Objective: To investigate the efficacy and safety of using pegylated recombinant human granulocyte-colonystimulating factor (PEG-rhG-CSF) in preventing neutropenia in multiple chemotherapy cycles. Methods: A multicenter, prospective, open-label, singlearmstudy was designed. Patients with malignant tumors, such as lung, ovarian, and colorectal cancers, who received multiple cycles of chemotherapy with the prophylactic use of PEG-rhG-CSF for 2-4 consecutive cycles participated in the study. Results: After the prophylactic use of PEG-rhG-CSF, the incidence of grade IV neutropenia decreased from 4.76% (13/273) in the first cycle to 1.83% (5/273), 1.15% (2/174), and 2.08% (2/96) in subsequent cycles. Meanwhile, the incidence of grade III neutropenia decreased from 11.36% (31/ 273) in the first cycle to 6.23% (17/273), 2.87% (5/174), and 3.13% (3/96) in subsequent cycles. The incidence of febrile neutropenia (FN) during the first cycle was 0.73% (2/273). The duration of FN was 2 days in one case and 5 days in another case. FN was not observed during the second, third, or fourth cycle. After the secondary prophylactic use of PEG-rhG-CSF, the incidence of grade IV neutropenia decreased from 25% (7/28) to 3.57% (1/28), 0% (0/28), and 6.67% (1/15) in subsequent cycles. Meanwhile, the incidence of grade III neutropenia decreased from 71.43% (20/28) to 10.71% (3/28), 14.29% (4/28), and 0% (0/15) in subsequent cycles. The proportion of patients who received antibiotic therapy during the entire chemotherapy period was 10.48% (44/420). Conclusion: The application of PEG-rhG-CSF once per chemotherapy cycle can effectively reduce the occurrence of neutropenia in patients under multiple cycles of chemotherapy treatment with good safety.

Objective To investigate the clinical value of cell block for kirsten rat sarcoma viral oncogene (KRAS) mutation detection in non-small cell lung cancer(NSCLC). Methods 215 cases of cell block from pleural effusion of non-small cell lung cancer were collected. 7 types of KRAS mutation and 404 cases of tissue block were detected by ARMS-PCR method. The consistency of KRAS mutation was examined in 74 patients with tissue block and cell block. Results KRAS mutations were found in 24 of 215 cell blocks ( positive detection rate of 11. 16%) . KRAS mutation was detected in 37 of 404 tissue blocks ( positive detection rate of 9. 16%) . There were 69 cases in the 74 (93. 24%) cases having the same result as tissue block. KRAS mutation was detected in 8 of 74 (10. 81%) cell blocks, and 13 of 74 (17. 57%) tissue blocks. Conclusion The rate of KRAS mutation in cell blocks of non-small cell lung cancer is higher than in matched tissue blocks. The patients with malignant pleural effusion are likely tend to KRAS mutation compare to those not.

患者女性，57岁，无吸烟史。因咳痰伴痰中带血1个月于2012年3月就诊陆军总医院，PET-CT检查提示：右肺癌，肺门、纵隔多发淋巴结转移，L2骨转移。免疫组织化学检测：肺来源可能性大。心包积液检测示：查见鳞癌（图1），EGFR基因突变阴性。诊断为：1）右肺鳞癌Ⅳ期（pT4N3M1），肺门、纵隔多发淋巴结转移癌，骨转移癌，心包积液。2）高血压Ⅲ级高危。患者拒绝放、化疗，服用靶向药物治疗。遂于2012年3月开始口服靶向药物吉非替尼250 mg qd。2个月疗效评价：疗效稳定（SD），见图2。2015年7月患者出现腰部疼痛，2015年9月16日复查胸部CT示：双肺部多发结节，右肺部结节明显增大。考虑其为缓慢进展，继续给予患者服用吉非替尼并加用甲磺酸阿帕替尼500 mg qd。因患者为高血压Ⅲ级，服阿帕替尼期间严密监测患者血压、定期复查尿常规。患者耐受情况好，未见明显不良反应。2个月后复查CT示：肺部，疗效评价病灶稳定（SD），见图3。患者2016年2月5日因出现头痛、四肢抽搐，外院胸部CT提示病变进展（PD）。阿帕替尼无疾病生存期为5个月余。经激素、利尿、放疗对症治疗后，头痛及四肢抽搐缓解，改行阿帕替尼联合AZD9291治疗。2016年3月7日患者复查骨扫描未见新发骨转移癌灶，胸部CT提示肺病灶未见增大，疗效评价SD，现患者正在随访中。

