• Korean Journal of Veterinary Research
• /
• v.48 no.3
• /
• pp.251-258
• /
• 2008

The neurotoxicity of C-terminal fragments of amyloid precusor protein (CT) is known to play some roles in Alzheimer's disease progression. In this study, we investigated the effects of the recombinant C-terminal 105 amino acid fragment of amyloid precusor protein (CT105) on cholinergic function using CT105-injected rat. To study the effects of CT105 on septohippocampal pathway, choline acetyltransferase (ChAT) positive neurons were examined in the medial septum and in the diagonal band after an injection of CT105 peptide into the lateral ventricle. Immunohistological analysis revealed that the number of ChAT-immunopositive cells decreased significantly in both medial septum and diagonal band. In addition, CT105 decreased ChAT-immunopositive cells in the hippocampal area, particulary in the dentate gyros. To study the effect of amyloid beta peptide ($A{\beta}$) and CT105 on the cholinergic system, each peptide was injected into the left lateral ventricle, and acetylcholine (ACh) levels were monitored in hippocampus. ACh level in the hippocampal area was reduced to 60% of control level in $A{\beta}$-treated group, and the level was reduced to 15% of control level in CT105-treated group, at one week after the injection. ACh level was further reduced to 35% of control in $A{\beta}$-treated group, whereas the level was slightly increased to 30% of control in CT105-treated group at 4 weeks after the injection. Taken together, the results in the present study suggest that CT105 impairs the septohippocampal pathway by reducing acetylcholine synthesis and release, which results in damage of learning and memory.

• IMMUNE NETWORK
• /
• v.1 no.2
• /
• pp.143-150
• /
• 2001

Background : Many investigators have found transforming growth factor-${\beta}1$ (TGF-${\beta}1$) to be elevated in tumors. Changes in responsiveness to TGF-${\beta}1$ have been linked to malignant transformation, tumor progression and tumor regression. Many malignant cell lines of epithelial or hematopoietic origin are refractory to the antiproliferative effects of TGF-${\beta}1$. However, a little is known about the association of TGF-${\beta}1$ with progression of malignant tumor. Methods : In this study, we measured the plasma level of TGF-${\beta}1$ in various cancer patients and evaluated the utility of plasma TGF-${\beta}1$ as a possible tumor marker. Plasma TGF-${\beta}1$ levels were measured using enzyme-linked immunosorbent assay in cancer patients and normal controls. Carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) as tumor marker were compared with TGF-${\beta}1$ in the aspects of sensitivity and specificity. Results : The mean of plasma TGF-${\beta}1$ levels was $1.219{\pm}0.834ng/ml$ in normal controls, $5.491{\pm}3.598ng/ml$ in breast cancer, $12.670{\pm}10.386ng/ml$ in lung cancer, $5.747{\pm}3.228ng/ml$ in hepatocellular carcinoma and $10.854{\pm}7.996ng/ml$ in cervical cancer. In comparison with CEA and AFP, TGF-${\beta}1$ is more sensitive. Conclusion : We conclude that the high levels of TGF-${\beta}1$ are common in the plasma of cancer patients. These results suggest that the plasma TGF-${\beta}1$ level can be a potent tumor marker in various cancer patients.

