依托泊苷联合卡铂用于复发性髓母细胞瘤患儿的疗效与安全性

目的:探讨依托泊苷联合卡铂用于复发性髓母细胞瘤患儿的疗效与安全性。方法:选取浙江大学医学院附属儿童医院在2011年1月至2014年6月收治的72例复发性髓母细胞瘤患儿（3～15岁）,随机分为CE组和对照组,每组36例,CE组采用依托泊苷＋卡铂给药方式化疗;对照组采用经典伊立替康＋替莫唑胺＋长春新碱方案化疗。比较两组患儿临床疗效、卡诺夫斯基健康状况量表（KPS）评分、儿科生活质量测定量表4.0（PedsQLTM4.0）评分、总生存期（OS）、无事件生存（EFS）,记录患儿治疗期间药物不良反应的发生情况。结果:治疗后CE组和对照组完全缓解率（CR）分别为41.67%（15/36）和27.78%（10/36）,总缓解率（OR）分别为94.44%（34/36）和77.78%（28/36）,差异有统计学意义（P<0.05）。两组患儿治疗前KPS评分及PedsQLTM4.0评分无统计学差异（P＞0.05）,治疗后CE组和对照组的KPS评分分别为（80±8）和（75±10）分,PedsQLTM4.0评分分别为（89±11）和（84±11）分,差异均有统计学意义（均P<0.05）。截至末次随访时间,CE组有3例失访,对照组有2例失访。截至末次随访时间,CE组和对照组总生存率分别为78.8%（26/33）和55.9%（19/34）,差异有统计学意义（P<0.05）,无事件生存率分别为72.7%（24/33）和52.9%（18/34）,差异无统计学意义（P＞0.05）。CE组化疗期间共出现10例3级以上不良反应,发生率为27.78%（10/36）,对照组化疗期间共出现9例3级以上不良反应,发生率为25.00%（9/36）,差异无统计学意义（P＞0.05）。结论:依托泊苷联合卡铂方案能够明显提高患儿临床缓解率,延长患儿总生存率,同时不增加化疗不良反应,但对无事件生存率的影响并不明显。     

CYP2D6基因多态性对托烷司琼预防化疗所致恶心呕吐效果的影响

肿瘤对人类健康造成很大威胁。化疗作为一种全身性的治疗方法,在肿瘤治疗中的地位不可动摇。化疗所致恶心呕吐（chemotherapy induced nausea and vomiting, CINV）是化疗过程中常见的不良反应,严重影响了患者的情绪、生活质量和肿瘤的控制。CINV的防治对肿瘤患者来说非常重要。托烷司琼是较常用的5-羟色胺Ⅲ亚型（5-hydroxytryptamine type 3, 5-HT3）受体拮抗剂,在防治CINV方面具有很好的临床效果,但仍有部分患者使用托烷司琼后效果不佳。越来越多的研究表明这些个体差异可能与基因多态性密切相关。本文就细胞色素P450 2D6（cytochrome P450 2D6, CYP2D6）基因多态性对托烷司琼预防CINV效果的影响作一综述,以期为基因多态性指导下的临床个体化用药提供思路。     

NMNAT1 Is a Survival Factor in Actinomycin D-Induced Osteosarcoma Cell Death

Osteosarcoma is a frequent and extremely aggressive type of pediatric cancer. New therapeutic approaches are needed to improve the overall survival of osteosarcoma patients. Our previous results suggest that NMNAT1, a key enzyme in nuclear NAD⁺ synthesis, facilitates the survival of cisplatin-treated osteosarcoma cells. A high-throughput cytotoxicity screening was performed to identify novel pathways or compounds linked to the cancer-promoting role of NMNAT1. Nine compounds caused higher toxicity in the NMNAT1 KO U2OS cells compared to their wild type counterparts, and actinomycin D (ActD) was the most potent. ActD-treatment of NMNAT1 KO cells increased caspase activity and secondary necrosis. The reduced NAD⁺ content in NMNAT1 KO cells was further decreased by ActD, which partially inhibited NAD⁺-dependent enzymes, including the DNA nick sensor enzyme PARP1 and the NAD⁺-dependent deacetylase SIRT1. Impaired PARP1 activity increased DNA damage in ActD-treated NMNAT1 knockout cells, while SIRT1 impairment increased acetylation of the p53 protein, causing the upregulation of pro-apoptotic proteins (NOXA, BAX). Proliferation was decreased through both PARP- and SIRT-dependent pathways. On the one hand, PARP inhibitors sensitized wild type but not NMNAT1 KO cells to ActD-induced anti-clonogenic effects; on the other hand, over-acetylated p53 induced the expression of the anti-proliferative p21 protein leading to cell cycle arrest. Based on our results, NMNAT1 acts as a survival factor in ActD-treated osteosarcoma cells. By inhibiting both PARP1- and SIRT1-dependent cellular pathways, NMNAT1 inhibition can be a promising new tool in osteosarcoma chemotherapy.     

