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Xie F.-J.,Zhejiang Cancer Hospital | Lu H.-Y.,Zhejiang Cancer Hospital | Lu H.-Y.,Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology Lung and Esophagus | Zheng Q.-Q.,Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology Lung and Esophagus | And 7 more authors.
OncoTargets and Therapy | Year: 2016

FGFR1 amplification is recognized as a novel therapy target for non-small-cell lung cancer (NSCLC), especially in squamous cell carcinoma (SCC). However, the association between FGFR1 amplification and the clinicopathological characteristics of NSCLC remains controversial. We performed a meta-analysis of 17 eligible studies to examine the correlation between FGFR1 gene amplification and clinicopathological characteristics. FGFR1 amplification was closely related to these clinicopathological features, including sex (odds ratio [OR] 2.05, 95% confidence interval [CI] 1.50-2.80), smoking (OR 3.31, 95% CI 2.02-5.44), and histology (OR 3.60, 95% CI 2.82-4.59). FGFR1 amplification was associated with shorter overall survival, and no significant heterogeneity existed between studies (I2=3.8%). We should note that publication bias may partly account for these results, but our findings remained significant after the trim-and-fill method (hazard ratio 1.22, 95% CI 1.06-1.40). However, no significant correlation was found with poor disease-free survival (hazard ratio 1.43, 95% CI 0.96-2.12). In conclusion, this study showed that FGFR1 amplification was significantly associated with sex, smoking, and histology. FGFR1 amplification could be a marker of poor prognosis in NSCLC patients, especially in SCC patients. © 2016 Xie et al.


PubMed | Zhejiang Cancer Hospital, Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology Lung and Esophagus and Zhejiang University of Technology
Type: | Journal: OncoTargets and therapy | Year: 2016

FGFR1 amplification is recognized as a novel therapy target for non-small-cell lung cancer (NSCLC), especially in squamous cell carcinoma (SCC). However, the association between FGFR1 amplification and the clinicopathological characteristics of NSCLC remains controversial. We performed a meta-analysis of 17 eligible studies to examine the correlation between FGFR1 gene amplification and clinicopathological characteristics. FGFR1 amplification was closely related to these clinicopathological features, including sex (odds ratio [OR] 2.05, 95% confidence interval [CI] 1.50-2.80), smoking (OR 3.31, 95% CI 2.02-5.44), and histology (OR 3.60, 95% CI 2.82-4.59). FGFR1 amplification was associated with shorter overall survival, and no significant heterogeneity existed between studies (I (2)=3.8%). We should note that publication bias may partly account for these results, but our findings remained significant after the trim-and-fill method (hazard ratio 1.22, 95% CI 1.06-1.40). However, no significant correlation was found with poor disease-free survival (hazard ratio 1.43, 95% CI 0.96-2.12). In conclusion, this study showed that FGFR1 amplification was significantly associated with sex, smoking, and histology. FGFR1 amplification could be a marker of poor prognosis in NSCLC patients, especially in SCC patients.


Fang L.,Zhejiang Chinese Medical University | Fang L.,Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology Lung and Esophagus | Song Y.,Zhejiang Chinese Medical University | Weng X.,Zhejiang Chinese Medical University | And 5 more authors.
Biomedical Chromatography | Year: 2015

The quantification of intracranial gefitinib (GEF) exposure is limited owing to the sensitivity of analytical equipment. Although mass spectrometry (MS) is the preferred method because of its high sensitivity, the equipment is not available in many laboratories, especially in developing Asian countries. In this paper, we developed a highly sensitive high performance liquid chromatography-diode array detector (HPLC-DAD) method for the assay of GEF in human cerebrospinal fluid (CSF) and plasma. GEF was extracted from CSF and plasma by solid-phase extraction and liquid-liquid extraction, respectively. The chromatographic separation was performed on a C18 column with gradient elution of 0.1% triethylamine solution and acetonitrile, then finally detected at 344 nm. This method was validated and proved to be highly sensitive with a lower limit of quantitation value of 0.11 ng/mL in CSF and 11 ng/mL in plasma. The blood-brain barrier penetration ratio of GEF ranged from 1.48 to 2.41%. This method provides a reliable MS-independent solution for the quantitation of GEF in patients' CSF and plasma. © 2015 John Wiley & Sons, Ltd.


