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Neoantigen cancer vaccines:a new star on the horizon

Cancer Biology & Medicine 2024年第4期21卷 274-311页

作者： Xiaoling Li Jian You Liping Hong Weijiang Liu Peng Guo xishan hao Cell Biotechnology Laboratory Tianjin Cancer Hospital Airport HospitalTianjin 300308China National Clinical Research Center for Cancer Tianjin 300060China Haihe Laboratory of Synthetic Biology Tianjin 300090China Department of Thoracic Oncology Tianjin Cancer Hospital Airport HospitalTianjin 300308China Department of Thoracic Oncology Surgery Tianjin Medical University Cancer Institute&HospitalTianjin 300060China Tianjin Medical University Cancer Institute&Hospital Tianjin 300060China

Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances within this field is the targeting of neoantigens,which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells.Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment,early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors.Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens.Consequently,personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences.This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines,and also discusses challenges and future perspectives for this innovative approach,particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.

关键词： Immunotherapy neoantigen cancer vaccine solid tumors high-throughput sequencing bioinformatics PDOs AI HLA TCR

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Epigenetic modulation of the tumor immune microenvironment by nanoinducers to potentiate cancer immunotherapy

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Cancer Biology & Medicine 2022年第1期19卷 1-3页

作者： Ning Zhang xishan hao Translational Cancer Research Center Peking UniversityPeking University First HospitalBeijing 100034China Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China

Epigenetic dysregulation is a key factor leading to oncogenesis and tumor progression1. To date, seven agents in three epigenetic target classes have been approved by the U.S. Food and Drug Administration for the treatment of diverse malignancies. Despite this approval for clinical application, the mechanisms of many epigenetic modulators are not completely understood, because many genes are epigenetically regulated.

关键词： immunotherapy clinical approval

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The mutation landscape of multiple cancer predisposition genes in Chinese familial/hereditary breast cancer families

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Cancer Biology & Medicine 2022年第6期19卷 850-870页

作者： Li Dong Hailian Zhang Huan Zhang Yingnan Ye Yanan Cheng Lijuan Li Lijuan Wei Lei Han Yandong Cao Shixia Li xishan hao Juntian Liu Jinpu Yu Cancer Molecular Diagnostics Core The Second Department of Breast Cancer Cancer Prevention Center Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerKey Laboratory of Breast Cancer Prevention and TherapyTianjin Medical UniversityMinistry of EducationTianjin 300060China Department of Oncology Tianjin Third Central HospitalTianjin Institute of Hepatobiliary DiseaseTianjin Key Laboratory of Artificial CellArtificial Cell Engineering Technology Research Center of Public Health MinistryTianjin 300170China Analyses Technology Co.Ltd. Beijing 102600China

Objective:Approximately 5%–10%of breast cancer(BC)patients display familial traits that are genetically inherited among the members of a family.The purpose of this study was to profile the germline mutations in 43 genes with different penetration rates and their correlations with phenotypic traits in Chinese familial BC families.Methods:Ion Torrent S5™-based next generation sequencing was conducted on 116 subjects from 27 Chinese familial BC families.Results:Eighty-one germline mutations in 27 BC predisposition genes were identified in 82.8%(96/116)of the cases.Among these,80.8%of the mutated genes were related to DNA damage repair.Fourteen possible disease-causing variants were identified in 13 of 27 BC families.Only 25.9%(7/27)of the BC families exhibited hereditary deficiency in BRCA1/2 genes,while 22.2%of the BC families exhibited defects in non-BRCA genes.In all,41.7%(40/96)of the mutation carriers had BRCA mutations,88.5%(85/96)had non-BRCA mutations,and 30.2%(29/96)had both BRCA and non-BRCA mutations.The BC patients with BRCA mutations had a higher risk of axillary lymph node metastases than those without mutations(P<0.05).However,the BC patients with non-BRCA mutations frequently had a higher occurrence of benign breast diseases than those without mutations(P<0.05).Conclusions:In addition to BRCA1/2,genetic variants in non-BRCA DNA repair genes might play significant roles in the development of familial/hereditary BC.Therefore,profiling of multiple BC predisposition genes should be more valuable for screening potential pathogenic germline mutations in Chinese familial/hereditary BC.

