长春瑞滨对人肺腺癌973细胞放射增敏作用的实验研究

目的:探讨长春瑞滨(NVB)对非小细胞肺癌细胞放射效应影响及其与放射的最佳结合序贯。方法:以指数生长期的人肺腺癌973细胞为研究对象,采用克隆形成分析法进行0.1nM及1nMNVB与放射不同结合序贯实验,研究NVB与放射结合效应,利用"多靶单击"数学模型(SF=1-(1-е-D/D0)N)进行曲线拟合,获得细胞存活曲线及平均致死剂量、准阈剂量、D0比和增敏比等参数,进行效应评估。结果:0.1nM及1nMNVB照前、照后给药组的增敏比(SER)分别为0.957和0.989,1.295和1.042;0.1nM及1nMNVB照前、照后给药组的D0比分别为1.073和1.099,1.374和1.106。表明0.1nMNVB照前、照后给药时均无放射增敏作用;1nMNVB照前、照后给药时均与放射效应具有较明显协同作用,且照前给药组的协同作用明显强于照后给药组。结论:0.1nMNVB不具有增强放射效应的作用,1nMNVB具有较明显放射效应增强作用,且照前给药组的协同作用明显强于照后给药组。     

吉西他滨联合X射线照射对肺癌细胞系放射增敏作用的初步研究

目的 探讨吉西他滨(GEM)是否对非小细胞肺癌具有放射增敏作用,并对GEM的放射增敏机制进行初步探讨.方法 用克隆形成分析法观察GEM对p53基因突变的人肺腺癌细胞系(973细胞)的放射增敏效应.流式细胞术观察照射前后973细胞周期分布和细胞凋亡,分析其与p53基因突变是否为放射增敏机制.结果 10 nmol/L GEM照前、照后给药均具有极轻微放射增敏作用;100 nmol/L GEM照前、照后给药时均具有明显放射增敏作用,且照前给药组的增敏作用明显强于照后给药组.p53基因突变影响细胞周期再分布及细胞凋亡,但与GEM的放射增敏作用无关.结论 100 nmol/L GEM具有明显放射增敏作用,p53基因突变、细胞周期再分布及细胞凋亡不是GEM放射增敏作用的主要机制.     

5—氟脲嘧啶,顺铂不同时相给药对放疗效果的影响

5－FU、DDP既是有效的化疗药物又对辐射有增敏作用。作为增敏药物在其与放射合用时要达到最大的增敏效果，必然有最佳的放化时间顺序。为探讨此问题，我们采用离体细胞克隆培养技术，观察了5-Fu DDP联合放射，在放射前、中、后不同时相给药5小时，对人肺腺癌Anip973细胞的影响。结果，3个放化结合组DEF值均大于1，细胞存活率比单照和单纯给药明显减低；先药后照组细胞杀灭倍数为4.57，大于给药中间照射组和先照后药组；DEF值以先药后照组为最高（2．2）；细胞平均存活率，先药后照组低于其它两组，分别为0．096，0．125，0．115.本实验结果显示，5－Fu＋DDP联合放射的增敏作用，在放射前给药并保持一定的药物作用时间，效果最好。     

吉西他滨联合放射线照射对人胆管癌细胞放射增敏作用的实验研究

目的 研究和探讨吉西他滨联合放射线照射对胆管癌细胞的放射增敏作用.方法 取指数生长期的胆管癌细胞(QBC939),采用细胞克隆形成分析法检测吉西他滨单药毒性,确定IC10、IC50和IC90作为下一步实验的药物浓度.将QBC939细胞分为对照组、单纯药物组、单纯照射组及照射前、后吉西他滨IC10、IC50和IC90浓度下作用24 h组,X线照射剂量为0、1、2、4、6、8、10 Gy.采用多靶单击数学模型拟合细胞存活曲线,分别用D0、Dq比计算放射增敏比(SERD0、SERD).结果 吉西他滨对QBC939细胞的Ic10、IC50和IC90值分别为0.1、11.0、21.5 nmol/L.吉西他滨低浓度(IC10)时只在照后给药且较低照射剂量区域(≤2 Gy)表现出放射增敏作用(SERDq=1.52);中浓度(IC50)时照前给药增敏作用最广泛(SERD0=1.27,SERDq=116.93),照后给药只在较低剂量区域(≤2 Gy)有放射增敏作用(SERDq=81.85);高浓度(IC90)时照射前后给药均具有一定放射增敏作用,但照前给药的作用明显强于照后给药.结论 吉西他滨与X线联合应用具有一定的放射增敏作用,但应注意药物浓度及给药顺序.     

