人肝癌裸鼠连续传代的病理变化特征

目的：探讨裸鼠人肝癌20年连续传代的病理变化特征。方法：裸鼠人肝癌组织模型（SMMU-LTNM）连续观察20年（1987—2007年），皮下移植瘤传至228代，建立腹腔移植瘤、肝原位移植瘤及NOD-SCID小鼠肝原位移植瘤的病理资料，经光镜、电镜、图像分析、染色体分析、周围血液AFP检测等方法分析病理变化特征。结果：（1）上述4种肿瘤模型的局部侵袭和转移均长期存在：皮下移植瘤的局部侵袭率为59．70％（40／67），肺内转移率为37．10％（23／62）；腹腔移植瘤的肺内转移率为59．02％（36／61）；肝原位移植瘤的肝内转移率为18．18％（4／22），肺内转移率为31．82％（7／22）；NOD—SCID小鼠肝原位移植瘤的肺内转移率为53．85％。（2）皮下移植瘤的组织学变化：第10代前的瘤细胞分化和组织结构与原人肝癌近似，以Ⅱ级分化、粗梁型为主；第11代至225代瘤细胞以分化Ⅲ级、团块型为主，电镜下亦证实瘤细胞分化更差。（3）AFP检测第32代前为92500μg／L，第33代至130代AFP下降为6729μg／L，220代AFP检测为1000—5000μg／L。（4）腹腔移植瘤的瘤细胞群体与肺转移瘤的瘤细胞群体DNA含量分布范围明显增宽，2C-6C不等，峰值明显右移，前者的分布范围比后者更宽；DNA含量分别为2．60±0．20和2．10±0．26。（5）染色体检测，第55—206代（相隔12年）部分瘤细胞染色体变为裸鼠染色体。结论：裸鼠皮下移植瘤可连续传代20年，局部侵袭及转移的恶性生物学行为不变；瘤细胞分化更差，AFP下降，部分瘤细胞染色体变为裸鼠染色体。这些病理变化可能与裸鼠内环境影响和瘤细胞的多潜能分化有关。     

瘤内注射戊二醛治疗小鼠移植性肿瘤的实验观察

目的：通过瘤内注射戊二醛（Glutar）治疗小鼠移植性肿瘤，探讨戊二醛抗瘤效应。方法：将32只小鼠随机平分为四组。接种H22小鼠肝癌细胞株。7天后依照分组移植瘤内注射2％戊二醛、无水乙醇、丝裂霉素。结果：给药7天移植瘤体积：戊二醛、乙醇、丝裂霉素组均小于对照组（P＜0．05）。戊二醛组值最小，病理见瘤细胞坏死。21天后小鼠生存：戊二醛组（5／8）高于对照组（2／8）。结论：戊二醛瘤内注射能够起到抑制肿瘤增长，延缓荷瘤鼠生存的作用。     

蛞蝓糖蛋白提出多糖对肺腺癌作用的实验研究

目的：探讨蛞蝓糖蛋白提出多糖（LE—DZ）在体内外对肺腺癌的抑制作用。方法：细胞计数法检测LE—DZ对人肺腺癌A549细胞生长增殖的抑制作用,并绘制细胞生长曲线;平板克隆实验测定细胞集落形成率;建立小鼠Lewis肺癌模型,测皮下移植瘤体积绘制体积生长曲线,测移植瘤重量,计数小鼠肺表面转移结节数,并计算出抑瘤率和肺转移抑制率;光镜和电镜观察肿瘤组织病理变化。结果：在体外,1、10、100μg/ml浓度LE-DZ均能抑制人肺腺癌A549细胞增殖,并呈浓度和时间依赖性;与对照组比较,细胞集落形成率明显下降（P〈0．05）。在体内,LE—DZ能够抑制小鼠Lewis肺癌移植瘤生长和自发性肺转移,25、50、100μg／ml浓度LE—DZ瘤重抑制率分别为19．65％、39．81％、50．96％,肺转移抑制率分别为23．08％、43．27％、68．27％,且呈浓度依赖性。病理学观察结果,LE—DZ可引起肿瘤细胞坏死,诱导肿瘤细胞凋亡。结论：LE—DZ在体外能抑制肺腺癌A549细胞增殖,在体内能抑制小鼠Lewis肺癌皮下移植瘤生长和自发性肺转移,并诱导癌细胞凋亡。     

