Fe3O4-As2O3-PLA复合体联合热疗对骨肉瘤治疗的细胞学研究

目的 研究磁性三氧化砷-聚乳酸纳米粒子(Fe₃O₄-As₂O₃-PLA)复合体联合磁流体热疗对骨肉瘤细胞株UMR-106的生长的影响。方法 磁性三氧化砷-聚乳酸纳米粒子复合体的制备,透射电镜及荧光光度计对其形态及载药量进行观察,高频交变磁场中对其进行体外升温实验,骨肉瘤细胞的培养,四甲基偶氮唑蓝(MTT)比色法检测磁性三氧化砷-聚乳酸纳米粒子复合体联合磁流体热疗对骨肉瘤细胞株UMR-106生长的影响,流式细胞仪(FCM)检测凋亡细胞。结果 所制备的磁性三氧化砷-聚乳酸纳米粒子复合体比较均匀,粒径在60~70 nm,载药量约为10.3%,在输出电流Ⅰ=300 A的高频交变磁场中具有升温能力,且能达到肿瘤治疗的有效温度(41℃~46℃),磁性三氧化砷-聚乳酸纳米粒子复合体联合磁性热疗能抑制骨肉瘤细胞株UMR-106的生长,促进其调亡,且较单纯的As₂O₃液组及单纯的Fe₃O₄磁性纳米粒子热疗组的治疗效果明显。结论 Fe₃O₄-As₂O₃-PLA复合体联合磁性热疗可同时发挥As₂O₃的细胞毒性作用和磁感应加热的联合定向治疗作用,效果优于单纯的As₂O₃液组及单纯的Fe₃O₄磁性纳米粒子热疗组,为临床治疗骨肉瘤提供新的治疗方法。     

氧化应激及炎性反应与缺血性脑卒中的关系

 目的 探讨氧化应激及炎性反应指标在缺血性脑卒中的临床意义。方法 检测缺血性脑卒中(ischemic stroke, IS)患者和健康对照组血清中总抗氧化能力(total antioxidant capacity,TAC)、氧化型低密度脂蛋白(oxidized low density lipoprotein ,Ox-LDL)、超氧化物歧化酶(super oxide dismutase ,SOD)、超敏C反应蛋白(high sensitivity C reactive protein,Hs-CRP)等指标的表达,采用ELISA方法检测血清TAC、Ox-LDL;在贝克曼库尔特AU5821全自动生化分析仪上检测其他指标的水平。结果 (1)治疗组较正常对照组血清中TAC显著性降低,几乎为健康人水平的1/12(P＜0.01),高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、SOD的水平有所下降(P＜0.05);(2)Hs-CRP 、Ox-LDL、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)的水平显著性升高(均P＜0.01),治疗组血清中Hs-CRP约为对照组的16倍,其OX-LDL水平约为1.7倍,LDL-C约为1.6倍。治疗组较对照组血清中氧化应激及炎性反应指标的表达差异有统计学意义。结论 脑卒中的发生可能与氧化应激、炎性反应有重大关系。     

Pomegranate juice intake attenuates the increase in oxidative stress induced by intravenous iron during hemodialysis

The hemodialysis (HD) procedure induces oxidative stress (OS), which is further aggravated by intravenous (IV) iron administration, aimed at correcting anemia of patients with HD. We have recently shown that 1 year of pomegranate juice (PJ) intake attenuated OS and inflammation in patients with HD. In the current study, we hypothesized that a single dose of PJ can attenuate the enhanced OS and inflammation induced by both the dialysis procedure and IV iron administration during HD session. Twenty-seven patients with HD were randomized to receive PJ or placebo during 1 dialysis session with IV iron. Blood samples were drawn before and after the session to asses OS biomarkers such as advanced oxidation protein products and myeloperoxidase (MPO), whereas polymorphonuclear leukocyte (PMNL) counts served as an indirect measure of inflammation. At the end of the dialysis session, an increase in advanced oxidation protein products and MPO levels as well as a decrease in PMNLs counts were observed in the placebo group, whereas no significant changes occurred in the PJ group. The postdialysis increase in MPO levels in the placebo group is a direct result of PMNL degranulation, associated with postdialysis decrease in PMNL counts. Degranulation of PMNLs leads to the release of other cell moieties, such as inflammatory mediators and proteases that enhance inflammation. We conclude that PJ intake attenuated the increase in systemic OS and inflammation induced by IV iron administration during the dialysis session. These beneficial effects illuminate the previously observed attenuation in OS and inflammation in patients with HD on prolonged PJ intake.     

