环氧合酶-2及其选择性抑制剂塞来昔布对结肠癌肝转移瘤VEGF、FGF-2影响的实验研究

目的 :研究环氧化酶 2及其选择性抑制剂塞来昔布和血管生成因子VEGF、FGF 2间的关系 ,从而探讨环氧化酶 2对结肠癌肝转移瘤血管形成的影响。方法 :以细胞培养法建立稳定的结肠癌细胞株HT 2 9和HCT 116 ,利用脾切除法建立结肠癌肝转移动物模型 ,免疫组化检测结肠癌肝转移瘤VEGF、FGF 2蛋白表达。结果 :结肠癌肝脏转移率 ,HT 2 9组、HCT 116组、塞来昔布组分别为 83 33%、16 6 7%、33 33%。肝脏转移瘤VEGF、FGF 2的表达 ,HT 2 9组与HCT 116组、塞来昔布组比较均表达增强 ,有显著统计学意义 (P <0 0 1～ 0 0 5 ) ;塞来昔布组与HCT 116组比较无显著性差异 (P >0 0 5 )。结论 :环氧合酶 2与结肠癌肝转移瘤血管生成密切相关 ,其高表达促进了结肠癌肝转移瘤新生血管生成。其机制可能是上调促血管生成因子VEGF、FGF 2的表达     

The multifunctionality of FGF-2 in the adrenal medulla

 Chromaffin cells of the adrenal medulla and their tumor counterparts, the pheochromocytoma (PC12) cells, are well-established model systems in neurobiology. The development of sympathoadrenal progenitor cells to chromaffin cells can be studied with regard to developmental signals which trigger the differentiation. With regard to potential treatments of neurological disorders like Parkinson’s disease chromaffin cell grafting can be used as one therapeutical approach. The beneficial effect of chromaffin cell grafts is possibly not only related to the release of dopamine but may also be linked to the release of growth factors. One of the growth factors that is synthesized by chromaffin and PC12 cells is basic fibroblast growth factor (FGF-2). The experimental data available so far, are in agreement with different functional roles of FGF-2. This article summarizes the putative physiological functions of FGF-2 in the adrenal medulla. Three differential functional roles of FGF-2 are discussed: (1) as a differentiation factor for sympathoadrenal progenitor cells; (2) as a target-derived neurotrophic factor for preganglionic sympathetic neurons which innervate adrenal medullary cells; (3) as an auto-/paracrine factor in the adrenal medulla. Accepted: 21 August 1996     

Chondromyxoid fibroma resembles in vitro chondrogenesis, but differs in expression of signalling molecules

Chondromyxoid fibroma is a rare benign cartilaginous bone tumour characterized by morphological features that resemble different steps of chondrogenesis in terms of both cellular morphology, ranging from spindled to rounded cells, and the extracellular matrix formed, which ranges from fibrous to cartilaginous. The presence in chondromyxoid fibroma of signalling molecules that regulate the spatial expression of proteins involved in normal cartilage proliferation and differentiation was investigated in samples from 20 patients and compared with articular chondrocytes from 11 normal donors cultivated in 3D pellet culture. Sections were stained with safranin-O and H&E, and immunohistochemistry was performed for p16, cyclin D1, FGFR3, BCL2, p21, PTHLH, PTHR1 and N-cadherin. Expression patterns were analysed using hierarchical clustering. In chondromyxoid fibroma, specific morphological features correlated with a distinct pattern of expression. Comparison with normal chondrocytes in pellet culture showed a striking morphological resemblance, but with an unmistakably different pattern of expression. N-cadherin, PTHLH, and PTHR1 were expressed to a significantly higher level (p < 0.01) in articular chondrocyte pellets but, conversely, there was significantly lower expression of cyclin D1, p16 and BCL2 (p < 0.05) in these cells. Morphological similarities reflect common steps in cartilage differentiation, albeit driven by different molecular mechanisms. The proteins we have found to be differentially expressed seem crucial for neoplastic chondrogenesis.     

