间变大细胞性淋巴瘤研究进展

间变大细胞性淋巴瘤是一种罕见的淋巴瘤,其发病率很低.临床上对其认识仍有不足,易漏诊误诊此病.现就其在形态学、免疫和遗传学、临床表现、治疗和预后等方面的研究进展进行综述.     

ALK阴性间变性大细胞淋巴瘤3例临床病理分析

目的 探讨间变性淋巴瘤激酶(ALK)阴性间变性大细胞淋巴瘤(ALK-ALCL)的临床病理学特征、诊断及鉴别诊断。方法 回顾性分析2017年至2022年郑州市第一人民医院及河南省儿童医院病理科诊断的3例ALK-ALCL患者的临床特征、病理形态、免疫表型,并复习相关文献。结果 3例女性患者年龄分别为8岁、52岁、60岁;1例发热,咳嗽,颈部淋巴结肿大;1例发热、乏力,右半结肠占位,腹腔淋巴结肿大;1例右下肢皮肤肿块,颈部、纵隔、腹腔淋巴结肿大。镜下见瘤细胞片状、弥漫性生长,局部浸润被膜下淋巴窦,瘤细胞大小不等、形态多样,可见单核、多核瘤巨细胞,胞质丰富、淡染、嗜酸,胞核圆形、卵圆形、不规则形、肾形、胚胎样,染色质弥散、凝聚,核仁大小不等,嗜酸或嗜碱,间质见数量不等的淋巴细胞、嗜酸性粒细胞、组织细胞。免疫组化显示3例CD30、CD3、上皮细胞膜抗原、CD43均阳性,ALK、CD20、Pax-5、CD15、CD79a、CD8、细胞毒相关标记物-1、颗粒酶B均阴性,2例CD4、CD5阳性,Ki-67增殖指数30%～60%。结论 ALK-ALCL临床罕见,病理形态多样,容易误诊,诊断需依据临床特点...     

原发系统型间变性大细胞淋巴瘤40例临床特征及预后分析

目的 分析原发系统型间变性大细胞淋巴瘤(ALCL)的临床特征及预后因素.方法 回顾性分析2013年1月至2018年12月期间在浙江大学医学院附属第一医院住院治疗的40例ALCL患者的临床资料,总结其临床特征并分析其预后相关因素.结果 ①40例患者中男29例,女11例,中位年龄41(14～67)岁,Ann Arbor分期...     

系统性间变大细胞淋巴瘤临床特征及预后分析

目的:分析系统性间变大细胞淋巴瘤(systemic anaplastic large cell lymphoma,ALCL)的临床病理特征;探讨患者临床、病理特征,尤其是间变淋巴瘤激酶(anaplastic lymphoma kinase, ALK)是否表达与预后的关系。方法:回顾性分析本院43例病理确诊为ALCL患者的临床病理特征、治疗及生存资料。结果:ALK阳性患者及ALK阴性患者在临床特征及治疗方案无显著差异,两组患者无进展生存期(progress free survival,PFS)及总生存期(overall survival,OS)无显著差异。单因素分析提示:患者是否合并噬血细胞综合征(hemophagocytic lymphohistiocytosis, HLH)是PFS及OS的影响因素(P0.05);多因素分析提示:是否合并HLH仍为PFS的独立影响因素(P0.05)。结论:ALK阳性及阴性ALCL患者生存无显著差异,发病时是否合并HLH是影响患者生存的预后因素。     

25例间变性大细胞淋巴瘤的临床分析

间变性大细胞淋巴瘤（anaplastic cell lymphomaALCL）是一种比较少见的恶性肿瘤。由于细胞表面表达ki-1（CD30）抗原，称ki-1阳性大细胞淋巴瘤。继而发现酪氨酸激酶（间变淋巴瘤激酶，anaplastic lymphoma kinase，ALK）的异常与其发生有关，从而对ALCL的实质有了进一步了解。在WHO新的淋巴瘤分类中，ALCL的B细胞型被归为弥漫大B细胞淋巴瘤，现在的ALCL仅指具有T细胞或非T非B细胞表型的淋巴瘤。我们发现25例ALCL患者的临床表现、治疗和预后有一定的差异，现报告如下。     

