1.Neoadjuvant immunotherapy combined with stereotactic body radiation therapy for stage Ⅲ/N2 non-small cell lung cancer: Three cases reports
Zhen WANG ; Haoyu GU ; Jing LUO ; Xixu ZHU ; Yong SONG ; Yi SHEN ; Yong QIANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(08):1210-1216
We reported three cases of stageⅢ/N2 non-small cell lung cancer (NSCLC) treated with neoadjuvant immunotherapy and stereotactic body radiation therapy (SBRT) in our hospital, including 2 males and 1 female with a mean age of 65.7 years. The patients received two doses of the programmed cell death protein-1 inhibitor toripalimab after 1 week of SBRT. Thereafter, surgery was planned 4-6 weeks after the second dose. One patient achieved pathologic complete response, one achieved major pathologic response (MPR), and one did not achieve MPR with 20% residual tumor. There were few side effects of toripalimab combined with SBRT as a neoadjuvant treatment, and the treatment did not cause a delay of surgery.
2.Asiatic acid inhibits lung cancer cell growthandby destroying mitochondria.
Tiancong WU ; Ji GENG ; Wenjie GUO ; Jing GAO ; Xixu ZHU
Acta Pharmaceutica Sinica B 2017;7(1):65-72
Asiatic acid (AA), a pentacyclic triterpene found in, displays significant anti-proliferative effects on cancer cellsalthough the underlying mechanism of this effect remains unknown. This study investigated the efficacy and mechanism of action of AA against lung cancer bothand. Using the MTT assay, AA was found to induce apoptosis in a dose- and time-dependent manner, an effect enhanced by pretreatment with an autophagy inhibitor. It also elevated expression of microtubule-associated protein 1 light chain 3 (LC3) and decreased the expression of p62. Furthermore, exposure to AA resulted in collapse of the mitochondrial membrane potential and generation of reactive oxygen species (ROS), suggesting mitochondria are the target of AA. In the mouse lung cancer xenograft model, oral administration of AA significantly inhibited tumor volume and weight accompanied by significant apoptosis of lung cancer cells. In addition, it led to a significant decrease in the expression of proliferating cell nuclear antigen (PCNA). In summary, the results show that AA significantly reduces lung cancer cell growth bothandand that the associated apoptosis is mediated through mitochondrial damage.
3.Study on the application of personalization customized oral positioning stent in head and neck cancer patients with intensity modulated radiation therapy
Feng CHEN ; Lei ZHU ; Xixu ZHU ; Meng ZHANG ; Shengqi ZANG ; Rui MU ; Junshu SHEN ; Han ZHOU ; Xiaolei SHI ; Lei JIN
Journal of Medical Postgraduates 2017;30(5):491-494
Objective Head and neck cancer radiotherapy patients often appear a series of oral complications including mucositis, xerostomia, pain, dysphagia.The purpose of this study was to investigate whether personalization customized positioning oral stent was able to push normal tissue off the high dose target area and maintain accurate repeatable stable positions, thus protecting the normal tissue during radiotherapy of the nasopharyngeal carcinoma patients.Methods 15 newly diagnosed nasopharyngeal carcinoma patients were collected from March to August 2016 in Department of Radiation Oncology, Nanjing General Hospital of Nanjing Military Region and randomly divided into trial group and control group.Two groups of patients were treated with intensity modulated radiation therapy (IMRT).Trial group patients wear personalization customized oral positioning stents during radiotherapy while the control group did not wear.After radiotherapy, we compared the exposure doses of clinical target area(CTV) and normal oral tissue in two groups.ResultsThe left parotid gland radiotherapy doses of the trail group and the control group were 2223.557±294.549 cGy and 2900.563±374.660 cGy, the difference was statistically significant(t=3.847, P=0.002);the right parotid gland radiotherapy doses of the trail group and control group were 2284.957±256.673 cGy and 2994.670±339.264 cGy, the difference was statistically significant(t=4.512, P=0.001).The mean exposure doses of CTV in two groups were no statistically significant difference (6142.829±135.986 cGy vs 173.306±6221.825 cGy, t=0.971, P=0.349.Conclusion During the intensity modulated radiation therapy, patients with personalization customized oral positioning stents can keep the mandible in a precise repeatable stable position.And it can reduce the exposure dose of bilateral parotid without affect the radiotherapy effect of the clinical target area.
4.Advantages of tracking no less than three gold markers in radiotherapy with CyberKnife
Shenghua JING ; Xiaowei YANG ; Nuo XU ; Jiahua PENG ; Xixu ZHU ; Bing LI
Chinese Journal of Radiation Oncology 2016;25(9):968-970
Objective To analyze the differences between CyberKnife radiotherapy with different numbers of gold markers.Methods A total of 424 patients undergoing CyberKnife with gold markers from 2013 to 2014 were enrolled and analyzed.In these patients,330 patients with no less than 3 gold markers were assigned to observation group and 94 patients with less than 3 gold markers were assigned to control group.The setup error and treatment error were recorded and analyzed for each patient.Results The mean setup error and mean treatment error were 0.031 mm and 0.314 mm in the observation group and 0.057 mm and 1.122 mm in the control group,respectively.Conclusion Tracking no less than 3 gold markers can substantially improve the accuracy and quality of treatment.
