• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9355-9360
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• 2014

Background: Oral squamous cell carcinoma (OSCC) remains as one of the most difficult malignancies to control because of its high propensity for local invasion and cervical lymph node dissemination. In this study, we evaluate the efficacy of our novel pH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting HER2 expression profile in OSCC model in rat. Results: DOX-MTX- nanoparticle complexes caused significant decrease in mRNA level of HER2 compared to untreated cancers (p<0.05) and this finding was more pronounced with the IV mode (p<0.000). Surprisingly, HER2 mRNA was not affected in DOX treated as compared to the control group (p>0.05). On the other hand, in the DOX-MTX NP treated group, fewer tumors characterized with advanced stage and decreased HER2 paralleled improved clinical outcome (P<0.05). Moreover, the effectiveness of the oral route in the group treated with nanodrug accounted for the enhanced bioavailability of nanoparticulated DOX-MTX compared to free DOX. Furthermore, there was no significant difference in mRNA level of HER2 (p>0.05). Conclusions: Influence of HER2 gene expression is a new feature and mechanism of action observed only in dual action DOX-MTX-NPs treated groups. Down-regulation of HER2 mRNA as a promising marker and prognosticator of OSCC adds to the cytotoxic benefits of DOX in its new formulation. Both oral and IV application of this nanodrug could be used, with no preferences in term of their safety or toxicity. As HER2 is expressed abundantly by a wide spectrum of tumors, i DOX-MTX NPs may be useful for a wide-spectrum of lesions. However, molecular mechanisms underlying HER2 down regulation induced by DOX-MTX NPs remain to be addressed.

• Journal of the Korean Chemical Society
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• v.52 no.1
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• pp.57-65
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• 2008

are nanometer or micrometer scale vesicles that can be used as drug delivery carriers. However, plain liposomes are plagued by rapid opsonization, making their circulation time in bloodstream be shortened. In this study, model protein, bovine serum albumin (BSA)-coated liposomes were prepared by coating cationic liposomes with BSA molecules at higher pH than isoelectric point of BSA. The BSA molecules coated on the liposomal surface were denatured by thermal treatment at above 60oC. While both plain and cationic liposomes had about mean particle diameter of 1041 nm, BSA-coated cationic liposomes (BCL) had mean particle diameter of 1091 nm. Encapsulation of model drug, doxorubicin (DOX), in liposomes were carried out by using remote loading method and the loading efficiency of DOX to liposomes was about 90%. The mean particle diameter of BCL did not increase in blood plasma and adsorption of plasma protein was much less than plain or cationic liposomes. These results suggest that BCL can be used as a long-circulating liposomes in bloodstream.

• Journal of Pharmacopuncture
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• v.22 no.1
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• pp.28-34
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• 2019

Background: Breast cancer is a complex, heterogeneous disease and one of the most common malignancies in women worldwide. The efficacy of chemotherapy as an important breast cancer treatment option has been severely limited because of the inherent or acquired resistance of cancer cells. The molecular chaperone heat shock protein 90 (HSP90) upregulated in response to cellular stress is required for functions such as conformational maturation, activation and stability in more than 200 client proteins, mostly of the signaling type. In this study, the expression of HSP90 isoforms including $HSP90{\alpha}$ and $HSP90{\beta}$ in breast cancer cell lines before and after treatment with doxorubicin (DOX) was assessed. Material and Methods: The cell cytotoxicity of DOX in MDA-MB-231 and MCF-7 cell lines was determined using the MTT assay. immunofluorescence and western blotting techniques were used to determine the expression of $HSP90{\beta}$ in the cell lines before and after DOX treatment. Immunofluorescence was also conducted to ascertain the expression of $HSP90{\alpha}$. Results: The MTT assay results showed that the MDA-MB-231 cells ($IC_{50}=14.521{\mu}M$) were more sensitive than the MCF-7 cells ($IC_{50}=16.3315{\mu}M$) to DOX. The immunofluorescence results indicated that the expression of $HSP90{\alpha}$ in both cell lines decreased after exposure to DOX. The western blot and immunofluorescence analyses showed that $HSP90{\beta}$ expression decreased in the MCF-7 cells but increased in the MDA-MB-231 cells after DOX treatment. Conclusion: The obtained results suggested that $HSP90{\alpha}$ and $HSP90{\beta}$ expression levels were reduced in the MCF-7 cells after exposure to DOX. In the MDA-MB-231 cells, $HSP90{\alpha}$ expression was reduced while $HSP90{\beta}$ was found to be overexpressed following DOX treatment.

