扶正抑癌汤联合腹腔镜辅助小切口根治手术治疗胃癌临床研究

目的:探讨扶正抑癌汤联合腹腔镜辅助小切口根治手术治疗胃癌的效果及对患者免疫功能的影响。方法:选择80例胃癌患者,按随机数字表法分为观察组和对照组各40例。对照组行腹腔镜辅助小切口根治手术治疗,观察组予以扶正抑癌汤联合腹腔镜辅助小切口根治术手术治疗,比较2组患者临床疗效及免疫功能。结果:治疗前,2组中医症状评分比较,差异无统计学意义(P>0.05)。治疗后,2组中医症状评分较治疗前下降(P<0.05),且观察组中医症状评分低于对照组(P<0.05)。治疗前,2组癌胚抗原(CEA)、糖类抗原199 (CA199)、糖类抗原125 (CA125)水平比较,差异无统计学意义(P>0.05)。治疗后,2组CEA、CA199、CA125水平较治疗前下降(P<0.05),且观察组CEA、CA199、CA125水平低于对照组(P<0.05)。治疗前,2组CD4^+、CD8^+、CD4^+/CD8^+水平比较,差异无统计学意义(P>0.05)。治疗后,2组CD4^+、CD8^+、CD4^+/CD8^+水平较治疗前升高(P<0.05),且观察组CD4^+、CD8^+、CD4^+/CD8^+水平高于对照组(P<0.05)。结论:扶正抑癌汤联合腹腔镜辅助小切口根治手术治疗胃癌效果显著,可有效降低相关肿瘤标志物水平,并改善患者免疫功能。     

A synthetic peptide targeting the BH4 domain of Bcl-2 induces apoptosis in multiple myeloma and follicular lymphoma cells alone or in combination with agents targeting the BH3-binding pocket of Bcl-2

Bcl-2 inhibits apoptosis by two distinct mechanisms but only one is targeted to treat Bcl-2-positive malignancies. In this mechanism, the BH1-3 domains of Bcl-2 form a hydrophobic pocket, binding and inhibiting pro-apoptotic proteins, including Bim. In the other mechanism, the BH4 domain mediates interaction of Bcl-2 with inositol 1,4, 5-trisphosphate receptors (IP₃Rs), inhibiting pro-apoptotic Ca²⁺ signals. The current anti-Bcl-2 agents, ABT-263 (Navitoclax) and ABT-199 (Venetoclax), induce apoptosis by displacing pro-apoptotic proteins from the hydrophobic pocket, but do not inhibit Bcl-2-IP₃R interaction. Therefore, to target this interaction we developed BIRD-2 (Bcl-2 IP₃ Receptor Disruptor-2), a decoy peptide that binds to the BH4 domain, blocking Bcl-2-IP₃R interaction and thus inducing Ca²⁺-mediated apoptosis in chronic lymphocytic leukemia, multiple myeloma, and follicular lymphoma cells, including cells resistant to ABT-263, ABT-199, or the Bruton’s tyrosine kinase inhibitor Ibrutinib. Moreover, combining BIRD-2 with ABT-263 or ABT-199 enhances apoptosis induction compared to single agent treatment. Overall, these findings provide strong rationale for developing novel therapeutic agents that mimic the action of BIRD-2 in targeting the BH4 domain of Bcl-2 and disrupting Bcl-2-IP₃R interaction.     

Interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitors: an updated patent review (2016-2018)

Introduction: Interleukin-1 receptor-associated kinase 4 (IRAK4) is the most upstream kinase in Toll/Interleukin-1 receptor (TIR) signaling. Human and rodent genetics support the role of IRAK4 in immune function and the involvement of IRAK4-dependent signaling in certain cancers is hypothesized. The accumulating evidence has motivated the discovery of IRAK4 inhibitors that could be used therapeutically.

Areas covered: This review summarizes patents published in 2016–2018 claiming IRAK4 inhibitors. Representative analogues from each patent are presented with a focus on compounds that have been profiled in cellular and in vivo assays.

Expert opinion: The last three years have seen an increased number of IRAK4 inhibitors with which to assess the therapeutic potential of the target. At least 5 companies are believed to have advanced to the clinic. Pfizer is in phase II for rheumatoid arthritis (RA). The outcomes of these studies should inform on the therapeutic potential in autoimmune disease and cancer.     

CA153联合CA199对良恶性腹腔积液的鉴别诊断价值

目的探讨腹腔积液中CA153联合CA199对良恶性腹腔积液的鉴别诊断价值。方法选择98例腹腔积液患者,经手术病理诊断为恶性腹腔积液者为观察组(48例),良性腹腔积液者为对照组(50例)。检测并比较2组患者腹腔积液中的CA153、CA199水平及CA153、CA199的阳性结果,分析CA153及CA155单用及联合应用对恶性腹腔积液的诊断效能。结果观察组腹腔积液中的CA153及CA199水平均明显高于对照组,P <0. 05。观察组CA153及CA199阳性率明显高于对照组,P <0. 05。CA153、CA199对恶性腹腔积液诊断的敏感性、特异性及准确性对比,差异无统计学意义(P> 0. 05);CA153+CA199的敏感性、特异性及准确性明显高于单项CA153及CA199(P <0. 05)。结论 CA153与CA199单项检测对恶性腹腔积液的诊断价值有限,CA153+CA199对恶性腹腔积液的诊断价值较高,值得临床推广应用。     

