Connective tissue growth factor (CTGF) is a novel fibrotic mediator, which is considered to mediate fibrosis through extracellular matrix (ECM) synthesis in diabetic cardiovascular complications. Statins have significant immunomodulatory effects and reduce vascular injury. We therefore examined whether fluvastatin has anti-fibrotic effects in vascular smooth muscle cells (VSMCs) and elucidated its putative transduction signals. We show that advanced glycation end products (AGEs) stimulated CTGF mRNA and protein expression in a time-dependent manner. AGE-induced CTGF expression was mediated via ERK1/2, JNK, and Egr-1 pathways, but not p38; consequently, cell proliferation and migration and ECM accumulation were regulated by CTGF signaling pathway. AGE-stimulated VSMC proliferation, migration, and ECM accumulation were blocked by fluvastatin. However, the inhibitory effect of fluvastatin was restored by administration of CTGF recombinant protein. AGE-induced VSMC proliferation was dependent on cell cycle arrest, thereby increasing G1/G0 phase. Fluvastatin repressed cell cycle regulatory genes cyclin D1 and Cdk4 and augmented cyclin-dependent kinase inhibitors p27 and p21 in AGE-induced VSMCs. Taken together, fluvastatin suppressed AGE-induced VSMC proliferation, migration, and ECM accumulation by targeting CTGF signaling mechanism. These findings might be evidence for CTGF as a potential therapeutic target in diabetic vasculature complication.
Cell Cycle ; Cell Cycle Checkpoints ; Cell Proliferation ; Connective Tissue Growth Factor* ; Connective Tissue* ; Cyclin D1 ; Extracellular Matrix* ; Fibrosis ; Genes, Regulator ; Glycosylation End Products, Advanced ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Muscle, Smooth, Vascular* ; Phosphotransferases ; RNA, Messenger ; Vascular System Injuries

Angiotensin II (Ang II), a key mediator of hypertensive, causes structural changes in the arteries (vascular remodeling), which involve alterations in cell growth, vascular smooth muscle cell (VSMC) hypertrophy. Ang II promotes fibrotic factor like IGFBP5, which mediates the profibrotic effects of Ang II in the heart and kidneys, lung and so on. The purpose of this study was to identify the signaling pathway of IGFBP5 on cell proliferation and migration of Ang II-stimulated VSMC. We have been interested in Ang II-induced IGFBP5 and were curious to determine whether a Pitavastatin would ameliorate the effects. Herein, we investigated the question of whether Ang II induced the levels of IGFBP5 protein followed by proliferation and migration in VSMC. Pretreatment with the specific Angiotensin receptor type 1 (AT1) inhibitor (Losartan), Angiotensin receptor type 2 (AT2) inhibitor (PD123319), MAPK inhibitor (U0126), ERK1/2 inhibitor (PD98059), P38 inhibitor (SB600125) and PI3K inhibitor (LY294002) resulted in significantly inhibited IGFBP5 production, proliferation, and migration in Ang II-stimulated VSMC. In addition, IGFBP5 knockdown resulted in modulation of Ang II induced proliferation and migration via IGFBP5 induction. In addition, Pitavastatin modulated Ang II induced proliferation and migration in VSMC. Taken together, our results indicated that Ang II induces IGFBP5 through AT1, ERK1/2, P38, and PI3K signaling pathways, which were inhibited by Pitavastatin. These findings may suggest that Pitavastatin has an effect on vascular disease including hypertension.
Angiotensin II ; Angiotensins ; Arteries ; Cell Proliferation ; Heart ; Hypertension ; Hypertrophy ; Insulin-Like Growth Factor Binding Protein 5* ; Kidney ; Lung ; Muscle, Smooth, Vascular ; Vascular Diseases