Lasers in skin cancer prophylaxis

In recent years, novel approaches have been developed in medical oncology, and antiangiogenic treatments have had a role in the treatment of colorectal, renal and breast cancers. The role of these agents in brain tumors is, however, controversial, since these drugs may induce modifications in neuroradiological patterns without even affecting the real tumor burden. Moreover, despite the intriguing results in terms of progression-free survival and response rate obtained with these agents, data about survival are superimposable with historical controls. Thus, there is a need for solid end points to evaluate the role of these agents in Phase II trials in the field of neuro-oncology.     

Serum MicroRNA-210 as a Predictive Biomarker for Treatment Response and Prognosis in Patients with Hepatocellular Carcinoma undergoing Transarterial Chemoembolization

PurposeTo investigate whether serum microRNA-210 (miR-210) level can serve as an indicator of prognosis and a predictor of efficacy of transarterial chemoembolization in patients with hepatocellular carcinoma (HCC).Materials and MethodsSerum miR-210 level was measured in 113 patients with HCC before transarterial chemoembolization (t1), 3 days after transarterial chemoembolization (t2), and 4 weeks after transarterial chemoembolization (t3) and compared with 39 healthy control subjects. The correlations between miR-210 levels and clinicopathologic factors, tumor responsiveness, and prognosis were analyzed. The modified Response Evaluation Criteria in Solid Tumors assessment was conducted at t3.ResultsA higher mean baseline miR-210 level was observed in patients with HCC compared with control subjects (3.69 ± 2.04 vs 1.08 ± 0.45, P < .001). A positive correlation between baseline miR-210 level and tumor size (P < .001), vascular invasion (P = .005), tumor differentiation (P = .037), and Barcelona Clinic Liver Cancer stage (P < .001) was observed. Elevated baseline miR-210 level also served as an independent prognostic factor predicting poor overall survival (risk ratio, 2.082; P = .003). Patients who did not respond to transarterial chemoembolization had higher baseline miR-210 levels than patients who did respond to treatment (4.34 ± 1.67 vs 3.28 ± 2.15, P < .001). In addition, miR-210 levels increased significantly 4 weeks after transarterial chemoembolization in nonresponders (5.79 ± 2.06 at t3 vs 4.34 ± 1.67 at t1, P < .001), whereas no significant change was observed in responders (3.53 ± 2.20 at t3 vs 3.28 ± 2.15 at t1, P = .116). Lastly, an inverse correlation was identified between miR-210 change t1–t3 with the time to radiologic progression (P < .001).ConclusionsSerum miR-210 may represent a novel biomarker for predicting efficacy of transarterial chemoembolization and overall survival for patients with HCC.     

Does the geriatric nutrition risk index predict the prognosis of patients with oral squamous cell carcinoma?

Malnutrition is associated with the prognosis of malignant disease. The geriatric nutritional risk index (GNRI), based on serum albumin (ALB) levels and the present and ideal body weight, is a simple screening tool with which to predict the risk of malnutrition and mortality in patients. We hypothesised that nutritional markers could predict the prognosis of patients with oral squamous cell carcinoma (OSCC). The primary predictor variable was the GNRI score and the primary outcome variable was overall survival (OS). Univariate and multivariate analyses were performed using a Cox proportional hazard model to identify independent prognostic factors. The sample comprised 155 patients, of whom 17 presented with a low GNRI score (≤98) and 138 with a high GNRI score (≥ 98). There was a significant difference in OS when patients were stratified according to GNRI scores, with OS rates of 29.2% and 76.4% for scores of 98 and under and scores of over 98, respectively (p < 0.001). Univariate analyses showed that OS was significantly associated with GNRI score, age, T classification, N classification, stage, body mass index (BMI), prognostic nutrition index, and ALB levels. Analysis identified three independent predictive factors for OS: age (hazard ratio (HR) 2.184; 95% confidence interval (CI) 1.119 to 4.261; p = 0.022), stage (HR 2.684; 95% CI 1.457 to 5.367; p = 0.011), and GNRI score (HR 4.559; 95% CI 2.172 to 9.570; p <0.001). The results suggest that the GNRI score (>98 vs ≤98) is a good prognostic marker in patients with OSCC, along with age and stage.     

