• 【吸入类固醇/长效β2激动剂联合产品可使成年哮喘患者的肺功能提高24小时。】 复制标题 收藏 收藏
    DOI:10.1186/1465-9921-7-110 复制DOI
    作者列表:Lötvall J,Langley S,Woodcock A
    BACKGROUND & AIMS: BACKGROUND:The combination of inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA) is recommended by treatment guidelines for the treatment of persistent asthma. Two such combination products, salmeterol/fluticasone propionate (SFC, Seretide GSK, UK) and formoterol/budesonide (FBC, Symbicort, AstraZeneca, UK) are commercially available. OBJECTIVES:The purpose of these studies was to evaluate and compare the duration of bronchodilation of both combination products up to 24 hours after a single dose. METHODS:Two randomised, double blind, placebo-controlled, crossover studies were performed. Study A was conducted in 33 asthmatic adults receiving 400-1200 mcg of budesonide or equivalent. Serial forced expiratory volume in one second (FEV1) was measured over 24 hours to determine the duration of effect of both SFC (50/100 mcg) and FBC (4.5/160 mcg). Study B was conducted in 75 asthmatic adults receiving 800-1200 mcg of budesonide or equivalent and comprised a 4 week run-in of 400 mcg bd Becotide followed by 4 weeks treatment with either SFC 50/100 mcg bd or FBC 4.5/160 mcg bd taken in a cross-over manner. Serial 24-hour FEV1 was measured after the first dose and the last dose after each 4-weeks treatment period to determine the offset of action of each treatment. RESULTS:In study A, a single inhalation of SFC and FBC produced a sustained bronchodilation at 16 hours with an adjusted mean increase in FEV1 from pre-dose of 0.22 L (95% CI 0.19, 0.35 L) for SFC and 0.25 L (95% CI 0.21, 0.37 L) for FBC, which was significantly greater than placebo for both treatments (-0.05 L; p < 0.001). In study B, the slope of decline in FEV1 from 2-24 hours post dose was -16.0 ml/hr for SFC and -14.2 ml/hr for FBC. The weighted mean AUC over 24 hours was 0.21 Lxmin and 0.22 Lxmin and mean change from pre-dose FEV1 at 12 hours was 0.21 L for SFC and 0.20 L for FBC respectively CONCLUSION:Both SFC and FBC produced a similar sustained bronchodilator effect which was prolonged beyond 12 hours post dose and was clearly measurable at 24 h.
    背景与目标: 摘要背景:吸入性糖皮质激素(ICS)和长效β2-激动剂(LABA)的结合被治疗指南推荐用于持续性哮喘的治疗。两种这样的组合产品,沙美特罗/丙酸氟替卡松(SFC,英国Seretide GSK)和福莫特罗/布地奈德(FBC,Symbicort,阿斯利康,英国)可商购。
    目的:这些研究的目的是评估和比较两种组合产品在单剂给药后直至24小时的支气管扩张持续时间。
    方法:进行了两项随机,双盲,安慰剂对照,交叉研究。研究A在接受400-1200 mcg布地奈德或同等剂量的33位哮喘成人中进行。在24小时内测量一秒钟的连续呼气量(FEV1),以确定SFC(50/100 mcg)和FBC(4.5 / 160 mcg)的作用持续时间。研究B在75位接受800-1200 mcg布地奈德或同等水平的哮喘成年人中进行,包括4周400 mcg bd的Becotide磨合,然后用SFC 50/100 mcg bd或FBC 4.5 / 160 mcg bd进行4周治疗以交叉方式拍摄。在每4周治疗期后的第一剂和最后一剂之后,测量连续的24小时FEV1,以确定每种治疗的作用抵消。
    结果:在研究A中,单次吸入SFC和FBC在16小时产生了持续的支气管扩张,FEC1的平均调整值从给药前的0.22 L(95%CI 0.19,0.35 L)和0.25 L(95 FBC的%CI 0.21,0.37 L),均显着高于两种治疗的安慰剂(-0.05 L; p <0.001)。在研究B中,从剂量后2-24小时开始,FEV1的下降斜率对于SFC为-16.0 ml / hr,对于FBC为-14.2 ml / hr。在24小时内,加权平均AUC为0.21 Lxmin和0.22 Lxmin,对于SFC,从剂量前FEV1在12小时的平均变化分别为0.21 Lx和FBC 0.20 L
    结论:SFC和FBC均产生相似的持续支气管扩张药作用,给药后延长至12小时以上,并且在24 h时明显可测量。
  • 【放射性碘125种子定位在新辅助化疗后在保乳治疗中的作用。】 复制标题 收藏 收藏
    DOI:10.1093/annonc/mds475 复制DOI
    作者列表:Gobardhan PD,de Wall LL,van der Laan L,ten Tije AJ,van der Meer DC,Tetteroo E,Poortmans PM,Luiten EJ
    BACKGROUND & AIMS: BACKGROUND:Neoadjuvant chemotherapy (NAC) is increasingly used in the framework of breast-conserving therapy (BCT). Localization of the initial tumor is essential to guide surgical resection after NAC. This study describes the results obtained with I-125 seed localization in BCT including NAC. PATIENTS AND METHODS:Between January 2009 and December 2010, 85 patients treated with NAC and BCT after I-125 seed localization were included. Radiological and pathological response and resection margins were retrospectively evaluated. RESULTS:BCT was carried out in 85 patients without secondary local excisions. Nineteen patients with unifocal tumors and seven patients with multifocal tumors showed a complete pathological response (P = 0.18). Tumor-free resection margins were obtained in 78 patients (50 patients with unifocal and 28 patients with multifocal tumors, P = 0.27). Focally involved margins were found in four patients (two patients with a unifocal and two patients with a multifocal tumor, P = 0.27). A subsequent mastectomy was carried out in three patients (two patients with multifocal tumors, P = 0.29). CONCLUSIONS:BCT after NAC can be carried out successfully after initial localization with I-125 seeds in both unifocal and multifocal breast tumors with complete resection rates of >90%.
