• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.161-168
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• 2017

Understanding the crosstalk mechanisms between perivascular cells (PVCs) and cancer cells might be beneficial in preventing cancer development and metastasis. In this study, we investigated the paracrine influence of PVCs derived from human umbilical cords on the proliferation of lung adenocarcinoma epithelial cells (A549) and erythroleukemia cells (TF-$1{\alpha}$ and K562) in vitro using $Transwell^{(R)}$ co-culture systems. PVCs promoted the proliferation of A549 cells without inducing morphological changes, but had no effect on the proliferation of TF-$1{\alpha}$ and K562 cells. To identify the factors secreted from PVCs, conditioned media harvested from PVC cultures were analyzed by antibody arrays. We identified a set of cytokines, including persephin (PSPN), a neurotrophic factor, and a key regulator of oral squamous cell carcinoma progression. Supplementation with PSPN significantly increased the proliferation of A549 cells. These results suggested that PVCs produced a differential effect on the proliferation of cancer cells in a cell-type dependent manner. Further, secretome analyses of PVCs and the elucidation of the molecular mechanisms could facilitate the discovery of therapeutic target(s) for lung cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.2
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• pp.201-208
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• 1997

It is becoming increasingly clear that the inflammatory reaction can be ascribed to a complex array of mediators generated and released from activated phagocytes. In this study, the effect of PAF on interleukin-1(IL-1) activity by rat alveolar macrophages(AM) was examined using thymocyte proliferation assay in the supernate of sample obtained after 24 hr culture. When AM were cultured with PAF alone, no change in IL-1 activity was observed. However, the combined addition of PAF and muramyl dipeptide(MDP) or lipopolysaccharide(LPS) to AM cultures markedly enhanced IL-1 activity by 2-3 fold compared with AM cultures with the stimulant alone in a concentration dependent fashion. The peack effect was found at $10^{-8}$ M PAF with MDP and $10^{-14}$ M PAF with LPS. the effect of PAF was also tested in silica, toxic respirable dust, -added AM cultures as well as in the cultures containing bacterial compounds. Although silica did not stimulate the IL-1 activity, PAF could enhance IL-1 activity by 2 fold above the value of the silica-treated AM cultures with the peak response at $10^{-12}$ M PAF. Optimal enhancement of IL-1 activity occured when MDP and PAF were present together at the initiation of the 24 hr AM cultures. Additionaly, the biologically inactive precursor/metabolite of PAF, lyso-PAF failed to induce enhancement of IL-1 activity. When the specific, but structurally different PAF receptor antagonists, BN 52021($10^{-5}$ M) and CV 3988($10^{-5}$ M) was treated 15 min before addition of PAF($10^{-8}$ M) and MDP$(10\;{\mu}g/ml)$ to the AM cultures, it markedly inhibited the enhancement of IL-1 activity induced by PAF. The effects of these PAF antagonists were also observed in LPS$(10\;{\mu}g/ml)$-stimulated cells. Collectively, these data suggest that PAF enhances IL-1 activity by interaction with a specific receptor.

• Journal of Chest Surgery
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• v.25 no.6
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• pp.598-604
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• 1992

Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and acounts for 6% to 15% of all cases of childhood cancer, Rhabdomyosarcoma in seventh most common form of childhood neoplasms, following acute leukemia, tumors of the central nervous system, lymphoma neuroblastoma, Wilm`s tumor, bone tumor. Rhabdomyosarcoma can arise anywhere in the body, but primary site in the thorax is relatively rare. We experienced a case of aveolar rhabdomyosarcoma arising from intercostal muscle, A 12 year-old woman was suffered from the intermittent left chest pain radiating to the scapular area and dyspnea, On physical examination, pulmonary friction rub was heard on the left upper lobe area. Qn adimission, the chest simple radiography revealed a 7 x 6, 5cm sized radio-opaque mass with pleural effusion in the superior mediastinum and the CT showed a well difined radio-opaque mass including the destructed 2nd rib and pleural effusion. The percutaneous tra-nsthoracic needle aspiration biopsy was likely to show blastoma. After the chemotherapy[vincristine, actinomycin-D, cyclophosphamde] was done to treat blastoma, the pleural effussion was subsided and the mass was slightly decreased by 4.5x 4. 5cm. For treatment and diagnosis, we performed en-bloc resection and the defected chest was reconstucted with Gortex patch. Grossly, the specimen was colored graysh-white and arised in between two ribs The microscopic findings showed that the tumor cells were small round with scant pinkish cytoplasm on the H-E stain and the tumor cell nests were grouped by reticulum fibers and showed alveolar pattern on the silver stain The electromicroscopic finding presented that the cytoplasm contained tangled fibrillar and flocculent materials. The histopathologic findings were compatable with laveolar rhabdomyosarcoma. She was discharged without any complication. After discharge, she has been treated with radiation theraphy and chemotheraphy, and not recurred untill last follow-up We report a case of alveolar rhabdomyosarcoma arising to intercostal muscle, developed in 12 year-old waman, with brief review of literatures.

