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Han H.-B.,Beijing Cancer Hospital and Institute | Gu J.,Peking University | Zuo H.-J.,Beijing Cancer Hospital and Institute | Chen Z.-G.,Peking University | And 5 more authors.
Journal of Pathology | Year: 2012

Accumulating evidence shows that microRNAs, functioning as either oncogenes or tumour suppressors by negatively regulating downstream target genes that are actively involved in tumour initiation and progression, may be promising biomarkers and therapy targets. Data mining through a microRNA chip database indicated that let-7c may be associated with tumour metastasis. Here, we confirmed that down-regulation of let-7c in primary cancer tissues was significantly associated with metastases, advanced TNM stages and poor survival of colorectal cancer patients. Moreover, ectopic expression of let-7c in a highly metastatic Lovo cell line remarkably suppressed cell migration and invasion in vitro by the down-regulation of K-RAS, MMP11 and PBX3, as well as tumour growth and metastases in vivo, whereas inhibition of let-7c in low-metastatic HT29 cells increased cell motility and invasion by the enhanced gene expression of K-RAS, MMP11 and PBX3. Interestingly, the luciferase reporters' activities with the 3′-UTRs of K-RAS, MMP11 and PBX3 were inhibited significantly by let-7c. Importantly, rescue experiments involving the over-expression of these genes without their 3′-UTRs completely reversed the effects of let-7c on tumour metastasis, both in vitro and in vivo. Finally, the levels of let-7c were inversely correlated with those of MMP11 and PBX3, but not with those of K-RAS. Taken together, these results demonstrate that let-7c, apart from its tumour growth suppression role, also functions as a tumour metastasis suppressor in colorectal cancer by directly destabilizing the mRNAs of MMP11 and PBX3 at least. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Zhang L.,Peking University | Lu Y.,Peking University | Fang Y.,Beijing Cancer Hospital and Institute
British Journal of Nutrition | Year: 2014

The scored Patient-Generated Subjective Global Assessment (PG-SGA) is considered to be the most appropriate tool for detecting malnutrition in cancer patients. In particular, malignant tumours derived from the gastrointestinal tract may impair nutrient intake and absorption and cause malnutrition. We carried out a cross-sectional study to assess the nutritional status and related factors of patients with gastrointestinal cancer. Nutritional status was determined using the scored PG-SGA in patients (n 498) with advanced gastrointestinal cancer admitted to the Gastrointestinal Medical Oncology Unit at Beijing Cancer Hospital between 1 August 2012 and 28 February 2013. The possible related factors including age, sex, hospitalisation frequency and pathology were explored. We found that 98 % of the patients required nutrition intervention and 54 % of the patients required improved nutrition-related symptom management and/or urgent nutritional support (PG-SGA score ≥ 9). Factors related to malnutrition were age (r 0.103, P< 0.01), hospitalisation frequency (r - 0.196, P< 0.01) and sex (the prevalence of malnutrition was higher in men than in women (9.88 v. 8.54, P< 0.01)). Patients with rectal cancer had a lower risk of malnutrition than patients with other types of gastrointestinal cancer (F= 35.895, P< 0.01). More attention should be paid to the nutritional status of gastrointestinal patients, especially those at a higher risk of malnutrition, such as elderly patients, those hospitalised for the first time, male patients and those with other types of gastrointestinal cancer except rectal cancer. The nutritional status of these patients should be evaluated and they should be given proper nutrition education and nutritional support in a timely manner. © The Authors 2013.


Li J.,Beijing Cancer Hospital and Institute | Gong J.F.,Beijing Cancer Hospital and Institute | Wu A.W.,Peking University | Shen L.,Beijing Cancer Hospital and Institute
European Journal of Surgical Oncology | Year: 2011

Aims: This study aims to determine whether adjuvant treatment with imatinib improves recurrence-free survival (RFS) in Chinese patients undergoing complete resection of localized primary gastrointestinal stromal tumor (GIST) compared with those not receiving adjuvant therapy. We also sought a correlation between c-KIT mutations and RFS. Methods: Patients who had undergone complete tumor resection with intermediate or high risk of recurrence were enrolled in a single-center, non-randomized, prospective study. Patients either received adjuvant imatinib therapy (400 mg once-daily) for 3 years or did not. Mutation analyses of c-KIT were performed on available archival tumor samples. Results: 105 patients were enrolled: 56 in the treatment group and 49 in the control group. Median follow-up was 45(43.1-46.9) months. RFS at 1, 2 and 3 years were higher in the treatment group than in the control group (100% vs. 90% at 1 year; 96% vs. 57% at 2 years; 89% versus 48% at 3 years, P < 0.001, HR = 0.188). Subgroup analyses showed that adjuvant therapy significantly decreased the risk of recurrence in patients whether at high risk or at intermediate risk compared with control patients (3-year RFS: 95% vs. 72%, in intermediate risk; 85% versus 31% in high risk; P < 0.001). In addition, imatinib adjuvant treatment decreased the risk of death (P = 0.039, HR = 0.254). Conclusions: Adjuvant imatinib can improve 1-, 2- and 3-year RFS rates in patients at intermediate or high risk of recurrence after complete tumor resection. © 2010 Elsevier B.V. All rights reserved.


