• International Journal of Oral Biology
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• v.37 no.3
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• pp.91-102
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• 2012

Bcl-2 protects tumor cells from the apoptotic effects of various anti-neoplastic agents. Increased expression of Bcl-2 has been associated with a poor response to chemotherapy in various malignancies, including leukemia. Hence, bypassing the resistance conferred by anti-apoptotic factors such as Bcl-2 represents an attractive therapeutic strategy against cancer cells, including leukemic cells. This study was undertaken to examine whether the anticancer drug, cisplatin and the synthetic chenodeoxycholic acid (CDCA) derivative, HS-1200 show anti-tumor activity in U937 and U937/Bcl-2 cells. Viability assays revealed that HS-1200 overcomes the resistance conferred by Bcl-2 in human leukemic U937 cells. Various apoptosis assessment assays further demonstrated that HS-1200 overcomes the resistance conferred by Bcl-2 in human leukemic U937 cells by inducing apoptosis. In addition HS-1200, but not cisplatin, overcomes the anti-apoptotic effects of Bcl-2 in Bcl-2 over-expressing human leukemic cells (U937/Bcl-2 cells). Notably, we observed that the HS-1200-induced formation of mature promyelocytic leukemia (PML) nuclear bodies (NBs) correlates with a suppression of the anti-apoptotic effects of Bcl-2 in human leukemic cells over-expressing this protein (U937/Bcl-2 cells). Furthermore, HS-1200 was found to induce the association between PML and SUMO-1, Daxx, Sp100, p53 or CBP in the aggregated PML-NBs of U937/Bcl-2 cells. Thus, PML protein and the formation of mature PML-NBs could be considered as therapeutic targets that may help to bypass the resistance to apoptosis conferred by Bcl-2. Elucidating the exact mechanism by which PML regulates Bcl-2 will require further work.

• Journal of Preventive Medicine and Public Health
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• v.45 no.5
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• pp.283-290
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• 2012

Objectives: People who have chronic diseases, as well as gait imbalance or psychiatric drug use, may be susceptible to injuries from falls and slips. The purpose of this study was to evaluate the effect of musculoskeletal diseases on incidental fall-related injuries among adults in Korea. Methods: We analyzed data from the 4th Korea National Health and Nutrition Examination Survey (2007-2009), which are national data obtained by a rolling survey sampling method. The 1-year incidence of fall-related injuries was defined by health service utilization within the last year due to injury occurring after a slip and fall, and musculoskeletal diseases included osteoarthritis, rheumatoid arthritis, osteoporosis, and back pain. To evaluate the effects of preexisting musculoskeletal diseases, adults diagnosed before the last year were considered the exposed group, and adults who had never been diagnosed were the unexposed group. Results: The weighted lifetime prevalence of musculoskeletal disease was 32 540 per 100 000 persons. Musculoskeletal diseases were associated with a higher risk of fall-related injury after adjustment for sex, age, residence, household income, education, occupation, visual disturbance, paralysis due to stroke, and medication for depression (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.03 to 1.93). As the number of comorbid musculoskeletal diseases increased, the risk of fall-induced injuries increased (p-value for trend <0.001). In particular, patients who had any musculoskeletal condition were at much higher risk of recurrent fall-related injuries (OR, 6.20; 95% CI, 1.06 to 36.08). Conclusions: One must take into account the risk of fall-related injuries and provide prevention strategies among adults who have musculoskeletal diseases.

• Journal of Medicine and Life Science
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• v.17 no.2
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• pp.47-52
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• 2020

Glucagon regulates glucose and fat metabolism as well as being involved in the production of ketone bodies. The new antidiabetic drug, a sodium-glucose co-transporter-2 inhibitor, increases glucagon, and reduces the risk of cardiovascular death and hospitalization due to heart failure. The presence of metabolic syndrome is an important risk factor for cardiovascular diseases(CVD) in type 2 diabetes(T2DM) patients. We, thus, investigated the association between glucagon levels and metabolic syndrome in T2DM patients. This cross-sectional study involved 317 T2DM patients. Fasting and postprandial (30 min after ingestion of a standard mixed meal) glucagon levels were measured. Metabolic syndrome was defined according to the criteria of the International Diabetes Federation. A multiple regression logistic analysis was employed for statistical evaluation. A total of 219 (69%) subjects had metabolic syndrome. The fasting and postprandial glucagon levels did not differ between the group with metabolic syndrome and the group without. Postprandial glucagon levels increased significantly with the increase in the number of metabolic syndrome components, but the fasting levels did not. However, a hierarchical logistic regression analysis revealed that the postprandial glucagon levels did not contribute significantly to metabolic syndrome even after adjusting for other covariates. Fasting and postprandial glucagon levels are not associated with metabolic syndrome in T2DM patients. However, further studies are needed to investigate the relationship between glucagon and cardiovascular risk in patients with T2DM.

