PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Inetetamab combined with S-1 and oxaliplatin as first-line treatment for human epidermal growth factor receptor 2-positive gastric cancer

BACKGROUND Patients with human epidermal growth factor receptor 2(HER2)-positive advanced gastric cancer have poor outcomes.Trastuzumab combined with chemotherapy is the first-line standard treatment for HER2-positive advanced gastric cancer.Inetetamab is a novel anti-HER2 drug,and its efficacy and safety in gastric cancer have not yet been reported.AIM To evaluate the efficacy and safety of the S-1 plus oxaliplatin(SOX)regimen combined with inetetamab as a first-line treatment for HER2-positive advanced gastric cancer.METHODS Thirty-eight patients with HER2-positive advanced gastric cancer or gastroeso-phageal junction adenocarcinoma were randomly divided into two groups:One group received inetetamab combined with the SOX regimen,and the other group received trastuzumab combined with the SOX regimen.After 4-6 cycles,patients with stable disease received maintenance therapy.The primary endpoints were progression-free survival(PFS)and overall survival(OS),and the secondary endpoints were the objective response rate,disease control rate,and adverse events(AEs).RESULTS Thirty-seven patients completed the trial,with 18 patients in the inetetamab group and 19 patients in the trastuzumab group.In the inetetamab group,the median PFS was 8.5 months,whereas it was 7.3 months in the trastuzumab group(P=0.046);this difference was significant.The median OS in the inetetamab group vs the trastuzumab group was 15.4 months vs 14.3 months(P=0.33),and the objective response rate was 50%vs 42%(P=0.63),respectively;these differences were not significant.Common AEs included leukopenia,thrombocytopenia,nausea,and vomiting.The incidence rates of grade≥3 AEs were 56%in the inetetamab group and 47%in the trastuzumab group(P=0.63),with no significant difference.CONCLUSION In the first-line treatment of HER2-positive advanced gastric cancer,inetetamab and trastuzumab showed comparable efficacy.The inetetamab group showed superior PFS,and both groups had good safety.

Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer

Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance.Human epidermal growth factor receptor 2(HER2)is one of the most important targets in targeted therapy for gastric cancer.Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer.The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified.However,monoclonal antibodies,due to their large molecular weight,inability to penetrate the blood-brain barrier,and drug resistance,lead to decreased therapeutic efficacy,so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer.Small-molecule tyrosine kinase inhibitors,such as lapatinib and pyrrotinib,have the advantages of small molecular weight,penetrating the blood-brain barrier and high oral bioavailability,and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future.Antibo-drug conjugate,such as T-DM1 and T-DXd,can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing,and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab.Therefore,after more detailed stratification of gastric cancer patients,various gastric cancer drugs targeting HER2 are expected to play a more significant role.

Inetetamab combined with tegafur as second-line treatment for human epidermal growth factor receptor-2-positive gastric cancer: A case report

BACKGROUND Human epidermal growth factor receptor-2(HER-2)plays a vital role in tumor cell proliferation and metastasis.However,the prognosis of HER2-positive gastric cancer is poor.Inetetamab,a novel anti-HER2 targeting drug independently developed in China,exhibits more potent antibody-dependent cell-mediated cytotoxicity than trastuzumab,which is administered as the first-line treatment for HER2-positive gastric cancer in combination with chemotherapy.In this case,the efficacy and safety of inetetamab combined with tegafur was investigated as a second-line treatment for HER2-positive gastric cancer.CASE SUMMARY A 52-year-old male patient with HER2-positive gastric cancer presented with abdominal distension,poor appetite,and fatigue two years after receiving six cycles of oxaliplatin combined with tegafur as first-line treatment after surgery,followed by tegafur monotherapy for six months.The patient was diagnosed with postoperative recurrence of gastric adenocarcinoma.He received 17 cycles of a combination of inetetamab,an innovative domestically developed anti-HER2 monoclonal antibody,and tegafur chemotherapy as the second-line treatment(inetetamab 200 mg on day 1,every 3 wk combined with tegafur twice daily on days 1–14,every 3 wk).Evaluation of the efficacy of the second-line treatment revealed that the patient achieved a stable condition and progression-free survival of 17 months.He tolerated the treatment well without exhibiting any grade 3-4 adverse events.CONCLUSION Inetetamab combined with chemotherapy for the treatment of metastatic HER2-positive gastric cancer demonstrates significant survival benefits and acceptable safety.

