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[Fusobacterium nucleatum upregulates ABCG2 by activating the E-cadherin/β-catenin signaling pathway to promote oxaliplatin resistance in colorectal cancer]. [核梭杆菌通过激活E-cadherin/β-catenin信号通路上调ABCG2,促进结直肠癌患者奥沙利铂耐药]。
Q3 Medicine Pub Date : 2025-04-23 DOI: 10.3760/cma.j.cn112152-20240719-00297
F Q Xu, B W Li, Y Liu, Y W Wei

Objective: To investigate whether F.nucleatum affects the chemotherapy resistance of colorectal cancer by regulating ABC subfamily G subtype 2 (ABCG2), in view of the fact that the correlation between the two has not been reported. Methods: Oxaliplatin was used to interfere with colorectal cancer cells and co-cultured with F.nucleatum to establish a chemotherapy-induced model of microbial infection. Calcein AM/PI cell staining, trypan blue staining, and cell counting kit 8 (CCK-8) method were used to detect cell activity. Real-time fluorescence quantitative polymerase chain reaction and western blot were used to detect ABCG2 mRNA and protein expression levels in colorectal cancer cells. The target gene was knocked down by constructing shRNA plasmids. The HCT-116 cell F.nucleatum infection model was constructed and transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analyses were performed to determine the differential gene expression enrichment pathways. Genistein (GST) was used as an E-cadherin blocker, and triclabendazole sulfoxide (TCBZSO) was used as an ABCG2 blocker. Immunofluorescence was used to detect E-cadherin and β-catenin protein expressions and intracellular localization levels. The subcutaneous xenograft model of nude mice was constructed in vivo, and the expression level of ABCG2 protein in tissues was detected by immunohistochemical staining. Results: CCK-8 results showed that F. nucleatum+oxaliplatin group [HT-29, (92.26±1.66)%; HCT-116, (82.13±1.84)%] cell relative survival rate was higher than that of oxaliplatin group [HT-29, (79.64±3.72)%; HCT-116, (67.56±2.96)%; P<0.001]. The relative survival rate of oxaliplatin and F. nucleatum co-culture group with ABCG2-knockdown HCT-116 cells [(61.44±1.48)%] was lower than that of F. nucleatum and oxaliplatin co-cultured with HCT-116 cells [(69.29±4.45)%, P=0.015]. GO enrichment analysis showed that HCT-116 cells co-cultured with F.nucleatum were significantly enriched in "β-catenin binding", "cadherin binding" and "regulation of Wnt signaling pathway". RT-qPCR results showed that the relative expression of ABCG2 mRNA in F.nucleatum + genistein group was significantly lower than that in F.nucleatum group (P<0.001). The results in vivo showed that the tumor weight in the F.n+L-OHP+TCBZSO group [(0.12±0.02)g] was lower than that in the F.n+L-OHP group [(0.33±0.05)g, P<0.001]. Immunohistochemistry suggested that the promotion of ABCG2 protein expression by F. nucleatum was blocked after TCBZSO intervention. Conclusion: F. nucleatum up-regulates ABCG2 expression through E-cadherin/β-catenin signaling pathway to promote colorectal cancer resistance to oxaliplatin.

目的:鉴于未见相关报道,探讨核梭菌是否通过调节ABC亚家族G亚型2 (ABCG2)影响结直肠癌化疗耐药。方法:采用奥沙利铂对结直肠癌细胞进行干扰,并与具核梭菌共培养,建立化疗诱导的微生物感染模型。采用钙黄蛋白AM/PI细胞染色、台盼蓝染色、细胞计数试剂盒8 (CCK-8)法检测细胞活性。采用实时荧光定量聚合酶链反应和western blot检测结直肠癌细胞中ABCG2 mRNA和蛋白的表达水平。通过构建shRNA质粒敲除靶基因。构建HCT-116细胞核仁梭菌感染模型,进行转录组测序、京都基因基因组百科全书(KEGG)和基因本体(GO)分析,确定差异基因表达富集途径。用染料木黄酮(GST)作为E-cadherin阻滞剂,用三氯咪唑亚砜(TCBZSO)作为ABCG2阻滞剂。免疫荧光法检测E-cadherin和β-catenin蛋白表达及细胞内定位水平。在体内构建裸鼠皮下异种移植瘤模型,免疫组化染色检测组织中ABCG2蛋白的表达水平。结果:CCK-8结果显示,核仁梭菌+奥沙利铂组[HT-29,(92.26±1.66)%;HCT-116,(82.13±1.84)%]细胞相对存活率高于奥沙利铂组[HT-29,(79.64±3.72)%;hct - 116(67.56±2.96)%;P < 0.001)。abcg2敲除HCT-116细胞的奥沙利铂与具核梭菌共培养组的相对存活率[(61.44±1.48)%]低于具核梭菌与奥沙利铂共培养HCT-116细胞组[(69.29±4.45)%,P=0.015]。GO富集分析显示,与F.nucleatum共培养的HCT-116细胞“β-catenin结合”、“cadherin结合”和“Wnt信号通路调控”显著富集。RT-qPCR结果显示,ABCG2 mRNA的相对表达量在核桃仁+染料木素组显著低于核桃仁组(P<0.001)。体内实验结果显示,F.n+L-OHP+TCBZSO组肿瘤重量[(0.12±0.02)g]低于F.n+L-OHP组[(0.33±0.05)g, P<0.001]。免疫组化结果显示,TCBZSO干预后,核仁梭菌对ABCG2蛋白表达的促进作用被阻断。结论:核梭菌通过E-cadherin/β-catenin信号通路上调ABCG2表达,促进结直肠癌对奥沙利铂的耐药。
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引用次数: 0
[Epidemiology and survival analysis of nasopharynx cancer in Guangdong Province from 2011 to 2019]. 2011 - 2019年广东省鼻咽癌流行病学及生存分析
Q3 Medicine Pub Date : 2025-04-23 DOI: 10.3760/cma.j.cn112152-20240110-00020
Y Liao, X R Song, L F Lin, Y Wang, Y J Xu, B F Han, M K Liu, D Q Chen, D J Zhao, X J Xu, R L Meng, W W Wei

