鼠肾包膜下人卵巢癌移植癌体积变化及病理学对照研究

人卵巢癌细胞系经裸鼠传代后，移植于正常免疫功能Ｃ５７ＢＬ／６纯系小鼠肾包膜下，双侧肾脏多位点移植，３２只小鼠共移植瘤块１２９个，分别在移植术后４、６、８、１０、１２和１４天切取移植瘤，测量体积变化并观察病理组织学特征。     

人卵巢癌细胞系在不同品系免疫小鼠肾包膜下生长规律的探讨

用肾包膜下移植法将经裸鼠传代的人卵巢癌细胞系ＳＫＯＶ３，移植于纯系小鼠Ｃ５７ＢＬ／６和杂交一代小鼠ＢＣＦ１和ＢＤＦ１的肾包膜下，观察移植后不同时间移植瘤的体积和病理组织学变化。结果表明，移植瘤体积在术后第６～８天最大，淋巴细胞浸润在８～１２天最严重，瘤细胞在移植后１０天内形态仍完整。同时比较了３种品系小鼠的差异，为肿瘤免疫学研究提供了短期实验的人卵巢癌免疫功能动物模型。     

抗独特型抗体免疫治疗卵巢癌的动物实验研究

目的：研究抗独特型抗体对卵巢癌的免疫治疗作用，为临床试验提供动物实验依据。方法：用人卵巢癌抗独特型抗体（Ａｂ２）免疫杂交一代小鼠ＢＣＦ１，为实验组；用正常小鼠ＩｇＧ免疫小鼠ＢＣＦ１，为对照组。两组均免疫３次，于末次免疫后１周，将经裸鼠传代的人卵巢癌细胞系移植于ＢＣＦ１小鼠肾脏包膜下，分别于移植后第２、４、６、８和１０天处死小鼠，取血清进行抗独特型抗体（Ａｂ３）分析。移植瘤行组织学检查，观察宿主淋巴细胞浸润情况及瘤细胞可见率。结果：实验组小鼠肾脏包膜下人卵巢癌细胞系很快受到排斥，在移植后第６天，淋巴细胞浸润即达高峰，而对照组在第１０天才达高峰；瘤细胞可见率，在移植第６天后即明显降低，而对照组呈逐渐下降。结论：Ａｂ２作为抗原免疫小鼠后，能够排斥瘤细胞的生长。     

构建卵巢上皮性癌原位移植瘤动物模型的新方法

构建卵巢上皮性癌（卵巢癌）的动物模型方法包括：裸鼠皮下移植瘤模型，腹腔移植瘤模型，裸鼠网膜移植瘤模型，原位移植-转移瘤模型等。原位移植因为可以提供给被移植物类似于人体的微环境所以有广阔的应用前景。目前的原位移植技术主要是用细胞株构建裸鼠皮下移植瘤作为供瘤体，切成小块后在解剖显微镜下打开卵巢的包膜，将组织块植入卵巢实质。该技术只能间接反应卵巢癌细胞株的特点；此外难度高，需要解剖显微镜等特殊仪器。本研究在实验过程中巧妙地使用了一种新方法，将细胞悬液直接注射到小鼠的卵巢实质内，成功地建立了糖尿病合并重症联合免疫缺陷（NOD／SCID）小鼠卵巢癌模型，现报道如下。     

人卵巢癌裸鼠腹腔及网膜移植的研究

目的：建立既符合卵巢癌临床特征，又便于实验观察和分析的人卵巢癌裸鼠异种移植模型。方法：将体外培养的卵巢癌Ａｏ细胞接种于裸鼠皮下和腹腔内，并切取皮下移植瘤；在麻醉状态下对裸鼠进行网膜局部手术移植。结果：腹腔种植成瘤率为７０％（７／１０），肿瘤结节大小不一，分布广泛，其中２只腹水形成；网膜移植全部成瘤，移植瘤呈单一生长，易分离和切除，肿瘤重量一致性较好。结论：人卵巢癌裸鼠网膜异种移植模型直接反映肿瘤生物学行为，便于观察和分析实验结果，适于在卵巢癌实验研究中应用。     

顺铂耐药卵巢癌细胞鼠肾包膜下动物模型的建立及其临床意义

目的 :建立顺铂耐药卵巢癌细胞鼠肾包膜下动物模型 ,探讨其临床意义。方法 :采取肾包膜下纤维蛋白细胞凝块移植法 ,用环磷酰胺免疫抑制小鼠建立顺铂耐药卵巢癌模型。结果 :移植后 7d肿瘤体积明显增大 ,顺铂耐受细胞组与非耐受细胞组体积无明显差异 (P >0 .0 5) ;移植后细胞形态学特征无改变 ;在用顺铂治疗后 ,耐药细胞组肿瘤体积较非耐药细胞组体积大 (P <0 .0 5)。结论 :该动物模型可作为短期体内实验模型 ,能保持细胞的耐药性     

