黏着斑激酶在结肠癌细胞中的表达及对其迁移的影响

[目的]观察局部黏着斑激酶（FAK）在结肠癌细胞中的表达及对结肠癌细胞侵袭动力和生长的影响。[方法]应用RT-PCR、Western blot方法测定结肠癌细胞株（HT-29）和正常肠上皮细胞中FAK的表达；在血小板源性生长因子（PDGF）刺激肿瘤细胞后，应用细胞黏附分析和体外侵袭试验方法，测定不同时间点细胞的体外黏附能力变化及侵袭能力，同时行FAK表达测定。[结果]结肠癌细胞较正常上皮细胞存在较高水平的FAK表达。PDGF干预组与非干预组比较，能促进HT-29的黏附功能（90．0％）和侵袭能力（54．5％），在该过程中，FAK的表达和活性升高（P〈0．05）。[结论]FAK对结肠癌细胞的体外黏附与迁移发挥重要的作用。     

整合素ανβ6对结肠癌细胞胞外基质降解的调控作用

目的 探讨整合素ανβ6在结肠癌细胞侵袭中的作用,并揭示癌细胞调控胞外基质降解的相关分子机制.方法 利用质粒构建ανβ6特异性siRNA表达载体,细胞侵袭实验检测沉默ανβ6对结肠癌细胞HT29体外侵袭能力的影响;分别通过Western blot实验、明胶酶谱实验检测沉默ανβ6对结肠癌细胞胞外信号调节激酶(ERK)、尿激酶型纤溶酶原激活物(uPA)及基质金属蛋白酶(MMP-2、MMP-9)表达的影响;[3H]标记的Ⅳ型胶原降解分析检测沉默ανβ6对结肠癌细胞胞外基质降解能力的影响.结果 特异性siRNA表达载体可有效抑制HT29细胞中ανβ6的表达和结肠癌细胞的体外侵袭能力,显著抑制结肠癌细胞ERK1/2的表达,并抑制其活化形式磷酸化ERK1/2的表达;沉默ανβ6表达显著抑制结肠癌细胞uPA,pro-MMP-9和pro-MMP-2的分泌,以及丝裂原活化蛋白激酶(MAPK)依赖的胞外基质降解.结论 整合素ανβ6通过MAPK信号通路调控uPA、MMP-9和MMP-2的分泌及活性,从而调控细胞外基质的降解,在结肠癌侵袭转移中发挥了重要作用.     

尼美舒利抑制结肠癌侵袭和转移的作用机制研究

目的观察选择性环氧合酶-2(COX-2)抑制剂尼美舒利对结肠癌细胞Caco-2同质性黏附能力,E-钙黏蛋白和CD44v6表达的影响.探讨其在抑制肿瘤侵袭和转移中的作用机制.方法培养结肠癌细胞细胞株Caco-2,用不同浓度的尼美舒利进行干预,观察细胞同质性黏附能力的变化.用Western blot检测E-钙黏蛋白表达的变化,用免疫细胞化学法检测CD44v6的变化.结果尼美舒利能增加Caco-2细胞的同质性黏附能力,增加E-钙黏蛋的表达,并呈剂量依赖性.结论尼美舒利可以通过增强结肠癌细胞的同质性黏附能力,增加E-钙黏蛋白的表达,减少CD44v6的表达来抑制肿瘤细胞的侵袭和转移.     

肠复康对人结肠癌细胞HT-29增殖及浸润转移的影响

[目的] 探讨肠复康中药对人结肠癌细胞HT-29增殖及浸润转移影响的分子机制。[方法] 采用体外培养，应用免疫组化方法，检测其对核增殖抗原Ki-67、金属基质蛋白酶(MMP2)及其相应组织抑制物(TIMP2)表达的影响。[结果] 经中药血清处理过的HT-29细胞表现出增殖受抑，MMP2表达减少及TIMP2分泌增加，且其表达与中药血清浓度有量效关系，以30％血清组效果最明显。[结论] 中药肠复康通过抑制Ki-67的表达及影响MMP2、TIMP2的相互平衡来影响结肠癌细胞的增殖及浸润转移。     

