Prognostic factors and survival outcomes of women with uterine leiomyosarcoma: A Turkish Uterine Sarcoma Group Study-003

To assess the clinicopathological features, prognostic factors, and survival rates associated with uterine leiomyosarcoma (uLMS). Databases from 15 participating gynecological oncology centers in Turkey were searched retrospectively for women who had been treated for stage I-IV uLMS between 1996 and 2018. Of 302 consecutive women with uLMS, there were 234 patients with Federation of Gynecology and Obstetrics (FIGO) stage I disease and 68 with FIGO stage II-IV disease. All patients underwent total hysterectomy. Lymphadenectomy was performed in 161 (54.5%) cases. A total of 195 patients received adjuvant treatment. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 42% and 54%, respectively. Presence of lymphovascular space invasion (LVSI), higher degree of nuclear atypia, and absence of lymphadenectomy were negatively correlated with DFS, while LVSI, mitotic count, higher degree of nuclear atypia, FIGO stage II-IV disease, and suboptimal surgery significantly decreased OS. LVSI and higher degree of nuclear atypia appear to be prognostic indicators for uLMS. Lymphadenectomy seems to have a significant effect on DFS but not on OS.     

Anti-hepatoma human single-chain Fv antibody and adriamycin conjugates with potent antitumor activity

To construct an improved biological missile, an immunoconjugate ADM–Dex–ScFv-SA3 was synthesized, which was composed of a hepatocellular carcinoma-specific, single-chain Fv antibody (ScFv-SA3) and a highly potent cytotoxic drug, adriamycin (ADM), as the warhead. Oxidized Dextran T10 (Dex-T10) was used as a linker to connect these two moieties. The 40 KD soluble anti-hepatoma human Trx-ScFv-SA3 protein was expressed in E. coli BL21 (DE3), using a prokaryotic expression vector, pET21a (+)-Trx-ScFv-SA3-His. It was purified using a His-Tag Ni-Agarose column and identified by western blot. The activity of Trx-ScFv-SA3 was verified by enzyme-linked immunosorbent assay (ELISA) and immunocytochemistry to confirm that it specifically binds to the hepatocellular carcinoma cell line HepG2. To prepare ADM–Dex–ScFv-SA3, ADM was conjugated to the antibody at a molar ratio of 14.21:1. The antitumor effect of the conjugate was tested by MTT assay, plate colony formation assay and xenografts in a nude mice experimental model. In vitro experiments revealed that ADM–Dex–ScFv-SA3 could bind to tumor cells selectively and inhibit the proliferation and the colony formation ability of HepG2 cells. In vivo experiments showed that ADM–Dex–ScFv-SA3 suppressed the tumor growth and prolonged the median survival time in tumor-bearing mice. Tumor histology slides indicated a significantly slower tumor tissue proliferation in the ADM–Dex–ScFv-SA3 group. These data indicate that the targeted drug, ADM–Dex–ScFv-SA3, may be a highly potent and selective therapy for the treatment of hepatoma.     

Novel vaccine concept based on back-boost effect in viral infection

A novel vaccine concept is discussed based on recent evidence of a “back-boost” effect in Influenza infection. The initial immune response to the infection is imprinted through an immune memory pathway. The immune memory in the back-boost mechanism could be used in reversed order as a “forward-boost” in the proposed vaccine concept.     

低剂量结合雌激素与标准剂量CEE联合天然黄体酮或地屈孕酮对围绝经期综合征患者骨密度的影响研究

目的探讨低剂量雌激素与标准剂量雌激素联合天然黄体酮或地屈孕酮对围绝经期综合征患者骨密度的影响。方法选取2015年1月至2017年1月间我院收治的围绝经期综合征患者83例,按照随机数字表法将其分为Ⅰ组、Ⅱ组、Ⅲ组、Ⅳ组,Ⅰ组28例采用低剂量雌激素联合天然黄体酮治疗,Ⅱ组27例采用低剂量雌激素联合地屈孕酮治疗,Ⅲ组26例采用标准剂量雌激素联合天然黄体酮治疗,Ⅳ组26例采用标准剂量雌激素联合地屈孕酮治疗,对比各组治疗前后体内相关激素水平、更年期Kupperman评分结果、不良反应等。结果治疗前四组临床症状及促卵泡素(FSH)、黄体生成素(LH)、雌二醇(E2)等各项指标对比差异无统计学意义(P0. 05);治疗1个周期及3个周期后,各组Greene评分均有所降低,且各组FSH、E2、LH较治疗前有不同程度的好转,其中Ⅰ组和Ⅲ组FSH高于其他组别,E2、LH水平明显低于其他组,差异有统计学意义(P0. 05),治疗前各组L_(1～4)骨密度、股骨颈骨密度差异对比无统计学意义(P0. 05);治疗后各组L_(1～4)骨密度、股骨颈骨密度均有所提升,但相比之下,Ⅰ组和Ⅲ组的L_(1～4)骨密度、股骨颈骨密度好转情况更加显著,差异有统计学意义(P0. 05)。结论采用低剂量雌激素联合天然黄体酮既能满足患者症状缓解的需求,同时也有助于体内激素水平的改善,且不会对骨密度造成负面影响,建议采纳。     

Targeting AMCase reduces esophageal eosinophilic inflammation and remodeling in a mouse model of egg induced eosinophilic esophagitis

