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RELATIONSHIP BETWEEN DRINKING WATER,VEGETABLES AND CANCER DEATH IN THE HIGH INCIDENCE AREA OF DIGESTIVE TRACT CANCER
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作者 韩存芝 荆洁线 +3 位作者 赵先文 刘副民 郭晋纲 曹继荣 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 1997年第2期96-99,共4页
The Paper analyzed of investigation datas on thedeath causes of digestive tract cancer in high-incidencearea between 70s and 80s. The results showed that thecancer-adjusted mortalities were 224.14/100000 and226.66/100... The Paper analyzed of investigation datas on thedeath causes of digestive tract cancer in high-incidencearea between 70s and 80s. The results showed that thecancer-adjusted mortalities were 224.14/100000 and226.66/100000: it was 7 times as high as low-incidence(31.19/100000 and 29.82/100000). In 70s, the cancer deathof esophagus, stomach and liver (87.41/100000,73.93/100000 and 8.59/100000) were 28 times, 10 timesand 4 times as high as low-incidence area (3.70/100000,10.57/100000 and 1.94/100000), respectively (P<0.001). In80s, the cancer death of esophagus, stomach and liver(68.26/100000, 109.39/100000 and 23.89/100000) were 17times, 10 times and 4 times as high as low-incidence area(4.54/100000, 10.84/100000 and 6.35/100000), respectively(P<0.001). In high-incidence area, the cancer death ofesophagus was lower, of stomach and liver were higherin 80s than 70s, respectively (P<0.01)- The result alsoshowed that the nitrate content of drinking water andvegetables were 21.45mg/1 and 1185.27mg/kg in high-incidence area; it were significant higher than that in low-incidence area (2.14mg/1 and 41.6omg/kg), the nitritecontent (0.01mg/l) of drinking water in high-incidencearea was significant higher than that in low-incidencearea (0.004mg/l), but the nitrite content among vegetableswas no significant difference between the two regions(N0.05). Our results suggest that the nitrate and nitritecontents increase in drinking water and vegetables maybe an important risk factor of upper alimentary cancer inhigh-incidence area. 展开更多
关键词 Digestive tract cancer Drinking water Vegetable cancer death
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Analysis of Esophageal Cancer Death at Different Educational Levels in Inner Mongolia from 2009 to 2015
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作者 Rina Su Hao Wu +7 位作者 Fengqing Li Yan Zhang Huixia Li Lin Sun Sitana Ha Junjie An Chengyi Zhang Juan Sun 《Health》 2021年第11期1270-1277,共8页
<strong>Objective: </strong>This study aimed to clarify the death characteristics of esophageal cancer in Inner Mongolia and the population distribution with various education levels. <strong>Methods... <strong>Objective: </strong>This study aimed to clarify the death characteristics of esophageal cancer in Inner Mongolia and the population distribution with various education levels. <strong>Methods:</strong> The mortality rate of esophageal cancer was calculated using the monitoring point of Death Registry System in Inner Mongolia from 2009 to 2015. The gender, age, region, ethnicity at two education levels of percentage were calculated and the <em>χ</em><sup>2</sup> test was executed. <strong>Result:</strong> The mortality rate of esophageal cancer was 10.10/105, China Adjustment Mortality was 10.97/10<sup>5</sup>, World Adjustment Mortality was 9.08/10<sup>5</sup> in Inner Mongolia. The death of esophageal cancer showed statistical significance at two educational levels (P < 0.05). High school and below accounted for 93.9% at the education level, and above high school accounted for 3.5%. In addition, there were significant differences in the percentage of death by gender, age and region at two educational levels (P < 0.05). <strong>Conclusion:</strong> Education level has a certain relation with the death of esophageal cancer. To improve the health level, health education plans can be formulated according to esophageal cancer prevention relevant policy with different education levels. 展开更多
关键词 Esophageal cancer death Education Level
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Population attributable risks of cigarette smoking for deaths of all causes, all cancers and other chronic diseases among adults aged 40-74 years in urban Shanghai, China 被引量:6
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作者 Ying-Ying Wang Wei Zhang +6 位作者 Hong-Lan Li Jing Gao Yu-Ting Tan Yu-Tang Gao Xiao-Ou Shu Wei Zheng Yong-Bing Xiang 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2015年第1期59-65,共7页
