间充质干细胞对支气管肺发育不良防治的研究进展

 支气管肺发育不良（broncho-pulmonary dysplasia，BPD）是早产儿最常见的并发症之一，也是影响早产儿预后的重要因素。然而目前临床对BPD的治疗方法有限且疗效不佳，寻找BPD新的防治方案迫在眉睫。近些年，基础实验及临床研究均发现间充质干细胞移植对BPD有一定疗效，极可能成为治疗BPD新的有效手段。此文从基础和临床研究两个层面总结间充质干细胞对BPD防治作用，并对其远景进行展望。     

原发性肺鳞癌中EGFR和ALK基因突变的临床研究北大核心

目的:探讨赣南地区原发性肺鳞癌患者EGFR和ALK基因突变的特点,科学指导此类患者优选靶向用药。方法:入组73例原发性肺鳞癌病例,采用ARMS-PNA技术检测EGFR基因第18、19、20、21外显子突变,应用不平衡法检测其中60例病例的ALK融合基因,回顾性分析EGFR和ALK基因突变患者的临床病理特征。结果:EGFR基因突变8例,阳性率为10.96%(8/73),4例为L858R突变,3例为19del突变,1例为G719X突变。女性患者突变率(66.67%,2/3)明显高于男性患者(8.57%,6/70)(P=0.030),EGFR基因突变在高龄(≥60岁)、进展期(N_(1-3)、Ⅲ+Ⅳ期)患者中相对较高,但差异无统计学意义(P>0.05)。EGFR基因突变与吸烟史、T分期以及肿瘤分布位置均无相关性(P>0.05);ALK融合基因表达2例,阳性率3.33%(2/60),与患者性别、年龄、吸烟史、TNM分期及肿瘤分布类型等各临床病理特征均无相关性(P>0.05);未发现EGFR和ALK基因共存突变病例。结论:赣南地区原发性肺鳞癌患者EGFR和ALK基因突变率相对不高,EGFR基因突变以L858R和19del突变为主,且好发于女性患者,可能是患者病情进展的预测因子之一。     

What is the Potential Interplay between Microbiome and Tumor Microenvironment in Oral Squamous Cell Carcinomas?

Oral cancer, with an around 50% mortality rate, is one of the most common malignancies world-wide. It is often detected in advanced or terminal stage and has a poor prognosis, although substantial progress in cancer management. Microbiome has become an increasingly recognized factor that may contribute to the cancerous development. Oral microbiological population comprising more than 700 bacterial species, varies since saliva and different habitats of oral cavity. A shift of composition of oral microbiome from usual condition to functional inflammation to pathological state has been discovered amongst patients with premalignant disorders and oral carcinoma, with evidence suggesting the tumor microenvironment (TME) could strongly exacerbate the influence of oral microorganisms. The complex interactions taking place in either cancer formation or progression have been evaluated in several publications, however given their results’ heterogeneity, a review is needed to correctly untangle the potential correlation in this group of pro-carcinogenesis. In this review, we briefly summarize our current knowledge of the role of oral microbiome, focusing on its potential crosstalk with TME in oral squamous cell carcinomas (OSCC) more precisely, and pave the way for manipulating oral microbiome to deal with OSCC in the future.     

Growth and Nutritional Outcomes in Children Post-Haematopoietic Stem Cell Transplant without Exposure to Total Body Irradiation

AimsPoor growth in childhood cancer survivors who undergo haematopoietic stem cell transplant (HSCT) without exposure to radiation is reported anecdotally, although literature to support this is limited. The aims of this study were to assess the change in height standard deviation score (SDS) and the final adult height (FAH) in children who underwent chemotherapy-only conditioned HSCT and to identify predictors of poor growth.Materials and methodsWe conducted a retrospective hospital medical record review (1984–2010) of children (1–10 years) who underwent chemotherapy-only conditioned HSCT, noting anthropology measurements at cancer diagnosis, HSCT, 10 years old and FAH.ResultsThe median age at HSCT of the 53 patients was 4.5 years, 75% had a haematological malignancy and 25% a solid tumour. Half of the cohort underwent allogenic HSCT and most (89%) conditioned with busulphan. The mean change in height SDS from primary cancer diagnosis to FAH was –1.21 (±1.18 SD), equivalent to 7–8.5 cm loss, with a mean FAH of –0.91 SDS (±1.10 SD). The greatest height loss occurred between diagnosis and HSCT (–0.77 SDS, 95% confidence interval –1.42, –0.12, P = 0.01), with no catch-up growth seen by FAH. Patients with solid tumours had the greatest height loss. Overall body mass index SDS did not change significantly over time, or by cancer type.ConclusionsChemotherapy-only conditioned HSCT during childhood can impact FAH, with the greatest height loss occurring prior to HSCT and no catch-up growth after treatment finishes. Children transplanted for a solid tumour malignancy seem to be more at risk, possibly due to intensive treatment regimens, both pre-transplant and during conditioning.     

