Different distributions of interstitial cells of Cajal and platelet-derived growth factor receptor-α positive cells in colonic smooth muscle cell/interstitial cell of Cajal/plateletderived growth factor receptor-α positive cell syncytium in mice

AIM To investigate the distribution and function of interstitialcells of Cajal(ICCs) and platelet-derived growth factor receptor-α positive(PDGFRα+) cells in the proximal and distal colon.METHODS The comparison of colonic transit in the proximal and distal ends was performed by colonic migrating motor complexes(CMMCs). The tension of the colonic smooth muscle was examined by smooth muscle spontaneous contractile experiments with both ends of the smooth muscle strip tied with a silk thread. Intracellular recordings were used to assess electrical field stimulation(EFS)-induced inhibitory junction potentials(IJP) on the colonic smooth muscle. Western blot analysis was used to examine the expression levels of ICCs and PDGFRα in the colonic smooth muscle.RESULTS Treatment with NG-nitro-L-arginine methyl ester hydrochloride(L-NAME) significantly increased the CMMC frequency and spontaneous contractions, especially in the proximal colon, while treatment with MRS2500 increased only distal CMMC activity and smooth muscle contractions. Both CMMCs and spontaneous contractions were markedly inhibited by NPPB, especially in the proximal colon. Accordingly, CyPPA sharply inhibited the distal contraction of both CMMCs and spontaneous contractions. Additionally, the amplitude of stimulationinduced nitric oxide(NO)/ICC-dependent slow IJPs(sIJPs) by intracellular recordings from the smooth muscles in the proximal colon was larger than that in the distal colon, while the amplitude of electric field stimulationinduced purinergic/PDGFRα-dependent fast IJPs(fIJPs) in the distal colon was larger than that in the proximal colon. Consistently, protein expression levels of c-Kit and anoctamin-1(ANO1) in the proximal colon were much higher, while protein expression levels of PDGFRα and small conductance calcium-activated potassium channel 3(SK3) in the distal colon were much higher.CONCLUSION The ICCs are mainly distributed in the proximal colon and there are more PDGFRα+ cells are in the distal colon, which generates a pressure gradient between the two ends of the colon to propel the feces to the anus.

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

AIM: To investigate whether the expression of platelet-derived 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 expression.RESULTS: 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 colon.CONCLUSION: 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.

Vascular endothelial growth factor/platelet-derived growth factor receptor pathway is involved in bone marrow mesenchymal stem cell differentiation and directional migration toward gliomas

BACKGROUND： Vascular endothelial growth factor （VEGF） induces bone marrow-derived mesenchymal stem cell （BMSC） differentiation into vascular endothelial-like cells and promotes BMSC migration toward gliomas. However, the molecular mechanisms by which VEGF induces BMSC differentiation and migration remain poorly understood. OBJECTIVE; To investigate the role of platelet-derived growth factor （PDGF） receptor （PDGFR） in BMSC differentiation and migration induced by VEGE DESIGN, TIME AND SETTING： A parallel, controlled, in vitro experiment was performed at the Molecular Neurobiology ＆ Neural Regeneration and Repairing Laboratory, Anhui Provincial Hospital of Anhui Medical University, China from June 2008 to March 2009. MATERIALS： U87 glioma cells were purchased from Shanghai Institutes for Biological Sciences; mouse anti-human PDGFR and VEGF receptor （VEGFR） monoclonal antibodies were purchased from Peprotech, USA. METHODS： Isolated BMSCs were precultured with neutralizing antibody for VEGFR-1, VEGFR-2, PDGFR-α, and PDGFR-β to block biological activity of related receptors, followed by induced differentiation with 50μg/L VEGF. BMSCs induced with 50μg/L VEGF alone served as the VEGF-induced group. The control group remained untreated. MAIN OUTCOME MEASURES： Cell surface markers were identified by flow cytometry; BMSC surface cytokine receptor expression was detected by reverse transcription-polymerase chain reaction; the Transwell model was used to observe cell migration. RESULTS： After blocking the PDGFR, VEGF did not induce BMSC cell surface marker CD-31 or von Willebrand factor （vWF） expression. However, inhibition with VEGF receptor blocking agents, VEGF induced BMSCs to express CD-31 and vWE Following inhibition of the PDGFR, the number of cells migrating through the polycarbonate membrane Transwell chamber was decreased, as well as the number of BMSCs migrating to glioma cells. However, through the use of VEGF receptor blocking agents, the number of migrating cells remained unchanged. VEGF preculture increased the number of BMSCs migrating to gliomas. CONCLUSION： VEGF interacts with PDGFRs on the BMSC surface to attract BMSC directional migration and induce BMSC differentiation. The VEGF/PDGFR pathway participates in BMSC directional migration to glioma. VEGF pretreatment increased efficiency of BMSC migration to glioma.

