Publications by authors named "Charles Yen"

5 Publications

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Single-layer boron-doped graphene quantum dots for contrast-enhanced in vivo T-weighted MRI.

Nanoscale Horiz 2020 03 3;5(3):573-579. Epub 2020 Jan 3.

Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195, USA.

Gadolinium (Gd)-based chelates are used as clinical T contrast agents for magnetic resonance imaging (MRI) due to their demonstrated high sensitivity and positive contrast enhancement capability. However, there has been an increasing safety concern about their use in medicine because of the toxicity of the metal ions released from these contrast agents when used in vivo. Although significant effort has been made in developing metal-free MRI contrast agents, none have matched the magnetic properties achieved by the gold standard clinical contrast agent, Gd diethylene penta-acetic acid (Gd-DTPA). Here, we report the development of a single-layer, boron-doped graphene quantum dot (termed SL-BGQD) that demonstrates better T contrast enhancement than Gd-DTPA. The SL-BGQD is shown to provide significantly higher positive contrast enhancement than the Gd-DTPA contrast agent in imaging vital organs, including kidneys, liver, and spleen, and especially, vasculatures. Further, our results show that the SL-BQGD is able to bypass the blood-brain barrier and allows sustained imaging for at least one hour with a single injection. Hematological and histopathological analyses show that the SL-BGQD demonstrates a non-toxic profile in wild-type mice and may, therefore, serve as an improved, safer alternative to currently available clinical MRI contrast agents.
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http://dx.doi.org/10.1039/c9nh00608gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386463PMC
March 2020

Nitrogen and Boron Dual-Doped Graphene Quantum Dots for Near-Infrared Second Window Imaging and Photothermal Therapy.

Appl Mater Today 2019 Mar 6;14:108-117. Epub 2018 Dec 6.

Department of Materials Science and Engineering, University of Washington, Seattle 98195, United States.

Fluorescence imaging of biological systems in the second near-infrared window (NIR-II) has recently drawn much attention because of its negligible background noise of autofluorescence and low tissue scattering. Here we present a new NIR-II fluorescent agent, graphene quantum dots dual-doped with both nitrogen and boron (N-B-GQDs). N-B-GQDs have an ultra-small size (~ 5 nm), are highly stable in serum, and demonstrate a peak fluorescent emission at 1000 nm and high photostability. In addition to the NIR-II imaging capability, N-B-GQDs efficiently absorb and convert NIR light into heat when irradiated by an external NIR source, demonstrating a photothermal therapeutic effect that kills cancer cells in vitro and completely suppresses tumor growth in a glioma xenograft mouse model. N-B-GQDs demonstrate a safe profile, prolonged blood half-life, and rapid excretion in mice, which are the characteristics favorable for in vivo biomedical applications.
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http://dx.doi.org/10.1016/j.apmt.2018.11.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752708PMC
March 2019

Biconcave Carbon Nanodisks for Enhanced Drug Accumulation and Chemo-Photothermal Tumor Therapy.

Adv Healthc Mater 2019 04 11;8(8):e1801505. Epub 2019 Mar 11.

Department of Materials Science and Engineering, University of Washington, Seattle, Washington, DC, 98195, USA.

It is considered a significant challenge to construct nanocarriers that have high drug loading capacity and can overcome physiological barriers to deliver efficacious amounts of drugs to solid tumors. Here, the development of a safe, biconcave carbon nanodisk to address this challenge for treating breast cancer is reported. The nanodisk demonstrates fluorescent imaging capability, an exceedingly high loading capacity (947.8 mg g , 94.78 wt%) for doxorubicin (DOX), and pH-responsive drug release. It exhibits a higher uptake rate by tumor cells and greater accumulation in tumors in a mouse model than its carbon nanosphere counterpart. In addition, the nanodisk absorbs and transforms near-infrared (NIR) light to heat, which enables simultaneous NIR-responsive drug release for chemotherapy and generation of thermal energy for tumor cell destruction. Notably, this NIR-activated dual therapy demonstrates a near complete suppression of tumor growth in a mouse model of triple-negative breast cancer when DOX-loaded nanodisks are administered systemically.
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http://dx.doi.org/10.1002/adhm.201801505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483846PMC
April 2019

Loss of FHIT expression in breast cancer is correlated with poor prognostic markers.

