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Objective@#To evaluate the prognostic factors of T1-2N0M0 esophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy.@*Methods@#The clinical data of 196 patients with T1-2N0M0 ESCC who were treated with definitive radiotherapy in 10 hospitals were retrospectively analyzed. All sites were members of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG). Radiochemotherapy were applied to 78 patients, while the other 118 patients received radiotherapy only. 96 patients were treated with three-dimensional conformal radiotherapy (3DCRT) and 100 treated with intensity-modulated radiotherapy (IMRT). The median dose of plan target volume(PTV) and gross target volume(GTV) were both 60 Gy. The median follow-up time was 59.2 months. Log rank test and Cox regression analysis were used for univariat and multivariate analysis, respectively.@*Results@#The percentage of normal lung receiving at least 20 Gy (V20) was (18.65±7.20)%, with average dose of (10.81±42.05) Gy. The percentage of normal heart receiving at least 30 Gy (V30) was (14.21±12.28)%. The maximum dose of exposure in spinal cord was (39.65±8.13) Gy. The incidence of radiation pneumonia and radiation esophagitis were 14.80%(29/196) and 65.82%(129/196), respectively. The adverse events were mostly grade 1-2, without grade 4 toxicity. Median overall survival (OS) and progression-free survival (PFS) were 70.1 months and 62.3 months, respectively. The 1-, 3- and 5-year OS rates of all patients were 75.1%、57.4% and 53.2%, respectively. The 1-, 3- and 5-year PFS rates were 75.1%、57.4% and 53.2%, respectively. Multivariate analysis demonstrated that patients′age (HR=1.023, P=0.038) and tumor diameter (HR=1.243, P=0.028)were the independent prognostic factors for OS, while tumor volume were the independent prognostic factor for PFS.@*Conclusions@#Definitive radiotherapy is a promising therapeutic method in patients with T1-2N0M0 ESCC. Patients′ age, tumor diameter and tumor volume may impact patients′ prognosis.
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Objective:To evaluate the effect of definitive radiotherapy with different doses on overall survival (OS) and identify the prognostic factors of patients with non-metastatic esophageal squamous cell carcinoma (ESCC).Methods:Clinical data of 2 344 ESCC patients treated with definitive radiotherapy (RT) alone or chemoradiotherapy from 2002 to 2016 in 10 hospitals were collected and analyzed retrospectively. After the propensity score matching (PSM)(1 to 2 ratio), all patients were divided into the low-dose group (equivalent dose in 2 Gy fractions, EQD 2Gy<60 Gy; n=303) and high-dose group (EQD 2Gy≥60 Gy; n=606) based on the dose of radiation. Survival analysis was conducted by Kaplan- Meier method. Multivariate prognostic analysis was performed by Cox′s regression model. Results:The median follow-up time was 59.6 months. After the PSM, the 1-, 3- and 5-year overall survival (OS) rate was 66.5%, 34.7%, 27.2% in the low-dose group, 72.9%, 41.7% and 34.7% in the high-dose group, respectively ( P=0.018). The 1-, 3-and 5-year progression-free survival rate was 52.2%, 27.2%, 23.1% in the low-dose group, 58.3%, 38.1% and 33.9% in the high-dose group, respectively ( P=0.001). The outcomes of univariate analysis indicated that cervical/upper esophagus location, early (stage Ⅱ) AJCC clinical stage, node negative status, tumor length ≤5 cm, receiving intensity-modulated radiation therapy (IMRT), receiving concurrent chemotherapy and EQD 2Gy≥60 Gy were closely associated with better OS (all P<0.05). Multivariable analysis demonstrated that tumor location, regional lymph node metastasis, concurrent chemotherapy and EQD 2Gy were the independent prognostic factors for OS (all P<0.05). Conclusion:Three-dimensional conformal or IMRT with EQD 2Gy≥60 Gy yields favorable survival outcomes for patients with locally advanced ESCC.
