Anti-tumor Effect and Mechanism of SEA-Fab’ Coupled Protein on Gastric Tumor

Superantigen(SAg)has strong ability tosti mulate actevated T lymphocytes,which hasbeen shownto be highly efficient for i mmunothera-py for tumor.Methods and compositions emplo-ying SAg in combination with i mmunotherapeuticproteins have been found to provide more effectivetreat ment than either component used alone[1].Inthis study,SEA-Fab’coupled protein was synthe-sized to study the anti-tumor effect and mechanismof SEA-Fab’.1MATERIALS AND METHODS1.1MaterialsSEA lyophilized po…     

The Protective Effect of Rosuvastatin on Ischemic-Brain Injury and Its Mechanism

The statins, which lower plasma cholesterol levels, are 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors. To date, stains have developed to third generation, which include five commonly used stains: lovastatin, pravastatin, simvastatin, fluvastatin and atorvastatin. Recently, a new statin, named rosuvas-tatin, was used in the third stage of clinical trial. Rosu-vastatin, in contrast to most other statins, has the more powerful capability to lower plasma cholesterol levels,…     

Postconditioning＇s Protection of THSG on Cardiac Ischemia-reperfusion Injury and Mechanism

Summary 2,3,5,4′-tetra-hydroxystilbene-2-O-glucoside (THSG), the water-soluble active components extracted from dried tuber root ofPolygonum multi florum (Polygonaceae), can promote the release of nitric oxide (NO) from vascular endothelial cells and has strong antioxidation. The post-conditioning's protection of THSG on cardiac ischemia-reperfusion injury and the mechanism were investigated. After reperfusion for 3 h following occlusion of rat left anterior descending coronary artery (LAD) for 30 min. SαT recovery speed, arrhythmia and cardiac infarct size were observed. The ischemic size and infarct size was identified by using Evans blue and TTC staining methods re-spectively. The results showed that the infarct size in THSG 7. 5 mg/kg postconditioning group was significantly decreased from 43.6%±9.1% in mode group to 16.5%±6.5% (P<0.01). SαT recovery was quicker and the incidence of arrhythmia (55.6% vs 100%,P<0.05) was significantly lower than in control group. The infarct size in THSG+glybenclamide group was greater than in THSG group, but equivalent to that in control group (46.8%±9.8% vs 43.6%±9.1%,P>0.05), SαT recovery speed slower and the incidence of arrhythmia also lower (33.3% vs 100%,P<0.01), suggesting that glybenclamide could abolish the effects of THSG postconditioning reducing the cardiac infart size. It was concluded that THSG administration before reperfusion could effectively alleviate the cardiac reperfusion injury and possessed the postconditioning effects of reducing cardiac infarct size, which might be related with the K_ATP channel opening. YE Shaojian, female, born in 1963, Associate Professor, M. D., Ph. D.     

Effect and Mechanism of Superantigen Staphylococcal Enterotoxin Therapy for Mouse Gastric Tumor

Summary:The anti-tumor effect and mechanism of the staphylococcal enterotoxin A(SEA)werestudied.The mouse gastric tumor model was produced by subcutaneously inoculating gastric tumorcells(MGC80-3).The experimental group was treated with SEA,and the control group was treatedwith normal saline.The percentage of tumor generation and tumor mass was measured.The resultsshowed that the percentage of the tumor tumor generation in the SEA-treated mice was lower than in thecontrol group,but there was no significant difference(P>0.05).However,the tumor mass in theexperimental group was significantly lighter than in the control group,with the difference bing verysignificant(P<0.001).There were more CD_4~+ T cells and CD_8~+ T cells in the tumor of the micetreated with SEA than those of the control group.SEA has an obvious anti-tumor effect on mice gas-tric tumor.The mechanism might be that SEA induces the effect of superantigen-dependent cell me-diated cytotoxicity to the tumor cells.     