Objective: To analyze the epidemiological characteristics and survival rate of nasopharynx cancer (NPC) in Guangdong Province from 2011 to 2019. Methods: Based on the cancer registry data of Guangdong Province from 2011 to 2019, the crude rate, age-standardized rate (the standard population was the fifth Chinese national census of 2000) and age-specific rate of incidence and mortality of NPC were calculated, and the regional distribution characteristics were also explored. The average annual percentage change (AAPC) of the incidence and mortality rates were analyzed by using Joinpoint regression model. The observed survival rate was estimated by period survival method, and the expected survival rate was calculated by Ederer Ⅱ method. Results: The crude incidence rate and age standardized incidence rate of NPC showed a decreasing trend, and the AAPC was -1.9% and -2.1%, respectively (P<0.05). The crude mortality rate and age standardized mortality rate of NPC also showed a decreasing trend, and the AAPC was -4.8% and -4.6%, respectively (P<0.05). The incidence and mortality rates are both higher in men than those in women during the nine years. The age-specific incidence rate of NPC reached its peak in the 50-64 years old age group, and the mortality rate reached its peak in the 65-74 years old age group in Guangdong province. In 2019, the age-standardized incidence rate of NPC was 9.49/100 000 (13.89/100 000 in men and 5.19/100 000 in women). The incidence and mortality of NPC varied greatly among different areas, and the areas with highest incidence and mortality rate were both in Zhaoqing. In 2020, the five-year observed survival rate of NPC in Guangdong Province was 67.2%, the 5-year relative survival rate was 75.3% and the 5-year standardized relative survival rate was 68.9%. Conclusions: Both the incidence and mortality rates of NPC in Guangdong province show decreasing trend, and the decreasing level of the mortality rate is higher than that of the incidence rate, but the two rates are still at high levels. The prevention and control work should focus on male, middle-aged and elderly population and Zhaoqing, Zhongshan, Foshan areas.

目的:分析广东省2011 - 2019年鼻咽癌(NPC)的流行病学特征及生存率。方法:基于广东省2011 - 2019年肿瘤登记数据,计算鼻咽癌粗发病率、年龄标准化率(标准人口为2000年第五次全国人口普查)和年龄分发病率、死亡率,并探讨其区域分布特征。采用Joinpoint回归模型分析发病率和死亡率的年均百分率变化(AAPC)。观察生存率采用周期生存法估算,预期生存率采用EdererⅡ法计算。结果:鼻咽癌粗发病率和年龄标准化发病率呈下降趋势,AAPC分别为-1.9%和-2.1% (P<0.05)。鼻咽癌粗死亡率和年龄标准化死亡率也呈下降趋势,AAPC分别为-4.8%和-4.6% (P<0.05)。在这9年中,男性的发病率和死亡率都高于女性。广东省鼻咽癌的年龄特异性发病率在50 ~ 64岁年龄组最高,死亡率在65 ~ 74岁年龄组最高。2019年鼻咽癌年龄标准化发病率为9.49/10万(男性13.89/10万,女性5.19/10万)。不同地区鼻咽癌的发病率和死亡率差异较大,发病率和死亡率最高的地区均在肇庆。2020年广东省鼻咽癌5年观察生存率为67.2%,5年相对生存率为75.3%,5年标准化相对生存率为68.9%。结论:广东省鼻咽癌发病率和死亡率均呈下降趋势,死亡率下降水平高于发病率下降水平,但两者仍处于较高水平。防控工作以男性、中老年人群和肇庆、中山、佛山地区为重点。
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引用次数: 0
[Clinical practice guideline on anaplastic lymphoma kinase-tyrosine kinase inhibitors for non-small cell lung cancer (2025 edition)]. [非小细胞肺癌间变性淋巴瘤激酶-酪氨酸激酶抑制剂临床实践指南(2025年版)]。
Q3 Medicine Pub Date : 2025-04-23 DOI: 10.3760/cma.j.cn112152-20241130-00546

Anaplastic lymphoma kinase (ALK) fusion represents one of pivotal driver genes within the realm of non-small cell lung cancer (NSCLC). ALK-tyrosine kinase inhibitors (ALK-TKIs) have demonstrated remarkable therapeutic efficacy for patients afflicted with ALK-positive NSCLC. As of December 31, 2024, eight ALK-TKIs, including crizotinib, ceritinib, alectinib, ensartinib, brigatinib, lorlatinib, iruplinalkib, and invonalkib have garnered approval from the China National Medical Products Administration (NMPA) (Ranking according to the approval time for marketing by NMPA), providing targeted treatment agents for ALK-positive NSCLC patients. To standardize the application of ALK-TKIs, The Chinese Association for Clinical Oncologists and the Medical Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care has organized experts to compile the "Clinical practice guideline on anaplastic lymphoma kinase-tyrosine kinase inhibitors for non-small cell lung cancer (2025 edition)". This guideline provides recommendations in four aspects, encompassing ALK fusion testing, ALK-TKI targeted therapy, ALK-TKI adverse events management, and patient post-treatment follow-up, thus serving as a valuable reference for the standardized treatment of Chinese ALK fusion-positive NSCLC.

间变性淋巴瘤激酶(ALK)融合是非小细胞肺癌(NSCLC)领域的关键驱动基因之一。alk -酪氨酸激酶抑制剂(ALK-TKIs)对alk阳性非小细胞肺癌的治疗效果显著。截至2024年12月31日,克唑替尼、塞瑞替尼、阿勒替尼、恩沙替尼、布加替尼、洛拉替尼、伊鲁普那基布、invonalkib等8个ALK-TKIs已获得中国国家药品监督管理局(NMPA)批准(按NMPA批准上市时间排序),为alk阳性NSCLC患者提供靶向治疗药物。为规范ALK-TKIs的应用,中国临床肿瘤学会、中国医疗卫生国际交流促进会肿瘤内科分会组织专家编写了《非小细胞肺癌间变性淋巴瘤激酶-酪氨酸激酶抑制剂临床应用指南(2025版)》。本指南从ALK融合检测、ALK- tki靶向治疗、ALK- tki不良事件管理、患者治疗后随访四个方面提出建议,为中国ALK融合阳性NSCLC的规范化治疗提供了有价值的参考。
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引用次数: 0
[Epidemiological characteristics of cancer mortality in the elderly in Qidong, 1972-2021]. 1972-2021年启东市老年人癌症死亡率流行病学特征分析
Q3 Medicine Pub Date : 2025-03-23 DOI: 10.3760/cma.j.cn112152-20240529-00224
Y S Chen, J Wang, X H Tang, J Zhu

