血清MG7-Ag与PG联合检测对胃癌早期诊断的临床应用价值

目的:探讨联合检测血清中MG7-Ag和胃蛋白酶原(PG)对胃癌早期诊断的临床价值.方法:采用酶联免疫吸附实验(ELISA)检测血清胃癌相关抗原MG7,胃蛋白酶原A和C含量,分析三种指标对胃癌早期诊断的临床应用价值及与胃癌临床生物学行为的关系.结果:sMG7Ag含量从浅表性胃炎、胃粘膜糜烂溃疡、萎缩性胃炎/异型增生到胃癌组有升高趋势,各组间比较统计学上均有极显著性差异(P＜0.01);胃癌组sMG7Ag含量最高.sPGA含量从浅表性胃炎、胃粘膜糜烂溃疡、萎缩性胃炎/异型增生到胃癌组依次降低,sPGC浓度从浅表性胃炎、胃粘膜糜烂溃疡、萎缩性胃炎/异型增生到胃痛组有升高趋势,但各组间比较均无显著性差异(P>0.05);各组sPGA/sPGC比值依次下降,浅表性胃炎组与胃癌组比较统计学有极显著差异(P＜0.01),与萎缩性胃炎/异型增生组相比有显著差异(P＜0.05).胃癌患者血清MG7-Ag、PGA、PGC的阳性表达率分别为51.61%,32.26%,64.52%;联合检测刚性率MG7-Ag PGA=70.97%,MG7-Ag PGC=87.10%,PGA PGC=70.97%,MG7-Ag PGA PGC=93.55%(P＜0.05).结论:血清MG7-Ag、PGA、PGC对胃癌诊断有特异性,可作为胃癌早期诊断的有效指标,也可作为监测病情、判定疗效之用.     

MG7和PGC在胃癌及癌前疾病中的表达及意义

[目的]探讨胃癌相关抗原（MG7）和胃蛋白酶原C（PGC）在不同胃疾病中的动态表达,并对其在胃癌前疾病及胃癌诊断中的价值评价。[方法]采用免疫组织化学染色检测125例胃黏膜标本中MG7和PGC的表达情况。[结果]①MG7-Ag在12例正常胃黏膜中无表达,在31例胃癌中表达率为93．55％,由浅表性胃炎或胃糜烂溃疡→萎缩性胃炎或异型增生→胃癌,MG7-Ag表达率依次逐渐上升（P〈0．05）。PGC—Ag在12例正常胃黏膜中全部阳性表达（100％）,在31例胃癌中表达率显著下降（6．45％）,从浅表性胃炎或胃糜烂溃疡→萎缩性胃炎或异型增生→胃癌,PGC—Ag表达率依次逐渐下降（P〈0．05）。②单独应用MG7和PGC诊断试验的灵敏度高;将MG7和PGC联合进行串联试验,提高了诊断胃癌的特异度和准确度。[结论]①MG7抗原和PGC抗原两个指标与胃疾病的发生发展有良好的相关性。②MG7抗原和PGC抗原联合检测可以提高特异度,可以用于胃癌的诊断和癌前疾病的筛查。     

血清MG7-Ag与PG联合检测对胃癌早期诊断的临床应用价值

目的：探讨联合检测血清中MG7-Ag和胃蛋白酶原（PG）对胃癌早期诊断的临床价值。方法：采用酶联免疫吸附实验（ELISA）检测血清胃癌相关抗原MG7，胃蛋白酶原A和C含量，分析三种指标对胃癌早期诊断的临床应用价值及与胃癌临床生物学行为的关系。结果：sMG7Ag含量从浅表性胃炎、胃粘膜糜烂溃疡、萎缩性胃炎／异型增生到胃癌组有升高趋势，各组间比较统计学上均有极显著性差异（P〈0．01）；胃癌组sMG7Ag含量最高。sPGA含量从浅表性胃炎、胃粘膜糜烂溃疡、萎缩性胃炎／异型增生到胃癌组依次降低，sPGC浓度从浅表性胃炎、胃粘膜糜烂溃疡、萎缩性胃炎／异型增生到胃癌组有升高趋势，但各组间比较均无显著性差异（P〉0．05）；各组sPGA／sPGC比值依次下降，浅表性胃炎组与胃癌组比较统计学有极显著差异（P〈0．01），与萎缩性胃炎／异型增生组相比有显著差异（P〈0．05）。胃癌患者血清MG7-Ag、PGA、PGC的阳性表达率分别为51．61％，32．26％，64．52％；联合检测阳性率MG7-Ag＋PGA=70．97％，MG7-Ag＋PGC=87．10％．PGA＋PGC：70．97％，MG7-Ag＋PGA＋PGC=93．55％（P〈0．05）。结论：血清MG7-Ag、PGA、PGC对胃癌诊断有特异性，可作为胃癌早期诊断的有效指标，也可作为监测病情、判定疗效之用。     

