食蟹猴妊娠早期血清生殖激素的变化

目的:通过研究食蟹猴妊娠早期生殖激素的变化,为进行食蟹猴胚胎-胎仔发育毒性试验提供数据支持。方法:食蟹猴在怀孕第0天(gestation day 0,GD0)和怀孕第20天(GD20)采血分离血清检测孕酮水平。怀孕的雌猴于GD27～GD100每周采血1次,采用化学发光法检测血清中雌二醇、孕酮和催乳素的水平。结果:怀孕雌猴GD20的孕酮水平显著高于GD0。GD0～GD27孕酮水平缓慢上升,GD27达到高峰后下降,在GD48至最低,随后至GD100呈逐渐上升趋势。GD0～GD27雌二醇水平也缓慢上升,之后降低,在GD34达到最低水平,随后呈上升趋势,至GD100达到最高。催乳素水平从CD0开始缓慢上升,GD69达最高,后趋于平稳。结论:食蟹猴妊娠早期主要生殖激素随妊娠发展呈现动态变化,孕酮水平可作为早孕诊断的辅助参考。     

裸小鼠人肺癌术后转移模型的建立及动态观察

目的：建立裸小鼠人肺癌术后转移模型,动态观察肿瘤转移情况,为研究肺癌转移机制和术后抗转移治疗提供动物模型。方法：采用组织块法建立裸小鼠人非小细胞肺癌NCI-H460皮下移植瘤模型。4周后,随机挑选25只裸小鼠作为手术组切除肿瘤组织,建立术后转移模型,其余15只裸小鼠作为对照组。每2周两组各处死5只裸小鼠,动态观察其远处各脏器转移情况。动物明显消瘦时结束实验,并采用免疫组化法检测MMP-2、OPN、CD44v6、CD62等蛋白在转移灶及原发灶的表达情况。结果：对照组裸小鼠10周时所携瘤体严重坏死,并出现明显消瘦,解剖发现各阶段均无转移。手术组裸小鼠于10周、12周各发现1例肺转移（1/5）,14周时裸小鼠明显消瘦,肺转移率达100%（5/5）,有肉眼明显可见的肺转移结节,其他脏器未见转移。免疫组化结果表明,MMP-2、OPN、CD44v6、CD62、E-cadherin、TIMP-2在肺转移灶内的表达明显高于原发灶,CD54和MMP-9在转移灶内的表达则低于原发灶。结论：本模型模拟了临床肿瘤根除术后发生远处转移的过程,结果提示肺癌转移的发生可能与部分粘附分子的表达异常相关,同时为研究肺癌转移机制和术后抗转移治疗提供了理想的动物模型。     

人源性CD3抗体诱导食蟹猴T淋巴细胞培养方法的建立

目的： 在初步分析人、食蟹猴和猪CD3蛋白同源性的基础上,建立利用人源性CD3抗体诱导食蟹猴外周血T淋巴细 胞的体外分离培养技术。 方法： 从NCBI 查询获取人类、食蟹猴和猪CD3蛋白各自的氨基酸序列,并用DNAMAN 软件进行序列 比对、同源性分析和构建系统进化树。Western blotting检测三种T细胞膜上CD3蛋白的表达水平。分离健康食蟹猴PBMC,分为 3组,A组加入抗人CD3抗体单刺激、B组加入IL-2单刺激、C组加入抗人CD3抗体和IL-2共刺激。倒置显微镜下观察细胞生 长状态并计数,绘制细胞生长曲线,锥虫蓝染色检测细胞活性,流式细胞术检测T细胞表面标志物CD3、CD4、CD8的表达。 结 果： 食蟹猴、猪的CD3蛋白氨基酸序列与人类的同源性分别为86.9% 、65.6%,T细胞膜上CD3蛋白的表达量分别为人的79%、 17%。A组细胞不增殖;C组细胞增殖能力、细胞活性及CD3表达率［(93.8±3.6)% vs (70.3±4.7)%,P<0.01］均显著高于B组,细胞 生长曲线呈S形,符合Logistic生长曲线;C组T细胞高表达CD3,T细胞纯度较高,且CD8 + T 细胞占比较多。 结论： 食蟹猴外周血 T淋巴细胞膜表面能表达和人同源性很高的CD3蛋白,在人源性CD3抗体、IL-2和1%PHA共刺激下能诱导食蟹猴外周血T淋巴 细胞的增殖分化,获得生长状态良好、增殖能力强、纯度较高的T淋巴细胞。     

