Modulation of the antioxidant/pro-oxidant balance,cytotoxicity and antiviral actions of grape seed extracts

Grape seed extracts (GSEs) were investigated in yeast cells harbouring defects in their antioxidant system (regarding the cellular growth and growth recovery from H₂O₂ insult). GSEs antioxidant activity was detected in wild-type and mutant strains Δcta1, Δgsh1 and Δoye2glr1, while pro-oxidant activity in Δsod1 cells was seen. Assessment of proliferation of prostate cancer PC3 and HBV-replicating HepG2 2.2.15 cells treated with GSEs has shown higher cytotoxicity of red grape seed extract (RW) than white grape seed extract (WW) subjective to dose and period of administration. No antiviral effect was detected by measuring the secreted virion particles in HepG2 2.2.15 cells treated with GSEs. The GSEs play a dual antioxidant/pro-oxidant role in vivo according with the cellular antioxidant system deficiencies and exhibit cytotoxic properties in PC3 and HepG2 2.2.15 cell lines, but no antiviral action against HBV.     

人食管、胃、大肠癌组织中HSP70蛋白表达分析

采用Western Blot方法,检测、分析人食管、胃、大肠的正常组织、癌旁组织及癌组织中的HSP70蛋白表达差异。在不同器官的不同组织中,HSP70的表达情况有较大差异。在人胃、食管、大肠三个器官的正常组织、癌旁组织和癌组织中,HSP70的表达量依次升高。消化道癌组织中大量表达的HSP70蛋白可能在上述组织癌变进程中起一定作用,为深入研究消化道肿瘤的致病机理和治疗提供理论依据。     

纳米羟基磷灰石对肝癌细胞端粒酶基因表达的影响

研究羟基磷灰石（HAP）纳米粒子对Bel-7402人肝癌细胞端粒酶基因表达的影响。采用均相沉淀法制备出稳定单分散的HAP纳米粒子,应用透射电镜、电位粒度仪对其进行表征。HAP纳米粒子作用Bel-7402肝癌细胞4 h后,采用原位杂交技术检测Bel-7402肝癌细胞的端粒酶基因表达。结果表明HAP纳米粒子作用组的Bel-7402肝癌细胞的端粒酶阳性细胞比例为61.38%,而对照组的端粒酶阳性细胞比例为87.89%,2组有显著性差异（P〈0.01）。HAP纳米粒子可使Bel-7402肝癌细胞的端粒酶基因表达下调。     

Iron‐Oxide‐Based Nanovector for Tumor Targeted siRNA Delivery in an Orthotopic Hepatocellular Carcinoma Xenograft Mouse Model

Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. Small interfering RNA (siRNA) holds promise as a new class of therapeutics for HCC, as it can achieve sequence‐specific gene knockdown with low cytotoxicity. However, the main challenge in the clinical application of siRNA lies in the lack of effective delivery approaches that need to be highly specific and thus incur low or no systemic toxicity. Here, a nonviral nanoparticle‐based gene carrier is presented that can specifically deliver siRNA to HCC. The nanovector (NP‐siRNA‐GPC3 Ab) is made of an iron oxide core coated with chitosan‐polyethylene glycol (PEG) grafted polyethyleneimine copolymer, which is further functionalized with siRNA and conjugated with a monoclonal antibody (Ab) against human glypican‐3 (GPC3) receptor highly expressed in HCC. A rat RH7777 HCC cell line that coexpresses human GPC3 and firefly luciferase (Luc) is established to evaluate the nanovector. The nanoparticle‐mediated delivery of siRNA against Luc effectively suppresses Luc expression in vitro without notable cytotoxicity. Significantly, NP‐siLuc‐GPC3 Ab administered intravenously in an orthotopic model of HCC is able to specifically bound to tumor and induce remarkable inhibition of Luc expression. The findings demonstrate the potential of using this nanovector for targeted delivery of therapeutic siRNA to HCC.     

In situ and minimally invasive breast cancer: morphologic and kinetic features on contrast-enhanced MR imaging

Purpose: This retrospective study was undertaken to investigate the morphologic and dynamic features of in situ and minimally invasive breast cancer on contrast-enhanced (c.-e.) MR imaging and to examine possible associations to pathology features. Material and methods: A total of 71 patients underwent MR imaging. T1-weighted FLASH-3D images were obtained before and after intravenous administration of Gd-DTPA. Histopathologic analysis of 78 lesions revealed ductal carcinoma in situ (DCIS)n=50 and DCIS with microinvasionn=28. MR features were correlated with histopathologic findings. Results: Enhancement in DCIS was focal (73%), diffuse (10%) or ductal (17%). No enhancement occurred in two cases (4%). In 65% enhancement speed was classified as delayed. There was a tendency toward a more ill-defined (83 vs. 43%) enhancement pattern in high grade DCIS and a more ductal (29 vs. 12%) and faster (50 vs. 29%) enhancement in comedo type DCIS. However, significant differences in the enhancement behaviour could neither be demonstrated between high grade and non high grade DCIS nor between comedo and non comedo type DCIS. No significant differences were noted between pure and microinvasive DCIS. Conclusion: In this retrospective analysis the majority (96%) of DCIS lesions show contrast enhancement. However, in only about 50% of DCIS the criteria of a so-called ‘typical’ enhancement behaviour was fulfilled, that means strong, early, focal ill-circumscribed or ductal. Enhancement that follows a duct is often associated with malignancy, however this feature was only present in 17% of the cases. c.-e. MR imaging allowed the detection of 25 additional foci of DCIS. Therefore malignant in situ lesions can be present with atypical enhancement, and should be taken into consideration in high-risk patients in particular.     

