• Journal of Life Science
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• v.33 no.11
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• pp.887-896
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• 2023

The inflammatory response have been considered as one of important targets for cancer treatment because they play a key role during all steps of tumor development including initiation, promotion, malignant conversion and progression. To investigate the anti-inflammatory response during anti-tumor activity of an aqueous extracts of Ecklonia cava (AEC), alterations on the distribution of mast cells and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), nuclear factor (NF)-κB, inflammasome compositional protein and inflammatory cytokines were examined in CT26 colon tumor-bearing BALB/cKorl syngeneic mice after administrating AEC for five weeks. After treatment of AEC, total weight of tumor and necrotic region of tumor section were significantly decreased compared to vehicle treated group. The number of infiltered mast cells was higher in AEC treated group than vehicle treated group, while the expression levels of COX-2 and iNOS were decreased in AEC treated group. Also, similar decrease pattern were detected in the expression levels of NF-κB, NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 (Cas-1) after AEC treatment although the decrease rate was varied. Furthermore, the mRNA expressions of three inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α) and interleukin-6 (IL-6) were remarkably decreased in AEC treated group compared to vehicle treated group. These results suggest that inhibition of inflammatory response may be tightly associated with anti-tumor activity of AEC in CT26 colon tumor-bearing BALB/cKorl syngeneic mice.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.180-190
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• 2000

Background: Genomic instability, which is manifested by the replication error(RER) phenotype, has been proposed for the promotion of genetic alterations necessary for carcinogenesis. Merlo et al. reported frequent microsatellite instability in primary small cell lung cancers. However, Kim et al. found that instability occurred in only 1% of the loci tested and did not resemble the replication error-positive phenotype. The significance of microsatellite instability in the tumorigenesis of small cell lung cancer as well as the relationship between microsatellite instability and its clinical prognosis was investigated in our study. Methods: Fifteen primary small cell lung cancers were chosen for this study. The DNAs extracted from paraffin-embedded tissue blocks with primary tumor and corresponding control tissue were investigated. Forty microsatellite markers on chromosome 1p, 2p, 3p, 5q, 6p, 6q, 9p, 9q, 13q, and 17p were used in the microsatellite analysis. Results: Thirteen(86.7%) of 15 tumors exhibited LOH in at least one of the tested microsatellite markers. Three of 13 tumors exhibiting LOH lost a larger area in chromosome 9p. LOH was shown in 72.7% on chromosome 2p, 40% on 3p, 50% on 5q, 46.7% on 9p, 69.2% on 13q, and 66.7% on 17p(Table 1). Nine(60%) of 15 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Nine cases exhibiting shifted bands showed altered loci ranging 2.5~52.5%(mean $9.4%\pm16.19$)(Table 2). Shifted bands occurred in 5.7% (34 of 600) of the loci tested(Table 2). Nine cases with shifted bands exhibited LOH ranging between 0~83.3%, and the median survival duration of those cases was 35 weeks. Six cases without shifted bands exhibited LOH ranging between 0~83.3%, and the median survival duration of those cases was 73 weeks. There was no significant difference between median survival durations of the two groups(p=0.4712). Conclusion: Microsatellite instability as well as the inactivation of several tumor suppressor genes may play important roles in the development and progression process of tumors. However, the relationship between microsatellite instability and its clinical prognosis in primary small cell lung cancer could not be established.

• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.415-428
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• 2003

Background : This study assessed the efficacy and toxicity of etoposide and carboplatin(EC) combination regimen as a first line therapy for small cell lung cancer(SCLC), and determined the efficacy and toxicity of topotecan for relapsed SCLC. Methods : One hundred and ten patients with previously untreated SCLC received etoposide($100mg/m^2$ i.v., day 1 to 3) and carboplatin($300mg/m^2$ i.v., day 1) combination chemotherapy every 3 weeks. For patients with relapsed SCLC after EC therapy, topotecan($1.5mg/m^2$) was administered for 5 consecutive days every 3 weeks. Response rate, survival and toxicity profiles were assessed. Response was recorded as CR(complete remission), PR(partial remission), SD(stable disease) and PD(progressive disease). Results : One hundred and one patients were assessed for response to EC. Overall response rate to EC was 57.4%(CR 15.8%, PR 41.6%) with a time to progression of 10.3 months(median). The toxicity was tolerable and there was no treatment-related death. Twenty one relapsed SCLC patients were treated with topotecan. Of those who relapsed within 3 months of EC(refractory relapse, RR), 15.4%(2/13) showed PR, while of those who relapsed after 3 months(sensitive relapse, SR), 25%(2/8) exhibited PR. Grade 4 neutropenia was noted in 9.5% and 14.3% showed thrombocytopenia(G4). Conclusion : The EC regimen showed a moderate response rate for SCLC with minimal toxicity. The use of topotecan for relapsed SCLC warrants further investigation.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.275-282
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• 1998

