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Pivotal roles of tumor-draining lymph nodes in the abscopal effects from combined immunotherapy and radiotherapy

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Cancer Communications 2022年第10期42卷 971-986页

作者： Zhaoyun Liu Zhiyong Yu Dawei Chen Vivek Verma Chenxi Yuan Minglei Wang Fei Wang Qing Fan Xingwu Wang Yang Li Yuequn Ma Meng Wu Jinming Yu Department of oncology Shandong University Cancer CenterJinanShandong 250117P.R.China Department of radiation oncology and Shandong Provincial Key Laboratory of radiation oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandong 250117P.R.China Breast Cancer Center Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandong 250117P.R.China Department of radiation oncology The University of Texas MD Anderson Cancer CenterHoustonTexas 77030United States Department of Pharmacy Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandong 250117P.R.China Research Unit of radiation oncology Chinese Academy of Medical SciencesJinanShandong 250117P.R.China

Background:Currently,due to synergy enhancement of anti-tumor effects and potent stimulation of abscopal effects,combination therapy with irradiation and programmed cell death protein 1/programmed death-ligand 1(PD-1/PD-L1)immune checkpoint inhibition(immuno-radiotherapy,iRT)has revolutionized the therapeutic *** has been demonstrated that tumor-draining lymph nodes(TDLN)are essential for effective antitumor immunity induced by radiotherapy,immunotherapy,or *** that the function of TDLN in iRT remains unclear,this study aimed to investigate the function and mechanism of TDLN in iRT-induced abscopal ***:The function of TDLN was evaluated using unilateral or bilateral MC38 and B16F10 subcutaneous tumor models with or without indicated *** flow cytometry,multiple immunofluorescence analysis,and NanoString analysis were utilized to detect the composition and function of the immune cells in the primary and abscopal tumor ***ally,we tempted to interrogate the possible mechanisms via RNA-sequencing of tumor-infiltrating lymphocytes and ***:TDLN deficiency impaired the control of tumor growth by monother*** TDLN removal rather than unilateral TDLN removal substantially curtailed iRT-stimulated anti-tumor and abscopal ***,in the absence of TDLN,the infiltration of CD45+and CD8+T cells was substantially reduced in both primary and abscopal tumors,and the anti-tumor function of CD8+T cells was attenuated as ***,the polarization of tumor-associated macrophages in primary and abscopal tumors were found to be dependent on intact bilateral ***-sequencing data indicated that impaired infiltration and anti-tumor effects of immune cells partially attributed to the altered secretion of components from the tumor ***:TDLN play a critical role in iRT by promoting the infiltration of CD8+T cells and maintaining the M1/M2 macrophage ratio.

关键词： immuno-radiotherapy tumor-draining lymph node T cells tumor-associated macrophage

Radiotherapy combined with nimotuzumab for elderly esophageal cancer patients:A phaseⅡclinical trial

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Chinese Journal of Cancer Research 2021年第1期33卷 53-60页

作者： Xu Yang Yirui Zhai Nan Bi Tao Zhang Lei Deng Wenqing Wang Xin Wang Dongfu Chen Zongmei Zhou Luhua Wang Jun Liang Department of radiation oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100121China

Objective:To investigate the safety and efficacy of nimotuzumab combined with radiotherapy for elderly patients with non-resectable esophageal carcinoma(EC).Methods:Eligible patients were aged 70 years or older and had treatment-naive,histologically proven inoperable locally advanced *** patients received radiotherapy with a total dose of 50-60 Gy in 25-30 fractions,concurrent with weekly infusion of *** primary end point was the rate of more than grade 3 ***:From June 2011 to July 2016,46 patients with stageⅡ-IV EC with a median age of 76.5 years were *** were 10,28 and 8 patients with stageⅡ,III and IV disease,*** common acute toxicities included esophagitis(grade 1-2,75.4%;grade 3,8.7%),pneumonitis(grade 1,4.3%;grade 2,6.5%;grade3,2.2%),leukopenia(grade 1-2,60.9%;grade 3-4,4.4%),gastrointestinal reaction(grade 1-2,17.3%;grade 3,2.2%),thrombocytopenia(grade 1-2,21.7%;grade 3,2.2%),and radiothermitis(grade 1-2,39.2%).The incidence of grade 3-4 adverse effects was 17.4%.No grade 5 toxicities were *** complete response,partial response,stable disease,and progressive disease were observed in 1(2.2%),31(67.4%),12(26.1%),and 2(4.3%)patients,*** median overall survival(OS)and progression-free survival(PFS)were 17 and 10 months,*** 2-,3-,and 5-year OS and PFS rates were 30.4%,21.7%,19.6%,and 26.1%,19.6%,19.6%,***:Nimotuzumab combined with radiotherapy is a safe and effective therapy for elderly patients who are not surgical *** studies are warranted to confirm its therapeutic effects in elderly EC patients.

