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.

BIRC3 induces the phosphoinositide 3-kinase-Akt pathway activation to promote trastuzumab resistance in human epidermal growth factor receptor 2-positive gastric cancer

BACKGROUND Trastuzumab-targeted therapy is currently the standard of care for advanced human epidermal growth factor receptor 2(HER2)-positive gastric cancer.However,the emergence of resistance to trastuzumab poses significant challenges.AIM To identify the key genes associated with trastuzumab resistance.These results provide a basis for the development of interventions to address drug resistance and improve patient outcomes.METHODS High-throughput sequencing and bioinformatics were used to identify the differentially expressed pivotal gene BIRC3 and delineate its potential function and pathway regulation.Tumor samples were collected from patients with HER2-positive gastric cancer to evaluate the correlation between BIRC3 expression and trastuzumab resistance.We established gastric cancer cell lines with both highly expressed and suppressed levels of BIRC3,followed by comprehensive in vitro and in vivo experiments to confirm the involvement of BIRC3 in trastuzumab resistance and to elucidate its underlying mechanisms.RESULTS In patients with HER2-positive gastric cancer,there is a significant correlation between elevated BIRC3 expression in tumor tissues and higher T stage,tumor node metastasis stage,as well as poor overall survival and progressionfree survival.BIRC3 is highly expressed in trastuzumab-resistant gastric cancer cell lines,where it inhibits tumor cell apoptosis and enhances trastuzumab resistance by promoting the phosphorylation and activation of the phosphoinositide 3-kinase-Akt(PI3K-AKT)pathway in HER2-positive gastric cancer cells,both in vivo and in vitro.CONCLUSION This study revealed a robust association between high BIRC3 expression and an unfavorable prognosis in patients with HER2-positive gastric cancer.Thus,the high expression of BIRC3 stimulated PI3K-AKT phosphorylation and activation,stimulating the proliferation of HER2-positive tumor cells and suppressing apoptosis,ultimately leading to trastuzumab resistance.

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.

Study on the Hook Effect in the Detection of Beta2-Microglobulin with Different Reagents in Fully Automated Biochemical Analyzers

Objective:To investigate the hook effect in the detection of beta2-microglobulin(β2-MG)with different reagents as well as on two fully automated biochemical analyzers and their solutions.Methods:Using immunoturbidimetric assay forβ2-MG as the research object,β2-MG levels were detected by different concentration gradients ofβ2-microglobulin samples in Liedemann,Mack,and Myriad reagents of three manufacturers on two automatic biochemical analyzers,and the difference of the hook effect was comparatively analyzed.Results:Leadman reagent showed the hook effect on the Beckman AU5800 automated biochemistry analyzer,while both Maccura and Mindray reagents did not show the hook effect.After the experiments,we found the limit value of the pre-zone check of Leadman reagent,and changed the parameters of the instrument,when the limit value of the pre-zone check was reached,the instrument automatically diluted the specimen five times and then detected it again.After changing the parameters of the instrument,the correlation between the three methods of detecting samples of different concentrations was r>0.99.Conclusion:Before selecting the application of immunoturbidimetric reagents,we have to carry out the risk assessment of the hook effect and selectively set the parameters of the pre-zone check based on the highest concentration that may occur in the clinic;for the items that may have the hook effect,we have to selectively set the parameters of the pre-zone check when the ratio of average reaction rate and the immediate reaction rate is at the limit value,and the phenomenon of antigen excess may occur,the instrument will carry out automatic dilution before detection,so as to avoid the issuance of erroneous results of high-value samples due to the hook effect.

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。

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。

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。

3D-STI参数评价抗HER-2药物对乳腺癌患者心室功能变化的价值

目的 探讨三维斑点追踪成像(Three Dimensional Speckle Tracking Imaging,3D-STI)参数评价抗人表皮生长因子受体-2(Human Epidermal Growth Factor Receptor-2,HER-2)药物对乳腺癌患者心室功能变化的价值。方法 选取我院2021年6月至2022年6月收治的50例需行辅助化疗乳腺癌患者作为观察组,选择同期30名健康志愿者作为对照组。比较对照组与观察组化疗前,化疗第2、4、6周期常规超声心动图指标与3D-STI参数,以临床病理诊断为“金标准”,并绘制3D-STI参数受试者工作特征(Receiver Operating Characteristic,ROC)曲线。结果 观察组化疗第6周期E/A值低于对照组和化疗前(P<0.05),观察组化疗第2、4、6周期左心室扭转、心肌综合指数值低于对照组和化疗前(P<0.05),观察组化疗第4、6周期整体纵向应变(GlobalLongitudinalStrain,GLS)低于对照组和化疗前(P<0.05);ROC曲线显示GLS敏感度最高,为96.00%,整体圆周应变特异性最高,为96.67%。结论 3D-STI参数可评估乳腺癌患者抗HER-2药物化疗后心室功能变化,为临床早期干预提供诊断依据。

