Wuhan Nano Tumor Diagnosis Engineering Research Center

Wuhan, China

Wuhan Nano Tumor Diagnosis Engineering Research Center

Wuhan, China

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Qu Y.-G.,The Central Hospital of Enshi Autonomous Prefecture | Zhang Q.,Wuhan Nano Tumor Diagnosis Engineering Research Center | Pan Q.,Traditional Chinese Medical Hospital of Wenling | Zhao X.-D.,Hubei University | And 3 more authors.
International Journal of Nanomedicine | Year: 2014

Background: Epidermal growth factor receptor (EGFR) mutation status plays an important role in therapeutic decision making for non-small cell lung cancer (NSCLC) patients. Since EGFR mutation-specific antibodies (E746-A750del and L858R) have been developed, EGFR mutation detection by immunohistochemistry (IHC) is a suitable screening test. On this basis, we want to establish a new screening test, quantum dots immunofluorescence histochemistry (QDs-IHC), to assess EGFR gene mutation in NSCLC tissues, and we compared it to traditional IHC and amplification refractory mutation system (ARMS).Materials and methods: EGFR gene mutations were detected by QDs-IHC, IHC, and ADx-ARMS in 65 cases of NSCLC composed of 55 formalin-fixed, paraffin-embedded specimens and ten pleural effusion cell blocks, including 13 squamous cell carcinomas, two adenosquamous carcinomas, and 50 adenocarcinomas.Results: Positive rates of EGFR gene mutations detected by QDs-IHC, IHC, and ADx-ARMS were 40.0%, 36.9%, and 46.2%, respectively, in 65 cases of NSCLC patients. The sensitivity of QDs-IHC when detecting EGFR mutations, as compared to ADx-ARMS, was 86.7% (26/30); the specificity for both antibodies was 100.0% (26/26). IHC sensitivity was 80.0% (24/30) and the specificity was 92.31% (24/26). When detecting EGFR mutations, QDs-IHC and ADx-ARMS had perfect consistency (κ =0.882; P˂0.01). Excellent agreement was observed between IHC and ADx-ARMS when detecting EGFR mutations (κ =0.826; P˂0.01).Conclusion: QDs-IHC is a simple and standardized method to detect EGFR mutations with its high sensitivity and specificity, as compared with real-time polymerase chain reaction. In addition, the development of specific antibodies against EGFR mutation proteins might be useful for the diagnosis and treatment of lung cancer. © 2014 Qu et al.


Sun J.,Maternal and Child Health Hospital of Hubei Province | Gao J.,Wuhan Nano Tumor Diagnosis Engineering Research Center | Hu J.B.,Maternal and Child Health Hospital of Hubei Province | Fan L.F.,Wuhan University | And 3 more authors.
Oncology Reports | Year: 2012

Altered expression of caveolin-1 (Cav-1) is observed in various types of cancers. However, little research has been reported regarding the correlation between the expression of Cav-1 and cervical cancer. Here, we investigated the clinical significance of Cav-1 expression using quantum dot (QD)-based immunofluorescence staining in cervical cancer and its correlation with high-risk human papilloma virus (HPV) infection detected by chromogenic in situ hybridization. Our results showed that the positive rates of Cav-1 protein in normal cervical mucosa, CIN, cervical adenocarcinoma and SCC were: 0, 33, 19 and 55%, respectively. The differences in Cav-1 protein expression in cervical SCC compared to the other three groups were all statistically significant. Absence of stromal Cav-1 protein in 58 cases of cervical SCC was 67%. The positive rates of the Cav-1 protein in tumour and stromal cells of cervical SCC were not correlated with clinicopathological parameters. In the cervical SCC tissues, Cav-1 expression in tumour cells was not associated with stromal Cav-1 expression, but a positive correlation existed with the PCNA protein and high-risk of HPV infection. The results presented here suggest that expression of Cav-1 in the tumour cells, rather than in the stromal tissue surrounding the tumour, may promote cervical SCC cell proliferation, and correlates with high-risk HPV infection.


