The tumor-inhibiting effect of isomeric dichloro(diphenylethylenediamine)platinum(II) complexes

Summary Ring unsubstituted dichloro(diphenylethylenediamine)platinum(II) complexes show a dependence of their antitumor activity on the configuration and position of phenyl rings in ethylenediamine ligand. Dichloro(1,1-diphenylethylenediamine)platinum(II) (1d) and meso-dichloro(1,2-diphenylethylenediamine)-platinum(II) (meso-2d) have a weaker effect on the human breast-cancer cell line MDA-MB 231 and on rat leukemia L5222 than (±)-dichloro(1,2-diphenylethylenediamine)platinum(II) ((+)-2d) and its enantiomers (+)-2d and (-)-2d which cause marked and comparable inhibition of both tumors; (±)-2d is also active on ADJ/PC 6 plasmacytoma of the mouse and on cisplatin-, daunomycin-, and cisplatin/daunomycin-resistant Ehrlich ascites tumors of the mouse. The differences in activity of the diastereomers (±)-2d and meso-2d, for which distinct influences on the DNA secondary structure can be demonstrated CD spectroscopically may be explained by a steric hindrance of the drug-DNA interaction.Supported by the Wilhelm-Sander-Stiftung and by the Verband der Chemischen Industrie, Fonds der Chemischen Industrie.Dedicated to Dr. A. von Schlichtegroll on his 60th birthday     

EGFR and KRAS mutational profiling in fresh non-small cell lung cancer (NSCLC) cells

Purpose

Knowledge of tumor mutational status has become a priority for effective NSCLC-tailored treatment. NSCLC diagnosis is more often reached through biopsy; thus, there is a clear need to implement for routine tumor molecular profiling on small cytological samples. This work aims to screen and compare the EGFR and KRAS mutational prevalence in fresh tumor cells and in corresponding routinely processed samples derived from trans-thoracic fine-needle aspiration. The latter currently represents the most appropriate diagnostic procedure in case of peripheral lesions, such as adenocarcinomas, which account for almost 40 % of all NSCLCs and for the highest EGFR mutational rates.

Methods

Two hundred and forty-four patients carrying peripheral lung masses underwent CT-guided aspiration. The obtained material was split, and a part was addressed to conventional histopathological analysis while the remaining one was stored at ?20 °C. In case of confirmation of adenocarcinoma, tumor genomic DNA was extracted from both fresh and fixed material, and EGFR and KRAS sequencing was performed.

Results

We identified 136 adenocarcinomas; from 134, we could recover enough material for the study. A full match was demonstrated between EGFR/KRAS mutational prevalences through the two approaches tested. We found EGFR mutations in 13 patients (9.7 %); 7 were females and 11 never or former smokers. KRAS mutations occurred in 20 (14.9 %) patients. EGFR and KRAS mutations were mutually exclusive.

Conclusions

Mutational screening on fresh cancer cells is an achievable, safe and cost-effective procedure which might allow routinely tumor molecular profiling as powerful integration of conventional histopathological analysis.     

cis-Dichlorodiammineplatinum(II) in non-small cell carcinoma of the lung.

The role of cis-dichlorodiammineplatinum(II) (cis-platinum) as a single agent in non-small cell lung cancer has not been clearly defined, and extensive phase II studies have not been conducted. However, objective responses were noted in several early clinical trials. A review of these reports, including combinations with conventional agents, shows 15 partial responses among 100 patients. Results are presented on a new protocol using high-dose cis-platinum with mannitol-induced diuresis combined with cyclophosphamide and Adriamycin. An overall partial response rate of 28% was observed, including a 38% response rate in good performance status patients, with a median survival of 16 months in responding patients. Data from recent combination protocols do not define the activity of cis-platinum as a single agent, but suggest that it may be useful in non-small cell carcinoma of the lung.     

不同用药顺序吉非替尼、多西他赛联用对非小细胞肺癌细胞的体外抑制作用

目的探讨不同用药顺序吉非替尼、多西他赛(DXT)联用对非小细胞肺癌(NSCLC)细胞的体外抑制作用。方法选择人肺癌细胞株PC-9、PC-9/G、A549,用MTT法、流式细胞技术分别检测不同顺序吉非替尼、DXT联用对3种细胞存活率、周期及凋亡的影响;用药顺序分先用DXT、后用吉非替尼(D→G组)及先用吉非替尼、后用DXT组(G→D组)。结果与G→D组比较,D→G组细胞存活率显著减少,可使细胞阻滞在G2～M期,并增强DXT诱导的细胞凋亡(P均<0.05);G→D组可使细胞阻滞在G0～G1期,并减少DXT诱导的细胞凋亡。结论先用DXT、后用吉非替尼为抑制NSCLC细胞增殖的最佳联用方案。     

Therapy for stage I and stage II non-small cell lung cancer

Despite complete resection of what seems to be all evident tumor, one third to three quarters of patients with stages I and II NSCLC ultimately succumb to this neoplasm. Patients who are cured of an original NSCLC or small cell cancer remain at risk for a new primary lung cancer. Although the importance of lifelong surveillance is clear, the extent and timing of optimal follow-up remain undefined. Although clinicians refer to the development after treatment of clinically discernible sites of tumor as "recurrence," it is probably more accurate to consider these foci as "persistence"--that is, the locoregional site was not sterilized by surgery, and the distant implants were present from the outset but undetected. Although data are sparse, induction and improved adjuvant therapy for early NSCLC may be helpful. Much further experience is needed. Further study and application of biologic indicators in addition to TNM staging likely will help identify patients at high risk for surgical failure who may benefit by combination treatment.     

