Artemin及其受体GFRα3在胰腺导管癌组织中的表达及意义

目的 探讨Artemin及其受体GFRα3(glial cell line-derived neurotrophic factor receptor α3)在胰腺导管癌组织中的表达及意义.方法 采用免疫组化、PCR、荧光定量RT-PCR和基因测序等方法检测100例人胰腺导管癌组织标本和40例正常胰腺组织的Artemin、GFRα3表达,分析它们与临床病理学特征,尤其与嗜神经转移的关系.结果 100例标本中64例存在神经转移,转移率为64%.Artemin、GFRα3蛋白在胰腺癌组织中的表达量分别为正常胰腺组织的(2.697±0.231)倍和(2.599±0.588)倍;mRNA的表达量分别为正常胰腺组织的7.01和4.63倍.胰腺癌组织Artemin、GFRα3蛋白表达与肿瘤部位、分化程度、TNM分期、神经侵犯、淋巴结转移相关(P＜0.01),与患者年龄、性别、肿瘤大小均无关.且靠近神经组织的癌细胞Artemin、GFRα3阳性程度高于远离神经组织癌细胞.结论 Artemin、GFRα3参与胰腺癌的发生,两者在胰腺癌组织中的高表达和胰腺癌嗜神经性关系密切.     

TGF-β/Smads信号通路相关蛋白在胰腺上皮内瘤变和胰腺癌组织中的表达

目的探讨转化生长因子(TGF)-β/Smads信号转导通路中Smads相关蛋白、TGF-β1及其Ⅰ、Ⅱ型受体在胰腺上皮内瘤变(PanIN)和胰腺癌组织中表达的意义.方法用EnVision和SP免疫组化技术检测266灶不同级别PanINs和121例胰腺癌组织中Smads相关蛋白、TGF-β1及其Ⅰ、Ⅱ型受体的表达并联系临床病理学指标进行相关分析.结果高级别PanINs病灶Smad4表达率(60.6%,20/33)显著低于低级别PanINs Smad4表达率(79.8%,186/233)(P<0.05);而高级别PanINs中Smad7、TGF-β1、TGF-βRⅡ表达率明显高于低级别PanINs(P<0.05).胰腺癌组织中,Smad4蛋白表达率在淋巴结转移组和神经受累组显著低于各自对照组(P<0.05);Smad7、TGF-β1及其Ⅰ、Ⅱ型受体的表达率在淋巴结转移组和神经受累组则分别显著高于各自对照组(P<0.05).胰腺上皮内瘤变和胰腺癌组织中Smad2、4、7蛋白,TGF-β1及其Ⅰ、Ⅱ型受体表达率的差异具有非常显著性(P<0.01).结论从低级别PanINs到高级别PanINs再到胰腺癌中,Smad4蛋白表达率逐渐降低,而Smad7、TGF-β1及其Ⅰ、Ⅱ型受体表达率逐渐升高,支持胰腺癌形成的分子模型.     

神经生长因子及其受体在人胰腺导管癌组织中的表达

Objective To investigate nerve growth factor (β-NGF) and its receptors expression in human pancreatic ductal adenocarcinoma. Methods Expression and distribution of β-NGF, tyrosine kinase A (TrKA) and P75NGFR were detected in operation tissue specimens of pancreatic ductal adenocarcinoma with immunohistochemistry and real-time PCR. Relations of β-NGF and its receptors with clinicalpathological characters, especially nerve invasion were analyzed. Results β-NGF and TrKA expression are higher in pancreatic adenocarcinoma than normal pancreas, and the differences are significant (P < 0. 01). Β-NGF and TrKA expression are associated with the differentiation grades(DG), lymphatic node metastasis, nerve invasion and surgical pathological stages. Poorer of DG and later stages, more expression of β-NGF and TrKA. Β-NGF and TrKA expression have positive correlations. Β-NGF, TrKA and P75NGFR mRNA expression have significantly increased 3.84,4. 23 and 2. 41 times than normal tissues by real-time PCR, respectively. Conclusions β-NGF and TrKA might play potential rules in carcinogenesis for pancreatic cancer,have affinity with clinicopathological characters of pancreatic cancer. Β-NGF and TrKA may have mutual effect in signal transduction leading to perineural invasion of pancreatic carcinoma.     

