• Title/Summary/Keyword: Growth Differentiation Factor 15

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MiR-323-5p acts as a Tumor Suppressor by Targeting the Insulin-like Growth Factor 1 Receptor in Human Glioma Cells

  • Lian, Hai-Wei;Zhou, Yun;Jian, Zhi-Hong;Liu, Ren-Zhong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10181-10185
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    • 2015
  • Background: MicroRNAs, small noncoding RNA molecules, can regulate mammalian cell growth, apoptosis and differentiation by controlling the expression of target genes. The aim of this study was to investigate the function of miR-323-5p in the glioma cell line, U251. Materials and Methods: After over-expression of miR-323-5p using miR-323-5p mimics, cell growth, apoptosis and migration were tested by MTT, flow cytometry and cell wound healing assay, respectively. We also assessed the influence of miR-323-5p on the mRNA expression of IGF-1R by quantitative real-time reverse transcriptase PCR (qRT-PCR), and on the protein levels by Western blot analysi. In addition, dual-luciferase reporter assays were performed to determine the target site of miR-323-5p to IGF-1R 3'UTR. Results: Our findings showed that over-expression of miR-323-5p could promote apoptosis of U251 and inhibit the proliferation and migration of the glioma cells. Conclusions: This study demonstrated that increased expression of miR-323-5p might be related to glioma progression, which indicates a potential role of miR-323-5p for clinical therapy.

EXPRESSION OF THE EPIDERMAL GROWTH FACTOR RECEPTOR AND CELL CYCLE ANALYSIS IN THE HEAD AND NECK SQUAMOUS CELL CARCINOMAS (두경부 편평세포암종에서 상피성장인자수용체의 발현과 세포주기에 관한 연구)

  • Kim, Kyoung-Won;Kim, Myung-Jin
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.26 no.2
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    • pp.154-163
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    • 2000
  • Growth factors and the receptors play an important role in the regulation of the growth and development of mammalian cells. In particular, epidermal growth factor is a polypeptide with potent mitogenic activity that stimulates proliferation of various normal and neoplastic cells through the interaction with its specific receptor(EGFR). EGFR has been described as a parameter of poor prognosis in many human neoplasms such as breast, bladder, and vulvar cancers. The objectives of this study are the evaluation of the expression of EGFR and cell cycle analysis in the head and neck squamous cell carcinomas(SCC), and the evaluation of the correlation between clinico-patholgic features and expression of EGFR and S-phase fraction. 37 head and neck squamous cell carcinoma specimens were evaluated for expression of EGFR by Western blot analysis and S-phase fraction by cell cycle analysis using the flow cytometry. The obtained results were as follows : 1. The expressions of EGFR were observed in 20 specimens(54%) among 37 head and neck SCC specimens. In case of oral SCC, 15 specimens(56%) out of 27 specimens were observed, and in case of nasopharyngeal SCC 5 specimens(50%) out of 10 specimens. 2. There was no correlation between clinical features(location, stage) of head and neck SCC and expression of EGFR (p>0.05). 3. There was a significant correlation between histo-pathological differentiation of head and neck SCC and expression of EGFR (p<0.02). 4. There was a significant correlation between expression of EGFR and S-phase fraction of cell cycle in the head and neck SCC (p<0.05). The above results suggest that expression of EGFR and S-phase fraction of cell cycle are adjunctive prognostic marker in the head and neck squamous cell carcinomas.

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Effects of Electroacupuncture and Electrical Stimulation on VEGF Expression After Muscle Crush Injury in Rats (전침 자극과 전기 자극의 적용이 근육압좌손상이 유발된 흰쥐의 골격근 내 혈관내피성장인자 발현에 미치는 영향)

  • Kim, Min-Hee;Lee, Hyun-Min;Park, Eun-Se;Nam, Ki-Won;Kim, Jin-Sang
    • Physical Therapy Korea
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    • v.13 no.2
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    • pp.9-15
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    • 2006
  • Skeletal muscle injury occurs frequently in sports medicine and is the most general form of injury followed by physical impact. There are growth factors which conduct proliferation, differentiation, and synthesis of myogenic prodromal cells and regulate vascular generation for the continued survival of myocytes. The purpose of the present study was to confirm the effects of electroacupuncture (EA) and electrical stimulation (ES) on muscle recovery processes according to vascular endothelial growth factor (VEGF) expression. Eighteen Sprague-Dawley rats were separated into 2 experimental groups and a controlled group. All animals had suffered from crush damage in the extensor digitorum longus for 30 seconds and were killed 1, 3, and 7 days after injury. 30 Hz and 1 mA impulsion for 15 minutes was applied to the EA experimental groups Zusanli (ST36) and Taichong (LR3) using electroacupuncture and the same stimulation was applied to the ES group using an electrical node. Hematoxyline-Eosin staining and VEGF immunohistochemistry were used to ascertain the resulting muscle recovery. There were few morphological differences between the EA and ES groups, and both groups were observed to have tendencies to decrease atrophy as time passed. In the controlled group, gradually diminishing atrophy could be observed, but their forms were mostly disheveled. There were few differences in VEGF expression between the EA and ES groups, and tendencies to have an increased quantity of VEGF with the lapse of time were observed in both groups. In the controlled group, a little VEGF expression could be observed merely 7 days after injury. In conclusion, EA and ES contributed to muscle recovery processes and could be used for the treatment of muscle injury.

