STEAP1 Inhibits Breast Cancer Metastasis and Is Associated With Epithelial–Mesenchymal Transition Procession

Purpose

Six-transmembrane epithelial antigen of prostate 1 (STEAP1) is a cell surface antigen overexpressed in multiple cancers and is associated with malignancy and disease prognosis. The aims of this study were to evaluate STEAP1 expression in breast cancer and to determine the mechanisms involved.

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。     

术前低PSA的Gleason 8~10分前列腺癌患者临床特点

背景与目的:前列腺癌的发病率逐渐上升,其中有些患者在诊断为高级别前列腺癌甚至转移性前列腺癌时,其前列腺特异性抗原(prostate-specific antigen,PSA)数值却处于很低的水平。探讨术前低血清PSA的Gleason 8~10分前列腺癌患者临床特点。方法:收集2013年1月-2018年1月江苏省苏北人民医院收治的72例接受前列腺癌根治术的高Gleason评分前列腺癌患者的临床资料。根据术前血清PSA水平分为4组:A组<4.0 ng/mL(9例)、B组4.0~10.0 ng/mL(12例)、C组10.0~20.0 ng/mL(15例)和D组>20.0 ng/mL(36例)。4组平均年龄分别为(68.8±8.6)、(68.9±6.0)、(71.6±6.0)和(68.4±6.4)岁。平均随访时间分别为(21.6±12.1)、(18.8±7.2)、(25.0±13.4)和(24.8±12.5)个月。切缘阳性例数分别为3例(33.3%)、5例(41.7%)、5例(33.0%)和15例(41.7%)。精囊侵犯例数分别为6例(66.7%)、2例(16.7%)、2例(13.3%)和14例(38.9%)。淋巴结转移例数分别为2例(22.2%)、3例(25.0%)、4例(26.7%)和13例(36.1%)。预后评价指标为无生化复发天数(biochemical progression-free day,bPFD)与前列腺癌特异性死亡(prostate cancer-specific death,PCSD)。4组平均PFD分别为(90.00±38.40)、(306.17±79.00)、(223.14±63.30)和(145.03±62.50)d。PCSD例数分别为4例(44.4%)、0例(0.0%)、1例(6.7%)和5例(13.9%)。组间年龄、随访时间、PFD使用单因素方差分析,进一步两两比较采用最小显著差别(least significant difference,LSD)法;组间临床病理学特征采用χ2检验、Fisher精确检验;PCSD使用Kaplan-Meier生存分析,生存曲线间比较使用log-rank检验。结果:A组与其余3组相比,年龄、随访时间、切缘阳性、淋巴结转移的差异均无统计学意义(P>0.05)。A组与B、C两组相比,精囊侵犯、PFD的差异均有统计学意义(P<0.05)。但A组与D组相比,精囊侵犯、PFD的差异无统计学意义(P>0.05)。生存分析显示,A组相较于B组在随访时间内生存状况更差,但差异无统计学意义(P=0.092),A组与C、D两组的生存差异有统计学意义(P<0.05)。结论:具有术前低血清PSA水平的高Gleason评分前列腺癌患者相较于PSA更高水平的患者预后更差,易出现精囊侵犯、术后生化复发快且PCSD例数多。     