Vitamin B6 Addiction in Acute Myeloid Leukemia

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单中心卵巢畸胎瘤患者中合并抗N-甲基-D-天冬氨酸受体脑炎的比例调查及临床特征分析

目的 探究卵巢畸胎瘤患者中发生抗N-甲基-D-天冬氨酸受体（NMDAR）脑炎的比例,并将合并抗NMDAR脑炎的卵巢畸胎瘤患者与未合并抗NMDAR脑炎的卵巢畸胎瘤患者的临床特征进行总结对比。方法 收集卵巢畸胎瘤患者的临床资料,将其分为合并抗NMDAR脑炎组与未合并抗NMDAR脑炎组,对其临床特征进行对比分析。结果 共收集到168例卵巢畸胎瘤患者,其中14例（8.3%）合并抗NMDAR脑炎;合并抗NMDAR脑炎的卵巢畸胎瘤患者年龄低于未合并抗NMDAR脑炎的卵巢畸胎瘤患者[（23.8±5.5）岁 vs. （29.8±9.1）岁,P = 0.016]。合并抗NMDAR脑炎的卵巢畸胎瘤患者肿瘤标志物以癌抗原125及血清铁蛋白升高为主,而未合并抗NMDAR脑炎的卵巢畸胎瘤患者肿瘤标志物以糖类抗原199升高为主。合并抗NMDAR脑炎与未合并抗NMDAR脑炎的卵巢畸胎瘤患者的肿瘤组织均可含有神经组织。结论 卵巢畸胎瘤患者中发生抗NDMAR脑炎的比例不低,对于无明显症状的卵巢畸胎瘤患者,可考虑积极行手术治疗,以降低发生抗NMDAR脑炎的风险。     

HPV与血清肿瘤标志物检测在宫颈癌诊断中的效能

目的:观察人乳头瘤病毒(HPV)与血清肿瘤标志物检测在宫颈癌诊断中的效能。方法:选取120例疑似宫颈癌患者作为研究对象,其中经手术病理确诊为宫颈癌54例设为宫颈癌组,宫颈良性肿瘤66例设为良性肿瘤组。另选取同期70例健康女性为对照组。比较三组HPV阳性检出率、血清肿瘤标志物糖类抗原(CA)125、CA153和CA199水平,以术后病理检查结果为“金标准”,比较HPV及CA125、CA153、CA199单独检测与联合检测在宫颈癌诊断中的效能。结果:宫颈癌组HPV16、HPV18单独检测与联合检测阳性率均高于良性肿瘤组和对照组,差异有统计学意义(P<0.05);宫颈癌组CA125、CA153、CA199水平均高于良性肿瘤组和对照组,差异有统计学意义(P<0.05);HPV与血清肿瘤标志物联合检测的灵敏度、准确度均高于单独检测,特异度低于CA153、CA199单独检测,高于HPV、CA125单独检测,差异有统计学意义(P<0.05)。结论:HPV与CA125、CA153、CA199联合检测可提高宫颈癌诊断的准确度和灵敏度。     

胆固醇、SAAG、CEA和CA199对良恶性腹水鉴别诊断意义

目的探讨癌胚抗原(CEA)、癌抗原199(CA199)、胆固醇(Ch)和血清-腹水白蛋白梯度(SAAG)检测对良恶性腹水的鉴别价值。方法检测54例恶性腹水、48例良性腹水中CEA、CA199、Ch和ALB水平,同时在±0.5h内检测血清ALB,计算SAAG。并计算CEA、CA199、Ch和SAAG诊断性能指标。结果恶性腹水CEA、CA199、Ch和SAAG检测水平明显高于良性腹水,差异有极显著性(P<0.001)。从敏感性和有效率看,均以Ch最高,CA199最低,但CA199特异性为100%。CEA+CA199+Ch联合检测敏感性为90.7%,特异性为100%。结论CEA、CA199、Ch和SAAG检测对良恶性腹水具有鉴别价值,CEA+CA199+Ch联合检测对鉴别良恶性胸腹水具有十分重要的意义。     

CA199和CA242与胃癌病程发展关系

目的探讨血清CA199和CA242水平与胃癌病程发展关系.方法 CA199采用微粒子酶免疫分析,CA242用酶免疫法,检测胃癌患者270例,良性胃病32例,正常人52名.结果 CA199和CA242水平:胃癌组与良性胃病和正常人组比较,均有非常显著性差异(P＜0.01);两标志物水平可随胃癌临床TNM分期递增而升高,I-Ⅱ期与Ⅲ期比较有显著差异(P＜0.05),I-Ⅱ期与Ⅳ期和肝转移组比较有非常显著性差异(P＜0.01);两标志物与胃癌组织学分型未有明显差异.结论检测血清CA199和CA242水平,即有助于对胃癌的临床分期诊断,又可作为判断胃癌肝转移的一项新的实验指标.     

血清糖类抗原（CA－50）测定在喉癌诊断中的初步应用

本文应用ＩＲＭＡ法测定了２０例喉鳞状细胞癌患者和２０例正常成人血清ＣＡ－５０值，并对其中１６例喉癌患者进行了术前、术后自身对照观察，结果发现：喉癌患者血清ＣＡ－５０值明显高于正常对照（Ｐ＜０．０１），异常阳性率为５０％；喉癌组术前、术后ＣＡ－５０比较无显著差异。初步研究可示，血清ＣＡ－５０作为肿瘤标志在喉癌辅助诊断中具有一定的研究价值。