Proteases and their inhibitors as prognostic factors for high-grade serous ovarian cancer

Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance.     

Ghrelin after chemotherapy as a prognostic predictor of progression-free survival in patients with muscle-invasive bladder cancer

BackgroundAlthough the patients with muscle-invasive bladder cancer (MIBC) generally have poor prognosis, the utility of these biomarkers for the prediction of oncological outcomes in MIBC has not been completely explored. Ghrelin regulates processes associated with cancer, including cell proliferation, apoptosis, cell migration, cell invasion, and angiogenesis. Thus, we aimed to evaluate the impact of serum ghrelin levels on survival in MIBC.MethodsIn this study, we reviewed the clinical and pathological records of 56 patients who were diagnosed with MIBC between November 2015 and November 2019 at Gifu and Hirosaki University Hospitals. We focused on 27 patients who had received chemotherapy and collected blood samples before and after chemotherapy. Blood samples were collected before chemotherapy and after completing two cycles of chemotherapy. Serum acyl (AG) and desacyl ghrelin (DG) were measured using AG and DG enzyme-linked immunosorbent assay kits (SCETI, Tokyo, Japan), respectively.ResultsThe 3-year overall and progression-free survival (PFS) rates were 82.9% and 68.3%, respectively. According to the AG level after chemotherapy, the 3-year PFS rates were 77.5% and 53.0% in patients with AG levels ≥1.34 and <1.34 pg/mL, respectively (P=0.038). With regard to DG levels after chemotherapy, the 3-year PFS rates were 90.9% and 43.3% in patients with DG levels <92.3 and ≥92.3 pg/mL, respectively (P=0.039). On multivariate analysis, serum AG levels were significantly associated with PFS.ConclusionsThis study suggested the usefulness of the ghrelin as a prognostic predictor of PFS in patients with MIBC.     

IDO1 高表达与肺鳞癌临床分期及不良预后相关

目的 探讨不同分期肺鳞癌组织中 IDO1 的表达情况及与预后的关系。 方法 纳入河北医科大学 附属医院邢台市人民医院胸外科自 2017 年 1 月至 2019 年 1 月开展手术根治的肺鳞癌患者, 留取患者术中 癌组织标本, 用免疫组织化学染色法检测 IDO1 的表达情况, 并对患者进行术后随访。 结果 肺鳞癌组织 中有 IDO1 蛋白表达, 且临床Ⅱ ~ Ⅲ期阳性细胞数显著高于Ⅰ期。 截止随访结束时, 30 例患者中 28 例存 活, 2 例死亡, 疾病稳定 22 例 (73. 3 % ), 疾病进展 8 例 (26. 7 % )。 IDO1 高表达组和低表达组的无进展 生存期 (PFS) 分别为 26 个月和 40 个月, 差异具有统计学意义 (P< 0. 05); 高临床分期和低临床分期 PFS 分别为 33 个月和 40 个月, 差异具有统计学意义 (P< 0. 05)。 结论 IDO1 在肺鳞癌中表达量与临床分期有 关, 临床分期越高表达量越高, 患者预后也越差; IDO1 能指导临床分期和预后。     

基于伪F统计量的模糊聚类方法在医疗质量综合评价中的应用

目的探讨一种新的基于伪F统计量的最佳聚类分析方法,该方法不需要预先选择类的数目作为先验值.并有效地应用于医疗质量的综合评价.方法首先,应用FCM模糊聚类法(Fuzzy Clustering Method)进行聚类,然后应用PFS(Pseudo F-statistics)统计量作为一个判别函数来确定最佳类数目.结果将该方法应用于某院2002年度各科室医疗质量综合评价,得到了一种合理的综合评价结果.结论该方法基于没有聚类数据的任何先验知识和组成成分信息的前提下,考虑如何确定数据的分类结构.根据应用的情况,发现该方法是医疗质量综合评价的有力工具.     

The circulating tumor DNA (ctDNA) alteration level predicts therapeutic response in metastatic breast cancer: Novel prognostic indexes based on ctDNA

PurposeCirculating tumor DNA (ctDNA) has good clinical guiding value for metastatic breast cancer (MBC) patients. This study aimed to apply a novel genetic analysis approach for therapeutic prediction based on ctDNA alterations.MethodThis nonrandomized, multicenter study recruited 223 MBC patients (NCT05079074). Plasma samples were collected for target-capture deep sequencing of ctDNA at baseline, after the 2nd cycle of treatment, and when progressive disease (PD) was evaluated. Samples were categorized into four levels according to the number of ctDNA alterations: level 1 (no alterations), level 2 (1–2 alterations), level 3 (3–4 alterations) and level 4 (≥5 alterations). According to ctDNA alteration level and variant allele frequency (VAF), a novel ctDNA-level Response Evaluation Criterion in Solid Tumors (ctle-RECIST) was established to assess treatment response and predict progression-free survival (PFS).ResultsThe median PFS in level 1 (6.63 months) patients was significantly longer than that in level 2–4 patients (level 2: 5.70 months; level 3–4: 4.90 months, p < 0.05). After 2 cycles of treatment, based on ctle-RECIST, the median PFS of level-based disease control rate (lev-DCR) patients was significantly longer than that of level-based PD (lev-PD) patients [HR 2.42 (1.52–3.85), p < 0.001]. In addition, we found that ctDNA level assessment could be a good supplement to radiologic assessment. The median PFS in the dual-DCR group tended to be longer than that in the single-DCR group [HR 1.41 (0.93–2.13), p = 0.107].ConclusionThe ctDNA alteration level and ctle-RECIST could be novel biomarkers of prognosis and could complement radiologic assessment in MBC.     

