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Pirfenidone suppresses the abnormal activation of human Müller cells after platelet-derived growth factor-BB stimulation

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International Journal of Ophthalmology(English edition) 2019年第7期12卷 1075-1082页

作者： Yi-Jin Tao Qin Chen Li Wang Xiao Yang Qing Cun Wen-Yan Yang Hua Zhong Department of Ophthalmology the First Affiliated Hospital of Kunming Medical University Kunming 650031Yunnan Province China Department of Ophthalmology the First Affiliated Hospital of Nanjing Medical University Nanjing 210029Jiangsu ProvinceChina

AIM: To determine the effect of pirfenidone on the activated human Müller cells by platelet-derived growth factor-BB(PDGF-BB). METHODS: The primary human Müller cells were separated from retinal tissues and established the pathogenic model by stimulated with PDGF-BB. The Müller cells behaviour of normal group and the model group was measured by MTT assay, Trypan blue assay, cell migration assay, and collagen contraction assay. The expression of transforming growth factor(TGF)-β1,-β2, and pigment epithelium-derived factor(PEDF) was estimated with realtime polymerase chain reaction(PCR), Western blot and immunofluorescence analyses. RESULTS: A pathogenic/proliferative model of Müller cells was established by stimulating normal cultured Müller cells with 10 ng/mL PDGF-BB for 48 h. After treated with 0.2 and 0.3 mg/mL pirfenidone, the proliferation, migration and collagen contraction was statistically significantly depressed in the model group compared with the normal groups. The expression levels of TGF-β1 and TGF-β2 were significantly down-regulated, while the PEDF expression was significantly up-regulated after treated with 0.2 and 0.3 mg/mL pirfenidone in the model group. CONCLUSION: Pirfenidone effectively suppress the proliferation, migration and collagen contraction of the human Müller cells stimulated with PDGF-BB through down-regulation of TGF-β1/TGF-β2 and up-regulation of PEDF.

关键词： pirfenidone Müller cells platelet-derived growth factor-BB transforming growth factor-β proliferative vitreoretinopathy

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Clinical Significance of platelet-derived Growth Factor-C Expression in Colorectal Cancer

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Journal of Cancer Therapy 2014年第1期5卷 11-20页

作者： Shinichi Yamauchi Satoru Iida Megumi Ishiguro Toshiaki Ishikawa Hiroyuki Uetake Kenichi Sugihara Department of Surgical Oncology Graduate School Tokyo Medical and Dental University Tokyo Japan Department of Translational Oncology Graduate School Tokyo Medical and Dental University Tokyo Japan

platelet-derived growth factors (PDGFs) are known to be associated with tumor growth and angiogenesis through their activation of the receptor tyrosine kinases, PDGF receptors alpha and beta. Several studies revealed the participation of the PDGF family in colorectal cancer (CRC). However, the role of platelet derived growth factor-C (PDGFC) in CRC is less well studied. This study aimed to determine the correlation between PDGFC expression and the prognosis of patients with CRCs. Tumor samples were obtained from patients with CRC who underwent surgical resection between 2002 and 2006. The mRNA expression of PDGFC was investigated by quantitative reverse transcription-polymerase chain reaction in 85 patients with stage I-IV CRC. PDGFC protein expression was analyzed by immunohistochemistry, and the relationship between PDGFC protein expression and clinicopathologic features was investigated in 245 patients with stage I-III CRC. PDGFC mRNA expression in cancer tissues was significantly higher in patients with distant metastases than in those without metastases (P = 0.016). PDGFC protein overexpression was associated with significantly worse overall and relapse-free survival (P P < 0.0001, respectively). Moreover, PDGFC protein overexpression was an independent risk factor for CRC recurrence (relative risk = 3.395, 95% confidence interval = 1.895 - 6.081, P < 0.001). In the present study, PDGFC overexpression appeared to be predictive of recurrence and poor prognosis in patients with CRC.