Expression of NG2 and platelet-derived growth factor receptor alpha in the developing neonatal rat brain

Platelet-derived growth factor receptor alpha （PDGFRct） is a marker of oligodendrocyte precursor cells in the central nervous system. NG2 is also considered a marker of oligodendrocyte precursor cells. However, whether there are differences in the distribution and morphol- ogy of oligodendrocyte precursor cells labeled by NG2 or PDGFRa in the developing neonatal rat brain remains unclear. In this study, by immunohistochemical staining, NG2 positive （NG2＋） cells were ubiquitous in the molecular layer, external pyramidal layer, internal pyramidal layer, and polymorphic layer of the cerebral cortex, and corpus callosum, external capsule, piriform cortex, and medial septal nucleus. NG2~ cells were stellate or fusiform in shape with long processes that were progressively decreased and shortened over the course of brain development. The distribution and morphology of PDGFRct positive （PDGFRa＋） cells were coincident with NG2＋ cells. The co- localization of NG2 and PDGFRu in the cell bodies and processes of some cells was confirmed by double immunofluorescence labeling. Moreover, cells double-labeled for NG2 and PDGFRa were predominantly in the early postnatal stage of development. The numbers of NG2＋/PDGFRa＋ cells and PDGFRa＋ cells decreased, but the number of NG2＋ cells increased from postnatal days 3 to 14 in the developing brain. In addition, amoeboid microglial cells of the corpus callosum, newborn brain macrophages in the normal developing brain, did not express NG2 or PDGFRu, but NG2 expression was detected in amoeboid microglia after hypoxia. The present results suggest that NG2 and PDGFRct are specific markers of oligodendrocyte precursor cells at different stages during early development. Additionally, the NG2 protein is involved in inflammatory and pathological processes of amoeboid microglial cells.

Effects of ribozyme targeting platelet-derived growth factor receptor β subunit gene on the proliferation and apoptosis of hepatic stellate cells in vitro

Background Activation and proliferation of hepatic stellate cells (HSC) is essentially involved in the development and progression of hepatic fibrosis. The most potent growth factor for HSC is platelet-derived growth factor receptor (PDGF) and PDGF receptor β subunit (PDGFR-β) is the predominant signal transduction pathyway of PDGF which is overexpressed in activated HSC. This study investigated the cleavage activity of hammerhead ribozyme targeting PDGFR-β mRNA in HSC and the effect on biological characteristics of HSC.Methods Expression vector of anti-PDGFR-β ribozyme was constructed and transfected into rat activated HSC with lipofectamin. The positive cell clones were gained by G418 selection. The expression of PDGFR-β, α-smooth muscle actin, and typeⅠand type Ⅲ collagen were detected by using Northern blot, Western blot and immunocytochemical staining, respectively. The cell proliferation was determined with MTT colorimetric assay. The cell apoptosis was analyzed by using flow cytometry, acridine orange fluorescence vital staining and transmission electron microscopy.Results The expression of PDGFR-β at mRNA and protein level was markedly reduced in ribozyme-transfected HSC by 49%-57% ( P <0.05-0.01). The proliferation and α-smooth muscle actin expression of ribozyme-transfected HSC were significantly decreased ( P <0.05-0.01), and the type Ⅰ and type Ⅲ collagen synthesis were also reduced ( P <0.01). In addition, the proliferative response of ribozyme-transfected HSC to PDGF BB was significantly inhibited. Otherwise, the apoptotic cells were significantly increased in ribozyme-transfected HSC ( P <0.01), and typical apoptotic cells could be found under transmission electron microscopy.Conclusions The anti-PDGFR-β ribozyme effectively cleaved the target RNA and significantly inhibited its expression, which blocked the signal transduction of PDGF at receptor level, inhibited HSC proliferation and collagen synthesis, and induced HSC apoptosis. These results suggest that inhibiting PDGFR-β expression of HSC may be a new target for the therapy of liver fibrogenesis, and ribozyme may be a useful tool for inhibiting PDGFR-β expression.