肝素酶抑制剂对结肠癌细胞侵袭迁移及MMP-2、MMP-9表达的影响

目的探讨肝素酶(Hpa)抑制剂对结肠癌细胞侵袭迁移及基质金属蛋白酶(MMP)-2、MMP-9表达的影响。方法用不同浓度的Hpa抑制剂OGT2115作用于结肠癌细胞SW480,噻唑蓝(MTT)检测细胞增殖,计算半数抑制浓度。用半数抑制浓度的OGT2115作用于SW480细胞,细胞划痕实验检测细胞迁移能力,Transwell小室检测细胞侵袭,酶联免疫吸附法(ELISA)检测培养液上清Hpa活性,Western印迹检测细胞MMP-2、MMP-9表达水平。结果 Hpa抑制剂能够呈浓度依赖地抑制结肠癌细胞增殖活力,其半数抑制浓度为(5.82±0.34)μmol/L。6μmol/L的OGT2115作用后结肠癌细胞迁移率从(46.84±3.54)%降至(25.11±1.32)%,侵袭细胞数目从(153.24±11.84)个减少到(96.87±8.26)个,培养液上清Hpa活性明显降低,细胞中MMP-2、MMP-9表达水平明显下降。结论 Hpa抑制剂OGT2115可以抑制结肠癌细胞侵袭迁移和MMP-2、MMP-9表达。     

熊果酸对卵巢癌细胞黏附、运动和侵袭的影响

目的探讨熊果酸(UA)对人高转移卵巢癌细胞HO-8910黏附、运动和侵袭的影响。方法以不同浓度的UA处理高转移卵巢癌细胞HO-8910,采用MTT法及细胞黏附人工重组基底膜实验检测UA对HO-8910细胞的细胞毒作用及黏附能力的影响;Transwell小室法检测UA对HO-8910细胞侵袭能力和趋化运动能力的影响。结果不同浓度UA处理后,随着UA浓度从10μmol/L增加到30μmol/L,与对照组比较,对细胞黏附抑制率增强(P0.01),能显著降低HO-8910运动能力和侵袭能力(P0.01)。结论 UA能抑制卵巢癌细胞HO-8910黏附、运动和侵袭能力。     

肝癥口服液含药血清对人肝癌BEL-7402细胞系侵袭和转移的影响

目的:探讨肝癥口服液含药血清对人肝癌BEL-7402细胞系侵袭和转移的影响及其机制.方法:应用细胞培养技术培养人肝癌细胞株BEL-7402,采用血清药理学的方法,以原发性肝癌患者服用肝癥口服液前后血清处理肝癌细胞,通过Boyden小室模型测定其侵袭力和黏附力,细胞迁移实验测定细胞运动能力,同时观察细胞形态,流式细胞术测定肝癌细胞基质金属蛋白酶2(MMP2),基质金属蛋白酶抑制剂2(TIMP2),整合素β_1(integrinβ_1)和上皮钙黏附素(E-cd)表达的改变.结果:肝癥口服液含药血清能明显抑制肝癌细胞侵袭力(25.79±2.31 vs 49.54±4.32,P<0.05)、黏附力(42.38±3.19 vs 68.67±5.36,P<0.05)及运动能力(34.72±3.43 vs 54.16±5.35,P<0.05).形态学观察发现,服药后血清组细胞形态较圆,伪足数目较少,MMP2阳性表达细胞减少(289.61±25.32 vs 439.28±22.45,P<0.05),TIMP2阳性表达细胞增多(348.75±34.58 vs 250.53±16.48,P<0.05),MMP2/TIMP2比值下降(0.83 vs 1.76,P<0.05);integrinβ_1表达减少(286.05±28.47 vs 389.57±21.23,P<0.05),E-cd的表达则增加(385.57±26.36 vs 230.72±13.41.P<0.05).结论:肝癥口服液含药血清能抑制肝癌BEL-7402细胞侵袭与转移,其机制可能与直接抑制细胞迁移运动,抑制细胞基质溶解相关基因蛋白MMP2表达,促进TIMP2表达;抑制黏附分子integrinβ_1的表达,促进E-cd表达有关.     

桂枝茯苓对宫颈癌HeLa细胞侵袭转移及MMP-2、MMP-9表达的影响

目的研究桂枝茯苓对宫颈癌侵袭和转移的影响，并初步探讨其作用机制。方法选用Transwell侵袭系统，观察桂枝茯苓对宫颈癌细胞侵袭转移的影响；用逆转录聚合酶链反应（RT-PCR）、Westernblot法检测桂枝茯苓对宫颈癌细胞MMP-2、MMP-9mRNA及蛋白表达的影响。结果桂枝茯苓100mg／ml组、50mg／ml组穿过的细胞数分别为9．00±1．58、9．60±2．07，较空白对照组的40．00±3．81明显减少（P〈0．05）。桂枝茯苓能够明显降低宫颈癌细胞MMP-2、MMP-9mRNA及蛋白表达水平（P均〈0．05）。结论桂枝茯苓能有效抑制宫颈癌侵袭和转移，其作用机制可能与降低宫颈癌细胞运动能力，抑制MMP-2、MMP-9的表达水平有关。     

