• Maxillofacial Plastic and Reconstructive Surgery
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• 제22권2호
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• pp.123-132
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• 2000

$TGF-{\beta}_1$ is a potent chemotactic factor for inflammatory cells and fibroblasts. It also stimulates the celluar source and components of extracellular matrix and the production of proteinase inhibitors. Collectively, these biologic activities lead to the accumulation and stabilization of the nascent matrix, which is vital to infection control. The objective of this study is to investigate production of $TGF-{\beta}$ in vitro fibroblast culture in the presence of Staphylococcus enterotoxin B(SEB) and/or lipopolysaccharide(LPS) and to elucidate the role of $TGF-{\beta}_1$ which may be responsible for infection control. The fibroblasts were originated from gingiva and facial dermis in 26 year-old male patient. In the presence of LPS($0.01{\mu}g$, $0.1{\mu}g$, $1.0{\mu}g$), SEB($0.01{\mu}g$, $0.l{\mu}g$, $1.0{\mu}g$) respectively, $cells(5{\times}10^3ml)$ were cultivated in vitro. At 1, 3, and 5 days after incubation, cells were counted. Also, $cells(2.5{\times}10^5ml)$ were cultivated in EMEM with LPS(0.01, 0.1 and $1.0{\mu}g$), SEB(0.01, 0.1 and $1.0{\mu}g$) respectively and $LPS(0.1{\mu}g)$ and $SEB(0.1{\mu}g)$ in combination for 24, 48, and 72 hours respectively. Culture supernatants were harvested at 1, 2, and 3 days after incubation period and triplicate culture supernatants were pooled and $TGF-{\beta}_1$ was assayed in duplicate. The results were as follows. 1. In gingival fibroblast induced with SEB and LPS respectively or in combination, the suppression of cell Proliferation occurred very significantly since 3 days after incubation, compared with the control and the production of $TGF-{\beta}_1$ occurred very significantly at 1 day after incubation, compared with the control. 2. In facial dermal fibroblast induced with SEB and LPS respectively or in combination, the suppression of cell proliferation occurred very significantly at 1 day after incubation, compared with the control. In SEB exposure, the production of $TGF-{\beta}_1$ was decreased very significantly at 1 day after incubation, compared with the control. However, in LPS, SEB and LPS exposure, the production of $TGF-{\beta}_1$ was increased very significantly at 1 day after incubation, compared with the control. In conclusion, the concentration of bacterial toxins and the incubation period correlated with cell proliferation and production of $TGF-{\beta}_1$ very significantly. The gingival and facial dermal fibroblasts have different phenotype each other The orchestrated understanding of fibroblast proliferation and $TGF-{\beta}_1$ production play an important part in host defense against the bacterial Infection and may prevent tissue necrosis such as necrotizing fasciitis and life-threatening syndrome such as multiple organ failure.

• 한국정밀공학회지
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• 제32권8호
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• pp.755-760
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• 2015

For proper wound healing, dermal contraction and remodeling are critical; during the natural healing process, differentiated fibroblasts called "myofibroblasts" typically undertake these functions. For severe wounds, however, a critical mass of dermal matrix and fibroblasts are lost, making self-regeneration impossible. To overcome this impairment, synthetic wound patches with embedded functional cells can be used to promote healing. In this study, we developed a polydioxanone (PDO)-based cell-embedded sheet on which dermal fibroblasts were cultured and induced for differentiation into myofibroblasts, whereby the following combinatorial physicochemical stimuli were also applied: aligned topology, electric field (EF), and growth factor. The results show that both the aligned topology and EF synergistically enhanced the expression of alpha smooth-muscle actin (${\alpha}$-SMA), a key myofibroblast marker. Our proof-of-concept (POC) experiments demonstrated the potential applicability of a myofibroblast-embedded PDO sheet as a wound patch.