星点设计-效应面法优化pH值响应及线粒体靶向双功能金丝桃苷脂质体的处方及其体外评价

目的 优化线粒体靶向金丝桃苷脂质体（DLD/Hyp-Lip）制备的最佳处方，并研究研究其在胎牛血清中的稳定性及体外释放行为，考察其线粒体靶向性。方法 采用薄膜分散法制备DLD/Hyp-Lip，以包封率和载药量为考察指标进行单因素实验，考察磷脂总量与金丝桃苷（hyperoside，Hyp）用量比、二硬脂酰磷脂酰乙醇胺-聚乙二醇（DSPE-PEG）与DLD用量比等条件对DLD/Hyp-Lip的影响，结合星点设计-效应面法优化DLD/Hyp-Lip处方。使用透射电子显微镜和粒径仪观察测定脂质体粒子外观、平均粒径和Zeta电位，采用血清稳定性实验和体外释药、线粒体靶向性对该载药系统进行评价。结果 DLD/Hyp-Lip最佳处方为磷脂总量和金丝桃苷用量比为12.50：1，磷脂总量与胆固醇用量比为6.00：1，DSPE-PEG与DLD用量比为3：5；测得金丝桃苷包封率为（95.57±0.56）%，载药量为（8.55±0.57）%。所制备的DLD/Hyp-Lip外观良好，平均粒径为（124.9±3.4）nm，Zeta电位为（-6.2±1.9）mV；在胎牛血清中性状稳定，在体外释放介质中24 h累积释放量达到40%。线粒体靶向实验表明DLD/Hyp-Lip可以促进药物聚集在线粒体部位。结论 采用此方法能够精准有效的优化DLD/Hyp-Lip的制备工艺，该方法操作简单方便，可以用于DLD/Hyp-Lip制备与处方的优化，制备的DLD/Hyp-Lip包封率高，粒径小，分布均匀，且具有良好的缓释作用，为DLD/Hyp-Lip的进一步体内研究奠定了基础。载金丝桃苷的DLD/Hyp-Lip具有良好的肝癌细胞线粒体靶向性，是一种潜在高效的肝癌细胞线粒体靶向给药系统。     

Narrowing the focus: Therapeutic cell surface targets for refractory triple-negative breast cancer

Triple-negative breast cancer (TNBC) is defined as a type of breast cancer with lack of expression of estrogen receptor, progesterone receptor and human epidermal growth factor 2 protein. In comparison to other types of breast cancer, TNBC characterizes for its aggressive behavior, more prone to early recurrence and a disease with poor response to molecular target therapy. Although TNBC is identified in only 25%-30% of American breast cancer cases annually, these tumors continue to be a therapeutic challenge for clinicians for several reasons: Tumor heterogeneity, limited and toxic systemic therapy options, and often resistance to current standard therapy, characterized by progressive disease on treatment, residual tumor after cytotoxic chemotherapy, and early recurrence after complete surgical excision. Cell-surface targeted therapies have been successful for breast cancer in general, however there are currently no approved cell-surface targeted therapies specifically indicated for TNBC. Recently, several cell-surface targets have been identified as candidates for treatment of TNBC and associated targeted therapies are in development. The purpose of this work is to review the current clinical challenges posed by TNBC, the therapeutic approaches currently in use, and provide an overview of developing cell surface targeting approaches to improve outcomes for treatment resistant TNBC.     

Colitis following the use of immune checkpoint inhibitors: A real-world analysis of spontaneous reports submitted to the FDA adverse event reporting system

BackgroundAlthough colitis has been reported in patients treated with immune checkpoint inhibitors (ICIs), associations between colitis and ICIs had not been thoroughly assessed in real-world studies. Here, we identified and characterized significant colitis-associated with ICIs.MethodsBased on the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to December 2019, the disproportionality analysis and Bayesian analysis, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN) and the multi-item gamma Poisson shrinker (MGPS) algorithms were adopted to data mining of the suspected adverse events of colitis after ICIs administrating. Clinical characteristics of patients with ICIs-associated colitis and the time to onset of colitis following different ICI regimens were collected.ResultsA total of 3786 reports of colitis adverse events were identified with ICIs. Seven ICI monotherapies were associated with the reporting of colitis. Statistically significant ROR, PRR, information component (IC), and empirical Bayesian geometric mean (EBGM) emerged for all ICI monotherapies and combination therapies. ICIs-associated colitis affected mostly male (53.51%), with a wide mean age range (60.65 to 72 years). Colitis adverse events were commonly reported in patients with melanoma and lung cancer. Adverse outcomes of colitis concerning ICI were mainly outcomes of hospitalization-initiated or prolonged and other serious. Among colitis cases, 17.43% cases of colitis concerning ICI lead to death. The adverse event of colitis occurred earliest in ipilimumab monotherapy with a median time to onset of 64.21 days (IQR: 27–69 days) among all monotherapies.ConclusionsICI may lead to severe and disabling ICIs-associated colitis during therapy. Analysis of FAERS data identified signals for adverse events of colitis with ICI regimens. Practitioners should consider the factors that may increase the likelihood of colitis. The findings support a continued surveillance and risk factor identification studies.     