Li J.-L.,Peking University | Ji J.-F.,Beijing Cancer Hospital and Institute | Cai Y.,Peking University | Li X.-F.,Peking University | And 8 more authors.
Radiotherapy and Oncology | Year: 2012

Purpose: We aimed to assess the safety and efficacy of preoperative intensity-modulated radiotherapy (IMRT) with oral capecitabine in patients with locally advanced mid-low rectal cancer using a concomitant boost technique. Materials and methods: Patients with resectable locally advanced mid-low rectal cancer (node-negative ≥T3 or any node-positive tumor) were eligible. The eligible patients received IMRT to 2 dose levels simultaneously (50.6 and 41.8 Gy in 22 fractions) with concurrent capecitabine 825 mg/m 2 twice daily 5 days/week. The primary end point included toxicity, postoperative complication, and pathological complete response rate (ypCR). The secondary endpoints included local recurrence rate, progression-free survival (PFS), and overall survival (OS). Results: Sixty-three eligible patients were enrolled; five patients did not undergo surgery. Of the 58 patients evaluable for pathologic response, the ypCR rate was 31.0% (95% CI 19.1-42.9). Grade 3 toxicities included diarrhea (9.5%), radiation dermatitis (3.2%), and neutropenia (1.6%). There was no Grade 4 toxicity reported. Four (6.9%) patients developed postoperative complications. Two-year local recurrence rate, PFS, and OS were 5.7%, 90.5%, and 96.0%, respectively. Conclusions: The design of preoperative concurrent boost IMRT with oral capecitabine could achieve high rate of ypCR with an acceptable toxicity profile. © 2011 Elsevier Ireland Ltd. All rights reserved.


Liu F.,Tsinghua University | Zhang J.,Beijing Cancer Hospital and Institute | Deng Y.,Tsinghua University | Wang D.,Tsinghua University | And 2 more authors.
Sensors and Actuators, B: Chemical | Year: 2011

Label-free and real-time information acquisition of molecular phenotype and its function on living cells plays a significant role in disease diagnosis and drug development. In this paper, SPR phase sensing was applied to monitor the interactions between EGFR antibody, EGFR1, and membrane proteins EGFR on living human gastric cancer BGC823 cells. When 50 μg/mL EGFR1 was added onto the fixed cells chip and the living cells chip, a significant difference in the binding amount could be observed from the immunofluorescence images. Quantitative results were obtained by following SPR detection, which were 722 RU and 438 RU, respectively. On the same living cells chip, SPR detection also showed markedly different results of cellular responses when it was stimulated by EGFR1 at different concentrations, such as adhesion and/or morphology variation, revealing the EGFR1's cytotoxic effect on the BGC823 cells. The results demonstrate SPR phase sensing is capable of real-time detection of molecular interactions and cellular responses on living cells, and suggest that further studies on the mechanism and the technique may allow SPR sensing become a powerful tool not only for the basic research of cell biology, but also for medical diagnosis and drug development. © 2010 Elsevier B.V. All rights reserved.


Liu X.,Capital Medical University | Wan X.,Capital Medical University | Li Z.,Beijing Cancer Hospital and Institute | Lin C.,Hotgen Biotechnology Co. | And 2 more authors.
Clinical Chemistry and Laboratory Medicine | Year: 2011

Background: This study was performed to quantify the expression of Golgi protein-73 (GP73) in healthy controls and in patients with liver disease, and to evaluate the correlations between GP73 and other serum markers in different liver diseases. Methods: Serum GP73 was measured in 478 healthy controls and 296 patients with different types of liver disease. Quantitative hepatitis B virus (HBV) DNA was determined in two chronic hepatitis B (CHB) groups. Other serum liver fibrosis markers were measured in the liver fibrosis group and α-fetoprotein (AFP) was measured in hepatocellular carcinoma (HCC) group. The correlations between GP73 and these markers were evaluated. Results: The GP73 value in hepatitis B e antigen (HBeAg)-positive CHB group, HBeAg-negative CHB group, liver fibrosis group and HCC group was significantly higher (p<0.001) than that in healthy controls. GP73 showed significant correlation with other markers in the liver fibrosis group and with AFP in the HCC group. Conclusions: Compared with healthy controls, GP73 in patients with liver disease was significantly increased. With the progression of liver disease, GP73 showed a significantly increasing trend. These results suggest that GP73 might be used as a serum marker for the diagnosis of liver diseases and for monitoring disease progression. © 2011 by Walter de Gruyter Berlin Boston 2011.