脂质体辅助递送CTLA-4 siRNA通过激活系统性抗肿瘤免疫反应抑制肾细胞癌生长

目的:探索携带CTLA-4 siRNA的适配子偶联脂质体颗粒是否可以激活肿瘤部位的抗肿瘤免疫反应，抑制肾细胞癌的生长。方法:采用薄膜水化法制备脂质体；使用透射电子显微镜观察脂质体的形态和结构；用Zetasizer测量Zeta电位；共孵育实验观察靶细胞对Lipo-siRNA的摄取；qPCR检测Lipo-siRNA对CTLA-4基因的沉默；小鼠移植瘤模型检测Lipo-siRNA的体内抑瘤能力；流式细胞术检测肿瘤浸润T细胞的激活状态；免疫荧光法检测肿瘤浸润T细胞的数目。结果:成功制备Lipo-siRNA，电镜结果显示其具有双层球状结构；Zetasizer测得其Zeta电位为(+20.53±2.66)mV；荧光显微镜观察结果表明Lipo-siRNA可以被靶细胞有效摄取，qPCR检测Lipo-siRNA可以显著降低CTLA-4基因的表达（P＜0.001）；小鼠移植瘤模型显示Lipo-siRNA较对照组而言可以显著抑制肿瘤生长（P＜0.001），降低肿瘤细胞中CTLA-4的表达（P＜0.001），提升肿瘤浸润T细胞的数量（P＜0.000 1），并且提高了肿瘤浸润T细胞中IL-2（P＜0.000 1）和IFN-γ（P＜0.000 1）的表达水平。结论:适配子偶联脂质体可以携带CTLA-4 siRNA靶向肿瘤细胞，激活肿瘤部位的抗肿瘤免疫反应，抑制肿瘤的生长，对肾细胞癌的治疗具有潜在的临床应用价值。     

Anti-thymocyte globulin and post-transplant cyclophosphamide predisposes to inferior outcome when using cryopreserved stem cell grafts

During 2020, the concurrent novel COVID-19 pandemic lead to widespread cryopreservation of allogeneic hematopoietic cell transplant grafts based on National Marrow Donor Program and European Society of Blood and Marrow Transplantation recommendations, in order to secure grafts before the start of conditioning chemotherapy. We sought to examine the impact of this change in practice on patient outcomes. We analyzed the outcomes of 483 patients who received hematopoietic stem cell transplantation (HSCT) between August 2017 and August 2020, at Princess Margaret Cancer Centre, Canada, in the retrospective study, comparing the outcomes between those who received cryopreserved or fresh peripheral blood stem cell grafts. Overall compared with those who received fresh grafts (n = 348), patients who received cryopreserved grafts (n = 135) had reduced survival and GRFS, reduced incidence of chronic graft-versus-host disease (GvHD), delay in neutrophil engraftment, and higher graft failure (GF), with no significant difference in relapse incidence or acute GvHD. However, recipients of cryopreserved matched-related donor HSCT showed significantly worse OS, NRM, GRFS compared with fresh grafts. Multivariable analysis of the entire cohort showed significant impact of cryopreservation on OS, relapse, cGvHD, GF, and GRFS. We conclude that cryopreservation was associated with inferior outcomes post-HSCT, possibly due to the combination of ATG and post-transplant cyclophosphamide impacting differential tolerance to cryopreservation on components of the stem cell graft; further studies are warranted to elucidate mechanisms for this observation.