Dihydroartemisinin enhances cell apoptosis in diffuse large B cell lymphoma by inhibiting the STAT3 activity

Background:Dihydroartemisinin(DHA)is reported to be a potential anticancer agent,and the mechanisms underlying the effects of DHA on diffuse large B cell lymphoma however are still obscure.This study aimed to assess the antitumor effect of DHA on diffuse large B cell lymphoma cells and to determine the potential underlying mechanisms of DHA-induced cell apoptosis.Methods:Here,the Cell Counting Kit 8 assay was conducted to study cell proliferation.We performed Annexin V-FITC/propidium iodide staining,real-time polymerase chain reaction,and western blot analysis to analyze cell apoptosis and potential molecular mechanisms.Results:The results showed that DHA substantially suppressed cell proliferation and induced cell apoptosis in vitro in a time-and concentration-dependent fashion.Moreover,STAT3 activity could be inhibited after stimulation with DHA.Conclusion:These results imply that the underlying anti-tumoral effect of DHA may increase apoptosis in diffuse large B cell lymphoma cells via the STAT3 signaling pathway.In addition,DHA might be an effective drug for diffuse large B cell lymphoma therapy.

Efficacy of rituximab in gastric diffuse large B cell lymphoma patients

AIM:To evaluate retrospectively the efficacy of rituximab plus chemotherapy in gastric diffuse large B cell lymphoma(DLBCL).METHODS:Sixty patients(median age:58 years)with histologically confirmed gastric DLBCL treated at four Italian institutions between 2000 and 2007,were included in this analysis.Patients were selected by stage (Ⅰ-Ⅳ,Lugano staging system),European Cooperative Oncology Group performance status(0-2)and treatment strategies.Treatment strategies were chemotherapy alone(group A,n=30)[scheduled as cyclophosphamide,doxorubicin,vincristine and prednisone (CHOP)and CHOP-like],and chemotherapy combined with rituximab(group B,n=30).The primary end point of the study was complete response(CR)rate;the secondary end points were disease-free survival (DFS)at 5 years and overall survival(OS).RESULTS:Median follow-up was 62 mo(range:31102 mo).We observed a significant difference between the two groups(A vs B)in terms of CR[76.6%(23/30) vs 100%,P=0.04)and DFS at 5 years[73.3%(22/30) vs 100%,P=0.03).To date,19 group A(63.3%) patients are alive and 11 have died,while all group B patients are alive.No significant differences in toxicity were observed between the two groups.CONCLUSION:Rituximab in combination with chemotherapy improves CR rate,DFS and OS.Further prospective trials are needed to confirm our results.

Diffuse large B cell lymphoma originating from the maxillary sinus with skin metastases:A case report and review of literature

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is the most common type of malignant lymphoma(ML),accounting for 30%-40%of cases of non-Hodgkin’s lymphoma(NHL)in adults.Primary paranasal sinus lymphoma is a rare presentation of extranodal NHL that accounts for only 0.17%of all lymphomas.ML from the maxillary sinus(MS)is a particularly rare presentation,and is thus often difficult to diagnose.We have reported the first known case of DLBCL originating from the MS with rapidly occurrent multiple skin metastasis.CASE SUMMARY An 81-year-old Japanese man visited our hospital due to continuous pain for 12 d in the left maxillary nerve area.His medical history included splenectomy due to a traffic injury,an old right cerebral infarction from when he was 74-years-old,hypertension,and type 2 diabetes mellitus.A plain head computed tomography(CT)scan revealed a 3 cm×3.1 cm×3 cm sized left MS.On day 25,left diplopia and ptosis occurred,and a follow-up CT on day 31 revealed the growth of the left MS mass.Based on an MS biopsy on day 50,we established a definitive diagnosis of DLBCL,non-germinal center B-cell-like originating from the left MS.The patient was admitted on day 62 due to rapid deterioration of his condition,and a plain CT scan revealed the further growth of the left MS mass,as well as multiple systemic metastasis,including of the skin.A skin biopsy on day 70 was found to be the same as that of the left MS mass.We notified the patient and his family of the disease,and they opted for palliative care,considering on his condition and age.The patient died on day 80.CONCLUSION This case suggests the need for careful,detailed examination,and for careful follow-up,when encountering patients presenting with a mass.

