Jianhua Fu

Sun Yat-Sen University Cancer Center, Shengcheng, Guangdong, China

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Publications (29)67.1 Total impact

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    ABSTRACT: Background Body mass index (BMI) has been associated with the risk of esophageal cancer. But the influence of BMI on postoperative complications and prognosis has always been controversial.Methods Between 2000 and 2007, 424 patients with esophageal squamous cell carcinoma (ESCC) underwent R0 esophagectomy at our center without neoadjuvant therapy. We performed univariate and multivariate analyses to identify prognostic factors for survival.ResultsPatients were divided into three groups according to Asian-specific BMI cut-off value: underweight (n = 45), normal weight (n = 228), and overweight and obese (n = 151). Mean follow-up time was 39 months. The five-year overall survival (OS) rate was 19%, 34%, and 42% for underweight, normal weight, and overweight and obese, respectively (P < 0.001). The five-year disease-free survival (DFS) rate was 24%, 41%, and 74% for underweight, normal weight, and overweight and obese, respectively (P < 0.001). Multivariate analysis showed that pT, pN, and BMI were independent prognostic factors for DFS and OS. The C-index to the combined model showed improved predictive ability when compared to the pN classification (0.779 vs. 0.734).Conclusion Preoperative BMI was an independent prognostic factor for OS and DFS. The proposed new prognostic model with the pN classification supplemented by BMI might improve the ability to discriminate ESCC patients' outcome.
    Thoracic Cancer 05/2015; DOI:10.1111/1759-7714.12259 · 0.65 Impact Factor
  • PLoS ONE 04/2015; 10(4):e0123246. DOI:10.1371/journal.pone.0123246 · 3.23 Impact Factor
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    ABSTRACT: Recently, we found that NHE9 mRNA was upregulated in chemoradiotherapy (CRT)-resistant esophageal squamous cell carcinoma (ESCC); however, the underlying mechanisms were unclear. Here, we aimed to clarify the functional contribution of NHE9 to CRT resistance, understand the molecular basis of NHE9-dependent resistance in ESCC, and identify potential therapeutic targets. Our results showed that NHE9 prevented CRT-induced apoptosis. Importantly, we found that RACK1 is a novel binding partner of NHE9 and that NHE9-dependent induction of CRT resistance requires the activation of RACK1-associated Src/Akt/β-catenin signaling. Moreover, upregulated Bcl-2 protein was also observed in cells exhibiting NHE9-induced CRT resistance. A higher NHE9 level was associated with a poor response to CRT and less decrease in T and N stage in ESCC patients. Furthermore, combining either Dasatinib or ABT-737 with CRT significantly reduced tumor volume, and the response to CRT was restored when these inhibitors were used together with CRT in a xenograft nude mouse model with NHE9 overexpression. Taken together, our findings demonstrate that NHE9 can be an effective predictor of CRT response and may be useful in the development of targeted therapies for CRT-resistant ESCC.
    Oncotarget 04/2015; · 6.63 Impact Factor
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    ABSTRACT: The survival rate of esophageal squamous cell cancer (ESCC) patients is still dismal. Therefore, novel prognostic biomarkers are critically needed for patients with ESCC. SLC9A9 has been reported to be downregulated in hormone-sensitive prostate cancer; however, the correlations between SLC9A9 and ESCC prognosis are unclear. The aim of this study is to evaluate the expression and prognostic significance of SLC9A9 in resectable ESCC. Fresh frozen or paraffin-embedded samples were collected from 167 or 59 patients with resectable ESCC, respectively. The expression of SLC9A9 was assessed by reverse transcription and quantitative real-time polymerase chain reaction analysis (167 patients) and immunohistochemistry (61 patients). The expression of SLC9A9 was not associated with patient clinicopathological characteristics at both transcription and protein levels. The 5-year overall survival in the high SLC9A9 messenger RNA (mRNA) group (n = 106) was poorer than that in the low expression group (n = 61) (34.6 vs. 65.9 %, P < 0.001). Notably, higher SLC9A9 protein expression was also correlated with lower 5-year overall survival (33.1 vs. 66.5 %, P = 0.023). Moreover, multivariate analysis revealed that SLC9A9 mRNA (HR, 2.41; 95 % CI, 1.47-3.97; P = 0.001) and protein (HR, 2.31; 95 %CI, 1.06-5.02; P = 0.034) were independent prognostic factors. In conclusion, the expression of SLC9A9 can be a prognostic predictor for ESCC.