Objective: To evaluate the population attributable risks (PARs) between cigarette smoking and deaths of all causes, all cancers, lung cancer and other chronic diseases in urban Shanghai. Methods: In total, 61,480 ... Objective: To evaluate the population attributable risks (PARs) between cigarette smoking and deaths of all causes, all cancers, lung cancer and other chronic diseases in urban Shanghai. Methods: In total, 61,480 men aged 40-74 years from 2002 to 2006 and 74,941 women aged 40-70 years from 1997 to 2000 were recruited to undergo baseline surveys in urban Shanghai, with response rates of 74.0% and 92.3%, respectively. A Cox proportional hazards regression model was used to estimate relative risks (RRs) and 95% confidence intervals (95% CIs) of deaths associated with cigarette smoking. PARs and 95 % CIs for deaths were estimated from smoking exposure rates and the estimated RRs. Results: Cigarette smoking was responsible for 23.9% (95% CI: 19.4-28.3%) and 2.4% (95% Ch 1.6- 3.2%) of all deaths in men and women, respectively, in our study population. Respiratory disease had the highest PAR in men [37.5% (95% CI: 21.5-51.6%)], followed by cancer [31.3% (95% Ch 24.6-37.7%)] and cardiovascular disease (CVD) [24.1% (95% CI: 16.7-31.2%)]. While the top three PARs were 12.7% (95% CI: 6.1-19.3%), 4.0% (95% CI: 2.4-5.6%), and 1.1% (95% CI: 0.0-2.3%), for respiratory disease, CVD, and cancer, respectively in women. For deaths of lung cancer, the PAR of smoking was 68.4% (95% CI: 58.2- 76.5%) in men. Conclusions: In urban Shanghai, 23.9% and 2.4% of all deaths in men and women could have been prevented if no people had smoked in the area. Effective control programs against cigarette smoking should be strongly advocated to reduce the increasing smoking-related death burden. 展开更多
关键词 Population attributable risk (PAR) SMOKING mortality cohort study all causes death cancer death lung cancer
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Panel Recommends 12 Steps for Cutting Cancer Deaths
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作者 Alicia Ault 汤阿宝 《当代外语研究》 2003年第8期4-6,共3页
If more Americans quit smoking,lost a little weight and started eating bet-ter,at least 60,000 cancer deaths could be avoided each year,according tO a re-port issued Monday by a government advisory panel. 假如有更多... If more Americans quit smoking,lost a little weight and started eating bet-ter,at least 60,000 cancer deaths could be avoided each year,according tO a re-port issued Monday by a government advisory panel. 假如有更多的美国人戒烟,适当减肥,并开始吃得更健康些,至少每年可以减少60 000死于癌症的病例。政府顾问团周一发表的一则报告如是说。 展开更多
关键词 癌症发病率 癌症预防 Panel Recommends 12 Steps for Cutting cancer deaths 美国癌症协会 IOM
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Anti program death-1/anti program death-ligand 1 in digestive cancers 被引量:12
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作者 Eléonore de Guillebon Pauline Roussille +1 位作者 Eric Frouin David Tougeron 《World Journal of Gastrointestinal Oncology》 SCIE CAS 2015年第8期95-101,共7页
Human tumors tend to activate the immune system regulatory checkpoints as a means of escaping immunosurveillance. For instance, interaction between program death-1(PD-1) and program death-ligand 1(PD-L1) will lead the... Human tumors tend to activate the immune system regulatory checkpoints as a means of escaping immunosurveillance. For instance, interaction between program death-1(PD-1) and program death-ligand 1(PD-L1) will lead the activated T cell to a state of anergy. PD-L1 is upregulated on a wide range of cancer cells. Anti-PD-1 and anti-PD-L1 monoclonal antibodies(m Abs), called immune checkpoint inhibitors(ICIs), have consequently been designed to restore T cell activity. Accumulating data are in favor of an association between PD-L1 expression in tumors and response to treatment. A PD-L1 expression is present in 30% to 50% of digestive cancers. Multiple anti-PD-1(nivolumab, pembrolizumab) and anti-PD-L1 m Abs(MPDL3280A, Medi4736) are under evaluation in digestive cancers. Preliminary results in metastatic gastric cancer with pembrolizumab are highly promising and phase Ⅱ will start soon. In metastatic colorectal cancer(CRC), a phase Ⅲ trial of MPDL3280 A as maintenance therapy will shortly be initiated. Trials are also ongoing in metastatic CRC with high immune T cell infiltration(i.e., microsatellite instability). Major challenges are ahead in order to determine how, when and for which patients we should use these ICIs. New radiologic criteria to evaluate tumor response to ICIs are awaiting prospective validation. The optimal therapeutic sequence and association with cytotoxic chemotherapy needs to be established. Finally, biomarker identification will be crucial to selection ofpatients likely to benefit from ICIs. 展开更多
