开胸术后慢性疼痛的产生机制及治疗现状简

近年来，越来越多的证据表明外科手术会导致慢性长期疼痛。胸科手术被认为是较疼痛的外科手术之一，这种慢性疼痛已经成为影响患者术后生活质量的一个显著问题。本文就胸科手术后疼痛综合征的产生机制及治疗现状予以综述。     

Promotion of autophagy as a mechanism for radiation sensitization of breast tumor cells

Radiation has long been a useful component of the treatment regimen for solid tumors. However, some malignancies are relatively resistant to radiation treatment while even tumors that may initially respond (to both radiation and chemotherapy) may eventually recover proliferative capacity. A variety of approaches have been utilized in the efforts to enhance radiation sensitivity. Recent studies have identified autophagy as a cell death pathway that may mediate the radiosensitizing effects of selected treatments. Studies in our laboratory support the premise that radiosensitization of breast tumor cells by vitamin D or vitamin D analogs is mediated through autophagy. In addition, promotion of autophagic cell death by a vitamin D analog in irradiated breast tumor cells delays and attenuates the proliferative recovery that may be a preclinical indicator of disease recurrence.     

The acute chest syndrome

Recent large clinical studies of the acute chest syndrome (ACS) have improved our understanding of its pathophysiology and epidemiology. However, there is still a need for better methods of distinguishing vaso-occlusion from fibrin or fat embolism, for rapid diagnostic tests to make positive identifications of microbial infection, for adjunctive therapies that would affect prognosis, and for identification of factors that influence prognosis. The difference in clinical course and severity between children and adults supports the results of current studies indicating multiple causes for ACS. The mainstay of successful treatment remains high-quality supportive care. The judicious use of transfusion therapy has a major role in preventing mortality in the absence of a specific therapy that consistently improves the clinical course.     

骨髓增生异常综合征转化为急性髓系白血病机制的研究进展

骨髓增生异常综合征(MDS)是一组源于造血干/祖细胞的克隆性疾病,有向急性髓系白血病(AML)转化的高风险.由于转化为AML后缺乏有效治疗手段,且预后差,目前唯一治愈的方法是通过骨髓移植,但是仅有少部分患者适合移植.因此对MDS转化为AML机制的研究对临床开发有效药物尤为重要.现就MDS转化为AML发生机制的研究进展进行综述.     

The postmastectomy pain syndrome: an epidemiological study on the prevalence of chronic pain after surgery for breast cancer

The prevalence of the postmastectomy pain syndrome (PMPS) and its clinical characteristics was assessed in a group of patients who had undergone surgery for breast cancer at the Department of Surgery, Odense University Hospital, within the period of 1 May 2003 to 30 April 2004. The study included 258 patients and a reference group of 774 women. A questionnaire was mailed to the patients 1 1/2 year after surgery and to the women in the reference group. The PMPS was defined as pain located in the area of the surgery or ipsilateral arm, present at least 4 days per week and with an average intensity of at least 3 on a numeric rating scale from 0 to 10. The prevalence of PMPS was found to be 23.9%. The odds ratio of developing PMPS was 2.88 (95% confidence interval 1.84-4.51). Significant risk factors were as follows: having undergone breast surgery earlier (OR 8.12), tumour located in the upper lateral quarter (OR 6.48) and young age (OR 1.04). This study shows that, although recent advances in the diagnostic and surgical procedures have reduced the frequency of the more invasive surgical procedures, there still is a considerable risk of developing PMPS after treatment of breast cancer.     

紫杉醇诱导急性白血病细胞S期特异性凋亡

背景与目的:化疗药物的细胞周期特异性是临床设计化疗方案的重要依据。一般认为,紫杉醇为G2/M期特异性化疗药物。但是近来的相关研究却表明,药物在体内的细胞周期特异性可能与体外不同。本研究旨在观察紫杉醇作用于不同生长状态下白血病细胞的细胞周期特异性有无改变。方法:利用流式细胞分析技术,对紫杉醇作用于人急性淋巴细胞性白血病细胞株Molt-4以及作用于17例急性白血病细胞所诱导的凋亡效应进行了观察。结果:紫杉醇诱导在对数生长状态下的Molt-4细胞株G2/M期特异性凋亡,在高密度状态下培养的Molt-4细胞为G0/G1期特异性凋亡,而在临床标本中诱导S期特异性凋亡。结论:紫杉醇在不同模型诱导不同的细胞周期特异性凋亡。与一般认为的不同,紫杉醇引起患者白血病细胞S期特异性凋亡。这些不同很可能与细胞处于不同的生长状态有关。     

