25 results on '"QINXIAN ZHANG"'
Search Results
2. Research of the mechanism on miRNA193 in exosomes promotes cisplatin resistance in esophageal cancer cells.
- Author
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Shifeng Shi, Xin Huang, Xiao Ma, Xiaoyan Zhu, and Qinxian Zhang
- Subjects
Medicine ,Science - Abstract
PURPOSE:Chemotherapy resistance of esophageal cancer is a key factor affecting the postoperative treatment of esophageal cancer. Among the media that transmit signals between cells, the exosomes secreted by tumor cells mediate information transmission between tumor cells, which can make sensitive cells obtain resistance. Although some cellular exosomes play an important role in tumor's acquired drug resistance, the related action mechanism is still not explored specifically. METHODS:To elucidate this process, we constructed a cisplatin-resistant esophageal cancer cell line, and proved that exosomes conferring cellular resistance in esophageal cancer can promote cisplatin resistance in sensitive cells. Through high-throughput sequencing analysis of the exosome and of cells after stimulation by exosomes, we determined that the miRNA193 in exosomes conferring cellular resistance played a key role in sensitive cells acquiring resistance to cisplatin. In vitro experiments showed that miRNA193 can regulate the cell cycle of esophageal cancer cells and inhibit apoptosis, so that sensitive cells can acquire resistance to cisplatin. An in vivo experiment proved that miRNA193 can promote tumor proliferation through the exosomes, and provide sensitive cells with slight resistance to cisplatin. RESULTS:Small RNA sequencing of exosomes showed that exosomes in drug-resistant cells have 189 up-regulated and 304 down-regulated miRNAs; transcriptome results showed that drug-sensitive cells treated with drug-resistant cellular exosomes have 3446 high-expression and 1709 low-expression genes; correlation analysis showed that drug-resistant cellular exosomes mainly affect the drug resistance of sensitive cells through paths such as cytokine-cytokine receptor interaction, and the VEGF and Jak-STAT signaling pathways; miRNA193, one of the high-expression miRNAs in drug-resistant cellular exosomes, can promote drug resistance by removing cisplatin's inhibition of the cell cycle of sensitive cells. CONCLUSION:Sensitive cells can become resistant to cisplatin through acquired drug-resistant cellular exosomes, and miRNA193 can make tumor cells acquire cisplatin resistance by regulating the cell cycle.
- Published
- 2020
- Full Text
- View/download PDF
3. Linc00210 drives Wnt/β-catenin signaling activation and liver tumor progression through CTNNBIP1-dependent manner
- Author
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Xiaomin Fu, Xiaoyan Zhu, Fujun Qin, Yong Zhang, Jizhen Lin, Yuechao Ding, Zihe Yang, Yiman Shang, Li Wang, Qinxian Zhang, and Quanli Gao
- Subjects
Linc00210 ,CTNNBIP1 ,Wnt/β-catenin ,Liver TICs ,Copy number alterations ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Liver tumor initiating cells (TICs) have self-renewal and differentiation properties, accounting for tumor initiation, metastasis and drug resistance. Long noncoding RNAs are involved in many physiological and pathological processes, including tumorigenesis. DNA copy number alterations (CNA) participate in tumor formation and progression, while the CNA of lncRNAs and their roles are largely unknown. Methods LncRNA CNA was determined by microarray analyses, realtime PCR and DNA FISH. Liver TICs were enriched by surface marker CD133 and oncosphere formation. TIC self-renewal was analyzed by oncosphere formation, tumor initiation and propagation. CRISPRi and ASO were used for lncRNA loss of function. RNA pulldown, western blot and double FISH were used to identify the interaction between lncRNA and CTNNBIP1. Results Using transcriptome microarray analysis, we identified a frequently amplified long noncoding RNA in liver cancer termed linc00210, which was highly expressed in liver cancer and liver TICs. Linc00210 copy number gain is associated with its high expression in liver cancer and liver TICs. Linc00210 promoted self-renewal and tumor initiating capacity of liver TICs through Wnt/β-catenin signaling. Linc00210 interacted with CTNNBIP1 and blocked its inhibitory role in Wnt/β-catenin activation. Linc00210 silencing cells showed enhanced interaction of β-catenin and CTNNBIP1, and impaired interaction of β-catenin and TCF/LEF components. We also confirmed linc00210 copy number gain using primary hepatocellular carcinoma (HCC) samples, and found the correlation between linc00210 CNA and Wnt/β-catenin activation. Of interest, linc00210, CTNNBIP1 and Wnt/β-catenin signaling targeting can efficiently inhibit tumor growth and progression, and liver TIC propagation. Conclusion With copy-number gain in liver TICs, linc00210 is highly expressed along with liver tumorigenesis. Linc00210 drives the self-renewal and propagation of liver TICs through activating Wnt/β-catenin signaling. Linc00210 interacts with CTNNBIP1 and blocks the combination between CTNNBIP1 and β-catenin, driving the activation of Wnt/β-catenin signaling. Linc00210-CTNNBIP1-Wnt/β-catenin axis can be targeted for liver TIC elimination.
- Published
- 2018
- Full Text
- View/download PDF
4. Generation of induced pluripotent stem cell line (ZZUi0012-A) from a patient with Fahr's disease caused by a novel mutation in SLC20A2 gene
- Author
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Qinxian Zhang, Zhuo Li, Huifang Sun, Shoutao Zhang, Jin Zhang, Yanlin Wang, Hui Fang, and Yuming Xu
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Several SLC20A2 mutations have been implicated as potential causes of Fahr's disease, a subtype of primary familial brain calcification (PFBC), but very few patient-derived induced pluripotent stem cell (iPSC) models have been established. We have identified a novel SLC20A2 mutation in a family with Fahr's disease. We subsequently obtained dermal fibroblasts from a patient in this family. These fibroblasts were successfully transformed into iPSCs by employing episomal plasmids expressing OCT3/4, SOX2, KLF4, LIN28, and L-MYC. Our approach offers a resource and a platform for further research into the mechanism of Fahr's disease and could facilitate development and screening of pharmaceutical and gene therapies.