关键词 PROGRAM death-1 PROGRAM death-ligand 1 Antibody DIGESTIVE cancer
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Autophagic cell death: A new frontier in cancer research
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作者 S. Zappavigna A. Luce +3 位作者 G. Vitale N. Merola S. Facchini M. Caraglia 《Advances in Bioscience and Biotechnology》 2013年第2期250-262,共13页
Autophagy is a conserved and tightly regulated cellular catabolic process that involves the lysosomal degradation pathway. Intracellular recycling of macromolecules and organelles provided by autophagy is an integral ... Autophagy is a conserved and tightly regulated cellular catabolic process that involves the lysosomal degradation pathway. Intracellular recycling of macromolecules and organelles provided by autophagy is an integral part of normal cellular function and permits cells survival under starvation conditions, maintaining cell growth and the homeostasis of organisms. In addition to its normal role in cell physiology, auto- phagy is closely linked to both tumorigenesis and cancer cell response to treatments. In fact, anticancer drugs can induce autophagy but it remains contro- versial whether this process leads to cancer cell death or protects cancer cells from cellular stress. The role of autophagy in cancer is complex and is likely dependent on tumor type, stage, and genetic context. However, recent evidences demonstrate a tight interconnection of autophagy with several cell death pathways and reveal an active contribution of auto- phagy to cell death. When autophagy is directly in- volved in the death process, the cell death process is designated “autophagic cell death” (ACD). In this review, we will give a comprehensive overview of the autophagic signaling pathway, its role and regulation in cancer cells;moreover, we will try to define the molecular mechanisms at the basis of the autophagic cell death showing that PPAR-γ activation plays a role in the induction of autophagy in cancer cells. 展开更多
关键词 AUTOPHAGY cancer CELLULAR death MTOR PPAR-Γ
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Discovery of a small-molecule bromodomain-containing protein 4 inhibitor that induces AMP-activated protein kinase-modulated autophagy-associated cell death in breast cancer 被引量:4
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作者 Jin ZHANG Jie LIU Liang OUYANG 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2017年第10期980-980,共1页
OBJECTIVE To discover a small-molecule bromodomain-containing protein 4(BRD4)inhibitor that induces AMP-activated protein kinase-modulated autophagy-associated cell death in breast cancer and exploreits potential mech... OBJECTIVE To discover a small-molecule bromodomain-containing protein 4(BRD4)inhibitor that induces AMP-activated protein kinase-modulated autophagy-associated cell death in breast cancer and exploreits potential mechanisms.METHODS BRD4 interactors were analyzed by PPI network prediction and The Cancer Genome Atlas(TCGA)analysis.The interaction between BRD4 and AMPK was confirmed by co-immunoprecipitation assay.Novel BRD4 inhibitors were designed and synthesized based upon pharmacophore analysis of BRD4(1),then screened by antiproliferative activity and Alpha Screen of BRD4(1).The selectivity of the best candidate compound 8f was validated by co-crystallization,FRET assay and co-immuno precipitation assay.The mechanisms of 8f were investigated by fluorescence microscopy,electron microscopy,Western blotting,immunocytochemistry,si RNA and GFP-m RFP-LC3 plasmid transfections,as well as immunohistochemistry and immunofluorescence.Potential mechanisms were discovered by i TRAQ-based proteomics analysis and the therapeutic effect of 8f was assessed by xenograft breast cancer mouse and zebrafish models.RESULTS We identified that BRD4 interacted with AMPK,which was remarkably downregulated in breast cancer.We next designed and synthesized 49 candidate compounds,and eventually discovered a selective small-molecule inhibitor of BRD4(8f).Subsequently,8f was discovered to induce autophagyassociated cell death(ACD)by BRD4-AMPK interaction,and thus activating AMPK-m TOR-ULK1-modulated autophagic pathway in breast cancer cells.Interestingly,the i TRAQ-based proteomics analyses revealed that 8f induced ACD pathways,involved in HMGB1,VDAC1/2 and e EF2.Moreover,8f displayed a therapeutic potential on both xenograft breast cancer mouse and zebrafish models.CONCLUSION We discovered a novel small-molecule inhibitor of BRD4 that induces BRD4-AMPK-modulated ACD in breast cancer,which may provide a candidate drug for future cancer therapy. 展开更多
