The purpose of this study was to investigate the effects of four restorative materials under various occlusal loading conditions on the stress distribution at the CEJ of buccal, palatal surface and central groove of occlusal surface of endodontically treated maxillary second premolar, using a 3D finte element analysis. A 3D finite element model of human maxillary second premolar was endodontically treated. After endodontic treatment, access cavity was filled with Amalgam, resin, ceramic or gold of different mechanical properties. A static 500N forces were applied at the buccal (Load-1) and palatal cusp (Load-2) and a static 170N forces were applied at the mesial marginal ridge and palatal cusp simultaneously as centric occlusion (Load-3). Under 3-type Loading condition, the value of tensile stress was analyzed after 4-type restoration at the CEJ of buccal and palatal surface and central groove of occlusal surface. Excessive high tensile stresses were observed along the palatal CEJ in Load-1 case and buccal CEJ in Load-2 in all of the restorations. There was no difference in magnitude of stress in relation to the type of restorations. Heavy tensile stress concentrations were observed around the loading point and along the central groove of occlusal surface in all of the restorations. There was slight difference in magnitude of stress between different types of restorations. High tensile stress concentrations around the loading points were observed and there was no difference in magnitude of stress between different types of restorations in Load-3.
Bicuspid ; Ceramics ; Finite Element Analysis ; Humans ; Tooth Cervix

In the current years, it has now become necessary to establish standards for micronutrient intake based on scientific evidence. This review discusses issues related to the development of the 2020 Dietary Reference Intakes for Koreans (KDRI) for magnesium (Mg), zinc (Zn), and copper (Cu), and future research directions. Following issues were encountered when establishing the KDRI for these minerals. First, characteristics of Korean subjects need to be applied to estimate nutrient requirements. When calculating the estimated average requirement (EAR), the KDRI used the results of balance studies for Mg absorption and factorial analysis for Zn, which is defined as the minimum amount to offset endogenous losses for Zn and Mg. For Cu, a combination of indicators, such as depletion/repletion studies, were applied, wherein all reference values were based on data obtained from other countries. Second, there was a limitation in that it was difficult to determine whether reference values of Mg, Zn, and Cu intakes in the 2020 KDRI were achievable. This might be due to the lack of representative previous studies on intakes of these nutrients, and an insufficient database for Mg, Zn, and Cu contents in foods. This lack of database for mineral content in food poses a problem when evaluating the appropriateness of intake. Third, data was insufficient to assess the adequacy of Mg, Zn, and Cu intakes from supplements when calculating reference values, considering the rise in both demand and intake of mineral supplements. Mg is more likely to be consumed as a multi-nutrient supplement in combination with other minerals than as a single supplement. Moreover, Zn-Cu interactions in the body need to be considered when determining the reference intake values of Zn and Cu. It is recommended to discuss these issues present in the 2020 KDRI development for Mg, Zn, and Cu intakes in a systematic way, and to find relevant solutions.

PURPOSE: The aim of this study was to quantitatively assess the intensity of tumor budding in rectal carcinoma and to determine how it correlates with the malignant potential. MATERIALS AND METHODS: Intensities of the tumor budding at the invasive front of the surgical specimens from 90 patients (male, 51) with well- or moderately- differentiated rectal carcinoma were investigated. Differences in the budding intensity among pathologic variables were compared, and recurrences and survivals were analyzed in accordance with degree of the budding intensity. The patients ranged in age from 33 to 75 years (mean, 55.4) with the median follow-up being 43 months (range, 12~108). RESULTS: Tumor budding was identified in 89 patients (98.9%) with a mean intensity of 7.5+/-5.3. The budding intensity was significantly higher in tumors with lymphatic invasion (p=0.0081), blood vessel invasion (p<0.0001), and perineural invasion (p=0.0013) than in those tumor without these findings. It became significantly higher with the increase in nodal stage (p<0.0001). The intensity of tumor budding in patients with relapse (29 patients) was significantly higher than that in patients without relapse (6.2+/-5.0 vs. 10.2+/-4.9; p=0.0005), but this difference in the intensity was observed only for the node-positive patients (8.0+/-3.4 vs. 11.9+/-5.1; p=0.0064). When the patients were stratified into two groups on either side of the mean of the intensity, the higher intensity group showed a significantly less favorable disease- free (DFS) and overall survival (OS) (p=0.0026 and 0.0205, respectively). Based on the multivariate analysis, the nodal stage and the intensity of budding proved to be the independent variables associated with DFS (p=0.023 and 0.03, respectively). CONCLUSION: Tumor budding at the invasive margin is a reliable pathologic index that indicates a higher malignant potential and a less favorable prognosis for patients with advanced rectal carcinoma.
Blood Vessels ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Prognosis ; Recurrence

