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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 *** 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 *** 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 *** made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of ***,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 *** 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 *** 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 ***:Ion Torrent S5™-based next generation sequencing was conducted on 116 subjects from 27 Chinese familial BC ***:Eighty-one germline mutations in 27 BC predisposition genes were identified in 82.8%(96/116)of the *** these,80.8%of the mutated genes were related to DNA damage *** possible disease-causing variants were identified in 13 of 27 BC *** 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 *** 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 *** 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 ***,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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Expression and Characterization of the Recombinant Human FLT-3 Ligand Extracellular Domain in Pichia Pastoris

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Chinese Journal of Clinical Oncology 2006年第6期3卷 400-407页

作者： Zongtang Huang xishan hao Department of Immunology Tianjin Medical University Cancer Institute ＆ Hospital Tianjin 300060 China

OBJECTIVE The FLT-3 ligand (fms-like tyrosine kinase receptor-3 ligand, FL) is a recently described growth factor affecting early hematopoietic progenitor cells. The FL plays a key role in the growth and differentiation of primitive hematopoietic cells. To yield a high-level of recombinant human FL protein, a recombinant Pichia Pastoris (P. pastoris)strain was *** An artificial expression frame, with the same encoding protein sequence for the FL extracellular domain cDNA, was synthesized by using favored genetic codons of P. pastoris. P. pastoris strain KM71 cells were transformed with the endonuclease Bgl Ⅱ linearized recombined plasmid, pPIC9K-FL. The plasmid then was linerized in the 5'AOX1 site and integrated into the yeast KM71 genome. KM71 was transformed with pPIC9K plasmids as a control for the production of recombinant *** blotting and Northern blotting tests were used to screen the genotype of the recombined strain. Biological activity was demonstrated in vitro with culturing of CD34+*** The recombinant human FL protein expressed into the yeast culture supertant was identified on the basis of its molecular weight and Western blotting analysis. Numerous bands were observed in the 10～100 kDa molecular mass range. SDS-PAGE showed that the expressed product, a 20 kDa protein, was secreted into the medium in the form of a soluble molecule. Western-blot analyses showed good antigenicity and specificity against polyclonal antibodies. A sharp band and a smeared band were observed at a molecular mass of approximately 20 kDa by Western blotting. The recombinant human FL protein was the major protein component observed in the culture supernatant. The highest yield (108 mg/L) was obtained when expression was induced with 0.5% methanol for 96 h. Deglycosylation with PNGase F resulted in a decrease in apparent molecular mass from 20 kDa to 18 kDa forming three bands all of which were also detected by rabbit anti-FL antibodies. Cult

关键词：核酸内切酶重组体免疫系统免疫生物学

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Effects of Different Operative Procedures on the Digestive and Nutritional Status of Patients Treated with a Gastrectomy for Gastric Cancer

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Chinese Journal of Clinical Oncology 2006年第3期3卷 216-222页

作者： Han Liang xishan hao Department of Gastrointestinal Surgical Oncology Tianjin Medical University Cancer Institute and Hospital Tianjin 300060 China.

Postgastrectomy syndromes evoked by the loss of several gastric functions after total or subtotal gastrectomy are very common. Dif- ferent kinds of reconstruction have been developed to overcome the problem. Patients with preservation of a duodenal passage and jejunal interposition with or without a pouch show a better quality of life and mini- mal symptoms postoperatively. A jejunal interposition with or without a pouch after proximal or distal subtotal gastrictomy seems to improve the nutritional condition and quality of life. The prognostic nutritional index (PNI), Visick score, Spitzer index and the European Organization for Re- search and Treatment of Cancer (EORTC) questionnaire (QLQ-C30) are available to evaluate the quality of life and nutritional status after gastrec- tomy.

关键词：营养状态消化道胃切除术胃癌

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Role for CD40L in the Therapy of Human Cancer

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Chinese Journal of Clinical Oncology 2005年第6期2卷 894-898页

作者： Feng Wei Xiubao Ren xishan hao Department of Immunology Tianjin Cancer Institute and Hospital Tianjin300060. China.

CD40L-CD40 interaction is central to the control of thymusdependent humoral .immunity and cell mediated immune ***40, a member of the tumor necrosis factor receptor (TNF- R) family,has been found on the surface of B lymphocytes, monocytes, hematopoietic progenitors, dendritic cells (DCs), endothelial cells, epithelial cells and so on. Its natural ligand (CD40 ligand, CD40L), CD154, a member of the tumor necrosis factor (TNF) family, is mainly expressed on activated CD4+ T lymphocytes. A direct growth-inhibitory effect can be found when ligated CD40 is on human breast, ovarian, cervical, bladder, non-small cell lung, and squamous epithelial carcinoma cells. This effect is related to the induction of cell cycle blockage and/or apoptosis. CD40L induces phenotypic and functional maturation of DCs, and can increase tumor immunogenicity through up-regulation of costimulatory molecular expression and cytokine production by epithelial cancer cells. As a result,CD40L can enhance tumor rejection immune responses. Furthermore, by means of a 'bystander effect', even CD40-negative tumor subsets can be eliminated by activated tumor-reactive cytotoxic T lymphocytes(CTL),This review summarizes recent findings on CD40L recombinant protein and gene therapy-based tumor treatment approaches.