关键词 bromodomain-containing protein 4(BRD4) BRD4-AMPK interaction small-molecule inhibitor of BRD4 Autophagy-associated cell death(ACD) breast cancer
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Advances in immuno-oncology biomarkers for gastroesophageal cancer:programmed death ligand 1,microsatellite instability,and beyond 被引量:10
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作者 Emily M Lin Jun Gong +1 位作者 Samuel J Klempner Joseph Chao 《World Journal of Gastroenterology》 SCIE CAS 2018年第25期2686-2697,共12页
Blockade of the programmed death ligand 1(PD-L1) and programmed cell death 1(PD-1) receptor axis represents an effective form of cancer immunotherapy. Preclinical evidence initially suggested that gastric and gastroes... Blockade of the programmed death ligand 1(PD-L1) and programmed cell death 1(PD-1) receptor axis represents an effective form of cancer immunotherapy. Preclinical evidence initially suggested that gastric and gastroesophageal junction(GEJ) cancers are potentially immunotherapy-sensitive tumors. Early phase clinical trials have demonstrated promising antitumor activity with PD-1/PD-L1 blockade in advanced or metastatic gastric/GEJ cancer. Microsatellite instability(MSI) and PD-L1 expression have been shown to predict higher response to PD-1 inhibitors as highlighted by the recent approvals of pembrolizumab in treatmentrefractory solid tumors with MSI status and the thirdline or greater treatment of PD-L1 positive advanced gastric/GEJ cancers. However, predictive and prognostic biomarkers remain an ongoing need. In this review, we detail the preclinical evidence and early tissue biomarker analyses illustrating potential predictive biomarkers to PD-1/PD-L1 blockade in gastric/GEJ cancer. We also review the clinical development of PD-1/PD-L1 inhibitors in gastric/GEJ cancer and highlight several areas in need of future investigation in order to optimize the efficacy of PD-1/PD-L1 blockade in gastric/GEJ cancer. 展开更多
关键词 IMMUNOTHERAPY programmed cell death 1 programmed death LIGAND 1 MICROSATELLITE instablility Gastric cancer
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Significance of 125I radioactive seed implantation on growth differentiation factor and programmed death receptor-1 during treatment of oral cancer 被引量:4
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作者 Gang Xue Yao Feng Jia-Bin Li 《World Journal of Clinical Cases》 SCIE 2020年第5期874-886,共13页
BACKGROUND Oral cancer(OC)is the most common malignant tumor in the oral cavity,and is mainly seen in middle-aged and elderly men.At present,OC is mainly treated clinically by surgery or combined with radiotherapy and... BACKGROUND Oral cancer(OC)is the most common malignant tumor in the oral cavity,and is mainly seen in middle-aged and elderly men.At present,OC is mainly treated clinically by surgery or combined with radiotherapy and chemotherapy;but recently,more and more studies have shown that the stress trauma caused by surgery and the side effects of radiotherapy and chemotherapy seriously affect the prognosis of patients.AIM To determine the significance of 125I radioactive seed implantation on growth differentiation factor 11(GDF11)and programmed death receptor-1(PD-1)during treatment of OC.METHODS A total of 184 OC patients admitted to The Second Affiliated Hospital of Jiamusi University from May 2015 to May 2017 were selected as the research subjects for prospective analysis.Of these patients,89 who received 125I radioactive seed implantation therapy were regarded as the research group(RG)and 95 patients who received surgical treatment were regarded as the control group(CG).The clinical efficacy,incidence of adverse reactions and changes in GDF11 and PD-1 before treatment(T0),2 wk after treatment(T1),4 wk after treatment(T2)and 6 wk after treatment(T3)were compared between the two groups.RESULTS The efficacy and recurrence rate in the RG were better than those in the CG(P<0.05),while the incidence of adverse reactions and survival rate were not different.There was no difference in GDF11 and PD-1 between the two groups at T0 and T1,but these factors were lower in the RG than in the CG at T2 and T3(P<0.05).Using receiver operating characteristic(ROC)curve analysis,GDF11 and PD-1 had good predictive value for efficacy and recurrence(P<0.001).CONCLUSION 125I radioactive seed implantation has clinical efficacy and can reduce the recurrence rate in patients with OC.This therapy has marked potential in clinical application.The detection of GDF11 and PD-1 in patients during treatment showed good predictive value for treatment efficacy and recurrence in OC patients,and may be potential targets for future OC treatment. 展开更多
