拓扑替康联合顺铂治疗小细胞肺癌44例疗效观察

目的：研究拓扑替康联合顺铂治疗小细胞肺癌的疗效。方法：对确诊的44例小细胞肺癌患者,应用拓扑替康联合顺铂静滴d1-d5,同时给予止吐治疗。结果：全组共化疗132个周期,44例患者中总有效率为45.5%,临床受益率81.8%,全组无治疗相关性死亡。结论：以拓扑替康联合顺铂的化疗方案对小细胞肺癌具有较好的疗效。

艾迪注射液配合化疗治疗晚期非小细胞肺癌的临床观察

为研究艾迪注射液对晚期非小细胞肺癌的治疗作用及对化疗所致毒副作用的影响 ,将 76例晚期非小细胞肺癌患者随机分为两组 ,分别按MVP方案化疗 ,MVP化疗基础上加用艾迪注射液 ,按WHO的统一评价标准评价两组的近期疗效和毒副作用并进行比较。结果发现两组间的近期疗效差异无显著性 (P >0 0 5 ) ,但是联合使用艾迪注射液组的Ⅱ度和Ⅱ度以上的胃肠道反应、白细胞下降率、血小板下降率均显著低于单纯MVP化疗组 (均P <0 0 5 )。初步研究结果提示 ,艾迪注射液能够显著减轻化疗药物引起的胃肠道反应 ,对骨髓具有保护作用。

培美曲塞联合顺铂治疗晚期非小细胞肺癌临床观察

目的:观察培美曲塞(PMT)联合顺铂(DDP)治疗晚期非小细胞肺癌(NSCLC)的近期疗效和不良反应。方法:既往治疗失败的ⅢB～Ⅳ期NSCLC患者27例,应用PP方案联合化疗:培美曲塞500mg/m2,静滴10分钟以上,第1天;顺铂25mg/m2,静滴2小时,第1～3天。每21天1周期,每例患者至少完成2个周期。结果:全组完全缓解(CR)2例,部分缓解(PR)6例,稳定(SD)13例,进展(PD)6例。客观有效率29.6%,1年生存率43.5%,两年生存率18.9%,起效时间4.5个月,中位无进展生存时间4.8个月,中位生存时间10.3个月,Ⅲ/Ⅳ级药物不良事件:粒细胞减少15.1%;贫血5.6%,白细胞减少症和血小板减少症发生率分别为4.8%和4.1%;发热性粒细胞减少1.3%,非造血系统Ⅲ/Ⅳ级,其中脱发11.9%;恶心7.2%,呕吐6.1%,食欲不振12.3%,乏力6.7%,静脉炎3.5%,末梢神经炎12.5%,局部皮疹2.6%,轻度肝功能损害14.7%,无肾脏毒性发生,全组无药物相关性死亡。结论:培美曲塞联合顺铂治疗晚期NSCLC具较好的临床疗效,且安全耐受性好,不良反应轻,是目前治疗晚期NSCLC较为理想的方案。

脐血CIK细胞联合吉西他滨与卡铂治疗晚期非小细胞肺癌患者的临床效果

目的研究分析脐血CIK细胞联合吉西他滨与卡铂治疗晚期非小细胞肺癌患者的临床效果。方法选取2013年2月至2014年2月本院收治的60例晚期非小细胞肺癌患者为研究对象，随机分成研究组（n=30，治疗方案：脐血CIK细胞＋吉西他滨＋卡铂）和对照组（n=30，治疗方案：吉西他滨＋卡铂）。比较两组临床有效率、不良反应发生情况以及生活质量变化情况。结果研究组和对照组有效率分别为66．67％、30．00％，差异有统计学意义（P〈0．05）；研究组肝肾功能损害、消化道反应等不良反应发生率均明显低于对照组（P〈0．05）；治疗后，两组生活质量均得到改善，且研究组生活质量评分更佳，P〈0．05。结论脐血CIK细胞联合吉西他滨与卡铂治疗晚期非小细胞肺癌患者具有理想的疗效，并且不良反应症状少，安全有效，患者生活质量得到明显提高，值得推广应用。

