Effect of stereotactic body radiation therapy on the survival of patients with pancreatic cancer recurrence after surgery / 中华胰腺病杂志

Objective To identify the effect of stereotactic body radiation therapy (SBRT) on the survival of patients with recurrent pancreatic cancer after surgery.Methods The data of 104 patients with recurrent pancreatic cancer after surgery who underwent SBRT in the Department of Radiation Oncology of Changhai Hospital,Navy Medical University from February 2012 to December 2016 were retrospectively analyzed.The prescription doses ranged from 35-40 Gy/4-8 f.Survival analysis was performed using the Kaplan-Meier method,and relevant factors affecting patients' survival were screened by the Cox proportional hazards model.Results The median overall survival (OS) and progression free survival (PFS) was 12.5 (11.0-14.0) months and 7.3 (6.0-8.7) months,respectively,while the 1-year rate of OS and PFS was 55.8％ and 22.1％,respectively.Multivariate analysis indicated that tumor stage,biological effect dose (α/β =10,BED10),the decrease of CA19-9 level after treatment,and follow-up chemotherapy were all related factors affecting overall survival;tumor stage,BED10,the degree of pain relief and the decrease of CA19-9 level after treatment were related factors affecting PFS.Conclusions Patients suffering recurrent pancreatic cancer with early tumor stage,normal CA19-9 level and mild pain before treatment could be better treated by SBRT,BED10 ≥60 Gy and follow-up chemotherapy after radiotherapy can prolong the survival of patients.

The study on the parameters of treatment plans for pancreatic cancer with cyber-nife system / 中华胰腺病杂志

[Abstact] Objective To analyze the related parameters of the treatment plans for the pancreatic cancer with the Cyber-knife system.Methods The clinical data of 129 patients with single-target pancreatic cancer for the first time who underwent CyberkKnife radiosurgery between January 2017 and December 2017 in Shanghai Changhai Hospital were retrospectively analyzed.The parameters were all selected from the MultiPlan @4.0.2 treatment planning system and the data were analyzed.Results The volume of the targets in 129 patients with pancreatic cancer was 3.355-238.936 cm3,with the average volume of 51.43 ± 55.64 cm3.Patients were averagely treated for 5 to 8 sessions,and the average prescription dose was 6 Gy × 6 fraction,which equaled to 58 Gy in the biological equivalent dose (BED).The collimators with 20 mm and 15 mm accounted for up to 31％ and 27％,respectively,which were the top 2 options.The finally designed the conformal index(CI),new conformal index(nCI),and the homogeneity index were 1.14 ± 0.09,1.29 ± 0.09 and 1.42 ± 0.04,respectively.The coverages of tumor target was 80.3％-95.6％,with the average of 90.0 ± 4.6％.The treatment nodes,beams and Mus are 79,180 and 7 060 in average.The estimated treatment time was 42 ± 8 minutes.The organs at risk can be protected very well.Conclusions Reasonable Cyber-knife treatment plan can guarantee that stereotactic body radiation therapy can effectively treat Pancreatic Cancer.

Analysis on the therapeutic effects of re-irradiation with stereotactic body radiation therapy for the advanced recurrent locally pancreatic cancer / 中华胰腺病杂志

Objective To investigate the safety and efficacy of re-irradiation with stereotactic body radiotherapy(SBRT) for treating locally recurrent advanced pancreatic cancer.Methods From 2014 to 2017,7 patients with stage Ⅲ pancreatic cancer were treated by re-irradiated with SBRT at Shanghai Changhai Hospital.SBRT was delivered via the G4 type cyberknife robotic stereotactic radiosurgery system in all the patients.The median dose of the first SBRT was 35Gy/5-7 fx,and the median dose of re-irradiation with SBRT was 31 Gy/5-8 fx.6 patients had undergone sequential chemotherapy either with gemcitabine or S-1 based therapy except one patient who refused the chemotherapy.Results There were 5 male and 2 female patients.The median overall survival (OS) of 7 patients was 30 months.Patients were re-irradiated with SBRT after a median interval of 10 months after the first SBRT.Median OS and locally relapse-free survival (LFRS) from re-irradiation were 13 months and 11 months,respectively.Three months after re-irradiation,3(42.9％) patients had partial remission and 4 patients had stable disease.Pain disappeared in 4 patients at the end of reirradiation and significant pain was alleviated in 2 patients 1 month after re-irradiation.There were no toxicities of grade 3 or higher grade during two courses of SBRT.Conclusions For patient with locally recurrent advanced pancreatic cancer,SBRT re irradiation regimen was associated with acceptable toxicity,which can effectively alleviate the pain,prolong the survival and improve the life quality.

