AIM: To investigate the differentiation of human mesenchymal stem cells (MSCs) into neuron-like cells induced by the supernatant of rat C6 glloma cells. METHODS: The heparin anticoagulant human bone marrow sampling was performed and human MSCs were separated flom human bone marrow using Percoll gradient method, followed by trypsinization and passage culture. When the MSCs at 4-6 passages reached a confluence of 90%, they were inoculated into a 24-well culture plate at a density of 2×103 per well. Cells were then divided into induction group and control group. In the induction group, C6 glioma cells were induced by the complete culture medium supplemented with 50% C6 glloma ceils supernatant (L-DMEM containing 0.1 fetal bovine serum), and half of the culture medium as replenished every 2 days. In the control group, cells were cultured in the complete culture medium. Both groups were treated 3 days and the expression of neuron-specific marker was monitored with S-P immunocytochemical stain. RESULTS: After an induction period of 24 hours, the differentiated MSCs showed typical neuron-like appearance, while the controlled cells exhibited no obvious alters. After 3 days of the induction, the neuron specific enola,se-positive rate of the cells in the induction was significantly higher than that in the control group (P < 0.01). The neurofilament protein-positive rate of cells in the induction group was (44.2±2.4)%, and the control group cells did not express neurofilament protein. Typical glial astrocyte marker glial fibrillary acidic protein was negatively expressed in both groups. CONCLUSION: Differentiation of MSCs into neuron-like cells can be induced by the supematant of rat C6 glioma cells in vitro.

Objective:To collect the clinical materials of primary liver cancer patients treated by gamma knife and analyze the treatment methods as well as short-term efficacy,and to provide a reference for the clinical treatment of primary liver cancer patients.Methods:A total of 633 patients with inoperable primary liver cancer were treated by body gamma knife.According to the TNM staging method of Union for International Cancer Control(UICC), there were 351 cases with clear TNM staging.Among them, there were 251 cases (71.5%) at T3 stage and 57 cases(16.2%) at T4 stage.The prescription dose of 200-600 cGy each time to the 40%-85% dose line covering the planned target volume(PTV), this program was performed 5 times per week, and the number of treatment ranged from 2 to 13.The biochemical and imaging changes were observed 2-3 months after treatment to evaluate the short-term efficacy.Results:During the treatment, 229(36.2%)patients had adverse reactions,100 (15.8%) patients appeared the reduced white blood cells, and 137 (21.6%) patients appeared the reduced platelets.On discharge from the hospital, 601 patients were improved, 22 patients had no obvious change, 5 cases were worse, and 5 cases died.The proportion of improved patients who received the cumulative dose between 3 000 cGy to 4 000 cGy was higher than those who received the cumulative dose less than 3 000 cGy(P<0.05).After treatment, the curative effects were evaluated in 45 patients during two and three months, including PR 77.8%(35/45) and SD 22.2%(10/45), and the total effective rate was 77.8%(35/45).No statistical differences in effective rates were found between different tumor diameter, single dose, and cumulative dose groups(P>0.05).Conclusion:The proportion of adverse reactions in the primary liver cancer patients treated with body gamma knife is relatively low and the short-term efficacy is ideal.Body gamma knife treatment is a safe and effective treatment method for the primary liver cancer patients.

Objective To evaluate the preliminary clinical efficacy of bevacizumab for cerebral radiation necrosis (CRN). Methods Nineteen patients with CRN for whom the treatment with steroids and mannitol failed were retrospectively analyzed with a total of 22 lesions. Except for 5 lesions confirmed by pathological evidence, all lesions were confirmed by the following imaging evidence:1. computed tomography (CT)?or magnetic resonance imaging (MRI)?enhanced lesions showed loss of tension and were accompanied by substantial edema;2. CT?or MRI?enhanced lesions had a low perfusion pressure;3. magnetic resonance spectroscopy indicated that the enhanced areas had a decreased choline peak; 4. positron emission tomography showed that the fluorodeoxyglucose uptake was substantially reduced in the enhanced areas. All patients were given 5 mg/ kg bevacizumab at an interval of 14 days for 2?6 cycles. MRI examination was performed in each cycle before treatment, and the enhanced lesions on T1?weighted images ( T1 WI) and edema on T2?weighted images (T2 WI) were compared before and after treatment. The clinical symptoms, Karnofsky Performance Status ( KPS), and adverse reactions in all patients were evaluated. Comparison before and after treatment was performed by paired t test. Results All 19 patients completed the treatment successfully and there were no severe adverse reactions. The clinical symptoms of patients were substantially improved after the second cycle of treatment, and the KPS score increased by 26?? 8 on average. The visible volume of enhanced lesions on MRI T1 WI was significantly reduced by 54?? 8% after treatment (P= 0?? 000), while the visible volume of edema on MRI T2 WI was reduced by 80?? 7% after treatment (P= 0?? 000). The follow?up time ranged from 3 to 12 months with a mean value of 5?? 6 months. Eleven patients kept clinical improvement in CRN, four patients had recurrence, and four patients died from tumor progression. Conclusions Bevacizumab is preliminarily confirmed to substantially improve the clinical symptoms and quality of life in patients with CRN.

