Introduction:Bladder cancer(BC)has a high incidence and mortality rate worldwide.Suppressor anaphasepromoting complex domain containing 2(SAPCDC2)is over-expressed in a variety of tumors.Objectives:This study investigated the effects of SAPCD2 knockdown on BC cells.Methods:T24 and UMUC3 cell models and the xenografted BC tumor model with SAPCD2 knockdown were established to observe the malignant phenotype of BC cells by cell counting kit-8 assay,colony formation test,wound healing,and Transwell assay,mRNA and proteins expressions were measured with quantitative real-time polymerase chain reaction,western blotting,and tissue immunohistochemistry.Lithium chloride agonist on the Wnt/β-catenin pathway was used to clarify the molecular mechanism of SAPCD2 knockdown.Results:SAPCD2 expression was significantly higher in BC cell lines than in SVHUC-1 cells.SAPCD2 knockdown inhibited viability and cloning,hindered the G0/G1 phase of the cell cycle in UMUC3 and T24 cells,and decreased the migration and invasiveness of BC cells.SAPCD2 knockdown inhibited expression levels of cyclin D1,cyclin B1,N-cadherin,vimentin,Snail,β-catenin,c-Myc,and cyclin-dependent kinase 4,while the P21 and E-cadherin were raised by SAPCD2 knockdown.Furthermore,lithium chloride reversed the effects of SAPCD2 knockdown on the expression levels of the above proteins in UMUC3 and T24 cells.In vivo,SAPCD2 knockdown inhibited the volume,weight,and expression of Ki-67 andβ-catenin in tumors and increased the E-cadherin expression.Conclusion:SAPCD2 knockdown inhibits the malignant phenotype of BC via a pathway involvingβ-catenin.
CHONG SHENJIAJUN YANYU RENZHIRONG ZHUXIAOLONG ZHANGSHUIXIANG TAO
It has been shown that the high expression of human epididymis protein 4(HE4)in most lung cancers is related to the poor prognosis of patients,but the mechanism of pathological transformation of HE4 in lung cancer is still unclear.The current study is expected to clarify the function and mechanism of HE4 in the occurrence and metastasis of lung adenocarcinoma(LUAD).Immunoblotting evaluated HE4 expression in lung cancer cell lines and biopsies,and through analysis of The Cancer Genome Atlas(TCGA)dataset.Frequent HE4 overexpression was demonstrated in LUAD,but not in lung squamous cell carcinoma(LUSC),indicating that HE4 can serve as a biomarker to distinguish between LUAD and LUSC.HE4 knockdown significantly inhibited cell growth,colony formation,wound healing,and invasion,and blocked the G1-phase of the cell cycle in LUAD cell lines through inactivation of the EGFR signaling downstream including PI3K/AKT/mTOR and RAF/MAPK pathways.The first-line EGFR inhibitor gefitinib and HE4 shRNA had no synergistic inhibitory effect on the growth of lung adenocarcinoma cells,while the third-line EGFR inhibitor osimertinib showed additive anti-proliferative effects.Moreover,we provided evidence that HE4 regulated EGFR expression by transcription regulation and protein interaction in LUAD.Our findings suggest that HE4 positively modulates the EGFR signaling pathway to promote growth and invasiveness in LUAD and highlight that targeting HE4 could be a novel strategy for LUAD treatment.
YUE ZHANGWENYU YANGXIAOWANG HANYUE QIAOHAITAO WANGTING CHENTIANYING LIWEN-BIN OU
To editor:Fetomaternal hemorrhage(FMH)refers to the fetal blood transfection into the maternal circulation,usually involving a bleeding volume exceeding 30 ml.This phenomenon can promptly trigger a sinusoidal fetal heart rate pattern,posing a significant risk of life-threatening fetal anemia and even mortality1,2 Upon suspicion of FMH,immediate intervention is essential to prevent neonatal death,often leading to the insufficient recognition of placental examination in many published reports.However,an increasing number of FMH case reports have underscored the potential subsequent risk of choriocarcinoma.
目的探讨CT影像学定量和定性特征和肺磨玻璃结节浸润程度的相关性,为磨玻璃结节患者术前规划提供参考价值。方法纳入2020年9月—2022年7月期间在昆明医科大学第三附属医院行手术治疗术后确诊为肺腺癌的磨玻璃结节患者的临床资料。根据病理诊断结果将其分为两组,非浸润腺癌组(包括原位腺癌和微浸润腺癌)和浸润性腺癌组。收集其影像学特征,并进行单因素logistic回归分析,将差异有统计学意义的指标纳入多因素logistic回归分析,最终确定浸润性腺癌发生风险的独立预测因素,建立预测模型。根据约登指数计算出灵敏度和特异度。使用曲线下面积(area under the curve,AUC)值、校准曲线和决策分析曲线评价模型的区分度、校准度和临床实用价值。结果555例纳入研究。非浸润腺癌组310例,其中女235例、男75例,年龄49(43,58)岁;浸润性腺癌组245例,其中女163例、男82例,年龄53(46,61)岁。二元logistic回归分析显示,肿瘤最大径[OR=4.707,95%CI(2.060,10.758)]、实性成分占比(consolidation tumor ratio,CTR)[OR=1.027,95%CI(1.011,1.043)]、最大CT值[OR=1.025,95%CI(1.004,1.047)]、平均CT值[OR=1.035,95%CI(1.008,1.063)]、毛刺征[OR=2.055,95%CI(1.148,3.679)]、血管集束征[OR=2.508,95%CI(1.345,4.676)]是浸润性腺癌发生的独立危险因素(P<0.05)。基于上述独立预测因素构建浸润性腺癌发病风险的预测模型。模型预测公式为Logit(P)=–1.293+1.549×肿瘤最大径+0.026×CTR+0.025×最大CT值+0.034×平均CT值+0.72×毛刺征+0.919×血管集束征。模型AUC值为0.910[95%CI(0.885,0.934)],说明模型预测浸润性腺癌具有良好的区分度,校准曲线显示预测模型具有良好的校准度,决策分析曲线显示模型具有良好的临床实用性。结论联合CT定量和定性特征的预测模型对磨玻璃结节侵袭性具有良好的预测能力。其预测效能高于任意单一指标。
Globally,marine bioinvasions threaten marine ecosystem structure and function,with the Mediterranean Sea being one of the most affected regions.Such invasions are expected to increase due to climate change.We conducted a risk screening of marine organisms(37 fishes,38 invertebrates,and 9 plants),both extant and‘horizon’(i.e.,not present in the area but likely to enter it).Based on expert knowledge for the Eastern Adriatic Sea coasts of Slovenia,Croatia,and Montenegro,screenings were conducted under both current and predicted climate conditions indicating with an increase in sea surface temperature and salinity of the Adriatic Sea together with changes in precipitation regime.Our aims were to:(1)identify non-native extant and horizon marine species that may pose threats to native biodiversity and(2)evaluate the risk of invasiveness of the selected species under current and predicted climate conditions.Of the 84 species screened,there was an increase in those ranked as‘high risk’from 33(39.3%)under current climate conditions and to 47(56.0%)under global warming scenarios.For those ranked as‘very high’risk,the increase was from 6(7.1%)to 21(25.0%).Amongst the screened species,the already established high-risk species Pacific oyster Magallana gigas and Atlantic blue crab Callinectes sapidus represent a threat to ecosystem services.Given the under-representation of marine species in the current European Union List,the species we have ranked as high to very high risk should be included.