关键词 125I radioactive seeds Oral cancer Growth differentiation factor 11 Programmed death receptor-1 Prognosis RECURRENCE
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Decision-Making Process for the Place of Death of Elderly Patients with Advanced Cancer and Their Families
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作者 Yoko Minamiguchi Kumi Suzuki 《Open Journal of Nursing》 2019年第12期1281-1305,共25页
Purpose: This study aims to understand how elderly patients with advanced cancer and their families make a decision for a place of death for the patient. Methods: Semi-structured interviews were conducted with 17 pair... Purpose: This study aims to understand how elderly patients with advanced cancer and their families make a decision for a place of death for the patient. Methods: Semi-structured interviews were conducted with 17 pairs of elderly patients and members of their family. The patients had finished anticancer treatment and made some decision about the preferred place of death. A modified grounded-theory approach was used for the data analysis. Results: Making a “tentative” decision for the place of death of the elderly patients is a process with the core category [carefully choosing the final place for self-fulfillment]. The patients were “conducting a comprehensive review of the place of death” and “embracing the wishes for a way of life without difficulty”. Involving the family in making a “tentative” decision about the place of death of the elderly patients is the process with the core category [realizing the wish of patients in the terminal condition for the way for death]. The families were “examining the place of death from different aspects” and “respecting the patient’s intention as far as possible”. Conclusions: When the patients [carefully choosing the final place for self-fulfillment], it was important to reconcile their wishes with the burden on the families. When the families were trying to [realize the wish of patients in the terminal condition for the way for dying], it was important to balance the respect for the patient intentions and homecare they can provide for the patient. For the patients and their families, it is essential to mutually understand the intentions and wishes of the other party in decision making about the place of death. 展开更多
关键词 Advanced cancer ELDERLY Patients PLACE of death FAMILY DECISION MAKING
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PD-1单抗后线辅助治疗晚期结直肠癌患者对胃肠功能、肿瘤标志物的影响 被引量:1
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作者 吴翔 岳春迪 李春芸 《临床和实验医学杂志》 2024年第9期941-945,共5页
目的分析程序性死亡受体-1(PD-1)单抗后线辅助治疗晚期结直肠癌患者对胃肠功能、肿瘤标志物的影响。方法前瞻性选取2020年1月至2023年1月海口市人民医院收治的105例晚期结直肠癌患者为研究对象,按照随机数字表法将患者分为对照组(n=50)... 目的分析程序性死亡受体-1(PD-1)单抗后线辅助治疗晚期结直肠癌患者对胃肠功能、肿瘤标志物的影响。方法前瞻性选取2020年1月至2023年1月海口市人民医院收治的105例晚期结直肠癌患者为研究对象,按照随机数字表法将患者分为对照组(n=50)、研究组(n=55)。对照组采用阿帕替尼治疗,研究组在对照组的基础上联合PD-1单抗后线治疗,3周为1个疗程,共治疗4个疗程。比较两组的临床疗效、胃肠功能改善时间,治疗前、治疗12周后的肿瘤标志物[癌胚抗原、糖类抗原(CA)72-4、CA199]、免疫功能(CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))指标以及不良反应发生情况。结果治疗12周后,研究组的客观缓解率(ORR)、病情控制率(DCR)分别为78.33%、90.91%,均高于对照组(58.00%、70.00%),差异均有统计学意义(P<0.05)。研究组患者的首次排便时间、首次排气时间、肠鸣音消退时间分别为(51.50±5.02)、(35.52±4.25)、(44.28±4.80)d,均短于对照组[(69.37±6.40)、(50.63±5.10)、(53.50±6.15)d],差异均有统计学意义(P<0.05)。治疗12周后,研究组癌胚抗原、CA72-4、CA199水平分别为(12.57±1.64)ng/mL、(17.60±3.45)U/mL、(58.29±8.70)kU/L,均低于对照组[(17.24±2.50)ng/mL、(27.59±4.67)U/mL、(82.65±12.29)kU/L],差异均有统计学意义(P<0.05)。治疗12周后,研究组CD4^(+)、CD4^(+)/CD8^(+)水平分别为(21.42±3.54)%、0.73±0.30,均低于对照组[(28.39±4.38)%、1.12±0.41],CD8^(+)水平为(30.36±4.52)%,高于对照组[(25.71±3.30)%],差异均有统计学意义(P<0.05)。研究组的不良反应发生率为9.09%,稍低于对照组(16.00%),但两组比较差异无统计学意义(P>0.05)。结论通过PD-1单抗后线辅助治疗可有效改善晚期结直肠癌患者的临床疗效,效果明显,改善胃肠功能,降低肿瘤标志物指标水平,调节机体免疫功能,可为临床干预此病提供参考。 展开更多
关键词 结直肠肿瘤 晚期结直肠癌 程序性死亡受体-1单抗 胃肠功能 肿瘤标志物
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血清细胞因子表达水平与非小细胞肺癌PD-1抑制剂疗效研究进展 被引量:1