• Radiation Oncology Journal
• /
• v.29 no.3
• /
• pp.156-163
• /
• 2011

Purpose: To evaluate long-term local control rate and toxicity in patients treated with external beam radiotherapy (EBRT) for pituitary adenomas. Materials and Methods: We retrospectively reviewed the medical records of 60 patients treated with EBRT for pituitary adenoma at Korea University Medical Center from 1996 and 2006. Thirty-five patients had hormone secreting tumors, 25 patients had non-secreting tumors. Fifty-seven patients had received postoperative radiotherapy (RT), and 3 had received RT alone. Median total dose was 54 Gy (range, 36 to 61.2 Gy). The definition of tumor progression were as follows: evidence of tumor progression on computed tomography or magnetic resonance imaging, worsening of clinical sign requiring additional operation or others, rising serum hormone level against a previously stable or falling value, and failure of controlling serum hormone level so that the hormone level had been far from optimal range until last follow-up. Age, sex, hormone secretion, tumor extension, tumor size, and radiation dose were analyzed for prognostic significance in tumor control. Results: Median follow-up was 5.7 years (range, 2 to 14.4 years). The 10-year actuarial local control rates for non-secreting and secreting adenomas were 96% and 66%, respectively. In univariate analysis, hormone secretion was significant prognostic factor (p = 0.042) and cavernous sinus extension was marginally significant factor (p = 0.054) for adverse local control. All other factors were not significant. In multivariate analysis, hormone secretion and gender were significant. Fifty-three patients had mass-effect symptoms (headache, dizziness, visual disturbance, hypopituitarism, loss of consciousness, and cranial nerve palsy). A total of 17 of 23 patients with headache and 27 of 34 patients with visual impairment were improved. Twenty-seven patients experienced symptoms of endocrine hypersecretion (galactorrhea, amenorrhea, irregular menstruation, decreased libido, gynecomastia, acromegaly, and Cushing's disease). Amenorrhea was abated in 7 of 10 patients, galactorrhea in 8 of 8 patients, acromegaly in 7 of 11 patients, Cushing's disease in 4 of 4 patients. Long-term complication was observed in 4 patients; 3 patients with cerebrovascular accident, 1 patient developed dementia. Of these patients, 3 of 4 received more than 60 Gy of irradiation. Conclusion: EBRT is highly effective in preventing recurrence and reducing mass effect of non-secreting adenoma. Effort to improve tumor control of secreting adenoma is required. Careful long-term follow-up is required when relatively high dose is applied. Modern radiosurgery or proton RT may be options to decrease late complications.

• Environmental Mutagens and Carcinogens
• /
• v.19 no.1
• /
• pp.46-55
• /
• 1999

To develop a chemopreventive strategy based on the different stages of premalignant lesions, we hypothesized that the inhibitory effect of chemopreventive agents is influenced by different promotion stages during carcinogenesis. DMBA-TPA-induced skin carcinogenesis was used with ICR mice and chlorophyllin (CHL) was applied as a chemopreventive agent. In vitro assay was performed with Salmonella typhi. TA100 to observe any anti-mutagenic activity of CHL against DMBA. Pre-initiation and pre-promotion effects of CHL were observed by CHL treatment before initiation and before promotion. To evaluate the inhibitory effect at different promotion stages, each group was divided into three subgroups after TPA promotion for 6, 18 and 24 weeks, respectively ; the first subgroup was immediately sacrificed after termination of TPA, the second subgroup was treated with CHL, and the third subgroup was sacrificed 8 weeks after termination of TPA without CHL treatment. The degrees of epithelial dysplasia, papilloma formation, and invasive carcinoma were observed histologically, and GST-Pi expression was observed immunohistochemically. ODC mRNA level was analyzed by reverse transcriptase-polymerase chain reaction. Results showed : CHL dose-dependently inhibited the mutation of Salmonella typhi. TA100; the incidence of epithelial dysplasia and papilloma formation was lower in pre-initiation and pre-promotion CHL-treated mice than DMBA-TPA-treated mice; no invasive carcinoma developed in pre-initiation CHL-treated groups, while 67% of DMBA-TPA treated mice had carcinomas; GST-Pi expression decreased when CHL was treated before initiation and before promotion; and when CHL was treated after termination of TPA application at 18 and 24- week-TPA promotion stages, respectively, the incidence of epithelial dysplasia and papilloma was markedly reduced compared to non-treated groups. When comparing the incidence of epithelial dysplasia and papilloma between the immediately-sacrificed subgroup and the non-treated group with a waiting period, we speculated that the 18-week-TPA promotion stage might belong to the promoter-independent progression stage. At the 18-week-TPA promotion stage, the level of ODC mRNA in the CHL-treated group was clearly reduced to the level of normal tissue. Taking these results together, CHL showed both anti-initiation and anti-promotion effects, while the inhibitory effect of CHL was prominent in the 18-week-TPA promotion stage. However, CHL seems to be incapable of completely blocking the progression in the 24-week-TPA promotion stage.

