Background: Primary central nervous system lymphoma (PCNSL) is a rare but aggressive non-Hodgkin lymphoma. Currently, high-dose methotrexate (HD-MTX)-based chemotherapy remains the standard first-line treatment. Previous clinical trials have reported that fotemustine-containing regimens offer promising efficacy and tolerability as an alternative option. Objectives: To compare the efficacy, safety, and feasibility of fotemustine-containing regimens with HD-MTX-containing regimens for newly diagnosed PCNSL. Design: A single-center, retrospective cohort study. Methods: We retrospectively analyzed 114 newly diagnosed PCNSL patients treated between April 2011 and December 2021. Patients were classified into two cohorts: those receiving fotemustine-containing regimens ( n = 72) and those receiving HD-MTX-containing regimens ( n = 42). The primary efficacy endpoint was the objective response rate (ORR). Secondary endpoints included complete response rate, progression-free survival (PFS), and overall survival (OS). Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Results: No significant difference in ORR was observed between the fotemustine-containing group and HD-MTX-containing group (68% vs 67%, p = 0.879). At a median follow-up of 28.5 months, the survival outcomes were comparable, with no statistically significant differences in either PFS (hazard ratio (HR) = 0.887, 95% confidence interval (CI): 0.522–1.508; p = 0.654) or OS (HR = 0.966, 95% CI: 0.494–1.888; p = 0.918). Notably, fotemustine-based therapy was associated with significantly fewer AEs, including leukopenia, thrombocytopenia, digestive tract toxicity, and mucositis (all p < 0.05). Conclusion: Fotemustine-containing chemotherapeutics appear to confer a safer profile with comparable efficacy relative to HD-MTX-based regimens in newly-diagnosed PCNSL patients.
Background: Approximately 60% of patients with large B-cell lymphoma (LBCL) achieve cure with standard first-line (1L) therapies, such as R-CHOP or DA-EPOCH-R. However, 10% of patients remain refractory to 1L treatment, and 30% of responders experienced relapse within two years. Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, is approved for the treatment of patients with relapsed/refractory LBCL. Furthermore, ZUMA-12, a multicenter phase 2 study investigating axi-cel as part of 1L treatment of high-risk LBCL patients, demonstrated high and durable response rates. With a median follow-up of 40.9 months, axi-cel achieved an objective response rate (ORR) of 92%, complete response (CR) rate of 86%, with responses ongoing in 73% of response-evaluable patients. This study aims to explore the efficacy and safety of CAR-T as consolidation in 1L treatment responders with high risk of relapse. Methods: This real-world case series study enrolled patients with B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), who received axi-cel as consolidation therapy after achieving CR or partial response (PR) to 1L treatment. Efficacy endpoints included complete metabolic response (CMR), 18-month overall survival (OS) rate, and progression-free survival (PFS) rate. Safety endpoints comprised the incidence of adverse events (AEs) including cytokine release syndrome (CRS), leukopenia, thrombocytopenia, and abnormal liver function. Additionally, this study explored the impact of post-infusion maintenance therapy on CAR-T cell expansion. Results: A total of 5 patients were enrolled in this study, with a median age of 66 years and a male-to-female ratio of 3:2. The lymphoma subtypes included 2 cases of non germinal center B-cell-like DLBCL (DLBCL-non-GCB), 2 cases of germinal center B-cell-like DLBCL (DLBCL-GCB), and 1 case of MCL. DLBCL patients had at least one of the following high-risk factors: International Prognostic Index (IPI) score≥4 /age-adjusted IPI (aaIPI) ≥2, double expression, or Ki-67 >90%. High-risk features in the MCL patient included advanced age and Ki-67 >30%. All 4 DLBCL patients received R-CHOP or R-CHOP-like regimens as 1L therapy, while the MCL patient received bendamustine and rituximab (BR) as 1L therapy. Leukapheresis was performed prior to initiation of 1L chemotherapy in the MCL patient and 2 DLBCL patients, while the remaining two underwent leukapheresis after 3 and 4 cycles of chemotherapy, respectively. Before lymphodepletion, 2 patients had achieved CR and 3 achieved PR, and the median time from leukapheresis to infusion was 95 days. With a median follow-up of 21 months