• Journal of Ginseng Research
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• v.47 no.5
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• pp.627-637
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• 2023

Background: Damage to the healthy intestinal epithelial layer and regulation of the intestinal immune system, closely interrelated, are considered pivotal parts of the curative treatment for inflammatory bowel disease (IBD). Plant-based diets and phytochemicals can support the immune microenvironment in the intestinal epithelial barrier for a balanced immune system by improving the intestinal microecological balance and may have therapeutic potential in colitis. However, there have been only a few reports on the therapeutic potential of plant-derived exosome-like nanoparticles (PENs) and the underlying mechanism in colitis. This study aimed to assess the therapeutic effect of PENs from Panax ginseng, ginseng-derived exosome-like nanoparticles (GENs), in a mouse model of IBD, with a focus on the intestinal immune microenvironment. Method: To evaluate the anti-inflammatory effect of GENs on acute colitis, we treated GENs in Caco2 and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages and analyzed the gene expression of proinflammatory cytokines and anti-inflammatory cytokines such as TNF-α, IL-6, and IL-10 by real-time PCR (RT-PCR). Furthermore, we further examined bacterial DNA from feces and determined the alteration of gut microbiota composition in DSS-induced colitis mice after administration of GENs through 16S rRNA gene sequencing analysis. Result: GENs with low toxicity showed a long-lasting intestinal retention effect for 48 h, which could lead to effective suppression of pro-inflammatory cytokines such as TNF-α and IL-6 production through inhibition of NF-κB in DSS-induced colitis. As a result, it showed longer colon length and suppressed thickening of the colon wall in the mice treated with GENs. Due to the amelioration of the progression of DSS-induced colitis with GENs treatment, the prolonged survival rate was observed for 17 days compared to 9 days in the PBS-treated group. In the gut microbiota analysis, the ratio of Firmicutes/Bacteroidota was decreased, which means GENs have therapeutic effectiveness against IBD. Ingesting GENs would be expected to slow colitis progression, strengthen the gut microbiota, and maintain gut homeostasis by preventing bacterial dysbiosis. Conclusion: GENs have a therapeutic effect on colitis through modulation of the intestinal microbiota and immune microenvironment. GENs not only ameliorate the inflammation in the damaged intestine by downregulating pro-inflammatory cytokines but also help balance the microbiota on the intestinal barrier and thereby improve the digestive system.

• Journal of Nutrition and Health
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• v.42 no.3
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• pp.213-220
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• 2009

Studies on the relationship between blood fatty acids and the risk of breast cancer have not yielded definite conclusions. The role of fatty acids in the development and progression of breast cancer is unclear. We conducted a case-control study to determine serum phospholipid fatty acid composition in benign breast tumor and breast cancer. Subjects consisted of 27 benign breast tumor and 68 breast cancer patients, and 28 matched controls. The levels of fatty acids were measured by gas chromatography. Higher arachidonic and palmitic acids were observed in breast cancer patients as compared with control and benign breast tumor patients. The percentage of total saturated fatty acids in breast cancer was higher than in control and benign breast tumor patients. The level of stearic acid was lower in benign breast tumor and breast cancer patients. Saturation index, the ratio of stearic to oleic acid, was lower in benign breast tumor and breast cancer patients compared to the control. Moreover, stearic acid was negatively and arachidonic acid was positively correlated with the cancer stage. In conclusion, our results support that serum phospholipid compositions of specific fatty acids are associated with the risk of benign breast tumor as well as breast cancer. Further studies are necessary to investigate mechanisms linked to the breast cancer etiology.

• Radiation Oncology Journal
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• v.25 no.2
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• pp.70-78
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• 2007

