三氧化二砷对胃癌BGC-823细胞增殖及细胞周期的影响

[目的]探讨三氧化二砷（AS2O3）对胃癌BGC-823细胞增殖的抑制作用及对细胞周期的影响。[方法]应用MTT方法检测三氧化二砷对胃癌BGC-823细胞增殖的抑制作用，流式细胞仪进行细胞周期解析及凋亡检测．[结果]三氧化二砷对胃癌BGC823细胞具有杀伤作用，且呈时间-浓度依赖性抑制肿瘤细胞的增殖．72h抑制细胞50％增殖的药物浓度约为3．3μmol／L，与对照组比差异显著（P=0．0048）；5μmol／LAs2O3作用24h，细胞形态学可见典型的凋亡细胞及M期阻滞；流式细胞仪进行细胞周期解析结果提示，G2/M期细胞由正常对照的25％增加到46．3％，出现了明显的G2/M期阻滞，亚二倍体凋亡细胞由4％增加到18％。[结论]三氧化二砷抑制胃癌细胞的增殖．诱导细胞周期阻滞及凋亡。     

奥曲肽对人胃癌BGC-823细胞增殖和凋亡影响的研究

目的：研究生长抑素类似物奥曲肽（octreotide,OCT）对胃癌BGC-823细胞增殖、凋亡、细胞周期的影响及其可能的作用机制。方法：不同浓度的OCT作用于体外培养的人胃癌BGC-823细胞,以5～FU作为阳性对照,应用M1Tr法分析细胞增殖的抑制作用,流式细胞仪测定细胞周期分布和凋亡率,AO—EB染色观察细胞形态变化。结果：OCT对BGC-823细胞的生长、增殖产生抑制作用,该抑制作用具有量效、时效关系和饱和性;OCT作用后细胞呈典型的凋亡形态学改变,流式细胞仪检测的细胞凋亡率和AO—EB染色测得细胞凋亡率与对照组相比较差异有显著性（P〈0．05）;BGC-823细胞经OCT作用后,G1期细胞数明显增加,S细胞数明显减少,细胞被阻滞于G1／S期。结论：10^-5-10^-3g/L浓度的OCT能够抑制胃癌BGC-823细胞增殖,机制可能与其诱导肿瘤细胞的凋亡和出现G1／S期阻滞有关。     

大蒜素对人胃癌细胞株SGC-7901和BGC-823生长的影响

目的：研究大蒜素对人胃癌细胞株SGC-7901、BGC-823增殖抑制作用及对细胞周期的影响。方法：传代培养人胃癌细胞，MTT法测定细胞增殖抑制率并测定药物半数抑制率（IC50）；流式细胞仪检测细胞周期的改变。结果：大蒜素对SGC-7901和BGC-823两种细胞的生长均有明显的抑制作用，且呈浓度依赖性，72h IC50分别为20和30μg／mL；以72h IC50浓度大蒜素分别作用于两种胃癌细胞株24、48h后，流式细胞检测与对照组比G0／G1期细胞减少，G2／M期细胞明显增加，P〈0．01。提示两种胃癌细胞株经大蒜素处理后．细胞周期阻滞于G2／M期。结论：大蒜素可使人胃癌细胞株SGC-7901和BGC-823细胞的增殖明显受到抑制；细胞周期被阻滞在G2／M期。     

奥曲肽对人胃癌BGC-823细胞增殖和凋亡影响的研究

目的:研究生长抑素类似物奥曲肽(octreotide,OCT)对胃癌BGC-823细胞增殖、凋亡、细胞周期的影响及其可能的作用机制.方法:不同浓度的OCT作用于体外培养的人胃癌BGC-823细胞,以5-FU作为阳性对照,应用MTT法分析细胞增殖的抑制作用,流式细胞仪测定细胞周期分布和凋亡率,AO-EB染色观察细胞形态变化.结果:OCT对BGC-823细胞的生长、增殖产生抑制作用,该抑制作用具有量效、时效关系和饱和性;OCT作用后细胞呈典型的凋亡形态学改变,流式细胞仪检测的细胞凋亡率和AO-EB染色测得细胞凋亡率与对照组相比较差异有显著性(P<0.05);BGC-823细胞经OCT作用后,G1期细胞数明显增加,S细胞数明显减少,细胞被阻滞于G1/S 期.结论:10-5-10-3g/L 浓度的OCT能够抑制胃癌BGC-823细胞增殖,机制可能与其诱导肿瘤细胞的凋亡和出现G1/S期阻滞有关.     