对ALK阴性间变性大细胞淋巴瘤的新认识

ALK阴性的间变性大细胞淋巴瘤(ALK-ALCL)虽然具有和ALK+ ALCL相似的形态学特征,CD30亦呈强阳性,但缺乏相对特异的ALK蛋白表达.近来研究表明,两种ALCL不仅在分子和遗传学水平上存在实质性区别,而且在治疗反应,预后和长期生存等方面,ALK-ALCL远远差于ALK+ ALCL,如ALK-ALCL的受累人群一般为老年人,大部分患者合并B组症状,诊断时已处于疾病晚期,国际预后指数评分较高,常规治疗疗效较差,5年生存率低于49%等.鉴于此,本文对ALK-ALCL的基础细胞形态和组织病理、免疫麦型、细胞遗传学和分子标靶以及诊疗新进展作一综述.     

间变性大细胞淋巴瘤2例报告

间变性大细胞淋巴瘤（ALCL）,又称Ki-1淋巴瘤,是非霍奇金淋巴瘤（NHL）的一种亚型。ALCL占淋巴瘤的2％～8％,国内少见报道。近2年来我院通过免疫组化诊断2例ALCL,分别用CHOP方案和全反式维甲酸（ATRA）治     

窦内间变性大细胞淋巴瘤1例

患者男性 ,14岁 ,学生。左颈部无痛性包块 6月余。 6个月前偶然发现左颈部有一蚕豆大包块 ,质较硬 ,可移动 ,无任何自觉症状。 2月后包块增至核桃大。患者一般情况好 ,发育正常 ,营养良好 ,体型微胖 ,无发烧及其他不适。后行左颈部包块活检 ,术中见包块与周围组织无粘连 ,表面光滑 ,完整取出。病理检查　结节状肿物 1个 ,外有完整包膜 ,体积 2ｃｍ× 1 7ｃｍ× 2ｃｍ ,切面灰白色 ,质较脆。显微镜下见淋巴结组织结构存在 ,淋巴窦内散在瘤细胞 ,大小不等 ,圆形卵圆形为主 ;染色质中等 ,可见核仁 ,胞浆丰富 ,嗜双色 (图 1) ,免疫组化染色窦内…     

T细胞前淋巴细胞白血病转ALK阴性间变性大细胞淋巴瘤一例

目的报道1例T细胞前淋巴细胞白血病(T-PLL)转变为间变性淋巴瘤激酶(ALK)阴性的间变性大细胞淋巴瘤(ALCL,ALK-),并进行文献复习。方法采用MIC标准诊断。形态学检查包括骨髓涂片(瑞特染色法)、胸水涂片,细胞块、淋巴结活检、免疫化学染色;R显带技术进行细胞遗传学分析;多色流式细胞仪分析免疫表型。结果该患者以T-PLL起病,骨髓中异常细胞表型:CD2+、CD3+、cCD3+、CD4+、CD7+、CD8-、CD10-、HLA-DR+、cTDT-、TCRα/β+,CD38、CD5部分阳性。染色体核型:46,XX。6个月后确诊为ALCL,染色体核型:94,XXX,-X,1q-x2,+3mar。结论 T-PLL可转变为ALCL,ALK-。     