• IMMUNE NETWORK
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• 제3권1호
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• pp.38-46
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• 2003

Background: Platelet-activating factor (PAF) induces nuclear factor $(NF)-{\kappa}B$ activation and angiogenesis and increases tumor growth and pulmonary tumor metastasis in vivo. The role of $NF-{\kappa}B$ activation in PAF-induced angiogenesis in a mouse model of Matrigel implantation, and in PAF-mediated pulmonary tumor metastasis were investigated. Methods: Angiogenesis using Matrigel and experimental pulmonary tumor metastasis were tested in a mouse model. Electrophoretic mobility shift assay was done for the assessment of $NF-{\kappa}B$ translocation to the nucleus. Expression of angiogenic factors, such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\alpha}$, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were tested by RT-PCR and ELISA. Results: PAF induced a dose- and time-dependent angiogenic response. PAF-induced angiogenesis was significantly blocked by PAF antagonist, CV6209, and inhibitors of $NF-{\kappa}B$ expression or action, including antisense oligonucleotides to p65 subunit of $NF-{\kappa}B$ (p65 AS) and antioxidants such as ${\alpha}$-tocopherol and N-acetyl-L-cysteine. In vitro, PAF activated the transcription factor, $NF-{\kappa}B$ and induced mRNA expression of $TNF-{\alpha}$, $IL-1{\alpha}$, bFGF, VEGF, and its receptor, KDR. The PAF-induced expression of the above mentioned factors was inhibited by p65 AS or antioxidants. Also, protein synthesis of VEGF was increased by PAF and inhibited by p65 AS or antioxidants. The angiogenic effect of PAF was blocked when anti-VEGF antibodies was treated or antibodies against $TNF-{\alpha}$, $IL-1{\alpha}$, and bFGF was co-administrated, but not by antibodies against $TNF-{\alpha}$, $IL-1{\alpha}$, and bFGF each alone. PAF-augmented pulmonary tumor metastasis was inhibited by p65 AS or antioxidants. Conclusion: These data indicate that PAF increases angiogenesis and pulmonary tumor metastasis through $NF-{\kappa}B$ activation and expression of $NF-{\kappa}B$-dependent angiogenic factors.

• 대한한방내과학회지
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• 제26권4호
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• pp.753-760
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• 2005

목적 : 본 연구는 100명의 암환자를 대상으로 항암단의 항혈관형성 효과를 측정하기 위하여 고안되었다. 방법 : 100명의 암환자 전체의 치료전후의 VEGF, bFGF 및 혈소판 수치의 변화량을 측정하였고, 병기, 삶의 질 및 암종별로 환자를 나누어 각각의 치료전후의 VEGF, bFGF 및 혈소판 수치의 변화량을 측정하여 통계적 유의성을 살펴보았다. 결과 : 항암단으로 치료한 암환자의 bFGF 수치는 치료전 후 통계적으로 유의성 있게 감소하였다. 특히 유방암 환자에서 bFGF 수치의 감소가 눈에 띄었다. 비록 통계적으로 유의하지는 않았지만 VEGF수치도 항암단으로 치료 후 다소 감소하는 경향을 보였다. 결론 : 따라서 항암단이 암환자 치료에 있어 항혈관형성 약물로써 작용한다고 추론할 수 있다.

• BMB Reports
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• 제28권2호
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• pp.87-93
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• 1995

To investigate the biological functions of the EGF-like domain of mouse betacellulin (BTC), mouse BTC(33-80), a 48-residue peptide corresponding to the EGF-like domain, was synthesized by stepwise solidphase methods using a 9-fluorenylmethoxycarbonyl (Fmoc) strategy. The homogeneity of synthetic mouse BTC(33-80) was confirmed by analytical reversed phase (RP)-HPLC, amimo acid analysis, and fast atom bombardment mass spectrometer (FAB-MS). Three disulfide bond pairings of synthetic mouse BTC(33-80) were established by amino acid analysis of cysteine-containing fragments derived from thermolytic digestion. These were consistent with the pairings of EGF and transforming growth factor ($TGF-{\alpha}$). The EGF-Iike domain of mouse BTC showed equipotent activity in both EGF-receptor binding on A-431 epidermoid carcinoma cells, and mitogenesis on NIH-3T3 fibroblast cells, as compared with authentic h-EGF. Results suggest that the EGF-Iike domain of BTC plays a significant role in mitogenic activity with an EGF-receptor mediated system.