5.Ionizing Radiation Reduces TKI Resistance Caused by T790M Mutation in NSCLC Cell Lines
LI JING ; WU XINHU ; WANG ZHEN ; SHEN ZETIAN ; SUN NI ; ZHU XIXU
Chinese Journal of Lung Cancer 2015;(8):475-480
Background and objectiveEpidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), which targets EGFR, plays an important role in non-small cell lung cancer (NSCLC) treatment. Patients with somatic acti-vating mutations in theEGFR gene exhibit signiifcant initial response but eventually develop resistance to TKI. hTe second mutation (T790M) of theEGFR gene is the possible main cause of drug resistance. hTe aim of this study is to investigate the effect of ionizing radiation on EGFR-TKI resistance caused by T790M mutation in NSCLC cell lines.MethodsWe selected H1975 and H3255 as research subjects and tested the mutation states by real-time PCR analysis. Radiosensitivity was deter-mined by clone-forming test, and drug resistance was detected in different groups by MTT assay.Results H1975 is anEGFR double mutant (L858R plus T790M), whereas H3255 is anEGFR single mutant (L858R). hTe cell survival fractions of H1975 and H3255 did not vary in different treatment groups (P=0.952). hTus, T790M mutation did not affect the radiosensitivity of NSCLC cell lines. hTe IC50 of H1975 in the 2.5 Gy group [(0.678; 2±0.373) μmol/L] was statistically signiifcant compared with that in the 0 Gy normal control group [(3.520±0.821) μmol/L] (P=0.008). hTe drug tolerance of the H1975 cell line by 89.5 dropped to 39.2 times.ConclusionIonizing radiation can reduce TKI resistance caused by T790M mutation in NSCLC cell lines. Our results provide a research basis for futurein vivo and clinical studies. Radiotherapy combined with EGFR-TKI treatment can be a promising strategy to overcome T790M-mediated drug resistance.
6.Clinical effect of temozolomid combined with concurrent radiotherapy on high grade intracranial glioma
Zetian SHEN ; Xinhu WU ; Bing LI ; Zhen WANG ; Xixu ZHU
Cancer Research and Clinic 2014;26(2):102-105
Objective To evaluate the survival and adverse effects of adjuvant concurrent temozolomid (TMZ) combined with radiochemotherapy in postoperative patients with high grade intracranial glioma.Methods 84 postoperative patients with high grade intracranial glioma were randomly divided into the observation group (42 cases including 25 grade Ⅲ cases and 17 grade Ⅳ cases) and the control group (42 cases including 23 grade Ⅲ cases and 19 grade Ⅳ cases).All patients were treated with concurrent radiochemotherapy after surgical operations,the total radiation dose was 60-66 Gy.The patients in observation group were given daily oral TMZ 75 mg/m2 during radiotherapy.4 weeks after radiotherapy,all of the patients received 6 cycles of TMZ,each cycle lasted 5 days with 28 days interval between each cycles.150 mg/m2 of TMZ was given for the first cycle for 5 days,followed by 200 mg/m2 of drug for the rest of the cycles if no significant drug related toxicities were observed.Results The overall response rates (CR+ PR) were 71.7 % (33/46) in the observation group,and 32.6 % (15/46) in the control group,and with significant difference between the two groups (P < 0.001).The 1,2 and 3 year survival rates of patients in the observation group were 71.7 %,47.8 %,36.9 %,and 56.5 %,26.1%,15.2 % in the control group.The significant differences were found in 2-year and 3-year survival rates between the two groups (P =0.031,0.018).The median recurrent period in the observation group were 22 and 12 months in the control group,and with singnificant difference (P =0.015).The main side effects were limited to grade Ⅰ or Ⅱ.Conclusions Concurrent TMZ combined with radiotherapy in the treatment of high grade gliomas has better clinical efficacy,and can improve the 2-year and 3-year survival rates.Patients tolerate the strategy well and no severe toxicities are observed.
7.Effect of EGFR mutation on radiation-induced DNA repair in pulmonary adenocarcinoma cells
Zhen WANG ; Xinhu WU ; Zhibing LIU ; Jing LI ; Zetian SHEN ; Xixu ZHU
Chinese Journal of Radiological Medicine and Protection 2013;33(4):355-359
Objective To observe the effect of EGFR mutation on radiation induced DNA repair in pulmonary adenocarcinoma ceils.Methods A549 cells with wild-type EGFR and H1975 cells with mutated-type of EGFR were irradiated by 4 Gy of 6 MV X-rays.After irradiation,the formation of nuclear γ-H2AX foci was assayed with immunostaining method,the level of DNA-PKcs-EGFR interaction was detected with coimmunoprecipitation,and nuclear RAD51 expression and EGFR nuclear translocation were detected using Western blot.Results DNA repair in the H1975 cells was significantly lower than that in A549 cells.In the irradiated H1975 cells,there was no EGFR translocation with further nuclear DNA-PKcs binding,and the expression of nucleus RAD51 was not altered.But in the irradiated A549 cells,EGFRDNA-PKcs interaction and nucleus RAD51 were increased.Conclusions Lung adenocarcinoma cell line with mutations in the tyrosine kinase domain (TKD) of EGFR exhibits a high radiosensitivity due to the reduction of the non-homologous end-joining (NHEJ) and homologous recombination (HR) DNA DSB repair kinetics.