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作者 张鹏 李桂香 《兰州大学学报(医学版)》 2024年第1期82-86,共5页
程序性死亡受体-1(PD-1)/程序性死亡分子配体-1信号通路抑制剂激活机体免系统后产生的细胞因子在抗肿瘤细胞过程中发挥关键作用。本文回顾近年来接受PD-1抑制剂治疗的非小细胞肺癌患者血清细胞因子表达水平与临床获益的相关性研究,揭示... 程序性死亡受体-1(PD-1)/程序性死亡分子配体-1信号通路抑制剂激活机体免系统后产生的细胞因子在抗肿瘤细胞过程中发挥关键作用。本文回顾近年来接受PD-1抑制剂治疗的非小细胞肺癌患者血清细胞因子表达水平与临床获益的相关性研究,揭示非小细胞肺癌患者PD-1治疗前后白介素-6、白介素-8、肿瘤坏死因子、干扰素、白介素-17A等细胞因子水平变化,为寻找经济、便捷的PD-1抑制剂疗效生物标志物提供思路和线索。 展开更多
关键词 非小细胞肺癌 程序性死亡受体-1抑制剂 细胞因子 疗效预测
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Discovery of a small molecule targeting ULK1-modulated cell death of triple negative breast cancer in vitro and in vivo 被引量:10
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作者 Lei-lei FU Yu-qian ZHAO Bo LIU 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2017年第10期957-958,共2页
OBJECTIVE To discover a small molecule targeting ULK1-modulated cell death of triple negative breast cancer and exploreits potential mechanisms.METHODS ULK1 expression was analyzed by The Cancer Genome Atlas(TCGA)anal... OBJECTIVE To discover a small molecule targeting ULK1-modulated cell death of triple negative breast cancer and exploreits potential mechanisms.METHODS ULK1 expression was analyzed by The Cancer Genome Atlas(TCGA)analysis and tissue microarray(TMA)analysis.ULK1agonist was designed by using in silico screening,as well as modified by chemical synthesis and screened by kinase and anti-proliferative activities.The amino acid residues that key to the activation site of LYN-1604 were determined by site-directed mutagenesis,as well as in vitro kinase assay and ADP-Glo kinase assay.The mechanisms of LYN-1604 induced cell death were investigated by fluorescence microscope,western blotting,flow cytometry analysis,immunocytochemistry,as well as si RNA and GFP-m RFP-LC3 plasmid transfections.Potential ULK1 interactors were discovered by performing comparative microarray analysis and the therapeutic effect of LYN-1604 was assessed by xenograft breast cancer mouse model.RESULTS We found that ULK1 was remarkably downregulated in breast cancer tissue samples,especial y in triple negative breast cancer(TNBC).32 candidate smal molecules were synthesized,and we discovered a small molecule named LYN-1604 as the best candidate ULK1agonist.Additionally,we identified that three amino acid residues(LYS50,LEU53 and TYR89)were key to the activation site of LYN-1604 and ULK1.Subsequently,we demonstrated that LYN-1604 could induce autophagy-associated cell death via ULK complex(ULK1-m ATG13-FIP200-ATG101)in MDA-MB-231 cells.We also found that LYN-1604 induced cell death involved in ATF3,RAD21 and caspase 3,accompanied with autophagy and apoptosis.Moreover,we demonstrated that LYN-1604 had a good therapeutic potential on TNBC by targeting ULK1-modulated cell death in vivo.CONCLUSION We discovered a small molecule(LYN-1604)has therapeutic potential by targeting ULK1-modulated cell death associated with autophagy and apoptosis of TNBC in vitro and in vivo,which could be utilized as a new anti-TNBC drug candidate. 展开更多
关键词 UNC-51-like kinase 1(ULK1) cell death AUTOPHAGY ULK1 agonist triple negative breast cancer(TNBC)
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Modulation of cell death pathways in cancer stem cells: Targeting histone demethylases
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作者 Ravi Thakur Durga Prasad Mishra 《Advances in Bioscience and Biotechnology》 2012年第6期720-730,共11页
Cancer stem cells (CSCs) are tumor initiating cells within the tumor mass;that play a critical role in cancer pathogenesis. CSCs regulate cancer cell survival, metastatic potential, resistance to conventional radio-ch... Cancer stem cells (CSCs) are tumor initiating cells within the tumor mass;that play a critical role in cancer pathogenesis. CSCs regulate cancer cell survival, metastatic potential, resistance to conventional radio-chemotherapy, disease relapse and poor prognosis. Recent studies have established that the drug resistant cancers and cancer cell lines possess high stem cell like traits compared to their drug sensitive counterparts. Histone demethylases are recently been linked to drug induced reversible tolerant state in cancers. Lysine histone demethylases are enzymes those demethylate lysines in histones and can act as transcriptional repressors or activators. Apart from histones other cellular proteins like E2F1, Rb, STAT3 and p53 are also regulated by methylation and demethylation cycles. In cancer cells these enzymes regulate cell survival, migration, invasion, and proliferation. This review summarizes the current progress of research on the role of histone demethylases in supporting drug tolerant cancer stem cell state and their potential as a drug target. 展开更多