Clinicopathological and Prognostic Significance of Hypoxia-inducible Factor-1 alpha in Lung Cancer: a Systematic Review with Meta-analysis

Hypoxia-inducible factor-1 alpha（HIF-1α） plays a vital role in the initiation, evaluation and prognosis in lung cancer. The prognostic value of HIF-1α reported in diverse study remains disputable. Accordingly, a meta-analysis was implemented to further understand the prognostic role of HIF-1α in lung cancer. The relationship between HIF-1α and the clinicopathological characteristics and prognosis of lung cancer were investigated by a meta-analysis. Pub Med and Embase were searched from their inception to January 2015 for observational studies. Fixed-effects or random-effects meta-analyses were used to calculate odds ratios and 95% confidence intervals of different comparisons. A total of 20 studies met the criteria. The results showed that HIF-1α expression in lung cancer tissues was significantly higher than that in normal lung tissues. Expression of HIF-1α in patients with squamous cell carcinoma was significantly higher than that of patients with adenocarcinomas. Similarly, non-small cell lung cancer（NSCLC） patients had higher HIF-1α expression than small cell lung cancer（SCLC） patients. Moreover, lymph node metastasized tissues had higher HIF-1α expression than non-lymph node metastasized tissues. A high level HIF-1α expression was well correlated with the expression of vascular endothelial growth factor and epidermal growth factor receptor in the NSCLC. Notably, NSCLC or SCLC patients with positive HIF-1α expression in tumor tissues had lower overall survival rate than patients with negative HIF-1α expression. It was suggested that HIF-1α expression may be a prognostic biomarker and a potential therapeutic target for lung cancer.

Basic fibroblast growth factor gene transfection in repair of internal carotid artery aneurysm wall

Surgery or interventional therapy has some risks in the treatment of cerebral aneurysm. We established an internal carotid artery aneurysm model by dripping elastase in the crotch of the right internal and external carotid arteries of New Zealand rabbits. Following model induction, lentivirus carrying basic fibroblast growth factor was injected through the ear vein. We found that the longer the action time of the lentivirus, the smaller the aneurysm volume. Moreover, platelet-derived growth factor expression in the aneurysm increased, but smooth muscle 22 alpha and hypertension-related gene 1 mRNA expression decreased. At 1,2, 3, and 4 weeks following model establishment, following 1 week of injection of lentivirus carrying basic fibroblast growth factor, the later the intervention time, the more severe the blood vessel damage, and the bigger the aneurysm volume, the lower the smooth muscle 22 aJpha and hypertension-related gene ~ mRNA expression. Simultaneously, platelet-derived growth factor expression decreased. These data suggest that recombinant lentivirus carrying basic fibroblast growth factor can repair damaged cells in the aneurysmal wall and inhibit aneurysm dynamic growth, and that the effect is dependent on therapeutic duration.

食管鳞癌组织中EGFR、KRAS及PIK3CA基因突变的检测及其临床意义分析

目的分析食管鳞癌组织中表皮生长因子受体(EGFR)、Kirsten鼠类肉瘤病毒癌基因(KRAS)和磷脂酰肌醇3激酶(PIK3CA)基因的突变情况及其与患者临床特征的关系。方法选取2006年1月至2012年12月在新疆医科大学第一附属医院确诊的210例食管鳞癌患者的组织标本进行DNA提取和目标位点扩增,再利用一代测序的方法对EGFR18号和21号外显子、KRAS2号外显子、PIK3CA9号外显子进行测序,探讨各基因突变情况及其与临床病理特征的关系,并分析不同基因突变之间的相关性。结果210例食管鳞癌标本中EGFR基因突变率为27.14%,KRAS基因突变率为14.29%,PIK3CA基因突变率为18.59%,EGFR和KRAS双基因联合突变率为4.76%,EGFR和PIK3CA双基因联合突变率为5.71%,EGFR、KRAS、PIK3CA三基因联合突变率为1.43%。EGFR基因突变与性别、肿瘤直径、分化程度具有相关性(P<0.05),KRAS基因突变与肿瘤直径、分化程度、T分期、临床分期具有相关性(P<0.05),PIK3CA基因突变与性别、肿瘤直径、分化程度具有相关性(P<0.05),EGFR和PIK3CA联合突变与性别、肿瘤直径、分化程度具有相关性(P<0.05)。EGFR基因突变与KRAS基因突变具有相关性(P<0.05),而EGFR基因突变与PIK3CA基因突变之间无相关性(P>0.05)。结论食管鳞癌组织中EGFR基因突变率最高,PIK3CA基因突变率次之,KRAS基因突变率最低;EGFR与KRAS或PIK3CA基因突变联合检测具有一定的临床意义。

