β-葡萄糖醛酸酶在胰腺癌患者血清及组织中活性变化的临床意义

目的 联合检测胰腺癌患者血清及组织中β-葡萄糖醛酸酶(β-G)水平,分析其活性变化的临床意义.方法 选择行手术治疗的40例胰腺癌患者作为实验组,同期健康体检者作为对照组,采用酶联免疫吸附法检测外周血清中β-G的水平,免疫组织化学法检测入组患者的胰腺癌组织及癌旁组织中β-G的阳性细胞百分率及阳性表达程度.结果 实验组手术前血清β-G水平为(16.59±1.69) ng/ml,出院前为(9.23±1.21) ng/ml,较治疗前明显降低,但高于对照组,差异有统计学意义(P＜0.05);胰腺癌组织中β-G阳性细胞百分率为(62.5±4.1)％,明显高于癌旁组织,差异有统计学意义(P ＜0.05);12例淋巴结转移者胰腺癌组织β-G阳性细胞百分率与无淋巴结转移者比较无显著差异(P＞0.05);中低分化腺癌β-G阳性表达率高达85％,明显高于高分化腺癌,差异有统计学意义(P＜0.05).结论 胰腺癌患者血清及组织中β-G水平升高,且肿瘤分化程度越低,其表达强度越强,与是否出现淋巴结转移无关.     

胰腺癌患者血清转化生长因子-α水平检测及手术前后对比研究

目的研究转化生长因子-α(TGF-α)在胰腺癌患者血清中的表达水平,探讨其与胰腺癌临床病理特征与预后的关系。方法应用放射免疫分析法(RIA法)检测65例胰腺癌患者的血清TGF-α水平,以30例正常人作为对照,并比较35例胰腺癌患者手术前后血清TGF-α水平。结果血清TGF-α与临床分期、细胞分化程度有关;与胰腺癌患者性别、年龄无关。胰腺癌患者血清TGF-α水平明显高于正常对照组(P<0.01);Ⅳ期胰腺癌血清TGF-α明显高于其它各期(P<0.01),Ⅲ期明显高于Ⅱ期(P<0.05),Ⅱ期明显高于Ⅰ期(P<0.01),低分化导管腺癌患者血清TGF-α水平显著高于中、高分化导管腺癌患者(P<0.05);胰腺癌患者根治性切除术后血清TGF-α水平明显低于术前(P<0.01)。结论检测血清TGF-α对评价胰腺癌疗效、病情监测及预后判断有一定的价值。     

胰腺癌患者血清可溶性Apo-1/Fas水平变化及其临床意义

目的探讨胰腺癌患者血清可溶性Apo1/Fas(sApo1/Fas)水平的变化,以及化疗对血清sApo1/Fas的影响。方法采用酶联免疫吸附试验(ELISA)检测并比较58例胰腺癌患者和30例正常人的血清sApo1/Fas水平,比较48例胰腺癌患者化疗前后血清sApo1/Fas水平。结果胰腺癌患者血清sApo1/Fas为(8.37±1.49)ng/L,明显高于正常对照组(P<0.01)。胰腺癌患者血清sApo1/Fas水平与临床分期有关,Ⅳ期胰腺癌血清sApo1/Fas水平明显高于其他各期(P<0.01),Ⅲ期明显高于Ⅱ期(P<0.01);与胰腺癌患者的性别、年龄、病理类型无关。近期有效(完全缓解和部分缓解)的患者化疗前后血清sApo1/Fas分别为(8.07±1.54)ng/L和(7.39±1.49)ng/L,化疗后血清sApo1/Fas水平低于化疗前(P<0.01)。结论血清sApo1/Fas水平可能与胰腺癌的病情发展有关,血清sApo1/Fas检测对胰腺癌的疗效观察、病情监测及预后判断有重要的参考意义。     