• Korean journal of health promotion
• /
• v.18 no.4
• /
• pp.147-158
• /
• 2018

Background: This study was designed to investigate the effects of usual negative emotional experiences on biological aging progression of human. Methods: A total of 237 subjects who visited the Health Promotion Center at Chungnam National University Hospital from May 2013 through September 2013 was enrolled. Each subject had been drawn up a structured questionnaire about usual experiences of depression, anxiety, anger, and anger expression. The degree of biological aging progression of each subject was computed by a specific formula which consisted of chronological age and biological age reflecting obesity and aging of main organs. Results: Trait anger and low education level showed the significant correlations with biological aging (r=0.160, P=0.014, and r=-0.189, P=0.024, respectively). Trait anger and low education level solely displayed the significant $R^2s$ for biological aging in consequence of multivariate analyses; $R^2=0.044$, P=0.020, and $R^2=0.022$, P=0.038, respectively. Conclusions: This study suggests that the significant relationship between usual anger experience (i.e., trait anger) and biological aging would be present. In addition, lower education level may be related with biological aging.

• Korean Journal of Head & Neck Oncology
• /
• v.18 no.2
• /
• pp.216-218
• /
• 2002

A 38-year-old man, who was diagnosed nasopharyngeal carcinoma (stage T4N2Mx) had rapidly growing lower neck mass (at level IV area) with local inflammation sign during concurrent chemoradiotherapy. After we performed Color Doppler sonography and fine needle aspiration biopsy of the neck mass, we differentiated neck soft tissue infection from tumor extension. Size of the mass decreased after antibiotics therapy. It was difficult to differentiate neck infection from tumor progression during treatment in naspharyngeal carcinoma.

• Environmental Mutagens and Carcinogens
• /
• v.24 no.1
• /
• pp.1-9
• /
• 2004

Three D-type cyelins (D1, D2, and D3) are expressed in G1 phase of the cell cyele and have been implicated in cell transformation and neoplasia in human and mouse. Cyclin D1 overexpression or amplification was described in various human cancers. However, there is controversy about the role of cyclin D2 in cell cyele progression and human carcinogenesis. Specially, loss of cyelin D2 is involved in a vital tumor suppressor function in normal breast tissue, and that its loss may be related to tumorigenesis. The author examined to effect over-expression of cyclin D2 on the cell proliferation, apoptosis, and cell cycle using cyclin D2 transfected stable T47D breast cancer cells to investigate whether cyclinD2 functions as a positive regulator or negative regulator in cell proliferation. Overexpression of cyclin D2 led to the suppression of cell growth in cyclin D2 transfected T47D in both in its expression level and a time dependent manner with up to 50% reduction of cell growth at 72 hours. Therefore, the authors performed the cell cycle phase analysis using the flow cytometry to investigate the effect of cyclin D2 on the cell cycle phase in cyclin D2 transfected stable T47D cells. The flow cytometry analysis revealed increased sub G0 phase in cyclin D2 transfeted cells up to 23% at 72 hours. To confirm these results induced by overexpression of cyclinD2, the apoptotic bodies were counted in control and cyclin D2 transfected T47 cells. There are markedly increases of apoptotic bodies in cyclin D2-transfected cells up to 18%. These results suggested that Cyclin D2 suppresses the cell proliferation in breast cancers cells via the induction of apotosis.