PURPOSE: This study aimed to identify the factors influencing human papillomavirus (HPV) vaccination adoption stages using the Precaution Adoption Process model. METHODS: A total of 173 female university students from B metropolitan city participated. Demographics, factors contributing to action, knowledge, health beliefs, and self-efficacy related to the HPV vaccination were measured. The collected data were analyzed using descriptive statistics and multiple logistic regression analysis using SPSS for Windows version 21.0. RESULTS: Factors that contributed to the transition from the unaware and unengaged stages to the undecided about action stage included age, economic status, experience of recommendation from doctors, perceived severity of cervical cancer, and perceived barriers. Factors that contributed to the transition from the undecided about action stage to the deciding to act stage were perceived benefit and self-efficacy of the HPV vaccination. Factors that contributed to the transition from the deciding to act stage to the acting and maintenance stages were experience of recommendation from doctors and perceived severity of cervical cancer. CONCLUSION: These results suggest that aggressive HPV vaccination campaigns increase awareness. Further studies should develop tailored strategies for promoting HPV vaccination that emphasize health beliefs and self-efficacy.
Demography ; Female ; Humans ; Logistic Models ; Papillomavirus Vaccines ; Uterine Cervical Neoplasms ; Vaccination*

A 22-year old female visited CNUH due to palpable neck mass. Cytologic examination of a fine needle aspiration was performed and the result was Pap class II. Routine chest x-ray shows solitary pulmonary nodule. For rule-out malignancy, FNA at neck mass was repeated and pathologic finding was dysplasia. She was admitted to MI department for evaluation of solitary pulmonary nodule and percutaneous needle aspiration was done. Pathologic diagnosis was adenoid cystic carcinoma. Thereafter, the lesions were treated by excisional biopsy of submandibular gland mass with left supraomohyoid neck dissection and wedge resection of right lower lobe at ENT department and thoracic and cardiovascular surgery department, respectively Final diagnosis was adenoid cystic carcinoma arising in submandibular gland with solitary lung metastasis. According to TMN staging system, surgical staging is stage IV of T2N0M1. Clinical follow-up to postoperative 13 months in this case showed that she is alive and well without evidence of recrrence.
Adenoids* ; Biopsy ; Biopsy, Fine-Needle ; Carcinoma, Adenoid Cystic* ; Diagnosis ; Female ; Follow-Up Studies ; Humans ; Lung* ; Neck ; Neck Dissection ; Needles ; Neoplasm Metastasis ; Salivary Glands* ; Solitary Pulmonary Nodule ; Submandibular Gland ; Thorax

No abstract available.
Giant Cell Tumors* ; Giant Cells* ; Ribs*

BACKGROUND: Despite modem diagnostic, staging, and therapeutic advances, esp. with molecular biologic techniques, the 5-year survival rate of all cases of lung cancer does not exceed 15%. Also, the incidence of lung cancer of both sex in Korea is increasing year by year and the lung cancer is one of the leading causes of cancer death. Therefore, it is strongly needed to develop the new combination of treatment modalities including neoadjuvant chemotherapy and to identify tumor specific characteristics with staging or prognostic markers. Here we present the clinical significance of several biologic tumor markers to use as a prognostic markers in patients with non-small cell lung cancers. METHOD: The survival has correlated with the expressibility of proliferative cell nuclear antigen (PCNA), epidermal growth factor receptor(EGFR), p53 and/or blood group antigen A(BGAA) using immunohistochemistry in 46 patients with non-small cell lung cancers. RESULTS: 1) The expression rates of PCNA, EGFR, p53 and BGAA were 80.6%, 61.3%, 45.9% and 64.3%, respectively and those were not correlated to cell types or clinical stges. 2) The expression of BGAA was correlated with better survival in median survival and in 2-year survival rate and that of PCNA was correlated with worse survival in median survival and 2-year survival rate. 3) The expression of EGFR or p53 was not valuable to predict prognosis in non-small cell lung cancers. 4) With simultaneous applications of PCNA, EGFR and p53 immunostain, the patients with 2 or more negative expressions showed better prognosis than the patients with 2 or more positive expressions. CONCLUSION: It is suggested that the expression of blood group antigen may be a positive prognostic factor and that of PCNA may be a negative prognostic factor. Also, the combination of expressions of PCNA, EGFR and p53 may be used as a negative prognostic factor.
Biomarkers* ; Drug Therapy ; Epidermal Growth Factor ; Humans ; Immunohistochemistry ; Incidence ; Korea ; Lung Neoplasms* ; Lung* ; Modems ; Prognosis ; Proliferating Cell Nuclear Antigen ; Survival Rate ; Biomarkers, Tumor