• Journal of Chest Surgery
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• 제34권5호
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• pp.377-385
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• 2001

배경: Cisplain과 같은 세포돗성 약제에 대한 내성은 폐암 치료 실패의 중요한 원인이다. 이러한 항암제에 대한 내성의 발생기전은 복잡하고 아직 완전히 알려져 있지 않지만 불량한 예후의 원인으로 생각된다. 특히 약제 내성이 발생한 환자의 경우 기존의 종양의 급속한 성장뿐 아니라 새로운 전이 병소가 급속히 발생 및 진단됨은 약제 내성을 가진 종양이 전이에의 용이성을 획득하는게 아닌가 의심케한다. 이를 규명하기 위해 Cisplatin에 내성을 지닌 비소세포폐암 세포주 H460/CISm이 전이 능력을 Cisplatin에 민감한 비소세포폐암 세로주 H460과 비교하고자 한다. 대상 및 방법: 약제 내성 세포주를 확보하기 위하여 H460세포에 cisplatin을 점차적으로 증가시켜 처리한 후 배양하였다. H460 세포와 H460/CIS 세로에서의 혈관신생인자와 성장관련인 자의 발현양상, gelatin zymography 분석 그리고 in vivo 실험으로 nude 마우스에서의 자발적 전이 능력의 차이를 비교하였다. 결과: H460 세포를 이식한 마우스에 폐에서는 종양이 형성되지 않았으나 H460/CIS세포를 이식한 마우스 10마리중 8마리에서 종양이 형성되었다. 또한 H460/CIS 세포주에서 전이 관련 유전자로 알려진 angiopoietin-1, vascular endothelial growth factor, basic fibroblast growth factor, matrix metalloproteinase 2 등이 더 발현되었고, 전이의 침습성을 유발하는 gelatinase의 활성이 증가된 것을 확인할 수 있었다. 결론: 본 여구 결과를 통해 cisplatin에 내성을 가진 비소세포폐암세포에서 전이 능력이 증가될 수 있다고 여겨지며 이러한 사실을 토대로 초기 비소세포폐암 환자의 수술 전 항암약물요법의 타당성에 대해서 이야기 하기 위해서는 많은 임상적 연구가 필요하리라 생각된다.

• Journal of Gastric Cancer
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• 제24권1호
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• pp.29-56
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• 2024

In recent years, remarkable progress has been made in the molecular profiling of gastric cancer. This progress has led to the development of various molecular classifications to uncover subtype-specific dependencies that can be targeted for therapeutic interventions. Human epidermal growth factor receptor 2 (HER2) is a crucial biomarker for advanced gastric cancer. The recent promising results of novel approaches, including combination therapies or newer potent agents such as antibody-drug conjugates, have once again brought attention to anti-HER2 targeted treatments. In HER2-negative diseases, the combination of cytotoxic chemotherapy and programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors has become the established standard of care in first-line settings. In the context of gastric cancer, potential biomarkers such as PD-L1 expression, Epstein-Barr virus, microsatellite instability, and tumor mutational burden are being considered for immunotherapy. Recently, promising results have been reported in studies on anti-Claudin18.2 and fibroblast growth factor receptor 2 treatments. Currently, many ongoing trials are aimed at identifying potential targets using novel approaches. Further investigations will be conducted to enhance the progress of these therapies, addressing challenges such as primary and acquired resistance, tumor heterogeneity, and clonal evolution. We believe that these efforts will improve patient prognoses. Herein, we discuss the current evidence of potential targets for systemic treatment, clinical considerations, and future perspectives.

• Journal of Periodontal and Implant Science
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• 제45권3호
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• pp.111-119
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• 2015

