1,181 research outputs found
YC-1 inhibits proliferation of breast cancer cells by down-regulating EZH2 expression via activation of c-Cbl and ERK
No full textBACKGROUND AND PURPOSE
YC-1 exhibits potent anticancer activity via numerous actions in many cancer cell lines. Hence, we investigated the in vivo antitumour efficacy of YC-1 in an MDA-MB-468 xenograft model and elucidated the mechanism of down-regulation of enhancer of zeste homology 2 (EZH2) by YC-1 in breast cancer cells.
EXPERIMENTAL APPROACH
In YC-1-treated breast cancer cells and tumour specimens from YC-1-treated MDA-MB-468 xenografts, EZH2 expression was analysed by Western blotting. Pharmacological inhibitors and short hairpin RNA-mediated knockdown were applied to identify possible signalling pathways involved in EZH2 down-regulation by YC-1.
KEY RESULTS
YC-1 reduced the viability of breast cancer cells and tumour growth in MDA-MB-468 xenografts. In breast cancer cells, YC-1 down-regulated EZH2 expression in a concentration-and time-dependent manner. Depletion of EZH2 reduced the proliferation and susceptibility of breast cancer cells to YC-1-induced apoptosis. EZH2 expression was suppressed in tumour specimens from YC-1-treated MDA-MB-468 xenograft mice. YC-1 enhanced both the degradation rate and ubiquitination of EZH2. The down-regulation of EZH2 by YC-1 was associated with activation of PKA and Src-Raf-ERK-mediated signalling pathways. Furthermore, depletion of Casitas B-lineage lymphoma (c-Cbl), an E3 ubiquitin ligase, abolished YC-1-induced apoptosis and suppression of EZH2. YC-1 rapidly activated c-Cbl to induce signalling associated with ERK and EZH2.
CONCLUSION AND IMPLICATIONS
We discovered that YC-1 induces apoptosis and inhibits tumour growth of breast cancer cells via down-regulation of EZH2 by activating c-Cbl and ERK. These data suggest that YC-1 is a potential anticancer drug candidate for triple-negative breast cancer
Differentially expressed miRNAs between Bama minipigs (YB) and Landrace (YC).
No full text<p>YB, YC represent Bama minipigs and Landrace pigs, respectively. miRNAs underlined represents this differential miRNAs is p ≤ 0.01 and the higher signal≥500.</p><p>Differentially expressed miRNAs between Bama minipigs (YB) and Landrace (YC).</p
YC-1 inhibits proliferation of breast cancer cells by downregulating EZH2 expression via activation of c-Cbl and ERK
No full text[[abstract]]Background and Purpose
YC-1 exhibits potent anticancer activity via numerous actions in many cancer cell lines. Hence, we investigated the in vivo antitumour efficacy of YC-1 in an MDA-MB-468 xenograft model and elucidated the mechanism of down-regulation of enhancer of zeste homology 2 (EZH2) by YC-1 in breast cancer cells.
Experimental Approach
In YC–1-treated breast cancer cells and tumour specimens from YC–1-treated MDA-MB-468 xenografts, EZH2 expression was analysed by Western blotting. Pharmacological inhibitors and short hairpin RNA-mediated knockdown were applied to identify possible signalling pathways involved in EZH2 down-regulation by YC-1.
Key Results
YC-1 reduced the viability of breast cancer cells and tumour growth in MDA-MB-468 xenografts. In breast cancer cells, YC-1 down-regulated EZH2 expression in a concentration- and time-dependent manner. Depletion of EZH2 reduced the proliferation and susceptibility of breast cancer cells to YC–1-induced apoptosis. EZH2 expression was suppressed in tumour specimens from YC–1-treated MDA-MB-468 xenograft mice. YC-1 enhanced both the degradation rate and ubiquitination of EZH2. The down-regulation of EZH2 by YC-1 was associated with activation of PKA and Src–Raf–ERK-mediated signalling pathways. Furthermore, depletion of Casitas B-lineage lymphoma (c-Cbl), an E3 ubiquitin ligase, abolished YC–1-induced apoptosis and suppression of EZH2. YC-1 rapidly activated c-Cbl to induce signalling associated with ERK and EZH2.