Comparative Study on Cancer Cell Apoptosis between Gastric and Intestinal-type Human Gastric Carcinoma

It has been generally accepted that constancy of to-tal cell number in tissues depends on the balance of cell proliferation and apoptosis. Abnormality of either side will induce malignant conversion of cells. We employed the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay and im-munohistochemical method (SABC) and histochemical method (AB-PAS) to study the relationship between apoptosis of cancer cells and the expression of oncogeneMDM2, expre…     

Mechanism and Correlated Factors of SAM Phenomenon after Aortic Valve Replacement

To investigate the mechanism and correlated factors of systolic anterior motion (SAM) phenomenon after aortic valve replacement, 48 patients with severe aortic valvular stenosis were studied. Tested by echo-Doppler one week after aortic valve replacement, the patients were divided into two groups: SAM group and non-SAM group. The data of the left ventricular end-diastolic di-ameters, the left ventricular end-systolic diameters, the left ventricular outflow diameters, the thick-ness of the interventricular septum, the posterior wall of left ventricle, the blood velocities of left ventricular outflow and intra-cavitary gradients were recorded and compared. The results showed that no patients died during or after the operation. The blood velocities of left ventricular outflow was in-creased significantly in 9 patients (>2.5 m/s), and 6 of them developed SAM phenomenon. There was significant difference in all indexes (P<0.05 or P<0.01) except the posterior wall of left ventricle (P>0.05) between two groups. These indicated that the present of SAM phenomenon after aortic valve replacement may be directly related to the increase of blood velocities of left ventricular out-flow and intra-cavitary gradients. It is also suggested that smaller left ventricular diastolic diameters, left ventricular systolic diameters, left ventricular outflow diameters and hypertrophy of interven-tricular septum may be the anatomy basis of SAM phenomenon.     

Effect of universal salt iodization on antithyroid drugs

Iodine deficiency disease （IDD） is common in China. An universal salt iodization （USl） program has been implemented by the Chinese government since 1996. As a result, the goiter rate in 8- to 10-year old children decreased from 20.4% in 1995 to 5.8% in 2002.1 But the adverse effects of iodine excess such as iodine-induced hyperthyroidism, iodine-induced goiters, iodine-induced hypothyroidism, etc. have become a great concern to healthcare professionals as well as the general population. The impact of USI on antithyroid drugs （ATDs） might become a potential challenge to address. With a special grant from the Department of Disease Control, the Health Ministry of China, we conducted a prospective study on the effects of USI on ATDs at the thyroid section of the Endocrinology Clinic of Peking Union Medical College Hospital （PUMCH）, Beijing.     

Research of Active Immunotherapy on Unexplained Recurrent Spontaneous Abortion（URSA）

There are many factors which may cause URSA except for chromosome abnormality, dyscrinism, infection, autoimmunologic disease, uterine malformation and etc. And 40%- 70% of them can not be identified and we called unexplained recurrent spontaneous abortio…     

SWA-Fab''''对肿瘤细胞的凋亡作用

目的研究SEA-Fab'对肿瘤细胞的凋亡作用及单克隆抗体于肿瘤定向治疗作用.方法实验分为三组SEA-Fab'、SEA及对照组,三组肿瘤细胞分别用SEA-Fab'、SEA及PBMC+Walker-256细胞处理,在24～72 h内观察肿瘤细胞的凋亡情况.结果SEA-Fab'组、SEA组的肿瘤细胞指数分别为(34.6%～68.9%)和(15.5%～31.9%)高于对照组(5.5%～12.5%),差异存在显著性,SEA-Fab'组高于SEA组差异显著.结论SEA-Fab'在激活T细胞和杀死肿瘤细胞效果好于SEA,将来有可能利用单克隆抗体来作定向靶位治疗.     

苦参碱对胃癌抑制作用的实验研究

目的 建立稳定的裸鼠胃癌模型,观察苦参碱的抗肿瘤作用.方法 将20只胃癌模型裸鼠随机分为4组,分别为对照组、高浓度苦参碱(100 mg/kg·d-1,HM)组、低浓度苦参碱(50 mg,/kg·d-1,LM)组、环磷酰胺(20 mg/kg·d-,CTX)组.测定各组胃癌成瘤和区域淋巴结肿大情况,并采用病理学检查来明确有无癌肿浸润生长及区域淋巴结转移.结果 建立裸鼠胃癌模型的成功率为100％.大体样本观察发现,HM组、LM组和CTX组胃癌成瘤肿物大小明显小于对照组;并无明显的区域淋巴结肿大;差异有统计学意义(P＜0.05).镜下观察发现,HM组无腹腔内区域淋巴结转移并无癌肿浸润生长,与CTX组无明显差异,但与对照组相比差异有显著性意义(P＜0.05).结论 苦参碱有良好的抗肿瘤和抗转移活性;苦参碱对人胃癌潜在抑制作用提供理论基础.     

