• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.94-103
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• 2024

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of fat in the liver, and there is a global increase in its incidence owing to changes in lifestyle and diet. Recent findings suggest that p53 is involved in the development of non-alcoholic fatty liver disease; however, the association between p53 expression and the disease remains unclear. Doxorubicin, an anticancer agent, increases the expression of p53. Therefore, this study aimed to investigate the role of doxorubicin-induced p53 upregulation in free fatty acid (FFA)-induced intracellular lipid accumulation. HepG2 cells were pretreated with 0.5 ㎍/mL of doxorubicin for 12 h, followed by treatment with FFA (0.5 mM) for 24 h to induce steatosis. Doxorubicin pretreatment upregulated p53 expression and downregulated the expression of endoplasmic reticulum stress- and lipid synthesis-associated genes in the FFA -treated HepG2 cells. Additionally, doxorubicin treatment upregulated the expression of AMP-activated protein kinase, a key modulator of lipid metabolism. Notably, siRNA-targeted p53 knockdown reversed the effects of doxorubicin in HepG2 cells. Moreover, doxorubicin treatment suppressed FFA -induced lipid accumulation in HepG2 spheroids. Conclusively, these results suggest that doxorubicin possesses potential application for the regulation of lipid metabolism by enhance the expression of p53 an in vitro NAFLD model.

• BMB Reports
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• v.51 no.11
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• pp.572-577
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• 2018

Recent studies showed that the PD-1/PD-L1 checkpoint blockade is a dramatic therapy for melanoma by enhancing antitumor immune activity. Currently, major strategies for the PD-1/PD-L1 blockade have mainly focused on the use of antibodies and compounds. Seeking an alternative approach, others employ endogenous proteins as blocking agents. The extracellular domain of PD-1 (ePD1) includes the binding site with PD-L1. Accordingly, we constructed a PD-1-based recombinantly tailored fusion protein (dFv-ePD1) that consists of bivalent variable fragments (dFv) of an MMP-2/9-targeted antibody and ePD1. The melanoma-binding intensity and antitumor activity were also investigated. We found the intense and selective binding capability of the protein dFv-ePD1 to human melanoma specimens was confirmed by a tissue microarray. In addition, dFv-ePD1 significantly suppressed the migration and invasion of mouse melanoma B16-F1 cells, and displayed cytotoxicity to cancer cells in vitro. Notably, dFv-ePD1 significantly inhibited the growth of mouse melanoma B16-F1 tumor cells in mice and in vivo fluorescence imaging showed that dFv-ePD was gradually accumulated into the B16-F1 tumor. Also the B16-F1 tumor fluorescence intensity at the tumor site was stronger than that of dFv. This study indicates that the recombinant protein dFv-ePD1 has an intensive melanoma-binding capability and exerts potent therapeutic efficacy against melanoma. The novel format of the PD-L1-blocked agent may play an active role in antitumor immunotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.117-122
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• 2014

Background: Breast cancer is the most common malignancy and the second leading cause of cancer-related death among women in the developed countries. Despite advances in screening, improved local therapies and adjuvant systemic treatments, median survival of metastatic breast cancer patients (MBC) is in the range of 2-3 years at most. We aimed to investigate whether the prognostic factors and therapeutic responses of our Turkish patients are similar to those in the literature. Materials and Methods: We reviewed the medical records of MBC patients who had been treated in our institution between 1999-2009 and analyzed their clinicopathological features and survival outcomes retrospectively Results: A hundred and sixty patients were included. Median age was 47 (23-82), median follow up was 24 (2-186) months. At the time of diagnosis 59% of patients were under the age of 50 and 46% were postmenopausal. The majority (37%) had multiple sites of metastases. Forty percent received endocrine therapy and 40% chemotherapy as first line metastatic treatment. Thirty (20%) patients were treated with molecular targeting agents like trastuzumab, lapatinib and sunitinib, frequently combined with a chemotherapy agent. Five-year overall survival (OS) was 32% and median OS was 38 months for the whole group. Five year progression free survival (PFS) was 10% and median PFS was 10 months. Menopausal status, hormone receptor expression and disease free status had a significant impact on overall survival in the multivariate analysis (p 0.018, p 0.018 and p:0.003, respectively). Conclusions: All our patients were treated with the modern oncologic therapies recommended by the international guidelines. From our data, MBC patients live up to 3-4 years, indicating that further improvement beyond that requires development of new treatment modalities. The survival outcomes of our patients were consistent with the data reported in the literature.