Fibroblast growth factor 17 is over-expressed in human prostate cancer

Over-expression of fibroblast growth factor 8 (FGF8) in human prostate cancer is associated with clinically aggressive disease. Among different members of the FGF family, FGF17 and FGF8 share high sequence homology and have similar patterns of expression during embryogenesis. In this study, the clinical significance of FGF17 expression and its in vitro function in prostate cancer cells were tested. Forty resected prostate specimens from patients with benign prostatic hyperplasia (BPH, n = 12) and prostate cancer (CaP, n = 28; Gleason sum scores 3-10) were studied using semi-quantitative RT-PCR. In addition, 85 cases of CaP (Gleason sum scores 5-9) and 20 cases of BPH were examined using immunohistochemistry and findings were correlated with clinical parameters. In vitro experiments using prostate cancer cell lines examined the functional significance of FGF17 in prostate cancer. These studies revealed a significant linear correlation between increasing Gleason sum scores and FGF17 expression using both immunohistochemistry (p < 0.0001, rho = 0.99) and RT-PCR (p = 0.008, rho = 0.99). Immunohistochemistry demonstrated upregulation of FGF17 in CaP compared with BPH (p < 0.0001) and, when comparing high-grade CaP (Gleason sum score 7-10) with BPH, RT-PCR showed a fourfold upregulation of FGF17 mRNA expression (p < 0.0001). Men with tumours displaying high levels of FGF17 expression had a worse outcome on survival analysis (p = 0.044) and a higher risk of progression with metastases (p < 0.0001). Proliferation assays showed low-dose recombinant (r) FGF17 (1 ng/ml) to be a more potent mitogen than rFGF1 and rFGF8 in prostate cancer cell lines (LNCaP, DU145, and PC3M) (p < 0.001). Furthermore, FGF8 was shown to induce expression of FGF17 in these cell lines. These data support a role for FGF17, and a model of co-expression of multiple FGFs, with FGF17 as a potential mediator of FGF8 function, in human prostate carcinogenesis.     

bFGF在骨组织工程学中的研究进展

碱性成纤维细胞生长因子 (b FGF)是近年来研究较为广泛的生长因子之一 ,对骨组织有着广泛的生物学效应。本文就 b FGF的研究进展及其目前在骨组织工程学研究方面的应用做一综述     

Burosumab for the Treatment of Tumor-Induced Osteomalacia

Tumor-induced osteomalacia (TIO) is caused by phosphaturic mesenchymal tumors producing fibroblast growth factor 23 (FGF23) and is characterized by impaired phosphate metabolism, skeletal health, and quality of life. UX023T-CL201 is an ongoing, open-label, phase 2 study investigating the safety and efficacy of burosumab, a fully human monoclonal antibody that inhibits FGF23, in adults with TIO or cutaneous skeletal hypophosphatemia syndrome (CSHS). Key endpoints were changes in serum phosphorus and osteomalacia assessed by transiliac bone biopsies at week 48. This report focuses on 14 patients with TIO, excluding two diagnosed with X-linked hypophosphatemia post-enrollment and one with CSHS. Serum phosphorus increased from baseline (0.52 mmol/L) and was maintained after dose titration from week 22 (0.91 mmol/L) to week 144 (0.82 mmol/L, p < 0.0001). Most measures of osteomalacia were improved at week 48: osteoid volume/bone, osteoid thickness, and mineralization lag time decreased; osteoid surface/bone surface showed no change. Of 249 fractures/pseudofractures detected across 14 patients at baseline, 33% were fully healed and 13% were partially healed at week 144. Patients reported a reduction in pain and fatigue and an increase in physical health. Two patients discontinued: one to treat an adverse event (AE) of neoplasm progression and one failed to meet dosing criteria (receiving minimal burosumab). Sixteen serious AEs occurred in seven patients, and there was one death; all serious AEs were considered unrelated to treatment. Nine patients had 16 treatment-related AEs; all were mild to moderate in severity. In adults with TIO, burosumab exhibited an acceptable safety profile and was associated with improvements in phosphate metabolism and osteomalacia. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..     

VEGF,bFGF及PCNA在宫颈癌中的表达及其与肿瘤增殖和血管生成的关系

目的 :探讨有关细胞因子在调控宫颈癌增殖及其血管生成中的作用。方法 :应用免疫组织化学及其组织形态学定量分析方法 ,对血管内皮细胞生长因子 (VEGF) ,碱性成纤维细胞生长因子(b FGF)和增殖细胞核抗原 (PCNA)在宫颈癌中的表达进行研究。结果 :1肿瘤细胞增殖与 VEGF的表达呈正向关系 ,而与 b FGF的表达无关 ;2 VEGF,b FGF的表达分别与微血管密度有正相关性 ,而当 VEGF和 b FGF共同表达时 ,微血管密度显著增加 ;3VEGF,b FGF在不同个体的表达具有异质性。结论 :VEGF有促进肿瘤细胞增殖及血管生成的作用。VEGF,b FGF在肿瘤血管生成过程中可能起协同作用