以全血细胞减少为首发表现的脾边缘区淋巴瘤1例报告

脾边缘区淋巴瘤(splenic marginal zone lymphoma,SMZL)是指原发于脾脏的B淋巴细胞性非霍奇金淋巴瘤。SMZL的发病率低,国内以全血细胞减少为首发表现的SMZL报道较少。为提高临床医务人员对SMZL的认识,现将本院诊治的1例报道如下。1病例资料患者女性,76岁,以“腹胀、纳差1年,全血细胞减少3 d”为主诉于2016年6月23日于本院就诊。1年前曾于本院就诊,患者无明显诱因出现腹胀,伴有纳差,无腹痛、腹泻,无畏寒发热,无瘀斑瘀点,无咳嗽咳痰等不适,建议患者进一步检查明确原因,患者予以拒绝。     

Overexpression of FoxM1 offers a promising therapeutic target in diffuse large B-cell lymphoma

Background

FoxM1 has been shown to play a critical role in the pathogenesis of various epithelial malignancies. However, its role in lymphoid malignancies has not been fully clarified. We, therefore, investigated the role of FoxM1 expression in a large cohort of diffuse large B-cell lymphoma samples and panel of cell lines.

Design and Methods

FoxM1 expression was investigated in a large series of diffuse large B-cell lymphoma tissues in a tissue microarray format by immunohistochemistry. Apoptosis was measured by flow cytometry and protein expression was detected by immunoblotting using diffuse large B-cell lymphoma cell lines following treatment with either pharmacological inhibitor of FoxM1 or small interference RNA knockdown strategy. Invasion/migration and soft agar colony assays were also performed following treatment with FoxM1 inhibitor.

Results

FoxM1 expression was detected in 84.6% of diffuse large B-cell lymphoma tumors and found to be significantly associated with proliferative tumor marker Ki67 (P<0.0001), matrix metalloproteinases-2 (P=0.0008), matrix metalloproteinases-9 (P=0.0002), S-phase kinase associated protein-2 (P<0.0001) and inversely associated with p27 expression (P=0.0215). Expression of small interference RNA targeted against FoxM1 or treatment of diffuse large B-cell lymphoma cells with thiostrepton caused its downregulation accompanied by decreased expression of matrix metalloproteinases-2 and matrix metalloproteinases-9. Inhibition of FoxM1 in diffuse large B-cell lymphoma cells also decreased invasive and migratory capability, and induced caspase dependent apoptosis via activation of the mitochondrial apoptotic pathway. Finally, combined thiostrepton and bortezomib at sub-toxic doses led to efficient apoptosis in diffuse large B-cell lymphoma cells.

Conclusions

Altogether, these results suggest that FoxM1 is over-expressed in the majority of diffuse large B-cell lymphoma samples. These data also indicate that targeting FoxM1 signaling can serve as a potential therapeutic modality in the management of diffuse large B-cell lymphoma.     

Phase I trial of a novel human monoclonal antibody mAb216 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia

Background

This phase I trial was conducted to determine the safety and pharmacokinetics of monoclonal antibody 216, a human monoclonal Immunoglobulin M antibody targeting a linear B-cell lactosamine antigen, administered alone and in combination with vincristine in patients with relapsed or refractory B-cell acute lymphoblastic leukemia, and to preliminarily assess tumor targeting and efficacy.

Design and Methods

Three cohorts of patients received escalating doses of monoclonal antibody 216 administered as an intravenous infusion. In the case of poor response to the first dose of monoclonal antibody 216 alone, defined as less than 75% reduction in peripheral blood blast count, a second dose of the antibody with vincristine was given between days 4 and 7. Responses were assessed weekly until day 35. Serum concentration of monoclonal antibody 216 was measured before and after infusion. Monoclonal antibody 216 targeting was determined with an anti-idiotypic antibody to monoclonal antibody 216 and preliminary efficacy was analyzed by changes in peripheral blood blasts.

