Immunotherapy against antigenic tumors: a game with a lot of players

Our understanding of how immune responses are generated and regulated drives the design of possible immunotherapies for cancer patients. For that reason, we first describe briefly the actual immunological theories and their common perspectives about cancer vaccine development. Second, we describe cancer vaccines that are able to induce tumor-specific immune responses in cancer patients. However, these responses are not always followed by tumor rejection. At the end of the review, we discuss two possible reasons that might explain this dichotomy of cancer immunology. First, the immune response generated, although detectable, may not be quantitatively sufficient to reject the tumor. Second, the tumor microenvironment may modulate tumor cell susceptibility to the systemic immune response induced by the immunization. Finally, we discuss what, in our opinion, might be the best way to improve cancer vaccine strategies and how the relationship between the tumor and its surroundings might be studied in more details. Received 21 June 2001; received after revision 15 August 2001; accepted 15 August 2001     

Initiation of cancer and other diseases by catechol ortho-quinones: a unifying mechanism

Exposure to estrogens is a risk factor for breast and other human cancers. Initiation of breast, prostate and other cancers has been hypothesized to result from reaction of specific estrogen metabolites, catechol estrogen-3,4-quinones, with DNA to form depurinating adducts at the N-7 of guanine and N-3 of adenine by 1,4-Michael addition. The catechol of the carcinogenic synthetic estrogen hexestrol, a hydrogenated derivative of diethylstilbestrol, is metabolized to its quinone, which reacts with DNA to form depurinating adducts at the N-7 of guanine and N-3 of adenine. The catecholamine dopamine and the metabolite catechol (1,2-dihydroxybenzene) of the leukemogen benzene can also be oxidized to their quinones, which react with DNA to form predominantly analogous depurinating adducts. Apurinic sites formed by depurinating adducts are converted into tumor-initiating mutations by error-prone repair. These mutations could initiate cancer by estrogens and benzene, and Parkinson's disease by the neurotransmitter dopamine. These data suggest a unifying molecular mechanism of initiation for many cancers and neurodegenerative diseases and lay the groundwork for designing strategies to assess risk and prevent these diseases. Received 4 September 2001; received after revision 28 November 2001; accepted 2 December 2001     

姜黄素对鼻咽癌细胞株CNE-2Z-H5裸鼠移植瘤增殖的影响

目的研究姜黄素对人低分化鼻咽癌细胞系亚克隆株CNE-2Z-H5裸鼠移植瘤生长和增殖的影响。方法复制人低分化鼻咽癌细胞系亚克隆株CNE-2Z-H5裸鼠移植瘤模型,观察姜黄素对移植瘤生长的影响。结果裸鼠体内实验显示姜黄素可以抑制移植瘤的生长。不同浓度姜黄素组移植瘤瘤重与溶剂对照组比较有降低趋势,高剂量组降低更明显,差异有极显著性(P<0.001),抑瘤率达59.75%。结论姜黄素可以抑制CNE-2Z-H5细胞裸鼠移植瘤的生长,其可能在鼻咽癌的治疗中具有一定的价值,值得进一步深入研究。     

大鼠胶原诱导性关节炎早期外周血TNF-α与性激素水平的动态观察及相关性研究

同步观察大鼠胶原诱导性关节炎早期血浆肿瘤坏死因子-α(TNF-α)与性激素水平的变化,探讨TNF-α和性激素在类风湿关节炎(RA)发病中的作用及其相关性。用Ⅱ型胶原与完全弗氏佐剂诱导SD大鼠胶原性关节炎(CIA),检测CIA大鼠不同时间点的血浆TNF-α、雌二醇和睾酮,同时观察其发病时间、滑膜新生血管形成、关节炎指数评分。随着CIA免疫时间的延长,滑膜轻度增厚,滑膜新生血管开始增多,关节炎指数评分渐增加,TNF-α含量也升高,睾酮水平下降,雌二醇水平无明显变化;TNF-α含量与睾酮水平呈负相关关系(r=-0.364,P<0.05),血浆TNF-α含量与雌二醇水平无明显相关关系(r=-0.209,P>0.05)。TNF-α在RA炎症反应的细胞因子网络中起重要作用,性激素与RA的发病也有密切关系,雄激素是天然的抗炎激素,雌激素的作用可能与其浓度有关。     

海萝多糖抗突变与抗肿瘤作用的研究

用海萝多糖粗提物灌胃昆明种小鼠,观察海萝多糖粗提物对环磷酰胺(CP)诱发小鼠染色体突变和精子畸变的抑制作用和对荷S180肉瘤小鼠的抑瘤作用.实验结果显示:海萝多糖粗提物可使环磷酰胺诱发的小鼠骨髓嗜多染红细胞(PCE)微核率和精子畸形率明显降低,具有显著的抗突变作用,且呈现一定的剂量效应关系;海萝粗多糖对S180肉瘤也有明显的抑制作用,并有一定的剂量关系.结果表明,海萝多糖粗提物有明显的抗突变、抗肿瘤作用.     

