In the present study, we show that the expression of type 2 glucose transporter isoform (GLUT2) could be regulated by PPAR-gamma in the liver. Rosiglitazone, PPAR-gamma agonist, activated the GLUT2 mRNA level in the primary cultured hepatocytes and Alexander cells, when these cells were transfected with PPAR-gamma/RXR-alpha. We have localized the peroxisome proliferator response element in the mouse GLUT2 promoter by serial deletion studies and site-directed mutagenesis. Chromatin immunoprecipitation assay using ob/ob mice also showed that PPAR-gamma rather than PPAR-alpha binds to the -197/-184 region of GLUT2 promoter. Taken together, liver GLUT2 may be a direct target of PPAR-gamma ligand contributing to glucose transport into liver in a condition when PAPR-gamma expression is increased as in type 2 diabetes or in severe obesity.
Animals ; Cells, Cultured ; Chromatin Immunoprecipitation ; Gene Expression Regulation ; Genes, Reporter ; Hepatocytes/*metabolism ; Liver/metabolism ; Male ; Mice ; Mice, Inbred ICR ; Mice, Transgenic ; Monosaccharide Transport Proteins/*biosynthesis/genetics ; Mutagenesis, Site-Directed ; PPAR alpha/genetics/metabolism ; PPAR gamma/agonists/genetics/*metabolism ; *Promoter Regions (Genetics) ; Protein Isoforms/biosynthesis ; Research Support, Non-U.S. Gov't ; *Response Elements ; Thiazolidinediones/pharmacology

Dental caries is the most common chronic disease in the dental field. Streptococcus mutans (S. mutans) is the most important bacteria in the formation of dental plaque and dental caries. In a previous study, we confirmed that the essential oil of Chrysanthemum boreale has antibacterial activity against S. mutans. Alpha-pinene is one of the major chemical components of Chrysanthemum boreale essential oil. In the present study, we investigated the inhibitory effects of α-pinene on cariogenic properties such as growth, acid production, biofilm formation, and bactericidal activity on S. mutans. Alpha-pinene at a concentration range of 0.25-0.5 mg/mL significantly inhibited the growth of S. mutans and acid production of S. mutans. Biofilm formation was significantly inhibited at < 0.0625 mg/mL α-pinene, similar to the data from scanning electronic microscopy. Under confocal laser scanning microscopy, the bacterial viability was decreased by α-pinene in a dose-dependent manner. These results suggested that α-pinene may be a useful agent for inhibiting the cariogenic properties of S. mutans.
Bacteria ; Biofilms ; Chronic Disease ; Chrysanthemum ; Dental Caries ; Dental Plaque ; Microbial Viability ; Microscopy ; Microscopy, Confocal ; Plants* ; Streptococcus mutans

Ludwig’s angina is a rapidly progressive and gangrenous cellulitis in the submandibular, sublingual spaces, and neck. It is characterized by an elevated tongue and laryngeal edema, resulting in airway compromise and, rarely, in sudden death. The most common cause is an odontogenic infection of a molar tooth. Infection can spread to the superior mediastinum and buccal area through anatomical structures. Herein, we report the sudden death of a 45-year-old male who was not diagnosed with Ludwig’s angina. He died in the emergency room 20 minutes after loss of consciousness. Intubation was impossible owing to severe laryngeal edema. The C-reactive protein level was 33.81 mg/dL. On autopsy, a diffuse light green abscess of the submandibular space was detected, along with severe edema of the epiglottis, aryepiglottic fold, and vocal cords. Subsequently, we confirmed that the airway obstruction was caused by Ludwig’s angina based on a literature review. In conclusion, this report emphasizes the need to identify the infection source and perform a detailed dissection according to the anatomical structure in the autopsy procedure for Ludwig’s angina.

PURPOSE: Accurate testing for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) is essential for breast cancer treatment. At present, immunohistochemistry (IHC)/florescence in situ hybridization (FISH) are widely accepted as the standard testing methods. To investigate the value of NanoString nCounter®, we performed its comparative analysis with IHC/FISH and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) for the assessment of ER, PR, and HER2. METHODS: Data on IHC/FISH results for ER, PR, and HER2 in 240 patients from a single tertiary hospital in Korea were collected and compared with NanoString nCounter® and qRT-PCR results at a single institution. RESULTS: Expression levels for each gene using NanoString nCounter® showed good correlation with the corresponding data for protein expression by IHC (p<0.001) and gene amplification status for HER2 (p<0.001). Comparisons between gene expression and IHC data showed good overall agreement with a high area under the curve (AUC) for ESR1/ER (AUC=0.939), PgR/PR (AUC=0.796), and HER2/HER2 (AUC=0.989) (p<0.001). CONCLUSION: The quantification of ER, PgR, and HER2 mRNA expression with NanoString nCounter® may be a viable alternative to conventional IHC/FISH methods.
Breast Neoplasms* ; Breast* ; Estrogens ; Gene Amplification ; Gene Expression ; Humans ; Immunohistochemistry* ; In Situ Hybridization* ; Korea ; Polymerase Chain Reaction ; Real-Time Polymerase Chain Reaction* ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone ; Reverse Transcription ; RNA, Messenger ; Tertiary Care Centers