Results

Thirteen patients were enrolled. One episode of grade 3 epistaxis was the only dose-limiting toxicity observed. All patients showed a poor response to the first monoclonal antibody 216 infusion with a decrease in peripheral blasts from 6–65% in 9 patients. In 8 patients, addition of vincristine to monoclonal antibody 216 resulted in an average reduction of the peripheral blasts of 81%. One patient without peripheral blasts achieved a hypoplastic marrow without evidence of leukemia after one infusion of monoclonal antibody 216 and monoclonal antibody 216/vincristine each. Monoclonal antibody 216 was detected on peripheral blasts in all patients.

Conclusions

Treatment with monoclonal antibody 216 in combination with vincristine is feasible and well tolerated in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Binding of monoclonal antibody 216 to leukemic blasts was efficient, and favorable early responses were observed.     

TLR signaling in B-cell development and activation

Expression of Toll-like receptors (TLRs) in B cells provides a cell-intrinsic mechanism for innate signals regulating adaptive immune responses. In combination with other signaling pathways in B cells, including through the B-cell receptor (BCR), TLR signaling plays multiple roles in B-cell differentiation and activation. The outcome of TLR signaling in B cells is largely context-dependent, which partly explains discrepancies among in vitro and in vivo studies, or studies using different immunogens. We focus on recent findings on how B-cell-intrinsic TLR signaling regulates antibody responses, including germinal center formation and autoantibody production in autoimmune disease models. In addition, TLR signaling also acts on the precursors of B cells, which could influence the immune response of animals by shaping the composition of the immune system. With TLR signaling modulating immune responses at these different levels, much more needs to be understood before we can depict the complete functions of innate signaling in host defense.     

Somatostatin receptors: From signaling to clinical practice

Somatostatin is a peptide with a potent and broad antisecretory action, which makes it an invaluable drug target for the pharmacological management of pituitary adenomas and neuroendocrine tumors. Somatostatin receptors (SSTR1, 2A and B, 3, 4 and 5) belong to the G protein coupled receptor family and have a wide expression pattern in both normal tissues and solid tumors. Investigating the function of each SSTR in several tumor types has provided a wealth of information about the common but also distinct signaling cascades that suppress tumor cell proliferation, survival and angiogenesis. This provided the rationale for developing multireceptor-targeted somatostatin analogs and combination therapies with signaling-targeted agents such as inhibitors of the mammalian (or mechanistic) target of rapamycin (mTOR). The ability of SSTR to internalize and the development of rabiolabeled somatostatin analogs have improved the diagnosis and treatment of neuroendocrine tumors.     

弥漫大 B 细胞淋巴瘤患者 Th17细胞及相关细胞因子水平与预后的关系

目的：探讨弥漫大B细胞淋巴瘤（ DLBCL）患者Th17细胞及相关细胞因子水平与预后的关系及其意义。方法将60例DLBCL患者按照国际预后指数（IPI）评分分为低中危组32例和中高危组28例,另选健康者30例作为对照组。采用流式细胞术检测各组外周血中Th17细胞比例,ELISA检测外周血相关细胞因子白细胞介素（ IL）－17、IL－21、IL－23、转化生长因子－β（ TGF－β）的表达水平,分别比较各组之间Th17细胞及相关细胞因子水平的差异,并分析其与IPI评分的相关性;分析随访的54例患者Th17细胞水平与生存率的关系。结果（1）中高危组Th17细胞、IL－17、IL－21均低于对照组和低中危组,IL－23低于对照组,TGF－β高于对照组和低中危组,差异均有统计学意义（P＜0．05）。（2）DLBCL患者Th17细胞、IL－17、IL－21与IPI评分呈负相关,TGF－β与IPI评分呈正相关,相关性有统计学意义（P＜0．05）。（3）高Th17细胞者和低Th17细胞者3年生存率分别为82．1％和45．0％,Th17细胞水平对DLBCL患者生存的影响有统计学意义（P＝0．021）。结论 DLBCL患者Th17细胞及相关细胞因子水平与IPI评分密切相关,Th17细胞与IPI评分呈负相关。 Th17细胞对预后有影响,可能在DLBCL的发生发展中起着抑制作用。     