癌痛发生机制的研究进展

癌痛是肿瘤患者的主要症状之一，严重影响患者的生活质量。目前对癌痛产生的机制认识尚不足，癌痛的形成可能与癌细胞、肿瘤微环境、中枢神经系统以及免疫系统之间复杂的相互作用相关。深入研究癌痛产生的机制，将为临床肿瘤患者疼痛治疗提供重要的理论依据和指导方向。     

单药紫杉醇与紫杉醇联合奥沙利铂二线治疗晚期非小细胞肺癌临床疗效比较

背景与目的 对于一线化疗失败的晚期非小细胞肺癌患者,紫杉烷类被证明有不错的疗效.除了常用的多西紫杉醇外,紫杉醇(paclitaxel)作为另一种常见的紫杉烷类,在很多临床研究中也显现了类似的作用.本文旨在比较单药紫杉醇与紫杉醇联合奥沙利铂治疗一线化疗失败的晚期非小细胞肺癌患者的毒性及疗效.方法 2000年9月-2007年9月共66例一线化疗失败的晚期非小细胞肺癌患者入组.分为单药紫杉醇组和紫杉醇联合奥沙利铂组,前者44例,后者22例,ECOG评分0分-2分.治疗方案:单药组:紫杉醇175 mg/m2,d1;紫杉醇联合铂类组:紫杉醇175 mg/m2,d1;奥沙利铂130 mg/m2,d1,3周-4周重复.比较两组近期、远期疗效及不良反应.结果 单药紫杉醇组和紫杉醇联合奥沙利铂组的客观有效率分别为13.6%和18.2%(P=0.720);中位疾病进展时间分别为3.2个月和4.5个月(P=0.382);中位生存期分别为6.9个月和8.2个月(P=0.444),差异均尤统计学意义.在毒副作用方面,两药组血液学毒性发生率明显高于单药组,3/4级白细胞减少两组分别为1例与4例(P=0.039),血小板减少、贫血发生都属于1/2级.非血液学毒性方面3/4级恶心呕吐发生率两组虽无统计学差异(P=0.108),但全部共2例均发生于两药组.两药组的肢端麻木发生率明显高于单药组(63.3%vs34.1%),且2例3级患者也出现于两药组(P=0.111).结论 紫杉醇单药治疗一线化疗失败的晚期非小细胞肺癌患者耐受性较好,特别对于ECOG评分较差或者老年患者,不会降低有效率和生存率.     

肝癌患者淀粉酶糖链异常、证型差异及相关机制

目的：研究肝癌患者的血清淀粉酶糖链变化、中医证型差异及与自由基的相关性。方法：凝集素亲和沉淀法检测肝癌患者、肝硬化患者、肝炎患者血清淀粉酶的多种凝集素结合率；同时检测血清丙二醛（malindialdehyde，MDA）、血清淀粉酶活性，分析淀粉酶的各凝集素结合率与自由基的相关性，分析以上指标在不同证型肝癌患者间的差异。结果：肝癌患者血清淀粉酶的ConA、PSA、PNA、LCA结合率明显高于肝炎组及正常组；肝硬化组淀粉酶的ConA、PSA、PNA、LCA的结合率亦明显高于肝炎组及正常组，肝癌肝郁脾虚患者血清淀粉酶的PSA、LCA的结合率明显高于肝癌肝肾阴虚患者，肝癌肝郁脾虚患者血清淀粉酶的ConA结合率明显高于肝癌气滞血瘀患者；血清淀粉酶的PSA、PNA、LCA结合率与MDA水平呈显著正相关。结论：肝癌患者血清淀粉酶分子中核心岩藻糖基化的高甘露糖型、杂合型糖链增多，其糖链末端唾液酸基、岩藻糖基减少，致D-半乳糖的暴露增多，此外，肝癌患者血清淀粉酶糖链末端D-半乳糖基亦减少，致N-乙酰氨基葡萄糖基暴露增多，肝硬化患者血清淀粉酶糖链亦有以上变化，这可能与自由基损害糖链有关。肝癌肝郁脾虚患者血清淀粉酶分子中核心岩藻糖基化的高甘露糖型、杂合型糖链增多，其糖链末端的D-半乳糖基减少，致N-乙酰氨基葡萄糖基暴露增多；而肝癌气滞血瘀和肝癌肝肾阴虚患者血清淀粉酶糖链无此变化，表明肝郁脾虚在肝癌患者血清淀粉酶异常糖链的形成方面可能起重要作用。     

癌痛的发生机制及其相关药物治疗的研究现状

癌痛是一种机制独特而复杂的慢性疼痛,在动物模型中表现出对痛觉过敏、超敏等疼痛相关行为,其相应的脊髓节段内发生独特的神经化学改变.癌痛的发生与外周传入神经敏化和中枢敏化有关,在癌痛早期,以肿瘤细胞、炎症细胞产生的致痛物质以及破骨细胞的持续活化所致的初级传人神经敏化为主;在癌痛后期,肿瘤生长引起的神经压迫与损伤参与了癌痛的...     

