Purpose:To investigate genetically a diagnostic method of occult metastasis of lymph node in patients with squamous cell carcinoma of the esophagus.Methods:Using assays of reverse transcriptase polymerase chain reaction technique (RT PCR), MUC1 gene mRNA in thirty negative and thirty positive control lymph nodes was detected to evaluate diagnostic sensitivity and specificity. Eighty seven negative regional lymph nodes by conventional histologic examination (pN 0 ) from thirty patients with esophageal carcinoma were studied to detect MUC1 gene mRNA to diagnose lymph node occult metastasis.Results:MUC1 mRNA was not identified in any specimen of negative control group (specificity =100%); MUC1 mRNA was identified in twenty five of positive control specimen (sensitivity =83%). MUC1mRNA was identified in nine lymph nodes (10.3%) from eight patients with pN 0 esophageal carcinoma. Conclusions: Nodal occult metastasis could be diagnosed by the detection of expression of MUC1mRNA of lymph node in patients with pN 0 esophageal carcinoma.

Purpose:To investigate the correlation between early postoperative metastasis with occult micrometastasis of mediastinal lymph nodes in patients with stageⅠa non small cell lung carcinoma (NSCLC).Methods:Using RT PCR assay, detection of the expression of MUC1 mRNA was used to diagnose occult micrometastasis in mediastinal lymph nodes. All the patients underwent checked up at least once a year to detect early metastatic lesions after surgery, by means of CT scan of chest and brain, ultrasound examination of liver and adrenal glands, and bone scanning. The patients with and without occult nodal micrometastasis were divided into two different groups. Difference in early metastatic rate between two groups of patients was compared by ? 2 test, and odds ratio (OR) was calculated.Results:Occult nodal micrometastasis was diagnosed in sixteen patients (32.0%). Early metastatic rate (31.25%) in the patients with occult nodal micrometastasis was higher than that (5.88%) in the patients without occult nodal micrometastasis ( P

Objective To investigate the expression of chemokine receptor CCR7 and its correlation with lymph node metastasis and prognosis in esophageal cancer after esophagectomy. Methods One hundred and eighty-four patients with middle third squamous cell carcinoma of the esophagus were enrolled in this study. All patients underwent operation in Provincial Hospital Affiliated to Shandong University between June, 2003 and June, 2005. The expression of CCR7 was detected by immunohistochemistry. All statistic analyses were performed with SPSS 13.0 statistical software. According to the clinico-patho-logic factors, the difference of CCR7 expression was compared by x2 test. Kaplan-meier method was performed to calculate the survival rate, Cox regression multivariate analysis was performed to determine independent prognostic factors. Results The expression rate of CCR7 in stage Ⅰ , stage Ⅱ and stage Ⅲ patients was 25.0 % , 70.3% and 85.5% , respectively. The difference of CCR7 expression between stage Ⅱ and stageⅢ was statistically significant (x2 =5.0, P =0.02). The CCR7 expression rate in T1, T2 and T3 patients was 33.3% , 64.9% and 80.9% , respectively. The difference of CCR7 expression between T2and T3 was statistically significant (x2 =5.4, P =0.01). The level of expression of CCR7 in patients with lymph node metastasis was significantly higher than those without metastasis (x2 =10.8, P = 0.00). The 5-year survival rate instage Ⅰ , stage Ⅱand stage Ⅲ patients was 100.0% , 38. 3% and 22.4% , respectively. The 5-year survival rate in patients with CCR7 overexpression was significantly lower than those without CCR7 overexpression (x2 = 23.7, P = 0.00). The 5-year survival rate in T2, T3, NO and N1 patients with CCR7 overexpression was significantly lower than those without CCR7 overexpression The result of Cox analysis demonstrated that T , N and CCR7 overexpression were independent prognostic factors. Conclusion CCR7 expression was detected in esophageal squamous cell carcinoma and was found to be significantly associated with T stage,N stage and lymph node metastasis. The patients with CCR7 expression was significantly lower the 5-year survival rate than without CCR7 expression. T stage, lymph node metastasis and CCR7 expression were independent prognostic factors.

