1.Interaction effects of DNA methylation and histone modification key enzymes in gastric cancer
Fuli GAO ; Ying Lü ; Yinxin ZHU ; Jun CAO ; Xiaoping ZOU
Chinese Journal of Digestion 2013;(2):106-110
Objective To study the expression and interactions of DNA methyltransferase 1 (DNMT1),enhancer of zeste homolog 2 (EZH2) and histone deacetylase 1 (HDAC1) in gastric cancer cell lines and tissue specimens.Methods The expression of DNMT1,EZH2 and HDAC1 was detected at mRNA and protein level in gastric cancer lines MKN28,SGC7901,BGC823,AGS,normal gastric epithelium cell line GES-1 and 10 pairs of fresh gastric cancer tissues and corresponding normal gastric tissues by real-time polymerase chain reaction and Western blot.Whether DNMT1,EZH2 and HDAC1 forming complex or not was detected by co-immunoprecipitation (Co-IP) in well-differentiated gastric cancer cell line MKN28,medium-differentiated gastric cancer cell line SGC7901,lowdifferentiated gastric cancer cell line BCG823,normal gastric epithelium cell line GES-1,mediumdifferentiated,medium to low-differentiated,low-differentiated gastric cancer tissues and corresponding normal gastric tissues.Results Compared with that of normal gastric epithelium cell and gastric tissue,the expression of DNMT1,EZH2 and HDAC1 in gastric cancer cell lines and gastric tissue was higher.The results of Co-IP indicated that DNMT1,EZH2 and HDAC1 formed complex in the high,medium,and poor differentiated gastric cancer cells and the medium,mediumlow,poor differentiated gastric cancer tissues,but not in normal gastric epithelium cell and tissue.Conclusion DNMT1,EZH2 and HDAC1 highly expressed in gastric cancer and there was interaction effects among them,which might be an important mechanism in the correlation between DNA methylation and histone modifications in gastric cancer.
2.30 Cases of Ulcerative Colonitis Treated with a Combinative Use of Three Drugs
Wenxian ZHANG ; Runying ZHOU ; Lizhu LI ; Fuli GAO
Herald of Medicine 2001;(1):37-
Objective: To observe the effectiveness of combinative use of gentamycin, metronidazole and rifampin in the treatment of ulcerative colonitis and explore the etiology of the disease. Methods: 30 and 26 patients were allocated to treatment group and control group, respectively. Maintained clysis with a combination of gentamycin, metronidazole and rifampin in warm normal saline were administered to those in the treatment group twice a day for two weeks, while SASP and prednisone were administered to those in the control group for two weeks. Results: The alleviation rate of the treatment group is higher than that of the control group. Conclusion: Combinative use of gentamycin, metronidazole and rifampin for maintained clysis is a effective treatment for ulcerative colonitis.
3.Study of effect of lung tumor location and volume on dosimetric parameters using Alderson Rando phantom
Fuli ZHANG ; Mingmin ZHENG ; Jianping CHEN ; Junmao GAO
Chinese Journal of Radiation Oncology 2009;18(6):452-454
Objective To study the effect of the location and volume of tumors on the normal lung dose-volume parameters for lung cancer. Methods An sphere with a diameter of 2 cm made of tissue-equiv-alent material used for simulating tumor was inserted into the superior lobe, middle lobe, inferior lobe of the right lung, and superior lobe, inferior lobe of the left lung of the Rando phantom, respectively. 5-field sIM-RT plans were designed. The prescribed dose was 60 Gy/2 Gy/30 f, and 99% of the planning target volume received this dose. Dose-volume parameters of normal lung tissue including V_5, V_(10), V_(20), V_(30), V_50 and mean lung dose were analyzed and compared. Results For the dose-volume parameters, the diameter and the po-sition of the tumor have a significant effect (P < 0.05). With the diameter expanding from 2 cm to 3 cm,the parameters associated with tumor in various lobes increased by a range between 3.83%-125.38%,while the parameters linked with tumor in different lobes increased by a range between 10.46%-51.46% with the diameter expanding from 3 cm to 4 cm. Conclusions Location and diameter of sphere-like tumor have obvious effect on dose-volume parameters. Knowing about the degree of influence will help oncologists and physicists to evaluate treatment planning better and reduce radiation pneumonitis.