关键词 cancer Stem Cells HISTONE LYSINE Demethylases Cell death LSD1 KDM5A
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血清中PD-L1含量与胃癌病人预后的关系
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作者 陈长强 严晓伟 +3 位作者 胡皆乐 包皙婷 项明 姜松耀 《外科理论与实践》 2024年第3期230-235,共6页
目的:分析胃癌病人血清中程序性死亡配体1(programmed death-ligand 1,PD-L1)含量及其与肿瘤分期和预后的关系。方法:收集我院2018年8月至2019年12月60例胃癌病人血清,15例健康成人血清作为对照,通过酶联免疫吸附试验(ELISA)检测血清PD... 目的:分析胃癌病人血清中程序性死亡配体1(programmed death-ligand 1,PD-L1)含量及其与肿瘤分期和预后的关系。方法:收集我院2018年8月至2019年12月60例胃癌病人血清,15例健康成人血清作为对照,通过酶联免疫吸附试验(ELISA)检测血清PD-L1的含量,比较胃癌病人与健康成人血清PD-L1含量的差异,分析胃癌病人血清PD-L1的含量与病期及预后的关系。免疫组织化学检测肿瘤组织内PD-L1的表达情况,并分析其与血清中PD-L1含量的相关性。结果:胃癌组血清中PD-L1的含量明显高于对照组。Ⅲ、Ⅳ期胃癌病人血清PD-L1含量明显高于Ⅰ、Ⅱ期胃癌病人。胃癌病人合并腹膜转移者血清PD-L1含量明显升高,提示预后不良。生存分析显示,血清PD-L1含量高的胃癌病人生存期明显短于低者。检测肿瘤组织标本中PD-L1的表达水平,发现其与血清中PD-L1含量无明显相关性。结论:胃癌病人血清中PD-L1含量高于健康成人。随病期进展逐渐升高。胃癌伴腹膜转移的病人血清中PD-L1升高明显。血清中PD-L1含量与肿瘤组织中的PD-L1表达不相关。 展开更多
关键词 胃癌 程序性死亡配体1 血清
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Clinical Predictors for Reduced Long-Term Survival and Cause of Death after Curative Resection for Rectal Cancer
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作者 Ola Røkke Thomas Heggelund +2 位作者 Jūratė Šaltytė Benth Marianne Steffensen Røkke Kjell Øvrebø 《Journal of Cancer Therapy》 2021年第1期31-46,共16页
<strong>Purpose:</strong> <span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">To identify clinical predictors for redu... <strong>Purpose:</strong> <span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">To identify clinical predictors for reduced long-term survival and </span><span><span style="font-family:Verdana;">describe the cause of death after surgical treatment for rectal cancer. </span><b><span style="font-family:Verdana;">Me</span></b></span><b><span style="font-family:Verdana;">thods:</span></b> <span style="font-family:Verdana;">A retrospective follow-up study of 442 consecutive, unselected patients</span><span style="font-family:Verdana;"> treated for rectal cancer at a tertiary centre from 1990 until 2000 and followed for 17 </span><span style="font-family:Verdana;">years or until death. Predictors for death were assessed by Cox regression</span><span style="font-family:Verdana;"> analysis. The cause of death was obtained from the Norwegian Cause of Death Registry. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">254 men and 188 women with a median age of 71 years (21 - 95 years) were resected for rectal cancer with low anterior resection (n = 266), abdominoperineal resection (n = 125), Hartmann’s procedure (n = 19) or diverting stoma only (n = 32). Median follow-up was 5 years (0 - 17 years). The relative five-year survival rates for stages I, II, III and IV was 83.9%, 65.2%, 41.1% and 9.3%, respectively. The proportion of deaths due to recurrence from colorectal cancer in stages I, II, III and IV was 23.5%, 55.8%, 72.3% and 98.0%, respectively. Heart, lung and cerebrovascular disease and other malignancies were the cause of death in the other patients. Higher age, </span><span style="font-family:Verdana;">abdominoperineal resection compared to low anterior resection, lack of</span><span style="font-family:Verdana;"> lymph node dissection compared to total mesorectal excision (TME), postoperative reoperations, TNM stages II and III compared to stage I and residual tumours after surgery were all significant independent predictors of reduced survival in the adjusted Cox regression model. </span><b><span style="font-family:Verdana;">Conclusions: </span></b><span style="font-family:Verdana;">Age, tu</span><span style="font-family:Verdana;">mour stage, type of surgery, lymph node dissection, residual tumour after</span><span style="font-family:Verdana;"> surgery and reoperations are predictors for survival after surgery for rectal cancer. In the patients who died, the cause of death was due to a condition other than colorectal cancer recurrence in 32.3% of the patients. The five-year relative survival rate was related to tumour stage.</span></span></span></span> 展开更多
关键词 Rectal cancer PREDICTORS SURVIVAL RECURRENCE REOPERATION COMPLICATION Cause of death
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Use of programmed cell death protein ligand 1 assay to predict the outcomes of non-small cell lung cancer patients treated with immune checkpoint inhibitors 被引量:9
