姜黄素抑制胃腺癌SGC7901细胞增殖和表皮生长因子受体表达的研究

背景：姜黄素是一种有价值的植物抗癌物。有研究报道其能抑制多种肿瘤细胞生长，诱导肿瘤细胞凋亡。目的：探讨姜黄素对胃癌细胞增殖的影响及其可能机制。方法：①胃腺癌SGC7901细胞经常规培养，给予不同浓度的姜黄素处理，观察细胞生长情况，采用甲基噻唑基四唑（MTT）比色法检测细胞增殖，计算抑制率。②以不同浓度的姜黄素处理胃腺癌SGC7901细胞，采用免疫荧光染色和流式细胞术（FCM）检测表皮生长因子受体（EGFR）表达的变化。③以低浓度姜黄素或转化生长因子（TGF）-α处理胃腺癌SGC7901细胞，或以低浓度姜黄素和TGF-α同时处理细胞，采用MTT比色法检测细胞增殖，计算抑制率。结果：①姜黄素可显著抑制胃腺癌SGC7901细胞增殖，并随其浓度的增加而作用增强（P均〈0．001）。当给予10、20、30μmol／L姜黄素作用72h时，抑制率分别为22．4％、46．9％和67．2％。②姜黄素使胃癌细胞EGFR表达显著下降。当给予10、20、30μmol／L姜黄素作用48h时，EGFR表达分别下降了10．5％、17．1％和30．0％。③当给予5I．μmol／L低浓度姜黄素处理细胞72h时，细胞增殖速度无明显变化；给予30μg/L TGF-α处理，细胞增殖速度加快；同时给予5μmol/L低浓度姜黄素和30μg/L TGF-α处理时，则TGF—α刺激的胃癌细胞增殖明显受抑制，抑制率为21．5％。结论：姜黄素能抑制胃腺癌SGC7901细胞增殖，并能抑制其EGFR的表达，进而抑制TGF—α的促细胞增殖作用。     

姜黄素抑制胃癌细胞cyclin D1表达的研究

[目的]研究姜黄素对胃癌细胞cyclin D1表达的影响,探讨其抗肿瘤作用机制。[方法]①胃腺癌SGC7901细胞在体外常规培养,用免疫荧光染色、流式细胞仪(FCM)检测转化生长因子α(TGF-α)及其受体即表皮生长因子受体(EGFR)的表达情况。②胃腺癌SGC7901细胞先用无血清培养48 h,以便于观察不同处理后细胞cyclin D1表达的变化。然后用2.5%低浓度血清培养,并加入TGF-α或大蒜油处理,或同时加入TGF-α和大蒜油处理,用免疫荧光染色、FCM检测细胞cyclin D1表达的变化。[结果]①胃癌细胞常规培养48 h后,TGF-α和EG-FR表达的阳性率分别为46.80%和57.78%。②当在细胞培养液中加入30μg/L TGF-α作用5 h,细胞cyclin D1表达的阳性率增加了8.43%(P<0.01);当加入20μmol/L姜黄素作用5 h,cyclin D1表达的阳性率下降了21.37%(P<0.01);同时加入TGF-α和姜黄素处理细胞,与单加TGF-α比较,cyclin D1表达下降了25.32%(P<0.01),下降程度大于单加姜黄素引起的下降程度。[结论]姜黄素可通过抑制TGF-α的自分泌、旁分泌促增殖环路,发挥其抑制胃癌细胞增殖作用。推测这是姜黄素抗肿瘤作用机制之一。     

钒化钠抑制人胃癌SGC7901细胞增殖的作用机理

目的通过观察钒化钠对人胃癌SGC7901细胞周期蛋白cyclinD1表达的影响,探讨其对人胃癌SGC7901细胞增殖抑制的作用机理。方法应用MTT法测定钒化钠对人胃癌SGC7901细胞的生长抑制作用;用Western-blot法检测钒化钠对人胃癌SGC7901细胞周期蛋白cyclinD1表达水平的变化。结果一定浓度的钒化钠使人胃癌SGC7901细胞增殖周期密切相关的cyclinD1蛋白表达降低。结论一定浓度的钒化钠能明显抑制人胃癌SGC7901细胞的生长,钒化钠的抗肿瘤机制可能与cyclinD1蛋白表达降低有关。     