亚砷酸钠对人胃癌细胞株BGC-823的作用机制

 目的探讨亚砷酸钠对人胃癌细胞株BGC-823的作用机制。方法采用MTT法、光镜、电镜、流式细胞仪检测和免疫细胞化学法研究亚砷酸钠对BGC-823细胞生物学行为的影响。结果不同浓度的亚砷酸钠均可有效抑制BGC-823细胞生长,且具有浓度和时间依赖性,其中效浓度为4.86μmol/L。流式细胞仪检测发现亚砷酸钠作用不同时间后,细胞均出现G2/M期阻滞。形态学观察显示亚砷酸钠作用72h后,细胞出现典型的凋亡和坏死形态学改变。免疫细胞化学法发现亚砷酸钠能显著上调细胞Caspase-3蛋白的表达。结论亚砷酸钠对BGC-823细胞的生长有明显的抑制作用,并可诱导细胞周期阻滞及细胞凋亡和坏死,其机制可能与其抑制ROS的清除,上调Caspase-3蛋白的表达有关。     

尼美舒利对胃癌细胞BGC823 COX-2、VEGF表达的影响

目的 研究尼美舒利（Nimesulide）对人胃癌细胞株BGC-823增殖和凋亡的干预作用，揭示其抗癌机制。方法 采用MTT法、流式细胞仪等检测细胞增殖、细胞周期和凋亡率以及细胞的形态学改变，同时检测尼美舒利对胃癌细胞COX-2、VEGF表达的影响。结果 尼美舒利抑制胃癌细胞的IC50μM／L。增殖抑制率达到80．31％，流式细胞仪分析发现100-200μM／L的尼美舒利作用48h后，细胞被阻滞于S期，凋亡率分别为5．69％，10．58％；光学显微镜观察到凋亡典型的形态学特征；免疫细胞化学结果显示尼美舒利作用后能降低COX2、VEGF蛋白表达，与对照组比较，具有非常显著性差异（P〈0．01）。结论 尼美舒利能显著抑制人胃癌细胞株BGC-823的生长，此作用可能与降低COX2、VEGF蛋白表达有关。     

曲古菌素A对胃癌细胞系BGC-823组蛋白H4乙酰化水平及细胞凋亡的作用

[目的]探讨组蛋白去乙酰化酶（HDAC）抑制剂曲古菌素A（TSA）对胃癌细胞系BGC-823中组蛋白H4乙酰化水平及细胞凋亡的影响。[方法]免疫细胞化学法检测TSA干预前后胃癌细胞系BGC-823中乙酰化组蛋白H4的表达，流式细胞仪检测细胞周期及细胞凋亡率。[结果]TSA干预后胃癌细胞系BGC-823中乙酰化组蛋白H4的表达水平明显升高，乙酰化组蛋白H4阳性细胞数从1．38±1．02上升至31．6±1．02，与未干预相比两者表达有显著性差异（P〈0．01），流式细胞仪分析显示G2期细胞增多，从0．01％上升至19．17％，细胞凋亡率增加到29．9％。[结论]TSA可促进胃癌细胞系BGC-823中乙酰化组蛋白H4的表达，诱导BGC-823细胞凋亡。     

舒林酸对胃癌细胞生长抑制作用的体外观察

背景与目的:体外研究舒林酸对人胃癌BGC-823细胞的生长抑制作用,探讨其作用机制。材料与方法:将舒林酸作用于人胃癌BGC-823细胞,并设置不同的作用浓度和作用时间。以体外药物敏感实验(单核细胞直接细胞毒测定Mono-nuclearcelldireccytotoxicityassay,MTT)检测舒林酸在不同浓度及不同作用时间下对人胃癌BGC-823细胞的增殖抑制效应;流式细胞仪检测胃癌细胞周期分布;透射电镜观察药物作用后细胞凋亡的形态学改变;免疫组化检测细胞增殖(ki-67)、凋亡抑制基因(bcl-2)及还氧合酶(COX-2)蛋白的表达。结果:舒林酸对人胃癌BGC-823细胞有生长抑制作用,使G0/G1期比例增高,S期比例降低;透射电镜观察到细胞凋亡的形态特征及凋亡小体,而ki-67、bcl-2及COX-2蛋白表达阳性率显著降低;上述作用均呈时间和剂量依赖性。结论:舒林酸在体外具有良好的抑制胃癌BGC-823细胞生长的作用,其机制涉及影响细胞周期分布、诱导细胞凋亡及抑制COX-2、ki-67及bcl-2蛋白的表达。     

