首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 15 毫秒
1.
The overall response rates and long‐term survival of primary central nervous system lymphoma (PCNSL) are still significantly inferior to the results achieved in similar subtypes of extranodal non‐Hodgkin's lymphoma. It is clearly necessary to investigate new therapeutic methods on PCNSL. We encountered three patients histologically documented PCNSL as diffuse large B‐cell lymphoma (DLBCL). They were treated with R‐IDARAM which comprised rituximab, idarubicin, dexamethasone, cytarabine and methotrexate. Patient 1 received stereotactic brachytherapy (SBT) prior to chemotherapy performed with iodine‐125 seeds (cumulative therapeutic dose 50 Gy). After six cycles of R‐IDARAM at 3‐weekly intervals, radiotherapy was applied at a dosage of 2000–4000 cGy in conventional schedule (180 or 200 cGy/day) to whole brain or spinal cord in all patients. Complete remission (CR) was achieved after first two cycles of R‐IDARAM in all patients. All three patients remained in CR at the time of this report with a median duration of follow‐up of 23 months (ranging from 13 to 41 months). Three patients have been alive for 41, 13, 16 months respectively until now. The patient with the longest survival time was the one given SBT prior to chemotherapy. This study suggests that R‐IDARAM combining with radiotherapy maybe a high effective regimen in PCNSL patients especially those with primary central nervous system DLBCL. A comprehensive treatment combining internal radiotherapy by SBT, modified R‐IDARAM and followed reduced external radiotherapy may be a new treatment concept for PCNSL with higher efficiency and lower toxicity.  相似文献   

2.
Fluorescent semiconductor quantum dots (QDs) are newfound nanocrystal probes which have been used in bioimaging filed in recent years. The purpose of this study is to evaluate the diagnostic value of specific QDs coupled to rituximab monoclonal antibody against CD20 tumor markers for patients with diffuse large B-cell lymphoma (DLBCL). In current study rituximab-conjugated quantum dots (QDs-rituximab) were prepared against CD20 tumor markers for detection of CD20-positive cells (human Raji cell line) using flowcytometry. A total of 27 tumor tissue samples were collected from patients with DLBCL and 27 subjects with negative pathological tests as healthy ones, which stained by QD-rituximab. The detection signals were obtained from QDs using fluorescence microscopy. The flowcytometry results demonstrated a remarkable difference in fluorescent intensity and FL2-H + (CD20-positive cells percentage) between two groups. Both factors were significantly higher in Raji in comparison with K562 cell line (P < 0.05). Lot of green fluorescence signals was observed due to the selectively binding of QD-rituximab to CD20 tumor markers which overexpressed in tumor tissues and a few signals observed on the defined healthy ones. Based on these observations the cut-off point was 46.8 dots and the sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 89.5%, 91.3%, and 100%, respectively (LR+, 9.52; LR−, 0). The QD - rituximab could be beneficial as a bioimaging tool with high sensitivity to provide an accurate molecular imaging technique for identifying CD20 tumor markers for early diagnosis of the patients with DLBCL.  相似文献   

3.
目的 评价联合应用益生菌在标准四联疗法的不同阶段对幽门螺杆菌(H. pylori)感染补救治疗的疗效。方法 采用回顾性研究,收集首次根除失败因病情需要接受H.pylori补救根除治疗的患者共200例,随机分为4个治疗组,所有患者均采用标准四联疗法(每次服用埃索美拉唑钠肠溶片20 mg+枸橼酸铋钾220 mg+阿莫西林1 000 mg+呋喃唑酮100 mg)进行治疗。其中A组为单纯四联治疗,不加服金双歧;B组为四联治疗前2周服用金双歧2 000 mg/次;C组为标准四联治疗同时服用金双歧2 000 mg/次;D组为四联治疗结束后开始加用金双歧2 000 mg/次。疗程均为2周,所有患者均随访至少4周,记录其治疗期间发生的不良反应及症状。疗程结束4周后采用13C尿素呼气试验判断H. pylori是否根除。结果 A组、B组、C组和D组患者ITT分析的根除率分别为78.0%(38/50)、80.0%(40/50)、74.0%(37/50)和72.0%(36/50),差异无统计学意义(χ2=1.096,P=0.778);4组患者PP分析的根除率分别为81.3%(39/48)、85.1%(40/47)、78.7%(37/47)和78.3%(36/46),差异无统计学意义(χ2=0.891,P=0.828)。4组患者7 d、14 d不良反应发生率差异有统计学意义(P0.05)。结论 含呋喃唑酮、阿莫西林的标准四联疗法治疗H. pylori感染根除率较高(>80%),可作为首次根除治疗失败后的补救治疗方案,在补救治疗的不同时期加用益生菌并不能明显提高根除率,但能降低7 d、14 d治疗期间的不良反应发生率。  相似文献   

