The Effect of Different Doses of Cigarette Smoke in a Mouse Lung Tumor Model

Few studies have used Balb/c mice as an animal model for lung carcinogenesis. In this study, we investigated the effect of different doses of cigarette smoking in the urethane-induced Balb/c mouse lung cancer model. After injection of 3mg/kg urethane intraperitoneally, the mice were then exposed to tobacco smoke once or twice a day, five times a week, in a closed chamber. The animals were randomly divided into four groups. The control group (G0) received urethane only. The experimental groups (G1, G2 and G3) received urethane and exposure to the smoke of 3 cigarettes for 10 minutes once a day, 3 cigarettes for 10 minutes twice a day, and 6 cigarettes for 10 minutes twice a day, respectively. The mice were sacrificed after 16 weeks of exposure, and the number of nodules and hyperplasia in the lungs was counted. The results showed no statistically significant difference in the mean number of nodules and hyperplasia among the different groups, suggesting that the Balb/c mice are not suitable to study the pathogenesis of tobacco smoking-induced tumor progression in the lungs.     

Morphological Assessment of Prostatotropic Activity of (3,5-Dimethyl-4-Hydroxy)Benzyl Thiododecane on a Model of Benign Prostatic Hyperplasia in Rats

Bulletin of Experimental Biology and Medicine - Prostatotropic activity of (3,5-dimethyl-4-hydroxy)benzyl thiododecane (T-DD) was evaluated on a model of benign prostatic hyperplasia induced in...     

King Cobra (Ophiophagus hannah) Venom L-Amino Acid Oxidase Induces Apoptosis in PC-3 Cells and Suppresses PC-3 Solid Tumor Growth in a Tumor Xenograft Mouse Model

King cobra (Ophiophagus hannah) venom L-amino acid oxidase (OH-LAAO), a heat stable enzyme, has been shown to exhibit very potent anti-proliferative activity against human breast and lung tumorigenic cells but not in their non-tumorigenic counterparts. We further examine its in vitro and in vivo anti-tumor activity in a human prostate adenocarcinoma (PC-3) model. OH-LAAO demonstrated potent cytotoxicity against PC-3 cells with IC₅₀ of 0.05 µg/mL after 72 h incubation in vitro. It induced apoptosis as evidenced with an increase in caspase-3/7 cleavages and an increase in annexin V-stained cells. To examine its in vivo anti-tumor activity, we treated PC-3 tumor xenograft implanted subcutaneously in immunodeficient NU/NU (nude) mice with 1 µg/g OH-LAAO given intraperitoneally (i.p.). After 8 weeks of treatment, OH-LAAO treated PC-3 tumors were markedly inhibited, when compared to the control group (P <0.05). TUNEL staining analysis on the tumor sections showed a significantly increase of apoptotic cells in the LAAO-treated animals. Histological examinations of the vital organs in these two groups showed no significant differences with normal tissues, indicating no obvious tissue damage. The treatment also did not cause any significant changes on the body weight of the mice during the duration of the study. These observations suggest that OH-LAAO cytotoxic effects may be specific to tumor xenografts and less to normal organs. Given its potent anti-tumor activities shown in vitro as well as in vivo, the king cobra venom LAAO can potentially be developed to treat prostate cancer and other solid tumors.     

Pharmacological properties of N-methoxy-3-(3,5-ditert-butyl-4-hydroxybenzylidene)-2-pyrrolidone (E-5110), a novel nonsteroidal antiinflammatory agent

The antiinflammatory activity of a novel pyrrolidone derivative E-5110 was investigated using anti-inflammatory, analgesic and antipyretic animal models in comparison to indomethacin (IND) and piroxicam (PIR). The acute antiinflammatory activity of E-5110 on carrageenin paw edema was similar to IND, and half of PIR. E-5110 inhibited the pleural exudate volume and leucocyte infiltration in a reversed passive Arthus reaction more potent than IND. The chronic inflammatory responses in the established adjuvant- and type II collagen-induced arthritis were suppressed by E-5110 similar to IND and PIR. The analgesic potency of E-5110 was similar to IND and PIR, but the antipyretic activity of E-5110 was more potent than that of IND, and slightly more potent than that of PIR. The ulcerogenic effect of E-5110 on rat gastric mucosa was less than that of the reference drugs.     