    背景与目标: 背景:新辅助化疗(NAC)越来越多地用于保乳治疗(BCT)的框架中。初始肿瘤的定位对于NAC术后的手术切除至关重要。这项研究描述了I-125种子在包括NAC在内的BCT中的定位结果。
    患者与方法:2009年1月至2010年12月,纳入85例I-125种子定位后接受NAC和BCT治疗的患者。回顾性评估放射学和病理学反应以及切除范围。
    结果:85例患者均进行了BCT检查,未进行次要局部切除。 19例单灶性肿瘤患者和7例多灶性肿瘤患者表现出完全的病理反应(P = 0.18)。 78例患者获得了无肿瘤切除切缘(50例单灶患者和28例多灶肿瘤患者,P = 0.27)。在四名患者中发现了局部受累边缘(两名患有单灶的患者和两名患有多灶性肿瘤的患者,P = 0.27)。随后在三名患者中进行了乳房切除术(两名患有多灶性肿瘤的患者,P = 0.29)。
    结论:NAC后的BCT可以在单灶和多灶乳腺肿瘤中首次定位I-125种子后成功进行,完全切除率> 90%。
  • 【[用于膀胱尿路上皮癌的化学疗法-2012年更新]。】 复制标题 收藏 收藏
    DOI:10.1055/s-0032-1327699 复制DOI
    作者列表:Niegisch G,Lorch A,Albers P
    BACKGROUND & AIMS: :Despite adequate surgical treatment by radical cystectomy and pelvic lymphadenectomy, about half of patients suffering from muscle-invasive urothelial bladder cancer will die. Both overall and cancer-specific survival has been improved by neoadjuvant chemotherapy. However, it is still not possible to predict who is likely to benefit from neoadjuvant treatment and who will not. In contrast to neoadjuvant chemotherapy, the efficacy of adjuvant chemotherapy has not definitely been proven. In metastatic urothelial cancer chemotherapy is usually a palliative treatment option. However, in a significant proportion of patients, disease stabilisation and even long-term response can be achieved. Important advances to tailor first- and second-line chemotherapy have recently been reported for clinical prognostic parameters. This review discusses the current standards and developments in the chemotherapeutic treatment of urothelial bladder cancer. Furthermore, it should provide a framework for reasonable treatment choices in daily clinical practice.
    背景与目标: :尽管通过彻底的膀胱切除术和盆腔淋巴结清扫术进行了适当的手术治疗,但约有一半患有肌肉浸润性膀胱尿路上皮癌的患者会死亡。新辅助化疗改善了总生存期和癌症特异性生存期。但是,仍无法预测谁可能从新辅助治疗中受益,而谁则不会。与新辅助化疗相反,辅助化疗的功效尚未得到肯定的证实。在转移性尿路上皮癌中,化疗通常是姑息治疗的选择。但是,在相当大比例的患者中,可以实现疾病稳定甚至长期反应。最近已经报道了调整一线和二线化疗的重要进展,可用于临床预后指标。这篇综述讨论了尿路上皮膀胱癌的化学治疗的当前标准和发展。此外,它应该为日常临床实践中合理的治疗选择提供一个框架。
  • 【新辅助化疗前后Ki-67改变对各种亚型乳腺癌的不同预后意义。】 复制标题 收藏 收藏
    DOI:10.1007/s10549-012-2344-6 复制DOI
    作者列表:Matsubara N,Mukai H,Fujii S,Wada N
    BACKGROUND & AIMS: :In a neoadjuvant setting, three parameters for Ki-67 could be obtained: pre-treatment Ki-67, post-treatment Ki-67 and Ki-67 change between pre- and post-treatments. It is uncertain which of the three parameters has the greatest prognostic significance, and whether this parameter has significance in each subtype of breast cancer. A total of 385 patients who received neoadjuvant anthracycline followed by taxane chemotherapy and subsequent surgery for breast cancer were analyzed retrospectively. By immunohistochemistry (IHC), patients were divided into four subtypes (Luminal A, Luminal B, Triple negative, and HER2). Ki-67 was examined by IHC in pre-treatment core needle samples and post-treatment surgical excision specimens. The relapse-free survival (RFS) rate was compared among each subtype. The median follow-up period was 56 months. The rate of pathological complete response was higher for HER2 (34.8 %) and Triple negative (24.3 %) subtypes than for Luminal B (8.3 %) and Luminal A (3.8 %) subtypes (p < 0.0001). A reduction in Ki-67 was observed in 58.5, 83.4, 70.2, and 74.2 % of patients in the Luminal A, Luminal B, Triple negative, and HER2 subtypes, respectively. Ki-67 change between pre- and post-treatments was an independent prognostic factor, but pre-treatment Ki-67 and post-treatment Ki-67 were not independent prognostic factors in a multivariate analysis. The RFS was significantly different between patients whose Ki-67 was reduced and those not reduced for Luminal B (81.4 vs. 50.0 %, p = 0.006), Triple negative (74.8 vs. 43.5 %, p = 0.006) and HER2 (82.7 vs. 59.0 %, p = 0.009). However, for Luminal A, the difference in RFS was not associated with changes of Ki-67 (78.8 vs. 75.3 %, p = 0.193). Ki-67 change between pre- and post-neoadjuvant chemotherapy is an independent prognostic factor in patients of Luminal B, Triple negative, and HER2 subtypes. Pre-treatment Ki-67 and post-treatment Ki-67 were not independent prognostic factors in a multivariate analysis.