布比卡因合并高温的体外序贯效应研究

本实验采用人宫颈癌细胞系Hela对布比卡因合并44℃,30分钟高温的序贯效应进行了研究。先布比卡因后加温组(BH序贯)与先热后药组(HB序贯)相比,细胞存活率明显下降(BH47.7％,HB63％,P<0.01),细胞死亡率由22.75％增至31.5％(P<0.01),提示BH序贯所产生的热增敏效应强于NB序贯。细胞形态学观察也表明BH序贯产生的细胞损伤程度明显高于相反序贯。     

紫杉醇联合放射线照射对肺腺癌细胞放射增敏作用的研究

目的 探讨化疗药紫杉醇是否对肺腺癌A973细胞有放射增敏作用.方法 取指数生长期的人肺腺癌细胞A973,采用成克隆分析法检测紫杉醇毒性,确定IC10、IC50和IC90剂量作为药物浓度.分析照射前后紫杉醇IC10、IC50和IC90浓度下作用24 h,照射剂最分别为0、1、2、4、6、8、10 Gy时的细胞存活分数,并用多靶单击模型拟合细胞存活曲线.采用流式细胞术分析不同浓度紫杉醇作用0、2、4、6、10、18、24 h,A973细胞周期分布变化.结果 紫杉醇对A973细胞的IC10、IC50和IC90剂量分别为0.5、2.6和8.7 nmol/L.IC10剂量紫杉醇照前给药增敏比为0.97(D0值比)、1.01(D0值比)、1.00(SF2值比),照后给药为0.97、1.02、1.02;IC50剂量照前给药为1.06、129.00、2.61,照后给药为0.94、129.00、2.14;IC90剂量照前给药为1.00、120.00、2.09,照后给药为0.98、120.00、2.09.IC10剂量紫杉醇对A973细胞无明显的G2+M期阻滞作用,而IC50和IC90剂量紫杉醇分别于2和18 h将A973细胞阻滞在G2+M期.结论 紫杉醇对肺腺癌细胞A973产生明显的放射增敏作用,且照射前后给药均有相似的增敏作用,中高浓度剂量联合小剂量X线照射增敏效果最好.     

三氧化二砷对纤维肉瘤细胞放射增敏作用的研究

目的 研究和探讨三氧化二砷（As2O3）是否对纤维肉瘤细胞有放射增敏作用。方法以人纤维肉瘤细胞HTl080为实验对象，首先检测As2O3的单药毒性，确定IC10、IC50和IC90。放射增敏作用的实验分为空白对照组、单纯给药组、单纯照射组（包括1、2、4、6、8、10Gy剂量）、照射前加药组（于照射前24h加入设定浓度的As2O3，药物作用24h后进行照射）和照射后加药组（于照射后即刻加入设定浓度的As2O3，药物作用24h）。所有实验均重复3次。采用克隆形成分析法观察单纯照射和照射联合As2O3对细胞的杀伤作用。计算细胞的存活分数，用多靶单击模型进行拟合并做图。结果 HT1080细胞的IC10、IC50和IC90剂量分别为0．57、3．67和12．0μmol／L。无毒剂量的As2O3照射前给药增敏比（SER）为0．86（Do值比）、0．98（SF2值比），照射后给药SER为0．99（Do值比）、1．09（SF2值比）。IC50剂量的As2O3照射前给药SER为0．90（Do值比）、0．87（SF2值比），照射后给药SER为1．14（Do值比）、1．08（SF2值比）。IC90剂量的As2O3照射前给药和照射后给药的SER均为1．14（Do值比）、3．20（SF2值比），As2O3对低剂量照射的放射增敏作用好于高剂量照射（SERSF2〉SERDo）。结论 As2O3对HT1080纤维肉瘤细胞具有一定的放射增敏作用，为临床放疗和As2O3联合应用提供了实验依据。     