紫杉醇与肿瘤疫苗联合应用对小鼠Lewis肺癌皮下移植瘤的治疗效果

目的： 〖HT5"SS〗评价化疗药物紫杉醇联合应用肿瘤疫苗对小鼠Lewis肺癌皮下移植瘤的治疗效果。〖HT5W〗方法： 〖HT5"SS〗以编码有GMCSF的腺病毒感染Lewis肺癌细胞3LL,制备肿瘤疫苗3LL/GMCSF。以2×104个3LL瘤细胞皮下注射C57BL/6（H2b）小鼠腹股沟部,制备小鼠皮下移植瘤。检测体内、外应用紫杉醇对Lewis肺癌细胞3LL的杀伤敏感性。在小鼠Lewis肺癌皮下移植瘤体内首先以紫杉醇化疗,随后以肿瘤疫苗3LL/GMCSF免疫;或反之,首先以肿瘤疫苗免疫,随后以紫杉醇化疗,观察肿瘤生长和小鼠生存状况,以及检测小鼠体内对肿瘤的特异性杀伤效率和免疫应答记忆反应。〖HT5W〗结果〖HT5"SS〗： 紫杉醇体外作用于3LL肿瘤细胞,24 h后在浓度为100 nmol/L时可使32.10 %的3LL肿瘤细胞发生死亡;但体内注射紫杉醇（5、10和25 mg/kg）不能使所有3LL荷瘤小鼠肿瘤消退。体内使用紫杉醇后应用3LL/GMCSF肿瘤疫苗,70%的荷瘤小鼠发生显著的肿瘤消退,与单纯化疗的小鼠相比生存时间明显延长（70.0 vs 27.5 d）; 化疗后应用肿瘤疫苗诱导了体内对3LL的特异性杀伤,第3天体内杀伤率达41.35%;同时,存活小鼠能抵抗2×104 3LL肿瘤细胞的再次攻击。接种3LL/GMCSF肿瘤疫苗后应用紫杉醇化疗却不能使肿瘤消退。〖HT5W〗结论： 〖HT5"SS〗化疗后应用肿瘤疫苗免疫可诱导出抗原特异性免疫效应,使荷瘤小鼠肿瘤消退并延长生存时间,为临床开展化疗后的肿瘤疫苗主动免疫提供了实验依据。     

补肾抗癌方对 TAM 诱导的小鼠 Lewis 肺癌中 VEGF表达影响

目的：探讨补肾抗癌方对不同活化表型的肿瘤相关巨噬细胞（ TAM）诱导的肺腺癌小鼠移植瘤模型中血管内皮生长因子（VEGF）表达的影响。方法构建不同活化表型TAM的肺腺癌小鼠移植瘤模型,将50只C57BL／6J小鼠随机分成5组：空白组;TAM模型对照组;TAM中药组;活化TAM模型对照组;活化TAM中药组。于接种后给予相应药物干预,第21天处死各组小鼠,剥离皮下肿瘤,流式细胞仪检测TAM的数量;采用免疫组织化学法检测小鼠皮下移植瘤组织中VEGF表达。结果在建模第21天,各中药组小鼠移植瘤体积明显小于各模型对照组,TAM模型对照组小鼠移植瘤体积明显小于活化TAM模型对照组,各中药组小鼠移植瘤组织中CD206表达水平显著低于各模型对照组,各中药组小鼠移植瘤组织中VEGF表达水平低于各模型对照组。结论补肾抗癌方可能通过抑制TAM和VEGF表达从而达到抗肿瘤的效果。     