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- 2019
- Full Text
- View/download PDF
5. Lymphotoxin-α Plays Only a Minor Role in Host Resistance to Respiratory Infection with Virulent Type A Francisella tularensis in Mice
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Deng Zhang, Rhonda KuoLee, Greg Harris, Qinxian Zhang, J. Wayne Conlan, and Wangxue Chen
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Pathology ,RB1-214 - Abstract
This study examined the role of lymphotoxin (LT)-α in host defense against airborne infection with Francisella tularensis, a gram-negative facultative intracellular bacterium and the causative agent of tularemia. Following a low-dose aerosol infection with the highly virulent type A strain of F. tularensis, mice deficient in LT α (LTα−/−) consistently harbored approximately 10-fold fewer bacteria in their spleens at day 2 and 10-fold more bacteria in their lungs at day 4 than LTα+/+ mice. However, the mortality and median time to death were indistinguishable between the two mouse strains. In addition, the inflammatory responses to the infection, as reflected by the cytokine levels and leukocyte influx in the bronchoalveolar lavage fluid and histopathological analysis, were generally similar between LTα−/− and LTα+/+ mice. These data suggest that although LTα does not contribute significantly to the resistance and host responses of mice to airborne type A F. tularensis infection, it does play a subtle role in the multiplication/dissemination of F. tularensis.
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- 2008
- Full Text
- View/download PDF
6. Knocking Out SST Gene of BGC823 Gastric Cancer Cell by CRISPR/Cas9 Enhances Migration, Invasion and Expression of SEMA5A and KLF2
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Ruixian Ding, Wei Chen, Yaru Zhang, Qinxian Zhang, Chonghua Chen, Haodong Li, Xiaoyan Zhu, and Jinlu Tang
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0301 basic medicine ,endocrine system ,fungi ,Cell ,Transfection ,Biology ,Cell biology ,Blot ,03 medical and health sciences ,fluids and secretions ,030104 developmental biology ,0302 clinical medicine ,Plasmid ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,parasitic diseases ,KLF2 ,medicine ,CRISPR ,Gene ,hormones, hormone substitutes, and hormone antagonists ,Subgenomic mRNA - Abstract
Background The impact and potential molecular mechanisms of SST in the occurrence and development of GC have not been determined. Materials and Methods Two pairs of sgRNA and reporter were designed according to targeting sequence of SST gene for double-nicking. Plasmids were transfected into 293T for selecting sgRNA with higher cutting efficiency. The subline which has knocked-out SST gene were selected by FACS and verified by sequencing and expression level. Moreover, the migration and invasion ability was evaluated by wound healing and transwell after knocking out SST. Besides, the protein expression of SEMA5A and KLF2 were observed by Western blotting and LSCM. Last, we detected the expression levels of SST, SEMA5A, and KLF2 in GC tissues by Western blotting. Results The results revealed that the new subline 1E9, which had knocked out SST gene, was established by CRISPR/Cas9. In addition, the knockout of SST in GC cells markedly increased migration and invasion ability. The results also demonstrated that the knockout of SST increased the expression of SEMA5A and KLF2. The expression level of SST was decreased in GC tissues, and its decrease was associated with overexpression of SEMA5A and KLF2. Conclusion SST plays an inhibitory role in the migration and invasion of GC cell BGC823. The protein expression levels of SEMA5A and KLF2 were enhanced in GC cells and tissues lacking SST expression.
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- 2020
7. Correction: A Virus-infected, Reprogrammed Somatic Cell-derived Tumor Cell (VIReST) Vaccination Regime can Prevent Initiation and Progression of Pancreatic Cancer
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Jianzeng Dong, Zhe Zhang, Duanqing Pei, Pentao Liu, Margueritte El Khouri, Yongchao Chu, Yunshu Dong, Wenli Yan, Shengdian Wang, Jun Wang, Jiekai Chen, Dongling Gao, Yaohe Wang, Ai Nagano, Zhongxian Zhang, Xiaozhu Li, Zhizhong Wang, Qinxian Zhang, Nicholas R. Lemoine, Jing Liu, Louisa S. Chard, Shuangshuang Lu, Pan Du, Claude Chelala, and Lirong Zhang
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0301 basic medicine ,Oncolytic adenovirus ,Cancer Research ,business.industry ,Cancer ,medicine.disease ,Oncolytic virus ,Vaccination ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Pancreatic tumor ,030220 oncology & carcinogenesis ,Pancreatic cancer ,Cancer research ,Medicine ,Stem cell ,business ,Induced pluripotent stem cell - Abstract
Purpose: Pancreatic cancer remains one of the most lethal cancers, and late detection renders most tumors refractory to conventional therapies. Development of cancer prophylaxis may be the most realistic option for improving mortality associated with this disease. Here, we develop a novel individualized prophylactic and therapeutic vaccination regimen using induced pluripotent stem cells (iPSC), gene editing, and tumor-targeted replicating oncolytic viruses. Experimental Design: We created a Virus-Infected, Reprogrammed Somatic cell-derived Tumor cell (VIReST) regime. iPSCs from healthy cells were induced to pancreatic tumor cells using in situ gene editing via stable provision of KRasG12D and p53R172H tumor driver mutations. These cells were preinfected with oncolytic Adenovirus (AdV) as prime or Vaccinia virus (VV) as boost, to improve vaccine immunogenicity, prior to delivery of vaccines in a sequential regime to young KPC transgenic mice, genetically programmed to develop pancreatic cancer, to prevent and delay disease development. Results: Tumor cells preinfected with oncolytic AdV as prime or VV as boost were the best regime to induce tumor-specific immunity. iPSC-derived tumor cells were highly related in antigen repertoire to pancreatic cancer cells of KPC transgenic mice, suggesting that an individual9s stem cells can provide an antigenically matched whole tumor cell vaccine. The VIReST vaccination primed tumor-specific T-cell responses, resulting in delayed disease emergence and progression and significantly prolonged survival of KPC transgenic mice. Importantly, this regime was well-tolerated and nontoxic. Conclusions: These results provide both proof of concept and a robust technology platform for the development of personalized prophylactic cancer vaccines to prevent pancreatic malignancies in at-risk individuals.