Objective To evaluate the clinical efficacy and safety of stereotactic radiotherapy (SRT) combined with bevacizumab for brain metastases in patients with lung adenocarcinoma.MethodsThe clinical data of 95 patients with brain metastases of lung adenocarcinoma were retrospectively analyzed, including 36 patients treated with SRT and bevacizumab (bevacizumab group) and 59 patients treated with SRT, corticosteroids, and mannitol (traditional drug group).The tumor response rate, peritumoral edema control rate, improvement in Karnofsky Performance Scale (KPS) score, and adverse reactions were analyzed.Results Compared with the traditional drug group, the bevacizumab group had significantly higher tumor response rate (P=0.033) and peritumoral edema control rate (P=0.000) at 1-4 weeks after treatment, as well as an obvious improvement in KPS score and reduced doses of corticosteroids and mannitol.In addition, the adverse reactions in the bevacizumab group were mild and controllable.Conclusions SRT combined with bevacizumab for brain metastases in patients with lung adenocarcinoma can achieve higher short-term tumor response rate and peritumoral edema control rate and improve patients' quality of life.

Objective:To explore the reasonable timing of radiotherapy for epidermal growth factor receptor ( EGFR) mutation-positive non-small cell lung cancer patients with brain metastasis in the era of third-generation targeted drugs. Methods:Clinical data of EGFR mutation-positive non-small cell lung cancer patients with brain metastasis who received first-line treatment with third-generation targeted drugs and stereotactic radiotherapy at Shanghai Armed Police Corps Hospital from September 2019 to May 2022 were retrospectively analyzed. According to the timing of radiotherapy before / after targeted drug resistance, all patients were divided into the early and salvage radiotherapy groups. The proportion of brain metastasis, physical fitness, complete response rate, objective response rate, delaying the progression of brain metastasis and overall survival (OS) were compared between two groups. Kaplan-Meier method was used for survival analysis, log-rank test was used for univariate prognostic analysis, and factors with P <0.1 were included in Cox multivariate analysis. Results:A total of 85 patients were included, including 51 (60%) cases receiving early radiotherapy. Patients who participated in early radiotherapy had a higher proportion of symptomatic brain metastasis (82% vs. 56%, P=0.013) and poorer physical fitness (Kanofsky performance score <70: 61% vs. 26%, P=0.002) compared to patients who underwent salvage radiotherapy. Early radiotherapy significantly improved the complete response rate of intracranial lesions (35% vs. 12%, P=0.015) and objective response rate (88% vs. 71%, P=0.041), delayed the progression of brain metastasis (median intracranial progression free survival: 23.0 months vs. 16.0 months, P=0.005; median intracranial secondary progression free survival: 31.0 months vs. 22.0 months, P=0.021), and improved OS (median OS: 44.0 months vs. 35.0 months, P=0.046). In multivariate analysis, diagnosis-specific graded prognostic assessment score <2.5, mutation of EGFR exon 21, and salvage brain radiotherapy were adverse prognostic factors for OS. Conclusion:In the era of third-generation targeted drugs therapy, early involvement of stereotactic radiotherapy in non-small cell lung cancer patients with brain metastasis can bring greater clinical benefits.