    背景与目标: :在新辅助条件下,可以获得Ki-67的三个参数:治疗前Ki-67,治疗后Ki-67和Ki-67在治疗前和治疗后的变化。尚不确定这三个参数中的哪一个具有最大的预后意义,以及该参数在每种乳腺癌亚型中是否具有意义。回顾性分析了总共385例接受新辅助蒽环类药物,紫杉烷化学疗法以及随后的乳腺癌手术的患者。通过免疫组织化学(IHC),将患者分为四个亚型(A型,B型,三阴性和HER2型)。 IHC在预处理核心针样品和治疗后手术切除样品中对Ki-67进行了检查。比较了每个亚型的无复发生存率。中位随访期为56个月。 HER2(34.8%)和三阴性(24.3%)亚型的病理完全缓解率高于Luminal B(8.3%)和Luminal A(3.8%)亚型(p <0.0001)。在Luminal A,Luminal B,三阴性和HER2亚型的患者中,分别有58.5%,83.4%,70.2%和74.2%的患者观察到Ki-67降低。在多变量分析中,治疗前后Ki-67的变化是独立的预后因素,但治疗前Ki-67和治疗后Ki-67并非独立的预后因素。对于Luminal B患者,Ki-67降低和未降低的患者的RFS显着不同(81.4 vs. 50.0%,p = 0.006),三阴性(74.8 vs. 43.5%,p = 0.006)和HER2(82.7vs。 59.0%,p = 0.009)。但是,对于Luminal A,RFS的差异与Ki-67的变化无关(分别为78.8%和75.3%,p = 0.193)。新辅助化疗前后的Ki-67改变是Luminal B,三阴性和HER2亚型患者的独立预后因素。在多变量分析中,治疗前Ki-67和治疗后Ki-67并非独立的预后因素。
  • 【一例化疗后多药耐药基因(MDR1)过表达的恶性神经鞘瘤。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Suto R,Abe Y,Lee YH,Ueyama Y,Yamazaki H,Kijima H,Hiraoka N,Fukuda H,Tamaoki N,Nakamura M
    BACKGROUND & AIMS: A 19-year-old:female patient with malignant schwannoma in the right knee was treated by combination chemotherapy including lipophilic anticancer compounds (cyclophosphamide, doxorubicin, vincristine and dacarbazine). The tumor was radically removed after chemotherapy, but metastatic lesions were noted in the right inguinal nodes. The patient died due to the cachexic state six months after surgery. In human neoplasm, P-glycoprotein (P-Gp) encoded by human multidrug resistance gene MDR1 is known to be related with multidrug resistant phenotype. Northern blot analysis revealed apparent MDR1 expression in the metastatic lesion, while the primary lesion showed faint MDR1 expression detected by only reverse transcriptase-polymerase chain reaction. P-Gp positive tumor cells were immunohistochemically detected both in the metastatic lesion and the primary lesion. The P-Gp-positive tumor cells in the metastatic lesion showed anaplastic features with highly atypical nuclei. These results suggest that MDR1 overexpression is related to the multidrug resistance phenomenon in the malignant schwannoma with morphological differences.

    背景与目标: 一名19岁的女性右膝恶性神经鞘瘤患者接受了包括亲脂性抗癌化合物(环磷酰胺,阿霉素,长春新碱和达卡巴嗪)的联合化疗。化疗后肿瘤被彻底清除,但右侧腹股沟淋巴结中发现转移灶。该患者在术后六个月因恶病质死亡。在人类肿瘤中,已知由人类多药耐药基因MDR1编码的P-糖蛋白(P-Gp)与多药耐药表型有关。 Northern印迹分析显示转移性病变中明显的MDR1表达,而原发性病变仅通过逆转录酶-聚合酶链反应检测到微弱的MDR1表达。在转移性病变和原发性病变中均免疫组织化学检测到了P-Gp阳性肿瘤细胞。转移性病变中的P-Gp阳性肿瘤细胞表现出高度非典型性的间变性特征。这些结果表明,MDR1过表达与恶性神经鞘瘤的多药耐药现象有关,但在形态学上存在差异。

  • 【哮喘患者通过不同装置吸入沙丁胺醇对支气管扩张剂反应的起效速度:一种基于功能拮抗作用的生物测定法。】 复制标题 收藏 收藏
    DOI:10.1111/j.1365-2125.2006.02641.x 复制DOI
    作者列表:Lavorini F,Geri P,Mariani L,Marmai C,Maluccio NM,Pistolesi M,Fontana GA
    BACKGROUND & AIMS: AIMS:To evaluate the speed of onset of bronchodilation following salbutamol administered via a metered-dose inhaler with a spacer (pMDI + Volumatic) and a dry-powder inhaler (Diskus), as well as the relative potencies of these devices in asthmatic patients with methacholine-induced bronchoconstriction. METHODS:Eighteen patients inhaled methacholine (MCh) until FEV(1) decreased by 35% of control. Following administration of placebo, 200 microg salbutamol or 400 microg salbutamol through the pMDI + Volumatic or the Diskus, we calculated the time elapsed from drug administration and the appearance of a 90% increase in post-MCh forced vital capacity (FVC), FEV(1) and volume-adjusted mid-expiratory flow (recovery times). The salbutamol doses to be delivered by the two inhalation devices to achieve similar recovery times and the relative potencies of the devices were calculated by using the 2-by-2 Finney parallel regression method. RESULTS:For all functional variables, recovery times were significantly (P < 0.01) shorter in pMDI + Volumatic than Diskus trials. The salbutamol doses to be delivered by the Diskus to achieve recovery times for FVC, FEV(1) and volume-adjusted mid-expiratory flow similar to those obtained with 200 microg salbutamol administered via the pMDI + Volumatic were 558 (95% CI 537, 579) microg, 395 (95% CI 388, 404) microg and 404 (95% CI 393, 415) microg, respectively, and corresponded to relative potencies of 2.79 (95% CI 2.68, 2.90), 1.98 (95% CI 1.94, 2.02), and 2.02 (95% CI 1.96, 2.07). CONCLUSIONS:Administration of salbutamol via the pMDI + Volumatic provides faster reversal of induced bronchoconstriction than via the Diskus. The salbutamol dose targeting the lungs with the pMDI + Volumatic is approximately twice that with the Diskus.