NS398 induces apoptosis in non-small cell lung cancer cells

Purpose  

Non-steroidal anti-inflammatory drugs (NSAIDs) can induce the apoptosis of many tumor cells and inhibit their growth. NS398 is an NSAID that inhibits COX-2 expression and induces tumor apoptosis via other pathways. The current study aims to observe the effects of NS398 on A549 cell apoptosis and investigate the apoptosis mechanism.     

晚期非小细胞肺癌组织中LRP表达与铂类耐药性及预后的相关性研究

［摘要］　目的　探讨晚期非小细胞肺癌(NSCLC)组织中肺耐药蛋白（LRP）的表达与铂类化疗耐药及其预后的关系。方法　采用免疫组织化学SP法对89例晚期NSCLC碏块进行免疫组织化学染色,检测LRP的表达水平,并分析其与患者的性别、年龄、吸烟史、组织分型、分化程度、远处转移、淋巴结转移及含铂化疗方案疗效的关系。结果　在NSCLC患者组织中,LRP的阳性表达率为77.5%,与年龄、吸烟史、组织分型、分化程度和淋巴结转移无关（P均>0.05）,而LRP表达阳性组和阴性组的含铂类方案化疗疗效、有效率、总反应率、无进展生存时间和总生存时间比较差异无统计学意义（P均>0.05）。女性患者肿瘤组织LRP表达阳性率（95.5%）高于男性患者(71.6%)（P=0.043）;在远处转移的患者中,LPR阳性表达率为87.3%,而无远处转移的患者LRP阳性表达率为61.8%,差异有统计学意义（P=0.005）。结论　LRP基因的阳性表达与远处转移有关,且LRP阳性表达患者无疾病进展时间及总生存时间均低于LRP阴性表达患者,提示其可能作为判断预后指标。     

A novel paradigm in the treatment of oligometastatic non-small cell lung cancer

Background

Stage IV non-small cell lung cancer (NSCLC) is thought to uniformly carry a poor prognosis with a median survival of less than 1 year and 5-year survival of less than 5%. In patients with a low volume (i.e. single site) of distant disease, the prognosis is slightly more favorable than that of more advanced (i.e. multiple sites of metastases) disease. For those with limited metastases, we developed a paradigm of adding concurrent chemotherapy and radiotherapy to the primary tumor once the tumor demonstrated chemotherapy sensitivity.

Methods

Charts of patients from 1999-2006 with non-small cell lung cancer were reviewed to find those with a single extra-thoracic site of disease treated with combined modality therapy. We found nine patients of 640 who met these criteria. Initial treatment consisted of induction chemotherapy, except for brain metastases which were managed first (n=1). If patients experienced a response to chemotherapy without new metastases, the extra-thoracic site was treated for total control with curative dose chemoradiotherapy to the primary site. Survival, time to progression, and sites of progression were assessed.

Results

Median survival was 28 months (95% CI 18-50 mo) with median time to progression of 15 months (95% CI 8-24 mo). All except one patient progressed in the CNS, either with brain metastases (n=7) or leptomeningeal disease (n=1).

Conclusions

Such an approach offers the potential for enhanced quality and quantity of survival by incorporating aggressive RT for select patients without disease progression after induction chemotherapy. Patients tended to fail in the CNS, suggesting the importance of continued surveillance of the neuraxis or possibly prophylactic cranial irradiation. Future plans will correlate outcomes with molecular markers.     

CIK细胞联合化疗对晚期非小细胞肺癌疗效观察

目的研究CIK细胞联合化疗对晚期非小细胞肺癌(NSCLC)患者生活质量、免疫功能影响以及其疗效和不良反应。方法 70例NSCLC患者随机分为对照组(长春瑞滨+顺铂:NP,35例)和联合组(CIK+NP,35例)。对两组疾病总有效率、总控制率、生活质量、免疫功能和不良反应进行对比。结果联合组总有效率28.6%与对照组22.9%无统计学差异,但总控制率77.1%明显高于对照组51.4%;联合组患者生活质量优于对照组;联合组患者治疗后外周血CD3+、CD4+、CD4+/CD8+百分率明显高于治疗前以及同期对照组水平;联合组不良反应小于对照组。结论 CIK细胞联合NP化疗方案副作用小,能提高患者机体免疫功能,能有效改善NSCLC患者生活质量。