A novel mesenchymal stem cell-based regimen for acute myeloid leukemia differentiation therapy

Currently the main treatment of acute myeloid leukemia (AML) is chemotherapy combining hematopoietic stem cell transplantation. However, the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice. Thus, there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects. Here, we revealed that umbilical cord-derived mesenchymal stem cells (UC-MSC) efficiently induced AML cell differentiation by shuttling the neutrophil elastase (NE)-packaged extracellular vesicles (EVs) into AML cells. Interestingly, the generation and release of NE-packaged EVs could be dramatically increased by vitamin D receptor (VDR) activation in UC-MSC. Chemical activation of VDR by using its agonist 1α,25-dihydroxyvitamin D3 efficiently enhanced the pro-differentiation capacity of UC-MSC and then alleviated malignant burden in AML mouse model. Based on these discoveries, to evade the risk of hypercalcemia, we synthetized and identified sw-22, a novel non-steroidal VDR agonist, which exerted a synergistic pro-differentiation function with UC-MSC on mitigating the progress of AML. Collectively, our findings provided a non-gene editing MSC-based therapeutic regimen to overcome the differentiation blockade in AML.

Modified FOLFOX4 vs docetaxel-oxaliplatin program neoadjuvant chemotherapy in postoperative stage Ⅲ gastric cancer / 中华普通外科杂志

Objective To compare the efficacy and safety of modified FOLFOX4 program with docetaxel-oxaliplatin-5-fluorouracil (DOF) program as neoadjuvant chemotherapy in stage Ⅲ gastric cancer patients.Methods In 86 cases of stage Ⅲ gastric cancer patients,42 received modified FOLFOX4 chemotherapy,44 cases were treated by DOF program.After two cycles of chemotherapy,the treatment effect and adverse reactions were evaluated.Results The total effectiveness in modified FOLFOX4 group and DOF group was 60％ (25/42) and 68％ (30/44) respectively (P ＞ 0.05).Tumor control rate was 83％ (35/42) and 89％ (39/44) respectively (P ＞ 0.05).The incidence of nausea,vomiting and leukopenia was higher in DOF group than modified FOLFOX4 group (P ＜ 0.05).The D2 lymph node dissection rate between modified FOLFOX4 group and DOF group was 80％ (20/25) and 87％ (26/30) respectively (P ＞ 0.05),the R0 resection rate was 72％ (18/25) and 83％ (25/30) respectively (P ＞ 0.05).In 43 R0 resection patients using FOLFOX4 the median survival time was 38.7 months,1-,3-year survival rate was 90％,and 60％ ; while that in DOF group the median survival time was 39.6 months,1-,3-year survival rate was 95％,and 75％.Multivariate analysis showed that postoperative TNM stage only was an independent risk factor for prognosis.Conclusions TNM stage was the independent risk factor for prognosis of gastric carcinoma patients after radical gastrectomy.

Intravenous chemotherapy in combination with TACE for the treatment of hepatic metastasis of gastric cancer / 中华普通外科杂志

Objective To evaluate efficacy and safety of intravenous chemotherapy combined with TACE in the treatment of gastric cancer with hepatic metastasis.Methods In this study 60 gastric cancer patients with hepatic metastasis were divided into two groups randomly,the trial group (30 cases) took intravenous chemotherapy consisted of docetaxel 60 mg/m2 intravenous drip d1,oxaliplatin 80 mg/m2 intravenous drip d1 followed by 5-fiuorouracil 500 mg/m2 intravenous drip d1-5 after TACE.The control group (30 cases) took the same chemotherapy protocol and one treatment cycle covering 4 weeks.Results The overall response rate in trial group was 53％ and the increase rate of Karnofsky was 70％ while that was 37％ and 40％ respectively in the control group (P ＜ 0.05).The median overall survival of trial group was 13 months and which was 8 months in the control group (P ＜ 0.05),meanwhile the toxicities and side reactions of trial group didn't increase notably.Conclusions Intravenous chemotherapy combined with TACE is safe and more effective in the treatment of gastric cancer with hepatic metastasis.

Radiosensitization and relative mechanisms of vanillin derivative BVAN08 on human glioma U-251 cells / 中华放射医学与防护杂志

Objective To provide more convincing evidences and experimental data for exploring vanillin derivative BVAN08,6-bromine-5-hydroxy-4-methoxy-benzaldehyde,as a new anticancer drug,and to investigate the effect on the growth,radiosensitization of human glioma cell line U-251 and the relative mechanism.Methods The effect of BVAN08 on cell proliferation of U-251 and radiosensitivity to 60Co γ-rays (irradiation dose rate 2.3 Gy/min) were analyzed with MTT and colony-forming ability assay.Change in cellular morphology was observed by using light microscope.Change in cell cycle and apoptosis was detected with flow cytometry.The autophagy was observed by using TEM (irradiation dose rate is transmission electron microscope).DNA-PKcs protein level was detected through Western blot analysis.Results BVAN08 exhibited a dose- and time-dependent inhibition on the proliferation of U-251 cells during the concentration range of 10-100 mol/L (t = 1.83-3.07,P ＜ 0.05).IC50 at 48 h and 72 h after administration with BVAN08 were 55.3 and 52.7 mol/L,respectively.Obvious G2/M arrest was induced in U-251 cells after 4 h administration with BVAN08,and reached peak at 12 h.The G2/M population reached 63.3% in U-251 cells after 12 h administration of 60 μmol/L BVAN08 and kept increasing with the time,while both apoptosis and autophagic cell death were induced.The most effective radiosensitization time for BVAN08 treatment was 12 h before irradiation.The enhancement ratio of radiosensitivity was 3.14 for 20 μmol/L of BVAN08 12 h before 2 Gy irradiation.Conclusions BVAN08 can nduce apoptosis as well as autophygic cell death of U-251 cells,and sensitize U-251 cells.The mechanism of its radiosensitizing effect might be associated with the induction of G2/M arrest and inhibition of DNA-PKcs expression.BVAN08 seemed to be a romising radiosensitizing anticancer drug.

