Enfermedad fúngica invasora por hongos filamentosos en pacientes hematológicos

Invasive mould infections (IMI) are a persistent problem with high morbidity and mortality rates among patients receiving chemotherapy for hematological malignancies and hematopoietic stem cell transplant recipients. Management of IMI in this setting has become increasingly complex with the advent of new antifungal agents and diagnostic tests, which have resulted in different therapeutic strategies (prophylactic, empirical, pre-emptive, and directed). A proper assessment of the individual risk for IMI appears to be critical in order to use the best prophylactic and therapeutic approach and increase the survival rates. Among the available antifungal drugs, the most frequently used in the hematologic patient are fluconazole, mould-active azoles (itraconazole, posaconazole and voriconazole), candins (anidulafungin, caspofungin and micafungin), and lipid formulations of amphotericin B. Specific recommendations for their use, and criteria for selecting the antifungal agents are discussed in this paper.     

Intratumoral interferon-α gene transfer enhances tumor immunity after allogeneic hematopoietic stem cell transplantation

One of the major challenges in the treatment of solid cancers by allogenic hematopoietic stem cell transfer (alloHSCT) is the specific enhancement of antitumor immunity. Interferon (IFN) is a cytokine with pleiotropic biological functions including an immunomoduration, and our preclinical studies have shown that an intratumoral IFN-α gene transfer induced strong local tumor control and systemic tumor-specific immunity. In the present study, we examined whether the IFN-α gene transfer could enhance recognition of tumor-associated antigens by donor T cells and augment the antitumor activity of alloHSCT. First, when a mouse IFN-α adenovirus vector (Ad-mIFN) was injected into subcutaneous xenografts of syngeneic renal and colon cancer cells, tumor growth was significantly suppressed in a dose-dependent manner. A significant tumor cell death and infiltration of immune cells was recognized in the Ad-mIFN-injected tumors, and the dendrtic cells isolated from the tumors showed a strong Th1-oriented response. The antitumor effect of Ad-mIFN was then examined in a murine model of minor histocompatibility antigen-mismatched alloHSCT. The intratumoral IFN-α gene transfer caused significant tumor suppression in the alloHSCT recipients, and this suppression was evident not only in the gene-transduced tumors but also in simultaneously inoculated distant tumors which did not receive the vector injection. A cytotoxicity assay showed specific tumor cell lysis by donor T cells responding to IFN-α. Graft-versus-host disease was not exacerbated serologically or clinically in the mice treated with IFN-α. This combination strategy deserves evaluation in future clinical trials for human solid cancers.     

Membrane glycolipids in stem cells

Stem cells, such as embryonic stem cells, hematopoietic stem cells, neural stem cells, mesenchymal stem cells, and very small embryonic-like stem cells, are undifferentiated cells that are endowed with a high potential for proliferation and the capacity for self-renewal with retention of pluri/multipotency to differentiate into their progenies. Recently, studies regarding the biological functions of glycolipids and cell surface microdomains (caveolae, lipid rafts, or glycolipid-enriched microdomains) in stem cells are emerging. In this review, we introduce the expression patterns of glycolipids and the functional roles of cell surface microdomains in stem cells.     

造血干细胞移植治疗白血病患者负性因素干预措施的护理研究

目的针对造血干细胞移植治疗白血病患者不同阶段存在负性因素的特点进行干预并观察其临床效果。方法对96例白血病患者在造血干细胞移植前期-预处理期-移植期-移植后期的不同阶段负性因素实施心理支持,全环境保护方案,并发症的预防、观察与处理,健康教育等干预措施。结果减轻或消除负性因素对患者的影响,减少了并发症的发生,缩短留住无菌层流室的时间,提高白血病患者移植后的生活质量。结论制定一整套合理的、规范的、系统的护理流程,使患者获得最佳护理方案,有效减轻负性因素对患者的影响。     

Fibroblast growth factor signaling in embryonic and cancer stem cells

Cancer stem cells are cancer cells that originate from the transformation of normal stem cells. The most important property of any stem cell is the ability to self-renew. Through this property, there are striking parallels between normal stem cells and cancer stem cells. Both cell types share various markers of “stemness”. In particular, normal stem cells and cancer stem cells utilize similar molecular mechanisms to drive self-renewal, and similar signaling pathways may induce their differentiation.The fibroblast growth factor 2 (FGF-2) pathway is one of the most significant regulators of human embryonic stem cell (hESC) self-renewal and cancer cell tumorigenesis. Here we summarize recent data on the effects of FGF-2 and its receptors on hESCs and leukemic stem/progenitor cells. Also, we discuss the similarities of these findings with stem cell renewal and differentiation phenotypes.     