Effect of Asymptomatic Natural Infections due to Common Mouse Pathogens on the Metastatic Progression of B16 Murine Melanoma in C57BL/6 Mice

To investigate whether the presence of infections in C57BL/6 mice influences the metastatic ability of B16 melanoma (B16M) cells, we compared the susceptibility to metastasis development of pathogen-free mice with that of mice from a colony endemically infected with several mouse pathogens. We found that, compared to seronegative controls, mice that were seropositive at least to Mouse Hepatitis Virus (MHV) and Mycoplasma pulmonis: (i) exhibited a higher interindividual variability in all the parameters quantifying metastatic progression; (ii) had elevated serum levels of proinflammatory cytokines both before and at the end of the experiment; (iii) were more susceptible to hepatic metastasis. Interestingly, final levels of tumor necrosis factor (TNF)-α and interleukin (IL)-18 correlated with the extent of hepatic colonization by the melanoma cells. To confirm the metastasis-enhancing effect of MHV and M. pulmonis we measured the ability of B16M cells to metastasize in pathogen-free animals housed for increasing time-intervals in the vicinity of MHV⁺ animals. Notably, susceptibility to metastasis was lower in animals seronegative to MHV than in MHV⁺ mice, whereas the latter were less susceptible to metastasis than MHV⁺ M. pulmonis⁺ mice. Seropositive animals had increased levels of TNF-α and IL-18 suggesting that MHV and M. pulmonis enhance the metastatic ability of melanoma cells by inducing the release of proinflammatory cytokines. While our results highlight the importance of using pathogen-free animals in metastasis studies, they emphasize the need for a comprehensive health monitoring of the mice used in such studies, particularly in case of using facilities lacking appropriate containment measures.     

Rho蛋白对肿瘤细胞骨架活动及生长调节的影响

近年来对 Rho 家族蛋白的研究进展很快,Rho 家族蛋白最主要的功能是调节肌动蛋白细胞骨架的重组,从而调节细胞的的形态变化和运动.Rho 族蛋白与肿瘤关系密切,在其调节子和效应子作用下,该族蛋白的活化能增强细胞的运动能力,诱导细胞周期进展的基因表达,促进胞外基质的降解和重建,因此,在调节肿瘤细胞增殖、凋亡和浸润转移等生物学行为中发挥重要作用.对 Rho 蛋白的深入研究有助于进一步判断其在这些行为过程中的作用机制,从而为肿瘤治疗提供新的依据.     

Infradian 4-Day Rhythm of Proliferative Activity of L-929 Mouse Fibroblast Culture in the Logarithmic Growth Phase Is Exogenous

Bulletin of Experimental Biology and Medicine - We studied the dynamic of proliferative activity of cultured mouse transformed fibroblast-like L-929 cells in the logarithmic growth phase. During a...     

B细胞生长因子活性上清对人—人杂交瘤细胞生长影响的研究

本研究用金黄色葡萄球菌(Cowan 1株)死菌制剂(SAC)刺激人B淋巴细胞建立了人B细胞生长因子(BCGF)的检测系统。发现经PHA刺激的人扁桃体细胞培养上清可以促进SAC活化的B细胞的生长,~3H-TdR掺入率提高了2～3倍。同时,用~3H-TdR掺入法和有限稀释法观察了该上清对人-人B细胞杂交瘤生长和克隆率的影响,发现其可以促进人-人B细胞杂交瘤的生长、~3H-TdR掺入率提高2～3倍,可提高克隆率3倍以上。但人-人B细胞杂交瘤可吸收掉上述BCGF活性上清中的促杂交瘤细胞生长因子(HGF)活性,而对BCGF活性无明显影响。提示该上清同时具有人BCGF和HGF活性,部分BCGF活性与HGF活性可能是由不问的分子所介导。     

