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531.
Nuo Xu Xin Zhang Xun Wang Hai-yan Ge Xiao-ying Wang David Garfield Ping Yang Yuan-lin Song Chun-xue Bai 《Acta pharmacologica Sinica》2012,33(5):675-681
Aim:
Gefitinib is effective in only approximately 20% of patients with non-small-cell lung cancer (NSCLC), and the underlying mechanism remains unclear. FoxM1 is upregulated in NSCLC and associated with a poor prognosis in NSCLC patients. In this study, we examined the possible role of FoxM1 in gefitinib resistance and the related mechanisms.Methods:
Gefitinib resistant human lung adenocarcinoma cell line SPC-A-1 and gefitinib-sensitive human lung mucoepidermoid carcinoma cell line NCI-H292 were used. mRNA and protein expression of FoxM1 and other factors were tested with quantitative RT PCR and Western blot analysis. RNA interference was performed to suppress FoxM1 expression in SPC-A-1 cells, and lentiviral infection was used to overexpress FoxM1 in H292 cells. MTT assay and flow cytometry were used to examine the proliferation and apoptosis of the cells.Results:
Treatment of SPC-A-1 cells with gefitinib (1 and 10 μmol/L) upregulated the expression of FoxM1 in time- and concentration-dependent manners, while gefitinib (1 μmol/L) downregulated in H292 cells. In SPC-A-1 cells treated with gefitinib (1 μmol/L), the expression of several downstream targets of FoxM1, including survivin, cyclin B1, SKP2, PLK1, Aurora B kinase and CDC25B, were significantly upregulated. Overexpression of FoxM1 increased the resistance in H292 cells, while attenuated FoxM1 expression restored the sensitivity to gefitinib in SPC-A-1 cells by inhibiting proliferation and inducing apoptosis.Conclusion:
The results suggest that FoxM1 plays an important role in the resistance of NSCLC cells to gefitinib in vitro. FoxM1 could be used as a therapeutic target to overcome the resistance to gefitinib. 相似文献532.
533.
目的观察吉非替尼治疗晚期肺腺癌的近期疗效及毒副反应。方法 25例经放疗和化疗方案为"TP"或"GP"治疗无效或失败的肺腺癌患者。吉非替尼250 mg次/,口服,1次/d;服用至病情进展或出现不可耐受的毒副反应。结果本组25例患者均可评价疗效,完全缓解0例,部分缓解6例,稳定10例,进展9例,有效率24%,疾病控制率64%,中位生存期5.2个月(1~18个月),1年生存率52%;主要毒副反应是皮疹、皮肤瘙痒、皮肤干燥、腹泻和恶心,多为Ⅰ~Ⅱ度。结论吉非替尼治疗晚期肺腺癌有一定疗效,安全易耐受,无明显毒副反应。 相似文献
534.
Yongmei Yin Yiting Geng Xiaodong Li Xiaoli Hu Xiaofeng Chen Wei Li Yongqian Shu 《南京医科大学学报(自然科学版)》2009,29(6):392-397
Objective
To assess the efficacy and toxicity of gefitinib as a single agent treatment in Chinese patients with advanced non-small cell lung cancer (NSCLC).Methods
Forty-five patients with advanced NSCLC were treated with gefitinib at 250 mg daily until the disease progressed or the patient could not tolerate the toxicity.Results
None of the patients achieved a complete response (CR), while 15 patients achieved a partial remission (PR) and 17 experienced a stable disease (SD). Thirteen patients continued to have a progressive disease (PD). The response rate and the disease control rate were 33.3% and 71.1%, respectively. The symptom remission rate was 72.5%, and the median remission time was 8 days. The median survival time was 15.3 months. The median progression-free survival time was 6.0 months. The most common toxicities included rash (53.3%) and diarrhea (33.3%). Dehydration and pruritus of the skin developed in 26.7% and 22.2% of the patients, respectively. Hepatic toxicity occurred in 6.7% of patients and oral ulceration occurred in 4.4% of patients.Conclusion
Single agent treatment with gefitinib is effective against advanced NSCLC, and is well tolerated in Chinese patients. 相似文献535.