Silicone Oil-Free Polymer Syringes for the Storage of Therapeutic Proteins

Prefilled syringes are a popular choice for the delivery of biopharmaceuticals. However, glass syringes might not be the optimal primary packaging material for all biopharmaceuticals. There is evidence that the necessary lubricant silicone oil in glass syringes can interact with proteins and can be shed from the surface into the product solution. In recent years, silicone oil-free polymer syringes were developed. Despite several advantages, however, a major shortcoming of these polymer systems is their relatively high gas permeability, which might be a limitation for the storage of oxygen sensitive biopharmaceuticals. So far, no long-term protein stability studies regarding such polymer systems have been published. In this study, 2 therapeutic proteins were stored in glass syringes and in silicone oil-free polymer syringes. In addition, polymer syringes stored in nitrogen-filled aluminum pouches or covered with oxygen-tight labels were included. Similar chemical protein stability was achieved at 4°C for all syringes. However, in contrast to the polymer syringes, high particle counts were observed in the glass syringes. Polymer syringes stored in nitrogen-filled aluminum pouches presented a promising alternative for the storage of biopharmaceuticals as they do not expose patients to silicone oil and silicone oil-protein aggregates.     

金复康口服液联合培美曲塞治疗非小细胞肺癌的临床研究

目的研究金复康口服液联合注射用培美曲塞二钠治疗非小细胞肺癌的临床疗效。方法选取2016年1月—2018年1月南京市胸科医院诊治的120例非小细胞肺癌患者作为研究对象,采用随机对照表法将患者分为对照组和治疗组,每组各60例。对照组静脉滴注注射用培美曲塞二钠500 mg/m~2,静脉输注10 min以上;治疗组患者在对照组治疗的基础上口服金复康口服液,30 mL/次,3次/d。21 d为1个疗程,两组均持续治疗2个疗程。观察两组患者的临床疗效,同时比较两组治疗前后的生活质量(QOL)评分、KPS评分、无进展生存期(PFS)、总生存期(OS)和免疫功能指标水平。结果治疗后,对照组和治疗组的客观缓解率和疾病控制率比较差异无统计学意义。治疗后,两组患者QOL和KPS评分均显著升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组QOL评分和KPS评分显著高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组患者PFS和OS显著长于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者CD3+、CD4+、NK和CD4+/CD8+水平显著升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组免疫功能指标水平显著高于对照组,两组比较差异具有统计学意义(P0.05)。结论金复康口服液联合注射用培美曲塞二钠治疗非小细胞肺癌具有较好的临床疗效,能够改善患者生活质量,提高免疫功能,且安全性较高,具有一定临床推广应用价值。     

肺癌患者血清肿瘤标记物检测的临床意义及预后评估

目的评估血清癌胚抗原(CEA)、细胞角蛋白19片段(CYFRA21-1)和特异性烯醇化酶(NSE)水平在肺癌诊断中的价值,探讨三项肿瘤标记物血清水平与患者临床特征、化疗疗效和预后的关系。方法采用化学发光法检测227例肺癌患者和60例肺良性疾病患者血清中CEA、CYFRA21-1、NSE含量,同时收集患者完整的临床资料,随访患者无进展生存时间(PFS),使用SPSS17.0软件对所得数据进行统计分析。结果 1肺癌组血清CEA、CYFRA21-1、NSE水平明显高于肺良性疾病组(P0.01);CEA、CYFRA21-1、NSE的ROC曲线下面积分别是0.8、0.6、0.8,均大于0.5。腺癌、鳞癌、小细胞肺癌分别以CEA、CYFRA21-1、NSE检测灵敏度最高(P0.01)。三项肿瘤标记物联合检测较单项检测诊断灵敏度显著提高。2与I+II期患者比较,IV期肺癌患者CEA、CYFRA21-1、NSE水平明显升高(P0.05);胸外转移组三项肿瘤标记物均显著高于无转移组(P0.05)。3疾病进展(PD)组患者的治疗前血清CYFRA21-1、NSE水平明显高于疾病控制(DC)组(P0.05)。4治疗前血清CYFRA21-1、NSE水平正常的患者PFS明显长于升高者(P0.05)。结论血清CEA、CYFRA21-1和NSE检测有助于肺癌的诊断,联合检测更优,且对鉴别肺癌与肺部良性疾病、有无转移的评价及肺癌不同病理类型和分期有一定的参考价值;同时,治疗前CYFRA21-1和NSE血清水平可以评估肺癌的预后,观察治疗效果。