奥沙利铂在胃癌细胞侵袭与转移中的作用

目的 通过不同浓度奥沙利铂对胃癌细胞基质金属蛋白酶-2(MMP2)及其组织抑制物-2(TIMP-2)基因表达调节的研究，了解奥沙利铂在胃癌细胞侵袭与转移中的作用。方法 将不同浓度的奥沙利铂与胃癌细胞共同培养24h，采用RT-PCR方法检测胃癌细胞MMP2、TIMP-2基因表达。结果 低浓度的奥沙利铂(6μg／m1)可完全抑制MMP2的基因表达，而TIMP-2的基因表达增加；高浓度的奥沙利铂(12μg／ml)使TIMP-2基因表达进一步增加。结论 奥沙利铂可通过调节MMP2及TIMP-2的基因表达来发挥抑制胃癌细胞侵袭与转移的作用。     

胰星状细胞对胰腺癌细胞株Patu8988侵袭和转移的影响

目的:探讨永生化人胰星状细胞(IPSC)对胰腺癌细胞株Patu8988侵袭和转移的影响.方法:制备IPSC上清,用IPSC上清和Patu8988共培养,以单独培养的Patu8988为对照,比较实验组与对照组细胞的增殖、黏附能力.侵袭、迁移能力,克隆形成以及抵抗H2O2诱导的Patu8988凋亡能力.结果:与单独培养的胰腺癌细胞株Patu8988相比,IPSC上清对胰腺癌细胞株Patu8988细胞的增殖、黏附、迁移、侵袭能力及克隆形成能力有促进作用(均p<0.05),并能抑制H2O2诱导的Patu8988的凋亡(P<0.05).结论:胰星状细胞可能通过增强胰腺癌细胞株Patu8988的增殖、黏附、迁移、侵袭能力及克隆形成能力,并抑制其的凋亡,在胰腺癌的发展和转移中起重要作用.     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

124例耐多药结核分枝杆菌基因突变特征分析

目的对临床分离的耐多药结核分枝杆菌相关基因的突变特征进行分析。方法对124例耐多药结核分枝杆菌以及50株敏感株的耐药相关基因(包括异烟肼inh A、kat G、oxyR-ahp C间隔区以及利福平rpo B)进行序列测定,分析其基因突变情况。结果异烟肼耐药inh A基因突变率为14.5%;kat G基因突变率为70.2%(87/124),主要位于315位;oxyR-ahp C间隔区突变率为15.3%;inh A、kat G两种基因同时突变率75.0%,三种基因同时突变率为89.5%。利福平rpo B基因突变的检出率高达95.2%,突变主要发生在531、526、516位点。结论我省耐多药菌异烟肼耐药相关基因最常见突变为kat G 315、inh A C-T(-15)、axyR-ahp C间隔区(-10)C-T,利福平为rpo B531、526、516。结合MDR-TB耐药相关基因的特征分析,可以建立一种快速、准确、特异的适合于我省的检测结核菌耐多药性的新方法。     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

CagA-Hp抗体IgG与胃炎的组织学分析

研究幽门螺杆菌(Hp)感染与胃炎的关系。方法对204例慢性胃炎患者胃粘膜进行观察分析,并测定其中137例Hp阳性患者血清CagA-Hp抗体IgG水平,与组织学对照。结果慢性萎缩性胃炎伴肠上皮化生患者血清CagA抗体IgG明显高于对照组(P＜0.01);其他类型胃炎患者血清CagA抗体IgG水平无明显增高(P＞0.05)。结论CagA-Hp可能是导致慢性萎缩性胃炎伴肠上皮化生的因素之一,对这类患者应密切随访观察。     

慢阻肺急性加重期患者预后的影响因素分析

目的探讨慢性阻塞性肺病急性加重期(AECOPD)患者预后的相关危险因素。方法回顾性调查、收集58例AECOPD患者可能影响其预后的相关因素,并对其分别进行单因素分析。并进行Logistic多元逐步回归进行多因素分析,筛选影响AECOPD患者预后的独立危险因素。结果单因素分析后将结果 P0.1的因素纳入多因素Logistic回归,分析发现是否合并呼吸衰竭、气促程度、白细胞计数、APACHEⅡ、应用抗氧化剂、慢阻肺治疗依从性为影响AECOPD患者预后不佳的独立因素(P0.05)。结论根据AECOPD患者预后的独立危险因素,及早判断,选择合适的后续治疗方案,对提高其生存率及生存质量具有重要意义。