• Journal of Music and Human Behavior
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• v.17 no.1
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• pp.71-96
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• 2020

The purpose of this study was to identify research that included the rhythmic auditory stimulation (RAS) technique and to compare this body of research within the field of music therapy with that in physical therapy. Forty-five studies were identified that were published from January 1999 through November 2018, and these were analyzed in terms of intervention procedure, type of rhythmic cueing, and therapeutic basis described by the researcher. While research in both fields used rhythmic cueing as the primary therapeutic agent, differences were found in the area targeted by training and specific type of rhythmic cueing used. Research conducted in the field of music therapy focused primarily on gait function, while research in the field of physical therapy tended to address gait-related physical issues, such as balance, muscle strength, and proprioceptive sensation as well as gait. While all of the identified studies from the field of music therapy used music for cueing, a metronome was used more often for cueing in physical therapy research. In terms of description of theoretical basis, theory of entrainment was more sufficiently described in music therapy research. These results indicate that while music therapy research maximized the role of various elements of music in intervening in gait function, physical therapy research addressed gait in relation to other physical functions. Considering that both aspects are essential for gait training, this study supports the need for a multidisciplinary approach to neurological rehabilitation with RAS.

• Korean Journal of Microbiology
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• v.43 no.3
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• pp.159-165
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• 2007

For the development of basic genetic materials for specific and effective therapeutic approach to suppress multiplication of hepatitis C virus (HCV), HCV internal ribosome entry site (IRES)-targeting hammerhead ribozyme which activity is allosterically regulated by HCV regulatory protein, NS5B RNA replicase, was developed. The ribozyme targeted most effectively to +382 nucleotide (nt) site of HCV IRES RNA. The allosteric ribozyme was designed to be composed of sequence of RNA aptamer to HCV NS5B, communication module sequence which can transfer structural transition for inducing ribozyme activity upon binding NS5B to the aptamer, and sequence of ribozyme targeting +382 nt of HCV IRES. Noticeably, we employed in vitro selection technology to identify the most appropriate communication module sequence which can induce ribozyme activity depending on the US5B protein. We demonstrated that the ribozyme was nonfunctional either in the absence of any proteins or in the presence of control bovine serum albumin. In sharp contrast, the allosteric ribozyme can induce activity of cleavage reaction with HCV IRES RNA in the presence of the HCV NS5B protein. This allosteric ribozyme can be used as lead compound for specific and effective anti-HCV agent, tool for highthroughput screening to isolate lead chemicals for HCV therapeutics, and ligand for biosensor system for HCV diagnosis.

• Design & Manufacturing
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• v.11 no.2
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• pp.1-8
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• 2017

In this study, we applied microcellular foaming injection molding process to improve the performance of system air-conditioner drain fan which had been produced by injection molding process and studied the optimization of process conditions through 6-sigma process and response surface method (RSM) to reduce weight and deformation of products. Additive type, melt temperature, mold temperature, and injection screw shape were selected as the factor affecting the weight and deformation of the products by carrying out analysis of trivial many through ANOVA and design of experiment (DOE) method. Among the effect factor, we set the addictive type to Long G/F and screw shape to foaming screw which had the highest level of weight reduction and deformation reduction. The amount of foaming agent gas was set at 60 ml, which was the limit beyond which the weight of product did not decrease any more. For melt temperature and mold temperature, we studied the conditions where both weight and deformation were minimized using the RSM. As a result, we set the melt temperature to $250^{\circ}C$, fixed mold temperature to $20^{\circ}C$, and moving mold temperature to $40^{\circ}C$. The improvement effect was analyzed by appling the selected optimal conditions to the production process using the microcellular foaming injection molding. The results showed that the mean weight of product was measured to be 1,420g which was 19% lower than that measured in the current process. The standard deviations of the weights were found to be similar to those in the current process and it showed a low dispersion. The mean deformation was measured to be 0.9237mm, which represented a 57% reduction compared to the mean deformation in the current process, and the standard deviation decreased from 0.3298mm to 0.1398mm. Moreover, we analyzed the process capability for deformation, and the results showed that the short-term process capability increased from 2.73 to 6.60 which was even higher than targeted level of 6.0.

