• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3197-3203
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• 2013

Background: microRNAs (miRNAs) that regulate proliferation, invasion and metastasis are considered to be the principal molecular basis of tumor heterogeneity. Breast cancer is not a homogeneous tissue. Thus, it is very important to perform microarray-based miRNA screening of tumors at different sites. Methods: Breast tissue samples from the centers and edges of tumors of 30 patients were classified into 5 clinicopathological subtypes. In each group, 6 specimens were examined by microRNA array. All differential miRNAs were analyzed between the edges and centers of the tumors. Results: Seventeen kinds of miRNAs were heterogeneously distributed in the tumors from different clinicopathological subtypes that included 1 kind of miRNA in Luminal A and Luminal B Her2+ subtypes, 4 kinds in Luminal A and Her2 overexpression subtypes, 6 kinds in Luminal B Ki67+ and Luminal B Her2+ subtypes, 2 kinds between Luminal B Ki67+ and triple-negative breast cancer (TNBC) subtypes, 2 kinds between Luminal B Her2+ and TNBC subtypes, and 2 kinds between Luminal B Ki67+, Luminal B Her2+, and TNBC subtypes. Twenty kinds of miRNAs were homogenously distributed in the tumors from different clinicopathological subtypes that included 6 kinds of miRNAs in Luminal B Ki67+ and Luminal B Her2+ subtypes, 1 kind in Luminal B Ki67+ and Her2 overexpression subtypes, 10 kinds between Luminal B Ki67+ and TNBC subtypes, 2 kinds in Luminal B Her2+ and TNBC subtypes, and 1 kind between Luminal B Ki67+, Luminal B Her2+, and TNBC subtypes. Conclusions: A total of 37 miRNAs were significantly distributed in tumors from the centers to edges, and in all clinicopathological subtypes.

• Korean Journal of Head & Neck Oncology
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• v.24 no.2
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• pp.155-161
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• 2008

Head and neck squamous cell carcinoma(HNSCC) still has poor outcome, and laryngeal cancer is the most frequent subtype of HNSCC. Therefore, there is a need to develop novel treatments to improve the outcome of patients with HNSCC. It is critical to gain further understanding on the molecular and chromosomal alteration of HNSCC to identify novel therapeutic targets but genetic etiology of squamous cell carcinoma of the larynx is so complex that target genes have not yet been clearly identified. Array based CGH(array-CGH) allows investigation of general changes in target oncogenes and tumor suppressor genes, which should, in turn, lead to a better understanding of the cancer process. In this study, We used genomic wide array-CGH in tissue specimens to map genomic alterations found in laryngeal squamous cell carcinomas. As results, gains of MAP2, EPHA3, EVI1, LOC389174, NAALADL2, USP47, CTDP1, MASP1, AHRR, and KCNQ5, with losses of SRRM1L, ANKRD19, FLJ39303, ZNF141, DSCAM, GPR27, PROK2, ARPP-21, and B3GAT1 were observed frequently in laryngeal squamous cell carcinoma tissue specimens. These data about the patterns of genomic alterations could be a basic step for understanding more detailed genetic events in the carcinogenesis and also provide information for diagnosis and treatment in laryngeal squamous cell carcinoma. The high resolution of array-CGH combined with human genome database would give a chance to find out possible target genes which were gained or lost clones.

• BMB Reports
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• v.56 no.3
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• pp.153-159
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• 2023

Neuronal differentiation is highly coordinated through a cascade of gene expression, mediated via interactions between trans-acting transcription factors and cis-regulatory elements of their target genes. However, the mechanisms of transcriptional regulation that determine neuronal cell-fate are not fully understood. Here, we show that the nuclear transcription factor Y (NF-Y) subunit, NFYA-1, is necessary and sufficient to express the flp-3 neuropeptide gene in the IL1 neurons of C. elegans. flp-3 expression is decreased in dorsal and lateral, but not ventral IL1s of nfya-1 mutants. The expression of another terminally differentiated gene, eat-4 vesicular glutamate transporter, is abolished, whereas the unc-8 DEG/ENaC gene and pan-neuronal genes are expressed normally in IL1s of nfya-1 mutants. nfya-1 is expressed in and acts in IL1s to regulate flp-3 and eat-4 expression. Ectopic expression of NFYA-1 drives the expression of flp-3 gene in other cell-types. Promoter analysis of IL1-expressed genes results in the identification of several cis-regulatory motifs which are necessary for IL1 expression, including a putative CCAAT-box located in the flp-3 promoter that NFYA-1 directly interacts with. NFYA-1 and NFYA-2, together with NFYB-1 and NFYC-1, exhibit partly or fully redundant roles in the regulation of flp-3 or unc-8 expression, respectively. Taken together, our data indicate that the NF-Y complex regulates neuronal subtype-specification via regulating a set of terminal-differentiation genes.