Purpose : The effect of hyperfractionated radiotherapy on locally advanced non-small lung cancer was studied by a retrospective analysis. Materials & Methods : We analyzed sixty one patients of biopsy-confirmed, IIIA and IIIB non-small cell lung cancer. Using the ECOG performance scale, all the patients were scored less than 2. They were treated by curative hyperfractionated radiotherapy alone from Oct. 1992 to Oct. 1995 at the Department of Radiation Oncology. All the patients received 120cGy b.i.d with more than 6 hours interval between each fraction. The total dose of radiation was reached up to 6400-7080 cGy with a mean dose of 6934 cGy. The results were analyzed retrospectively. Results : The overall survival rate was 53 1$\%$ in 1 year, 9.9$\%$ in 2 years with a median survival time (MST) of 13.9 months. The progression free survival (PFS) rate was 37.0$\%$ in 1 year, 8.9$\%$ in 2 years. Twenty two Patients were classified as complete responders to this treatment and their MST was 19.5 months When this was compared with that of partial responders (MST: 11 7months), it was statistically significant (p=0.0003). Twenty nine patients of stage IIIA showed a better overall survival rate (1yr 63.3$\%$, 2yr 16.8$\%$) than IIIB patients (1yr 43.3$\%$, 2yr 3.6$\%$), which was also statistically significant (p=0.003). Patients with adenocarcinoma showed a better survival rate (1yr 64.3$\%$, 2yr 21.4$\%$) than that of squamous cell counterpart (1yr 49.4$\%$, 2yr 7.4$\%$), although this was not significant statistically (p=0.61). Two patients developed fatal radiation-induced pneumonia right after the completion of the treatment which progressed rapidly and they all died within 2 months. One patient developed radiation-induced fibrosis after 13 months. He refused further treatment and died soon after the development of fibrosis. Conclusion : Among locally advanced NSCLC, hyperfractionated radiotherapy was effective on stage IIIA patients by increasing MST with acceptable toxicities. Acute radiation-induced pneumonia should be carefully monitored and must be avoided during or after this treatment.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.42 no.4
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• pp.403-412
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• 2016

The tight junction, one of Intercellular junctions, performs a variety of biological functions by bonding adjacent cells, including the barrier function to control the movement of the electrolyte and water. Recent studies have revealed that unusual expression of tight junction-related genes have been shown to be related in cancer development and progression. Recently, there are many reports that control of tight junction proteins expression is closely related to the skin moisture. In this study, we are focusing on the regulating mechanism of tight junction-associated genes by the steviol and its derivatives. Steviol, used as a sweetner, is known to chemical compound isolated from stevia plant. The MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay was carried out in HaCaT cells (human keratinocyte cell line) in order to determine the cytotoxicity. As a result, while steviol showing cytotoxicity from $250{\mu}M$, steviol derivatives are not cytotoxic more than $250{\mu}M$ concentration. We have observed a change in the tight junction protein via quantitative real-time PCR. Claudin 8 among tight junction proteins is only significantly reduced up to 30% in the presence of steviol. In addition, cell migration was inhibited by steviol, not by stevioside and rebaudioside. Finally, we could observe that steviol, not stevioside and rebaudioside, is able to increase the skin barrier permeability through the transepithelial electric resistance (TEER) measurements. These results suggest that the steviol and its derivatives are specifically acts on the tight junction related gene expression, but steviol derivatives are more suitable as a cosmetic material.

• Journal of Chest Surgery
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• v.40 no.11
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• pp.765-769
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• 2007