间变性大细胞淋巴瘤临床病理和免疫组化观察

目的：探讨间变化大细胞淋巴瘤（anaplastic large cell lymphoma,ALCL)的病理形态和免疫组化在诊断上的价值。以提高对本病的认识。方法：观察24例ALCL病理形态以及采用链菌素亲生物素-过氧化酶连结法进行免疫组化标记。结果：瘤细胞形态多样，沿窦或滤胞间浸润，或呈巢状分布，免疫组化标记24例CD30均呈阳性，其中23例为T细胞性，1例为裸细胞性，CD15均阴性，ALKP80标记12例，其中3例阳性，结论：ALCL的病理学改变是多样性的，免疫组化在本病的诊断和鉴别诊断中具有重要意义。     

MiR-206 inhibits Head and neck squamous cell carcinoma cell progression by targeting HDAC6 via PTEN/AKT/mTOR pathway

As a kind of endogenous noncoding small RNA, microRNA (miRNA) plays important roles of regulation to various physiological functions, while its affections on senescence of human Head and neck squamous cell carcinoma (HNSCC) are still unknown. The objective of this study was to investigate the effect of miR-206 in HNSCC tissues, adjacent normal tissues and cell lines, and explore its biological functions in HNSCC.In our study, the level of miR-206 in HNSCC tissues and adjacent normal tissues was detected via real-time qPCR. The effect of miR-206 on cell proliferation was tested by MTT assay, colony formation and cell cycle assays. In order to explore the effect of miR-206 on HNSCC cell migration and invasion, we performed wound healing assays and transwell assays. Luciferase reporter assays were designed to identify the interaction between 3′UTR of HDAC6 and miR-206. The level of signaling pathway-related proteins was determined by western blot. The expression of miR-206 was found to be observably decreased in HNSCC tissues and cell lines through real time-PCR. Restoration of miR-206 weaked cell proliferation, invasion and migration in HNSCC cells and the cell cycle was arrest in S phase. Further explores have shown that miR-206 could inhibit HNSCC cells proliferation by targeting the HDAC6 via PTEN/AKT/mTOR pathway. Taken together, our results demonstrated that miR-206 plays a critical role in HNSCC progression by targeting HDAC6 via PTEN/AKT/mTOR pathway, which might be a potential target for diagnostic and therapeutic in HNSCC.     

槲皮素通过PI3K/AKT/mTOR通路减轻脓毒症小鼠心肌损伤

目的基于磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(AKT)/哺乳动物雷帕霉素靶蛋白(mTOR)通路探究槲皮素减轻脓毒症小鼠心肌损伤的分子机制,为槲皮素治疗脓毒症提供理论依据。方法采用盲肠结扎穿孔法构建脓毒症小鼠模型,将造模成功的小鼠随机分为模型组、槲皮素组(200 mg/kg)、抑制剂组(PI3K/mTOR抑制剂NVP-BEZ235 60 mg/kg)和槲皮素+抑制剂组(槲皮素200 mg/kg+PI3K/mTOR抑制剂NVP-BEZ235 60 mg/kg),每组15只,另取15只小鼠作为假手术组。假手术组和模型组小鼠灌胃等体积生理盐水,其余各组灌胃相对应药物,给药体积10 m L/kg。给药24 h后,超声检测平均动脉压(MAP)、左心室收缩压(LVSP)、左心室等容舒张期压力下降最大速率(-dp/dtmax)和左心室等容舒张期压力上升最大速率(+dp/dtmax);全自动生化分析仪检测血清肌酸激酶同工酶(CK-MB)和心肌肌钙蛋白I(cTnI)水平;苏木素-伊红(HE)染色观察心肌组织病理学变化;酶联免疫吸附(ELISA)法检测心肌组织白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、丙二醛(MDA)和超氧化物歧化酶(SOD)含量;蛋白免疫印迹(Western blot)法检测心肌组织PI3K、AKT和mTOR蛋白磷酸化水平。结果心肌组织病理损伤:模型组小鼠心肌组织出现结构紊乱、心肌细胞变性、心肌纤维断裂、心肌横纹模糊、细胞间质水肿等病理损伤;槲皮素组较模型组减轻,抑制剂组较模型组加重;槲皮素+抑制剂组较槲皮素组加重。MAP、LVSP、-dp/dtmax、+dp/dtmax、SOD含量及PI3K、AKT、mTOR蛋白磷酸化水平:模型组较假手术组降低;槲皮素组较模型组升高,抑制剂组较模型组降低;槲皮素+抑制剂组较槲皮素组降低,较抑制剂组升高,差异均有统计学意义(P <0.05)。CK-MB、cTnI水平及TNF-α、IL-6、MDA含量:模型组较假手术组升高;槲皮素组较模型组降低,抑制剂组较模型组升高;槲皮素+抑制剂组较槲皮素组升高,较抑制剂组降低,差异均有统计学意义(P <0.05)。结论槲皮素可能通过上调PI3K/AKT/mTOR通路降低脓毒症小鼠心肌组织炎症和氧化应激反应,从而减轻心肌损伤。     