8.Clinical observation on compound matrine combined with intensity modulation radiotherapy in the treatment of local advanced nasopharyngeal carcinoma
Zetian SHEN ; Xinhu WU ; Bing LI ; Xixu ZHU
Cancer Research and Clinic 2011;23(9):623-625
ObjectiveTo detect the efficacy of compound matrine combined with intensity modulated radiotherapy (IMRT) for patients with locally advanced nasopharyngeal carcinoma (NPC). MethodsA total of 96 patients with locally advanced NPC were randomized into compound matrine combined with IMRT group (the therapeutic group) (n =48) and IMRT group (control group) (n =48). The nasopharyngeal DT and lymph nodes Dr were 66-78 Gy/(33-39 f)in 6-8 weeks,60-70 Gy/(30-35 f)in 6-8 weeks, respectively.The prophylactic dose of neck was 50-54 Gy.ResultsThe NPC efficacy of the therapeutic group was 93.8 %(45/48)and control group was 79.2 %(38/48).There was significant difference between the two groups in curative effect (P <0.05). The lymph nodes efficacy of the therapeutic group was 87.5 % (44/48) and control group was 75.0 % (30/48). There was significant difference between the two groups in curative effect (P <0.05). The side effects of mucosa were fewer in therapeutic group while the infection rate of pharynx oralis was higher in control group (P <0.01). ConclusionCompound matrine combined injection can improve shortterm curative effect of IMRT of locally advanced NPC and significantly decreased side effect of radiotherapy.
9.Percutaneous gold seed fiducials implantation in CT-guided for 132 solid tumors before cyberknife radiosurgery treatment
Zetian SHEN ; Xixu ZHU ; Lei WANG ; Xinhu WU
Cancer Research and Clinic 2010;22(10):666-668
Objective To evaluate the technical points and security of CT-guided in percutaneous gold seed fiducials implantation for 132 solid tumors before cyberknife radiosurgery treatment. Methods 132 solid tumors were implanted with gold seed fiducials guided by CT before cyberknife radiosurgery treatment.The complications were analyzed. The methods for the prevention and treatment of the complications were suggested. Results Of 132 cases, the achievement rate of puncture was 99.2%(131/132), including 16 (12.1%) cases of pain in the location of puncture, 10(7.6%) cases of tachycardia, and 6 (4.5%) cases of hypertension. Among the 68 cases of lung cancer, there were 3(4.4%) cases of slight pneumothorax, 3(4.4%)cases of generous pneumothorax. Among the 50 cases of liver cancer, there were 1 (2.0%) case of gold seed fiducials transmigration, 2 (4.0%) cases of small amount bleeding from needle channel. Conclusion Percutaneous gold seed fiducials implantation in CT-guided for solid tumors before cyberknife radiosurgery treatment is a slight trauma and safe method.
10.Characteristics of multivoxel proton MR spectroscopy in brain tumors: comparison of histological pathology
Xixu ZHU ; Ling ZHENG ; Lin LI ; Guangming LU ; Junpeng WANG ; Handong WANG ; Jianmin TIAN
Journal of Medical Postgraduates 2003;0(10):-
Objective: To investigate the multivoxel proton MR spectroscopy findings of brain tumors and the clinical value in differential diagnosis. Methods:Sixty patients with brain tumors underwent multivoxel proton MR spectroscopic examination with PRESS sequence. Distribution of the 60 final diagnoses of neoplasms was as follow: meningioma (n=22), glioma (n=21), lymphoma (n=3), metastasis (n=5), acoustic neuroma, pituitary tumor, PNET (n=2, respectively), vascularblastoma, arachnoid cyst, neurofibromatosis (n=1,respectively). The concentrations of NAA, Cho, Cr, Lac-Lip were obtained in the tumors and the contralateral normal brain region. The ratios of NAA/Cr, Cho/Cr, NAA/Cho, tumor NAA/normal NAA, tumor Cho/normal Cho, tumor Cr/normal Cr were calculated. Results: 1H MRS showed decreased NAA, Cr and elevated Cho. NAA concentrations in meningioma, glioma, lymphoma decreased significantly to acoustic neuroma, metastasis, but Cho in tumors changed without significance. NAA/Cr ratio was significantly lower in glioma than in acoustic neuroma and metastasis, and p value was 0.014, 0.027, respectively. No significance was found in tumor Cho/Cr data. Conclusion:Multivoxel proton MR spectroscopy is available for study of tumor metabolites. The tumor NAA/normal NAA, NAA/Cr were helpful for the diagnosis and differential diagnosis of intracranial tumors.

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