Human epidermal growth factor receptor 2 expression level and combined positive score can evaluate efficacy of advanced gastric cancer

BACKGROUND Although treatment options for gastric cancer(GC)continue to advance,the overall prognosis for patients with GC remains poor.At present,the predictors of treatment efficacy remain controversial except for high microsatellite instability.AIM To develop methods to identify groups of patients with GC who would benefit the most from receiving the combination of a programmed cell death protein 1(PD-1)inhibitor and chemotherapy.METHODS We acquired data from 63 patients with human epidermal growth factor receptor 2(HER2)-negative GC with a histological diagnosis of GC at the Cancer Hospital,Chinese Academy of Medical Sciences between November 2020 and October 2022.All of the patients screened received a PD-1 inhibitor combined with chemotherapy as the first-line treatment.RESULTS As of July 1,2023,the objective response rate was 61.9%,and the disease control rate was 96.8%.The median progression-free survival(mPFS)for all patients was 6.3 months.The median overall survival was not achieved.Survival analysis showed that patients with a combined positive score(CPS)≥1 exhibited an extended trend in progression-free survival(PFS)when compared to patients with a CPS of 0 after receiving a PD-1 inhibitor combined with oxaliplatin and tegafur as the first-line treatment.PFS exhibited a trend for prolongation as the expression level of HER2 increased.Based on PFS,we divided patients into two groups:A treatment group with excellent efficacy and a treatment group with poor efficacy.The mPFS of the excellent efficacy group was 8 months,with a mPFS of 9.1 months after excluding a cohort of patients who received interrupted therapy due to surgery.The mPFS was 4.5 months in patients in the group with poor efficacy who did not receive surgery.Using good/poor efficacy as the endpoint of our study,univariate analysis revealed that both CPS score(P=0.004)and HER2 expression level(P=0.015)were both factors that exerted significant influence on the efficacy of treatment the combination of a PD-1 inhibitor and chemotherapy in patients with advanced GC(AGC).Finally,multivariate analysis confirmed that CPS score was a significant influencing factor.CONCLUSION CPS score and HER2 expression both impacted the efficacy of immunotherapy combined with chemotherapy in AGC patients who were non-positive for HER2.

负载骨形态发生蛋白2水凝胶诱导牙髓干细胞的成骨分化

背景:前期研究证明,甲基丙烯酸酐改性明胶/经处理牙本质基质复合水凝胶支架可促进人牙髓干细胞的增殖及分化。水凝胶负载骨形态发生蛋白2被认为是骨修复中有前景的材料。目的:观察负载不同质量浓度骨形态发生蛋白2的甲基丙烯酸酐改性明胶/经处理牙本质基质复合水凝胶对人牙髓干细胞成骨向分化的诱导作用。方法:制备含0,50,100,200μg/mL骨形态发生蛋白2的甲基丙烯酸酐改性明胶/经处理牙本质基质复合水凝胶,分别记为GelMA/TDM、BMP-2(50 ng/mL)GelMA/TDM、BMP-2(100 ng/mL)GelMA/TDM、BMP-2(200 ng/mL)GelMA/TDM,检测复合水凝胶对骨形态发生蛋白2的体外缓释性能。采用改良组织块酶消化法提取人牙髓干细胞,分别接种于4种水凝胶表面,采用CCK-8法检测细胞增殖,DAPI染色检测细胞黏附;对各组水凝胶表面的人牙髓干细胞进行成骨诱导,进行碱性磷酸酶染色、碱性磷酸酶活性检测与茜素红染色,采用RT-PCR法检测相关成骨基因(Runx2、骨形态发生蛋白2、骨桥蛋白、骨钙素、Ⅰ型胶原)表达。结果与结论:①甲基丙烯酸酐改性明胶/经处理牙本质基质复合水凝胶可持续释放骨形态发生蛋白2长达21 d,在第3-6天释放较快,第6天之后释放趋于平稳;②4种水凝胶均可促进人牙髓干细胞的增殖,其中以BMP-2(100 ng/mL)-GelMA/TDM复合水凝胶的作用最明显;相较于GelMA/TDM复合水凝胶,BMP-2-GelMA/TDM复合水凝胶可促进人牙髓干细胞的黏附,其中以BMP-2(200 ng/mL)-GelMA/TDM复合水凝胶的作用最明显;③相较于GelMA/TDM复合水凝胶,BMP-2-GelMA/TDM复合水凝胶可提升碱性磷酸酶活性、钙结节含量与相关成骨基因表达,综合分析显示BMP-2(100 ng/mL)-GelMA/TDM复合水凝胶的作用更明显;④结果表明,BMP-2(100 ng/mL)-GelMA/TDM复合水凝胶促进牙髓干细胞成骨向分化的能力更明显。