LINC00941 promoted in vitro progression and glycolysis of laryngocarcinoma by upregulating PKM via activating the PI3K/AKT/mTOR signaling pathway

BackgroundLINC00941 has been proved to be related to various tumors, but its relationship with laryngocarcinoma remains vague.MethodsLINC00941 expression in laryngocarcinoma tumor and laryngocarcinoma cells was determined by real time‐quantitative polymerase chain reaction (RT‐qPCR). Besides, the five‐year survival of laryngocarcinoma patients with different LINC00941 expression was analyzed with Kaplan–Meier survival analysis, and the clinical characteristics of laryngocarcinoma patients were also recorded. After transfection, cell viability, cell proliferation, apoptosis, cell cycle, migration, and invasion were detected by cell counting kit‐8 (CCK‐8), colony formation, flow cytometry, cell scratch, and Transwell assays, respectively. Glycolysis was assessed by the colorimetric method. Expressions of proliferation‐associated proteins, migration‐associated proteins, glycolysis‐associated proteins, and phosphatidylinositol 3‐kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signal pathway‐associated proteins were detected by Western blot.ResultsIn laryngocarcinoma tumor tissues and cells, LINC00941 was highly expressed. High expression of LINC00941 decreased the 5‐year survival of laryngocarcinoma patients, and it was positively related to lymph node metastasis and clinical stages. LINC00941 overexpression decreased apoptosis but promoted cell viability, proliferation, cell‐cycle progression, migration, and invasion, and glucose consumption and lactate production in laryngocarcinoma cells. Moreover, LINC00941 overexpression elevated expressions of Ki‐67, PCNA, MMP2, N‐Cadherin, HK2, PFKFB4, and PKM, activated the PI3K/AKT/mTOR signal pathway but reduced E‐Cadherin expression, while LINC00941 silencing had the opposite effects. PKM overexpression reversed the effects of LINC00941 silencing on cellular and glycolytic phenotypes.ConclusionLINC00941 promoted in vitro progression and glycolysis of laryngocarcinoma cells by upregulating PKM via activating the PI3K/AKT/mTOR signaling pathway.     

HL-60 细胞 Nucleostemin 表达下调对 PI3K / AKT / mTOR 通路相关分子的影响简

本研究旨在探讨白血病细胞中nucleostemin （NS）基因下调对其非依赖p53通路的候选途径PI3 K/A KT/mTOR的相关分子表达的影响.通过重组慢病毒表达载体NS-RNAi-GV248转染至p53缺失型HL-60细胞以干扰NS基因的表达.用Real-time PCR技术评价转染后HL-60细胞NS基因的表达情况并检测干扰前后PI3 K/AKT/mTOR信号通路中相关分子水平表达的变化.结果表明：重组慢病毒载体NS-RNAi-GV248成功感染了HL-60细胞,在荧光显微镜下可见GFP荧光水平较高,大于80％.Real-time PCR结果显示,NS基因mRNA的抑制率在HL-60细胞中为56.5％;干扰NS的表达后PI3K、AKT和GβL基因mRNA表达量分别为0.491±0.084、0.398±0.164、0.472±0.097,下调明显,与空白对照组（分别为1.002±0.171、1.000±0.411、1.001 ±0.206）比较差异有统计学意义（P＜0.05）.结论：在HL-60细胞中PI3K/AKT/mTOR通路相关分子的变化与NS基因的下调呈正相关,两者的关联性为证明PI3 K/AKT/mTOR信号通路可能是NS的一种非依赖p53作用途径提供了依据.     