    背景与目标: 目的:评估沙丁胺醇通过带间隔垫片的定量吸入器(pMDI Volumatic)和干粉吸入器(Diskus)给药后支气管扩张的发生速度,以及这些装置在哮喘患者中使用乙酰甲胆碱的相对效力引起的支气管收缩。
    方法:十八例患者吸入乙酰甲胆碱(MCh),直到FEV(1)降低至对照组的35%。通过pMDI Volumatic或Diskus给予安慰剂,200μg沙丁胺醇或400μg沙丁胺醇后,我们计算了药物给药所花费的时间以及MCh后强制肺活量(FVC),FEV(90)出现90%的增加)和经过体积调整的呼气中气流量(恢复时间)。通过使用2乘2 Finney平行回归方法计算两个吸入装置要达到相似的恢复时间所要输送的沙丁胺醇剂量,以及该装置的相对效能。
    结果:对于所有功能变量,pMDI Volumatic的恢复时间比Diskus试验明显缩短(P <0.01)。与通过pMDI Volumatic施用200微克沙丁胺醇获得的FVC,FEV(1)和经体积调节的呼气中流的恢复时间相比,由Diskus输送的沙丁胺醇的剂量为558(95%CI 537,579) )微克,395(95%CI 388、404)微克和404(95%CI 393、415)微克,分别对应于2.79(95%CI 2.68、2.90),1.98(95%CI 1.94, 2.02)和2.02(95%CI 1.96,2.07)。
    结论:通过pMDI Volumatic给予沙丁胺醇比通过Diskus可以更快地逆转诱导的支气管收缩。使用pMDI Volumatic靶向肺的沙丁胺醇剂量约为使用Diskus的两倍。
  • 【成人胸腺功能:证据来自于清髓性化学疗法和干细胞输注后的免疫恢复模式。】 复制标题 收藏 收藏
    DOI:10.1046/j.1365-2141.1997.982913.x 复制DOI
    作者列表:Cavenagh JD,Milne TM,Macey MG,Newland AC
    BACKGROUND & AIMS: :We studied 45 patients aged 14-66 years who had undergone stem cell transplantation for a variety of malignant conditions at least 12 months previously. Compared to normal controls, they had significantly reduced absolute numbers of CD4+, CD4+ CD45RA+ and CD4+ CD45RO+ T cells and a reduced CD4+ CD45RA+:CD4+ CD45RO+ ratio. In all subsets T-cell numbers were significantly greater 24 months, compared to 12-24 months, after transplantation and there was a nonsignificant trend towards lower T-cell numbers with increasing age. We conclude that the thymus, or putative thymic-equivalent tissue, remains functional in older adults.
    背景与目标: :我们研究了45位14-66岁的患者,这些患者至少在12个月前经历了各种恶性疾病的干细胞移植。与正常对照相比,他们的CD4,CD4 CD45RA和CD4 CD45RO T细胞绝对数显着降低,并且CD4 CD45RA:CD4 CD45RO比值降低。与移植后的12-24个月相比,所有亚组中的T细胞数量在24个月中均显着增加,并且随着年龄的增长,T细胞数量降低的趋势不明显。我们得出的结论是,在老年人中,胸腺或假定的胸腺等效组织仍保持功能。
  • 【铂类化学疗法治疗的转移性或复发性宫颈癌患者的预后和预测因素。】 复制标题 收藏 收藏
    DOI:10.1186/s12885-017-3435-x 复制DOI
    作者列表:Karageorgopoulou S,Kostakis ID,Gazouli M,Markaki S,Papadimitriou M,Bournakis E,Dimopoulos MA,Papadimitriou CA
    BACKGROUND & AIMS: BACKGROUND:Recognizing resistance or susceptibility to the current standard cisplatin and paclitaxel treatment could improve therapeutic outcomes of metastatic or recurrent cervical cancer. METHODS:Forty-five tissue samples from patients participating in a phase II trial of cisplatin and ifosfamide, with or without paclitaxel were collected for retrograde analysis. Immunohistochemistry and genotyping was performed to test ERCC1, III β-tubulin, COX-2, CD4, CD8 and ERCC1 (C8092A and N118 N) and MDR1 (C3435T and G2677 T) gene polymorphisms, as possible predictive and prognostic markers. Results were statistically analyzed and correlated with patient characteristics and outcomes. RESULTS:Patients with higher levels of ERCC1 expression had shorter PFS and OS than patients with low ERCC1 expression (mPFS:5.1 vs 10.2 months, p = 0.027; mOS:10.5 vs. 21.4 months, p = 0.006). Patients with TT in the site of ERCC1 N118 N and GT in the site of MDR1 G2677 T polymorphisms had significantly longer PFS (p = 0.006 and p = 0.027 respectively). ERCC1 expression and the ERCC1 N118 N polymorphism remained independent predictors of PFS. Interestingly, high III beta tubulin expression was associated with chemotherapy resistance and fewer responses [5/20 (25%)] compared to lower III β-tubulin expression [15/23 (65.2%)] (p = 0.008). Finally, ΙΙΙ β-tubulin levels and chemotherapy regimen were independent predictors of response to treatment. CONCLUSIONS:ERCC1 expression proved to be a significant prognostic factor for survival in our metastatic or recurrent cervical cancer population treated with cisplatin based chemotherapy. ERCC1 N118 N and MDR1 G2677 T polymorphism also proved of prognostic significance for disease progression, while overexpression of III β-tubulin was positively correlated with chemotherapy resistance.