白桦酯醇对人卵巢癌裸鼠移植瘤的抑制作用及对凋亡的影响

目的:探讨白桦酯醇对人卵巢癌裸鼠移植瘤凋亡作用的影响.方法:建立人卵巢癌裸鼠移植瘤模型,将16只裸小鼠随机分为对照组、白桦酯醇组,观察并记录各组裸鼠及其移植瘤的生长情况,计算肿瘤体积.免疫组化检测各组裸鼠皮下移植瘤中P53、Bax、Bcl-2及凋亡指数的表达水平.透射电镜下观察肿瘤组织的超微结构.结果:①白桦酯醇组裸鼠移植瘤的体积较对照组明显变小(P<0.01).②白桦酯醇组的P53、Bax表达较对照组均明显增高(P<0.01),与凋亡指数变化呈同向变化趋势,Bcl-2表达较对照组无明显变化(P>0.05).③白桦酯醇可诱导裸鼠移植瘤细胞的凋亡.结论:白桦酯醇对裸鼠移植瘤有明显抑制作用,可能与肿瘤细胞的凋亡作用有关.     

卡铂多相脂质体对移植U_（14）腹水瘤小鼠生存期的影响

将小鼠宫颈癌瘤株１４号（Ｕ１４）移植至Ｋｍ小鼠腹腔形成腹水瘤模型并随机分为３组。脂质体组一次性腹腔注射卡铂多相脂质体１．５ｍｇ／０．７５ｍｌ，水剂组一次性腹腔注射卡铂水剂１．５ｍｇ／０．７５ｍｌ，对照组腹腔注射０．７５ｍｌ生理盐水。结果表明，对照组自移植后第５天开始死亡，平均生存９．８６天；水剂组第８天开始死亡，平均生存１１．４３天；脂质体组第１０夫开始死亡，平均生存１４．１４天。脂质体组与对照组生存期比率（Ｔ／Ｃ）为１４３．４１％（Ｐ＜０．０２５），接近显效标准；水剂组Ｔ／Ｃ为１１５．９２％（Ｐ＞０．２），未达有效标准。用药７天后脂质体组小鼠腹围增长率与其它两组比较为最低。提示卡铂多相脂质体腹腔注射对小鼠腹腔内移植瘤抑制作用明显，能显著延长荷瘤小鼠的寿命。     

卵巢肿瘤原位移植动物模型的建立

目的:建立能够模拟临床肿瘤发展过程的卵巢癌动物模型。方法:将处于对数生长期的人卵巢癌细胞株SKOV3(2×106个/只)、A2780多水平细胞数(2×106个/只、5×106个/只、1×107个/只、1.5×107个/只和2×107个/只)裸鼠皮下注射,A2780(1.5×107个/只)腹腔注射。取SKOV3第3代连续传代皮下瘤组织进行裸鼠右侧卵巢包膜下移植。结果:卵巢癌细胞株SKOV3皮下注射、组织块原位移植成瘤率均100%。原位移植卵巢癌裸鼠6～8周时剖腹探查见局部形成较大包块,与周围组织发生粘连,腹腔暗红色血性积液伴脏器广泛性转移,淋巴结转移。卵巢癌A2780细胞株多水平细胞数皮下注射均未成瘤;腹腔注射8周时剖腹探查见腹腔内生成2～3 mL无色澄清腹水,双侧卵巢增大,脾脏明显增大,未能发现任何腹腔瘤块。结论:成功建立了临床转移模式的SKOV3卵巢癌肿瘤细胞原位移植动物模型;卵巢癌A2780细胞接种未能成瘤,可能是因其对宿主体内非特异性免疫反应较敏感。     

白细胞介素-15治疗3AO裸鼠移植瘤的实验研究

目的:探讨白细胞介素-15(IL-15)治疗3AO裸鼠皮下移植瘤的效果及其机制。方法:建立3AO裸鼠皮下移植瘤模型,随机分为5组,每组12只。I组为顺铂(cD-DP)3mg/kg;Ⅱ组、Ⅲ组分别为IL-1550μg/kg,100μg/kg;Ⅳ组为cDDP1.5mg/kg加IL-1550μg/kg;Ⅴ组为对照组,注射生理盐水(各组药物均腹腔注射,按每只裸鼠0.2ml配制),1次/d,连用1周。观察移植瘤成瘤率、裸鼠生存期、生存延长率及肿瘤生长曲线。停药1天,1周,2周后,观察移植瘤细胞凋亡率及细胞周期,NK细胞群计数;测定裸鼠脾脏重量;对移植瘤及裸鼠肝、脾、肾行常规病理学检查。结果:实验组与对照组相比荷瘤裸鼠生存延长率,脾脏重量,移植瘤细胞凋亡率,NK细胞群计数均有明显差异。病理学检查示各治疗组均见肿瘤坏死,肿瘤细胞周围及肿瘤内淋巴细胞明显浸润。IL-15治疗组脾脏有充血增生表现,肝脏肝细胞嗜酸性变性,肝细胞水肿,周围有浊肿;cDDP治疗组肾脏近曲小管和远曲小管细胞水肿,管腔变小;对照组裸鼠肝、脾、肾未见明显病理改变。结论:IL-15对人卵巢癌裸鼠皮下移植瘤有明显的抑制作用,其机制可能与IL-15增强NK细胞的细胞毒活性,诱导NK细胞及细胞因子产生有关。     

HLA-G transgenic mice.

