The present study is to elucidate the mechanisms underlying Gleevec-induced apoptosis of chronic myeloid leukemia (CML) K562 cells in vitro. The apoptotic cell death and cell cycle distribution after Gleevec treatment and the effect of PDCD4 siRNA on Gleevec-induced apoptosis of K562 cells were analyzed by flow cytometry. The effect of Gleevec on p-Crkl, caspase-3, PARP and PDCD4 protein levels, and the knockdown efficacy of PDCD4 siRNA were detected by Western blotting. The results showed that Gleevec dramatically suppressed the phosphorylation level of Crkl in a dose-dependent manner and induced significant apoptosis and G0/G1 cell cycle arrest of K562 cells in time- and dose-dependent manners. In addition, Gleevec activated caspase-3 and its downstream substrates PARP, and the caspase pan inhibitor Z-VAD-FMK (50 micromol x L(-1)) markedly reduced Gleevec-induced apoptosis from 47.97% +/- 10.56% to 31.05% +/- 9.206% (P < 0.05). Moreover, Gleevec significantly increased the protein expression of programmed cell death 4 (PDCD4). PDCD4 knockdown by siRNA reduced Gleevec-induced apoptosis from 46.97% +/- 14.32% to 42.8% +/- 11.43%. In summary, Gleevec induced apoptosis in K562 cells via caspase-3 activation.

Objective To seek a optimization method for lung cancer planning with Helical TomoTherapy for reducing the low dose area of total lung.Methods CT images of thirty patients with unilateral lung cancer were selected.Seven plans (Groups A,B,C,D,E,F and G) were generated for each patient using an identical optimization procedure with the conditions that implemented contralateral lung with unblocked (control group),1/4 directional block,1/2 directional block,directional block,1/4 complete block,1/2 complete block and complete block,respectively.The benefits in different schemes of reducing the low dose area of normal lung tissue were estimated,in order to provide a reference treatment plan scheme in clinical.Results Groups B,C,D and E had less influence on the target than that of group A.And there were no statistical difference between the target dosimetric parameters.The median dose and average dose of group F were increased within 0.5 Gy.The conformal index of group G had great influence on the target.The low dose area of total lung were reduced effectively in Groups C,D,E,F and G,the average decrease of V5 and V10 was 8.06％-45.26％ and 6.21％-33.95％,respectively.The V20 decreased by 1.71％-3.78％ in directional block group,while V20 increased in complete block group (2.07％-5.07％).The single treatment time was increased by 8.51％-79.22％.Conclusions The results showed that the low dose area of total lung was higher for the plan without any block limitation.It could reduce the low dose area of total lung with directional block.We should lengthen the blocking arc of contralateral lung with directional block based on the fractional treatment time and the patient's physical condition.A certain arc of contralateral lung with complete block could effectively reduce low dose area.When complete block was used,it is suggested that the arc was no more than half of the contralateral lung.

Objective To evaluate the efficacy and side effects of whole body γ/-knife in patients with limited pancreatic carcinoma. Methods 111 patients with limited pancreatic carcinoma treated with the Stereotactie Gamma Ray Whole-Body Therapeutic System (Whole Body T-knife) were retrospectively an-alyzed. Patients were supine, fixed with a stereotactic body frame and vacuum bag, and then simulated by low-speed computed tomography. GTV, CTV and PTV were defined on the contrast-enhanced CT scans. It was required that 50% isedose line covered 100% of PTV and 70% isedose line covered more than 80% of GTV. The prescription dose was defined as 50% isodose. All patients were treated 5 fractions per week. The fractionated dose was 3-4 Gy for pancreatic head carcinoma, and 4-5 Gy for pancreatic body/tail carcino-ma. Irradiation of 40-51 Gy and 60-70 Gy were delivered to PTV and GTV margins, respectively. Re-suits The complete response rate, partial response rate and overall response rate of the primary tumors were 29.7%, 42.3% and 72.1%, respectively. The follow-up rate was 95.5%. The number of patients fol-lowed-up at 1-,2- and 3-year was 105,89 and 60. The 1-, 2- and 3-year overall survival rates were 49.3%,24.5% and 18.1%. For patients with stage Ⅰ/Ⅱ disease,the number of patients followed-up at 1-,2-,3-,4-and 5-year was 55,44,29,16 and 11 ;The 1-, 2-, 3-,4- and 5-year overall survival rates were 68%,34%, 30%, 21% and 17%, respectively. For patients with stage Ⅲ disease,the number of patients fol-lowed-up at 1-,2- and 3-year was 50,45 and 31 ;The 1-, 2- and 3-year overall survival rates were 28%,14% and 4%, respectively (χ~2=16.67, P=0.000). The acute side effects including nausea, vomiting and diarrhea were 71.2% of RTOG grade 1 -2 and 3.6% of RTOG grade 3. No treatment delay occurred.Conclusions With fractionated dose of 3-5 Gy,5 fractions per week and 40-51 Gy as total dose to PTV,whole body γ-knife is safe and effective to treat limited pancreatic carcinoma. The local control and overall survival could be improved.