神经生长因子及其受体在人胰腺导管癌组织中的表达

Objective To investigate nerve growth factor (β-NGF) and its receptors expression in human pancreatic ductal adenocarcinoma. Methods Expression and distribution of β-NGF, tyrosine kinase A (TrKA) and P75NGFR were detected in operation tissue specimens of pancreatic ductal adenocarcinoma with immunohistochemistry and real-time PCR. Relations of β-NGF and its receptors with clinicalpathological characters, especially nerve invasion were analyzed. Results β-NGF and TrKA expression are higher in pancreatic adenocarcinoma than normal pancreas, and the differences are significant (P < 0. 01). Β-NGF and TrKA expression are associated with the differentiation grades(DG), lymphatic node metastasis, nerve invasion and surgical pathological stages. Poorer of DG and later stages, more expression of β-NGF and TrKA. Β-NGF and TrKA expression have positive correlations. Β-NGF, TrKA and P75NGFR mRNA expression have significantly increased 3.84,4. 23 and 2. 41 times than normal tissues by real-time PCR, respectively. Conclusions β-NGF and TrKA might play potential rules in carcinogenesis for pancreatic cancer,have affinity with clinicopathological characters of pancreatic cancer. Β-NGF and TrKA may have mutual effect in signal transduction leading to perineural invasion of pancreatic carcinoma.     

神经生长因子及其受体在人胰腺导管癌组织中的表达

Objective To investigate nerve growth factor (β-NGF) and its receptors expression in human pancreatic ductal adenocarcinoma. Methods Expression and distribution of β-NGF, tyrosine kinase A (TrKA) and P75NGFR were detected in operation tissue specimens of pancreatic ductal adenocarcinoma with immunohistochemistry and real-time PCR. Relations of β-NGF and its receptors with clinicalpathological characters, especially nerve invasion were analyzed. Results β-NGF and TrKA expression are higher in pancreatic adenocarcinoma than normal pancreas, and the differences are significant (P < 0. 01). Β-NGF and TrKA expression are associated with the differentiation grades(DG), lymphatic node metastasis, nerve invasion and surgical pathological stages. Poorer of DG and later stages, more expression of β-NGF and TrKA. Β-NGF and TrKA expression have positive correlations. Β-NGF, TrKA and P75NGFR mRNA expression have significantly increased 3.84,4. 23 and 2. 41 times than normal tissues by real-time PCR, respectively. Conclusions β-NGF and TrKA might play potential rules in carcinogenesis for pancreatic cancer,have affinity with clinicopathological characters of pancreatic cancer. Β-NGF and TrKA may have mutual effect in signal transduction leading to perineural invasion of pancreatic carcinoma.     

神经生长因子及其受体在人胰腺导管癌组织中的表达

Objective To investigate nerve growth factor (β-NGF) and its receptors expression in human pancreatic ductal adenocarcinoma. Methods Expression and distribution of β-NGF, tyrosine kinase A (TrKA) and P75NGFR were detected in operation tissue specimens of pancreatic ductal adenocarcinoma with immunohistochemistry and real-time PCR. Relations of β-NGF and its receptors with clinicalpathological characters, especially nerve invasion were analyzed. Results β-NGF and TrKA expression are higher in pancreatic adenocarcinoma than normal pancreas, and the differences are significant (P < 0. 01). Β-NGF and TrKA expression are associated with the differentiation grades(DG), lymphatic node metastasis, nerve invasion and surgical pathological stages. Poorer of DG and later stages, more expression of β-NGF and TrKA. Β-NGF and TrKA expression have positive correlations. Β-NGF, TrKA and P75NGFR mRNA expression have significantly increased 3.84,4. 23 and 2. 41 times than normal tissues by real-time PCR, respectively. Conclusions β-NGF and TrKA might play potential rules in carcinogenesis for pancreatic cancer,have affinity with clinicopathological characters of pancreatic cancer. Β-NGF and TrKA may have mutual effect in signal transduction leading to perineural invasion of pancreatic carcinoma.     