早期非小细胞肺癌的放射治疗

在早期非小细胞肺癌(NSCLC)中,有部分患者因各种原因采用单纯放射治疗.多数学者认为,其照射剂量应不低于60Gy.靶区范围的制定,要结合肿瘤的生物学规律和患者的具体情况,体现治疗的个体化.超分割和大剂量分割放射治疗在一定程度上提高了NSCLC的疗效.立体定向放射治疗为早期NSCLC的治疗提供了一种新的治疗手段,初步的临床实践表明是安全、可行的.     

EYA2在非小细胞肺癌中的表达

目的 探讨EYA2在非小细胞肺癌(NSCLC)中的表达及其与临床参数之间的关系.方法 59例NSCLC组织及癌旁正常肺组织,分别行Western blot分析及免疫组织化学染色,比较癌组织与肺组织之间EYA2表达差异,分析EYA2表达与肺癌临床参数之间的关系.结果 EYA2在NSCLC组织中的表达水平升高.EYA2分布于NSCLC细胞浆及细胞核中,胞浆中表达更明显.EYA2的表达与NSCLC病理类型有关,与分化程度、TNM分期、淋巴结转移等因素无关.EYA2在肺腺癌中表达明显升高,而在鳞癌中无变化.结论 EYA2在肺腺癌中表达水平升高,可能作为转录激活因子参与肺腺癌的发生、发展.     

EYA2在非小细胞肺癌中的表达

目的 探讨EYA2在非小细胞肺癌(NSCLC)中的表达及其与临床参数之间的关系.方法 59例NSCLC组织及癌旁正常肺组织,分别行Western blot分析及免疫组织化学染色,比较癌组织与肺组织之间EYA2表达差异,分析EYA2表达与肺癌临床参数之间的关系.结果 EYA2在NSCLC组织中的表达水平升高.EYA2分布于NSCLC细胞浆及细胞核中,胞浆中表达更明显.EYA2的表达与NSCLC病理类型有关,与分化程度、TNM分期、淋巴结转移等因素无关.EYA2在肺腺癌中表达明显升高,而在鳞癌中无变化.结论 EYA2在肺腺癌中表达水平升高,可能作为转录激活因子参与肺腺癌的发生、发展.     

EYA2在非小细胞肺癌中的表达

目的 探讨EYA2在非小细胞肺癌(NSCLC)中的表达及其与临床参数之间的关系.方法 59例NSCLC组织及癌旁正常肺组织,分别行Western blot分析及免疫组织化学染色,比较癌组织与肺组织之间EYA2表达差异,分析EYA2表达与肺癌临床参数之间的关系.结果 EYA2在NSCLC组织中的表达水平升高.EYA2分布于NSCLC细胞浆及细胞核中,胞浆中表达更明显.EYA2的表达与NSCLC病理类型有关,与分化程度、TNM分期、淋巴结转移等因素无关.EYA2在肺腺癌中表达明显升高,而在鳞癌中无变化.结论 EYA2在肺腺癌中表达水平升高,可能作为转录激活因子参与肺腺癌的发生、发展.     

