• Oncology Letters
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• v.18 no.6
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• pp.6852-6868
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• 2019

There is a wide disparity in the incidence, malignancy and mortality of different types of cancer between each sex. The sex-specificity of cancer seems to be dependent on the type of cancer. Cancer incidence and mortality have been demonstrated as sex-specific in a number of different types of cancer, such as liver cancer, whereas sex-specificity is not noticeable in certain other types of cancer, including colon and lung cancer. The present study aimed to elucidate the molecular basis for sex-biased gene expression in cancer. The mRNA expression of the epithelial-to-mesenchymal transition-associated genes was investigated, including E-cadherin (also termed CDH1), vimentin (VIM), discoidin domain receptor 1 (DDR1) and zinc finger E-box binding homeobox 1 (ZEB1) in female- and male-derived cancer cell lines by reverse transcription (RT)-PCR and the Broad-Novartis Cancer Cell Line Encyclopedia (CCLE) database analysis. A negative correlation was observed between DDR1 and ZEB1 only in the female-derived cancer cell lines via RT-PCR analysis. A negative correlation between DDR1 index (defined by the logarithmic value of DDR1 divided by ZEB1, based on the mRNA data from the RT-PCR analysis) and an invasive phenotype was observed in cancer cell lines in a sex-specific manner. Analysis of the CCLE database demonstrated that DDR1 and ZEB1, which are already known to be sex-biased, were negatively correlated in female-derived liver cancer cell lines, but not in male-derived liver cancer cell lines. In contrast, cell lines of colon and lung cancer did not reveal any sex-dependent difference in the correlation between DDR1 and ZEB1. Kaplan-Meier survival curves using the transcriptomic datasets such as Gene Expression Omnibus, European Genome-phenome Archiva and The Cancer Genome Atlas databases suggested a sex-biased difference in the correlation between DDR1 expression pattern and overall survival in patients with liver cancer. The results of the present study indicate that sex factors may affect the regulation of gene expression, contributing to the sex-biased progression of the different types of cancer, particularly liver cancer. Overall, these findings suggest that analyses of the correlation between DDR1 and ZEB1 may prove useful when investigating sex-biased cancers.

• International Journal of Stem Cells
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• v.15 no.3
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• pp.258-269
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• 2022

Background and Objectives: Currently, safety pharmacological tests for the central nervous system depend on animal behavioral analysis. However, due to the subjectivity of behavioral analysis and differences between species, there is a limit to appropriate nervous system toxicity assessment, therefore a new neurotoxicity assessment that can simulate the human central nervous system is required. Methods and Results: In our study, we developed an in vitro neurotoxicity assessment focusing on neuronal function. To minimize the differences between species and fast screening, hiPSC-derived neurons and a microelectrode array (MEA) that could simultaneously measure the action potentials of the neuronal networks were used. After analyzing the molecular and electrophysiological characters of our neuronal network, we conducted a neurotoxicity assessment on neurotransmitters, neurotoxicants, illicit drugs, and new psychoactive substances (NPS). We found that most substances used in our experiments responded more sensitively to our MEA-based neurotoxicity assessment than to the conventional neurotoxicity assessment. Also, this is the first paper that evaluates various illicit drugs and NPS using MEA-based neurotoxicity assessment using hiPSC-derived neurons. Conclusions: Our study expanded the scope of application of neurotoxicity assessment using hiPSC-derived neurons to NPS, and accumulated evaluation data of various toxic substances for hiPSC-derived neurons.

• The Korean Journal of Physiology
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• v.19 no.1
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• pp.15-23
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• 1985