• Journal of Gastric Cancer
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• v.20 no.2
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• pp.115-126
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• 2020

Peritoneal metastasis (PM) frequently occurs in patients with gastric cancer (GC) and confers a dismal prognosis despite advances in systemic chemotherapy. While systemic chemotherapy has poor peritoneal penetration, intraperitoneal (IP) chemotherapy remains sequestered, resulting in high peritoneal drug concentrations with less systemic side-effects. The first application of IP treatment was hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) for gastric cancer peritoneal metastasis (GCPM); but was associated with an increased morbidity and mortality rate without significantly improving overall survival (OS). While CRS confers limited benefit, the potential role of prophylactic HIPEC and laparoscopic neoadjuvant HIPEC are currently being evaluated. Combination systemic and IP chemotherapy (SIPC) gained popularity in the 1990s, since it provided the benefits of IP treatment while reducing surgical morbidity, demonstrating promising early results in multiple Phase II trials. Unfortunately, these findings were not confirmed in the recent PHOENIX-GC randomized controlled trial; therefore, the appropriate treatment for GCPM remains controversial. Small observational studies from Japan and Singapore have reported successful downstaging of PM in GC patients receiving SIPC who subsequently underwent conversion gastrectomy with a median OS of 21.6-34.6 months. Recently, the most significant development in IP-directed therapy is pressurized IP aerosol chemotherapy (PIPAC). Given that aerosol chemotherapy achieves a wider distribution and deeper penetration, the outcomes of multiple ongoing trials assessing its efficacy are eagerly awaited. Indeed, IP-directed therapy has evolved rapidly in the last 3 decades, with an encouraging trend toward improved outcomes in GCPM, and may offer some hope for an otherwise fatal disease.

• The Journal of Korea Assosiation for Disability and Oral Health
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• v.9 no.1
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• pp.30-35
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• 2013

The four principles of treatment of odontogenic infection are as follows : (1) removal of the cause, (2) establishment of drainage, (3) institution of antibiotic therapy, and (4) provision of supportive care, including proper rest and nutrition. A separate incision is required to establish drainage, especially in the case of extensive fascial space infections. There are four principle causes for active bleeding in the immediate incision & drainage phase; (1) vascular wall alteration (infection, scurvy, chemicals), (2) disorder of platelet function, (3) thrombocytopenic purpuras, (4) disorders of coagulation (liver disease, anticoagulation drug). If the hemorrhage from incision & drainage site is aggressive, the site must be packed with proper wet gauze and wound closure & drainage dressing are applied. The specific causes of bleeding may be associated with hypoxia, changes in the pH of blood & chemical changes affecting vascular contractility and blood clotting. This is a case report of bleeding control by the circumferential suture & drainage on active bleeding incision & drainage site of temporal space abscess due to advanced odontogenic infection in a multiple medically compromised disabled patient.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.33 no.5
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• pp.445-448
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• 2011

Mortality associated with maxillofacial infection is relatively low due to the development of antibiotics, and improved oral care. However, inappropriate treatment, delayed treatment, old age, underlying systemic disease, and drug-resistant microorganisms can potentially result in life threatening situations such as cavernous sinus thrombosis, mediastinitis, and sepsis. Sepsis is the most dangerous state with high mortality, ranging from 20~60%. The treatment of sepsis involves properly monitoring vital functions, fluid resuscitation, surgical drainage, and empirical use of high doses of antibiotics until culture results are available. Ventilatory support maybe be required as well. We encountered a 64-year-old patient who died from sepsis that developed as the result of an odontogenic infection. The initial diagnosis was right temporal, infraorbital, buccal, pterygomandibular space abscess. Despite surgical and medical supportive care, the condition progressed to sepsis and after four days the patient died due to multiple organ failure.

• Bulletin of the Korean Chemical Society
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• v.26 no.11
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• pp.1728-1734
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• 2005

The interactions of Cu(II)-meso-Tetrakis(n-N-methylpyridiniumyl)porphyrin (n = 2,3,4), respectively referred to as o-, m- and p-CuTMPyP, and DNA, poly$[d(A-T)_2]$ and poly$[d(G-C)_2]$ were investigated by circular and linear dichroism (CD and LD). In the o-CuTMPyP case, in which the rotation of the pyridinium ring is prevented, the shape of the CD spectrum when associated to DNA and poly$[d(A-T)_2]$ resembles and is characterized by a positive band at a low drug to DNA concentration ratio (R ratio) and is bisignate at a high R ratio. The former CD spectrum shape has been attributed to porphyrin that is bound monomerically outside of DNA while the latter can be attributed to those that are stacked. When o-CuTMPyP is bound to poly$[d(G-C)_2]$, the excitonic CD appeared at a relatively high R ratio. In contrast, a characteristic negative CD band in the Soret region was apparent for both m- and p-CuTMPyP when bound to DNA and poly$[d(G-C)_2]$ at the low R ratios, indicating that the porphyrin molecule intercalates. However, the DNA is bent near the intercalation site and the plane of the porphyrin molecule tilts relative to the DNA helix axis, as judged by the magnitude of the reduced LD. Various stacking patterns were identified by the shape of the CD spectrum for m- and p-CuTMPyP when bound to poly$[d(A-T)_2]$. Three species for the former complex and two for the latter complex were found which may reflect the extent of the stacking.