4.
ObjectivesCurrent guidelines tend to treat HIV positive (HIV+) patients as their seronegative counterparts with diffuse large B-cell lymphoma (DLBCL) but little is known about their radiotherapy responses differences.Patients and MethodsA retrospective cohort of all consecutive HIV+ DBCL patients treated with chemotherapy between 2004 and 2018 was assessed. All patients had biopsy-proven lymphomas. They were included if the proposed radical treatment was done without progression or death during chemotherapy and had at least 6 months of follow-up or were followed until death.ResultsFifty-three (53) patients were selected, with a median age at diagnosis of 41.39 years (20–65 years). Median follow-up of 35.16 months (1.4–178.7 months). Male patients accounted for 54.7% and most had a good performance in the ECOG scale at diagnoses (81.1% are ECOG 0−1). Median overall survival was not reached. Mean OS was 41.5 months with 16 deaths. Age had an impact on OS, with patients older than 60 years at more risk (p = 0.044), as did longtime use of HAART, with those that started antiretroviral therapy within the diagnose of the lymphoma at greatest risk (p = 0.044). RT did not have an impact on OS (p = 0.384) or PFS (p = 0.420), although survival curves show better OS in the radiotherapy group. Toxicities were rare, since none of the patients had grade 3 or superior toxicity.ConclusionRT did not impact survival or progression in our limited sample, but a longer OS may occur after the first-year post RT. RT should be tested in prospective data in the HIV+ population with DLBCL.  相似文献   

5.
MicroRNAs are naturally occurring small RNA species that regulate gene expression and are frequently abnormally expressed in cancers. However, the role of microRNAs in lymphoma is poorly understood. Therefore, we undertook a comprehensive study of microRNA expression in two of the most common lymphomas: diffuse large B-cell lymphoma (DLBCL) ( n = 80) and follicular lymphoma (FCL) ( n = 18) using microarrays containing probes for 464 human microRNAs. Unsupervised cluster analysis revealed distinct expression patterns between these two lymphomas and specific microRNA signatures (including members of the miR-17–92 cluster) were derived that correctly predicted lymphoma type in >95% of cases. Furthermore, we identified microRNAs in de novo DLBCL ( n = 64) associated with germinal centre-like and non-germinal centre-like immunophenotypes, international prognostic index status and event-free survival in CHOP and rituximab (R)-CHOP treated patients. Despite the indolent nature of FCL a significant proportion of cases undergo high-grade transformation to more aggressive DLBCL. In order to see if transformation is associated with changes in microRNA expression we compared transformed DLBCL cases ( n = 16) with de novo DLBCL, as well as FCL cases that underwent subsequent transformation ( n = 7) with FCL cases that had not transformed at a median follow-up of 60 months ( n = 11). Differential expression of 12 microRNAs correctly predicted >85% of transformed versus de novo DLBCL cases; six microRNAs ( miR-223, 217, 222 , 221 and let-7i and 7b) were found which could similarly predict or transformation in FCL ( P < 0.05). These data suggest that microRNAs have potential as diagnostic and prognostic markers in these lymphomas and may be used to identify FCL patients at risk of high-grade transformation.  相似文献   