布比卡因合并高温不同序贯对Hela细胞热敏感性的影响

我们曾证实局部麻醉药布比卡因(bupivacaine)与加温合并应用后可增加肿瘤细胞的热杀伤效应。为进一步探讨不同序贯处理的热增敏差异并为今后临床治疗方案的设计提供理论依据,本实验观察了不同给药顺序对细胞热敏感性的影响,初步结果证实先给药后加温序贯处理可达最大热增敏效应。 实验所用细胞为人宫颈癌细胞系Hela,细胞浓度为1×10~6/ml。将等量接种的细胞分为5组:(1)正常对照组(C组);(2)药物组(B组),每毫升细胞悬液中加入50μg布比卡因,37℃作用60分钟;(3)加温组(H组),44℃,30-分钟水浴加温;(4)先给药后加温组(BH组);(5)先加温后给药组(HB组)。观察指标为细胞生长曲线(连     

吉西他滨对非小细胞肺癌细胞放射增敏的实验研究

目的　研究低浓度吉西他滨对非小细胞肺癌细胞系A5 4 9(wtp5 3)的放射增敏作用、并探讨用药后最佳放射时间。方法　①以不同浓度的吉西他滨与A5 4 9细胞作用 2 4h ,MTT法选择生长抑制率≤ 10 %的药物浓度 (IC10 )。②将细胞分为对照组 (Ct)、单纯用药组 (Ch)、单纯照射组 (R1、R2 )、未弃药照射组 (CR)及弃药后照射组 (DCR1、DCR2 )。R1组行单纯60 Co2Gy照射 ;Ch组单纯用药 ;CR组及DCR1组均用IC10 浓度作用 2 4h ,CR组于 2 4h末、DCR1分别于弃药后 30min、1、3、6、12及 2 4h予60 Co2Gy照射。比较细胞存活分数 ,选择最佳弃药时间 (T)。③用IC10 药物浓度作用DCR2 2 4h ,于弃药后T时间经60 Co0 .5、1.0、2 .0、4 .0、6 .0、8.0Gy剂量照射 ,绘制细胞存活曲线 ;与R2 组 (同剂量单纯照射 )比较 ,计算增敏比 (D0 值比和Dq 值比 )。结果　IC10 浓度吉西他滨的放射增敏作用在弃药后 3h最为明显 [增敏比分别为 1.88(D0 值比 )、1.90 (Dq 值比 ) ];弃药 6h后与对照组比较差异无显著性意义 (P >0 .0 5 ) ;这种增敏作用在照射剂量较低时 ( 0 .5、1.0Gy)即已明显表现出来。结论　低浓度吉西他滨对离体非小细胞肺癌A5 4 9(wtp5 3)细胞系具有较好的放射增敏作用 ,且最佳照射时间为弃药后 3h。     

CpG ODN107增强人鼻咽癌CNE-2细胞对β射线照射的敏感性

目的：筛选能提高鼻咽癌CNE-2细胞对β射线放射敏感性的CpGODN序列，观察筛选获得的CpGODN序列放射增敏的作用特点，为寻找新的鼻咽癌放疗增敏剂提供实验依据。方法：应用MTT实验筛选21种CpGODN序列中对人鼻咽癌CNE-2细胞放射增敏作用最强的序列，以MTT实验、集落形成实验、划痕实验和流式细胞术检测该最强作用序列与β射线联合作用对CNE-2细胞的增殖、集落形成、细胞迁移、细胞周期与凋亡的影响。结果：筛选实验显示CpGODN107对CNE-2细胞具有最高的增敏比（1．59&#177;0．06），CpGODN107和β射线联合作用能以剂量依赖方式显著抑制CNE-2细胞的增殖，抑制效应显著高于单纯照射（P〈0．05，P〈0．01）；联合作用显著抑制CNE-2细胞集落形成和迁移能力，显著诱导细胞周期阻滞于G0／G1期，显著增加细胞凋亡（P〈0．01），上述作用效应均明显强于单纯B射线照射（P〈0．05或P〈0．01）。结论：CpGODN107可显著增强人鼻咽癌CNE-2细胞对β射线的照射敏感性，其放射增敏作用可能与诱导细胞周期阻滞和凋亡有关。     