We have generated a number of transgenic mice using DNA segments derived from the HLA-G gene. Using these mice we have examined the pattern of expression dictated by HLA-G promoter elements in mice and shown that HLA-G functions both as a restriction element and a transplantation antigen recognized by murine T cells. In addition, we have shown that trophoblast cells expressing H-2Kb under the control of HLA-G promoter elements affect maternal T cell phenotype and responsiveness during pregnancy. Using these same HLA-G/H-2Kb transgenic mice we have shown that trophoblast cells, expressing an inducible enzyme that degrades tryptophan, protects allogeneic conceptus expressing paternally-inherited transgenes from attack by maternal T cells that leads to fetal rejection.     

Galactose inhibition of ovulation in mice

Clinical evidence suggests an association between galactosemia and premature ovarian failure. In the present study, adult female mice were fed a diet consisting of 50% galactose for either 2, 4, or 6 weeks. At all times there was a decrease in the normal ovulatory response, as evidenced by a reduction in the number of corpora lutea when compared with controls. Additionally, the exposure of galactose-treated mice to a superovulatory regimen of pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) failed to induce an increased ovulatory response. Morphologic alterations, such as the increase in interstitial tissue and the appearance of lipofuscin, coupled with the failure to respond to exogenous gonadotropins, suggest that the reduced ovulatory response may be occurring at the level of the ovary. This effect, however, is reversible with cessation of galactose treatment.     

Variation in immunophenotype of lactating mice

Immunological factors have been shown to play a crucial role in mammary remodelling in rodent models of lactation, particularly at the stage of mammary involution. However, the relationship between immunological factors and the ability of normal mammary gland to produce milk, as well as the genetic components contributing to lactation performance remain largely unknown. In this study, we assessed the lactation and immunological phenotypes of 11 inbred mouse strains, namely 129X1/SvJ (129), A/J, AKR, C3H/HeJ (C3H), CBA/CaH (CBA), C57BL/6J (C57), DBA/1J, DBA/2J, FVB/N (FVB), QSi5 and SJL/J (SJL) to identify potential links. Leukocyte analyses showed no direct link between the fraction of splenic leukocytes and lactation performance. However, significant strain differences were discovered in the fraction of CD8+ T lymphocytes (P=0.016) and CD11b+Gr-1 mid-low monocytes (P<0.001). Cytokine profiles in plasma were examined and a subset of plasma cytokines, namely CCL2, CCL3, CCL5, CSF2, CSF3, IL10, IL15, IL1B, IL4, IL5, IL7 and TNF, were fitted to a linear regression model for prediction of lactation performance (R-sq=62%, S=0.309). Significant strain differences in the plasma cytokine levels were also discovered amongst these inbred strains. Analysis of immunological phenotypes showed strong correlations between splenic immune cell subsets and their regulating cytokine levels in plasma. The results demonstrate the extent of genetic variability in the immunological phenotypes of lactating mice, and provide a basis for understanding the role of cytokines in milk production, and identifying potential biomarkers of lactation performance.     

Sperm reservoir in mice: involvement of ADAMs

Mammalian sperm migrate over long distances through the female genital tract before reaching the oviduct where fertilization occurs. This process is more complex than predicted by the movement of sperm. The oviduct is composed of three major segments: the uterotubal junction, the isthmus and the ampulla. These structures appear to play roles for the success of fertilization. Gene knockout approaches of several genes in mice suggest that the migration of spermatozoa in the oviduct is regulated to allow competent gametes encounter ensuring the success of fertilization with minimum risk of polyspermy. The sperm of male mice deleted for following genes: Calmegin, Calsperin, Angiotensin-Converting-Enzyme, Adam1a, Adam2 or Adam3 are morphologically normal and motile, but not able to pass through the uterotubal junction. The precise mechanism of how these molecules facilitate the passage of spermatozoa through the uterotubal junction is still unknown, but Adam3 seems to be the major factor in this process since it is implicated in these six lines of mutant mice.     

Gene knockout mice in the study of parturition

OBJECTIVE: To review recent studies of parturition control in mice with relevance to understanding the control of human parturition. METHODS: Assimilation of published studies of gene knockout mice with mutations in neuropeptides, prostaglandin synthetic enzymes and receptors, and other molecules implicated in parturition. RESULTS: The central role of prostaglandins in murine labor is demonstrated by mice with gene mutations at multiple levels of the prostaglandin synthetic pathway. In addition, novel molecules such as steroid 5 alpha-reductase are found to play an essential role in the progression of labor. Surprisingly, deficiency of neuropeptides such as oxytocin and corticotropin-releasing hormone have little effect on parturition. CONCLUSION: Molecular genetic analyses in mice provide an efficient way to define molecules critical for murine parturition. Extrapolation of the importance of these molecules to human parturition provides the next challenge.     

Chemical induction of ovarian epithelial carcinoma in mice

Murine ovaries were treated with silk sutures saturated with a solution of 7,12-dimethylbenz(a)anthracene in beeswax. One of 35 animals developed an epithelial carcinoma. This tumor was not successfully transplanted into young animals.