    背景与目标: 背景:认识到对当前标准顺铂和紫杉醇治疗的耐药性或易感性可以改善转移性或复发性宫颈癌的治疗效果。
    方法:从参与顺铂和异环磷酰胺II期试验(有或没有紫杉醇)的患者中收集45份组织样本进行逆行分析。进行免疫组织化学和基因分型以测试ERCC1,IIIβ-微管蛋白,COX-2,CD4,CD8和ERCC1(C8092A和N118 N)和MDR1(C3435T和G2677T)基因多态性,作为可能的预测和预后标志物。对结果进行统计分析,并与患者特征和结局相关联。
    结果:ERCC1表达水平较高的患者的PFS和OS短于ERCC1表达水平较低的患者(mPFS:5.1 vs 10.2个月,p = 0.027; mOS:10.5 vs. 21.4个月,p = 0.006)。 ERCC1 N118 N位点为TT的患者,MDR1 G2677 T位点为GT的患者的PFS明显更长(分别为p = 0.006和p = 0.027)。 ERCC1表达和ERCC1 N118 N多态性仍然是PFS的独立预测因子。有趣的是,与较低的IIIβ-微管蛋白表达[15/23(65.2%)]相比,较高的IIIβ-微管蛋白表达与化疗耐药性相关且反应较少[5/20(25%)](p = 0.008)。最后,IIβ-微管蛋白水平和化疗方案是对治疗反应的独立预测因子。
    结论:ERCC1表达被证明是我们基于顺铂化疗的转移性或复发性宫颈癌患者生存的重要预后因素。 ERCC1 N118 N和MDR1 G2677 T多态性也证明对疾病进展具有预后意义,而IIIβ-微管蛋白的过表达与化疗耐药性呈正相关。
  • 【蒽环类药物治疗的HER2 / neu阴性乳腺癌患者的左心室收缩功能:12个月内左心室射血分数和心肌应变显像的比较分析。】 复制标题 收藏 收藏
    DOI:10.1016/j.ejca.2013.06.046 复制DOI
    作者列表:Stoodley PW,Richards DA,Boyd A,Hui R,Harnett PR,Meikle SR,Byth K,Stuart K,Clarke JL,Thomas L
    BACKGROUND & AIMS: AIM:Anthracycline agents are undermined by their cardiotoxicity. As life expectancy following treatment is greatly improved, techniques that ensure early detection and timely management of cardiotoxicity are essential. The aim of the present study was to evaluate left ventricular (LV) systolic function with LV ejection fraction (LVEF) and two-dimensional myocardial strain up to 12 months after anthracycline chemotherapy, specifically in HER2/neu negative breast cancer patients. METHODS:Seventy-eight consecutive anthracycline naïve breast cancer patients were studied before and immediately after anthracycline chemotherapy. Fifty HER2/neu negative patients were studied over 12 months with serial echocardiograms at four time points. All patients were treated with standard regimens containing anthracyclines. RESULTS:Global systolic strain was significantly reduced immediately after, and 6 months after anthracyclines (-19.0 ± 2.3% to -17.5 ± 2.3% (P<0.001) and -18.2 ± 2.2% (P=0.01) respectively). A non-uniform reduction in strain was observed each time with relative sparing of the LV apex. LVEF remained largely unchanged at both time points. Global strain normalised by 12 months in the majority of patients. Persistently reduced strain was observed in 16% (n=8); these patients had a greater reduction in strain at 6 months (≤ -17.2%), and had received higher cumulative anthracycline doses. CONCLUSION:Myocardial strain imaging is more sensitive than LVEF for the early detection and intermediate term monitoring of LV systolic function following anthracycline chemotherapy in HER2/neu negative breast cancer patients, and may aid in the development of improved monitoring protocols.