6.
目的将奖励性操作式条件反射方法应用于学习记忆研究。方法首次采用奖励性操作式条件反射方法,设置单次操作训练、连续多次操作训练、信号辨识与消退四种检测模式,研究Wistar大鼠和SHR大鼠学习记忆能力。结果奖赏训练中,SHR组鼻触次数显著增多(vs.Wistar&Donepezil,P〈0.05);单次操作训练中,三组动物对操作反应的获得无显著差异;连续多次操作学习任务中,SHR组错误操作次数增多(vs.Wistar,P〈0.05),奖赏获得次数减少(vs.Donepezil,P〈0.001),反应准确率显著降低(vs.Wistar&Donepezil,P〈0.05);信号辨识任务中SHR组错误反应次数显著增多(vs.Wistar&Donepezil,P〈0.05),而反应准确率降低,组间差异有显著性(vs.Wistar&Donepezil,P〈0.05);消退实验中,三组动物差异无显著性。神经递质检测发现,SHR组大鼠谷氨酸[(1.0639±0.07086)mg/g]、乙酰胆碱[(2.7760±0.2609)μg/g]与五羟色胺[(1.2200±0.1137)μg/g]含量均显著低于Wistar组大鼠(P〈0.05),多奈哌齐组大鼠乙酰胆碱含量显著增加[(3.9344±0.2747)μg/g](vs.Wistar,P〈0.05;vs.SHR,P〈0.001)。结论奖励性操作式条件反射方法可作为一种正性增强条件反射检测新方法应用于大鼠学习记忆研究。  相似文献   

7.
8.
The effect of repeated conditioning procedures (25 runs), consisting of soiling (milk and meat products) and cleaning steps, on the hygienic status, physico-chemical properties and surface chemical composition of stainless steel (SS) surfaces, was investigated. Five SSs differing in grade and finish were used. Both soiling and surface cleaning/conditioning procedures resulted in a similar increase in the surface contamination with carbon, while the changes in the basic component of the surface free energy depended on the conditioning procedure. The passive film was also affected, the Fe/Cr ratio in particular. The hygienic status was also changed, especially with milk as shown by monitoring the number of residual adhering Bacillus cereus spores after contaminating the surface with spores followed by cleaning. The results show that in food environments, the presence and the nature of conditioning molecules play a major role in the hygienic status of SS surfaces.  相似文献   

9.
Most of our knowledge on learning and memory formation results from extensive studies on a small number of animal species. Although features and cellular pathways of learning and memory are highly similar in this diverse group of species, there are also subtle differences. Closely related species of parasitic wasps display substantial variation in memory dynamics and can be instrumental to understanding both the adaptive benefit of and mechanisms underlying this variation. Parasitic wasps of the genus Nasonia offer excellent opportunities for multidisciplinary research on this topic. Genetic and genomic resources available for Nasonia are unrivaled among parasitic wasps, providing tools for genetic dissection of mechanisms that cause differences in learning. This study presents a robust, high‐throughput method for olfactory conditioning of Nasonia using a host encounter as reward. A T‐maze olfactometer facilitates high‐throughput memory retention testing and employs standardized odors of equal detectability, as quantified by electroantennogram recordings. Using this setup, differences in memory retention between Nasonia species were shown. In both Nasonia vitripennis and Nasonia longicornis, memory was observed up to at least 5 days after a single conditioning trial, whereas Nasonia giraulti lost its memory after 2 days. This difference in learning may be an adaptation to species‐specific differences in ecological factors, for example, host preference. The high‐throughput methods for conditioning and memory retention testing are essential tools to study both ultimate and proximate factors that cause variation in learning and memory formation in Nasonia and other parasitic wasp species.  相似文献   