Conclusion and Implications
We discovered that YC-1 induces apoptosis and inhibits tumour growth of breast cancer cells via down-regulation of EZH2 by activating c-Cbl and ERK. These data suggest that YC-1 is a potential anticancer drug candidate for triple-negative breast cancer
YC-1 enhances the anti-tumor activity of sorafenib through inhibition of signal transducer and activator of transcription 3 (STAT3) in hepatocellular carcinoma
No full textBackground: Traditional systemic chemotherapy does not provide survival benefits in patients with hepatocellular carcinoma (HCC). Molecular targeted therapy shows promise for HCC treatment, however, the duration of effectiveness for targeted therapies is finite and combination therapies offer the potential for improved effectiveness. Methods: Sorafenib, a multikinase inhibitor, and YC-1, a soluble guanylyl cyclase (sGC) activator, were tested in HCC by proliferation assay, cell cycle analysis and western blot in vitro and orthotopic and ectopic HCC models in vivo. Results: In vitro, combination of sorafenib and YC-1 synergistically inhibited proliferation and colony formation of HepG2, BEL-7402 and HCCLM3 cells. The combination also induced S cell cycle arrest and apoptosis, as observed by activated PARP and caspase 8. Sorafenib and YC-1 respectively suppressed the expression of phosphorylated STAT3 (p-STAT3) (Y705) in a dose-and time-dependent manner. Combination of sorafenib and YC-1 significantly inhibited the expression of p-STAT3 (Y705) (S727), p-ERK1/2, cyclin D1 and survivin and SHP-1 activity compared with sorafenib or YC-1 used alone in all tested HCC cell lines. In vivo, sorafenib-YC-1 combination significantly suppressed the growth of HepG2 tumor xenografts with decreased cell proliferation and increased apoptosis observed by PCNA and PARP. Similar results were also confirmed in a HCCLM3 orthotopic model. There was a reduction in CD31-positive blood vessels and reduced VEGF expression, which suggested a combinational effect of sorafenib and YC-1 on angiogenesis. The reduced expression of p-STAT3, cyclin D1 and survivin was also observed with the combination of sorafenib and YC-1. Conclusions: Our data show that sorafenib-YC-1 combination is a novel potent therapeutic agent that can target the STAT3 signaling pathway to inhibit HCC tumor growth.Biochemistry & Molecular BiologyOncologySCI(E)[email protected]; [email protected]
Cultural adaptation of the young children's participation and environment measure (YC-PEM) for use by Hispanic families of young children with special health care needs (CSHCN)
No full textIncludes bibliographical references.2016 Summer.Culture informs the occupations in which children engage as well as how they are enacted. Hence, occupational therapists need assessments that are culturally relevant in order to deliver culturally competent practice. Current approaches to cultural adaptation of assessments present with three major limitations: (a) use of inconsistent translation process; (b) current processes assess for some, but not all, elements of cultural equivalence; and (c) limited evidence to guide decision making about whether to undertake cultural adaptation with and without language translation. To our knowledge, this is the first study to systematically develop and compare multiple versions of a culturally adapted questionnaire for potential use by a Hispanic population of young children with special health care needs (CSHCN). The purpose of this study is two-fold: (a) to examine similarities and differences of culturally adapting an occupation-centered pediatric assessment with and without translation; and (b) to examine the feasibility of developing a culturally adapted assessment with and without translation. The Young Children’s Participation and Environment Measure (YC-PEM) underwent cultural adaptation processes (i.e., language translation and cognitive testing) to establish Spanish and English pilot versions for potential use by caregivers of young CSHCN of Mexican descent. Following language translation to develop a Spanish YC-PEM pilot version, 7 caregivers (4 with Spanish as their primary language; 3 with English as their primary language) completed cognitive testing to inform decisions regarding content revisions to the YC-PEM Spanish and English pilot versions. Participant responses were content coded to established cultural equivalencies (i.e., semantic/idiomatic, item, conceptual). Coded data were then summed to draw comparisons on the number of revisions needed to achieve cultural equivalence between the two pilot versions. Feasibility was assessed according to resources required, data collection procedures, and data quality. Results suggest that a greater number of revisions are required to achieve cultural equivalence for the