Wortmannin对胃癌SGC7901细胞增殖及Cyclin H和Cyclin D1蛋白表达的影响

目的观察Wortmannin对胃癌SGC7901细胞增殖及细胞周期调控蛋白Cyclin H和Cyclin D1表达的影响，探讨Wortmannin抑制细胞增殖的机制。方法采用MTT法观察Wortmannin对胃癌细胞SGC7901增殖的影响，采用免疫细胞化学方法检测Cyclin H和Cyclin D1的表达。结果以不同浓度Wortmannin处理人中分化胃腺癌SGC7901细胞系48h后，该细胞的增殖受抑，呈剂量依赖性，随药物浓度的增大，OD值明显减少，同时增殖抑制率明显升高，且与对照组相比存在显著性差异（P〈0．05）；Wortmannin在下调Cyclin H同时亦可下调Cydin D1表达。结论Wortmannin有明显的抑制人中分化胃腺癌SGC7901细胞系增殖的作用，其分子机制可能是Wortmannin通过下调Cyclin H和Cyclin D1的表达，来抑制胃癌SGC7901细胞增殖，达到抗肿瘤的作用，因此该药有望成为胃癌化疗的一种新药。     

NS-398对人胃癌细胞株增殖及COX-2表达的影响

目的 体外观察选择性环氧化酶2(COX-2)抑制剂NS-398对人胃癌细胞株SGC7901细胞增殖及COX-2表达的影响。方法 采用噻唑蓝(MTT)法观察NS-398对SGC7901细胞增殖的影响，流式细胞仪(FCM)研究NS-398对SGC790l细胞凋亡的作用．免疫细胞化学观察COX-2蛋白的表达。结果 体外NS-398能减少SGC790l细胞株COX-2的表达．对SGC7901有细胞毒作用．可增加细胞凋亡率。结论 体外NS-398对SGC7901细胞增殖有抑制作用。可能与抑制COX-2表达及诱导细胞凋亡有关。     

免疫抑制酸性蛋白单克隆抗体MI-2体外抗肿瘤作用的观察

作者采用MTT比色法观察了本室自制免疫抑制酸性蛋白单克隆抗体MI-2的体外抗肿瘤作用。结果表明:MI-2在浓度为7.81 μg/ml时即可明显抑制胃癌细胞株SGC 7901的生长(抑制率7.5％±2.4％,P<0.01),并见剂量依赖型表现;在LAK细胞与SGC 7901胃癌细胞的效靶比为10:1时,加入1.95 μg/ml的MI-2即可明显增强LAK细胞的细胞毒作用(增强效应为206.3％,P<0.01),也呈剂量依赖性表现。作者还发现MI-2的这种抗肿瘤作用与补体无关。     

PTK抑制剂对TGFα刺激的胃癌细胞增殖和DNA合成的抑制作用

目的探索蛋白酪氨酸激酶(PTK）剂Tyrphostin51对TGFα刺激的胃癌细胞增殖和DNA合成的抑制作用。方法利用细胞体外培养技术,观察PTK抑制剂Typhostin51对胃癌SGC7901细胞生长的抑制作用,用3H-TdR掺入法检测其对细胞DNA合成的影响;探索其对TGFα刺激的细胞生长和DNA合成的抑制效应。结果在TGFα刺激下,SGC7901增殖加快,细胞生长曲线上移,DNA合成增加;在Tyrphostin51作用下,细胞增殖有所减慢,生长曲线稍下移,DNA合成也减少;而TGFα刺激的细胞生长和DNA合成明显地被Tyrphostin51所抑制。结论PTK抑制剂Tyrphostin51能减缓血清刺激、明显抑制TGFα刺激的胃癌SGC7901细胞生长和DNA合成。     