    Tumor Biology 04/2015; DOI:10.1007/s13277-015-3392-4 · 3.61 Impact Factor
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    ABSTRACT: Primary lung cancer is the fourth most frequently diagnosed cancer, but gastric metastasis from lung cancer is extremely rare. Little is known about its clinicopathological features, prognosis and optimal treatment strategy. The present study reports a case of primary lung cancer that metastasized to the stomach and to the best of our knowledge, is the first to identify discordance in epidermal growth factor receptor (EGFR) mutation status between the primary tumor and gastric metastasis. The study also systematically searched the Medline database for similar cases to provide a literature review. Data concerning the clinicopathological features, treatment strategies and outcomes were extracted and analyzed. In total, 22 eligible cases were identified from 16 studies. The average age at presentation was 67.3 years and there was a male predominance of 90.9%. Epigastric pain (45.5%) was the most common chief complaint, followed by melena (22.7%), nausea/vomiting (13.6%) and hematemesis (9.1%). Three patients were asymptomatic. Five patients sought the initial consultation for gastrointestinal symptoms. The median time between the primary lung cancer diagnosis and the confirmation of gastric metastasis was five months. Endoscopically, gastric lesions were described as polypoid masses or volcano-like ulcers, mostly involving the gastric corpus, which were identified in 62.5% of the 16 cases in which information regarding the site of metastasis was available. Gastric metastases were reported from adenocarcinoma, squamous cell carcinoma, small cell lung cancer and pleomorphic carcinoma of the lung. The median survival following comprehensive treatment strategies was four months, and the one-year post-metastasis survival rate was 35.3%. In conclusion, although primary lung cancer metastasis to the stomach is rare, clinicians should be aware of the possibility of its occurrence. Comprehensive and personalized treatment may be beneficial to patients. EGFR tyrosine-kinase inhibitor therapy may be the treatment of choice for non-small cell lung carcinoma patients harboring an activating EGFR mutation in the metastatic lesion.
    Oncology letters 03/2015; 9(3):1373-1379. DOI:10.3892/ol.2014.2830 · 0.99 Impact Factor
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    ABSTRACT: Backgroud and objectivesHealth-related quality of life (HRQL) is of great importance in cancer management. The aim was to identify factors that influence postoperative HRQL in esophageal carcinoma patients.MethodsA prospective cohort study was conducted to enroll 196 patients with esophageal carcinoma from November 2012 to June 2013. Sociademographic and clinicopathological parameters were recorded in detail. EORTC-QLQ C30 and ES18 were used to assess HRQL before surgery, at discharge, 1 and 6 months after discharge. Logistic regression models were used to identify factors independently influencing quality of life at 6 months after discharge.ResultsHRQL dramatically decreased after esophagectomy, but restored within 6 months in the most scales. Multivariate logistic regression analysis showed that gender (P = 0.002) and anastomotic stricture (P = 0.001) were the independent predictors of poor global quality-of-life 6 months after discharge. Anastomotic stricture occurred in 22 patients (11.2%), and their performance in social function (P = 0.04), problems with eating (P = 0.006), choking when swallowing (P < 0.001) were significantly poorer at 6 months after discharge. There were not significant differences in global quality-of-life between patients with and without anastomotic leakage at three postoperative assessments.Conclusions Postoperative HRQL is restored within 6 months after discharge. Occurrence of anastomotic stricture significantly decreases HRQL after esophagectomy. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 11/2014; 111(4). DOI:10.1002/jso.23837 · 2.84 Impact Factor
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    ABSTRACT: Alcohol is a well-established cause of esophageal carcinoma, but its effect on survival is little known and contradictory. To clarify whether drinking is an independent predictor of survival in esophageal carcinoma, 2151 Chinese patients, receiving surgical resection from January 1997 to December 2008, were followed until March 2014. Cox proportional hazards analysis was applied to evaluate the prognostic effect of alcohol consumption. The median follow-up was 64 months. The median overall survival (42 months) and disease-free survival (33 months) for never-drinkers were significantly higher than ever-drinkers (27 and 22 months, respectively). In the multivariate Cox model that was adjusted for age, weight loss, AJCC stage, radicality of surgery, adjuvant treatment, smoking status and gender, the HRs of ever-drinking were 1.22(1.06-1.41, p=0.005) on overall survival, and 1.16(1.01-1.34, p=0.037) on disease-free survival. The hazardous effect on overall and disease-free survival of drinking grew statistically significantly in a dose-dependent manner with increasing amount of alcohol consumption per day (both p value for trend <0.05). The predictive effect of drinking on overall survival (p=0.596) or disease-free survival (p=0.207) was not significant in the subgroup with esophageal adenocarcinoma (n=195). The current study revealed that the survival is shortened, of those patients who consume alcohol before diagnosis of esophageal squamous cell carcinoma, which are not attributable to differences in stage, smoking status and gender. Alcohol control should be emphasized to reduce mortality of esophageal carcinoma, and further outcome studies should include alcohol as potential prognosticator.This article is protected by copyright. All rights reserved.
