• Mass Spectrometry Letters
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• v.13 no.3
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• pp.84-94
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• 2022

Neoadjuvant chemoradiotherapy (nCRT) is a standard therapy used for locally advanced rectal cancer prior to surgery, which can more effectively reduce the locoregional recurrence rate and radiation toxicity compared to postoperative chemoradiotherapy. The response of patients to nCRT varies, and thus, robust biomarkers for predicting a pathological complete response are necessary. This study aimed to identify possible biomarkers involved in the complete response/non-response of rectal cancer patients to nCRT. Comparative proteomic analysis was performed on rectal tissue samples before and after nCRT. Proteins were extracted for label-free proteomic analysis. Western blot and real-time PCR were performed using rectal cancer cell line SNU-503 and radiation-resistant rectal cancer cell line SNU-503R80Gy. A total of 135 up- and 93 down-regulated proteins were identified in the complete response group. Six possible biomarkers were selected to evaluate the expression of proteins and mRNA in SNU-503 and SNU-503R80Gy cell lines. Lyso-phosphatidylcholine acyltransferase 2, annexin A13, aldo-ketose reductase family 1 member B1, and cathelicidin antimicrobial peptide appeared to be potential biomarkers for predicting a pathological complete response to nCRT. This study identified differentially expressed proteins and some potential biomarkers in the complete response group, which would be further validated in future studies.

• BMB Reports
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• v.55 no.10
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• pp.506-511
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• 2022

Advanced hepatocellular carcinoma (HCC) is among the most challenging cancers to overcome, and there is a need for better therapeutic strategies. Among the different cancer drugs that have been used in clinics, sorafenib is considered the standard first-line drug for advanced HCC. Here, to identify a chemical compound displaying a synergistic effect with sorafenib in HCC, we screened a focused chemical library and found that MG149, a histone acetyltransferase inhibitor targeting the MYST family, exhibited the most synergistic anticancer effect with sorafenib on HCC cells. The combination of sorafenib and MG149 exerted a synergistic anti-proliferation effect on HCC cells by inducing apoptotic cell death. We revealed that cotreatment with sorafenib and MG149 aggravated endoplasmic reticulum (ER) stress to promote the death of HCC cells rather than adaptive cell survival. In addition, combined treatment with sorafenib and MG149 significantly increased the intracellular levels of unfolded proteins and reactive oxygen species, which upregulated ER stress. Collectively, these results suggest that MG149 has the potential to improve the efficacy of sorafenib in advanced HCC via the upregulation of cytotoxic ER stress.

• Journal of Life Science
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• v.33 no.9
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• pp.724-729
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• 2023

In this experiment, we aimed to investigate the role of copper in regulating the biosynthesis of a myokine called apelin in mammalian skeletal muscle cells. Our approach involved culturing skeletal muscle cells and subjecting them to treatments with copper sulfate or a copper chelator known as bathocuproinedisulfonic acid (BCS). We employed standard techniques, such as reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, to assess the synthesis of apelin at different stages, including transcription, translation, and post-translational modifications. Our findings demonstrated that copper had an inhibitory effect on apelin biosynthesis at all three stages: transcription, translation, and post-translation. However, when we treated the cells with BCS, the biosynthesis of apelin was restored to its original state. This finding suggests that copper is required for the synthesis of apelin in mammalian skeletal muscle cells. This study represents the first documented evidence of the inorganic copper-dependent regulation of apelin biosynthesis, shedding light on potential strategies for the prevention and treatment of sarcopenia induced by copper imbalances.

• Archives of Plastic Surgery
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• v.50 no.4
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• pp.377-383
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• 2023

Background Squamous cell carcinoma (SCC) is the most common malignancy on the lower lip. Surgical excision, the standard treatment for SCC, requires full-thickness excision. However, no consensus exists about the appropriate surgical margin. Therefore, we investigated the appropriate surgical margin and excision technique by analyzing 23 years of surgical experience with lower-lip SCC. Methods We reviewed 44 patients with lower-lip SCC who underwent surgery from November 1997 to October 2020. Frozen biopsy was performed with an appropriate margin on the left and right sides of the lesion, and the margin below the lesion was the skin above the sulcus boundary. If the frozen biopsy result was positive, an additional session was performed to secure a negative margin. Full-thickness excision was performed until the final negative margin. In each patient, the total number of sessions performed, final surgical margin, and recurrence were analyzed. Results Forty-one cases ended in the first session, 2 ended in the second session, and 1 ended in the third session. The final surgical margins (left and right; n = 88) were 5 mm (66%), 7 mm (9%), 8 mm (2.3%), 10 mm (20.4%), and 15 mm (2.3%). During an average follow-up of 67.4 months (range, 12-227 months), recurrence occurred in one patient. Conclusion The final surgical margin was 5 mm in 66% (58/88) of the cases, and 97.7% (86/88) were within 10 mm. Therefore, we set the first frozen biopsy margin to 5 mm, and we suggest that a 5-mm additional excision is appropriate when frozen biopsy results are positive.

