老年胃癌及癌前病变中p16及cyclinD1蛋白的表达

目的　探讨老年胃癌及癌前病变中p16、cyclinD1蛋白的表达、相互关系及其意义。　 方法 　应用免疫组化链霉卵白素 (SP)法检测老年胃癌、不典型增生、萎缩性胃炎、浅表性胃炎及正常胃组织中p16、cyclinD1蛋白的表达。　结果　p16蛋白在正常胃粘膜表达率最高 (85 7% ) ,并随病变进展 (浅表性胃炎 -萎缩性胃炎 -不典型增生 -腺癌 ) ,表达率呈下降趋势 (分别为 84 4% ,76 9% ,2 9 0 % ,3 4 3 % ) ,其中不典型增生 ,腺癌组与正常组比较有显著差异 (P <0 0 5 ) ,cy clinD1蛋白随病变发展 (萎缩性胃炎、不典型增生、腺癌 )表达率升高 (分别为 19 2 % ,3 8 7% ,5 5 7% ) ,其中腺癌与萎缩性胃炎比较差异显著 (P <0 0 5 )。相关性分析显示大多数受检老年胃癌组织中 ,p16与cyclinD1呈反向表达。　 结论　p16和cyclinD1在胃上皮癌变过程中起着重要作用 ,其在胃癌中的反向表达趋势提示两者可能存在相互抑制机制。p16蛋白低表达和cyclinD1蛋白高表达可能是胃癌发生过程中的早期分子事件。     

新的肿瘤标志物的GP87在老年胃癌及胃癌前病变组织中表达的研究

目的 探讨新的肿瘤标志物ＧＰ８７例在老年胃癌及胃癌前病变中表达的情况，从而确定其在上述病变中的应用价值。方法 采用ｓＡＢＣ免疫组化染色法对２８３例标本进行染色分析。结果 正常胃体、胃窦均为阴性，浅表性胃炎组织阳性率为７．１％，明显低于癌症组及癌前病变组（Ｐ〈０．０１）。胃癌组阳性率为６２．０％，明显低于癌前病变各组阳性率（Ｐ〈０．０５），癌旁粘膜组阳性率亦较高，在８０．０％左右。结论 新的肿瘤标志     

新的肿瘤标志物GP87在老年胃癌及胃癌前病变组织中表达的研究

目的探讨新的肿瘤标志物ＧＰ８７在老年胃癌及胃癌前病变中表达的情况,从而确定其在上述病变中的应用价值。方法采用ｓＡＢＣ免疫组化染色法对２８３例标本进行染色分析。结果正常胃体、胃窦均为阴性,浅表性胃炎组阳性率为７．１％,明显低于癌症组及癌前病变组（Ｐ＜０．０１）。胃癌组阳性率为６２．０％,明显低于癌前病变各组阳性率（Ｐ＜０．０５）,癌旁粘膜组阳性率亦较高,在８０．０％左右。结论新的肿瘤标志物ＧＰ８７在胃癌及胃癌前病变中均有较高表达,特别是在胃癌前病变中的表达更高,故认为ＧＰ８７是检测胃癌前病变较好的肿瘤标志物,可用于胃癌高危人群的普查,筛选出具有明确癌前病变的病人,定期随访、长期追踪,无疑有助于发现早期胃癌。     

老年胃癌及癌前病变中幽门螺杆菌感染情况的研究

采用ＰＣＲ方法检测老年胃癌及癌前病变组织中幽门螺杆菌（ＨＰ）感染情况。结果显示：正常组ＨＰ感染率为１５．０％，浅表性胃炎组为７０．０％，胃癌组为６３．３％；萎缩性胃炎组阳性率为８６．８％，不典型增生组为８４．０％，肠化生组为７５．０％。胃癌组中，高、中分化癌阳性率明显高于低分化组（Ｐ＜０．０１），肠型胃癌阳性率明显高于弥漫型（Ｐ＜０．０１）。萎缩性胃炎组及不典型增生组，中、重度者阳性率明显高于轻度者（Ｐ＜０．０５）。以上结果证明，ＨＰ与胃癌、癌前病变、胃炎均有密切相关性     