EYA2在非小细胞肺癌中的表达

目的 探讨EYA2在非小细胞肺癌(NSCLC)中的表达及其与临床参数之间的关系.方法 59例NSCLC组织及癌旁正常肺组织,分别行Western blot分析及免疫组织化学染色,比较癌组织与肺组织之间EYA2表达差异,分析EYA2表达与肺癌临床参数之间的关系.结果 EYA2在NSCLC组织中的表达水平升高.EYA2分布于NSCLC细胞浆及细胞核中,胞浆中表达更明显.EYA2的表达与NSCLC病理类型有关,与分化程度、TNM分期、淋巴结转移等因素无关.EYA2在肺腺癌中表达明显升高,而在鳞癌中无变化.结论 EYA2在肺腺癌中表达水平升高,可能作为转录激活因子参与肺腺癌的发生、发展.     

EYA2在非小细胞肺癌中的表达

目的 探讨EYA2在非小细胞肺癌(NSCLC)中的表达及其与临床参数之间的关系.方法 59例NSCLC组织及癌旁正常肺组织,分别行Western blot分析及免疫组织化学染色,比较癌组织与肺组织之间EYA2表达差异,分析EYA2表达与肺癌临床参数之间的关系.结果 EYA2在NSCLC组织中的表达水平升高.EYA2分布于NSCLC细胞浆及细胞核中,胞浆中表达更明显.EYA2的表达与NSCLC病理类型有关,与分化程度、TNM分期、淋巴结转移等因素无关.EYA2在肺腺癌中表达明显升高,而在鳞癌中无变化.结论 EYA2在肺腺癌中表达水平升高,可能作为转录激活因子参与肺腺癌的发生、发展.     

小细胞肺癌的靶向治疗

小细胞肺癌（SCLC）靶向治疗药物包括血管生成抑制剂、酪氨酸激酶抑制剂和信号通路抑制剂等。研究表明血管生成抑制剂如贝伐珠单抗疗效并不显著;酪氨酸激酶抑制剂如舒尼替尼等可能更适合单药治疗;信号通路抑制剂如 Amuvatinib、LDE225等正在进行Ⅰ、Ⅱ期临床试验。目前认为 SCLC对于靶向治疗不敏感,或更具有选择性和针对性,有待于进一步研究。     

Inhibition of human small cell lung cancer cell growth by methylprednisolone

Methylprednisolone (MP) inhibited cancer cell growth at concentrations between 0 and 2.0 mM. IC50 was 0.96 mM in H82, 0.44 mM in H345, 0.86 mM in H510A, 0.54 mM in N592 and 0.52 mM in H2081. The growth inhibition was not disturbed by addition of 1 microM RU38486. DNA fragmentation were observed in H510A and N592 at MP concentration of 0.2 mM. Glucocorticoid (GC) receptor mRNA expression was detectable only in H510A. We concluded that MP has potency as an anti-cancer agent at a high concentration. The effect was probably not through GC receptor binding, and growth inhibition was independent of apoptosis induction.     

Factors associated with human small aggressive non small cell lung cancer.

BACKGROUND: Some non-small cell lung cancers (NSCLC) progress to distant lymph nodes or metastasize while relatively small. Such small aggressive NSCLCs (SA-NSCLC) are no longer resectable with curative intent, carry a grave prognosis, and may involve unique biological pathways. This is a study of factors associated with SA-NSCLC. METHODS: A nested case-case study was embedded in the National Cancer Institute's Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. SA-NSCLC cases had stage T1, N3, and/or M1 NSCLC (n = 48) and non-SA-NSCLC cases had T2 to T3, N0 to N2, and M0 NSCLC (n = 329). Associations were assessed by multiple logistic regression. RESULTS: SA-NSCLCs were associated with younger age at diagnosis [odds ratio (OR)(>or=65 versus <65), 0.44; 95% confidence interval (95% CI), 0.22-0.88], female gender, family history of lung cancer, and the interaction gender*family history of lung cancer and were inversely associated with ibuprofen use (OR(yes versus no), 0.29; 95% CI, 0.11-0.76). The ORs for associating gender (women versus men) with SA-NSCLC in those with and without a family history of lung cancer were 11.76 (95% CI, 2.00-69.22) and 1.86 (95% CI, 0.88-3.96), respectively. These associations held adjusted for histology and time from screening to diagnosis and when alternative controls were assessed. CONCLUSION: SA-NSCLC was associated with female gender, especially in those with a family history of lung cancer. If these exploratory findings, which are subject to bias, are validated as causal, elucidation of the genetic and female factors involved may improve understanding of cancer progression and lead to preventions and therapies. Ibuprofen may inhibit lung cancer progression.     