Satouchi M Negoro S Funada Y Urata Y Shimada T Yoshimura S Kotani Y Sakuma T Watanabe H Adachi S Takada Y Yatabe Y Mitsudomi T 《British journal of cancer》2007,96(8):1191-1196
This study aimed to identify predictive factors associated with prognostic benefits of gefitinib. A total of 221 Japanese patients who received gefitinib (250 mg day(-1)) were examined retrospectively and potential predictive factors analysed. Overall response rate (ORR) was 24.4% and median survival time (MST) was 8.0 months. In a log-rank test, survival was significantly better in females, patients with adenocarcinoma, never-smokers, favourable performance status (PS) and patients with epidermal growth factor receptor (EGFR) mutation. The lower the smoking exposure (Brinkman Index (BI)=cigarettes per day x years smoked), the better the MST (BI 0: 14.5 months, BI <500: 9.5 months, BI 500 to <1000: 6.9 months, BI > or =1000: 4.0 months). Positive-EGFR mutation status and PS 0-1 were independent predictors of favourable prognosis by multivariate analysis. Prognosis was significantly different according to EGFR mutation status (with the same smoking status), but not according to smoking status (with the same EGFR mutation status). EGFR mutation status is the most important independent predictor of survival benefit with gefitinib treatment. Although differences in prognosis were observed according to relative smoking status and smoking exposure, the results suggested that smoking is not a direct predictor of prognosis, yet is a surrogate marker of EGFR mutation status. 相似文献
536.
Posadas EM Liel MS Kwitkowski V Minasian L Godwin AK Hussain MM Espina V Wood BJ Steinberg SM Kohn EC 《Cancer》2007,109(7):1323-1330
BACKGROUND: The primary objective of this study was to evaluate the biochemical effects of gefitinib on its target signal-transduction pathways in patients with recurrent epithelial ovarian cancer (EOC). The secondary objectives included assessing clinical activity and toxicity and determining the association between biochemical and clinical outcomes. METHODS: Twenty-four heavily pretreated patients with EOC who had good end-organ function and performance status and who had measurable disease received gefitinib 500 mg daily. Prospectively planned core-needle tumor biopsies were obtained before treatment and after 4 weeks. Protein expression of total and phosphorylated (p) epidermal growth factor receptor (EGFR), protein kinase B (AKT), and extracellular regulated kinase (ERK) was quantified in microdissected tumor cells using tissue lysate array proteomics. RESULTS: All tumor samples had detectable levels of EGFR and p-EGFR. A decrease in the quantity of both EGFR and p-EGFR was observed with gefitinib therapy in >50% of patients. This was not associated with clinical benefit, nor were responses observed. However, trends for increased gastrointestinal and skin toxicity were observed with greater phosphorylation or quantities of EGFR, ERK, and AKT in tumor samples (P = .05). Gefitinib had limited clinical activity as monotherapy despite documented target inhibition. CONCLUSIONS: The results from this study demonstrated that gefitinib inhibited the phosphorylation of EGFR in EOC tumor cells, providing proof of target in a clinical setting. Combinatorial therapy with molecular therapeutics against complementary targets may prove successful. 相似文献
537.
《药学学报(英文版)》2022,12(1):92-106
Nanoparticulate drug delivery systems (Nano-DDSs) have emerged as possible solution to the obstacles of anticancer drug delivery. However, the clinical outcomes and translation are restricted by several drawbacks, such as low drug loading, premature drug leakage and carrier-related toxicity. Recently, pure drug nano-assemblies (PDNAs), fabricated by the self-assembly or co-assembly of pure drug molecules, have attracted considerable attention. Their facile and reproducible preparation technique helps to remove the bottleneck of nanomedicines including quality control, scale-up production and clinical translation. Acting as both carriers and cargos, the carrier-free PDNAs have an ultra-high or even 100% drug loading. In addition, combination therapies based on PDNAs could possibly address the most intractable problems in cancer treatment, such as tumor metastasis and drug resistance. In the present review, the latest development of PDNAs for cancer treatment is overviewed. First, PDNAs are classified according to the composition of drug molecules, and the assembly mechanisms are discussed. Furthermore, the co-delivery of PDNAs for combination therapies is summarized, with special focus on the improvement of therapeutic outcomes. Finally, future prospects and challenges of PDNAs for efficient cancer therapy are spotlighted. 相似文献
538.