双靶向新辅助药物联合不同化疗治疗HER-2阳性乳腺癌临床疗效比较

目的探讨双靶向新辅助药物联合不同化学药物治疗(简称化疗)的方案治疗人类表皮生长因子受体-2(HER-2)阳性乳腺癌的临床疗效。方法选取凉山彝族自治州第一人民医院2019年1月至2022年12月收治的HER-2阳性乳腺癌患者110例,按治疗方案的不同分为TcbHP组和AC-THP组,各55例。TcbHP组患者予曲妥珠单抗和帕妥珠单抗联合紫杉类(多西他赛或紫杉醇)和卡铂治疗,以21 d为1个周期,共治疗6个周期;AC-THP组患者予曲妥珠单抗和帕妥珠单抗联合蒽环类药物(吡柔比星或表柔比星)和环磷酰胺治疗,以21 d为1个周期,曲妥珠单抗和帕妥珠单抗及其他药物分别治疗4个周期,共8个周期。结果TcbHP组患者病理完全缓解率为61.80%,稍高于AC-THP组的50.90%(P>0.05)。治疗后,TcbHP组恶心,呕吐,腹泻,心脏毒性及手足综合征程度均显著低于AC-THP组(P<0.05);各肿瘤标志物[糖类抗原(CA19-9,CA125,CA153),癌胚抗原(CEA)]水平均显著低于AC-THP组(P<0.05);左心室射血分数(LVEF)及血清心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶MB(CK-MB)、氨基末端脑钠肽前体(NT-proBNP)水平均无明显变化(P>0.05),且均显著优于AC-THP组(P<0.05)。结论TcbHP方案治疗HER-2阳性乳腺癌的疗效与AC-THP方案相当,但前者降低肿瘤标志物生成的作用更明显,且心脏毒性风险相对更低。

胃癌组织中SDF-1、HER2及Slug表达与患者临床病理特征的相关性

目的分析基质细胞衍生因子1(SDF-1)、人表皮生长因子受体2(HER2)、锌指转录因子(Slug)在胃癌组织内的表达及与患者临床病理特征间的关系。方法选取73例胃癌患者,采集其癌组织与癌旁正常组织,以免疫组织化学法检测对比两者SDF-1、HER2及Slug的表达差异;另收集患者的年龄等资料,统计分析SDF-1、HER2及Slug表达与胃癌患者各项临床病理特征间的联系。结果癌组织的SDF-1、HER2、Slug阳性表达率高于癌旁正常组织,差异有统计学意义(P<0.05)。SDF-1、HER2、Slug阳性表达与胃癌患者的年龄、性别无关(P>0.05),与患者的临床分期、淋巴结转移、分化程度有关(P<0.05)。结论SDF-1、HER2、Slug在胃癌组织内呈异常高表达,且其参与胃癌的侵袭、发展过程。

乳腺癌患者HER2、CA153表达与声触诊组织成像定量技术参数的相关性分析

目的:分析乳腺癌患者人表皮生长因子受体2(HER2)、糖类抗原153(CA153)表达与声触诊组织成像定量(VTIQ)技术参数的相关性。方法:选取2018年5月至2020年5月合肥市第三人民医院收治的80例女性乳腺癌患者,其中世界卫生组织(WHO)分期Ⅰ期14例、Ⅱ期22例、Ⅲ期31例、Ⅳ期13例;另选取同时间段收治的53例女性乳腺良性疾病患者为对照。所有患者先行常规超声检查,随后进入超声VTIQ成像模式获得剪切波速度(SWV)均值参数;采用免疫组织化学法检测乳腺组织中HER2表达,采用罗氏E411电化学发光免疫分析仪检测血清CA153水平;采用Pearson法分析乳腺癌患者血清CA153水平与SWV均值的相关性。结果:与良性患者比较,乳腺癌患者VTIQ技术参数SWV均值、血清CA153水平及HRR2阳性表达率均显著升高,差异有统计学意义(F=39.107,78.353,P<0.05);与乳腺癌Ⅰ+Ⅱ期患者比较,乳腺癌Ⅲ、Ⅳ期患者VTIQ技术参数SWV均值、血清CA153水平、HRR2阳性表达率均显著升高,差异有统计学意义(t=2.685、3.556、8.326、10.455,P<0.05);与乳腺癌Ⅲ期比较,乳腺癌Ⅳ期患者VTIQ技术参数SWV均值、血清CA153水平、HRR2阳性表达率均显著升高,差异有统计学意义(t=4.632、8.659,P<0.05)。与HER2阴性表达乳腺癌患者SWV均值比较,HER2阳性表达乳腺癌患者SWV均值升高,差异有统计学意义(χ^(2)=59.751,P<0.05)。乳腺癌患者血清CA153水平与SWV均值呈正相关(r=0.501,P<0.05)。结论:乳腺癌患者VTIQ参数SWV均值与乳腺癌患者生物标志物HER2、CA153表达水平密切相关。

THP方案新辅助治疗HER-2阳性乳腺癌的真实世界研究

目的 了解THP方案在真实世界临床实践的应用状况,同时评价该方案的疗效、安全性和耐受性。方法 选择在保定市第一中心医院等河北省11家三级甲等医院接受THP方案新辅助治疗并完成序贯手术的HER-2阳性乳腺癌患者70例为研究对象,制订专用的患者资料信息收集表,专人负责收集符合纳入标准患者的临床病理资料。评估THP方案的有效性、安全性和耐受性。主要研究终点为病理完全缓解(pCR)率、≥3级不良反应的发生率、既定治疗方案完成率。结果 总人群pCR率为54.3%。亚组分析显示,cTNMⅠ-Ⅱ期、激素受体阴性、HER-2 IHC3+患者的pCR率分别显示出高于c TNMⅢ期、激素受体阳性、HER-2 IHC2+/FISH+患者的趋势,但差异无统计学意义(P>0.05)。4周期患者的pCR率显著高于4周期以上患者(P<0.05)。≥3级不良反应发生率为4.3%。既定方案完成率为98.6%。结论THP方案在河北省得到广泛应用,是HER-2阳性乳腺癌患者新辅助治疗的有效方案,安全性及耐受性良好,可以考虑作为激素受体阴性、肿瘤负荷较小、对联合化疗耐受性差患者的新辅助备选方案。