since infusion, the best CMR rate was 100 %, and all patients achieved CMR within one month after infusion. The 18-month OS and PFS rates were both 100%. The median peak CAR-T cell counts were 74.65 cells/μL, and the median CAR-T cell counts at 30 days post-infusion were 7.26 cells/μL. Following infusion, 3 patients received IL-2 monotherapy (n=1) or PD-1 inhibitor combined with IL-2 (n=2). At 6 months post-infusion, CAR-T cells were detectable in the peripheral blood of all 3 treated patients, whereas only one of the 2 patients who did not receive PD-1 inhibitor or IL-2 had detectable CAR-T cells. CRS of any grade occurred in 100% of patients (including 1 case of capillary leak syndrome), with no grade ≥3 CRS and no incidence of immune effector cell-associated neurotoxicity syndrome (ICANS). The median time from CAR-T cell infusion to the onset of CRS was 4 days, and the median time from CRS onset to resolution was 3 days. After infusion, the incidence rates of grade ≥3 leukopenia, grade ≥3 thrombocytopenia, and liver dysfunction were 60%, 20%, and 60%, respectively. Conclusions: Consolidation therapy with CAR-T following 1L treatment demonstrated encouraging rates of CMR, PFS, and OS in B-cell lymphoma patients with high risk of relapse. Administration of PD-1 inhibitors and/or IL-2 post-infusion may support sustained expansion and persistence of CAR-T cells. The safety profile was manageable: all CRS were mild, and no ICANS were observed, providing a valuable insight for CAR-T consolidation following 1L treatment. However, the small sample size of this study warrants validation in a larger cohort study.
Background: High-dose methotrexate (HD-MTX)-based chemotherapy followed by whole-brain radiotherapy is the most commonly used approach for patients with newly diagnosed Primary central nervous system lymphoma (PCNSL). However, HD-MTX is a hospital-based drug requiring adequate fluid management and may not be well tolerated in elderly patients with an increased prevalence of comorbid illness. Fotemustine is a third-generation nitrosourea, which is easily penetrated through the blood-brain barrier (BBB) due to its high fat-soluble and low molecular weight, and is indicated for primary brain tumors and disseminated malignant melanoma. Our Center has innovatively conducted three prospective clinical trials using fotemustine-based regimens for the treatment of newly diagnosed PCNSL patients (Wu J et al, J Neurooncol 2018, Wu J et al, Cancer Biol Med 2021, Zhang X et al, ASH 2022), the results of the above studies suggest that the fotemustine-containing regimen has efficacy in the treatment of newly diagnosed PCNSL and has few toxic side effects. Therefore, this study increased the sample size, extended the follow-up time and set up a control group to analyze the efficacy and safety of fotemustine-containing regimens compared with HD-MTX-containing regimens in the treatment of newly diagnosed PCNSL patients. Methods: From April 2011 to December 2021, 114 patients with newly diagnosed PCNSL who received HD-MTX-containing regimens (HD-MTX plus cytarabine [HD-MA], rituximab, HD-MTX plus temozolomide [R-MT]) or fotemustine-containing regimens (fotemustine, teniposide plus dexamethasone [FTD], fotemustine, temozolomide plus dexamethasone [FVD], rituximab, fotemustine, pemetrexed plus dexamethasone [RFPD]) were retrospectively analyzed in this study. Among them, 27 and 15 patients received the HD-MA and R-MT protocol, respectively; 15, 12, and 45 patients received the FTD, FVD and R-FPD protocol, respectively. Results: Of the 114 patients, the objective response rate (ORR) did not differ significantly between the HD-MTX-containing group and the fotemustine-containing group (67% vs 68%, P=0.879). The median follow-up time for 114 patients was 28.5 months (range 2-122 months). Neither the progression free survival (PFS) (P=0.783) nor the overall survival (OS) (P=0.918) exhibited remarkably difference between HD-MTX-containing group and fotemustine-containing group. Notably, we noted that patients treated with HD-MTX-containing regimens experienced more serious adverse events, including leukopenia, anemia, thrombocytopenia, digestive tract toxicity, and mucosis (all P < 0.05) than those undergoing fotemustine-containing therapeutics. Conclusion: Fotemustine-based chemotherapeutics conferred a safer effect on newly-diagnosed PCNSL patients compared with HD-MTX-containing regimens together with comparable efficiency.
