2种人卵巢癌裸鼠皮下移植瘤模型制备方法的比较

目的比较直接接种人卵巢癌COCl细胞和COCl细胞经体内传代后接种Balb／c—nu裸鼠皮下移植瘤模型制备方法的成瘤率。方法雌性突变系Banb／c—nu小鼠40只，分为对照组及实验组，每组20只。COCl细胞注射于裸鼠一侧背部皮下，对照组细胞培养后即接种，观察统计数据后处死，取瘤体制成单细胞悬液再接种于实验组裸鼠，比较两种不同方法接种的成瘤率，并观察成瘤时间、瘤重及肿瘤生长速度。结果实验组成瘤率为70％，对照组仅为30％。结论经过裸鼠体内传代后的COCl细胞用于制备人卵巢癌裸鼠皮下移植瘤模型具有较高的成瘤率。     

抗瘤I号对小鼠脾淋巴细胞增殖及外周血白细胞数的影响

抗瘤Ｉ号（ＡＴ－Ｉ）是临床抗肿瘤及辅助肿瘤治疗有效的中药胶囊剂，具有肯定的抑瘤效应及调节小鼠脾细胞ＩＬ－２，ＩＬ－６产生和ＮＫ细胞活性的作用，为了探讨其辅助肿瘤治疗的机理，观察了ＡＴ－Ｉ对正常、免疫受抑制和荷瘤小鼠脾淋巴细胞增殖和外周血ＷＢＣ数的影响，结果提示：ＡＴ－Ｉ低剂量能促进脾细胞增殖，大剂量反呈现抑制效应；同时，ＡＴ－Ｉ还能纠正环磷酰胺减少外周血ＷＢＣ数的不良反应．     

125Ⅰ籽源薄层片植入治疗小鼠移植瘤的效果及可行性研究

目的采用125Ⅰ籽源薄层片在荷瘤鼠体内模拟临床植入治疗肿瘤残基,观察对肿瘤的抑制效果、可行性和安全性.方法小鼠皮下接种艾氏腹水瘤细胞后24 h,治疗组在接种部位分别植入1粒表观活度为23.3 MBq(0.63 mCi)和29.6 MBq(0.8 mCi)二种剂量的125Ⅰ籽源薄层片,对照组植入无放射活性的空籽源薄层片.治疗15 d,测量肿瘤体积并绘制肿瘤生长曲线.处死小鼠后称取瘤重并计算肿瘤抑制率.流式细胞仪检测和电镜观察肿瘤细胞的凋亡情况,常规病理切片观察对肿瘤组织的破坏程度、载体支架周围的组织反应等.结果治疗15 d,动态观察125Ⅰ籽源薄层片的抑瘤效果显示,2个治疗组随治疗时间的延长,照射累积剂量增加,抑瘤效果显著增加,成瘤率分别是63.6%和63.6%(对照组100%),肿瘤倍增时间从1.6 d延长为2.74 d和2.84 d,抑瘤率分别为63.0%和75.8%,凋亡率较对照组显著增加约2倍(P＜0.001).电镜超微结构观察显示肿瘤细胞出现核固缩、染色质边集和凋亡小体,但2个治疗组间无显著差异.病理切片显示,125Ⅰ籽源薄层片周围从内向外有少量炎症细胞浸润,纤维组织增生包裹了载体支架阻止了籽源的移位;邻近籽源的肿瘤细胞由凝固性坏死向外逐渐减弱为变性坏死;其它周围组织无明显变化.结论125Ⅰ籽源薄层片能明显抑制小鼠艾氏腹水瘤生长,促进肿瘤细胞凋亡,是植入治疗肿瘤残基切实可行又安全的方法.     

癌肿宁对荷肝癌(H_(22))小鼠的抑瘤作用及其对IL-2和NK细胞活性的影响

目的:探讨中药复方癌肿宁治疗实验性肝癌的疗效和机理。方法:建立荷实体型肝癌(H_(22))小鼠模型,观察经癌肿宁治疗对其肿瘤生长、NK细胞活性和IL-2活性的影响。结果:癌肿宁能显著抑制肿瘤的生长,其最高抑瘤率达56.66％,并可明显增强IL-2和NK细胞活性。结论:癌肿宁有明显的抗肝癌作用,并显著提高荷瘤小鼠的抗肿瘤免疫功能。     