小鼠可移植性网织细胞肉瘤L_Ⅱ自发转移性的观察

本实验将小鼠可移植性网织细胞肉瘤ＬⅡ接种子近交系６１５小鼠体内进行自发转移特性的观察。实验分为两组，Ａ组将定量（１×１０）的ＬⅡ瘤细胞接种于小鼠右后肢肌肉内，Ｂ组将等量的瘤细胞接种于小鼠右肋部皮下，待荷瘤小鼠自然死亡或濒死状态时处死，取出全肺及各部位淋巴结进行组织学检查。结果发现２４只右后肢肌肉接种的动物，中间存活时间为２８天，全部实验动物均发生淋巴结和肺转移；２３只右肋皮下接种的动物，中间存活时间为３９天，有９５．７％（２２／２３只）发生淋巴结转移，６０．９％（１４／２３只）出现肺转移，而淋巴结合并肺转移者５６．５％（１３／２３只）。结果表明，本瘤株具有淋巴结合并肺部双向转移的特性。     

小鼠可移植性网织细胞肉瘤L_Ⅱ自发转移性的观察

本实验将小鼠可移植性网织细胞肉瘤ＬⅡ接种子近交系６１５小鼠体内进行自发转移特性的观察。实验分为两组，Ａ组将定量（１×１０）的ＬⅡ瘤细胞接种于小鼠右后肢肌肉内，Ｂ组将等量的瘤细胞接种于小鼠右肋部皮下，待荷瘤小鼠自然死亡或濒死状态时处死，取出全肺及各部位淋巴结进行组织学检查。结果发现２４只右后肢肌肉接种的动物，中间存活时间为２８天，全部实验动物均发生淋巴结和肺转移；２３只右肋皮下接种的动物，中间存活时间为３９天，有９５．７％（２２／２３只）发生淋巴结转移，６０．９％（１４／２３只）出现肺转移，而淋巴结合并肺转移者５６．５％（１３／２３只）。结果表明，本瘤株具有淋巴结合并肺部双向转移的特性。     

小鼠Lewis肺癌胸腔与皮下移植模型的比较研究

目的：建立小鼠Lewis肺癌胸腔移植模型与皮下移植模型，比较两种模型生存时间、生活状态以及肿瘤进展情况，寻找适合评价肺癌发展进程的模型。方法：将传代培养的Lewis肺癌细胞（LLC）接种于C57BL／6近交系小鼠的腋后线第6肋间胸腔内和腋后部皮下，建立两组肺癌模型：胸腔组和皮下组。观察两组模型的成瘤率、小鼠的存活时间和生活状态及肿瘤的浸润和转移情况。结果：小鼠Lewis肺癌胸腔组和皮下组接种成瘤率100％。胸腔组小鼠中位生存时间13．5（8～18）d，皮下组中位生存时间45（25～71）d，胸腔组的生存期范围离散程度较皮下组小，P=0．023。胸腔组小鼠在生存过程中可出现肿瘤局部浸润和远处转移的晚期肺癌特征，而皮下组则很少出现上述情况。病程中胸腔组小鼠恶病质状态较皮下组严重，胸腔组小鼠体质量下降、饲料消耗量、游泳试验和常压耐缺氧试验时间均较皮下组严重，差异有统计学意义。结论：小鼠Lewis肺癌胸腔移植模型较皮下移植模型更能反映肺癌发展的进程，胸腔移植模型可作为晚期肺癌的动物模型。     

BALB／C小鼠黑色素瘤肿瘤模型的建立及对荷瘤鼠的影响

目的建立小鼠不同部位黑色素瘤模型，为不同研究目的提供合适的动物肿瘤模型。方法接种B16小鼠黑色素瘤细胞于BALB／C小鼠足部、腹腔和尾静脉，建立移植瘤模型和肺部转移瘤模型。观察B16实体瘤的形态学特点，接种细胞数与肿瘤生成的关系，肿瘤生长对小鼠生存时间、血清肿瘤坏死因子（sTNF）和唾液酸（SA）的影响。结果足部接种5X10瘤细胞后10天，肿瘤进入对数生长，成瘤率近100％；腹腔接种瘤细胞数大于5000个／只，成瘤率与接种细胞数成正比；接种3X10细胞／只，10天后在小鼠腹壁和肠系膜可见散在黑色素瘤结节，荷瘤鼠sTNF和SA水平明显高于正常小鼠，且与肿瘤的大小和数量成正比，小鼠平均存活59天；尾静脉接种后3周，肺部可见大小不等转移瘤灶，两肺平均瘤灶数可达192.11士92。结论B16黑色素瘤细胞株在BALB／C小白鼠具有很高的成瘤率和转移特性，且较C57／B16小黑鼠模型具有方便、稳定和观察容易等优点，是一较理想的模型。     