translated (Spanish) version of the YC-PEM. However, issues concerning conceptual equivalence were identified in both the Spanish and English versions. Feasibility results indicate that language translation processes require high resource investment, but may increase translation quality. However, use of questionnaire (i.e., paper, PDF) cognitive testing versus interview methods (e.g., phone, face-to-face) may have limited data saturation. Study results lend preliminary support to the need for and feasibility of pursuing cultural adaptation of the YC-PEM with and without language translation. Larger and more diverse samples are needed to examine the effects of acculturation status on revisions needed to achieve cultural equivalence. Also, interview methods may help improve data quality and confirm study findings
FOURIER TRANSFORM MICROWAVE SPECTRUM OF THE YC (XA) RADICAL
No full textAuthor Institution: Department of Chemistry, Department of Astronomy, and Steward Observatory, University of Arizona, Tucson, AZ 85721The pure rotational spectrum of YC (XA) in the range 4 - 40 GHz has been measured using Fourier transform microwave (FTMW) techniques. The species was produced using Discharge Assisted Laser Ablation Spectroscopy (DALAS) in a supersonic jet expansion of yttrium vapor and HCCH or CH, diluted in argon carrier gas. Three rotational transitions (N = 1 0, 2 1, and 3 2) have been recorded each exhibiting fine structure and hyperfine splittings due to the yttrium nuclear spin of I(Y) = 1/2. The data have been analyzed wtih a case (b) asymmetric top Hamiltonian, and rotational, fine, and hyperfine constants have been determined. The spectrum of this species was previously measured by PPMODR methods, and our data have refined the spectroscopic constants. Measurements of the C isotopologues are currently underway to establish a precise structure for YC
Low Parasitic Capacitance and Low-Power CMOS Capacitive Fingerprint Sensor
No full text[[abstract]]In this paper, a low parasitic capacitance and low-power CMOS capacitive fingerprint sensor readout circuit is presented. The side effect of parasitic capacitance has been under control with novel layout structure in sensor cell, and minimal size switch is used to reduce non-ideal effects of MOS switch and achieve good linearity. Power dissipation is also reduced with quiescent current control in buffer amplifier of sensor cell. A prototype chip with 32 x 32 array size has been fabricated using TSMC 0.35 mu m CMOS process. The chip works at 3.3V power supply and operates at 4MHz clock rate. Capacitance value from 0ff to 60fF can be sensed, corresponding analog output voltage is from 3.02V to 1.57V and the digital output is 6 bits. The overall power consumption is less than 5.5mW.[[note]]SC
Single-cell genetic models to evaluate orphan gene function: The case of QQS regulating carbon and nitrogen allocation
No full textWe demonstrate two synthetic single-cell systems that can be used to better understand how the acquisition of an orphan gene can affect complex phenotypes. The Arabidopsis orphan gene, Qua-Quine Starch (QQS) has been identified as a regulator of carbon (C) and nitrogen (N) partitioning across multiple plant species. QQS modulates this important biotechnological trait by replacing NF-YB (Nuclear Factor Y, subunit B) in its interaction with NF-YC. In this study, we expand on these prior findings by developing Chlamydomonas reinhardtii and Saccharomyces cerevisiae strains, to refactor the functional interactions between QQS and NF-Y subunits to affect modulations in C and N allocation. Expression of QQS in C. reinhardtii modulates C (i.e., starch) and N (i.e., protein) allocation by affecting interactions between NF-YC and NF-YB subunits. Studies in S. cerevisiae revealed similar functional interactions between QQS and the NF-YC homolog (HAP5), modulating C (i.e., glycogen) and N (i.e., protein) allocation. However, in S. cerevisiae both the NF-YA (HAP2) and NF-YB (HAP3) homologs appear to have redundant functions to enable QQS and HAP5 to affect C and N allocation. The genetically tractable systems that developed herein exhibit the plasticity to modulate highly complex phenotypes.This article is published as Wang L, Tonsager AJ, Zheng W, Wang Y, Stessman D, Fang W, Stenback KE, Campbell A, Tanvir R, Zhang J, Cothron S, Wan D, Meng Y, Spalding MH, Nikolau BJ and Li L (2023) Single-cell genetic models to evaluate orphan gene function: The case of QQS regulating carbon and nitrogen allocation. Front. Plant Sci. 14:1126139. doi: 10.3389/fpls.2023.1126139.© 2023 Wang, Tonsager, Zheng, Wang, Stessman, Fang, Stenback, Campbell, Tanvir, Zhang, Cothron, Wan, Meng, Spalding, Nikolau and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
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