Cyclin D1和bcl-2在B细胞淋巴瘤中的表达及其在鉴别诊断中的意义

B细胞淋巴瘤根据免疫表型可分为不同亚型,且不同亚型侵袭度不同,预后也有很大差异.Cyclin D1是已被证实与肿瘤有最直接关系的细胞周期蛋白,在大多B细胞淋巴瘤[套细胞淋巴瘤(MCL)、慢性淋巴细胞白血病(CLL)、边缘区淋巴瘤(MZL)、弥漫大B细胞淋巴瘤(DLBCL)等」中均有表达.多数B细胞淋巴瘤[滤泡性淋巴瘤(FL)、DLBCL等]都能可见易位活化的bcl-2表达增强.Cyclin D1及bcl-2作为B细胞淋巴瘤重要的细胞周期蛋白及抗凋亡基因,在淋巴瘤的鉴别诊断中起重要作用,其检测及检测手段的灵敏度和特异度具有重要的临床价值.     

原发性纵隔大B细胞淋巴瘤研究进展

原发性纵隔大B细胞淋巴瘤(PMBCL)是弥漫大B细胞淋巴瘤(DLBCL)的一种特殊类型,具有独特的临床表现及病理学、分子生物学特征.目前尚无标准的治疗方案,回顾性分析表明第三代的化疗方案优于CHOP方案,利妥昔单抗的应用缓解了这种差异,是否需要接受联合放疗尚无定论.未来将脱氧葡萄糖-正电子发射计算机断层显像(FDG-PET)用于PMBCL的疗效评估,如果能提供可靠的预后信息,就可以减轻治疗强度.     

Stress-induced DNA damage: a case study in diffuse large B-cell lymphoma

DNA damage is one of the mechanisms of mutagenesis. Sequence integrity may be affected by the action of thermal changes, chemical agents, both endogenous and exogenous, and other environmental issues. Abnormally high mutation rates are referred to as genomic instability: a phenomenon closely related to the onset of cancer. Mutant genotypes may be able to confer some kind of selective advantage on subclonal cell populations, leading them to multiply until dominance in a localized tissue environment that later becomes the tumour. Cellular stress, especially that of oxidative and ionic nature, is a recognized trigger for DNA-damaging processes. A physico-chemical model has shown that high hysteresis rates in DNA denaturation curves may be indicative of dissipative processes inducing DNA damage, thus potentially leading to uncontrolled mutagenesis and genome instability. We here study selectively to what extent this phenomenon may occur by analysing the sequence length and composition effects on the thermodynamic behaviour and the presence of hysteresis in pressure-driven DNA denaturation; pronounced hysteresis in the denaturation/renaturation curves may indicate thermal susceptibility to DNA damage. In particular, we consider highly mutated regions of the genome characterized in diffuse large B-cell lymphoma on a recent whole exome next-generation sequencing effort.     

间变性淋巴瘤激酶抑制剂的研究进展

研究发现非小细胞肺癌的形成与多种致癌突变密切相关,其中间变性淋巴瘤激酶重排备受关注,针对棘皮动物微管相关蛋白质4-间变性淋巴瘤激酶融合基因的抑制剂克唑替尼对于治疗晚期ALK阳性非小细胞肺癌患者是有效的,2011年获得美国食品药品监督管理局批准上市,但出现了耐药性,第二代间变性淋巴瘤激酶抑制剂的出现,克服了耐药机制,并显示出治疗非小细胞肺癌患者的活性。本论文按化学结构的不同介绍了克唑替尼、Ceritinib、Alectinib、Brigatinib、RXDX-101、PF-06463922、ASP3026、X-396、CEP-37440等间变性淋巴瘤激酶抑制剂及临床研究等,为非小细胞肺癌的靶向治疗药物的开发提供了参考。     

The Biology of Classic Hairy Cell Leukemia

Classic hairy cell leukemia (HCL) is a rare mature B-cell malignancy associated with pancytopenia and infectious complications due to progressive infiltration of the bone marrow and spleen. Despite tremendous therapeutic advances achieved with the implementation of purine analogues such as cladribine into clinical practice, the culprit biologic alterations driving this fascinating hematologic disease have long stayed concealed. Nearly 10 years ago, BRAF V600E was finally identified as a key activating mutation detectable in almost all HCL patients and throughout the entire course of the disease. However, additional oncogenic biologic features seem mandatory to enable HCL transformation, an open issue still under active investigation. This review summarizes the current understanding of key pathogenic mechanisms implicated in HCL and discusses major hurdles to overcome in the context of other BRAF-mutated malignancies.     