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Induction of Apoptosis by IGFBP3 Overexpression in Hepatocellular Carcinoma Cells

  • Han, Jian-Jun;Xue, De-Wen;Han, Qiu-Rong;Liang, Xiao-Hong;Xie, Li;Li, Sheng;Wu, Hui-Yong;Song, Bao
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10085-10089
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    • 2015
  • Background: The insulin-like growth factor (IGF) system comprises a group of proteins that play key roles in regulating cell growth, differentiation, and apoptosis in a variety of cellular systems. The aim of this study was to investigate the role of insulin-like growth factor binding protein 3 (IGFBP3) in hepatocellular carcinoma. Materials and Methods: Expression of IGF2, IGFBP3, and PTEN was analyzed by qRT-PCR. Lentivirus vectors were used to overexpress IGFBP3 in hepatocellular carcinoma cell (HCC) lines. The effect of IGFBP3 on proliferation was investigated by MTT and colony formation assays. Results: Expression of IGF2, IGFBP3, and PTEN in several HCC cell lines was lower than in normal cell lines. After 5-aza-2'-deoxycytidine/trichostatin A treatment, significant demethylation of the promoter region of IGFBP3 was observed in HCC cells. Overexpression of IGFBP3 induced apoptosis and reduced colony formation in HUH7 cells. Conclusions: Expression of IGF2, IGFBP3, and PTEN in several HCC cell lines was lower than in normal cell lines. After 5-aza-2'-deoxycytidine/trichostatin A treatment, significant demethylation of the promoter region of IGFBP3 was observed in HCC cells. Overexpression of IGFBP3 induced apoptosis and reduced colony formation in HUH7 cells.

Trichostatin A-induced Apoptosis is Mediated by Krüppel-like Factor 4 in Ovarian and Lung Cancer

  • Zohre, Sadeghi;Kazem, Nejati-Koshki;Abolfazl, Akbarzadeh;Mohammad, Rahmati-Yamchi;Aliakbar, Movassaghpour;Effat, Alizadeh;Zahra, Davoudi;Hassan, Dariushnejad;Nosratollah, Zarghami
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6581-6586
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    • 2014
  • Background: The istone deacetylase (HDAC) inhibitor trichostatin A (TSA) is known to mediate the regulation of gene expression and antiproliferation activity in cancer cells. Kr$\ddot{u}$ppel-like factor 4 (klf4) is a zinc finger-containing transcription factor of the SP/KLF family, that is expressed in a variety of tissues and regulates cell proliferation, differentiation, tumorigenesis, and apoptosis. It may either either function as a tumor suppressor or an oncogene depending on genetic context of tumors. Aims: In this study, we tested the possibility that TSA may increase klf4 expression and cancer cell growth inhibition and apoptosis in SKOV-3 and A549 cells. Materials and Methods: The cytotoxicity of TSA was determined using the MTT assay test, while klf4 gene expression was assessed by real time PCR andto ability of TSA to induce apoptosis using a Vybrant Apoptosis Assay kit. Results: Our results showed that TSA exerted dose and time dependent cytotoxicity effect on SKOV-3 and A549 cells. Moreover TSA up-regulated klf4 expression. Flow cytometric analysis demonstrated that apoptosis was increased after TSA treatment. Conclusions: Taken together, this study showed that TSA increased klf4 expression in SKOV3 and A549 cell lines, consequently, klf4 may played a tumor-suppressor role by increasing both cell growth inhibition and apoptosis. This study sheds light on the details of molecular mechanisms of HDACI-induced cell cycle arrest and apoptosis.