Previous biochemical studies indicate that $(Na^++K^+)-ATPase$ is composed of two subunits, ${\alpha}$ and ${\beta}$, in a form of ${\alpha}_2{\beta}_2$ with a molecular weight of approximately 300,000 daltons. There is also suggestive evidence that the $Na^+$, $K^+$ pump in human erythrocytes occurs in a complex with some glycolytic enzymes. We assessed here in situ assembly size of the $(Na^++K^+)-ATPase$ of human erythrocytes by applying classical target theory to radiation inactivation data of the ouabain-sensitive sodium flux and ATP hydrolysis of intact cells and ghosts. Cells(in the presence of cryoprotective agent) and ghosts were irradiated at $-45^{\circ}C$ to $-50^{\circ}C$ with an increasing dose of a 1.5 MeV electron beam, and after thawing, the pump and/or enzyme activities were assayed. Each activity measured was decreased as a simple exponential function of radiation dose, from which a radiation sensitive volume (target size) was calculated. When intact cells were used, the target size of both $(Na^++K^+)-ATPase$ and $Na^+$, $K^+$ pump was found to be approximately 600,000 daltons. This target size of the ATPase was reduced to approximately 325,000 daltons if the cells were pretreated with strophanthidin. When ghosts were used, the target size of the ATPase was again approximately 325,000 daltons. Our target size measurement suggests that, in intact cells, the $(Na^++K^+)-ATPase/Na^+,K^+$ pump exists either as a dimer of $(\alpha\beta)_2$ which is a functional unit or as a monomer of $(\alpha\beta)_2$ but in tight complex with other enzyme or enzymes. The results also suggest that this dimeric or heterocomplex association is dissociated during ghost preparation and strophanthidin treatment.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.6
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• pp.464-468
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• 2008

Purpose: Effective half life of I-131 ($T_{eff}$) in patients with differentiated thyroid cancer treated by I-131 is must-know value for dose calculation and determination of release time from isolation room. There has been no report about $T_{eff}$ in Koreans. Thus, author tried to measure dose rate without radiation exposure to faculty members and calculated $T_{eff}$. Methods: Probe of radiation survey meter was fixed at the wall of isolation room, and body of survey meter was placed outside the room. With this simple arrangement, author could measure radiation frequently without radiation exposure to faculty members in 68 patient (F=55, M=13, age=$47{\pm}13.7$) treated by I-131 ($3.7{\sim}7.4\;GBq$) for differentiated thyroid cancer from Jan 2006 to Dec 2006. From this data, $T_{eff}$, 48 hr retention rate, and the time necessary to whole body retention of I-131 become less than 1.1 GBq were calculated. Serum creatinine levels were measured before and after thyroid hormone withdrawal. Results: $T_{eff}$ was $15.4{\pm}4.3\;hr$ ($9.4{\sim}32.5\;hr$). There was a loose correlation between $T_{eff}$ and serum creatinine concentration (r=0.45). 48hr retention was $4.9{\pm}4.2%$ ($1{\sim}23%$). Time necessary to whole body retention of I-131 become less than 1.1 GBq was calculated as $47.1{\pm}13.2\;hr$ for 9.25 GBq, $42.1{\pm}11.9\;hr$ for 7.4 GBq, $35.7{\pm}10.0\;hr$ for 5.55 GBq, and $26.7{\pm}7.5\;hr$ for 3.7 GBq dose of I-131. Conclusion: Author successfully measured radiation dose rates in isolated patients treated by high dose of I-131 without radiation exposure to the faculty members with simple arrangement of survey meter probe. Using those data, $T_{eff}$ and some other indices were calculated.

• Clinical and Experimental Pediatrics
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• v.51 no.3
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• pp.315-322
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• 2008

Purpose : Prader-Willi syndrome (PWS) is a complex genetic disorder, caused by the deletion of the paternally derived 15q11-13 region or the maternal uniparental disomy of chromosome 15 (mUPD(15)). In this study, we compared phenotypic differences between those patients whose disease was caused by microdeletion and those caused by mUPD(15). In addition, a comparison of the efficacy of growth hormone (GH) therapy between these two PWS genotypes was analyzed. Methods : Fifty-three patients were diagnosed as having PWS based on molecular and cytogenetic analyses and clinical features. Data that included maternal age, birth weight, a feeding problem in the neonatal period, cryptorchidism, developmental delay or mental retardation, short stature, hypopigmentation, changes in height, weight, and body mass indexes (BMI) before and after GH treatment were obtained by a retrospective review of medical records. The data from the patients with microdeletion were compared with those from the patients with mUPD(15). Results : Of the 53 patients with genetically confirmed PWS, 39 cases had microdeletion and 14 mUPD(15). Maternal ages were significantly higher in the mUPD(15) group, and hypopigmentation and a feeding problem in the neonatal period were more frequent in the microdeletion group. Growth hormone was administered to 20 patients [14 with microdeletion, 6 with mUPD(15)]. There were no differences between the two groups in height velocity, weight and height SDS, and BMI after GH therapy. Conclusion : Phenotype and genotype correlations were observed in Korean PWS patients, such as more advanced maternal ages in the mUPD(15) group and more feeding problems and hypopigmentations in the microdeletion group. Further long-term prospective studies are needed to correlate other aspects of the phenotypes.