Role for p16(INK4a) in progression of gastrointestinal stromal tumors of the stomach: alteration of p16(INK4a) network members

Gastrointestinal stromal tumors feature a wide spectrum of biologic behavior, ranging from benign to extremely malignant. To determine the role of p16^INK4a alteration in progression of gastrointestinal stromal tumors of the stomach, we have investigated protein expression and gene methylation in correlation with clinicopathologic factors and survival. In addition to immunohistochemical analysis of p16^INK4a in a series of 95 cases, real-time quantitative methylation specific polymerase chain reaction for p16^INK4a and immunostaining for cyclin D1, cyclin E, pRb, DP-1, E2F-1, and Ki-67 were also evaluated in randomly selected samples. The p16^INK4a labeling indices ranged from 0% to 74% (median, 21%), demonstrating a significant inverse correlation with size (P = .046). On univariate (P = .003) and multivariate (P = .067) analyses, loss of p16^INK4a expression increased the likelihood of a poor tumor-related survival. In addition, size (P = .036) and the mitotic index (P = .005) had independent prognostic influence. The p16^INK4a methylation index, which ranged from 0% to 100% (median, 17%), was significantly higher in larger tumors (P < .001) and in high-risk category lesions (P = .001) and inversely correlated with protein expression. Hierarchical cluster analysis based on expression of p16^INK4a network members identified 2 clusters in 27 randomly selected tumor samples, containing 11 and 16 tumors each. Former cluster samples demonstrated higher risk category (P = .022), higher p16^INK4a methylation (P < .001), and more reduced pRb expression (P < .018). In addition, p16^INK4a network members clustered into 2 groups: (1) showing down-regulated p16^INK4a protein and up-regulating of both cyclin D1 and DP-1 and (2) down-regulated pRb and up-regulated E2F-1. We conclude that p16^INK4a alteration has an important role in progression of gastrointestinal stromal tumors of the stomach. Furthermore, the study provides a possible link between regulation of p16^INK4a network members and gastrointestinal stromal tumors.     

Effects of Angelicin on Ovalbumin (OVA)-Induced Airway Inflammation in a Mouse Model of Asthma

Angelicin, a furocoumarin found in Psoralea corylifolia L. fruit, has been reported to have anti-inflammatory activity. The purpose of this study was to determine the protective effects of angelicin on allergic asthma induced by ovalbumin (OVA) in mice. Mice were sensitized to OVA (on days 0 and 14) and challenged with OVA three times (on days 21 to 23). Angelicin (2.5, 5, 10 mg/kg) was given intraperitoneally 1 h before OVA treatment after the initial OVA sensitization. The production of IL-4, IL-5, and IL-13 in BALF and IgE in the serum were measured by ELISA. Lung histological changes were detected by using hematoxylin and eosin (H&E) stain. The results showed that angelicin significantly inhibited inflammatory cells infiltration into the lungs. Histological studies showed that angelicin significantly attenuated OVA-induced lung injury. Meanwhile, treatment of angelicin dose-dependently inhibited OVA-induced the production of IL-4, IL-5, and IL-13 in BALF and IgE in the serum. Furthermore, angelicin was found to inhibit airway hyperresponsiveness and NF-kB activation. In conclusion, our results suggested that angelicin inhibited allergic airway inflammation and hyperresponsiveness by inhibiting NF-kB activation.     

In Vivo Effects of Human Bone Marrow Mesenchymal Stromal Cells on the Development of Experimental B16 Melanoma in Mice

Bulletin of Experimental Biology and Medicine - Experiments on F1(CBA×C57BL/6) mice with experimental metastatic melanoma B16 F10 showed that single intravenous injection of xenogeneic bone...     