• Korean Journal of Veterinary Research
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• v.32 no.2
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• pp.157-164
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• 1992

Changes in the both inward current and conductance of membrane by the fertilization were observed using the one microelectrode voltage clamp(or switch clamp) technique. Unfertilized eggs and both 1- and 2-cell stage eggs after fertilization were donated from the superovulated mouse (ICR, more than 6 weeks old) treated with PMSG(pregnant mare serum gonadotropin, Sigma) and HCG(human chorionic gonadotropin, Sigma) and naturally mated ones, respectively in this experiment. Membrane potential was held at -90mV and the voltage step was applied from -80mV to 50mV with interval of 10mV or 20mV for 300ms. since both of amplitudes and time courses in the membrane currents were various according to the states of cells and clamping condition, results were presented by their $averages{\pm}SEM$(standard mean error)and ratios or percentages. Inward currents began to appear in response to the step depolarization from -60mV and reached its maximum at -50mV. However, since the potential was not clamped evenly during the voltage step, current-voltage(I-V) relationship might be positively shifted 10 or 20mV. From the steady-state currents plotted in the I-V curve, outward rectification was markedly observed. Peak inward currents$(i_{in})$ at -50mV were $-0.62{\pm}0.23nA$(n=4),$-0.52{\pm}0.25nA$(n=5) and $-0.37{\pm}0.25nA$(n=6), in the 1-cell stage, 2-cell stage fertilized eggs and in the unfertilized eggs, respectively. Pure inward current (difference between steady-state and peak, $i_{in. pure}$) were $-1.01{\pm}0.23nA$, $-0.69{\pm}0.43nA$ and $-0.68{\pm}0.29nA$, respectively in the 1-cell stage fertilized eggs, unfertilized eggs and 2-cell stage fertilized eggs. These results suggested that the outward current in fertilized eggs of 2-cell stage was more increased than those in the unfertilized eggs. Pure inward currents in the all stages of eggs showed a similar fashion in the I-V relationship from -50mV to 50mV and reversal potential at 50mV. Time constant of inactivation$({\tau})$ in the inward current was decreased as the membrane potential was depolarized in the unfertilized and 2-cell stage eggs but in the 1-cell stage eggs t was not likely to be affected significantly. Slope conductances were 14.2nS, 8.9n5 and 7.7nS in the 1-cell, 2-cell stage fertilized eggs and the unfertilized eggs, respectively. Membranes between two cells within a zona pellucida seem to be electrical-connected in the 2-cell stage eggs from the observation made in the analysis for the electronic spread and decay to the current stimuli. Both of inward current and membrane conductance were increased after fertilization in the mouse eggs. Inward current seems to be carried by the same ion or through the same channels up to the 2-cell stage and ion that carried inward current was thought to play important function after fertilization in the mouse eggs.

• The Korean Journal of Nuclear Medicine Technology
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• v.13 no.3
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• pp.171-174
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• 2009

Purpose: Cancerous death rate 1 place from 2008 year domestic is the lung cancer. The body count which is caused by in the lung cancer every year is increasing. At this lung cancer is the most non small cell lung cancer. $Monototal^{TM}$ test is short reaction time. it is known as the experiment where the example standard of living is high about non small cell lung cancer. This is the study evaluate usefulness of $Monototal^{TM}$ kit. Materials and Methods: $Monototal^{TM}$ were measured using IRMA kit, using 40 CEA positive patients sample which are diagnosed NSCLC, 15 SCC positive patients sample which are diagnosed NSCLC, 40 Cyfra 21-1 positive sample, 20 negative sample in Seoul national university from March to April, 2009. Results: According to result of the $Monototal^{TM}$ test, which is benignancy rate 87.5% in CEA positive patients sample, 93.3% SCC positive patients sample and 100% Cyfra 21-1 positive sample Conclusions: We recommend that using of $Monototal^{TM}$ parallel with different tumor markers. It was useful that diagnosis and convalescence presumption of Non small cell lung cancer.

• Journal of Pharmaceutical Investigation
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• v.33 no.2
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• pp.145-149
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• 2003

Manufacturing facilities of the pharmaceuticals must meet certain level of the cleanness required so that foreign substances such as dust, moisture, heat, microorganism, or virus do not contaminate the product. In case of radiopharmaceuticals for medical treatment and diagnosis, not only should the operators and environment be protected from radiation but also need to be isolated from the foreign contaminant. Therefore, manufacturing facilities for radiopharmaceuticals must satisfy the design standards of both hot cell and clean room which are specified by GMP. However, standards of maintaining negative pressure for preventing spread of radioactive contaminant in isolated facilities conflict with the standards of maintaining positive pressure for keeping cleanness. To solve this problem, air pressure of hot cell was designed lower than in the adjacent area to meet standards of the radiation safety. To keep higher cleanness in certain part of the hot cell for filling, minimal relative positive pressure allows. In order to effectively maintain the cleanness that is required for production of Tc-99m generator, which takes 70% of whole demand of radiopharmaceuticals, the rooms placed in each side of production room are used as a buffer area and three lead hot cells are installed in production room. In this research, we established the appropriate engineered design concept for Tc-99m generator manufacturing facility, which satisfies both GMP cleanness standard for preventing particles, bacteria, other contaminants and the regulations of radiation safety for supervising and controlling the amount of radiation exposure and exhausted radioactivity. And the concept of multi-barrier buffer zones is introduced to apply negative air pressure for hot cell with first priority and to continue relative positive air pressure for clean room.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.551-557
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• 2015