Expression Profiles of ASIC1/2 and TRPV1/4 in Common Skin Tumors

The acid-sensing ion channels ASIC1 and ASIC2, as well as the transient receptor potential vanilloid channels TRPV1 and TRPV4, are proton-gated cation channels that can be activated by low extracellular pH (pH_e), which is a hallmark of the tumor microenvironment in solid tumors. However, the role of these channels in the development of skin tumors is still unclear. In this study, we investigated the expression profiles of ASIC1, ASIC2, TRPV1 and TRPV4 in malignant melanoma (MM), squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and in nevus cell nevi (NCN). We conducted immunohistochemistry using paraffin-embedded tissue samples from patients and found that most skin tumors express ASIC1/2 and TRPV1/4. Striking results were that BCCs are often negative for ASIC2, while nearly all SCCs express this marker. Epidermal MM sometimes seem to lack ASIC1 in contrast to NCN. Dermal portions of MM show strong expression of TRPV1 more frequently than dermal NCN portions. Some NCN show a decreasing ASIC1/2 expression in deeper dermal tumor tissue, while MM seem to not lose ASIC1/2 in deeper dermal portions. ASIC1, ASIC2, TRPV1 and TRPV4 in skin tumors might be involved in tumor progression, thus being potential diagnostic and therapeutic targets.     

MIR29A Impedes Metastatic Behaviors in Hepatocellular Carcinoma via Targeting LOX,LOXL2, and VEGFA

Primary liver cancer accounts for the third most deadly type of malignant tumor globally, and approximately 80% of the cases are hepatocellular carcinoma (HCC), which highly relies on the activity of hypoxia responsive pathways to bolster its metastatic behaviors. MicroRNA-29a (MIR29A) has been shown to exert a hepatoprotective effect on hepatocellular damage and liver fibrosis induced by cholestasis and diet stress, while its clinical and biological role on the activity hypoxia responsive genes including LOX, LOXL2, and VEGFA remains unclear. TCGA datasets were retrieved to confirm the differential expression and prognostic significance of all genes in the HCC and normal tissue. The Gene Expression Omnibus (GEO) dataset was used to corroborate the differential expression and diagnostic value of MIR29A. The bioinformatic identification were conducted to examine the interaction of MIR29A with LOX, LOXL2, and VEGFA. The suppressive activity of MIR29A on LOX, LOXL2, and VEGF was verified by qPCR, immunoblotting, and luciferase. The effect of overexpression of MIR29A-3p mimics in vitro on apoptosis markers (caspase-9, -3, and poly (ADP-ribose) polymerase (PARP)); cell viability and wound healing performance were examined using immunoblot and a WST-1 assay and a wound healing assay, respectively. The HCC tissue presented low expression of MIR29A, yet high expression of LOX, LOXL2, and VEGFA as compared to normal control. Serum MIR29A of HCC patients showed decreased levels as compared to that of normal control, with an area under curve (AUC) of 0.751 of a receiver operating characteristic (ROC) curve. Low expression of MIR29A and high expression of LOX, LOXL2, and VEGFA indicated poor overall survival (OS). MIR29A-3p was shown to target the 3′UTR of LOX, LOXL2, and VEGFA. Overexpression of MIR29A-3p mimic in HepG2 cells led to downregulated gene and protein expression levels of LOX, LOXL2, and VEGFA, wherein luciferase reporter assay confirmed that MIR29A-3p exerts the inhibitory activity via directly binding to the 3′UTR of LOX and VEGFA. Furthermore, overexpression of MIR29A-3p mimic induced the activity of caspase-9 and -3 and PARP, while it inhibited the cell viability and wound healing performance. Collectively, this study provides novel insight into a clinical-applicable panel consisting of MIR29, LOX, LOXL2, and VEGFA and demonstrates an anti-HCC effect of MIR29A via comprehensively suppressing the expression of LOX, LOXL2, and VEGFA, paving the way to a prospective theragnostic approach for HCC.     

胰腺癌不同调强方式的剂量学比较

目的 比较胰腺癌患者固定野调强放疗（FF-IMRT）与容积调强放疗（VMAT）的剂量学差异，为临床选择合适的照射技术提供参考。方法 选择10例胰腺癌术后患者，分别根据其同一CT模拟定位图像设计FF-IMRT计划和VMAT计划，处方剂量50Gy/25次。分析分析DVH曲线，评估靶区、危及器官和正常组织的剂量分布，并统计二者跳数（MU）和治疗时间的差别。结果 FF-IMRT计划和VMAT计划的靶区剂量分布均无有统计学差异。与FF-IMRT计划相比，VMAT计划中肝脏、胃、小肠、Body的V5出现有统计学意义的升高，而肝脏的V10和V20,胃的V10,小肠的V10、V20、V50，左肾的V20，右肾的V30、Dmean、Dmax，以及Body的V10、V20、Dmax有不同程度下降，脊髓的Dmax升高1.85Gy。另外，VMAT计划的MU数减少了126.9MU(20.48%)，治疗时间明显缩短。结论 胰腺癌患者选择VMAT计划，可以在不降低计划水平上的剂量分布的前提下，大大减少跳数，减少每次治疗时间。