Organ endangering dose and side effects in two courses of stereotactic body radiation therapy for pancreatic cancer / 中华胰腺病杂志

Objective To assess the cumulative doses and side effects after two courses of stereotactic body radiation therapy (SBRT) for pancreatic cancer. Methods Twenty-four pancreatic cancer patients who received two courses of SBRT were enrolled. Organ endangering dose accumulations were calculated by rigid and non-rigid registration. All doses were recalculated to an equivalent dose of 2 Gy per fraction. Results The median of accumulated maximal dosage (Dmax) and dosage per 1cc(D1cc) of the stomach,duodenum and the bowel were 43.87 and 35.28 Gy 3,35.53 and 26.59 Gy3,45.08 and 36.18 Gy3; and the median volume under the dosage of 10Gy (V10) was 107.40,23.98 and 169.26cc, respectively. The median accumulated Dmaxand the dosage of 35% volume(D0.35) of the spinal cord was 8.42 and 7.83Gy3. The median cumulative Dmeanand D2/3of the left and right kidney were 5.18 and 3.65 Gy3, 3.50 and 2.57 Gy3, respectively. The median cumulative Dmeanand D50%of the liver was 5.18 and 3.64Gy3,respectively. The median summed dose to the overlapping radiation field of the two courses was 93.38 Gy3. No grade 3-4 toxicity occurred. Conclusions The cumulative doses to organs at risk as dose constraints were safe and acceptable,which could be used as a reference to evaluate whether a second SBRT could be done after initial SBRT for pancreatic cancer.

The application of different Auto-shells and optimization steps of CyberKnife treatment plans for pancreatic cancer / 中华胰腺病杂志

Objective To propose the method of dose distribution calculated by one-step optimization with 7 shells (Cao method) and compare with that by three-step optimization with 4 shells (Blanck method) and CyberKnife treatment plans for pancreatic cancer. Methods 20 cases of pancreatic cancer who underwent CyberKnife treatment were retrospectively analyzed,and CT was performed to localize and delineate the target area and endangering organs. Dosage was optimized and evaluated with Blanck method and Cao method. The planning target volume (PTV) conformity index (CI), new conformity index (nCI), homogeneity index (HI),gradient index (GI), coverage, dose-volume and doses to organs at risk were compared. Results Compared with Blanck method, CI (1.11 ± 0.05 vs 1.15 ± 0.05), nCI (1.20 ± 0.06 vs 1.23 ± 0.06), coverage [(92.48 ± 1.85)% vs (93.53 ± 2.15)%], volumes encompassed by 100% and 30% prescription dose line (36.46 ± 16.64 vs 38.19 ± 17.68; 286.19 ± 126.52 vs 320.93 ± 154.82) and monitor unit (56 369 ± 20 019 vs 57 814 ± 20 531) were significantly decreased,while GI was increased (3.22 ± 0.19 vs 3.11 ± 0.19), and all the differences were statistically significant (P<0.05). Additionally, Dmax of the intestine (21.17 ± 2.90 vs 20.63 ± 3.13), D10cc of the stomach (12.78 ± 2.57 vs 13.11 ± 2.43), D5ccof the duodenum (11.01 ± 3.45 vs 11.50 ± 3.25), D10ccof the duodenum (9.30 ± 3.31 vs 9.78 ± 3.07) and D0.35ccof the spinal cord (6.09 ± 0.98 vs 6.59 ± 0.92) were all significantly decreased (P<0.05). No significant differences were found on other parameters. Conclusions Better dose distributions are accessible by one-step optimization with 7 shells in CyberKnife treatment plans for pancreatic cancer.