Guillain-Barrésyndrome and hemophagocytic syndrome heralding the diagnosis of diffuse large B cell lymphoma:A case report

BACKGROUND Central nervous system(CNS)lesions and peripheral neuropathy are rare among patients with non-Hodgkin’s lymphoma(NHL).Lymphomatous infiltration or local oppression usually accounts for CNS or peripheral nerve lesions.The incidence of peripheral neuropathy was 5%.Guillain-Barrésyndrome(GBS)is rare and may occur in less than 0.3%of patients with NHL.Hemophagocytic syndrome(HPS)is a rare complication of NHL.It has been reported that 1%of patients with hematological malignancies develop HPS.Diffuse large B-cell lymphoma(DLBCL)combined with GBS has been reported in 10 cases.CASE SUMMARY We report the case of a 53-year-old man who was initially hospitalized because of abnormal feelings in the lower limbs and urinary incontinence.He was finally diagnosed with DLBCL combined with GBS and HPS after 16 d,which was earlier than previously reported.Immunoglobulin pulse therapy,dexamethasone,and etoposide were immediately administered.The neurological symptoms did not improve,but cytopenia was relieved.However,GBS-related clinical symptoms were relieved partially after one cycle of rituximab-cyclophosphamide,hydroxydaunorubicin,vincristine,and prednisone(R-CHOP)chemotherapy and disappeared after six cycles of R-CHOP.CONCLUSION GBS and HPS heralding the diagnosis of Epstein-Barr virus DLBCL are rare.Herein,we report a rare case of DLBCL combined with GBS and HPS,and share our clinical experience.Traditional therapies may be effective if GBS occurs before lymphoma is diagnosed.Rapid diagnosis and treatment of DLBCL are crucial.

Diagnosis and therapy of primary lung diffuse large B cell lymphoma： a case report

Objective： We studied the diagnosis and therapy of primary lung diffuse large B cell lymphoma （DLBCL）. Methods： Analysis the clinical manifestations, pathologic character and immunohistochemical character of one lung diffuse B cell lymphoma patent. Results： In visual observation, it＇s a gray irregular fobulated mass, section was gray, fish-like, and number of necrotic foci. Observed under the microscope, subepithelial respiratory center oocyte-like cells diffuse proliferative, infiltration in lung tissue. Immunohistochemistry： CD20 （＋）, CD79a （＋）, CD3 （-）, CD45RO （-）, PCK （-）. Conclusion： Diffuse large B cell lymphoma is the most common subtype in non-Hodgkin lymphoma, but the primary lung diffuse large B cell lymphoma is rare. This disease is lack of typical clinical manifestations, so easily misdiagnosed. The diagnosis of diffuse large B cell lymphoma should be based on pathology and immunohistochemistry.

Occurrence of MYD88L265P and CD79B mutations in diffuse large b cell lymphoma with bone marrow infiltration:A case report

BACKGROUNDOver the past 20 years,we have gained a deep understanding of the biologicalheterogeneity of diffuse large B cell lymphoma(DLBCL)and have developed arange of new treatment programs based on the characteristics of the disease,bringing us to the era of immune-chemotherapy.However,the effectiveness andmolecular mechanisms of targeted-immunotherapy remain unclear in DLBCL.Targeted-immunotherapy may be beneficial for specific subgroups of patients,thus requiring biomarker assessment.CASE SUMMARYHere,we report a case of MCD subtype DLBCL with MYD88L265P and CD79Bmutations,considered in the initial stage as lymphoplasmic lymphoma(LPL)orWaldenstrom macroglobulinemia(WM).Flow cytometry supported this view;however,the immunohistochemical results of the lymph nodes overturned theabove diagnosis,and the patient was eventually diagnosed with MCD subtypeDLBCL.The presence of a monoclonal IgM component in the serum and infiltrationof small lymphocytes with a phenotype compatible with WM into the bonemarrow led us to propose a hypothesis that the case we report may have transformedfrom LPL/WM.CONCLUSIONThis highlights the possible transformation from WM to DLBCL,CD79B mutationmay be a potential biomarker for predicting this conversion.

