Efficacy of edelfosine lipid nanoparticles in breast cancer cells

Breast cancer is a heterogeneous group of neoplasms predominantly originating in the terminal duct lobular units. It represents the leading cause of cancer death in women and the survival frequencies for patients at advanced stages of the disease remain low. New treatment options need to be researched to improve these rates. The anti-tumor ether lipid edelfosine (ET) is the prototype of a novel generation of promising anticancer drugs. However, it presents several drawbacks for its use in cancer therapy, including gastrointestinal and hemolytic toxicity and low oral bioavailability. To overcome these obstacles, ET was encapsulated in Precirol ATO 5 lipid nanoparticles (ET-LN), and its anti-tumor potential was in vitro tested in breast cancer. The formulated ET-LN were more effective in inhibiting cell proliferation and notably decreased cell viability, showing that the cytotoxic effect of ET was considerably enhanced when ET was encapsulated. In addition, ET and ET-LN were able to promote cell cycle arrest at G1 phase. Moreover, although both treatments provoked an apoptotic effect in a time-dependent manner, such anti-tumor effects were noticeably improved with ET-LN treatment. Therefore, our results indicate that encapsulating ET in LN played an essential role in improving the efficacy of the drug.     

子宫内膜异位症患者腹腔液中sICAM-1、TGF-β1、LN与盆腔粘连的关系

目的:探讨子宫内膜异位症(内异症)患者腹腔液中可溶性细胞黏附分子-1(sICAM-1)、转化生长因子-β1(TGF-β1)、层粘连蛋白(LN)与盆腔粘连的关系。方法:采用酶联免疫吸附试验及放射免疫分析方法测定内异症不同粘连程度腹腔液中sICAM-1、TGF-β1、LN的含量,并进行分析。结果:子宫内膜异位症患者中有粘连的各组腹腔液中sICAM-1、TGF-β1、LN高于无粘连组,差异有统计学意义(P<0.05),sICAM-1在粘连组组间比较差异无统计学意义(P>0.05),TGF-β1在轻、中、重度粘连各组之间比较,中、重度组之间比较,差异无统计学意义(P>0.05),但中、重度粘连组与轻度粘连组比较,差异有统计学意义(P<0.05),LN在有粘连各组间比较,差异无统计学意义(P>0.05)。结论:黏附相关因子sICAM-1、TGF-β1、LN在内异症盆腔粘连过程中起着重要作用。     

Long-term persistence of immunity induced by OVA-coupled gas-filled microbubble vaccination partially protects mice against infection by OVA-expressing Listeria

Vaccination aims at generating memory immune responses able to protect individuals against pathogenic challenges over long periods of time. Subunit vaccine formulations based on safe, but poorly immunogenic, antigenic entities must be combined with adjuvant molecules to make them efficient against infections. We have previously shown that gas-filled microbubbles (MB) are potent antigen-delivery systems. This study compares the ability of various ovalbumin-associated MB (OVA-MB) formulations to induce antigen-specific memory immune responses and evaluates long-term protection toward bacterial infections. When initially testing dendritic cells reactivity to MB constituents, palmitic acid exhibited the highest degree of activation. Subcutaneous immunization of naïve wild-type mice with the OVA-MB formulation comprising the highest palmitic acid content and devoid of PEG2000 was found to trigger the more pronounced Th1-type response, as reflected by robust IFN-γ and IL-2 production. Both T cell and antibody responses persisted for at least 6 months after immunization. At that time, systemic infection with OVA-expressing Listeria monocytgenes was performed. Partial protection of vaccinated mice was demonstrated by reduction of the bacterial load in both the spleen and liver. We conclude that antigen-bound MB exhibit promising properties as a vaccine candidate ensuring prolonged maintenance of protective immunity.     

Long term follow-up of infliximab efficacy in pulmonary and extra-pulmonary sarcoidosis refractory to conventional therapy

Introduction

Infliximab, a humanized, chimeric, monoclonal antibody against tumor necrosis alpha (TNF-α), has been shown to reduce the pulmonary and extra-pulmonary manifestations of sarcoidosis, however, there is little information regarding sustained efficacy with long-term use of infliximab. We retrospectively investigate whether a reduction in disease response is maintained, over a prolonged course of therapy (up to 85 months) with infliximab, and report on adverse events associated with its use.

Methods

Subjects with multi-organ sarcoidosis were prescribed infliximab, between January 2000 to June 2010 due to failure of conventional therapy and were identified from the Drexel University College of Medicine sarcoidosis clinic. Retrospective patient reported symptom and objective clinical data analyses of pulmonary and extra-pulmonary findings were evaluated pre-infliximab and post or concurrent infliximab therapy. Any adverse events or reasons for discontinuation during infliximab therapy were reported.

Results

Twenty-six patients with biopsy proven sarcoidosis received anti-TNF therapy and met the criteria for study inclusion. Clinical evidence of sustained resolution or improvement was demonstrated in 58.5% of all organs assessed (p =<0.001). No clinical change in disease activity was seen in 35.8% of all organs evaluated. Despite infliximab treatment, 5.7% had progressive disease activity. Adverse events were seen in 57.7% of patients treated with infliximab over a 46.2 month average duration of therapy. Three (12%) patients had an adverse event that required permanent discontinuation.

Conclusions

Infliximab is efficacious in the treatment of extra-pulmonary sarcoidosis and the efficacy is maintained with prolonged treatment. In patients with pulmonary sarcoid, sustained improvement in pulmonary imaging was seen after initiation of infliximab, however, post-treatment pulmonary function testing was not conclusive. Long-term infliximab therapy was well tolerated for our study group.     