Studies of AMCase inhibition in mouse models of lung eosinophilic inflammation have produced conflicting results with some studies demonstrating inhibition of eosinophilic inflammation and others not. No studies have investigated the role of AMCase inhibition in eosinophilic esophagitis (EoE). We have used a mouse model of egg (OVA) induced EoE to determine whether pharmacologic inhibition of AMCase with allosamidin reduced eosinophilic inflammation and remodeling in the esophagus in EoE. Administration of intra-esophageal OVA for 6 weeks to BALB/c mice induced increased levels of esophageal eosinophils, mast cells, and features of esophageal remodeling (fibrosis, basal zone hyperplasia, deposition of the extracellular matrix protein fibronectin). Administration of intraperitoneal (ip) allosamidin to BALB/c mice significantly inhibited AMCase enzymatic activity in the esophagus. Pharmacologic inhibition of AMCase with ip allosamidin inhibited both OVA induced increases in esophageal eosinophilic inflammation and OVA induced esophageal remodeling (fibrosis, epithelial basal zone hyperplasia, extracellular matrix deposition of fibronectin). This inhibition of eosinophilic inflammation in the esophagus by ip allosamidin was associated with reduced eotaxin-1 expression in the esophagus. Oral allosamidin inhibited eosinophilic inflammation in the epithelium but did not inhibit esophageal remodeling. These studies suggest that pharmacologic inhibition of AMCase results in inhibition of eosinophilic inflammation and remodeling in the esophagus in a mouse model of egg induced EoE partially through effects in the esophagus on reducing chemokines (i.e. eotaxin-1) implicated in the pathogenesis of EoE.     

中-重度压力性尿失禁仿生物理治疗与TVT-O手术疗效的对比研究

目的探讨仿生物理治疗及无张力经闭孔阴道吊带术(tension-free vaginal tape obturator technique,TVT-O)治疗压力性尿失禁的疗效,并行对比分析。方法选取确诊为中-重度压力性尿失禁的患者108例为研究对象,根据患者意愿分为非手术组及手术组,非手术组54例,应用Phenix USB4盆底功能治疗仪进行系统仿生物理治疗3疗程,行疗效分析;手术组54例,实施TVT-O术,行疗效分析。结果非手术组1个疗程仿生物理治疗后评估,44例有效,有效率81.48%,入组成员继续坚持2疗程仿生物理治疗,疗程结束后1年复查,52例有效,其中46例治愈,1年有效率96.30%,治愈率85.19%;手术组术后即时评估,50例有效,有效率92.59%,术后1年复查,49例有效,其中47例治愈,术后1年有效率90.74%,治愈率87.04%。非手术组治疗1疗程有效率显著低于TVT-O术后即时疗效,差异有统计学意义,P0.05;但两组治疗后1年有效率及治愈率比较,差异均无统计学意义(P0.05),且手术组患者出现了围手术期相关并发症及远期并发症。结论 SUI的仿生物理治疗是一项有效的保守治疗方法,能有效缓解症状甚至治愈,预防病情进一步加重,对于中-重度压力性尿失禁患者而言,其远期治疗效果与手术治疗效果相当,但能有效避免手术并发症,值得在临床广泛推广。     

The immune checkpoints CTLA-4 and PD-L1 in carcinomas of the uterine cervix

BackgroundEvasion of immune control is a major feature of malignant tumors. This tumor aspect is poorly studied in cervical lesions.Aim of the studyTo investigate the expression of PD-L1 and CTLA-4 in lesions of the uterine cervix.Material and methodsSixty-three cervical lesions from 52 patients were immunohistochemically studied. The 63 lesions included 27 invasive adenocarcinomas, 19 squamous cell carcinomas (SCCs), 7 adenocarcinomas in situ, and 10 high-grade squamous intraepithelial lesions (CIN3).ResultsCTLA-4 and PD-L1 tumor cell expression was found in 61.5 % and 26.9 % of the invasive cases, respectively. CTLA-4 tumor cell expression and PD-L1 tumor and immune cell expression were more often found in SCCs than in adenocarcinomas. CTLA-4 tumor cell expression was more often found in advanced FIGO tumors. PD-L1 and CTLA-4 immune cell expression was associated with lymph node metastasis. CTLA-4 expression did not affect survival. The prognosis was worse for PD-L1-expressing tumors.ConclusionCTLA-4 and PD-L1 are potential therapeutic targets in cervical cancer.     

Ureteroileoneocystostomy: the use of an ileal segment for ureteral substitution in gynecologic oncology.

OBJECTIVE: The aim of this study was to assess the results of the use of an ileal segment to restore the functional integrity of the renal tract where lower ureteric resection is necessary in gynecologic oncology surgery. METHODS: All patients in whom ureteroileoneocystostomy (UINC) was performed between March 1988 and December 2000 were identified and a retrospective review of their case notes was conducted. RESULTS: A total of 12 UINC procedures were performed on eight patients. The primary diagnoses were ovarian cancer in six cases, endometrial stromal sarcoma in one case, and vaginal carcinoma in one case. The average age of the patients at the time of their first UINC procedure was 56 years. Bilateral UINC was performed at a single episode in one patient and unilateral UINC in seven patients. Subsequent obstruction necessitated repeat or revision of the original procedure in two cases and contralateral UINC in one case. Complications included one death at 38 days from aspiration pneumonia not directly related to UINC, one pelvic abscess causing ureteric obstruction, and three cases of recurrent urinary tract infection. Follow-up ranged from 38 days to 77 months following the initial UINC procedure, with a mean of 34 months. Aside from the single postoperative death, the procedure was successful in 82% (9/11) of anastamoses on the first occasion and 100% (2/2) of anastamoses at repeat or revision surgery. There were no cases of renal failure secondary to a failed UINC. CONCLUSIONS: Ureteroileoneocystostomy is a safe and effective procedure that should be considered in cases where lower ureteric resection is necessary.