Expression and clinical value of programmed cell death-ligand 1(PD-L1)in diffuse large B cell lymphoma:a retrospective study

Background: The programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses.Diffuse large B-cell lymphoma(DLBCL) is the most common lymphoid malignancy in adults. In the present study, we aimed to detect the expression of PD-L1 in DLBCL and to analyze its relationship with prognosis.Methods: We reviewed medical records of 204 newly diagnosed DLBCL patients in Sun Yat-sen University Cancer Center between October 2005 and August 2012. The expression of PD-L1 in tumor tissues from these 204 patients was detected using immunohistochemical(IHC) assay. The expression of anaplastic lymphoma kinase(ALK), CD5,CD30, and C-Myc in tumor specimens from 109 patients was detected using IHC, and Epstein-Barr virus(EBV)-encoded RNAs(EBERs) were detected using fluorescence in situ hybridization. The Spearman method was used for correlation analysis. The Kaplan-Meier method with log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis.Results: Of the 204 patients, 100(49.0%) were PD-L1-positive in tumor cells and 44(21.6%) were PD-L1-positive in tumor microenvironment. PD-L1 expression in tumor cells and tumor microenvironment were more common in the non-germinal center B-cell-like(GCB) subtype than in the GCB subtype(P = 0.02 and P= 0.04). Patients with PD-L1 expression in tumor microenvironment were more likely to be resistant to first-line chemotherapy when compared with the patients without PD-L1 expression in tumor microenvironment(P = 0.03). PD-L1 expression in tumor microenvironment was negatively correlated with C-Myc expression(r =-0.20, P = 0.04). No correlations were detected between PD-L1 expression and the expression of ALK, CD5, and CD30 as well as EBERs. The 5-year overall survival(OS)rates were 50.0% and 67.3% in patients with and without PD-L1 expression in tumor cells(P = 0.02). PD-L1 expression in tumor cells was an independent risk predictor for OS(P < 0.01).Conclusions: PD-L1 expression is more common in the non-GCB subtype than in the GCB subtype. PD-L1 expression in tumor microenvironment has a negative correlation with C-Myc. PD-L1 positivity predicts short survival in DLBCL patients. For patients with PD-L1 expression, more strategy such as anti-PD-L1 antibody treatment should be recommended.

Prognostic value of ^(18)F-fluorodeoxyglucose positron emission tomography using Deauville criteria in diffuse large B cell lymphoma treated with autologous hematopoietic stem cell transplantation

Objective: High-dose chemotherapy(HDC) followed by autologous hematopoietic stem cell transplantation(auto-HSCT) plays an important role in improving outcomes of diffuse large B cell lymphoma(DLBCL) patients.18 F-fluorodeoxyglucose(18 F-FDG) positron emission tomography(PET)/computed tomography(CT) has been widely accepted in response assessment and prediction of prognosis in DLBCL. Here, we report the value of 18 FFDG PET/CT pre-and post-HSCT in predicting outcomes of patients with DLBCL.Methods: DLBCL patients who had PET/CT scan before and after HSCT were included. PET results were interpreted based upon Deauville criteria. The prognostic value of 18 F-FDG PET/CT in auto-HSCT was evaluated.Results: Eighty-four patients were enrolled. In univariate analysis, pre-and post-HSCT PET findings were correlated with 3-year progression-free survival(PFS) [hazard ratio(HR)=4.391, P=0.001; HR=7.607, P<0.001] and overall survival(OS)(HR=4.792, P=0.008; HR=26.138, P<0.001). Patients receiving upfront auto-HSCT after firstline treatment had better outcomes than relapsed/refractory DLBCL patients(3-year PFS, P<0.001; 3-year OS,P<0.001). In the relapsed/refractory patients, pre-and post-HSCT PET findings were also associated with 3-year PFS(P=0.003 vs. P<0.001) and OS(P=0.027 vs. P<0.001). A significant correlation was observed between clinical response to chemotherapy before auto-HSCT and outcomes of patients in the entire cohort(3-year PFS, P<0.001;3-year OS, P<0.001) and in the subgroup of 21 patients with positive pre-HSCT PET(3-year PFS, P=0.084; 3-year OS, P=0.240). A significant association between survival and post-HSCT PET findings was observed in multivariate analysis(HR=5.168, P<0.001).Conclusions: PET results before and after HSCT are useful prognostic factors for DLBCL patients receiving HSCT. Patients who responded to chemotherapy, even those with positive pre-HSCT PET, are appropriate candidates for auto-HSCT.