Objective: To analysis the prevalence characteristics of cancer mortality among the elderly in Qidong City, Jiangsu Province, from 1972 to 2021, and to provide scientific basis for the development of precise prevention and control strategies for cancer in the elderly. Methods: Data of cancers were obtained from Qidong Cancer Registry, a descriptive study method was used to calculate the crude mortality rate (CMR) of cancer among the elderly (≥60 years old). The China age-standardized rate (ASR-C) was calculated using the age structure of the Chinese population in 2000, and world age-standardized rate (ASR-W) was calculated using Segi's world standard population. Joinpoint regression analysis was performed using Joinpoint 4.9.1.0 software to calculate the annual percentage change (APC) and average annual percentage change (AAPC) of mortality. Results: From 1972 to 2021, there were 74 723 cancer deaths in the elderly in Qidong, with CMR of 752.08/105, ASR-C of 666.03/105 (994.22/105 for males and 470.29/105 for females) and ASR-W of 681.11/105. The ASR-C showed little fluctuation before 2000, increased rapidly from 2001 to 2011, and then decreased from 2011 to 2021. From 2017 to 2021, the CMR was 791.01/105, the ASR-C was 689.80/105 (956.77/105 for males and 469.98/105 for females), and the ASR-W was 657.53 /105. The CMR for the 60-64, 65-69, 70-74, 75-79, and 80+ age groups from 2012 to 2021 were 385.42/105 505.51/105, 721.64/105, 1 213.28/105, and 1 705.32/105, respectively. The CMR of elderly under 75 years old were lower from 2012 to 2021 than in other periods, while those of elderly people aged more than 75 years were higher from 2012 to 2021 than in other periods. The AAPC for ASR-C of all cancers over the 50 years was 0.22%, with APC of -1.59% in 2008-2021 (both P<0.05). Over the 50 years, the top five cancers in terms of mortality were lung cancer, gastric cancer, liver cancer, colorectal cancer, and esophageal cancer. Their AAPCs of ASR-C were 1.61%, -2.36%, -0.10%, 1.44%, and -2.03%, respectively. The increasing trends of mortality rates for lung cancer and colorectal cancer and the decreasing trends for gastric cancer and esophageal cancer were statistically significant (P<0.05). Conclusions: The mortality of cancers among elderly is at a high level in Qidong. The overall mortality since 2008 have shown a decreasing trend, and the prevention and control of some cancers have been effective.

目的:分析江苏省启东市1972 - 2021年老年人癌症死亡率流行特征,为制定精准的老年人癌症防治策略提供科学依据。方法:癌症数据来自启东市癌症登记处,采用描述性研究方法计算老年人(≥60岁)癌症的粗死亡率(CMR)。采用2000年中国人口年龄结构计算中国年龄标准化率(ASR-C),采用Segi世界标准人口计算世界年龄标准化率(ASR-W)。采用Joinpoint 4.9.1.0软件进行Joinpoint回归分析,计算死亡率年变化百分数(APC)和平均年变化百分数(AAPC)。结果1972 - 2021年,启东市老年人癌症死亡74 723例,CMR为752.08/105,ASR-C为666.03/105(男性994.22/105,女性470.29/105),ASR-W为681.11/105。ASR-C在2000年之前波动不大,2001 - 2011年快速上升,2011 - 2021年下降。2017 - 2021年,CMR为791.01/105,ASR-C为689.80/105(男性为956.77/105,女性为469.98/105),ASR-W为657.53 /105。2012 - 2021年60 ~ 64岁、65 ~ 69岁、70 ~ 74岁、75 ~ 79岁和80岁以上年龄组的CMR分别为385.42/105、505.51/105、721.64/105、1 213.28/105和1 705.32/105。2012 - 2021年75岁以下老年人CMR低于其他时期,而2012 - 2021年75岁以上老年人CMR高于其他时期。50年间所有癌症ASR-C的AAPC为0.22%,2008-2021年APC为-1.59% (P均<0.05)。50年来,死亡率排名前五的癌症分别是肺癌、胃癌、肝癌、结直肠癌和食道癌。ASR-C的AAPCs分别为1.61%、-2.36%、-0.10%、1.44%和-2.03%。肺癌、结直肠癌死亡率上升趋势,胃癌、食管癌死亡率下降趋势均有统计学意义(P<0.05)。结论:启东市老年人癌症死亡率较高。2008年以来,中国总体死亡率呈下降趋势,部分癌症防控工作取得成效。
{"title":"[Epidemiological characteristics of cancer mortality in the elderly in Qidong, 1972-2021].","authors":"Y S Chen, J Wang, X H Tang, J Zhu","doi":"10.3760/cma.j.cn112152-20240529-00224","DOIUrl":"10.3760/cma.j.cn112152-20240529-00224","url":null,"abstract":"<p><p><b>Objective:</b> To analysis the prevalence characteristics of cancer mortality among the elderly in Qidong City, Jiangsu Province, from 1972 to 2021, and to provide scientific basis for the development of precise prevention and control strategies for cancer in the elderly. <b>Methods:</b> Data of cancers were obtained from Qidong Cancer Registry, a descriptive study method was used to calculate the crude mortality rate (CMR) of cancer among the elderly (≥60 years old). The China age-standardized rate (ASR-C) was calculated using the age structure of the Chinese population in 2000, and world age-standardized rate (ASR-W) was calculated using Segi's world standard population. Joinpoint regression analysis was performed using Joinpoint 4.9.1.0 software to calculate the annual percentage change (APC) and average annual percentage change (AAPC) of mortality. <b>Results:</b> From 1972 to 2021, there were 74 723 cancer deaths in the elderly in Qidong, with CMR of 752.08/10<sup>5</sup>, ASR-C of 666.03/10<sup>5</sup> (994.22/10<sup>5</sup> for males and 470.29/10<sup>5</sup> for females) and ASR-W of 681.11/10<sup>5</sup>. The ASR-C showed little fluctuation before 2000, increased rapidly from 2001 to 2011, and then decreased from 2011 to 2021. From 2017 to 2021, the CMR was 791.01/10<sup>5</sup>, the ASR-C was 689.80/10<sup>5</sup> (956.77/10<sup>5</sup> for males and 469.98/10<sup>5</sup> for females), and the ASR-W was 657.53 /10<sup>5</sup>. The CMR for the 60-64, 65-69, 70-74, 75-79, and 80+ age groups from 2012 to 2021 were 385.42/10<sup>5</sup> 505.51/10<sup>5</sup>, 721.64/10<sup>5</sup>, 1 213.28/10<sup>5</sup>, and 1 705.32/10<sup>5</sup>, respectively. The CMR of elderly under 75 years old were lower from 2012 to 2021 than in other periods, while those of elderly people aged more than 75 years were higher from 2012 to 2021 than in other periods. The AAPC for ASR-C of all cancers over the 50 years was 0.22%, with APC of -1.59% in 2008-2021 (both <i>P</i><0.05). Over the 50 years, the top five cancers in terms of mortality were lung cancer, gastric cancer, liver cancer, colorectal cancer, and esophageal cancer. Their AAPCs of ASR-C were 1.61%, -2.36%, -0.10%, 1.44%, and -2.03%, respectively. The increasing trends of mortality rates for lung cancer and colorectal cancer and the decreasing trends for gastric cancer and esophageal cancer were statistically significant (<i>P</i><0.05). <b>Conclusions:</b> The mortality of cancers among elderly is at a high level in Qidong. The overall mortality since 2008 have shown a decreasing trend, and the prevention and control of some cancers have been effective.</p>","PeriodicalId":39868,"journal":{"name":"中华肿瘤杂志","volume":"47 3","pages":"237-243"},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Cancer incidence, mortality and trends among elderly in Hebei province, 2011-2020]. 2011-2020年河北省老年人癌症发病率、死亡率及趋势分析
Q3 Medicine Pub Date : 2025-03-23 DOI: 10.3760/cma.j.cn112152-20240110-00019
Y Y Liu, D J Li, S S Wu, S Zhang, Y F Fu, Y T He