- Published
- 2021
8. Exosomal miRNA-107 induces myeloid-derived suppressor cell expansion in gastric cancer
- Author
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Yan Tong, ZhenQiang Zhang, Qinxian Zhang, Dai Zhang, Xiaoyan Zhu, Hao Rong, ShiChun Tu, HuiJie Feng, WenBo Li, Wei Wang, Qian Feng, XuRan Zhang, and WeiHong Ren
- Subjects
0301 basic medicine ,Tumor microenvironment ,biology ,Chemistry ,Exosome ,Microvesicles ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Cancer cell ,Myeloid-derived Suppressor Cell ,Cancer research ,biology.protein ,PTEN ,Protein kinase B ,PI3K/AKT/mTOR pathway - Abstract
Background: Myeloid-derived suppressor cells (MDSCs) promote immunosuppression in the tumor microenvironment, support tumor growth and survival, and may contribute to immunotherapy resistance. Recent studies showed that tumor-derived exosomes (TDEs) can induce MDSCs accumulation and expansion, the mechanisms of which are largely unknown. Methods: The morphologies and sizes of the exosomes was observed by using a JEM-1400 transmission electron microscope. MicroRNA(miR)-107 and ARG1, DICER1, PTEN, PI3K, AKT, mTOR, and NF-kB mRNAs were quantified by quantitative reverse tanscription PCR. Dual-Luciferase Reports Assay were used to examine the expression of genes which was targeted by miR-107. The expression of proteins were analyzed by using western blot. Results: MiR-107 was not only overexpressed in gastric cancer cells but also enriched in their secreted TDEs. Also, these miR-107 enriched TDEs could be taken up by HLA-DR-CD33+MDSCs, where miR-107 was able to target and suppress expression of DICER1 and PTEN genes. Dampened DICER1 expression supported expansion of MDSCs , while decreased PTEN led to activation of the PI3K pathway, resulting in increased ARG1 expression. Furthemore, gastric cancer-derived miR-107 TDEs, when dosed intravenously into mice, were also capable of inducing expansion of CD11b+Gr1+/high MDSCs in mouse peripheral blood and altering expression of DICER1, PTEN, ARG1, and NOS2 in the MDSCs. Conclusions: Our findings demonstrate for the first time that gastric cancer-secreted exosomes are able to deliver miR-107 to the host MDSCs where they induce their expansion and activition by targeting DICER1 and PTEN genes, thereby may provide novel cancer therapeutics target for gastric cancer.
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- 2019
9. Research of the mechanism on miRNA193 in exosomes promotes cisplatin resistance in esophageal cancer cells
- Author
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Xiaoyan Zhu, Qinxian Zhang, Shifeng Shi, Xin Huang, and Xiao Ma
- Subjects
0301 basic medicine ,Esophageal Neoplasms ,Molecular biology ,Apoptosis ,Exosomes ,Biochemistry ,Transcriptome ,Mice ,0302 clinical medicine ,Sequencing techniques ,Medicine and Health Sciences ,Cell Cycle and Cell Division ,Multidisciplinary ,Cell Death ,Chemistry ,Cell Cycle ,RNA sequencing ,Animal Models ,Cell cycle ,Gene Expression Regulation, Neoplastic ,Nucleic acids ,Oncology ,Experimental Organism Systems ,Cell Processes ,030220 oncology & carcinogenesis ,Medicine ,Female ,Cellular Structures and Organelles ,medicine.drug ,Research Article ,Esophageal Cancer ,Science ,Mice, Nude ,Antineoplastic Agents ,Mouse Models ,Research and Analysis Methods ,Exosome ,03 medical and health sciences ,Model Organisms ,Cell Line, Tumor ,microRNA ,Gastrointestinal Tumors ,medicine ,Genetics ,Animals ,Humans ,Vesicles ,Non-coding RNA ,Cisplatin ,Natural antisense transcripts ,Biology and Life Sciences ,Cancers and Neoplasms ,Cell Biology ,Microvesicles ,Gene regulation ,MicroRNAs ,030104 developmental biology ,Molecular biology techniques ,Cell culture ,Drug Resistance, Neoplasm ,Cancer research ,Animal Studies ,RNA ,Gene expression - Abstract
PurposeChemotherapy resistance of esophageal cancer is a key factor affecting the postoperative treatment of esophageal cancer. Among the media that transmit signals between cells, the exosomes secreted by tumor cells mediate information transmission between tumor cells, which can make sensitive cells obtain resistance. Although some cellular exosomes play an important role in tumor’s acquired drug resistance, the related action mechanism is still not explored specifically.MethodsTo elucidate this process, we constructed a cisplatin-resistant esophageal cancer cell line, and proved that exosomes conferring cellular resistance in esophageal cancer can promote cisplatin resistance in sensitive cells. Through high-throughput sequencing analysis of the exosome and of cells after stimulation by exosomes, we determined that the miRNA193 in exosomes conferring cellular resistance played a key role in sensitive cells acquiring resistance to cisplatin. In vitro experiments showed that miRNA193 can regulate the cell cycle of esophageal cancer cells and inhibit apoptosis, so that sensitive cells can acquire resistance to cisplatin. An in vivo experiment proved that miRNA193 can promote tumor proliferation through the exosomes, and provide sensitive cells with slight resistance to cisplatin.ResultsSmall RNA sequencing of exosomes showed that exosomes in drug-resistant cells have 189 up-regulated and 304 down-regulated miRNAs; transcriptome results showed that drug-resistant cells treated with drug-resistant cellular exosomes have 3446 high-expression and 1709 low-expression genes; correlation analysis showed that drug-resistant cellular exosomes mainly affect the drug resistance of sensitive cells through paths such as cytokine–cytokine receptor interaction, and the VEGF and Jak-STAT signaling pathways; miRNA193, one of the high-expression miRNAs in drug-resistant cellular exosomes, can promote drug resistance by removing cisplatin’s inhibition of the cell cycle of sensitive cells.ConclusionSensitive cells can become resistant to cisplatin through acquired drug-resistant cellular exosomes, and miRNA193 can make tumor cells acquire cisplatin resistance by regulating the cell cycle.
- Published
- 2020
10. LncAPC drives Wnt/β-catenin activation and liver TIC self-renewal through EZH2 mediated APC transcriptional inhibition
- Author
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Lu Han, Xiaoyan Zhu, Qinxian Zhang, Yuechao Ding, Jizhen Lin, Fujun Qin, Yong Zhang, Zihe Yang, and Xiaomin Fu
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Transcriptional Activation ,0301 basic medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,Cancer Research ,Liver tumor ,Adenomatous Polyposis Coli Protein ,Mice, Nude ,Biology ,Metastasis ,03 medical and health sciences ,Cell Line, Tumor ,mental disorders ,medicine ,Animals ,Humans ,Gene silencing ,Enhancer of Zeste Homolog 2 Protein ,Cell Self Renewal ,Wnt Signaling Pathway ,Molecular Biology ,Mice, Inbred BALB C ,Gene knockdown ,Liver Neoplasms ,EZH2 ,Wnt signaling pathway ,medicine.disease ,nervous system diseases ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Catenin ,Neoplastic Stem Cells ,Cancer research ,RNA, Long Noncoding ,Liver cancer ,human activities - Abstract
Liver tumor initiating cells (TICs), a small subset cells in tumor bulk, are responsible for liver tumor initiation, metastasis, and relapse. However, the regulatory mechanism of liver TICs remains largely unknown. Here we found a long noncoding RNA lncAPC, locating near from APC locus, was highly expressed in liver cancer and liver TICs. LncAPC was required for liver TIC self-renewal. Silencing and overexpressing lncAPC showed impaired and enhanced sphere formation capacity of liver TICs, respectively. By recruiting EZH2 to APC promoter, LncAPC inhibits APC transcription and thus drives the activation of Wnt/β-catenin signaling. Attenuate binding between EZH2 and APC promoter was observed upon lncAPC knockdown. What is more, lncAPC-EZH2-APC axis can be targeted to eliminate liver TICs. Altogether, LncAPC promotes liver TIC self-renewal through EZH2-dependent APC transcriptional inhibition.