关键词： platelet-derived Growth Factor-C Colorectal Cancer Prognosis mRNA Expression Immunohistochemistry

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Effects of interleukin-1α on platelet-derived growth factor release from bovine cerebral microvascular endothelial cells

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Journal of Medical Colleges of PLA(China) 1997年第1期12卷 21-24页

作者：李坚张珉芮耀诚

The present study showed that, interleukin-1α (IL-1α) stimulateal cultured bovine cerebral microvascular endothelial cells (BCMEC) releasing growth factor which promoted bovine cerebral microvascular smooth muscle cells (BCMSMC) proliferation in a dose-dependent manner. The mitogenic activity in conditioned medium of BCMEC stimulated by IL-1α was neutralized significantly by the antibody to platelet-derived growth factor (PDGF). Imperatorin (Imp), iso-Imperatorin (iso Imp) and 6-(α,α-phenylacetylpiperazinyl)phenyl-5-methyl-4,5-dihydro-3 (2H)-pyridazinone (PMDP) did not affect the releasing of PDGF from IL-1α stimulated BCMEC, but inhibited the promotion of PDGF on the proliferation of BCMSMC. We concluded that the promotion of IL-1α on the proliferation of BCMSMC should be mediated by some growth factors, such as PDGF.

关键词： interleukin-1 platelet-derived growth factor cerebral microvascular cell cell division

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Deficiency of platelet-derived growth factor receptor-α-positive cells in Hirschsprung's disease colon

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World Journal of Gastroenterology 2016年第12期22卷 3335-3340页

作者： Anne-Marie O'Donnell David Coyle Prem Puri National Children's Research Centre Our Lady's Children's Hospital Crumlin

AIM: To investigate whether the expression of plateletderived growth factor receptor-α-positive(PDGFRα^+)-cells is altered in Hirschsprung's disease(HD).METHODS: HD tissue specimens(n = 10) were collected at the time of pull-through surgery, while colonic control samples were obtained at the time of colostomy closure in patients with imperforate anus(n = 10). Immunolabelling of PDGFRα^+-cells was visualized using confocal microscopy to assess the distribution of these cells, while Western blot analysis was undertaken to quantify PDGFRα protein ***: Confocal microscopy revealed PDGFRα+-cells within the mucosa, myenteric plexus and smooth muscle in normal controls, with a marked reduction in PDGFRα^+-cells in the HD specimens. Western blotting revealed high levels of PDGFRα protein expression in normal controls, while there was a striking decrease in PDGFRα protein expression in the HD ***: These findings suggest that the altered distribution of PDGFRα^+-cells in both the aganglionic and ganglionic HD bowel may contribute to the motility dysfunction in HD.

关键词： platelet-derived growth factor receptor alpha Hirschsprung’s disease Gastrointestinal motility Agang

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Regenerative Surgery for the Rehabilitation of a Patient after Surgery and Radiation Therapy for Head and Neck Cancer: A Case Report

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Journal of Biomedical Science and Engineering 2014年第6期7卷 361-367页

作者： M. Scala A. Orsi A. Rattaro M. Trapasso Susanna Polotto F. Spagnolo P. Mereu P. L. Santi Department of Plastic Surgery I.R.C.C.S. Azienda Ospedaliera Universitaria San Martino-IST Genova Italy

Oral cancer is usually treated combining surgery, radiation therapy and chemotherapy, following effective therapeutic protocols. Severe maxillary and mandibular bone atrophy resulting after therapies are usually treated with autologous bone grafting procedures even though these techniques often present a significant risk of postoperative complications and disadvantages. We describe the case of a 59-year-old woman presenting severe bone defect after being treated with surgery and radiotherapy for recurrent oral verrucous squamous cell carcinoma. We performed bone regeneration using platelet-derived Growth Factors (PDGF) in combination with autologous bone chips. Our procedure of bone regeneration allowed the placement of dental implants and the achievement of a good aesthetic and functional result. Regenerative surgery may enable the regeneration of substantial bone defects. Moreover, PDGF application decreases the risk of implant failure in irradiated patients.