• Korean Journal of Veterinary Service
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• v.45 no.1
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• pp.31-38
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• 2022

Swine influenza (SI) is an important respiratory disease in pigs and epidemic worldwide, which is caused by influenza A virus (IAV) belonging to the family of Orthomyxoviridae. As seen again in the 2009 swine-origin influenza A H1N1 pandemic, pigs are known to be susceptible to swine, avian, and human IAVs, and can serve as a 'mixing vessel' for the generation of novel IAV variants. To this end, the emergence of swine influenza viruses must be kept under close surveillance. Herein, we report the isolation and phylogenetic study of a swine IAV, A/swine/Korea/21810/2021 (sw21810, H3N2 subtype). BLASTN sequence analysis of 8 gene segments of the isolated virus revealed a high degree of nucleotide similarity (94.76 to 100%) to porcine strains circulating in Korea and the United States. Out of 8 genome segments, the HA gene was closely related to that of isolates from cluster I. Additionally, the NA gene of the isolate belonged to a Korean Swine H1N1 origin, and the PB2, PB1, NP and NS genes of the isolate were grouped into that of the Triple reassortant swine H3N2 origin virus. The PA and M genes of the isolate belonged to 2009 Pandemic H1N1 lineage. Human infection with mutants was most common through contact with infected pigs. Our results suggest the need for periodic close monitoring of this novel swine H3N2 influenza virus from a public health perspective.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.2
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• pp.157-165
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• 2023

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and current therapeutic strategies are limited in their effectiveness. The expressions of Rab5 and the M2 tumor-associated macrophage marker CD163 in tissues were detected by Western blot. The migration and invasion of cells were determined using a Transwell assay. The expressions of the exosome markers were evaluated by Western blot. The polarization of human macrophages (THP-1) was determined by incubation of THP-1 cells with conditioned medium or exosomes collected from MDA-MB-231 cells with indicated transfections or by a coculture system of THP-1 and MDA-MB-231 cells. The M1 and M2 macrophage markers were evaluated by qRT-PCR. The expression of Rab5 in TNBC was significantly higher than that in normal breast tissue. Rab5 expressions in triple-negative and luminal A breast cancer were higher than those in other molecular subtypes. Higher CD163 expression was observed in triple-negative breast cancer and in triple-negative and luminal B subtypes. Rab5 knockdown suppressed but Rab5 overexpression promoted the migration and invasion capacity of MDA-MB-231 cells. The levels of CD63 and CD9 in the medium of Rab5 knockdown cells were lower than those in control cells, whereas higher levels of CD63 and CD9 were observed in Rab5 overexpression cells. Rab5 knockdown decreased the excretion but did not alter the diameter of the exosomes. Knockdown of Rab5 facilitated the anti-tumor polarization of macrophages, which was partially reversed by Rab5 overexpression. Therefore, Rab5 is expected to be a potential therapeutic target for triple-negative breast cancer.

• The Journal of Internal Korean Medicine
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• v.45 no.1
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• pp.1-10
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• 2024