人肺腺癌干细胞的分离及鉴定

目的：从人肺腺癌细胞株中分离及鉴定具有干细胞特征的高致瘤性癌干细胞。方法：采用磁性细胞分选（magnetic activated cell sorting，MACS）技术将肺腺癌细胞分成多个亚群，然后应用流式细胞及RT-PCR技术检测干细胞相关标志表达，通过NOD-SCID小鼠移植评估其致瘤性。结果：在A549和SPC-A肺腺癌细胞中发现一个新颖的癌细胞亚群，此类癌细胞的表型特征为CD24^＋IGF-1R^＋，具有高侵袭性和高致瘤性，在NOD-SCID小鼠中仅需移植100个细胞即可形成肿瘤，其致瘤能力是上述标志阴性细胞的1000倍。此外，这些细胞表达胚胎干细胞标志（OCT4和Bmi-1）及肺干细胞标志（CCSP，SP-C，TTF-1和Gremlin），类似小鼠肺脏细支气管肺泡干细胞（bronchioalveolar stem cells，BASC），并具有自主生长特性，能够在无血清条件下长期培养。结论：人体肺腺癌中CD24^＋IGF-1R^＋细胞属于BASC样癌干细胞。     

Development and characterization of the BALB/cNIV mouse strain

The strain BALB/cNIV/Crgl was developed by infecting BALB/c/Crgl mice with mouse mammary tumor virus from C3Hf mice. A BALB/c normal mammary duct was transplanted into the gland-free fat pad of a hormone-stimulated female C3Hf X BALB/c F1 mouse. A hyperplastic alveolar nodule was found in the BALB/c ductal outgrowth and was transplanted into another hybrid gland-free fat pad. The resultant hyperplastic alveolar outgrowth was finally transplanted to female BALB/c mice. The hyperplastic alveolar outgrowth contained an exogenous, infectious mouse mammary tumor virus named the nodule-inducing virus, which was thought to be derived from the endogenous low oncogenic mouse mammary tumor virus found in C3Hf mice. The hyperplastic alveolar outgrowth-bearing BALB/c mice were inbred for four generations, and one family was selected as the strain BALB/cNIV/Crgl. It was found that (a) the mouse mammary tumor virus found in the BALB/cNIV strain was milk transmitted, but not transmitted by infected males; (b) the BALB/cNIV breeding females had a low tumor incidence (40%) and a longer latent period (14 months) than did female BALB/cfC3H mice (92% at 8 months); (c) the BALB/cNIV nodule outgrowths had low tumor-producing capabilities (50%) and longer latent periods (13.4 months) than did nodule outgrowths derived from female BALB/cfC3H mice (100% at 7.7 months).     

Transplantable mouse pancreatic acinar cancer cell line (MPC-83) and its characteristics

The transplantable mouse pancreas cancer cell line (MPC-83) has been established for two years, and transplanted serially into Kunming strain (KM) mice subcutaneously for 55 generations on Feb. 11, 1985. The transplantability rate in KM, BALB/C and Swiss mice was 100%. The tumor cells of some passages were stored in liquid nitrogen, and their revival was fine. It is the first transplantable pancreas cancer cell line ever established in China. The primary tumor was derived from a spontaneous pancreas cancer of a outbred male KM mouse. It was a poor-differentiated pancreatic acinar cell cancer. The transplanted tumors from all generations were similar to the primary one in both histology and histochemistry. The esterase staining was positive. By electron-microscopy, the zymogen granules were seen in the cytoplasm of its 1st, 25th and 33rd passages. The chromosome numbers in 28th, 32nd and 35th passages were hypertriploid with a modal number of 60 to 69, and some abnormal submetacentric chromosomes could be seen. The mean survival time of the tumor-bearing mice was 22 days. Metastases could be found in the lung (80%), sometimes in pancreas, omentum and other abdominal organs nearby with bloody cancerous ascites (10.5%). The fat necrosis might be noted around the tumor. These phenomena were similar to the clinical characteristics of human pancreas cancer. The preliminary therapeutic test shows that MPC-83 is sensitive to anticancer drugs such as 5-FU, Cyclophosphamide and cis-platin. This modal may be used for study of pancreas cancer, the mechanism of metastasis and antimetastatic agents of tumor, basic research and anticancer drugs.     

