Giganteaside D induces ROS-mediated apoptosis in human hepatocellular carcinoma cells through the MAPK pathway

Purpose

Every year, almost one million individuals are diagnosed with hepatocellular carcinoma (HCC) worldwide and more than 690,000 patients die of it. At present, most therapeutic anti-HCC agents are not effective, which is due to the appearance of chemo-resistance and/or toxic side effects. Therefore, it is imperative to find novel more effective anti-HCC agents. Here, we evaluated the effect of giganteaside D (GD), an oleanolic acid saponin from P. scabiosaefolia, on the growth and apoptosis of HCC cells.

Methods and results

Using MTT and clonogenic assays, we found that GD exhibited a significant growth inhibitory effect on the HCC-derived cell lines HepG2 and Bel-7402. In addition, we found that GD induced mitochondria-mediated apoptosis in these HCC-derived cells, as indicated by a decreased mitochondrial potential, activation of Caspase-9 and Caspase-3, cleavage of PARP and release of Cytochrome C from the mitochondria. Besides, we found that GD stimulated the generation of reactive oxygen species (ROS) and that blockage of ROS attenuated the GD-induced mitochondria-mediated apoptosis. Additionally, we found that GD treatment led to a decrease in phosphorylated Erk (p-Erk) and triggered the generation of p-JNK, both components of the mitogen-activated protein kinase (MAPK) signaling pathway. Inhibition of Erk or JNK by specific inhibitors or siRNAs augmented or attenuated the cytotoxic and apoptotic effects of GD.

Conclusions

From our results we conclude that GD can induce ROS-mediated apoptosis in HCC-derived cells through the MAPK pathway. This observation may open up avenues to explore the future use of GD as a HCC chemotherapeutic agent.

     

When is a pathology review indicated in endometrial cancer?

OBJECTIVE: Discrepancies may exist between an original pathology report and formal pathology review, with subsequent implications for treatment. We conducted a study of pathology review in endometrial cancer from a population-based study to identify areas of discrepancy and effect on treatment. METHODS: This was a retrospective cohort study in Ontario, Canada from 1996 to 2000. We identified hysterectomy cases from patients with endometrial cancer that were subject to formal pathology review by a gynecologic pathologist at one of six tertiary care centers. Sarcomas and other rare histologic subtypes with fewer than five cases were excluded. We evaluated discrepancy between original pathology and review by demographics, stage, grade, and risk group. Four risk groups were defined: 1) low (stage I), 2) intermediate (stage I and II), 3) high-risk (stage I and II), and 4) advanced stage (all stage III and IV). Reclassification from one risk group to another upon pathology review represented a potential change in treatment. Factors associated with significant discrepancy were identified by a multivariable logistic regression model. RESULTS: Formal pathology review was available on 450 cases. There were no differences by age, year, or hospital type. The overall discrepancy rate was 42.7% (95% confidence interval 38.2-47.3%). The intermediate-risk group had the highest rate of reclassification into another group (33.1%). The most significant rates of discrepancy were associated with endometrioid grades 2 and 3 tumors and stage IIA disease (39.8%, 50.9%, and 79.6%, respectively). CONCLUSION: There was significant discrepancy between original pathology and formal review in endometrial cancer, with implications for guidelines on pathology review at a population level. LEVEL OF EVIDENCE: III     

NMDA受体依赖的神经元存活及保护作用的机制

NMDA受体属于谷氨酸受体,它在突触传递和突触可塑性中都发挥着非常重要的作用,其介导的兴奋性毒性是脑缺血、缺氧和脑外伤等导致脑损伤的重要分子机制.但是,近年来的研究发现,在生理和某些病理情况下,NMDA受体的激活具有促进神经元存活及保护神经元免受损伤的作用.     

慢性乙型肝炎患者的HDV感染

作者对69例经病理确诊为慢性乙型肝炎患者,检测了肝内δ抗原(ABC免疫组化法)和血清δ抗体(ELISA法),结果57例肝组织有 7例检出δ抗原,39例血清中 7例检出δ抗体,无 1例 δ抗原和抗体同时阳性。HDV 标志的总检出率为20.3％(14/69)。CPH和CAH之间的HDVM检出率无显著性差异。HDV感染与无HDV感染者之间,HBV复制标志无差异。HDV 感染者蛋白质代谢紊乱程度较重。发现3例肝内δ抗原和血清HB-DNA均为阳性,显示重叠HDV感染,对HBV复制未见明显抑制。     

Improvement of heat－tolerance by training I．Evaluation of effects of long－distance running and march training on heat－toleran

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一种“新”的不稳定性胸腰椎压缩劈裂骨折

本文报道9例在CT 和X 线平片上都有同一类型病理变化、发病机理和临床过程的胸腰椎压缩劈裂骨折.CT 上的共同病理变化为:(1)骨折椎的上椎间盘损伤;(2)椎体上1/2的压缩骨折:(3)椎体下1/2的矢状劈裂骨折:(4)椎管前部出现椎体中柱骨折块:(5)椎板骨折.通过对本类骨折的力学分析,作者认为这是—种独立的不稳定性爆裂骨折,且有神经性不稳定的特征.临床治疗应切开复位,并使用有撑开效应的固定器.     

非胰岛细胞瘤性低血糖的研究进展

非胰岛细胞瘤性低血糖(NICTH)是一种胰岛细胞瘤以外的其他肿瘤导致的低血糖症。肿瘤组织分泌过多的胰岛素样生长因子Ⅱ(IGF-Ⅱ)的一种前体形式物质,因其相对分子质量较大,大多数文献称之为big-IGF-Ⅱ,它能产生类胰岛素样活性,故目前认为是导致患者反复出现低血糖的病因。诊断上主要依靠高水平的big-IGF-Ⅱ测定。NICTH的治疗方式较多,但治愈手段主要为手术切除肿瘤组织。现就NICTH的发病机制、临床表现、诊断及治疗等方面的研究进展予以综述。     

Novel Amdoparvovirus Infecting Farmed Raccoon Dogs and Arctic Foxes

A new amdoparvovirus, named raccoon dog and fox amdoparvovirus (RFAV), was identified in farmed sick raccoon dogs and arctic foxes. Phylogenetic analyses showed that RFAV belongs to a new species within the genus Amdoparvovirus of the family Parvoviridae. An RFAV strain was isolated in Crandell feline kidney cell culture.     

医用电子仪器专业存在问题与解决方案的探索

医用电子仪器专业是一门新兴的交叉边沿性学科，分析近年来医电专业开设过程中所存在的问题．并对解决方案进行了探讨。