人胃癌相关抗原MG7在胃癌前病变组织中的表达及其与COX-2表达的相关性分析

目的:探讨人胃癌相关抗原MG7在胃癌前病变组织中的表达及其与COX-2表达的相关性.方法: 采用常规ABC免疫组化染色法联合检测334例胃癌前病变患者的胃黏膜中MG7抗原和COX-2抗原的表达情况.结果: 在胃癌前病变组织(包括肠上皮化生和不典型增生)中MG7-Ag和COX-2的表达阳性率分别为49.1%和56.6%,从慢性浅表性胃炎、慢性萎缩性胃炎、肠上皮化生、不典型增生到胃癌MG7-Ag和COX-2的表达均呈上升趋势,差异具有显著性(P<0.05).MG7-Ag和COX-2在胃癌前病变组织中表达具有相关性.结论: MG7-Ag和COX-2在胃癌前病变组织中有一定的相关性.     

双重染色内镜联合检测MG7-Ag抗原对胃癌早期诊断的意义

目的探讨双重染色内镜联合检测MG7-Ag抗原对胃癌早期诊断的意义。方法选取2014年1月至2015年6月间因上消化道症状在湖北省宜昌市三峡大学仁和医院就诊的106例患者,患者均接受普通内镜和双重染色内镜检查,根据检测结果分为浅表性胃炎组(35例)、胃溃疡组(33例)、萎缩性胃炎组(20例)和胃癌组(18例),比较各组患者血清MG7-Ag的水平。结果胃癌组患者血清MG7-Ag水平和阳性率明显高于浅表性胃炎组、胃溃疡组和萎缩性胃炎组,差异有统计学意义(P<0.05)。萎缩性胃炎组患者血清MG7-Ag水平和阳性率明显高于浅表性胃炎组、胃溃疡组,差异有统计学意义(P<0.05)。结论双重染色内镜联合检测血清MG7-Ag对提高胃癌早期诊断有重要意义。     

环氧合酶-2在胃癌与癌前病变和其他胃黏膜组织中表达的研究

目的:研究胃癌与癌前病变和其他胃黏膜组织中环氧合酶-2(COX-2)的表达情况,探讨COX-2蛋白作为肿瘤分子标记物对胃癌和癌前病变进行辅助诊断的意义.方法:收集胃镜活检的正常胃黏膜、慢性浅表性胃炎、慢性萎缩性胃炎、胃黏膜肠化生、胃黏膜不典型性增生和胃癌组织,用免疫组织化学染色法检测COX-2蛋白在各种组织中的阳性表达情况.以正常胃黏膜组织和正常兔血清作阴性对照.结果:COX-2蛋白在胃癌前病变和和胃癌组织中的表达阳性率为48%-84%.胃癌和胃黏膜不典型性增生标本中COX-2蛋白表达阳性率显著高于正常胃黏膜、慢性浅表性胃炎、慢性萎缩性胃炎和胃黏膜肠上皮化生标本(P<0.05).而胃癌组织COX-2蛋白表达的阳性率与胃黏膜不典型性增生组之间无显著性差异(P>0.05).此外,慢性萎缩性胃炎和胃黏膜肠化生标本与正常胃黏膜和慢性浅表性胃炎标本之间COX-2蛋白表达阳性率亦有显著性差异(P<0.05);所有病变组的COX-2蛋白表达阳性率均比正常胃黏膜组显著性地升高 (P<0.05).结论:胃癌与癌前病变组织中COX-2蛋白的表达显著升高,COX-2蛋白可作为肿瘤标记物对胃癌和胃癌前病变进行辅助诊断.     