Influence of combined treatment sequence of stereotactic body radiation therapy and chemotherapy on the survival of very elderly patients with locally advanced pancreatic cancer / 中华胰腺病杂志

Objective To investigated the influence of different combined treatment sequence of stereotactic body radiation therapy (SBRT) and chemotherapy (CT) on the survival of very elderly patients with locally advanced pancreatic cancer ( LAPC) .Methods The data of LAPC patients ≥60 years old treated by CyberKnife SBRT at Shanghai Changhai Hospital from January 2012 to December 2016 was retrospectively analyzed.According to treatment sequences , patients were divided into three groups:CT+SBRT group ( first chemotherapy and then SBRT ) , SBRT+CT group ( first SBRT and then chemotherapy ) and CT+SBRT+CT group ( first chemotherapy , then SBRT and finally chemotherapy ) .Patients were recommended to receive a 6-month chemotherapy .Intravenous administration of 1000 mg/m2 gemcitabine was initiated on day 1, 8, and 15 every 4 weeks or S-1 was orally given at a dose of 80 mg/m2 for 28 days followed by a 14-day rest , which repeated for 6 cycles.Radiotherapy parameters: the median total prescription dose was 36(30-45)Gy; the median per fraction dose was 7(5-9)Gy;the median number of fractions was 5(5-8) fractions;the median biological equivalent dose (BED10) were 61.92(48-85.5) Gy, respectively.The interval between SBRT and chemotherapy ranged from 2 to 3 weeks.Patients were followed every 3 months.The main outcome measures were overall survival ( OS) and median progression free survival ( PFS) .Second outcome measure was adverse events.Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE 4.0) was employed to evaluate adverse events , and RTOG/EORTC was used to assess the adverse events of radiotherapy .Overall survival (OS) and PFS were calculated by Kaplan-Meier method.Univariate and multivariate logistic regression model were used to analyze the independent risk factors .Results A total of 260 patients were enrolled in the study , including 28 patients treated with CT+SBRT, 163 patients undergoing SBRT +CT and 69 patients treated with CT+SBRT+CT.The median OS and PFS were 13.2(95％CI 12.8-13.6)months and 8.2(95％CI 7.7-8.7)months, respectively.OS in CT +SBRT, SBRT +CT and CT +SBRT +CT group was 12.2 (10.9-13.9),13.4 ( 12.9-13.9 ) and 13.1 ( 12.7-13.5 ) months, and the differences were not statistically significant(P=0.425).PFS in CT+SBRT, SBRT+CT and CT+SBRT+CT group was 6.4(5.9-6.9), 8.3(7.8-8.8) and 8.2(7.2-9.2)months, and the differences were statistically significant (P=0.008).In univariate analysis , ECOG, SIRI, the extent of decreased CA 19-9 after treatment and BED 10 were important factors of OS.In multivariate analysis, the CA19-9 response and BED10 were independent factors for OS . Multivariate analysis showed that the extent of decreased CA 19-9 after treatment and BED 10 were important factors of OS.In CT+SBRT group, patients had lower ECOG score (χ2 =115.325,P<0.001) and earlier clinical staging (χ2 =24.788, P<0.001 ).In SBRT +CT group, patients had advanced staging (χ2 =159.759,P<0.001) and lymph node metastasis(χ2 =40.925,P<0.001).Only 1 patient experienced grade 3 radiotherapy associated duodenitis .The adverse events of patients who were first treated by chemotherapy included grade 3 neutropenia in 4 patients and grade 3 gastrointestinal reaction in 5 patients.The adverse events of patients who were first treated by radiotherapy included grade 3 neutropenia or/and leucopenia in 18 patients and grade 3 abdominal pain, nausea or vomit in 16 patients.The adverse events of CT +SBRT+CT patients included grade 3 neutropenia or/and leucopenia in 4 patients and grade 3 abdominal pain or nausea in 5 patients.There was no grade ≥4 adverse events.Conclusions For very elderly patients with LAPC , the survival of patients who received pre-SBRT chemotherapy , post-SBRT chemotherapy and pre-and post-SBRT chemotherapy was comparable , but SBRT+CT group and CT +SBRT+CT group had longer PFS than CT +SBRT group.