In our previous study, we have shown that berberine has both anti-adipogenic and anti-inflammatory effects on 3T3-L1 adipocytes, and the anti-adipogenic effect is due to the down-regulation of adipogenic enzymes and transcription factors. Here we focused more on anti-inflammatory effect of berberine using real time RT-PCR and found it changes expressions of adipokines. We hypothesized that anti-adipogenicity of berberine mediates anti-inflammtory effect and explored leptin as a candidate mediator of this signaling. We studied this hypothesis by western blot analysis, but our results showed that berberine has no effect on the phosphorylations of STAT-3 and ERK which have important roles on leptin signaling. These results led us to conclude that the anti-inflammatory effect of berberine is not mediated by the inhibition of leptin signal transduction. Moreover, we have found that berberine down-regulates NF-kappaB signaling, one of the inflammation-related signaling pathway, through western blot analysis. Taken together, the anti-inflammatory effect of berberine is not mediated by leptin, and berberine induces anti-inflammatory effect independent of leptin signaling.
Adipocytes ; Adipokines ; Berberine ; Blotting, Western ; Down-Regulation ; Inflammation ; Leptin ; NF-kappa B ; Phosphorylation ; Signal Transduction ; Transcription Factors

PURPOSE: Breast cancer shows various molecular and genetic alterations in its development and progression. Microsatellite alterations, and especially microsatellite instability (MSI) and loss of heterozygosity (LOH), have recently been postulated as a novel mechanism of carcinogenesis and as a useful prognostic factor for several gastrointestinal malignancies. LOH is related to the allelic loss of various tumor suppressor genes; however, MSI has been found to be the result of an erroneous DNA mismatch repair system and this has been known to be involved in the carcinogenesis of the hereditary non-polyposis colon cancers and some portion of the sporadic colorectal or gastric cancers. Yet MSI has rarely been studied in invasive ductal carcinoma. Our objectives were to evaluate the MSI and p53 protein expression in invasive ductal carcinomas and to correlate this with various clinicopathological factors. METHODS: The MSI analysis was performed by using polymerase chain reaction with five polymorphic microsatellite markers (the BAT25, BAT26, D2S123, D5S346 and D17S250 loci as recommended by the 1998 NCI International Workshop on Microsatellite Instabilitis and RER phenotypes) in 50 surgically resected tumors and each of their non-tumorous counterpart. The p53 protein expression was studied using immunohistochemistry. RESULTS: MSI and a p53 protein expression were detected in 22% and 54% of the tumors and non-tumorous tissues, respectively. MSI was more frequently detected in tumor grade I, T-stage I, non-metastatic tumor and tumor stage I. Also there were rare cases showing a high grade and stage with metastasis in the MSI-high group, in which more than 3 microsatellite loci had MSI. The p53 expression results correlated well with a higher tumor grade. Correlation between MSI and the p53 expression was not found. CONCLUSION: These results may suggest that MSI may be involved in some portions in mammary carcinogenesis and tumor invasion. Also the clinical use of the MSI status may help to determine a better prognosis among invasive ductal cancer patients.
Breast Neoplasms ; Carcinogenesis ; Carcinoma, Ductal* ; Colonic Neoplasms ; DNA Mismatch Repair ; Education ; Genes, Tumor Suppressor ; Humans ; Immunohistochemistry ; Loss of Heterozygosity ; Microsatellite Instability* ; Microsatellite Repeats* ; Neoplasm Metastasis ; Polymerase Chain Reaction ; Prognosis ; Stomach Neoplasms