Background Esophageal carcinoma is the eighth prevalent malignancy and ranks the sixth in carcinoma-related death worldwide. Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) has been identified as a tumor suppressor in multiple carcinomas. However, its roles and molecular mechanisms underlying esophageal carcinoma progression are still undefined till now. Methods RT-qPCR assay was employed to detect the expression of TIPE2 mRNA. TIPE2 protein expression was measured by using western blot assay. Ad-V and Ad-TIPE2 adenoviruses were constructed to overexpress TIPE2. The effects of TIPE2 overexpression on cell proliferation, invasion and apoptosis were assessed by MTT and Edu incorporation assays, transwell invasion assay and flow cytometry analysis, respectively. The effect of TIPE2 overexpression on xenograft tumor growth was determined by measuring tumor volume and weight, together with immunohistochemistry assay. The effect of TIPE2 overexpression on the Wnt/β-catenin signaling pathway was evaluated by detecting the protein levels of β-catenin, c-Myc and cyclinD1 in EC9076 cells and xenograft tumors of esophageal carcinoma. Results TIPE2 expression was downregulated in esophageal carcinoma tissues and cells. Adenovirus-mediated TIPE2 overexpression suppressed cell proliferation and invasion, and induced apoptosis in esophageal carcinoma cells. Enforced expression of TIPE2 inhibited tumor growth in vivo, as evidenced by the reduced tumor volume, tumor weight and proliferating cell nuclear antigen expression. Overexpression of TIPE2 inhibited the Wnt/β-catenin signaling pathway in esophageal carcinoma in vitro and in vivo. Conclusions These results suggest that TIPE2 suppressed progression and tumorigenesis of esophageal carcinoma via inhibition of the Wnt/β-catenin pathway.
Lymphoma is a highly heterogeneous lymphohematopoietic tumor. As our understanding of the biological and pathological characteristics of lymphoma improves, we are identifying an increasing number of lymphoma subtypes. Genotyping has enhanced our ability to diagnose, treat, and monitor the prognosis of lymphoma. Despite significant improvements in treatment effectiveness, traditional methods for assessing disease response and monitoring prognosis are imperfect, and there is no significant improvement in overall remission rates for lymphoma patients. Minimal Residual Disease (MRD) is often indicative of refractory disease or early relapse. For lymphoma patients, personalized MRD monitoring techniques offer an efficient means to estimate disease remission levels, predict early relapse risk, and assess the effectiveness of new drug regimens. In this review, we delve into the MRD procedures in lymphoma, including sample selection and requirements, detection methods and their limitations and advantages, result interpretation. Besides, we also introduce the clinical applications of MRD detection in lymphoma.
OBJECTIVE:To analyze the current treatment status and prognostic regression of the chronic NK cell lymphoproliferative disorder (CLPD-NK).METHODS:We retrospectively analyzed the clinical features, treatment and prognosis of 18 patients with CLPD-NK who were treated at our Hospital between September 2016 and September 2022.RESULTS:Eighteen patients were included: three patients were treated with chemotherapy, five patients underwent immune-related therapy, one patient was treated with glucocorticoids alone, five patients were administered granulocyte colony-stimulating factor, blood transfusion therapy, or anti-infection therapy, followed by observation and follow-up, and four patients were observed without treatment. Fifteen patients survived, including two patients who achieved complete remission (CR) and seven patients who achieved partial remission (PR), of whom one patient progressed to Aggressive NK-cell leukemia (ANKL) and sustained remission after multiple lines of treatment; three patients were not reviewed, of which one patient was still in active disease, three patients developed hemophagocytic syndrome during treatment and eventually died, one of them had positive Epstein-Barr virus (EBV) expression. The 5-years overall survival rate was 83%.CONCLUSION:Most patients with CLPD-NK have inert progression and a good prognosis, whereas some patients have a poor prognosis after progressing to ANKL and combined with hemophagocytic syndrome. Abnormal NK cells invading the center suggest a high possibility of ANKL development, and immunosuppressants and hormones are effective treatments for this disease.