神经生长因子及其受体在人胰腺导管癌组织中的表达

Objective To investigate nerve growth factor (β-NGF) and its receptors expression in human pancreatic ductal adenocarcinoma. Methods Expression and distribution of β-NGF, tyrosine kinase A (TrKA) and P75NGFR were detected in operation tissue specimens of pancreatic ductal adenocarcinoma with immunohistochemistry and real-time PCR. Relations of β-NGF and its receptors with clinicalpathological characters, especially nerve invasion were analyzed. Results β-NGF and TrKA expression are higher in pancreatic adenocarcinoma than normal pancreas, and the differences are significant (P < 0. 01). Β-NGF and TrKA expression are associated with the differentiation grades(DG), lymphatic node metastasis, nerve invasion and surgical pathological stages. Poorer of DG and later stages, more expression of β-NGF and TrKA. Β-NGF and TrKA expression have positive correlations. Β-NGF, TrKA and P75NGFR mRNA expression have significantly increased 3.84,4. 23 and 2. 41 times than normal tissues by real-time PCR, respectively. Conclusions β-NGF and TrKA might play potential rules in carcinogenesis for pancreatic cancer,have affinity with clinicopathological characters of pancreatic cancer. Β-NGF and TrKA may have mutual effect in signal transduction leading to perineural invasion of pancreatic carcinoma.     

神经生长因子及其受体在人胰腺导管癌组织中的表达

Objective To investigate nerve growth factor (β-NGF) and its receptors expression in human pancreatic ductal adenocarcinoma. Methods Expression and distribution of β-NGF, tyrosine kinase A (TrKA) and P75NGFR were detected in operation tissue specimens of pancreatic ductal adenocarcinoma with immunohistochemistry and real-time PCR. Relations of β-NGF and its receptors with clinicalpathological characters, especially nerve invasion were analyzed. Results β-NGF and TrKA expression are higher in pancreatic adenocarcinoma than normal pancreas, and the differences are significant (P < 0. 01). Β-NGF and TrKA expression are associated with the differentiation grades(DG), lymphatic node metastasis, nerve invasion and surgical pathological stages. Poorer of DG and later stages, more expression of β-NGF and TrKA. Β-NGF and TrKA expression have positive correlations. Β-NGF, TrKA and P75NGFR mRNA expression have significantly increased 3.84,4. 23 and 2. 41 times than normal tissues by real-time PCR, respectively. Conclusions β-NGF and TrKA might play potential rules in carcinogenesis for pancreatic cancer,have affinity with clinicopathological characters of pancreatic cancer. Β-NGF and TrKA may have mutual effect in signal transduction leading to perineural invasion of pancreatic carcinoma.     

神经生长因子及其受体在人胰腺导管癌组织中的表达

Objective To investigate nerve growth factor (β-NGF) and its receptors expression in human pancreatic ductal adenocarcinoma. Methods Expression and distribution of β-NGF, tyrosine kinase A (TrKA) and P75NGFR were detected in operation tissue specimens of pancreatic ductal adenocarcinoma with immunohistochemistry and real-time PCR. Relations of β-NGF and its receptors with clinicalpathological characters, especially nerve invasion were analyzed. Results β-NGF and TrKA expression are higher in pancreatic adenocarcinoma than normal pancreas, and the differences are significant (P < 0. 01). Β-NGF and TrKA expression are associated with the differentiation grades(DG), lymphatic node metastasis, nerve invasion and surgical pathological stages. Poorer of DG and later stages, more expression of β-NGF and TrKA. Β-NGF and TrKA expression have positive correlations. Β-NGF, TrKA and P75NGFR mRNA expression have significantly increased 3.84,4. 23 and 2. 41 times than normal tissues by real-time PCR, respectively. Conclusions β-NGF and TrKA might play potential rules in carcinogenesis for pancreatic cancer,have affinity with clinicopathological characters of pancreatic cancer. Β-NGF and TrKA may have mutual effect in signal transduction leading to perineural invasion of pancreatic carcinoma.     