褪黑素对阿霉素抗雌激素受体阴性乳腺癌细胞MDA—MB-231作用的影响及其机制

目的探讨生理浓度（10^-9mol／L）褪黑素和药理浓度（10^-5moL／L）褪黑素对阿霉素抑制雌激素受体阴性乳腺癌细胞MDA-MB-231作用影响及其机制。方法（1）应用四甲基偶氮唑蓝（Mar）法检测经不同浓度褪黑素孵育后阿霉素对MDA—MB-231的抑制率和IC50变化。（2）应用流式细胞学方法观察不同浓度褪黑素、阿霉素以及两药联用时对MDA-MB-231细胞周期分布和凋亡的影响。（3）应用western blot法检测不同浓度褪黑素、阿霉素单药和两药联用对MDA—MB-231细胞p53和bcl-2蛋白表达的影响。结果（1）阿霉素对乳腺癌MDA—MB-231细胞具有明显的抑制作用,且呈剂量时间依赖性。IC50值为（1．00±0．09）μg／ml,经生理浓度和药理浓度褪黑素孵育后IC50分别降为（0．85±0.06）μg／ml和（0．47±0．03）μg／ml,前者与孵育前相比未,差异无统计学意义（P〉0．05）,后者相比差异无统计学意义（P〈0．01）。（2）流式细胞学检测结果显示,阿霉素对细胞MDA．MB-231有凋亡促进作用,随浓度增高凋亡率未见增加（P〉0．05）。生理浓度褪黑素联合阿霉素与相应浓度的阿霉素单药相比,凋亡率未见明显增加（P〉0．05）。药理浓度褪黑素联合阿霉素与相应浓度阿霉素单药比较,凋亡率明显提高（P〈0．05）,但联合组随着阿霉素浓度增加凋亡率并未见明显变化（P〉0．05）。（3）MDA-MB-231乳腺癌细胞株中呈p53蛋白低表达、bcl-2蛋白高表达。药理浓度褪黑素可显著增高细胞p53蛋白并降低bcl-2蛋白表达（P〈0．01）。药理浓度褪黑素联合不同浓度阿霉素对两蛋白表达未见显著性差异（P〉0．05）;阿霉素对两种蛋白表达未见明显影响（P〉0．05）。结论（1）生理浓度褪黑素（10^-9mol／L）对阿霉素的抗雌激素受体阴性乳腺癌细胞作用未见明显影响,药理浓度（10^-9mol／L）以上褪黑素表现出对阿霉素明显的增敏作用。（2）阿霉素较低浓度时,凋亡促进作用可能是褪黑素对其增敏机制的一部分,随着阿霉素浓度的提高,褪黑素的细胞毒增敏机制可能占主要地位。（3）药理浓度褪黑素能提高雌激素受体阴性乳腺癌细胞p53蛋白表达并降低bcl-2蛋白表达,并具有剂量依赖性。涉及p53和bcl-2的凋亡通路可能是褪黑素对阿霉素增敏机制的一部分。     

Randomized Phase II Study of Paclitaxel plus Alisertib versus Paclitaxel plus Placebo as Second-Line Therapy for SCLC: Primary and Correlative Biomarker Analyses