• The Korean Journal of Physiology
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• v.30 no.1
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• pp.77-83
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• 1996

Platelet-activating factor(PAF) is a phospholipid mediator of pulmonary inflammation, and immunologic reaction. In this study, the role of PAF on tumor necrosis factor$(TNF_{-{\alpha}})$ production by rat alveolar macrophages(AM) was examined. When PAF $(10^{-12}{\sim}10{-16}\;M)$ alone was added to AM culture, $(TNF_{-{\alpha}})$ production was not significantly increased above the resting level. In contrast, the combined addition of PAF $(10^{-6}\;M)$ and muramyl dipeptide(MDP) $(1.0\;{\mu}g\ml)$ to AM cultures markedly enhanced $(TNF_{-{\alpha}})$ production with 8.2 fold increase compared with AM culture in resting state. This potentiative effect was 313% above the sum of the separate effects of PAF and MDP. To characterize MDP effects on $(TNF_{-{\alpha}})$ production, the dose-response of AM cultured with various concentrations of MDP was tested. High level of MDP $(10\;{\mu}g\ml)$ could not significantly enhance the potentiation effect on $(TNF_{-{\alpha}})$ production compared with AM cultures with low level of MDP $(0.1\;{\mu}g\ml)$, i.e. 112.5% vs 107.8%, respectively when $10^{-10}$ M of PAF was simultaneously added to the cell culture. These data support that the potentiation of TNF. g production in AM culture is mediated by PAF rather than MDf It was also evaluated whether the similar result was obtained in silica, respirable toxic particle-treated AM culture. $(TNF_{-{\alpha}})$ production was also significantly enhanced in the PAF $(10^{-6}\;M)$ and silica $(50\;{\mu}g\ml)$-added cell cultures with 4.7 fold above the value of silica alone-stimulated cells. These results indicate that PAF can potentiate $(TNF_{-{\alpha}})$ production by MDP-or silica- stimulated AM and suggest that PAF may play a potent role in lung inflammation and disease associated with microbe and occupational dust exposures.

• Korean Journal of Veterinary Research
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• v.16 no.1
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• pp.97-103
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• 1976

In order to clarify the histopathological changes resulting from nitrate poisoning, rabbits were experimentally poisoned by the oral administration of $KNO_3$ or $NaNO_2$ and examined clinically and histopathologically. In addition, the quantitative changes of glycogen level in hepatic cells were histochemically observed. The results obtained were summarized as follows: 1. Clinical symptoms observed from the acute cases which died within 2 hours after the administration were severe cyanosis of visible mucosa, frequent urination, and dyspnea. However, in chronic cases administrated daily with $KNO_3$ for 43, 50 and 74 days respectively, no marked symptoms were observed. 2. Macroscopic changes observed in acute cases were severe methemoglobinemia, cloudy swelling of hepatic cells, hemorrhage and hyperemia of gastric mucosa, and hyperemia of other organs. In chronic cases there were marked hyperemia, dark-red coloring and increasing of consistency in liver and kidney, and swelling of spleen. 3. Microscopic changes observed in acute cases were hemorrhage and hyperemia of various organs, cloudy swelling and centrilobular necrosis of hepatic cells and necrosis of convoluted tubular epithelium in kidney. In chronic cases there were round cell infiltration of the interlobular connective tissue and epithelial proliferation of interlobular bile ducts in the liver, and necrosis of the convoluted tubular epithelium and proliferation of interstitial connective tissue in kidney, thickening of alveolar septa of lungs, activated hemopoiesis of bone marrow, and myeloid metaplasia of sqlenic pulp. 4. Glycogen storage in liver cells was decreased in acute cases, on the contrary, increased in chronic cases.

• International Journal of Oral Biology
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• v.44 no.4
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• pp.182-190
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• 2019

Periodontitis is an inflammatory disease of the supportive tissues surrounding the teeth, and is characterized by irreversible destruction of the gingiva, periodontal ligament (PDL), and alveolar bone, which results in the loss of teeth. In the present study, we elucidated the correlation between periodontitis and apelin (APLN), an adipokine and a regulatory peptide, respectively, which are involved in inflammation and bone remodeling. The expression of APLN is negatively correlated with periodontitis progression in gingival tissue. In addition, treatment with TNF-α downregulated the expression of APLN in PDL cells and gingival fibroblasts, indicating the protective role played by APLN against periodontitis progression. The overexpression of APLN or treatment with exogenous APLN suppressed the TNF-α-mediated catabolic gene expression of MMP1, IL6, and PTGS2 in PDL cells. Moreover, the inhibition of the APLNA-PJ axis by ML221, an APJ inhibitor, induced catabolic gene expression in PDL cells. Thus, the results of this study provided evidence to support APLN as a regulatory factor of the inflammatory response during periodontitis.