神经生长因子及其受体在人胰腺导管癌组织中的表达

Objective To investigate nerve growth factor (β-NGF) and its receptors expression in human pancreatic ductal adenocarcinoma. Methods Expression and distribution of β-NGF, tyrosine kinase A (TrKA) and P75NGFR were detected in operation tissue specimens of pancreatic ductal adenocarcinoma with immunohistochemistry and real-time PCR. Relations of β-NGF and its receptors with clinicalpathological characters, especially nerve invasion were analyzed. Results β-NGF and TrKA expression are higher in pancreatic adenocarcinoma than normal pancreas, and the differences are significant (P < 0. 01). Β-NGF and TrKA expression are associated with the differentiation grades(DG), lymphatic node metastasis, nerve invasion and surgical pathological stages. Poorer of DG and later stages, more expression of β-NGF and TrKA. Β-NGF and TrKA expression have positive correlations. Β-NGF, TrKA and P75NGFR mRNA expression have significantly increased 3.84,4. 23 and 2. 41 times than normal tissues by real-time PCR, respectively. Conclusions β-NGF and TrKA might play potential rules in carcinogenesis for pancreatic cancer,have affinity with clinicopathological characters of pancreatic cancer. Β-NGF and TrKA may have mutual effect in signal transduction leading to perineural invasion of pancreatic carcinoma.     

脑源性神经营养因子在胰腺导管腺癌中的表达及其临床意义

目的 探讨脑源性神经营养因子（BDNF）在胰腺导管腺癌中的表达及其临床意义.方法 采用免疫组化SP法检测46例胰腺导管腺癌、38例胰腺良性疾病及20例正常胰腺组织中的BDNF表达,应用蛋白质印迹法和RT-PCR法检测BDNF蛋白及mRNA表达量,并分析BDNF表达与胰腺导管腺癌临床病理参数的相关性.结果 胰腺导管腺癌组织中BDNF阳性表达率为52.2％ （24/46）,胰腺良性疾病组织为7.8％ （3/38）,而正常胰腺组织未见BDNF阳性表达.正常胰腺、胰腺良性疾病、胰腺癌组织中BDNF蛋白表达量分别为0.38±0.01、0.56±0.01、0.97±0.01,mRNA表达量分别为0.85±0.14、1.67±0.21、3.45±0.67,胰腺癌和胰腺良性疾病的表达量均显著高于正常胰腺,胰腺癌又显著高于胰腺良性疾病,差异均具有统计学意义（P值均＜0.01）.BDNF阳性表达与胰腺导管腺癌的神经浸润、淋巴结转移存在相关性（P值均＜0.05）,而与患者性别、年龄及肿瘤大小、部位、分化程度等无相关性.结论 BDNF参与胰腺癌的发生、发展,并可能与胰腺癌患者预后有关.     

胰腺癌513例神经浸润的病理分析

目的 探讨胰腺癌神经浸润的特征及其与其他临床病理参数之间的关系.方法 光镜下观察491例胰腺导管腺癌、22例其他胰腺恶性肿瘤、41例胰腺良性病变和21例慢性胰腺炎组织中的神经浸润状况,分析其与其他病理学指标的相关性.结果 胰腺导管腺癌的神经浸润率为74%,显著高于其他类型恶性肿瘤的23%(P＜0.01).导管腺癌癌细胞通常穿越外周神经中膜到达内部的神经纤维束,有的甚至横断整根神经纤维.但神经浸润与导管腺癌的分化程度无关.52%的胰腺导管腺癌癌旁组织呈慢性炎症改变,且程度严重,远高于其他类型胰腺癌(14%)及胰腺良性病变(15%)的慢性炎症发生率(P＜0.01).胰腺导管腺癌淋巴细胞浸润神经的发生率为65%,远高于其他恶性肿瘤的36%和胰腺良性病变的22%(P＜0.01).胰腺导管腺癌的神经浸润与癌旁慢性胰腺炎症以及淋巴细胞浸润神经均相关,但与淋巴结转移无关.结论 神经浸润是胰腺导管腺癌特征性的生物学行为之一.     

