toxicity is a significant burden even among highly insured gynecologic oncology patients. Age, malignancy type and income were correlated with high financial burden.
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