PDGFRα^(+)细胞上P2Y1-SK3通路对功能性消化不良大鼠胃肠动力的调控机制

目的探究血小板衍生生长因子受体α^(+)(PDGFRα^(+))细胞上P2Y1-小电导Ca^(2+)激活K^(+)(SK3)通道对功能性消化不良(FD)大鼠胃肠动力的影响。方法将30只SD大鼠随机分为空白组、模型组、P2Y1受体抑制剂(MRS2500)组,每组10只。除空白组外,其余两组采用多因素干预法建立FD大鼠模型。造模成功后抑制剂组予以尾静脉注射P2Y1抑制剂MRS2500,其他组不采取干预措施。处理结束后进行行为学和胃肠动力学检测;用BL-420S生物信号系统采集并分析胃肠生物电信息;取胃窦组织评估病理变化;采用免疫印迹、实时荧光定量PCR技术检测各组大鼠胃窦PDGFRα、C-kit(卡介尔间质细胞特异性指标)、P2Y1和SK3的表达情况;采用免疫荧光法检测胃窦PDGFRα和C-kit、P2Y1、SK3的组织表达和共定位情况;用钙检测试剂盒检测胃窦组织中Ca^(2+)含量变化。结果FD模型建立后,大鼠活动度、体重增长速度和进食量都显著降低,胃肠动力减弱,胃窦内PDGFRα、C-kit、P2Y1和SK3表达水平降低。MRS2500干预后,P2Y1受体抑制剂组大鼠较模型组大鼠体重增长率和进食量升高,胃肠动力减弱情况改善,PDGFRα、P2Y1和SK3表达水平进一步降低,C-kit表达水平升高,Ca^(2+)含量降低。PDGFRα与C-kit在胃窦中不存在共表达,而PDGFRα与P2Y1、SK3共表达。结论长期的饮食和情绪失调会刺激肠神经系统释放抑制性神经递质,这一过程通过PDGFRα^(+)细胞上P2Y1受体引起SK3通道的Ca^(2+)敏感性降低,在多因素刺激诱导的FD模型大鼠胃肠动力障碍中起重要作用。

电针通过PLC/IP3通路改善功能性消化不良大鼠胃肠动力障碍

目的确定电针是否调节了血小板衍生生长因子受体α阳性(PDGFRα+)细胞中磷脂酶C(PLC)/肌醇-1,4,5-三磷酸酯(PLC/IP3)通路,从而改善功能性消化不良(FD)胃肠动力障碍。方法将40只SD大鼠随机分为5组:空白组、模型组、电针组、U73122(PLC抑制剂)组、U73122+电针组,每组8只。除空白组外所有大鼠采用多因素应激干预法建立FD大鼠模型。造模成功后,U73122组予以腹腔注射抑制剂,电针组取足三里和太冲穴,U73122+电针组在针刺前2 h注射抑制剂。10 d后行胃肠动力学检测;采用免疫印迹法检测PDGFRα、PLC、P-PLC、IP3的蛋白表达水平;用免疫荧光检测PDGFRα和PLC、IP3的平均荧光密度和共定位表达情况;电子显微镜观察胃窦区域缝隙连接(GJ)情况。结果造模后大鼠胃肠动力减弱,PDGFRα、PLC和IP3的蛋白表达水平显著降低,GJ增宽,细胞形态改变;与模型组比较,电针组、U73122组和U73122+电针组大鼠胃肠动力显著改善,胃窦PDGFRα、PLC、P-PLC、IP3表达水平上升,GJ稍紧密,细胞形态恢复;U73122组和U73122+电针组胃窦PDGFRα、PLC、P-PLC、IP3表达水平无明显差异;PDGFRα与PLC和IP3存在荧光共定位。结论电针通过激活PDGFRα+细胞中的PLC/IP3通路改善FD大鼠的胃肠动力障碍。

