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Zhao H.,Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology Lung and Esophagus | Chen W.,Chinese Institute of Basic Medical Sciences | Du P.,Chinese Institute of Basic Medical Sciences | Sun A.,Chinese Institute of Basic Medical Sciences | And 3 more authors.
Tumor Biology | Year: 2015

Apoptosis is an important mechanism of malignant tumor formation and progression. Single nucleotide polymorphisms (SNPs) located within cell death genes may influence cancer risk. We explored the relationship between FasL −844T/C and/or Fas −1377G/A SNPs and pulmonary adenocarcinoma (AD). Two hundred seventy-five patients with pulmonary AD of South China admitted into Zhejiang Cancer Hospital from July 2007 to October 2011 were randomly selected, and their clinicopathological data were collected at the same time. Two hundred ninety-seven cases of healthy individuals were selected as control. FasL −844T/C and Fas −1377G/A SNPs were detected by PCR-RFLP technique to evaluate the relationships between these two SNPs and pulmonary AD. Age, FasL −844 and Fas −1377 SNPs were associated with increased risk of pulmonary AD susceptibility in main effect analysis. FasL −844CC and Fas −1377 AA were associated with an increased risk for the development of pulmonary AD only in age <60 years people, but not in those ≥60 years. FasL −844CC genotype was associated with an increased risk for pulmonary AD (adjusted OR = 2.010, 95 % CI 1.196–3.379, P = 0.008) compared with TT genotype. However, Fas −1377 AA was a risk factor only when FasL −844 genotype was CC. Fas −1377 genotypes showed significant effect modification of pulmonary AD risk by FasL −844 genotype with test of the interaction term adjusting for age, gender, and FasL −844 SNP. Fas −1377G/A was not associated with the clinicopathological factors, while FasL −844C/T was associated with tumor stage and lymph node metastasis in age ≥60 years people and tumor stage in those <60 years. In conclusion, FasL −844 SNP is associated with the susceptibility of pulmonary AD in age <60 years people. Fas −1377 SNP may modify the association of FasL −844 SNP with the risk of pulmonary AD. FasL −844 genotype plays an important role in the occurrence and progression of pulmonary AD. © 2015, The Author(s). Source


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. Source


Zhao H.,Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology Lung and Esophagus | Zhao H.,Wenzhou University | Mao W.,Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology Lung and Esophagus | Mao W.,Wenzhou University | And 6 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2016

Fas-FasL system plays an important role in cancer initiation, development and progression. FasL -844T/C mutation has been shown to be significant in the genetic susceptibility to cancer. We explored the relationship between FasL gene -844T/C SNP and pulmonary squamous cell carcinoma (SCC). 330 patients with pulmonary SCC in south China were recruited from July 2007 to Oct 2011 in Zhejiang Cancer Hospital and their clinicopathological data were collected. 297 cases of cancer-free individuals were selected as control group. PCR-RFLP technique was carried out to detect FasL -844T/C single nucleotide polymorphism (SNP). Fas -1377G/A SNP was also detected to investigate whether it interfered with the functional effect of the FasL -844T/C in pulmonary SCC development. χ2 test and logistic regression were used to analysis the association between FasL -844T/C, Fas -1377G/A polymorphism or other clinicopathological parameters and pulmonary SCC. Gender, smoking and FasL -844 genotypes could increase risk of pulmonary SCC susceptibility mainly in age <60 group. However, only smoking was associated with pulmonary SCC in age <60 group. Compared with TT genotype, FasL -844CC was risk factor for development of pulmonary SCC (adjusted OR=1.518, 95% CI=1.100-2.094, P=0.011). After grouping patients with smoking pack-years, it was a risk factor for pulmonary SCC in ≥20 pack-years group. There was no effect modification between FasL -844 SNP and smoking or gender by test of the interaction term (P<0.05). FasL -844C/T was significant associated with stage, lymph node metastasis and vascular tumor thrombus in age ≥60. Our results show that FasL -844T/C SNP is associated with the occurrence of pulmonary SCC in heavy smoking and younger people, and the development and metastasis in elder people. © 2016, E-Century Publishing Corporation. All rights reserved. Source


Wang Z.,Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology Lung and Esophagus | Cai X.-J.,Integrated Chinese and Western Medicine Hospital of Zhejiang Province | Qin J.,Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology Lung and Esophagus | Xie F.-J.,Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology Lung and Esophagus | And 2 more authors.
Oncotarget | Year: 2016

Blood-tumor barrier (BTB) reduce the permeability for drugs into tumor tissues. We found that histamine might serve as an essential regulator of BTB function. Further, we aim to determine the role of H2 receptor expression in BTB permeability, and elucidate the underlying mechanisms thereof. Transmission electron microscopy showed that histamine disrupted the integrity of tight junctions (TJ) and increased the number of pinosomes in the cytoplasm. Horseradish peroxidase (HRP) and trans-endothelial resistance detection (TEER) assays revealed that histamine could open BTB and this action was inhibited by cimetidine. Western blot and immunofluorescence assays showed that histamine decreased the expression of tight junction proteins zonula occluden-1(ZO-1), occludin, and claudin-5. Further, quantitative RT-PCR assay showed that the expression of H2 receptor could represent and predicted histamine-induced BTB permeability. In conclusion, histamine opened BTB by down-regulating the TJ-associated proteins. The levels of H2 receptor expression was correlated with the histamine-induced BTB permeability. Source


Lu H.-Y.,Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology Lung and Esophagus | Wang X.-J.,Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology Lung and Esophagus | Mao W.-M.,Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology Lung and Esophagus
Oncology Letters | Year: 2012

Lung cancer is the leading cause of cancer-related mortality. Small cell lung cancer (SCLC) accounted for 12.95% of all lung cancer histological types in 2002. Despite trends toward modest improvement in survival, the outcome remains extremely poor. Chemotherapy is the cornerstone of treatment in SCLC. More than two-thirds of patients who succumb to lung cancer in the United States are over 65 years old. Elderly patients tolerate chemotherapy poorly and need novel therapeutic agents. Targeted drugs have less toxicity than chemotherapy drugs, but no targeted agents have been approved for use in the treatment of SCLC patients to date. Certain new targeted agents, including gefitinib, bevacizumab and Bcl-2 inhibitors, offer a promise of improved outcomes, however negative results are more commonly reported than positive. This review focuses on targeted therapies in SCLC. Source

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