High-dose Chemotherapy Combined with Autologous Hematopoietic Stem Cell Transplantation as Frontline Therapy for Intermediate/High-risk Diffuse Large B Cell Lymphoma

The role of autologous hematopoietic stem cell transplantation(auto-HSCT)following high-dose chemotherapy has been validated and accepted as a standard treatment for patients with relapsed diffuse large B-cell lymphoma(DLBCL).However,its clinical efficacy as frontline therapy remains to be elucidated.This study aimed to examine the feasibility of frontline auto-HSCT for newly diagnosed intermediate/high-risk DLBCL patients.We retrospectively reviewed the data of 223 patients treated with frontline auto-HSCT or chemotherapy alone(year 2008-2014)from four hospitals.The median follow-up time was 29.4 months.Between the two treatment arms among the intermediate/high-risk DLBCL patients,the 3-year overall survival(OS)and progression-free survival(PFS)rates of patients given frontline auto-HSCT were 87.6%and 81.9%,respectively,and the chemotherapy-alone group showed 3-year OS and PFS rates of 64.9%and 59.59%,respectively.Compared with the chemotherapy-alone group,the frontline auto-HSCT could eliminate the adverse impact of non-germinal center B-cell(GCB)type.In addition,in the frontline auto-HSCT group,patients who achieved complete response(CR)at auto-HSCT had a longer survival time than those who did not achieve CR.Our results suggested that frontline auto-HSCT could improve the prognosis of intennediate/high-risk DLBCL patients.

The Diagnostic and Prognostic Impact of Serum miRNA-21 in a Sample of Hepatitis C/None Hepatitis Diffuse Large B Cell Lymphoma Egyptian Patients

Background: Circulating microRNAs are potential biomarkers of diagnostic and prognostic impact in various inflammatory and malignant diseases. Aim: Linking inflammation with malignancy, we studied miRNA-21 in sera of hepatitis-C-virus (HCV) and none hepatitis diffuse large B-cell lymphoma (DLBCL) patients, aiming to identify its differential expression and prognosis in DLBCL with its subtypes;germinal center B-cell (GCB) and activated B-cell-like (ABC) and to evaluate its relation with HCV. Subjects and Methods: MiRNA-21 expression was measured using TaqMan quantitative RT-PCR in sera of 30 newly diagnosed DLBCL patients (HCV positive (n = 10), HCV negative (n = 20)) and 20 controls (HCV positive (n = 10), HCV negative (n = 10)). Results: MiRNA-21 expression was significantly higher in DLBCL patients than in control (p = 0.00). Significant positive correlations between miRNA-21 and LDH, IPI and disease stage were detected (p Conclusion: Our study shows that miRNA-21 is over expressed in our patients with DLBCL, displaying higher levels in ABC than in GCB subtypes. MiRNA-21 is associated with poor response to treatment and survival in DLBCL. MiRNA-21 is a potential marker of necro-inflammation independent of its role in tumorogenesis, showing higher expression in HCV positive DLBCL patients compared to none hepatitis patients.