- Published
- 2017
11. Expression profile of cytokines in gastric cancer patients using proteomic antibody microarray
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Ruo Feng, Xiaoqiang Quan, Xiao‑Yan Zhu, Yi Ding, and Qinxian Zhang
- Subjects
0301 basic medicine ,Cancer Research ,Antibody microarray ,Oncogene ,gastric cancer ,Articles ,Biology ,Proteomics ,Molecular biology ,Flavin adenine dinucleotide binding ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Endopeptidase activity ,proteomics ,Oncology ,030220 oncology & carcinogenesis ,Signal transduction ,KEGG ,Chloroplast thylakoid membrane ,antibody microarray - Abstract
Gastric cancer (GC) is often a deadly disease due to the late diagnosis and chemoresistance that characterizes many cases of this disease. The aim of this study was to explore a panel of candidate cytokines as diagnostic and predictive biomarkers for GC. Sixteen tissue samples of GC and adjacent noncancerous mucosa were selected from GC patients (n=8) for antibody microarray analysis. Proteomic chip-based analysis was performed to simultaneously identify 507 cytokines using a cytokine antibody array in the gastric tissues to screen for differential proteins related in cases of GC. Fold changes of protein expression >2.0 or
- Published
- 2017
12. A Virus-Infected, Reprogrammed Somatic Cell-Derived Tumor Cell (VIReST) Vaccination Regime Can Prevent Initiation and Progression of Pancreatic Cancer
- Author
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Shuangshuang Lu, Zhe Zhang, Pan Du, Louisa S. Chard, Wenli Yan, Margueritte El Khouri, Zhizhong Wang, Zhongxian Zhang, Yongchao Chu, Dongling Gao, Qinxian Zhang, Lirong Zhang, Ai Nagano, Jun Wang, Claude Chelala, Jing Liu, Jiekai Chen, Pentao Liu, Yunshu Dong, Shengdian Wang, Xiaozhu Li, Jianzeng Dong, Nick R. Lemoine, Duanqing Pei, and Yaohe Wang
- Subjects
Male ,Oncolytic Virotherapy ,Cancer Research ,T-Lymphocytes ,Induced Pluripotent Stem Cells ,Mice, Transgenic ,Neoplasms, Experimental ,Cancer Vaccines ,Pancreatic Neoplasms ,Survival Rate ,Mice ,Oncolytic Viruses ,Lymphocytes, Tumor-Infiltrating ,Treatment Outcome ,Oncology ,Chlorocebus aethiops ,Disease Progression ,Animals - Abstract
Purpose: Pancreatic cancer remains one of the most lethal cancers, and late detection renders most tumors refractory to conventional therapies. Development of cancer prophylaxis may be the most realistic option for improving mortality associated with this disease. Here, we develop a novel individualized prophylactic and therapeutic vaccination regimen using induced pluripotent stem cells (iPSC), gene editing, and tumor-targeted replicating oncolytic viruses. Experimental Design: We created a Virus-Infected, Reprogrammed Somatic cell-derived Tumor cell (VIReST) regime. iPSCs from healthy cells were induced to pancreatic tumor cells using in situ gene editing via stable provision of KRasG12D and p53R172H tumor driver mutations. These cells were preinfected with oncolytic Adenovirus (AdV) as prime or Vaccinia virus (VV) as boost, to improve vaccine immunogenicity, prior to delivery of vaccines in a sequential regime to young KPC transgenic mice, genetically programmed to develop pancreatic cancer, to prevent and delay disease development. Results: Tumor cells preinfected with oncolytic AdV as prime or VV as boost were the best regime to induce tumor-specific immunity. iPSC-derived tumor cells were highly related in antigen repertoire to pancreatic cancer cells of KPC transgenic mice, suggesting that an individual's stem cells can provide an antigenically matched whole tumor cell vaccine. The VIReST vaccination primed tumor-specific T-cell responses, resulting in delayed disease emergence and progression and significantly prolonged survival of KPC transgenic mice. Importantly, this regime was well-tolerated and nontoxic. Conclusions: These results provide both proof of concept and a robust technology platform for the development of personalized prophylactic cancer vaccines to prevent pancreatic malignancies in at-risk individuals.
- Published
- 2019
13. EGFR, ALK, RET, KRAS and BRAF alterations in never-smokers with non-small cell lung cancer
- Author
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Qinxian Zhang, Yan-Qing Li, Jun Qi, Yu Dong, Bo Jin, Ying Li, Ren Xu, Baohui Han, Weihong Ren, and Hui-Qing Tao
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Mutation rate ,EGFR ,never-smokers ,medicine.disease_cause ,BRAF ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Carcinoma ,KRAS ,Anaplastic lymphoma kinase ,Epidermal growth factor receptor ,Lung cancer ,neoplasms ,biology ,Oncogene ,Cancer ,Articles ,medicine.disease ,respiratory tract diseases ,lung cancer ,030104 developmental biology ,ALK ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,RET - Abstract
Non-small cell lung cancer (NSCLC), caused by various mutations in a spectrum of cancer driver genes, may have distinct pathological characteristics and drug responses. Extensive genetic screening and pathological characterization is required for the design of customized therapies to improve patient outcomes. Notably, NSCLC in never-smokers exhibits distinctive clinicopathological features, which are frequently associated with tumorigenic mutations, and thus may be treated as a unique disease entity. However, to the best of our knowledge, these mutations have not been extensively and accurately characterized in an NSCLC study with a large sample size. Therefore, the present study enrolled a large cohort of NSCLC patients, which consisted of 358 never-smokers, for the screening of genetic alterations in the epidermal growth factor receptor (EGFR), ret proto-oncogene (RET), anaplastic lymphoma kinase (ALK), Kirsten rat sarcoma viral oncogene homolog (KRAS) and B-Raf proto-oncogene serine/threonine kinase (BRAF) tumorigenic genes. It was identified that the mutation rate was 47.8, 7.5, 3.6, 1.4 and 0.3% for EGFR, ALK, KRAS, RET and BRAF, respectively. In addition, clinicopathological features associated with these mutations were characterized. EGFR mutations were more frequently observed in female and older patients. By contrast, KRAS mutations were more frequently detected in male patients, and ALK and RET translocations in younger patients. The cancer cells were frequently well-differentiated in carcinoma cases exhibiting EGFR mutations, however, were less differentiated in those with ALK translocations. In conclusion, the present study determined the frequency of oncogenic alterations and associated clinicopathological features in NSCLC exhibited by never-smokers using a large sample size. The results of the present study may enrich our knowledge of NSCLC in never-smokers and provide useful insights for improvement of the outcome of molecularly targeted therapies for the treatment of NSCLC.