HumanLibrary与IC^2高校图书馆服务拓展研究

Human Library与IC2是近年来国内外高校图书馆兴起的两种全新服务模式。该文阐述了Human Library的内涵与外延,介绍了IC2的服务理念。分别从创新服务模式的推广、制度建设和服务仓库的搭建三个方面提出高校图书馆Human Library与IC2服务构建策略。

脓毒症合并2型糖尿病患者单核细胞人白细胞DR抗原的表达水平分析

目的观察2型糖尿病(T2DM)对脓毒症患者外周血单核细胞表面人白细胞DR抗原(HLA-DR)表达水平的影响。方法选取首都医科大学附属北京朝阳医院2021年3月至2022年2月收治的65例脓毒症合并T2DM(脓毒症合并T2DM组)、67例脓毒症未合并T2DM(脓毒症组)、60例T2DM患者(T2DM组)作为研究对象,以45例同期本院健康体检志愿者作为健康对照组。收集受试者性别、年龄、既往史、糖化血红蛋白(HbAlc)、入院时血糖、白细胞计数(WBC)淋巴细胞计数(LYM)超敏C-反应蛋白(hs-CRP)、主要感染部位,入院24h内进行序贯器官衰竭评分(SOFA)。采用流式细胞术检测外周血HLA-DR+CD14^(+)细胞表达百分比及平均荧光强度(MFI);并随访28d,观察T2DM对脓毒症患者28d预后的影响,比较不同预后患者HLA-DR^(+)CD14^(+)水平的差异。结果T2DM组HLA-DR^(+)CD14^(+)细胞表达百分比和MFI均明显低于健康对照组[HLA-DR^(+)CD14^(+)细胞表达百分比:87.72%(76.18%,93.64%)比94.86%(92.91%,95.70%),HLA-DR^(+)CD14^(+)MFI:10.80(8.45,14.45)比12.40(1.45,15.28)],脓毒症合并T2DM组和脓毒症组HLA-DRCD14^(+)细胞表达百分比和MFI均较健康对照组及T2DM组进一步降低[HLA-DR^(+)CD14^(+)细胞表达百分比:70.78%(42.22%,84.73%)、68.95%(44.95%,87.00%)比94.86%(92.91%,95.70%)、87.72%(76.18%,93.64%),HLA-DR^(+)CD14^(+)MFI:5.50(3.81,9.20)、5.29(3.35,9.59)比12.40(1.45,15.28)、10.80(8.45,14.45),均P<0.05]。脓毒症组和毒症合并T2DM组两组HLA-DR^(+)CD14^(+)细胞表达百分比和MFI、SOFA评分、28d病死率比较差异均无统计学意义(均P>0.05)。脓毒症组和脓毒症合并T2DM组死亡者的年龄明显大于生存者[岁:脓毒症组为68(60,74)比61(52,69),脓毒症合并T2DM组为66(64,73)比60(53,68),均P<0.05],SOFA评分明显高于生存者[分:脓毒症组为14(11,16)比8(5,11),脓毒症合并T2DM组为12(9,16)比8(6,11),均P<0.05],死亡组的HLA-DR^(+)CD14^(+)百分比和HLA-DR^(+)CD14^(+)MFI均明显低于生存组[HLA-DR^(+)CD14^(+)细胞表达百分比:脓毒症组为44.94%(28.01%,64.45%)比77.14%(47.41%,88.35%),脓毒症合并T2DM组为40.68%(34.83%,66.64%)比73.46%(58.44%,85.31%);HLA-DR^(+)CD14^(+)MFI:脓毒症组为3.92(2.30,5.44)比7.07(3.39,10.55),脓毒症合并T2DM组为3.90(3.34,6.04)比6.81(4.41,9.32),均P<0.05]。相关性分析显示:T2DM组、脓毒症组和脓毒症合并T2DM组HLA-DR^(+)CD14^(+)细胞表达百分比与hs-CRP均呈负相关(r值分别为-0.448、-0.628、-0.457,均P<0.001),MFI与hs-CRP亦呈负相关(r值分别为-0.289、-0.540、-0.323,均P<0.05)。脓毒症组和脓毒症合并T2DM组的HLA-DR^(+)CD14^(+)百分比与SOFA评分均呈负相关(r值分别为-0.520、-0.558,均P<0.001),MFI与SOFA评分也均呈负相关(r值分别为-0.327、-0.482,均P<0.01)。结论仑HLA-DR^(+)CD14^(+)水平在T2DM和脓毒症时均下降,但当脓毒症合并T2DM时,HLA-DR+CD14^(+)水平未发现进一步下降。