Diagnostic and Prognostic Value of Nuclear Factor Kappa-B in Diffuse Large B Cell Lymphoma in Egyptian Patients with Hepatitis C Virus Genotype 4

Background: Members of the NFκB [p65] family have potential diagnostic and prognostic role in various inflammatory diseases and Lymphomas. Aim: We studied NFκB [p65] in paraffin blocks of hepatitis-C-virus [HCV] positive genotype-4 and HCV negative diffuse large B-cell lymphoma [DLBCL] patients, aiming at identification of its differential expression and prognosis in DLBCL and its subtypes;GCB and ABC. This is to establish its relation to HCV infection and its role in lymphogenesis. Besides assessing the role of new directly acting antiviral drugs [Sofusbuvir/Ledipasvir] concomitantly administered to [CHOP] combination in HCV positive DLBCL. Subjects and Methods: NFκB [p65] expression was assessed using Anti-NFκB [p65] antibody semi-quantitative technique in 30 newly diagnosed DLBCL patients [HCV positive [n = 15], HCV negative [n = 15]. Results: NFκB [p65] expression was higher in the HCV positive DLBCL patients than their HCV negative counterpart, with a positive correlation with the viral load [r = 0.536, p = 0.088]. NFκB [p65] expression was significantly more frequently detected in the ABC subtype than GCB subtype [p = 0.04]. Patients who expressed NFκB [p65] had higher incidence of extranodal involvement, advanced stages, higher LDH levels and IPI score. Besides, the expression of NFκB [P65] revealed an inferior overall response [OR] [p = 0.044]. Higher complete response rates to CHOP concomitantly with antiviral [ledipasvir/sofosbuvir] were encountered in the HCV positive group. In HCV positive group, NFκB [P65] displayed a positive relationship with the viral load and liver enzymes [p = 0.04], besides an inverse relation with serum albumin. This raises the possibility that NFκB [p65] expression is suggestive of the hepatic necro-inflammation in HCV patients. The ABC group presented more in advanced stages than GCB. Higher frequency of the ABC subgroup exhibited intermediate to high viral load, while it was less in the GCB. A statistically significant difference was found in the NFκB [p65] positive patients as regards MUM1 expression among the two groups [p ≤ 0.001]. Double positive [CD10+, MUM1+] and triple negative [CD10-, BCL6-, MUM1-] cases were encountered in the HCV positive group, and were characterized with a high NFκB [p65] expression. Conclusion: NFκB [p65] is expressed in patients with DLBCL, more frequently in ABC than in GCB subtypes. Expression of NFκB [p65] is associated with poor response to therapy in DLBCL. The NFκB [p65] disclosed an increased expression in HCV positive DLBCL compared to HCV negative group. The viral load displayed a positive correlation with the NFκB [p65] expression. Simultaneous administration of DAAs in combination with CHOP disclosed a better response and high tolerability.

基线PET/CT显像骨髓^(18)F-FDG摄取模式预测DLBCL预后的价值

目的:探讨弥漫大B细胞淋巴瘤(DLBCL)治疗前^(18)F-脱氧葡萄糖(^(18)F-FDG)PET/CT显像中骨髓摄取模式对预测DLBCL患者预后的价值。方法:回顾性分析156例DLBCL患者的临床资料,所有患者治疗前均行骨髓活检、骨髓涂片、流式细胞分析和^(18)F-FDG PET/CT扫描。以正常肝脏^(18)F-FDG摄取为标准,将患者骨髓摄取模式分为骨髓摄取局灶型增高(f PET+)、骨髓摄取弥漫型增高(d PET+)及骨髓摄取正常型(n PET)。生存分析采用Kaplan-Meier法,组间差异比较采用log-rank检验,采用多因素Cox回归分析确定与预后相关的危险因素。结果:156例患者中,f PET+17例,d PET+28例,n PET 111例。临床诊断骨髓浸润阳性21例,阴性135例。复发进展62例,死亡18例。单因素分析显示,Ann Arbor分期Ⅲ/Ⅳ期、B症状、NCCN-IPI评分、乳酸脱氢酶、骨髓浸润及f PET+与患者无进展生存期(PFS)有关(均P<0.05);Ann Arbor分期Ⅲ/Ⅳ期、NCCN-IPI评分、乳酸脱氢酶、骨髓浸润及f PET+与患者总生存期(OS)有关(均P<0.05);多因素分析显示,Ann Arbor分期III/IV期、乳酸脱氢酶和f PET+(均P<0.05)是PFS独立预测因子。在OS的多变量分析中没有独立预测因子。结论:DLBCL患者治疗前^(18)F-FDG显像中骨髓摄取模式对预后有预测价值,f PET+是患者PFS的独立危险因素。

