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1.
肺癌是目前全球发病率和死亡率均居前列的恶性肿瘤,其中肺鳞癌经手术、放化疗等综合治疗后,其疗效仍不满意。随着分子靶向治疗在肺腺癌中取得了令人瞩目的成果,而肺鳞癌患者中EGFR基因突变及ALK融合基因少见,急需探索新的靶点指导肺鳞癌患者的临床治疗。研究表明,FGFR家族(FGFR1-4)是肺鳞癌中突变频率较高的基因,FGFR基因的激活突变和扩增与肺鳞癌的发生和发展密切相关,同时许多小分子 FGFR 抑制剂在临床应用中已经取得较好的治疗效果。目前,许多FGFR抑制剂治疗肺鳞癌的临床试验也正在进行研究,针对FGFR靶点的基因治疗可为肺鳞癌的治疗提供一种新的策略。本文就FGFR在肺鳞癌的靶向治疗中的最新研究进展进行综述。 相似文献
2.
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 总被引:2,自引:0,他引:2
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 相似文献
3.
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 相似文献
4.
FGF signaling segregates biliary cell-lineage from chick hepatoblasts cooperatively with BMP4 and ECM components in vitro. 总被引:2,自引:0,他引:2
Masaaki Yanai Norifumi Tatsumi Noboru Hasunuma Kenjiro Katsu Fumio Endo Yuji Yokouchi 《Developmental dynamics》2008,237(5):1268-1283
Intrahepatic bile ducts (IHBDs) are indispensable for transporting bile secreted from hepatocytes to the hepatic duct. The biliary epithelial cells (BECs) of the IHBD arise from bipotent hepatoblasts around the portal vein, suggesting the portal mesenchyme is essential for their development. However, except for Notch or Activin/TGF-beta signaling molecules, it is not known which molecules regulate IHBD development. Here, we found that FGF receptors and BMP4 are specifically expressed in the developing IHBD and the hepatic mesenchyme, respectively. Using a mesenchyme-free culture of liver bud, we showed that bFGF and FGF7 induce the hepatoblasts to differentiate into BECs, and that BMP4 enhances bFGF-induced BEC differentiation. The extracellular matrix (ECM) components in the hepatic mesenchyme induced BEC differentiation. Forced expression of a constitutively active form of the FGF receptor partially induced BEC differentiation markers in vivo. These data strongly suggest that bFGF and FGF7 promote BEC differentiation cooperatively with BMP4 and ECMs in vivo. 相似文献
5.
Romeo S Bovée JV Grogan SP Taminiau AH Eilers PH Cleton-Jansen AM Mainil-Varlet P Hogendoorn PC 《The Journal of pathology》2005,206(2):135-142
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. 相似文献
6.
Fibroblast growth factor 2 induces differentiation and apoptosis of Askin tumour cells 总被引:7,自引:0,他引:7
Kim MS Kim CJ Jung HS Seo MR Juhnn YS Shin HY Ahn HS Thiele CJ Chi JG 《The Journal of pathology》2004,202(1):103-112
Peripheral primitive neuroectodermal tumour (PNET)/Ewing's sarcoma (ES) and neuroblastoma (NB) are related tumours of neural crest origin with primitive neural characteristics. Fibroblast growth factor 2 (FGF2) is a critical signalling molecule for primitive neural crest cells. The treatment of NB cells with FGF2 variably affects biological characteristics such as growth and differentiation, while in PNET/ES, FGF2 predominantly induces apoptosis. The JK-GMS Askin tumour cell line can be induced to differentiate upon treatment with nerve growth factor (NGF), indicating the integrity of the cellular machinery necessary for differentiation. The present study assesses whether FGF2 can induce differentiation in JK-GMS cells. JK-GMS cells expressed high-affinity FGF receptors (FGFRs), and treatment with FGF2 induced phosphorylation of FGFR1 together with activation of extracellular signal-regulated kinases (ERK1/ERK2) and c-Jun N-terminal kinase (JNK). Subsequent biological effects were growth inhibition, neuronal differentiation, and apoptosis, and these changes were associated with increased expression of neurofilaments, reduction of c-myc and bcl-2 expression, and activation of caspase 3. Treatment of the cells with a specific inhibitor of the MAPK/extracellular signal-regulated kinase (MEK)-1, PD98059, predominantly inhibited the effects of FGF2 on growth, differentiation, and apoptosis, while an inhibitor of JNK reduced apoptosis, indicating that the ERK1/2 and JNK pathways are critical components of FGF2-mediated effects in JK-GMS cells. Additional comparative analyses of FGF2-mediated effects in two ES cell lines (CADO-ES, RD-ES) and a PNET cell line (SK-N-MC) showed pronounced differentiation in SK-N-MC, but not in CADO-ES or RD-ES cells. This study demonstrates that FGF2 can induce neuronal differentiation of PNET including Askin tumour. These findings clearly indicate that the FGF2-mediated signalling pathway plays a critical role in controlling the major properties of PNET cells and may provide a potential therapeutic target for PNET. 相似文献
7.
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. 相似文献
8.
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 相似文献
9.
10.
Jason R Spence Juan-Carlos Aycinena Katia Del Rio-Tsonis 《Developmental dynamics》2007,236(5):1161-1174
The embryonic chick is able to regenerate the retina after it has been removed. We have previously shown that proliferating stem/progenitor cells present in the ciliary body/ciliary marginal zone (CB/CMZ) of the chick eye are responsible for regeneration, which can be induced by ectopic fibroblast growth factor-2 (FGF2) or Sonic hedgehog (Shh). Here, we reveal the mechanisms showing how FGF2 and Shh signaling are interdependent during retina regeneration. If the FGF pathway is inhibited, regeneration stimulated by Shh is inhibited. Likewise, if the Hedgehog pathway is inhibited, regeneration stimulated by FGF2 is inhibited. We examined early signaling events in the CB/CMZ and found that FGF2 or Shh induced a robust Erk phosphorylation during the early stages of retina regeneration. Shh also up-regulated the expression of several members of the FGF signaling pathway. We show that ectopic FGF2 or Shh overexpression increased the number of phosphohistone 3 (PH3)-positive cells in the CB/CMZ and inhibition of either pathway decreased the number of PH3-positive cells. Additionally, both FGF and Hh signaling are required for cell survival in the CB/CMZ, whereas Hh and not FGF signaling plays a role in maintaining the identity of the retinal progenitor population in this region. Combined, our results support a model where the FGF and Hedgehog pathways work together to stimulate retina regeneration. 相似文献