异基因造血干细胞移植治疗耳道复发的急性早幼粒细胞白血病一例并文献复习

目的:探讨急性早幼粒细胞白血病(APL)髓外复发的相关因素及治疗.方法:对1例APL缓解后耳道复发患者的临床资料进行回顾性分析,并复习相关文献.结果:患者2015年8月诊断为APL(低危型),经诱导后达完全缓解,随后进行巩固、维持治疗,并多次行腰椎穿刺术及椎管内注射化疗药物预防中枢神经系统白血病.2017年3月发现左外...     

造血干细胞移植术对肠道菌群结构的影响

目的监测造血干细胞移植术（Hematopoietic stem cell transplantation,HSCT）前后肠道菌群结构的动态变化。方法收集3例造血干细胞移植患者手术前后8个时间点的粪便样品,提取样品总DNA进行16S rRNA基因的V3区的bar coded 454焦磷酸测序,并用MANOVA、聚类分析、Pearson相关等统计方法对菌群结构的变化进行动态分析。结果 HSCT移植前,经过放、化疗及预防性抗生素治疗,患者的肠道菌群结构和组成发生显著的改变,多样性明显减少;移植4周后,菌群多样性有恢复的趋势,但菌群结构和组成与治疗前仍有明显的差异。整个HSCT过程中,Escherichia/Shigella及Enterococcus属变成肠道中最优势的细菌类群。结论肠道菌群结构在HSCT术前已发生显著的改变,机会致病菌Escherichia/Shigella及Enterococcus属成为HSCT患者肠道中最优势的细菌类群。     

小鼠造血干细胞增殖和分化的分子生物学证据

本文采用Ｙ染色体特异的性别决定基因（Ｓｒｙ）作为新的细胞遗传标志,通过ＰＣＲ技术来追踪观察造血干细胞的增殖与分化性能。该方法具有简便、灵敏和特异等优点。雌性受体小鼠输注雄鼠骨髓细胞和１３天脾结节（ＣＦＵ－Ｓ１３）细胞后,Ｓｒｙ ＰＣＲ测试受体小鼠的ＣＦＵ－Ｓ结果表明,它们均为供体来源的ＸＹ细胞。用Ｓｒｙ ＰＣＲ骨髓细胞和骨髓中脾结节生成细胞（ＣＰＵ－Ｓ）的长期重建造血能力,结果表明,在存活雌性小鼠     

造血微环境的细胞和分子机理

造血干细胞（hematopoietic stem cell;HSC）是造血前体细胞;存在于特定的三维空间结构中;即通常所说的造血微环境或造血干细胞壁龛（niche）。造血微环境控制着HSC的自我更新和分化。目前关于造血微环境的结构、细胞组成和分子机理还不太清楚;阐明其中的细胞和分子机制是将来更好地将HSC用于临床的关键所在。综述造血微环境的细胞组成以及HSC和微环境之间的信号通路的研究进展。     

全身放疗在造血干细胞移植中的研究进展

全身照射疗法(TBI)是一种姑息治疗,该方法已经成功地应用在慢性淋巴细胞白血病或滤泡性淋巴瘤等无干细胞支持的放射敏感的疾病中。目前,在血液系统恶性疾病中造血干细胞移植是较为有效的治疗手段之一,其中全身放射治疗与大剂量化疗是造血干细胞移植疗法的经典预处理方案。TBI方法主要应用在造血移植环境中,具有较强的周期非特异性抗肿瘤效应和免疫抑制效能。TBI给予干细胞移植病人超过正常骨髓的辐射耐受量,通过重建病人的造血和免疫来达到治疗目的。     

