黄酒多酚诱导沉默调节蛋白3表达减轻阿霉素心肌损伤研究

背景 阿霉素（DOX）是一种常见的强效蒽环类抗肿瘤药物,被广泛应用于各类肿瘤尤其是实体性肿瘤的治疗中。然而,DOX有较强的心脏毒性,临床表现为不可逆性心肌病和充血性心力衰竭。黄酒多酚（YWPC）是从绍兴黄酒中提取的多酚类物质,具有抗炎、抗氧化等生理活性,对DOX所致心肌损伤有一定缓解作用,但其作用机制还不明晰。 目的 通过体内外实验探讨YWPC减轻DOX心肌损伤的作用机制。 方法 动物实验：使用SD大鼠建立DOX心肌损伤模型,分为对照组、YWPC组、DOX组与DOX+YWPC组;取心脏组织进行MASSON染色、原位末端标记（TUNEL）染色及免疫组织化学染色,取血清测定乳酸脱氢酶（LDH）水平,并用动物组织蛋白、Western Blot法检测凋亡水平〔B淋巴细胞瘤-2蛋白（Bcl-2）、Bcl-2相关X蛋白（Bax）〕及沉默调节蛋白3（SIRT3）表达水平变化。体外实验：通过1 μmol/L DOX干预H9C2细胞24 h建立DOX诱导H9C2细胞损伤模型,先将一批H9C2细胞分为对照组、DOX组、DOX+YWPC（1 mg/L）组、DOX+YWPC（10 mg/L）与DOX+YWPC（100 mg/L）5组,采用CCK-8法检测H9C2细胞活力,通过Western Blot法检测凋亡水平及SIRT3表达水平变化;之后将另一批H9C2细胞分为对照组、DOX组、DOX+YWPC组、DOX+SIRT3抑制剂（3-TYP）组及DOX+YWPC+3-TYP组,通过3-TYP抑制SIRT3蛋白活性,通过Western Blot法检测凋亡水平及SIRT3表达水平变化,进一步明确SIRT3在YWPC减轻DOX心肌损伤中的作用。 结果 动物实验中,大鼠心肌切片通过MASSON染色后可见：DOX组大鼠心肌纤维排列紊乱,大量蓝色胶原纤维贯穿心肌纤维;DOX+YWPC组大鼠心肌切片纹理部分恢复,蓝色胶原纤维减少。DOX组胶原纤维占比、血清LDH水平高于对照组、DOX+YWPC组（P<0.05）。DOX组Bcl-2/Bax比值、SIRT3表达水平低于对照组、DOX+YWPC组（P<0.05）;DOX组大鼠心肌切片中代表凋亡的绿色亮点明显增多,呈片状分布,而经YWPC治疗后凋亡亮点减少。体外实验中,DOX组吸光度值、Bcl-2/Bax比值、SIRT3表达水平低于对照组、DOX+YWPC（1 mg/L）组、DOX+YWPC（10 mg/L）组、DOX+YWPC（100 mg/L）组（P<0.05）,DOX组、DOX+3-TYP组Bcl-2/Bax比值、SIRT3表达水平低于对照组（P<0.05）;DOX+YWPC+3-TYP组Bcl-2/Bax比值低于DOX+YWPC组（P<0.05）,DOX+YWPC组与DOX+YWPC+3-TYP组SIRT3表达水平比较,差异无统计学意义（P>0.05）。 结论 YWPC可以通过调节SIRT3表达水平减轻DOX心肌损伤,抑制SIRT3会降低YWPC的作用。     

抗肿瘤药物诱导的机化性肺炎的研究进展

药物引起的肺损害越来越受到重视,其中最常见的表现是间质性肺疾病（ILD）,已有不少研究探讨药物诱导的ILD（DIILD）的诊断、治疗及预后,但DIILD中仍有很多亚型,根据病理不同可分为普通型间质性肺炎、非特异性间质性肺炎、机化性肺炎（OP）、过敏性肺炎、弥漫性肺泡损伤等,每一亚型的治疗和管理策略可能存在差异,需要进一步阐明。本文聚焦于DIILD中较为常见的OP亚类,定义药物诱导的OP（DIOP）,对药物中最常见的抗肿瘤药物进行研究,了解抗肿瘤药物潜在的致OP机制,研究DIOP的诊断、鉴别诊断、治疗及预后,旨在更好地指导抗肿瘤药物诱导的OP相关诊疗。     

