• Journal of Periodontal and Implant Science
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• v.31 no.3
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• pp.555-564
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• 2001

The purpose of this study is to evaluate the bioresorbability of Calcium Polyphosphate added with $Na_2O$ and chitosan. Though calcium phosphate ceramics meet some of the needs for bone replacement, they have some limitation of unresorbability and fibrous encapsulation without direct bone apposition during bone remodelling. To solve these problem, we developed a new ceramic, calcium polyphosphate(CPP), and report the biologic response to CPP in extraction sites of beagle dog. Porous CPP granules were prepared by condensation of anhydrous $Ca(H_2PO_4)_2$ to form non-crystalline $Ca(PO_3)_2$. CPP granules added with $Na_2O$ and chitosan were implanted in extraction sockets and histologic observation were performed at 12 weeks later. Histologic observation at 12 weeks revealed that CPP matrix were mingled with and directly apposed to new bone without any intervention of fibrous connective tissue. CPP granules added with chitosan were well adatped without any adverse tissue reaction and resorbed slowly and spontaneously. CPP granules added with $Na_2O$ and chitosan show multinucleated giant cells and osteoblast-like cells around grafted material and newly formed bone. This result revealed that CPP, regardless of its additive component, had a high affinity for bone and had been resorbed slowly. From this results, it was suggested that CPP is promising ceramic as a bone substitute and addition of $Na_2O$ and chitosan help biodegradation. In further study , it will be determined which concentration of $Na_2O$ help biodegradation and the other additive components increase the degradation rate.

• Radiation Oncology Journal
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• v.25 no.1
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• pp.43-53
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• 2007

[ $\underline{Purpose}$ ]: To evaluate the relationship between the expression of EGFR, p53, Cox-2, Bcl-2 and the clinical parameters of NPC (nasopharyngeal carcinoma) patients treated with radiotherapy with/without chemotherapy, and to determine if these could be used as a biologic marker. $\underline{Materials\;and\;Methods}$: This study retrospectively examined 75 NPC patients who were pathologically diagnosed at St. Mary's Hospital and Kangnam St Mary's Hospital from March 1988 to August 2002 and treated with radiotherapy with/without chemotherapy. The levels of EGFR, p53, Cox-2, and Bcl-2 expression were determined immunohistochemically. The relationship between the levels of EGFR, p53, Cox-2 and Bcl-2 expression and the H- E staining findings including the WHO classification, TNM stage, tumor response to chemotherapy and radiotherapy, disease free survival (DFS), and overall survival (OS) was analyzed. $\underline{Results}$: At a median follow up of 50.8 months (range: $5.5{\sim}201$ months), the 3 years OS rate and PFS rate were 68.7% and 68.2%, respectively. The five year OS rate and PFS rate were 53.5% and 51.1%, respectively. The median OS duration and PFS duration were 85.5 months and 61.1 months, respectively. The WHO classification correlated with the complete response rate, lymph node metastasis and distant metastasis. The expression of p53 was associated with increased mitosis and poor overall survival. The expression of Bcl-2 correlated with the DFS and WHO classification. The expression of Cox-2 correlated with a poor overall survival and response rate in the lymph node. However, EGFR was not correlated with any factors. $\underline{Conclusion}$: These results suggest that the expression of p53, Cox-2, Bcl-2 plays role in predicting prognostic factors for NPC treated with radiotherapy with/without chemotherapy. However, further study on a larger number of patients will be needed to identify more useful biomarkers of NPC.