BMP signaling and stem cell regulation

Stem cells play an essential role in cellular specialization and pattern formation during embryogenesis and in tissue regeneration in adults. This is mainly due to a stem cell's ability to replenish itself (self-renewal) and, at the same time, produce differentiated progeny. Realization of these special stem cell features has changed the prospective of the field. However, regulation of stem cell self-renewal and maintenance of its potentiality require a complicated regulatory network of both extracellular cues and intrinsic programs. Understanding how signaling regulates stem cell behavior will shed light on the molecular mechanisms underlying stem cell self-renewal. In this review, we focus on comparing the progress of recent research regarding the roles of the BMP signaling pathway in different stem cell systems, including embryonic stem cells, germline stem cells, hematopoietic stem cells, and intestinal stem cells. We hope this comparison, together with a brief look at other signaling pathways, will bring a more balanced view of BMP signaling in regulation of stem cell properties, and further point to a general principle that self-renewal of stem cells may require a combination of maintenance of proliferation potential, inhibition of apoptosis, and blocking of differentiation.     

Enfermedades invasoras por hongos levaduriformes en pacientes neutropénicos

Invasive fungal diseases caused by yeasts still play an important role in the morbidity and mortality in neutropenic patients with haematological malignancies. Although the overall incidence of invasive candidiasis has decreased due to widespread use of antifungal prophylaxis, the incidence of non-Candida albicans Candida species is increasing compared with that of C. albicans, and mortality of invasive candidiasis continues to be high. In addition, there has been an increase in invasive infections caused by an array of uncommon yeasts, including species of the genus Malassezia, Rhodotorula, Trichosporon and Saprochaete, characterised by their resistance to echinocandins and poor prognosis.     

Hematopoietic stem cell-derived adipocytes and fibroblasts in the tumor microenvironment

The tumor microenvironment(TME) is complex and constantly evolving. This is due, in part, to the crosstalk between tumor cells and the multiple cell types that comprise the TME, which results in a heterogeneous population of tumor cells and TME cells. This review will focus on two stromal cell types, the cancerassociated adipocyte(CAA) and the cancer-associated fibroblast(CAF). In the clinic, the presence of CAAs and CAFs in the TME translates to poor prognosis in multiple tumor types. CAAs and CAFs have an activated phenotype and produce growth factors, inflammatory factors, cytokines, chemokines, extracellular matrix components, and proteases in an accelerated and aberrant fashion. Through this activated state, CAAs and CAFs remodel the TME, thereby driving all aspects of tumor progression, including tumor growth and survival, chemoresistance, tumor vascularization, tumor invasion, and tumor cell metastasis. Similarities in the tumorpromoting functions of CAAs and CAFs suggest that a multipronged therapeutic approach may be necessary to achieve maximal impact on disease. While CAAs and CAFs are thought to arise from tissues adjacent to the tumor, multiple alternative origins for CAAs and CAFs have recently been identified. Recent studies from our lab and others suggest that the hematopoietic stem cell, through the myeloid lineage, may serve as a progenitor for CAAs and CAFs. We hypothesize that the multiple origins of CAAs and CAFs may contribute to the heterogeneity seen in the TME. Thus, a better understanding of the origin of CAAs and CAFs, how this origin impacts their functions in the TME, and thetemporal participation of uniquely originating TME cells may lead to novel or improved anti-tumor therapeutics.     

超细支气管镜检查在2例异基因造血干细胞移植后BOS的临床应用价值

目的：探讨超细支气管镜检查在异基因造血干细胞移植（Allo-HSCT）后闭塞性细支气管炎综合征（BOS）中的诊断和治疗作用。方法：回顾性分析2例移植术后3月诊断为BOS患者的临床资料,分析BOS的诊断和治疗特点。结果：我院2例患者从Allo-HSCT到诊断为BOS时间均为移植后3月内,临床表现活动后胸闷气促,肺功能呈混合性通气功能障碍,超细支气管镜检查直视下,观察到左右多部位6级及以上细支气管管腔口薄膜样增生物阻塞管腔,使用活检钳机械扩张或冷冻等方式可以打通闭塞气道,术中、后未发生检查相关并发症,经治疗后患者症状较前明显改善,其中1例患者后续随访其气管镜镜下见原闭塞细支气管管腔治疗后呈持续开放状态。结论：超细支气管镜检查可有效诊断Allo-HSCT后发生BOS,还可通过呼吸介入治疗打开细支气管达到短期肺功能改善。