一种新型分子探针——荷瘤裸鼠体内实验显像

目的通过荷瘤裸鼠体内实验研究验证hTERT反义分子探针(99mTc-hTERT ASON)作为新型分子显像剂的可行性,探讨其在整体动物水平上的应用价值。方法以双功能螯合剂法制备放射性核素99mTc标记的反义分子探针(99mTc-hTERT ASON)。建立荷MCF-7乳腺癌动物模型,进行体内生物分布与显像实验。所有结果通过统计学软件SPSS12.0进行分析。结果99mTc-hTERT ASON标记率达到76%±5%(n=5),放射性化学纯度达到96%以上,比活度为1850kBq/μg。99mTc-hTERT ASON主要分布在肾脏与肝脏组织;99mTc-hTERT ASON的肿瘤摄取率与肿瘤/非肿瘤比值(T/NT)均高于对照组(P<0.05);6h时99mTc-hTERT ASON的肿瘤/血液比值(T/B)与肿瘤/肌肉比值(T/M)分别为2.02与8.85。在注射99mTc-hTERT ASON后4～8h,荷瘤裸鼠肿瘤部位出现明显放射性浓聚。结论99mTc-hTERT ASON能特异性地聚集于肿瘤组织中,且T/NT比值较高,有望应用于肿瘤的基因显像研究。     

The antioxidant and immunomodulatory compound 3-[(4-chlorophenyl)selanyl]-1-methyl-1H-indole attenuates depression-like behavior and cognitive impairment developed in a mouse model of breast tumor

Psychiatric alterations are often found in patients with breast cancer even before the initiation of adjuvant therapy, resulting in a poor quality of life. It has become accepted that neuroinflammation and oxidative stress are involved in the pathophysiology of depression and cognitive impairment. Herein, we tested the hypothesis that treatment with the antioxidant and immunomodulatory selenium-containing compound 3-[(4-chlorophenyl)selanyl]-1-methyl-1H-indole (CMI) could attenuate behavioral and neurochemical alterations in a mammary (4T1) tumor model. Female BALB/c mice were subcutaneously inoculated with 4T1 cancer cells (1 × 10⁵ cells/mice) or PBS. From days 14 to 20, mice received daily gavage with canola oil or CMI. On day 21, mice were submitted to behavioral tests followed by euthanasia. We found that CMI did not alter tumor growth, body weight, and body temperature in tumor-bearing mice. Importantly, treatment with CMI abrogated tumor-induced depression-like behavior and cognitive impairment. By the time CMI improved the behavioral alterations, it had reduced tumor-induced neuroinflammation (altered expression of NFκB, IL-1β, TNF-α, IL-10, IDO, and COX-2) and oxidative stress (altered expression of iNOS and Nrf2, and levels of reactive species, nitric oxide, lipid peroxidation, and superoxide dismutase activity) in the prefrontal cortices and hippocampi of mice. A molecular docking approach suggested the ability of CMI to inhibit the activity of iNOS and COX-2. Together, our results indicate that CMI treatment may attenuate depression and cognitive impairment in 4T1 tumor-bearing mice, and be a groundbreaking strategy for the treatment of cancer-related psychiatric symptoms to improve the quality of life of cancer patients.     

Suppression of Anti-tumor CD4+ T Cell Responsiveness in the Tumor-bearing State and Its Recovery in in vitro Culture Free of Tumor Burden

We investigated whether the responsiveness of anti-tumor CD4⁺ T cells suppressed in the tumor-bearing state is reversed in conditions free of tumor burden. Spleen cells from BALB/c mice bearing a syngeneic tumor (CSA1M) 1–3 wk after inoculation with CSA1M cells produced interleukin-2 (IL-2) and IL-4 upon in vitro culture without addition of exogenous tumor antigens. This lymphokine production was achieved through collaboration between anti-CSA1M CD4⁺ T cells and antigen-presenting cells (APC) that had been pulsed with CSA1M tumor antigens in vivo in the tumor-bearing state. However, spleen cells from late (8–10 wk) tumor-bearing stages produced reduced levels of lymphokine production despite the presence of comparable proportions of CD4⁺ T cells. Because APC in these cell populations exhibited enhanced capacities to present tumor antigens, reduced responsiveness was ascribed to the dysfunction of CD4⁺ T cells themselves. When spleen cells from early tumor-bearing mice were preincubated for 1–2 days and recultured in fresh medium, the magnitude of lymphokine production by these cells was not changed. In contrast, the same protocol of preincubation and reculture for cells from late tumor-bearing mice resulted in the recovery of anti-tumor lymphokine-producing capacity. The recovered capacity was comparable to or slightly higher than that expressed by cells from early tumor-bearing stages. Since the CD4⁺ T cell content did not significantly differ before and after preincubation, enhanced lymphokine production was due to the recovered responsiveness of anti-tumor CD4⁺ helper T cells. The recovery of anti-tumor responsiveness was also induced in vivo by tumor removal at the late tumor-bearing stage: spleen cells from mice 2–4 wk after tumor resection efficiently produced IL-2 and IL-4. These results indicate that the immunodysfunction of anti-tumor CD4⁺ T cells induced in the tumor-bearing state is reversible because release from tumor burden either by preincubation in vitro or by tumor removal in vivo results in almost complete recovery of the potent anti-tumor responsiveness initially expressed.     