三维适形放射治疗非小细胞肺癌的临床研究

目的：探讨三维适形放疗治疗非小细胞肺癌（NSCLC）的临床疗效。方法：60例NSCLC中鳞癌38例，腺癌19例，腺鳞癌3例。中心型者前期采用常规放射治疗，2．0Gy／次，5次／周，总剂量40．0Gy，后程采用3DCRT，5．0Gy／次，3次／周，总剂量30．0Gy。再程放射治疗者和外周型者对病灶直接采用3DCRT，5．0Gy／次，3次／周，总剂量50．0Gy，外周型者患侧肺门及纵膈淋巴引流区常规预防照射，2．0Gy／次，5次／周，总剂量50．0Gy。结果：60例近期疗效19例完全缓解，29例部分缓解，肿瘤总有效率为80％（48／60）；1，2，3年生存率分别为80．0％；36．67％；20．oH。结论：三维适形放疗对NSCLC近期有较好效果，副反应可耐受，远期效果尚需进一步观察。

mTOR信号传导通路及其相关药物与非小细胞肺癌

哺乳动物雷帕霉素靶蛋白（mTOR）处于细胞生长繁殖、细胞周期调控、生物合成、细胞迁移等信号通路调控的中心位置，因此在肿瘤以及肺癌的发生、发展，特别是在治疗和预后中具有重要的作用。mTOR磷酸化激活后，通过调控4EBP和P70S6K两条不同的下游通路，分别控制特定亚组mRNA的翻译，进而影响生物合成。对非小细胞肺癌来讲，mTOR能够加快细胞周期G1-S期的转换，促进细胞增殖。雷帕霉素、西罗莫司、依维莫司等mTOR信号通路的阻断药物在肺癌的治疗中显示出了希望。

美国FDA批准酪氨酸激酶抑制剂类抗癌药Afatinib用于一线治疗晚期非小细胞肺癌

美国FDA于2013年7月12日批准了Boe-hringerIngelheim公司开发的酪氨酸激酶抑制剂类抗癌药afatinib（Gilotrif）用于一线治疗携有表皮生长因子受体（EGFR）突变基因（主要为外显子19缺失和外显子21L858R替换）的转移性晚期非小细胞肺癌（NSCLC）患者，同时也批准了一项EGFR突变基因的诊断试验方法。

Alectinib treatment for 2 non-small cell lung carcinoma patients carrying different novel ALK fusions

The genomic fusions of the anaplastic lymphoma kinase(ALK)gene have been widely recognized as effective therapeutic targets for non-small cell lung carcinoma(NSCLC).The Second Xiangya Hospital of Central South University has treated 2 NSCLC patients with 2 distinct novel ALK gene fusions.Case 1 was a 55-year-old male with a solid nodule located in the right hilar lobe on enhanced CT scan.Case 2 was a 47-year-old female with enhanced CT showing involvement of the left upper lobe of lung.Histopathological examination of tumor tissues confirmed lung adenocarcinoma in both cases.Immunohistochemical(IHC)staining demonstrated positivity for thyroid transcription factor 1(TTF-1)and ALK-D5F3 in tumor cells,while negativity for P40.The next-generation sequencing(NGS)tests identified a PNPT1-ALK(Exon22:Exon20)fusion variant in case 1 and a TCEAL2-ALK(Exon3:Exon19)fusion variant in case 2.The TCEAL2-ALK fusion was further confirmed by amplification refractory mutation system(ARMS)-PCR at the mRNA level.Both patients were treated with oral alectinib at a dosage of 600 mg twice daily.The tumors in both patients were significantly decreased after alectinib treatment,achieving partial response.At the time of submission,there was an absence of disease progression and the progression-free survival(PFS)had surpassed 1 year.It offered compelling evidences that the individuals with NSCLC and harboring either a PNPT1-ALK(Exon22:Exon20)fusion or a TCEAL2-ALK(Exon3:Exon19)fusion,experience favorable therapeutic outcomes through the administration of alectinib.This study expands the known ALK fusion variants database and supports the precision treatment of NSCLC using ALK tyrosine kinase inhibitors(TKIs).

Transfection of the Human Sodium/Iodide Symporter(NIS) Gene with Liposomes and the Expression of the NIS Protein in Human Lung A549 Cancer Cells

OBJECTIVE To examine the possibility of human sodium iodide symporter （hNIS） protein expression in lung cancer cells. METHODS Human lung A549 cancer cells were thawed and cultured in vitro. The cells were divided into an experimental group transfected with a recombinant pcDNA3-hNIS plasmid and a control group transfected only with a pcDNA3 plasmid. The recombinant plasmid vector encoding the hNIS gene （pcDNA3-hNIS） was amplified, purified and identified. The hNIS gene was followed by DNA sequencing. A Western blot and an immunohistochemical assay were applied to detect the hNIS protein expression in the transfected human lung A549 cancer cells. RESULTS Restriction enzyme digestion and DNA sequencing results showed the size and direction of the inserted gene in the recombinant pcD- NA3-hNIS plasmid was correct. The Western blot method and immunohistochemical analysis showed a positive NIS protein expression in the experimental group. The NIS protein was detected mainly in the cell membranes showing a positive rate up to 70.6% with no expression of the NIS protein in the control group. There was a significant difference between two groups （P=0.000）. CONCLUSION The hNIS gene was transfected effectively into human lung A549 cancer cells mediated by Lipofectamine 2000, and was expressed with its protein in vitro.

