• The Korea Journal of Herbology
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• v.24 no.3
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• pp.161-167
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• 2009

Objectives : Maekmoondong-tang (MMDT), a Korean herbal medicine, has been used to treat severe dry cough in patients with bronchitis and pharyngitis. MMDT has been reported to have anti-inflammatory, anti-allergic, immunomodulatory, secretory-modulating, and metabolic regulatory actions. However, there are no evidence in regard to the effects of MMDT on carcinogenesis and metastasis. Here, we investigated the effects of 70% ethanol extract of MMDT on cell viability, apoptosis, and motility in human hepatocarcinoma HepG2 cells. Methods : Cell viability was measured using the CCK-8 assay, and the apoptosis induction was evaluated by caspase-3 activity. To detect apoptotic features, the cells treated with MMDT were stained with 4'-6-diamidino-2-phenylindole (DAPI). Cell motility was examined by Boyden chamber assay and Real-time Cell Index of Migration assay. Gelatin zymography also performed to measure matrix metalloproteinase (MMP)-2/9 activity. Results : We found that MMDT significantly inhibited cell proliferation and increased caspase-3 activity in a dose-dependent manner in HepG2 cells. Apoptotic features such as chromatin condensation and apoptotic bodies were observed in MMDT-treated cells by DAPI staining. MMDT also suppressed PMA-induced cell motility and activities of MMP-2/9. Conclusions : Our results exhibited that MMDT possess the anti-carcinogenetic and anti-metastatic activities via caspase-3 activation and down-regulation of cell motility and invasion in HepG2 cells. Therefore, these findings suggest that MMDT could be potentially applied to the prevention and treatment of cancer.

• Journal of Microbiology and Biotechnology
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• v.33 no.9
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• pp.1213-1227
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• 2023

Fetal growth restriction (FGR) is a prevalent obstetric condition. This study aimed to investigate the role of Toll-like receptor 9 (TLR9) in regulating the inflammatory response and gut microbiota structure in FGR. An FGR animal model was established in rats, and ODN1668 and hydroxychloroquine (HCQ) were administered. Changes in gut microbiota structure were assessed using 16S rRNA sequencing, and fecal microbiota transplantation (FMT) was conducted. HTR-8/Svneo cells were treated with ODN1668 and HCQ to evaluate cell growth. Histopathological analysis was performed, and relative factor levels were measured. The results showed that FGR rats exhibited elevated levels of TLR9 and myeloid differentiating primary response gene 88 (MyD88). In vitro experiments demonstrated that TLR9 inhibited trophoblast cell proliferation and invasion. TLR9 upregulated lipopolysaccharide (LPS), LPS-binding protein (LBP), interleukin (IL)-1β and tumor necrosis factor (TNF)-α while downregulating IL-10. TLR9 activated the TARF3-TBK1-IRF3 signaling pathway. In vivo experiments showed HCQ reduced inflammation in FGR rats, and the relative cytokine expression followed a similar trend to that observed in vitro. TLR9 stimulated neutrophil activation. HCQ in FGR rats resulted in changes in the abundance of Eubacterium_coprostanoligenes_group at the family level and the abundance of Eubacterium_coprostanoligenes_group and Bacteroides at the genus level. TLR9 and associated inflammatory factors were correlated with Bacteroides, Prevotella, Streptococcus, and Prevotellaceae_Ga6A1_group. FMT from FGR rats interfered with the therapeutic effects of HCQ. In conclusion, our findings suggest that TLR9 regulates the inflammatory response and gut microbiota structure in FGR, providing new insights into the pathogenesis of FGR and suggesting potential therapeutic interventions.