BACKGROUND: There is considerable experimental evidence to indicate that tumor growth is dependent on angiogenesis. To investigate how tumor angiogenesis correlates with clinical factors and prognosis in breast carcinoma, we counted microvessels (capillaries and venules) and graded the density of micro vessels within the invasive ductal carcinomas of 59 patients. METHODS: Using light microscopy, we highlighted the vessels by staining their endothelial cells immu nohistochemically for rabbit antihuman factor-VIII related antigen (Dako L1809, USA). The microvessels were carefully counted (per 200 field) in the most active areas of neovascularization without knowledge of either the outcome in the patient or the clinical variables. RESULTS: The mean age was 47.8 years. There was no statistical correlation between angiogenesis and either estrogen receptor status or age. However, there was a statistical correlation with tumor size (p< or =0.05). There was a statistical difference between lymph-node-metastasis positive group and negative group (p= 0.006). Angiogenesis correlated statistically with TMN stage (microvessels count:stage I= 31.27, stage II= 40.74, and stage III= 78.9)(p= 0.001). There was a statistical correction between angiogenesis and follow-up results (microvessels counts:disease free group= 42.11, living metastatic group= 63.64, and expired group= 73.60)(p= 0.031). CONCLUSIONS: In this study, the degree of angiogenesis (the number of microvessels per 200 field in the area of most intensive neovascularization) may have a predictive value in invasive breast carci nomas. Therefore, assessment of tumor angiogenesis may give us useful information for selecting thera peutic and follow-up plan for patients with breast carcinomas.
Breast Neoplasms* ; Breast* ; Carcinoma, Ductal ; Endothelial Cells ; Estrogens ; Follow-Up Studies ; Humans ; Microscopy ; Microvessels ; Noma ; Prognosis

BACKGROUND: E2F1 plays a critical role in the G1-to-S phase transition by inducing various genes that encode S phase-activating proteins and that modulate such diverse cellular functions as DNA synthesis, mitosis and apoptosis. The purpose of this study was to assess the E2F1 expression in relation to the clinicopathologic parameters and other tumor markers in gastrointestinal stromal tumors. METHODS: Immunohistochemical stainings for obtaining the E2F1, p53, and Ki-67 labeling indices were performed on a tissue microarray of 72 gastrointestinal stromal tumor specimens. The clinicopathologic parameters that were analyzed including the risk grade system by Miettinen et al. and the disease-free survival (DFS) rate. RESULTS: 1) An E2F1 expression was correlated with a larger tumor size, a p53 expression and a shorter period of DFS (p=0.014, p=0.007, and p=0.039). 2) A p53 expression was significantly associated with a high risk grade, a larger tumor size, high mitotic counts and a shorter period of DFS (p=0.003, p=0.044, p<0.001, and p<0.0001). 3) A high-risk grade and the epithelioid type were significantly associated with a shorter period of DFS (p=0.0006 and p=0.0008). CONCLUSIONS: E2F1, as well as p53, may be a potentially novel independent prognostic factor for predicting a worse outcome for those patients suffering with Gastrointestinal stromal tumors.
Apoptosis ; Disease-Free Survival ; DNA ; E2F1 Transcription Factor ; Gastrointestinal Stromal Tumors ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; Mitosis ; Phase Transition ; Proteins ; Stress, Psychological ; Tumor Markers, Biological ; Tumor Suppressor Protein p53