关键词： Nimotuzumab esophageal neoplasm elderly radiotherapy treatment outcome

Role of Complementary and Alternative Medicine in Prevention and Treatment of COVID-19:An Overhyped Hope

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Chinese Journal of Integrative Medicine 2020年第8期26卷 565-567页

作者： Abhishek Shankar Anusha Dubey Deepak Saini Chandra Prakash Prasad Department of radiation oncology Lady Hardinge Medical College and SSK HospitalDelhi 110001India Division of Cancer Control and Prevention Indian Society of Clinical OncologyDelhi 110049India Department of medical oncology(Lab) Dr BR Ambedkar Institute Rotary Cancer HospitalAll India Institute of Medical SciencesDelhi 110029India

The entire mankind across the globe is suffering with COVID-19 outbreak and searching for definite vaccine or treatment for *** country is trying hard to get a breakthrough for definitive therapy in the form of antiviral therapy,plasma therapy and vaccine against this virus,as current management is symptom directed *** of the countries are also trying complementary and alternative medicine(CAM),including traditional,Herbal treatment,alone or in combination with standard management.

关键词： vaccine breakthrough treatment

N-acetylcysteine protect lymphocytes and cytokines against heavy ion irradiation via counteracting the glutamate

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Nuclear Science and Techniques 2013年第3期24卷 39-44页

作者： XIE Yi ZHANG Hong WANG Yipei LIU Yang CHEN Yingtai Institute of Modern Physics Chinese Academy of Sciences Key Laboratory of Heavy Ion radiation Biology and Medicine of Chinese Academy of sciences Key Laboratory of Heavy Ion radiation Medicine of Gansu Province Department of Chemistry & Biochemistry University of Delaware Department of Abdominal Surgical oncology Cancer Institute and HospitalChinese Academy of Medical Sciences

We evaluated the protective effect of N-acetylcysteine (NAC) on immunity system irradiated by 12C6+ ion beam. Kun-Ming mice were whole-body irradiated by 12C6+ ion at doses of 0, 0.5, 1, 1.5, 2, 2.5 and 3 Gy. The results showed that in saline group, the lymphocytes DNA double-strand breaks (DSBs), maleic dialdehyde, thymocytes number in G 0 /G 1 and apoptosis percentage increased with dose increment, and the levels of interferon-γ, glutathione, superoxide radical (SOD) and natural killer cells activity decreased with dose increment. However, there were no significant changes in NAC-treated group. The data indicated that pre-treatment with NAC could significantly remove the ROS by counteracting the glutamate, decrease excessive lipid peroxidation reaction and SOD damages, and protect DNA, lymphocytes and cytokines against irradiation.

关键词： N-乙酰半胱氨酸重离子辐照细胞因子保护作用谷氨酸 DNA双链断裂超氧化物歧化酶超氧阴离子自由基

Radioimmunotherapy-induced intratumoral changes in cervical squamous cell carcinoma at single-cell resolution

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Cancer Communications 2022年第12期42卷 1407-1411页

作者： Chao Liu Hao Yu Rui Huang Tianyu Lei Xiaohui Li Ming Liu Qingyu Huang Qilian Du Ligang Xing Jinming Yu Department of radiation oncology and Shandong Provincial Key Laboratory of radiation oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandong 250117P.R.China Research Unit of radiation oncology Chinese Academy of Medical SciencesJinanShandong 250117P.R.China Department of Gynecologic oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandong 250117P.R.China Department of oncology Renmin Hospital ofWuhan UniversityWuhanHubei 430060P.R.China