FK228 augmented temozolomide sensitivity in human glioma cells by blocking PI3K/AKT/mTOR signal pathways

Temozolomide is a novel cytotoxic agent currently used as first-line chemotherapy for glioblastoma multiforme (GBM). Romidepsin (FK228), a histone deacetylase inhibitor, is a promising new class of antineoplastic agent with the capacity to induce growth arrest and/or apoptosis of cancer cells. However, combination of the two drugs in glioma remains largely unknown. In the present study, we evaluated the combinatory effects of FK228 with TMZ in glioma, and its molecular mechanisms responsible for these effects. Glioma cell lines were treated with TMZ, FK228 or the combination of drugs. The resistance effect including cytotoxicity and apoptosis was determined in glioma cells, respectively. We further evaluated the effects of FK228 in the PI3K/Akt-signaling pathway in vitro. Mice engrafted with 5 × 10⁶ LN382 cells were treated with TMZ, FK228 or the combination of two drugs, and tumor weights and volumes were measured, respectively. FK228 enhanced the cytotoxic effects of TMZ in glioma cells compared to vehicle-treated controls or each drug alone. The combination of FK228 and TMZ-induced apoptosis was demonstrated by increased expression of cleaved-Caspase 3, Bax, cleaved-PARP, and decreased Bcl-2 expression. Furthermore, the expression of key components of the PI3K/Akt-signaling pathway showed that combination of FK228 and TMZ block PI3K/Akt pathways in vitro. This block effect was also confirmed in vivo in mice models. Mice treated with both FK228 and TMZ drugs showed significantly reduced tumor weights and volumes, compared to each drug alone. Our results suggested that FK228 augmented temozolomide sensitivity in human glioma cells partially by blocking PI3K/AKT/mTOR signal pathways. It thus may provide a promising target for improving the therapeutic outcome of TMZ-resistant gliomas, although further studies will be needed.     

Brentuximab vedotin in anaplastic large cell lymphoma

Objective: We aimed to investigate the influence of natalizumab (NTZ) treatment on multiple sclerosis course in patients with and without spinal involvement.

Methods: Annualized relapse rate (ARR), disability progression and occurrence of new brain and spinal T2 lesions (N2TL) in 68 spinal (S-P) versus 68 non-spinal matched patients (NS-P) were retrospectively collected and compared between before (2 years) and after NTZ treatment using multivariate regression models.

Results: Mean duration of NTZ treatment was 31.3 ± 16.3 months in S-P and 32.1 ± 15.1 months in N-SP (p = 0.56). The mean ARR after NTZ treatment was similarly reduced in both S-P (0.07 ± 0.19) and N-SP (0.07 ± 0.16) (p < 0.001 for both). Disability progression after NTZ start was similarly low in S-P and NS-P. However, when compared to before NTZ start, disability progression was significantly reduced in S-P (p = 0.017), but not in NS-P (p = 0.68). This was largely mediated by a higher disability progression before NTZ start in S-P than N-SP. The risk of developing N2TL during NTZ was not different between S-P and NS-P (p = 0.10).

Conclusions: NTZ similarly reduced the occurrence of relapses and NT2L in S-P and NS-P, whereas the effect on disability progression was particularly evident in the presence of spinal involvement. NTZ appears to be a treatment of high efficacy in both S-P and NS-P.     