Song J.,Hubei University of Medicine | Liang S.,Hubei University of Medicine | Luo X.,Hubei University of Medicine | Huang Y.,Wuhan Nano Tumor Diagnosis Engineering Research Center | And 2 more authors.
Medical Journal of Wuhan University | Year: 2014

Objective: To detect the expression of caveolin-1 (Cav-1) and its correlation with autophagy marker-microtubule associated protein light chain 3 (LC3B) in human pulmonary invasive adenocarcinoma (PIA) tissues, and to investigate their clinicopathologic significance. Methods: The quantum dots immunofluorescent histochemistry (QDs-IHC) was used to detect the expression of Cav-1 and LC3B proteins in 68 cases of PIA and 10 cases of noncancerous lung tissues, and mRNA levels of Cav-1 and LC3B were detected by quantitative real-time PCR (q-PCR) methods in 10 cases of PIA and 10 cases of noncancerous lung tissues. Results: Compared with noncancerous lung tissues, proteins and mRNA levels of Cav-1 and LC3B in the PIA tissues were significantly decreased (P<0.05). Expression of Cav-1protein in the tumor cells and stroma was significantly related with histopathological grade of acinar predominant PIA (P<0.05), but not correlated with the other clinicopathologic parameters (P>0.05). Positive rates of LC3B protein in the lepidic predominant PIA was 60.0% (9/15), significantly higher than 35.71% (10/28) of acinar predominant PIA (P<0.05). There was positive correlation between Cav-1 and LC3B in the tumor cells (P<0.05, rs=0.267). Conclusion: Absent expression of Cav-1in the tumor cell and stroma may promote pulmonary invasive adenocarcinoma formation and its mechanism may correlate with inadequate autophagy in the tumor cells.


Wang H.-Y.,Jingzhou Second Peoples Hospital | Yang G.-F.,Hubei University | Huang Y.-H.,Wuhan Nano Tumor Diagnosis Engineering Research Center | Huang Q.-W.,Jingzhou Second Peoples Hospital | And 4 more authors.
Oncology Letters | Year: 2014

Infection by an oncogenic human papillomavirus (HPV), in particular HPV16 and 18, is a high risk factor for developing cervical cancer; however, viral infection alone is not sufficient for cancer progression. Autophagy is hypothesized to be an important process during carcinogenesis. The aim of the present study was to investigate the association between autophagy and high-risk HPV (hrHPV) infection in human cervical squamous cell carcinomas (SCCs), and to analyze the clinical significance of this association. Quantum dot (QD)-based immunofluorescence histochemistry was used to detect the expression of autophagy markers, Beclin-1 and microtubule-associated proteins 1A/1B light chain 3B (LC3B) proteins, in 104 cases of cervical cancer (including 80 SCCs and 24 adenocarcinomas) and 20 normal cervical tissues. hrHPV (HPV16/18) infection was detected by QDs based fluorescence in situ hybridization in cervical cancers. The results revealed that the expression levels of Beclin-1 and LC3B were significantly lower in cervical cancer cells when compared with those of normal cervical squamous epithelial cells, and were found to negatively correlate with hrHPV infection. The expression levels of Beclin-1 and LC3B were not associated with age, tumor grade, tumor stage, tumor node metastasis stage or lymph node metastasis. However, a positive correlation was identified between Beclin-1 and LC3B protein expression. In addition, the absence of autophagy in combination with hrHPV infection may accelerate the progression of cervical SCC. In conclusion, decreased expression of Beclin-1 and LC3B may be important in cervical carcinogenesis. The hrHPV-host cell interaction may inhibit autophagy, which may aid virus duplication and infection, as well as cervical cancer development.


Zhao X.,Wuhan University | He Y.,Wuhan University | Gao J.,Wuhan Nano Tumor Diagnosis Engineering Research Center | Fan L.,Wuhan University | And 4 more authors.
PLoS ONE | Year: 2013

Aims: Altered expression of epithelial or stromal caveolin-1 (Cav-1) is observed in various types of human cancers. However, the clinical significance of Cav-1 expression in gastric cancer (GC) remains largely unknown. The present study aims to explore the clinicopathological significance and prognostic value of both tumor cells and cancer associated fibroblasts (CAFs) Cav-1 in GC. Methods and Results: Quantum dots immunofluorescence histochemistry was performed to examine the expression of Cav-1 in 20 cases of gastritis without intestinal metaplasia (IM), 20 cases of gastritis with IM and 286 cases of GC. Positive rates of epithelial Cav-1 in gastritis without IM, gastritis with IM and GC showed a decreasing trend (P = 0.012). Low expression of Cav-1 in CAFs but not in tumor cells was an independent predictor of poor prognosis in GC patients (P = 0.034 and 0.005 respectively in disease free survival and overall survival). Cav-1 level in tumor cells and CAFs showed no significant correlation with classic clinicopathological features. Conclusions: Loss of epithelial Cav-1 may promote malignant progression and low CAFs Cav-1 level herald worse outcome of GC patient, suggesting CAFs Cav-1 may be a candidate therapeutic target and a useful prognostic marker of GC. © 2013 Zhao et al.