Tomotherapy plans were produced using a combination of field widths (1 cm, 2.5 cm and 5 cm) and pitches (0.15, 0.30, and 0.45) for seven patients with brain metastases from lung cancer, the plans were compared with dosimetric parameters, protection of organs at risk (OAR) dose and treatment times. All plans were defined that CTV with 30Gy and GTV 50 Gy by ten fraction synchronously. The results showed that the mean dose and CI for GTV was statistical difference (P = 0.002 1, P = 0.012 8), OARs were within the normal range, the treatment time increased inversely proportional to the jaw width, but had lesser impact on the pitch. This study showed plans produced with 5 cm jaw was an effective method for patients with brain metastases from lung cancer.
Aged ; Brain Neoplasms ; diagnostic imaging ; secondary ; Female ; Humans ; Lung Neoplasms ; pathology ; Male ; Middle Aged ; Radiotherapy Planning, Computer-Assisted ; methods ; Radiotherapy, Intensity-Modulated ; methods ; Tomography, Spiral Computed

Objective To study the dose characteristics of Body γ Knife and Tomotherapy treatment plans for hepatocellular carcinoma,and compare their differences between organs at risk (OAR) dose and the range of low dose.Methods CT simulation images of twelve patients with hepatocellular carcinoma were selected,the target volume and OAR were drew by doctor.Body γ Knife and Tomotherapy treatment plans were optimized with their own planning station.The dosimetric characteristics were evaluated by dose volume histograms and were compared.To analyze the difference between the two techniques,the paired t-test was applied.Results The Dmax and Dmean of target with Body γ Knife were higher than Tomotherapy (P =0.002,0.000),but the conformal index of PTV of Tomotherapy was superior to the Body γ Knife (P =0.001).The Dmax of spinal cord and left kidney with Body γ Knife was lower than Tomotherapy (P =0.013,0.012),and it was also in the Dean of stomach and left kidney (P =0.010,0.023).In the volume dose comparison,the V40,V35,V30,V25 and V20 of normal tissue (all Body-PTV) and liver (all liver-GTV) with Body γ Knife were higher than Tomotherapy (P =0.001,0.001,0.001,0.007,0.029),but the V10 and V5 were lower (P =0.019,0.031),the Dmax of stomach,Dmean of right kidney and liver were no statistical difference (P =0.247,0.308,0.401).Conclusions Both treatment plans could meet the clinical dosimetric need,by the same prescription dose,Dmax and Dmean of target of Body γ Knife were higher than Tomotherapy.Tomotherapy had excellent dose-target conformal and could reduce the range of V25-V40 of OAR and normal tissue,but the range of V5-V10 was increased obviously.

Objective To analyze the result of dose-escalated radiotherapy vs conventional radiotherapy for spinal metastases. Methods Ninety patients (118 lesions) underwent radiotherapy..There were 52 patients (63 lesions) in target in target radiotherapy (TIT) receiving PTV 30~40 Gy, GTV 50~60 Gy/15~25 f. 38 patients (55 lesions) received PTV 30~40 Gy/10~20 f in the conventional radiotherapy. Results The overall responses were 90.4% and 81.6%,respectively.but no significant difference was found. There were 31 and 25 improved lesions, 28 and 20 steady lesions, 4 and 10 worsening lesions,in two goups, respectively. 1-year local control rates and survival were 84.7%vs 68.6%and 49.4%vs 32.2%, respectively. The significant differences were found in 1-year local control rates and survival. The main acute adverse reactions were mainly hematologic toxicities , no significant difference was found. Conclusion TIT for spinal metastases is a more safe and effective treatment, with better efficacy and fewer side-reactions.