Purification and Characterization of Cytotoxins from Agkistrodon acutus Venom and Their Anticancer Activity

Aim To investigate the anticancer activity of two new cytotoxins from thevenom of Agkistrodon acutus. Methods The venom was isolated by FPLC column chromatography consistingof DEAE Sepharose FF and Source 30S. The cytotoxic activity on tumor cells was detected by MITmethod. Purity and molecular weight were determined by SDS-PAGE (silver staining). Their stabilitiesto temperature and pH were also detected. Results Two pure cytotoxins named ACTX-6 and ACTX-8 wereobtained. Their molecular weights are 98 kDa and 27 kDa, respectively. ACTX-6 consists of twosubunits bonded together by disulfide bonds. Conclusion ACTX-6 and ATCX-8 have highest inhibitoryactivity on lung cancer cell A549. ACTX-6 is stable to heat while ACTX-8 not. ACTX-6 is stablebetween pH 7-9 and ACTX-8 between pH 6 - 9.

The Promoter Hypermethylation of DAPK Gene and pl6 Gene in Sera from Chinese Non-small Cell Lung Cancer Patients

Objective： To evaluate the clinical significance of the aberrant methylation of DAPK gene and p16 gene in sera from 65 NSCLC patients from Nanjing General Hospital of Nanjing Command, China. Methods： A methylation-specific PCR （MSP） was performed for the detection of promoter hypermethylation of DAPK gene and p16 gene in blood DNA from 65 cases of NSCLC, and to analyze the relation of the aberrant methylation of DAPK gene and p16 gene and the clinicopathological data. Results： 30.8% （20/65） of the sera from 65 cases of NSCLC showed hypermethylation for DAPK promoter and 43.1% （28/65） the same for p16 promoter, whereas no methylated DAPK gene promoter and p16 gene promoter were found in sera from the patients with lung benign diseases and normal controls. Methylated DAPK gene promoter and p16 gene promoter in sera were not closely correlated with the pathological classification, stage, metastasis and differentiation in NSCLC. Conclusion： Detection of the aberrant methylation of DAPK gene and p16 gene in blood DNA from NSCLC patients might offer an effective means for the earlier auxiliary diagnosis of the malignancy.

Expression of Hypoxia Inducible Factor lα and Its Significance in Non-small Cell Lung Cancer

Objective： To explore the expression level and its clinical significance of hypoxia inducible factor 1α （HIF-1α ） in non-small lung cancer. Methods： The expression of HIF-1α was detected in 68 human non-small lung cancer samples by immunohistochemistry. Results： （1） Thirty-nine （57.35%） out of the 68 human non-small lung cancer samples was positive for HIF-1α ; （2） The positive rate of HIF-1α in adenocarcinoma and squamous carcinoma was 54.76% （23/42） and 61.54% （16/26） respectively. No significant difference was found between adenocarcinoma and squamous carcinoma of non-small lung cancer in the expression of HIF-1α （P〉0.05）. The positive rate of HIF-1α in middle-high differentiation was 74.28% （26/35）, significantly higher than in low differentiation （39.39%, 13/33） （P〈0.05）; （3） The positive expression of HIF-1α was not correlated to the sexes, ages, tumor stage and lymph node status. Conclusion： The expression of HIF-1α is higher in non-small lung cancer and is correlated to differentiation.

Effects of Selenium Dioxide on Apoptosis, Bcl-2 and P53 Expression, Intracellular Reactive Oxygen Species and Calcium Level in Three Human Lung Cancer Cell Lines

Objective: To evaluate the anti-tumor effects of SeO2 and its mechanisms on three human lung cancer cell lines. Methods: Three lung cancer cells A549, GLC-82 and PG were treated with 3-30 μmol/L SeO2. Flow cytometry was used to detect apoptosis, and analyze the changes of expression of p53 and Bcl-2, as well as ROS and Ca2+ level within cells. Results:SeO2 markedly inhibited cell proliferation and viability, and prompted apoptosis after 48 h treatment. SeO2 at 10 μmol/L induced 47.8% apoptosis in A549 cells, 40.8% in GLC-82 cells, 18.2% in PG cells. SeO2 at 30 μmol/L induced 37.8% apoposis in PG cells,but did not increase apoptotic raes in other two cells. SeO2 could down-regulate the mean fluorescent intensity of Bcl-2 from 65.8 to 9.6 in A549, but not in GLC-82 and in PG cells, up-regulate wild type p53 level in all three cells. SeO2 decreased the ROS and Ca2+ level markedly within three tested cells. Conclusion: SeO2 showed anti-tumor effect via apoptosis pathway in three lung cancer cell lines. The decrease of ROS and Ca2+ level within cells as well as regulation of Bcl-2 and p53 expression may play important roles in above apoptotic procedure.