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Purpose: This study investigated the outcome of elderly patients (≥65 years) with thoracic esophageal squamous cell carcinoma (TESCC) treated with esophagectomy and postoperative radiotherapy (PORT) or definitive radiotherapy (DRT). Patients and Methods: One hundred and ninety patients (median age of 72 years) who received PORT (n = 68) or DRT (n = 122) for TESCC were analyzed. Majority of them showed locally advanced disease (T3/4: 70.5%, N+: 70.5%, Stage III: 51.6%). Compared to patients who received DRT, those who received PORT had lower Age-Adjusted Charlson Comorbidity Index (AACCI) scores (2.49 ± 0.61 vs. 3.73 ± 1.28, χ2 = 7.283; P = 0.000) and higher Karnofsky Performance Scale (KPS) (χ2 = 9.016; P = 0.003) and were of younger ages (68.90 ± 3.00 vs. 75.17 ± 5.71, χ2 = 9.925; P = 0.000). Results: Overall survival (OS) was significantly higher in the PORT group (median, 61.2 months; 95% confidence interval [CI], 46.04–76.36) than in the DRT group (median, 24.37 months; 95% CI, 15.43–33.31). Multivariate analysis showed that treatment method (hazard ratio [HR]: 2.38, 95% CI, 1.46–3.90; P = 0.001), clinical T stage (HR: 0.57, 95% CI, 0.34–0.95; P = 0.031), and lymph node metastasis (HR: 0.51, 95% CI, 0.31–0.84; P = 0.008) were independent prognostic factors. Regarding subgroup analysis, OS of patients receiving PORT was significantly higher than that of DRT in the T3–4 group (HR: 2.98, 95% CI, 1.80–4.92; P = 0.000) and the N+ group (HR: 2.20, 95% CI, 1.26–3.83; P = 0.006). Conclusions: The efficacy of PORT for the treatment of elderly TESCC patients was superior to DRT. With regard to AACCI, KPS, and age, DRT is still a treatment option for elderly TESCC patients, especially for those >75 years of age
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Objective To retrospectively analyze the effect of tumor length on the prognosis in stage Ⅱ/Ⅲ esophageal squamous cell carcinoma (ESCC) patients treated with definitive radiotherapy and to evaluate the role of tumor length in clinical stage for non-operative ESCC patients.Methods The data of 2 086 ESCC patients who were treated with definitive radiotherapy from 2002 to 2016 in 10 hospitals (3JECROG) were analyzed.The effect of tumor length on overall survival (OS) was analyzed and stratified analysis of tumor length was done in different stages of ESCC.Results The median OS and median progression-free survival (PFS) time of the whole group were 25.6 months and 18.2 months respectively.The Cox multivariate analysis showed that treatment moda,aga,alinical stage and tumor length were independent prognostic factors.The median,1-,3-,and 5-year OS were 28.9 months,77.3％,45.0％,and 36.3％ versus 21.9 months,69.9％,37.9％,and 28.1％ for patients with ≤ 5 cm and patients ＞ 5 cm respectively (P＜0.05).For stage Ⅱ patienta,abe median OS were 42.1 and 38.9 months respectively in ≤ 5 cm group and＞5 cm group (P=0.303).And for stage Ⅲ patienta,abe median OS were 23.9 and 19.3 months respectively in ≤5 cm group and＞5 cm group (P＜0.001).The median OS with N1was 24.1 and 18.4 montha,aespectively in ≤5 cm group and＞5 cm group (P＜0.001).Conclusions The tumor length was an independent prognostic factor for stage Ⅱ/Ⅲ patients treated definitive radiotherapy.The tumor length may be helpful in clinical staging of ESCa,aspecially for stage Ⅲ and N1.
