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排序方式: 共有156条查询结果,搜索用时 23 毫秒
1.
Dimitrios Stagos Gregorios D. Amoutzias Antonios Matakos Argyris Spyrou Aristides M. Tsatsakis Dimitrios Kouretas 《Food and chemical toxicology》2012
Primary liver cancer or hepatocellular carcinoma (HCC) is one of the most frequent tumors representing the fifth commonest malignancy worldwide and the third cause of mortality from cancer. Currently, the treatments for HCC are not so effective and new strategies are needed for its fight. Chemoprevention, the use of natural or synthetic chemical agents to reverse, suppress or prevent carcinogenesis is considered an important way for confronting HCC. Many of the chemopreventive agents are phytochemicals, namely non-nutritive plant chemicals with protective or disease preventive properties. In this review, we focus on plant polyphenols, one of the most important classes of phytochemicals, their chemopreventive properties against HCC and discuss the molecular mechanisms accounting for this activity. 相似文献
2.
3.
Melatonin modulates dysregulated circadian clocks in mice with diethylnitrosamine‐induced hepatocellular carcinoma 下载免费PDF全文
Diana I. Sánchez Bárbara González‐Fernández Irene Crespo Beatriz San‐Miguel Marcelino Álvarez Javier González‐Gallego María Jesús Tuñón 《Journal of pineal research》2018,65(3)
Disruption of circadian rhythms, which are regulated by the circadian clock machinery, plays an important role in different long‐term diseases including hepatocellular carcinoma (HCC ). Melatonin has been reported to alleviate promotion and progression of HCC , but the potential contribution of circadian clock modulation is unknown. We investigated the effects of melatonin in mice which received diethylnitrosamine (DEN ) (35 mg/kg body weight ip) once a week for 8 weeks. Melatonin was given at 5 or 10 mg kg?1d?1 ip beginning 4 weeks after the onset of DEN administration and ending at the sacrifice time (10, 20, 30, or 40 weeks). Liver expression of Bmal1, Clock, Npas2, Rorα, and Sirt1 increased, whereas Cry1, Per1, Per2, Per3, CK 1ε, Rev‐erbα, and Rev‐erbβ decreased following DEN administration. Melatonin treatment prevented changes in the expression of clock genes, and this effect was accompanied by an upregulation of the MT 1 receptor and reduced levels of the hypoxia‐inducible factors Hif‐1α and Hif‐2α. An increased expression of p21, p53, and PARP 1/2, a higher Bax/Bcl‐2 ratio, and a lower expression of Cyclin D1, CDK 6, HSP 70, HSP 90, and GRP 78 proteins were also observed in melatonin‐treated mice. Melatonin significantly potentiated the suppression of proliferation and cell cycle arrest induced by the synthetic REV ‐ERB agonist SR 9009 in human Hep3B cells, and BMAL 1 knocking down attenuated the pro‐apoptotic and antiproliferative effect of melatonin. Results support a contribution of changes in the circadian clock components to the beneficial effects of melatonin in HCC and highlight the usefulness of strategies modulating the circadian machinery in hepatocarcinogenesis. 相似文献
4.
Kazuyuki Hanajiri Hiroshi Mitsui Toshiyuki Maruyama Naoaki Hashimoto Masataka Sata Masao Omata 《Journal of gastroenterology and hepatology》2009,24(5):866-871
Background and Aim: There have so far been few reports describing echographic studies of chemically-induced carcinogenesis in rodent livers. Using echography, we observed diethylnitrosamine-induced liver tumors in rats and examined the effect of an intratumoral injection of an inhibitor of c-Jun N-terminal kinase.
Methods: Male Wistar rats were given 100 ppm of diethylnitrosamine for 6 weeks and their liver nodules were examined by echography weekly. The size of the nodules was measured and they were examined histologically. The effect of SP600125, an inhibitor of c-Jun N-terminal kinase, on the growth of rat hepatoma cell line McA-RH7777 was tested in vitro . Thereafter, SP600125 was injected into the liver nodules under echographic guidance in vivo and the changes in the proliferating cell nuclear antigen expression and size of the nodules were examined.