Rap1GAP1在人胰腺癌组织中的表达及意义

目的通过检测Rap1GAP1在人胰腺癌中的表达情况及rap1GAP1在三种人胰腺癌细胞系中的突变情况,探讨其在人胰腺癌发生发展过程中的作用。方法(1)采用免疫组织化学Envision两步法,检测73例人胰腺癌组织及其癌旁胰腺组织中Rap1GAP1的表达情况,并分析其与胰腺癌临床病理特征之间的关系;(2)采用RT-PCR和测序法检测三种人胰腺癌细胞系中rap1GAP1的突变情况。结果(1)Rap1GAP1在癌旁胰腺组织、胰腺上皮内肿瘤(pancreatic intraepithelialneoplasia,PanIN)1a、1b、2及3级和浸润性胰腺癌中的阳性率分别为100%、93.8%、92.3%、70.0%、57.9%和13.7%。癌旁胰腺组织、各级PanIN与浸润性癌之间的表达差异有统计学意义(P<0.01);Rap1GAP1在高、中和低分化胰腺癌中阳性率分别为26.9%、7.1%和0,显示Rap1GAP1的表达与胰腺癌的分化程度有关(P<0.05)。而Rap1GAP1的表达与患者的年龄、性别、淋巴结转移情况和临床分期无关。(2)Panc-1、MiaPaCa-2细胞系中存在rap1GAP1关键区域(催化结构域)的大片段缺失,而Aspc-1细胞系含有完整的编码rap1GAP催化结构域的外显子。结论相比于癌旁胰腺组织和各级PanIN,浸润性胰腺癌中 Rap1GAP1的表达显著降低。另外,Rap1GAP1在低分化胰腺癌中的表达显著降低。提示Rap1GAP1可能是胰腺癌发生发展过程中的一个晚期事件。三种人胰腺癌细胞系中的突变分析结果提示其表达降低可能与遗传学上的大片段缺失有关。     

EB病毒LMP1与E-cadherin、ICAM-1在鼻咽癌组织中的表达及其相关性

 目的研究EB病毒潜伏膜蛋白1(LMP1)对鼻咽癌细胞黏附分子E-cadherin和ICAM-1表达的影响,探讨LMP1在鼻咽癌转移中的作用及其相关的机制。方法应用免疫组织化学(SP法)分别检测LMP1、E-cadherin和ICAM-1蛋白在31例鼻咽粘膜慢性炎、32例鼻咽癌和24例鼻咽癌颈部淋巴结转移灶中的表达。结果LMP1和ICAM-1蛋白在鼻咽癌和鼻咽癌淋巴结转移灶中的阳性表达率显著高于在鼻咽粘膜慢性炎组织中的阳性表达率,E-cadherin蛋白在鼻咽癌和鼻咽癌淋巴结转移灶中的阳性表达率则显著低于在鼻咽粘膜慢性炎组织中的阳性表达率。Spearman相关分析显示,在鼻咽癌组织和鼻咽癌淋巴结转移灶中,LMP1与E-cadherin的表达呈负相关,而与ICAM-1的表达呈正相关。结论在鼻咽癌和鼻咽癌颈部淋巴结转移灶中LMP1可能通过抑制E-cadherin的表达和促进ICAM-1的表达进而影响肿瘤细胞的黏附性,促进鼻咽癌的侵袭和转移。     

Neuropilin-1 在胰腺癌组织及细胞系中的表达

 目的 了解Neuropilin-1在胰腺癌组织、癌旁组织及胰腺癌细胞系中的表达情况。方法 运用免疫组化法和RT-PCR法分别检测Neuropilin-1及其mRNA在胰腺癌组织、癌旁组织及细胞系中的表达。结果 免疫组化检测发现18例胰腺癌组织标本中Neuropilin-1均呈高表达，而癌旁组织中无一例表达；RT-PCR检测rnRNA的表达结果显示14例胰腺癌组织中有9例表达，癌旁组织中无一例表达，Panc-1、Asps-1、Bxp-3细胞系中均表达。结论 Neuropilin-1表达于大多数胰腺癌组织及细胞系中，而在癌旁组织中不表达，提示Neuropilin-1的表达可能与胰腺癌的发生发展密切相关。     