• Korean Journal of Agricultural Science
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• v.29 no.2
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• pp.43-52
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• 2002

This study was performed to provide the basic data for preservation and improvement of genetic resources according to finding genetic construction obtained from analysis of genetic characteristics of $\beta$-casein gene in Korean Native goat and Saanen using the PCR-RFLP. This study confirmed the amplified products of 481bp fragments obtained from the amplification of $\beta$-casein loci by PCR. The $\beta$-casein AB genotype showed 481, 284 and 197bp, and $\beta$-casein BB genotype showed 284 and 197bp fragments in Korean Native goat and Saanen. The frequencies of $\beta$-casein genotype in Korean Native goat were 6.25 and 93.75% for AA and AB and the frequencies of $\beta$-casein genotype in Saanen were 57.14 and 42.86% for AA and AB types. The frequencies of $\beta$-casein A and B alleles were 0.031 and 0.969 in Korean Native goat and the frequencies of $\beta$-casein A and B alleles are 0.286 and 0.714 in Saanen, respectively. The nucleotide sequence of $\beta$-casein gene of Korean Native goat was 97.71% higher homology with 11 nucleotide sequences difference of that of goat reported in GeneBank (M90556). Therefore, this study of molecular genetic characteristics by the analysis of genetic polymorphism and sequencing for $\beta$-casein gene should be used as basic and applying data for preservation and improvement of genetic resources in Korean Native goat breeding.

• Journal of Chest Surgery
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• v.43 no.3
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• pp.266-272
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• 2010

Background: Deep vein thrombosis (DVT) is a serious disease that causes life-threatening pulmonary embolism and chronic venous insufficiency. Anticoagulation is the standard therapy for DVT. However, the results of standard anticoagulation for treating DVT have been disappointing, so endovascular treatment is commonly performed nowadays. The aim of this study was to evaluate the efficacy of an endovascular procedure for treating patients with DVT. Material and Method: We retrospectively evaluated the clinical data of 29 DVT patients who underwent an endovascular procedure between December 2006 and July 2008. We compared the results of the 29 patients with the results of another 45 patients who were treated with only aspirin and heparin. Result: The patient’s mean age was 55.4 years in the intervention group and 53.7 years in the control group. DVT occurred more frequently in the females. Catheter-directed thrombolysis was performed in 22 patients (75.8%). Aspiration thrombectomy was performed in 18 patients (62%) and a endovascular stent was placed in 25 patients (86.2%). Fifteen patients (51.7%) underwent percutaneous insertion of a retrievable IVC filter for the prevention of pulmonary embolism. In the control group, thirty nine patients (86.7%) were treated with low-molecular heparin, and seven patients (15.6%) who were contraindicated for warfarin were treated with aspirin. No bleeding complications occurred during thrombolysis or anticoagulation. We analyzed the statistical data according to recurrence of DVT and the incidence of post-thrombotic syndrome (PTS) during the follow-up period. The intervention group had a significantly lower incidence of PTS (p-value=0.008), but they had the same result as the control group for the recurrence of DVT. In addition, death from the DVT did not occur in the intervention group. Thus, we obtained better clinical outcomes in the intervention group as compared to those in the anticoagulation only group. Conclusion: Endovascular procedures are effective alternative modalities, as compared to systemic anticoagulation, for the treatment of DVT. But more studies are needed to determine the specific indications and to validate the long-term efficacy of endovascular procedures for the treatment of DVT.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.6
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• pp.302-308
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• 2006