• Korean Journal of Pharmacognosy
• /
• v.45 no.4
• /
• pp.288-293
• /
• 2014

The present study was conducted to evaluate the hair growth-promoting effect of Clitocybin A from mushroom Clitocybe aurantiaca with dermal papilla cells (DPCs), which play important roles in the regulation of hair cycle. Clitocybin A significantly increased the proliferation of immortalized rat vibrissa DPCs. Flow cytometry analysis revealed that Clitocybin A promoted cell-cycle progression through G0/G1 to S phase in immortalized rat vibrissa DPCs. In addition, Clitocybin A increased the level of cell cycle proteins such as cyclin D1, phospho-pRB, and phospho-CDK2. To elucidate the molecular mechanisms of Clitocybin A on the proliferation of DPCs, we examined the activation of wnt/${\beta}$-catenin signaling which is known to regulate hair follicle development, differentiation and hair growth. Clitocybin A activated wnt/${\beta}$-catenin signaling via the increase of phospho(ser552)-${\beta}$-catenin, phospho(ser675)-${\beta}$-catenin and phospho(ser9)-$GSK3{\beta}$. Furthermore, Clitocybin A markedly increased the activation of extracellular signal-regulated kinase (ERK). These results suggest that the Clitocybin A may induce hair growth by proliferation of DPCs via cell-cycle progression as well as the activation of Wnt/${\beta}$-catenin signaling and ERK pathway.

• Journal of Microbiology and Biotechnology
• /
• v.13 no.4
• /
• pp.607-612
• /
• 2003

To elucidate the action mechanism of MCS-C2, a novel analogue of toyocamycin and sangivamycin, its effect on the expression of cell cycle-related proteins in the human myelocytic leukemia cell line HL-60 was examined using Western blotting and a flow cytometric analysis. MCS-C2, a selective inhibitor of cyclin-dependent kinases, was found to inhibit cell growth in a time- and dose-dependent manner, and inhibits cell cycle progression by inducing the arrest at G1 and G2/M phases, in HL-60 cells. The flow cytometric analysis revealed an appreciable arrest of cells in the G2/M phase of the cell cycle after treatment with MCS-C2. The HL-60 cell population increased gradually from 13% at 0 h, to 28% at 12 h in the G2/M phase, after exposure to $2{\;}\mu\textrm{M}$ MCS-C2. Furthermore, Western blot analysis demonstrated that MCS-C2 induced the cell cycle arrest at G1 phase through the inhibition of pRb phosphorylation. Hypophosphorylated pRb accumulated after treatment with $5{\;}\mu\textrm{M}$ MCS-C2 for 12 h, whereas, the level of hyperphosphorylated pRb was reduced. Thus, treatment of the cell with MCS-C2 suppressed the hyperphosphorylated form of pRb with a commensurate increase in the hypophosphorylated form.

• International Journal of Contents
• /
• v.14 no.3
• /
• pp.7-16
• /
• 2018

The extent and depth of the event plan determines the scope of pedagogical experience in situations and consequently the quality of immersive learning based on our simulated world. In contrast to planning in conventional narrative-based systems mainly pursuing dramatic interests, planning in virtual world-based pedagogical systems strive to provide realistic experiences in immersed situations. Instead of story plot comprising predetermined situations, our inter-event planning method aims at simulating diverse situations that each involve multiple events coupled via their associated agents' conditions and meaningful associations between events occurring in a background world. The specific techniques to realize our planning method include, two-phase planning based on inter-event search and intra-event decomposition (down to the animated action level); autonomous and independent agents to behave proactively with their own belief and planning capability; full-blown background world to be used as the comprehensive stage for all events to occur in; coupling events via realistic association types including deontic associations as well as conventional causality; separation of agents from event roles; temporal scheduling; and parallel and concurrent event progression mechanism. Combining all these techniques, diverse exogenous events can be derived and seamlessly (i.e., semantically meaningfully) integrated with the original event to form a wide scope of situations providing chances of abundant pedagogical experiences. For effective implementation of plan execution, we devise an execution scheme based on multiple priority queues, particularly to realize concurrent progression of many simultaneous events to simulate its corresponding reality. Specific execution mechanisms include modeling an action in terms of its component motions, adjustability of priority for agent across different events, and concurrent and parallel execution method for multiple actions and its expansion for multiple events.