Colorectal stem cells have many bio-markers, including Lgr5 which expression is associated with THE stage of disease , also regulating the cell cycle , anothers is +4 stem cell , which is associated with tumor heteroge-neity, also expressed Bmi1, arresting cell cycle.Besides there is Msi1.Many studies show that those markers are highly expressed in colorectal cancer , which activate Notch and Wnt signaling pathway , and can promote the pro-gress of tumor .

Musashi1 (Msi1) is an evolutionary conservative RNA-binding protein (RBP),and it is a stem marker in a variety of organizations,including intestinal,neural system.Msi1 maintains the balance between self-renewal and differentiation.Recently,many researchers report that Msi1 is overexpressed in many types of tumors,especially in colorectal neoplasms,participating in the regulation of cell cycle,proliferation,apoptosis and so on.Msi1 becomes a key regulator of many cancers,which is expected to turn into a new target for cancer therapy.

Objective To compare the local control (LC), long-term overall survival (OS), and clinical adverse reactions in esophageal carcinoma patients receiving concurrent chemoradiotherapy at different radiotherapy doses.Methods A total of 373 esophageal carcinoma patients who received concurrent chemoradiotherapy in our hospital during 2004-2013 were included in this retrospective study.These patients were divided into<60 Gy group (n=99), 60 Gy group (n=155), and>60 Gy group (n=119) based on the dose of radiation.The Kaplan-Meier method was used to calculate LC and OS rates;the log-rank test was used for survival comparison and univariate prognostic analysis;the Cox model was used for multivariate prognostic analysis.Results The 3-, 5-, 7-, and 10-year sample sizes were 97,96,56, and 38 in the<60 Gy group, 146,141,72, and 17 in the 60 Gy group, and 118,115,56, and 20 in the>60 Gy group.The 3-, 5-, 7-, and 10-year LC rates were 55.3%, 51.4%, 48.9%, and 48.9% in the<60 Gy group, 65.1%, 60.1%, 55.1%, and 55.1% in the 60 Gy group, and 49.4%, 45.1%, 37.7%, and 37.7%(8-year) in the>60 Gy group (P=0.020).The 3-, 5-, 7-, and 10-year OS rates were 35.4%, 26.1%, 22.0%, and 22.0% in the<60 Gy group, 49.0%, 41.3%, 32.1%, and 28.9% in the 60 Gy group, and 31.1%, 25.2%, 14.5%, and 12.9%(8-year) in the>60 Gy group (P=0.000).The univariate analysis showed that for stage Ⅱ esophageal carcinoma patients with gross tumor volume (GTV) ≤44 cm3, the LC rate was higher in the 60 Gy group than in the<60 Gy group (P=0.040,0.035), and the OS rate was higher in the 60 Gy group than in the other two groups (P=0.001,0.003 and P=0.045,0.006).Similarly, for stage Ⅲ esophageal carcinoma patients with GTV>44 cm3, the LC rate was higher in the 60 Gy than in the>60 Gy group (P=0.011,0.015), and the OS rate was higher in the 60 Gy group than in the other two groups (P=0.045,0.006 and P=0.033,0.002).The incidence rates of acute radiation esophagitis and radiation pneumonia were significantly higher in the>60 Gy group than in the other two group (P=0.007,0.033).Furthermore, the multivariate analysis indicated that radiotherapy dose, T stage, and N stage were independent prognostic factors for esophageal carcinoma (P=0.004,0.008,0.037).Conclusions Concurrent chemoradiotherapy at 60 Gy is most efficacious for patients with esophageal carcinoma, and the radiotherapy dose of>60 Gy significantly increases the incidence of adverse reactions.