MicroRNA-133a在5-氟尿嘧啶促进胃癌细胞BGC823及SGC7901细胞凋亡中的功能研究

[目的]研究microRNA-133a(miR-133a)在5-氟尿嘧啶(5-Fu)诱导胃癌细胞BGC823及SGC7901凋亡中的作用。[方法]用荧光定量PCR检测经5-Fu(IC50值)处理过胃癌细胞miR-133a的表达;构建过表达miR-133a的胃癌细胞株并行细胞增殖、细胞流式验证miR-133a的生物学功能;5-Fu分别处理过表达及敲低miR-133a的胃癌细胞株后,行细胞增殖、细胞流式、Western Blot观察细胞生长及凋亡情况。[结果]5-Fu诱导BGC823及SGC7901内源性miR-133a的表达(50%,P0.0001,24h),miR-133a促进胃癌细胞凋亡,敲低miR-133a可以抑制5-Fu对胃癌细胞的促凋亡作用。[结论]5-Fu通过诱导胃癌细胞BGC823及SGC7901内源性miR-133a的表达,促进胃癌细胞凋亡。     

奥曲肽对胃癌细胞系生长和胰岛素样生长因子-Ⅰ、Ⅱ含量的影响

背景:生长抑素类似物奥曲肽对上皮细胞的增殖和胃肠激素的分泌具有抑制作用,并能抑制某些肿瘤的生长。目的:研究奥曲肽对胃癌细胞系体外生长的抑制作用和对胰岛素样生长因子(IGF)鄄Ⅰ、IGF鄄Ⅱ含量的影响。方法:应用四甲基偶氮唑蓝(MTT)比色法检测经奥曲肽处理的人胃癌细胞系SGC7901的生长情况,并以放射免疫测定检测SGC7901细胞培养液中IGF鄄Ⅰ、IGF鄄Ⅱ的含量。结果:0.01、0.1、1.0和10.0μg/ml奥曲肽对SGC7901细胞的生长均有抑制作用(与阴性对照组比较,P<0.01),抑制率分别为7.5%、11.2%、20.8%和19.9%,其抑制作用具有良好的量效关系和饱和现象。经0.1和1.0μg/ml奥曲肽处理的SGC7901细胞,培养液中IGF鄄Ⅰ、IGF鄄Ⅱ的含量显著低于阴性对照组(P<0.01)。结论:奥曲肽能显著抑制胃癌细胞系SGC7901的体外生长,下调细胞培养液中IGF鄄Ⅰ、IGF鄄Ⅱ的含量。奥曲肽可能通过抑制IGF鄄Ⅰ、IGF鄄Ⅱ的分泌而发挥抑制胃癌生长的作用。     

TGFα对胃癌细胞周期的促进作用

目的:探索TGFα对胃癌细胞周期的促进作用,为进一步从多个环节阻断其自分泌、旁分泌环路及胞内信号传导通路奠定基础。方法:利用细胞体外培养技术,观察TGFα对胃癌SGC7901细胞的促增殖作用;细胞经G_1期同步化后,用流式细胞仪检测TGFα作用不同时间的细胞周期变化,用~3H-TdR掺入法检测TGFα对细胞DNA合成的影响。结果:TGFα对胃癌SGC7901具有明显的促增殖作用,细胞生长曲线上移;TGFα作用4、6h的S期细胞和作用8、10h的G_2~ M期细胞均明显增加;作用5h的DNA合成也显著高于对照组。结论:TGFα能够刺激胃癌SGC7901细胞生长,明显促进其细胞周期进程。     

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。     

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.     

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。     

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。     

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     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.     

Angiographic diagnosis of the degree of serosal invasion of carcinoma of the colon

Angiography using Prostaglandin El^® was performed on 38 patients with carcinoma of the colon in order to diagnose the degree of serosal cancer invasion. The findings at angiography were classified into four groups:1) AG-S3, abnormal change (irregularity and/or encasement) up to marginal vessels; 2) AG-S2, abnormality up to vasa recta; 3) AG-S1, abnormality of penetrating branches of vasa recta within the wall of the colon; and 4) AG-S0, no distinct findings of abovementioned vessels. These angiographic findings were compared with both macroscopic and microscopic serosal cancer invasion. Angiographic diagnosis is in accord with the macroscopic findings in 84.2 percent of cases. Angiographic diagnosis is in accord with the microscopic findings in 32.4 percent of cases. Macroscopic findings confirm the angiographic diagnosis precisely but the conflict with microscopic findings should not be overlooked. This may be the result of inflammatory change, adhesion, and fibrosis around carcinoma of the colon.