不同牵引正畸方式治疗烧伤爪形手的生物力学分析

目的 研究烧伤爪形手畸形的形成及两种牵引正畸治疗中针对软组织的生物力学分析。方法 建立包含皮肤和瘢痕的手部有限元模型,对烧伤爪形手畸形的瘢痕挛缩-肌腱韧带挛缩-瘢痕切除并植皮-牵引正畸治疗全过程进行数值模拟,对相关软组织进行生物力学分析,并对比两种牵引方式的优劣。结果 瘢痕挛缩时,相关的屈肌和伸肌都被拉伸;掌指关节处背侧韧带松弛,多数侧副韧带紧张。手术治疗后,畸形有较大程度缓解;肌腱紧张或松弛程度减小;紧张的侧副韧带松弛,挛缩的背侧韧带被拉伸。牵引正畸治疗对手术治疗具有增益的效果。对于烧伤爪形手畸形,本文所设定的经过瘢痕松解后直接施加动态牵引的治疗方案安全有效,且对肌腱伸长有较好的促进作用;从牵引效果来看,拉长式牵引方法较拮抗式牵引更具有优势。结论 研究结果可以为临床介入和患者预后的改善提供参考。     

高山红景天多糖对小鼠抗柯萨奇B5病毒感染能力的研究

对感染柯萨奇Ｂ５病毒（ＣＶＢ）小鼠模型研究结果表明，高山红景天多糖对发病小鼠心肌功能改善和免疫功能提高均具有明显的促进作用。增强了小鼠抗ＣＶＢ５感染的能力，并对由ＣＢＶ感染性疾病也有一定的防治作用。     

健康儿童同足异趾甲襞微循环对比分析

目的：探讨儿童同足异趾甲襞微循环检测时质量控制。方法：用WX－753B微循环显微镜和图像处理系统，观察52名6岁健康儿童的左足五趾甲襞微循环十九项指标，并进行五趾甲襞微循环之间的两两比较。结果：同足异趾间的甲襞微循环形态学指标存在显著性差异，而流态和襻周状态指标各趾间无显著性差异。拇趾甲襞管襻清晰度较好、数目最多、襻长最长、直径最大、而小趾则相反。结论：同足异趾间甲襞微循环存在一定差异，因此，观测儿童足甲襞微循环时，特别是动态监测病例，应选择同一足趾甲襞观测，观测部位则以拇趾甲襞最佳。     

cRGD肽二聚体对B16黑色素瘤细胞的体外抑制作用及在荷瘤鼠体内分布及显像研究

目的 探讨cRGD肽二聚体对B16黑色素瘤细胞的体外抑制作用及其在荷B16黑色素瘤细胞小鼠动物模型体内的分布及显像研究.方法 用MTT法检测不同浓度及作用时间cRGD肽二聚体对B16黑色素瘤细胞体外增殖能力的影响.采用直接标记法标记99 Tcm-c(RGD)2.建立荷B16黑色素瘤株动物模型,待肿瘤体积为1.0 ～ 1.5cm3左右时,分别于30min、1h、2h、3h、4h、5h及6h时,进行荷瘤鼠体内生物分布及动态显像研究.结果 cRGD肽二聚体浓度为500mg/L、作用48h时,对B16黑色素瘤细胞的增殖具有明显的抑制作用.室温下、ρ(SnCl2·2H20)=1 g/L、反应时间为30 min时,99Tcm-c(RGD)2的标记率可达(87.42±3.21)％,标记产物经Sephadex G10分离纯化后放射化学纯度大于95％;静脉注射后30min行小鼠全身SPECT显像,肿瘤部位可见明显显像剂聚集,但肿瘤与周围组织的对比度较低;延迟至6小时肿瘤仍清晰可见,且随时间延迟肿瘤与周围组织的对比度增高,此时肿瘤/血液为2.15±0.24,肿瘤/肌肉为5.07 ±0.03.结论 该结构cRGD肽二聚体对B16黑色素瘤细胞株具有一定的体外抑制作用,且动物体内肿瘤组织摄取率高,显像清晰,证明其可进一步应用于聚合物多肽靶向药物的研发.     