[ $\underline{Purpose}$ ]: This study analyzed the tumor response, overall survival, progression free survival and related prognostic factors in patients with muscle invasive bladder cancer subjected to bladder preserving treatment. $\underline{Materials\;and\;Methods}$: Between August 1995 and June 2004, 37 patients with muscle invasive (transitional cell carcinoma, clinically stage T2-4) bladder cancer were enrolled for the treatment protocol of bladder preservation. There were 33 males and 4 females, and the median age was 67 years (range $38{\sim}86\;years$). Transurethral resection of the bladder (TURB) was performed in 17 patients who underwent complete resection. The median radiation dose administered was 64.8 Gy (range $55.8{\sim}67\;Gy$). The survival rate was calculated by the Kaplan-Meier method. $\underline{Results}$: An evaluation of the response rate was determined by abdomen-pelvic CT and cystoscopy at three months after radiotherapy. A complete response was seen in 17 patients (46%). The survival rate at three years was 54.7%, with 54 months of median survival (range $3{\sim}91$ months). During the study, 17 patients died and 13 patients had died from bladder cancer. The progression free survival rate at three years was 37.2%. There were 24 patients (64.9%) who had disease recurrence: 16 patients (43.2%) had local recurrence, 6 patients (16.2%) had a distant recurrence, and 2 patients (5.4%) had both a local and distant recurrence. The survival rate (p=0.0009) and progression free survival rates (p=0.001) were statistically significant when compared to the response rate after radiotherapy. $\underline{Conclusion}$: The availability of complete TURB and appropriate chemoradiotherapy were important predictors for bladder preservation and survival.

• Tuberculosis and Respiratory Diseases
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• v.58 no.3
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• pp.285-290
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• 2005

Background : Some malignancies including lymphoma, head and neck cancer, and lung cancer are believed to be associated with the reactivation of tuberculosis (TB) because cyclic anti-cancer chemotherapy can induce the leukopenia or immunological deterioration. This report describes the clinical characteristics and treatment response of TB that developed during cyclic anti-cancer chemotherapy in patients with a solid tumor. Materials and Methods : From January 1 2000 to July 31 2004, patients with TB diagnosed microbiologically, pathologically, or clinically during anti-cancer chemotherapy in a tertiary hospital were enrolled, and their medical records were reviewed. Patients with the known risk factors for the reactivation of TB were excluded. Results : Twenty-two patients were enrolled and their mean age was 56.5 years (range 21-78). The male to female ratio was 3.4:1 and pulmonary TB was the main variant (20 patients, 90.9%). Gastric cancer (10 patients, 45.4%) and lymphoma (4 patients, 18.2%) were the leading underlying malignancies. The other malignancies included lung cancer, head and neck cancer, breast cancer, cervix cancer, and ovary cancer. Fifteen patients (68.2%) had a healed scar on a simple chest radiograph suggesting a previous TB infection. Among these patients, new TB lesions involved the same lobe or the ipsilateral pleura in 13 patients (87.6%). An isoniazid and rifampicin based regimen were started in all the subjects except for one patient with a hepatic dysfunction. The mean duration of medication was $9.9{\pm}2.4$ months and no adverse events resulting in a regimen change were observed. With the exception of 5 patients who died of the progression of the underlying malignancy, 70.6% (12/17) completed the anti-TB treatment. Conclusion : The clinical characteristics and response to anti-TB treatment for TB that developed during anticancer chemotherapy for a solid tumor were not different from those of patients who developed TB in the general population.

• Journal of Gastric Cancer
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• v.5 no.4 s.20
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• pp.273-280
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• 2005

Purpose: Cyclin G2 has been reported to be a negative cell-cycle regulator in various cancer tissues. However, the pattern of cyclin G2 expression in gastric cancer is relatively unknown. We investigated the expression of cyclin G2 in gastric cancer tissues and evaluated the clinical significance of its expression. Materials and Methods: Well-preserved gastric cancer tissues were consecutively obtained from 172 patients who underwent gastric cancer operations at Samsung Medical Center between November 1994 and December 1997. Cyclin G2 expression in the tissues was examined immunohistochemically, and the clinicopathological features and prognostic significance according to the expression were analyzed. Results: Of the 172 gastric cancer tissues, cyclin G2 expression was positive in 43 tissues (25.0%). According to the stage, cyclin G2 expression was lower in more advanced stages (P<0.001). Negative expression of cyclin G2 was positively correlated with more advanced depth of tumor invasion (P<0.05), presence of lymph-node metastasis (P<0.05) and presence of lymphatic invasion (P<0.05). The prognosis of the cyclin G2(+) group was significantly better than that of the cyclin G2(-) group (P<0.001). Multivariate analysis revealed that T stage, lymph-node metastasis, distant metastasis, and lymphatic invasion were independent prognostic factors, but the expression of cyclin G2 was not. Conclusion: Cyclin G2 was expressed in 25% of the gastric cancer tissues, and negative expression of cyclin G2 was associated with more advanced tumor progression. Cyclin G2 may be a negative cell-cycle regulator in gastric cancer, and further studies are necessary to elucidate its exact role in the mechanism of carcinogenesis.