OBJECTIVE: Triptolide (TP) has been reported to suppress the expression of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), of which main function is to inactivate the extracellular signal-regulated kinase-1/2 (ERK-1/2), the p38 MAPK and the c-Jun N-terminal kinase-1/2 (JNK-1/2), and to exert antiproliferative and pro-apoptotic activities. However, the mechanisms underlying antiproliferative and pro-apoptotic activities of TP are not fully understood. The purpose of this study was to examine whether the down-regulation of MKP-1 expression by TP would account for antiproliferative activity of TP in immortalized HT22 hippocampal cells. METHODS: MKP-1 expression and MAPK phosphorylation were analyzed by Western blot. Cell proliferation was assessed by 3H-thymidine incorporation. Small interfering RNA (siRNA) against MKP-1, vanadate (a phosphatase inhibitor), U0126 (a specific inhibitor for ERK-1/2), SB203580 (a specific inhibitor for p38 MAPK), and SP600125 (a specific inhibitor for JNK-1/2) were employed to evaluate a possible mechanism of antiproliferative action of TP. RESULTS: At its non-cytotoxic dose, TP suppressed MKP-1 expression, reduced cell growth, and induced persistent ERK-1/2 activation. Similar growth inhibition and ERK-1/2 activation were observed when MKP-1 expression was blocked by MKP-1 siRNA and its activity was inhibited by vanadate. The antiproliferative effects of TP, MKP-1 siRNA, and vanadate were significantly abolished by U0126, but not by SB203580 or SP600125. CONCLUSION: Our findings suggest that TP inhibits the growth of immortalized HT22 hippocampal cells via persistent ERK-1/2 activation by suppressing MKP-1 expression. Additionally, this study provides evidence supporting that MKP-1 may play an important role in regulation of neuronal cell growth.
Anthracenes ; Blotting, Western ; Butadienes ; Cell Proliferation ; Diterpenes ; Down-Regulation ; Epoxy Compounds ; Imidazoles ; Neurons ; Nitriles ; p38 Mitogen-Activated Protein Kinases ; Phenanthrenes ; Phosphorylation ; Protein Kinases ; Pyridines ; RNA, Small Interfering ; Vanadates

We made fusion protein of fastatin and FIII 9-10, termed tetra-cell adhesion molecule (T-CAM) that can interact simultaneously with alphavbeta3 and alpha5beta1 integrins, both playing important roles in tumor angiogenesis. T-CAM can serve as a cell adhesion substrate mediating adhesion and migration of endothelial cells in alphavbeta3 and alpha5beta1 integrin-dependent manner. T-CAM showed pronounced anti-angiogenic activities such as inhibition of endothelial cell tube formation, endothelial cell proliferation, and induction of endothelial cell apoptosis. T-CAM also inhibited angiogenesis and tumor growth in mouse xenograft model. The anti-angiogenic and anti-tumoral activity of molecule like fastatin could be improved by fusing it with integrin-recognizing cell adhesion domain from other distinct proteins. The strategy of combining two distinct anti-angiogenic molecules or cell adhesion domains could facilitate designing improved anticancer agent of therapeutic value.
Angiogenesis Inhibitors/chemistry/*pharmacology ; Animals ; Antineoplastic Agents/chemistry/*pharmacology ; Base Sequence ; Benzocaine/chemistry/*pharmacology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Chloramphenicol/chemistry/*pharmacology ; DNA Primers ; Drug Combinations ; Factor VIII/chemistry/*pharmacology ; Humans ; Integrin alpha5beta1/*physiology ; Integrin alphaVbeta3/*physiology ; Male ; Mice ; Mice, Inbred BALB C ; Nitrofurazone/chemistry/*pharmacology ; Recombinant Fusion Proteins/chemistry/*pharmacology