关键词： CD40L 生物治疗人类肿瘤

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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 *** 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 *** 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 *** 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 expres

关键词：乳腺癌肿瘤细胞骨髓细胞生存

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Investigation of the Relationship between the Intracellular Ca^(2+) Levels and Caspases-3 and 8 Expression in Rat Mammary Gland Carcinoma Undergoing Apoptosis

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Chinese Journal of Clinical Oncology 2007年第3期4卷 210-215页

作者： Hui Sun Jing Zhang Zhongli Zhan Baocun Sun xishan hao Pathology Department Tianjin Medica University Cancer Hospital Tianjin 300060 China

OBJECTIVE To investigate the relationship between the level of cas-pase-3 and 8 expression and intracellular Ca2+ levels in BCML-TA299 breast cancer cells in the process of apoptosis. METHODS Mice were divided into three IFNа-treated groups and one control group as follows: an intratumoral injection, subcutaneous injection, preventive injection, and a control without injection. The cellular DNA content, changes in the cell cycle and the relationship between the cell Ca2+ concen-trations and the expression of caspase-3 and 8 were examined. RESULTS After injection of IFN-α-2b by different routes, the morphologic transformation of the breast cancer cells in each group was observed. There was a typical apoptotic response in the intratumoral-injection group. The expression of caspase-3 and 8 was diverse among the experimental groups, and correlated with the cellular Ca2+ concentration. Caspase-3 and 8 expres-sion and the cellular Ca2+ level were higher following intratumoral injection compared to the other treatments (P<0.01). Among the experimental groups, the cell cycle displayed definitive changes. CONCLUSION a) Both caspase-3 and 8 and the intracellular Ca2+ are elevated in the process of cell apoptosis in BCML-TA299 breast cancer tis-sues. These changes may play important roles in the occurrence and devel-opment of breast cancer; b) Variation in the route of IFN-α-2b administration can produce different responses in the expression of caspase-3 and 8 and the concentration of Ca2+ in apoptotic tumor cells.

关键词：乳腺癌钙离子细胞凋亡基因表达

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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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Influence of Perioperative Blood Transfusion on Prognosis in Patients with Colon Cancer

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The Chinese-German Journal of Clinical Oncology 2006年第4期5卷 261-267页

作者： LIANG Han WANG Xiaona WANG Baogui PAN Yuan LIU Ning WANG Dianchang hao xishan Department of Gastrointestinal Oncological Surgery Tianjin Cancer Hospital Tianjin Medical University Tianjin 300060 China

客观：探索起作用的仙子的影响有结肠癌的病人的手术后的幸存上的输血。方法：Univariate 和 multivariateretrospective 分析总共在 10 年的一个时期期间通过手术被对待的 723 个结肠癌病人的在幸存上被执行。结果：Kaplan-Meier 估计... 详细信息

客观：探索起作用的仙子的影响有结肠癌的病人的手术后的幸存上的输血。方法：Univariate 和 multivariateretrospective 分析总共在 10 年的一个时期期间通过手术被对待的 723 个结肠癌病人的在幸存上被执行。结果：Kaplan-Meier 估计显示出起作用的那超过 800 mL 仙子输血幸存预言者。输血显著地影响了病人的预后 40 岁并且更年轻，那些 undergoinghelicoloectomy 左边，那些与乳头状腺癌，那些与大肿瘤(直径≥ 8cm ) ，那些与阶段Ⅰ肿瘤，那些与没有肝转移的淋巴的节点转移和那些。在里面多变量分析仅仅肿瘤地点，操作的 radicality，淋巴的侵略，肝转移，肿瘤侵略的深度和 TNM 舞台保留了他们的 ***：Perioperative 输血是为有到某程度的结肠癌的病人的预示的因素。输血的指示必须严格地被限制，特殊比 40 岁年轻的住院病人与右边损害，乳头状腺癌，大肿瘤(直径≥ 8 厘米) ，阶段Ⅰ肿瘤和淋巴的节点转移或没有肝转移。Butperioperative 输血不能为有阶段Ⅳ疾病并且与远转移的病人是有害的。

关键词：牙周炎输血反应结肠癌治疗

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