Role of genotype-based approach in the clinical management of adult acute myeloid leukemia with normal cytogenetics

Acute myeloid leukemia (AML) is the most common form of acute leukemia affecting adults. Although it is a complex disease driven by numerous genetic and epigenetic abnormalities, nearly 50% of patients exhibit a normal karyotype (CN-AML) with an intermediate cytogenetic risk. However, a widespread genomic analysis has recently shown the recurrence of genomic aberrations in this category (mutations of FLT3, CEBPA, NPM1, RUNX1, TET2, IDH1/2, DNMT3A, ASXL1, MLL and WT1) thus revealing its marked genomic heterogeneity. In this perspective, a global gene expression analysis of AML patients provides an independent prognostic marker to categorize each patient into clinic-pathologic subgroups based on its molecular genetic defects. Consistently such classification, taking into account the uniqueness of each AML patient, furnishes an individualized treatment approach leading a step closer to personalized medicine. Overall the genome-wide analysis of AML patients, by providing novel insights into biology of this tumor, furnishes accurate prognostic markers as well as useful tools for selecting the most appropriate treatment option. Moreover it provides novel therapeutic targets useful to enhance efficacy of the current anti-AML therapeutics. Here we describe the prognostic relevance of such new genetic data and discuss how this approach can be used to improve survival and treatment of AML patients.     

Multidrug resistance-associated protein 3 confers resistance to chemoradiotherapy for rectal cancer by regulating reactive oxygen species and caspase-3-dependent apoptotic pathway

This study aimed to clarify the role of multidrug resistance-associated protein 3 (MRP3) in resistance to neoadjuvant chemoradiotherapy and long-term prognosis of advanced rectal cancer. Immunohistochemistry was used to measure MRP3 expression in biopsy specimens of 144 stage II–III rectal cancer patients who received preoperative chemoradiotherapy. The effect of MRP3 expression on short-term pathological response and postoperative long-term prognosis were assessed using the Cox proportional hazards model. Short interfering RNAs targeting MRP3 were synthesized and used to transfect human colorectal carcinoma cell lines. The effect of MRP3 down-regulation on cell proliferation and apoptosis in response to 5-fluorouracil and/or irradiation were examined in vitro and in xenograft mouse models, respectively. The content of intracellular reactive oxygen species and the activity of caspase-3-dependent apoptotic pathway in response to irradiation were further evaluated. High expression (immunoreactive score > 6) of MRP3 significantly predicted poor pathological response to chemoradiotherapy (tumor regression grade ≤ 2 vs. ≥3, p = 0.002) in univariate analysis and unfavorable long-term prognosis (5-year overall survival: HR = 1.612, 95% CI, 1.094–2.375, p = 0.016; 5-year disease-free survival: HR = 1.513, 95% CI, 1.041–2.200, p = 0.030) in multivariate Cox analysis. MRP3 down-regulation significantly increased 5-fluorouracil or irradiation-induced cell apoptosis and attenuated tumor growth following irradiation in animal models. MRP3 inhibition significantly reduced intracellular reactive oxygen species exporting from cells following irradiation, and increased expression of cleaved poly ADP-ribose polymerase and caspase-3. Aberrant expression of MRP3 in rectal cancer confers chemo-radioresistance. MRP3 might be a predictive factor and an attractive target in treating advanced rectal cancer.     

A systematic review of dual targeting in HER2-positive breast cancer

Background

Human epidermal growth factor receptor 2 (HER2) is overexpresed in 15–20% of all breast cancers. Treatment with trastuzumab has led to an improved outcome and prolonged survival of HER2-positive breast cancer patients and today the drug is established as standard of care in both the adjuvant and metastatic settings. However, trastuzumab resistance is common and a major focus in the treatment of HER2-positive breast cancer has been developing therapeutic agents to either potentiate the effect of trastuzumab or to target cells which have become resistant to trastuzumab. The present review addresses efficacy and toxicity of dual targeting in HER2-positive breast cancer.

Materials and methods

A computer-based literature search was carried out using PubMed; data reported at international meetings and clinicaltrials.gov was included.

Results

This paper describes efficacy and safety of lapatinib, pertuzumab or trastuzumab-DM1 in combination with trastuzumab in the (neo)adjuvant and metastatic settings. Furthermore, combinations of trastuzumab and drugs targeting the downstream pathway are described.

Conclusion

Dual blockade is likely to represent a substantial advance for patients with HER2-positive breast cancer. However, the relevant subpopulation remains to be defined and side effects including cardiotoxicity might be a limiting factor to the use. There is an urgent need for prospective biomarker-driven trials to identify patients for whom dual targeting is cost-effective.