• The korean journal of orthodontics
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• v.26 no.5 s.58
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• pp.581-590
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• 1996

Bone resorptiion was predominate in compression site, bone formation in tension site of periodontal ligament during tooth movement. The biologic response at compressiion site was different from tension site. Thus the CGHP immuno-positive nerve fiber will respond differently to mechanical force according to the area( compression or tension site). The purpose of this study was to investigate this response of CGRP immune-positive nerve fiber in the periodontal ligament according to the duration of applied force and the area (compression or tension site) during experimental tooth movement. The experimental animals were 7 week old male rat (approximately 200 gm). The orthodontic force was applied mesially to the right maxillary molar using the Ni-Ti coil spring during 12hours, 1, 3, 7, and 120days. Immunohistochemical staining using antibody against CGRP was performed after sacrifice. The results were as follows. The CGRP immune-positive nerve bundle showed reduced immunoreactivity and nerve fibers reduced in density after application of orthodontic force for 12 hours and 1day. The CGRP immune-positive nerve fibers showed many thin branches at the apical periodontal ligament after application of force for 3 days as compared with normal. The tension site in the apical periodontal ligament showed more branches than the compression site. In 7 day group, the CGRP immune-positive nerve fibers increased in terms of the number and had many thin branches in the apical periodontal ligament. The tension site had more branches than the compression site. In 12 day group, the CGRP immune-positive nerve fibers showed similar distribution to normal control at compression site of apical periodontal ligament, but the fibers at the tension site increased in number. The CGRP immuno-positive nerve fibers showed more increased at tension site than compression site after application of orthodontic force. Therefore it seems to have some relation to the bone remodeling besides the local inflammatory process.

• IMMUNE NETWORK
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• v.1 no.3
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• pp.244-249
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• 2001

The transforming growth $factor-{\beta}$ ($TGF-{\beta}$) is a multifunctional cytokine modulating the onset and course of autoimmune disease as shown in experimental models. In synovial inflammation, there is a potential role for $TGF-{\beta}$ in repairment, the inhibition of cartilage and bone destruction, and the down-regulation of immune response. The biologic effects of $TGF-{\beta}$ depend on the cell type, the isoform and the availability of active $TGF-{\beta}$. We investigated $TGF-{\beta}$ expression in patients with rheumatoid arthritis (RA) and compared to those of osteoarthritis (OA). And we determined a correlation between $TGF-{\beta}1$ and $TGF-{\beta}2$, and also the relationships between each $TGF-{\beta}$ isoform and the parameters for disease activity of RA. Methods: The study population consisted of 20 patients with RA and 20 patients with OA. The commercial ELISA kit was used to study $TGF-{\beta}1$ and $TGF-{\beta}2$ levels in peripheral blood (PB) and synovial fluids (SF). Results: 1) While PB $TGF-{\beta}1$ level was of no difference between RA and OA patient groups, SF $TGF-{\beta}1$ level was higher in RA group than OA group. Similarly, PB $TGF-{\beta}2$ levels of RA and OA groups was not different, but SF $TGF-{\beta}2$ levels was higher in RA group than OA group. 2) In patients with RA, the $TGF-{\beta}1$ levels were higher than $TGF-{\beta}2$ in both the PB and SF, while in patients with OA, there showed higher readings for $TGF-{\beta}1$ than $TGF-{\beta}2$ in SF but no difference between $TGF-{\beta}1$ and $TGF-{\beta}2$ levels in PB. 3) In patients with RA, there were no correlations between PB $TGF-{\beta}1$ and PB $TGF-{\beta}2$ levels, nor between SF $TGF-{\beta}1$ and SF $TGF-{\beta}2$ levels. At the same way, there was no correlation between PB $TGF-{\beta}1$ and SF $TGF-{\beta}1$ levels, nor between each levels of $TGF-{\beta}2$ in patients with RA. 4) There was also no correlation between each $TGF-{\beta}$ isoform and the parameters for disease activity such as ESR, CRP, tender joint count, swollen joint count, rheumatoid factor, and the duration of morning stiffness except between in PB $TGF-{\beta}1$ and disease duration of RA (r=0.637, p<0.01). Conclusion: Each $TGF-{\beta}$ isoforms were higher in synovial fluid of patients with RA than that of patients with OA. The data from the RA patients demonstrated different patterns of expressions of the isoforms depending on which compartment (PB or SF) was investigated. The quantification of different $TGF-{\beta}$ isoform is thought to be important when $TGF-{\beta}$ is measured under disease conditions of RA.