4.Dosimetric Comparison of Bone Marrow-Sparing Intensity-Modulated Radiotherapy Versus Conventional Intensity-Modulatedr Radiotherapy for Treatment of Cervical Cancer
Fuli ZHANG ; Jing CHEN ; Junmao GAO ; Jianping CHEN ; Mingmin ZHENG
Chinese Journal of Medical Physics 2010;27(1):1599-1602
Objective:To compare bone marrow-sparing intensity-modulated radiotherapy(BMS-IMRT)with conventional (four-field box[3DCRT]and anteroposterior-posteroanterior[CRT])techniques in the treatment of cervical cancer.Methods:For a cohort of 10 patients,BMS-IMRT,3DCRT and CRT planning were designed.The prescribed dose was 45Gy/1.8Gy/25f,95%of the planning target volume received this dose.Doses were computed with a commercially available TPS.Plans were compared according to dose-volume histogram (DVH)analysis in terms of PTV homogeneity and conformity indices(HI and CI)as well as OARs dose and volume parameters.Results:BMS-IMRT had an advantages over 3DCRT and CRT in terms of CI,but inferior to the latter two for HI.BMS-IMRT was superior to 3DCRT in reducing the dose to PBM,small bowel,bladder and rectum.Compared with CRT,BMS-IMRT reduced the volume irradiated to the doses from 30Gy to 40Gy,but increased the volume irradiated to the low doses from 5Gy to 20Gy.In addition,BMS-IMRT reduced the volume of small bowel,bladder,rectum at nearly all dose levels.Conclusion:BMS-IMRT reduced irradiation of PBM compared with 3DCRT technique.Compared with CRT technique,BMS-IMRT reduced the volume of PBM irradiated to high doses.Therefore,for patients with cervical cancer after hysterectomy,BMS-IMRT might reduce acute hematologic toxicity(HT)compared with conventional techniques.
5.A dosimetric study of helical tomotherapy for nasopharyngeal carcinoma
Xinge CAO ; Yadi WANG ; Yongqian ZHANG ; Fuli ZHANG ; Junmao GAO
Chinese Journal of Radiation Oncology 2016;25(8):802-806
Objective To use helical tomotherapy ( HT ) for determining the difference between actual doses and planning doses to the target volume and organs at risk ( OARs ) in patients with nasopharyngeal carcinoma receiving radiotherapy, and to provide guidance for the clinical treatment. Methods Localization and delineation of the target volume and OARs were performed by computed tomography ( CT) in 21 patients with nasopharyngeal carcinoma receiving radical radiotherapy using HT. All patients underwent megavoltage CT ( MVCT) scan prior to treatment. The obtained MVCT images were used for dose reconstruction in the adaptive module of HT, in which the actual dose was obtained and the non?image?guided dose was simulated. Each single dose distribution and the corresponding CT image were sent to software MIM6. 0 for superimposition, and the overall dose was obtained. The initial plan, image?guided plan, and non?image?guided plan were named Plan?1, 2, and 3, respectively. The dose distribution in the target volume and OARs was compared between the three plans with t ? test or wilcoxon test . Results Compared with those in Plan?1, the D98 values for the planning gross tumor volume ( PGTV) and planning target volume ( PTV) in Plan?2 were significantly reduced by 1. 16% and 2. 3%, respectively ( P=0. 025;P=0. 043);the volumes of the left and right parotids in Plan?2 were significantly reduced by 46. 0% and 46. 5% on average, respectively ( P=0. 000);the distances between the midline and the center?of?mass for left and right parotids were significantly reduced by 6. 9% and 6. 5%, respectively ( P=0. 000);the V26 and Dmean for both parotid glands were significantly elevated by 32. 8% and 25. 2%, respectively ( P=0. 000) . Compared with those in Plan?1, the D98 values for PGTV, PTV?1, and PTV?2 in Plan?3 were significantly reduced by 2. 0%, 1. 9%, and 2. 4%, respectively ( P=0. 001;P=0. 007;P=0. 036);the V26 and Dmean for both parotid glands in Plan?3 were significantly elevated by 33. 6% and 25. 3%, respectively ( P=0. 000);Dmax to the spinal cord was significantly increased by 6. 9%( P=0. 005) . There was no significant difference in D2 to the spinal cord between Plan?2 and Plan?1( P=0. 392) . Conclusions The doses to both parotid glands increase during HT for nasopharyngeal carcinoma, which is closely associated with the shift of the parotid glands toward the midline. Image?guided radiotherapy does not enhance the dose to the target volume, but reduces the dose to the spinal cord.