Value of double contrast-enhanced ultrasonography in the preoperative TN staging for gastric cancer / 中华普通外科杂志

Objective To compare the accuracy of endoscopic ultrasound (EUS) with double contrast enhanced ultrasound ( DCUS) in the preoperative staging of gastric malignancies. Methods This study included 162 patients with biopsy proven gastric cancer who underwent surgical resection as primary management of their malignancies. All patients underwent DCUS and EUS prior to surgical intervention with the results of the ultrasound findings compared with the pathological stages of the resected specimen. Results Among the 162 gastric cancer patients, there were 42 cases of T1, 49 cases of T2, 56 cases of T3, and 15 cases of T4 tumors. The overall accuracy of DCUS and EUS for the determination of loco-regional tumor infiltration ( T Staging) was 77. 2% and 74. 7% , (χ2 = 0. 273, P = 0. 603). Comparison of ultrasound techniques revealed that DCUS was superior to EUS only for a tumor depth of T3 (χ2 =5. 009, P = 0.025). Lymph nodes were correctly staged with DCUS and EUS in 78.4% and 57. 4% of cases, respectively ( χ2 = 16. 370,P =0.001). Using DCUS, the sensitivity of the technique was 78. 4% with a specificity of 78. 5%. In comparison, EUS had a sensitivity of 49. 5% with a specificity of 69. 2%. DCUS also detected a higher incidence of positive lymph nodes than EUS for poorly differentiated (81. 5% vs. 42. 6% ,χ2 =17. 338, P < 0. 01) and overall tumor types (78.4% vs. 49. 5% , χ2 = 17.523, P < 0. 01). Conclusions Double contrast-enhanced ultrasonography offers another noninvasive approach for the preoperative evaluation of gastric cancer. DCUS was comparable to EUS in tumor depth evaluation. DCUS offers an advantage in the detection of lymph node metastases, especially in poorly differentiated tumors.

Correlation between residual level of DNA double-strand breaks and the radiosensitivity of cancer cells / 中华放射医学与防护杂志

Objective To understand the variation of the DNA double-strand break rejoining capacity among different cultured cancer cell lines and the primary cancer cells from brain cancer patients,and to explore the predictor of radiotherapy responses of cancers. Methods DNA double-strand breaks (DSBs) were induced by 60Co γ-irradiation. Pulsed-field gel electrophoresis was used to analyze the initial production and rejoining of DNA DSBs. Radiosensitivity was determined by in vitro assay of clonogenic-forming capacity. Results A wide variation of radiosensitivity, e.g. The survival parameter of D0 varied from 0.65 to 2.15 Gy, was displayed among the eight cell lines derived from different type of cancers. Although differential level of initial DNA DSBs induced by 20 Gy γ-rays was observed among various cell lines, it was not correlated with the radiosensitivity. The deficiency of DNA DSB rejoining in radiosensitive cell lines was shown either in the early rapid-rejoining phase (SX-10 cells) or in the late slow-rejoining phase (A2780 cells). A significant relationship was observed between the residual level of DNA DSBs measured at 2 h post-20 Gy irradiation and the cellular radioseusitivity (D0 or SF2). The kinetic curves of rejoining DNA DSBs in the primary human brain tumor cells indicated a variation on DSB rejoining capacity among different individual tumor. The residual level of DNA DSBs after 2 h of rejoining post 20 Gy irradiation in primary human brain tumor cells is compatible to the results obtained in vitro culture cancer cell lines. Conclusions The residual level of DNA DSBs is correlated with radioresistance of cancer cells, and the residual DNA damage is a useful parameter in predicting the response of tumor tissue to radiotherapy.

Preliminary study on the mechanism of reading recovery in a pure alexia by using functional MRI / 中华放射学杂志

Objective To observe the changes of the brain function during reading recovery by using functional MRI (fMRI),and to provide the experimental data in elucidating the mechanism on the recovery of reading and language function.Methods fMRI was performed in a native Chinese patient with pure alexia on the 45 th and 130 th day after the onset,respectively.Three kinds of Chinese characters were presented during the scan and the patient was asked to make the judgement weather he could recognize the characters or not.The brain activation maps were acquired after postprocessing,and the activated location and volume were compared between the first and second experiments.Results In both experiments,Broca area,Wernicke area,and the right extrastriate were significantly activated,while the left extrastriate around the lesion was markedly activated only in the second experiment,and the volume of activation in the right extrastriate in the second experiment was about 3 times as large as that in the first experiment.Conclusion The left extrastriate cortex is one of the key areas responsible for reading function in the brain.The recovery of reading function can be compensated in contralateral corresponding cortical area,or it can be the result of reorganization in ipsilateral peri-lesion cortex.Both mechanisms may simultaneously play important roles in reading recovery.