Ma J.,Shandong University | Zhang J.,Shandong University | Ning T.,Beijing Cancer Hospital and Institute | Chen Z.,Shandong University | Xu C.,Shandong University
Journal of Human Genetics | Year: 2012

Genetic variations in MDM2, PTEN and P53 might be involved in cancer susceptibility. To assess the contribution of polymorphisms in these three genes to the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese population, we genotyped MDM2 T309G, Del1518, PTEN rs701848, rs2735343 and P53 Arg72Pro polymorphisms using PCR-restriction fragment length polymorphism analysis in 226 ESCC cases and 226 cancer-free controls. Here we showed that the risk of ESCC was elevated in subjects with any of the variant genotypes of PTEN rs2735343 and P53 Arg72Pro polymorphisms, but not any genotype of MDM2 or PTEN rs701848. Moreover, multiplicative interactions were observed between PTEN rs2735343 and P53 Arg72Pro or smoking status on risk of ESCC. Our study firstly indicated that PTEN rs2735343 might be a susceptibility factor for ESCC and reaffirmed the role of P53 Arg72Pro in ESCC in this Chinese population, but did not replicate the positive association between MDM2 T309G and ESCC found previously. © 2012 The Japan Society of Human Genetics All rights reserved.


Chen Z.,Beijing Cancer Hospital and Institute | Li M.,Beijing Cancer Hospital and Institute | Yuan Y.,Beijing Cancer Hospital and Institute | Wang Q.,Beijing Cancer Hospital and Institute | And 2 more authors.
Diseases of the Colon and Rectum | Year: 2010

Purpose: Accumulating evidence suggests that cancer/testis antigens may serve as indicators of tumor malignant phenotype. The purpose of this study is to evaluate cancer/testis antigen genes in predicting metastasis of colorectal cancer to the liver. Methods: The expression levels of 25 cancer/testis antigen genes were determined by reverse-transcription polymerase chain reaction in 288 colorectal cancer tissue samples from the primary tumor or liver metastasis. Pearson x2 and multiple logistic regression analyses were performed to assess the association between risk factors and probability of liver metastasis of colorectal cancer. Results: No significant difference was detected between the primary tumor and liver metastasis in expression pattern of cancer/testis antigen genes in colorectal cancer tissue samples. However, 3 cancer/testis antigen genes (PAGE4, SCP-1, and SPANX) and 3 clinicopathologic parameters (lymph node involvement, vessel cancer embolus, and tumor invasion depth) correlated significantly with liver metastasis of colorectal cancer (P <.05). A logistic regression model was constructed for prediction of liver metastasis based on a panel consisting of PAGE4, lymph node involvement, and presence or absence of vessel cancer embolus. The predicted risk of liver metastasis based on the panel was consistent with the actual risk observed. The probability of developing liver metastasis as estimated by the panel was 86.9% when all 3 factors were positive, representing an up to 20% improvement in the prediction level compared with the classic methods of lymph node involvement and vessel cancer embolus. Conclusions: A new predictive panel including PAGE4 expression may help predict liver metastasis of colorectal cancer. © 2009 The ASCRS.


Li H.,Beijing Cancer Hospital and Institute
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2012

Esophageal cancer (EC) is one of the common malignant tumors in China. Esophagectomy based on multi-disciplinary principle improves the quality of life and survival of esophageal cancer patients, but a lot of patients will suffer recurrence or metastasis after surgery. TNM stage is the most important factor which affects the prognosis of patients with esophageal cancer. Besides, there are other prognostic factors, such as abnormal expression of the proteins. Exploration of these proteins may provide new clues to improve prognosis in esophageal squamous cell cancer (ESCC). We reviewed the literatures related to abnormal protein expression in ESCC, and tried to elucidate the prognostic value and potential clinical application of these proteins in ESCC.


Ma S.H.,Beijing Cancer Hospital and Institute
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2012

To evaluate the long-term survival of multidisciplinary treatment based on thoracic surgery for cervical esophageal squamous cell carcinoma. The clinical characters and follow-up data of forty-one cervical esophageal cancer patients who accepted multidisciplinary treatment based on surgery with preservation of pharynx and larynx were retrospectively reviewed, and the long-term survival was compared with 480 non-cervical esophageal cancers who accepted surgery in the same period done by the same surgical team. There were 28 males and 13 females with a mean age of 62 years old. In the cervical esophageal cancer group, 30 patients accepted neoadjuvant chemotherapy, 25 patients accepted adjuvant chemotherapy, and 21 patients accepted both. Six patients received postoperative radiation. Four patients underwent exploratory surgery alone, and 37 cases underwent radical surgery and cervical anastomosis. One case died during the perioperative period. The 1-, 3-, 5- and 8-year survival rates were 96.8%, 52.6%, 35.1%, and 35.1% in the 36 patients with cervical esophageal cancer who underwent radical surgery, and were 85.0%, 54.3%, 45.0%, and 36.7% respectively in the 457 non-cervical esophageal cancer patients. There was no significant difference between the cervical group and non-cervical group(P=0.91). Cervical esophageal cancer should be treated in a multidisciplinary approach to obtain satisfactory long-term outcomes.

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