    Cancer Science 10/2014; 105(12). DOI:10.1111/cas.12552 · 3.53 Impact Factor
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    ABSTRACT: Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare malignancy. Methods: A total of 69 patients with PSC treated at a single institution in southern China with long-term follow-up were evaluated in this study. We analyzed the clinical characteristics, immunohistochemical profiles, epidermal growth factor receptor mutation status, K-RAS mutation status, treatments, and prognosis. Results: PSC mainly occurred in young male patients with a history of smoking. Most patients received multimodality treatments and the majority had early-stage disease. The median survival time was 19.1 months, and the 5-year survival rate was 17.4%. The patients without distant metastasis, with normal or higher body mass index (>=18.5), with normal hemoglobin, with smaller tumor size (<=4 cm), and those who received complete resection had significantly better overall survival (P<0.05). The patients with pleomorphic carcinoma had much worse prognosis. In a Cox regression model, M stage, pathology, and having received a complete resection were independent prognostic factors (P<0.05). Conclusions: PSC is a unique lung malignancy with poor prognosis. Patients receiving complete resection had better prognosis, likely a reflection of early-stage disease. Neither neoadjuvant nor adjuvant chemotherapy improved patient survival for those with early-stage disease. The retrospective design and small sample size limited the generalizability. Future multicenter collaborations may be necessary to determine the optimal treatment.
    American Journal of Clinical Oncology 07/2014; DOI:10.1097/COC.0000000000000101 · 2.61 Impact Factor
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    ABSTRACT: Background Primary lymphoepithelioma-like carcinoma (LELC) of the lung is uncommon in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) targeted therapy has been applied in advanced common NSCLC. Whether EGFR-targeted therapy is also suitable for LELC of the lung remains unclear. As we know, EGFR gene mutation is a predictive factor. Therefore, EGFR gene mutations in exons 19 and 21 in Chinese patients with LELC of the lung were investigated. Methods Clinicopathological information was obtained by a retrospective review of the medical history recorded in the patients' charts. EGFR gene mutations in exons 19 and 21 were analyzed in 32 samples of LELC of the lung by TaqMan real-time polymerase chain reaction (RT-PCR). ResultsEleven (34.4%) of the patients were male and 21 (65.6%) patients female. The mean age at diagnosis was 50.9 years (range, 25–71 years). Seven (21.9%) of the patients were smokers. In situ hybridization for Epstein-Barr virus-encoded small RNAs (EBERs) showed positive signals in all 32 patients. None of the tumors had mutations in exons 19 and 21. EGFR-targeted therapy was used in three patients with advanced disease and one patient with distant recurrence. However, no obvious therapeutic effect was found. Conclusion These data showed that LELC of the lung, a special histological type of lung cancer, lacked EGFR gene mutations in exons 19 and 21, which suggested that there was no opportunity for EGFR-targeted therapy for patients with LELC of the lung.