Background: The curative treatment of choice for empyema is decortication of the pleura. The risks of this treatment however are increased for the patient with reduced pulmonary function, complicated calcification or septic shock. In the past, open window thoracostomy was a final stage treatment for chronic empyema. Relatively safe treatment of empyema could be achieved in difficult cases with a closure of the open window after open drainage and use of a myocutaneous flap (one stage or staged). Material and Method: A retrospective study of the cause, progression and final outcome of empyema patients who received open window thoracostomy was performed. 21 patients were followed from 1995 to 2004 in the department of Thoracic and Cardiovascular Surgery in the College of Medicine, Pusan National University. Result: The average age of the patients was $57.5{\pm}15.5$ years (range $25{\sim}78$ years), of whom 16 (76.2%) were men and five (23.8%) were women. Pulmonary function test results showed an average FEV1 of $1.58{\pm}0.49 L$. The type of empyema was tuberculous empyema in 13 cases (61.9%), aspergillosis in three cases (14.3%), parapneumonic empyema in three cases (14.3%) and post-resectional empyema in two cases (10%). Bronchopulmonary fistula was seen in 14 cases. Eight cases were complicated by severe calcification of the pleura. For the four cases of bronchopulmonary fistula, the patients' serratus anterior muscle was covered in their first operation. The average number of ribs resected was $4{\pm}1$. Closure of the open window thoracostomy was performed in 12 cases. The average time to closure after open drainage was $10.22{\pm}3.11$ months and the average defect of the empyemal cavity before the final operation was $330{\pm}110 cc$. Among the 12 cases, there were two cases of spontaneous closure. In two cases closure was only achieved by using the reserved skin fold during the first surgery. Of the remaining eight cases, in seven we used the myocutaneous flap (four cases of lattisimus dorsi muscle and three cases of pectoralis major muscle), and in one case we used soft tissue. As regards complications of the closure, tissue necrosis occurred in one case, which led to failed closure, and there was one case of abdominal hernia in the rectus abdominis muscle flap. One patient died within 30 days of the surgery and one patient died of metastatic cancer. Conclusion: A staged operation with a final closure using open window thoracostomy, which consists of open drainage, transposition of the muscle and a myocutaneous flap, can be a safe and effective option for the chronic empyema patient who is difficult to cure with traditional surgical methods.

• Journal of Chest Surgery
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• v.41 no.5
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• pp.586-590
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• 2008

Background: Non-small cell lung cancer (NSCLC) patients histologically proven to have stage N2 disease by media-stinoscope or thoracoscope underwent subsequent neoadjuvant chemoradiotherapy. This study was designed to find out if there were any differences in survival or recurrence rates between N2 positive and N2 negative patients. Material and Method: Between January 1998 and December 2005, we retrospectively analyzed 69 patients who were divided into three groups. Group A consisted of patients whose N stage was downstaged, group B of patients whose N stage was the same, and Group C of patients who could not undergo surgery because of disease progression during neoadjuvant chemoradiotherapy. We analyzed and compared the mean survival, three-year survival, mean disease-free survival, and three-year disease-free survival rates for the three groups. Result: There were no demographic differences among the groups. The mean survival was 58, 47, and 21 months for groups A, B, and C, respectively. The mean survival was longest in group A, but no statistically significant difference was found on A-B or B-C group comparison (p>0.05). However, a significant difference was noted between group A and group C (p : 0.01). Three-year survival rates were 67%, 41%, and 21.6% for groups A, B, and C, respectively, with a statistical difference similar to that seen in mean survival. The mean disease-free survival was 44 months in group A and 45 months in group B, with no statistically significant difference noted. No significant differences were noted in the three-year disease-free survival rates (55.1%, 46.8%). Conclusion: There were no significant differences in survival or recurrence rates with changes in N stage after neoadjuvant chemoradiotherapy. However, mean survival, three-year survival, and three-year disease-free survival rates tended to be higher in downstaged patients. Nevertheless, the difference was statistically insignificant, and therefore further studies with more patients and longer follow-up are necessary to clarify the positive effects on the survival and prognosis of downstaged patients.

• Clinical and Experimental Pediatrics
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• v.48 no.2
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• pp.178-185
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• 2005

Purpose : The purpose of this study was to evaluate the outcome of children with juvenile myelomonocytic leukemia(JMML) treated with allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods : Eleven JMML patients aged 8-39 months underwent allo-HSCT. The sources of grafts were unrelated donors(n=7), HLA-matched siblings(n=3) and an HLA 1-antigen mismatched familial donor. All patients had received chemotherapy ${\pm}13$-cis-retinoic acid(CRA) before transplant, and CRA was used, posttransplant, in six patients. Results : Only three patients were in complete remission(CR) at the time of transplantation. Initial chimeric status revealed complete donor chimerism(CC) in five patients, mixed chimerism(MC) in five and autologous recovery(AR) in one. One patient with MC having persistent splenomegaly eventually turned to CC and CR after rapid tapering of cyclosporine, combined with daily use of CRA. An AR case relapsed shortly after transplant but was rescued with second, unrelated cord blood transplantation. Ultimately, six patients are alive, event-free, with a median follow-up of 15.5 months posttransplant. All three deaths occurred in patients who failed to achieve CC, leading to disease progression. Conclusion : We suggest that graft-versus-leukemia effect play an important role and CRA a possible role in posttransplant leukemic involution in JMML. In patients whose leukemic burden is still high with MC after transplant, early tapering of immunosuppressants and introduction of CRA might provide a chance of a cure for some patients.