异种免疫诱导中和性抗体抑制小鼠肺癌生长

目的 研究异种固定化完整细胞作为肿瘤疫苗的潜力,初步探讨其诱导的免疫反应的抗肿瘤机制。方法 分别使用固定的人肺癌细胞免疫小鼠,再接种小鼠自发肺腺癌鼠肿瘤进行肿瘤挑战,观察肿瘤细胞免疫后对小鼠肿瘤生长的影响。采用免疫组织化学法观察小鼠肿瘤浸润T细胞的情况,采用MTT法检测小鼠免疫血清对人肺癌细胞生长的影响。结果 采用人肺腺癌和鳞癌固定的完整细胞免疫小鼠后均明显地抑制小鼠肺腺癌肿瘤的生长（P<0.05）,抑瘤率分别为40.8%及49.2%,显著优于采用人肺腺癌和鳞癌细胞碎片免疫的效果。小鼠免疫血清在体外可抑制人肺癌细胞的生长。结论 异种人肺癌固定的完整细胞诱导了有效的小鼠抗鼠肺癌的体液免疫反应,显著抑制肿瘤生长,其抑制作用可能与诱导小鼠产生抗肺癌中和性抗体有关。     

糖化重组生存素腺病毒疫苗抗肿瘤作用的实验研究

背景与目的：生存素在调控细胞凋亡和有丝分裂过程中起着重要作用,在正常分化的组织中不表达或表达极低,而在胚胎组织和大部分肿瘤组织中广泛表达,而这一特点为恶性肿瘤的基因治疗提供了很好的靶标.本研究制备糖化重组生存素腺病毒疫苗,观察其抗肿瘤作用并探讨其作用机制.方法：将重组生存素腺病毒和甘露聚糖在氧化条件下偶联,同时建立小鼠结肠癌和Lewis肺癌模型,以糖化重组生存素腺病毒疫苗治疗荷瘤小鼠,观察肿瘤体积和小鼠生存时间.对小鼠肿瘤组织作TUNEL染色观察肿瘤细胞凋亡.为了检测疫苗的保护作用,预先以糖化重组生存素腺病毒疫苗免疫接种小鼠,或合用抗CD4、CD8和NK单克隆抗体阻断相应的淋巴细胞亚群,再接种肿瘤,观察小鼠肿瘤生长情况.结果：糖化重组生存素腺病毒疫苗治疗组小鼠肿瘤生长受到明显抑制,无明显不良反应发生,小鼠的生存时间明显延长,肿瘤细胞凋亡明显增加.同时,糖化重组生存素腺病毒疫苗能诱导小鼠产生抗肿瘤免疫,这一免疫反应依赖于CD4和CD8淋巴细胞,也部分依赖于NK细胞.结论：糖化重组生存素腺病毒疫苗能诱导机体产生特异性的主动免疫反应,诱导肿瘤细胞凋亡,具有明确的抗肿瘤作用,值得进一步研究.     

小鼠SP2/0细胞移植瘤的遗传修饰位点

BACKGROUND & OBJECTIVE: Our previous study found that BALB/c mice are highly susceptible to transplanted SP2/0 tumors, whereas C57BL/6J mice are barely susceptible. This study was to detect genetic modifier loci that would influence the size of transplanted SP2/0 tumors using these two inbred mouse strains and their F2 progenies. METHODS: A total of 5x106 SP2/0 cells were inoculated subcutaneously in the left hide legs of 208 F2 mice derived from BALB/c and C57BL/6J strains. At the 17th day since inoculation, all mice were killed, the number and weight of transplanted tumors were recorded. A whole genomic scan using 85 microsatellite markers covering all chromosomes of the mouse, and composite interval mapping analysis were conducted in 208 F2 mice. RESULTS: Eight loci, with the percent of the total variance explanation of >/= 10% and P value of 相似文献   