    背景与目标: 目的:蒽环类药物被其心脏毒性所破坏。随着治疗后预期寿命的大大提高,确保早期发现和及时处理心脏毒性的技术至关重要。本研究的目的是评估蒽环类药物化疗后长达12个月的左心室(LV)收缩功能,左室射血分数(LVEF)和二维心肌劳损,特别是在HER2 / neu阴性乳腺癌患者中。
    方法:在蒽环类药物化疗之前和之后立即研究了88例连续使用蒽环类药物的初治乳腺癌患者。在12个月的时间里,通过四个系列的连续超声心动图研究了50例HER2 / neu阴性患者。所有患者均接受含蒽环类药物的标准治疗方案。
    结果:蒽环类药物治疗后和治疗后6个月,整体收缩应变显着降低(分别为-19.0±2.3%至-17.5±2.3%(P <0.001)和-18.2±2.2%(P = 0.01))。每次观察到应变不均匀降低,但LV根尖相对较少。在两个时间点,LVEF基本上保持不变。大多数患者的总应变在12个月后恢复正常。观察到永久降低的应变为16%(n = 8);这些患者在6个月时的应变降低更大(≤-17.2%),并且接受了更高的蒽环类药物累积剂量。
    结论:对于HER2 / neu阴性乳腺癌患者,蒽环类药物化疗后,心肌应变成像对LV收缩功能的早期检测和中期监测比LVEF更为敏感,可能有助于开发改进的监测方案。
  • 【化学疗法针对毛囊的血管网络,而非干细胞。】 复制标题 收藏 收藏
    DOI:10.1038/sj.jid.5700486 复制DOI
    作者列表:Amoh Y,Li L,Katsuoka K,Hoffman RM
    BACKGROUND & AIMS: :Chemotherapy-induced alopecia is a major problem in clinical oncology. Doxorubicin, a widely used cancer chemotherapy drug, induces disruption of the hair cycle and subsequent alopecia. We show in this report that doxorubicin causes disruption of the hair-follicle-associated blood vessel network resulting in a greatly reduced density of these blood vessels. Dystrophic hair follicles were also observed with abnormal melanogenesis in the mice treated with doxorubicin. Visualization of the effect of doxorubicin on hair-follicle angiogenesis was made possible by the use of transgenic mice in which green fluorescent protein was driven by regulatory elements of the nestin gene (ND-GFP). In these transgenic mice, the hair-follicle stem cells and the follicle structure as well as the blood vessels associated with the hair follicles express ND-GFP. The hair-follicle stem cells did not appear to be affected by doxorubicin, which may explain why hair regrows after chemotherapy. These results suggest that inhibition of hair-follicle-associated angiogenesis by doxorubicin may be an important factor in hair-follicle dystrophy associated with chemotherapy-induced alopecia. The ND-GFP mouse model is thus useful for the study of the role of angiogenesis in the hair-follicle cycle and the effect of drugs on processes associated with chemotherapy-induced alopecia.
    背景与目标: 化学疗法引起的脱发是临床肿瘤学中的主要问题。阿霉素是一种广泛使用的癌症化学治疗药物,可引起毛发周期破坏和随后的脱发。我们在这份报告中表明,阿霉素会导致毛囊相关血管网络的破坏,从而导致这些血管的密度大大降低。在用阿霉素治疗的小鼠中还观察到营养不良的毛囊黑色素生成异常。通过使用其中巢蛋白基因(ND-GFP)调控元件驱动绿色荧光蛋白的转基因小鼠,可以看到阿霉素对毛囊血管生成的作用。在这些转基因小鼠中,毛囊干细胞,毛囊结构以及与毛囊相关的血管均表达ND-GFP。毛囊干细胞似乎没有受到阿霉素的影响,这可以解释为什么化疗后头发会长大。这些结果表明,阿霉素抑制与毛囊相关的血管生成可能是与化学疗法引起的脱发有关的毛囊营养不良的重要因素。因此,ND-GFP小鼠模型可用于研究血管生成在毛囊周期中的作用以及药物对与化学疗法引起的脱发相关的过程的作用。
  • 【通过抑制肿瘤增殖和血管生成,靶向胰岛素样生长因子I受体的抗体增强了多发性骨髓瘤对化学疗法的抗肿瘤反应。】 复制标题 收藏 收藏
    DOI:10.1007/s00262-006-0196-9 复制DOI
    作者列表:Wu KD,Zhou L,Burtrum D,Ludwig DL,Moore MA
    BACKGROUND & AIMS: :Although many multiple myeloma (MM) patients initially respond to cytotoxic therapy, most eventually relapse. Novel therapeutic strategies employing a combination of chemotherapy with targeted biologics may significantly enhance the response of tumor cells to treatment. We tested a fully human anti-IGF-IR antibody (A12) against MM, and showed specific inhibition of IGF-I or serum-induced IGF-IR signaling in MM cells in vitro. The A12 as a single agent was demonstrated to exert modest to significant inhibition of tumor growth in vivo in various subcutaneous xenograft MM models. The A12 was also evaluated in a disseminated xenograft MM.1S NOD/SCID model as monotherapy or in combination with other drugs (bortezomib, melphalan) currently in clinical use. The tumor burden, as determined by luciferase bioimaging, was sharply decreased, and overall survival significantly prolonged when the therapies were combined. Immunohistochemical analysis demonstrated that the A12 treated tumors had significantly decreased vascularization compared to control tumors. Furthermore, most MM lines constitutively secreted significant quantities of VEGF, and this was enhanced following IGF-I treatment. Inhibition of IGF-IR by the A12 in vitro suppressed both constitutive and IGF-I-induced secretion of VEGF, indicating that a putative anti-angiogenic mechanism associated with the A12 treatment may contribute to its anti-tumor effect.
