• Proceedings of the Plant Resources Society of Korea Conference
• /
• 2019.04a
• /
• pp.113-113
• /
• 2019

Diallyl trisulfide (DATS) is an organic polysulfide compound found in garlic. Although certain studies have demonstrated that DATS possesses strong anti-inflammatory activity, the underlying molecular mechanisms remain largely unresolved. In this study, we examined whether DATS exerts anti-inflammatory activity and investigated the possible mechanisms. Our results indicated that DATS significantly suppressed the lipopolysaccharide (LPS)-induced release of nitric oxide (NO) and prostaglandin E2 by inhibiting inducible NO synthase and cyclooxygenase-2 expression at the transcriptional and post-transcriptional levels in RAW 264.7 macrophages. DATS also down-regulated Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 expression, and inhibited nuclear translocation of nuclear transcription factor-kappa B (NF-${\kappa}B$) in LPS-stimulated 264.7 macrophages. Furthermore, we found that these inhibitory effects of DATS were associated with the inhibition of chemokine receptor (CXCR4) and ligand (CXCL12) expression, and reactive oxygen species generation. Overall, the present data indicated that DATS had anti-inflammatory effects on LPS-activated macrophages, possibly via inhibiting the TLR4/NF-kB and/or chemokine signaling pathways, and DATS could be a potential drug therapy for inflammation and its associated diseases.

• Radiation Oncology Journal
• /
• v.10 no.2
• /
• pp.193-204
• /
• 1992

During the period between March 1983 and December 1990, 74 patients with esophageal carcinoma (EG) were treated with radiation therapy (RT) at the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, Catholic University Medical College. Of these, 6 patients were lost to follow-up, and 13 patients were interrupted. So the remaining 55 patients were analyzed, retrospectively. 32 patients were irradiated with curative aim, 12 patients with palliative intent, 10 patients postoperatively, and 1 patient pre- and post-operatively. Among these 55 patients, 28 patients were treated with chemoradiation modality, and 27 patients with RT alone. All patients were followed for a minimum of 20 months or until death. Of 32 patients irradiated by curative aim, 22 patients (69%) showed partial remission (PR), 6 patients (19%) complete remission (CR). Overall mean survival and two-year survival rate were 15.6 months and 22%. With respect to sex, age, pathologic differentiation, tumor location, tumor size, stage, RT aim, RT response, RT dose, use of chemotherapy and functional categories (FC) of dysphagia at initiation of RT and at finishing RT: Tumor size, stage, RT response had great influences on prognosis and FC at finishing RT had a slight influence on prognosis. Especially, the mean survival and 2-year survival rate in patients with postoperative RT were 24.7 months and 63%, which could be compared with 29.1 months and 43% in radically treated patients with CR. And the mean survival duration and 2-year survival rate in patients irradiated with doses more than 60 Gy were 22.4 months and 29%, and 50~60 Gy were 12.2 months and 12%, respectively. However, no significant difference was shown statistically. Among 12 patients treated with palliative intent, 9 patients (75%) had good improvement in dysphagia and the mean duration of palliative response was 10.6 months.

• Journal of Gastric Cancer
• /
• v.6 no.4
• /
• pp.237-243
• /
• 2006

Purpose: This study was conducted to evaluate the treatment outcomes and the prognosis for gastric cancer patients with hepatic metastasis. Materials and Methods: This retrospective study was based on the medical records of 85 gastric cancer patients with hepatic metastasis (62 synchronous and, 23 metachronous) who received chemotherapy with or without resectional therapy from March 1990 to March 2006. The survival rate was analyzed according to clinicopathologic factors and therapeutic factors, such as whether or not a gastrectomy, a hepatic resection, and/or chemotherapy had been performed. Results: The median survival of gastric cancer patients with hepatic metastasis was 11 months (synchronous: 11 months and metachronous: 17 months). The rates of gastrectomies and hepatic resections in the synchronous group were 24.1% and 16.1%, respectively A 23.5% prevalence of extra-hepatic metastasis was observed. The median survivals of patients who underwent a gastrectomy with a hepatic resection, a gastrectomy alone, and non-surgical treatment were 60, 18, and 9 months, respectively (P<0.05). The disease-free median survival of the metachronous group was 8 ($3{\sim}39$) months. There was no difference in initial pathologic stage and frequency of hepatic metastasis after the gastrectomy in the metachronous group. In the synchronous group, extra-hepatic metastasis, a gastrectomy as the operative procedure, a hepatic resection as the operative procedure and the response to chemotherapy were statistically significant in the univariate analysis, and a hepatic resection as the operative procedure, the response to chemotherapy, and extra-hepatic metastasis were independant prognostic factors identified by the multivariate analysis. In the metachronous group, extra-hepatic metastasis, the response to chemotherapy and differentiation were statistically significant in the univariate analysis, and extra-hepatic metastasis was an independent prognostic factor identified by the multivariate analysis. Conclusion: An aggressive surgical therapy and effective chemotherapy are necessary in the treatment of gastric cancer patients with hepatic metastasis. (J Korean Gastric Cancer Assoc 2006;6:237-243)