Objective: With the aggravation of population aging, the burden of malignant tumors in the elderly population is becoming more and more heavy. This study aims to analyze the incidence and mortality of malignant tumors in the elderly population in Hebei Province in the past decade. Methods: The incidence and mortality data of malignant tumors in people aged ≥60 years old in 38 cancer registration areas in Hebei Province from 2011 to 2020 were collected, and the incidence and mortality were analyzed by gender, urban and rural areas, and age groups. The age standardized rates were calculated using the 2000 Chinese population census and Segi's world population. The trend of incidence and mortality was analyzed using the Joinpoint model and the average annual percent change (AAPC). Results: From 2011 to 2020, 216 200 new cases of malignant tumors were reported in the elderly population in the cancer registration areas of Hebei Province, and 170 700 deaths were reported. The peak ages of incident cases number for males and females were 65-69 years old and 60-64 years old, respectively. The crude incidence rate of malignant tumors in the elderly was 905.42/105, and the crude mortality rate was 714.96/105. In general, the incidence and mortality in rural areas were higher than those in urban areas, and the incidence and mortality in males were higher than those in females. The peak ages of incidence and mortality were 80-84 years old and 85+ years old, respectively. From 2011 to 2020, lung cancer, gastric cancer, esophageal cancer, female breast cancer, and colorectal cancer were the main malignant tumors of incidence rate in the elderly population in Hebei Province, and lung cancer, gastric cancer, liver cancer, esophageal cancer, and colorectal cancer were the main malignant tumors in the mortality rate. From 2011 to 2020, the incidence and mortality of malignant tumors in the elderly population in Hebei Province showed a decreasing trend, and AAPC for the age-standardized incidence and mortality were -4.69% and -5.53%, respectively. The rank of incidence and mortality rate of each cancer had changed, but the top two were still lung cancer and stomach cancer. Conclusions: The incidence and mortality of cancer in the elderly population in Hebei province have decreased, but the burden is still heavy. Lung cancer and stomach cancer are still the focus of prevention and treatment in the elderly population in Hebei province.

目的:随着人口老龄化的加剧,老年人群的恶性肿瘤负担越来越重。本研究旨在分析近十年来河北省老年人群恶性肿瘤的发病率和死亡率。研究方法收集2011-2020年河北省38个肿瘤登记地区≥60岁老年人群恶性肿瘤的发病率和死亡率数据,按性别、城乡、年龄组对发病率和死亡率进行分析。采用 2000 年中国人口普查和 Segi 世界人口计算年龄标准化率。采用 Joinpoint 模型和年均百分比变化(AAPC)分析了发病率和死亡率的趋势。结果显示从 2011 年到 2020 年,河北省肿瘤登记地区老年人口中新发恶性肿瘤病例 216 200 例,死亡 170 700 例。男性和女性发病高峰年龄分别为 65-69 岁和 60-64 岁。老年人恶性肿瘤的粗发病率为 905.42/105,粗死亡率为 714.96/105。总体而言,农村地区的发病率和死亡率高于城市地区,男性的发病率和死亡率高于女性。发病和死亡的高峰年龄分别为 80-84 岁和 85 岁以上。从 2011 年到 2020 年,河北省老年人群恶性肿瘤发病率以肺癌、胃癌、食管癌、女性乳腺癌和结直肠癌为主,死亡率以肺癌、胃癌、肝癌、食管癌和结直肠癌为主。2011-2020年,河北省老年人口恶性肿瘤发病率和死亡率呈下降趋势,年龄标准化发病率和死亡率的AAPC分别为-4.69%和-5.53%。各种癌症的发病率和死亡率的排名发生了变化,但排名前两位的仍然是肺癌和胃癌。结论河北省老年人群癌症发病率和死亡率有所下降,但负担仍然较重。肺癌和胃癌仍是河北省老年人群的防治重点。
{"title":"[Cancer incidence, mortality and trends among elderly in Hebei province, 2011-2020].","authors":"Y Y Liu, D J Li, S S Wu, S Zhang, Y F Fu, Y T He","doi":"10.3760/cma.j.cn112152-20240110-00019","DOIUrl":"10.3760/cma.j.cn112152-20240110-00019","url":null,"abstract":"<p><p><b>Objective:</b> With the aggravation of population aging, the burden of malignant tumors in the elderly population is becoming more and more heavy. This study aims to analyze the incidence and mortality of malignant tumors in the elderly population in Hebei Province in the past decade. <b>Methods:</b> The incidence and mortality data of malignant tumors in people aged ≥60 years old in 38 cancer registration areas in Hebei Province from 2011 to 2020 were collected, and the incidence and mortality were analyzed by gender, urban and rural areas, and age groups. The age standardized rates were calculated using the 2000 Chinese population census and Segi's world population. The trend of incidence and mortality was analyzed using the Joinpoint model and the average annual percent change (AAPC). <b>Results:</b> From 2011 to 2020, 216 200 new cases of malignant tumors were reported in the elderly population in the cancer registration areas of Hebei Province, and 170 700 deaths were reported. The peak ages of incident cases number for males and females were 65-69 years old and 60-64 years old, respectively. The crude incidence rate of malignant tumors in the elderly was 905.42/10<sup>5</sup>, and the crude mortality rate was 714.96/10<sup>5</sup>. In general, the incidence and mortality in rural areas were higher than those in urban areas, and the incidence and mortality in males were higher than those in females. The peak ages of incidence and mortality were 80-84 years old and 85+ years old, respectively. From 2011 to 2020, lung cancer, gastric cancer, esophageal cancer, female breast cancer, and colorectal cancer were the main malignant tumors of incidence rate in the elderly population in Hebei Province, and lung cancer, gastric cancer, liver cancer, esophageal cancer, and colorectal cancer were the main malignant tumors in the mortality rate. From 2011 to 2020, the incidence and mortality of malignant tumors in the elderly population in Hebei Province showed a decreasing trend, and AAPC for the age-standardized incidence and mortality were -4.69% and -5.53%, respectively. The rank of incidence and mortality rate of each cancer had changed, but the top two were still lung cancer and stomach cancer. <b>Conclusions:</b> The incidence and mortality of cancer in the elderly population in Hebei province have decreased, but the burden is still heavy. Lung cancer and stomach cancer are still the focus of prevention and treatment in the elderly population in Hebei province.</p>","PeriodicalId":39868,"journal":{"name":"中华肿瘤杂志","volume":"47 3","pages":"228-236"},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Evolution of grading for solitary fibrous tumors of the central nervous system: a clinical pathological and prognostic analysis]. [中枢神经系统孤立性纤维性肿瘤分级的演变:临床病理和预后分析]。
Q3 Medicine Pub Date : 2025-03-23 DOI: 10.3760/cma.j.cn112152-20240810-00336
X L Li, H Zhang, C C Hu, J F Zhou, M Y Zhuang, X X Fan, L W Hu, Y P Chen, Q Huang, S Zhang, X F Wang