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作者 Carmelo Tibaldi Alice Lunghi Editta Baldini 《World Journal of Clinical Oncology》 CAS 2017年第4期320-328,共9页
The recent discovery of immune checkpoints inhibitors, especially anti-programmed cell death protein 1(PD-1)and anti-programmed cell death protein ligand 1(PD-L1) monoclonal antibodies, has opened new scenarios in the... The recent discovery of immune checkpoints inhibitors, especially anti-programmed cell death protein 1(PD-1)and anti-programmed cell death protein ligand 1(PD-L1) monoclonal antibodies, has opened new scenarios in the management of non-small cell lung cancer(NSCLC) and this new class of drugs has achieved a rapid development in the treatment of this disease. However, considering the costs of these drugs and the fact that only a subset of patients experience long-term disease control, the identification of predictive biomarkers for the selection of candidates suitable for treatment has become a priority. The research focused mainly on the expression of the PD-L1 receptor on both tumor cells and/or immune infiltrates determined by immunohistochemistry(IHC). However, different checkpoint inhibitors were tested, different IHC assays were used, different targets were considered(tumor cells, immune infiltrates or both) and different expression thresholds were employed in clinical trials. In some trials the assay was used prospectively to select the patients, while in other trials it was evaluated retrospectively. Some confusion emerges, which makes it difficult to easily compare the literature data and to translate them in practice management. This mini-review shows the possibilities and pitfalls of the PD-L1 expression to predict the activity and efficacy of anti PD1/PD-L1 monoclonal antibodies in the treatment of NSCLC. 展开更多
关键词 Predictive biomarkers Immunotherapy CHECKPOINT INHIBITORS Programmed CELL death protein ligand 1 NON-SMALL CELL lung cancer
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信迪利单抗注射液联合注射用紫杉醇(白蛋白结合型)治疗复发或难治性ES-SCLC的临床研究
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作者 李卉惠 李广欣 +4 位作者 赵鹏飞 林海珊 赵磊 俞静 张颖 《中国医院用药评价与分析》 2024年第8期901-904,909,共5页
目的:评估信迪利单抗注射液联合注射用紫杉醇(白蛋白结合型)在复发或难治性广泛期(ES)小细胞肺癌(SCLC)患者二线治疗中的疗效和安全性。方法:选择2022年1月至2023年1月首都医科大学附属北京友谊医院收治的一线应用依托泊苷/铂类药物化... 目的:评估信迪利单抗注射液联合注射用紫杉醇(白蛋白结合型)在复发或难治性广泛期(ES)小细胞肺癌(SCLC)患者二线治疗中的疗效和安全性。方法:选择2022年1月至2023年1月首都医科大学附属北京友谊医院收治的一线应用依托泊苷/铂类药物化疗后进展的ES-SCLC患者74例,根据随机数字表法分为研究组38例和对照组36例。研究组患者给予信迪利单抗注射液联合注射用紫杉醇(白蛋白结合型)治疗,对照组患者给予注射用盐酸托泊替康治疗。观察两组患者的客观缓解率(ORR)、疾病控制率(DCR)、无进展生存期(PFS)、总生存期(OS)及不良反应。结果:研究组、对照组患者的ORR分别为26.3%(10/38)、13.9%(5/36)(P=0.035),DCR分别为84.2%(32/38)、72.2%(26/36)(P=0.042),中位PFS分别为6.00、3.45个月(P=0.013),中位OS分别为10.30、8.75个月(P=0.007),上述差异均有统计学意义。两组患者不良反应发生率的差异无统计学意义(P>0.05)。结论:与注射用盐酸托泊替康相比,信迪利单抗注射液联合紫杉醇(白蛋白结合型)延长了复发或难治性ES-SCLC患者的生存期,且不良反应可耐受。 展开更多
关键词 信迪利单抗 紫杉醇 安全性 有效性 小细胞肺癌 程序性死亡受体配体1
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铜调节的细胞死亡相关基因与前列腺癌关系分析 被引量:1
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作者 李伟 程丰 +1 位作者 朱俊雷 王锁刚 《现代泌尿外科杂志》 2024年第1期46-50,68,共6页
目的基于美国癌症肿瘤基因图谱(the cancer genome atlas,TCGA)数据库分析铜调节的细胞死亡相关基因与前列腺癌患者预后和免疫细胞浸润的关系。方法从TCGA数据库下载所有前列腺癌患者的基因数据,其中包括前列腺癌组织501例,正常组织52... 目的基于美国癌症肿瘤基因图谱(the cancer genome atlas,TCGA)数据库分析铜调节的细胞死亡相关基因与前列腺癌患者预后和免疫细胞浸润的关系。方法从TCGA数据库下载所有前列腺癌患者的基因数据,其中包括前列腺癌组织501例,正常组织52例。运用R软件提取前列腺癌患者中铜调节的细胞死亡相关基因表达矩阵,进行差异分析、多因素回归分析筛选出预后基因,对预后基因进行生存分析,同时探讨预后相关基因与免疫细胞之间的相关性。结果甘氨酸裂解系统蛋白H(GCSH)与前列腺癌患者的预后显著相关,同时发现其与前列腺癌患者中的树突细胞、CD8^(+)T细胞、浆细胞也显著相关(P<0.05)。结论GCSH基因在前列腺癌的发生、发展中起重要作用,有望成为前列腺癌预后的标志物。 展开更多
关键词 前列腺癌 铜调节的细胞死亡 肿瘤微环境 甘氨酸裂解系统蛋白H 美国癌症肿瘤基因图谱数据库 标志物
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互动式死亡焦虑舒缓工作坊在肿瘤医院护生死亡教育中的应用
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作者 李惠艳 张丽敏 +1 位作者 安旭姝 周春鹤 《中国继续医学教育》 2024年第3期125-128,共4页
目的探析肿瘤医院护生死亡教育中应用互动式死亡焦虑舒缓工作坊的价值。方法在2021年2月—2022年12月哈尔滨医科大学附属肿瘤医院护生中选取42名配合研究,依据随机数字表法分2组,各21名。对照组以传统教学方法为主,观察组以互动式死亡... 目的探析肿瘤医院护生死亡教育中应用互动式死亡焦虑舒缓工作坊的价值。方法在2021年2月—2022年12月哈尔滨医科大学附属肿瘤医院护生中选取42名配合研究,依据随机数字表法分2组,各21名。对照组以传统教学方法为主,观察组以互动式死亡焦虑舒缓工作坊教学方式实施死亡教育。比较2组死亡焦虑评分、教学满意度、对死亡态度评分。结果干预前2组护生的死亡焦虑评分比较差异无统计学意义(P>0.05),干预后观察组护生的死亡焦虑评分[(6.12±1.35)分]较对照组低,护生对教学满意度95.24%高于对照组66.67%,观察组死亡逃避[(12.32±2.12)分]、死亡恐惧[(18.35±2.12)分]、逃离接受的评分[(12.32±1.23)分]低于对照组,自然接受[(19.98±1.35)分]、趋近接受[(28.35±1.3)分]高于对照组,差异均有统计学意义(P<0.05)。结论互动式死亡焦虑舒缓工作坊应用在肿瘤医院护生死亡教育中的效果明显,可提升护生的参与积极性,改善护生对死亡的焦虑情绪,增强护生面对死亡的态度,其满意此种教学方法,临床上可借鉴。 展开更多
关键词 互动式 死亡焦虑舒缓工作坊 肿瘤医院护生 死亡教育 死亡焦虑评分 死亡态度评分
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