• Korean Journal of Radiology
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• v.22 no.11
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• pp.1786-1796
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• 2021

Objective: To evaluate the prognostic implications of preoperative magnetic resonance imaging (MRI) features of hepatocellular carcinoma (HCC) with a focus on those with targetoid appearance based on the Liver Imaging Reporting and Data System (LI-RADS), as well as known microvascular invasion (MVI) features. Materials and Methods: This retrospective study included 242 patients (190 male; mean age, 57.1 years) who underwent surgical resection of a single HCC (≤ 5 cm) as well as preoperative gadoxetic acid-enhanced MRI between January 2012 and March 2015. LI-RADS category was assigned, and the LR-M category was further classified into two groups according to rim arterial-phase hyperenhancement (APHE). The imaging features associated with MVI were also assessed. The overall survival (OS), recurrence-free survival (RFS), and their associated factors were evaluated. Results: Among the 242 HCCs, 190 (78.5%), 25 (10.3%), and 27 (11.2%) were classified as LR-4/5, LR-M with rim APHE, and LR-M without rim APHE, respectively. LR-M with rim APHE (vs. LR-4/5; hazard ratio [HR] for OS, 5.48 [p = 0.002]; HR for RFS, 2.09 [p = 0.042]) and tumor size (per cm increase; HR for OS, 6.04 [p = 0.009]; HR for RFS, 1.77 [p = 0.014]) but not MVI imaging features (p > 0.05) were independent factors associated with OS and RFS. Compared to the 5-year OS and RFS rates in the LR-4/5 group (93.9% and 66.8%, respectively), the LR-M with rim APHE group had significantly lower rates (68.0% and 45.8%, respectively, both p < 0.05), while the LR-M without rim APHE group did not significantly differ in the survival rates (91.3% and 80.2%, respectively, both p > 0.05). Conclusion: Further classification of LR-M according to the presence of rim APHE may help predict the postoperative prognosis of patients with a single HCC.

• Parasites, Hosts and Diseases
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• v.62 no.1
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• pp.53-63
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• 2024

The intracellular parasite Babesia microti is among the most significant species causing human babesiosis and is an emerging threat to human health worldwide. Unravelling the pathogenic molecular mechanisms of babesiosis is crucial in developing new diagnostic and preventive methods. This study assessed how priming with B. microti surface antigen 1 (BHSA 1) and seroreactive antigen 5-1-1 (BHSA 5-1-1) mediate protection against B. microti infection. The results showed that 500 ㎍/ml rBMSA1 and rBMSA5-1-1 partially inhibited the invasion of B. microti in vitro by 42.0±3.0%, and 48.0±2.1%, respectively. Blood smears revealed that peak infection at 7 days post-infection (dpi) was 19.6%, 24.7%, and 46.7% in the rBMSA1, rBmSA5-1-1, compared to the control groups (healthy mice infected with B. microti only), respectively. Routine blood tests showed higher white blood cell, red blood cell counts, and haemoglobin levels in the 2 groups (BMSA1 and BMSA5 5-1-1) than in the infection control group at 0-28 dpi. Moreover, the 2 groups had higher serum interferon-γ, tumor necrosis factor-α and Interleukin-17A levels, and lower IL-10 levels than the infection control group throughout the study. These 2 potential vaccine candidate proteins partially inhibit in vitro and in vivo B. microti infection and enhance host immunological response against B. microti infection.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.28 no.1
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• pp.25-33
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• 2024

Backgrounds/Aims: Parenchymal-sparing anatomical hepatectomy (Ps-AH) based on portal ramification of the right anterior section (RAS) is a new technique to avoid unnecessarily transecting too much liver parenchyma, especially in cases of major anatomical hepatectomy. Methods: We prospectively assessed 26 patients with primary hepatic malignancies having undergone major Ps-AH based on portal ramification of the RAS from August 2018 to August 2022 (48 months). The perioperative indications, clinical data, intra-operative index, pathological postoperative specimens, postoperative complications, and follow-up results were retrospectively evaluated. Results: Among the 26 patients analyzed, there was just one case that had intrahepatic cholangiocarcinoma The preoperative level of α-Fetoprotein was 25.2 ng/mL. All cases (100%) had Child-Pugh A liver function preoperatively. The ventral/dorsal RAS was preserved in 19 and 7 patients, respectively. The mean surgical margin was 6.2 mm. The mean surgical time was 228.5 minutes, while the mean blood loss was 255 mL. In pathology, 5 cases (19.2%) had microvascular invasion, and in the group of HCC patients, 92% of all cases had moderate or poor tumor differentiation. Six cases (23.1%) of postoperative complications were graded over III according to the Clavien-Dindo system, including in three patients resistant ascites or intra-abdominal abscess that required intervention. Conclusions: Parenchymal-sparing anatomical hepatectomy based on portal ramification of the RAS to achieve R0-resection was safe and effective, with favorable short-term outcomes. This technique can be used widely in clinical practice.