Generation of monoclonal antibodies against human lung squamous cell carcinoma and adenocarcinoma using mice rendered tolerant to normal human lung

Four murine monoclonal antibodies against human lung carcinoma were generated using a novel immunization procedure. BALB/c mice were rendered neonatally tolerant to normal human lung tissues and subsequently immunized with human lung tumor tissues. The lower level of antibody-reactivity to the tolerogen was seen in the sera of mice rendered neonatally tolerant as compared with the level of reactivity in the sera of nontolerant mice. The mice which maintained a sufficiently tolerant state were selected for hybridoma production. Two monoclonal antibodies, KM-32 and KM-34, were developed from mice immunized with lung squamous cell carcinoma tissues and two other monoclonal antibodies, KM-52 and KM-93, were developed from mice immunized with lung adenocarcinoma tissues. Distribution of antigens detected by the monoclonal antibodies were investigated by enzyme-linked immunosorbent assay using membrane fractions prepared from a number of tumorous and normal tissues and various human normal and tumor cell lines. KM-32 recognized a carbohydrate antigen expressed predominantly on lung squamous cell carcinoma cells and its carbohydrate structure appeared to be associated with blood group A antigen. KM-93 recognized a sialylated carbohydrate epitope on the antigen expressed on lung adeno-carcinoma cells and a few other tumor cells. KM-34 and KM-52 detected protein or glycoprotein antigens and they showed predominant reactivity to lung squamous cell carcinoma and lung adenocarcinoma, respectively. KM-32 and KM-34 antibodies showed complement-dependent cytotoxicity against a lung tumor cell line. These results suggest that the tolerance technique is useful for efficient screening of murine monoclonal antibodies specific to human tumors. The efficacy of these four monoclonal antibodies in diagnosis and therapy of lung cancer will be the subject of a sequential study.     

MLL5基因敲除对小鼠结肠癌CT26细胞移植瘤生长的影响及其机制

目的：探讨混合谱系白血病5(MLL5)基因在小鼠结肠癌CT26细胞移植瘤生长中的作用及其分子机制。方法：利用CRISPR/Cas9技术构建MLL5基因缺失、MLL5和DDX58双基因缺失的结肠癌CT26细胞模型,用Sanger测序和WB法验证敲除效果。将基因敲除的CT26细胞接种到野生型BALB/c小鼠和免疫缺陷型NSG小鼠皮下,构建基因缺失结肠癌CT26细胞移植瘤小鼠模型,并观察移植瘤的生长及荷瘤小鼠的总生存期（OS）。结果：在野生型小鼠中,MLL5基因缺失的CT26细胞移植瘤生长速度显著性低于野生型癌细胞移植瘤,并延长荷瘤小鼠的OS(P<0.01);在NSG小鼠中,MLL5基因缺失对CT26细胞移植瘤的生长速度以及荷瘤小鼠的OS没有明显改变。MLL5基因缺失提高了癌细胞中视黄酸诱导基因1(RIG-1)蛋白水平,DDX58基因缺失可逆转MLL5基因缺失在CT26细胞移植瘤中的作用。结论：MLL5基因缺失可提高结肠癌CT26细胞中RIG-1蛋白水平、促进肿瘤免疫,从而抑制荷瘤小鼠肿瘤生长,提示MLL5可能成为结肠癌治疗的新靶点。     

Alien histocompatibility determinants on the cell surface of sarcomas induced by methylcholanthrene. I. In vivo studies.