PubMed | Hangzhou First Peoples Hospital, Nanjing Medical University, Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology Lung and Esophagus, Zhejiang Cancer Hospital and Zhejiang Chinese Medical University
Type: Journal Article | Journal: Cancer chemotherapy and pharmacology | Year: 2015

Whole-brain radiation therapy (WBRT) is generally considered as an efficient strategy to improve blood-brain barrier (BBB) permeability by damaging BBB structure and is therefore, used as a promising pretreatment of chemotherapy. However, the impact of radiotherapy on leaky BBB is still controversial for the reason that BBB of metastatic brain tumor lesion had been breached by tumor metastasizing. Herein, we conducted a self-controlled study to evaluate the effect of WBRT on the permeability of BBB in non-small cell lung cancer (NSCLC) patients with brain metastases (BM).A prospective self-controlled research was performed. Radiation-naive NSCLC patients with BM were enrolled and treated with gefitinib for 2 weeks, and then concurrently combined with WBRT for 2 weeks. Plasma and cerebrospinal fluid (CSF) before and after WBRT were collected on day 15 and 29 after the initiation of gefitinib treatment. The concentrations of gefitinib in these samples were measured by HPLC.Three patients were enrolled and evaluated. The concentrations of gefitinib in plasma and CSF pre-WBRT were comparable to those of post-WBRT. Consequently, no significant change was noted in the CSF-to-plasma ratios of gefitinib before and after WBRT (2.79 1.47 vs. 2.35 1.74 %, p = 0.123).The WBRT may not affect the BBB permeability by determining the concentration of gefitinib in NSCLC patients with BM.


PubMed | Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology Lung and Esophagus and Zhejiang Chinese Medical University
Type: Journal Article | Journal: Biomedical chromatography : BMC | Year: 2015

The quantification of intracranial gefitinib (GEF) exposure is limited owing to the sensitivity of analytical equipment. Although mass spectrometry (MS) is the preferred method because of its high sensitivity, the equipment is not available in many laboratories, especially in developing Asian countries. In this paper, we developed a highly sensitive high performance liquid chromatography-diode array detector (HPLC-DAD) method for the assay of GEF in human cerebrospinal fluid (CSF) and plasma. GEF was extracted from CSF and plasma by solid-phase extraction and liquid-liquid extraction, respectively. The chromatographic separation was performed on a C18 column with gradient elution of 0.1% triethylamine solution and acetonitrile, then finally detected at 344 nm. This method was validated and proved to be highly sensitive with a lower limit of quantitation value of 0.11 ng/mL in CSF and 11 ng/mL in plasma. The blood-brain barrier penetration ratio of GEF ranged from 1.48 to 2.41%. This method provides a reliable MS-independent solution for the quantitation of GEF in patients CSF and plasma.


Xu W.,Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology Lung and Esophagus | Xu W.,Zhejiang Cancer Hospital | Ying Y.,Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology Lung and Esophagus | Shan L.,Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology Lung and Esophagus | And 14 more authors.
Journal of Translational Medicine | Year: 2015

Background: NIPBL, the sister chromatid cohesion 2 (SCC2) human homolog, is a cohesin loading factor which is essential for deposition of cohesin onto the sister chromatid. Recent studies have shown that NIPBL contribute to sister chromatid cohesion and plays a critical role in development, DNA repair, and gene regulation. In this study, we measured the expression of NIPBL in clinical non-small cell lung cancer specimens, and determined its effects on cellular processes and chemosensitivity in vitro. Methods: NIPBL immunohistochemistry was performed on 123 lung adenocarcinoma samples. Through knockdown of NIPBL protein expression, non-small cell lung cancer cell lines were used to test the potential involvement of NIPBL silencing on cell proliferation, migration, invasion, and apoptosis. Chemosensitivity was assessed with clonogenic assays, and chromatin immunoprecipitation assays were performed to analyze the relationship between NIPBL and signal transducers and activators of transcription 3 (STAT3). Results: Immunohistochemical analysis showed that high expression of NIPBL was strongly correlated with poor prognosis, tumor differentiation, and lymph node metastasis. Survival analysis further indicated that NIPBL expression was a potential prognostic factor for non-small cell lung cancer. Knockdown of NIPBL in non-small cell lung cancer cell lines significantly reduced cellular proliferation, migration, and invasion, and enhanced cellular apoptosis and sensitivity to cisplatin, paclitaxel, and gemcitabine hydrochloride. NIPBL bound to the promoter region of the STAT3 gene, directly regulating the expression of STAT3. Conclusions: These data suggested that NIPBL played a significant role in lung carcinogenesis. NIPBL expression conferred poor prognosis and resistance to chemotherapy in non-small cell lung cancer, suggesting that NIPBL may be a novel therapeutic target. © Xu et al.; licensee BioMed Central.

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