• The Korean Journal of Nuclear Medicine Technology
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• v.13 no.3
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• pp.43-47
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• 2009

Purpose: The menstrual cycle of normal premenopausal patients was divide into menstrual flow phase, proliferative phase, ovulatory phase, secretory phase. The aim of this study was to ovarian and endometrial $^{18}F$-FDG uptake during the menstrual cycle in normal premenopausal patients. Materials and Methods: We identified 200 incidental $^{18}F$-FDG uptake in the ovary. The patient fasted at least 6 hours before receiving an intravenous injection of 370-592 MBq (10-16mCi) of $^{18}F$-FDG. Scanning from the base of the skull though the mid thigh was performed using the Discovery Ste PET/CT system (GE Healthcare, Milwaukee, WI, USA). Ovarian and endometrial $^{18}F$-FDG uptake (expressed as standardized uptake value) was measured on PET/CT image. Results: Two peaks of increased endometrial $^{18}F$-FDG uptake were identified during the menstrual cycle. The $SUV_{avg}$ and $SUV_{max}$ was $2.89{\pm}1.04$ and $3.17{\pm}1.59$ in menstruating patients, $2.4{\pm}0.88$ and $2.98{\pm}1.14$ in proliferative phase patients, $3.59{\pm}1.76$ and $3.17{\pm}1.67$ in ovulatory phase patients, $2.58{\pm}1.39$ and $3.1{\pm}1.8$ in secretory phase patients. Conclusions: Increased ovarian and endometrial $^{18}F$-FDG uptake could be found the time of menstrual flow and ovulatory phase of menstrual cycle. Increased uptake in endometrial adjacent to a cervical tumor does not necessarily reflect endometrial tumor invasion. Since increased uptake was dependent on the menstrual cycle, it can be avoided by scheduling PET/CT just after menstruation. Non-menstrual-related endometrial uptake may be instrumental in establishing a diagnosis in a premenopaual patient.

• Radiation Oncology Journal
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• v.23 no.3
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• pp.131-136
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• 2005

Purpose: The aim of this study was to evaluate the clinical results of postoperative radiotherapy for parotid gland malignancy, and determine prognostic factors for locoregional control and survival. Materials and Methods: Between 1980 and 2002, 130 patients with parotid malignancy were registered In the database of the Department of Radiation Oncology, Seoul National University Hospital. The subjects of this analysis were the 72 of these 130 patients who underwent postoperative Irradiation, There were 42 males and 30 females, with a median age of 46.5 years. The most common histological type was a mucoepidermoid carcinoma. There were 6, 23, 23 and 20 patients in Stages I, II, III and IV, respectively. The median dose to the tumor bed was 60 Gy, with a median fraction size of 1.8 Gy. Results: The overall 5 and 10 year survival rates were 85 and $76\%$, respectively, The five-year locoregional control rate was $85\%$, which reached a plateau phase after 6 years. Sex and histological type were found to be statistically significant for overall survival from a multivariate analysis. No other factors, Including age, facial nerve palsy and stage, were related to overall survival. For locoregional control, nodal involvement and positive resection margin were associated with poor local control. Histological type, tumor size, perineural invasion and type of surgery were not significant for locoregional control. Conclusion: A high survival rate of parotid gland malignancies, with surgery and postoperative radiotherapy, was confirmed. Sex and histological type were significant prognostic factors for overall survival. Nodal Involvement and a positive resection margin were associated with poor locoregional control.