Dear Editor,Increasing numbers of studies have revealed the immunomodulating effects of radiotherapy when combined with immune checkpoint inhibitors,as radioimmunotherapy has proven to be a promising treatment[1].Radioimmunotherapy has shown significantly improved tumor responses than radiotherapy or immunotherapy alone in various malignant tumors[2–4].It has also been applied to cervical cancer in multiple ongoing clinical trials(NCT03612791[5]and NCT02635360[6]).However,tumor recurrence andmetastasis are often *** such,investigations into radioimmunotherapy-induced tumor ecosystem evolution are essential for guiding improvements in treatment strategies that achieve better long-term disease *** date,several studies have investigated radiochemotherapy-induced tumor ecosystem evolution using bulk RNA-sequencing and immune staining[7,8].However,these findings were limited owing to the cellular heterogeneity in ***-cell RNA-sequencing(scRNA-seq)enables the characterization of cell compositions and transcriptomic states in the tumor at single-cell resolution.

关键词： cervical chemotherapy treatment

THE　LATE　RESPONSE　OF　PIG　SKIN　TO　FRACTIONATED　DOSES　OF　35　MeV　P→Be　FAST　NEUTRON　IRradiation

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Chinese Journal of Cancer Research 1994年第3期6卷 229-231页

作者：王俊杰狄薇李亚钢申文江唐锦华常微克罗醒萱 Department of radiation oncology First Teaching Hospital Beijing Medical University Beijing Department of radiation oncology Beijing Institute of Cancer Research Beijing Department of Neutron Hihg Energy Physical Institute Chinese Academy of Sciences Beijing

The late damage in pig skin to fractionated doses of 35 MeV fast neutron was studied. Neutron fractionation scheme comprised of 12 fractions in 42 days. The latent period of late damage of 19. 8 , 22. 2 , 24. 6 and 27. 0 G y groups were 17. 00±1. 53, 13. 67±1. 45, 14. 00±2. 31 and 17. 00±2. 00 , weeks , respectively(P>0. 05). The ED50 value for late damage was 2 1 . 0 G y. The mean latency of late pig skin damage was not related to the total dose. However, the incidence of late damage was related to the total dose. The late damage in pig skin was characterized by a dusky/mauve erythema which could progress to dermal necrosis. The mean latency for the development of necroses was longer and it was harder to heal than the pig skin early reaction.

关键词： Fast neutron Late damage ED_(50).

^(68)Gallium-labelled PSMA-PET/CT as a diagnostic and clinical decision-making tool in Asian prostate cancer patients following prostatectomy

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Cancer Biology & Medicine 2019年第1期16卷 157-165页

作者： Janice S.H.Tan Charles X.Y.Goh Yen Sin Koh Youquan Li Jeffrey K.L.Tuan Eu Tiong Chua Terence W.K.Tan Michael L.C.Wang Lui Shiong Lee Kae Jack Tay Ravindran Kanesvaran Chee Keong Toh Aaron K.T.Tong Winnie W.C.Lam Melvin L.K.Chua Division of radiation oncology National Cancer Centre Singapore Department of Nuclear Medicine and Molecular Imaging Singapore General Hospital Radiological sciences Academic Clinical Programme Duke-NUS Medical School oncology Academic Clinical Programme Duke-NUS Medical School Department of Urology Singapore General Hospital Department of Surgery Sengkang General Hospital Division of medical oncology National Cancer Centre Singapore Division of medical sciences National Cancer Centre Singapore