Background: Differentiating morphologic features based on hematoxylin-eosin (HE) staining is the most common method to classify pathological subtypes of non-small-cell lung cancer (NSCLC). However, its accuracy and inter-observer reproducibility in pathological diagnosis of poorly differentiated NSCLC remained to be improved. Materials and Methods: We attempted to explore the role of immunohistochemistry (IHC) staining in diagnosing pulmonary squamous cell carcinoma (SQCC) with poorly differentiated features by HE staining or with elevated serum adenocarcinoma-specific tumor markers (AD-TMs). We also compared the difference of epidermal growth factor receptor (EGFR) mutation rate between patients with confirmed SQCC and those with revised pathological subtype. Logistic regression analyses were used to test the association between different factors and diagnostic accuracy. Results: A total of 132 patients who met the eligible criteria and had adequate specimens for IHC confirmation were included. Pathological revised cases in poor differentiated subgroup, biopsy samples and high-level AD-TMs cases were more than those with high/moderate differentiation, surgical specimens and normal-level AD-TMs. Moreover, biopsy sample was a significant factor decreasing diagnostic accuracy of pathological subtype (OR, 4.037; 95% CI 1.446-11.267, p=0.008). Additionally, EGFR mutation rate was higher in patients with pathological diagnostic changes than those with confirmed SQCC (16.7% vs 4.4%, p=0.157). Conclusions: Diagnosis based on HE staining only might cause pathological misinterpretation in NSCLC patients with poor differentiation or high-level AD-TMs, especially those with biopsy samples. HE staining and IHC should be combined as pathological diagnostic standard. The occurrence of EGFR mutations in pulmonary SQCC might be overestimated.

• Journal of the Korean Applied Science and Technology
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• v.32 no.1
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• pp.108-115
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• 2015

Vinca alkaloid compounds including vincamine from Vinca minor L. have been extracted by ethanol and hot water extraction methods. Antimicrobial properties of those extracts have been investigated against dandruff causing microorganism Malassezia furfur, yeast, Gram positive and negative bacteria. Vincamine standard and ethanol extract showed no sign of antimicrobial activity, whereas hot-water extract had the activity against M. furfur. Furthermore hot water extract had antimicrobial activity against Gram positive Bacillus sp. and Gram negative Escherichia coli. Cytotoxic properties of those extracts have also been investigated with HaCaT cell (human keratinocyte), HT-29 cell (human colorectal adenocarcinoma cell) and Raw cell, showing no significant cytotoxic effects. We also measured the ROS using dichlorofluorescein diacetate (DCFDA), a popular fluorescence-based probe for reactive oxygen species detection. The result showed the increasement of reactive oxygen species formation (20%) in HaCaT and HT-29 cell lines.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.2
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• pp.103-109
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• 2005

In spite of the ongoing advances, standard therapies for oral cancer still has some limitations in efficacy and in ability to prolong survival rate of advanced disease and result in significant functional defect and severe cosmetic deformity. Currently gene therapy using tumor suppressor gene is considered as a potent candidate for new therapeutic approaches that can improve efficacy and reduce complications. The purpose of this research is to identify the role of adenoviral vector to transfer HCCS-1 tumor suppressor gene in oral cancer cells and to find out whether there is a possibility for it to serve in the field of gene therapy. The human SCC-25 cell line was used for transfection. To determine the efficiency of the adenovirus as a gene delivery vector cell line was transduced with LacZ gene and analysed with X-gal staining. Northern blot was performed to confirm the tranfection with HSCC-1 gene and cell viability was assessed by cell cytotoxicity assay. We had successfully construct the recombinant HSCC-1 adenovirus(Ad5CMV-HCCS-1). DNA extracted from Ad5CMV-HCCS-1 revealed HCCS-1 gene is incorporated. The transduction efficiencies were over than 50% of SCC-25 cells with a MOI of 2 and over 95% with a MOI of 50. Northern blot analysis showed that a single 0.6kb mRNA transcript was expressed in Ad5CMV-HCCS-1 transduced SCC-25 cells. There was no or very low transcription HCCS-1 mRNA in wild and Ad5CMV-LacZ transduced SCC-25 cells. Cells transduced with Ad5CMV-HCCS-1 showed significant growth inhibition. By day 6, Ad5CMV-HCCS-1 treated cell count was decreased to 30% of mock-infected cells, while that of Ad5CMV-LacZ treated cells was 90% of mock-infected cells (p<0.05). Finally, these result suggest that the Ad5CMV-HCCS-1 has potential as a gene therapy tool for oral cancer.