毛兰素诱导胃癌细胞SGC-7901凋亡的实验研究

[目的]研究毛兰素诱导胃癌细胞SGC-7901凋亡的机制。[方法]MTT法检测毛兰素对人胃癌细胞SGC-7901的增殖抑制作用，Annexin—Ⅴ／PI双染色法流式细胞仪检测细胞凋亡率，PI染色法流式细胞仪定量检测细胞周期分布变化，同时比色法检测细胞caspase-3活性变化。[结果]毛兰素能明显抑制胃癌细胞SGC-7901增殖，且呈浓度依赖关系，48h IC50值为0．056μg／ml；毛兰素能诱导胃癌细胞SGC-7901凋广且呈时间和浓度依赖性，使细胞周期阻滞于S期,但未见caspase-3激活。[结论]毛兰素能诱导胃癌细胞SGC-7901凋亡，可能与使细胞周期阻滞于S期有关，但未见caspase-3激活。     

舒林酸抗胃癌细胞体外生长的实验研究

目的观察舒林酸对胃癌BGC-823细胞增殖、凋亡的影响,探讨其作用机制。方法将不同浓度的舒林酸体外作用于人胃癌BGC-823细胞,采用倒置显微镜观察BGC-823细胞形态改变,四甲基偶氮唑蓝（MTT）比色法检测胃癌细胞增殖,流式细胞仪检测胃癌细胞周期分布及凋亡,透射电镜观察凋亡,免疫组化检测ki-67、bcl-2及环氧合酶-2（COX-2）蛋白的表达。结果舒林酸作用后,细胞伪足回缩,变小、变圆,排列松散或聚集成团,出现悬浮现象,瘤巨细胞减少或不见瘤巨细胞。舒林酸可抑制BGC-823细胞增殖,使G0／G1期细胞比例增高,S期细胞比例降低。1．2mmol／L舒林酸作用48h,G0／G1期细胞增至93．8％,S期细胞比例降至3．4％。舒林酸作用后,细胞凋亡率显著上升,1．2mmol／L舒林酸作用48h,细胞凋亡率升至54．9％,而ki-67、bcl-2及COX-2蛋白表达阳性率显著降低;透射电镜可观察到细胞凋亡的形态特征及凋亡小体。上述作用均呈时间和剂量依赖性。结论舒林酸可抑制胃癌BGC--823细胞体外生长,其机制涉及影响细胞周期分布、诱导细胞凋亡及抑制ki-67、bcl-2及COX-2蛋白的表达。     

Prognostic Significance of Inflammation-associated Blood Cell Markers in Nonmetastatic Clear Cell Renal Cell Carcinoma

ObjectivesOur objective was to evaluate the effect of the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and red blood cell distribution width (RDW) on the survival outcomes of nonmetastatic clear cell renal cell carcinoma (ccRCC).Materials and MethodsWe accessed our single-center, urologic-oncologic registry to extract the data for patients who had undergone nephrectomy for nonmetastatic ccRCC. The optimal cutoff for these markers was determined using X-tile software, and survival analyses using Cox regression were performed.ResultsA total of 687 patients had undergone nephrectomy. The optimal cutoffs for NLR, PLR, LMR, and RDW were 3.3, 210, 2.4, and 14.3%, respectively. The NLR, PLR, LMR, and RDW were significantly associated with a larger pathologic tumor size, and stage, more aggressive Fuhrman grade, and the presence of tumor necrosis. After adjusting for age, baseline Eastern Cooperative Oncology Group, pathologic tumor and nodal stage, and Fuhrman grade, only PLR remained an independent prognostic marker for both cancer-specific survival (hazard ratio, 2.69; 95% confidence interval, 1.36-5.33; P = .004) and overall survival (hazard ratio, 2.19; 95% confidence interval, 1.36-3.50; P = .001). When the PLR was included with the Leibovich score and University of California, Los Angeles, integrated staging system, the Harrell’s c-index increased from 0.854 to 0.876 and 0.751 to 0.810, respectively, for cancer-specific survival at 5 years after nephrectomy. When risk stratified by the Leibovich risk group and UCLA integrated staging system, PLR was a significant prognostic factor only within the intermediate- to high-risk groups.ConclusionsPLR is a robust prognostic marker in nonmetastatic ccRCC that clearly outperforms other inflammatory indexes in those who had undergone nephrectomy. However, its prognostic effect was limited in the low-risk category of ccRCC.     

Cell kinetics

Cell kinetic concepts have pervaded radiation therapy since the early part of the 20th century and have been instrumental in the development of modern radiotherapy. In this review, the fundamental radiobiological concepts that have been developed based on cell kinetic knowledge will be revisited and discussed in the context of contemporary radiation therapy. This will include how the proliferation characteristics, variation in sensitivity during the cell cycle and the extent of radiation-induced cell cycle delay translate into a variable time for the expression of damage, how cell kinetics interacts with hypoxia and how the response to fractionated radiation schedules is influenced by cell kinetics in terms of repair, redistribution, reoxygenation and repopulation. The promise of combining radiation with new biologically targeted agents and the potential of non-invasive positron emission tomography imaging of proliferation are areas where cell kinetics will continue to influence radiotherapy practice.     