- Published
- 2016
14. EML4-ALK translocation is associated with early onset of disease and other clinicopathological features in Chinese female never-smokers with non-small-cell lung cancer
- Author
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Weihong Ren, Jie Ma, Qinxian Zhang, Bin Zhang, Jianyun Lan, Hui Men, and Wencai Li
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Cancer Research ,Pathology ,medicine.medical_specialty ,Chromosomal translocation ,Fusion gene ,Gefitinib ,hemic and lymphatic diseases ,EML4-ALK translocation ,medicine ,Lung cancer ,Crizotinib ,medicine.diagnostic_test ,business.industry ,Cancer ,Articles ,never smokers ,medicine.disease ,respiratory tract diseases ,lung cancer ,female ,Oncology ,Cancer research ,Erlotinib ,business ,medicine.drug ,Fluorescence in situ hybridization - Abstract
Non-small-cell lung cancer (NSCLC) with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation is resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib, but responds to the ALK-TKI crizotinib. Characterization of EML4-ALK translocation may provide invaluable information to facilitate disease diagnosis and improve the outcome of customized treatment. Although the occurrence of EML4-ALK translocation is likely to be affected by the smoking habits and gender of patients, the translocation has not been characterized extensively in female never-smokers with NSCLC. Therefore, 280 female never-smokers that were diagnosed with NSCLC were enrolled in the present study, and characteristics of EML4-ALK translocation, including the frequency, were determined in these NSCLC patients. EML4-ALK fusion variants were detected using Multiplex one-step reverse transcription-polymerase chain reaction and subsequently confirmed by DNA sequencing and Vysis ALK Break Apart fluorescence in situ hybridization analysis. The EML4-ALK fusion variants were detected in 21 carcinoma tissue specimens, accounting for 7.5% of the enrolled patients. Out of these patients with EML4-ALK fusion variants, EML4-ALK fusion variant 1 was identified in 12 patients, indicating that variant 1 is the most common type of EML4-ALK fusion gene in the present cohort of patients. ALK mRNA was aberrantly expressed in all the tissues with EML4-ALK translocation, but not in the carcinoma tissues without EML4-ALK translocation. In addition, the EML4-ALK translocation was more frequently found in younger patients. The median age of patients with EML4-ALK translocation was 50.95±2.29 years, which was significantly younger (P
- Published
- 2015
15. Corrigendum to ‘Generation of induced pluripotent stem cell line (ZZUi0012-a) from a patient with Fahr's disease caused by a novel mutation in SLC20A2 gene’ [stem cell research volume 35, March 2019, 101,395]
- Author
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Zhuo Li, Jin Zhang, Yuming Xu, Yanlin Wang, Shoutao Zhang, Qinxian Zhang, Hui Fang, and Huifang Sun
- Subjects
Cancer research ,Cell Biology ,General Medicine ,Stem cell ,Biology ,Induced pluripotent stem cell ,Fahr's disease ,Gene ,Novel mutation ,Developmental Biology - Published
- 2019
16. RETRACTED ARTICLE: Linc00210 drives Wnt/β-catenin signaling activation and liver tumor progression through CTNNBIP1-dependent manner
- Author
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Zihe Yang, Fujun Qin, Jizhen Lin, Yuechao Ding, Yiman Shang, Qinxian Zhang, Yong Zhang, Quanli Gao, Xiaoyan Zhu, Xiaomin Fu, and Li Wang
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0301 basic medicine ,Cancer Research ,Liver tumor ,CTNNBIP1 ,Wnt signaling pathway ,Tumor initiation ,Biology ,medicine.disease ,medicine.disease_cause ,Metastasis ,Transcriptome ,03 medical and health sciences ,030104 developmental biology ,Oncology ,medicine ,Cancer research ,Molecular Medicine ,Liver cancer ,Carcinogenesis - Abstract
Background Liver tumor initiating cells (TICs) have self-renewal and differentiation properties, accounting for tumor initiation, metastasis and drug resistance. Long noncoding RNAs are involved in many physiological and pathological processes, including tumorigenesis. DNA copy number alterations (CNA) participate in tumor formation and progression, while the CNA of lncRNAs and their roles are largely unknown. Methods LncRNA CNA was determined by microarray analyses, realtime PCR and DNA FISH. Liver TICs were enriched by surface marker CD133 and oncosphere formation. TIC self-renewal was analyzed by oncosphere formation, tumor initiation and propagation. CRISPRi and ASO were used for lncRNA loss of function. RNA pulldown, western blot and double FISH were used to identify the interaction between lncRNA and CTNNBIP1. Results Using transcriptome microarray analysis, we identified a frequently amplified long noncoding RNA in liver cancer termed linc00210, which was highly expressed in liver cancer and liver TICs. Linc00210 copy number gain is associated with its high expression in liver cancer and liver TICs. Linc00210 promoted self-renewal and tumor initiating capacity of liver TICs through Wnt/β-catenin signaling. Linc00210 interacted with CTNNBIP1 and blocked its inhibitory role in Wnt/β-catenin activation. Linc00210 silencing cells showed enhanced interaction of β-catenin and CTNNBIP1, and impaired interaction of β-catenin and TCF/LEF components. We also confirmed linc00210 copy number gain using primary hepatocellular carcinoma (HCC) samples, and found the correlation between linc00210 CNA and Wnt/β-catenin activation. Of interest, linc00210, CTNNBIP1 and Wnt/β-catenin signaling targeting can efficiently inhibit tumor growth and progression, and liver TIC propagation. Conclusion With copy-number gain in liver TICs, linc00210 is highly expressed along with liver tumorigenesis. Linc00210 drives the self-renewal and propagation of liver TICs through activating Wnt/β-catenin signaling. Linc00210 interacts with CTNNBIP1 and blocks the combination between CTNNBIP1 and β-catenin, driving the activation of Wnt/β-catenin signaling. Linc00210-CTNNBIP1-Wnt/β-catenin axis can be targeted for liver TIC elimination.