Objective: The 5th edition of the WHO classification of central nervous system (CNS) tumors in 2021 made significant revisions to the nomenclature and grading system of solitary fibrous tumors (SFT). This study aimed to explore the changes in the grading of CNS SFT and its relationship with clinical pathological features and prognosis. Methods: This study retrospectively reviewed the clinical and pathological data of 82 patients with CNS SFT diagnosed at the First Affiliated Hospital of Fujian Medical University from March 2006 to June 2021, reassessed their grading according to the WHO 5th edition CNS tumor classification, and conducted a comprehensive analysis of their histological morphology, immunohistochemical characteristics, and clinical imaging data. Results: The age of the patients ranged from 21 to 83 years, with a median age of 48 years. Follow-up was completed for 82 patients, during which 10 patients died, 24 recurred, and 5 metastasized. MRI imaging showed that SFT exhibited isointense signals on T1-weighted imaging (T1WI) and complex signals on T2-weighted imaging (T2WI), with signal intensity decreasing as the content of collagen fibers increased. According to the 2021 grading criteria, there was a significant change in the grading of SFT, with the number of grade 1 SFT increasing from 10 cases under the 2016 standard to 39 cases, while the number of grade 2 and 3 SFT decreased accordingly. The 2016 grading system was significantly correlated with the overall survival (OS) of patients (P=0.009), while the 2021 grading system did not reach statistical significance. Both grading systems were correlated with histological phenotype, Ki-67 index, mitotic figures, and necrosis (P<0.05). All cases expressed STAT6, and showed varying degrees of expression of vimentin, CD99, BCL-2, and CD34. The staining intensity of type Ⅳ collagen fibers, as analyzed semi-quantitatively, was correlated with the OS of the patients (P=0.017). Conclusions: The new grading system for CNS SFT has undergone significant changes, and its association with OS requires further validation. In-depth study of the content and fine structure of collagen fibers in SFT may have important clinical significance for the prognosis assessment and the formulation of treatment plans for patients. Moreover, quantitative analysis of T2WI signal intensity may provide a new method for preoperative preliminary assessment of the collagen fiber content in SFT.