6.Position modification and actual radiation dose in parotids for head and neck cancers treated with TomoTherapy
Huayong JIANG ; Yongqian ZHANG ; Yadi WANG ; Weidong XU ; Junmao GAO ; Fuli ZHANG ; Bo YAO
Chinese Journal of Radiological Medicine and Protection 2014;34(11):845-849
Objective To analyze the impact of parotid's position and volume changing on radiation dose for head and neck cancer treated with TomoTherapy.Methods Totally 12 patients with head and neck cancer were treated with TomoTherapy.Before the treatment,the dose distribution was recalculated with MVCT images,which would obtain the parameters of position,volume and actual radiation dose for parotids.Results The volume of parotids in Plan2 was significantly lower than in Plan1,and the percentage reduction was 29.06% and 31.78% for left and right parotid,respectively (Z =6.77,3.06,P < 0.05).Distance between the COM (center of mass) of parotids and the midline of body was significantly smaller in Plan2 than in Plan1,and the percentage reduction was 6.72% and 6.19% (t =5.14,5.80,P < 0.05) at left and right side,respectively.Average dose and V26 for both parotids were higher than those in Plan1,increasing by an average of 37.74%,25.08% (Z =-6.03,-5.31,P < 0.05) for left parotid and 30.45%,19.33% (Z =-5.43,-3.26,P <0.05) for right parotid,respectively.Conclusions The actual radiation dose to parotids was significantly increased during the radiation therapy for patients with head and neck cancer.There was a linear correlation between the decrease of distance between the COM of parotids and the midline of body and the percentage increase of parotids' radiation dose.No correlation between the reduction of parotids' volume and dose to parotids.In order to reduce the parotids' radiation dose,modification of treatment plan at the appropriate time is essential.
7.Chemoradiation effect of combined preoperative intensity-modulated radiotherapy with oral capecitabine in patients with locally advanced mid-low rectal cancer using a simultaneous integrated boost of tomotherapy
Weidong XU ; Junmao GAO ; Yihong ZHAO ; Gang CHEN ; Junfeng DU ; Fuli ZHANG
Clinical Medicine of China 2015;31(6):553-556
Objective 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 simultaneous integrated boost (SIB) of tomotherapy.Methods Total 16 patients with resectable locally advanced mid-low rectal cancer (patients with T3 to T4 and/or N ± rectal cancer) were enroll in current study.Patients were received IMRT to 2 dose levels simultaneously (55 and 47.5 Gy in 25 fractions) with concurrent capecitabine 825 mg/m2 twice daily,5 days/week.Total mesorectal excision was performed at 8 to 9 week after the completion of chemoradiation.The primary end point included side effect,the rate of sphinctersparing,postoperative complication and pathological complete response rate (pCR) were observed.Side effects were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.Results All patients were received chemoradiotion therapy without any break.Tomotherapy showed superiority with respect to target coverage,homogeneity and conformality.Two patients refused to perform radical surgery because of almost complete primary tumor regression and complete symptom relief after neoadjuvant therapy.Fourteen patients underwent surgical resection and 11 patients (78.6%) underwent sphincter-sparing lower anterior resection.Four patients(28.6%) had a pathological complete response.The incidence of grade 1-2 hematologic,gastro-intestinal toxicities were 62.5% (10/16) and 18.8% (3/16).The incidence of grade 3 skin toxicities were 68.8%(10/16).Grade Ⅳ side effect was not observed.Surgical complications (incisional infection on thirteen after surgery) were observed in 1 patient.Conclusion Preoperative simultaneous integrated boost of tomotherapy with concurrent oral capecitabine is safe and well tolerated in patients with a promising local control.However,a larger number of patients and a long follow-up are required to assess its potential superiority.