• Journal of the korean academy of Pediatric Dentistry
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• v.30 no.2
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• pp.308-319
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• 2003

Mechanical forces are known to have an effect on bone formation, maintenance and remodeling, and there is evidence that the development of the mandibular condyle in the rat or mouse is influenced by altered functional force. However, studies are lacking in molecular-biologic mechanism such as the identification of differentiation factor induced from functional force. Here a mouse model was used to investigate the functional stress-responsive gene or factors which is related to the altered force by comparing the expression genes of functional state and hypo-functional state of the mouse mandible. ICR mice were provisioned with either a soft, mushy diet (soft-diet group) or hard rat pellets (hard-diet group) beginning at weaning for the alteration of functional force and subsequently sacrificed at 89 days of age. Incisor of mice in group 1 were trimmed twice a week to reduce occlusal forces. After killing the animals, mandibular bone including condyle were collected for RNA extraction, subtractive hybridization, northern blot analysis and mRNA in-situ hybridization. The results as follows; 1. A total of 39 clones were sequenced, and 11 individual sequence types were subsequently identified by subtractive hybridization, as 28 clones were represented twice in the analyzed sets. 2. Consequently four candidate clones, FS-s (functional stress-specific)2, -5, -18, and -22 were identified and characterized by homolgy search and northern analysis. Four of these clones, FS-s2, -5, -18, and -22, were shown to be expressed differentially in the hard-diet group. 3. Histologic sections showed that osteoblastic activity along the bone trabeculae and active bone remodeling were significantly lower in soft than in hard diet animals. A soft diet seems to enable a longer period of endochondral ossification in the mandibular condyle. 4. Although the mRNAs of FS-s2, -5, -18, and -22 were expressed rarely by cells of the soft-diet group, highest expression was detected in the cells of the hard-diet group. Together with the above results, it is suggested that FS-s2, -5, -18, and -22 could act as an important factors controlling the tissue changes in response to functional stress. The exact functional significance of these findings remains to be established.

• Tuberculosis and Respiratory Diseases
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• v.43 no.2
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• pp.210-220
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• 1996

Background : Neutrophils or monocytes separated in vitro by the adherence to plastic surface are known to be activated by surface adherence itself and subsequent experimental data might be altered by surface adherence. In the process of surface adherence, adhesion molecules have a clear role in intracellular signal pathway of cellular activation. Human alveolar macrophages(HAM) are frequently purified by the adherence procedure after bronchoalveolar lavage. But the experimental data of many reports about alveolar macrophages have ignored the possibility of adhesion-induced cellular activation. Method : Bronchoalveolar lavage was performed in the person whose lung of either side was confirmed to be normal by chest CT. With the measurement of hydrogen peroxide release from adherent HAM to plastic surface and non-adherent HAM with or without additional stimulation of phorbol myristate acetate(PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP), we observed the effect of the adherence to plastic surface. We also evaluated the effect of various biological surfaces on adhesion-induced activation of HAM. Then, to define the intracellular pathway of signal transduction, pretreatment with cycloheximide, pertussis toxin and anti-CD11/CD18 monoclonal antibody was done and we measured hydrogen peroxide in the culture supernatant of HAM. Results : 1) The adherence itself to plastic surface directly stimulated hydrogen peroxide release from human alveolar macrophages and chemical stimuli such as phorbol myristate acetate(PMA) or N-formyl-methionyl-leucyl-phenylalanine(fMLP) colud not increase hydrogen peroxide release in these adherent macrophages which is already activated. 2) PMA activated human alveolar macrophages irrespective of the state of adhesion. However, fMLP stimulated the release of hydrogen peroxide from the adherent macrophages, but not from the non-adherent macrophages. 3) HAM adherent to A549 cell(type II alveolar epithelium-like human cell line) monolayer released more hydrogen peroxide in response to both PMA and fMLP. This adherence-dependent effect of fMLP was blocked by pretreatment of macrophages with cycloheximide, pertussis toxin and anti-CD18 monoclonal antibody, Conclusion : These results suggest that the stimulatory effect of PMA and fMLP can not be found in adherent macrophage because of the activation of human alveolar macrophage by the adherence to plastic surface and the cells adhered to biologic surface such as alveolar epithelial cells are appropriately responsive to these stimuli. It is also likely that the effect of fMLP on the adherent macrophage requires new protein synthesis via G protein pathway and is dependent on the adhesion between alveolar macrophages and alveolar epithelial cells by virtue of CD11/CD18 adhesion molecules.