厄洛替尼联合贝伐珠单抗一线治疗EGFR敏感突变阳性晚期非小细胞肺癌的临床观察

目的观察厄洛替尼联合贝伐珠单抗一线治疗表皮生长因子受体(EGFR)敏感突变阳性晚期非小细胞肺癌的临床效果。方法采用前瞻性随机对照研究,选择EGFR敏感突变阳性晚期非小细胞肺癌患者作为研究对象。采用随机数字表法将患者分为对照组与观察组,对照组采用厄洛替尼治疗,观察组采用厄洛替尼联合贝伐珠单抗治疗。比较2组患者临床疗效、血清肿瘤标志物水平[癌胚抗原(CEA)、细胞角蛋白21-1片段(CYFRA21-1)、血管内皮生长因子(VEGF)]、免疫功能[白细胞分化抗原3(CD3)、白细胞分化抗原4(CD4)、白细胞分化抗原8(CD8)]以及用药不良反应情况。结果治疗3个月后,观察组患者客观缓解率(ORR)、疾病控制率(DCR)均高于对照组,差异有统计学意义(P<0.05)。治疗后,观察组血清CEA、CYFRA21-1、VEGF水平低于对照组,差异有统计学意义(P<0.05);观察组CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)高于对照组,CD8^(+)低于对照组,差异有统计学意义(P<0.05)。2组患者治疗不良反应发生率比较,差异无统计学意义(P>0.05)。结论厄洛替尼联合贝伐珠单抗一线治疗EGFR敏感突变阳性晚期非小细胞肺癌可以有效提高临床疗效,改善患者免疫功能。

EGFR、Her-2、HIF-1α、p53对进展期食管鳞癌新辅助化疗疗效的预测价值

目的:探讨食管鳞癌相关因子EGFR、Her-2、HIF-1α和p53对进展期食管鳞癌新辅助化疗疗效的预测价值。方法:回顾性分析日照市人民医院2011年1月-2015年1月行紫杉醇联合顺铂方案新辅助化疗的进展期食管鳞癌(Ⅲ期)患者94例,采用免疫组化方法检测食管鳞癌组织中EGFR、Her-2、HIF-1α和p53的表达情况,应用RECIST1.1标准和病理组织学相结合方法行化疗疗效评估,Logistic多因素回归分析各指标与化疗疗效关系。结果:本研究组患者新辅助化疗总有效率为56.38%(53/94),全部为部分缓解。疾病稳定占41.49%(39/94),疾病进展占2.13%(2/94)。新辅助化疗前后各因子表达差异无统计学意义(均P>0.05)。Her-2表达阳性、阴性者化疗有效率分别为81.82%(9/11)、53.01%(44/83),两者比较差异有统计学意义(P=0.01)。p53表达阳性、阴性者化疗有效率分别为31.37%(16/51)、86.05%(37/43),两者差异有统计学意义(P<0.01)。Her-2阳性表达同时p53阴性表达者7例,其中化疗有效5例。EGFR和HIF-1α表达与化疗敏感性无关(P>0.05)。多因素分析显示,Her-2和p53是新辅助化疗的独立影响因素(均P<0.05)。结论:Her-2和p53作为新辅助化疗独立影响因子,可在化疗前对疗效进行预测,可能对患者新辅助化疗选择提供临床依据。

肺泡型细胞内表皮生长因子和转化生长因子α、β_1及其受体基因表达的研究

分离培养成年大鼠的肺泡 型细胞 ,通过斑点杂交、原位杂交和免疫组织化学染色 ,研究肺泡 型细胞内表皮生长因子 (EGF)、转化生长因子 α和 β1 (TGFα、TGFβ1 )及其受体基因的表达。结果显示肺泡 型细胞可表达 EGF、TGFα和TGFβ1 ,也可表达相应的 EGF受体 (EGFR)、TGFβ受体 型和 型 (TβR 、TβR )。表明肺泡 型细胞是合成和分泌 EGF、TGFα和 TGFβ1 的细胞之一 ;细胞凭借其 EGFR、TβR的存在 ,其增殖与分化可能受 EGF、TGFα和 TGFβ1 的旁分泌和自分泌两种途径调控。