Groups of BALB/c mice were immunized to normal tissues (skin and/or liver plus kidney) of C3Hf, C57Bl/6, DBA/2 and AKR strains and challenged with either of two syngeneic 3-methylcholanthrene-induced immunogenic sarcomas, ST2 and TZ15, or with a "spontaneous" non-immunogenic BALB/c sarcoma, B2. It was found that anti-C3Hf and anti-DBA/2 immune mice were significantly protected against the growth of ST2, whereas anti-AKR immune mice rejected TZ15; no protection was elicited by immunizing with normal tissues of any strain against B2, which lacked individual tumor-associated transplantation antigens (TATA). The reciprocal experiment, i.e. the immunization of BALB/c mice with tumor cells and challenge with skin grafts of different strains, was also carried out with ST2 and TZ15. Accelerated rejection of all the various allogeneic skins was observed in anti-ST2 immune mice and of AKR and C3Hf skin in anti-TZ15 immune animals. In addition the Winn test demonstrated that lymph-node cells of BALB/c mice immune to C3Hf or DBA/2 tissues were specifically inhibitory for ST2, and that lymph-node cells immune to AKR tissues protected against TZ15. In a further experiment both ST2 and TZ15 tumors were left to grow in (C3Hf X BALB/c)F1, (C57Bl/6 X BALB/c)F1, (BALB/c X DBA/2)F1 and (BALB/c X AKR)F1 mice; the tumors were then excised and the "immune" mice challenged with the related tumor to measure their immune response in comparison with that elicited by the same procedure in BALB/c mice. ST2 was highly immunogenic in syngeneic BALB/c mice and in all the hybrid combinations except (C3Hf X BALB/c)F1 mice, where it completely lost its immunogenicity; TZ15 showed a certain loss of immunogenic strength in (BALB/c X AKR)F1 hybrids. It was concluded that TATA of ST2 contain antigenic determinants expressed on the normal cells of C3Hf and DBA/2 strains, and that TATA of TZ15 are likely to share antigens with AKR normal tissues.     

肿瘤疫苗与白介素-12联合免疫治疗小鼠肉瘤的研究

目的:探讨混合热休克蛋白(HSP)/肽与白介素-12(IL-12)和环磷酰胺(CTX)联合治疗小鼠肉瘤的作用及机制。方法:以S-180肉瘤为模型,将瘤组织剪碎,裂解,离心,取上清经Sephacryl S-200层析,截取相对分子质量(50～200)×103段,经SDS-PAGE电泳及Western-blot法鉴定。用提取的HSP/肽免疫小鼠后,再用低剂量CTX及IL-12治疗(强化疫苗),观察无瘤生存率、抑瘤生长率、抑制转移率和存活期。用流式细胞仪,ELISPOT及乳酸脱氢酶等方法检测免疫功能的变化。结果:HSP疫苗与IL-12和CTX联合治疗小鼠S-180肉瘤,80.0%肿瘤完全消退,且100.0%抑制了肺部转移,达长期生存,而对照组全部在40d内死亡。检测表明HSP/肽疫苗形成了免疫预存,从而使IL-12和CTX发挥了抗瘤作用。结论:HSP/肽与IL-12和CTX联合治疗诱发了机体细胞免疫功能,产生强大的抗瘤作用,可能具有临床应用前景。     

二烯丙基二硫对人胃癌细胞裸鼠移植瘤的抗肿瘤作用

背景与目的:既往研究发现二烯丙基二硫(diallyldisulfide,DADS)在体外可抑制多种肿瘤细胞生长,但在体内抗肿瘤作用的研究报道较少。本实验旨在探讨DADS对人胃癌细胞移植瘤在BALB/C裸鼠体内生长的影响。方法:未经药物处理和经30mg/LDADS处理1天的胃癌细胞MGC803接种于裸鼠皮下;观察体外DADS处理MGC803细胞裸鼠移植瘤的成瘤情况和未处理MGC803细胞移植瘤成瘤后腹腔注射DADS对胃癌移植瘤在BALB/c裸鼠体内生长情况的影响。Westernblot检测瘤组织中增殖细胞核抗原(proliferatingcellnuclearantigen,PCNA)的表达情况。结果:30mg/LDADS处理的MGC803细胞移植裸鼠体内无一成瘤。荷瘤裸鼠腹腔注射DADS剂量为50、100和200mg/kg时的抑瘤率分别为27.8%、66.1%和73.0%,同时可抑制移植瘤癌细胞PCNA的表达。结论:DADS可明显降低胃癌细胞裸鼠移植瘤的成瘤性,并对移植瘤生长有明显抑制作用。