• Korean Journal of Oriental Medicine
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• v.18 no.1
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• pp.75-84
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• 2012

Objective : The purpose of this study was to investigate the anti-cancer effects of Sophorae Radix and the effects of Doxorubicin (DOX) in human breast adenocarcinoma cells (MCF-7). Method : We used human breast adenocarcinoma cell line, MCF-7 cells. We examined cell death by MTT assay and caspase 3 assay with Sophorae Radix. To examine the inhibitory effects of Sophorae Radix, cell cycle analysis was done the MCF-7 cells after three days with Sophorae Radix. The reversibility of Sophorae Radix was examined on one day to five days treatment with 100 ${\mu}g/ml$ Sophorae Radix. Result : Sophorae Radix inhibited the growth of MCF-7 cells in a dose-dependent fashion. Also we showed that Sophorae Radix induced apoptosis in MCF-7 cells by MTT assay, caspase 3 assay and sub-G1 analysis. Sophorae Radix combined with DOX markedly inhibited the growth of MCF-7 cells compared to Sophorae Radix or DOX alone. After 3 days treatment of MCF-7 cells with Sophorae Radix, the fraction of cells in sub-G1 phase was much higher than that of the control group. Conclusion : Our findings provide insight into unraveling the effects of Sophorae Radix in human breast adenocarcinoma cells and developing therapeutic agents against breast cancer.

• BMB Reports
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• v.54 no.9
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• pp.470-475
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• 2021

Low-dose metronomic chemotherapy has been introduced as a less toxic and effective strategy to inhibit tumor angiogenesis, but its anti-angiogenic mechanism on endothelial progenitor cells (EPCs) has not been fully elucidated. Here, we investigated the functional role of regulated in development and DNA damage response 1 (REDD1), an endogenous inhibitor of mTORC1, in low-dose doxorubicin (DOX)-mediated dysregulation of EPC functions. DOX treatment induced REDD1 expression in bone marrow mononuclear cells (BMMNCs) and subsequently reduced mTORC1-dependent translation of endothelial growth factor (VEGF) receptor (Vegfr)-2 mRNA, but not that of the mRNA transcripts for Vegfr-1, epidermal growth factor receptor, and insulin-like growth factor-1 receptor. This selective event was a risk factor for the inhibition of BMMNC differentiation into EPCs and their angiogenic responses to VEGF-A, but was not observed in Redd1-deficient BMMNCs. Low-dose metronomic DOX treatment reduced the mobilization of circulating EPCs in B16 melanoma-bearing wild-type but not Redd1-deficient mice. However, REDD1 overexpression inhibited the differentiation and mobilization of EPCs in both wild-type and Redd1-deficient mice. These data suggest that REDD1 is crucial for metronomic DOX-mediated EPC dysfunction through the translational repression of Vegfr-2 transcript, providing REDD1 as a potential therapeutic target for the inhibition of tumor angiogenesis and tumor progression.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.351.2-351.2
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• 2002

We have previously reported the synthesis and cytotoxic activities of a series of azaanthraquinone derivatives on the model of doxorubicin(Dox). Dox is known to intercalate into DNA and to inhibit topoisomerase II activity. But in the case of Quinone compounds like Dox. its use is limited because of systemic toxicities. primarily cardiotoxicity and myelosuppression. In this study. we describe the synthesis of benzoquinoxaline derivatives as DACA analogue. DACA has a neutral chromophore and acridine moiety and posions both topoisomerases I and ll with DNA intercalating activity. In order to delineate the SAR of benzoquinoxaline derivatives. an effcient sythetic rout to the target compounds without quinone group. Various attempted removal of quinone from benzoquinoxlinedione was unsuccessful. Diels-Alder rout applied for the synthesis of the target compounds will be discussed.