• Journal of Haehwa Medicine
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• v.21 no.1
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• pp.11-21
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• 2012

New onset diabetes is a major complication after kidney transplantation. However, the natural course of posttransplantation diabetes mellitus (PTDM) remains unclear. The aim of this study was to demonstrate the detailed natural courses of PTDM according to the onset and persistency of hyperglycemia, and to investigate risk factors for development of different courses of PTDM in renal allograft recipients. The purpose of this study is to develop novel immune suppressants for PTDM using of action mechanism of them. The use of immunosuppressive drugs in transplanted patients is associated with the development of diabetes, possibly due to ${\beta}$-cell toxicity. To better understand the mechanisms leading to post-transplant diabetes, we investigated the actions of prolonged exposure of ${\beta}$-cells to therapeutical levels of tacrolimus (FK506) or cyclosporin A(CsA). The immunosuppressive drug cyclosporine(CsA) is a potent agent widely used after organ transplantations and various autoimmune disorders. After using CsA, some patients suffer severe complications including renal and vascular toxicity. The renal or vascular toxicity is influenced by the degree of the endothelial damage. FK506(tacrolimus) is a widely used immunosuppressive agent in the treatment of various medical conditions, including autoimmune disease, bone marrow and organ transplantations. We found some interesting clusters and confirmed the feasibility of cDNA microarray in the study of Immunosuppressant. In this study, we investigated gene expression patterns induced by Immunosuppressant in RIN-m5F of rat insulinoma cell line. Gene expressions evaluated using cDNA microarry in two clusters were increased or decreased. this study provides comprehensive comparison of the patterns of gene expression changes induced by CsA and FK506 in ${\beta}$-cells. This study could establish that the mode of action mechanism by which currently used insulin inhibitors inducing PTDM could be elucidated at least in part, which raises the possibility that novel immune suppressive PTDM can be developed. The molecular biological study on PTDM will also contribute the progress in diabetes research field as well as in that of PTDM.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4481-4485
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• 2012

Background: Chemotherapy induced leutropenia has been shown to be associated with improved treatment outcomes in selected solid tumors. We studied the association of chemotherapy induced leutropenia with treatment related outcomes in advanced non-small-cell lung cancer. Methods: This is a prospective analysis of patients receiving chemotherapy for advanced NSCLC at the Shandong Cancer Hospital from 2005-07.The chemotherapy included cisplatin $35mg/m^2$, IV on $d_{1,2}$ and vinorelbine $25mg/m^2$ IV on $d_{1,8}$ every 21 days. Patients were stratified into three groups (A) those experiencing grades 0 leucopenia, group (B) grades 1-2 and group (C) grades 3-4. The outcomes studied were response rate (RR), disease control rate (DCR), and time to progression (TTP). Results: 128 patients were studied. The RRs in groups A, B and C were 30.8%, 56.8% and 71.4%, respectively, p=0.010. The DCRs were 61.5%, 83.8% and 92.9%, respectively, p=0.009 and the median TTPs were 150 days (95%CI: 91-209), 189 days (95%CI: 181-197) and 207 days (95%CI: 172-242), p=0.009. The differences in RR and TTP were significant. In patients whose CIL kept on 10 days at least, the TTP was significantly prolonged, p=0.0213, and the same was the case for those experiencing grades 1-2 leucopenia and ECOG 0, p=0.0412. Conclusions: Occurrence of CIL correlated with RR and TTP in patients with advanced NSCLC receiving cisplatin and vinorelbine chemotherapy, especially in patients experiencing grades 1-2 leucopenia and ECOG 0, and the same for those with CIL persisting for 10 days at least. CIL could be a biological measure of drug activity and a marker of efficacy.

• Biomedical Science Letters
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• v.24 no.2
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• pp.134-137
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• 2018

S100A8 and S100A9 are involved in pathogenesis of cancer by induction or inhibition of cancer as well as inflammation. In this study, we investigated the association of S100A8 and S100A9 with pathogenesis of leukemia using human monocytic leukemia cells, THP-1. The expression of TLR4, which is a known receptor of S100A8 and S100A9, was examined by using flow cytometry and Western blotting. THP-1 cells have high surface and cytosol expression of TLR4. S100A8 and S100A9 suppressed the cell survival, and this suppression was found to be associated with apoptosis because they increased the number of apoptotic cells in a dose- and a time-dependent manners. However, S100A8 and S100A9 had no effect on the survival and apoptosis of monocytes isolated from the peripheral blood. We next examined the apoptotic effect of lipopolysaccharide (LPS) and monophosphoryl lipid A (MPLA), which are other ligands of TLR4, in THP-1 cells. Lipopolysaccharide had no effect on cell survival, but MPLA is effective on the cell apoptosis. These results suggest that S100A8 and S100A9 may regulate leukemia cell survival via TLR4, which is an essential receptor in the pro-apoptotic mechanism induced by S100A8 and S100A9. These findings may shed light on development of a possible therapeutic drug for leukemia treatment.