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OBJECTIVE To observe whether mitochondria can be transferred from mesenchymal stem cells(MSCs)to irradiated cells by establishing a mitochondrial fluorescent reporting system.METHODS The lentiviral vector pSIN-EF1α-COX8A-DsRed2(named COX8A-DsRed2)that might guide the expres-sion of red fluorescence protein in the membrane of mitochondria was constructed.A lentivirus(named Lv-COX8A-DsRed2)was prepared in 293T cell line.Dental pulp stem cells(DPSCs)(named DPSC-COX8A-DsRed2)was infected with Lv-COX8A-DsRed2.The intracellular expression of the red fluores-cence protein in DPSC was observed under fluorescence microcopy.The mitochondrial localization of the expressed red fluorescent probe in DPSC-COX8A-DsRed2 was confirmed according to TOMM20 immunostaining and MitoTracker Green staining results,which could specifically label mitochondria.The IEC-6 cells that received 10 Gy X-ray radiation were used as an injured cell model.The co-culture system was established by supplementing DPSC-COX8A-DsRed2 into the culture plate with the irradi-ated IEC-6 labelled by CFSE for 24 h.RESULTS The imaging results of fluorescent microcopy obser-vation showed that DPSC-COX8A-DsRed2 expressed the mitochondrial fluorescent reporting system,which was co-located with TOMM20 protein and Mito Tracker Green.The imaging results of confocal fluorescence microcopy showed that the mitochondria with red fluorescent protein were transferred from DPSC-COX8A-DsRed2 to the irradiated IEC-6 cells,suggesting that the established mitochondrial fluorescent reporting system could indicate mitochondrial transfer from donor cells to injured ones.CONCLUSION DPSC-COX8A-DsRed2 stably expressing the mitochondrial fluorescent reporting system is established,which can be used to track mitochondrial transfer.
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Objective:To explore the influence of body mass index (BMI) changes on the doses to normal tissues and adverse reactions of the lower digestive system and urinary system in the brachytherapy for cervical cancer.Methods:Clinical data of 80 cervical cancer patients who received radical radiotherapy in our hospital from January 2020 to February 2021 were retrospectively analyzed. All patients received external beam radiation ± chemotherapy + brachytherapy. The delineation method of target areas and organs at risk (OAR) was determined based on the recommended scheme of GEC-ESTRO. The target areas included high risk (HR)-CTV and intermediate risk (IR)-CTV, and OAR consisted of rectum, sigmoid colon, bladder, and small intestine. The target area dose was evaluated by D 90% of the HR-CTV. The OAR volume dose was evaluated by using D2cm3. Correlation analysis was used to compare the dosimetric relationship between BMI and D2cm3, D1cm3 and D0.1cm3 in bladder, rectum, colon and small intestine. Logistic regression analysis was adopted to analyze the risk factors of acute and late adverse reactions in the lower gastrointestinal system and urinary system. Whether BMI was a risk factor was validated. Results:BMI was negatively correlated with the D2cm3, D1cm3 and D0.1cm3 of the small intestine ( P=0.034, 0.024, 0.034), and the correlation coefficients were -0.240, -0.255, and -0.241, respectively. Logistic regression analysis showed that BMI was not a risk factor for the occurrence of acute and late adverse reactions in the lower gastrointestinal system and urinary system. For every 1 Gy increase of D2cm3, D1cm3 and D0.1cm3 in the small intestine, the relative risk of acute adverse reactions in the lower gastrointestinal system was increased by 16.6%, 15.1%,and 12.7%, respectively. Conclusions:In brachytherapy for cervical cancer, there is a negative correlation between BMI and D2cm3, D1cm3 and D0.1cm3 of the small intestine. As the BMI of patients declines, the radiation dose to the small intestine shows an increasing trend, which may increase the risk of acute adverse reactions in the lower gastrointestinal system.