Objective To disclose whether the down-regulation of Musashi1 gene can sensitize human colon carcinoma cell line HCT116 to radiation. Methods Lentviral vectors were used to knockdown the expression of Musashi1 gene in HCT116 cell line ( HCT116-Musashi1 ) and its negative control ( NC) . Cell survival was measured by the colony formation assay, cell apoptosis and cell cycle distribution were measured by a flow cytometry. Results HCT116-Musashi1 silence and its negative control cells were established successfully. The result of cell survival assay showed that D0 , Dq , N, SF2 were 1.55, 0.88, 1.76 Gy and 0.43 for the Musashil silence group, 2.17, 1.51, 2.01 Gy and 0.64 for control cells, and 1.99, 1.45, 2.07 Gy and 0.62 for siRN NC, respectively. The radiosensitivity of Musashi1 silence group was significantly higher than that of control and siRNA NC, and SER was 1.40 and 1.28 respectively. After 8 Gy irradiation, the apoptosis rate of silence group was always higher than other two groups at 24, 48, and 72 h after irradiation(F =65.16, P <0.05), but there was no statistically significant difference between control and NC (P>0.05). After 12 Gy irradiation, the percentage of cells in G2/M phase decreased significantly in the silence group compared with control group and NC group( F=65. 398,P<0. 05). Conclusions Knockdown of Musashi1 in HCT116 cells increases the radiosensitivity through promoting cell apoptosis and reversing G2/M arrest, indicating that Musashi1 may be a new target of radiotherapy.

Objective To determine the efficacy of primary tumor of esophageal cancer,according to the result of magnetic resonance imaging before and after chemoradiotherapy of esophageal cancer,combined with clinical efficacy evaluation,and to verify the reliable evaluation of the short-term curative effect of magnetic resonance on esophageal cancer,combined with the original CT and esophagogram evaluation criteria.Methods From May 2010 to March 2014,totally 83 patients with esophageal carcinoma treated with 3D-CRT or IMRT were enrolled.The prescribed doses were ranged from 50-64 Gy with median dose of 60 Gy and 1.8-2.0 Gy per fraction,of which 34 of the patients received concurrent chemotherapy of FP or TP.All the patients performed the examinations of DWI,CT scan and esophagogram before and after radiotherapy.The treatment efficacy was evaluated by short-term therapeutic effect evaluation criterion of versions 1989 and 2013 and the hyperintense expression on DWI sequence.Results According to the short-term therapeutic effect evaluation criterion of versions 1989 and 2013 based on the examination of esophagogram and CT scan,45 patients achieved complete remission (CR) after treatment(54.2％) and 38 achieved partly remission(PR) (45.8％) version 1989,while 35 patients achieved CR (42.2％) and 48 achieved PR (57.8％) version vesion 2013.In the two differentcriterions,the local control rate and survival rate of the complete remission group in 1 to 5 years were better than those in the partial remission group.According to the examination of DWI,48 patients' hyperintense disappeared completely at the end of treatment (which was defined to CR),25 patients had a slightly hyperintense expression and 10 patients still had hyperintense expression on DWI sequence (which two defined to PR),the local control and survival rates of the former group were superior to the latter groups (x2 =6.125,11.652,P ＜0.05).The TE results evaluated by DWI and TE evaluation criterion of version 2013 were compared according to Kappa test,as a result,the Kappa coefficient 0.478.According to the examination of esophagogram,CT scan and DW1,25 patients achieved CR and 58 achieved PR in all exams,and the local control and survival rates of the former group were superior to the latter group (x2 =5.559,10.014,P ＜0.05).Conclusions The esophagogram and CT based TE evaluation criterion could well indicate local control status of esophageal cancer,and the examination of DWI could afford visualized and quantifying reference information about the TE of esophageal cancer.The expression of hyperintense at the end of treatment may indicate a high risk of recurrence and metastasis.The therapeutic effect evaluated by esophagogram,CT scan and DWI maybe more objective and more accurate.