Bcl-2、COX-2在宫颈癌新辅助化疗前后的表达及临床意义的研究

目的：探讨Bcl-2、COX-2在宫颈癌新辅助化疗前后表达的意义,以及新辅助化疗（NACT）对宫颈癌的近期临床疗效。方法对32例宫颈癌患者,采集NACT治疗前后的宫颈癌组织标本,采用免疫组织化学SP法检测组织中的Bcl-2及COX-2表达。结果①经NACT后,治疗总有效率（CR＋PR）为75％,无效率（PD＋SD）为25％。②宫颈癌组织中Bcl-2、COX-2的表达均出现明显下降,差异均有统计学意义（P＜0.05）;临床有效组中Bcl-2、COX-2的表达在NACT后出现显著下降（P＜0.05）,无效组中Bcl-2、COX-2的表达在NACT前后无明显统计学意义（P＞0.05）。结论 Bcl-2、COX-2的表达情况对评价宫颈癌患者新辅助化疗效具有肯定的临床意义,宫颈癌行NACT后近期疗效良好。     

Cyclin D1 and t(11;14)-positive B-cell neoplasms resembling marginal zone B-cell lymphoma: a morphological variant of mantle cell lymphoma

We describe 3 unusual B-cell non-Hodgkin's lymphomas in which the entire tumors histologically mimicked marginal zone B-cell lymphoma. All patients were male (mean age, 65 years). Excisional biopsy from lymph node (2 of 3) and parotid gland (1 of 3) showed proliferation of monocytoid B-cells with plasmacytoid features (2 of 3) and conspicuous absence of large lymphoma cells (3 of 3). By immunohistochemistry, cyclin D1 was positive (3 of 3), CD23 was negative (3 of 3), and aberrant expression of CD5/CD43 was present in 1 case. Ki67 labeling was greater than 50% in 1 case and 10% to 25% in the other 2 cases. Evidence of the t(11;14) was detectable in all by molecular techniques. One patient died within 15 months, and the other 2 patients had widely disseminated diseases at the last follow-up (8 months). Based on these features, we believed that the best classification for these lesions is the marginal zone B-cell lymphoma-like mantle cell lymphoma.     

Epstein-Barr virus-associated lymphoproliferative disorders

Epstein-Barr virus (EBV) is a member of the human herpesvirus family that was initially isolated from a cultured Burkitt lymphoma cell line by Epstein et al in 1964. Subsequent studies have proven that it is the causative agent in most cases of infectious mononucleosis. Primary infection is usually asymptomatic in childhood; but in adulthood, it is associated with a self-limiting infectious mononucleosis syndrome in approximately one third of the cases. EBV has been linked to many human neoplasms including hematopoietic, epithelial, and mesenchymal tumors. In this review, we will only discuss the EBV-associated lymphoproliferative disorders, dividing them into B-cell, T/NK-cell, and HIV-related lymphoproliferative disorders.     

Simultaneous occurrence of peripheral T-cell lymphoma unspecified and B-cell small lymphocytic lymphoma. Report of 2 cases

We report on 2 composite lymphomas occurring in elderly patients, morphologically characterized by the combination of peripheral T-cell lymphoma (PTCL) unspecified and B-cell small lymphocytic lymphoma. Immunohistochemistry provided objective confirmation of the coexistence of the 2 malignancies, as did molecular biology by revealing clonal T-cell receptor gamma and immunoglobulin heavy chain gene rearrangements. One of the patients had no history of indolent lymphoma either at the personal and family level, whereas the other showed a strong familial predisposition, his mother and sister having suffered from B-cell chronic lymphocytic leukemia. Epstein-Barr virus was detected in the PTCL component of 1 case, but was negative in the other. To the best of our knowledge, the simultaneous occurrence of PTCL unspecified and B-cell small lymphocytic lymphoma is an exceptional event; the possible pathogenetic correlations between the 2 neoplasms are discussed.