    Thoracic Cancer 01/2014; 5(1). DOI:10.1111/1759-7714.12060 · 0.65 Impact Factor
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    ABSTRACT: To evaluate the feasibility and safety of recurrent laryngeal nerve (RLN) lymph node (LN) dissection, this study compared the postoperative complications and survival between modern two-field lymphadenectomy (MTL) and modified standard two-field lymphadenectomy (MSTL) by using the propensity score matching method. After generating propensity scores given the covariates of age, sex, tumor length, tumor location, tumor grade, and clinical stage, 254 patients with MTL were matched to 254 MSTL patients using the nearest available score matching. The LNs resected during MSTL were paraesophageal and preparatracheal LNs in the upper mediastinum, in addition to those resected during standard two-field lymphadenectomy. RLN LNs were those most commonly affected by nodal metastasis in our series (26 %). Metastasis in RLN LNs was found in around 35, 25, and 20 % of patients with cancer in the upper, middle, and lower thoracic esophagus, respectively. LN metastasis was confined to the RLN region in 49 patients. Even 35 % of patients with pT1 tumors had positive RLN LNs. MTL increased the mean number of resected LNs when compared to MSTL (29 vs.15; p < 0.001). Recurrence was more frequent in those assigned MSTL than those assigned MTL (p < 0.001). The 5-year overall survival (OS) and disease-free survival (DFS) rate for MTL were 50.7 and 42 % compared to 35.3 and 28.2 % for MSTL (both p < 0.001), respectively. Postoperative complications were more frequent following MTL when compared to the MSTL. However, no statistically significant difference in postoperative complications was observed between the two groups. Adding the removal of RLN LNs might improve OS and DFS with acceptable morbidity for patients with ESCC.
    Journal of Gastrointestinal Surgery 11/2013; 18(1). DOI:10.1007/s11605-013-2411-2 · 2.39 Impact Factor
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    ABSTRACT: Background The purpose of this study is to investigate the ability of the 7th edition of the American Joint Committee on Cancer tumor-nodes-metastasis (AJCC/TNM) staging system to distinguish between patients at higher risk and to predict the overall survival in patients who underwent surgical resection for esophageal squamous cell carcinoma (ESCC). Methods Between 1998 and 2008, 560 patients with ESCC underwent R0 tri-incisional esophagectomy at our center without neoadjuvant or adjuvant therapy. We performed univariate and multivariate analyses to identify prognostic factors for survival. ResultsThe five-year overall survival rate was 44.1%, with a median survival of 44 months. Gender, pT status, pN status, and the retrieved lymph nodes (LNs) category (<15 vs. ≥15) were found to be significant prognostic factors, whereas histology grade and tumor location were not significant prognostic factors in our analysis. When classified as all eight sub-stages, there were similar survival curves between stages IB and IIA (P = 0.799), and stages IIIC and IV (P = 0.635). Multivariate Cox proportional hazard regression analysis indicated that gender, pT category, pN category, and the retrieved LNs category (<15 vs. ≥15) were significantly associated with patient survival. Conclusion The 7th edition AJCC staging system proposed a new descriptor for “N” classification. Further stratification of pN status according to number of positive LNs in the 7th edition is valuable. However, we did not find tumor location and histology grade were significant prognostic factors. Moreover, adding a substantially higher threshold of LNs retrieved in the next revision of the AJCC/TNM staging system for ESCC may be more valuable.