He Y.,Wuhan University | Zhao X.,Wuhan University | Gao J.,Wuhan Nano Tumor Diagnosis Engineering Research Center | Fan L.,Wuhan University | And 4 more authors.
International Journal of Molecular Sciences | Year: 2012

Caveolin-1 (Cav-1) expression deficiency and autophagy in tumor stromal fibroblasts (hereafter fibroblasts) are involved in tumor proliferation and progression, particularly in breast and prostate cancer. The aim of this study was to detect the expression of fibroblastic Cav-1 and LC3B, markers of autophagy, in gastric cancer (GC) and to analyze their clinical significances. Furthermore, because Epstein-Barr virus (EBV)-associated GC (EBVaGC) is a unique subtype of GC; we compared the differential expression of fibroblastic Cav-1 and LC3B in EBVaGC and non-EBVaGC. Quantum dots (QDs)-based immunofluorescence histochemistry was used to examine the expression of fibroblastic Cav-1 and LC3B in 118 cases of GC with adequate stroma. QDs-based double immunofluorescence labeling was performed to detect the coexpression of Cav-1 and LC3B proteins. EBV-encoded small RNA was detected by QDs-based fluorescence in situ hybridization to identify EBVaGC. Multivariate analysis indicated that low fibroblastic Cav-1 level was an independent prognosticator (p = 0.029) that predicted poorer survival of GC patients. Positive fibroblastic LC3B was correlated with lower invasion (p = 0.032) and was positively associated with Cav-1 expression (r = 0.432, p < 0.001). EBV infection did not affect fibroblastic Cav-1 and LC3B expression. In conclusion, positive fibroblastic LC3B correlates with lower invasion, and low expression of fibroblastic Cav-1 is a novel predictor of poor GC prognosis. © 2012 by the authors; licensee MDPI, Basel, Switzerland.


He Y.,Wuhan University | Zhao X.,Wuhan University | Subahan N.R.,Wuhan University | Fan L.,Wuhan University | And 2 more authors.
Tumor Biology | Year: 2014

Use of the autophagy-related markers beclin-1 (BECN1) and microtubule-associated protein light chain 3B (LC3B) as prognostic markers has been extensively investigated in various kinds of cancers. However, their prognostic roles are still controversial and not firmly validated. We systematically reviewed the evidence from various studies concerning the relationship between BECN1 and LC3B expression in cancers and overall survival (OS)/disease-free survival (DFS) to elucidate this issue. PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched in July 2013 (then updated in April 2014) to identify eligible cohort studies that reported associations between BECN1 or LC3B expression and OS/DFS in cancer patients. Combined hazard ratios (HRs) with 95 % confidence intervals (95 % CIs) were pooled using fixed-effects or random-effects models according to heterogeneity in different groups. A total of 23 studies in distinct cancers were eligible for systematic review and meta-analysis. Our pooled results identified that a high expression of BECN1 is associated with favorable OS in gastric cancer (HR = 0.49, 95 % CI = 0.34–0.72) and lymphoma (HR = 0.25, 95 % CI = 0.11–0.57), whereas a high expression of LC3B predicts adverse OS in breast cancer (HR = 1.98, 95 % CI = 1.25–3.13). This systematic review and meta-analysis indicated that the autophagy-related marker BECN1 might be a predictive factor of favorable prognosis in gastric cancer, breast cancer, and lymphoma and LC3B might predict unfavorable prognosis of breast cancer. Nevertheless, due to the limited number and retrospective design of the original studies, more powerful prospective cohorts are required to verify these conclusions. © 2014, International Society of Oncology and BioMarkers (ISOBM).