Immunohistochemical Staining of Insulin-like Growth Factor-1 in Human Lung Cancer Cells (폐암의 조직학적 형태에 따른 인슐린양 성장인자-1의 면역조직학적 염색의 비교)

  • Park, Ji-Hyun;Kang, Myoung-Jae;Lee, Heung-Bum;Lee, Yong-Chul;Rhee, Yang-Kuen
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.3
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    • pp.324-330
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    • 2000
  • Objective : Lung cancer arises after a series of morphological changes, which take several years to progress from normal epithelium to invasive cancer. Multiple molecular changes and growth factor production have been documented in lung cancers, both small cell and non-small cell types. Insulin-like growth factors(IGFs) are important mitogenic and anabolic peptides, both in vivo and in vitro, and are thought to be significant autocrine-paracrine factors involved in normal and malignant cell proliferation. In this study, the degree of expression of IGF-1 on the immunohistochemical staining in human non-small cell lung cancer(NSCLC) cells and small cell lung cancer (SCLC) cells were investigated. Methods : Immunohistochemical staining for IGF-1 was performed in 15 cases of small cell carcinoma, 15 cases of squamous cell carcinoma, 15 cases of adenocarcinoma, and 12 cases of bronchoalveolar carcinoma. Results : The expression of IGF-1 on the immunohistochemical staining significantly increased in NSCLC cells than in SCLC cells. Conclusion : These results suggest the expression of IGF-1 in human lung cancer cells. The immunohistochemical staining of IGF-1 in lung cancer cell lines may assist in the differentiation of NSCLC and SCLC.

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Backbone NMR assignments of the FAS1-3/FAS1-4 domains of transforming growth factor-beta-induced protein

  • Kang, Dong-Hoon;Yi, Jong-Jae;Sim, Dae-Won;Park, Jung-Wook;Lee, Sung-Hee;Kim, Eun-Hee;Jeon, Young-Ho;Son, Woo Sung;Won, Hyung-Sik;Kim, Ji-Hun
    • Journal of the Korean Magnetic Resonance Society
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    • v.24 no.1
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    • pp.1-8
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    • 2020
  • An extracellular matrix protein, transforming growth factor-beta-induced protein (TGFBIp/βig-h3), which is induced by transforming growth factor-β in the human cornea, skin, and matrix of many connective tissues, is associated with the adhesion, migration, proliferation, and differentiation of various cells. TGFBIp contains four homologous repeat domains, known as FAS1 domains, where certain mutations have been considered to cause corneal dystrophies. In this study, backbone NMR assignments of FAS1-3/FAS1-4 tandem domain were obtained and compared with those previously known for the isolated FAS1-4 domain. The results corroborate in solution the inter-domain interaction between FAS1-3 and FAS1-4 in TGFBIp.

Study of Growth Disturbance and Endocrine, in the view of Oriental Medicine (소아 성장장애와 내분비에 대한 한의학적 고찰)

  • Jun Chan-Il
    • The Journal of Pediatrics of Korean Medicine
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    • v.15 no.1
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    • pp.105-115
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    • 2001
  • The relation of endocrine in the western medicine and zangfu-organ functions in Korean medicine, related to growth disturbance, was studied and derived the following results. 1. The hormone most related to growth disturbance is, directly secreted from the anterior pituitary or is stimulated and secreted in the target grands, growth hormone, thyroid, adrenocortical hormone, gonadial hormone and is insulin secreted from $\beta$ cell of langerhans' slands of pancreas. 2. the pituitary has the most close relation with the kidney in the five zang-organ. Because the kidney is innate origin(先天之本) and promotes qi and blood(生化氣血), stores the essence of life(藏精), dominates the bones(主骨) and promotes the marrow(生骨髓). Especially it is connected with brain(通於腦). 3. In the children growth, the endocrine action in the pituitary has the most close relation with the kidney, As in the reports of the brain and spinal cord, bone, store essence of life, sexual maturation and decline(kidney-qi, sexual functions of both sexes(天癸)) etc, and cause of cretinism, dwarf in the main subject. 4. Somatomedin is the most important factor of the growth factors, IGF in another word. The unification of IGF and secretion is controlled firstly according to growth hormone, however is very closely related to the nutrition status in the non-hormonic causes. Also, it is affected very much by the insulin. 5. Insulin is one of the important hormone related to the growth and is secreted from the pancreas. Pancreas belongs to the functional system of spleen in oriental medicine, thus the growth disturbance, occurred due to error in insulin secretion and nutrition(in another words, the lack of postnatal essential substance from food-stuff(水穀精氣)), is closely related to the spleen. 6. From the results driven above, the hormone action of endocrine and problem in secretion, related to the growth disturbance, must be focused on the differentiation of symptoms and signs of the kidney and the spleen in oriental medicine.