Objective:To compare the efficacy and side effects of multi-fraction stereotactic radiotherapy (SRT) and single-fraction stereotactic radiosurgery (SRS) in the treatment of brain metastases from colorectal cancer.Methods:A total of 98 patients with brain metastases from colorectal cancer searched from the database of Professional Committee of Brain Metastasis of Shanghai Anticancer Association were recruited in this study. Among them, 46 patients weretreated with SRT and 52 patients with SRS. Clinical characteristics of all patients were analyzed between two groups and the local tumor control rate, median survival time and the incidence of radiation-induced brain injury were compared between two groups.Results:The objective remission rates (ORR) in the SRT and SRS groups were 76.1% and 67.3%, respectively. The 12-month local tumor control rates were 88.3% and 83.9% between two groups, with no statistical difference ( P=0.689). The median overall survival time of all patients was 11.6 months, 10.8 months in the SRT group and 12.7 months in the SRS group. There was no statistical difference between two groups ( P=0.129). Multivariate analysis showed that the main factors leading to poor prognosis included the number of tumors of >3( P=0.026), low GPA score ( P=0.035), and lack of systematic treatment mode and bevacizumab ( P=0.001). There was no statistical difference in the incidence of acute and late radiation-induced brain injury between two groups. Conclusions:Both SRT and SRS are effective therapies for brain metastases from colorectal cancer. The synergistic application of systematic treatment mode may be one of the main reasons affecting the survival time of the patients.

Objective: To compare the clinical efficacy of stereotactic radiotherapy (SRT) and stereotactic radiosurgery (SRS) in the treatment of brain metastases from January 2006 to December 2016, lung adenocarcinoma and analyze the related factors. Methods: In this multi-center retrospective analysis, clinical data of 208 patients with brain metastases from lung adenocarcinoma were retrospectively analyzed and assigned into the SRT (n=86) and SRS groups (n=122). The clinical characteristics of patients in two groups were analyzed. The local tumor control rate, median survival time and radiation brain injury were statistically compared between two groups. Results: At the end of follow-up, the objective response rates (ORR) were 70.9% and 71.3% in the SRT and SRS groups (P=0.772). The local tumor control rates at 12 months were 89% and 86% in the SRT and SRS groups (P=0.383). The median overall survival time of all patients was 14.3 months, 15.6 months in the SRT group and 13.7 months in the SRS group (P=0.349). Multivariate analysis showed that large target volume (P<0.001), low GPA score (P=0.012) and no insensitive gene mutation (P<0.001) were the main factors of poor prognosis. The incidence of late radiation brain injury was 5.8% and 14.8% in two groups (P=0.043). Conclusions SRT and SRS yield similar clinical efficacy in the treatment of brain metastases from lung adenocarcinoma. SRT may have a lower incidence of late radiation brain injury than SRS.

OBJECTIVETo investigate the changes of blood glucose in pancreatic cancer patients associated with diabetes mellitus (DM) after radiotherapy and analyze the related factors.

METHODSClinical data of 69 cases of stage I to III pancreatic carcinoma associated with DM were retrospectively analyzed. All patients were divided into four groups according to the history of DM, and the clinical characteristics and blood glucose changes after stereotactic radiotherapy were analyzed. The correlation between blood glucose and serum tumor markers was analyzed.

RESULTSNo significant differences were found in clinical characteristics of the four groups. The history of DM <12 months accounted for 39.1% of the pancreatic cancer patients, much more higher than that of patients with a longer disease course. After radiotherapy, the blood glucose changes were not significantly different between the two groups with DM history <12 months and 12-24 months (P = 0.519), but there were significant differences between the patients with DM history <12 months and those with DM history 25-36 months and >36 months (P < 0.05 for both). After radiotherapy, CA199/CEA was reduced and blood glucose was also improved in the patients with DM history <12 months and 12-24 months, and the reduction of CA199/CEA showed a significant positive correlation with the improvement of blood glucose (r = 0.834 and r = 0.660, P < 0.01 for both), however, no significant correlation was found between the two parameters in patients with DM history 25-36 months and >36 months (r = 0.319 and r = 0.439, P > 0.05 for both).

CONCLUSIONSHyperglycemia in diabetic patients with a disease course <24 months might be a clinical manifestation secondarily developed in pancreatic cancer patients. Therefore, patients with new onset diabetes should be closely followed-up for early detection of pancreatic cancer.

Aged ; Biomarkers, Tumor ; blood ; Blood Glucose ; Diabetes Mellitus ; blood ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms ; blood ; Retrospective Studies ; Time Factors