    背景与目标: :尽管许多多发性骨髓瘤(MM)患者最初对细胞毒性疗法有反应,但大多数最终会复发。采用化学疗法与靶向生物制剂相结合的新型治疗策略可以显着增强肿瘤细胞对治疗的反应。我们测试了针对MM的完全人源抗IGF-IR抗体(A12),并显示了MM细胞在体外对IGF-1或血清诱导的IGF-1R信号的特异性抑制。在各种皮下异种移植MM模型中,A12作为单一药剂被证明在体内对肿瘤生长具有中等至显着的抑制作用。还以单一疗法或与目前临床上使用的其他药物(硼替佐米,美法仑)联用的弥漫性异种移植MM.1S NOD / SCID模型评估了A12。通过萤光素酶生物显像确定的肿瘤负荷显着降低,并且当联合治疗时,总生存期显着延长。免疫组织化学分析表明,与对照肿瘤相比,A12治疗的肿瘤的血管形成明显减少。此外,大多数MM系组成型地分泌大量的VEGF,并且在IGF-I处理后其增强。在体外通过A12抑制IGF-IR抑制了组成型和IGF-I诱导的VEGF分泌,这表明与A12治疗相关的推定抗血管生成机制可能有助于其抗肿瘤作用。
  • 【腹腔镜肾切除术治疗Wilms肿瘤后的进一步经验。】 复制标题 收藏 收藏
    DOI:10.1111/j.1464-410X.2006.06214.x 复制DOI
    作者列表:Duarte RJ,Dénes FT,Cristofani LM,Odone-Filho V,Srougi M
    BACKGROUND & AIMS: OBJECTIVE:To report the results of laparoscopic nephrectomy for unilateral Wilms' tumour in children treated with chemotherapy before surgery. PATIENTS AND METHODS:Eight children with unilateral nonmetastatic Wilms' tumour included in the International Society of Pediatric Oncology 2001 protocol were treated with vincristine/actinomycin D and then had laparoscopic nephrectomy and lymph-node sampling. A Veress needle puncture was made and a four-trocar transperitoneal approach was used in all cases. The tumour was extracted with no morcellation through a Pfannenstiel incision. RESULTS:All eight tumours were completely removed, with lymph node samples; intraoperative bleeding was minimal (50 mL). There were no complications after surgery and patients were discharged after 2-3 days. No recurrences of disease, port-site implantation or long-term complications were detected. CONCLUSIONS:Laparoscopic nephrectomy for unilateral Wilms' tumour is feasible in children after chemotherapy; it is safe and allows the complete surgical approach required for treating this tumour. Although the patients had a good long-term follow-up, more patients are needed to compare the results of laparoscopic techniques with open surgery.
    背景与目标: 目的:报道腹腔镜肾切除术治疗儿童化疗前单侧Wilms肿瘤的结果。
    患者与方法:将国际儿童肿瘤学会2001年方案中纳入的8例单侧非转移性Wilms肿瘤患儿用长春新碱/放线菌素D治疗,然后进行腹腔镜肾切除术和淋巴结取样。在所有情况下均进行了Veress穿刺,并使用了四针经腹膜入路。通过Pfannenstiel切口在没有粉碎的情况下提取肿瘤。
    结果:8例肿瘤全部切除,淋巴结清扫。术中出血极少(50 mL)。手术后无并发症,2-3天后出院。没有发现疾病复发,港口植入或长期并发症。
    结论:腹腔镜肾切除术治疗儿童单侧Wilms肿瘤是可行的。它是安全的,并允许治疗该肿瘤所需的完整手术方法。尽管患者长期随访良好,但仍需要更多患者将腹腔镜技术与开放手术的结果进行比较。
  • 【参芪扶正注射液在局部晚期乳腺癌新辅助化疗中的临床效果及其对T淋巴细胞亚群的影响。】 复制标题 收藏 收藏
    DOI:10.1016/s0254-6272(08)60010-2 复制DOI
    作者列表:Dai Z,Wan X,Kang H,Ji Z,Liu L,Liu X,Song L,Min W,Ma X
    BACKGROUND & AIMS: OBJECTIVE:To evaluate clinical effects of shenqi fuzheng Injection ([Chinese characters: see text]) in the neoadjuvant chemotherapy for local advanced breast cancer and the effects on T-lymphocyte subsets. METHODS:During the period from 2000 to 2005, 126 patients with local advanced breast cancer were treated with the neoadjuvant chemotherapy. They were randomly divided into the following two groups: a control group of 61 cases treated by chemotherapy alone and a study group of 65 cases treated by chemotherapy plus shenqi fuzheng injection. All the cases of both groups were given the CEF (CTX 500 mg/m2, d1,8; EPI 40 mg/m2, d1, 8; and 5-Fu 500 mg/m2 d1,8) regimen. The clinical effects, the effects on T-lymphocyte subgroup and NK cells, and the toxic side effects were observed. RESULTS:All the patients completed two cycles of the chemotherapy, and the efficacy and the toxic side effects were evaluated. For the primary tumor in the breast, the total effective rate was 69.2% (45/65) in the study group and 49.2% (30/61) in the control group with a statistically significant difference in the intergroup comparison (chi2 = 5.251, P = 0.022, < 0.05). There was no progression of the disease in both the groups, and there were no grade IV toxic side effects in the two groups. The major toxic responses were myelosuppression and gastrointestinal reaction, which were milder in the study group than the control group, and with a shorter recovery course in the former than the latter. Besides, an obvious rise of the T-lymphocyte subgroup and NK cells was found in the study group after the neoadjuvant chemotherapy, with a very significant difference from the controls (P < 0.01). CONCLUSIONS:Shenqi fuzheng Injection can improve and regulate immune function of the patients with local advanced breast cancer given the neoadjuvant chemotherapy, and therefore it can enhance the curative effect and reduce the side effect as well.