胃癌及癌前病变中HP感染与p16、CyclinD1表达的关系

目的：探讨胃癌发生、发展过程中幽门螺杆菌（HP）与p16、CyclinD1基因表达的关系。方法：免疫组化S－P法检测p16、CyclinD1。结果：在癌前病变中,HP阳性组的P16阳性表达率低于HP阴性组（P＜0．01）CyclinD1阳性表达率高于HP阴性组（P＜0．01）;在胃癌中HP阳性组的PH阳性表达率与胃癌的浸润,分化程度有关,且低于HP阴性组（P＜0．05）。CyclinD1阳性表达率在HP阳性和表性组间无差异（＞0．05）。结论：在胃癌前病变阶段,HP可能诱导癌基因PH失活和原癌基因CyclinD1激活,影响了p16和CyclinD1的表达,在胃癌中,HP感染对PH表达缺失仍起着重要作用,但不影响CyclinD1的表达。     

胃癌及癌前病变中的TFF-1、EGFR表达与血管再生的相关性研究

目的 探讨胃癌及癌前病变中三叶因子-1(trefoil factorl,TFF-1)、表皮生长因子受体(epidermal growthfactor receptor,EGFR)与血管形成的关系.方法 将121例患者存档标本分为萎缩性胃炎伴肠化生、不典型增生、高分化胃癌和低分化胃癌4组,另取29例体检正常人标本作为正常组.采用免疫组化SP方法测定TFF-1、EGFR值;同时所有对象用抗CD 34血管标记物表达测微血管密度(microvessel density,MDV)值,并进行相关性分析.结果 在正常对照组及萎缩性胃炎伴肠化生、不典型增生、高分化胃癌和低分化胃癌各组中,TFF-1阳性表达率分别为100.0%、85.18%、81.82%、64.00%、38.39%,呈逐渐减弱趋势.后4组与正常组比较有显著差异,高分化胃癌组表达高于低分化胃癌组(P<0.05);而EGFR在正常组、萎缩性胃炎伴肠化生、不典型增生、高分化胃癌和低分化胃癌组中的表达分别为24.13%、40.74%、42.42%、56.00%、72.22%,呈逐渐增加趋势.后4组与正常组比较有显著差异,高分化胃癌组表达低于低分胃癌组(P<0.05).结论 实验结果显示TFF-1与EGFR呈负相关(r=-0.913,P<0.01).EGFR值与MDV呈正相关(r=0.936,P<0.01).TFF-1与EGFR在胃癌的早期诊断中起重要作用,可以作为判断肿瘤转移与否及手术前肿瘤是否复发的评判标准.     

rasP21,GST—π在胃癌及癌前病变组织中的表达

ｒａｓＰ2 1是ｒａｓ基因共同编码的一种分子量为 2 1ＫＤ的蛋白质 ,ｒａｓ癌基因激活致Ｐ2 1过量表达[1] ,人胎盘型谷胱苷肽Ｓ 转移酶 (ＧＳＴ π)是一种重要的肿瘤标志[1] ,本研究应用免疫组化技术 (Ｓ Ｐ法 )对ｒａｓＰ2 1、ＧＳＴ π进行检测 ,观察其在胃癌及癌前病变组织中的表达 ,观察其分布和量的变化 ,探讨胃粘膜癌变过程中两种标记物复合表达的内在联系及意义。材料和方法一、材料选择我院病理科 1993年 6月至 2 0 0 0年 9月期间胃镜活检或手术切除标本共 168例 ,其中肠上皮化生4 0例 ,不典型增生 76例 (轻度 2 0例 ,中度 34例 ,重…     