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Alteration of TGFB1, GDF9, and BMPR2 gene expression in preantral follicles of an estradiol valerate-induced polycystic ovary mouse model can lead to anovulation, polycystic morphology, obesity, and absence of hyperandrogenism

  • Asghari, Reza;Shokri-Asl, Vahid;Rezaei, Hanieh;Tavallaie, Mahmood;Khafaei, Mostafa;Abdolmaleki, Amir;Seghinsara, Abbas Majdi
    • Clinical and Experimental Reproductive Medicine
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    • v.48 no.3
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    • pp.245-254
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    • 2021
  • Objective: In humans, polycystic ovary syndrome (PCOS) is an androgen-dependent ovarian disorder. Aberrant gene expression in folliculogenesis can arrest the transition of preantral to antral follicles, leading to PCOS. We explored the possible role of altered gene expression in preantral follicles of estradiol valerate (EV) induced polycystic ovaries (PCO) in a mouse model. Methods: Twenty female balb/c mice (8 weeks, 20.0±1.5 g) were grouped into control and PCO groups. PCO was induced by intramuscular EV injection. After 8 weeks, the animals were killed by cervical dislocation. Blood serum (for hormonal assessments using the enzyme-linked immunosorbent assay technique) was aspirated, and ovaries (the right ovary for histological examinations and the left for quantitative real-time polymerase) were dissected. Results: Compared to the control group, the PCO group showed significantly lower values for the mean body weight, number of preantral and antral follicles, serum levels of estradiol, luteinizing hormone, testosterone, and follicle-stimulating hormone, and gene expression of TGFB1, GDF9 and BMPR2 (p<0.05). Serum progesterone levels were significantly higher in the PCO animals than in the control group (p<0.05). No significant between-group differences (p>0.05) were found in BMP6 or BMP15 expression. Conclusion: In animals with EV-induced PCO, the preantral follicles did not develop into antral follicles. In this mouse model, the gene expression of TGFB1, GDF9, and BMPR2 was lower in preantral follicles, which is probably related to the pathologic conditions of PCO. Hypoandrogenism was also detected in this EV-induced murine PCO model.

Chondrogenesis of Human Adipose Tissue Derived Mesenchymal Stem Cells (ATMSCs) Seeded in Gelatin-Chondroitin-Glucosamine Scaffold (Gelatin-Chondroitin-Glucosamine Scaffold에 접종한 인간지방조직-유래 중간엽 줄기세포의 연골형성)

  • Kim, Eung-Bae;Hong, Soon-Gab;Do, Byung-Rok;Kim, Hae-Kwon;Lee, Joon-Yeong
    • Development and Reproduction
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    • v.15 no.2
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    • pp.99-111
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    • 2011
  • The present experiment was performed to evaluate the chondrogenic differentiation potential of human adipose tissue-derived mesenchymal stem cells (ATMSCs) in the chondrogenic induction medium (CIM) with transforming growth factor-${\beta}1$ (TGF-${\beta}1$) and to evaluate the chondrogenic differentiation of ATMSCs seeded in gelatin-chondroitinglucosamine scaffold (GCG-scaffold). ATMSCs and mouse chondrocytes were cultured in the basic medium and CIM without TGF-${\beta}1$ (CIM1) or with TGF-${\beta}1$ (CIM2) for chondrogenic differentiation potential. The chondrogenic differentiation of ATMSCs was evaluated by glycosaminoglycan (GAG) synthesis and histochemical staining. In pellet culture, GAG synthesis of ATMSCs and chondrocyte was increased in culture on 14 days, but higher in CIM1 than basic medium, especially highest in CIM2. Cartilage matrix was observed in ATMSCs cultured in CIM2 on 14 days by Safranin O and trichrome staining. In well plate culture, proliferation of ATMSCs was continuously increased in culture on 10 days and higher in CIM than basic medium. The cell adhesion rate of ATMSCs seeded in flask or scaffolds was continuously increased during culture period, but higher in scaffold than flask. GAG synthesis of ATMSCs seeded in scaffolds showed no change in control group. In the CIM groups, GAG synthesis of ATMSCs was continuously increased than control group during culture period, especially very high in CIM2 and in the GCG-scaffold was slightly higher than the gelatin scaffold (G-scaffold). The present results demonstrated that ATMSCs showed an low chondrogenic differentiation potential, compared to mouse chondrocytes for 14 days of culture. TGF-${\beta}1$ is important factor in chondrogenic differentiation of ATMSCs. Gelatin scaffold was considered to increasing the effective chondrogenic differentiation environment. ATMSCs seeded in GCG-scaffold was more effective in chondrogenesis than in G-scaffold. Conclusively, the present results demonstrated that the treatment of chondroitin and glucosamine in the scaffold was more effective to promote the cartilage matrix formation.