miR-551b-3p在胰腺癌细胞和组织中的表达及其临床意义

目的研究miR-551b-3p在胰腺癌细胞和组织中的表达,探讨其在胰腺癌发生发展中的临床意义。方法利用实时定量聚合酶链反应(RT-PCR)技术分别检测4种胰腺癌细胞和正常胰腺导管上皮细胞,以及76对胰腺癌组织和癌旁组织中miR-551b-3p的表达水平,并对miR-551b-3p的表达与胰腺癌患者临床病理学特征进行分析。结果 miR-551b-3p在PANC-1、Aspc-1、SW1990和Miapaca-2四种胰腺癌细胞中的相对表达量分别为(0.125±0.012)、(0.179±0.005)、(0.672±0.025)、(0.577±0.019),低于其在正常胰腺导管上皮细胞HPDE6C-7中的相对表达量,差异有统计学意义(P0.05)。在胰腺癌组织和癌旁组织中miR-551b-3p的ΔCt值分别为(7.254±0.112)和(3.993±0.098),差异有统计学意义(P0.001)。TNM分期Ⅰ、Ⅱ、Ⅲ和Ⅳ期胰腺癌组织中miR-551b-3p的ΔCt值分别为(4.343±0.032)、(5.325±0.112)、(6.987±0.098)和(9.132±0.212),差异有统计学意义(P0.001)。有淋巴结转移和无淋巴结转移患者的胰腺癌组织中miR-551b-3p的ΔCt值分别为(8.492±0.021)和(6.676±0.103),差异有统计学意义(P=0.012)。高、中、低分化胰腺癌组织中miR-551b-3p的ΔCt值分别为(5.349±0.092)、(6.129±0.112)、(8.454±0.065),差异有统计学意义(P=0.002)。结论 miR-551b-3p的表达与胰腺癌的分化程度、淋巴结转移以及TNM分期相关。miR-551b-3p可能是提示胰腺癌临床进展的潜在标志物。     

Relationship between autophagy and perineural invasion,clinicopathological features,and prognosis in pancreatic cancer

AIM To investigate the relationship between autophagy and perineural invasion(PNI), clinical features, and prognosis in patients with pancreatic cancer. METHODS Clinical and pathological data were retrospectively collected from 109 patients with pancreatic ductal adenocarcinoma who underwent radical resection at the First Affiliated Hospital of Zhengzhou University from January 2011 to August 2016. Expression levels of the autophagy-related protein microtubuleassociated protein 1 A/1 B-light chain 3(LC3) and PNI marker ubiquitin carboxy-terminal hydrolase(UCH) in pancreatic cancer tissues were detected by immunohistochemistry. The correlations among LC3 expression, PNI, and clinical pathological features in pancreatic cancer were analyzed. The patients were followed for further survival analysis. RESULTS In 109 cases of pancreatic cancer, 68.8%(75/109) had evidence of PNI and 61.5%(67/109) had high LC3 expression. PNI was associated with lymph node metastasis, pancreatitis, and CA19-9 levels(P 0.05). LC3 expression was related to lymph node metastasis(P 0.05) and was positively correlated with neural invasion(P 0.05, r = 0.227). Multivariate logistic regression analysis indicated that LC3 expression, lymph node metastasis, pancreatitis, and CA19-9 level were factors that influenced neural invasion, whereas only neural invasion itself was an independent factor for high LC3 expression. Univariate analysis showed that LC3 expression, neural invasion, and CA19-9 level were related to the overall survival of pancreatic cancer patients(P 0.05). Multivariate COX regression analysis indicated that PNI and LC3 expression were independent risk factors for poor prognosis in pancreatic cancer(P 0.05). CONCLUSION PNI in patients with pancreatic cancer is positively related to autophagy. Neural invasion and LC3 expression are independent risk factors for pancreatic cancer with a poor prognosis.     