• Proceedings of the KACD Conference
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• 2003.11a
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• pp.546.2-546
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• 2003

Dental follicle is the mesenchymal tissue which surrounds developing tooth germ. During tooth root development, periodontal components such as cementum, periodontal ligament and alveolar bone are considered to be created by progenitors present in the dental follicle. However, little is known about these progenitors. Previously we observed that cultured bovine dental follicle cells (BDFC) contained putative cementoblast progenitors. To further analyze the biology of these cells, we have attempted to immortalize BDFC by expression of the polycomb group protein Bmi-1 and human telomerase reverse transcriptase (hTERT). The BDFC expressing Bmi-1 and hTERT showed extended life span by 90 population doublings more than normal BDFC, and still contained cells with potential to differentiate into cementoblasts upon implantation into immunodeficiency mice. Among them, we established a clonal cell line designated as BCPb8, which formed cemetum-like mineralized tissue reactive to anti-cementum specific monoclonal antibody, 3G9, and expressed mRNA for bone sialoprotein, osteocalcin, osteopontin and type I collagen upon implantation. Thus with the combination of hTERT and Bmi-1, we succeeded in immortalization of cementoblast progenitor in BDFC without affecting differentiation potential. The BCPb8 progenitor cell line could be a useful tool not only to study cementogenesis but also to develop regeneration therapy for periodontitis.

• Journal of Periodontal and Implant Science
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• v.25 no.3
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• pp.623-634
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• 1995

Periodontitis is characterized by gingival inflammation and results in periodontal pocket formation with loss of the supporting alveolar bone and connective tissue around the teeth. Therapeutic modalities should therefore aim not only at eliminating the gingival inflammatory process and preventing the progression of periodontal disease but also at reestablishing and regenerating the periodontal tissue previously lost to the disease. To achieve periodontal regeneration, progenitor cells must migrate to the denuded root surface, attach to it, proliferate and mature into an organized and functional fibrous attachment apparatus. Likewise, progenitor bone cells must also migrate, proliferate, and mature in conjunction with the regenerating periodontal ligament. Significant advances have been made during the last decade in understanding the factors controlling the migration, attachment and proliferation of cells. A group of naturally occuring molecules known as polypeptide growth factors in conjunction with certain matrix proteins are key regulators of these biological events. Of these, the fibroblast growth factor(FGF), platelet-derived growth factor(PDGF) , insulin like growth factor(CIGFs), transforming growth factor(TGFs), epidermal growth factor(EGF) and bone morphogenetic growth factor(BMPs) apper to have an important role in periodontal wound healing. The purpose of this study was to determine the effects of BMP on periodontal ligament cells. Human periodontal ligament cells were cultured from extracted tooth for non-periodontal reason. Cultured periodontal ligament cells were treated with BMP. Cellular activities were determined by MTT(3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay and ALP(alkaline phosphatase) activity. The results were as follows ; Regardless of cultured time, cellular activities were stimulated by BMP. Also, BMP greatly increased alkaline phosphatase(ALP) in periodontal ligament cells. These results suggest that BMP not only have no cytotoxic effect on periodontal ligament cells, but also have osteogenic stimulatory effect on periodontal ligament cells.

• Clinical and Experimental Pediatrics
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• v.58 no.12
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• pp.505-508
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• 2015

It is uncommon for pediatric patients with rhabdomyosarcoma to present with clinical and/or laboratory features of disseminated intravascular coagulation (DIC). We report a case of metastatic alveolar rhabdomyosarcoma with severe bleeding because of DIC in a 13-year-old boy. He experienced persistent oozing at the site of a previous operation, gross hematuria, and massive epistaxis. Two weeks after initiating combination chemotherapy consisting of vincristine, doxorubicin, and cyclophosphamide, the patients' laboratory indications of DIC began to resolve. During this period, the patient received massive blood transfusion of a total of 311 units (26 units of red blood cells, 26 units of fresh frozen plasma, 74 units of platelet concentrates, 17 units of single donor platelets, and 168 units of cryoprecipitate), antithrombin-III and a synthetic protease inhibitor. Despite chemotherapy and radiation therapy, he died 1 year later because of disease progression. In children with metastatic rhabdomyosarcoma and massive DIC, prompt chemotherapy and aggressive supportive care is important to decrease malignancy-triggered procoagulant activities.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6441-6446
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• 2012

Background: Radiation therapy plays an important role in lung carcinoma treatment. However, the incidence of symptomatic radiation-induced lung injury is high. This study aimed to evaluate radioprotective effects of flavonoids extracted from Astragalus complanatus and mechanisms of action against radiation damage. Methods: Alteration in antioxidant status and levles of several cytokines were investigated in BABL/C mice treated with 4 mg/kg b.wt. flavonoids after exposure to 10Gy thoracic radiation. Results: Serum levels of SOD in the flavonoids+radiation group were significantly higher compared to the radiation control group, while TGF-${\beta}1$ and IL-6 were lower. Mice in the radiation control group displayed more severe lung damage compared with the flavonoids+radiation group. The expression of TGF-${\beta}1$ and TNF-${\alpha}$ in the radiation control group was markedly increased in alveolar epithelial cells and macrophages of the alveolar septum. Conclusions: From the results of the present study, flavonoids could be excellent candidates as protective agents against radiation-induced lung injury.