目的:2021年WHO第五版中枢神经系统(CNS)肿瘤分类对孤立性纤维性肿瘤(SFT)的命名和分级体系进行了重大修订。本研究旨在探讨中枢神经系统SFT分级的变化及其与临床病理特征和预后的关系。方法:回顾性分析2006年3月至2021年6月在福建医科大学第一附属医院诊断的82例中枢神经系统SFT患者的临床和病理资料,根据WHO第5版中枢神经系统肿瘤分类重新评估其分级,并对其组织形态、免疫组织化学特征和临床影像学资料进行综合分析。结果:患者年龄21 ~ 83岁,中位年龄48岁。随访82例,死亡10例,复发24例,转移5例。MRI成像显示SFT在t1加权成像(T1WI)上表现为等信号,在t2加权成像(T2WI)上表现为复杂信号,信号强度随着胶原纤维含量的增加而降低。根据2021年的分级标准,SFT的分级发生了明显变化,一级SFT的数量从2016年标准下的10例增加到39例,而二级和三级SFT的数量相应减少。2016年分级系统与患者总生存期(OS)显著相关(P=0.009),而2021年分级系统未达到统计学意义。两种分级系统均与组织学表型、Ki-67指数、有丝分裂数和坏死相关(P<0.05)。所有病例均表达STAT6, vimentin、CD99、BCL-2、CD34均有不同程度表达。半定量分析Ⅳ型胶原纤维的染色强度与患者的OS相关(P=0.017)。结论:新的中枢神经系统SFT评分体系发生了显著变化,其与OS的相关性有待进一步验证。深入研究SFT中胶原纤维的含量和精细结构,对患者的预后评估和制定治疗方案具有重要的临床意义。此外,定量分析T2WI信号强度可为术前初步评估SFT中胶原纤维含量提供一种新的方法。
{"title":"[Evolution of grading for solitary fibrous tumors of the central nervous system: a clinical pathological and prognostic analysis].","authors":"X L Li, H Zhang, C C Hu, J F Zhou, M Y Zhuang, X X Fan, L W Hu, Y P Chen, Q Huang, S Zhang, X F Wang","doi":"10.3760/cma.j.cn112152-20240810-00336","DOIUrl":"10.3760/cma.j.cn112152-20240810-00336","url":null,"abstract":"<p><p><b>Objective:</b> The 5th edition of the WHO classification of central nervous system (CNS) tumors in 2021 made significant revisions to the nomenclature and grading system of solitary fibrous tumors (SFT). This study aimed to explore the changes in the grading of CNS SFT and its relationship with clinical pathological features and prognosis. <b>Methods:</b> This study retrospectively reviewed the clinical and pathological data of 82 patients with CNS SFT diagnosed at the First Affiliated Hospital of Fujian Medical University from March 2006 to June 2021, reassessed their grading according to the WHO 5th edition CNS tumor classification, and conducted a comprehensive analysis of their histological morphology, immunohistochemical characteristics, and clinical imaging data. <b>Results:</b> The age of the patients ranged from 21 to 83 years, with a median age of 48 years. Follow-up was completed for 82 patients, during which 10 patients died, 24 recurred, and 5 metastasized. MRI imaging showed that SFT exhibited isointense signals on T1-weighted imaging (T1WI) and complex signals on T2-weighted imaging (T2WI), with signal intensity decreasing as the content of collagen fibers increased. According to the 2021 grading criteria, there was a significant change in the grading of SFT, with the number of grade 1 SFT increasing from 10 cases under the 2016 standard to 39 cases, while the number of grade 2 and 3 SFT decreased accordingly. The 2016 grading system was significantly correlated with the overall survival (OS) of patients (<i>P</i>=0.009), while the 2021 grading system did not reach statistical significance. Both grading systems were correlated with histological phenotype, Ki-67 index, mitotic figures, and necrosis (<i>P</i><0.05). All cases expressed STAT6, and showed varying degrees of expression of vimentin, CD99, BCL-2, and CD34. The staining intensity of type Ⅳ collagen fibers, as analyzed semi-quantitatively, was correlated with the OS of the patients (<i>P</i>=0.017). <b>Conclusions:</b> The new grading system for CNS SFT has undergone significant changes, and its association with OS requires further validation. In-depth study of the content and fine structure of collagen fibers in SFT may have important clinical significance for the prognosis assessment and the formulation of treatment plans for patients. Moreover, quantitative analysis of T2WI signal intensity may provide a new method for preoperative preliminary assessment of the collagen fiber content in SFT.</p>","PeriodicalId":39868,"journal":{"name":"中华肿瘤杂志","volume":"47 3","pages":"275-282"},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[The expert consensus on the diagnosis and treatment of skull base and head-neck sarcomas (2024 edition)]. [颅底头颈部肉瘤诊治专家共识(2024年版)]。
Q3 Medicine Pub Date : 2025-03-23 DOI: 10.3760/cma.j.cn112152-20240603-00235

Skull base sarcomas of the head and neck originate from the mesenchymal tissues of the skull base and head and neck region, exhibiting a highly aggressive behavior and can occur at all ages. Skull base sarcomas are rare in adults, with an incidence of less than 1% of head and neck tumors. However, in the pediatric population, the incidence can be as high as 35%. These tumors can arise in various locations, involving soft tissues, bones, or nerves of the skull base, face, and neck. The pathological types of skull base sarcomas are diverse, primarily including liposarcoma, angiosarcoma, leiomyosarcoma, rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, undifferentiated pleomorphic sarcoma. Treatment typically involves a multimodal approach, with surgery being the preferred method. However, the surgical challenges posed by skull base sarcomas and the inconsistent efficacy of radiotherapy and chemotherapy contribute to the overall difficulty in treatment. Currently, there are no established guidelines or consensus for the diagnosis and management of skull base sarcomas in China. In response, Chinese Anti-Cancer Association Cancer Neurology Committee, Chinese Medical Education Association Head and Neck Oncology Professional Committee and Chinese Medical Education Association Oncology Chemotherapy Youth Committee have organized multidisciplinary expert discussions. Based on evidence from clinical research, we have summarized clinical application recommendations in the areas of epidemiology, histopathology, molecular pathology, imaging, surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy, with the aim of providing clinical practice evidence to enhance the treatment of skull base sarcomas and improve patient prognosis and quality of life.

头颈部的颅底肉瘤起源于颅底和头颈部的间充质组织,表现出高度侵袭性,可发生于所有年龄。颅底肉瘤在成人中很少见,发病率不到头颈部肿瘤的1%。然而,在儿科人群中,发病率可高达35%。这些肿瘤可以出现在不同的部位,包括软组织、骨骼或颅底、面部和颈部的神经。颅底肉瘤病理类型多样,主要有脂肪肉瘤、血管肉瘤、平滑肌肉瘤、横纹肌肉瘤、尤文氏肉瘤、骨肉瘤、未分化多形性肉瘤等。治疗通常包括多模式方法,手术是首选方法。然而,颅底肉瘤手术难度大,放化疗效果不一致,导致治疗总体困难。目前,对于颅底肉瘤的诊断和治疗,中国尚无明确的指南或共识。对此,中国抗癌协会肿瘤神经学专业委员会、中华医学教育协会头颈肿瘤专业委员会、中华医学教育协会肿瘤化疗青年专业委员会组织了多学科专家讨论。根据临床研究证据,总结流行病学、组织病理学、分子病理学、影像学、手术、放疗、化疗、靶向治疗、免疫治疗等方面的临床应用建议,以期为加强颅底肉瘤的治疗,改善患者预后和生活质量提供临床实践依据。
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引用次数: 0
[Clinicopathological features of primary pulmonary epithelioid hemangioendothelioma: a study of 7 cases]. 原发性肺上皮样血管内皮瘤7例临床病理特征分析
Q3 Medicine Pub Date : 2025-03-23 DOI: 10.3760/cma.j.cn112152-20240421-00163
W Li, J K Li, X Zheng, L L Chen, Y H Yang