10.
Protease inhibitors are an important new class of agents for the treatment of human immunodeficiency virus (HIV) infection. The purpose of our trial was to determine the feasibility of combining the protease inhibitor saquinavir with a 96-hour continuous intravenous infusion of cyclophosphamide (800 mg/M2), doxorubicin (50mg/M2, and etoposide (240 mg/M2) (CDE) plus filgrastim in patients with non-Hodgkin's lymphoma associated with HIV infection. The effect of saquinavir on CDE-induced myelosuppression, CD4 lymphopenia, and non-hematologic toxicity was also sought. Twelve patients with HIV-related lymphoma received CDE every 28 or more days. All patients received saquinavir (600 mg PO TID), filgrastim andPneumocystis carinii and fungal prophylaxis. Patients also received either stavudine (n=2) or boths stavudine and didanosine (n=10). Toxicity was analyzed using the NCI Common Toxicity Criteria for each cycle and the data were compared with the data from our prior study of CDE plus didanosine. An interim analysis was performed after accrual of the first 12 patients in order to assess toxicity. Severe (grade 3 or 4) mucositis occurred in eight of 12 patients (67%) treated with CDE plus saquinavir compared with three of 25 patients (12%) in our prior study treated with CDE without saquinavir (P<0.001). In logistic regression analysis, saquinavir use was the only factor associated with a significantly greater risk of severe mucositis (relative risk 7.9;P=0.03). Saquinavir use was not associated with a significant difference in the incidence of febrile neutropenia, prolonged neutropenia, chemotherapy dose reduction, or in the degree of myelosuppression. The decrease in CD4 lymphocytes for patients treated with saquinavir (absolute decrease of 23/μL, or a 26% decrease from baseline) was significantly less than for patients treated without saquinavir in the prior study (absolute decrease of 91/μL, or 42% decrease from baseline;P=0.05). Four of 10 patients (40%) treated with saquinavir had an increase in CD4 lymphocytes of ≥10/μL compared with none of 25 patients (0%) treated without saquinavir (P<0.001). Combination of the protease inhibitor saquinavir with infusional CDE in patients with HIV-associated lymphoma was associated with a significant increase in the incidence of severe mucositis. This finding suggests that saquinavir may alter the metabolism of one of more of the cytotoxic agents in the CDE regimen, and underscores the need for careful investigation regarding the use of the protease inhibitors in patients receiving chemotherapy.  相似文献   

11.
12.
Interactions of two tubicolous, deposit-feeding polychaetes, Clymenella torquata (Leidy) and Polydora ligni Webster, with a filter-feeding bivalve, Gemma gemma (Totten), were examined to test the functional group hypothesis that small, filter-feeding bivalves with large young should attain high densities with tube-builders of any trophic mode because the large young escape predation by tube-builders. The prediction was not supported by Polydora and Gemma, since the two species have not been reported to coexist in high densities in nature. In laboratory experiments, Polydora reduced recruitment and adult survival of Gemma relative to a control. Polydora preyed on juvenile clams and reduced the time which adult clams had their siphons in the feeding position, relative to a control.For Clymenella and Gemma, the functional group hypothesis made the correct prediction (i.e. the two species are reported to coexist in high densities in nature), but for the wrong reason. The size of Gemma's offspring is not related to the intensity of Clymenella predation. Clymenella does not ingest Gemma since the worm does not usually feed from the zone occupied by the clam. In contrast to Polydora, Clymenella did not reduce the time which clams fully extend and open their siphons relative to a control. In laboratory experiments Clymenella increased adult bivalve growth, survival after one year, and recruit size after one month. Clam life history characteristics were similar in the Clymenella and Clymenella plus Polydora treatments because the number of surviving Polydora was reduced by a negative interaction with Clymenella.The tube-builders had different effects on the filter-feeder, Gemma, because these tube-building species differ in feeding position, diet and behavior. Thus, the functional group hypothesis was too general to predict and explain the species interactions and distributions.  相似文献   

13.
Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by human herpes virus-8 infection, and is generally resistant to chemotherapy. Hybrid liposomes, composed of dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene (21) dodecyl ether (C12(EO)21) (HL-21), were rapidly accumulated in the membrane of PEL cells. HL-21 also increased membrane fluidity of PEL cells, and induced caspase-3 activation along with cell death. These results suggest that HL-21 should be an effective and attractive regent for PEL treatment.  相似文献   