Purpose: Although several neuroanatomical models of panic disorder have been proposed, little is known regarding the neurological mechanisms underlying cognitive-behavioral therapy (CBT) in patients with panic disorder. This study was performed to identify the brain structures that show changes of regnioal cerebral blood flow (rCBF) after CBT in patients with panic disorder. Materials and Methods: Seven patients who were diagnosed as panic disorder by DSM-IV were treated with CBT for 8 weeks and twelve healthy volunteers joined in this study. Serial $^{99m}Tc-ECD$ brain perfusion SPECT images were acquisited and PDSS-SR (Self-Report version of Panic Disorder Severity Scale) and ACQ (Agoraphobic Cognitive Question) scores were measured just before and after CBT in all patients. Data were analyzed using SPM2. Results: Subjective symptoms were improved, and PDSS-SR and ACQ scores were significantly reduced ($14.9{\pm}3.9\;vs.\;7.0{\pm}1.8$, p<0.05; $30.3{\pm}8.5\;vs.\;21.6{\pm}3.4$, p<0.05, respectively) after CBT in panic patients. Before CBT, a significant increase of rCBF was found in the cingulate gylus, thalamus, midbrain, both medial frontal and temporal lobes of the panic patients compared to the normal volunteers. After CBT, we observed a significant rCBF decrease in the left parahippocamus, right insula and cingulate gyrus, both frontal and temporal lobes, and a significant rCBF increase in both the occipital lobes, left insula, both frontal and left parietal lobes. Conclusion: These data suggested that CBT is effective for panic disorder and diminish the activity of the brain areas associated with fear in panic disorder.

• Journal of the Korean Applied Science and Technology
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• v.37 no.5
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• pp.1323-1329
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• 2020

To characterize the molecular structure of PhE-gal synthesized using Escherichia coli 𝛽-gal, NMR (¹H- and ¹³C-) spectroscopy and mass spectrometry of PhE-gal were conducted. ¹H NMR spectrum of PhE-gal showed multiple peaks corresponding to the galactosyl group, which is an evidence of galactosylation on 2-phenylethanol (PhE). Downfield proton peaks at 𝛿_H 7.30~7.21 ppm showed the presence of aromatic protons of PhE as well as benzyl CH₂ protons at 𝛿_H 2.88 ppm. Up field proton peaks at 𝛿_H 4.31 ppm, 4.07 ppm and multiple peaks from 𝛿_H 3.86~3.38 ppm are indicative of galactocylation on PhE. ¹³C NMR spectrum revealed the presence of 12 carbons suggestive of PhE-gal. Among 12 carbon peaks from PhE-gal, the four peaks at 138.7, 129.0, 128.6 and 126.5 were assigned aromatic carbons in the phenyl ring. Three peaks at 129.0, 128.6 and 126.5 showed high intensities, indicating CH aromatic carbons. ¹³C NMR data of PhE-gal showed 6 monosaccharide peaks from galactose and 2 peaks from aliphatic chain of PhE, indicating that PhE-gal was galactosyl PhE. The mass value (sodium adduct ion of PhE-gal, m/z = 307.1181) from mass spectrometry analysis of PhE-gal, and ¹H and ¹³C NMR spectral data were in good agreement with the expecting structure of PhE-gal. We are expecting that through future study it will eventually be able to develop a new additive with low cytotoxicity.

• Journal of Food Hygiene and Safety
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• v.24 no.4
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• pp.352-356
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• 2009

The purpose of this study was to introduce the toxicological study review to evaluate the safety of PDMS on the 69th JECFA meeting. Polydimethylsiloxane is a polymer and its ADI was established at 23rd JECFA meeting in 1979. The ADI was maintained although the specification was expanded at its 26th, 29 th, 37 th meetings. Recently, it was reported that PDMS with low molecular weight and viscosity has high absorption rate and different toxicity, so it was submitted at 69th meeting. Toxicological studies of PDMS were submitted from the sponsor and additional information is collected from a document searching. The toxicological studies were reviewed in accordance with the 'Guidelines for the preparation of toxicological working papers for the Joint FAO/WHO Expert Committee on Food Additives'. In the available acute, sub-chronic and chronic toxicity studies on PDMS, dose-related increases in incidence and severity of ocular lesions(corneal crystal, inflammation of the corneal epithelium etc.) were consistently observed after oral dosing. It seems to be a local irritant effect, but the mechanism by which the ocular lesions arose is unclear, although the lack of absorption of PDMS indicates that it is unlikely to be a direct systemic effect. Consequently, the relevance of the ocular lesions for food use of PDMS could not be determined. The ADI of PDMS was re-established from 0-1.5 mg/kg bw/day to 0-0.8 mg/kg bw/day by applying additional safety factor 2 based on its ocular toxicity. The result of 0-0.8 mg/kg bw/day is a temporary ADI until further data are provided to 2010.