• Journal of Chest Surgery
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• v.32 no.6
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• pp.536-542
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• 1999

Background: The purpose of this study is to improve the quality of the diagnostic procedures in the preoperative evaluation so as to reduce the unnecessary thoracotomy and to ensure resectability in non-small cell lung cancer. Material and Method: Of 616 patients who underwent thoracotomy for primary lung cancer from January 1990 to December 1996, 59 patients(9.6%) turned out to have inoperable lesions after the thoracotomy. We reprospectively reviewed the bronchoscopic findings, methods of tissue diagnosis, CT scans, pulmonary function test and lung perfusion scan, reasons for nonresectability, and adjuvant therapy, and then followed up on the survival rate after exploratory thoracotomy. Result: The cell types were squamous cell carcinoma in 38, adenocarcinoma in 15, large cell carcinoma in 3 and others in 3. Primary loci were RUL in 20, RML in 6, RLL in 8, LUL in 13, LLL in 4 and others in 8. The reasons for non-resectability were various; direct tumor invaison to mediastinal structures(n=41), seeding on pleural cavity(n=8), poor pulmonary function(n=2), invasions to extranodal mediastinal lymph node(n=2), technical non- resectability due to extensive chest wall invasion (n=3), small cell carcinoma (n=1), malignant lymphoma(n=1), and multiple rib metastases(n=1). In the follow-up of 58 patients, 1-year survival rate was 55.2% and 2-year survival rate was 17.2% and the mean survival time was 14 months. When compared according to cell types or postoperative adjuvant therapeutic modalities, no significant difference in the survival rates were found. The squamous cell carcinoma was frequently accompanied by local extension to contiguous structures and was the main cause of non-resectability. In adenocarcinoma, pleural seeding with malignant effusion was frequently encountered, and was the major reason for non-resectability. Conclusion: These data revealed that if appropriate preoperative diagnostic tools had been available, many unnecessary thoracotomies could have been avoided. Both the use of thoracoscopy in selected cases of adenocarcinoma and the more aggressive surgical approach to the locally advanced tumor could reduce the incidence of unnecessary thoracotomies for non-small cell lung cancers.

• Journal of Gastric Cancer
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• v.8 no.3
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• pp.136-140
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• 2008

Purpose: Stage IV early gastric carcinoma (EGC) is a rare disease. We report here on 10 cases of EGC that showed metastasis in more than 15 lymph nodes. Materials and Methods: A total of 8354 cases of gastric carcinoma in patients who underwent surgical procedures between January 2001 and January 2007 at Samsung Medical Center were studied, and 10 cases were classified as stage IV EGC. We investigated their clinicopathologic characteristics. Results: There were 5 males and 5 females. Their ages at operation ranged from 46 to 76 years with a mean age of 61. All of the 10 patients had undergone curative resection for gastric cancer. The pathological diagnosis confirmed that all of the patients had tumor confined to the submucosa. The median size of the tumors was 5.3cm and the mean number of dissected nodes was 45.5 with a mean number of 22.2 involved nodes. Six cases were classified as the diffuse type and 4 were classified as the intestinal type by Lauren's classification. Histologically, 3 cases were signet ring cell carcinoma, 3 were poorly differentiated, 2 were moderately differentiated and 2 were well differentiated adenocarcinoma. Endolymphatic invasion was found in 9 cases. The median follow-up was 31 months. Adjuvant chemotherapy was done in 9 patients, and the patient who did not receive chemotherapy died by cerebrovascular accident. 2 patient had recurrence of gastric cancer and 7 survived without recurrence. Conclusion: More cases should be collected and further studies on the molecular and cellular tumor characteristics are required to characterize these tumors that show aggressive lymphatic spread.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.265-272
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• 2004

Background : RASSF1A, which is one of tumor suppressor genes, is frequently inactivated by hypermethylation of the promoter region in a variety of human cancers, including lung cancer. This study was performed to investigate the association between RASSF1A methylation and the clinicopathological factors in patients with squamous cell carcinoma of the lung. Methods : Eighty-one samples from the patients with squamous cell carcinoma of lung were examined. The promoter methyation of RASSF1A was analyzed by methylation specific PCR and sequencing. Statistical analysis was made to examine the association between RASSF1A methylation and the clinicopathological parameters. Results : RASSF1A methylation was observed in 37.0 % (30 of 81) of the patients with squamous cell carcinoma of the lung. RASSF1A methylation was found to be associated with cellular differentiation(p=0.0097) and the overall survival(p=0.0635). However, there was no association between RASSF1A methylation and the other clinicopathological parameters, such as the pathological TNM stage, the recurrence rate, lymph node invasion and the amount of cigarettes smoked. Conclusion : RASSF1A methylation might be associated with a poor prognosis in patients with squamous carcinoma of the lung. A larger scale study is needed.