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Objective To compare the therapeutic effects between three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) in patients with stage Ⅱ/Ⅲ esophageal cancer and investigate the prognostic factors.Methods Medical record of 2 132 patients with stage Ⅱ/Ⅲ esophageal cancer who underwent definitive radiotherapy with/without chemotherapy in 10 hospitals from January 2002 to December 2016 from were retrospectively analyzed.Among these patients,37.9％ of them were aged ≥ 70 years,33.9％ with neck and upper esophageal tumors and 66.1％ with middle and lower esophageal and borderline tumors.The median gross tumor volume (GTV) and lymph node gross tumor volume (GTVnd) was 41.6 cm3.Among them,32％ were stage Ⅱ] and 68％ were stage Ⅲ.A total of 723 patients received 3DCRT and 1 409 cases received IMRT.Patients received an equivalent dose in 2 Gy (EQD2) ≥ 60 Gy accounted for 86.1％,and 41.1％ of them received concurrent chemoradiotherapy.Results The median follow-up time was 60.8 months.The 1-,3-and 5-year overall survival (OS) of all patients was 73.9％,41.7％ and 32.6％,and the 1-,3-and 5-year progression-free survival (PFS) was 62.2％,37.3％ and 32％,respectively.Multivariate analysis demonstrated that age,primary tumor location,clinical stage,tumor target volume,EQD2 and concurrent chemoradiotherapy were the independent prognostic factors for OS.Age,primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS.The OS and PFS did not significantly differ among the low-risk,low-/moderate-risk,moderate-/high-risk and high-risk groups according to age≥70 years,tumor diameter＞5 cm,tumor volume ≥41.6 cm3 and stage Ⅲ (P＜0.001).After the propensity score matching (PSM) method,neither 3DCRT nor IMRT yielded significant advantages in OS or PFS (P=0.971;P=0.658).However,IMRT tended to yield survival benefits in low-risk patients (P=0.125).Conclusions Both 3DCRT and IMRT yield relatively high OS rate in patients with stage Ⅱ/Ⅲ esophageal cancer.The prognosis model established in this investigation can properly predict the survival of patients.Low-risk patients tend to obtain survival benefits from IMRT.
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Objective To explore the feasibility of the Star-VIBE sequence in esophageal MRI,and compare it with the conventional VIBE sequence.Methods Fifteen healthy volunteers underwent Star-VIBE and VIBE sequences scanning after injecting MRI contrast agent.Two groups of MR images were independently scored in the ability to display esophageal wall,respiratory motion artifacts,cardiovascular pulsation artifacts,overall motion artifacts and overall image quality by the two radiologists,respectively.SNR of esophagus,CNR between esophagus and paravertebral muscles were measured and compared.Results Star-VIBE was superior to VIBE in the ability to display esophageal wall,respiratory motion artifacts,cardiovascular pulsation artifacts,overall motion artifacts and overall image quality (the ability to display esophageal wall:Z＝－3.268,P＝0.001;respiratory motion artifacts:Z＝－3.205,P＝0.001;cardiovascular pulsation artifacts:Z＝－4.644, P＝0.000;overall motion artifacts:Z＝－3.904,P＝0.000;overall image quality:Z＝－2.808,P＝0.005),while no significant differences were found on SNR and CNR between the two sequences (SNR:t＝－1.5 3 9 ,P＝0.1 3 5 ;CNR:t＝－0.874,P＝0.3 89 ).Conclusion The Star-VIBE sequence is insensitive to the physiological motion artifacts,and it can provide better image quality than the conventional VIBE sequence in esophageal MRI.
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Objective To evaluate the survival and prognostic factors of esophageal cancer treated with definitive ( chemo ) radiotherapy by applying novel radiation techniques including three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT). Methods Clinical data of 2762 patients with non-operated esophageal squamous cell carcinoma who underwent definitive ( chemo ) radiotherapy from 2002 to 2016 in 10 hospitals were retrospectively analyzed.The prognostic factors were also identified and analyzed. Results The median follow-up time was 60. 8 months. The 1-, 2-, 3-and 5-year overall survival (OS) of all patients was 71. 4％,48. 9％,39. 3％,and 30. 9％,respectively.The 1-,2-,3-and 5-year progression-free survival (PFS) was 59.5％,41.5％,35.2％,and 30％,respectively.The median survival was 23 months.The median time to progression was 17. 2 months.Multivariate analysis demonstrated that age, primary tumor location, clinical stage, tumor target volume, EQD2 and treatment mode were the independent prognostic factors for OS.Primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS. Conclusions In this first large-scale multi-center retrospective analysis of definitive ( chemo) radiotherapy for esophageal squamous cell carcinoma in China, the 5-year OS of patients with esophageal squamous cell carcinoma is significantly improved by 3DCRT, IMRT combined with chemotherapy drugs. However, the findings remain to be validated by prospective clinical trials with high-level medical evidence.