Purpose: The purpose of this animal study was to perform a histological and histomorphometric analysis in order to elucidate the effect of fibroblast growth factor-2 (FGF-2) on injured periodontal ligament (PDL) and cementum after tooth replantation in dogs. Methods: The roots of 36 mandibular premolars from six mongrel dogs were used in this study. The roots were randomly divided into three groups: (1) a positive control group (n=12), in which the PDL was retained; (2) a negative control group (n=12), in which the PDL and the cementum between the notches were removed; and (3) an experimental group (n=12), in which the PDL and the cementum between the notches were removed and the roots were soaked in an FGF-2 solution ($30{\mu}g/0.1mL$). After treating the root surfaces, the extracted roots were replanted into extraction sockets. The animals were sacrificed four and eight weeks after surgery for histologic and histomorphometric evaluation. Results: At four and eight weeks, normal PDLs covered the roots in the positive control group. In the negative control group, most replanted roots showed signs of replacement resorption. In the experimental group, new PDL-like tissue and cementum-like tissue were observed to partially occupy the region between the root surfaces and the newly formed bone. Histomorphometric analysis showed that the mean length of the newly formed cementum-like tissue on the roots treated with FGF-2 was significantly greater than that of the tissue on the roots in the negative control group (four weeks, P=0.008; eight weeks, P=0.042). However, no significant differences were observed between the roots treated with FGF-2 and the negative control roots with respect to newly formed PDL-like tissue. Conclusions: The results of this study suggest that use of FGF-2 on injured root surfaces promotes cementogenesis after tooth replacement in dogs.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제33권1호
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• pp.11-19
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• 2007

This study was to evaluate the expression of vascular endothelial growth factor receptors (VEGFRs) in tumor and stromal cells of tougue squamous cell carcinoma (SCC). We also wanted to characterize the differences, from the angiogenic aspect, between cancer-associated stromal cells and non-malignant stromal cells. Paraffin-embedded tumor specimens from eleven patients with tongue SCCs were studied. Immunohistochemical staining for VEGFR-1,-2, and -3 was performed on the tumor cells, stromal fibroblasts and tumor-associated macrophages of the specimens. The expression of all 3 receptors was detected in the tumor cells themselves of the biopsy specimens. All 3 receptors were also expressed on stromal cells, except that VEGFR-2 was not expressed in stromal fibroblasts. In radical excision specimens, the staining intensity for VEGFR-1, -2 in the tumor cells and VEGFR-1,-3 in the tumor-associated macrophages was significantly lower than that in the biopsy specimens (P < 0.05). By using the general marker of fibroblast and macrophage, 5B5 and CD68, respectively, we performed double immunofluorescence staining for 5B5 and each VEGFR in the stromal fibroblasts and for CD68 and each VEGFR in the tumor-associated macrophages of the radical excision specimens. We used 4 cases of fibroma and 4 cases of chronic inflammation tissue as the controls. It was found that only each marker was expressed in the control group, however, 5B5/VEGFR-1 and 5B5/VEGFR-3 in the stromal fibroblasts, and CD68/VEGFR-1 and CD68/VEGFR-3 in the tumor-associated macrophages were double stained in the radical excision specimens. Although our study used small number of specimens, the results of our study showed that in tongue SCC, in association with the angiogenesis, the stromal cells showed the activated phenotype and this was different from the nonmalignant stromal cells.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제27권5호
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• pp.424-430
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• 2005

The oral cavity is humid environment mainly due to the continuous salivary flow. The reaction of oral mucosa to fluid flow is important for homeostasis and pathogenesis. The objective of this study is the screening the change of gene expression after the application of fluid induced shear stress (FISS) on the gingival fibroblast using cDNA microarray assay. The immortalized human gingival fibroblasts were grown and FISS was applied using a cone viscometer at a rotational velocity of 40 rpm, respectively for periods of 2 and 4 hours. The synthesis of cDNA was done from the extracted total RNA and cDNA microarray assay was done subsequently. The genes that showed over 1.6 in the Cy3/Cy5 or the Cy5/Cy3 value were regarded as genes influenced significantly by the FISS application ion (/M/>0.7). The " RUNX-1" was increased its expression in 2 hours group and " RUN and SH3 domain containing 1" was increased its expression in 4 hours group. The "CC020415", "cyclin L1", "interferon regulatory factor1", "early growth response 1", "immediate early response 2", and "immediate early response 3" genes were increased their expression in 2 and 4 hours after FISS application. In conclusion, we could find many genes that were probably related to the FISS application. Interestingly, most of them were placed in similar molecular pathways and these findings improve the reliability of chip data and usefulness in overall screening. From this experiment, we could find many items for further study and it will make improvement in the understanding of intracellular events in response to FISS.