PURPOSE: To evaluate the sensitivity and specificity of the DNA chip method in diagnosing patients with granular corneal dystrophy type II (GCD II) induced by mutation of the betaigh3 gene. METHODS: Two hundred twenty-seven patients who visited Severance Eye hospital, corneal dystrophy clinic, from 1 July 2006 to 30 September 2007 were included in this study after history taking and review of their medical records. All subjects were examined by slit lamp microscopy, and blood sampling was done. The sampled blood was used in DNA sequencing and the DNA chip method. RESULTS: Among 227 subjects, 125 (54.6%) patients had GCD II and 103 (45.4%) patients showed normal results according to the DNA sequencing method. The sensitivity and specificity of the DNA chip method were both 100%, while the sensitivity of the slit lamp method was 99.19% and the specificity was 100%. CONCLUSIONS: The DNA chip method for diagnosing GCD II is a more simple, time-saving, and accurate method than DNA sequencing method, and the sensitivity and specificity were both 100%.
DNA ; Eye ; Humans ; Medical Records ; Microscopy ; Oligonucleotide Array Sequence Analysis ; Sensitivity and Specificity ; Sequence Analysis, DNA

Streptococcus mutans (S. mutans) is one of the most important bacteria in the formation of dental plaque and dental caries. S. mutans adheres to an acquired pellicle formed on the tooth surface, and aggregates with many oral bacteria. It initiates plaque formation by synthesizing glucan from sucrose, which is catalyzed by glucosyltransferases. Propolis is a resinous mixture produced by honeybees, by mixing saliva and beeswax with secretions gathered from wood sap and flower pollen. Bees prevent pathogenic invasions by coating the propolis to the outer and inner surface of the honeycomb. Propolis has traditionally been used for the treatment of allergic rhinitis, asthma and dermatitis. We investigated the inhibitory effects of propolis ethanol extract on biofilm formation and gene expression of S. mutans. The biofilm formation of S. mutans was determined by scanning electron microscopy (SEM) and safranin staining. We observed that the extract of propolis had an inhibitory effect on the formation of S. mutans biofilms at concentrations higher than 0.2 mg/ml. Real-time PCR analysis showed that the gene expression of biofilm formation, such as gbpB, spaP, brpA, relA and vicR of S. mutans, was significantly decreased in a dose dependent manner. The ethanol extract of propolis showed concentration dependent growth inhibition of S. mutans, and significant inhibition of acid production at concentrations of 0.025, 0.05, 0.1 and 0.2 mg/ml, compared to the control group. These results suggest that the ethanol extract of propolis inhibits gene expression related to biofilm formation in S. mutans
Asthma ; Bacteria ; Bees ; Biofilms* ; Dental Caries ; Dental Plaque ; Dermatitis ; Ethanol* ; Flowers ; Gene Expression ; Glucosyltransferases ; Microscopy, Electron, Scanning ; Pollen ; Propolis* ; Real-Time Polymerase Chain Reaction ; Rhinitis, Allergic ; Saliva ; Streptococcus mutans* ; Streptococcus* ; Sucrose ; Tooth ; Wood

This study was performed to evaluate the efficacy and toxicity of low-dose paclitaxel/cisplatin chemotherapy in patients with metastatic or recurrent gastric cancer that had failed 5-fluorouracil/platinum-based chemotherapy. Thirty-two patients with documented progression on or within 6 months after discontinuing 5-fluorouracil/platinum-based chemotherapy were enrolled. As a second-line treatment, paclitaxel (145 mg/m2) and cisplatin (60 mg/m2) was administered on day 1 every 3 weeks. Among 32 patients enrolled, 8 (25%) responded partially to paclitaxel/cisplatin, 8 (25%) had stable disease, and 14 (44%) had progressive disease. Two patients (6%) were not evaluable. The median time to progression (TTP) and overall survival for all patients were 2.9 months and 9.1 months, respectively. The most common hematologic toxicity was anemia (47%). Grade 3 neutropenia developed in three patients (9%), but no other grade 3/4 hematologic toxicity occurred. The most common non-hematologic toxicities were emesis (31%) and peripheral neuropathy (38%). Three cases (9%) of grade 3/4 emesis and 2 cases (6%) of grade 3 peripheral neuropathy developed. In conclusion, low-dose paclitaxel and cisplatin chemotherapy showed moderate activity with favorable toxicity profiles. However, relatively short TTP of this regimen warrants the development of more effective paclitaxel-based regimens other than combination with cisplatin in these patients as second-line therapies.
Adenocarcinoma/*drug therapy ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse ; Cisplatin/administration & dosage/adverse effects ; Female ; Fluorouracil/administration & dosage/adverse effects ; Humans ; Leucovorin/administration & dosage/adverse effects ; Male ; Middle Aged ; Organoplatinum Compounds/administration & dosage/adverse effects ; Paclitaxel/administration & dosage/adverse effects ; Stomach Neoplasms/*drug therapy/mortality ; Survival Rate ; Treatment Failure