蒿甲醚对胃癌细胞和胰腺癌细胞的体外杀伤作用

目的观察蒿甲醚(ART)在体外对胃癌细胞株和胰腺癌细胞株的杀伤作用以及对细胞增殖和细胞凋亡的影响。方法选择人胃癌细胞株SGC-7901和MKN-45及胰腺癌细胞株SW-1990和BXPC-3,采用MTT法检测不同浓度ART对不同肿瘤细胞的抑制作用;应用流式细胞仪检测ART对肿瘤细胞细胞周期和细胞凋亡的影响。结果MTT结果显示ART对各株肿瘤细胞均具有显著的杀伤作用(P<0.05),且其细胞毒作用与时间-剂量呈正相关(P<0.05);流式细胞仪检测显示,ART使各株肿瘤细胞阻滞于G0/G1期,并诱导细胞凋亡。结论ART在体外对SGC-7901、MKN-45、SW-1990、BXPC-3细胞株有明显的细胞毒作用,且具有时间-剂量效应关系;其抑制作用与阻滞细胞周期和诱导肿瘤细胞凋亡有关。     

灭活肿瘤细胞免疫小鼠诱生的自身抗体及其作用探讨

目的探讨灭活肿瘤细胞免疫诱导机体产生抗dsDNA自身抗体及该自身抗体与抗肿瘤效应的关联性。方法以灭活SP2／0肿瘤细胞3次免疫Balb／c小鼠,末次免疫2周后采血,ELISA法检测血清中抗dsDNA自身抗体的表达水平。进一步用自身或不同来源的肿瘤细胞攻击经灭活SP2／0免疫的Balb／c小鼠,观察免疫保护效应;或以免疫血清与肿瘤细胞共孵育后接种小鼠,观察肿瘤生长和生存。结果灭活肿瘤细胞免疫小鼠可诱导产生较高滴度的抗dsDNA自身抗体。体内攻击实验表明：抗dsDNA自身抗体滴度的降低与肿瘤细胞攻击后小鼠肿瘤生长呈负相关,免疫血清与肿瘤细胞孵育后接种小鼠可明显延缓小鼠的成瘤时间,延长生存期。结论灭活肿瘤细胞免疫小鼠诱生的抗dsDNA自身抗体与体内抗肿瘤效应具有关联性。     

桑黄胞外多糖抗肿瘤活性研究

目的研究桑黄胞外多糖对小鼠S180实体瘤、腹水瘤的生长抑制作用。方法将昆明种小鼠接种S180实体瘤或腹水瘤后随机分组,灌胃给予不同剂量100、200、400mg/(kg·d)的桑黄胞外多糖,以灌胃生理盐水和环磷酰胺为空白对照组和阳性对照组。检测受试药物对小鼠S180实体瘤生长的抑制作用以及对荷瘤小鼠脾脏指数和胸腺指数的影响,计算腹水型荷瘤小鼠的存活时间。结果桑黄胞外多糖显著增加荷瘤小鼠的脾脏指数和胸腺指数;3个剂量的桑黄胞外多糖对S180实体瘤的抑瘤率分别为31.25%、36.86%、44.38%;并且可以降低S180腹水瘤细胞的分裂指数,延长腹水型荷瘤小鼠的存活时间。结论桑黄胞外多糖具有较强的抗肿瘤作用。     

胃癌组织中Angiopoietin-2、TRAIL与凋亡关系的研究

目的研究血管生成素-2(Angiopoietin-2)、肿瘤坏死因子相关凋亡诱导配体(TNF related apoptosis indueing ligand,TRAIL)在胃癌组织中的表达,探讨二者与细胞凋亡的关系.方法应用免疫组化技术检测67例胃腺癌组织中及相对应的正常胃黏膜中Angiopoietin-2、TRAIL蛋白的表达,用原位末端标记(TUNEL)技术检测癌组织中的凋亡指数(AI).结果angiopoietin-2在胃癌组织中明显表达(52.39%),而在癌旁正常黏膜呈弱表达(7.46%),低分化癌的angiopoietin-2的表达水平高于中高分化癌,有淋巴结转移者的angiopoietin-2的表达高于无淋巴结转移者(P均<0.05).TRAIL在正常胃黏膜中的阳性表达率97.01%高于癌组织中的阳性表达率47.76%(P<0.05);TRAIL蛋白的表达与肿瘤的分化程度有关,分化程度越低,TRAIL的表达率越低(P<0.05),TRAIL蛋白表达与胃癌的直径、部位、大体分型,浸润深度及有无淋巴结转移及患者的年龄、性别无关(P>0.05).胃癌组织中细胞凋亡指数为1.85±0.66.angiopoietin-2蛋白表达阳性组与阴性组、TRAIL蛋白阳性组与阴性组中凋亡指数分别存在着显著性差异(P<0.05);Angiopoietin-2与TRAIL蛋白表达之间无明显的相关性(rs=0.112,P>0.05).结论Angiopoientin-2可抑制肿瘤细胞凋亡,促进肿瘤的恶性进展;TRAIL可诱导胃癌细胞发生凋亡.     