ICAM-1在人脑胶质瘤的表达及临床意义

目的 探讨ICAM-1在人脑胶质瘤的表达及临床意义.方法 采用免疫组织化学法检测胶质瘤组织中ICAM-1的表达情况.结果 82例人脑胶质瘤腊块组织中全部呈ICAM-1阳性表达,阳性率100%.实验对照为脑外伤手术减压的脑组织11例,未见ICAM-1表达.胶质瘤高度恶性组ICAM-1阳性表达强度高于低度恶性组,差异有显著性(P<0.01).ICAM-1表达与胶质瘤各病理类型无明显相关(P>0.05).结论 ICAM-1可能在胶质瘤的发生、发展及恶性变中发挥着一定的作用,并有助于胶质瘤恶性度分级及预后判断.     

食管鳞癌中ICAM-1蛋白的表达及意义

目的 研究细胞间粘附分子-1(ICAM-1)在食管鳞癌组织中的表达及意义.方法 采用免疫组织化学S-P法检测49例食管鳞癌组织及38例正常食管黏膜组织中ICAM-1蛋白的表达.结果 食管鳞癌组织中ICAM-1蛋白表达率为46.9%(23/49),显著高于其在正常食管黏膜组织中的表达0.0%(0/38);ICAM-1蛋白表达率在有淋巴结转移组明显高于无淋巴结转移组;其表达率随癌组织浸润深度的加深而增加;在不同分化程度的癌组织中其阳性率也有一定差异,Ⅰ级与Ⅱ、Ⅲ级之间差异有统计学意义(P＜0.05).结论 ICAM-1在食管鳞癌的发生发展中起重要作用,与肿瘤的浸润转移密切相关.     

肝细胞癌VEGF、uPA和ICAM-1蛋白的表达及意义

转移和复发是肝癌患者术后主要的死亡原因 ,也是影响患者长期存活和治疗效果的主要障碍。我们通过检测血管内皮生长因子 (VEGF)、尿激酶型纤溶酶原激活物 (uPA)、细胞间黏附分子 1(ICAM 1)蛋白及增殖细胞核抗原 (PCNA)在肝癌中的表达 ,探讨与肝癌转移、复发有关的分子生物学机制。一、材料与方法1.组织标本 :12 3例选自同济医院病理科保存的肝外科中心 1998年 1月～ 1999年 12月肝癌患者手术标本。其中 ,临床无转移肝癌 (A组 ) 4 2例 ,肝内转移肝癌 (B组 ) 5 0例 ,伴门静脉主干癌栓肝癌 31例 (门静脉癌栓原发灶标本为C组 ,癌栓标本…     

Serum levels of E-selectin, ICAM-1 and VCAM-1 in colorectal cancer patients: correlations with clinicopathological features, patient survival and tumour surgery

The serum concentrations of the cell adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 63 patients with colorectal cancer and in 51 controls by an enzyme-linked immunosorbent assay (ELISA). Their relationship to clinicopathological variables and patient survival and changes in their levels after surgery were examined. Colorectal cancer patients showed significantly higher serum levels of E-selectin, ICAM-1 and VCAM-1 compared with healthy controls. There was a significant association between the serum levels of these molecules, disease stage and the presence of both lymph node and distant metastases. Both ICAM-1 and VCAM-1 levels correlated with serum E-selectin and carcinoembryonic antigen (CEA) levels. Serum levels of all three molecules decreased significantly after radical resection of the tumour. Elevated pre-operative E-selectin, ICAM-1 and VCAM-1 levels were significant prognostic factors, although not independent of stage, for patient survival. These findings suggest that serum concentrations of E-selectin, ICAM-1 and VCAM-1 may reflect tumour progression and metastasis. Since these markers are linked to CEA levels, it is uncertain whether their measurement will prove cost-effective in colorectal cancer management.     