• Journal of Gastric Cancer
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• v.3 no.3
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• pp.122-127
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• 2003

Purpose: The incidence rate and the mortality rate of gastric cancer have decreased in developed countries over the last several decades. On the other hand, they remain high in far eastern countries such as Korea, Japan, China and in many developing countries. The cure of patients with gastric carcinomas can be achieved mostly through complete surgical resection, but most gastric cancer patients are in advanced stages when diagnosed and have poor prognoses. therefore, the development of an effective systemic therapy is essential for far advanced gastric cancer patients. Until recently, the most commonly used combination chemotherapy was based on 5-flurouracil or cisplatin, but the results were not satisfactory, so recently etoposide, adriamycin and cisplatin (EAP-II) combination chemotherapy was introduced in patients with advanced gastric cancer. Early studies showed a high response rate and the ability to convert unresectable cases to resectable ones, but later studies couldn't duplicate the result. the purpose of this study was to evaluate the relative efficacy & toxicity of EAP-II chemotherapy and ELF chemotherapy which is based on 5-flurouracil. Materials and Methods: Between July 1992 and July 2002, sixty-five patients with inoperable advanced gastric cancer were enrolled for this study. Thirty-seven patient received EAP-II chemotherapy:etoposide (20 mg/$m^{2}$ IV for $1\∼5 days$), adriamycin (20 mg/$m^{2}$ IV for $1\∼5 days$) and cisplatin (20 mg/$m^{2}$ IV for $1\∼5 days$) and Twenty-eight patients receieved ELF chemotherapy : etoposide (100 mg/$m^{2}$ IV for $1\∼3 days$), leucovorin (20 mg/$m^{2}$ IV for $1\∼5 days$) and 5-FU (500 mg/$m^{2}$ IV for $1\∼5 days$). Each treatment schedule for each group was repeated every four weeks: EAP-II means 3.4 cycles per patient..ELF means 4.1 cycles per patient Results: Total respones rates were $5.4\%$ in the ELF group and $3.6\%$ in the EAP group (P-value>0.05). The median times to progression were 144 days in the ELF group and 92 days in the EAP-II group (P-value<0.05), and themedian overall survival times were 189 days in the ELF group and 139 days in the EAP-II group (P-value>0.05). The difference in the survival curves for the two regimens was not statistically significant. Non-hematologic toxicitis & hematologic toxicitis were more frequently observed for the EAP-II regimen. Anemia: $27.6\%$ in ELF vs $54\%$ in EAP-II; Leukopenia: $8.5\%$ in ELF vs $19\%$ in EAP-II; nausea & vomiting: $45.9\%$ in ELF vs $67.8\%$ in EAP-II. Conclusion: EAP-II regimen is not superior to ELF regimen in the tratment of inoperable advanced gastric cancer (J Korean Gastric Cancer Assoc 2003;3:122-127)

• Journal of the Korean Society of Radiology
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• v.82 no.1
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• pp.128-138
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• 2021

Purpose We evaluated the risk factors for progression to chronic complicated bronchopleural fistula (BPF) after pulmonary resection using follow-up CT. Materials and Methods We retrospectively reviewed 45 cases with BPF that had undergone pulmonary resection during 2010-2018. We compared the clinical and radiological characteristics of those with complicated BPF (n = 24) and those without complicated (sterilized) BPF (n = 21). The clinical and radiological risk factors for progression to chronic complicated BPF were examined by logistic regression analysis. Results The thickness of the pleural cavity wall (p = 0.022), the size of the pleural cavity (p = 0.029), and the size increase of BPF on follow-up (p = 0.012) were significantly different between the two groups. The risk factors for progression to chronic complicated BPF were age > 70 years (odds ratio, 6.43; 95% confidence interval, 1.2-33.7), the thickness of the cavity wall > 5 mm (odds ratio, 52.5; 95% confidence interval, 5.1-545.4), and an increase in the size of the pleural cavity on follow-up CT (odds ratio, 12.5; 95% confidence interval, 2.1-73.5), only in the univariate analysis. Conclusion The risk factors for progression to chronic complicated BPF can be evaluated using follow-up CT.