依立替康致小细胞肺癌荷瘤鼠腹泻模型的建立

目的建立依立替康（irinotecan,CPT-11）致小细胞肺癌（small-cell lung cancer,SCLC）荷瘤鼠腹泻模型。方法培养LTEP/P人SCLC细胞株,传代3-4代后收集细胞,接种于BALB/C SPF裸鼠,接种成功后用瘤块继续接种于其它裸鼠。荷瘤鼠按高、中、低3个剂量分别静注CPT-11,连续4天,观察腹泻情况。结果高剂量组荷瘤鼠腹泻最严重,中剂量组次之,低剂量组不明显。结论以30-40 mg/（kg.d）剂量连续4天静注CPT-11,可建立稳定可靠的小细胞肺癌荷瘤鼠腹泻模型。     

Mechanism of vinorelbine-induced radiosensitization of human small cell lung cancer cells

Vinorelbine (Navelbine, KW-2307), a semisynthetic vinca alkaloid, is a potent inhibitor of mitotic microtubule polymerization. The aims of this study were to demonstrate vinorelbine-induced radiosensitization of human small cell lung cancer (SCLC) SBC-3 cells and to elucidate the mechanisms of radiosensitization. A clonogenic assay demonstrated that SBC-3 cells were sensitized to radiation by vinorelbine using different schedules combining exposure to both. The sensitizer enhancement ratios (SERs) at a cell survival level of 10% were 1.42+/-0.21 to 1.33+/-0.06, and 1.22+/-0.07 depending on schedule. Vinorelbine-induced radiosensitization did not depend on the schedule of the combined exposure. Flow cytometric analyses showed that the cells did not accumulate in the radiosensitive G(2)/M phase of the cell cycle after concurrent treatment with vinorelbine and radiation. The results of an alkaline filter elution assay demonstrated that in the presence of vinorelbine at 1 n M radiation-induced DNA strand breaks were not completely repaired at 24 h postradiation. We conclude that human SCLC SBC-3 cells are sensitized to radiation by vinorelbine and that a possible mechanisms of vinorelbine-induced radiosensitization may at least in part be associated with impairment of DNA repair following radiation-induced DNA damage.     

Management of small cell lung cancer

Small cell lung cancer is a tumor that has a very poor prognosis without treatment. It is however, highly responsive to chemotherapy and radiotherapy. Pretreatment clinical and laboratory parameters – in addition to staging – can prognosticate outcome and help define the aim of treatment. Different schedules of chemotherapy have been developed and varied strategies, such as chemotherapy dose intensification have been tried to improve outcomes. New agents, such as irinotecan, gemcitabine and topotecan have also been tested. Clinical trials have helped to define strategies of integrating thoracic radiotherapy and prophylactic cranial radiotherapy into management of those patients with limited disease to improve survival further. Despite good initial responses to treatment, most patients eventually relapse. Maintenance strategies with ongoing chemotherapy or novel agents, such as interferon, matrix metalloproteinase inhibitors, thalidomide and vaccines are discussed.     

Management of small cell lung cancer

Small cell lung cancer remains an important malignancy with increasing lung cancer rates in many countries. It is important to distinguish between better and poorer prognostic patient groups in order to target therapy more effectively. Modern chemotherapy usually includes a platinum combination and in selected patient groups combined modality with thoracic and prophylactic cranial irradiation. For poorer prognostic groups, treatment is less well defined and less commonly researched. Nevertheless the integration of combined modality treatments and novel drugs beckons towards an exciting avenue for future research.     

