Rucaparib in the landscape of PARP inhibition in ovarian cancer

Introduction: The landscape of poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer is rapidly evolving and becoming increasingly complex. Ovarian cancer is leading therapeutic innovation by providing the proof of concept for DNA repair as a target. Three different PARP inhibitors have now received approvals in the US and Europe in different indications. Subtle but crucial differences can be found among the licensed indications for each PARP inhibitor in terms of histology, type of BRCA mutation (germline and/or somatic), number of prior lines of chemotherapy and whether the indication is in the treatment or maintenance settings.

Areas covered: We review the latest clinical data regarding the PARP inhibitor rucaparib in ovarian cancer, provide an update on the evolving landscape of PARP inhibition in ovarian cancer, and summarize avenues of ongoing and future research.

Expert opinion: All eligible patients should be offered a PARP inhibitor. SOLO1 trial results demonstrated an unprecedented benefit maintenance with PARP inhibitors in first line. Results from trials evaluating PARP inhibitors as maintenance in first line regardless of BRCA status and from trials evaluating combinatorial strategies are eagerly awaited.     

双环[1.1.1]戊烷衍生物的合成研究进展

双环[1.1.1]戊烷（BCP）是一种具有三维立体结构的桥环骨架，其作为苯环、叔丁基和炔烃的生物电子等排体，已经在药物化学领域得到广泛的应用。随着BCP应用范围的扩大，BCP及其衍生物的合成日益成为研究的热点。本文对BCP衍生物的主要合成策略和方法进行总结，旨在为新药研发人员提供参考。     

In vivo induction of CD4+ T cell responses by antigens covalently linked to synthetic microspheres does not require adjuvant

Macrophages, dendritic cells or B lymphocytes have been shownto play a major role in the presentation of soluble antigensto CD4⁺ T cells. In contrast, the capacity of these cells topresent particulate antigens such as bacterial or parasiticantigens to T cells remains controversial. To investigate thisquestion, well defined particulate antigens were prepared bycovalent linkage of proteins or peptides to 1 µm in diametersynthetic microspheres. The T cell immunogenicity of such particulateantigens was analyzed in vitro and in vivo. In vitro, a solubleprotein such as hen egg lysozyme (HEL) coupled to beads stimulateda strong proliferative T cell response of lymph node cells fromHEL-primed mice or of specific T cell hybridomas. HEL coupledto beads was presented to the specific T cell hybridomas bysplenocytes or by peritoneal macrophages, but not by lymphomaB cells. Immunization of mice with several different proteinantigens or with a synthetic peptide covalently linked to beadsinduced strong CD4⁺ T cell responses in the absence of adjuvant.The strong in vivo immunogenicity of proteins coupled to beadsdid not result from a non-specific adjuvant effect of beadssince covalent linkage of the antigen to beads was strictlyrequired to induce T cell responses in the absence of adjuvant.In vivo treatment by carrageenan showed that macrophages arerequired for the in vivo stimulation of T cell responses bythese particulate antigens. Thus, these results demonstratedthe role of phagocytic cells, especially macrophages, for invivo presentation of particulate antigens. These particulateantigens represent an interesting approach for the developmentof new vaccines, and for the in vivo analysis of the role ofvarious antigen presenting cells in T cell activation and differentiation.     

The modified Evan's blue dye procedure fails to detect aspiration in the tracheostomized patient: Five case reports

The modified Evan's blue dye procedure (MEBD) is a method of performing tracheal suctioning of the patient through the tracheostomy tube after administration of color-contrasted food and liquid. The MEBD is done when radiographic or fiberoptic procedures are not available or practical. In 5 tracheostomized patients, the MEBD does not detect aspiration.     

ONCOCYTES OF THE THYROID: A NEUTRAL RED DYE UPTAKE STUDY

Oncocytosis and oncocytomas have attracted attention because on the one hand there have been reports of the favourable prognosis and generally benign nature of oncocytic tumours, while on the other hand, Hurthle cell change in thyroid neoplasms have been reported to be correlated with aggressive biological behaviour and a significantly worse clinical course. Presently, there appear to be two schools of thought on the significance of oncocytosis: (i) a process where there is redifferentiation of cells with involvement in the pathogenesis of cancer; and (ii) a compensatory process for ‘functional exhaustion’ of the cell. Many aspects of oncocytosis seem unclear. In this study, transmission electron microscopy is used to demonstrate the presence of thyroid oncocytes in the hemithyroidectomy specimen of a patient with focal lymphocytic thyroiditis. Tissue sections from this specimen did not display preferential uptake of neutral red dye, a distinctive characteristic of M-phase cancer cells which was previously reported. The findings seem to suggest that oncocytes are not cells with distinctive proliferative potentials. If that were the case, then oncogenesis or cancer cell progression and oncocytosis may not be convergent processes.     