    背景与目标: 目的:评价参芪扶正注射液在局部晚期乳腺癌新辅助化疗中的临床疗效以及对T淋巴细胞亚群的影响。
    方法:在2000年至2005年期间,对126例局部晚期乳腺癌患者进行了新辅助化疗。他们被随机分为以下两组:对照组61例单独接受化疗,研究组65例接受化学疗法加参芪扶正注射液治疗。两组的所有病例均接受CEF(CTX 500 mg / m2,d1,8; EPI 40 mg / m2,d1,8;和5-Fu 500 mg / m2 d1,8)方案。观察其临床效果,对T淋巴细胞亚群和NK细胞的影响以及毒性副作用。
    结果:所有患者均完成了两个化疗周期,并评价了疗效和毒副作用。对于乳腺原发肿瘤,研究组的总有效率为69.2%(45/65),对照组为49.2%(30/61),组间比较的差异有统计学意义(chi2 = 5.251, P = 0.022,<0.05)。两组均无疾病进展,且两组均无IV级毒性副反应。主要的毒性反应是骨髓抑制和胃肠道反应,研究组的毒性反应轻于对照组,前者的恢复过程短于对照组。此外,在新辅助化疗后的研究组中,T淋巴细胞亚群和NK细胞明显升高,与对照组相比有非常显着的差异(P <0.01)。
    结论:参芪扶正注射液可改善和调节新辅助化疗后局部晚期乳腺癌患者的免疫功能,因此可提高疗效,减少副作用。
  • 【小儿鼻咽癌的单一机构经验:铂类化疗加IMRT相关的高毒性发生率。】 复制标题 收藏 收藏
    DOI:10.1097/MPH.0b013e3180959af4 复制DOI
    作者列表:Louis CU,Paulino AC,Gottschalk S,Bertuch AA,Chintagumpala M,Heslop HE,Russell HV
    BACKGROUND & AIMS: BACKGROUND:Chemotherapy and intensity-modulated radiotherapy (IMRT) have decreased treatment-related complications in adult patients with nasopharyngeal carcinoma (NPC). Our aim was to evaluate the toxicity profile of IMRT plus chemotherapy in pediatric NPC patients. OBSERVATIONS:Five patients were treated with chemotherapy and IMRT. All patients experienced grade 3-4 acute toxicities. With a median follow-up of 6.3 years, all patients experienced >or=3 long-term toxicities. The most common toxicities were hypothyroidism, xerostomia, hearing loss, and dental disease. CONCLUSIONS:We did not observe a significant decrease in long-term toxicities with IMRT plus chemotherapy in our small cohort of pediatric NPC patients.
    背景与目标: 背景:化学疗法和调强放射疗法(IMRT)减少了成人鼻咽癌(NPC)患者的治疗相关并发症。我们的目的是评估IMRT联合化疗对小儿NPC患者的毒性。
    观察:5例患者接受了化疗和IMRT治疗。所有患者均经历3-4级急性毒性。中位随访时间为6.3年,所有患者均经历了≥3的长期毒性。最常见的毒性是甲状腺功能减退,口干,听力下降和牙齿疾病。
    结论:在我们的小儿NPC患者队列中,IMRT联合化疗未观察到长期毒性显着降低。
  • 【多个胃肠道区域的基因表达分析揭示了细胞毒性化疗后常见细胞调节途径的激活。】 复制标题 收藏 收藏
    DOI:10.1002/ijc.22895 复制DOI
    作者列表:Bowen JM,Gibson RJ,Tsykin A,Stringer AM,Logan RM,Keefe DM
    BACKGROUND & AIMS: :Gastrointestinal mucositis involves many changes at the gene level, affecting epithelial/subepithelial interactions and leading to overt damage. The regional specificity and time course of these changes, and how they relate to subsequent mucositis development however remain unknown. The aim of this study was to determine the early time course of gene expression changes along the gastrointestinal tract of the DA rat following chemotherapy. Female DA rats were treated with a single dose of 200 mg/kg irinotecan to induce mucositis, and were killed at short intervals following treatment. Small sections of stomach, jejunum and colon were harvested for analysis of genetic profiles. RNA was hybridised to high density Affymetrix oligonucleotide microarrays. Data analysis was carried out with software package, TimeCourse, freely available through Bioconductor. As early as 1 hr following chemotherapy, expression of hundreds of genes was altered, including those for transcription factors, stress response proteins and protein turnover. These genes are involved in cell proliferation, differentiation and apoptosis along with other cellular processes. At early time points, there was a significant response involving the mitogen-activated protein kinase pathway, cell cycle regulation and cytokine receptor signalling. At later time points, changes to the complement cascade became prominent. We have shown that changes in gene expression following chemotherapy occur by 1 hr, and persist for at least 72 hr after treatment. Many of these changes are highly likely to be specifically related to the subsequent development of gastrointestinal mucositis.
    背景与目标: :胃肠道粘膜炎在基因水平上涉及许多变化,影响上皮/耻骨上皮相互作用并导致明显的损害。这些变化的区域特异性和时程,以及它们与随后的粘膜炎发展之间的关系仍然未知。这项研究的目的是确定化学疗法后DA大鼠胃肠道基因表达变化的早期过程。用单剂量200 mg / kg伊立替康治疗雌性DA大鼠,以诱导粘膜炎,并在治疗后短时间处死。收集胃,空肠和结肠的小部分用于遗传特征分析。 RNA与高密度Affymetrix寡核苷酸微阵列杂交。数据分析是使用TimeCourse软件包进行的,该软件包可通过Bioconductor免费获得。化疗后1小时,数百种基因的表达发生了变化,包括转录因子,应激反应蛋白和蛋白更新的基因。这些基因与其他细胞过程一起参与细胞增殖,分化和凋亡。在早期时间点,有明显的反应,涉及丝裂原激活的蛋白激酶途径,细胞周期调节和细胞因子受体信号传导。在随后的时间点,补体级联的改变变得很明显。我们已经显示,化疗后基因表达的变化在1小时内发生,并在治疗后持续至少72小时。这些变化中的许多极有可能与胃肠道粘膜炎的后续发展特别相关。

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