Treatment of small cell lung cancer

The treatment of choice for limited small-cell lung cancer (SCLC) is platinum-based chemotherapy combined with early, concurrent thoracic radiotherapy with a hyperfractionated regimen. The standard chemotherapy for extensive SCLC in Japan is the combination of irinotecan and cisplatin. There are expectations for new and effective molecular-target-based drugs for SCLC.     

Management of small cell lung cancer

Opinion statement Small cell lung cancer (SCLC) is an aggressive type of lung cancer characterized by rapid growth and early metastasis. It is chemosensitive and radiosensitive, yet decades of research investigating multimodality treatments have failed to control or cure this disease in most patients. First-line treatment of limited-stage disease consists of chemotherapy (often etoposide/cisplatin or etoposide/carboplatin) combined with thoracic radiation therapy (TRT), followed by prophylactic cranial irradiation to decrease brain metastases as a site of disease progression for those who experience complete remission or a very good partial response to multimodality treatment. In a Japanese trial, the combination of irinotecan and cisplatin had initially shown promise in treating patients with extensive-stage SCLC, but a confirmatory trial in the United States did not find a difference in overall survival with irinotecan/cisplatin versus etoposide/cisplatin. Adding a third drug to the etoposide/cisplatin combination, as well as other triplet therapies, has mostly been ineffective in improving outcomes. Variables in chemotherapy administration, including maintenance therapy, alternating non-cross-resistance regimens, and dose intensification, have not been shown to increase survival at large. In terms of radiation therapy, early administration of TRT concurrent with chemotherapy, and hyperfractionation, have been beneficial in treatment of limited-stage disease. In patients who relapse, second-line therapy options consist of reinduction of previous chemotherapy or administration of a single agent. Targeted biological therapies for SCLC are now being investigated, and although a great deal of research remains to be done, these agents and their derivatives may provide the most hope for future treatment of SCLC.     

小细胞肺癌的治疗进展与现状

肺癌为一种恶性程度较高的肿瘤性疾病,其病死率居各种恶性肿瘤之首,发病率逐年上升,近年随着禁烟教育力度的增强和普及,发病率已出现下降势头。小细胞肺癌(SCLC)是一种以生长迅速、早期转移、高度侵袭性为特点的肺癌类型。小细胞肺癌的肿瘤细胞对化疗和放疗都非常敏感,但几十年来多方案的临床试验并没能找到彻底治愈小细胞肺癌的有效方法,多数患者在一线治疗以后仍会复发或转移。局限期小细胞肺癌的一线治疗包括双药化疗(足量EP方案:依托泊甙 顺铂/卡铂)联合胸腔放射治疗(TRT)。当联合方案达完全缓解(CR)或疗效较好的部分缓解(PR)患者,应后续应用预防性脑照射(PCI),可明显降低未来复发性脑转移的风险。日本和德国的临床研究显示含有伊立替康的IP方案及IC方案(伊立替康 顺铂/卡铂)治疗广泛期小细胞肺癌效果可比标准EP方案。各种强化疗法并不能提高小细胞肺癌患者的生存率。胸腔放疗方案的研究显示局限期小细胞肺癌患者早期同步应用超分割放疗方案配合化疗可以改善预后,可能与放疗越早介入越能有效减少耐药克隆株的发生有关。对于小细胞肺癌复发患者,可依据是敏感复发或是难治复发相应选择再次应用首次化疗方案或用二线单药化疗方案。培美曲塞联合铂类方案已应用于SCLC的一线及二线治疗。PET-CT的应用对小细胞肺癌的精确分期非常重要。真正符合Ⅰ_A期及Ⅰ_B期(TNM分期)的小细胞肺癌患者可考虑手术治疗,术后应行正规化疗。生物靶向治疗小细胞肺癌的若干研究性试验正在进行之中,这些生物制剂及其衍生物有可能会为未来小细胞肺癌的治疗带来一线曙光。