Calculation of Life-Time Death Probability due Malignant Tumors Based on a Sampling Survey Area in China

Purpose: To calculate the probability of one person’s life-time death caused by a malignant tumor andprovide theoretical basis for cancer prevention. Materials and Methods: The probability of one person’s deathcaused by a tumor was calculated by a probability additive formula and based on an abridged life table. Alldata for age-specific mortality were from the third retrospective investigation of death cause in China. Results:The probability of one person’s death caused by malignant tumor was 18.7% calculated by the probabilityadditive formula. On the same way, the life-time death probability caused by lung cancer, gastric cancer, livercancer, esophageal cancer, colorectal and anal cancer were 4.47%, 3.62%, 3.25%, 2.25%, 1.11%, respectively.Conclusions: Malignant tumor is still the main cause of death in one’s life time and the most common causesof cancer death were lung, gastric, liver, esophageal, colorectal and anal cancers. Targeted forms of cancerprevention and treatment strategies should be worked out to improve people’s health and prolong life in China.The probability additive formula is a more scientific and objective method to calculate the probability of oneperson’s life-time death than cumulative death probability .     

Comparison of Life-Time Death Probability due to Malignant Tumors in Different Regions of China Based on Chinese Surveillance Sites

Objective: To estimate and comparably analyze the life-time death probability (LDP) caused by malignant tumorsin different regions in 2004 and 2014. Methods: LDP was calculated by a probability additive formula and based on anabridged life table. Data on age-specific mortality was obtained from the National Cause-of- Death Surveillance Datasetin 2014 using surveillance sites in China and data on age-specific mortality was collected from the third retrospectiveinvestigation of death cause in China in 2004. Results: LDP caused by malignant tumors, lung cancer, gastric cancer,liver cancer, esophageal cancer, colorectal, and anal cancer were 19.2%, 5.6%, 2.8%, 2.8%, 1.7%, 1.3%, respectively. Inaddition, we calculated LDP caused by malignant tumors in three different regions of China. LDP caused by malignanttumors were 21.2%, 6.1%, 3.1%, 2.8%, 2.0%, and 1.5% in the eastern region, were 18.3%, 5.5%, 2.7%, 3.0%, 1.5%,and 1.1% in the central region, and were 16.7%, 4.6%, 2.3%, 2.8%, 1.6%, and 1.2% in the western region, respectively.Additionally, LDP caused by malignant tumors in 2004 and 2015 were compared. We found that LDPs caused bymalignant tumors, lung cancer, and colorectal cancer have increased in the past decade, while LDPs caused by gastriccancer, liver cancer, and esophageal cancer have experienced a decreasing trend. Conclusions: Malignant tumorswere still the main cause of death in one’s life time, giving rise to LDP. LDP caused by malignant tumours has twodivisions. First, traditional upper digestive system cancers related to long-term chronic infection, such as esophagealcancer, gastric cancer, and liver cancer, which has shown a significant downward trend. Second, lung and colorectalcancers related to the environmental factors and lifestyle, which are on the rise.     

Household air pollution and risk of incident lung cancer in urban China: A prospective cohort study