Clinical Course Of Patients with Small Cell Lung Cancer As Second Primary Malignancy

Objective： To evaluate the clinical course of patients with small cell lung cancer （SCLC） as second primary malignancy. Methods： Among the 355 patients diagnosed with SCLC at Helen and Harry Gray Cancer Center of Hartford Hospital Connecticut USA between 1988 and 1998, the records of 48 patients, which had been diagnosed with other malignancies before their diagnosis of SCLC, were retro- spectively reviewed. Results： Forty-eight patients （13.5%） were diagnosed with other malignancies prior to their SCLC among which 43 had documented smoking history and 93% of them （40/43） were current/former smokers. Of the 28-second primary SCLC patients who were treated with standard method, 11 （39.3%） achieved CR. 12 （42.8%） achieved PR, and the RR was 82.1%. The median survival of the 28 treated with standard method was 11.3 months （5.1-77.7 months）, while that of the rest 19 untreated patients （1 of 20 was lost to follow-up） was only 2.0 months （0.5 34.0 months）. There was no significant difference in the median survival and RR between 165 treated first primary SCLC （13.5 months and 77.6% respectively） and 28 treated secondary primary SCLC （11.3 months and 82.1% respectively） （P〉0.05）. The patients who had prostate cancer were older and subjected to less treatments than those with skin cancer, so their survival was shorter than the latter （3.5 months vs. 15 months, P〈0.05）. Conclusion： The response and survival of the treated patients with SCLC as a second malignancy showed no difference as compared to the treated ones with SCLC only. Therefore, an active medical treatment is important to relieve symptom and prolong survival of the second primary SCLC patients.

Tumor Angiogenesis Correlated with bFGF and FGFR-1 in Lung Cancer

To study the relationship between angiogenesis and the expression of bFGF andFGFR-1 in lung cancer. Methods: The specimens of 56 patients with lung cancer treated with surgerywere collected. Anti-Von Willebrand factor antibody was used to measure microvascular density (MVD)by means of SABC immunohistochemical technique, and antibody to basic fibroblast growth factor(bFGF) and its receptor (FGFR-1) to detect the expression of these three proteins in the tumortissues. The survival time was compared between low MVD and high MVD groups by the Kaplan-Meiermethod. Results: (1) The expression of MVD showed no significant difference in some clinicalcharacteristics, including sex, age, T stage, M stage and pathologic type, but significantdifference in N stage (P 【 0.01) and clinical stage (P 【 0.05). (2) Survival analysis showed thathigh MVD group was associated with a risk of death (P 【 0.01). (3) The expression of bFGF and FGFR-1were both related to lymphatic metastasis and clinical staging (P 【 0.05). (4) Significantdifference was seen between low MVD and high MVD groups in the bFGF expression in lung cancer (P 【0.01), whereas no correlation in FGFR-1. (5) High co-expression of bFGF and FGFR-1 was consistent intumor cells. Conclusion: (1) MVD is a good prognostic factor for patients of lung cancer, and thesame as bFGF. (2) The angiogenesis may be induced after bFGF binding to FGFR-1.

Prognostic Impact of Histopathologic Response after Neoadjuvant Chemotherapy in Stage Ⅲ_A Non-small Cell Lung Cancer