There is an urgent need for effective treatment of patients with relapsed/refractory diffuse large B‐cell lymphoma (R/R‐DLBCL). This trial investigated the efficacy of decitabine in combination with rituximab, cisplatin, cytarabine, dexamethasone (RDHAP) in R/R‐DLBCL.
Background: It is of great clinical significance to find out the ideal tumor biomarkers and therapeutic targets to improve the prognosis of patients with osteosarcoma (OS). Oxidative stress (OXS) can directly target intracellular macromolecules and exhibit dual effects of tumor promotion and suppression.Methods: OXS-related genes (OXRGs) were extracted from public databases, including TARGET and GEO. Univariate Cox regression analysis, Random Survival Forest algorithm, and LASSO regression were performed to identify prognostic genes and establish the OXS-signature. The efficacy of the OXS-signature was further evaluated by Kaplan-Meier curves and timeROC package. Evaluation of immunological characteristics was achieved based on ESTIMATE algorithm and ssGSEA. Submap algorithm was used to explore the response to anti-PD1 and anti-CTLA4 therapy for OS. Drug response prediction was conducted by using pRRophetic package. The expression values of related genes in the OXS-signature were detected with PCR assays.Results: Two OXS-clusters were identified for OS, with remarkable differences of clusters presented in prognosis. Kyoto Encyclopedia of Genes Genomes (KEGG) analysis showed that differentially expressed genes (DEGs) between the OXS-clusters were significantly enriched in several immune-related pathways. Patients with lower OS-scores attained better clinical outcomes, and presented more sensitivity to ICB therapy. By contrast, OS patients with higher OS-scores revealed more sensitivity to certain drugs. Furthermore, critical genes, RHBDL2 and CGREF1 from the model, were significantly higher expressed in OS cell lines.Conclusions: Our study identified the clusters and signature based on OXS, which would lay the foundation for molecular experimental research, disease prevention and treatment of OS.
Importance The L-asparaginase-based SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy regimen has shown higher response rates and survival benefit over an anthracycline-containing regimen. However, the safety profile was not satisfied. A well-tolerated regimen with promising efficacy is lacking. Objective To compare the efficacy and safety of the DDGP (dexamethasone, cisplatin, gemcitabine, and pegaspargase) regimen with the SMILE regimen in newly diagnosed advanced-stage (III/IV) extranodal natural killer/T-cell lymphoma (ENKL). Design, Setting, and Participants This was an open-label, multicenter, randomized clinical trial that took place across 12 participating hospitals in China from January 2011 to February 2019. Patients were eligible if they were 14 to 70 years old with newly diagnosed ENKL in stages III/IV and had an Eastern Cooperative Oncology Group performance status of 0 to 2. Eligible patients were evenly randomized to either the DDGP or SMILE group. Interventions Patients in each group were treated with the assigned regimen every 21 days for 6 cycles. Main Outcomes and Measures The primary end point was progression-free survival (PFS), and secondary end points included overall response rate and overall survival (OS). The adverse events between the DDGP and SMILE groups were compared. Results Among the 87 randomized patients, 80 received treatment (40 in the DDGP group and 40 in the SMILE group); the median (IQR) age was 43 (12) years, and 51 (64%) were male. The baseline characteristics were similar between the groups. At a median follow-up of 41.5 months, the median PFS was not reached in the DDGP group vs 6.8 months in the SMILE group (HR, 0.42; 95% CI, 0.23-0.77; P = .004), and the median OS was not reached in the DDGP group vs 75.2 months in the SMILE group (HR, 0.41; 95% CI, 0.19-0.89, P = .02). The PFS rate at 3 years and OS rate at 5 years were higher in the DDGP group vs the SMILE group (3-year PFS, 56.6% vs 41.8%; 5-year OS, 74.3% vs 51.7%). The overall response rate was higher in the DDGP group than in the SMILE group (90.0% vs 60.0%; P = .002). Grade 3 and 4 hematologic toxic effects were more frequently reported in the SMILE group vs the DDGP group (leukopenia, 85.0% vs 62.5%; neutropenia, 85.0% vs 65.0%). Conclusions and Relevance In this randomized clinical trial, the DDGP regimen showed promising preliminary results for patients with newly diagnosed local advanced ENKL. A confirmation trial based on larger population is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT01501149.
Doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) has been regarded as the standard treatment regimen for classical Hodgkin lymphoma. In recent years, ABVD-like regimens, which emerged due to shortages and the lung toxicity of bleomycin or the emergence of immune checkpoint inhibitors and antibody–drug conjugates, may be favorable, but have not yet been tested. We compared the outcomes of ABVD with ABVD-like regimens, which include bleomycin was completely or partially omitted; meanwhile, etoposide or PD-1 inhibitors were added. 5-Year progression-free survival (PFS) was higher for ABVD than ABVD-like regimens in young patients (82.1
目的 探讨基于微信平台的延续性干预在非霍奇金淋巴瘤化疗患者中的应用效果.方法 根据化疗过程中干预方式的不同将85例非霍奇金淋巴瘤患者分为对照组(n=41)和观察组(n=44),对照组患者给予常规护理干预,观察组患者给予基于微信平台的延续性干预.比较两组患者的健康疾病知识知晓率、治疗依从性、按时化疗率、护理满意度[McCloskey/Mueller工作满意度量表(MMSS)]、心理状态[焦虑自评量表(SAS)、抑郁自评量表(SDS)]、癌因性疲乏程度[癌症疲乏量表(CFS)]和不良反应发生情况.结果 观察组患者的健康知识知晓率、治疗依从率、按时化疗率、护理满意度均高于对照组,差异均有统计学意义(P﹤0.05).干预后,两组患者SAS、SDS评分均低于本组干预前,且观察组患者SAS、SDS评分均低于对照组,差异均有统计学意义(P﹤0.05).干预后,两组患者躯体、情感、认知评分均低于本组干预前,且观察组患者躯体、情感、认知评分均低于对照组,差异均有统计学意义(P﹤0.05).观察组患者的不良反应总发生率为9.09%,低于对照组患者的26.83%,差异有统计学意义(P﹤0.05).结论 基于微信平台的延续性干预在非霍奇金淋巴瘤患者化疗中应用效果好,可提高患者治疗依从性,降低癌因性疲乏程度及不良反应发生情况,且对预后有积极影响.
Background. Central nervous system lymphoma (CNSL) is an aggressive lymphoma. Orelabrutinib, an oral Bruton tyrosine kinase inhibitor, is a new treatment strategy for CNSL. This study aims to evaluate the efficacy and safety of orelabrutinib-based regimens in the treatment of patients with CNSL. Methods. Twenty-three patients with CNSL were included in this retrospective study. All patients received the orelabrutinib-based regimen. Efficacy was evaluated based on investigators’ assessment of overall response rate (ORR), complete response/unconfirmed complete response (CR/CRu), partial response (PR), stable disease (SD), progressive disease (PD), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). The safety of orelabrutinib-based regimens has also been evaluated. Results. A total of 17.39% of patients received orelabrutinib-based regimens for consolidation therapy, and 82.61% of patients for induction therapy (4 newly diagnosed CNSL, 15 relapsed/refractory CNSL). In the newly diagnosed CNSL group, the ORR was 100% (1 CR, 1 CRu, 2 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 100%, 100%, and 100%, respectively. Of the 15 relapsed/refractory CNSL patients, five therapy regimens were applied (orelabrutinib, n = 3; orelabrutinib/immunotherapy, n = 3; orelabrutinib/chemotherapy, n = 2; orelabrutinib/immunochemotherapy, n = 6; orelabrutinib/radiotherapy, n = 1). The ORR was 60.00% (4 CR, 5 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 92.30%, 67.70%, and 70.00%, respectively. Twenty-one patients reported adverse events (AEs), and 6 patients experienced grade ≥ 3 AEs. Conclusion. Orelabrutinib-based regimens were efficacious and well-tolerated in patients with CNSL. These combined therapies offer a new potential therapeutic strategy for patients with CNSL.