Objective To explore and improve the feasibility and prognostic value of barium radiography and computed tomography (CT)-based evaluation criteria in evaluation of the short-term efficacy of radiotherapy for esophageal cancer,and to provide a basis for clinical application.Methods The short-term treatment outcomes of 529 patients with esophageal carcinoma receiving three-dimensional radiotherapy from 2004 to 2015 were evaluated by the 2013 version of barium radiography and CT-based evaluation criteria.The local control (LC) and survival rates were calculated using the Kaplan-Meier method.The log-rank test was used for data analysis and univariate prognostic analysis.The agreement between two evaluation criteria was measured by the Kappa coefficient.Results According to the results of the survival analysis in all the patients using the evaluation criteria for short-term treatment outcomes,the 3-,5-,7-,and 9-year LC rates were 78.6％,69.8％,69.8％,and 63.4％ in the complete response (CR) group (n=52),and 56.4％,47.9％,46.2％,and 42.4％ in the partial response (PR) group (n=409),respectively;the 3-,5-,7-,and 9-year overall survival (OS) rates were 62.7％,49.1％,39.8％,and 39.8％ in the CR group,and 29.5％,21.6％,20.6％,and 19.5％ in the PR group,respectively;the median OS time was 50,17,and 5 months in the CR group,PR group,and non-response group (n=12),respectively (P=0.000).According to CT measurements,the short diameter of residual metastatic lymph node after radiotherapy was between 0.37-3.40 cm (median value=0.82 em).All patients were divided into groups based on the short diameter of residual metastatic lymph node after radiotherapy with a gradient of 0.5 cm.Patients with short diameters of residual metastatic lymph node of ≤ 1.00 cm had a significantly higher OS rate than those with short diameters of residual metastatic lymph node of＞ 1.00 cm (P =0.000).The lymph node volume of 1.00 cm3 in the original criteria was replaced by the short diameter of residual metastatic lymph node of 1.00 cm after radiotherapy and treatment outcomes were re-evaluated using the new criteria.The CR group still had significantly higher LC and OS rates than the PR group (P=0.000).There was a good agreement between the two evaluation criteria (Kappa =0.863).Conclusions The barium radiography and CT-based evaluation criteria for short-term treatment outcomes can accurately evaluate the short-term outcomes and predict prognosis in patients with esophageal carcinoma.Replacing the volume in the original criteria with the short diameter of residual metastatic lymph node after radiotherapy achieves similar results in prognostic prediction.

Objective To investigate the survival benefits of simultaneous integrated boost intensity-modulated radiotherapy ( SIB-IMRT ) in the treatment of esophageal squamous cell carcinoma ( ESCC ) . Methods From July 2003 to March 2014,1748 patients with ESCC received 3DCRT or IMRT in a single institution were enrolled in this retrospective study. Among them, 809 patients received conventional fractionated radiotherapy with the standard prescription dose and 110 patients received SIB-IMRT ( SIB-IMRT group).Survival analysis was performed and propensity score matching (PSM 1vs1) was conducted to evaluate and compare the survival benefits between SIB-IMRT and conventional fractionated radiotherapy. Results The baseline characteristics significantly differed between two groups. In the SIB group,the age was significantly younger ( 64 years vs. 66 years, P=0. 001 ) , the percentage of patients with cervical/upper thoracic tumors was considerably higher (53. 6％ vs. 31. 0％,P=0. 000) and the proportion of N2 patients was significantly higher ( 21. 8％ vs. 13. 7％,P=0. 027) compared with those in the other group. Accordingto the PSM of 1:1, 218 patients were successfully matched. After matching, the clinical data did not significantly differ between two groups. Prior to matching,the median survival time in the standard dose and SIB-IMRT groups were 23 and 21 months (P=0. 638).After matching,the median survival time in the SIB-IMRT group was 22 months,significantly longer than 18 months in the standard dose group (P=0. 000). Subgroup analysis demonstrated that patients with large tumors ( GTV volume>40 cm3 ) and middle/lower thoracic tumors obtained more survival benefits from SIB-IMRT. The median survival time of patients in the standard dose group was 14 months, significantly shorter than 21 months in the SIB-IMRT group ( P=0. 001).The median survival time of patients with middle/lower thoracic tumors in the SIB-IMRT group was 17 months,significantly longer than 9 months in the standard dose group (P=0. 000).Multivariate analysis using Cox regression model indicated that age, tumor site and radiotherapy modality were the independent prognostic factors. The HR of SIB-IMRT was 0. 551(P=0. 000),which was a factor for survival benefits. Conclusions SIB-IMRT possesses potential survival benefits for ESCC compared with conventional fractionated radiotherapy. Patients with large tumors and middle/lower thoracic tumors are more prone to obtaining benefits from SIB-IMRT than their counterparts.