IntroductionWe assessed the Aurora A kinase inhibitor, alisertib, plus paclitaxel (henceforth referred to as alisertib/paclitaxel) as second-line treatment for SCLC.MethodsIn this double-blind study, patients with relapsed or refractory SCLC were stratified by relapse type (sensitive versus resistant or refractory) and brain metastases and randomized 1:1 to alisertib/paclitaxel or placebo plus paclitaxel (henceforth referred to as placebo/paclitaxel) in 28-day cycles. The primary end point was progression-free survival (PFS). Associations of c-Myc expression in tumor tissue (prespecified) and genetic alterations in circulating tumor DNA (retrospective) with clinical outcome were evaluated.ResultsA total of 178 patients were enrolled (89 in each arm). The median PFS was 3.32 months with alisertib/paclitaxel versus 2.17 months with placebo/paclitaxel (hazard ratio [HR] = 0.77, 95% confidence limit [CI]: 0.557–1.067, p = 0.113 in the intent-to-treat population versus HR = 0.71, 95% CI: 0.509–0.985, p = 0.038 with corrected analysis applied). Among 140 patients with genetic alternations, patients with cell cycle regulator mutations (cyclin-dependent kinase 6 gene [CDK6], retinoblastoma-like 1 gene [RBL1], retinoblastoma-like 2 gene [RBL2], and retinoblastoma 1 gene [RB1]) had significantly improved PFS with alisertib/paclitaxel versus with placebo/paclitaxel (3.68 versus 1.80 months, respectively [HR = 0.395, 95% CI: 0.239–0.654, p = 0.0003]), and overall survival (7.20 versus 4.47 months, respectively [HR = 0.427, 95% CI: 0.259–0.704, p = 0.00085]). A subset of patients with c-Myc expression showed significantly improved PFS with alisertib/paclitaxel. The incidence of grade 3 or higher drug-related adverse events was 67% (58 patients) with alisertib/paclitaxel versus 22% (25 patients) with placebo/paclitaxel. Twelve patients (14%) versus 11 (12%) died on study, including four versus zero treatment-related deaths.ConclusionsEfficacy signals were seen with alisertib/paclitaxel in relapsed or refractory SCLC. c-Myc expression and mutations in cell cycle regulators may be potential predictive biomarkers of alisertib efficacy; further prospective validations are warranted.     

Acute Budd-Chiari syndrome as an initial presentation of acute promyelocytic leukemia

Budd-Chiari syndrome (BCS) is the constellation of clinical signs and symptoms resulting from occlusion of two or more hepatic veins, often due to an underlying thrombophilic disorder. Acute myeloid leukemia has been rarely reported to be associated with hepatic vein thrombosis due to hyperleukocytosis, hyperfibrinolysis and disseminated intravascular coagulation. We report a case of acute promyelocytic leukemia where the clinical onset of the hematological disease was with acute BCS.     

The hypereosinophilic syndrome in acute lymphocytic leukemia

A 21-year-old white man presented with marked peripheral blood eosinophilia that later evolved into acute lymphocytic leukemia (FAB2 ALL). He died precipitously from refractory congestive heart failure immediately after antileukemic therapy was started. Autopsy revealed multiorgan infiltration with eosinophils and the typical cardiac findings of L?fflers endocarditis. Clinical and pathologic features of this and the 14 other cases of ALL and the hypereosinophilic syndrome (HES) reported in the English-language literature are described. The eosinophilia in these cases is reactive and resolves with successful leukemia remission induction. Hydroxyurea is effective in rapidly lowering eosinophil counts. Early use of hydroxyurea in this disease may improve patient survival and decrease the risk of sudden cardiac death.     

电针联合中药镇痛贴对癌痛动物模型的镇痛作用及可能机理

目的:考察电针联合中药镇痛贴对癌痛动物模型的镇痛作用及可能机理。方法:将大鼠随机分为4组，其中1组为健康大鼠，为对照组，其余3组均为骨癌痛大鼠，分别为模型组、镇痛贴组和电针联合镇痛贴组，每组20只。结果:对照组大鼠的生活状态正常，其余组大鼠活动明显降低，喜昏睡，毛色暗淡，饮食减少，体重减少，跛行明显，尤其左后肢红肿。与模型组相比，镇痛贴组和电针联合镇痛贴组的活动略多于模型组(P＜0.05)，体重增长介于对照组和模型组之间。与对照组相比，其余各组的自发性运动疼痛评分(spontaneous ambulatory pain score,SAPS)均明显增高(P＜0.05)，随着时间的延长，SAPS增高明显(P＜0.05)。与模型组相比，镇痛贴组和电针联合镇痛贴组的SAPS明显降低(P＜0.05)。与镇痛贴组相比，电针联合镇痛贴组的SAPS明显降低(P＜0.05)。各组大鼠的痛阈值无统计学差异(P＞0.05)。对照组骨结构正常，模型组骨小梁广泛破坏，骨结构破坏严重。与对照组相比，其余各组的Toll 样受体4(Toll-like receptor 4,TLR4)和CD11b蛋白表达水平、TLR4和CD11b mRNA表达水平均明显增高(P＜0.05)；与模型组相比，镇痛贴组和电针联合镇痛贴组的TLR4和CD11b蛋白表达水平、TLR4和CD11b mRNA表达水平明显降低(P＜0.05)；与镇痛贴组相比，电针联合镇痛贴组的TLR4和CD11b蛋白表达水平、TLR4和CD11b mRNA表达水平明显降低(P＜0.05)。结论:电针联合中药镇痛贴可明显改善癌痛大鼠的疼痛感，与降低骨TLR4和CD11b表达水平相关。     