激光治疗肿瘤的计算研究

根据激光治疗肿瘤的机理建立了激光治疗肿瘤的理论计算模型,并应用有限元计算方法对双光纤照射椭球形肿瘤组织的模型进行了定量计算研究;研究结果表明,对于长轴为2.0 cm、短轴为1.2 cm的实心椭球形肿瘤体,将2个直径为0.4 mm的球状光纤对称放置在主轴上相距0.8~1.0 cm的范围内,可以使光动力学的效果和热疗的效果同时达到最佳值。     

姜黄素对鼻咽癌细胞株CNE-2Z—H5裸鼠移植瘤增殖的影响

目的：研究姜黄素对人低分化鼻咽癌细胞系亚克隆株CNE-2Z—HS裸鼠移植瘤生长和增殖的影响。方法：复制人低分化鼻咽癌细胞系亚克隆株CNE-2Z-H5裸鼠移植瘤模型，观察姜黄素对移植瘤生长的影响。结果裸鼠体内实验显示姜黄素可以抑制移植瘤的生长。不同浓度姜黄素组移植瘤瘤重与溶剂对照组比较有降低趋势，高剂量组降低更明显，差异有极显著性（P〈O．001），抑瘤率达59．75％。结论姜黄素可以抑制CNE-2Z—H5细胞裸鼠移植瘤的生长，其可能在鼻咽癌的治疗中具有一定的价值，值得进一步深入研究。     

骨桥蛋白在卵巢肿瘤组织的表达及其与恶性肿瘤侵袭转移的关系

目的:探讨骨桥蛋白(OPN)在卵巢肿瘤组织的表达及其与恶性肿瘤侵袭转移的关系。方法:采用免疫组织化学方法测定OPN在48例卵巢恶性肿瘤组织、8例卵巢临界恶性肿瘤组织、20例卵巢良性肿瘤组织及10例卵巢正常组织中的表达。结果:OPN在卵巢恶性肿瘤组织表达强度为0.485±0.134,显著高于卵巢正常组织及卵巢临界恶性及良性肿瘤组织表达强度(0.122±0.023,0.243±0.076及0.168±0.045,P<0.01);OPN的表达与恶性肿瘤的临床期别及分化程度相关,而与细胞组织学类型无关。结论:OPN在卵巢肿瘤的发生发展中起重要作用,并与卵巢恶性肿瘤的侵袭转移相关。     

Functional Imaging of Breast Tissue and Clinical Application

0Introduction Near infrared(NIR)techniquesarebasedonsensitive,quantitativemeasurementsoffunctionalcontrastbe tweenhealthyanddiseasedtissue.Recently,researchersshowgreatinterestinmeasuringfunctionalpropertiesofbreasttis suesuchashemoglobinconcentrationoroxygensaturationbyNIRspectroscopyandNIRimaging[1,2].NIRlightcanpene trateseveralcentimetersintotissuebeforeitisattenuatedbe lowdetection.ThemainintrinsicmechanismsofNIRlightat tenuationintissuearethescatteringduetoindexofrefractionvariatio…     

HSP70在肺癌组织中表达水平的研究

采用免疫组织化学ＳＡＢＣ法检测３９例肺部组织中ＨＳＰ７０的表达。结果显示：ＨＳＰ７０在高度分化的肺鳞癌和肺腺癌细胞中的阳性表达率与癌旁正常肺组织之间具有高度显著性差异（Ｐ〈０．０１）,ＨＳＰ７０的表达在高分化的肺鳞癌与肺腺癌之间则无显著性差异（Ｐ〉０．０５）,在低分化的肺鳞癌和肺腺癌组织中,ＨＳＰ７０呈阴性反应,ＨＳＰ７０在肺癌组织中表达水平的高低与肺癌细胞的分化程度密切相关,而与肺癌的组织学类型