血清细胞间黏附分子-1 在胰腺癌诊断和预后评估中的价值

[摘要] 目的：探讨血清细胞间黏附分子-1（intercellular adhesion molecule-1,ICAM-1）在胰腺癌诊断和预后评估中的价值。方法：选取2015 年4 月至2017 年12 月在湖北省肿瘤医院肝胆胰外科就诊的胰腺癌患者80 例（胰腺癌组）、胰腺良性疾病患者40例（良性疾病组）及同期健康体检者30 例（对照组）。分别检测3 组人群血清ICAM-1 和CA19-9 水平;采用受试者工作特征曲线（ROC）分析ICAM-1 对胰腺癌的诊断特性,采用COX回归模型分析血清ICAM-1 与胰腺癌患者预后是否独立相关。结果：胰腺癌组ICAM-1 和CA19-9 水平明显高于良性疾病组和对照组（均P<0.01）,良性疾病组CA19-9 水平明显高于对照组（P<0.01）。血清ICAM-1、CA19-9 以及两者联合的曲线下面积（AUC）为0.732（95%CI：0.658~0.807,P=0.000）、0.691（95%CI:0.620~0.762, P=0.000）、0.747（95%CI ：0.674~0.821,P=0.000）;ICAM-1与CA19-9之间呈显著正相关（r=0.472,P=0.000）。血清ICAM-1<2 308 U/ml患者的生存时间明显长于≥2 308 U/ml 的患者（χ2=28.357,P=0.000）;ICAM-17≥2 308 U/ml 是患者预后的独立影响因子,其OR为3.08（2.14~7.23）。结论：血清ICAM-1 有助于胰腺癌的早期诊断和预后评估。     

血清MMP-9和ICAM-1水平对非小细胞肺癌骨转移诊断和预后的意义

目的 探讨基质金属蛋白酶-9 (MMP-9）和细胞间粘附分子-1 (ICAM-l）在非小细胞肺癌（NSCLC）伴骨转移患者血清中的表达及其对预后的意义。方法 用ELISA 方法检测10 例健康对照者和70 例初治NSCLC 患者空腹血MMP-9 和ICAM-1 的表达,其中40 例NSCLC 患者伴骨转移Ⅳ期,30 例I ～Ⅱ期。结果 伴骨转移Ⅳ期NSCLC 患者血清MMP-9、ICAM-1 水平高于I～Ⅱ期NSCLC 患者,且两者均高于健康对照者。血清MMP-9、ICAM-1 水平与Ⅳ期伴骨转移患者的中位生存期显著相关,且血清MMP-9 水平可作为Ⅳ期伴骨转移NSCLC 的独立预后因素。结论 MMP-9和ICAM -1 均伴随NSCLC的发生发展以及疾病的进展而升高,对MMP-9 和ICAM-1表达的分析有助于评估Ⅳ期伴骨转移NSCLC 患者的预后,同时积极针对患者转移灶的治疗可以明显延长Ⅳ期伴骨转移NSCLC 患者生存期。     