子宫内膜癌患者新辅助化疗的预后影响因素分析

目的 分析化疗前血红蛋白及血小板水平对子宫内膜癌新辅助化疗后手术治疗疗效及预后的影响.方法 对新辅助化疗后行手术治疗的104例子宫内膜癌患者临床资料进行回顾性分析,分析影响子宫内膜癌患者新辅助化疗疗效的因素.单因素分析采用Х^2检验,多因素分析采用logistic回归法.结果 多因素Logistic回归分析FIGO分期（OR=3.234,95％ CI：1.324～ 13.454）和淋巴结转移（OR=8.235,95％CI：1.563～18.574）是影响子宫内膜癌新辅助化疗疗效的独立因素;多因素Cox回归模型分析显示：FIGO分期（HR=4.342,95％CI：1.643～ 15.856）和淋巴结转移（HR=3.853,95％ CI：1.864～9.675）是影响子宫内膜癌新辅助化疗5年生存率的独立因素.结论 对于接受新辅助化疗后手术治疗的子宫内膜癌患者的疗效及预后,与化疗前血红蛋白及血小板水平无明显相关性,与淋巴结转移、FIGO分期有关.     

胃复春片联合化疗治疗晚期非小细胞肺癌的临床观察

目的观察胃复春片联合化疗治疗晚期非小细胞肺癌（NSCLC）的临床疗效及毒副反应。方法68例晚期NSCLC患者随机数字表法分为两组,每组各34例,对照组采用单纯化疗（吉西他滨＋顺铂）,观察组采用胃复春片（1．436g／次,2次／d）联合化疗,完成2个周期治疗后进行疗效及毒副反应评价。结果对照组有效率为41．18％（14／34）,观察组有效率为52．94％（18／34）,两组差异无统计学意义（χ2=0．94,P〉0．05）。但观察组改善生活质量效果明显优于对照组（χ2=4．12,P〈0．05）,并且发生血小板、白细胞、血红蛋白减少及恶心呕吐等毒副反应明显低于对照组（χ2=4．66、5．96、4．12、5．90,均P〈0．05）。结论胃复春片联合化疗治疗晚期NSCLC有较好疗效,能有效减轻化疗毒副反应,提高了患者生活质量,值得临床推广。     

中药肿节风的抗肿瘤作用研究进展

检索中国期刊全文数据库（CNKI）（1979-2012）、中国生物医学文献数据库（CBM）（2004-2012）和万方数据库（2004-2012）,对肿节风抗癌作用方面的研究进展进行综述。肿节风具有抗肿瘤作用,主要机制与诱导细胞凋亡有关。针对肿节风功效开展大量药效学研究和机制探讨,在其有效化学成分上研究不够深入,更缺乏物质基础与药学作用的相关研究。肿节风抑瘤谱广,不良反应低,在临床上正被广泛使用,有很好的应用前景。     

Functional differentiation of cytotoxic cancer drugs and targeted cancer therapeutics

There is no nationally or internationally binding definition of the term “cytotoxic drug” although this term is used in a variety of regulations for pharmaceutical development and manufacturing of drugs as well as in regulations for protecting medical personnel from occupational exposure in pharmacy, hospital, and other healthcare settings. The term “cytotoxic drug” is frequently used as a synonym for any and all oncology or antineoplastic drugs. Pharmaceutical companies generate and receive requests for assessments of the potential hazards of drugs regularly – including cytotoxicity. This publication is intended to provide functional definitions that help to differentiate between generically-cytotoxic cancer drugs of significant risk to normal human tissues, and targeted cancer therapeutics that pose much lesser risks. Together with specific assessments, it provides comprehensible guidance on how to assess the relevant properties of cancer drugs, and how targeted therapeutics discriminate between cancer and normal cells. The position of several regulatory agencies in the long-term is clearly to regulate all drugs regardless of classification, according to scientific risk based data. Despite ongoing discussions on how to replace the term “cytotoxic drugs” in current regulations, it is expected that its use will continue for the near future.     

靶向药物联合化疗治疗晚期非小细胞肺癌的临床分析

目的 分析研究靶向药物联合化疗治疗晚期非小细胞肺癌（NSCLC）的疗效.方法 选取2011-2012年我院收治的晚期NSCLC患者46例,将其随机划分为两组.甲组采用常规的化疗药物治疗,乙组在给予常规化疗基础上使用靶向药物治疗,比较两组治疗效果.结果 甲组临床疗效优于乙组,差异有统计学意义（P＜0.05）;两组患者血红蛋白、血小板、白细胞下降及皮疹、消化道反应发生率比较差异无统计学意义（P＞0.05）.结论 给予晚期NSCLC患者采用靶向药物联合化疗治疗,可显著提高临床治疗效果.     