BACKGROUND: One quarter to one third of patients with NSCLC present with primary tumors that although confined to the thorax are too extensive for surgical resection. Until resently standard treatment for these patients had been thoracic radiation, which produces tumor regression in most patients but few cures and dismal 5-year survival rate. The fact that death for most patients with stage III tumors is caused by distant metastases has promped a reevaluation of combined modality treatment approaches that include systemic chemotherapy. Therefore, we report the results observed in a study to evaluate the effect of multimodality treatment in locally advanced non-small cell lung cancer from 1/91 to 8/93 in CNUH. METHOD: We grouped the patients according to the treatment modalities and evaluated response rate, median survival and the effect of prognostic variables. Among 67 patients evaluated, twenty seven patients classified with group A, received cisplatin and etoposide containing combination chemotherapy alone, eighteen patients, classified with group B, received chemotherapy and radiotherapy, fifteen patients, group C, received neoadjuvant or adjuvant chemotherapy and surgery with/without radiation therapy, seven patients, group D, received only supportive care. RESULT: The major response rate for group A and B was 37% and 61% respectively. There was no statistically significant difference in response rate between A and B groups(p=0.97). The analysis of prognostic factors showed that differences of age, sex, pathology, blood type, smoking year, stage and ECOG performance did not related to improvement in survival. Median survival time was 8.6 months for group A, 13.4 months for group B, 19.2 months for group C, and 5.4 months for group D, respectively and there was statistically significant difference(p=0.003), suggesting that multimodality therapy was associated with signigicant improvement in survival. Subset survival analysis showed a significant therapeutic effect for earlier stage and good performance state(p=0.007, 0.009, respectively). A possible survival advantages were observed for major response groups. CONCLUSION: It was suggested that multimodality therapy for the management of patients who had stage III disease, has yielded good median survival and long survival for seleted patients. But, it is necessory to validate above result with further investigation in large scale and in prospective randomized trials.
Carcinoma, Non-Small-Cell Lung* ; Chemotherapy, Adjuvant ; Cisplatin ; Drug Therapy ; Drug Therapy, Combination ; Etoposide ; Humans ; Neoplasm Metastasis ; Pathology ; Prospective Studies ; Radiotherapy ; Smoke ; Smoking ; Survival Rate ; Thorax

PURPOSE: As increasing overseas kidney transplant recipients, the post-transplantation management of these recipients is not unusual. Shortage of donor information and operative findings is an obstacle to post-transplant evaluation and management of overseas transplant recipients. We retrospectively reviewed the post-transplant clinical manifestation of overseas transplant recipient, and compared with those of domestic deceased donor transplant recipient. METHODS: Sixty overseas transplant recipients and 39 deceased donor transplant recipient in our center from January 2002 to August 2006 were enrolled in this study. Among the post-transplant outcomes, we focused the episodes of post-transplant complication, acute rejection and graft functional status. RESULTS: In comparison of pre-transplant clinical manifestation, overseas transplant recipients were more elderly, male predominant and less retransplantation than domestic deceased transplant cases. Remarkable surgical complications (35%, 21/60) were observed in overseas transplant recipients which was significantly higher than those of domestic transplant recipients (5.1%, 2/39 cases)(P=0.03). The urologic complication was major (14 cases) complication, and intraoperative hematoma (5 cases) and vascular complication (2 cases) succeed. Interventional procedure or surgical correction was performed in six recipients with urinary leakage obstruction. Excluding post-transplant acute tubular necrosis, the post-transplant outcomes, such as incidence of acute rejection, graft survival rate and graft function within post-transplant 3 year, of overseas transplant recipient were statistically similar with these of domestic deceased donor recipients. CONCLUSION: Considering that overseas transplant recipient had high incidence of surgical or urologic complication, the initial evaluation of post-transplant recipient was focused on completion of surgical procedure by using radiologic imaging study.
Aged ; Graft Rejection ; Hematoma ; Humans ; Incidence ; Kidney Transplantation* ; Kidney* ; Male ; Necrosis ; Retrospective Studies ; Survival Rate ; Tissue Donors* ; Transplantation ; Transplants