• Reproductive and Developmental Biology
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• v.32 no.4
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• pp.211-215
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• 2008

The HMG box containing protein (HBP) has a high mobility group domain and involved in the regulation of proliferation and differentiation of tissues. We screened HBP2 in glioblastoma using Suppression Subtractive Hybridization (SSH) and isolated human spermatogonial stem cell-like cells (hSSC-like cells) derived from patients of nonobstructive azoospermia (NOA). Expression of HBP2 was analyzed by RT-PCR in undifferentiated stem cells (human Embryonic Stem Cells, hSSC-like cells 2P) and spontaneous differentiated stem cells (hSSC-like cells 4P). It was overexpressed in hESC and hSSC-like cells 2P but not in hSSC-like cells 4P. Also, the expression level of HBP2 was downregulated in colon tumor tissues compared to normal tissues. Specifically in synchronized WI-38 cells, HBP2 was highly upregulated until the G1 phase of the cell cycle and gradually decreased during the S phase. Our results suggest that HBP2 was downregulated during the spontaneous differentiation of hSSC-like cells. HBP2 was differently expressed in colon tissues and was related to G1-progression in WI-38 cells. It may playa role in the maintenance of an undifferentiated hSSC-like cell state and transits from G1 to S in WI-38 cells. This research was important that it identified a biomarker for an undifferentiated state of hSSC-like cells and characterized its involvement to arrest during cell cycle in colon cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3879-3884
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• 2014

Background: In chronic hepatitis B (CHB), the presence of hepatic steatosis (HS) seems to be associated with known host and viral factors which may influence the long-term prognosis of chronic hepatitis B (CHB), probably leading to cirrhosis and hepatocellular carcinoma (HCC). Different from chronic hepatitis C (CHC), factors associated with HS in CHB are not clearly explored. Materials and Methods: 160 CHB patients were divided into two groups depending on the results of liver biopsy. Group I consisted of 71 patients with confirmed steatosis. Group II comprised 89 patients without steatosis. The groups were compared in terms of basal characteristics, body mass index (BMI), liver enzymes (ALT, AST, ALP), serum fasting blood sugar (FBS) and lipids, hepatitis B e antigen (HBeAg), viral load, and histological findings. Results: In terms of host factors, male gender, older age, BMI, high serum FBS and lipid levels were associated with HS. On the other hand, ALT levels, the HAI scores of necroinflammation and stage of fibrosis did not associate with HS. On multivariate analysis, parameters of sex, BMI, cholesterol and FBS levels were independently associated with HS. Regarding viral factors, HBeAg negativity was significantly associated with HS (81.7%, p value 0.006), but not HBV DNA level (p value 0.520). Conclusions: HS in CHB appears to be unrelated to the status of HBV replication. However, fibrosis progression in CHB is related to variable host factors. HS may be enhanced through these factors in HBV chronic patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.4101-4107
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• 2014

Protein phosphatase 1 (PP1) is a major serine/threonine phosphatase that controls gene expression and cell cycle progression. The active mutant IPP5 ($8-60hIPP5^m$), the latest member of the inhibitory molecules for PP1, has been shown to inhibit the growth of human cervix carcinoma cells (HeLa). In order to elucidate the underlying mechanisms, the present study assessed overexpression of $8-60hIPP5^m$ in HeLa cells. Flow cytometric and biochemical analyses showed that overexpression of $8-60hIPP5^m$ induced G2/M-phase arrest, which was accompanied by the upregulation of cyclin B1 and phosphorylation of G2/M-phase proteins ATM, p53, $p21^{cip1/waf1}$ and Cdc2, suggesting that $8-60hIPP5^m$ induces G2/M arrest through activation of the ATM/p53/$p21^{cip1/waf1}$/Cdc2/cyclin B1 pathways. We further showed that overexpression of $8-60hIPP5^m$ led to delayed nuclear translocation of cyclin B1. $8-60hIPP5^m$ also could translocate to the nucleus in G2/M phase and interact with $pp1{\alpha}$ and Cdc2 as demonstrated by co-precipitation assay. Taken together, our data demonstrate a novel role for $8-60hIPP5^m$ in regulation of cell cycle in HeLa cells, possibly contributing to the development of new therapeutic strategies for cervix carcinoma.