CA242,CEA,CA19-9在胃癌及癌前病变组织中表达的相关研究

目的研究胃癌及癌前病变组织中肿瘤相关抗原表达的临床意义。方法对所有病例均行电子胃境检查，经胃镜取3块病变组织（直径约0．5cm）送病理。经病理诊断分为胃癌组32例．癌前病变组33例，对照组（浅表胃炎组）30例，同时取病变组织2块放入5％EDTA二纳液1ml中消化分离细胞，测3组病人病变组织中CA242、CEA、CA19-9的含量，同时测血清中CA242、CEA、CA19-9的含量：对3组病人组织及血清中CA242、CEA、CA19-9的含量及组织／血清比值分别进行比较。结果（1）CA242、CEA、CA19-9在胃癌及癌前病变组织中的表达明显高于血清中的表达（P〈0，01）。（2）CA242、CEA、CA19-9。在癌前病变组织中的表达明显高于对照组（P〈0.01），且在重度癌前病变组织中的表达明显高于在 中度癌前病变组织中的表达（P〈0．01），而血清中癌前病变组肿瘤相关抗原的含量与对照组差异无显著性（P〉0．05），（3）组织中CA242、CEA，CA19-9检测对胃癌诊断的灵敏度分别是84．3％、90．63％、87．50％；特异性分别是66．67％、63．49%、69．84%。结论对组织CA232、CEA、CA19-9表达的检测可预测癌前病变的危险程度，能提高早期胃癌诊断率，而血清CA242、CEA、CA19-9。检测对癌前病变的危险程度及早期胃癌的诊断价值不大。     

荧光胃液分析对胃癌癌前病变诊断的临床研究

目的评估胃液荧光分析对胃癌癌前病变诊断的价值。方法收集980例胃内良、恶性疾病患者的胃液,用荧光胃液分析仪进行胃液荧光光谱检测。结果以ROC曲线最佳截断点KJF≥0.85为判断指标,诊断胃癌的灵敏度达82.0%,特异性为79.2%;重度萎缩性胃炎伴肠化及不典型增生的KJF值接近胃癌患者的值。结论荧光胃液分析对胃癌的诊断是一种安全、有效的方法,对胃癌癌前病变的诊断有一定的特异性。     

胃癌及癌前病变细胞凋亡的研究

细胞凋亡是由基因控制的细胞主动死亡,参与调节机体细胞增殖与死亡间的平衡稳定。肿瘤不仅存在细胞异常增殖,同时存在细胞凋亡异常,且具有长期共存的特点 [1]。我们通过观察胃癌及其癌前病变组织细胞凋亡的情况,探讨细胞凋亡与胃癌发生发展的关系。　　一、材料与方法　　1.研究对象：胃癌标本 33例,其中源自胃镜活检标本 27例,外科手术标本 6例,均行石蜡包埋常规切片待用,并行 Lauren分型：其中肠型 18例 (包括乳头状腺癌、管状腺癌 ),弥散型 15例 (包括印戒细胞癌、未分化癌 );结合临床资料分析, 33例胃癌标本中早期胃癌 12例…     

Three-weekly s-1 monotherapy as first-line treatment in elderly patients with recurrent or metastatic gastric cancer

Background/Aims

Elderly patients with advanced gastric cancer (AGC) have generally been excluded from clinical trials, and there are few data available on the treatment of these patients. The efficacy of palliative S-1 monotherapy as a first-line treatment regimen for elderly patients has not been well elucidated.

Methods

For this study, 25 AGC patients were enrolled between January 1, 2007 and March 31, 2009; 4 cases were recurrent AGC and 21 cases were metastatic AGC at the time of diagnosis. These patients received S-1 therapy at a dose of 40 mg/m² twice daily for 14 days every 3 weeks. All of the patients were older than 70 years.

Results

The median follow-up duration, the median progression-free survival, and the overall survival time were 8.7 months (range, 4.9 to 12.5 months), 4.9 months (range, 3.5 to 6.3 months), and 10.8 months (range, 6.6 to 15.0 months), respectively. Grade 3/4 nonhematologic toxicities were rare. Grade 3/4 neutropenia was noted in two patients. The partial response rate was 21.7% and stable disease was observed in 34.8% of the patients. Two patients (8%) died due to chemotherapy-associated toxicity during treatment (septic shock/intracranial hemorrhage).

