趋化因子及趋化因子受体在骨肉瘤中的研究进展

骨肉瘤，又称成骨肉瘤，是常见的恶性成骨性肿瘤之一，占恶性骨肿瘤总数的20%～45%，多数起源于骨间叶细胞。发病年龄多在15～25岁之间，男性多于女性。好发部位为长骨干骺端，其中以股骨远端和胫骨近端较多见，其次是肱骨和腓骨近端，随血液运行转移率高且早，发展迅速。骨肉瘤侵袭性强，约20%的患者发生转移，肺转移为常见[1]。随着新辅助化疗、保肢手术等的开展，骨肉瘤患者5年生存率提高到60%～70%[2]。但由于化疗耐药性、转移率高等问题的存在，患者仍面临着复发及肺转移的困扰。基因治疗、免疫治疗和分子靶向治疗等生物治疗技术的发展也为骨肉瘤的治疗开辟了新的道路，为骨肉瘤患者带来新的希望[3]。

1　TNF ligand and receptor superfamily membersTumor Necrosis Factor (TNF) supergene family and its cognate family of rel ated r eceptors (TNF-R) have expanded in the past few years to include at least 17 lig ands and 22 receptors (The New TNF Nomenclature Scheme, http://www.gene.ucl.ac.uk/users/nomenclature/genefamily/tnfinfo.html)[1]. With the exception of LTα,whichlacks a hydro phobic transmembrane region, allof the ligands are type Ⅱintegral membrane pro teins that may also function as soluble proteins. Many of the TNF superfamily ligands pair with a single, although some specific receptor, including TNFα, LT α, TRAIL, FasL, LIGHT and TRANCE/RANKL, bind to multiple receptors (Tab 1).

Expression of estrogen receptor alpha in preimplantation mice embryos

Objective:To study the expression of estrogen receptor alpha (ERα) in preimplantation mice embryos.Methods:Mice zygotes were collected from superovulated Kunming mice and cultured in vitro.Embryos at different developmental stages were collected at 0,24,36,48,72 and 96hours after cultivation.The expression of ERα in early mice embryos was detected by reverse transcription-PCR (RT-PCR) and immunocytochemistry.Results:The expression of ERα mRNA was detected in all of the examined embryonic stages.The relative amount of ERα mRNA showed no significant difference between 1-cell stage embryos and 4-cell stage embryos (P>0.05).However,the relative level of ERα mRNA significantly decreased (P<0.05) at 2-cell stage and was the lowest at this stage.Over 2-cell stage,the ERα mRNA relative level would increase and achieve the peak level at blastocyst stage.The location of immunocytochemistry showed that ERα immunopositive cells could be firstly detected at 8-cell stage,after which they are consistently detected until blastocyst stage.In addition,the intensity of ERα positive staining was higher at blastocyst stage compared with that at 8-cell stage and morula stage.Conclusion:ERα is expressed in preimplantation mice embryos in a temporal and spatial pattern and may be involved in regulating the development of early mice embryos,which probably plays crucial roles in early embryonic development.

Objective: To study transforming growth factor-β1(TGF-β1) autoproduction in keloid fibroblasts and theregulation effect of blocking TGF-β intracellular signalingon rhTGF-β1 autoproduction.Methods: Keloid fibroblasts cultured in vitro weretreated with either rhTGF-β1 (5 ng/ml ) or recombinantadenovirus containing a truncated type II TGF-β receptorgene (50 pfu/cell ). Their effects of regulating geneexpression of TGF-β1 and its receptor I and II wereobserved with Northern blot.Results: rhTGF-β1 up-regulated the gene expressionof TGF-β1 and receptor I, but not receptor II. Over-expression of the truncated receptor II down-regulated thegene expression of TGF-β1 and its receptor I, but notreceptor II.Conclusions: TGF-β1 autoproduction was observed inkeloid fibroblasts. Over-expression of the truncated TGF-βreceptor H decreased TGF-β1 autoproduction via blockingTGF-β receptor signaling.