消化道系统癌症患者化疗依从性调查及其影响因素的研究

目的: 探讨消化道系统癌症患者化疗依从性与其一般状况、化疗期症状、情绪体验及心理弹性的关系。方法: 采用一般资料调查表、安德森症状评估量表,癌症患者化疗依从性问卷和心理弹性量表对165例消化道系统癌症化疗患者进行调查。结果: (1)消化道系统癌症患者化疗依从性评分为（14.551±7.402）分;其化疗依从性受年龄、医疗支付方式、是否参与锻炼3个因素的影响（P<0.05）。(2)患者化疗依从性评分与安德森症状评估总分呈正相关（r＝0.812）,与心理弹性量表总分呈负相关（r＝-0.177）;(3)患者的安德森症状评估和心理弹性总分及其2个因子分进入其化疗依从性的多元回归方程。结论: 患者化疗期症状、情绪体验和心理弹性水平是影响其化疗依从性的重要因素,需要医护人员及相关部门采取有效的应对措施以提高患者化疗依从性。     

三维适形放疗配合腔内后装治疗宫颈癌的临床研究

Objective: The aim of our study was to evaluate the outcome and complications of cervical cancer patients undergoing conventional intracavitary brachytherapy (ICBT) treated with 3D-conformal radiotherapy (3DCRT). Methods: Sixty cervical cancer patients were divided randomly into the conformal group and the conventional group. Thirty patients treated with 3D-conformal radiotherapy in the 3DCRT group, when the whole pelvic received DT 40 Gy, a planning CT scan of each patient was obtained and the second 3DCRT therapy plan was taken. Then, continued to irradiate to 50 Gy. At last, 3DCRT was boosted at local involved volumes to the total close of 60 Gy. When 3DCRT was combined with intracavitary brachytherapy, the dose of brachytherapy to point A was 30 Gy/5 fractions. In the conventional group, after a total tumor dose of 40 Gy was delivered by the whole pelvic irradiation, the four-field technique was used to irradiate the total pelvic and regional nodes (median close of 10 Gy), and the involved volumes were boosted to 60 Gy and the dose of brachytherapy to point A was 30 Gy-36 Gy/5-6 fractions. Moreover, both groups were combined with intracavitary brachytherapy respectively. Results: The 1, 2, 3-year survival rates for the 3DCRT group and the conventional group were 96.7%, 93.3%, 90.0% and 86.6%, 76.7%,70% respectively (P = 0.04, P = 0.02 and P = 0.02). There was a statistically significant difference between the two groups.Compared to the two groups each other in toxic effects, except for the Ⅰ-Ⅱ grade rectal and bladder reaction and pelvic fibrosis which was lower in the 3DCRT group (P = 0. 007, P = 0. 006 and P = 0. 015), the side effects were similar and well tolerated in two groups. Conclusion: The all-course 3DCRT combined with intracavitary brachytherapy can be considered as an effective and feasible approach to cervical cancer and may significantly improve the survival rate and reduce the late toxicity. This new rote for 3DCRT merits need further evaluation with large patient numbers and longer follows up.     

Combinatorial Treatment of Tinzaparin and Chemotherapy Can Induce a Significant Antitumor Effect in Pancreatic Cancer

Pancreatic Cancer (PC) is recognized as a highly thrombogenic tumor; thus, low-molecular-weight heparin (LMWH) such as tinzaparin is routinely used for PC patients. On the basis of combinatorial therapy approaches to treat highly malignant and refractory cancers such as PC, we hypothesized that tinzaparin can augment the effectiveness of traditional chemotherapeutic drugs and induce efficient antitumor activity. PANC-1 and MIAPaCa-2 were incubated alone or in combination with tinzaparin, nab-paclitaxel and gemcitabine. In vivo evaluation of these compounds was performed in a NOD/SCID mouse using a model injected with PANC-1. Tinzaparin enhances the anti-tumor effects of nab-paclitaxel and gemcitabine in mtKRAS PC cell lines via apoptosis in in vitro experiments. The triple combination power acts through the induction of apoptosis, reduction of the proliferative potential and angiogenesis; hence, contributing to a decrease in tumor volume observed in vivo. The triple regimen provided an extra 24.3% tumor reduction compared to the double combination (gemcitabine plus nab-paclitaxel). Combinatorial strategies can create novel therapeutic approaches for the treatment of patients with PC, achieving a better clinical outcome and prolonged survival. Further prospective randomized research is needed and the investigation of various concentrations of tinzaparin above 150 UI/Kg, would potentially provide a valuable synergistic effect to the conventional therapeutic compounds.