Brentuximab vedotin in anaplastic large cell lymphoma

INTRODUCTION: Brentuximab vedotin , a novel anti-CD30 antibody-drug conjugate, delivers a cytotoxic agent into CD30(+) cells. CD30 expression is characteristic of anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma (HL). AREAS COVERED: We reviewed data on brentuximab vedotin, focusing on ALCL and discuss pharmacology, clinical trials leading to approval and future research directions. Systemic ALCL, 3% of adult NHL, is characterized by large anaplastic CD30(+) cells. The fusion protein NPM-ALK, when present in systemic ALCL, confers better prognosis, although even ALK- patients with IPI score ≥ 3 are high-risk. For patients with systemic ALCL, 25 - 45% relapse after frontline therapy, and > 50% of patients will relapse following high-dose chemotherapy with autologous stem-cell support. There has been no standard therapy for relapsed/refractory systemic ALCL. Brentuximab vedotin, combines a monoclonal antibody targeted to CD30 with a microtubule disrupting agent and was recently approved for treatment of patients with systemic ALCL that is refractory or relapsed after at least one multiagent chemotherapy regimen. EXPERT OPINION: Brentuximab vedotin provides targeted therapy to CD30(+) lymphomas, including ALCL and HL, with high response rates and manageable toxicity, predominantly myelosuppression and peripheral neuropathy.     

Schisandrin B suppresses glioma cell metastasis mediated by inhibition of mTOR/MMP-9 signal pathway

BackgroundMalignant glioma is the aggressive tumor in the brain and is characterized by high morbidity, high mortality. The main purpose of the present study was to investigate the therapeutic effects of Schisandrin B on glioma cells and preliminary explore the possible mechanism underlying anti-metastasis of Schisandrin B.MethodsTwo glioma cell lines, U251 and U87, were used in present study. The ability of metastasis of glioma cells was evaluated using transwell migration assay and invasion assay. Expression of Akt, mTOR, MMP-2 and MMP-9 was determined using Western blotting. Antagonist or agonist was used to activated or inactivated signal molecules.ResultsSchisandrin B suppressed cell migration and invasion in manner of dose dependent as well as inhibited expression of p-Akt, p-mTOR and MMP-9. Activation of PI3K by 740Y-P treatment leaded to upregulation of p-Akt, mTOR and MMP-9; inactivation of mTOR by Rapamycin treatment inhibited expression MMP-9 while activation of mTOR by l-Leucine treatment enhanced MMP-9 expression in Schisandrin B incubated cells. Anti-migration and invasion action of Schisandrin B was also reversed by mTOR activation.ConclusionOur findings demonstrate that Schisandrin B can suppress migration and invasion of glioma cell via PI3K/Akt-mTOR-MMP-9 signaling pathway.     

PI3K/AKT信号通路在急性白血病中调控机制的初步研究

本研究探讨PI3K/AKT通路中的PTEN、CCND1、mTOR、RICTOR、FOXO1基因在急性髓系白血病(AML)、急性淋巴细胞白血病(ALL)患者中与正常人中表达的差异,以期查明PI3K/AKT通路在白血病中是否存在通路失调。随机收集16例骨髓标本,其中白血病12例(AML 6例,ALL 6例),正常骨髓标本4例。用实时定量RT-PCR方法检测PI3K/AKT通路中的PTEN、CCND1、mTOR、RICTOR、FOXO1基因的表达变化;以管家基因GAPDH为内参,按2-△△Ct法计算目的基因相对表达量。结果表明:PTEN、mTOR、RICTOR在AML、ALL中总体呈低表达趋势,PTEN在12例标本中有10例低表达,mTOR在12例标本中9例低表达,RICTOR在12例标本中7例低表达;FOXO1,CCND1在AML、ALL中则呈高表达趋势,FOXO1在12例标本中有9例高表达,CCND1在12例标本中7例高表达。结论:PI3K/AKT信号通路基因在白血病细胞中被激活。