Objective: The clinicopathological features of pulmonary epithelioid hemangioendothelioma (PEHE) were analyzed to provide guidance for clinical practice. Methods: The clinical manifestations, imaging examination, pathological morphology and molecular characteristics, treatment and prognosis of patients with pulmonary epithelioid hemangioendothelioma were retrospectively collected. All cases were admitted to Fujian Medical University Union Hospital from January 2012 to May 2023. Results: Of 7 PEHE cases, 2 underwent tumor biopsy and 5 underwent tumor resection. There were 4 males and 3 females, with a median age of 58 years old. Six cases showed multiple bilateral nodules, and only one case showed a single lesion in the lower left lung lobe. Five patients presented with respiratory symptoms, like cough, sputum, hemoptysis, shortness of breath. There were round-like solid lesions with clear border and homogeneous density on lung CT. Histologically, it showed nodular growth with a distinctive myxohyaline stroma. Necrosis was seen in the center of some cases. Epithelioid tumor cells were arranged in cords, solid pattern or single cells, with abundant eosinophilic cytoplasm and occasional intracytoplasmic vacuoles. The plasmacytoid nucleus were round to oval in shape with obvious nucleoli, minimal pleomorphism and few mitoses. The tumor cells were positive for vascular endothelial markers: CD31 (7/7), CD34 (5/7), ERG (6/6), and Fli-1 (5/6); CKpan was focally positive in 3 cases (3/7), and TFE3 in 2 cases. Ki-67 index ranged from 5% to 10%. Additionally, the tumor cells partially express PD-L1 in two cases. Moreover, lung carcinoma-related gene detection was negative in one case. The TFE3 break-apart probe in two cases did not display a split signal. In terms of treatment, 4 cases were treated with surgery, 1 case was treated with chemotherapy and surgery, and 2 cases were follow-up observation. After the median 34.4 months follow-up time, one was lost to follow-up, six were survived. Their CT scans showed slight enlargement of pulmonary nodules without other organ metastases. Conclusions: PEHE is a rare vascular-derived tumor, which is usually characterized by multiple solid bilateral nodules with slow growth. It tends to lack specific clinical symptoms, and is prone to be misdiagnosed as a metastatic carcinoma. Diagnosis primarily rely on pathology, with the use of an immunohistochemical package being crucial for definitive and differential diagnosis.

目的:分析肺上皮样血管内皮瘤(PEHE)的临床病理特点,为临床提供指导。方法:回顾性收集肺上皮样血管内皮瘤患者的临床表现、影像学检查、病理形态及分子特征、治疗及预后。所有病例均于2012年1月至2023年5月在福建医科大学协和医院住院。结果:7例PEHE患者中2例行肿瘤活检,5例行肿瘤切除术。男4例,女3例,中位年龄58岁。6例表现为双侧多发结节,仅1例表现为左下肺叶单发病灶。5例患者出现咳嗽、咳痰、咯血、呼吸短促等呼吸道症状。肺部CT见圆形实性病灶,边界清晰,密度均匀。组织学上表现为结节状生长,间质粘液透明。部分病例中心可见坏死。上皮样肿瘤细胞呈索状、实状或单细胞排列,胞浆内嗜酸性丰富,偶见胞浆内空泡。浆细胞样核圆形至卵圆形,核仁明显,多形性极少,有丝分裂少。肿瘤细胞血管内皮标志物:CD31(7/7)、CD34(5/7)、ERG(6/6)、fl -1(5/6)阳性;CKpan局灶阳性3例(3/7),TFE3局灶阳性2例。Ki-67指数为5% ~ 10%。此外,2例肿瘤细胞部分表达PD-L1。肺癌相关基因检测阴性1例。在两种情况下,TFE3分离探针没有显示分离信号。治疗方面,手术治疗4例,化疗加手术治疗1例,随访观察2例。中位随访34.4个月后,1例失访,6例存活。CT扫描显示肺结节轻微肿大,无其他器官转移。结论:PEHE是一种罕见的血管源性肿瘤,多表现为双侧多发实性结节,生长缓慢。它往往缺乏特定的临床症状,并容易被误诊为转移性癌。诊断主要依靠病理,使用免疫组织化学包是决定性和鉴别诊断的关键。
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引用次数: 0
[Comparison of clinical outcomes between Ivor-Lewis and Mckeown esophagectomy for middle or lower esophageal cancer]. [Ivor-Lewis食管切除术与Mckeown食管切除术治疗中下段食管癌的临床疗效比较]。
Q3 Medicine Pub Date : 2025-03-23 DOI: 10.3760/cma.j.cn112152-20230713-00010
L G Yuan, Y S Mao

Objective: To compare the short-term and long-term clinical effects of Ivor-Lewis and Mckeown esophagectomy in the treatment of middle or lower thoracic esophageal cancer. Methods: The clinical data of 716 patients with middle and lower thoracic esophageal cancer who underwent radical resection of Ivor Lewis or McKeown esophageal cancer in the Department of Thoracic Surgery, Cancer Hospital, Chinese Academy of Medical Science from March 2015 to October 2018 were analyzed retrospectively, and the perioperative indicators, postoperative complications and survival of the two surgical methods were compared. Results: Among 716 patients, 135 patients underwent Ivor Lewis esophagectomy and 581 patients underwent McKeown esophagectomy. Mckeown group was significantly superior to Ivor Lewis group in terms of total number of lymph node dissection [median number was 27 (19~37) vs 25(18~33)], total number of lymph node dissection stations [median number was 5(4~7) vs 5(4~5)], and number of lymph nodes dissection along recurrent laryngeal nerve [median number was 3 (1~6) vs 0 (0~3), P<0.05]. However, the incidence of recurrent laryngeal nerve palsy in Mckeown group was significantly higher than that in Ivor Lewis group [10.7% (62/581) vs 1.5%(2/135), P<0.001]. There was no significant difference in the 1 -, 3 -, 5-year overall survival between the Ivor Lewis group(91.0%, 70.5%, 52.9%) and the Mckeown group (89.7%, 68.4%, 62.4%, P>0.05), and there was also no significant difference in the 1 -, 3 -, 5-year disease free survival between the Ivor Lewis group(77.0%, 54.1%, 44.0%) and the Mckeown group (78.3%, 59.0%, 52.8%, P>0.05). Conclusions: Ivor Lewis esophagectomy and Mckeown esophagectomy are feasible, safe, good short-term efficacy and similar survival rate for middle and lower thoracic esophageal cancer. Ivor Lewis surgery has lower incidence of recurrent laryngeal nerve palsy. Mckeown operation has more advantages in lymph node dissection, especially in lymph node dissection beside the recurrent laryngeal nerve.