• Journal of Life Science
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• v.34 no.5
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• pp.287-295
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• 2024

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide, necessitating novel therapeutic strategies. The chemotherapeutic agents used to treat HCC patients are toxic and have serious side effects. Therefore, we investigated the efficacy of anticancer drugs that reduce side effects by targeting tumor cells without causing cytotoxicity in healthy hepatocytes. Berberine, an isoquinoline alkaloid derived from plant compounds, has emerged as a potential candidate for cancer treatment due to its diverse pharmacological properties. The effect of berberine on HepG2 cell viability was determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay. HepG2 cell proliferation was determined through a colony-forming assay. The effects of berberine on HepG2 cell migration were evaluated using a wound-healing assay. Berberine inhibited the proliferation of HepG2 cells, as well as colony formation and migration. Berberine treatment increased the expression of autophagy-related genes and proteins, including Beclin-1 and LC3-II, and elevated the activities and mRNA expression of Caspase-9 and Caspase-3. Additionally, in experiments utilizing the Cell-Derived Xenograft animal model, berberine treatment reduced tumor size and weight in a concentration-dependent manner. These results demonstrate the potential of berberine as a versatile anticancer agent with efficacy in both cellular and animal models of hepatocellular carcinoma. The findings herein shed light on berberine's efficacy against HCC, presenting opportunities for targeted and personalized therapeutic interventions.

• Journal of Oral Medicine and Pain
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• v.36 no.1
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• pp.11-20
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• 2011

Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent. And it is known that antitmor activity of VPA is associated with its targeted at histone deacetylases. 17AAG, Inhibition of HSP90 leads to the proteasome degradation of the HSP90 client proteins, such as Akt, Raf/Ras, Erk, VEGF, cyclin D and p53, and causes potent antitumor activity. It is reported that 17AAG-induced HSP90 inhibition results in prevention of cell proliferation and induction of apoptosis in several types of cancer. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and the HSP90 inhibitor, 17AAG on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and 17AAG showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-3, caspase-7 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or 0.5 ${\mu}M$ 17AAG for 48 h did not induce apoptosis, the co-treatment with them induced prominently apoptosis. Therefore our data in this study provide the possibility that combination therapy with VPA and 17AAG could be considered as a novel therapeutic strategy for human osteosarcoma.

• The Korean Journal of Nuclear Medicine
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• v.32 no.6
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• pp.516-524
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• 1998

Purpose: Radiolabeled CEA79.4 antibody has a possibility to be used in radioimmunoscintigraphy or radioimmunotherapy of cancer. We investigated the in vitro properties and biodistribution of CEA79.4 antibody labeled with Re-188 or Tc-99m. Materials and Methods: CEA79.4 was reduced by 2-mercaptoethanol to produce-SH residue, and was labeled with Re-188 or Tc-99m. For direct labeling of Tc-99m, methylene-diphosphonate was used as transchelating agent. CEA79.4 in 50 mM Acetate Buffered Saline (ABS, pH 5.3) was labeled with Re-188, using stannous tartrate as reducing agent. In order to measure immunoreactivity and the affinity constant of radiolabeled antibody, cell binding assay and Scatchard analysis using human colon cancer cells SNU-C4, were performed. Biodistribution study of labeled CEA79.4 was carried out at 1, 14 and 24 hr in ICR mice. Results: Labeling efficiencies of Tc-99m and Re-188 labeled antibodies were $92.4{\pm}5.9%$ and $84.7{\pm}4.6%$, respectively, In vitro stability of Tc-99m-CEA79.4 in human serum was higher than Re-188-CEA79.4. Immunoreactivity and affinity constant of Tc-99m-CEA79.4 were 59.2% and $6.59{\times}10^9\;M^{-1}$, respectively, while those of Re-188-CEA79.4 were 41.6% and $4.2{\times}10^9\;M^{-1}$, respectively. After 24 hr of administrations of Re-188 and Tc-99m labeled antibody, the remaining antibodies in blood were 6.32 and 9.35% ID/g respectively. The biodistribution of each labeled antibody in other organs was similar because they did not accumulate in non-targeted organs. Conclusion: In vitro properties and biodistribution of Re-188-CEA79.4 were similar to those of Tc-99m-CEA79.4. It appears that Re-188-CEA79.4 can be used as a suitable agent for radioimmunotheraphy.