miR-365对胃癌SGC-7901细胞的作用及其机制

摘要 目的：探究miR-365对胃癌细胞的作用机制。方法：提取人正常胃黏膜上皮细胞ＲGM-1和胃癌SGC-7901内的miR-365,通过RT-PCR测定其表达的差异;采用脂质体转染的方法将miR-365转入细胞中。MTT法检测转染后的SGC-7901增殖情况;流式细胞术检测转染后细胞的凋亡情况;Western blotting检测转染48h后p21及Cyclin D1的表达。结果： miR-365的表达显著低于RGM-1细胞 (P<0.05)。转染miR-365 mimics后, miR-365转染组中miR-365表达显著高于空白对照组和阴性对照组。转染2d后,空白对照组中miR-365的OD值显著高于干扰组细胞,差异显著(P<0.05)。miR-365 转染组细胞的凋亡率明显增加 (P <0.05)。转染后的p21蛋白表达量显著升高,而Cyclin D1的表达量显著下降 (P <0.05).结论：转染miR-365促进细胞凋亡的同时也抑制了胃癌细胞的增殖。     

芒柄花黄素对人胃癌细胞MKN-45荷瘤裸鼠模型的抑制作用及机制研究

目的 研究芒柄花黄素对人胃癌细胞MKN-45荷瘤裸鼠模型的抑制作用及作用机制.方法 建立人胃癌MKN-45细胞荷瘤裸鼠癌症模型,经环磷酰胺(20 mg/kg)和芒柄花黄素(10、20、40mg/kg)干预14 d,观察荷瘤重量变化及应用TUNEL染色评估荷瘤组织中细胞凋亡数量,并用蛋白免疫印迹法(Western blot)检测荷瘤内源性p38丝裂原活化蛋白激酶(p38MAPK)及细胞周期蛋白(CyclinD)表达.结果 与模型对照组比较,芒柄花黄素明显抑制胃癌细胞MKN-45荷瘤裸鼠肿瘤的生长(P＜0.01),并且肿瘤组织中细胞凋亡计数增加(P＜0.01).同时,芒柄花黄素干预组肿瘤组织中的p38MAPK蛋白表达增加,CyclinD蛋白水平减少(P＜0.01).结论 芒柄花黄素具有明显抑制胃癌细胞MKN-45增殖作用,其机制与激活细胞内MAPK信号转导通路而诱导细胞凋亡有关.     

姜黄素转化产物抗肿瘤的研究

目的 利用红曲霉菌对姜黄素进行微生物转化,研究姜黄素转化总产物对H22荷瘤小鼠肿瘤的抑制作用及其可能机理,为进一步筛选新型高效的姜黄素类抗肿瘤新药奠定基础.方法 昆明种小鼠腋下接种H22细胞造成荷瘤小鼠模型,姜黄素红曲霉菌转化产物组、菌体对照组、底物对照组,分别以高、中、低剂量(2、1、0.5 g/kg)进行干预治疗;设立正常对照组、荷瘤模型组、环磷酰胺对照组.连续治疗12d,于末次给药后12 h,取血分离血清,测定肿瘤坏死因子(TNF-α)、白细胞介素-2 (IL-2);剥取肿瘤,称重,计算抑瘤率;取肝脏、胸腺、脾脏,称重计算脏器指数.结果 姜黄素转化产物高、中、低剂量组的抑瘤作用分别为37.08％、48.91％、26.55％,明显高于同剂量的菌体对照组和底物对照组,但并未高于环磷酰胺对照组.小鼠脏器指数结果显示转化产物各剂量组均高于荷瘤模型组,而菌体对照组、底物对照组与荷瘤模型组比较没有显著差异(P＞0.05).姜黄素转化产物各剂量组血清TNF-α和IL-2水平均高于荷瘤模型组,且高于菌体对照组及底物对照组,并有显著差异(P＜0.05).结论 姜黄素转化后对肿瘤的抑制作用增强,能够增加机体主要免疫器官的脏器指数,提高机体的免疫功能.姜黄素转化后可能是通过提高体内TNF-α水平来直接杀伤肿瘤,或提高IL-2水平增强T细胞免疫应答来抑制肿瘤生长.