人工合成成骨生长肽对辐射损伤小鼠造血功能的保护作用

目的　探讨人工合成成骨生长肽 (sOGP)对辐射损伤小鼠造血功能的保护作用 ,阐明其剂量 效应关系。方法　以 4 .0和 7.5Gy13 7Csγ射线照射小鼠为模型 ,采用皮下注射和肌肉注射 2种给药途径连续 8d给予sOGP ,剂量范围为 0 .0 39～ 6 4 0nmol/(kg·d) ,观察外周血象、骨髓有核细胞数、骨髓粒系造血祖细胞集落形成(CFU G)、骨髓细胞分类和骨髓切片组织学等的变化。结果　sOGP能加快受照小鼠外周血白细胞、骨髓有核细胞数的恢复 ,在一定的剂量范围内呈明显的剂量依赖性 ,并能刺激髓外造血 ;促进 (CFU G)形成作用显著高于重组人粒系集落刺激因子 (rhG CSF)约 2倍 ;骨髓病理学观察显示sOGP能加快受照小鼠骨髓造血组织损伤的恢复 ,刺激骨髓粒系增生。结论　sOGP可明显促进受照射小鼠造血功能的恢复 ,其机制可能是通过作用于早期造血阶段或 (及 )改善微环境进而促进造血。     

乳液聚合型品红成色剂的应用性能

测试了3种新型L-品红成色剂的应用性能。结果表明：与母体品红成色剂相比，L-品红成色剂能显著地减少在蓝光区的有害吸收；与工业用油溶性品红成色剂Ns相比，L-品红成色剂的一些照相性能更加优越。     

Synthesis of a new carrier for immunization: polytuftsin

Sequential poly(Arg-Thr-Lys-Pro) consisting mainly of the repeat of tuftsin Thr-Lys-Pro-Arg was synthesized by condensing the p-nitrophenyl ester of Arg(HCI)-Thr-Lys-(2-CI-Z)-Pro in the presence of HOBt . Two haptenic sequences of the Pre-S region of hepatitis B virus antigen (10–26 and 39–55) were prepared by solid phase and coupled to polytuftsin via glutaraldehyde. The peptides, either free or coupled to polytuftsin, were administrated to mice and the antisera were assayed by ELISA . Coupling the peptides to the polypeptide significantly improved the anti-peptide antibody titer in Freund complete adjuvant or in NaCI 0.9%. Cross-reaction between antibodies induced by the peptides and the native protein was also improved. Polytuftsin alone is very poorly immunogenic.     

595 nm可调脉冲染料激光治疗皮肤血管异常性疾病疗效分析

目的观察595nm可调脉冲染料激光治疗皮肤血管异常性疾病(血管畸形与血管瘤)的临床疗效。方法应用595nm可调脉冲染料激光治疗396例皮肤血管异常性疾病,观察临床疗效。结果毛细血管扩张和蜘蛛痣疗效最好,有效率为100%,其次是草莓状血管瘤,有效率为92.4%,鲜红斑痣为82.8%。面积越小,年龄越小,疗效越好(P<0.05);性别与疗效无明显差异。术中疼痛较轻,术后副作用少。结论595nm可调脉冲染料激光治疗皮肤血管异常性疾病安全性高,疗效确切。     

Does dye laser treatment with higher fluences in combination with cold air cooling improve the results of port‐wine stains?

BACKGROUND AND OBJECTIVE: The use of cold air cooling (CAC) and cryogen spray cooling during dye laser treatment of port-wine stains (PWS) has become a standard in recent years. Still unsolved is the question of which fluences are necessary in combination with CAC in order to achieve an optimum clearance and the lowest possible rate of side-effects. STUDY DESIGN: In a prospective study, we treated 11 patients with PWS with pulsed dye laser (Photogenica V, Cynosure, lambda = 585 nm, iota(p) = 0.5 ms, spot size = 7 mm). Each PWS was partitioned into three areas: (area 1) 6 J/cm(2) without CAC, (area 2) 6 J/cm(2) with CAC (level 4), (area 3) 9 J/cm(2) with CAC (level 4). RESULTS: Area 3 (mean, 59%) showed a slightly better clearance than area 1 (mean, 57%); in area 2, we observed a reduced clearance (mean, 45%). Compared with area 1, we achieved a reduction of pain through CAC in areas 2 and 3. The healing periods as well as the rate of side-effects were comparable in all areas. CONCLUSION: We observed a slight but not statistically relevant increase in clearance with the use of higher fluences and CAC compared with lower fluences without CAC. Because pain is lowered significantly when using CAC, and because this makes the treatment more comfortable for the patients, we tend to recommend the use of higher fluences (9 J/cm(2)) with simultaneous CAC for treating PWS.