2型糖尿病合并冠心病与HE4水平的关系

目的探讨2型糖尿病(type 2 diabetes mellitus,T2DM)合并冠心病(coronary heart disease,CHD)与血清人附睾分泌蛋白4(human epididymis protein-4,HE-4)的相关性。方法选取收治的T2DM患者116例作为观察组,根据是否合并CHD分为单纯T2DM组(n=95)、T2DM合并CHD组(n=21),另选择性别、年龄相匹配的健康人群50例作为对照组,检测入组患者静脉血清中HE4水平,同时检测炎症因子、肝肾功能、血脂、血常规及凝血功能等实验室指标,比较分析各组患者HE4水平变化,及与不同实验室指标的相关性。Logistic回归分析T2DM合并CHD的影响因素。结果与对照组相比,观察组患者HE4[(110.0±70.5)pmol/L vs.(50.5±15.5)pmol/L]显著上升(P<0.001),且T2DM合并CHD组HE4[(178.2±88.0)pmol/L]水平显著高于T2DM组[(94.6±56.2)pmol/L](P=0.003)。Spearman相关性分析显示,HE4与D-二聚体(D-Dimer)、纤维蛋白原(fibrinogen,FBG)、C反应蛋白(C-reaction protein,CRP)、同型半胱氨酸(homocysteine,HCY)呈显著正相关(P<0.05),与白蛋白(albumin,ALB)、前白蛋白(prealbumin,PA)、肾小球滤过率(estimated glomerular filtration rate,eGFR)呈显著负相关(P<0.05)。三种logistic回归模型分析均显示HE4是T2DM合并CHD的独立危险因素。HE4区分T2DM与T2DM合并CHD的受试者工作特征(ROC)曲线下面积分别为0.786(95%CI:0.649~0.924),高于eGFR(0.710,95%CI:0.593~0.827)、CRP(0.720,95%CI:0.604~0.835)、HCY(0.758,95%CI:0.652~0.864)。结论T2DM合并CHD与HE4水平升高有关,为研究T2DM合并CHD提供了新的思路和潜在靶点。

IL-1β通过激活ERK1/2信号通路抑制人脐带间充质干细胞CD200表达抑制巨噬细胞M2极化

目的探究白细胞介素1β(IL-1β)调控人脐带间充质干细胞CD200表达及其对巨噬细胞极化的影响及作用机制。方法无血清培养基分离培养获得人脐带间充质干细胞(hUC-MSC),形态学观察及流式细胞术检测CD73、CD90、CD105、CD14、CD34、CD45、人类白细胞抗原DR(HLA-DR)的表达,确定间充质干细胞属性;20 ng/mL IL-1β处理hUC-MSC 24 h,流式细胞术检测CD200阳性细胞率,实时定量PCR和Western blot法检测CD200 mRNA和蛋白表达水平;佛波酯(PMA)诱导THP-1巨噬细胞活化,并与IL-1β处理感染CD200过表达慢病毒的hUC-MSC共培养,流式细胞术检测CD11c和CD206阳性细胞比例;IL-1β联合细胞外信号调节激酶1/2(ERK1/2)特异性抑制剂PD98059处理hUC-MSC,Western blot法检测细胞丝裂原激活蛋白激酶(MAPK)信号分子与CD200的表达。结果IL-1β显著下调hUC-MSC CD200蛋白表达与CD200阳性细胞率;过表达CD200显著上调hUC-MSC CD200表达,且CD200过表达hUC-MSC提高巨噬细胞CD206阳性细胞比率;IL-1β激活hUC-MSC的ERK1/2信号通路,PD98059上调IL-1β处理后hUC-MSC中CD200的蛋白表达。结论IL-1β通过激活ERK1/2信号通路抑制CD200的表达,进而抑制hUC-MSC对巨噬细胞向M2型极化的促进作用。