关键词： Familial breast cancer predisposition genes DNA damage repair genes clinical features

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Autophagy inhibition enhances apigenin-induced apoptosis in human breast cancer cells

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Chinese Journal of Cancer Research 2013年第2期25卷 212-222页

作者： Xuchen Cao Bowen Liu Wenfeng Cao Weiran Zhang Fei Zhang Hongmeng Zhao Ran Meng Lin Zhang Ruifang Niu xishan hao Bin Zhang National Key Laboratory of Breast Cancer Prevention and Treatment Tianjin Medical University Department of Breast Cancer Surgery of the Cancer Hospital Tianjin Medical University Department of Pathology of the Cancer Institute Tianjin Medical University Tianjin Key Laboratory of Cancer Prevention and Treatment Tianjin Medical University

Apigenin （4＇,5,7-trihydroxyflavone） is a member of the flavone subclass of flavonoids present in fruits and vegetables. The involvement of autophagy in the apigenin-induced apoptotic death of human breast cancer cells was investigated. Cell proliferation and viability were assessed by 3-（4,5-dimethylthiazol- 2-yl）-2,5-diphenyltetrazolium bromide （MTT） and clonogenic assays. Flow cytometry, fluorescent staining and Western blot analysis were employed to detect apoptosis and autophagy, and the role of autophagy was assessed using autophagy inhibitors. Apigenin dose- and time-dependently repressed the proliferation and clonogenic survival of the human breast cancer T47D and MDA-MB-231 cell lines. The death of T47D and MDA-MB-231 cells was due to apoptosis associated with increased levels of Caspase3, PARP cleavage and Bax/Bcl-2 ratios. The results from flow cytometry and fluorescent staining also verified the occurrence of apoptosis. In addition, the apigenin-treated cells exhibited autophagy, as characterized by the appearance of autophagosomes under fluorescence microscopy and the accumulation of acidic vesicular organelles （AVOs） by flow cytometry. Furthermore, the results of the Western blot analysis revealed that the level of LC3-Ⅱ, the processed form of LC3-Ⅰ, was increased. Treatment with the autophagy inhibitor, 3-methyladenine （3-MA）, significantly enhanced the apoptosis induced by apigenin, which was accompanied by an increase in the level of PARP cleavage. Similar results were also confirmed by flow cytometry and fluorescence microscopy. These results indicate that apigenin has apoptosis- and autophagy-inducing effects in breast cancer cells. Autophagy plays a cyto-protective role in apigenin-induced apoptosis, and the combination of apigenin and an autophagy inhibitor may be a promising strategy for breast cancer control.

关键词： Apoptosis autophagy apigenin breast cancer 3-methyladenine

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Expression of Preprotachykinin-I (PPT-I), Neurokinin-1 (NK-1) and Neurokinin-2 (NK-2) in Breast Cancer Cells Improves Tumor Cell Survival in Bone Marrow in the Early Stage of Metastasis

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Clinical oncology and cancer resexreh 2009年第3期6卷 225-232页

作者： Huilai Zhang Huaqing Wang Pengfei Liu Zhi Yao xishan hao Department of Lymphoma Tianjin Medical University Cancer Institute and Hospital Tianjin Key Laboratory of Cancer Prevention and Therapy Tianjin 300060 China Basic Medical College Tianjin Medical University Tianjin 300070 China

OBJECTIVE To study the potential relationship between theexpression of PPT-I, NK-1, NK2 and the development of breastcancer cells in bone marrow stroma and to provide evidence ofpotential molecular mechanisms of bone metastasis in early stageof breast cancer patients.METHODS The cocultures of breast cancer cell line T-47D andmarrow-derived mesenchymal stem cells (MSC) were establishedwith equal numbers. T-47D cells were separated from the coculturesystem at 48 h and 96 h after coculture by MACS magnetic cellsorting (MicroBeads). The expression of PPT-I, NK-1, NK-2 inT-47D was then examined before and after coculture by real-timePCR and by Western blot. Alterations in cellular ultrastructureof T-47D cells were detected before and after coculture underelectron microscope. Finally, changes in cell cycle distributionwere examined by flow cytometry, and growth curves from beforeand after coculture were drawn and analyzed.RESULTS Following coculture of T-47D and MSC, the expressionof PPT-I mRNA and protein was significantly upregulated, whilethe expression of NK-1 and NK-2 mRNA and protein was greatlydownregulated. The analysis of cell cycle distribution by flowcytometry showed that the proportion of T-47D during S phasewas increased, and the duration of the G_2/M phase was sharplydecreased. Under electron microscope, we observed that thesynthesis of hereditary material was increased, but the hepatingranules were shown prominent stacking in T-47D cells. Theseresults suggest that although the synthesis of DNA was increased,the proliferation of cells was inhibited after coculture. The cellgrowth curve confirmed the findings from the observation underthe electron microscope and flow cytometry.CONCLUSION Tumor cells could survive through theupregulation in expression of preprotachykinin-I gene duringearly bone metastasis in breast cancer. The phenomenon of growthsuppression in breast cancer cells after coculture in the currentstudy could be induced by downregulation in expression of NK-1and NK-2.