• Journal of Life Science
• /
• v.17 no.5 s.85
• /
• pp.678-686
• /
• 2007

Human mesenchymal stem cells(hMSC), that have been reported to be present in bone marrow, adipose tissues, dermis, muscles and peripheral blood, have the potential to differentiate along different lineages including those forming bone, cartilage, fat, muscle and neuron. Therefore, hMSC are attractive candidates for cell and gene therapy. The optimal conditions for hMSC expansion require medium supplemented with fetal bovine serum(FBS). Some forms of cell therapy will involve multiple doses, raising a concern over immunological reactions caused by medium-derived FBS proteins. Previously, we have shown that hADSC can be cultured in human serum(HS) during their isolation and expansion, and that they maintain their proliferative capacity and ability for multilineage differentiation and promote engraftment of peripheral blood-derived CD34 cells mobilized from bone marrow in NOD/SCID mice. In this study we determined whether hADSC grown in HS maintain surface markers expression similar with cells grown in FBS during culture expansion and compared gene expression profile by Affymetrix microarray. Flow cytometry analysis showed that HLA-DR, CD117, CD29 and CD44 expression in HS-cultured hADSC during culture expansion were similar with that in FBS-cultured cells. However, the gene expression profile in HS-cultured hADSC was significantly different from that in FBS-cultured cells. Therefore, these data indicated that HS-cultured hADSC should be used in vivo animal study of hADSC transplantation for direct extrapolation of preclinical data into clinical application.

• Radiation Oncology Journal
• /
• v.27 no.4
• /
• pp.181-188
• /
• 2009

Purpose: The aim of this study was to evaluate the results of postoperative radiotherapy in a case of perihilar cholagiocarcinoma by analyzing overall survival rate, patterns of failure, prognostic factors for overall survival, and toxicity. Materials and Methods: Between January 1998 and March 2008, 38 patients with perihilar cholangiocarcinoma underwent a surgical resection and adjuvant radiotherapy. The median patient age was 59 years (range, 28 to 72 years), which included 23 men and 15 women. The extent of surgery was complete resection in 9 patients, microscopically positive margins in 25 patients, and a subtotal resection in 4 patients. The tumor bed and regional lymphatics initially received 45 Gy or 50 Gy, but was subsequently boosted to a total dose of 59.4 Gy or 60 Gy in incompletely resected patients. The median radiotherapy dose was 59.4 Gy. Concurrent chemotherapy was administered in 30 patients. The median follow-up period was 14 months (range, 6 to 45 months). Results: The 3-year overall survival and 3-year progression free survival rates were 30% and 8%, respectively. The median survival time was 28 months. A multivariate analysis showed that differentiation was the only significant factor for overall survival. The 3-year overall survival was 34% in R0 patients and 20% in R1 patients. No statistically significant differences in survival were found between the 2 groups (p=0.3067). The first site of failure was local in 18 patients (47%). No patient experienced grade 3 or higher acute toxicity and duodenal bleeding developed in 2 patients. Conclusion: Our results suggest that adjuvant RT might be a significant factor in patients with a positive margin following a radical resection. However, there was still a high locoregional recurrence rate following surgery and postoperative radiotherapy. Further study is necessary to enhance the effect of the adjuvant radiotherapy.