Conclusions

Oral S-1 chemotherapy seems to be effective as a first-line treatment regimen for elderly patients with metastatic or recurrent AGC. However, elderly patients receiving S-1 treatment should undergo continuous toxicity monitoring, since they are highly susceptible to adverse effects.     

Decreased expression of gastrokine 1 in gastric mucosa of gastric cancer patients

AIM: To investigate the expression of gastrokine 1(GKN1) in normal gastric mucosa, precancerous lesions and gastric cancer tissues, and to analyse its correlations with tumour site and pathological pattern.METHODS: Thirty gastric cancer patients(12 cases of diffuse type and 18 cases of intestinal type), 13 atrophic gastritis patients and 15 healthy volunteers with almost normal gastric mucosa(superficial gastritis) were enrolled in this study. Helicobacter pylori(H. pylori) infection was examined in all subjects. All gastric mucosa biopsy specimens were obtained. Cancer-adjacent specimens were taken from corresponding gastric cancer patients. Immunohistochemistry and real-time PCR were performed to determine the expressions of the GKN1 protein and m RNA, respectively.RESULTS: H. pylori infection had no significant association with age, gender, tumour site or pathological pattern in all subjects. Compared with the superficial gastritis and atrophic gastritis groups, the expression of GKN1 protein(P = 0.011) and m RNA(P < 0.001) in gastric cancer was significantly decreased. The GKN1 m RNA level in diffuse type gastric cancer was significantly lower than in intestinal type gastric cancer(0.296 ± 0.076 vs 0.525 ± 0.164, P < 0.001).CONCLUSION: Compared with almost normal gastric mucosa, GKN1 expression in the gastric mucosa of gastric cancer patients is decreased; this is associated with progression and prognosis of gastric cancer.     

胃液CEA、CA19-9联检在胃癌预后判断与复发筛查中的价值

目的探讨胃液中癌胚抗原(CEA)、糖链多肽抗原19-9(CA19-9)在胃癌预后判断和复发筛查中的价值. 方法应用免疫放射法检测了62例胃癌患者(术后复发组32例,未复发组30例)手术前后胃液中CEA、CA19-9变化,并进行随访观察.结果复发组CEA为(65.81±43.62)ng/ml,CA19-9为(172.53±159.38)U/ml.两组比较,有非常显著差异(P＜0.01).CEA、CA19-9联检可将敏感性提高至81.25%,并可在胃癌术后亚临床期检出复发.结论胃液CEA、CA19-9联检对胃癌疗效观察、预后判断和复发筛查具有重要意义.     

Cullin1蛋白在胃癌中的表达及临床意义

目的:研究Cullin1在胃癌细胞及胃癌组织中的表达,并分析Cullin1、临床分期与患者生存率之间的相关性.方法:采用Western blot法检测SGC-7901、BGC-823胃癌细胞与正常胃黏膜上皮细胞GES-1中、胃癌组织与癌旁组织中Cullin1蛋白表达差异.我们利用已经构建的胃癌数据库,采用免疫组织化学法检测792例胃癌组织中Cullin1表达.结果:我们研究发现,SGC-7901、BGC-823胃癌细胞中Cullin1表达水平均高于胃上皮细胞株GES-1(P<0.01).胃癌组织中Cullin1蛋白表达水平均高于癌旁组织(P<0.01).Cullin1过表达与胃癌TNM分期(P=0.011)、浸润深度(P=0.035,T1-T3与T4)及淋巴结转移(P=0.036)显著相关.此外,我们发现Cullin1的高表达与胃癌患者较差的总生存时间及3年生存率明显相关(P=0.042,0.026).Cox回归分析显示,Cullin1表达是胃癌患者3年生存率的一个独立的预后因子(P=0.028).结论:我们的数据表明,Cullin1可作为胃癌淋巴结转移、预后以及潜在治疗的一个重要标志和研究目标.     