ObjectiveThe prognostic nutritional index (PNI) is an important prognostic factor for survival outcomes in various hematological malignancies. The current study focused on exploring the predictive value of the PNI in newly diagnosed follicular lymphoma (FL) in China.Materials and methodsThe clinical indicators and follow-up data of 176 patients who received chemotherapy or immunotherapy combined with chemotherapy with FL in our hospital from January 2016 to March 2022 were retrospectively analyzed. Cox proportional hazard model was used for univariate and multivariate analyses. Kaplan–Meier curves were used to calculate survival rates and draw survival curves. The log-rank test was applied to compare differences between groups.ResultsThe optimal cut-off value of PNI was 44.3. All patients were divided into a high PNI group (>44.3) and a low PNI group (≤44.3). The low PNI group had a low CR rate and a high risk of death, with a tendency toward POD24, and Both OS and PFS were worse than those in the high PNI group. PNI was able to predict OS and PFS in FL patients and was the only independent predictor of OS (P = 0.014 HR 5.024; 95%CI 1.388∼18.178) in multivariate analysis. PNI could re-stratify patients into groups of high FLIPI score, high FLIPI2 score, no POD24, and rituximab combined with chemotherapy. Moreover, integrating PNI into the FLIPI and FLIPI2 models improved the area under the curve (AUC) for more accurate survival prediction and prognosis.ConclusionPNI is a significant prognostic indicator for newly diagnosed FL in China that can early identify patients with poor prognosis and guide clinical treatment decisions.
Castleman disease (CD) is a rare lymphoproliferative disorder. The mechanistic target of rapamycin (mTOR) pathway is a key regulator of various cellular functions, which may be related with the potential mechanisms of CD occurrence. We retrospectively collected the clinical information of 60 CD patients diagnosed in the First Affiliated Hospital of Zhengzhou University. And FFPE biopsy specimens were collected from 31 patients (12 unicentric CD patients and 19 multicentric CD patients) to detect the mTOR pathway protein expression. We are the first to demonstrate that thrombocytopenia and hypoalbuminemia are independent poor prognostic factors for CD. Moreover, mTOR activation was higher in CD compared to reactive lymphoid hyperplasia (used as a control group). This study offers some elucidation for the management and treatment of CD patients.
ObjectiveThe prognosis for patients with relapsed or refractory diffuse large B-cell lymphoma (R/R-DLBCL) after second-line treatment failure is extremely poor. This study prospectively observed the efficacy and safety of decitabine with a modified cisplatin, cytarabine, and dexamethasone (DHAP) regimen in R/R-DLBCL patients who failed second-line treatment.MethodsTwenty-one R/R-DLBCL patients were enrolled and treated with decitabine and a modified DHAP regimen. The primary endpoints were overall response rate (ORR) and safety. The secondary endpoints were progression-free survival (PFS) and overall survival (OS).ResultsORR reached 50% (complete response rate, 35%), five patients (25%) had stable disease (SD) with disease control rate (DCR) of 75%. Subgroup analysis revealed patients over fifty years old had a higher complete response rate compared to younger patients (P = 0.005), and relapsed patients had a better complete response rate than refractory patients (P = 0.031). Median PFS was 7 months (95% confidence interval, 5.1-8.9 months). Median OS was not achieved. One-year OS was 59.0% (95% CI, 35.5%-82.5%), and two-year OS was 51.6% (95% confidence interval, 26.9%-76.3%). The main adverse events (AEs) were grade 3/4 hematologic toxicities such as neutropenia (90%), anemia (50%), and thrombocytopenia (70%). Other main non-hematologic AEs were grade 1/2 nausea/vomiting (40%) and infection (50%). No renal toxicity or treatment-related death occurred.ConclusionDecitabine with a modified DHAP regimen can improve the treatment response and prognosis of R/R-DLBCL patients with good tolerance to AEs, suggesting this regimen has potential as a possible new treatment option for R/R-DLBCL patients after second-line treatment failure.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT03579082.