Objectives: This study investigated the pattern identification (PI) and clinical index of Parkinson's disease (PD) for personalized diagnosis and treatment. Methods: This prospective observational multi-center study recruited 100 patients diagnosed with PD from two Korean medicine hospitals. To cluster new subtypes of PD, items on a PI questionnaire (heat and cold, deficiency and excess, visceral PI) were evaluated along with pulse and tongue analysis. Gait analysis was performed and blood and feces molecular signature changes were assessed to explore biomarkers for new subtypes. In addition, unified PD rating scale II and III scores and the European quality of life 5-dimension questionnaire were assessed. Results: The clinical index obtained in this study analyzed the frequency statistics and hierarchical clustering analysis to classify new subtypes based on PI. Moreover, the biomarkers and current status of herbal medicine treatment were analyzed using the new subtypes. The results provide comprehensive data to investigate new subtypes and subtype-based biomarkers for the personalized diagnosis and treatment of PD patients. Ethical approval was obtained from the medical ethics committees of the two Korean medicine hospitals. All amendments to the research protocol were submitted and approved. Conclusions: An objective and standardized diagnostic tool is needed for the personalized treatment of PD by traditional Korean medicine. Therefore, we developed a clinical index as the basis for the PI clinical evaluation of PD. Trial Registration: This trial is registered with the Clinical Research Information Service (CRIS) (KCT0008677)

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5081-5086
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• 2012

Background: The liver is one of the most common metastatic sites of breast cancer, hepatic metastases developing in 6%-25% of patients with breast cancer and being associated with a poor prognosis. The aim of this study was to analyze the survival and clinical characteristics of patients with hepatic metastases from breast cancer of different molecular subtypes and to investigate the prognostic and predictive factors that effect clinical outcome. Methods: We retrospectively studied the charts of 104 patients with breast cancer hepatic metastases diagnosed at Sun Yat-sen University Cancer Center from December 1990 to June 2009. Subtypes were defined as luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) enriched, triple-negative (TN). Prognostic factor correlations with clinical features and treatment approaches were assessed at the diagnosis of hepatic metastases. Results: The median survival time was 16.0 months, and the one-, two- three-, four-, five-year survival rates were 63.5%, 31.7%, 15.6%, 10.8%, and 5.4%, respectively. Median survival periods after hepatic metastases were 19.3 months (luminal A), 13.3 months (luminal B), 18.9 months (HER2-enriched), and 16.1 months (TN, P=0.11). In multivariate analysis, a 2 year-interval from initial diagnosis to hepatic metastasis, treatment with endocrine therapy, and surgery were independent prognostic factors. Endocrine therapy could improve the survival of luminal subtypes (P=0.004) and was a favorable prognostic factor (median survival 23.4 months vs. 13.8 months, respectively, P=0.011). Luminal A group of patients treated with endocrine therapy did significantly better than the Luminal A group of patients treated without endocrine therapy (median survival of 48.9 vs. 13.8 months, P=0.003). Conclusions: Breast cancer subtypes were not associated with survival after hepatic metastases. Endocrine therapy was a significantly favorable treatment for patients with luminal subtype.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3939-3944
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• 2014

Background: To elucidate the role of rapamycin and PF4 on apoptosis regulation via Bax (pro-apoptosis), Bcl-2 (anti-apoptosis) and survivin activation on the growth in the 1-methyl-1-nitrosourea-induced invasive breast carcinoma model. Materials and Methods: Thirty five female Sprague Dawley rats at age 21-day old were divided into 4 groups; Group 1 (control, n=10), Group 2 (PF4, n=5), Group 3 (rapamycin, n=10) and Group 4 (rapamycin+PF4, n=10). MNU was administered intraperitionally, dosed at 70mg/kg body weight. The rats were treated when the tumors reached the size of $14.5{\pm}0.5mm$ and subsequently sacrificed after 5 days. Rapamycin and PF4 were administered as focal intralesional injections at the dose of $20{\mu}g$/lesion. The tumor tissue was then subjected to histopathological examinations for morphological appraisal and immunohistochemical assessment of the pro-apoptotic marker, Bax and anti-apoptotic markers, Bcl-2 and survivin. Results: The histopathological pattern of the untreated control cohort showed that the severity of the malignancy augments with mammary tumor growth. Tumors developing in untreated groups were more aggressive whilst those in treated groups demonstrated a transformation to a less aggressive subtype. Combined treatment resulted in a significant reduction of tumor size without phenotypic changes. Bax, the pro-apoptotic marker, was significantly expressed at higher levels in the rapamycin-treated and rapamycin+PF4-treated groups compared to controls (p<0.05). Consequently, survivin was also significantly downregulated in the rapamycin-treated and rapamycin+PF4-treated group and this was significantly different when compared to controls (p). Conclusions: In our rat model, it could be clearly shown that rapamycin specifically affects Bax and survivin signaling pathways in activation of apoptosis. We conclude that rapamycin plays a critical role in the induction of apoptosis in MNU-induced mammary carcinoma.