Objective: To explore clinical effcacy and side effects of crizotinib in advanced anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer.Methods: Retrospectively analysed 43 cases of ALK positive NSCLC patients, receiving oral treatment with crizotinib (250 mg) twice daily until the progress of the disease or the emergence of the side effects. Clinical effcacy was observed atfer 12-month followed-up.Results: hTe DCR of the patients treated with crizotinib was 93% (3/43), ORR was 62% (26/43), and median PFS was 7.0 months (95% CI, 6.0~8.0 months). hTe most frequent treatment-related AEs were gastrointestinal disturbance, followed by increased glutamic-pyruvic transaminase, vision disorder, and most toxicities were grade 1 and 2.Conclusion: Crizotinib, as targets for NSCLC patients with targeted therapy, has good effect and safety, minor adverse reactions.

Crizotinib is a tyrosine kinase inhibitor (TKI),which is a target for echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK).It can prolong the progression free survival (PFS)of ALK positive patients with advanced non-small cell lung cancer (NSCLC).The median PFS in the first-line and second-line mPFS is 10.9 months and 7.7 months.However,despite an initial benefit,patients inevitably experience tumor progression,due to the ALK fusion gene amplification and secondary mutations of ALK kinase domain.Clinical trials show the promising efficacy like next generation ALK inhibitors and heat shock protein 90 (HSP90)can overcome acquired resistance.

表皮生长因子受体酪氨酸激酶抑制剂( EGFR-TKI)开启了肺癌个体化治疗的新领域,而以间变性淋巴瘤激酶( ALK )、肝细胞生长因子受体 C ( C-MET)为主要靶点的克唑替尼于2011年8月26日获得美国食品与药物管理局批准使用[1-4]。通常认为,表皮生长因子受体( EGFR)和ALK、Kirsten鼠肉瘤病毒癌基因( KRAS)在非小细胞肺癌( NSCLC)中是互斥的,但Ulivi等[5]分析252例患者的EGFR与ALK,EGFR与KRAS以及ALK 与KRAS 基因双突变概率分别为1.6%,1.1%和2.5%。本文回顾性分析诊断C-MET和ALK双驱动共存型3例患者的临床资料并复习国内外相关文献,探讨双阳性患者服用克唑替尼的疗效及预后。

Objective: To investigate the clinical value of the cell blacks forROS1 (c-ros oncogene 1, receptor tyrosine kinase) fusion gene detection in non-small cell lung cancer (NSCLC).Methods: Selected 215 cases of cell block from pleural effusion of NSCLC and 404 cases of tissue block of NSCLC, detected the four types of ROS1 fusion by ARMS-PCR method. The consistency ofROS1 fusion was examined in 74 cases of patients with tissue block and cell block.Results:ROS1 fusion was found in 7 of 215 cell blocks, positive detection rate of 3.26% (7/215).ROS1 fusion was detected in 8 of 404 tissue blocks (positive detection rate of 1.98%). 71 cases in the 74 (95.95%) cases had the same result as tissue block.ROS1 fusion was detected in 2 of 74 (2.70%) cell blocks, and 5 of 74 (6.76%) tissue blocks.Conclusion: hTe rate ofROS1 fusion in cell blocks of non-small cell lung cancer is higher than in matched tissue blocks. The patients with malignant pleural effusion are likely tend toROS1 fusion.