Effects of TNFAIP3 and PDE4B on apoptosis and invasion of tumor cells in diffuse large B cell lymphoma

Objective: To study the effects of TNFAIP3 and PDE4B on apoptosis and invasion of tumor cells in diffuse large B cell lymphoma. Methods: A total of 68 patients who were diagnosed with diffuse large B cell lymphoma in Guangzhou 421 Hospital of PLA between August 2014 and July 2017 were selected as the DLBCL group of the study, and 34 patients who accepted lymph node biopsy due to lymphadenectasis and were diagnosed with reactive lymphoid hyperplasias in Guangzhou 421 Hospital of PLA during the same period were selected as the control group. The expression levels of TNFAIP3, PDE4B, apoptosis genes and invasion genes in lymph node tissue were determined. Results: TNFAIP3, PTEN, PTPL1 and Bax protein expression in lesion tissue of DLBCL group were significantly lower than those of control group whereas PDE4B, c-myc, AURKA, AURKB, PLK1, Ets-1, β-catenin, MMP7, MMP9 and CD44 protein expression were significantly higher than those of control group;PTEN, PTPL1 and Bax protein expression in DLBCL lesions were positively correlated with TNFAIP3 protein expression and negatively correlated with PDE4B protein expression;c-myc, AURKA, AURKB, PLK1, Ets-1, β-catenin, MMP7, MMP9 and CD44 protein expression were negatively correlated with TNFAIP3 protein expression and positively correlated with PDE4B protein expression. Conclusion: The low expression of TNFAIP3 and the high expression of PDE4B in diffuse large B cell lymphoma can antagonize tumor cell apoptosis and promote tumor cell invasion.

基于多模态影像学分析PCNS-DLBCL的临床表现及对预后的预测效能

目的:探究原发性中枢神经系统弥漫性大B细胞淋巴瘤(PCNS-DLBCL)的多模态影像学表现,并分析多模态影像学表现对预后的预测效能。方法:选取2020年8月至2022年12月我院收治的78例PCNS-DLBCL患者,统计分析多模态影像学检查结果,接受标准CHOP方案或利妥昔单克隆抗体联合标准CHOP方案(R-CHOP)作为一线治疗,化疗前均接受氟代脱氧葡萄糖正电子发射断层显像/计算机体层成像(18 F-FDG PET/CT)检查,获取病灶总糖酵解值(TLG)、代谢肿瘤体积(MTV)、SUVpeak、SUVmax等参数,根据预后结果分为未进展组和进展组、生存组和死亡组,比较其两两之间的影像学参数,分析各参数对PCNS-DLBCL患者疾病进展、死亡预后的预测价值。结果:78例PCNS-DLBCL患者多模态影像学检查共发现192个病灶,33例为单发病灶(33个病灶),45例为多发病灶(159个病灶)。单发病灶组、多发病灶组年龄、性别、病变分布、CT平扫、MRI T1WI、MRI T2WI、MRI增强扫描、FLAIR序列、MRS、DWI、FDG PET/CT影像学表现比较,差异均无统计学意义(P>0.05),单发组握拳征、裂隙征占比高于多发组(P<0.05)。随访1年,根据期间是否进展、是否存活分组,未进展组TLG、MTV、SUVpeak、SUVmax均低于进展组(P<0.05);生存组TLG、MTV、SUVpeak、SUVmax均低于死亡组(P<0.05);18 F-FDG PET/CT各参数联合预测PCNS-DLBCL患者疾病进展、死亡的AUC分别为0.901、0.930,大于各参数单独预测的AUC。结论:PCNS-DLBCL单发、多发病灶多模态影像学表现无明显差异,不同疾病进展情况、生存情况患者18 F-FDG PET/CT参数差异显著,TLG、MTV、SUVpeak、SUVmax对PCNS-DLBCL患者疾病进展、死亡有较高预测价值。