2型糖尿病患者血清人附睾蛋白4与蛋白尿的相关性研究

目的探讨人附睾蛋白4(human epididymis protein 4,HE4)与2型糖尿病(type 2 diabetes mellitus,T2DM)患者蛋白尿的相关性。方法选取2020年1月至2023年7月九江市第一人民医院收治的147例T2DM患者作为观察组,根据蛋白尿严重程度将观察组分为正常白蛋白尿组(101例)、微量白蛋白尿组(25例)、大量白蛋白尿组(21例);同期选取性别、年龄相匹配的50名健康体检者作为对照组。比较分析各组纳入者的HE4和临床指标变化,采用单因素和多因素线性回归分析探讨HE4与蛋白尿的相关性。结果相关性网络图显示HE4是连接血液白蛋白、尿微量白蛋白、尿微量白蛋白/尿肌酐(urinary microalbumin-to-creatinine ratio,UACR)及肾脏功能生物标志物的一个重要节点;与对照组比较,观察组患者的HE4水平显著升高(P<0.01),单因素和多因素线性回归分析均显示HE4与UACR呈正相关;Logistic回归结果显示校正年龄、性别、估算肾小球滤过率(estimated glomerular filtration rate,e GFR)、白蛋白(albumin,ALB)、血尿素氮(blood urea nitrogen,BUN)、血肌酐(serum creatinine,SCr)、尿酸(uricacid,UA)、乳酸脱氢酶(actate dehydrogenase,LDH)等混杂因素后,HE4水平升高是蛋白尿发生的危险因素(OR=1.110,95%CI:1.005~1.226)。结论HE4与UACR呈正相关,其水平升高可增加T2DM患者的蛋白尿发生风险。

HPVL1蛋白、TRIM22、HER-2联合检测在HPV阳性宫颈上皮内瘤变中的早期诊断价值

目的 探讨人乳头瘤病毒LI(HPVL1)蛋白、三结构域家族蛋白22(TRIM22)、人表皮生长因子受体-2(HER-2)联合检测在人乳头瘤病毒(HPV)阳性宫颈上皮内瘤变(CIN)中的早期诊断价值。方法 回顾性选取2021年1月至2023年6月承德医学院附属医院就诊的162例薄层液基细胞学(TCT)检查异常且HPV阳性的CIN患者为研究组,另选取同期经组织病理学诊断为正常宫颈组织的138名对象为对照组。免疫组织化学法检测宫颈组织中HPVL1蛋白、TRIM22、HER-2表达。比较对照组、研究组组织中HPVL1蛋白、TRIM22、HER-2表达,并比较不同分级CIN患者HPVL1蛋白、TRIM22、HER-2表达。多因素Logistic回归模型分析CIN发生的影响因素;受试者操作特征(ROC)曲线分析HPVL1蛋白、TRIM22、HER-2表达对CIN的早期诊断价值。结果 研究组组织中HPVL1蛋白及TRIM22蛋白阳性率分别为34.57%、32.72%,均显著低于对照组(74.64%、71.01%),HER-2阳性率为60.49%,显著高于对照组(10.87%),差异均有统计学意义(P<0.05)。CINⅠ级、CINⅡ级和CINⅢ级HPVL1蛋白和TRIM22阳性率呈下降趋势,HER-2阳性率呈上升趋势(P<0.05)。多因素Logistic回归分析结果显示,宫颈组织中HPVL1蛋白、TRIM22及HER-2表达均为CIN的影响因素(OR=5.110、5.231、9.652,P<0.05)。ROC曲线结果显示,HPVL1蛋白表达诊断CIN的曲线下面积(AUC)为0.700,敏感度为65.43%;TRIM22表达诊断CIN的AUC为0.691,敏感度为67.28%;HER-2表达诊断CIN的AUC为0.748,敏感度为60.49%。三者联合诊断CIN的AUC为0.814,显著高于单独诊断的AUC(P<0.05)。结论 宫颈组织中HPVL1蛋白、TRIM22及HER-2表达影响CIN的发生、发展,三者联合对CIN具有较高的诊断价值。

Correlation of human epidermal growth factor receptor 2 expression with clinicopathological characteristics and prognosis in gastric cancer