Cancer Epidemiol Biomarkers Prev 2005 Jul;14(7):1681-5

Division of Hematology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard 424, Houston, TX 77030, USA.

Objective: The fragile histidine triad (FHIT) gene is a putative tumor suppressor gene that is thought to be involved in the carcinogenesis of breast cancer. Loss of FHIT expression has been observed in up to 72% of breast cancers and has been associated with increased p53, a high proliferation index, and increased tumor size and grade. However, loss of FHIT expression has not been investigated in association with apoptosis and cyclooxygenase-2 (COX-2) expression in breast cancer. Furthermore, expression of FHIT in primary breast tumors and their metastatic axillary lymph nodes has also not been previously described. The purpose of this study was to evaluate the expression of FHIT, COX-2, bcl-2, and p53 in primary breast tumor tissue; correlate their expression with known clinical and pathologic markers; and in cases when tissue was available, evaluate the expression of FHIT and COX-2 in the corresponding metastatic axillary lymph node in the same patient.

Methods: Primary breast tumor specimens from 80 patients were examined for the presence of FHIT, COX-2, bcl-2, and p53 expression by immunohistochemistry using standard methods. When tissue was available, the expression of FHIT and COX-2 was also evaluated in the corresponding metastatic axillary lymph node specimen.

Results: FHIT expression in primary breast tumors was 56%. There was a significant correlation between FHIT expression in primary breast tumor and bcl-2 expression (P = 0.017). We also observed a significant inverse correlation between FHIT expression in primary breast tumor tissue and p53 expression (P = 0.023) in lymph node-negative cases. A significant inverse correlation between FHIT expression in the primary tumor and Ki-67 (P = 0.009) was also observed in lymph node-negative cases. FHIT expression in primary tumors correlated with FHIT expression in the metastatic lymph node (52.5%; P = 0.001). FHIT expression in primary tumors did not correlate with COX-2 expression.

Conclusion: Our results suggest that loss of FHIT expression in breast cancer is associated with poor prognostic features. Furthermore, loss of FHIT expression is also seen in metastatic axillary lymph node. The prognostic and predictive value of these findings needs to be further evaluated in larger trials with longer follow-up.
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http://dx.doi.org/10.1158/1055-9965.EPI-04-0278DOI Listing
July 2005

Correlation of Bcl-2 and p53 expression in primary breast tumors and corresponding metastatic lymph nodes.

Cancer 2003 Dec;98(12):2554-9

Division of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, Texas 77030, USA.

Background: The p53 tumor suppressor gene product participated in G1 cell cycle arrest or cell death. Loss of function was associated with poor outcome in patients with breast carcinoma. bcl-2 prevented apoptosis induced by c-myc or growth factor deprivation. High bcl-2 expression in breast tumor tissue specimens appears to be associated with favorable prognostic factors. However, Bcl-2 and p53 expression in primary tumor tissue specimens versus metastatic lymph node specimens in breast carcinoma has not been studied. The current study compared Bcl-2 and p53 expression in primary breast carcinoma tissue specimens with Bcl-2 and p53 expression in axillary lymph node specimens.

Methods: Primary breast tumor and corresponding axillary metastatic lymph node tissue specimens were obtained from 60 patients with breast carcinoma. They were evaluated for the presence of Bcl-2 and p53 expression by immunohistochemistry using standard methods.

Results: Bcl-2 expression in primary tumor tissue specimens (53%) was correlated with Bcl-2 expression in metastatic lymph node specimens (50 %; Pearson correlation = 0.656). p53 expression in primary tumor specimens (72%) was correlated with p53 expression in metastatic lymph node specimens (60 %; Pearson correlation = 0.800). A significant inverse correlation also was found between p53 and Bcl-2 expression in primary breast tumor tissue specimens (Pearson correlation = -0.310).

Conclusions: The current study suggested that Bcl-2 and p53 expression in axillary metastatic lymph node specimens is correlated with Bcl-2 and p53 expression in the primary tumor tissue specimens. The prognostic and predictive value of Bcl-2 and p53 expression in axillary lymph node metastasis in patients with breast carcinoma needs to be further evaluated in larger trials with longer follow-up.
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http://dx.doi.org/10.1002/cncr.11853DOI Listing
December 2003
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