- Published
- 2018
17. Generation of induced pluripotent stem cell line (ZZUi0012-A) from a patient with Fahr's disease caused by a novel mutation in SLC20A2 gene
- Author
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Hui Fang, Yanlin Wang, Shoutao Zhang, Jin Zhang, Qinxian Zhang, Huifang Sun, Zhuo Li, and Yuming Xu
- Subjects
Male ,0301 basic medicine ,Adolescent ,Induced Pluripotent Stem Cells ,Biology ,medicine.disease_cause ,LIN28 ,Cell Line ,Kruppel-Like Factor 4 ,03 medical and health sciences ,0302 clinical medicine ,Basal Ganglia Diseases ,SOX2 ,medicine ,Humans ,Cellular Reprogramming Techniques ,Induced pluripotent stem cell ,lcsh:QH301-705.5 ,Gene ,Mutation ,Sodium-Phosphate Cotransporter Proteins, Type III ,Calcinosis ,Neurodegenerative Diseases ,Dermis ,Cell Biology ,General Medicine ,Fibroblasts ,030104 developmental biology ,lcsh:Biology (General) ,Cell culture ,KLF4 ,Cancer research ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Several SLC20A2 mutations have been implicated as potential causes of Fahr's disease, a subtype of primary familial brain calcification (PFBC), but very few patient-derived induced pluripotent stem cell (iPSC) models have been established. We have identified a novel SLC20A2 mutation in a family with Fahr's disease. We subsequently obtained dermal fibroblasts from a patient in this family. These fibroblasts were successfully transformed into iPSCs by employing episomal plasmids expressing OCT3/4, SOX2, KLF4, LIN28, and L-MYC. Our approach offers a resource and a platform for further research into the mechanism of Fahr's disease and could facilitate development and screening of pharmaceutical and gene therapies.
- Published
- 2019
18. Lentiviral vector-mediated siRNA knockdown and concurrent rescue of Murine CIN85
- Author
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Xiaoan Zhang, Yumei Wang, Guang-Yao Sheng, and Qinxian Zhang
- Subjects
Small interfering RNA ,Health, Toxicology and Mutagenesis ,Blotting, Western ,Genetic Vectors ,Trans-acting siRNA ,Nerve Tissue Proteins ,Biology ,Toxicology ,Biochemistry ,Viral vector ,Mice ,RNA interference ,Animals ,Gene silencing ,RNA, Messenger ,RNA, Small Interfering ,Molecular Biology ,Gene ,Cells, Cultured ,Adaptor Proteins, Signal Transducing ,Messenger RNA ,Lentivirus ,General Medicine ,Molecular biology ,Neoplasm Proteins ,Cell biology ,RNA silencing ,Gene Knockdown Techniques ,Molecular Medicine ,RNA Interference ,Signal Transduction - Abstract
RNA interference (RNAi), an evolutionarily conserved process of gene silencing, is now a common tool in gene functional studies. However, potential “off-target effects” is one of major concerns in RNAi experiment associated with false positive results. Apart from continuing improvement in small interfering RNA (siRNA) designs, there is no method available to prevent the generation of “off-target effects” resulted from possible identity between siRNA and abundant cellular mRNA transcripts. In the present study, we have developed a lentiviral vector-mediated system that allows efficient siRNA silencing and concurrent rescue of targeted genes. While this approach does not eliminate potential “off-target effects,” concurrent rescue of a target gene allows a definite judgment with regard to a phenotype change, either from expected siRNA silencing or “off-target effects.” The system has been validated with murine CIN85 gene and may be generally applicable in molecular studies from broad fields. © 2011 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:55–59 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20331
- Published
- 2011
19. Production and purification of the isolated family 2a carbohydrate-binding module from Cellulomonas fimi
- Author
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Darrell Cockburn, Haiqiang Jing, Anthony J. Clarke, and Qinxian Zhang
- Subjects
Models, Molecular ,Signal peptide ,Protein Conformation ,Molecular Sequence Data ,Cellulase ,medicine.disease_cause ,Models, Biological ,Biophysical Phenomena ,chemistry.chemical_compound ,Escherichia coli ,medicine ,Amino Acid Sequence ,Cysteine ,Cellulose ,Cellulomonas ,chemistry.chemical_classification ,Binding Sites ,Base Sequence ,biology ,Chemistry ,Mutagenesis ,Substrate (chemistry) ,Recombinant Proteins ,Enzyme ,Amino Acid Substitution ,Biochemistry ,biology.protein ,Carbohydrate-binding module ,Protein Binding ,Biotechnology - Abstract
Cellulose is the most abundant polymer on Earth and in recent years, renewed interest has developed in its use for the production of biofuels and other value added products. Cellulose is degraded to glucose by the concerted action of cellulolytic enzymes that include cellulases, cellobiohydrolases, and β-glucosidases. In many cases, these enzymes are multi-modular, being comprised of distinct catalytic and carbohydrate-binding modules. The latter appear to aid in both the adsorption of the enzymes to the insoluble cellulose substrate and the destabilization of the hydrogen-bonding network within the crystalline substrate. To better understand these dynamic processes, we have engineered a carbohydrate-binding module that can be attached to the probe of an atomic force microscope. Thus, the coding sequence for the leader peptide and carbohydrate-binding module from the Cellulomonas fimi cellulase A (cenA) was cloned and over-expressed in Escherichia coli . Site-directed mutagenesis was used to replace Thr87 of this module with Cys to facilitate covalent binding of the module to gold-plated AFM probes. The recombinant proteins with cleavable N-terminal His-tags were purified to apparent homogeneity by a combination of affinity and anion-exchange chromatographies using Ni 2+ –NTA-agarose and Source Q, respectively. Their ability to bind insoluble cellulose was demonstrated using a cellulose-binding assay involving the micro-crystalline cellulose, Avicel.