8.Dosimetric Comparison of Inverse Three-Dimensional Conformal Radiotherapy and Intensity Modulated Radiotherapy for Non-Ssmall Cell Lung Cancer
Fuli ZHANG ; Weidong XU ; Junmao GAO ; Jianping CHEN ; Ping WANG ; Mingmin ZHENG
Chinese Journal of Medical Physics 2010;27(2):1704-1707,1720
Objective: To compare inverse three-dimensional conformal radiotherapy (Inv 3D-CRT) and intensity modulated ra-diotherapy (IMRT) for non-small cell lung cancer. Methods: For a cohort of 10 patients, Inv 3D-CRT and three groups of IMRT plannings were designed for per patient. The prescribed dose was 60 Gy/2 Gy/30f, 95% of the planning target volume received this dose. Dose was computed with a commercially available TPS using convolution/superposition (CS) algorithm. Plans were compared according to the PTV_(95)V_(20) ratio (PTV_(95)V_(20)) and D_(max)-D_(min). Results: Compared with Inv 3D-CRT, the PTV_(95)V_(20) ratio of three groups of IMRT increased by 1.08 (P = 0.014), 0.72 (P = 0.089) and 0.42 (P = 0.318), respectively. Conclusions: For NSCLC, IMRT can reduce the dose to the lungs compared with inverse 3D-CRT by improving the conformity of the plan and is worth spreading in clinical work.
9.Dosimetric comparison between bone marrow-sparing intensity-modulated radiotherapy and conventional intensity-modulated radiotherapy for cervical cancer
Fuli ZHANG ; Jing CHEN ; Jianping CHEN ; Mingmin ZHENG ; Ping WANG ; Junmao GAO
Chinese Journal of Radiation Oncology 2010;19(1):37-39
Objective To compare bone marrow-sparing intensity-modulated radiotherapy (BMS-IMRT) with conventional intensity-modulated radiotherapy (IMRT) without considering pelvic bone marrow (PBM) as a planning constraint in the treatment of cervical cancer after hysterectomy. Methods BMS-IM-RT and IMRT planning were separately designed in a cohort of 10 patients with cervical cancer after hysterec-tomy. The prescribed dose was 95% planning target volume receiving 45 Gy/25 f. A commercially available TPS with convolution/superposition (CS) algorithm was used for dose calculation. Plans were compared ac-cording to dose-volume histogram (DVH) analysis in terms of PTV homogeneity (HI), conformity index (CI) as well as dose and volume parameters of organ at risks (OARs). Results BMS-IMRT was better than IMRT in terms of CI, but inferior to the latter for HI. When compared with IMRT, V_5, V_(10), V_(20), V_(30) and V_(40) of PBM in BMS-IMRT were reduced by 1.81% ,8.61% ,31.81% ,29.50% and 28.29%, respec-tively. No statistically significant differences were found between BMS-IMRT and IMRT for dose distritutions of the small bowel, bladder or rectum. Conclusions For patients with cervical cancer after hysterectomy, BMS-IMRT can reduce the PBM volume irradiated by low dose, which may reduce acute hematologic toxici-ties.