关键词： Regenerative Surgery Radiation Therapy Head and Neck Squamous Cell Carcinoma platelet-derived Growth Factors Bone Chips

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Current Perspectives on Sunitinib Targeted Therapy for Tumors

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Journal of Cancer Therapy 2011年第4期2卷 535-541页

作者： Karolin Kamel Abdel-Aziz 不详

This review highlights therapeutic agents from recent cancer therapeutic trials showing the greatest potential for further clinical use for sunitinib in the near future. In fact, sunitinib is one of multi-tyrosine kinase inhibitors;tyrosine kinases are enzymes, which transfer phosphate groups from ATP to the hydroxyl group of tyrosine residues on signal transduction molecules. Phosphorylation of signal transduction molecules, in turn, induces dramatic changes in tumor growth, including activation of angiogenesis and DNA synthesis. Therefore, sustain efforts have been directed for developing inhibitors for angiogenesis, which is the marginal process for tumor growth and development through targeting TKs. Almost if not all angiogenesis inhibitors target the vascular endothelial growth factor (VEGF) signaling pathway.

关键词： platelet-derived Growth Factor (PDGF) Cytochrome P450 Enzyme (CYP3A4) Dose-Limiting Toxicities (DLTs) Hepatocyte Growth Factor (HGF) Tyrosine Kinases (TKs)

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Study of therapeutic effects of EGF and PDWHF on nonhealing cutaneousulcers in patients with diabetes mellitus

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Journal of Medical Colleges of PLA(China) 2000年第3期15卷 206-209页

作者：冯江杜文华王劲牟江洪

Objective:To study the therapeutic effects of epidermal growth factor (EGF) and platelet-derived wound healing factor (PDWHF) on the nonhealing cutaneous ulcers in 78 patients with diabetes mellitus. Methods: Seventy-eight patients were divided into group A in which the patients were treated with saline to serve as the control, group B in which the patients were treated with EGF and group C treated with PDWHF. General healing practice was administered. Wound closure index, healing rate and histological changes of the ulcerative wounds of the patients were observed in the treatment period of 8 weeks. Results:The wond closure index and healing rate were more significantly increased in groups B and C than in group A of the control with far more angiogenesis , fibroblast hyperplasia and collagen deposition in the former than in the latter. The therapeutic effects of PDWHF seemed to be superior to those of *** :It is suggested that the local application of a certain growth factor or of a combination of several growth factors in an efficient management to improve the healing of diabetic cutaneous ulcers.

关键词： diabetes mellitus epidermal growth factor platelet-derived wound healing factor

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DOG1 is useful for diagnosis of KIT-negative gastrointestinal stromal tumor of stomach

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World Journal of Gastroenterology 2013年第47期19卷 9133-9136页

作者： Takuya Wada Satoshi Tanabe Kenji Ishido Katsuhiko Higuchi Tohru Sasaki Chikatoshi Katada Mizutomo Azuma Akira Naruke Myunguchul Kim Wasaburo Koizumi Tetsuo Mikami Department of Gastroenterology Kitasato University East HospitalKanagawa 252-0380Japan Department of Pathology Kitasato University East HospitalKanagawa 252-0380Japan

Approximately 80%-95%of gastrointestinal stromal tumors(GISTs)show positive staining for KIT,while the other 5%-20%show negative *** the tumor is negative for KIT,but is positive for CD34,a histological diagnosis is ***,if the tumor is negative for KIT,CD34,S-100,and SMA,a definitive diagnosis is often ***,Discovered on GIST-1(DOG1)has received considerable attention as a useful molecule for the diagnosis of ***1,a membrane channel protein,is known to be overexpressed in *** the sensitivity and specificity of DOG1 are higher than those of KIT,positive staining for DOG1has been reported,even in KIT-negative *** GISTs most commonly arise in the stomach and are mainly characterized by epithelioid features *** describe our experience with a rare case of a KIT-negative GIST of the stomach that was diagnosed by positive immunohistochemical staining for DOG1 in a patient who presented with severe *** findings suggest that immunohistochemical staining for DOG1,in addition to gene analysis,is useful for the diagnosis of KIT-negative tumors that are suspected to be GISTs.