Objective To explore the clinical efficacy of crizotinib in treatment of advanced ALK positive NSCLC which compared with chemotherapy. Methods 86 ALK positive NSCLC patients were randomly divided into the treatment group (n=43) and the chemotherapy group (n=43). The treatment group was given crizotinib thera-py, and the chemotherapy group received standard chemotherapy ( pemetrexed plug, paclitaxel or gemcitabine com-bined with cisplatin or carboplatin) . All the patients were followed up for 12 months to assess the efficacy and toxici-ty. Results The ORR of the treatment group was 62% (26/43), which was significantly higher than 27. 9% of the chemotherapy group ( 12/43 ) , and the median progression free survival ( PFS ) was 7. 0 months in the treatment group (95% CI:6. 0-8. 0 months), higher than 3. 0 months in the chemotherapy group (95% CI:1. 180-4. 820 months) . The most frequent treatment-related AEs in the treatment group were gastrointestinal? disturbance, fol-lowed by increased glutamic-pyruvic transaminase, vision disorder, and most toxicities were grade 1 and 2. The most frequent treatment-related AEs in the chemotherapy group were nausea, fatigue, vomiting, and loss of appetite. Con-clusion The clinical efficacy of crizotinib in patients with ALK positive advanced NSCLC is better than that of con-ventional chemotherapy, which can prolong the median PFS and improve the quality of life.

Objective: To evaluate the curative effect and safety of icotinib on treatment of advanced non-small cell lung cancer.Methods: 37 patients of advanced non-small cell lung cancer without treatment of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) were enrolled in the group. All the patients orally took icotinib 125 mg 3 times a day, until the disease progressed or the patients could not tolerate. Effcacy and drug toxicity was observed atfer 12 months followed-up.Results:Response could be assessed in all the 37 patients. hTe objective response rate (ORR) was 56.7% (21/37) and the disease control rate (DCR) was 84.6% (35/37). The main adverse reactions were rash and diarrhea, mostly degreeⅠ orⅡ.Conclusion: Icotinib is an effective drug for the treatment of advanced non-small cell lung cancer, with an advantage of nice durability.

Objective: To investigate the clinical value of the cell blocks for gene ampliifcation detection of c-mesenchymal-epithelial transition (c-MET).Methods: Two hundred and iftfeen cases of cell block from pleural effusion of non-small cell lung cancer (NSCLC) were collected. Four hundred and four cases of tissue block were detected by RT-PCR method. hTe consistency ofc-MET ampliifcation was examined in 74 cases of patients with tissue block and cell block.Results:c-MET ampliifcation was found in 31 of 215 cell blocks (positive detection rate of 14.42%). c-MET ampliifcation was detected in 35 of 404 tissue blocks (positive detection rate of 8.66%). hTere were 68 cases in the 74 (91.89%) cases had the same consistency as tissue block.c-MET ampliifcation was detected in 9 of 74 (12.16%) cell blocks, and 13 of 74 (17.57%) tissue blocks.Conclusion: hTe rate ofc-MET ampliifcation in cell blocks of non-small cell lung cancer is higher than in matched tissue blocks. hTe patients with malignant pleural effusion are likely to tendc-MET ampliifcation.

Objective: To investigate the clinical value of the cell blacks for anaplastic lymphoma kinase (ALK) fusion gene detection in non-small cell lung cancer (NSCLC).Methods: 215 cases of cell block from pleural effusion of non-small cell lung cancer were collected. hTree types ofALK fusion and 404 cases of tissue block were detected by ARMS-PCR method. hTe consistency ofALK fusion was examined in 74 cases of patients with tissue block and cell block.Results:ALK fusion was found in 26 of 215 cell blocks, the positive detection rate was 12.09%.ALK fusion was detected in 25 of 404 tissue blocks, the positive detection rate was 6.19%. 67 cases in the 74 (90.54%) cases had the same result as tissue block.ALK fusion was detected in 11 of 74 (14.86%) cell blocks, and 14 of 74 (18.92%) tissue blocks.Conclusion: hTe rate ofALK fusion in cell blocks of non-small cell lung cancer is higher than that in matched tissue blocks. hTe patients with malignant pleural effusion are likely to tend toALK fusion.