基于人工免疫的进化性数据聚类分析的研究

文章提出了一种新型的基于人工免疫系统的进化性聚类分析方法,通过这种方法不仅可以实现对数据的聚类,过滤冗余数据,并且可以根据已知数据的趋势生成未知进化数据,以达到对数据的进化简约处理的功效.     

Magnetic resonance imaging and67ga scan versus computed tomography in the staging and in the monitoring of mediastinal malignant lymphoma: a prospective pilot study

Purpose: To assess the potential value of magnetic resonance imaging (MRI) combined with⁶⁷Ga single-photon emission computed tomography (SPECT) versus computed tomography (CT) in the staging and in the monitoring of mediastinal malignant lymphoma. Materials and methods: Twenty-three patients, referred to our institute for the evaluation of lymphoma, underwent CT,⁶⁷Ga scan, and MRI between April 1993 and February 1996 at sequential intervals. The tests studied (MRI,^67Ga, and CT) were performed according to the following schedule: 1) before start of therapy; 2) after four courses of chemotherapy; and 3) 2, 6, 12, and 18 months after the end of treatment. Results: All patients studied at the time of diagnosis had abnormal gallium accumulation in the mediastinum as well as pathologic CT and pathologic signal intensity at MRI. Six months after the end of treatment full consistency was found between the results of MRI and SPECT, whereas during treatment and 2 months after the end of therapy MRI and⁶⁷Ga scan were not in agreement in nine patients. In the 23 patients in follow-up, in CT there were nine false-positive and three false-negative findings; in SPECT three false negatives; in MRI one false positive and one false negative. Conclusion: MRI can give morphologic information similar to CT, even superior due to multiplanarity and with major precision in the distinction between fibrosis and active disease. MRI is thus an alternative to CT. The association with SPECT allows a great diagnostic accuracy in the positive and negative predictive value.     

Distinct Chemokine Receptor Expression Profiles in De Novo DLBCL,Transformed Follicular Lymphoma,Richter’s Trans-Formed DLBCL and Germinal Center B-Cells

Chemokine receptors and their ligands have been identified as playing an important role in the development of diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, and Richter syndrome (RS). Our aim was to investigate the different expression profiles in de novo DLBCL, transformed follicular lymphoma (tFL), and RS. Here, we profiled the mRNA expression levels of 18 chemokine receptors (CCR1–CCR9, CXCR1–CXCR7, CX3CR1 and XCR1) using RQ-PCR, as well as immunohistochemistry of seven chemokine receptors (CCR1, CCR4–CCR8 and CXCR2) in RS, de novo DLBCL, and tFL biopsy-derived tissues. Tonsil-derived germinal center B-cells (GC-B) served as non-neoplastic controls. The chemokine receptor expression profiles of de novo DLBCL and tFL substantially differed from those of GC-B, with at least 5-fold higher expression of 15 out of the 18 investigated chemokine receptors (CCR1–CCR9, CXCR1, CXCR2, CXCR6, CXCR7, CX3CR1 and XCR1) in these lymphoma subtypes. Interestingly, the de novo DLBCL and tFL exhibited at least 22-fold higher expression of CCR1, CCR5, CCR8, and CXCR6 compared with RS, whereas no significant difference in chemokine receptor expression profile was detected when comparing de novo DLBCL with tFL. Furthermore, in de novo DLBCL and tFLs, a high expression of CCR7 was associated with a poor overall survival in our study cohort, as well as in an independent patient cohort. Our data indicate that the chemokine receptor expression profile of RS differs substantially from that of de novo DLBCL and tFL. Thus, these multiple dysregulated chemokine receptors could represent novel clinical markers as diagnostic and prognostic tools. Moreover, this study highlights the relevance of chemokine signaling crosstalk in the tumor microenvironment of aggressive lymphomas.     

Predicting Antigenic Peptides from Rocio Virus NS1 Protein for Immunodiagnostic Testing Using Immunoinformatics and Molecular Dynamics Simulation

The mosquito-borne disease caused by the Rocio virus is a neglected threat, and new immune inputs for serological testing are urgently required for diagnosis in low-resource settings and epidemiological surveillance. We used in silico approaches to identify a specific antigenic peptide (p_ROCV2) in the NS1 protein of the Rocio virus that was theoretically predicted to be stable and exposed on its surface, where it demonstrated key properties allowing it to interact with antibodies. These findings related to the molecular dynamics of this peptide provide important insights for advancing diagnostic platforms and investigating therapeutic alternatives.