Role of nerve growth factor and its receptor in the morphogenesis of neural tube in early chick embryo

Expression of p75 nerve growth factor receptor (p75(NTR)) in the early neurogenesis of chick embryo showed that nerve growth factor receptor (NGFR) is localized in presumptive neuroectoblast and endoblast in the chick gastrula but not in the mesoblast. By stages 9, 10, and 11, NGFR positive cells were located distinctly in the region where the neural folds converge, meet and fuse. NGFR expression was also seen in developing notochord and somites, wherein the reaction was localized on the cell surfaces. Strong p75(NTR) reaction was seen on the roof of the neural tube where it detaches from the head ectoderm by stage 12. The study revealed that p75(NTR) is co-expressed with NGF in the same developmental stage(s) and in areas, where cell death occurs during neuronal development. Further, when the endogenous levels of NGF signaling were blocked by anti-NGF antibody, abnormalities were observed at the anterior end of the neural tube formation. As a result, embryos showed open neural tubes and a few were bent on one side of the body axis. In a small proportion of embryos, diffused somites were observed. The findings supports and confirms our previous study that NGF signaling plays a significant role in the shaping of neural tube in chick embryos through p75(NTR)-NGF receptor.     

Lumican蛋白在胰腺导管腺癌间质中的表达及其与Ki-67、VEGF及突变型P53表达的相关性

目的:观察细胞外基质蛋白Lumican在胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDA)中表达特征,分析Lumican与Ki-67、VEGF、突变型P53等肿瘤恶性表型相关分子的关联.方法:采用免疫组织化学染色(IHC)和逆转录-聚合酶链式反应(RT-PCR)检测PDA原发灶及对应癌旁胰腺组织中Lumican表达.IHC检测PDA原发灶Ki-67、VEGF及突变型P53表达.用SPSS软件行统计学分析.结果:PDA原发灶中,Lumican表达在mRNA及蛋白质水平均明显高于癌旁胰腺组织.就该蛋白在癌灶中的分布特性而言,Lumican蛋白主要定位于癌间质,阳性表达率为83.0%(83/100).低分化PDA中,癌间质过表达Lumican与TNM分期相关(x2=6.446,P<0.05),与年龄、性别、淋巴结转移、远处转移等无明显相关.高中分化PDA中,癌间质过表达Lumican与临床病理特征无关,而与Ki-67(r=-0.28,P=0.017)、VEGF(r=-0.264,P=0.025)及突变型P53(r=-0.253,P=0.032)表达呈明显负相关.结论:Lumican在PDA原发灶中表达高于癌旁胰腺组织,主要分布于癌间质.Lumican在癌间质过表达与低分化PDA的TNM分期相关,与高、中分化PDA的Ki-67、VEGF及突变型P53表达呈负相关.     

Nodal involvement is strongest predictor of poor survival in patients with invasive adenocarcinoma of the head of the pancreas

BACKGROUND/AIMS: Pancreatic cancer is a devastating disease with an extremely poor prognosis. The outcome of pancreatic head cancer after surgical resection is still difficult to predict. METHODOLOGY: Between September 1992 and December 2003, 100 consecutive patients with invasive adenocarcinoma of the head of the pancreas who underwent surgical resection were retrospectively analyzed to clarify the influence of clinicopathological factors. RESULTS: The overall 1-, 3-, and 5-year survival rates for the 100 patients with pancreatic head cancer were 55%, 16%, and 6%, respectively. Among the 16 clinicopathologic factors, 9 were significantly associated with outcome in univariate analysis: tumor type (invasive ductal cancer), poor histological differentiation, extrapancreatic plexus invasion, bile duct invasion, duodenal invasion, intrapancreatic nerve invasion, lymphatic invasion, venous invasion, and nodal involvement. Multivariate analysis confirmed that nodal involvement (p = 0.005) and extrapancreatic plexus invasion (p = 0.03) were significant independent factors for overall survival. CONCLUSIONS: Nodal involvement was the strongest predictor of poor survival after pancreatic resection for invasive adenocarcinoma of the head of the pancreas.