Objective: To explore the effect of radiotherapy on preventing the recurrence of lymph node metastasis of esophageal cancer after Ivor-Lewis esophagectomy. Methods: Three hundred and sixty-six pa-tients with middle third squamous cell carcinoma of the esophagus were enrolled in this study. All patients un-derwent Ivor-Lewis esophagectomy with two-field lymph node dissection in our hospital between June 1999 and June 2004. All statistical analyses were performed with SPSS 13.0 statistical software. Kaplan-Meier method was performed to calculate the relapse rate. Log-rank test was performed to compare the relapse rate. Cox regression analysis was performed to identify independent prognostic factors for postoperative lymph node metastasis. Results: Of the 366 cases, lymph node metastasis was found in 105 patients (28.5%)within 3 years after surgery, occupying 52.2% (105/201) of total recurrence. Of the 181 patients treated with postoperative radiotherapy, lymph node metastasis was found in 37 patients. The rate of lymph node metasta-sis was 20.4%, significantly lower than that in patients treated with chemotherapy alone and those without sys-temic adjuvant therapy (P<0.05). Chemotherapy was administered in 103 cases and lymph node metastasis was found in 33 patients. The rate of lymph node metastasis was 32.0%, lower than that in patients without systemic adjuvant therapy, but without statistical significance (P=0.17). The results of Cox analysis demon-strated that T stage, lymph node metastasis and postoperative adjuvant radiotherapy were independent prog-nostic factors. Conclusion: Ivor-Lewis esophagectomy for the middle third thoracic esophageal cancer was a safe surgical procedure. Postoperative radiotherapy is helpful for the control of local recurrence. T stage,lymph node metastasis and postoperative adjuvant radiotherapy are independent prognostic factors. Radio-therapy is helpful for preventing the recurrence of lymph node metastasis of esophageal cancer after Ivor-Lew-is esophagectomy.

Objective To investigate the risk factors with lymph node metastatic recurrence in patients with N0 esophageal cancer after Ivor-Lewis Esophagectomy. Methods The subjects were 82 patients with pN0 esophageal cancer who underwent Ivor-Lewis esophagectomy from January 2001 to January 2005. By using RT-PCR, VEGF-C mRNA was detected in tumor issues, and Mucin l( MUC1 )mRNA was detected in lymph nodes. The Kaplan-Meier method was used to calculate the survival rate and lymph nodal metastatic rate. Log-rank test was performed to compare the recurrence rate, and Cox regression multivariate analysis was performed to determine independent prognostic factors. Results VEGF-C mRNA was identified in 42 patients (51.22%), and MUC1 mRNA was identified in 23 patients(28.05% )from at least 1 lymph node station . The diagnosis of lymph node micrometastasis (LNMM) was based on the detection of MUC1 mRNA. The first recurrence exhibiting lymph node metastasis was recognized in 37 patients (45.1%) at the first 3 years after operation and this was significantly associated with T status ( P ＜ 0. 05 ). Lymph node metastatic rate for patients with VEGF-C mRNA expression in tumor issues was significantly higher than that for patients without VEGF-C mRNA expression( P ＜0. 01 ). And lymph node metastatic rate for patients with LNMM was significantly higher than that for patients without LNMM ( P ＜0. 01 ). The results of multivariate analysis confirmed that T status, VEGF-C mRNA expression in tumor issues and LNMM were independent relevant factors. Conclusion Status,VEGF-C mRNA expression in tumor issues and LNMM in patients with N0 esophageal cancer were independent risk factors for 3-year lymph node metastatic recurrence after Ivor-Lewis Esophagectomy.