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Stereotactic body radiation therapy (SBRT) adopts different tumor-killing mechanisms from the conventional fractionated radiotherapy.In SBRT,a single high-dose radiation can destroy the membrane of tumor cells and induce the release of tumor-associated antigen,also named in situ tumor vaccine,which stimulates the immune system to kill the residual tumor;a single-fraction radiation with a dose larger than 8-10 Gy can induce rapid apoptosis of vascular endothelial cells via the acid sphingomyelinase pathway at 1-6 hours after radiation,which causes tumor vascular occlusion and secondary tumor-killing effects.In order to understand whether SBRT improves the clinical treatment outcomes via the above mechanisms,this paper reviews the clinical research advances in SBRT for primary liver cancer.
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Objective To investigate the radiosensitiation effect of berberine on human nasopharyngeal carcinoma ( NPC) in hypoxia condition and explore the underlying mechanisms. Methods MTT assay, clonogenic assay and flow cytometry were performed to analyze cell proliferation, colony formation and apoptosis, respectively. Male nude mice inoculated subcutaneously with CNE-2 cells were used to examine the radiosensitization effect of berberine in vivo. The expressions of HIF-1α and VEGF were assessed by Western blot. Results Berberine efficiently inhibited the proliferation of CNE-2 cells in time-dependent and dose-dependent fashions with an IC50 of ( 14?9 ± 2?2 ) μmol/L. Clonogenic survival assay showed that berberine ( 5 μmol/L ) sensitized CNE-2 cells to ionizing radiation in hypoxia and its SERD0 was 1?27. Under hypoxic condition, berberine alone (5, 15 μmol/L) could induce apoptosis (t=5?01, 9?02,P<0?05) and it further promoted 8 Gy radiation-induced apoptosis (t =5?31, 9?91,P <0?05). Moreover, berberine significantly delayed the tumor growth in the combination group (berberine +irradiation) compared with the mice received irradiation alone or PBS (t =2?96, 14?52, P <0?05). Immunobloting assay showed that berberine inhibited the upregulation of HIF-1α and VEGF induced by hypoxia in CNE-2 cells. Conclusion Berberine confers radiosensitivity on hypoxic NPC in vitro and in vivo, which is probably associated with the downregulation of HIF-1α and VEGF expressions.
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Objective: To compare the difference of intensity modulated radiation therapy (IMRT),3-D imensional conformal radiation therapy (3DCRT) for patients with upper esophageal carcinoma. Methods: Ten patients with upper esophageal carcinoma were treated by intensity modulated radiation therapy and 3-D imensional conformal radiation therapy at the same TPS, the difference of exposure dose between target area and critical organ was compared by dose volume histogram(DVH) with the plan target volume (PTV) must reach 95% of the prescription dose. Results: There was significant difference in dose of 95% plan target volume (PTV) (P 0.05). Compared with 3D-CRT, IMRT planning has better dose distribution and protection of normal tissue. Conclusions: IMRT was better than 3DCRT, IMRT is the best radiation therapy.
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Objective:To investigate the anti-tumor effect of tetrandrine on human liver cancer cell line 7402 in vitro.Effects of tetrandrine on proliferation and apoptosis of human liver cancer cell 7402 were observed.Methods:The effects of tetrandrine on proliferation of 7402 cells was observed by MTT assay and clonogenic assay.Apoptosis was observed by acridine orange(AO)/ethidium bromide(EB) Fluorescent staining?DNA gel electrophoresis and flow cytometry,and the expression of apoptosis related gene was analyzed by immunohistochemical staining method.Results:Tetrandrine inhibits the proliferation of 7402 cells in a dose dependent manner and induces apoptosis.Immunohistochemical staining showed that the expression of Bcl-2 was decreased and the expression of Bax was increasd in 7402 cells treated with tetrandrine.Conclusion:Tetrandrine inhibits the proliferation of 7402 in the dose dependent manner,and induces apoptosis.The antitumor effect of tetrandrine may be due to the regulation of the expressions of Bcl-2 and Bax.