Objective: Prostate cancers(PCa) in Asian individuals are molecularly distinct from those found in their Caucasian *** is no risk stratification tool for Asian men with rapid biochemical recurrence(BCR) following radical prostatectomy(Rad P). This study aims to assess the detection rate of ^(68)Ga-prostate-specific membrane antigen-positron emission tomography/computed tomography(PSMA-PET/CT) for diagnosis of clinical recurrence and as a treatment decision making tool in Asian patients with BCR post-Rad ***: ^(68)Ga PSMA-PET and CT body with/without bone scan [conventional workup(CWU)] were performed in 55 Asian patients with BCR within 36 months post-Rad P. Two blinded reviewers assessed the images. Detection rates of ^(68)Ga PSMAPET/CT were evaluated, and impact on management was reviewed by comparison with ***: Median time to BCR post-Rad P was 8.1 months. Detection rate for ^(68)Ga PSMA-PET/CT was 80%(44/55). A positive scan was significantly associated with increasing prostate-specific antigen(PSA) level [odds ratio(OR) = 1.13(95% CI 1.05–1.30), P =0.017], but not with higher Gleason grade or shorter PSA doubling time. Compared to CWU, ^(68)Ga PSMA-PET/CT detected an additional 106 lesions in 33/44 patients with a positive scan, resulting in a change in management in 25/44(56.8%) patients: 10 to hormonal therapy(HT) and whole pelvis radiotherapy(RT) in addition to bed RT, and 15 to palliative HT ***: In the present report, we demonstrated the diagnostic and treatment decision utility of ^(68)Ga PSMA-PET/CT in Asian men with rapid BCR. Detection of small volume nodal and systemic recurrences at low PSA levels(< 1.0 ng/mL) highlights the role of the tool in assigning patients to treatment intensification with HT-RT or palliative HT in polymetastatic disease.

关键词： ^68Ga PSMA PET/CT prostate cancer Asian diagnostic recurrence prostatectomy salvage radiotherapy

Image quality of cone beam CT on respiratory motion

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Nuclear Science and Techniques 2011年第2期22卷 111-117页

作者： ZHANG Ke LI Minghui DAI Jianrong WANG Shi Department of radiation oncology Cancer Institute (Hospital) Chinese Academy of Medical Sciences Beijing 100021 China Department of Engineering Physics Tsinghua University Beijing 100084 China

In this study,the influence of respiratory motion on Cone Beam CT (CBCT) image quality was investigated by a motion simulating platform,an image quality phantom,and a kV X-ray CBCT.A total of 21 motion states in the superior-inferior direction and the anterior-posterior direction,separately or together,was simulated by considering different respiration amplitudes,periods and *** influence of motion on CBCT image quality was evaluated with the quality indexes of low contrast visibility,geometric accuracy,spatial resolution and uniformity of CT *** results showed that the quality indexes were affected by the motion more prominently in AP direction than in SI direction,and the image quality was affected by the respiration amplitude more prominently than the respiration period and the *** CBCT image quality and its characteristics influenced by the respiration motion,and may be exploited in finding solutions.

关键词：呼吸运动图像质量锥束CT 模拟平台质量指标空间分辨率运动状态低对比度

Chemotherapy-free radiotherapy combined with immune checkpoint inhibitors:a new regimen for locally advanced non-small cell lung cancer?

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Cancer Biology & Medicine 2023年第12期20卷 1035-1046页

作者： Lin Ma Liufu Deng Jianfeng Peng Jinming Yu Xiangjiao Meng Department of oncology Renmin Hospital of Wuhan UniversityWuhan 430000China Department of radiation oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinan 250117China School of Pharmacy Shanghai Jiao Tong UniversityShanghai 200240China

Maintenance immunotherapy after concurrent chemoradiotherapy remains the standard therapeutic approach in patients with unresectable locally advanced non-small cell lung cancer(LA-NSCLC).The efficacy of pembrolizumab without chemotherapy in stage IV NSCLC has incited interest in similar approaches for *** recent investigations involving the synergistic potential of immunotherapy combined with radiotherapy(i RT)have generated encouraging *** review discusses the existing studies and prospective directions of chemotherapy-free i RT strategies in unresectable *** the initial findings of chemotherapy-free i RT strategies have shown promising efficacy,we must consider the methodologic limitations of current studies and the myriad of challenges that accompany the implementation of chemotherapy-free i *** challenges include determining the optimal dose and fractionation,precise target volume delineation,and identification of additional suitable patient ***,the feasibility of chemotherapy-free i RT as a novel treatment modality for select patients with LA-NSCLC is contingent upon validation through randomized phase III trials.

关键词： Locally advanced non-small cell lung cancer(LA-NSCLC) radiotherapy immunotherapy new regimen challenges