目的:研究沙利度胺联合CHOP方案治疗弥漫大B细胞淋巴瘤的疗效与安全性.方法:选取郑州大学第一附属医院2017年2月—2019年2月收治的82例弥漫大B细胞淋巴瘤患者.采用随机数字表法分为实验组(n=41)和对照组(n=41),实验组在对照组的基础上加以沙利度胺治疗,对照组采用常规CHOP化疗方案治疗.对比两组患者临床疗效;对比两组患者治疗期间出现的不良反应;对比两组患者随访一年后的存活率.结果:相比于对照组总有效率78.04%(32/41),实验组97.56%(40/41)显著更高(P<0.05);实验组不良反应发生率4.86%(2/41)与对照组9.75%(4/41),差异无统计学意义(P>0.05);相比于对照组存活率78.04%(32/41),实验组97.56%(40/41)显著更高(P<0.05).结论:沙利度胺联合CHOP方案治疗弥漫大B细胞淋巴瘤的疗效较好,不会增加不良反应的发生,提高患者生存率.
Glycoprotein non-metastatic melanoma protein B (GPNMB) has been confirmed to be related to the pathogenesis of tumors. However, the potential impact of GPNMB on the progression of diffuse large B-cell lymphoma (DLBCL) is unclear. In this study, the expression levels of GPNMB and Yes-associated protein (YAP) were analyzed using qRT-PCT and Western blot assay. Cell counting kit-8, EdU, and flow cytometry assays were used to detect the proliferation and apoptosis of DLBCL cells. A nude mice xenograft model was established for in vivo research. Results showed that GPNMB and YAP1 were upregulated in DLBCL cell lines. Knockdown of GPNMB inhibited cell proliferation and promoted apoptosis in DLBCL cells. Additionally, the expression levels of YAP1 and the downstream effector of Hippo pathway (c-myc) were markedly decreased when GPNMB was knocked down. Moreover, knockdown of GPNMB inhibited the nuclear translocation of β-catenin protein, which could be abolished by YAP1 overexpression. Simultaneously, the anti-proliferative and pro-apoptotic effects of GPNMB knockdown could be reversed by YAP1 overexpression or LiCl (the activator of Wnt/β-catenin pathway). Furthermore, the mice xenograft model confirmed that inhibition of GPNMB restrained the tumorigenesis of DLBCL in vivo. In conclusion, GPNMB could partly activate the Wnt/β-catenin signaling pathway by targeting YAP1, so as to participate in tumorigenesis of DLBCL.