胰腺癌患者氩氦刀冷冻消融治疗前后CA242、CA199、CA125、CEA、TSGF的变化及临床意义

目的 探讨胰腺癌患者氩氦刀冷冻消融治疗前后血清糖类抗原242(CA242)、糖类抗原199(CA199)、糖类抗原125(CA125)、癌胚抗原(CEA)及恶性肿瘤特异生长因子(TSGF)水平变化及临床意义.方法 测定30例胰腺癌患者氩氦刀冷冻消融治疗前后及15例正常对照的血清CA242、CA199、CA125、CEA及TSGF的水平,并分析其与临床病理参数的相关性.结果 胰腺癌患者冷冻前后所有标志物的血清水平及阳性率均明显高于对照组(P<0.05),冷冻后CA199、CA125及CEA血清水平均明显下降(P<0.05),冷冻后CA199,CEA及TSGF的阳性检出率均明显降低(P<0.05).CEA血清水平与患者性别相关(P<0.05),CA242水平与肿瘤大小及临床分期均相关(P<0.05),CA199、CA125、CEA水平与患者年龄、肿瘤大小、临床分期、分化程度、淋巴结转移及肝转移均相关(P<0.05),而血清TSGF水平与所有的病理参数均无关( P>0.05).结论 CA199、CA125、CEA血清水平可作为胰腺癌疗效评估的重要指标,CA242、CA199、CA125及CEA在胰腺癌的预后评估中发挥重要的作用.     

胰腺癌患者氩氦刀冷冻消融治疗前后CA242、CA199、CA125、CEA、TSGF的变化及临床意义

目的：探讨胰腺癌患者氩氦刀冷冻消融治疗前后血清糖类抗原242（CA242）、糖类抗原199（CA199）、糖类抗原125（CA125）、癌胚抗原（CEA）及恶性肿瘤特异生长因子（TSGF）水平变化及临床意义。方法：测定30例胰腺癌患者氩氦刀冷冻消融治疗前后及15例正常对照的血清CA242、CA199、CA125、CEA及TSGF的水平,并分析其与临床病理参数的相关性。结果：胰腺癌患者冷冻前后所有标志物的血清水平及阳性率均明显高于对照组（P〈0.05）,冷冻后CA199、CA125及CEA血清水平均明显下降（P〈0.05）,冷冻后CA199,CEA及TSGF的阳性检出率均明显降低（P〈0.05）。CEA血清水平与患者性别相关（P〈0.05）,CA242水平与肿瘤大小及临床分期均相关（P〈0.05）,CA199、CA125、CEA水平与患者年龄、肿瘤大小、临床分期、分化程度、淋巴结转移及肝转移均相关（P〈0.05）,而血清TSGF水平与所有的病理参数均无关（P〉0.05）。结论：CA199、CA125、CEA血清水平可作为胰腺癌疗效评估的重要指标,CA242、CA199、CA125及CEA在胰腺癌的预后评估中发挥重要的作用。     

胰腺癌患者血清巨噬细胞抑制因子1的临床价值研究

目的 分析巨噬细胞抑制因子-1(MIC-1)在胰腺癌患者血清中浓度及其临床价值.方法 采用双抗体夹心ELISA法检测150例胰腺癌和胰腺良性疾病患者及120例正常对照人群血清MIC-1浓度,采用电化学发光免疫分析仪和全自动生化分析仪检测上述血清CA 199和胆红素浓度.结果 胰腺癌组MIC-1浓度显著高于胰腺良性疾病组...     

胰腺癌患者血清中巨噬细胞抑制因子-1的大样本临床研究

目的 探讨巨噬细胞抑制因子1(MIC-1)在胰腺癌诊断、早期诊断及治疗监测中的临床价值.方法 应用自主研制的MIC-1检测试剂盒检测552例不同临床分期的胰腺癌患者、115例胰腺良性肿瘤患者、21例慢性胰腺炎及200例健康人血清样本中MIC-1水平,并对部分早期肿瘤患者的病程进行随访监测;应用罗氏Cobas 601电化...     

Phase 1 clinical trials in 83 patients with pancreatic cancer

BACKGROUND:

The outcomes of patients with pancreatic cancer treated on early phase clinical trials have not been systematically analyzed. The purpose of this study was to report the presenting characteristics and outcomes of patients with locally advanced or metastatic pancreatic cancer treated on phase 1 clinical trials at a single institution.

METHODS:

The authors reviewed the records of consecutive patients with metastatic pancreatic cancer who were treated in the Phase I Clinical Trials Program at The University of Texas M. D. Anderson Cancer Center from November 2004 to March 2009. Data recorded and analyzed included survival, response, and disease characteristics.