AIM:To investigate human epidermal growth factor receptor 2(HER2) gene amplification and protein expression in Chinese patients with resectable gastric cancer and the association with clinicopathological characteristics and survival.METHODS:One hundred and ninety-seven gastric cancer patients who underwent curative surgery procedures were enrolled into this study.HER2 gene amplification and protein expression were examined using fluorescence in-situ hybridization(FISH) and immunohistochemistry(IHC) analysis on formalin-fixed paraffinembedded gastric cancer samples from all patients.For scoring,Hofmann's HER2 gastric cancer scoring system was adopted.All cases showing IHC3+ or FISH positiv-ity were defined as HER2 positive.Patient clinicopathological data and survival information were collected.Finally,χ 2 statistical analysis was performed to analyze the HER2 positivity rate amongst the subgroups with different clinicopathological characteristics including;gender,age,tumor location,Lauren classification,differentiation,TNM staging,depth of invasion,lymph node metastases and distant metastasis.The probability of survival for different subgroups with different clinicopathological characteristics was calculated using the Kaplan-Meier method and survival curves plotted using log rank inspection.RESULTS:According to Hofmann's HER2 gastric cancer scoring criteria,31 cases(15.74%) were identified as HER2 gene amplified and 19 cases(9.64%) were scored as strongly positive for HER2 membrane staining(3+),25 cases(12.69%) were moderately positive(2+) and 153 cases(77.66%) were HER2 negative(0/1+).The concordance rate between IHC and FISH analyses was 88.83%(175/197).Thirty-six cases were defined as positive for HER2 gene amplification and/or protein expression,with 24 of these cases being eligible for Herceptin treatment according to United States recommendations,and 29 of these cases eligible according to EU recommendations.Highly consistent results were detected between IHC3+,IHC0/1 and FISH(73.68% and 95.42%),but low consistency was observed between IHC2+ and FISH(40.00%).The positivity rates in intestinal type and well-differentiated gastric cancer were higher than those in diffuse/mixed type and poorly-differentiated gastric cancer respectively(28.57% vs 13.43%,P = 0.0103;37.25% vs 11.64%,P < 0.0001),but were not correlated with gender,age,tumor location or TNM stage,depth of invasion,lymph node metastases and distant metastasis.In poorly-differentiated gastric cancer patients,those without lymph node metastasis showed a higher HER2 positivity rate than those with lymph node metastasis(26.47% vs 7.14%,P = 0.0021).This association was not present in thosepatients with well-differentiated gastric cancer(28.57% vs 43.33%,P = 0.2832).Within our patient cohort,26 cases were lost to follow-up.The median survival time for the remaining 171 patients was 18 mo.The median survival times of the HER2 positive and negative groups were 17 and 18.5 mo respectively.Overall survival was not significantly different between HER2-positive and negative groups(χ 2 = 0.9157,P = 0.3386),but in patients presenting well-differentiated tumors,the overall survival of the HER2-positive group was significantly worse than that of the HER2-negative group(P = 0.0123).In contrast,patients with poorly differentiated and diffuse/mixed subtype gastric cancers showed no significant differences in overall survival associated with HER2.Furthermore,the median survival time of the HER2 positive group did not show any statistically significant differences when compared to the subgroups of gender,age,tumor location,TNM classification,lymph node metastases and distant metastasis.CONCLUSION:Patients with intestinal type gastric cancer(GC),well-differentiated GC and poorly-differentiated GC without lymph node metastasis,may all represent suitable candidates for targeted therapy using Herceptin.

伊尼妥单抗治疗人表皮生长因子受体2阳性转移性乳腺癌伴胃肠功能紊乱1例

乳腺癌是女性常见的肿瘤,如今乳腺癌实体肿瘤通过相应的治疗可取得较好的疗效,但人表皮生长因子受体2(HER2)阳性乳腺癌侵袭性较强、恶性程度高,需引起患者及医务人员的重视。本文回顾性分析1例激素受体阴性、HER2阳性伴胃肠功能紊乱的乳腺癌患者诊治经过。患者初诊为局部晚期炎症乳腺癌伴腋窝淋巴结转移,给予新辅助化疗及手术治疗。术后3年后病情进展,予以伊尼妥单抗联合白蛋白紫杉醇,后续伊尼妥单抗单独靶向治疗,病情持续缓解。提示对于HER2阳性晚期乳腺癌,伊尼妥单抗是个很好的单抗类药物选择。