VEGFR1阳性造血祖细胞簇与人大肠癌转移的关系

目的观察血管内皮生长因子受体1(VEGFR1)阳性造血祖细胞与人大肠癌转移的关系及机制。方法将人大肠癌细胞株SW480/M5瘤块原位接种至裸鼠结肠,建立大肠癌原位移植肝转移裸鼠模型,应用FCM观察转移灶内VEGFR1阳性造血祖细胞与大肠癌细胞的数量与比例及其相互关系,应用Western blot观察转移相关因子的表达。结果肿瘤转移灶及尚未形成转移的常见部位均可见VEGFR1阳性造血祖细胞细胞簇,并且与肿瘤转移的时间呈正相关,而无肿瘤裸鼠未见此细胞簇形成;在肿瘤转移过程中,基质金属蛋白酶9、基质细胞衍生因子1蛋白表达逐渐增强。结论VEGFR1阳性造血祖细胞簇形成总是伴随大肠癌转移,可能促进转移相关因子表达,促成转移的发生。

雌激素受体α和胰岛素样生长因子1对小鼠前列腺平滑肌细胞增殖的影响

目的:探讨在雌激素对前列腺平滑肌细胞(PSMC)生物学效应中,雌激素受体α(ERα)和胰岛素样生长因子1(IGF1)对细胞增殖的影响。方法:构建pGSadeno-ERα腺病毒载体,体外转染原代培养的小鼠PSMC后,以半定量逆转录PCR和Western印迹分别检测ERαmRNA和蛋白质的表达;成功获取ERα下调细胞后,加入10-8mol/L17β雌二醇,6h后Western印迹检测细胞IGF1的表达;以噻唑蓝比色分析法(MTT法)评价转染后雌激素或外源性IGF1对PSMC的增殖活性。结果:加入17β雌二醇后,正常对照组PSMC增殖明显,IGF1基因表达水平明显增高(P<0.05);而在ERα下调细胞组中,PSMC增殖、IGF1基因表达水平均无明显变化(P>0.05)。外源性IGF1作用于ERα下调的PSMC后,未能激活细胞增殖(P>0.05)。结论:雌激素在对PSMC的生物学效应中,通过ERα的介导刺激产生IGF1,并且IGF1在ERα的共同参与下促进细胞的增殖。

辐射对骨髓间充质干细胞增殖分化及相关基因表达的影响

为观察大鼠局部大剂量辐射后,骨髓间充质干细胞增殖分化及相关基因的表达,以137Csγ射线对大鼠股骨头部位局部照射,吸收剂量为30Gy,剂量率为0.83Gy/min,照后两周取股骨头进行骨髓间充质干细胞(BMSCs)培养,四甲基偶氮唑盐比色法(MTT)绘制生长曲线及进行集落计数,RT-PCR检测Cbf-α1,PPAR-γ,VEGF-a和KDR的表达。骨髓间充质干细胞大剂量辐射后细胞增殖能力明显降低,集落形成数目减少;Cbf-α1,PPAR-γ,VEGF-a和KDR的表达均降低,其中Cbf-α1,PPAR-γ,VEGF-a表达降低幅度分别达18.98%,9.46%和57.34%,与对照组相比差异显著(p<0.05)。故体外大剂量局部辐射明显损伤骨髓间充质干细胞,使其增殖分化及相关基因的表达降低。

EGFR及VEGFR抑制剂联合调强放疗治疗局部晚期EGFR突变阳性非小细胞肺癌的临床研究分析

目的观察表皮生长因子受体(EGFR)及血管内皮生长因子受体(VEGFR)抑制剂联合调强放疗治疗局部晚期EGFR突变阳性非小细胞肺癌(NSCLC)的临床价值。方法 60例局部晚期EGFR突变阳性NSCLC患者,采用随机数字表法分为A组、B组和C组,每组20例。A组患者给予单纯调强放疗, B组患者给予EGFR抑制剂联合调强放疗, C组患者给予EGFR抑制剂、VEGFR抑制剂联合调强放疗。对比三组患者治疗前后肿瘤体积、癌胚抗原(CEA)水平、卡氏功能状态(KPS)评分及临床疗效、毒副反应、消化道反应、放射性肺炎发生情况。结果治疗前,三组肿瘤体积、CEA水平对比差异无统计学意义(P>0.05);治疗后, C组患者肿瘤体积小于A组、B组, CEA水平低于A组、B组,差异有统计学意义(P<0.05)。C组治疗总有效率为85.0%,高于A组的45.0%、B组的55.0%,差异有统计学意义(P<0.05)。A组、B组、C组患者毒副反应发生率分别为20.0%、25.0%、20.0%,比较差异无统计学意义(P>0.05)。C组患者消化道反应发生率为10.0%,低于A组的25.0%、B组的25.0%,但差异无统计学意义(P>0.05)。治疗前,三组患者KPS评分比较差异无统计学意义(P>0.05);治疗后,三组患者KPS评分均高于本组治疗前,且C组高于A组、B组,差异具有统计学意义(P<0.05)。C组患者放射性肺炎发生率为20.0%,低于A组的30.0%、B组的40.0%,但差异无统计学意义(P>0.05)。结论针对局部晚期EGFR突变阳性NSCLC患者行EGFR、VEGFR抑制剂联合调强放疗治疗,对于促进病灶缓解、改善患者生活质量作用显著,且不增加不良反应,值得临床借鉴。