1A6/DRIM 表达及血清 MG7- Ag 含量在胃癌早期诊断中的价值

目的：对不同类型胃黏膜活检组织1A6/ DRIM 表达和血清 MG7- Ag 检测,探讨两者的相关性及胃癌前病变风险预测的临床应用价值。方法：131例胃黏膜活检组织及其血清标本（浅表性胃炎30例,胃黏膜糜烂溃疡26例,萎缩性胃炎伴肠上皮化生21例,胃癌54例）,采用酶联免疫吸附实验（ELISA）检测血清 MG7- Ag 含量;免疫组化 SP 法检测胃黏膜组织标本中1A6/ DRIM 的表达水平。结果：从浅表性胃炎、胃黏膜糜烂溃疡、萎缩性胃炎伴肠上皮化生到胃癌,血清 MG7- Ag 含量呈逐渐升高趋势,并且各组间比较差异均有显著性（P ﹤0.05）,胃癌患者血清 MG7- Ag 含量明显高于其他胃病患者,差异有显著性（P ﹤0.01）。1A6/ DRIM在54例胃癌组织中阳性表达34例（63.0%）,在其他胃病患者中阳性表达9例（11.7%）,差异有显著性（P ﹤0.05）。随着病变组织中1A6/ DRIM 表达的上升,血清 MG7- Ag 含量有上升趋势,两者具有良好的相关性（rs=0.346,P =0.001）。血清 MG7- Ag 和1A6/ DRIM 组织表达水平与胃癌分化程度呈负相关,二者有良好的相关性。结论：MG7- Ag 可以作为胃癌的血清学检测指标,对早期胃癌进行筛查,结合组织学1A6/ DRIM 基因表达的检查,有助于胃癌高危个体的筛查和诊断,提高胃癌早期诊断水平。     

胃癌及癌前病变细胞凋亡与Caspase-9,Bax表达的关系

目的:探讨细胞凋亡基因Caspase-9和Bax在胃癌前病变和胃癌发展中的作用.方法:应用免疫组化S-P法检测 Caspase-9和Bax在57例胃癌及48例非癌胃黏膜组织的表达,用原位末端标记法(TUNEL法)检测相应胃组织细胞凋亡.结果:Caspase-9蛋白在非癌胃黏膜组(慢性浅表性胃炎、慢性萎缩性胃炎、肠上皮化生、不典型增生)阳性表达率分别为 100.00%、86.67%、50.00%、42.85%,呈逐渐下降趋势.慢性浅表性胃炎组中Caspase-9蛋白阳性表达率与肠上皮化生、不典型性增生有显著性差异(P＜0.05),肠上皮化生组Caspase-9蛋白阳性表达率高于不典型增生组,但无统计学差异(P＞0.05).Bax蛋白在48例非癌胃组织中的阳性表达率分别为:慢性浅表性胃炎100.00%、慢性萎缩性胃炎80.00%、肠上皮化生56.25%、不典型增生57.14%,呈逐渐下降趋势,其中慢性浅表性胃炎组Bax蛋白阳性表达率与肠上皮化生、不典型增生有显著性差异(P＜0.05).慢性浅表性胃炎、慢性萎缩性胃炎 、肠上皮化生、不典型增生、胃癌组织中,AI值( 细胞凋亡指数)分别为(14.72±2.68)%、(10.02±2.34)%、(7.55±2.80)%、(6.09±2.35)%、(3.26±1.23)%,呈逐渐下降趋势,有显著性差异(P＜0.05).结论:Caspase-9和Bax可能参与胃癌癌前病变的形成,促进胃癌的发生.     

血清MG7-Ag联合G-17检测在胃癌诊断中的临床价值

目的 探讨血清胃癌相关抗原(MG7-Ag)联合胃泌素-17(G-17)检测用于诊断胃癌的临床价值.方法 选择胃癌患者60例(胃癌组),胃部良性病变患者50例(良性病变组),癌前病变患者58例(癌前病变组),同时选择同期进行体检的健康志愿者50例作为对照组.检测所有患者以及健康对照组志愿者血清中MG7-Ag以及G-17的表达含量,分析2种检测指标用于诊断胃癌的临床效能.结果良性病变组、癌前病变组以及胃癌组患者血清中MG7-Ag以及G-17的表达含量显著高于健康对照组(P<0.05).胃癌进展期患者血清中MG7-Ag和G-17的含量水平显著高于早期胃癌患者(P<0.05);淋巴结转移患者血清中MG7-Ag和G-17的含量水平显著高于淋巴结非转移胃癌患者(P<0.05).与MG7-Ag、G-17单独用于诊断胃癌相比,MG7-Ag联合G-17用于诊断胃癌的敏感性、特异性更强,且阳性预测值和阴性预测值升高,其中,MG7-Ag联合G-17的敏感性、特异性,阳性预测值和阴性预测值均比MG7-Ag检测显著升高(P<0.05).结论MG7-Ag联合G-17用于诊断胃癌的特异度高,误诊率低,可以提高诊断准确性.     