关键词： KIT negative Gastrointestinal stromal tumors Discovered on gastrointestinal stromal tumor-1 platelet-derived growth factor receptor alpha

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The correlation of serum PDGF and Ang-2 contents with atherosclerotic plaque features in patients with coronary heart disease

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Journal of Hainan Medical University 2017年第8期23卷 39-42页

作者： Yan-Bing Xi Clinical Laboratory Department General Hospital of Hubei Jianghan OilfieldQianjiang CityHubei Province433121

Objective:To study the correlation of serum PDGF and Ang-2 contents with atherosclerotic plaque features in patients with coronary heart ***: A total of 80 patients with coronary heart disease who were treated in our hospital between January 2013 and April 2016 were collected as the observation group, and 50 healthy subjects who received medical examination in our hospital during the same period were selected as the normal control group. Serum PDGF and Ang-2 contents of two groups of patients were detected, and the observation group were further divided into the high PDGF group and low PDGF group (n = 40) as well as the high Ang-2 group and low Ang-2 group (n = 40) according to the median of PDGF and Ang-2 contents. Ultrasonic contrast technology was used to assess the atherosclerotic plaque characteristics in patients with coronary heart ***: Serum PDGF and Ang-2 contents of observation group were significantly higher than those of control group;ultrasound parameters P and AUC levels of high PDGF group were higher than those of low PDGF group while Tp and MTT levels were lower than those of low PDGF group;ultrasound parameters P and AUC levels of high Ang-2 group were higher than those of low Ang-2 group while Tp and MTT levels were lower than those of low Ang-2 ***:Serum PDGF and Ang-2 contents increase in patients with coronary heart disease and are negatively correlated with the atherosclerotic plaque stability.

关键词： Coronary heart disease platelet-derived growth factor Angiogenin 2 Atherosclerotic plaque

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Greater omentum gastrointestinal stromal tumor with PDGFRA-mutation and hemoperitoneum

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World Journal of Gastrointestinal Oncology 2012年第5期4卷 119-124页

作者： Yoko Murayama Masayuki Yamamoto Ryuichiro Iwasaki Tamana Miyazaki Yukiko Saji Yoshinori Doi Haruki Fukuda Seiichi Hirota Masahiro Hiratsuka Department of Gastroenterology and Hepatology Itami City HospitalItami 6648540Japan Department of Surgery Itami City HospitalItami 6648540Japan Department of Gastroenterology and Hepatology Otemae HospitalOsaka 5400008Japan Department of Pathology Itami City HospitalItami 6648540Japan Department of Surgical Pathology Hyogo College of MedicineNishinomiya 6638501Japan

Although gastrointestinal stromal tumor(GIST) occurs generally in the digestive tract,omental GIST is very *** report the first case of an adult greater omental GIST with a new platelet-derived growth factor receptor α gene(PDGFRA)-mutation with hemoperitoneum.A 43-year-old man was admitted to our hospital complaining of acute abdominal *** contrast-enhanced computed tomography revealed a huge mass in the right abdominal cavity,and a large accumulation of fluid in the pelvic cavity,suggesting *** diagnosed the rupture as an intra-abdominal tumor,and an emergency tumorectomy was performed with resection of the greater *** tumor was located in the distal right side ofthe greater omentum,and showed no continuity with the gastric *** tumor occurred primarily in the greater *** resected tumor was about 19 cm × 12 cm × 14 cm in diameter,and weighed 1529 ***,the tumor was composed of epithelioidshaped cells with high cellularity,and was positive for CD117 and CD34,and negative for S-100,α-smooth muscle *** mitosis was 6/50 under high power *** case showed exon 18 mutation of PDGFRA with 846(Asp to Glu) substitution,848(Asn to Lys) *** is the first report of this PDGFRA mutation in omental GIST,and this might play an important role in the tumorigenesis of this *** on these findings,the tumor was diagnosed as high risk GIST primarily occurring in the greater *** patient was treated with imatinib at a dose of 400 mg/d as adjuvant chemotherapy,and has been followed up for 24 mo with no evidence of recurrence.

关键词： Gastrointestinal stromal tumor Greater omentum Hemoperitoneum platelet-derived growth factor receptor α gene KIT

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