- Published
- 2009
20. Expression profile of cytokines in gastric cancer patients using proteomic antibody microarray.
- Author
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Xiaoqiang Quan, Yi Ding, Ruo Feng, Xiaoyan Zhu, and Qinxian Zhang
- Subjects
STOMACH cancer patients ,CYTOKINE genetics ,STOMACH cancer ,CANCER diagnosis ,PROTEIN expression ,GENE ontology - Abstract
Gastric cancer (GC) is often a deadly disease due to the late diagnosis and chemoresistance that characterizes many cases of this disease. The aim of this study was to explore a panel of candidate cytokines as diagnostic and predictive biomarkers for GC. Sixteen tissue samples of GC and adjacent noncancerous mucosa were selected from GC patients (n=8) for antibody microarray analysis. Proteomic chip-based analysis was performed to simultaneously identify 507 cytokines using a cytokine antibody array in the gastric tissues to screen for differential proteins related in cases of GC. Fold changes of protein expression >2.0 or <0.5 were considered significant. The proteins that showed significant differences in levels between the cancerous and non-cancerous samples were analyzed using bioinformatics analysis. One hundred and five cytokines that were significantly different (p<0.05) between GC tissues and normal gastric mucosa were identified. Gene Ontology (GO) enrichment analysis showed that these differentially expressed proteins are involved in many biological and immunological processes, mainly in response to stress, chloroplast thylakoid membrane, vacuole, photosynthesis, aspartic-type endopeptidase activity and flavin adenine dinucleotide binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that these proteins mainly were involved in the process of cytokine-cytokine receptor interaction, transforming growth factor-β (TGF-β) signaling pathway, pathways in cancer, tumor necrosis factor (TNF) signaling pathway, and mitogenactivated protein kinase (MAPK) signaling pathway. These findings suggest that the differentially expressed proteins could be associated with GC in patients. Further study of these cytokines may provide a promising approach for diagnosis, classification and prognosis of GC. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
21. Endoplasmic Reticulum Stress-Mediated Signaling Pathway of Gastric Cancer Apoptosis
- Author
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Qinxian Zhang, Ruo Feng, Xiuhua Ren, Jing Cao, Yan-Wen You, Yi Ding, Wei-Dong Zang, and Yu-Ying Xu
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Male ,Time Factors ,Blotting, Western ,Mice, Nude ,Apoptosis ,Biology ,CHOP ,Transfection ,Mice ,chemistry.chemical_compound ,Microscopy, Electron, Transmission ,Stomach Neoplasms ,In vivo ,Cell Line, Tumor ,In Situ Nick-End Labeling ,Animals ,Humans ,Endoplasmic Reticulum Chaperone BiP ,Heat-Shock Proteins ,Mice, Inbred BALB C ,TUNEL assay ,Dose-Response Relationship, Drug ,Hepatology ,Reverse Transcriptase Polymerase Chain Reaction ,Tunicamycin ,Endoplasmic reticulum ,Gastroenterology ,General Medicine ,Endoplasmic Reticulum Stress ,Molecular biology ,Tumor Burden ,Gene Expression Regulation, Neoplastic ,Proto-Oncogene Proteins c-bcl-2 ,chemistry ,Unfolded protein response ,RNA Interference ,Signal transduction ,Transcription Factor CHOP ,Signal Transduction - Abstract
Background/Aims: To investigate ER stress-mediated CHOP-signaling pathway of gastric cancer apoptosis in vitro and in vivo. Methodology: Based on the dose-and time-response experiments about tunicamycin (TM), gastric cancer cell line BGC823 was treated with 10µg/mL of TM for 24h. BGC823 apoptosis was detected with TUNEL assay and ultrastructural changes in BGC823 cells under ER stress were observed with transmission electron microscopy (TEM). RT-PCR and western blotting were used to determine the expression of ERS-related proteins, glucose-regulated protein 78 (GRP78) and CHOP and apoptosis-associated protein B-cell lymphoma 2 (Bcl-2). After the knockdown of CHOP, the changes were also observed in vitro and in vivo. Results: TEM assay showed that after treatment with TM, BGC823 cell size became smaller with ER dilation, vacuolization and karyopyknosis. RT-PCR and western blotting indicated that TM up-regulated GRP78 and CHOP expression and down-regulated Bcl-2 expression. The knockdown of CHOP could convert Bcl-2 expression and reduce BGC823 apoptosis caused by ERS in vitro and in vivo, but failed to influence GRP78. Conclusions: TM can induce ESR and regulate downstream molecules CHOP up-regulation and Bcl-2 down-regulation which lead to BGC823 apoptosis. This study may provide a new theoretical basis for the pathogenesis of gastric cancer.
- Published
- 2012
22. Prevalence characterization of extended-spectrum beta-lactamases among Escherichia coli isolates collected in Zhengzhou
- Author
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Zhijian Zhang, Qinxian Zhang, and Xiaobing Guo
- Subjects
Microbiology (medical) ,China ,medicine.medical_treatment ,Clinical Biochemistry ,Drug resistance ,Microbial Sensitivity Tests ,Biology ,medicine.disease_cause ,Polymerase Chain Reaction ,beta-Lactamases ,Microbiology ,law.invention ,Agar plate ,law ,Genotype ,medicine ,polycyclic compounds ,Escherichia coli ,Immunology and Allergy ,Humans ,Polymerase chain reaction ,Electrophoresis, Agar Gel ,Molecular epidemiology ,β lactamases ,Biochemistry (medical) ,Public Health, Environmental and Occupational Health ,Hematology ,Original Articles ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,Medical Laboratory Technology ,Beta-lactamase ,bacteria ,Plasmids - Abstract
Objectives: To determine the prevalence and the diversity of extended-spectrum β-lactamases (ESBLs) among Escherichia coli isolates in Zhengzhou, China. Methods: Clinical isolates were collected and investigated from the first affiliated hospital of Zhengzhou University and its associated health-care facilities in Zhengzhou, China, during the period from January 2006 to June 2008. Antibiograms were performed on Mueller–Hinton agar plates with the disc-diffusion method and MICs were determined by the agar-dilution method. Total DNA was extracted with a Qiagen mini kit and screened by PCR. Results: Of 94 nonduplicate ESBL-positive isolates, TEM-type was encoded in 74 and 79% of the ESBL isolates. Fifty-six isolates were SHV type ESBLs. CTX-M-1, CTX-M-14, CTX-M-25, and CTX-M-38 types were encoded in 30, 54, 6, and 4, respectively. OXA-1-type β-lactamases were encoded in six and OXA-20-type was encoded in two isolates. Conclusions: We describe a complex ESBL epidemiology. The study revealed a high rate of ESBL-producing E. coli isolates. TEM and CTX-M enzymes dominated in ESBL-positive E. coli isolates in Zhengzhou, China. J. Clin. Lab. Anal. 23:404–407, 2009. © 2009 Wiley-Liss, Inc.