血清骨桥蛋白、胃癌相关抗原和组织多肽特异性抗原诊断胃癌的临床价值

目的 探讨血清骨桥蛋白(OPN)、胃癌相关抗原(MG7-Ag)和组织多肽特异性抗原(TPS)对诊断胃癌的临床价值.方法 选择胃癌病例86例、癌前病变病例45例、胃良性病变病例48例与健康对照50例,采用ELISA法检测血清OPN、MG7-Ag与TPS.结果 胃癌组血清OPN、MG7-Ag和TPS水平及阳性率均高于其他3组,差异均有统计学意义(P<0.01).胃癌TNMⅢ/Ⅳ期病例、低分化胃癌病例及淋巴结转移的病例血清中OPN、MG7-Ag与TPS的水平分别高于Ⅰ/Ⅱ期、高/中分化及无淋巴结转移的病例(P均<0.05).OPN、MG7-Ag、TPS之间均呈显著的正相关关系(P均<0.05).结论 OPN、MG7-Ag与TPS在胃癌患者体内呈高表达,检测OPN、MG7-Ag、TPS对胃癌的早期诊断具有重要的意义.     

Role of acidosis-sensitive microRNAs in gene expression and functional parameters of tumors in vitro and in vivo

Background: The acidic extracellular environment of tumors has been shown to affect the malignant progression of tumor cells by modulating proliferation, cell death or metastatic potential. The aim of the study was to analyze whether acidosis-dependent miRNAs play a role in the signaling cascade from low pH through changes in gene expression to functional properties of tumors in vitro and in vivo.Methods: In two experimental tumor lines the expression of 13 genes was tested under acidic conditions in combination with overexpression or downregulation of 4 pH-sensitive miRNAs (miR-7, 183, 203, 215). Additionally, the impact on proliferation, cell cycle distribution, apoptosis, necrosis, migration and cell adhesion were measured.Results: Most of the genes showed a pH-dependent expression, but only a few of them were additionally regulated by miRNAs in vitro (Brip1, Clspn, Rif1) or in vivo (Fstl, Tlr5, Txnip). Especially miR-215 overexpression was able to counteract the acidosis effect in some genes. The impact on proliferation was cell line-dependent and most pronounced with overexpression of miR-183 and miR-203, whereas apoptosis and necrosis were pH-dependent but not influenced by miRNAs. The tumor growth was markedly regulated by miR-183 and miR-7. In addition, acidosis had a strong effect on cell adhesion, which could be modulated by miR-7, miR-203 and miR-215.Conclusions: The results indicate that the acidosis effect on gene expression and functional properties of tumor cells could be mediated by pH-dependent miRNAs. Many effects were cell line dependent and therefore do not reflect universal intracellular signaling cascades. However, the role of miRNAs in the adaptation to an acidic environment may open new therapeutic strategies.     

Expression of thrombomodulin in astrocytomas of various malignancy and in gliotic and normal brains

Summary A total of 22 surgical specimens, 16 astrocytomas with various malignancy, 3 brains adjacent to tumor and 3 brains with non-neoplastic lesion, was investigated immunohistochemically for the expression of thrombomodulin (TM). This membrane protein is localized on the vascular endothelium of nearly every human tissue and plays a crucial role in the maintenance of antithrombotic property of the endothelial cells. Although the normal cerebral vessels were negative for TM, the tumor vessels were positive for TM. The increased expression of TM was, however, demonstrated not only in glioblastomas but also in low-grade astrocytomas. Furthermore, the vessels in the brains adjacent to tumor and gliotic brains were also positive for TM. Those observations suggested that the tendency of intratumoral bleeding, which is rather characteristic of glioblastomas, is not simply explained by the altered expression of vascular endothelial TM. In two cases of glioblastoma, not only the blood vessels but also the tumor cells were positive. Considering the mitogenic activity of thrombin, a ligand for TM, the increased expression of TM might be related to the tumor neovascularization and also the tumor growth.     