目的:比较Ivor-Lewis食管切除术与Mckeown食管切除术治疗胸椎中下段食管癌的近期和远期临床疗效。方法:回顾性分析2015年3月至2018年10月在中国医学科学院肿瘤医院胸外科行Ivor Lewis或McKeown食管癌根治术的716例胸椎中下段食管癌患者的临床资料,比较两种手术方式的围手术期指标、术后并发症及生存率。结果:716例患者中,Ivor Lewis食管切除术135例,McKeown食管切除术581例。Mckeown组淋巴结清扫总数[中位数为27 (19~37)vs 25(18~33)]、淋巴结清扫总站数[中位数为5(4~7)vs 5(4~5)]、喉返神经淋巴结清扫数[中位数为3 (1~6)vs 0 (0~3), P<0.05]均显著优于Ivor Lewis组。但Mckeown组喉返神经麻痹发生率明显高于Ivor Lewis组[10.7% (62/581)vs 1.5%(2/135), P<0.001]。Ivor Lewis组1、3、5年总生存率(91.0%、70.5%、52.9%)与Mckeown组(89.7%、68.4%、62.4%,P>0.05)比较差异无统计学意义;Ivor Lewis组1、3、5年无病生存率(77.0%、54.1%、44.0%)与Mckeown组(78.3%、59.0%、52.8%,P>0.05)比较差异无统计学意义。结论:Ivor Lewis食管切除术和Mckeown食管切除术治疗中、下段胸段食管癌可行、安全、近期疗效好、生存率相近。Ivor Lewis手术有较低的喉返神经麻痹发生率。Mckeown手术在淋巴结清扫,尤其是喉返神经旁淋巴结清扫方面更有优势。
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引用次数: 0
[MiR-4508 regulates chrysotile asbestos induced inflammation in human bronchial epithelial cells through the PI3K/AKT pathway]. [MiR-4508通过PI3K/AKT通路调控温石棉诱导的人支气管上皮细胞炎症]。
Q3 Medicine Pub Date : 2025-03-23 DOI: 10.3760/cma.j.cn112152-20231116-00315
Y J Wang, L Huang, J R He, X Zhang, T T Huo, F Q Dong, J Yang, J J Deng

Objective: To explore the molecular mechanism of miR-4508 regulating the inflammatory response of human bronchial epithelial cells induced by representative chrysotile asbestos. Methods: The chrysotile asbestos was ground into ultrafine dust using a horizontal planetary instrument, and human bronchial epithelium (16HBE) cells were taken as the object of infection. Cell survival rate was detected by cell counting kit-8 method, cytotoxicity was detected by lactate dehydrogenase (LDH) kit. The released of inflammatory factor IL-6 was detected by electrochemical luminescence. The released inflammatory factor IL-8 was detected by enzyme-linked immunosorbent assay. The expression level of miR-4508 was screened and verified by reverse transcription-quantitative real-time polymerase chain reaction. After 16HBE cells were treated with AKT inhibitor MK2206, the phosphorylation levels of AKT and PTEN were detected by western blot. The expression levels of AKT and PTEN and the contents of IL-6 and IL-8 were detected in miR-4508 overexpression and interference experiments. Results: With the increase of chrysotile asbestos exposure concentration, the cell survival rate decreased in a concentration-dependent manner, and the LDH content gradually increased. The secretion of IL-6 and IL-8 in chrysotile 25, 50 and 75 µg/ml groups were (325.92±8.61) pg/ml, (331.51±4.96) pg/ml, (378.74±13.77) pg/ml, and (94.95±3.11) pg/ml, (357.60±1.80) pg/ml, (537.19±3.11) pg/ml, respectively, while the group with 0 µg/ml chrysotile was (95.85±1.20) pg/ml and (7.81±0.00) pg/ml (P<0.05). In addition, chrysotile asbestos exposure to 16HBE could induce the high expression of miR-4508. After pretreatment with MK2206, the phosphorylation levels of AKT and PTEN were decreased, the contents of IL-6 and IL-8 were significantly decreased, and the expression level of miR-4508 was significantly reduced. Overexpression of miR-4508 significantly increased the expressions of AKT and PTEN, and the contents of IL-6 and IL-8 (P<0.01). After interfering with miR-4508, the expressions of AKT and PTEN were significantly decreased, and the contents of IL-6 and IL-8 were significantly decreased (P<0.01). Conclusions: Chrysotile asbestos can induce the inflammatory response of 16HBE cells and up-regulate the expression level of miR-4508. The up-regulation of miR-4508 promotes the 16HBE inflammatory response induced by chrysotile asbestos through the PI3K/AKT pathway.

目的:探讨miR-4508调控代表性温石棉诱导人支气管上皮细胞炎症反应的分子机制。方法:采用卧式行星仪器将温石棉磨成超细粉尘,取人支气管上皮(16HBE)细胞作为感染对象。采用细胞计数试剂盒-8法检测细胞存活率,乳酸脱氢酶(LDH)试剂盒检测细胞毒性。电化学发光法检测炎症因子IL-6的释放。采用酶联免疫吸附法检测炎症因子IL-8的释放。通过逆转录-实时定量聚合酶链反应筛选并验证miR-4508的表达水平。用AKT抑制剂MK2206处理16HBE细胞后,western blot检测AKT和PTEN的磷酸化水平。通过miR-4508过表达和干扰实验检测AKT、PTEN的表达水平以及IL-6、IL-8的含量。结果:随着温石棉暴露浓度的增加,细胞存活率呈浓度依赖性下降,LDH含量逐渐升高。温石棉25、50、75µg/ml组IL-6、IL-8分泌量分别为(325.92±8.61)pg/ml、(331.51±4.96)pg/ml、(378.74±13.77)pg/ml、(94.95±3.11)pg/ml、(357.60±1.80)pg/ml、(537.19±3.11)pg/ml,而0µg/ml温石棉组IL-6、IL-8分泌量分别为(95.85±1.20)pg/ml、(7.81±0.00)pg/ml (P<0.05)。此外,温石棉暴露于16HBE可诱导miR-4508高表达。MK2206预处理后,AKT、PTEN磷酸化水平降低,IL-6、IL-8含量显著降低,miR-4508表达水平显著降低。过表达miR-4508可显著提高AKT、PTEN的表达及IL-6、IL-8的含量(P<0.01)。干扰miR-4508后,AKT、PTEN表达显著降低,IL-6、IL-8含量显著降低(P<0.01)。结论:温石棉可诱导16HBE细胞的炎症反应,上调miR-4508的表达水平。miR-4508的上调通过PI3K/AKT通路促进温石棉诱导的16HBE炎症反应。
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中华肿瘤杂志
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