目的 探讨长链非编码RNA(lncRNA)LINC00460在非小细胞肺癌中的表达及作用机制.方法 使用回顾性调查法,选取90例非小细胞肺癌患者作为研究对象,按照非小细胞肺癌患者癌细胞组织中lncRNA LINC00460的表达水平,将高表达水平患者(≥8.45)设为观察组(56例),低表达水平患者(<8.45)设为对照组(34例),通过超声处理使50 mg样品组织均质化,根据RNA提取试剂盒的说明从组织中提取总RNA;严格按照逆转录试剂盒的说明书进行逆转录反应;严格按照STBR Premix Ex Taq试剂盒操作说明书进行qPCR扩增;通过2-ΔΔCt方法计算lncRNA LINC00460的相对表达水平.结果 90例非小细胞肺癌患者中癌旁组织lncRNA LINC00460的相对表达均值(1.58±0.86)低于癌组织(8.54±3.05)(P<0.05).2组患者癌组织中lncRNA LINC00460表达水平在性别、年龄、病理分型、肿瘤直径及血管侵犯方面进行对比,差异无统计学意义(P>0.05),但2组患者癌组织中lncRNA LINC00460表达水平在病理分级与有无发生淋巴结转移方面存在统计学差异(P<0.05).观察组和对照组患者无进展生存期分别为(9.4±1.2)月和(18.9±2.1)月,总生存期分别为(14.7±2.1)月和(22.7±1.6)月(P<0.05).lncRNA LINC01296的高表达水平,男性,肿瘤直径,血管侵犯和淋巴结转移是非小细胞肺癌患者预后不良的独立预测因子.结论 lncRNA LINC00460的表达在非小细胞肺癌患者的癌组织中上调,且影响非小细胞肺癌患者预后,是非小细胞肺癌预后的独立预测因子.
目的:探讨含培美曲塞(PEM)联合方案治疗原发性中枢神经系统淋巴瘤(PCNSL)的有效性和安全性.方法:收集16例中枢神经系统淋巴瘤患者的资料,其中7例已接受一线方案化疗后复发,9例为初治患者.化疗方案为PEM 600 mg/m2静脉滴注,第1天;联合伊达比星(IDA)和地塞米松(DXM),或福莫司汀(FTM)和DXM,或替莫唑胺(TMZ)和DXM.结果:7例复发难治患者均完成至少2个周期的化疗,部分缓解(PR)3例,稳定(SD)3例,病情进展(PD)1例(该例死亡).9例初治患者均完成至少4个周期的化疗,完全缓解1例,PR4例,SD3例,PD1例.主要不良反应为骨髓抑制,无因严重不良反应导致停药者,患者耐受性好.结论:含PEM联合方案对于PC-NSL具有较好安全性和临床治疗活性.
Extranodal natural killer/T‐cell lymphoma, nasal type (ENKL) is a rare peripheral T‐cell lymphoma that predominantly occurs in Asian and South American populations. The treatment of ENKL has been a challenge for a long time. This study was conducted to compare the clinical efficacy and safety of cisplatin, dexamethasone, gemcitabine, and pegaspargase (DDGP) and methotrexate, dexamethasone, ifosfamide, L‐asparaginase, and etoposide (SMILE) regimens for relapsed/refractory ENKL and explore the prognostic factors. From October 2014 to July 2019, 54 patients with relapsed/refractory ENKL who received DDGP or SMILE chemotherapy were retrospectively assessed in this study. Thirty‐one patients received DDGP chemotherapy and 23 patients received SMILE chemotherapy. A higher complete response rate was observed in patients treated with DDGP regimen (61.3% vs. 30.4%, P = 0.025). The DDGP group (95% confidence interval (CI) of 5‐year progression‐free survival (PFS): 24.6–66.2%; 95% CI of 5‐year overall survival (OS): 8.5–91.7%) was also significantly associated with longer 5‐year PFS and 5‐year OS (P = 0.008 for 5‐year PFS, P = 0.023 for 5‐year OS). More serious leucopenia (P = 0.021), neutropenia (P = 0.041), and allergy (P = 0.040) were observed in the SMILE group. Post‐treatment Epstein–Barr virus (EBV)‐DNA status (P = 0.001 for PFS, P = 0.018 for OS) was identified as a significant prognostic factor for PFS and OS in multivariate analysis. The present research suggested that compared with SMILE chemotherapy, DDGP chemotherapy can significantly improve the response and survival of relapsed/refractory ENKL with better tolerance. Post‐treatment EBV‐DNA status was identified as a significant prognostic factor for PFS and OS in relapsed/refractory ENKL.