PURPOSE: We aimed to assess the concordance of the immunohistochemical profiles of core biopsy before administrating neoadjuvant chemotherapy with that of the surgical specimens after a definitive operation for breast cancer. METHODS: We retrospectively reviewed the estrogen receptor (ER), progesterone receptor (PR), and HER-2 expressions in 130 consecutive patients who received neoadjuvant chemotherapy and were followed by surgery during the period between February 2002 and March 2006. The pathologic complete tumor response rate for this group was 4.6% (6/130). Both the pre- and post-operative immunohistochemical profiles were available in 32 of the 124 patients (25.8%). Immunohistochemical staining was done on the core biopsies before chemotherapy and on the surgical specimens after operation. RESULTS: There were 12 markers from 11 patients that were altered out of the 96 total markers (ER, PR, or HER-2) from 32 patients: 2 ER (2/12, 16.7%), 4 PR (4/12, 33.3%), and 6 HER-2 (6/12, 50.0%). One patient simultaneously had changes in the expressions of PR and HER-2. Conversion of the hormone receptor status occurred in 3 patients (3/32, 9.4%): this was positive to negative in two, and vice versa in one. In addition, there were 6 conversions (6/32, 18.8%) of the HER-2 status from negative to positive. CONCLUSION: The hormone receptor status changed in 9.4% of the 32 patients and the HER-2 status changed in 18.8% of the 32 patients after neoadjuvant chemotherapy. We have concluded that conducting only a single immunohistochemical study about ER, PR, and HER-2 may not be enough to exactly estimate the tumor marker status in the neoadjuvant setting.
Biopsy ; Breast Neoplasms* ; Breast* ; Drug Therapy* ; Estrogens* ; Humans ; Receptors, Progesterone* ; Retrospective Studies

PURPOSE: KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous Src inhibitors that failed to show clinical benefit during treatment of breast cancer, KX-01 can potentially overcome the therapeutic limitations of current Src inhibitors through inhibition of both Src and tubulin. The present study further evaluates the activity and mechanism of KX-01 in vitro and in vivo. MATERIALS AND METHODS: The antitumor effect of KX-01 in triple negative breast cancer (TNBC) cell lines was determined by MTT assay. Wound healing and immunofluorescence assays were performed to evaluate the action mechanisms of KX-01. Changes in the cell cycle and molecular changes induced by KX-01 were also evaluated. A MDA-MB-231 mouse xenograft model was used to demonstrate the in vivo effects. RESULTS: KX-01 effectively inhibited the growth of breast cancer cell lines. The expression of phospho-Src and proliferative-signaling molecules were down-regulated in KX-01-sensitive TNBC cell lines. In addition, migration inhibition was observed by wound healing assay. KX-01-induced G2/M cell cycle arrest and increased the aneuploid cell population in KX-01-sensitive cell lines. Multi-nucleated cells were significantly increased after KX-01 treatment. Furthermore, KX-01 effectively delayed tumor growth in a MDA-MB-231 mouse xenograft model. CONCLUSION: KX-01 effectively inhibited cell growth and migration of TNBC cells. Moreover, this study demonstrated that KX-01 showed antitumor effects through the inhibition of Src signaling and the induction of mitotic catastrophe. The antitumor effects of KX-01 were also demonstrated in vivo using a mouse xenograft model.
Aneuploidy ; Animals ; Breast Neoplasms ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Line ; Fluorescent Antibody Technique ; Heterografts ; In Vitro Techniques ; Mice ; Microtubules ; Mitosis* ; src-Family Kinases* ; Triple Negative Breast Neoplasms ; Tubulin ; Wound Healing

PURPOSE: This study evaluated the effect of surgery-radiotherapy interval (SRI) on outcomes in patients treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) and adjuvant four cycles of doxorubicin/cyclophosphamide (AC) followed by four cycles of taxane. MATERIALS AND METHODS: From 1999 to 2007, 397 eligible patients were diagnosed. The effect of SRI on outcomes was analyzed using a Cox proportional hazards model, and a maximal chi-square method was used to identify optimal cut-off value of SRI for each outcome. RESULTS: The median SRI was 6.7 months (range, 5.6 to 10.3 months). A SRI of 7 months was the significant cut-off value for distant metastasis-free survival (DMFS) and disease-free survival (DFS) using a maximal chi-square method. For overall survival, a significant cut-off value was not found. The patients with SRI > 7 months had worse 6-year DMFS and DFS than those with SRI ≤ 7 months on univariate analysis (DMFS, 81% vs. 91%, p=0.003; DFS, 78% vs. 89%, p=0.002). On multivariate analysis, SRI > 7 months did not affect DMFS and DFS. CONCLUSION: RT delayed for more than 7 months after BCS and adjuvant four cycles of AC followed by four cycles of taxane did not compromise clinical outcomes.
Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Humans ; Mastectomy, Segmental* ; Multivariate Analysis ; Proportional Hazards Models ; Radiotherapy ; Radiotherapy, Adjuvant ; Time-to-Treatment