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Objective: To construct and identify a lentiviral vector harboring RNAi sequence targeting the human high mobility group A1(HMGA1) gene.Methods: The effective sequence of siRNA targeting the HMGA1 gene confirmed in our previous study,the complementary DNA containing both sense and antisense Oligo DNA of the targeting sequence was designed,synthesized and cloned into the pGCL-GFP vector diced by the restriction enzyme of HpaⅠ and XhoⅠ,which contained the U6 promoter and green fluorescent protein(GFP).The resulting lentiviral vector containing HMGA1 shRNA was named LV-sh HMGA1 and confirmed by PCR and DNA sequencing.A total of 293T cells were cotransfected with LV-sh HMGA1,pHelper 1.0 and pHelper 2.0.All the virus stocks were produced by Lipofectamine2000-mediated transfection.The titer of the virus was tested according to the expression level of GFP.Results: PCR analysis and DNA sequencing demonstrated that the RNAi sequence targeting the human HMGA1 gene was successfully inserted into the lentiviral vector.The titer of the recombinant lentiviral vector was 5?107 TU/ml.Conclusion: The successful construction of the lentiviral vector of HMGA1 has prepared the ground for further studies on the functions of the HMGA1 gene with the RNAi technique.
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Objective: To study the expression and activity of the apoptosis protease-Caspase 3 in(E.coli) BL21(DE3). Methods: The cDNA of Caspase 3 was amplified by PCR and inserted into the plasmid pCMV-Myc,it is then cloned to prokaryotic expression vector pGEX-6p,after which Caspase 3 was induced by IPTG.The protein induced was identified by SDS-PAGE and Western blot. Results: After induced by IPTG for 3 hours,the concentration of Caspase 3 reached the highest level. Conclusion: Active Caspase 3 can be induced within E.coli BL21(DE3),further research can be done about the role of Caspase 3 in apoptosis.
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Human gliomas are one of the most aggressive tumors in brain.Radiotherapy plays an important role for patients with gliomas,as well as surgery.The efficacy of radiotherapy is associated with radiosensitivity of human gliomas.Radiosensitive genes of gliomas and apoptosis、cell cycle transformation、DNA damage induced by irradiation and DNA repair promoted by them are suggested to be associated with glioma radiosensitivity.The rediosensitive genes associated with apoptosis and DNA repairment are becoming hot spots of study.The other radiosensitivity genes are paid attention too.This paper makes a summary of current situation and progress for radiosensitive genes of human brain glomas.
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Objective:To investigate the effects of tetrandrine(Tet) on proliferaton and apoptosis of nasopharyngeal carcinoma cell line CNE.Methods:CNE cells were divided into groups and treated by Tet at different concentrations.Inhibitory effects of tetrandrine were determined by MTT assay.The morphologic changes of CNE cells were observed by transmission electron microscope.DNA fragmentations were determined by gel electrophoresis assay.Cell apoptosis was investigated by flow cytometer.The expressions of apoptosis-related genes were detected by retrotranscriptase polymerase chain reaction(RT-PCR).Results:Tetrandrine possessed inhibitory effect on CNE cell proliferation in a concentration-dependent manner(P
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A nucleotide diversity in DNA sequence is called polymorphism,which results in intersubjects variation in therapeutic drug effects and toxicity.Clinical studies were found that a single nucleotide polymorphism influenced response or drug toxicity in cancer chemotherapies,which were based on 5-fluorouracil,Irinotecan,platinum and so on.This review will focus on the recently development in the relation between drug effects or toxicity and polymorphism.