Cell Size Following Irradiation in Relation to Cell Cycle

The cell volume of Ehrlich ascites tumour cells was studied following a radiation dose of 5.0 Gy. The cell volume increased 12 to 30 hours after irradiation by about 20 per cent, was normal at about 50 hours, and increased again at 72 hours. In order to explain these changes the composition of the cells in cell cycle was studied. In addition, the cell volume of irradiated cells from the various parts of the cell cycle, separated by centrifugal elutriation, was measured. The changes in the mean cell volume of unseparated cells could be explained by variations in the cell cycle composition of the cell population. Irradiated cells from the various parts of the cell cycle did not deviate from the volume of non-irradiated cells. The cell volume doubled during the cell cycle. This increase was, however, not linear.     

Inhibition of Glioma Cell Proliferation by Neural Stem Cell Factor

Summary Neural stem cells (NSC) have unique differentiation-, proliferation-, and motility properties. To investigate whether they secrete factors that interfere with the proliferation of glioma cells, we grew glioma cells in conditioned medium (CM) obtained from cultures of neurospheres including neural stem / progenitor cells (NSPC) isolated from embryonic (E14)- or adult mouse brain or fetal human brain. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and BrdU-labeling assays showed that CM from NSPC (NSPC/CM) contained factor(s) that inhibited the proliferation of glioma cells by 28–87%. Filter-fractionation of NSPC/CM revealed that the 50,000–100,000 nominal molecular weight limit (NMWL) fraction contained the inhibitory activity. On the basis of these observations we transplanted 203G glioma cells and/or NSPC into the intrathecal space of the cisterna magna of mice to investigate whether NSPC interfere with the proliferation of glioma cells in vivo. Mice transplanted with both 203G and NSPC survived significantly longer than did mice transplanted only with 203G. We concluded that NSPC secrete factor(s) that may control glioma cell proliferation.     

High Occurrence of Non-Clear Cell Renal Cell Carcinoma in Oman

It is conventionally accepted that renal cell carcinoma (RCC) occurs in older patients and the clear cell type is the most common histology. However, ethnic variations exist and this study was carried out to determine the epidemiological pattern of RCC in Oman. Ninety RCC patients who presented to a tertiary care center in the Sultanate of Oman from 2010 to 2014 were studied. The main findings were that the median age of presentation was low, more patients presented with localized stage, and there was a higher incidence of non-clear (especially papillary) histology. Data from other Gulf countries and possible reasons for the different profile are discussed.     

Changes in Cell Characteristics Due to Culture Conditions in Cell Lines From Human Small Cell Lung Cancer

Eight cultured cell lines were established from human smallcell lung cancers. Every cell line showed the morphologicaland biochemical characteristics of small cell cancer. Changesin cell characteristics were observed in many of these celllines when culture conditions were changed: "oat cell type"changed to "intermediate cell type" and vice versa when serum-freemedium was changed to serum-supplemented medium; a deficiencyof vitamin A in the medium caused a change to squamous cellsand vice versa; and a tumor promoter (teleocidin B) enhancedthe adherence of these cells to the surface of plastic culturedishes. These findings provide evidence that many small celllung cancer cell lines can change their morphology with changesin the environment of the cells.     

Inhibition of Natural Killer Cell Cytotoxicity by Cell Growth-related Molecules

Certain MHC class I molecules on target cells are known to inhibit the cytotoxic action of NK cells. By using monoclonal antibody (mAb) Cho-1, we have found inhibitory non-MHC class I cell surface molecules that are noncovalently-associated with 200 kDa and 40 kDa antigens. Poly I-C-induced rat NK cells were not cytotoxic to rat fetus-derived fibroblast WFB cell line. In contrast, NK cells were cytotoxic to H- ras oncogene-induced transformants of WFB, W14 and W31. FACS analysis indicated that mAb Cho-1 reacts with WFB, but not with W14 and W31 cells. Thus, this antigen may disappear concomitantly with cell growth and transformation. Cho-1 antigens were also expressed on other NK-resistant lines, such as mouse BALB3T3 fibroblast, EL-4 lymphoma and human fibroblast HEPM. However, they were not expressed on NK-sensitive mouse YAC-1 and H- ras transformant (Brash) of BALB3T3 cells. Furthermore, treatment of target cells with IFN-γ clearly induced the cell surface expression of Cho-1 antigens, and conferred a resistance to NK cytolysis on target cells. These data strongly suggest that Cho-I antigen expression may correlate with target cell susceptibility to NK cells. Indeed, treatment of NK-resistant WFB as well as HEPM cells with F(ab')₂ fragments of mAb Cho-1 resulted in the acquisition of susceptibility to NK cytolysis. Cho-1 antigens may be novel molecules that regulate the NK resistance of cells.