Objective: Brain metastases have been recognized as an emerging complication in patients with anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC). This study will explore the efficacy of crizotinib in ALK-positive NSCLC with brain metastases.Methods: Selected 20 cases of brain metastatic ALK positive NSCLC patients, received crizotinib therapy to clinical observation.Results: Among patients with brain metastases before treatment, 12 had partial response (PR), 7 stable disease (SD) and 1 disease progression (PD). Objective response rate (ORR) was 60%, and disease control rate (DCR) was 95%. Median progression free survival (PFS) was 6 months (95% CI: 3.92~8.08).Conclusion: Crizotinib is effective for brain metastases in ALK positive NSCLC.

Lung cancer is the most frequently occurring lethal cancers in men and women population. The aim of the present study is to observe the overexpression pattern of phosphorylated MARCKS in the nicotine-derived nitrosamine ketone (NNK) induced lung cancer mice. Pathogen-free female A/J mice were used for the present experiment to induce lung cancer by the carcinogen namely, NNK. At different time intervals namely, 5(th), 6(th) and 7(th) month after NNK injection, lung tissue samples were collected. Immunohistochemistry in accordance with the immunoblotting techniques were used to confirm the over-expression of phosphorylated MARCKS in the NNK induced lung cancer mice model. The present study concludes that the phosphorylated MARCKS was over-expressed in the NNK induced lung cancer mice during the early stages of lung cancer and it may be used as a tool to detect the lung cancer in the initial stages.

OBJECTIVE To explore the mutation status of epidermal growth factor receptor (EGFR) fusion gene and microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene in superficial lymph nodes of non-small cell lung cancer (NSCLC). METHODS The technique of fluorescent quantitative polymerase chain reaction (FQ-PCR) was employed for detecting the mutation rate of EGFR gene and EML4-ALK fusion gene for 40 cases of superficial lymph node tissue of NSCLC inpatients at General Military Hospital of Beijing PLA Command from February 2013 to November 2014. And then the correlations were analyzed between EMIA-ALK fusion gene and EGFR gene with clinical features and the clinical efficacies of targeted therapy. RESULTS The mutation rate of EGFR gene was 35% (14/40) and 50% (10/20) in non-smokers and 46.7% (14/30) in adenocarcinoma patients. The mutation distribution was as follows: exon 18 (n = 1), exon 19 (n =8) and exon 21 (n =5). The mutation rate of EML4-ALK fusion gene was 2. 5% (1/40). EGFR gene mutation was predominantly present in non-smokers (P < 0. 05) and adenocarcinoma (P <0. 01) while no significant difference existed between gender, age or stage (P >0. 05). Those on a targeted therapy had a disease control rate of 93. 3%. CONCLUSIONS Both EGFR gene and EMI4-ALK fusion gene may be detected in superficial lymph nodes of NSCLC patients. The mutation rate of EGFR gene is high in adenocarcinoma and non-smokers while EML4-ALK fusion gene has a low mutation rate.

Breast cancer is the most common malignancy in Chinese women. The aim of the present study was to investigate the genetic alterations that occur in breast cancer cells in Chinese women. Comparative genomic hybridization (CGH) analysis was performed on 34 tumors obtained from patients with primary invasive ductal breast carcinoma (IDC). Recurrent genetic alterations in breast cancer include gains on chromosomes 1q (59%), 16p (50%), 17q (44%), 8q (38%), 11q (32%), 20q (32%), 1p (24%), 20p (24%), 19q (21%) and 19p (18%). Losses are common on chromosomes 6q (15%), 8p (12%), 18 (12%), 4q (9%), X (9%) and 17p (9%). In the present study, high-level amplifications were observed on chromosomes 1q32, 8p, 11q13, 17q and 20q. Overall, the chromosomal DNA gains observed were consistent with the changes reported in Caucasian populations. However, the incidence of chromosomal DNA loss was lower in the present study compared with the incidence reported in the literature. The present results demonstrate the pattern of chromosomal imbalances in the invasive ductal breast carcinomas of Chinese females.