肺癌患者化疗后三种肿瘤标志物的表达变化及意义

目的探讨肺癌患者化疗后的癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)和鳞状上皮细胞癌抗原(SCC-Ag)表达变化。方法选取2017年5月至2020年2月间南京市六合区人民医院收治的100例肺癌患者,将这些患者作为肺癌组,另随机选取同期100例健康体检人员作为健康组。统计分析两组人员化疗前的血清NSE、CEA、SCC-Ag表达水平、肺癌组化疗成功患者化疗前后的血清NSE、CEA、SCC-Ag表达水平、肺癌组化疗失败患者化疗前后的血清NSE、CEA、SCC-Ag表达水平。结果肺癌组患者化疗前的血清NSE、CEA和SCC-Ag表达水平均高于健康组,差异均有统计学意义(均P <0.05)。肺癌组化疗成功患者化疗后的血清NSE、CEA和SCC-Ag表达水平均低于化疗前,均高于健康组,差异均有统计学意义(P <0.05)。肺癌组化疗失败患者化疗后的血清NSE、CEA、SCC-Ag表达水平均高于化疗前,均高于健康组,差异均有统计学意义(P <0.05)。结论对肺癌患者的NSE、CEA、SCC-Ag表达水平进行检测能够将化疗效果有效反映出来,进而有效指导临床的下一步治疗工作,从而有效改善患者预后。     

Imaging Features of Pulmonary Immune-related Adverse Events

Pulmonary immune-related adverse events represent rare but potentially severe side effects of immunotherapies. Diagnosis is often challenging, as symptoms and imaging features are not specific and may mimic other lung diseases, thus potentially delaying appropriate patient management. In this setting, an accurate imaging evaluation is essential for a prompt detection and correct management of these drug-induced lung diseases. The purpose of this article is to review the different types of pulmonary immune-related adverse events, describe their imaging characteristics on both high-resolution computed tomography and positron emission tomography/computed tomography and stress their underlying diagnostic challenge by presenting the mimickers.     

Primary vaccination in adult patients after allogeneic hematopoietic stem cell transplantation – A single center retrospective efficacy analysis

Allogeneic hematopoietic stem cell transplantation (alloHSCT) results in a loss of humoral immunity and subsequent risk for severe infections. Thus, re-vaccination is required but may fail due to incomplete immune reconstitution. We retrospectively analyzed predictors of immune response to primary vaccination applied according to the EBMT (European Blood and Marrow Transplantation Group) recommendations. Serologic response to vaccination against diphtheria (D), tetanus (T), Bordetella pertussis (aP) and Haemophilus influenzae (Hib) (administrated as combined DTaP-Hib-IPV vaccination) was studied in 84 alloHSCT patients transplanted between 2008 and 2015 (age at alloHSCT: 18.6–70.6 years). All patients with a relapse-free survival of ≥9 months, at least 3 consecutive vaccinations and absence of intravenous immunoglobulin administration within 3 months before and after vaccination met the primary inclusion criteria. Additionally, immunological response to a pneumococcal conjugate vaccine was analyzed in a subgroup of 67 patients. Patients’ characteristics at the time of first vaccination were recorded. Responses were measured as vaccine-specific antibody titers. Regarding DTaP-Hib-IPV vaccination, 89.3% (n = 75) of all patients achieved protective titers to at least 3 of the 4 vaccine components and were thus considered responders. 10.7% (n = 9) of the patients were classified as non-responders with positive immune response to less than 3 components. Highest response was observed for Hib (97.4%), tetanus (95.2%) and pneumococcal vaccination (83.6%) while only 68.3% responded to vaccination against Bordetella pertussis. Significant risk factors for failure of vaccination response included low B cell counts (p < 0.001; cut-off: 0.05 B cells/nl) and low IgG levels (p = 0.026; mean IgG of responders 816 mg/dl vs. 475 mg/dl of non-responders). Further, a trend was observed that prior cGvHD impairs vaccination response as 88.9% of the non-responders but only 54.7% of the responders had prior cGvHD (p = 0.073). The results demonstrate, that the currently proposed vaccination strategy leads to seroprotection in the majority of alloHSCT patients.