Objective： To investigate prognostic impact of histopathologic response induced by neoadjuvant chemotherapy in patients with stage ⅢA non-small cell lung cancer （NSCLC）. Methods： Forty patients with stage ⅢA NSCLC underwent two cycles of neoadjuvant chemotherapy with mitomycin, vindosine, and cisplatin followed by surgery. Histopathologic response in resection of the tumor was examined after surgery. Tumor regression was classified as grade Ⅳ, grade Ⅲ, grade Ⅱ, and grade Ⅰ according to the extent of tumor necrosis and the extent of the vital tumor tissues. The tumor regression grading was correlated with the survival time of the patients. Results： After two cycles of chemotherapy, 19 （47.5%） of 40 patients had objective response （2 complete and 17 partial response）. In 40 resected tumor specimens, 2 （5%） were classified as regression grade Ⅳ, 16 （40%） as regression grade Ⅲ, 18 （45%） as regression gradeⅡ, and 4 （10%） as regression grade Ⅰ. The rate of complete surgical resection was significantly higher in patients with tumor regression grade Ⅲ-Ⅳ （〈10% vital tumor tissue）（P〈0.05）. The median survival time in patients classified as having tumor regression grade Ⅲ-Ⅳ was significantly longer than that in patients who had regression grade Ⅰ-Ⅱ （P〈0.05）. The 3-year survival rate in patients with regression grade Ⅲ-Ⅳ was markedly higher than that in patients who had regression grade Ⅰ-Ⅱ （P〈0.05）. Conclusion： The extent of tumor regression induced by neoadjuvant chemotherapy is a critical issue for successful therapeutic approach in patients with stage ⅢA NSCLC. In resected specimens of tumors after chemotherapy, the presence of marked tumor regression （regression grade Ⅲ-Ⅳ） is predictive for superior survival time.

Characterization of Two Human Lung Adenocarcinoma Cell Lines by Reciprocal Chromosome Painting

Lung cancer is a leading cause of cancer death worldwide. Some lung cancer patients correlate with a gas of radon besides smoking. To search for common chromosomal aberrations in lung cancer cell lines established from patients induced by different factors, a combined approach of chromosome sorting, forward and reverse chromosome painting was used to characterize karyotypes of two lung adenocarcinoma cell lines： A549 and GLC-82 with the latter line derived from a patient who has suffered long-term exposure to environmental radon gas pollution. The chromosome painting results revealed that complex chromosomal rearrangements occurred in these two lung adenocarcinoma cell lines. Thirteen and twenty-four abnormal chromosomes were identified An A549 and GLC-82 cell lines, respectively. Almost half of abnormal chromosomes in these two cell lines were formed by non-reciprocal translocations, the others were derived from deletions and duplication/or amplification in some chromosomal regions. Furthermore, two apparently common breakpoints, HSA8q24 and 12q14 were found in these two lung cancer cell lines.

Synergistic growth inhibitory effects of Phyllanthus emblica and Terminalia bellerica extracts with conventional cytotoxic agents:Doxorubicin and cisplatin against human hepatocellular carcinoma and lung cancer cells

AIM: To examine the growth inhibitory effects of Phyllanthus emblica (P. emblica) and Terminalia bellerica (T. bellerica) extracts on human hepatocellular carcinoma (HepG2), and lung carcinoma (A549) cells and their synergistic effect with doxorubicin or cisplatin. METHODS: HepG2 and A549 cells were treated with P. emblica and T. bellerica extracts either alone or in combination with doxorubicin or cisplatin and effects on cell growth were determined using the sulforhodamine B (SRB) assay. The isobologram and combination index (CI) method of Chou-Talalay were used to evaluate interactions between plant extracts and drugs. RESULTS: P. emblica and T. bellerica extracts demonstrated growth inhibitory activity, with a certain degree of selectivity against the two cancer cell lines tested. Synergistic effects (CI < 1) for P. emblica /doxorubicin or cisplatin at different dose levels were demonstrated in A549 and HepG2 cells. The T. bellerica/ cisplatin or doxorubicin also showed synergistic effects in A549 and HepG2 cells. In some instances, the combinations resulted in antagonistic effects. The dose reduction level was different and specific to each combination and cell line. CONCLUSION: The growth inhibitory activity of doxorubicin or cisplatin, as a single agent, may be modified by combinations of P. emblica or T. bellerica extracts and be synergistically enhanced in some cases. Depending on the combination ratio, the doses for each drug for a given degree of effect in the combination may be reduced. The mechanisms involved in this interaction between chemotherapeutic drugs and plant extracts remain unclear and should be further evaluated.

Advances in immunotherapy for treatment of lung cancer

Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the immunological system in tumor control has opened multiple doors to implement different strategies to enhance immune response against cancer cells. It is known that tumor cells elude immune response by several mechanisms. The development of monoclonal antibodies against the checkpoint inhibitor programmed cell death protein 1 （PD-1） and its ligand （PD-L1）, on T cells, has led to high activity in cancer patients with long lasting responses. Nivolumab, an anti PD-1 inhibitor, has been recently approved for the treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in a phase III trial. Pembrolizumab~ another anti PD-1 antibod）5 has received FDA breakthrough therapy designation for treatment of non-small cell lung cancer （NSCLC）, supported by data from a phase I trial. Clinical trials with anti PD-1/PD-L1 antibodies in NSCLC have demonstrated very good tolerability and activity, with response rates around 20% and a median duration of response of 18 months.