The optimization of enhancement scanning delay with CT-based simulation before cyberknife treatment for pancreatic cancer / 中华放射医学与防护杂志

Objective To assess the optimal delay time of enhanced scanning with CT-based simulation before cyberknife treatment for pancreatic cancer and to analyze the correlations between the target delineation and the rating items.Methods One hundred and twenty pancreatic cancer patients underwent Philips 16 big core spiral CT before cyberknife treatment.Patients were assigned to three groups randomly with scan delays of 25,45 and 65 s;30,50 and 70 s;and 35,55 and 75 s respectively.After the scanning,the images were evaluated by three associate professors in the field of radiation oncology.To achieve the optimal delay time,the data were compared with a random intercept model of mathematical mean,the Sidak method and One-way ANOVA.Pearson method was used to analyze the correlations between the target delineation and the rating items.Results The tumor boundaries,retroperitoneal lymph nodes,duodenal images,accuracy of target volume delineations in 45 and 65 s,50 and 70 s,55 and 75 s items rating difference had no statistically significant differences (P ＞ 0.05),but significantly superior to those in 25,30,35 s groups respectively(t =3.59-21.68,13.34-15.46,12.42-13.83,P ＜0.05).Therefore,the proposed delay time interval was 50-65 s,and the average value of the target volume delineation was the highest in 55 s group (3.91-± 0.50).When the scan delay time was 55 s,the target delineation was positively correlated with the tumor boundary (r =0.914 4,P ＜ 0.05),and negatively related to the value of other imaging (r =-0.926 3,P ＜ 0.05).Conclusions The recommended delay time interval of pancreatic cancer before cyberknife treatment CT enhanced scanning was 50-65 s,and the optimal time point was 55 s.The target volume delineation was positively correlated with the boundary of the tumor,and significant negatively related to the value of other imaging.

The application of CyberKnife stereotactic body radiotherapy in treatment of oligometastatic prostate cancer / 中华泌尿外科杂志

Objective To determine the effectiveness and safety of stereotactic body radiotherapy (SBRT)-CyberKnife for oligometastatic prostate cancer.Methods From May 2012 to February 2017,31 patients treated by CyberKnife were retrospectively reviewed,with a median age of 67 years(range 52 to 83 years),including 50 oligometastatic and 2 primary prostate cancer patients.The median PSA level was 8.4 ng/ml(range 0 to 300.0 ng/ml) and PSA test was performed every month.PSA progression-free survival (PSA-PFS),time to initiation of androgen deprivation therapy (ADT) and local control rate (LCR) were measured as the main outcomes.Results SBRT was well tolerated and were performed as planned in all patients.No SBRT related acute or late toxicities were observed.No bone fracture was observed in patients treated by bony targeted radiotherapy.The median follow-up after SBRT was 20.7.months (range 1.2-58.3 months).The median PSA-PFS was 5.3 months (range 0-58.3 months).1-year,2-year,and 4-year PSA-PFS was 52.0％,36.7％ and 36.7％ respe ctively.PSA level decrease was observed in 21 oligometastatic prostate cancer patients after SBRT,with median PSA-PFS of 12.3 months (range 1.2-58.3 months).PSA level increase was observed in 29 oligometastatic prostate cancer patients after SBRT.Six local recurrence were observed resulting in an actuarial 1-year,2-year and 3-year LCR of 90.4％,86.9％ and 82.6％,respectively.Twelve patients treated without ADT after SBRT,with median follow-up of 8.6 months (range 2.9-58.3 months) in this subgroup.Seven patients were added ADT after SBRT,with the median time from SBRT to initiation of ADT of 13.3 months (range 3.0-24.0 months) in this subgroup.Twelve patients were treated with ADT continuously after SBRT.Conclusions CyberKnife seems to be a safe and effective treatment with tolerated adverse events and good local control for patients with oligometastatic prostate cancer.