    Thoracic Cancer 11/2013; 4(4). DOI:10.1111/1759-7714.12039 · 0.65 Impact Factor
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    ABSTRACT: To assess the therapeutic outcome and failure pattern of three-dimensional conformal radiotherapy (3D-CRT)-based concurrent chemoradiotherapy (CCRT) for recurrence of esophageal squamous cell carcinoma (SCC) after radical surgery. Treatment outcome and failure pattern were retrospectively evaluated in 83 patients with localized cervical and thoracic recurrences after radical surgery for thoracic esophageal SCC. All patients were treated with 3DCRT-based CCRT (median radiation dose 60Gy), in which 39 received concurrent cisplatin plus 5-fluorouracil (PF), and 44 received concurrent docetaxel plus cisplatin (TP). Treatment response was evaluated at 1--3 months after CCRT. With a median follow-up of 34 months (range, 2--116 months), the 3-year overall survival (OS) of all the patients was 51.8% and the median OS time was 43.0 months. The overall tumor response rate was 75.9% (63/83), with a complete remission (CR) rate of 44.6% (37/83). In univariate analysis, tumor response after CCRT (p = 0.000), recurrence site (p = 0.028) and concurrent chemotherapy (p = 0.090) showed a trend favoring better OS. Multivariate analysis revealed that tumor response after CCRT (p = 0.000) and concurrent chemotherapy (p = 0.010) were independent predictors of OS. Forty-seven patients had progressive diseases after CCRT, 27 had local failure (27/47, 57.4%), 18 had distant metastasis (18/47, 38.3%) and 2 had both local and distant failures (2/47, 4.3%). 3DCRT-based CCRT is effective in postoperatively recurrent esophageal SCC. Patients that obtained complete remission after CCRT appeared to achieve long-term OS and might benefit from concurrent TP regimen. Local and distant failures remained high and prospective studies are needed to validate these factors.
    Radiation Oncology 10/2013; 8(1):241. DOI:10.1186/1748-717X-8-241 · 2.36 Impact Factor
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    ABSTRACT: BACKGROUND: The 7th edition of the American Joint Committee on Cancer (AJCC) cancer staging manual incorporates tumor grade and location for staging pT2-3N0M0 esophageal squamous cell carcinoma. Patients with pT3N0M0, classified as stage IIa according to the 6th edition of the AJCC cancer staging manual, can now be classified as stage Ib, IIa, or IIb. We aimed to discuss whether these changes affect survival and determine other potential prognostic factors. METHODS: We retrospectively analyzed 302 patients with postoperative pathologic stage T3N0M0 who underwent esophagectomy between 1990 and 2005 at Sun Yat-sen University Cancer Center. We performed univariate and multivariate analyses to identify prognostic factors for survival and used the Kaplan-Meier method to compare survival difference in each prognostic factor, including tumor grade and location. RESULTS: The 5-year overall survival rate was 46 %, with a median survival of 1,244.5 days. Gender, age, alcohol consumption, forced expiratory volume in 1 s (FEV1), and number of removed lymph nodes were independent prognostic factors in both univariate and multivariate analyses. Smoking was also a prognostic factor in survival analysis by the Kaplan-Meier method. However, histologic tumor grade and location had no significant influence on patient survival. CONCLUSIONS: Age, gender, alcohol consumption, FEV1, number of removed lymph nodes, and cigarette smoking are independent prognostic factors in patients with pT3N0M0 esophageal squamous cell carcinoma. However, tumor grade and location may not be as strong predictors in these patients as indicated in the 7th edition of the AJCC cancer staging manual.
    Annals of Surgical Oncology 09/2012; 20(2). DOI:10.1245/s10434-012-2656-0 · 3.94 Impact Factor
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    ABSTRACT: Smoking is well known as a risk factor for esophageal cancer, but controversial as a prognostic factor. Moreover, evidence is scarce that a dose-response relationship exists. We conducted a retrospective study on the effect and dose-response relationship of prediagnostic smoking on the postoperative disease-specific survival of patients with lymph node-negative esophageal squamous cell carcinoma (ESCC). We enrolled 643 patients with lymph node-negative ESCC who had undergone esophagectomy between 1990 and 2005 at the Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China. The patients' demographic, pathological, preoperative and cancer outcome data were obtained from medical records. These data were reviewed and analyzed using life table, Kaplan-Meier analysis and multivariate Cox regression. A significant reduction in 3- and 5-year survival rates was observed in smokers with lymph node-negative ESCC compared with those in non-smokers. The 3- and 5-year survival rates were 54% and 46% for smokers, and 67% and 64% for non-drinkers, respectively (P < 0.05). Multivariate Cox analysis revealed that smoking was an independent prognostic factor (P = 0.008, hazard ratio = 1.404). Both log-rank test (P = 0.065) and multivariate analysis (P = 0.091) showed no significant difference between the survival rates of light and heavy smokers. Prediagnostic smoking is an independent prognostic factor for patients with lymph node-negative ESCC, but the dose-response relationship needs further investigation.