• IMMUNE NETWORK
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• v.1 no.1
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• pp.61-69
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• 2001

Background: To determine the molecular structure of type II collagen-specific T-cell receptors associated with rheumatoid arthritis (RA). Methods: We generated CII-specific T-cell lines of 8 RA patients by prolonged in vitro culture with bovine CII (bCII) and the immunogenic peptide (256-270) of human CII. The proliferation response towards CII stimulation was measured from the uptake of 3H-thymidine. Changes in the secretion of Th 1 and Th2 cytokines in the culture supernatent were measured by ELISA. The TCR clonotypes of these T-cells were examined by RT-PCR/SSCP analyses of all 22 $V_{\beta}$ chains. Results: T-cells from patients' tissue exhibited strong proliferation index upon CII stimulation, which was maintained up to 6 months in the culture. The secretion of INF-$\gamma$from these T-cells increased along with the duration of culture time, while the amount of IL-4 production did not show significant changes. The SSCP band patterns of patients' T-cells appear as discrete bands unlike the smeary streak produced from normal samples. Some SSCP bands, each representing selected expansion of a TCR containing certain subtype of $V_{\beta}$ peptides, appeared to be identical in more than one patients. Among these, the expansion of SSCP band representing the $V_{\beta}$ 14 CDR3 region persisted after switching the antigen to the immunogenic human peptide (256-270). Conclusion: CII-reactive T-cells expressing distinct CDR3 motifs are selectively expanded in the peripheral blood and synovial fluid of RA patients, and their persistent proliferation upon CII stimulation, as well as the production Th 1-type cytokines, may play pivotal roles in RA pathogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1873-1880
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• 2015

Background: A recent genome-wide association study (GWAS) on patients with chronic hepatitis C (CHC) treated with peginterferon and ribavirin (pegIFN-${\alpha}$/RBV) identified a single nucleotide polymorphism (SNP) on chromosome 19 (rs12979860) which was strongly associated with a sustained virological response (SVR). The aim of this study was twofold: to study the relationship between IL28B rs12979860 and sustained virological response (SVR) to pegIFN-${\alpha}$/RVB therapy among CHC patients and to detect the rs12979860 polymorphism by high resolution melting curve (HRM) assay as a simple, fast, sensitive, and inexpensive method. Materials and Methods: The study examined outcomes in 100 patients with chronic hepatitis C in 2 provinces of Iran from December 2011 to June 2013. Two methods were applied to detect IL28B polymorphisms: PCR-sequencing as a gold standard method and HRM as a simple, fast, sensitive, and inexpensive method. Results: The frequencies of IL28B rs12979860 CC, CT, and TT alleles in chronic hepatitis C genotype 1a patients were 10% (10/100), 35% (35/100), and 6% (6/100) and in genotype 3a were 13% (13/100), 31% (31/100), and 5% (5/100), respectively. In genotype 3a infected patients, rs12979860 (CC and CT alleles) and in genotype 1a infected patients (CC allele) were significantly associated with a sustained virological response (SVR). The SVR rates for CC, CT and TT (IL28B rs12979860) were 18%, 34% and 4%, respectively. Multiple logistic regression analysis identified two independent factors that were significantly associated with SVR: IL-28B genotype (rs 12979860 CC vs TT and CT; odds ratio [ORs], 7.86 and 4.084, respectively), and HCV subtype 1a (OR, 7.46). In the present study, an association between SVR rates and IL28B polymorphisms was observed. Conclusions: The HRM assay described herein is rapid, inexpensive, sensitive and accurate for detecting rs12979860 alleles in CHC patients. This method can be readily adopted by any molecular diagnostic laboratory with HRM capability and will be clinically beneficial in predicting treatment response in HCV genotype 1 and 3 infected patients. In addition, it was demonstrated that CC and CT alleles in HCV-3a and the CC allele in HCV-1a were significantly associated with response to pegIFN-${\alpha}$/RBV treatment. The present results may help identify subjects for whom the therapy might be successful.