R-CHOP联合同步放疗对初治DLBCL中期评估后PR患者的疗效及安全性

目的探讨R-CHOP联合三维适形调强放疗(IMRT)治疗中期疗效评价为部分缓解(PR)的初治弥漫性大B细胞淋巴瘤(DLBCL)患者的临床疗效与安全性。方法对20例经一线R-CHOP治疗3周期后,中期疗效评价为PR的初治弥漫性大B细胞淋巴瘤患者,后续治疗采用同步放化疗(3周期R-CHOP联合局部残留病灶行IMRT放疗);收集患者的分期、性别、病理类型、是否为双表达型、是否合并HIV、年龄、乳酸脱氢酶水平(LDH)、B症状、结外累及部位数及国际预后指数(IPI评分)等一般临床资料,并在治疗结束后行即刻疗效评价[完全缓解(CR)、未确定的完全缓解(CRu)、部分缓解(PR)、客观有效率(CR+CRu+PR)],比较不同分期的疗效;根据随访结果记录复发患者的部位、时间及转归,以是否复发分组,分析复发相关危险因素;比较靶向化疗与同步放化疗期间的毒副反应,记录放疗局部放疗毒性。结果同步放化疗结束后弥漫性大B细胞淋巴瘤患者即刻疗效结果显示,CR高于CRu、PR、CR+CRu+PR为100%;局限期患者较进展期患者显示出更高的CR率,差异有统计学意义(P<0.05);共有患者出现复发7例,仅1例出现放疗部位复发,放疗显示出较好的局部控制(94.7%);对患者一般临床资料进行分析,结果提示患者为进展期、非生发中心来源亚型、>60岁、LDH升高、伴B症状、IPI评分高者更易复发(P<0.05);同步放化疗期间Ⅲ~Ⅳ度白细胞/中性粒细胞、血小板降低、感染、因毒副反应导致化疗延期>7 d的发生率高于单纯靶向化疗期间(P<0.05);放疗局部反应主要表现为照射野内Ⅰ~Ⅱ级放射性反应,未出现大于3级急性放射性炎症,耐受性好。结论R-CHOP联合三维适形调强放疗可以提高初治弥漫性大B细胞淋巴瘤的CR率,毒副反应可耐受,R-CHOP与放疗联合应用安全。

RPRD1B/CREPT facilitates the progression of diffuse large B-cell lymphoma by inhibiting apoptosis through the NF-κB signaling pathway

Objective:To investigate the role of RPRD1B in the progression of diffuse large B-cell lymphoma(DLBCL)and its potential as a therapeutic target.Methods:This study analyzed RPRD1B expression in DLBCL and normal tissues using public databases and assessed its prognostic impact through survival analysis.In vitro and in vivo experiments were conducted to explore the mechanisms by which RPRD1B influences tumor growth and apoptosis.Results:RPRD1B expression was significantly elevated in DLBCL compared to normal tissues and was associated with poor prognosis.In vitro and in vivo experiments demonstrated that RPRD1B promoted lymphoma cell proliferation and inhibited apoptosis through the NF-κB signaling pathway.Conclusions:RPRD1B plays a critical role in the progression of DLBCL by modulating apoptosis and cellular proliferation.Targeting RPRD1B may offer a novel therapeutic strategy for DLBCL,suggesting its potential as a prognostic marker and therapeutic target in hematological malignancies.

DLBCL患者血Th22细胞、IL-22水平及IL-22对DLBCL细胞株增殖和侵袭的影响

目的分析弥漫性大B细胞淋巴瘤(DLBCL)患者血辅助性T细胞22(Th22)细胞、白细胞介素-22(IL-22)水平及IL-22对DLBCL细胞株增殖和侵袭的影响。方法选择DLBCL患者40例(DLBCL组),按照临床分期分为不同亚组;另选同期体检健康者40例为对照组。流式细胞术检测各组Th22细胞比例,ELISA检测各组IL-22蛋白水平。MTT实验检测DLBCL细胞增殖情况,Transwell实验检测DLBCL细胞侵袭情况。结果与对照组比较,DLBCL组Th22细胞比例和IL-22水平升高;与Ⅰ~Ⅱ期比较,Ⅲ~Ⅳ期Th22细胞比例和IL-22水平升高(P<0.05)。化疗后Th22细胞比例低于化疗前,复发者Th22细胞比例高于新诊患者和对照组(P<0.05)。MTT和Transwell实验结果显示,IL-22促进DLBCL细胞的增殖和侵袭(P<0.05)。结论DLBCL患者Th22细胞比例及其细胞因子IL-22水平升高,IL-22促进DLBCL细胞增殖和侵袭,为DLBCL研究提供新策略。