    Cancer Science 08/2012; 103(11). DOI:10.1111/cas.12000 · 3.53 Impact Factor
  • Jingeng Liu · Dongping Rao · Jianhua Fu
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 06/2012; 42(4):759-60. DOI:10.1093/ejcts/ezs234 · 2.81 Impact Factor
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    ABSTRACT: OBJECTIVES; The demographic and clinicopathologic factors associated with 5-year survivors have not been well documented in oesophageal squamous cell carcinoma (OSCC). We evaluated factors predictive of actual 5-year survival in the present research. We analysed 1241 patients underwent oesophagectomy for invasive OSCC retrospectively. The demographic and clinicopathologic characteristics were compared between patients who were alive >5 years after oesophagectomy and patients who died within 5 years of oesophagectomy. Univariate analysis showed significant differences between the two groups regarding 11 different factors. Further analysis by logistic regression showed that eight factors were identified as independent predictors of actual 5-year survival. The independent positive predictors for actual 5-year survival are younger patients, female gender, absence of weight loss, R0 resection, lower pathological T stage, lower pathological N stage, higher histologic grade and more resected lymph nodes.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 12/2011; 41(3):e7-11. DOI:10.1093/ejcts/ezr240 · 2.81 Impact Factor
  • Jingeng Liu · Yi Hu · Xuan Xie · Jianhua Fu
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    ABSTRACT: Subcarinal node metastasis is common in patients with esophageal cancer. Some scholars have suggested that subcarinal nodes might not need to be sampled or dissected in patients with superficial squamous cell carcinoma of the thoracic esophagus. This research investigated the frequency of subcarinal node metastasis in patients with esophageal squamous cell carcinoma, identified the factors correlated to subcarinal node metastasis, and evaluated the clinical relevance of subcarinal node metastasis in thoracic esophageal squamous cell carcinoma. We retrospectively analyzed the clinical data of 1,812 consecutive patients with thoracic esophageal squamous cell carcinoma who underwent esophagectomy in the Cancer Center of Sun Yat-sen University. The surgical procedures included the left transthoracic procedure, Ivor-Lewis approach, and the cervical-thoracoabdominal procedure. The frequency of subcarinal node metastasis was 10.0%. The univariate and multivariate analysis showed that longer tumor length, higher pathologic T stage, lower histologic grade, and positive lymph node metastases of other groups were associated with a higher frequency of subcarinal node metastasis (all p<0.05). Patients with solitary subcarinal node metastasis had a significantly lower 5-year cumulative survival rate than those with solitary paraesophageal node metastasis (25.3% vs 39.6%, p<0.05). Longer tumor length, higher pathologic T stage, lower histologic grade, and positive lymph node metastases of other groups are associated with a higher frequency of subcarinal node metastasis. Subcarinal node metastasis indicates worse prognosis of patients with thoracic esophageal squamous cell carcinoma compared with paraesophageal node metastasis.
    The Annals of thoracic surgery 12/2011; 93(2):423-7. DOI:10.1016/j.athoracsur.2011.10.011 · 3.65 Impact Factor
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    ABSTRACT: The use of metal stents for malignant esophageal strictures for palliation is well accepted. However, utilization of metal stents for benign esophageal diseases has been controversial. Given the availability of removable, fully covered, self-expandable metal stents (RFCSEMSs), this study was undertaken to evaluate the effectiveness and safety of RFCSEMSs in patients with refractory benign esophagogastric anastomotic strictures. Twenty-four patients with RFCSEMSs were enrolled in this study. All patients had undergone endoscopic Savary-Gilliard bougie dilatation five times or more but there was no significant improvement in symptoms. For all 24 patients, the symptom of dysphagia was alleviated significantly while the stent was in place and for a short time after stent removal, and dysphagia scores decreased from 3-4 to 0-1. After 12 months of follow-up, 18 patients were free from dysphagia but the other 6 patients still suffered obvious dysphagia. RFCSEMSs are still not perfect and can induce some complications. The treatment failure rate of restenting was remarkably high after the first failure. Given that effective methods for treating refractory stricture have not been found, RFCSEMSs could be considered for treating refractory benign esophagogastric anastomotic stricture.