• Radiation Oncology Journal
• /
• v.19 no.2
• /
• pp.181-189
• /
• 2001

Purpose : Changes in the balance between MMP and TIMP can have a profound effect on the composition in the extracellular matrix (ECM) and affect various cellular functions including adhesion, migration, differentiation of cells, and fibrosis and invasion and metastasis of cancer cells. Radiation therapy is a popular treatment modality for benign and malignant tumor, but the study for radiation effect on MMP and TIMP is scarce. In the current study, we have examined the expression of TIMP in fibrosis-prone (C57BL/6) mice after radiation. Methods and Materials : Adult female mice of $10\~12$ weeks were used. The whole body were irradiated using a Varian CL-4/100 with 2 and 10 Gy. Immunohistochemical staining was peformed according to Avidin Biotin complex method and evaluated by observing high power field. For TIMP-1, TIMP-2 antibodies, reactivity was assessed in the parenchymal cell and in the stromal cell. The scale of staining was assessed by combining the quantitative and qualiative intensity of staining. Results : TIMP-1 immunoreactivity did not change in lung. But, in liver, TIMP-1 immunoreactivity was localized in cytoplasm of hepatocyte and Kupffer cell. in kidney, TIMP-1 immunoreactivity was localized in cytoplasm of some tubular cell. Temporal variations were not seen. Dose-response relationship was not seen except kidney. TIMP-2 immunoreactivity in lung was a score (++) at 0 Gy and elevated to a score (+++) at 2 Gy. TIMP-2 immunoreactivity was a score (++) in liver at 0 Gy. TIMP-2 immunoreactivity was localized in cytoplasm of hepatocyte and Kupffer cell as same as patterns of TIMP-1 immunoreactivity. The TIMP-2 immunoreactivity in liver was elevated to (+++) at 2 Gy. Immunoreactivity to TIMP-2 in kidney was a score (+++) at 0 Gy and was not changed at 10 Gy. The score of TIMP-2 immunoreactivity was reduced to (++) at 2 Gy. TIMP-2 immunoreactivity was confined to tubules in kidney. Temporal variation of TIMP-2 immunoreactivity was irregular. Dose-response relationship of TIMP-2 immunoreactivity was not seen. Conclusions : Differences between intensity of expression of TIMP-1 and TIMP-2 in each organ was present. Expression of TIMP was localized to specific cell in each organ. Irradiation increased TIMP-1 immunoreactivity in the liver and the kidney. Irradiation increased TIMP-2 immunoreactivity in the lung. But, in the liver and the kidney, TIMP-2 expression to radiation was irregular. Temporal variation of TIMP-2 immunoreactivity was irregular. Dose-response relationship of TIHP-2 immunoreactivity was not seen. In the future, we expect that the study of immunohistochemical staining of longer period of postirradiation and quantitative analysis using western blotting and northern blotting could define the role of TIMP in the radiation induced tissue fibrosis.

• Clinical and Experimental Pediatrics
• /
• v.52 no.2
• /
• pp.213-219
• /
• 2009

Purpose:Iron is a critical nutritional element that is essential for a variety of important biological processes, including cell growth and differentiation, electron transfer reactions, and oxygen transport, activation, and detoxification. Iron is also required for neoplastic cell growth due to its catalytic effects on the formation of hydroxyl radicals, suppression of host defense cell activities, and promotion of cancer cell multiplication. Chronic transfusion-dependent patients receiving chemotherapy may have iron overload, which requires iron-chelating therapy. We performed this study to demonstrate whether the iron chelating agent deferoxamine induces apoptosis in Saos-2 osteosarcoma cells, and to investigate the underlying apoptotic mechanism. Methods:To analyze the apoptotic effects of an iron chelator, cultured Saos-2 cells were treated with deferoxamine. We analyzed cell survival by trypan blue and crystal violet analysis, apoptosis by nuclear condensation, DNA fragmentation, and cell cycle analysis, and the expression of apoptotic related proteins by Western immunoblot analysis. Results:Deferoxamine inhibited the growth of Saos-2 cell in a time- and dose-dependent manner. The major mechanism for growth inhibition with the deferoxamine treatment was by the induction of apoptosis, which was supported by nuclear staining, DNA fragmentation analysis, and flow cytometric analysis. Furthermore, bcl-2 expression decreased, while bax, caspase-3, caspase-9, and PARP expression increased in Saos-2 cells treated with deferoxamine. Conclusion:These results demonstrated that the iron chelating agent deferoxamine induced growth inhibition and mitochondrial-dependent apoptosis in osteosarcoma Saos-2 cells, suggesting that iron chelating agents used in controlling neoplastic cell fate can be potentially developed as an adjuvant agent enhancing the anti-tumor effect for the treatment of osteosarcoma.