神经母细胞瘤细胞系裸鼠转移模型及局部皮下荷瘤模型的建立

目的 建立人神经母细胞瘤(NB)裸鼠荷瘤模型,研究NB的侵袭、转移机制以及实验治疗的可能性.方法 体外培养人NB细胞系,取对数生长期瘤细胞,以1×107个/0.1ml细胞悬液接种于裸小鼠右侧前肢肋腹部皮下,观察倚瘤的生物学特性,并进行病理组织学检查及基因芯片分析,检测皮下荷瘤组织、转移瘤组织和患儿原发肿瘤组织的神经元特异性烯醇化酶(NSE)表达.结果 48只裸鼠中,荷瘤成功36只,总荷瘤率为75.0%.其中5只裸鼠肿瘤体积很大,甚至达到裸鼠自身体重的1/2,但未发生转移;4只裸鼠接种部位无肿瘤生长,却发生全身转移;6只裸鼠既有局部肿瘤生长,又发生转移.本组有10只裸鼠发生转移,转移率为20.8%(10/48).结论 成功建立人NB裸鼠荷瘤模型并稳定传代,肿瘤的移植生长率和转移率均较高,是NB体内研究理想的动物模型.NB具有异质性,可能是NB转移的重要原因.     

苦参碱对小鼠H22 细胞抗肿瘤作用及其机制研究

目的观察苦参碱在体内和体外的抗肿瘤作用,探讨其可能的作用机制。方法 MTT法检测苦参碱对小鼠腹水瘤细胞H22的体外杀伤作用;通过建立动物肿瘤模型,免疫组化法检测其抑瘤率和肿瘤内血管密度,以及瘤体血管内皮生长因子。结果①体外实验显示,1.0、2.0、4.0mg·mL^-1苦参碱对H22肿瘤细胞的生长均有明显的抑制作用,并呈剂量依赖性,与对照组相比有显著性差异（P〈0.05）。②体内实验显示,苦参碱高、中、低剂量组对小鼠H22实体瘤均有抑制作用,并呈现一定的剂量效应关系,其中苦参碱高剂量组瘤重明显小于空白对照组,高剂量组的抑制作用明显强于中、低剂量组,P〈0.01;③免疫组化结果显示,苦参碱组和环磷酰胺组瘤组织内的VEGF蛋白表达阳性率和平均染色强度均低予对照组,组间有显著差异（P〈0.05）。苦参碱高剂量组MVD明显低于对照组,组间差异性非常显著（P〈0.01）,较环磷酰胺组无显著性差异（P〉0.05）。结论苦参碱能够提高H22肉瘤小鼠生存质量,具有抑制肿瘤新生血管生成的作用,可能是通过降低VEGF蛋白表达来实现的。     

红芪总多糖体内抗肿瘤的实验研究

目的:研究红芪总多糖(THPS)单用及与环磷酰胺(CTX)合用对荷瘤小鼠的抑瘤作用,并探讨其机制。方法:接种S180的昆明种小鼠腹腔注射低、中、高剂量THPS并联合使用CTX14天后,观察瘤重、抑瘤率、胸腺指数和脾指数,流式细胞仪检测T淋巴细胞亚群CD4 细胞和CD8 细胞数量。结果:与荷瘤对照组相比,中剂量THPS明显抑制小鼠S180瘤生长(P<0.01),增加胸腺指数(P<0.01)和脾指数(P<0.01),提高CD4 细胞数量(P<0.05);中剂量THPS与CTX合用后,与环磷酰胺组比较,明显降低瘤重(P<0.05),减轻CTX所致的胸腺指数(P<0.01)、脾指数(P<0.01)、CD4 细胞(P<0.01)和CD8 细胞(P<0.05)数量的下降。结论:中剂量的THPS具有抑制S180瘤生长,减轻CTX的免疫抑制作用,其机制与提高免疫器官的重量和T细胞介导的免疫应答有关。