1.Overexpression of bone morphogenetic protein 4 in STO fibroblast feeder cells represses the proliferation of mouse embryonic stem cells in vitro.
Gu Hee KIM ; Gong Rak LEE ; Hyung Im CHOI ; Neung Hwa PARK ; Hun Taeg CHUNG ; In Seob HAN
Experimental & Molecular Medicine 2012;44(7):457-463
Embryonic stem cells (ESCs) can be propagated in vitro on feeder layers of mouse STO fibroblast cells. The STO cells secrete several cytokines that are essential for ESCs to maintain their undifferentiated state. In this study, we found significant growth inhibition of mouse ESCs (mESCs) cultured on STO cells infected with adenovirus containing a dominant-negative mutant form of IkappaB (rAd-dnIkappaB). This blockage of the NF-kappaB signal pathway in STO cells led to a significant decrease in [3H]thymidine incorporation and colony formation of mESCs. Expression profile of cytokines secreted from the STO cells revealed an increase in the bone morphogenetic protein4 (BMP4) transcript level in the STO cells infected with adenoviral vector encoding dominant negative IkappaB (rAd-dnIkappaB). These results suggested that the NF-kappaB signaling pathway represses expression of BMP4 in STO feeder cells. Conditioned medium from the rAd-dnIkappaB-infected STO cells also significantly reduced the colony size of mESCs. Addition of BMP4 prevented colony formation of mESCs cultured in the conditioned medium. Our finding suggested that an excess of BMP4 in the conditioned medium also inhibits proliferation of mESCs.
Animals
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*Bone Morphogenetic Protein 4/genetics/metabolism
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Cell Differentiation/genetics
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Cell Proliferation
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Culture Media, Conditioned
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*Embryonic Stem Cells/cytology/metabolism
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*Feeder Cells/cytology/metabolism
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*Fibroblasts/cytology/metabolism
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Gene Expression Regulation/genetics
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*I-kappa B Proteins/genetics/metabolism
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Mice
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Mutation
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NF-kappa B/genetics/metabolism
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Signal Transduction
2.Axillary Lymph Node Metastases in Patients with T1 Breast Carcinoma: Correlation with Histopathologic and Immunohistochemical Characteristics of the Primary Tumor.
Hyu Kyung KIM ; Jae Rak CHUNG ; Chul Hee LEE ; Jae Hoo PARK ; Hong Rae CHO ; Byung Kyun KO ; Young Sae PARK ; Yeong Ju WOO ; Jae Hee SUH ; Sei Hyun AHN ; Gyung Yub GONG
Journal of the Korean Cancer Association 1999;31(6):1179-1187
PURPOSE: Axillary lymph node metastases (ALNM) are the most important prognostic indicator in breast carcinoma. Because of relatively low incidence of axillary metastasis in the patients with Tl breast carcinoma, axillary lymph node dissection is now no longer considered to be the standard treatment. A reliable prediction of ALNM.may reduce the need for axillary lymph node dissection and may facilitate to select appropriate treatment modality. We have attempted to identify histopathologic/immunohistochemical factors correlated with ALNM in the patients with Tl breast carcinoma. MATERIAL AND METHODS: Forty-one patients with Tl breast carcinoma who underwent modified radical mastectomy and axillary dissection between January 1993 and February 1999 were studied. We investigated the relationship between ALNM and the histopathologic/immunohistochemical factors (size, lymphatic-vascular invasion (LVI), histologic grade, age, estrogen receptor (ER) status, progesterone receptor (PR) status, p53 protein, cathepsin D (CD), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor (TGF)- B 2, and microvessel density (MVD)). RESULTS: Fourteen (34.2%) out of the 41 patients with Tl breast carcinoma had ALNM. There are five statistically significant factors correlated with ALNM; lymphatic-vascular invasion (P=0.002), histologic grade (P 0.047), immunohistochemical expression of CD (P=0.005) and TGF- B 2 (P=0.004), and microvessel density (P=0.002). CONCLUSION: The histopathologic/immunohistochemical features of the primary breast tumor, such as LVI, increase in MVD, TGF- B 2 and CD expression, and histologic grade might be useful predictors of ALNM in patients with Tl breast carcinoma.
Breast Neoplasms*
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Breast*
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Cathepsin D
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Estrogens
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Fibroblast Growth Factor 2
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Humans
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Incidence
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Lymph Node Excision
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Lymph Nodes*
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Mastectomy, Modified Radical
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Microvessels
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Neoplasm Metastasis*
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Receptors, Progesterone
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Transforming Growth Factors
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Vascular Endothelial Growth Factor A
3.Benzydamine inhibits osteoclast differentiation and bone resorption down-regulation of interleukin-1 expression.
Han Saem SON ; Jiae LEE ; Hye In LEE ; Narae KIM ; You-Jin JO ; Gong-Rak LEE ; Seong-Eun HONG ; Minjeong KWON ; Nam Young KIM ; Hyun Jin KIM ; Jin Ha PARK ; Soo Young LEE ; Woojin JEONG
Acta Pharmaceutica Sinica B 2020;10(3):462-474
Bone diseases such as osteoporosis and periodontitis are induced by excessive osteoclastic activity, which is closely associated with inflammation. Benzydamine (BA) has been used as a cytokine-suppressive or non-steroidal anti-inflammatory drug that inhibits the production of pro-inflammatory cytokines or prostaglandins. However, its role in osteoclast differentiation and function remains unknown. Here, we explored the role of BA in regulating osteoclast differentiation and elucidated the underlying mechanism. BA inhibited osteoclast differentiation and strongly suppressed interleukin-1 (IL-1) production. BA inhibited osteoclast formation and bone resorption when added to bone marrow-derived macrophages and differentiated osteoclasts, and the inhibitory effect was reversed by IL-1 treatment. The reporter assay and the inhibitor study of IL-1 transcription suggested that BA inhibited nuclear factor-B and activator protein-1 by regulating IB kinase, extracellular signal regulated kinase and P38, resulting in the down-regulation of IL-1 expression. BA also promoted osteoblast differentiation. Furthermore, BA protected lipopolysaccharide- and ovariectomy-induced bone loss in mice, suggesting therapeutic potential against inflammation-induced bone diseases and postmenopausal osteoporosis.