胃癌及癌前病变的中医分型与 Hp 感染、癌基因及抑癌基因表达的关系

根据中医理论将胃癌、异型增生、肠上皮化生、慢性胃炎各30例进行中医分型,分别为寒热夹杂21例,肝胃不和22例,胃阴不足29例,脾胃虚寒48例。应用 ABC 免疫组化法检测上述标本的 C-myc、p21、p53,以改良 Giemsa 法检测 HP。结果脾胃虚寒型 HP 阳性率(72.9%)与寒热夹杂型阳性率(38.1%)、肝胃不和型阳性率(40.9%)比较有非常显著差异(P<0.01)。C-myc、p21、p53阳性表达与 HP 感染、胃粘膜病变程度呈平行关系,各证型依次为脾胃虚寒>胃阴不足>肝胃不和>寒热夹杂。提示 HP 感染、癌基因及抑癌基因表达与胃癌及癌前病变中医分型有一定关系,有利于辨证辨病分型。     

Syndecan-1 and E-cadherin expression in differentiated type of early gastric cancer

AIM: To elucidate the role and alterations of syndecan-1 and E-cadherin expression in different cellular phenotypes of differentiated-type gastric cancers (DGCs). METHODS: A total of 120 DGCs at an early stage, and their adjacent mucosa, were studied both by immunohis-tochemistry. Syndecan-1 and E-cadherin were assessed by immunohistochemical staining with anti-syndecan-1 and anti-E-cadherin antibodies, respectively. Based on immunohistochemistry, DGCs and their surrounding mucosa were divided into four types: gastric type (G-type), ordinary type (O-type), complete-intestinal type (CI-type), and null type (N-type). RESULTS: Syndecan-1 expression was significantly lower in G-type cancers (29.4%) than in O-type (79.6%) and CI-type cancers (90%) (P<0.05, respectively), but E-cadherin did not show this result. In addition, syndecan-1 expression was significantly reduced in DGCs comprised partly of poorly differentiated adenocarcinoma or signet-ring cell carcinoma, compared to DGCs demonstrating papillary and/or tubular adenocarcinoma (P<0.05). G-type intestinal metaplasia (IM) surrounding the tumors was observed in 23.8% of G-type, 4.9% of O-type, and 6.7% of CI-type cancers (P<0.05; G-type vs O-type). Reduction of syndecan-1 expression was significant in G-type IM (25%) compared to non-G-type IM (75%; P<0.05). CONCLUSION: Loss of syndecan-1 plays a role in the growth of G-type cancers of DGCs at an early stage, and the reduction of syndecan-1 expression in IM surrounding the tumors may influence the growth of G-type cancer.     

胃癌组织KAI 1和nm23-H1蛋白的表达意义

目的:观察胃癌组织中KAI 1和nm23-H1蛋白的表达与临床病理生物学的关系,探讨KAI 1蛋白在胃癌发生、发展中的作用．方法:应用兔抗人KAI 1多克隆抗体和鼠抗人nm23-H1 单克隆抗体对87例手术切除胃癌标本以PV-9000免疫组化二步法进行染色,用x2检验进行统计学分析．结果:伴有淋巴结转移的胃癌组织中KAI 1蛋白表达阳性率(60％,39／65)明显低于无淋巴结转移的胃癌组织(95％,21／22,P<0．05),早中期胃癌组织中KAI 1蛋白表达阳性率(94％,16／17)显著高于晚期胃癌组织(63％, 44／70,P<0．05),KAI 1蛋白高表达者其生存期亦较长 (P<0．05);伴有淋巴结转移的胃癌组织中nm23-H1蛋白表达阳性率明显低于无淋巴结转移的胃癌组织(18％ vs 77％,P<0．05),早中期胃癌组织nm23-H1蛋白表达阳性率明显高于晚期胃癌组织(65％vs26％,P<0．05)．结论:KAI 1和nm23-H1蛋白均与胃癌侵袭转移有关, 且KAI 1表达与胃癌患者预后密切相关,将两种指标联合检测,可作为正确判断胃癌患者预后,指导临床治疗的分子生物学指标．