The optimization of CT localization enhanced scan time of pancreatic cancer in different positions before cyberknife treatment / 中华胰腺病杂志

Objective To explore the optimal delay time of enhanced scanning with CT based simulation before cyberknife treatment of carcinoma in different positions of the pancreas.Methods Philips 16 large aperture spiral CT scan was applied.Fifty-three patients with carcinoma in the head of the pancreas and 60 pancreatic cancer patients in the body or tail were randomly assigned to three groups with scan delays of 25,45,and 65 seconds in group A (25s group,pancreatic head n =18,pancreatic body or tail n =21);30,50,and 70 seconds in group B (3 0s,pancreatic head n =17,pancreatic body or tail n =19);and 35,55,and 70 seconds in group C (35s,pancreatic head n =18,pancreatic body or tail n =20),respectively.Images were evaluated by three associate professors of radiation oncology based on image quality score scale.The items rating in different time points were compared using a random intercept model of mathematical mean in three groups.Then the items rating of different time points were compared in pairs using the Sidak method.One-way ANOVA was used to compare the optimal time point of each group,so the optimal delay time of enhanced scanning with CT based simulation before cyberknife treatment of pancreatic cancer was obtained.Results The delayed time points with the highest scores for target delineation of the tumor in the pancreatic head and the pancreatic body or tail by CT enhanced scanning in three groups were 45 s/65 s,50 s/50 s,55 s/75 s,respectively.There was no significant difference in the scan time of 45 s,50 s and 55 s for the tumor in the pancreatic head.Similarly,no significant difference could be found in the scan time of 65 s,50 s and 75 s for the tumor in the pancreatic body and tail.Conclusions The recommended delay time interval for localizing the tumor in pancreatic head by CT enhanced scanning was 45 ～ 55 s,and for the tumor in the pancreatic body or tail was 50 ～75 s.

An initial report of CyberKnife stereotactic body radiotherapy in treatment of small hepatocellular carcinoma:a pilot study / 中华放射医学与防护杂志

Objective To determine the effectiveness and safety of patients treated with stereotactic body radiotherapy ( SBRT ) - CyberKnife for small hepatocellular carcinoma. Methods A prospective analysis of treatment details and outcomes for 33 patients with small hepatocellular carcinoma treated by CyberKnife at CyberKnife center of Shanghai Changhai Hospital from June 2014 to December 2016 was presented. Patients were followed every 3 months. WHO modified response evaluation criteria in solid Tumors( mRECIST) was used to evaluate efficacy, Common Terminology Criteria for Adverse Events Version 4. 0(CTCAE 4. 0) to evaluate treatment response, Kaplan-Meier method to calculate survival rate and local control rate and plot survival curves. Results There were 33 patients, 33 targets included in the study at the date of the last follow-up. 18 lesions (54. 5%) showed complete remission response, 7 lesions (21. 2%) showed partial remission response, 5 lesions (15. 2%) showed stable, and 3 lesions (9. 1%) progressed. Response rate was 75. 8%, and disease control rate was 90. 9%. 1- and 2-year local control rate was 100% and 83. 6%, respectively. The median disease progression free survival ( DPFS) was 15. 0 months. Non irradiated liver volume more than 100 ml, prior AFP less than 100 ng/ml, post-treatment CTCAE less than grade 2 could improve overall survival ( OS ) . V5 was a factor in grades 2 -4 hepatic toxicity ( P=0. 015 ) . All patients tolerated the radiosurgery, with grade 1 and grade 2 fatigue, and the gastrointestinal reactions and liver injury was the main side effect. 1 patient with grade 3 liver damage relieved at 6 months after treatment and 1 patient with grade 4 liver damage cured at 12 months after treatment. No grade 5 toxicity was encountered. Conclusions CyberKnife seems to be a safe and effective treatment measure with tolerated adverse reaction and good local control rate for patients with small hepatocellular carcinoma.