Objective To investigate the expression of MTA1 protein and its relationship to the prognosis in esophageal cancer after esophagectomy. Methods One hundred and sixty-five patients with middle third squamous cell carcinoma of the esophagus were enrolled in this study. All patients underwent operation in Provincial Hospital Affiliated to Shandong University between January 2002 and January 2004. The expression of MTA1 protein was detected by immunohistochemistry. All statistic analyses were performed with SPSS 10.0 statistical software. According to the clinicopathologic factors, the difference of MTA1 protein expression was compared by x2 test. Kaplan-meier method was performed to calculate the survival rate, Cox regression multivariate analysis was performed to determine independent prognostic factors. Results The 5-year survival rate in Ⅰ stage,Ⅱ stage and Ⅲstage was separately 100.0% 、38.3% and 22.4%, and the MTA1 protein expression rate in Ⅰ stage, Ⅱ stage and Ⅲ stage was separately 25.0% 、30.9% and 57.9%, the difference of MTA1 protein expression between Ⅱ stage and Ⅲ stage was statistically significant ( x2 = 11.6, P = 0. 00). The MTA1 protein expression rate in T1 stage, T2 stage and T3 stage was separately 42.9% 、13.3% and 50%. MTA1 protein expression rate in T2 stage patients and T3 stage patients was separately 13.3% and 50%, the difference of MTA1 protein expression between them was statistically significant (x2 = 13.2, P =0.00). The positive expression of MTA1 protein in patients with lymph node metastasis was significantly higher than those without metastasis ( x2 = 8.2, P = 0.04). The 5-year survival rate in patients with MTA1 protein positive expression was significantly lower than those without MTA1 protein positive expression (P =0.00 ), and the 5-year survival rate in T3 stage patients with MTA1 protein positive expression was significantly lower than those without MTA1 protein positive expression ( P =0.01 ), and the 5-year survival rate in N0 stage patients with MTA1 protein positive expression was significantly lower than those without MTA1 protein positive expression (P = 0.03 ), and the 5-year survival rate in N1 stage patients with MTA1 protein positive expression was significantly lower than those without MTA1 protein positive expression ( P =0.04). However, the 5-year survival rate in T2 stage patients with MTA1 protein positive expression was not significantly lower than those without MTA1 protein positive expression (P =0.20). The result of Cox analysis demonstrated that N stage and MTA1 protein positive expression were independent prognostic factors. Conclusion MTA1 protein overexpression was detected in esophageal squamous cell carcinoma and was found to be significantly associated with T stage and lymph node metastasis. The patients with MTA1 protein overexpression was significantly lower the 5-year survival rate than without MTA1 protein expression. Lymph node metastasis and MTA1 protein overexpression were independent prognostic factors.

Objective: To diagnose occult micrometastasis of mediastinal lymph node in patients with non small cell lung cancer (NSCLC) and to evaluate its prognostic significance. Methods: Using assays of reverse transcriptase polymerase chain reaction (RT PCR), two hundred and forty two stations of mediastinal lymph node, which were free from tumor determined by routine histopathological examination (pN 0), from fifty eight patients were studied to detect mRNA for MUC1 gene and diagnose nodal occult micrometastasis. Survival rate was calculated by method of Kaplan Meier and survival difference between patients with and without nodal occult micrometastasis was compared with Log Rank test; Logistic regression analysis was carried to determined independent predictive factors of prognosis. Results: The mRNA for MUC1 gene was identified in twenty three stations of lymph node from sixteen patients (27 6%), and nodal occult micrometastasis was diagnosed in those patients. TNM staging for those patients was up regulated from stage I A～II B to stage III A. The survival rate of 3 year in patients with nodal occult micrometastasis (43.7%) was lower than that in patients without nodal occult micrometastasis (73.8%) (P