Blood leukocyte subsets and cytokine profile after autologous peripheral blood stem cell transplantation

High-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) includes the risk of infectious complications due to neutropenia and therapy-induced immune deviation. In order to understand early immune recovery in this situation, we analyzed the distribution of cell subsets by flow cytometry and we measured cytokine production in a whole blood assay stimulated with lipopolysaccharide (LPS) in order to induce monocyte (MO) activation in 43 patients with solid tumors or lymphoma treated with two cycles of high-dose chemotherapy and PBSCT. Blood was collected at the following time points: before start of mobilization chemotherapy, before and after high-dose chemotherapy, and 10 and 30 days after PBSCT. In the lymphocyte compartment, we found a depletion of B cells and naive T cells and a transitory reduction of natural killer (NK) cells, whereas MO and neutrophils recovered rapidly. However, during early recovery, HLA-DR expression on MO and the percentage of CD16⁺ MO was considerably reduced. Production of proinflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-alpha upon LPS stimulation was severely impaired directly after chemotherapy and unexpectedly remained low during early recovery of myeloid cells, whereas production of IL-1RA was enhanced, indicating a shift of immune competent cells to an anti-inflammatory or anergic state early after PBSCT.This work was supported by Deutsche Krebshilfe (German Cancer Aid)     

抑郁情绪对肺癌病人化疗后认知功能的影响

目的 探讨抑郁情绪对肺癌病人化疗后认知功能的影响。方法 对四川大学华西医院肿瘤科2017年1—5月期间收治的76例肺癌病人分别在化疗前后采用抑郁自评量表(SDS)和简易精神状况检查表(MMSE)、前瞻性记忆问卷(PM)、回顾性记忆问卷(RM)进行测查。化疗后根据SDS评分,将病人分为抑郁组(34例)、未抑郁组(42例),比较化疗前后抑郁评分及认知神经心理学特征的变化。结果 76例病人顺利完成化疗前后的测试。化疗前病人在SDS、MMSE、PM、RM得分分别是(36.34±7.11)分、(27.52±1.72)分、(18.78±4.24)分、(17.97±4.34)分,化疗后得分分别是(49.21±12.45)分、(26.01±1.78)分、(20.52±3.70)分、(19.50±2.70)分,差异有统计学意义(P＜0.05)。化疗后抑郁组病人在MMSE、PM、RM得分分别是(25.02±1.09)分、(21.56±3.01)分、(21.23±3.21)分,未抑郁组病人得分分别是(27.11±1.47)分、(19.32±4.05)分、(17.50±2.30)分,差异有统计学意义(P＜0.05)。结论 肺癌病人化疗后存在不同程度的认知障碍,且认知障碍与抑郁状态呈正相关。     

Factors associated to persistence with hormonal therapy in women with breast cancer

OBJECTIVE

To analyze factors associated with persistence to breast cancer hormone therapy in order to contribute to the quality of care improvement.

METHODS

Retrospective longitudinal study, based on secondary data. A cohort of 5,861 women with breast cancer registered in different datasets of the Brazilian National Cancer Institute and the Brazilian Unified Health System were analyzed. All women were treated at this hospital, which provides free medication, and the follow-up period was from January 2004 to October 2010. Sociodemographic, behavioral, and clinical variables, as well as aspects of lifestyle and health care, were considered in the explanation of variations in the persistence to hormone therapy, applying the Kaplan-Meier method and the Cox proportional hazard model.

RESULTS

Overall persistence to hormone therapy was 79.0% at the end of the first year, and 31.0% in five years of treatment. The risk of discontinuing hormone therapy was higher among women under 35 years old, with more advanced disease (stages III and IV), alcohol drinkers, those undergoing chemotherapy, and for each additional hospitalization, exam performed, and month between diagnosis and beginning of treatment. In the opposite direction, the risk of discontinuity was lower among women who had at least finished high school, those with partner, with a family history of cancer, those who had undergone breast surgery, and who had outpatient visits to a Mastologist, and a Clinical Oncologist.

CONCLUSIONS

The majority of the women with breast cancer (69.0%) do not persist with hormone treatment for the five years recommended, increasing the risk of inadequate clinical results. The results show aspects of care that can provide better results.