The application of multiple b value DWI in evaluating the short-term efficacy of cyberknife for locally advanced pancreatic cancer / 中华胰腺病杂志

Objective To explore the value of Multiple b value DWI ( MbDWI ) in the short-term efficacy evaluation of cyberknife radiotherapy for locally advanced pancreatic cancer ( LAPC ) .Methods A total of 36 patients underwent both conventional sequence and respiratory triggered MbDWI ( b=0, 25, 50, 75, 100, 150, 200, 400, 600, 800, 1 000 s/mm2 ) before cyberknife radiotherapy, 1month and 3 months after the radiotherapy, respectively.ADCtot, f, Dfast and Dslow were calculated using single and double exponential model and the changes before and after radiotherapy were observed.Results Before radiotherapy, 1 month and 3 months after radiotherapy, the ADCtot values of solid lesions were (1.56 ±0.29) ×10-3 mm2/s, (1.75 ±0.31) ×10 -3 mm2/s and (18.6 ± 0.46) ×10 -3 mm2/s;the values of Dslow were (1.10 ±0.73) × 10 -3 mm2/s, ( 1.19 ±0.97 ) ×10 -3 mm2/s and ( 1.49 ±04.6 ) ×10 -3 mm2 s/; the values of Dfast were (83 .33 ±62 .57) ×10 -3 mm2/s,(124.57 ±123.10) ×10 -3 mm2/s and (108.07 ±96 .67) ×10 -3 mm2 /s; f values were (26.81 ±23.74)%,(23.61 ±22.75)% and (21.34 ±15.36)%, respectively.ADCtot values 1 month and 3 months after treatment were significantly higher than those before treatment and Dslow 3 months post-treatment was higher than that before treatment, and the differences were statistically significant ( both P<0.05) and no other differences between two groups were significant.There were no statistical differences on Dfast and f before and after radiotherapy.Conc lusions ADCtot and Dslow both showed a significant growth trend after cyberknife radiotherapy.The advanced degree of parenchymal cystic in the targeted lesion could reflect the short-term efficacy of cyberknife treatment.

Roles of interleukin-10 in acute graft-versus-host disease and graft rejection / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To study the role of interleukin (IL)-10 in acute-graft-versus-host disease (aGVHD) and graft rejection.</p><p><b>METHODS</b>Serum concentrations of IL-10 in 28 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) were measured by enzymed-linked immunosorbent assay (ELISA). IL-10 gene expression in peripheral mononuclear cells was measured by reverse-transcriptase polymerase chain reaction (RT-PCR) after transplantation.</p><p><b>RESULTS</b>Seven patients developed grade I GVHD, 7 patients developed grade II-IV GVHD, 4 patients had graft rejection. Before transplantation, the concentrations of IL-10 were higher in patients who later did not developed aGVHD. After transplantation, IL-10 levels increased in patients without aGVHD, but decreased in patients with aGVHD or graft rejection. And IL-10mRNA was more frequent in patients without aGVHD compared to those with aGVHD.</p><p><b>CONCLUSIONS</b>IL-10 plays a negative role in the development of aGVHD and graft rejection.</p>