胃癌患者EB病毒感染情况及其对癌组织p53、Bcl-2表达的影响

目的探究胃癌患者人类疱疹(EB)病毒感染情况及其对癌组织p53、B淋巴细胞瘤-2(Bcl-2)表达的影响。方法选取新乡市中心医院2019年8月至2023年1月收治的76例胃癌患者,采用原位杂交法检测患者癌组织及癌旁组织EB病毒编码小分子RNA表达,采用逆转录聚合酶链式反应(RT-PCR)法检测患者癌组织及癌旁组织p53、Bcl-2 mRNA表达,分析EB病毒感染与胃癌临床病理特征及癌组织p53、Bcl-2表达的关系。结果76例胃癌患者癌组织标本中EB病毒阳性率为27.63%(21/76),邻近癌旁组织标本中EB病毒阳性率为4.29%(3/76),胃癌患者癌组织EB病毒阳性率高于癌旁组织(P<0.05);与EB病毒阴性的胃癌患者比,EB病毒阳性患者中病灶位于近端胃、组织浸至浆膜层、有淋巴结转移的占比较多(P<0.05);胃癌患者癌组织p53及Bcl-2 mRNA表达均高于癌旁组织(P<0.05);EB病毒感染胃癌患者癌组织p53及Bcl-2 mRNA表达均高于未感染胃癌患者(P<0.05)。结论EB病毒感染与胃癌患者近端胃病变、组织浸至浆膜层及有淋巴结转移有关,EB病毒可能通过驱动宿主p53基因甲基化来上调p53表达,与Bcl-2协同促进癌细胞生长,这些可能为临床提供胃癌诊疗评估因子及免疫治疗新靶点。

A CT-based radiomics nomogram for prediction of human epidermal growth factor receptor 2 status in patients with gastric cancer

Objective: To develop and validate a computed tomography(CT)-based radiomics nomogram for predicting human epidermal growth factor receptor 2(HER2) status in patients with gastric cancer.Methods: This retrospective study included 134 patients with gastric cancer(HER2-negative: n=87;HER2-positive: n=47) from April 2013 to March 2018, who were then randomly divided into training(n=94) and validation(n=40) cohorts. Radiomics features were obtained from the CT images showing gastric cancer. Least absolute shrinkage and selection operator(LASSO) regression analysis was utilized for building the radiomics signature. A multivariable logistic regression method was applied to develop a prediction model incorporating the radiomics signature and independent clinicopathologic risk predictors, which were then visualized as a radiomics nomogram. The predictive performance of the nomogram was assessed in the training and validation cohorts.Results: The radiomics signature was significantly associated with HER2 status in both training(P<0.001) and validation(P=0.023) cohorts. The prediction model that incorporated the radiomics signature and carcinoembryonic antigen(CEA) level demonstrated good discriminative performance for HER2 status prediction,with an area under the curve(AUC) of 0.799 [95% confidence interval(95% CI): 0.704-0.894] in the training cohort and 0.771(95% CI: 0.607-0.934) in the validation cohort. The calibration curve of the radiomics nomogram also showed good calibration. Decision curve analysis showed that the radiomics nomogram was useful.Conclusions: We built and validated a radiomics nomogram with good performance for HER2 status prediction in gastric cancer. This radiomics nomogram could serve as a non-invasive tool to predict HER2 status and guide clinical treatment.