Liu X.-L.,China Three Gorges University | Li L.,China Three Gorges University | Gao J.,Wuhan Nano Tumor Diagnosis Engineering Research Center | Xue J.-L.,Wuhan University | Chen H.-L.,Wuhan University
Journal of Practical Oncology | Year: 2014

Objective: To investigate stromal caveolin-1 (Cav-1) protein expression and its correlation with autophagy marker-microtubule associated protein light chain 3 (LC3B) in human esophageal squamous cell carcinoma (SCC) and its clinicopathologic significance. Methods: Quantum dots immunofluorescent histochemistry was used to detect the expression of stromal Cav-1 and LC3B in 76 cases of esophageal SCC and 15 samples of noncancerous esophageal mucous epithelium tissues. Results: The positive rates of stromal Cav-1 and LC3B proteins in esophageal SCC were both significantly lower than those in noncancerous esophageal mucous epithelium tissues(28.9% vs 100.0%, 64.5% vs 100.0%, both P<0.05). Stromal Cav-1 protein expression was siginificantly correlated with TNM stage and lymph node metastasis (P<0.05), but not correlated with other clinicopathologic parameters (P>0.05). LC3B protein level was associated with tumor invasive depth, clinical TNM stage and lymph node metastasis (P<0.05). There was a positive correlation between stromal Cav-1 and LC3B in esophageal SCC tissues (r=0.353, P<0.05). Conclusion: Absent expression of stromal Cav-1 and LC3B proteins may synergistically promote the development and malignant progression of esophageal squamous cell carcinoma.


Zhao X.-D.,Wuhan University | He Y.-Y.,Wuhan University | Gao J.,Wuhan Nano Tumor Diagnosis Engineering Research Center | Zhao C.,Wuhan University | And 3 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2014

Background: The prognostic value of Bcl-2 protein expression in non-small cell lung cancer (NSCLC) is under debate. We therefore systematically reviewed the evidence for Bcl-2 protein effects on NSCLC survival to elucidate this issue. Materials and Methods: An electronic search in Pubmed and Embase complemented by manual searches in article references were conducted to identify eligible studies to evaluate the association between Bcl-2 protein expression and overall survival (OS) as well as disease free survival (DFS) of NSCLC patients. Combined hazard ratios (HRs) with corresponding 95% confidence intervals (95%CIs) were pooled using the random-effects model. Results: A total of 50 trials (including 52 cohorts) encompassing 7,765 patients were pooled in the meta-analysis regarding Bcl-2 expression and OS of NSCLC patients. High expression of Bcl-2 protein had a favorable impact (HR=0.76, 95%CI=0.67-0.86). In the group of Bcl-2 expression and DFS, 11 studies including 2,634 patients were included. The synthesized result indicated high expression of Bcl-2 protein might predict good DFS (HR=0.85, 95%CI=0.75-0.95). Conclusions: Our present meta-analysis demonstrated favorable prognostic values of Bcl-2 expression in patients with NSCLC. Further prospective trails are welcomed to validate the utility of assessing Bcl-2 in NSCLC patient management.


Hu Y.-C.,China Three Gorges University | Zhang Q.,Wuhan Nano Tumor Diagnosis Engineering Research Center | Huang Y.-H.,Wuhan Nano Tumor Diagnosis Engineering Research Center | Liu Y.-F.,China Three Gorges University | Chen H.-L.,Wuhan University
Asian Pacific Journal of Cancer Prevention | Year: 2014

Objective: Molecular pathology tests are often carried for clinicopathological diagnosis and pathologists have established large collections of formalin-fixed, paraffin-embedded tissue (FFPE) banks. However, extraction of DNA from FFPE is a laborious and challenging for researchers in clinical laboratories. The aim of this study was to compare two widely used DNA extraction methods: using a QIAamp DNA FFPE kit from Qiagen and a Cobas Sample Preparation Kit from Roche, and evaluated the effect of the DNA quality on molecular diagnostics. Methods: DNA from FFPE non-small cell lung carcinoma tissues including biopsy and surgical specimens was extracted with both QIAamp DNA FFPE and Cobas Sample Preparation Kits and EGFR mutations of nonsmall cell lung carcinomas were detected by real-time quantitative PCR using the extracted DNA. Results and Conclusion: Our results showed that DNA extracted by QIAamp and Cobas methods were both suitable to detect downstream EGFR mutation in surgical specimens. Howover, Cobas method could yield more DNA from biopsy specimens, and gain much better EGFR mutation results.

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