• Journal of Sensor Science and Technology
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• v.32 no.6
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• pp.412-417
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• 2023

There is increasing interest in the rapid and highly sensitive monitoring of cell viability in biological and toxicological research. Conventional methods depend on optical assays using Water Soluble Tetrazolium-8 (WST-8) or 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay, which requires a large volume of samples and special instruments, necessitating shipment of clinical samples to laboratories. This paper reports on the development of a rapid and sensitive electrochemical (EC) sensor using screen printed electrode (SPE) and surface modification using 4'-mercapto-N-phenylquinone diamine (4'-NPQD), as double electron mediators, for monitoring cell viability via the measurement of nicotinamide adenine dinucleotide (NADH). We used the sensor to observe the viability of MCF-7 and doxorubicin (Dox)-treated cells. The oxidation current of NADH was measured via chronoamperometry (CA), and the EC results showed a good linear relationship when compared with NADH quantification using WST-8 assay. The analysis time was only 10 s and limit of detection (LOD) of NADH was 1.78 µM. Our EC method has the potential to replace conventional WST assays for cell viability and cytotoxicity experiments.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1145-1148
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• 2014

Background: Single pegylated liposomal doxorubicin (PLD) is commonly used as a salvage treatment in platinum-resistant ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma (PPA) with a satisfactory outcome. However, the data for second generation PLD administered in this setting are still limited. We conducted a retrospective study to evaluate the outcome of patients who received single-agent second generation PLD (LIPO-DOX) after the development of clinical platinum resistance. The study period was between March 2008 and March 2013. LIPO-DOX was administered intravenously 40 $mg/m^2$ every 28 days until disease progression, but for not more than six cycles. The response rate was evaluated using the Gynecologic Cancer Intergroup (GCIG) criteria while the toxicity was evaluated according to WHO criteria. Twenty-nine patients met the inclusion criteria in the study period with an overall response rate of 13.8%. The median progression free survival and overall survival were three and eleven months, respectively. With the total of 96 cycles of chemotherapy, the patients developed grades 3 and 4 hematologic toxicity as follows: anemia, 0%, leukopenia, 9.6%, neutropenia, 32.3% and thrombocytopenia, 0%. In conclusion, the single agent second generation PLD demonstrated modest efficacy in patients with platinum-resistant ovarian cancer, fallopian tube cancer and PPA without serious toxicity.

• Biomedical Science Letters
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• v.27 no.1
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• pp.1-11
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• 2021

Cancer stem cells, which are known to drive tumor formation and maintenance, are a major obstacle in the effective treatment of various types of cancer. Trans-membrane glycoprotein mucin 1 antigen and cell surface glycogen CD44 antigen are well-known surface markers of breast cancer cells and breast cancer stem cells, respectively. To effectively treat cancer cells and cancer stem cells, we developed a new drug-encapsulating liposome conjugated with dual-DNA aptamers specific to the surface markers of breast cancer cells and their cancer stem cells. These two aptamer (Apt)-targeted liposomes, which were prepared to encapsulate doxorubicin (Dox), were named "Dual-Apt-Dox". Dual-Apt-Dox is significantly more cytotoxic to both cancer stem cells and cancer cells compared to liposomes lacking the aptamers. Furthermore, we demonstrated the inhibitory efficacy of Dual-Apt-Dox against the experimental lung metastasis of breast cancer stem cells and cancer cells in athymic nude mice. We also showed the potent antitumor effects of dual-aptamer-conjugated liposome systems by targeting cancer cells as well as cancer stem cells. Thus, our data indicate that dual-aptamer-conjugated liposome systems can prove to be effective drug delivery vehicles for breast cancer therapy.

• Journal of Pharmacopuncture
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• v.15 no.2
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• pp.15-19
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• 2012

The purpose of this study was to investigate the anti-cancer effects of Sophorae Radix (SR) and doxorubicin (DOX) in human gastric and colorectal adenocarcinoma cells. We used the human gastric and colorectal adenocarcinoma cell lines (MKN-45 and WIDR cells, respectively). We examined cell death by using the MTT(3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay and the caspase 3 assay with SR. To examine the inhibitory effects of SR, we performed a cell cycle (sub G1) analysis for the MKN-45 and WIDR cells after three days with SR. The reversibility of SR was examined for one-day to five-day treatments with SR. SR inhibited the growth of MKN-45 and WIDR cells in a dosedependent manner. Also, we showed that SR induced apoptosis in MKN-45 and WIDR cells by using the MTT assay, the caspase 3 assay and the sub-G1 analysis. SR combined with DOX markedly inhibited the growth of MKN-45 and WIDR cells compared to SR or DOX alone. After 3 days of treating MKN-45 and WIDR cells with SR, the fraction of cells in the sub-G1 phase was much higher than that of the control group. Our findings provide insights into unraveling the effects of SR on human gastric and colorectal adenocarcinoma cells and into developing therapeutic agents for use against gastric and colorectal adenocarcinomas.