14.
《Autophagy》2013,9(8):1415-1425
Autophagy is a lysosomal degradation process that may act as a mechanism of survival in a variety of cancers. While pharmacologic inhibition of autophagy with hydroxychloroquine (HCQ) is currently being explored in human clinical trials, it has never been evaluated in canine cancers. Non-Hodgkin lymphoma (NHL) is one of the most prevalent tumor types in dogs and has similar pathogenesis and response to treatment as human NHL. Clinical trials in canine patients are conducted in the same way as in human patients, thus, to determine a maximum dose of HCQ that can be combined with a standard chemotherapy, a Phase I, single arm, dose escalation trial was conducted in dogs with spontaneous NHL presenting as patients to an academic, tertiary-care veterinary teaching hospital. HCQ was administered daily by mouth throughout the trial, beginning 72 h prior to doxorubicin (DOX), which was given intravenously on a 21-d cycle. Peripheral blood mononuclear cells and biopsies were collected before and 3 d after HCQ treatment and assessed for autophagy inhibition and HCQ concentration. A total of 30 patients were enrolled in the trial. HCQ alone was well tolerated with only mild lethargy and gastrointestinal-related adverse events. The overall response rate (ORR) for dogs with lymphoma was 93.3%, with median progression-free interval (PFI) of 5 mo. Pharmacokinetic analysis revealed a 100-fold increase in HCQ in tumors compared with plasma. There was a trend that supported therapy-induced increase in LC3-II (the cleaved and lipidated form of microtubule-associated protein 1 light chain 3/LC3, which serves as a maker for autophagosomes) and SQSTM1/p62 (sequestosome 1) after treatment. The superior ORR and comparable PFI to single-agent DOX provide strong support for further evaluation via randomized, placebo-controlled trials in canine and human NHL.  相似文献   

15.
Autophagy is a lysosomal degradation process that may act as a mechanism of survival in a variety of cancers. While pharmacologic inhibition of autophagy with hydroxychloroquine (HCQ) is currently being explored in human clinical trials, it has never been evaluated in canine cancers. Non-Hodgkin lymphoma (NHL) is one of the most prevalent tumor types in dogs and has similar pathogenesis and response to treatment as human NHL. Clinical trials in canine patients are conducted in the same way as in human patients, thus, to determine a maximum dose of HCQ that can be combined with a standard chemotherapy, a Phase I, single arm, dose escalation trial was conducted in dogs with spontaneous NHL presenting as patients to an academic, tertiary-care veterinary teaching hospital. HCQ was administered daily by mouth throughout the trial, beginning 72 h prior to doxorubicin (DOX), which was given intravenously on a 21-d cycle. Peripheral blood mononuclear cells and biopsies were collected before and 3 d after HCQ treatment and assessed for autophagy inhibition and HCQ concentration. A total of 30 patients were enrolled in the trial. HCQ alone was well tolerated with only mild lethargy and gastrointestinal-related adverse events. The overall response rate (ORR) for dogs with lymphoma was 93.3%, with median progression-free interval (PFI) of 5 mo. Pharmacokinetic analysis revealed a 100-fold increase in HCQ in tumors compared with plasma. There was a trend that supported therapy-induced increase in LC3-II (the cleaved and lipidated form of microtubule-associated protein 1 light chain 3/LC3, which serves as a maker for autophagosomes) and SQSTM1/p62 (sequestosome 1) after treatment. The superior ORR and comparable PFI to single-agent DOX provide strong support for further evaluation via randomized, placebo-controlled trials in canine and human NHL.  相似文献   