骨髓浸润伴染色体异常的DLBCL患者临床特征及与预后的相关性分析

目的:探讨骨髓浸润伴染色体异常的弥漫大B细胞淋巴瘤(DLBCL)患者的临床特征,以及染色体异常程度与预后的相关性。方法:回顾性分析在山西省肿瘤医院诊断为骨髓浸润且具有完整染色体结果的88例DLBCL患者的临床资料,采用χ^(2)检验分析其临床特征,采用Kaplan-Meier方法进行无进展生存(PFS)和总体生存(OS)分析,log-rank方法进行比较分析。结果:88例患者中有31例检测出染色体异常(35.2%),其中复杂核型者15例(17.0%)。复杂核型患者BCL-2、BCL-6、C-MYC、Ki-67≥80%阳性检出率高,且多为双表达。生存分析发现复杂核型的DLBCL患者PFS和OS明显差于染色体正常及1-2条染色体异常患者。结论:骨髓浸润且染色体异常的DLBCL患者中,复杂核型患者的生存期更短。

FTO及其抑制剂对DLBCL利妥昔单抗耐药的影响

目的探讨脂肪量和肥胖相关蛋白(FTO)及其抑制剂对弥漫大B细胞淋巴瘤(DLBCL)利妥昔单抗耐药的影响。方法选取2种“双重打击”淋巴瘤衍生的细胞系,活化B细胞样(ABC型)OCI-LY8(LY8)和生发中心B细胞样(GCB型)OCI-LY18(LY18),采用梯度加药法构建利妥昔单抗耐药细胞系(LY8R、LY18R);运用CCK-8法检测不同浓度利妥昔单抗分别干扰亲本及耐药细胞后的细胞存活率并计算半数抑制浓度(IC_(50))值;AnnexinⅤ/PI双染法检测亲本及耐药细胞的凋亡率;RT-qRCR、免疫荧光和Western blot检测在耐药细胞株中去甲基化酶FTO的表达情况;在耐药细胞株中加入甲氯芬酸钠(MA)抑制FTO表达,用RT-qRCR和Western blot验证抑制情况,并通过Western blot分析抑制耐药株中FTO后,c-Myc和CEBPA的表达情况。结果与亲本细胞比较,在利妥昔单抗耐药的细胞株中,去甲基化酶FTO、c-Myc表达均增加,CEBPA表达降低,差异均有统计学意义(P<0.01)。耐药细胞株经MA处理后,FTO、c-Myc表达降低,CEBPA表达增高,差异均有统计学意义(P<0.01)。结论FTO在耐药株中表达明显增高,MA可抑制DLBCL耐药细胞中FTO表达,可能对利妥昔单抗耐药的DLBCL患者有治疗的潜能。

来那度胺联合R-CHOP治疗DLBCL改善ALC/AMC比值的研究进展

弥漫大B细胞淋巴瘤(diffuse large B-cell lymphomas,DLBCL)是非霍奇金淋巴瘤的主要亚型。DLBCL在临床表现、基因表达、治疗反应及预后方面均存在差异,外周血绝对淋巴细胞(ALC)/单核细胞(AMC)比值(ALC/AMC)作为宿主免疫和肿瘤微环境的替代指标,是预测DLBCL患者临床疗效的生物标志物。来那度胺是一种免疫调节药物,对DLBCL患者有效,对肿瘤微环境及宿主免疫反应有多种作用机制。来那度胺联合标准R-CHOP治疗以前未经治疗的DLBCL患者,似乎克服了单用R-CHOP治疗患者ALC/AMC比值的不良预后价值,本文对这一观点进行综述。