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Objective:To discuss the dosimetric contribution of the ovoid in the cervical cancer brachytherapy through the intracavity combined with interstitial(IC/IS)technique.Methods:The data on 20 patients with FIGO(2009)stageⅡ A, Ⅱ B or Ⅲ Bcervical cancer treated with radical radiotherapy in China-Japan Union Hospital of Jilin University during 2015-2017 was collected. External irradiation treatment was 45 Gy/1.8 Gy× 25 fractions. Brachytherapy was MRI-guided IC/IS brachytherapy with a prescription of 28 Gy/7 Gy× 4 fractions. All of 20 patients developed two kinds of plans, the ovoid group and the non-ovoid group. The original MRI-guided brachytherapy treatment plan was set(80 fractions)to the ovoid group. As contrast model that removed the ovoid and consisted of tandem combined with needles set to the non-ovoid group was built, and the same physicist designed the plan to make the dose of D90% for high-risk clinical target volume(HR-CTV)similar to the ovoid group. The dosimetric differences of the D90% and D98% for HR-CTV, D90% and D98% for intermediate-risk clinical target volume(IR-CTV)and D2 cm 3 for the bladder, rectum, sigmoid colon and small intestines between two groups of plans were analyze by paired t-test. Results:Compared with the ovoid group, the non-ovoid group showed no significant difference on HR-CTV D90%( P>0.05), but the HR-CTV D98%(6.99±0.60 vs. 6.78±0.76), IR-CTV D90%(4.71±0.58 vs. 4.26±0.57) and D98%(3.77±0.58 vs. 3.26±0.59) of the non-ovoid group decreased significantly( t=3.906, 9.860, 8.636, P<0.05). The sigmoid colon showed no significant difference( P>0.05), while the bladder (5.29±0.67 vs. 4.92±0.74), rectum (3.72±0.69 vs. 3.35±0.92) and small intestines (3.05±1.37 vs. 2.98±1.34) D2 cm 3of the non-ovoid group decreased significantly( t=8.758, 7.543, 8.059, P<0.05). Conclusions:Ovoid is very important for IC/IS technique in cervical cancer brachytherapy. Reasonable optimization of the dose weight ratio of the ovoid and the needle can bring better clinical benefits.
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Objective:To explore the application of 3D printing technology-assisted standardized applicator in the image-guided adaptive brachytherapy (IGABT) for cervical cancer.Methods:Twenty-three patients with stage Ⅲ B cervical cancer with extensive paracervical invasion after external irradiation (45 Gy/25f) were treated with IGABT, and the prescription dose was 7 Gy/f×4f. According to the regression of tumor on MRI before and after external irradiation, the range of brachytherapy was determined, and the under dose area of standard intracavitary/interstitial applicator (IC+ IS) was estimated. The virtual transperineal needle channel was inserted in the under dose area, the angle, spacing and depth of implantation were optimized. The auxiliary templates were designed with graphic design software, and 3D printing technology was utilized to print the auxiliary templates. The auxiliary templates were closely combined with the standardized applicator. Under the anesthesia condition, ultrasound-guided applicator was completed, and patients were scanned with MRI image after operation. The MRI images were introduced into treatment planning system (TPS) to delineate the target area and organs at risk, and the treatment plans were optimized to complete the plan evaluation and treatment. Results:The average printing time of templates was (3.5±1.0) h, 382 implant needles were inserted guided by auxiliary templates, (4.2±1.5) template-guided implant needles were used in each fraction and the weight ratio was (16.49±9.50)%. The total dose of HR-CTV D 90% EQD 2Gy, α/ β=10 was (90.45±3.03) Gy, and IR-CTV D 90% EQD 2Gy, α/ β=10 was (66.46±3.68) Gy. The D 2cm 3 EQD 2Gy, α/ β=3 of the bladder, rectum, small intestine and sigmoid colon were (82.69±2.60) Gy, (73.20±2.52) Gy, (69.35±3.32) Gy and (69.39±3.27) Gy, respectively, all of which met the clinical dose requirements. The 1-and 2-year local control rates were 96% and 87%, 87% and 70% for the distant metastasis-free survival rates, and 96% and 78% for thea overall survival rates, respectively. Conclusion:The auxiliary applicators made by 3D printing technology can effectively compensate for the dose insufficiency of the standard applicator in the paracervical and other areas during the clinical brachytherapy in patients with stage Ⅲ B cervical cancer, providing an effective method for the brachytherapy of advanced cervical cancer.
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In China, COVID-19 epidemic is currently showing a sporadic state, and the task of epidemic prevention is still arduous. Brachytherapy (BT) plays a critical role in the treatment of cancer. For some cancer receiving radiotherapy, use of BT can not be replaced or excessively delayed. Nevertheless, the recommendations or guidelines regarding the application of BT during COVID-19 epidemic have been rarely reported. In this article, a few recommendations on the application of BT during COVID-19 epidemic were retrieved and the work experience of Department of Radiation Oncology, China-Japan Union Hospital of Jilin University in the early epidemic period was summarized, aiming to provide relevant reference for the use of high-dose-rate BT for malignant tumor patients during COVID-19 epidemic.