RESULTS:

Eighty‐three patients were identified. The median age was 62 years (range, 39‐81 years). Of 78 patients evaluable for response, 2 (3%) had a partial response (PR), and 10 (13%) had stable disease (SD) for ≥4 months. With a median follow‐up for survivors of 3.7 months, the median survival from presentation in the phase 1 clinic was 5.0 months (95% confidence interval [CI], 3.3‐6.2). The median overall survival from diagnosis was 22.1 months (95% CI, 17.9‐26.5). The median time to treatment failure was 1.5 months (95% CI, 1.3‐1.8). Independent factors associated with lower rates of PR/SD were liver metastases (P = .001) and performance status >0 (P = .01). Independent factors associated with shorter survival were liver metastases (P = .007), low calcium level (P = .015), and elevated CEA level (>6 ng/mL) (P = .005).

CONCLUSIONS:

Our results suggest that phase 1 clinical trials offer a reasonable therapeutic approach for patients with advanced pancreatic cancer. Cancer 2011. © 2010 American Cancer Society.     

Osteoblast-derived WISP-1 increases VCAM-1 expression and enhances prostate cancer metastasis by down-regulating miR-126

Bone metastases of prostate cancer (PCa) may cause intractable pain. Wnt-induced secreted protein-1 (WISP-1) belongs to the CCN family (CTGF/CYR61/NOV) that plays a key role in bone formation. We found that osteoblast-conditioned medium (OBCM) stimulates migration and vascular cell adhesion molecule-1 (VCAM-1) expression in human PCa (PC3 and DU145) cells. Osteoblast transfection with WISP-1 shRNA reduced OBCM-mediated PCa migration and VCAM-1 expression. Stimulation of PCa with OBCM or WISP-1 elevated focal adhesion kinase (FAK) and p38 phosphorylation. Either FAK and p38 inhibitors or siRNA abolished osteoblast-derived WISP-1-induced migration and VCAM-1 expression. Osteoblast-derived WISP-1 inhibited miR-126 expression. Moreover, miR-216 mimic reversed the WISP-1-enhanced migration and VCAM-1 expression. This study suggests that osteoblast-derived WISP-1 promotes migration and VCAM-1 expression in human PCa cells by down-regulating miR-126 expression via αvβ1 integrin, FAK, and p38 signaling pathways. Thus, WISP-1 may be a new molecular therapeutic target in PCa bone metastasis.     

Cigarette smoking, elevated fasting serum glucose, and risk of pancreatic cancer in Korean men

Pancreatic cancer is one of the most fatal human cancers and continues to be a major unsolved health problem. The goal of this study was to estimate the independent effects and interactions between cigarette smoking and diabetes on the risk of pancreatic cancer in Korean male population. Cigarette smoking and the risk of incidence and death from pancreatic cancer were examined in a 10-year prospective cohort study of 446,407 Korean men aged 40 to 65 years who received health insurance from the National Health Insurance Corporation and who had a medical evaluation in 1992. Relative risks (RR) and 95% confidence intervals (CI) were calculated using a Cox proportional hazards model after adjusting for age, body mass index, exercise and alcohol use. Current smoking was associated with an increased risk of incidence (RR = 1.7, 95% CI = 1.6-1.9) and mortality (RR = 1.6, 95% CI = 1.4-1.7) from pancreatic cancer. The RR for pancreatic cancer increased with both duration and amount of smoking. Diabetes was also associated with an increased risk of both incidence (RR = 1.8, 95% CI = 1.5-2.2) and mortality (RR = 1.7, 95% CI = 1.4-2.1) from pancreatic cancer. There was no interaction between smoking and fasting serum glucose in terms of pancreatic cancer risk. Thus, our prospective study has demonstrated that cigarette smoking and elevated fasting serum glucose are independently associated with an increased risk of pancreatic cancer in a large cohort of Korean males.