PURPOSE: Breast cancer is one of the most frequent malignant tumors in Korea. The major tumor suppressor genes (TSGs) such as p16, Rb, E-cadherin and p53 may play important roles in cell cycle regulation, apoptosis and the regulation of the expression of other genes as well as tumor suppression. Microsatellite alteration such as loss of heterozygosity (LOH) have been reported to be a novel mechanism of carcinogenesis and a useful prognostic factor for many malignant tumors. Also, LOH is also known to be related with allelic loss of various TSGs. This study evaluated LOH of 4 TSGs in invasive ductal carcinomas (IDCs) and we correlated these results with the clinicopathological factors. METHODS: LOH analysis was carried out using a polymerase chain reaction with 12 polymorphic microsatellite markers of 4 TSGs in 50 surgically resected tumors and their non-tumorous counterparts. RESULTS: There was no detectable LOH in the normal tissue. LOH was detected in 86% of the 50 cases of IDCs. LOH was detected on all chromosomes and this showed a statistical difference between benign tumor and malignant tumor. LOH of p16, Rb, E-cadherin and p53 TSGs was detected in 36%, 26%, 54% and 60% of the tumors, respectively. LOH of the p16 and Rb genes was inversely correlated with tumor grade 1. The low rate of detecting LOH on the E-cadherin gene was noted in T1 tumor and stage I disease. LOH of the p53 gene correlated well with the tumor size and stage. The LOH-High results correlate well with the tumor size and stage and the LOH-High results are similar to those of the p53 gene LOH. CONCLUSION: These results suggest that LOH of the 4 major TSGs may contribute to the development and invasion of IDCs. Also, the combined use of various LOH markers may help in deciding the prognosis of IDCs.
Apoptosis ; Breast Neoplasms ; Cadherins ; Carcinogenesis ; Carcinoma, Ductal* ; Cell Cycle ; Genes, p53 ; Genes, Retinoblastoma ; Genes, Tumor Suppressor* ; Korea ; Loss of Heterozygosity* ; Microsatellite Repeats ; Polymerase Chain Reaction ; Prognosis

PURPOSE: The c-met protein, known as the hepatocyte growth factor (HGF) receptor, is a transmembrane 190 kDa heterodimer having tyrosine kinase activity, and it is encoded by the c-met oncogene. The HGF/c-met signaling pathway has been shown to demonstrate various cellular responses including mitogenic, proliferative, morphogenic and angiogenic activities. Although HGF and c-met are known to be expressed in a variety of organs and they play important roles in signal transduction, studies on its expression and its correlation to the clinicopathological parameters of breast cancer are very rare. METHODS: In this study, we examined the c-met mRNA and the c-met protein expression by utilizing RT-PCR and immunohistochemical methods for 50 cases of invasive ductal carcinomas (IDCs) and 20 cases of normal breast tissues. RESULTS: The c-met mRNA amplification was detected in 35 cases of IDCs (70%), but not in the normal tissues. The c-met protein overexpression was detected in 27 cases of IDCs (54%) and 2 cases of normal breast tissue (10%). Both the mRNA amplification and protein overexpression rates were significantly higher in tumor than in the normal breast tissue. The c-met mRNA amplification showed a tendency to increase in an invasive cancer and nodal metastasis. The c-met protein overexpression was significantly correlated with the well differentiated grade of tumor and it showed a tendency to decrease in the metastatic tumors. The concordance between both the mRNA amplification and protein expressions were not observed. CONCLUSION: These results suggest that the HGF/c-met signal pathway may be associated with the development of breast cancer. c-met mRNA amplification may play important roles both in tumor progression and metastasis. c-met protein overexpression may contribute to the morphogenesis of well-differentiated tumor.
Breast ; Breast Neoplasms ; Carcinoma, Ductal* ; Hepatocyte Growth Factor ; Morphogenesis ; Neoplasm Metastasis ; Oncogenes ; Protein-Tyrosine Kinases ; RNA, Messenger ; Signal Transduction

Pyoderma gangrenosum is a painful, chronic, ulcerating skin disease of unknown cause. It commences as an erythematous papulopustule and rapidly evolves to form an area of frank ulceration with undermined, violaceous edges and a bright outer halo of erythema. Diagnosis is clinical, there being no accepted histological diagnostic criteria. An underlying systemic illness is present in more than 50 percent of patients. Pyoderma gangrenosum develops in 0.8~5.0 percent of patients with inflammatory bowel disease, which is the most frequent underlying disease of pyoderma gangrenosum. There is no report of pyoderma gangrenosum associated with Crohn's disease in Korea. We recently experienced two cases of pyoderma gangrenosum, a 52-year old man with Crohn's disease and a 30-year old man with ulcerative colitis. The cases are presented with the review of literature.
Adult ; Colitis, Ulcerative ; Crohn Disease ; Diagnosis ; Erythema ; Humans ; Inflammatory Bowel Diseases* ; Korea ; Middle Aged ; Pyoderma Gangrenosum* ; Pyoderma* ; Skin Diseases ; Ulcer