目的 探讨肾上腺髓质素(adrenomedullin,AM)对转化生长因子β1(transforming growth factor-β1,TGF-β1)促肺成纤维细胞增殖及c-myc基因表达的影响.方法 体外原代培养人胚肺成纤维细胞(human fetal lung fibroblasts,HFLFs),分为对照组、AM组、TGF-β1组和AM+ TGF-β1组,采用MTT法观察各组光吸度(optical density,OD)值;各组提取细胞总RNA,采用反转录PCR观察c-myc基因mRNA表达情况.结果 AM+ TGF-β1组HFLFs细胞培养24、48、72 h时OD值(0.615±0.054、0.483±0.017、0.675±0.014)明显低于TGF-β1组(0.830±0.012、0.753±0.089、0.929±0.039) (P＜0.05),TGF-β1组HFLFs细胞培养72 h时OD值(o.929±0.039)明显高于对照组(0.605±0.274)(P＜0.05),AM组HFLFs细胞培养24、48 h时OD值(o.559±0.019、0.412±0.096)明显低于对照组(0.785±0.081、0.646±0.038) (P＜0.05);AM组c-myc mRNA相对表达量(0.450±0.025)明显低于对照组(P＜0.01);TGF-β1组c-myc mRNA相对表达量(1.160±0.100)高于对照组(P＜0.05);AM+ TGF-β1组c-myc mRNA相对表达量(0.340±0.030)低于TGF-β1组(P＜0.01).结论 AM能抑制肺成纤维细胞增殖和c-myc基因表达,AM可能具有抗纤维化作用.

肺癌发病率近年来不断上升。2014年,中国最新研究解析了2010年中国恶性肿瘤流行病谱,报告指出中国恶性肿瘤发病与死亡均居首位的是肺癌,每年新发与死亡病例分别约60万和49万[1]。对于多数肺癌晚期患者,含铂化疗方案作为主要治疗策略,患者的中位生存期也仅10个月左右[2]。新近发现的 EML4-ALK 融合基因突变作为 NSCLC 最新的分子亚型之一,目前的文献显示其突变率约占5%,相当于每年全球约有60,000患者患此病[3]。对于大多数局部复发或远处转移的肺癌患者而言,关于ALK 突变阳性意义与其预后的研究仍不明确,但有学者指出与表皮生长因子受体( epidermal growth factor receptor,EGFR)、鼠肉瘤病毒基因(Kirsten rat sarcoma virus, K-ras )、 ALK 基因突变均阴性的NSCLC 患者相比,ALK 基因重排与肺癌发生转移有着密切联系[4]。因此,EML4-ALK 融合基因阳性的NSCLC 患者在肿瘤生物学行为和转移模式上可能更加独特。本文主要围绕 EML4-ALK 融合基因阳性 NSCLC 患者的临床特征及其在肺癌转移灶中的表达特点、检测方法及 ALK 抑制剂等方面展开阐述。