    Dysphagia 08/2011; 27(2):260-4. DOI:10.1007/s00455-011-9361-1 · 1.60 Impact Factor
  • Kenneth K W To · Le Yu · Shuwen Liu · Jianhua Fu · Chi Hin Cho
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    ABSTRACT: Esophageal squamous cell carcinoma (ESCC) is a highly malignant disease that is generally not responding to chemotherapy. It is particularly predominant in China. Although ESCC is significantly associated with cigarette smoking, the relationship between its molecular pathogenesis and responsiveness to chemotherapy and cigarette smoke remains elusive. This study reported the constitutive activation of aryl hydrocarbon receptor (AhR), leading to ABCG2 upregulation and the multidrug resistance (MDR) phenotype, in ESCC cell lines with acquired cisplatin resistance. Reporter gene assay, chromatin immunoprecipitation analysis and specific gene knockdown confirmed that the enhanced AhR binding to a xenobiotic response element (XRE) within the ABCG2 promoter is responsible for ABCG2 overexpression. A HSP90 inhibitor (17-AAG) and two AhR antagonists (kaempferol and salicylamide) were shown to inhibit ABCG2 upregulation, thereby reversing the ABCG2-mediated MDR. Our data therefore advocate the use of these inhibitors as novel chemosensitizers for the treatment of esophageal cancer.
    Molecular Carcinogenesis 06/2011; 51(6):449-64. DOI:10.1002/mc.20810 · 4.77 Impact Factor
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    Xi Lin · Jianwei Wang · Feng Han · Jianhua Fu · Anhua Li
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    ABSTRACT: This study aims to evaluate the clinical utility of automated breast volume scanner (ABVS) against handheld ultrasound in detecting and diagnosing breast lesions. Eighty-one patients were subjected to both automated breast volume scanner and handheld ultrasound examination in the supine position. The number of lesions detected and the average scanning time (both device-specific and user-specific) for each device were compared. The diagnostic accuracy, sensitivity and specificity were calculated for each method. The maximum diameters of the lesions based on handheld ultrasound and ABVS were compared with the final pathological sizes. Of the 81 patients, both automated breast volume scanner and handheld ultrasound detected 95 breast lesions. Compared with the pathological diagnosis in 35 lesions, both ABVS and handheld ultrasound exhibited high sensitivity (both 100%) and high specificity (95.0%, and 85.0%, respectively). In addition, ABVS had a higher diagnostic accuracy (97.1%) than handheld ultrasound (91.4%) for breast neoplasms. More importantly, ABVS was capable of displaying the retraction phenomenon in coronal plane. All the invasive ductal carcinomas (12 lesions) presented the retraction phenomenon. In contrast, intraductal carcinomas (3 lesions) and benign lesions did not display such features. Thus, retraction phenomenon had a high specificity (100.0%) and high sensitivity (80.0%) in detecting breast cancer while it also had high accuracy (91.4%) in determining malignant from benign lesions. There was no significant difference in maximum diameters of pathology, 2D and ABVS (p>0.05), however the correlation coefficient revealed that ABVS had better correlation with pathology (r=0.616) than 2D (r=0.468). The user scanning time for the ABVS demonstrated no difference between two examiners (11.7 ± 1.3 min and 12.1 ± 1.4 min; p>0.05). However, device-specific scanning time was longer for ABVS than handheld ultrasound (11.9 ± 1.4 min vs. 6.8 ± 1.1 min, respectively; p<0.01). Automated breast volume scanner provides advantages of high diagnostic accuracy, better lesion size prediction, operator-independence and visualization of the whole breast. It is a promising modality in breast imaging.
    European journal of radiology 03/2011; 81(5):873-8. DOI:10.1016/j.ejrad.2011.02.038 · 2.16 Impact Factor

Publication Stats

108 Citations
67.10 Total Impact Points

Institutions

  • 2005–2015
    • Sun Yat-Sen University Cancer Center
      • Department of Radiation Oncology
      Shengcheng, Guangdong, China
  • 2010–2014
    • Sun Yat-Sen University
      • Department of Thoracic Surgery
      Shengcheng, Guangdong, China
  • 2002
    • Sun Yat-Sen University of Medical Sciences
      • Cancer Center
      Guangzhou, Guangdong Sheng, China