16.
17.
18.
Five patients at risk for primary central nervous system lymphoma (PCNSL) recurrence were treated with high-dose methylprednisolone, (HDMP) to prevent ‘trafficking’ of malignant lymphocytes into the central nervous system (CNS). HDMP was chosen because of its ability to stabilize the ‘blood brain barrier (BBB)’. Three men with newly diagnosed PCNSL, ages 62, 76 and 78 y, whose survival was projected to be 6.6 months, began treatment after achieving complete response (CR) to initial radiation therapy alone and survived 27, 37 and 59 months after treatment. In none was death from recurrent disease in CNS but one patient did die of systemic non-Hodgkin’s lymphoma (NHL) five years after PCNSL diagnosis. A 20 y old man was treated with HDMP after successful combined modality therapy and is alive 75+months after initial diagnosis without evidence of disease recurrence. A 34 y old man relapsed after combined modality initial treatment and failed to respond to HDMP when treatment was begun after unsuccessful salvage therapy; he died of disease 12 months after initial diagnosis. There were no treatment complications. The promising results in this pilot study from the basis for a North Central Cancer Treatment Group (NCCTG) 96-73-51, a Phase 2 clinical trial of brain radiotherapy and HDMP for PCNSL patients 70 y of age and older, a group of patients at high risk for toxicity from intensive combined modality therapy.  相似文献   

19.
Fast cyclic voltammetry can be used to measure dopamine release after oxygen and glucose deprivation (OGD) induced anoxic depolarization in vitro. Here we measure dopamine efflux with 1 s time resolution, which is appropriate to measure OGD-evoked dopamine efflux accurately. In the present study, we examined whether OGD-evoked dopamine efflux could be used to show pre-ischaemic conditioning in the rat caudate brain slice. Caudate slices were exposed to 0, 2, or 10 min OGD pre-ischaemic conditioning, then 60 min later exposed to a second OGD event of 15 min duration. We measured the OGD-evoked dopamine efflux using fast cyclic voltammetry and in some experiments caudate dopamine and DOPAC tissue levels were measured using HPLC and 20 μm cryostat sections were Nissl stained to indicate neuronal loss. We found that 10 but not 2 min OGD pre-ischaemic conditioning resulted in a longer time to onset of OGD-evoked dopamine efflux on the main OGD event (475 ± 31 and 287 ± 30 s for 10 Vs 0 min pre-ischaemic conditioning respectively). Further, 10 min OGD pre-ischaemic conditioning resulted in less dopamine efflux on the second OGD event (4.23 ± 1.12 and 8.14 ± 0.82 μM for 10 Vs 0 min pre-ischaemic conditioning respectively), despite these slices having similar tissue dopamine content and DOPAC/DA ratio, and the rate of dopamine release was slower in the main OGD event (21 ± 5 and 74 ± 8nM/s for 10 Vs 0 min pre-ischaemic conditioning respectively). These data suggest that 10 min OGD pre-ischaemic conditioning can evoke tolerance to a second OGD event and that voltammetric recording of OGD-evoked dopamine efflux is a useful model of pre-ischaemic conditioning in neuronal tissue.  相似文献   

20.
Background and aims. Eradication of Helicobacter pylori leads to regression of mucosa‐associated lymphoid tissue (MALT) lymphomas. In this study, we measured serum antibodies to H. pylori and H. pylori‐recombinant heat‐shock protein 60 (rHSP60) in patients with gastric MALT lymphoma to determine whether humoral immune responses to the bacterial antigens correlate with the efficacy of eradication therapy. Methods. Serum samples were obtained from 33 patients with H. pylori‐positive gastric MALT lymphoma before undergoing therapy to eradicate the bacteria. Anti‐H. pylori antibodies were measured in a commercial assay and in immunoassays to lysates and rHSP60 which were prepared from ATCC 43504 strain. Results. Helicobacter pylori were eradicated in all 33 patients, and the lymphoma completely regressed histologically in 26 patients (79%). Pre‐treatment titers of serum antibody to H. pylori and to rHSP60 in the patients whose tumor regressed were significantly higher than titers in patients whose tumors did not regress (p = .0011 and .035, respectively). By logistic regression analysis, age (odds ratio = 0.88, 95% confidence interval = 0.80–0.99), endoscopic appearance (0.053, 0.004–0.65), titers of anti‐H. pylori antibodies (67.6, 2.5–1800), and titers of anti‐rHSP60 antibody (6.4, 1.2–36) were identified as significantly associated factors with the outcome of MALT lymphoma. Conclusions. Measurement of serum antibodies to H. pylori and HSP60 might be useful for predicting the response of gastric MALT lymphoma to eradication of H. pylori.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号