- Published
- 2009
23. Lymphotoxin-α Plays Only a Minor Role in Host Resistance to Respiratory Infection with Virulent Type A Francisella tularensis in Mice
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Greg Harris, Wangxue Chen, Deng Zhang, Qinxian Zhang, J. Wayne Conlan, and Rhonda KuoLee
- Subjects
Lymphotoxin alpha ,Article Subject ,education ,Immunology ,Virulence ,Spleen ,behavioral disciplines and activities ,Tularemia ,03 medical and health sciences ,Mice ,mental disorders ,lcsh:Pathology ,medicine ,Animals ,Francisella tularensis ,Lung ,Lymphotoxin-alpha ,030304 developmental biology ,Aerosols ,Mice, Knockout ,0303 health sciences ,biology ,030306 microbiology ,Intracellular parasite ,Respiratory infection ,Cell Biology ,medicine.disease ,biology.organism_classification ,Virology ,3. Good health ,Mice, Inbred C57BL ,Survival Rate ,medicine.anatomical_structure ,Lymphotoxin ,Cytokines ,Bronchoalveolar Lavage Fluid ,psychological phenomena and processes ,lcsh:RB1-214 ,Research Article - Abstract
This study examined the role of lymphotoxin (LT)-αin host defense against airborne infection withFrancisella tularensis, a gram-negative facultative intracellular bacterium and the causative agent of tularemia. Following a low-dose aerosol infection with the highly virulent type A strain ofF. tularensis, mice deficient in LTα(LTα−/−) consistently harbored approximately 10-fold fewer bacteria in their spleens at day 2 and 10-fold more bacteria in their lungs at day 4 than LTα+/+ mice. However, the mortality and median time to death were indistinguishable between the two mouse strains. In addition, the inflammatory responses to the infection, as reflected by the cytokine levels and leukocyte influx in the bronchoalveolar lavage fluid and histopathological analysis, were generally similar between LTα−/− and LTα+/+ mice. These data suggest that although LTαdoes not contribute significantly to the resistance and host responses of mice to airborne type AF. tularensisinfection, it does play a subtle role in the multiplication/dissemination ofF. tularensis.
- Published
- 2008
24. EGFR, ALK, RET, KRAS and BRAF alterations in never-smokers with non-small cell lung cancer.
- Author
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YU DONG, WEIHONG REN, JUN QI, BO JIN, YING LI, HUIQING TAO, REN XU, YANQING LI, QINXIAN ZHANG, and BAOHUI HAN
- Subjects
LUNG cancer ,GENETIC mutation ,GENETIC testing ,CANCER genes ,EPIDERMAL growth factor receptors ,ANAPLASTIC lymphoma kinase ,PROTO-oncogenes - Abstract
Non-small cell lung cancer (NSCLC), caused by various mutations in a spectrum of cancer driver genes, may have distinct pathological characteristics and drug responses. Extensive genetic screening and pathological characterization is required for the design of customized therapies to improve patient outcomes. Notably, NSCLC in never-smokers exhibits distinctive clinicopathological features, which are frequently associated with tumorigenic mutations, and thus may be treated as a unique disease entity. However, to the best of our knowledge, these mutations have not been extensively and accurately characterized in an NSCLC study with a large sample size. Therefore, the present study enrolled a large cohort of NSCLC patients, which consisted of 358 never-smokers, for the screening of genetic alterations in the epidermal growth factor receptor (EGFR), ret proto-oncogene (RET), anaplastic lymphoma kinase (ALK), Kirsten rat sarcoma viral oncogene homolog (KRAS) and B-Raf proto-oncogene serine/threonine kinase (BRAF) tumorigenic genes. It was identified that the mutation rate was 47.8, 7.5, 3.6, 1.4 and 0.3% for EGFR, ALK, KRAS, RET and BRAF, respectively. In addition, clinicopathological features associated with these mutations were characterized. EGFR mutations were more frequently observed in female and older patients. By contrast, KRAS mutations were more frequently detected in male patients, and ALK and RET translocations in younger patients. The cancer cells were frequently well-differentiated in carcinoma cases exhibiting EGFR mutations, however, were less differentiated in those with ALK translocations. In conclusion, the present study determined the frequency of oncogenic alterations and associated clinicopathological features in NSCLC exhibited by never-smokers using a large sample size. The results of the present study may enrich our knowledge of NSCLC in never-smokers and provide useful insights for improvement of the outcome of molecularly targeted therapies for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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- View/download PDF
25. Expression of Nucleostemin, epidermal growth factor and epidermal growth factor receptor in human esophageal squamous cell carcinoma tissues.
- Author
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Gongyuan Zhang, Qiao Zhang, Qinxian Zhang, Lei Yin, Shenglei Li, Kuisheng Cheng, Yunhan Zhang, Honghui Xu, and Weidong Wu
- Subjects
EPIDERMAL growth factor ,MESSENGER RNA ,CANCER invasiveness ,POLYMERASE chain reaction ,TUMORS - Abstract
To determine the expression of nucleostemin (NS), epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) mRNA in human esophageal squamous cell carcinoma (ESCC) tissues and their association in a human ESCC cell line. The expression of NS, EGF and EGFR mRNA was determined in paired normal esophageal and ESCC tissues of 62 patients using in situ hybridization. The association between NS and EGF or EGFR was examined using immunoblotting and real time polymerase chain reaction in a human ESCC cell line transfected with NS siRNA or treated with a selective EGFR inhibitor. In normal esophageal and ESCC tissues, the positive detection rates were 21.0% (13/62) and 69.4% (43/62) for NS mRNA staining, 40.3% (25/62) and 77.4% (48/62) for EGF mRNA staining, and 30.6% (19/62) and 75.8% (41/62) for EGFR mRNA staining, respectively. These results indicated that NS, EGF and EGFR mRNA expression was upregulated mostly in ESCC tissues. Moreover, the expression of NS, EGF and EGFR mRNA was positively correlated with tumor grade, invasion and lymphatic metastasis of ESCC cells. NS mRNA was co-expressed with EGF and EGFR mRNA in ESCC tissues. The in vitro studies using a human ESCC cell line showed that knockdown of NS with NS siRNA significantly reduced EGF and EGFR expression. However, inhibition of the EGFR kinase activity with a specific EGFR kinase inhibitor had minimal effect on NS expression. The upregulation of NS, EGF and EGFR mRNA frequently occurs in ESCC tissues and is associated with malignancy of human esophageal squamous tumors. NS is required for EGF and EGFR expression. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
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