p16(INK4a) is selectively silenced in the tumoral progression of mycosis fungoides

Knowledge about the molecular mechanisms involved in the pathogenesis of tumoral progression in mycosis fungoides (MF) is still scarce. Because the 9p21 locus seems to be a good target for a detailed study in MF, this prompted us to compare the mechanisms of inactivation of the p16(INK4a), p15(INK4b), and p14(ARF) genes in aggressive and stable forms of MF, performing microsatellite analysis, methylation-specific polymerase chain reaction, direct sequencing, and p16(INK4a) protein expression by immunohistochemistry. Additionally, the p53 gene was also sequenced in tumoral lesions. Thirty-nine patients with stable MF were studied. Alterations in p16(INK4a) and p15(INK4b) genes were detected in 18% and 5% of the cases, respectively. None of the cases analyzed showed alterations of the p14(ARF) gene. In contrast with these findings, in the 11 patients with aggressive MF, alterations of the p16(INK4a), p15(INK4b), or p14(ARF) genes were found in 8 (73%), 3 (27%), and 2 (18%) cases, respectively. A significant proportion (4/11) of these alterations were already present in the p16(INK4a) gene in the initial plaque lesions in these aggressive forms of MF. Alterations in the p16(INK4a) gene, either methylation or loss of heterozygosity, were clearly more frequent than those in the p15(INK4b) and p14(ARF) genes. These p16(INK4A) alterations were confirmed using immunohistochemistry. None of the nine tumoral lesions analyzed showed mutations in exons 1-2 of the p16(INK4a) gene or in exons 5-8 of the p53 gene. These results seem to suggest that 9p21 alterations, and selectively p16(INK4a) silencing, could be a characteristic phenomenon in MF progression.     

Inhibition of ovulation in the rat by a leukotriene B(4) receptor antagonist

The involvement of leukotriene (LT) B(4) in the ovulatory process of the rat was investigated by the use of a LTB(4)-receptor antagonist (ZK158252 = L-ANT) administered either intrabursally in vivo or to the in-vitro perfused ovary. The in-vivo experiments revealed inhibition of human chorionic gonadotrophin (HCG)-induced ovulation by 500 micromol/l L-ANT (median 5.5, 25-75% range 1.0-6.0) compared with controls (median 9.0, range 6.25-13.5). In vitro, ovulation was induced by LH (0.2 microg/ml) + 3-isobutyl-1-methylxanthine (IBMX; 0.2 mmol/l). The ovary was perfused either for 20 h, to study ovulation rate, or for 10 h to examine ovarian concentrations of the ovulatory mediators matrix metalloproteinase (MMP)-2 and MMP-9, plasminogen activator (PA), prostaglandin (PG)E(2) and PGF(2 alpha). Addition of LH+IBMX resulted in a marked stimulation of steroid release and ovulations occurred in all ovaries (median 11.0, range 10.0-14.0). The L-ANT inhibited ovulation in a dose-dependent way (median 10.0, range 8.0-13.0 at 1 micromol/l; median 6.0, range 3.5-10.0 at 10 micromol/l; median 2.0, range 0.75-5.75 at 100 micromol/l). The intra-ovarian activity of PA was increased 1.5-fold by L-ANT (100 micromol/l), but the concentrations of PGE(2) and PGF(2 alpha) remained unaltered. While no changes in MMP-9 were observed, conversion from pro-MMP-2 to active MMP-2 was inhibited by L-ANT. These results suggest that activation of the LTB(4)-receptor within the ovary is involved in the ovulatory process and that the effects of LTB(4)-receptor activation are partly mediated via MMP-2.