• Radiation Oncology Journal
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• v.12 no.1
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• pp.81-90
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• 1994

Purpose : The aim of this study is to analyze the clinical results of thermo-irradiation treatment for surgically unresectable advanced hepatoma with or without hepatic arterial chemo-embolization (HACE), chemotherapy (CT) and interferon (IFN) therapy. Materials and Methods : Between February 1990 and December 1992, 45 Patients with surgically unresectable advanced hepatomas were treated by thermo-irradiation with or without hepatic arterial chemo-embolization and other treatment modalities. Among them, We analyzed retrospectively 25 patients who received more than three times of hyperthermias. Mean age was 50 years (range : 18-71 years) and male to female ratio was 20 : 5. In the study, treatment was administered as follows : 3 patients received radiation therapy(RT) and hyperthermia (HT). 3 received RT+HT+CT. 3 received RT+HT+HACE. 1 received RT+HT+CT+HACE. 2 received RT+HT+CT+IFN. 10 received RT+HT+HACE+IFN. 3 received RT+HT+CT+HACE+IFN. Radiation therapy was done by a 6 MV linear accelerator Patients were treated with daily fractions of 180 cGy to doses of 11Gy-50Gy (median 30Gy). Local hyperthermia was done by HEH-500C(Omron Co. Japan), 30-45 min/session, 2 sessions/wk and the number of HT sessions ranged from 3 to 17 (median 7 times). 15 patients of 25 were followed by abdominal CT scan or abdominal ultra-sonogram. The following factors were analyzed :Age, histologic grade, sex. number of hyperthermia, total RT dose, hepatic arterial chemo-embolization. Results : Of 25 patients. there were observed tumor regression (partial response and minimal response) in 6 (24$ \% $), no response in 8 (32$ \% $), progression in 1 (4$ \% $) and not evaluable ones in 10 (40$ \% $) radiographically. The over all 1-year survival was 25$ \% $, with a mean survival of 33 weeks. The treatment modes of partial and minimal responsive patients (PR+MR)were as follows : Two were treated with RT+HT+HACE, 2 were done with RT+HT+HACE+IFN Remaining 2 were treated with RT+HT+CT+HACE+IFN. The significant factor affecting the survival rate were RT dose (more than 25 Gy), HACE, number of HT (above 6 times), responsiveness after treatment (PR + MR). Age, sex, histologic differentiation, chemotherapy, interferon therapy were not statistically significant factors affecting the survival rate. Conclusion : Although follow-up duration was short, the thermo-irr3diBtion with/without hepatic arterial chemo-embolization was well tolerated and there were no serious complicatons. In future, it is considered the longer follow up and prospective, well controlled trials should be followed to evaluate the efficacies of survival advantage.

• Journal of Life Science
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• v.30 no.4
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• pp.331-342
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• 2020

The suppression of neuroinflammatory responses in microglial cells can be considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Asparagus cochinchinensis has traditionally been used as a medicine to treat fever, cough, kidney disease, breast cancer, inflammatory diseases, and brain diseases. In this study, we investigated the neuroprotective mechanism of an aqueous extract from A. cochinchinensis root (AEAC), particularly its anti-inflammatory effects on lipopolysaccharide (LPS)-activated BV-2 microglial cells. BV-2 cells were treated with four different concentrations of AEAC. No significant toxicity was detected in BV-2 cells treated with AEAC. Nitric oxide (NO), cyclooxygenase-2 (COX-2) mRNA, and inducible nitric oxide synthase (iNOS) mRNA levels were 21% lower in the AEAC+LPS group than in the Vehicle+LPS group. Lower proinflammatory (TNF-α and IL-1β) and anti-inflammatory cytokine (IL-6 and IL-10) levels were also detected in the AEAC+LPS group than in the Vehicle+LPS group, albeit at varying rates. Moreover, the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group compared to the Vehicle+LPS group, enhancement of the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group, while cell cycle arrest at the G2/M phase caused by LPS treatment was less severe in the AEAC+LPS group. The increase in reactive oxygen species (ROS) generation induced by LPS treatment was also lower in the AEAC-pretreated group than in the Vehicle+LPS group. This is the first study to show that AEAC exerts anti-neuroinflammatory activity against LPS stimulation by regulating the MAPK signaling pathway, the cell cycle, and ROS production.