患者,女,71岁。2012年9月患者无意中发现左小腿中段内侧一黄豆大小包块,触痛明显,伴皮肤肿胀,无皮温增高。在当地医院给予理疗后肿胀有所好转,但肿块进行性增大伴疼痛加剧。2013年3月在当地医院行左下肢MRI检查示：左胫骨中段骨质破坏伴软组织肿块,初步诊断为恶性骨肿瘤。随后在硬膜外麻醉下行肿物切除术,术后病理提示：转移性低分化腺癌,免疫组化：CK7(+), TTF-1(+), CK5/6-,提示肺来源肿瘤可能性大。为求进一步诊治,来我院。既往体健,无慢性病及传染病史,无有毒有害物质接触史,无烟酒嗜好。其兄患肺癌去世。查体无阳性发现。在我科行胸部CT 检查示：左肺下叶后基底段肿块影,考虑肿瘤性病变。行反转录多聚酶链反应( reverse transcriptase polymerase chain reaction,RT-PCR)法及荧光原位杂交( fluores-cence in situ hybridisation,FISH)法检测骨组织石蜡切片EML4-ALK融合基因均为阳性,用RT-PCR法及基因测序法检测EGFR基因19、20外显子突变。诊断：左肺腺癌Ⅳ期。左侧胫骨转移癌、左侧胫骨转移癌切除术后,2013-04-22开始口服单药吉非替尼250 mg/d,用药后出现轻度皮疹、脱屑等副反应,给予对症处理后好转。2013-04-24开始同步行左小腿局部放疗,剂量：PTV 2Gy/30Gy/15F/23d,无不适主诉,至2013-05-16放疗结束,期间定期复查血象,未见明显骨髓抑制。2013年6月患者入院全面复查未见疾病进展,继续口服吉非替尼治疗。随访至2014年6月,患者复查仍未见肺部病灶进展及肿瘤远处转移,目前继续口服吉非替尼治疗。

目的 探讨肺癌患者转移灶中棘皮动物微管相关蛋白样4-间变性淋巴瘤激酶(EML4-ALK)的阳性表达率及其与临床病理特征、血清指标的关系和使用靶向治疗后的效果.方法 使用实时荧光定量PCR法(FQ-PCR)对71例肺癌转移灶中EML4-ALK融合基因进行检测,同时检测患者血清标志物癌胚抗原(CEA)、癌糖原(cA125)及血管内皮生长因子(VEGF)水平,分析EML4-ALK融合基因在转移灶中表达情况及与血清标志物水平的相关性.结果 在淋巴结、脑、骨、体表软组织、肝、结肠和胸膜转移组织中检测到EML4-ALK融合基因阳性表达的组织有淋巴结、脑、骨和胸膜,总阳性表达率为7.04％.转移灶组织中EML4-ALK融合基因表达阳性率与病理类型、性别、年龄、吸烟状态、分化程度和分期因素无明显相关(P＞0.05),但临床上仍以腺癌、不吸烟者人群较多见.血清CEA、CA125、VEGF水平在EML4-ALK融合基因阳性组和阴性组中差异无统计学意义(P＞0.05).接受克唑替尼治疗的肺癌患者6个月疾病控制率为66％.结论 使用FQ-PCR技术检测肺癌转移灶中EML4-ALK融合基因是可行的,可以为腺癌、不吸烟这些优势人群提供靶向治疗策略.

目的 回顾口服吉非替尼治疗非小细胞肺癌(NSCLC)后因疾病进展死亡患者的近期疗效,并初步观察不同人群的疗效差异.方法 选取2008年8月至2012年8月应用吉非替尼治疗可评价近期疗效并因疾病进展死亡的15例NSCLC患者资料.口服吉非替尼,每次250 mg,每日1次,期间接受了营养、止痛、抗骨转移等支持对症治疗.治疗开始后每个月复查胸部CT以评价疗效,按实体瘤治疗反应评价标准评定肿瘤近期疗效.结果 15例患者中完全缓解1例,部分缓解5例,疾病稳定8例,疾病进展1例;有效率为40％(6/15),疾病控制率为93.3％(14/15),生存时间9～60个月,中位生存期18个月,中位疾病进展时间16.47个月.1年生存率为73.3％(11/15),2年生存率为26.7％(4/15).结论 吉非替尼能明显改善晚期NSCLC患者症状,延长生存时间.不良反应轻微,为肺癌患者提供了更为个体化的治疗,具有很好的临床应用前景.