SIP合胞体在小鼠结肠中的分布规律及功能研究

目的探讨平滑肌、Cajal间质细胞(ICC)和血小板衍生生长因子受体α(PDGFRα)阳性细胞合胞体(SIP合胞体)在小鼠结肠中的分布规律及功能。方法选用无特定病原体、10~12周龄C57BL/6J小鼠15只,麻醉处死后取出结肠并分离平滑肌组织。利用免疫组化染色和Western blot法检测小鼠近远端结肠平滑肌组织中c-Kit、钙激活氯通道蛋白1(ANO1)、PDGFRα、钙激活钾通道(SK3)蛋白表达情况,通过电生理学实验观察小鼠近远端结肠移行性复合运动(CMMC)和平滑肌自发性收缩情况。结果在ICC-ANO1-平滑肌通路中,小鼠近端结肠平滑肌组织中c-Kit、ANO1蛋白表达明显高于远端结肠(均P<0.05);电生理实验结果显示,一氧化氮合酶抑制剂L-NAME能明显增加CMMC和平滑肌自发性收缩,ANO1通道阻断剂NPPB对CMMC和平滑肌自发性收缩有明显抑制作用,且以上作用效果在近端结肠更显著。在PDGFRα阳性细胞-SK3-平滑肌通路中,小鼠近端结肠平滑肌组织中PDGFRα、SK3蛋白表达明显低于远端结肠(均P<0.05);SK3激动剂CyPPA可明显抑制远端结肠CMMC和平滑肌自发性收缩,SK3阻断剂apamin能增加CMMC和平滑肌自发性收缩,且以上作用效果在远端结肠更显著。结论ICC主要分布在近端结肠,PDGFRα阳性细胞主要分布在远端结肠,使结肠两端产生压力梯度并将粪便推进肛门。ICC-ANO1-平滑肌通路和PDGFRα阳性细胞-SK3-平滑肌通路保持相对平衡在结肠传输中起重要调节作用。

体外局部大剂量辐射对大鼠骨髓间充质干细胞分化的影响

介绍了30 Gyγ射线局部照射大鼠股骨头部位,观察辐射对骨髓间充质干细胞(BMSCs)分化的影响。辐照2周后取股骨进行骨髓间充质干细胞培养,经细胞诱导液诱导后进行碱性磷酸酶染色,油红O染色,CD31免疫荧光鉴定,同时RT-PCR检测Cbf-α1、PPAR-γ、VEGF-a和KDR的表达。大剂量辐射抑制BMSCs向相关细胞的分化,降低其Cbf-α1、PPAR-γ、VEGF-a和KDR的表达。诱导可促进体外培养BMSCs向成骨细胞、脂肪细胞和血管内皮细胞的分化,照射组Cbf-α1、PPAR-γ、VEGF-a和KDR mRNA水平明显上调,其中PPAR-γ和VEGF-a表达水平接近对照组。体外大剂量辐射抑制BMSCs向成骨细胞、脂肪细胞、内皮细胞分化,给予一定诱导,辐射损伤的BMSCs体外分化能力可以部分恢复,其相关基因的表达恢复明显,但其向成熟成骨细胞、脂肪细胞和内皮细胞分化的数目依然较少。

表皮生长因子受体酪氨酸激酶抑制剂在非小细胞肺癌治疗方面的研究进展

全世界肺癌的发病率不断增加,其中约80%为非小细胞肺癌(non-small cell lung cancer,NSCLC)。多数患者确诊时已失去手术切除机会,针对此类患者的治疗方法匮乏且疗效欠佳。近年来,表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs)为表皮生长因子受体(epidermal growth factor receptor,EGFR)基因敏突变患者带来了巨大的临床获益。随着临床和基础研究的不断深入,EGFR-TKIs越来越受到关注。本文结合相关文献围绕EGFR-TKIs在NSCLC治疗方面的研究进展作一综述。