Results: The four distinct lobes of rat livers were clearly observed by transabdominal echography. The nodules in the livers were first detected 6 weeks after the treatment began, when they were as small as 1.6 mm in diameter. The nodules thereafter became more malignant histologically as they grew larger than 4 mm. SP600125 decreased the expression of proliferating cell nuclear antigen and the growth of McA-RH7777 cells. After SP600125 was injected in vivo , the proliferating cell nuclear antigen level and the growth rate of the rat liver nodules all significantly decreased.
Conclusions: Our results indicate that echography is quite useful for follow-up studies of liver carcinogenesis in rats, and c-Jun N-terminal kinase might be another therapeutic target in liver neoplasms. 相似文献
Methods: Male Wistar rats were given 100 ppm of diethylnitrosamine for 6 weeks and their liver nodules were examined by echography weekly. The size of the nodules was measured and they were examined histologically. The effect of SP600125, an inhibitor of c-Jun N-terminal kinase, on the growth of rat hepatoma cell line McA-RH7777 was tested in vitro . Thereafter, SP600125 was injected into the liver nodules under echographic guidance in vivo and the changes in the proliferating cell nuclear antigen expression and size of the nodules were examined.
Results: The four distinct lobes of rat livers were clearly observed by transabdominal echography. The nodules in the livers were first detected 6 weeks after the treatment began, when they were as small as 1.6 mm in diameter. The nodules thereafter became more malignant histologically as they grew larger than 4 mm. SP600125 decreased the expression of proliferating cell nuclear antigen and the growth of McA-RH7777 cells. After SP600125 was injected in vivo , the proliferating cell nuclear antigen level and the growth rate of the rat liver nodules all significantly decreased.
Conclusions: Our results indicate that echography is quite useful for follow-up studies of liver carcinogenesis in rats, and c-Jun N-terminal kinase might be another therapeutic target in liver neoplasms. 相似文献
5.
目的研究p53对二乙基亚硝胺(DEN)诱导肝细胞恶变过程的影响,探讨p53功能缺失与细胞恶变的关系。方法使用p53特异性抑制剂pifithrin-α(PFT-α)和(或)人p53小RNA干扰质粒sip53抑制L02细胞p53的转录活性。采用荧光素酶报告基因法检测不同时间点、不同浓度DEN对p53功能正常和缺失的L02细胞AP-1转录激活活性的影响,检测不同DEN处理时间对p53转录激活活性的影响及PFT-α对AP-1转录激活活性的影响。转录激活活性用相对荧光强度表示。结果应用PFT-α或转染sip53质粒24h后,p53的转录活性明显下降。单纯DEN处理后AP-1的相对荧光强度轻度上调,而DEN+PFT-α和DEN+sip53处理的细胞内AP-1相对荧光强度与单纯DEN处理组比较均有上调,呈现时间和浓度双重依赖性;在作用24h时点或DEN浓度为100ng/L时作用达高峰,随后回落。DEN处理后p53相对荧光强度明显上调,且存在时间依赖性,在24h达高峰,随后回落。DEN+PFT-α处理的细胞p53相对荧光强度在各时间点的变化不明显,始终保持在较低水平。以PFT-α抑制p53功能后,L02细胞内AP-1的相对荧... 相似文献
6.