10.Improvement of left ventricle remodeling by transplanting various autologous bone marrow stem cells
Shuren LI ; Xiaoyong QI ; Jianqing ZHANG ; Tianhong WANG ; Yi DANG ; Cunliang MENG ; Huiliang LIU ; Yingxiao LI ; Fuli HU ; Di WU ; Jie DONG ; Liying XUN ; Lihui GAO ; Fuchang JIN
Chinese Journal of Tissue Engineering Research 2008;12(47):9371-9377
BACKGROUND:Bone marrow stem cell transplantation can improve heart function and prevent ventricle remodeling.At present,the adult bone marrow stem cells used for transplantation primarily included bone marrow mononuclear cells (BM-MNCs) and mesenchymal stem cells (MSCs),and endothelial progenitor cells.The curative effects and precise mechanisms of transplantation of various bone marrow stem cells remain unknown.OBJECTIVE:To compare the effects of transplantation of autologous BM-MNCs and MSCs via the coronary artery on ventricle remodeling subsequent to acute myocardial infarction (AMI). DESIGN,TIME AND SETTING:Randomized controlled animal experiment performed at the Center for Clinical Research,Hebei Provincial People's Hospital,Electron Microscope Room,Hebei Medical University between March 2005 and December 2006.MATERIALS:Thirty-six male Jizhong pigs,were randomly divided into 4 groups:control group (n = 6),infarct model group (n = 10),BM-MNC group (n = 10),and MSC group (n = 10).METHODS:Porcine autologous BM-MNCs were isolated by gradient density centrifugation,and MSCs were obtained by adherence method.Prior to transplantation,both BM-MNCs and MSCs were colloidal gold labeled.Except the infract model group,pigs in the other 3 groups were developed into AMI models by oppressing the left anterior descending branch with balloon catheter.Ninety minutes after modeling,(6.0±1.3)×107 autologous BM-MNCs and (4.5±2.1)x 107 MSCs were respectively transplanted into pigs in the BM-MNC group and the MSC group via the coronary artery and cultured for 28 days.MAIN OUTCOME MEASURES:Observation of pathological changes of cardiac muscle tissue by light and electron microscope;Examination of cardiac function by ultrasonograph;Detection of the number of blood vessels and apoptotic myocardial cells,and expression of nuclear factor-κB (NF-κB) and troponin Ⅰ and its correlation to cardiac function by immunohistochemistry;Detection of mRNA expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the cardiac tissue as well as its correlation to cardiac function by reverse transcription-polymerase chain reaction (RT-PCR).RESULTS:In the MSC group,there was proliferation of a great deal of blood vessels as well as growth of abnormal cell masses around the coronary vessels,while the BM-MNC group exhibited the "budding" of many capillary vessels.Prior to transplantation,cardiac function indices were basically similar among each group (F = 1.550,P>0.05).Twenty-eight days after transplantation,left ventricular ejection fraction was significantly lower in the control,BM-MNC,and MSC groups than in the infarct model group (F = 5.30,P<0.05),while endocardial fractional shortening was significantly higher (F = 10.67,P<0.01).Compared with the infarct model group,the number of blood vessels in the infarct zone and infarct border zone was increased in the BM-MNC group (F=29.56-34.87,P<0.01) and had no apparent change in the MSC group.In the BM-MNC and MSC groups,apoptotic myocardial cells in the infarct zone and infarct border zone were significantly reduced (F=14.31-35.34,P<0.01 ) and troponin I expression rate was significantly increased (F=19.05,P<0.01 ),as compared with the infarct model group.In addition,NF-κB positive rate in the infarct border zone was significantly lower in the BM-MNC and MSC groups than in the infarct model group (F=19.05,P<0.01).VEGF gene expression level in the infarct border zone was significandy higher in the BM-MNC group than in the infarct model group and MSC group (F = 49.41,P<0.01).bFGF gene expression level in the infarct border zone was significantly higher in the MSC group than in the infarct model and BM-MNC groups (F=4.71,P<0.01).LVEF was negatively correlated to myocardial cell apoptosis rate and NF-κB level (r=-0.441 1,P<0.05;r=-0.579 6,P<0.01 ).LVEF was positively correlated to number of blood vessels,VEGF and bFGF expression (r=0.775,P<0.01;r=0.565 1,P<0.05;r=0.573 5,P<0.05).CONCLUSION:Transplantation of both autologous BM-MNC and MSC via coronary artery can improve the condition of left ventricular remodeling subsequent to myocardial infarction.The improvement of cardiac functions is related to the increase of blood vessels,VEGF and bFGF expression,the decrease of myocardial cell apoptosis and NF-κ B level in cardiac muscle tissues after stem cell transplantation.BM-MNC transplantation better promotes blood vessel proliferation and VEGF expression in the cardiac tissue but produces worse effects on bFGF gene expression than MSC transplantation.