Conventional transbronchial needle aspiration decreases the rate of surgical sampling of intrathoracic lymphadenopathy

BACKGROUND: Previous studies have suggested a decreased need for the surgical biopsy of intrathoracic lymph nodes (LNs) due to improved diagnostic rates utilizing transbronchial needle aspiration (TBNA) with endobronchial ultrasound and endoscopic ultrasound. The goal of this study was to determine whether conventional TBNA using combined cytologic and histologic analysis of tissue specimens impacted the rates of surgical diagnostic biopsies of patients with intrathoracic lymphadenopathy. METHODS: Retrospective review at a single academic center. All mediastinal and hilar tissue samples submitted for pathologic analysis over an 8.4-year period were analyzed. Patients were categorized into a "before" group and an "after" group based on two different time periods. The before group underwent only cytologic analysis of Wang needle (19-gauge or 21-gauge) aspirates. The after group had cytologic analysis of aspirates as well as histologic analysis of needle "core" (19 gauge) biopsy specimens. The groups were compared for the rate of intrathoracic LNs sampled by surgical means vs TBNA and the number of times that TBNA averted the need for a surgical diagnostic procedure. RESULTS: The success of TBNA increased significantly in the after group compared to that in the before group. The yield for the successful sampling of mediastinal and hilar LNs increased from 53 to 91% (p < 0.001) in the before group vs the after group. TBNA averted a surgical biopsy in 35% of the before cases compared to 66% of the after cases (p < 0.001). CONCLUSIONS: Conventional TBNA using large-bore needles with both cytology and surgical pathology evaluation decreases the need for surgical sampling of the mediastinum to diagnose thoracic lymphadenopathy.     

Significance of extranodal extension of regional lymph nodes in surgically resected non-small cell lung cancer

STUDY OBJECTIVES: Regional lymph node (LN) involvement affects the prognosis of patients with surgically resected non-small cell lung cancer (NSCLC). The significance of extranodal extension in these groups of patients was prospectively studied to determine its clinicopathologic relationships and its influence on patient survival. METHODS: A total of 199 NSCLC patients who were proved to have regional LN involvement after resection were included. Histologic examinations including tumor cell type, grade of differentiation, vascular invasion, regional LN metastasis emphasizing the number and station of LN involvement, the presence or absence of extranodal extension, and the immunohistochemistry of p53 expression were obtained. The relationships between extranodal extension and histologic type, grade of differentiation, vascular invasion, tumor size, pathologic stage, p53 expression, or patient survival were analyzed. RESULTS: Extranodal extension was significantly higher in women, adenocarcinoma, advanced stage, tumors with vascular invasion, or p53 overexpression. The total number and positive rate of resected LNs with extranodal extension were significantly correlated with advanced stage, tumors with vascular invasion, or p53 overexpression. By multivariate analysis of survival, the presence or total number of LNs with extranodal extension, tumor stage, and p53 expression were significant prognostic factors. The 5-year survival rate of stage IIIA patients without extranodal extension (30.4%) was significantly better than that of stage II patients with extranodal extension (16.8%). No survival difference between extranodal positive stage II and IIIA patients was noted. CONCLUSIONS: Extranodal extension of regional LNs is an important prognostic factor in patients with surgically resected NSCLC.     

LN、MVD与实体瘤关系的研究进展

基底膜是一种维持器官正常结构及功能的特殊的细胞外基质,是上皮组织与基底膜结缔组织间的屏障,肿瘤侵袭、发展、恶变时首先要穿越突破基底膜。肿瘤组织的微血管密度能定量的反应出肿瘤血管的生长情况,进而可预示肿瘤生长、转移及复发的趋势。本文就LN的结构功能,MVD及预后功能及二者与实体瘤的关系等作一综述。     

COPD稳定期患者血清HA、LN、PCⅢ含量与BODE指数的关系

目的:探讨慢性阻塞性肺疾病(COPD)稳定期患者血清透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前肢原(PCⅢ)与BODE指数(B为体重指数,0为气流阻塞,D为呼吸困难,E为运动能力)的关系.方法:选择60例稳定期COPD患者、20例正常组对比,检测其外周血清HA、LN、PCⅢ含量水平,及其与BODE指数的相关性分析,探讨其在评价COPD患者病情严重程度及预后中的价值.结果:COPD患者血清HA、LN、PCⅢ含量水平均较正常对照组显著升高(P＜0.05、P＜0.001);中医证型以为血瘀证38.33％、肾阳虚证31.67％为主;相关性分析提示:血清HA、LN、PCⅢ水平,与BODE指数、MMRC、年龄、病史呈正相关(P＜0.05、P＜0.001),与FEV1％ pred、6MWD、BMI则呈负相关(P ＜0.05、P＜0.001).结论:肾虚血瘀是COPD基本病理机制.血清HA、LN、PCⅢ的水平在一定程度上反映了肺组织的损害及继发肺间质纤维化的病理过程,是反映肺疾病,尤其是肺间质性疾病的一项新指标.     

层粘连蛋白与脑微血管内皮细胞对神经干细胞分化的影响

目的 探讨层粘连蛋白(LN )与脑微血管内皮细胞(CMECs)在体外对神经干细胞(NSCs)分化的影响. 方法原代分离培养CMECs和NSCs.实验分为对照组(NSCs+NSCs完全培养基)和处理组(NSCs+NSCs完全培养基+LN+ CMECs),分别于6 h、1天、3天、7天等时间点用免疫细胞化学方法比较两组NSCs的分化情况. 结果从第1天开始处理组 NSCs的神经元分化率较对照组增加(P<0.05),从第3天开始, 处理组较对照组星型胶质细胞分化率下降(P<0.05). 结论 LN及CMECs可使NSCs神经元分化比率提高.