ObjectiveTo further evaluate the value of the stereotactic gamma-ray body radiation therapy ( γ-SBRT ) for patients with stage Ⅰ / Ⅱ non-small cell lung cancer ( NSCLC ) basing on the preliminary studies.MethodsTwenty-nine eligible patients with stage Ⅰ / Ⅱ NSCLC who is unable or unwilling to receive surgery underwent treatment prospectively with γ-SBRT (OUR-QGD).Patients were fixed by vacuum bag.Each patient underwent slow CT simulation at 5 s/slide with thickness of 5 mm and interval of 5 mm to take into consideration tumor motion.A total dose of 50 Gy was delivered at 5 Gy/fraction to 50％ isodose line covering 100％ of the PTV,with 60 Gy at 6 Gy/fraction to 60％ isodose line covering 90％ of the CTV,70 Gy at 7 Gy/fraction to 70％ isodose line covering 80％ of the GTV,and 10 times finished in 2 weeks,5 fractions per week.ResultsThe follow-up rate was 97％.The 6 month local tumor response rate was 93％,with CR 86％,and PR 7％.The 1-,2-year local control rates were both 93％.The 1-,2-year overall survival rates for the whole group,stage Ⅰ and stage Ⅱ were 97％ and 89％,100％ and 92％,67％ and 67％,respectively.The 1-,2-year progression-free survival were 90％ and 86％,respectively.34％ of the patients had acute radiation toxicities ( grade 1,2 and 3 in 6,2 and 2patients,respectively),and 38％ late radiation toxicities ( grade 1 and 2 in 10 and 1,patients).Conclusions γ-SBRT is a safe and effective treatment regimen,resulted in promising local control and survival with minor toxicity.

Objective To explore the efficacy and security of helical tomotherapy (radical radiotherapy) combined with targeted therapy for stage Ⅳ non-small cell lung cancer (NSCLC).Methods The data of 19 patients with stage Ⅳ NSCLC were retrospectively analyzed.The efficacy and security were observed by SPSS 20.0 statistical software.Results Among 19 patients, there were 6 cases complete remission (CR), 8 cases partial remission (PR), 4 cases stable disease (SD), 2 cases progressive disease (PD).The response (CR+PR) rate was 73.7 ％ (14/19).The 1-and 2-year local control rates were 73.7 ％, 47.4 ％,respectively.The 1-year progression-free survival rate was 31.6 ％.The median survival time was 13 months, and the 1-and 2-year overall survival rates were 52.6 ％, 26.3 ％, respectively.The median survival time of females, non-smokers or targeted therapy synchronous radiotherapy was longer than that of male, smokers or targeted therapy sequential radiotherapy, respectively (21 months vs 8 months, P =0.014;21 months vs 6 months, P =0.007;18 months vs 6 months, P =0.026).There were no significant differences of age, number of metastatical organs or targeted drug categories between two groups (P ＞ 0.05).All patients could tolerate the adverse reactions without treatment-related death.Conclusion The effect of helical tomotherapy combined with targeted therapy for stage Ⅳ NSCLC is desirable.

Objective To investigate the setup errors of head and neck tumor patients with head mask-ing by TomoTherapy with megavoltage CT (MVCT),and to measure the CTV -PTV margins.Methods There were 34 patients with head and neck tumor .All patients had received MVCT scanning before radiation was deliv-ered.The MVCT images were registered with the kilovoltage CT (kVCT)images,the setup errors of the left -right (x),anterior-posterior(y),superior-inferior(z)and transverse profile rotation(Roll)were obtained by matc-hing MVCT with kVCT,followed by calculating the reasonable CTV -PTV margins with the formula M=2.5∑+0.7σ.Results Six hundred and forty MVCT images in total were received for the patients ,the systemic ±random errors in x,y,z and Roll directions were ( -0.15 ±0.55) mm,(0.30 ±0.56) mm,(0.35 ±0.71) mm and (-0.07 ±0.52)°,the CTV-PTV margin in x,y and z directions were 3.31 mm,5.32 mm and 3.35 mm.Con-clusion we demonstrate a theoretic foundation for our CTV -PTV margins in head and neck tumor patients by analyzing the setup errors ,and it also can provide necessary quality assurance for precise radiation .

Objective To analyze the setup errors of bone metastases patients by tomotherapy with megavoltage CT (MVCT) and calculate the CTV-PTV margins.Methods 30 patients with bone metastases were enrolled.All patients received tomotherapy,fixed with body net and received MVCT scanning before radiation.The MVCT images were registered with the kilovoltage CT (kVCT) images,the setup errors of X (lateral),Y (vertical),Z (longitudina) and Roll (transverse profile rotation) were obtained according to the formula M =2.5Σ+0.7σ calculated CTV-PTV margin.Results 30 patients were received 494 MVCT images.The errors of systemic±random were (2.85±0.77) mm,(3.11±0.95) mm,(2.21±0.55) mm,and (0,55±0.24)° on X,Y,Z and Roll directions,respectively.The CTV-PTV margins were 3.64 mm,4.17 mm,and 2.86 mm on X,Y,Z directions,respectively.Conclusion The application of image-guided technology for bone metastases can correct positioning in time,which greatly reduces setup errors of the fractionated treatment,further improves the treat accuracy and has a positive value in guiding clinical radiotherapy.