Study on tumorigenic mechanism of human leukemia cell line in nude mice / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the tumorigenic mechanisms of human leukemia cell line HL60-n in nude mice.</p><p><b>METHODS</b>Different clone strains of HL60-n cells were established by limited dilution and their biological features were compared with parental HL-60 cells.</p><p><b>RESULTS</b>The colony yields in soft agar, especially the large colony yields of the high tumorigenic clone strains HL60-n/A, HL60-n/B were significantly higher than that of the HL-60 cells (P < 0.01). There was no significant difference between the low tumorigenic clone strains HL60-n/E, HL60-n/F and the HL-60 cells. Ultrastructurally, the nucleus was highly abnormal, the euchromatic element of nuclear chromatin increased, the heterochromatin sparse, and the microfilaments in cytoplasm increased and disarranged in the high tumorigenic cells as compared with HL-60 cells. Cell cycle analysis by flow cytometer showed higher S phase fractions in the high tumorigenic cells. The killing activities of NK cells to the high tumorigenic clone strains were significant lower than to the contrast (P < 0.01). The histopathological features produced by the low tumorigenic leukemia cells showed that there were many inflammatory cells infiltrated, the majority of them were lymphocytes, and many tumor cells were killed especially in vessel abundant areas. By contrast, there were few inflammatory cells infiltrated in the tumors produced by the high tumorigenic cell strains.</p><p><b>CONCLUSION</b>The mechanism of the high tumorigenic activity of the HL60-n cell line involved higher colony yields in soft agar, higher S phase fraction, decreased susceptibility to NK cell killing, and the inhibition of the host immunity.</p>

Expression of cell adhesion molecules in acute leukemia cell / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the role of cell adhesion molecule in the development and extramedullary infiltration (EI) of acute leukemia.</p><p><b>METHODS</b>The expressions of neural cell adhesion molecule (NCAM) gene, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) genes in 25 acute leukemia patients bone marrow cells were detected by microarray and reverse transcriptase-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>The expressions of NCAM, ICAM-1 and VCAM-1 gene were significantly higher in acute leukemia cells and leukemia cells with EI than in normal tissues and leukemia cells without EI, respectively, both by cDNA microarray and by RT-PCR.</p><p><b>CONCLUSION</b>The cDNA microarray is a powerful technique in analysis of acute leukemia cells associated genes. High expressions of cell adhesion molecule genes might be correlated with leukemia pathogenesis and infiltration of acute leukemia cell.</p>

STUDY OF IL-12 EXPRESSION IN THE PATHOGENESIS OF ACUTE GRAFT-VERSUS-HOST DISEASE / 解放军医学杂志

To investigate the potential role of interleukin 12 (IL 12) in human acute graft versus host disease (aGVHD). 26 patients undergoing allogeneic hematopoietic stem cell transplantation (allo HSCT) were included in this study. IL 12 protein and gene expression in peripheral blood mononuclear cells were measured using enzyme linked immunosorbent assay (ELISA)and reverse transcription polymerase chain reaction (RT PCR), respectively. The results showed that all the patients achieved engraftment.Among them, 10 patients developed grade ⅠGVHD, 5 patients deveolped grade Ⅲ or Ⅳ GVHD. IL 12 protein and gene expressions in peripheral blood mononuclear cells were significantly higher in patients with aGVHD compared with those without aGVHD.The levels of IL 12 correlated significantly with the severity of aGVHD .The results suggested that IL 12 might play an important role in the development of human aGVHD.

Role of IL-10 in acute graft-versus-host disease and graft rejection / 中国免疫学杂志

Objective:To study role of IL 10 in acute graft versus host disease(aGVHD)and graft rejection.Methods:20 patients undergoing allogeneic hematopoietic stem cell transplantation (allo HSCT),serum concentrations of IL 10 were measured by using enzymed linked immunosorbent assay(ELISA)during transplantation,IL 10 gene expression in peripheral mononuclear cells were measured by using reverse transcriptase polymerase chain reaction (RT PCR)after transplantation.Results:6 patients developed grade I GVHD.4 patients grade III IV GVHD,3 patients graft rejection. Before transplantation ,the concentrations of IL 10 with the patients who developed severe aGVHD or graft rejection were lower than those without aGVHD.After transplantation, the concentrations of IL 10 with the patients who developed severe aGVHD or graft rejection decreased,and those without aGVHD or graft rejection significantly increased. The result of RT PCR suggested that the expression of IL 10 mRNA decreased in the patients who developed aGVHD.Conclusion:IL 10 plays an important negative role in the development of aGVHD and graft rejection.