• Journal of Oral Medicine and Pain
• /
• v.35 no.3
• /
• pp.165-175
• /
• 2010

Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent as well, when findings indicated the substance inhibited proliferation and induced differentiation of primitive neuroectocdermal tumor cells in vivo (Cinatl et al., 1997). Antitmor activity of VPA is associated with its targeting histone deacetylases. Bile acids and their synthetic derivatives induced apoptosis in various kinds of cancer cells and anticancer effects. It has been reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis-inducing activity on various cancer cells in vitro. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and a CDCA derivative, HS-1200 on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and HS-1200 showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-7, caspase-3 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or $25\;{\mu}M$ HS-1200 for 48 h did not induce apoptosis, the co-treatment of them induced prominently apoptosis. Therefore our data provide the possibility that combination therapy of VPA and HS-1200 could be considered as a novel therapeutic strategy for human osteosarcoma.

• Tuberculosis and Respiratory Diseases
• /
• v.46 no.2
• /
• pp.185-194
• /
• 1999

Background: NF-$\kappa$B is a characteristic transcriptional factor whose functional activity is determined by post-translational modification of protein and subsequent change of subcellular localization. The involvement of the NF-$\kappa$B family of the transcription factors in the control of such vital cellular functions as immune response, acute phase reaction, replication of certain viruses and development and differentiation of cells has been clearly documented in many previous studies. Several recent observations have suggested that the NF-$\kappa$B might also be involved in the carcinogenesis of some hematological and solid tumors. Investigating the possibility that members of the NF-$\kappa$B family participate in the molecular control of malignant cell transformation could provide invaluable information on both molecular pathogenesis and cancer-related gene therapy. Method: To determine the expression patterns and functional roles of NF-$\kappa$B family transcription factors in human lung cancer cell lines NCI-H792, NCI-H709, NCI-H226 and NCI-H157 were analysed by western blot, using their respective antibodies. The nuclear and the cytoplasmic fraction of protein extract of these cell lines were subsequently obtained and NF-$\kappa$B expression in each fraction was again determined by western blot analysis. The type of NF-$\kappa$B complex present in the cells was determined by immunoprecipitation. To detect the binding ability of cell-line nuclear extracts to the KB consensus oligonucleotide, electrophoretic mobility shift assay(EMSA) was performed. Results: In the cultured human lung cancer cell lines tested, transcription factors of the NF-$\kappa$B family, namely the p50 and p65 subunit were expressed and localized in the nuclear fraction of the cellular extract by western blot analysis and immunocytochemistry. Immunoprecipitation assay showed that in the cell, the p50 and p65 subunits made NF-$\kappa$B complex. Finally it was shown by Electrophoretic Mobility Shift Assay(EMSA) that nuclear extracts of lung cancer cell lines are able to bind to NF-$\kappa$B consensus DNA sequences. Conclusion: These data suggest that in human lung cancer cell lines the NF-$\kappa$B p50/p65 complex might be activated. and strengthen the hypothesis that NF-$\kappa$B family transcription factors might be involved in the carcinogenesis of human lung cancer.

• Journal of Yeungnam Medical Science
• /
• v.11 no.1
• /
• pp.72-81
• /
• 1994

Total 55 patients with nonsmall cell lung cancer treated with radiation therapy at Department of Therapeutic Radiology, Yeungnam University Hospital, between May-1 1986 and April-30 1993 were retrospectively analyzed by clinical characteristics, failure patterns, follow up duration and survival ratio according to prognostic factors. Obtained results were as follows : 1. Male to female ratio was 17.3 2. Sixth and seventh decades were predominant age group. 3. The patients were 8 in stage I-II, 34 in stage IIIA, 13 in stage IIIb, respectively. 4. Forty five patients out of 55 were squamous cell carcinoma. 5. Primary tumor were originated from upper lobe bronchi predominantly. 6. The size of the primary tumor, lymph node involvement and the degree of differentiation were important in evaluation of prognosis. 7. In conclusion, for patients with poor prognostic factors systemic chemotherapy and multidisciplinary approach were recommended for better treatment outcome and improvement of survival.