肿瘤作为老年病的机制探讨

肿瘤起始于基因突变引起的转化细胞,多数情况下处于休眠状态或被免疫系统检出清除。研究表明肿瘤的特征与衰老的特征有诸多相似之处,是肿瘤作为老年病的生物学基础。随着年老体衰肿瘤起始细胞形成增多,伴以免疫衰退,老年人的肿瘤发病率和病死率升高,其核心机制是炎性衰老和免疫衰退。文章综述近年来肿瘤发生、发展与炎性衰老和免疫衰退关系的研究进展,阐述肿瘤作为老年病的假说和可能机制。     

一例表现为梗阻性急腹病的阑尾原发性结肠型腺瘤病例报道

We reported a case with an obstructive acute abdomen, and emergency exploratory laparotomy was performed. Appendiceal neoplasm was observed adhered to the ileum, and an ileohemicolectomy was performed. From the histopathological point of view the neoplasm was an infiltrating colonic type adenocarcinoma of the appendix, with extension to the periapendicular adipose tissue and fixation of an adjacent ileal loop secondary to infiltration of the intestinal wall. The tumor produced a moderate luminal stenosis of the intestine, this explained the clinical manifestations of the patient. Post-operative evolution was satisfactory and there had been no signs of recurrence in the 5 years since the operation. Based upon the comparison of clinical characteristics, pathological behavior （in relation to the growth and dissemination）, and therapeutic considerations, possibly colonic type adenocarcinoma of the appendix is a neoplasm similar to the carcinomas of ascending colon.     

Oxidative breakage of cellular DNA by plant polyphenols: a putative mechanism for anticancer properties

Plant polyphenols are important components of human diet and a number of them are considered to possess chemopreventive and therapeutic properties against cancer. They are recognized as naturally occurring antioxidants but also act as prooxidants catalyzing DNA degradation in the presence of transition metal ions such as copper. We have shown that several of these compounds are able to bind both DNA and Cu(II) forming a ternary complex. A redox reaction of the polyphenols and Cu(II) in the ternary complex may occur leading to the reduction of Cu(II) to Cu(I), whose reoxidation generates a variety of reactive oxygen species (ROS). We have further confirmed that the polyphenol-Cu(II) system is indeed capable of causing DNA degradation in cells such as lymphocytes. We have also shown that polyphenols alone (in the absence of added copper) are also capable of causing DNA breakage in cells. Neocuproine (a Cu(I) sequestering agent) inhibits such DNA degradation. It also inhibits the oxidative stress generated in lymphocytes indicating that the cellular DNA breakage involves the generation of Cu(I) and formation of ROS. It is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies. Therefore, cancer cells may be more subject to electron transfer between copper ions and polyphenols to generate ROS. Thus, our results are in support of our hypothesis that anticancer mechanism of plant polyphenols involves mobilization of endogenous copper possibly chromatin bound copper and the consequent prooxidant action.     

Modulation of phospholipase D by hexadecylphosphorylcholine: a putative novel mechanism for its antitumoral activity

Hexadecylphosphorylcholine (HePC, D-18506, INN: Mitelfosine) belongs to the family of alkylphosphocholines with anticancer activity. Previous reports have related its antitumoral activity to their ability to interfere with phospholipid metabolism. However a clear mechanism of action has not been established yet. We have investigated the effect of HePC on two enzymes recently reported to play a role in cell growth proliferation, phospholipase D (PLD) and choline kinase (ChoK). Our results demonstrate that treatment with HePC induces a rapid stimulation of PLD, that may be achieved by PKC dependent or independent mechanisms, depending on the cell line investigated. Both PLD1 and PLD2 isoenzymes are sensitive to HePC activation. By contrast, no effect was observed by HePC on ChoK, a new target for anticancer drug development. Furthermore, in all cell lines tested, a chronic exposure of the cells to HePC abrogates PLD activation by either phorbol esters or HePC itself with no effect on total cellular PLD levels. This is reflected in a strong inhibition of PLD activity. We suggest that the inhibitory effects on PLD by HePC may be related to its antitumoral action.