Objective To study the dose-and time-effects of X-ray irradiation on the expression of Pokemon gene in A549 cells of human lung adenocarcinoma.Methods A549 cells were cultured in vitro and exposed to X-rays with the doses of 2,4,6 and 8 Gy,respectively.Untreated A549 cells were used as control group.The relative levels of Pokemon mRNA expression in the cells were detected by using quantitative real-time PCR at 2,4,8,12,24,48 and 72 h after irradiation.Results The Pokemon mRNA expression levels decreased in the early period after irradiation(except 2 and 4 h after irradiation in 2 Gy group)and then increased in the later stage(48 h after irradiation)with significant statistical differences at the most time points in comparison with the control group(t=3.40-154.76,P<0.05).Conclusions Higher doses of X-rays may degrade the expression of Pokemon mRNA in the human A549 cells and induce apoptosis in the early period,hut also may upgrade its expression in the later period, which might be correlated with the cell cycle regulation and DNA damage repair in the A549 cells.

Anthocyanins are a ubiquitous group of water-soluble plant pigments of the flavonoid family, with anticancer property through HER-2 signaling pathway. Nowadays, molecular docking plays an important role in exposing the active sites and obtaining the bioactive conformation involving protein-ligand interactions. According to the crystal structure of HER-2 kinase domain and 12 main antitumor compounds of anthocyanins as well as ATP, a molecular docking study was performed by MVD program. All 12 compounds could bind to the same cavity of HER-2 kinase domain by high affinity (MolDock Score < -105 kJ/mol for anthocyanidins, < -130 kJ/mol for anthocyanidins-glc), where hydrophobic force and hydrogen bond played key roles. Additionally, this cavity overlapped with ATP binding (MolDock Score = -161 kJ/mol) domain; the binding of anthocyanins presumably interfered the H bond formation between ATP and HER-2. These results indicate that anthocyanins may competitively bind to ATP binding site in HER-2 kinase domain by suppressing HER-2 activation and downstream signaling cascade. This may provide useful theoretical instruction for the molecular mechanism of HER-2 kinase activity inhibition by anthocyanins in cancer prevention and treatment.
Anthocyanins ; chemistry ; Catalytic Domain ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Molecular Docking Simulation ; Phosphorylation ; Protein Interaction Domains and Motifs ; Receptor, ErbB-2 ; chemistry

Objective To investigate whether Ivor-Lewis esophagectomy combined with adjuvant radiotherapy prevents lymphatic metastatic recurrence in esophageal cancer patients.Methods 113 Stage Ⅱ A esophageal squamous cell carcinoma patients after Ivor-Lewis esophagectomy were accpected mRNA expression of Mucin1 gene detection.Positive patients were enrolled into adjuvant radiotherapy group(with postoperative adjuvant radiotherapy).Negative patients were enrolled into control group (without postoperative adjuvant radiotherapy or chemotherapy).The radiotherapy area consisted of the neck,supraclavicular region and the superior mediastinum(including praesophageal and pratracheal region).Survival difference was compared by x2 test,the Kaplan-Meier method was performed to calculate the survival rate and recurrence rate.Logistic regressive analysis was performed to determined independent risk factors.Results The radiotherapy area lymphatic metastatic recurrence rate in adjuvant radiotherapy group(16.7％,5/30) was lower than patients without postoperative adjuvant radiotherapy (45.8％,38/83) (P ＜ 0.05).Only compared to positive patients without postoperative adjuvant radiotherapy(60.0％,6/10),the rate (16.7％,5/30) was significantly lower(P ＜ 0.01).Cancer recurrence was recognized in 48.6％ (55/113) patients within 3 year after operation,including 38.1％ (43/113) patients with radiotherapy area recurrence.In logistic analysis the T status (P＜ 0.01) and adjuvant radiotherapy (P ＜ 0.05) were independent risk factors of lymph node metastasis in the first 3 years after operation.Conclusion In Mucin1 mRNA-positive esophageal squamous cell carcinoma patients,adjuvant radiotherapy could significantly reduce the lymph node metastasis rate in the radiotherapy area after Ivor-Lewis esophagectomy.Compared with traditional therapeutic methods,Ivor-Lewis esophagectomy combined with adjuvant radiotherapy can achieve similar curative effects in Mucin1 mRNA-positive patients.