Ryan M. Kiefer Stephen J. Hunt Santiago Pulido Stephen Pickup Emma E. Furth Michael C. Soulen Gregory J. Nadolski Terence P. Gade 《Journal of vascular and interventional radiology : JVIR》2017,28(7):1043-1050.e2
Purpose
To test the hypotheses that (i) heavier rats demonstrate improved survival with diminished fibrosis in a diethylnitrosamine (DEN)-induced model of hepatocellular carcinoma (HCC) and (ii) transarterial embolization via femoral artery access decreases procedure times versus carotid access.Materials and Methods
One hundred thirty-eight male Wistar rats ingested 0.01% DEN in water ad libitum for 12 weeks. T2-weighted magnetic resonance imaging was used for tumor surveillance. Rats underwent selective embolization of ≥ 5 mm tumors via carotid or femoral artery catheterization under fluoroscopic guidance. Rats were retrospectively categorized into 3 groups by initial weight (< 300, 300–400, > 400 g) for analyses of survival, tumor latency, and fibrosis. Access site was compared relative to procedural success, mortality, and time.Results
No significant differences in tumor latency were related to weight group (P = .310). Rats weighing < 300 g had shorter survival than both heavier groups (mean, 88 vs 108 d; P < .0001), and more severe fibrosis (< 300 g median, 4.0; 300–400 g median, 1.5; > 400 g median, 1.0; P = .015). No significant difference was found in periprocedural mortality based on access site; however, procedure times were shorter via femoral approach (mean, 71 ± 23 vs 127 ± 24 min; P < .0001).Conclusions
Greater initial body weight resulted in improved survival without prolonged tumor latency for rats with DEN-induced HCCs and was associated with less severe fibrosis. A femoral approach for embolization resulted in decreased procedure time. These modifications provide a translational animal model of HCC and transarterial embolization that may be suited for short-term survival studies. 相似文献7.
8.
Diethylnitrosamine-induced Hepatic Lesions are Greater in Rats Maintained under a Light-dark Cycle than under Constant Light,Related to the Locomotor Activity Rhythm 下载免费PDF全文
《Asian Pacific journal of cancer prevention》2008,9(4):619-624
Environmental lighting conditions affect circadian rhythm and carcinogenesis. The effect ofdiethylnitrosamine (DEN, i.p., 200 mg/kg) on carcinogenesis and circadian rhythmicity under a light-dark (LD)cycle, constant dark (DD) and constant light (LL) was analyzed in rats. After the recognition of entrainment inlocomotor activity rhythm to LD cycle, animals remained under the LD cycle or were released into DD or LL.Liver carcinogenicity, measured by GST-P immunostaining, was higher under the LD cycle than under DD andLL. Two weeks after DEN injection, locomotor activity in 24 hr had increased under the LD. Circadianrhythmicity might be coupled with the carcinogenicity of DEN. 相似文献
9.
The changes of carbamyl phosphate synthetase I(CPS 1)in diethylnitrosamine-(DEN)-inducedenzyme-altered liver cells were studied by means of immunohistochemical(PAP)and in situcDNA-mRNA hybridization methods.The experimental rats were treated with DEN,2-acetylaminofluorene(2-AAF)and 2/3 hepatectomy according to Solt-Farber's protocol andwere further promoted by oral daily administration of 0.05% phenobarbital in drinking water.The results showed that the average number of lesions showing abnormal expression of CPS1 was relatively constant over the course of the experiment(8 months),while the numberof normally expressing lesions gradually decreased.The former lesions were also largerin volume than the latter ones.We conclude that in DEN-initiated lesions the abnormallyexpressed CPS 1 lesions may grow continuously,thus leading to the formation of largernodules.We also suspect that some of these lesions have increased tendencies to developinto tumors. 相似文献
10.
二乙基亚硝胺联合N-亚硝基吗啉诱导大鼠肝癌模型的实验病理研究 总被引:4,自引:0,他引:4
目的建立二乙基亚硝胺(diethylnitrosamine,DEN)联合Ⅳ-亚硝基吗啉(N-nitrosomorpholine,NMOR)诱导SD大鼠的肝癌模型并初步动态观察肝脏病理形态变化及肝癌肺转移。方法按100mS/kg体重腹腔注射一次DEN,第二天开始给予含100ppmNMOR饮水供鼠自由饮用的方法诱导SD大鼠肝癌模型,病理常规HE染色动态观察。结果病理学检查证实DEN+NMOR成功诱导出具有转移能力的肝癌模型,20周时肝癌发生率为87.5%(21/24),肺转移发生率为47.6%(10/21)。病理过程大致经过肝细胞损伤期、肝细胞增生硬化期、肝细胞癌变和肺转移发生等时期。结论该肝癌模型可以作为研究人类肝癌发生、发展和转移的一种理想的动物模型。 相似文献