The role of alcohol in oral and pharyngeal cancer in non-smokers, and of tobacco in non-drinkers

Data from a hospital-based case-control study of oral and pharyngeal cancer conducted in Northern Italy were used to analyse the risk associated with alcohol in non-smokers and with tobacco in non-drinkers. Out of a total of 336 cases (291 males and 45 females) and 1,652 controls (1,272 males and 380 females) 27 cases and 572 controls described themselves as lifelong non-smokers. Odds ratios (ORs) were 1.5 for 14-55 vs. 0-13 alcoholic drinks per week and 2.2 for 56 or over; the trend in risk was statistically significant. Among 19 cases and 213 controls who described themselves as non-drinkers, the ORs were 3.8 and 12.9 for smokers of less than 15 and greater than or equal to 15 cigarettes per day, with a highly significant trend. This study therefore confirms that tobacco has an independent role in the aetiology of oral and pharyngeal cancer, and suggests that alcohol may have an independent role as well, even where, as in Northern Italy, wine is its predominant source. Indeed, ORs were similar to those for tobacco and alcohol individually, each adjusted for the other factor, in the overall data-set.     

Nitrate and nitrite in saliva and urine of inhabitants of areas of low and high incidence of cholangiocarcinoma in Thailand

Cholangiocarcinoma is one of the main liver diseases in northeast Thailand. Associations with exposure to liver fluke and N-nitrosodimethylamine in formation of the tumour have been demonstrated in animals. This study was carried out to compare possible endogenous formation of N-nitroso compounds in inhabitants of areas with low and high incidences of cholangiocarcinoma by examining the levels of nitrate and nitrite in their saliva and urine. Thirty-two subjects (16 males and 16 females) living in the north-east (high incidence) and 12 volunteers (6 males and 6 females) in Bangkok (low incidence) were allowed to take regular meals, and their saliva and urine were collected before, and 30, 60 and 120 min after each meal. Nitrate and nitrite concentrations in saliva of the group in the high-incidence area were significantly higher than those of the group in Bangkok: salivary nitrate was 2-2.8 times higher and nitrite 2-5.6 times higher in the north-eastern group when compared with levels at each corresponding time interval in the low-incidence group. Nitrate levels in urine were also significantly higher in the north-eastern group at some time intervals, but urinary nitrite levels were similar and very low in both groups throughout the day. This finding may indicate a greater possibility of in-vivo formation of N-nitroso compounds in the north-east area than in Bangkok and might be associated with the occurrence of cholangiocarcinoma in north-east Thailand.     

Synergistic anti-cancer effects of immunotoxin and cyclosporin in vitro and in vivo

Background:

The clinical use of immunotoxins (ITs) has been hampered by hepatotoxicity, and the induction of a strong human-anti-IT response. The human-anti-IT response results in neutralisation of the immunoconjugates, rendering repetitive treatment inefficacious.

Methods:

We evaluated the combination of cyclosporin A (CsA) with various Pseudomonas exotoxin A-based ITs in human breast, cervical, and prostate cancer cell lines measured by protein synthesis, cell viability, and TUNEL assay. Furthermore, expression of essential proteins were analysed by western blot. We used cervical cancer model in nude rats to evaluate the anti-metastatic effect of the combination. The anti-immunogenic response by the CsA treatment was investigated in immunocompetent rats.

Results:

The combination of CsA with ITs caused remarkable synergistic cytotoxicity, in several cancer cell lines, characterised by protein synthesis inhibition, decreased cell viability, and an increased apoptotic index. Furthermore, the combination strongly inhibited formation of metastases in a cervical cancer model in nude rats with a statistically significant increase in median survival time of the combination-treated animals, as compared with those receiving a suboptimal dose of IT alone. Notably, we found in immunocompetent rats that the anti-IT immunoresponse elicited by repeated administration of IT was efficiently abrogated by CsA; notably the antibody responds towards the highly immunogenic PE was shown to be prevented.

Conclusion:

The combination of ITs and CsA might constitute a significant improvement in the clinical potential of systemic IT treatment of cancer patients.