Household air pollution (HAP) is associated with the development of lung cancer, yet few studies investigated the exposure patterns and joint associations with tobacco smoking. In our study, we included 224 189 urban participants from China Kadoorie Biobank (CKB), 3288 of which diagnosed with lung cancer during the follow-up. Exposure to four HAP sources (solid fuels for cooking/heating/stove and environmental tobacco smoke exposure) was assessed at baseline. Distinct HAP patterns and their associations with lung cancer were examined through latent class analysis (LCA) and multivariable Cox regression. A total of 76.1% of the participants reported regular cooking and 52.2% reported winter heating, of which 9% and 24.7% used solid fuels, respectively. Solid fuel heating increased lung cancer risk (Hazards ratio [HR]: 1.25, 95% confidence interval [CI]: 1.08-1.46). LCA identified three HAP patterns; the “clean fuel cooking and solid fuel heating” pattern significantly increased lung cancer risk (HR: 1.25, 95% CI: 1.10-1.41), compared to low HAP pattern. An additive interaction was observed between heavy smoking and “clean fuel cooking and solid fuel heating” (relative excess risk [RERI]: 1.32, 95% CI: 0.29-2.47, attributable proportion [AP]: 0.23, 95% CI: 0.06-0.36). Cases resulting from solid fuel account for ~4% of total cases (population attribute fraction [PAF]_overall: 4.31%, 95% CI: 2.16%-6.47%, PAF_{ever smokers}: 4.38%, 95% CI: 1.54%-7.23%). Our results suggest that in urban China, solid fuel heating increased the risk of lung cancer, particularly among heavy smokers. The whole population could benefit from cleaner indoor air quality by reducing using solid fuels, especially smokers.     

大肠癌组织endostatin的表达与血管生成的关系

目的　探讨内皮抑制素 ( endostatin)蛋白在大肠癌组织中的表达及其与 VEGF、微血管密度 ( MVD)的关系。方法　应用免疫组化 S- P法 ,检测 6 8例大肠癌及其正常大肠组织 endostatin表达、VEGF表达及 MVD。结果　 endostatin蛋白可在大肠癌组织的肿瘤细胞、内皮细胞及浸润淋巴细胞中表达。 endostatin表达与 Dukes分期密切相关。endostatin高表达组的 MVD( 12 .35± 4.96 )明显低于 endostatm低表达组 ( 16 .38± 6 .2 8)。 VEGF染色阳性组与阴性组的 endostatin蛋白表达差异无显著性。结论　 endostatin在大肠癌组织的不同类型细胞中出现 ,与大肠癌血管生成密切相关 ,endostatin的表达水平随着 Dukes分期的进展而降低反映了血管生成促进因子和抑制因子之间平衡的转变。     

Anti-HER2 antibody enhances the growth inhibitory effect of anti-oestrogen on breast cancer cells expressing both oestrogen receptors and HER2

Anti-oestrogen is effective for the treatment of oestrogen receptor (ER)-positive breast carcinomas, but most of these tumours become resistant to anti-oestrogen. It has been suggested that anti-oestrogen therapy may induce a HER2 signalling pathway in breast cancer cells and this may cause resistance to anti-oestrogen. Thus, it is conceivable that combined therapy with anti-oestrogen and anti-HER2 antibody might be more effective. In the present study, we investigated the effect of combined treatment with a humanized anti-HER2 monoclonal antibody, rhumAbHER2 (trastuzumab), and an anti-oestrogen, ICI 182,780, on the cell growth of three human breast cancer cell lines which respectively express different levels of ER and HER2. The combined treatment enhanced the growth inhibitory effect on ML-20 cells, which express a high level of ER and a moderate level of HER2, but showed no additive effect on either KPL-4 cells, which express no ER and a moderate level of HER2, or MDA-MB-231 cells, which express no ER and a low level of HER2. It is also suggested that both the antibody and anti-oestrogen induce a G1-S blockade and apoptosis. These findings indicate that combined treatment with anti-HER2 antibody and anti-oestrogen may be useful for the treatment of patients with breast cancer expressing both ER and HER2.     

Additive Properties of Crude,Age Specific and Age Adjusted Rates for Cancer Incidence and Mortality