• Radiation Oncology Journal
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• v.24 no.3
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• pp.171-178
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• 2006

[ $\underline{Purpose}$ ]: To determine the efficacy and safety of concurrent chemotherapy and radiation therapy with high-dose-rate brachytherapy for cervical cancer. $\underline{Materials\;and\;Methods}$: From January 2001 to December 2002, 30 patients with cervical cancer were treated with concurrent chemotherapy (cisplatin and 5-FU) and definitive radiation therapy. The median age was 58 (range $34{\sim}74$) year old. The pathology of the biopsy sections was squamous cell carcinoma in 29 patients and one was adenocarcinoma. The distribution to FIGO staging system was as follows: stage IB, 7 (23%); IIA, 3 (10%); IIB, 12 (40%); IIIA, 3 (10%); IIIB, 5 (17%). All patients received pelvic external beam irradiation (EBRT) to a total dose of $45{\sim}50.4\;Gy$ (median: 50.4 Gy) over $5{\sim}5.5$ weeks. Ir-192 HDR intracavitary brachytherapy (ICBT) was given after a total dose of 41.4 Gy. HDR-ICBT was performed twice a week, with a fraction point A dose of 4 Gy and median dose to point A was 28 Gy (range: $16{\sim}32\;Gy$) in 7 fractions. The median cumulative biologic effective dose (BED) at point A (EBRT+ICBT) was $88\;Gy_{10}$ (range: $77{\sim}94\;Gy_{10}$). The median cumulative BED at ICRU 38 reference point (EBRT+ICBT) was $131\;Gy_3$ (range: $122{\sim}140\;Gy_3$) at point A, $109\;Gy_3$ (range: $88{\sim}125\;Gy_3$) at the rectum and $111\;Gy_3$ (range: $91{\sim}123\;Gy_3$) at the urinary bladder. Cisplatin ($60\;mg/m^2$) and 5-FU ($1,000\;mg/m^2$) was administered intravenously at 3 weeks interval from the first day of radiation for median 5 (range: $2{\sim}6$) cycles. The assessment was performed at 1 month after completion of radiation therapy by clinical examination and CT scan. The median follow-up time was 36 months (range: $8{\sim}50$ months). $\underline{: The complete response rate after concurrent chemoradiation therapy was 93.3%. The 3-yr actuarial pelvic control rate was 87% and 3-yr actuarial overall survival and disease-free survival rate was 93% and 87%, respectively. The local failure rate was 13% and distant metastatic rate was 3.3%. The crude rate of minor hematologic complications (RTOG grade 1-2) occurred in 3 patients (10%) and one patient had suffered from severe leukopenia (RTOG grade 4) during concurrent treatment. Acute minor enterocolitis (RTOG grade 1-2) occurred in 11 patients (37%) and one patient (3%) was suffered from colon perforation during radiation therapy. Late colitis of RTOG grade 1 occurred in 5 patients (15%). Acute cystitis of RTOG grade 1 occurred in 12 patients (40%) and late cystitis of RTOG grade 2 occurred in one patient (3%). No treatment related death was seen. $\underline{Conclusion}$: The results of this study suggest that the concurrent chemoradiation therapy with HDR brachytherapy could be accepted as an effective and safe treatment for cervical cancer.