关键词：乳腺癌肿瘤细胞骨髓细胞生存

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Antitumor Activities of Apple Extracts

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Chinese Journal of Clinical Oncology 2006年第1期3卷 37-40页

作者： Peng Zhao Yan Zhuang Jianzhong Liu xishan hao Ming Liu Tianjin Cancer Institute ＆ Hospital Tianjin Medical University Tianjin 300060 China The Third Affiliated Hospital of Harbin Medical University Harbin 150040 China

OBJECTIVE To examine the antitumor activities of fresh apple extracts. METHODS Fuji apple extracts were tested for their anti-LS^174T-pro-liferative activities, for their effect on expression of PCNA, and ability to induce apoptosis in a LS-174T cell line. RESULTS Apple extracts inhibited LS-174T cellular proliferation in a concentration and time dependent manner. The apple extracts equivalent to a concentration of 50 mg/ml inhibited the proliferation of the LS-174T cells by 34.5±1.2% after 48 h and 47.5±1.8% after 72 h respectively. Apple extracts inhibited PCNA expression and induced apoptosis of the LS-174T cells at concentrations above 12.5mg/ml. CONCLUSION Apple extracts can inhibit PCNA expression and induction of apoptosis in LS-174T cells which may contribute to their inhibitio-ry effect on cellular proliferation.

关键词：植物化学细胞凋亡抗癌活性苹果

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Interpretation of breast cancer screening guideline for Chinese women

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Cancer Biology & Medicine 2019年第4期16卷 825-835页

作者： Yubei Huang Zhongsheng Tong Kexin Chen Ying Wang Peifang Liu Lin Gu Juntian Liu Jinpu Yu Fengju Song Wenhua Zhao Yehui Shi Hui Li Huaiyuan Xiao xishan hao Department of Epidemiology and Statistics Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin 300060China Medicine Department of Breast Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin 300060China China Anti-Cancer Association Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin 300060China Department of Breast Imaging Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin 300060China The 2nd Surgery Department of Breast Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin 300060China Cancer Prevention Center Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin 300060China Cancer Molecular Diagnostics Core Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin 300060China Department of Gastrointestinal Cancer Biology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin 300060China Department of Research and Education Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin 300060China

Breast cancer is the most common malignant tumor in Chinese women.Early screening is the best way to improve the rates of early diagnosis and survival of breast cancer patients.The peak onset age for breast cancer in Chinese women is considerably younger than those in European and American women.It is imperative to develop breast cancer screening guideline that is suitable for Chinese women.By summarizing the current evidence on breast cancer screening in Chinese women,and referring to the latest guidelines and consensus on breast cancer screening in Europe,the United States,and East Asia,the China Anti-Cancer Association and National Clinical Research Center for Cancer(Tianjin Medical University Cancer Institute and Hospital)have formulated population-based guideline for breast cancer screening in Chinese women.The guideline provides recommendations on breast cancer screening for Chinese women at average or high risk of breast cancer according to the following three aspects:age of screening,screening methods,and screening interval.This article provides more detailed information to support the recommendations in this guideline and to provide more direction for current breast cancer screening practices in China.

关键词： Breast cancer screening ultrasound mammography guideline

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基于电子鼻和BP神经网络对‘黑珍珠’鲜食玉米产地的区分和识别

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食品工业科技 2024年第13期45卷 239-245页

作者：马洪江郝曦煜高铭于有强杨书恒刘士伟马喜山王文鑫段盛林王雪黑龙江北纬四十七绿色有机食品有限公司黑龙江齐齐哈尔161532 黑龙江飞鹤乳业有限公司北京100016 中国食品发酵工业研究院有限公司北京100015

以‘黑珍珠’鲜食玉米为研究对象,采用电子鼻技术分别测定了黑龙江、陕西两大产区共计200个鲜食玉米样品的气味传感器响应值原始数据,通过主成分分析(Principal component analysis,PCA)、判别因子分析(Discriminant function analysis,... 详细信息

以‘黑珍珠’鲜食玉米为研究对象,采用电子鼻技术分别测定了黑龙江、陕西两大产区共计200个鲜食玉米样品的气味传感器响应值原始数据,通过主成分分析(Principal component analysis,PCA)、判别因子分析(Discriminant function analysis,DFA)对不同产地鲜食玉米的挥发性风味进行了区分,采用软独立建模分析(Soft independent modeling class analogy,SIMCA)建立了黑龙江‘黑珍珠’鲜食玉米的判定模型,并通过Pytorch软件建立了反向传播神经网络(Back propagation neural network,BP神经网络)模型,对不同产地的‘黑珍珠’鲜食玉米进行鉴别区分。结果表明,不同产地的‘黑珍珠’鲜食玉米的挥发性风味虽有相似之处但具有明显的产地特征,SIMCA模型可实现对未知样品是否来自黑龙江产区的有效识别(正确率为97%),BP神经网络模型则可对未知产地的‘黑珍珠’鲜食玉米样品进行产地预测及鉴别,平均正确率达99.44%。采用电子鼻技术结合BP神经网络模型可以准确的区分和识别‘黑珍珠’鲜食玉米产地。