Background: In National Cancer Registry Programme (NCRP) reports, various rates are routinely provided for 50 cancer sites of males and 54 cancer sites of females. Very often, depending on our interest, we wish to see these rates for group of cancers like head and neck cancers, oral cancers, and reproductive cancers. In such a situation, the desired rates are calculated independently from the actual data and reported. The question is can we derive the rates for groups of cancers from the published reports when the data is provided only for the individual sites? Objective: In the present paper, an attempt is made to explore the mathematical properties of various rates to derive them directly for the group of cancer sites from the published data when the rates are provided only for the individual sites. Source of data: The cancer incidence data collected by two urban Population Based Cancer Registries (PBCRs), under the network of NCRP for the period of 2006-08 was considered for the study purposes. The Registries included were: Bangalore and Bhopal. Results: In the present communication, we have shown that the crude rate (CR), age specific rates and age-adjuste rates (AAR) all possess additive properties. This means, given the above rates for individual sites, the above rates can be calculated for groups of sites by simply adding them. In terms of formula it can be stated that CR(Site1+Site2+++ SiteN) = CR(Site1)+CR(Site2)+++ CR(SiteN). This formula holds good for age specific rates as well as for AAR. This property facilitates the calculation of various rates for defined groups of cancers by simply adding the above rates for individual sitesfrom which they are made up.     

Multivariate Analysis of Prognostic Factors in Gastric Cancer Patients Using Additive Hazards Regression Models

Background and Objectives: Gastric cancer is the second leading cause of cancer death worldwide and isthe most common type of cancer in Iran. The objective of this research was to apply additive hazards models tothe study of survival of patients with gastric cancer and to compare with results obtained using the Cox model.Methods: We retrospectively studied 213 patients with gastric cancer who were registered in one referral cancerregistry center in Tehran, Iran. Age at diagnosis, sex, presence of metastasis, tumor size, histology type, lymphnode metastasis, and pathologic stages were entered into analysis using the Cox model and additive hazardmodels. To visualize a covariate effect over time, the estimated cumulative regression function by the Aalen’smodel was examined. Results: The five-year survival rate and the median life expectancy in the studied patientswere 14.6% and 29.6 months, respectively. Multivariate Cox and Additive hazards models analysis identifiedage at diagnosis, tumor size and pathologic stage as independent prognostic factors for the survival of patientswith gastric cancer. Moreover, pathologic stage had a late or delayed effect according to the Aalen’s plot. Otherclinicopathological characteristics were not statistically significant. Conclusion: Since Cox and Aalen models givedifferent aspects of the association between risk factors and the study outcome, it seems desirable to use thentogether to give a more comprehensive understanding of data. Our results also suggest that early detection ofpatients at younger age and in primary stages is important to increase survival of patients with gastric cancer.     

Multivariate analysis of prognostic factors in gastric cancer patients using additive hazards regression models

Background & Objectives: Gastric cancer is the second leading cause of cancer death worldwide and is the most common type of cancer in Iran. The objective of this paper is to apply the additive hazards models to the study of survival of patients with gastric cancer and to compare results obtained by the additive hazards models and the Cox model. Methods: We retrospectively studied 213 patients with gastric cancer who were registered in one referral cancer registry center in Tehran, Iran. Age at diagnosis, sex, presence of metastasis, tumor size, histology type, lymph node metastasis, and pathologic stages were entered into analysis using the Cox model and additive hazard models. To visualize a covariate effect over time, the estimated cumulative regression function by the Aalen’s model is examined. Results: The five-year survival rate and the median life expectancy in the studied patients were 14.6% and 29.6 months, respectively. Multivariate Cox and Additive hazards models analysis identified that age at diagnosis, tumor size and pathologic stage were independent prognostic factors for the survival of patients with gastric cancer (P<0.05). Moreover, pathologic stage has a late or delayed effect according to the Aalen’s plot. Other clinicopathological characteristics were not statistically significant (P>0.05). Conclusion: Since Cox and additive models give different aspects of the association between risk factors and the study outcome, it seems desirable to use together to give a more comprehensive understanding of data. Our results also suggest that early detection of patients in younger age and in primary stages is important to increase survival of patients with gastric cancer.     

顺铂与阿霉素合用的抗瘤活性与剂量的关系

以体外培养瘤细胞集落形成率、荷瘤小鼠生命延长率(ILS)和小鼠实体瘤的抑瘤率作为药效的评价指标,观察顺铂(DDP)与阿霉素(ADM)合用的剂量效应关系。小剂量DDP与ADM的联用时相加作用明显。一种药已达有效量再与另一药小剂量合用其效应与单药足量的效应无显著差异;若两药有效量联合,虽能提高ILS,但表现出毒性增强。