Fetal bone marrow stromal cells support the in vitro expansion of human hematopoietic bone marrow progenitor cells: requirement for cell-to-cell interactions and colony-stimulating factors / 第二军医大学学报

Objective： To elucidate the role of bone marrow stromal cells in cooperation with exogenous cytokines in hematopoiesis. Methods： Fetal bone marrow stromal cells (FBMSC) was combined with cytokines including SCF,IL-3,IL-6,GM-CSF in a 5-day liquid culture system of adult bone marrow mononuclear cells, then we cultured bone marrow derived CD34+-enriched cells with FBMSC+SCF+IL-3+IL-6+G-CSF+EPO for 2 weeks. Results：FBMSC were in good cooperation with above mentioned exogenous cytokines. When CD34+-enriched cells from adult bone marrow were cultured with combinations of FBMSC, SCF, IL-3, IL-6, G-CSF and EPO, total nucleated cells, CFU-GM, BFU-E and CD34+ cells were increased by 119.6±30.9, 54.6±17.4, 25.2±4.4, 11.1±4.2 folds, respectively. Conclusion：FBMSC in cooperation with exogenous cytokines support the in vitro expansion of human hematopoietic progenitor cells efficiently.

Roles of Cytokines in Acute Graft-Versus-Host Disease / 中国实验血液学杂志

Acute graft-versus-host disease (aGVHD) is the major complication of allogeneic stem cell transplantation (allo-HSCT), significantly limits the application of the therapy. Current evidence suggests that dysregulated cytokine production is responsible for many manifestations of aGVHD. The mechanisms have been most clearly delineated in mouse models, detailed analysis of human tissue is required. Monitoring serum levels of cytokine sIL-2R, TNF-alpha and IFN-gamma after transplantation or cytokine gene expression before transplantation can predict prognossis of aGVHD. GVHD have graft-versus-leukemia (GVL) effect, and GVL can be seperated from GVHD. IL-2, IL-12, IL-11, KGF and G-CSF could possess the roles of reducing GVHD while preserving GVL.

Effect of Gancyclovir on Proliferation and Differentiation of Chronic MyeloidLeukemia Cells and Research of Its Mechanism / 中国肿瘤生物治疗杂志

Objective: To explore whether gancyclovir (GCV) can inhibit the proliferation and induce the erythro-differ-entiation of the K562 human myeloid leukemia cell line. Methods: 562 cells were cultured with GCV for 4 days to detect cellular changes cloning efficiency, benzidine-positive rate, flow eytometry analysis, and telomerase activity. Results: When 562 cells grew in the medium containing GCV, the cellular growth and division were gradually suppressed,growth fracture decreased and further differentiation towards the cell producing hemoglobins was found. Conclusion: GCVcan inhibit proliferation and induce erythro-differentiation of K562 cells.

Expression of mSDF-1?/GM-CSF fusion protein and its protective effect on radiotherapy-induced hematopoiesis damages / 中国肿瘤生物治疗杂志

Objective: To express mSDF-1?/GM-CS fusion protein in the Pichia pastoris expression system and investigate its in vivo promoting effects on hematopoiesis function and immune function.Methods: The mSDF-1?/GM-CS fusion gene was chemically synthesized and was cloned into pichia expression vector;the vector was then transfected into Pichia pastoris expression system.Then the expressed products were detected by SDS-PAGE,Western blotting and purified by ion exchange columns.Rat irradiation model was established by 60Co ? ray and were subcutaneously injected with the fusion protein.The hematopoietic and chemotactic activities of the fusion protein were investigated in vivo.Results: The expression vector pPIC9K-SDF1-L-GM-CSF was successfully constructed,and mSDF-1?/GM-CS fusion protein was successfully expressed by Pichia pastoris strain GSl15.The molecular weight of the protein was about 32000 D,with a concentration of 78 ng/ml.The numbers of bone marrow mononuclear cells and GM-CFU were significantly increased in rats after subcutaneous injection of the fusion protein(P