关键词：鲜食玉米电子鼻主成分分析软独立建模 BP神经网络产地鉴别

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Characterization of Natural Killer Cells in the Liver of Young Mice

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Chinese Journal of Clinical Oncology 2007年第1期4卷 33-37页

作者： Peng Zhao Jiansheng Guo Guangjun Wang Qiang Chi Dequan Wu Zhaolin Zeng Xuefeng Bai xishan hao Department of Colorectal Tumor Tianjin Medical University Cancer Institute and Hospital Tianjin 300060 China Traditional Chinese Medcine Hospital of Qiqihaer Qiqihaer 161000 China The 2nd Affiliated Hospital of Harbin Medical University Harbin 150086 China

OBJECTIVE To determine the quantity and quality of liver NK cells from young and adult mice and compare their characteristics. METHODS C57BL/6 mice were used at 2 weeks (young) and 8 weeks (adult) of age. The percentage and absolute number of NK cells in the liver and spleen were analyzed. The cytotoxicity of NK cells in the liver and spleen against various targets were detected by a 4 h 51Cr-release method. FACScan was used to analyze the expression of CD69, Mac-1, Ly49C/I and CD94 on the NK cells. Perforin mRNA levels were analyzed by the reverse transcription polymerase chain reaction (RT-PCR). RESUTLS The percentages of NK cells in the liver of young and adult mice were similar (11.9%±1.7% vs. 9.9%±1.6%, P>0.05), but the absolute number per liver weight was higher in the young animals (11.6±2.5x105/g vs. 3.4±0.8x105/g, P<0.05). The level of NK cytotoxicity was extremely high in the liver of young compared to adult mice (71.0%±5.5% vs. 23.8%±4.4%, P<0.05), but this difference was not observed in the spleen. Phenotypes of the liver NK cells from young and adult mice were completely different from each other. The liver NK cells from young mice were CD69high Mac-1lowLy49C/ Ilow, whereas NK cells from older mice displayed inverse antigen levels (CD-69low Mac-1high Ly49C/Ihigh). The expression levels of other NK cell-related markers were similar in both groups.The perforin mRNA level in the liver lymphocytes from young mice was consistently greater compared to adult mice. CONCLUSION From 2 to 8 weeks C57BL/6 mice liver NK cells undergo age-associated changes. At 2 weeks of age the liver NK cells showed a high level of NK cytotoxicity and a unique phenotype which was not apparent at 8 weeks of age.

关键词：年轻小白鼠肝脏 NK细胞特性衰老细胞毒性

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Investigation on complementarity between total mesorectal excision and radical resection in relation to postoperative local recurrence in patients receiving anus-reserve operation on rectal cancer

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The Chinese-German Journal of Clinical Oncology 2007年第4期6卷 325-327页

作者： Kai Liu Peng Zhao Yan Zhuang Xin Yue Jianzhong Liu Xinshu Dong xishan hao Department of Colorectal Surgery Cancer Hospital of Tianjin Medical University Tianjin 300060 China Department of Abdominal Surgery Cancer Hospital of Harbin Medical University Harbin 150040 China

Objective:To investigate the difference and complementarity between total mesorectal excision(TME)and radical resection in relation to postoperative local recurrence in patients receiving anus-reserve operation on rectal cancer.Methods:Clinical data of 81 cases during a period from 1975 to 2001 were retrospectively analyzed.Results:In the 81 cases with local recurrence,49 of them laid to anastomosis and mesorectum,17 lymph nodes and 15 multi-site relapse.The choice of operative procedure included abdominoperineal resection in 58 cases,Hartmann’s operation in 4 cases,simple double-pelvic stoma in 12 cases,exploration in 7 cases,and total pelvic or rear-pelvic resection in combination with other organs in 6 cases. The rate of resection was 84.0%(68/81).32 cases reached clinical radical degree,and the rate of radical resection was 39.5% (32/81).The 5-year survival rate was 34.4%(11/32).Conclusion:Based on actual condition of the patients,attention to radi- cal resection and total mesorectal excision are necessary,and reasonable adoption of the operative procedure could reduce the local recurrence of rectal cancer.

关键词：直肠癌保肛手术局部复发 TME 扩大根治术互补性

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