miRNA-27a与TOP2A蛋白在乳腺癌化疗中的表达水平及效能评估

目的探析微核糖核酸-27a(microRNA-27a,miRNA-27a)与DNA拓扑异构酶Ⅱα(TopoisomeraseⅡ-Alpha,TOP2A)蛋白在乳腺癌化疗中的表达水平及预测效能。方法回顾性分析2020年1月至2022年1月聊城市人民医院乳甲外科收治的47例乳腺癌患者的病案资料,均接受化疗治疗。用实时荧光定量PCR法进行血浆miRNA-27a表达水平的检测,用免疫组织化学法进行TOP2A蛋白表达情况的检测。比较乳腺癌患者化疗前后的miRNA-27a、TOP2A蛋白表达水平差异,采用Logistic回归分析法探析miRNA-27a、TOP2A蛋白与乳腺癌化疗预后不良的关系,绘制受试者工作特征(Receiver Operating Characteristic,ROC)曲线分析miRNA-27a、TOP2A蛋白在乳腺癌化疗疗效预测中的应用价值。结果47例患者开始化疗后第4个月的miRNA-27a、TOP2A蛋白检测值显著低于化疗前(入院时)(P<0.05)。开始化疗后第4个月,预后良好35例(74.47%),预后不良12例(25.53%),预后良好组的miRNA-27a、TOP2A蛋白检测值低于预后不良组。Logistic分析结果显示,miRNA-27a、TOP2A蛋白高表达是乳腺癌化疗预后不良的危险因素(P<0.05)。ROC曲线结果显示,miRNA-27a、TOP2A蛋白联合预测乳腺癌化疗预后不良的曲线下面积(0.875,95%CI:0.798~0.952)最大,敏感度、特异性分别为91.67%、94.29%(P<0.05)。结论miRNA-27a、TOP2A蛋白在乳腺癌化疗预后不良中呈高表达,若乳腺癌化疗患者miRNA-27a、TOP2A蛋白表达水平显著上升,侧面说明患者病情可能有恶化风险,化疗疗效有限。

Role of human epidermal growth factor receptor 2 in gastric cancer:Biological and pharmacological aspects

Amplification of the human epidermal growth factor receptor 2 (HER2) gene and overexpression of the HER2 protein is found in 15%-20% of patients with gastric and gastroesophageal junction cancer. The degree of HER2 overexpression and amplification varies with the location of the carcinoma, with higher expression in the gastroesophageal and proximal parts compared to the distal parts of the stomach. Further, HER2 overexpression and amplification also seems to be related to the Lauren histological classification, with higher levels found in the intestinal phenotype compared to the diffuse and mixed types. The prognostic properties of HER2 overexpression and amplification are still under debate, but a large number of studies seem to indicate that HER2 is a negative prognostic factor. The usefulness of HER2 targeted therapy in gastric cancer was demonstrated in the ToGA trial, where HER2-positive patients with advanced gastric and gastroesophageal junction adenocarcinoma were randomized to receive 5-FU/capecitabine and cisplatin, either alone or in combination with trastuzumab. A statically significant gain in overall survival was seen in patients who received the combined treatment of trastuzumab and chemotherapy. Patients with a strong overexpression of the HER2 protein (IHC3+) specifically benefited from the treatment, with a median overall survival of 17.9 mo. As a consequence of the positive results of the ToGA trial, patients with advanced gastric or gastroesophageal junction adenocarcinoma are now routinely tested for HER2. The ToGA trial must be characterized as a landmark in the treatment of gastric cancer and it has paved the way for a number of new HER2 targeted compounds such as pertuzumab, ado-trastuzumab emtansine, lapatinib, afatinib, and dacomitinib, which are currently undergoing phase II and III clinical testing. Overall, this review will discuss the current status of HER2 in gastric and gastroesophageal junction cancer and the future direction in relation to HER2 target therapy.

Establishment of a high-resolution 2-D reference map of human spermatozoal proteins from 12 fertile sperm-bank donors

Aim： To extend the analysis of the proteome of human spermatozoa and establish a 2-D gel electrophoresis （2-DE） reference map of human spermatozoal proteins in a pH range of 3.5-9.0. Methods： In order to reveal more protein spots, immobilized pH gradient strips （24 cm） of broad range of pH 3-10 and the narrower range of pH 6-9, as well as different overlapping narrow range pH immobilized pH gradient （IPG） strips, including 3.5-4.5, 4.0-5.0, 4.5-5.5, 5.0-6.0 and 5.5-6.7, were used. After 2-DE, several visually identical spots between the different pH range 2-D gel pairs were cut from the gels and confirmed by mass spectrometry and used as landmarks for computer analysis. Results： The 2-D reference map with pH value from 3.5 to 9.0 was synthesized by using the ImageMaster analysis software. The overlapping spots were excluded, so that every spot was counted only once. A total of 3 872 different protein spots were identified from the reference map, an approximately 3-fold increase compared to the broad range pH 3-10 IPG strip （1 306 spots）. Conclusion： The present 2-D pattern is a high resolution 2-D reference map for human fertile spermatozoal protein spots. A comprehensive knowledge of the protein composition of human spermatozoa is very meaningful in studying dysregulation of male fertility.