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1.
Theranostics ; 11(4): 1901-1917, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33408788

RESUMO

Rationale: Fc engineering has become the focus of antibody drug development. The current mutagenesis and in silico protein design methods are confined by the limited throughput and high cost, while the high-throughput phage display and yeast display technologies are not suitable for screening glycosylated Fc variants. Here we developed a mammalian cell display-based Fc engineering platform. Methods: By using mammalian cell display and next generation sequencing, we screened millions of Fc variants for optimized affinity and specificity for FcγRIIIa or FcγRIIb. The identified Fc variants with improved binding to FcγRIIIa were substituted into trastuzumab and rituximab and the effector function of antibodies were examined in the PBMC-based assay. On the other hand, the identified Fc variants with selectively enhanced FcγRIIb binding were applied to CD40 agonist antibody and the activities of the antibodies were measured on different cell assays. The immunostimulatory activity of CD40 antibodies was also evaluated by OVA-specific CD8+ T cell response model in FcγR/CD40-humanized mice. Results: Using this approach, we screened millions of Fc variant and successfully identified several novel Fc variants with enhanced FcγRIIIa or FcγRIIb binding. These identified Fc variants displayed a dramatic increase in antibody-dependent cellular cytotoxicity in PBMC-based assay. Novel variants with selectively enhanced FcγRIIb binding were also identified. CD40 agonist antibodies substituted with these Fc variants displayed activity more potent than the parental antibody in the in vitro and in vivo models. Conclusions: This approach increased the throughput of Fc variant screening from thousands to millions magnitude, enabled screening variants containing multiple mutations and could be integrated with glycoengineering technology, represents an ideal platform for Fc engineering. The initial efforts demonstrated the capability of the platform and the novel Fc variants could be substituted into nearly any antibody for the next generation of antibody therapeutics.

2.
Int J Cardiol ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33412177

RESUMO

BACKGROUND: Left ventricular thrombus (LVT) formation is a significant complication of acute myocardial infarction (AMI) due to its embolic potential. However, managing LVT requires balancing therapeutic benefits against bleeding risks. Our study provides a risk-benefit analysis of various antithrombotic regimens on long-term outcomes in treating post-AMI LVT patients. METHODS: We conducted a comprehensive literature search in Medline, Embase and SCOPUS up to 1 April 2020. All studies reporting outcomes of post-AMI LVT patients were included. RESULTS: 17 studies were included in total. Anticoagulation (47-100%) and triple therapy use (38-100%) varied largely across studies. On meta-analysis, administration of anticoagulation (OR 0.14, 95% CI 0.05-0.36, p < 0.001) and triple therapy (OR 0.22, 95% CI 0.07-0.66, p < 0.001) resulted in lower odds of mortality. Neither anticoagulation (p = 0.24) nor triple therapy (p = 0.73) was associated with bleeding. Triple therapy was associated with LVT resolution on meta-analysis (OR 2.53, 95% CI 1.53-4.19, p < 0.001) and regression analysis (OR 1.28, 95% CI 1.03-1.58, p = 0.03). Anticoagulation and triple therapy were independent predictors of systemic embolism ([OR 0.67, 95% CI 0.49-0.93, p = 0.02] and [OR 0.82, 95% CI 0.73-0.93, p = 0.001]) and stroke ([OR 0.62, 95% CI 0.41-0.94, p = 0.03] and [OR 0.73, 95% CI 0.55-0.96, p = 0.03]). CONCLUSIONS: While there is clear therapeutic benefit in anticoagulation for post-AMI LVT, the extent of bleeding risk is uncertain. Future trials are necessary to determine the optimal antithrombotic strategy for post-AMI LVT management.

3.
Life Sci ; 265: 118821, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33275988

RESUMO

Liver regeneration after partial hepatectomy (PH) is a complex and well-orchestrated process involving multiple factors such as cytokines, growth factors, and signaling pathways. MicroRNAs (miRNAs) participate in various biological processes including liver regeneration after PH. In the current study, we investigated the expression and function of human umbilical cord blood mesenchymal stem cell (hUCB-MSC) derived exosomal miRNAs on liver regeneration using a rat PH model. We found that hUCB-MSC derived exosomes promoted rat liver regeneration and ameliorated liver injury after PH. MicroRNA microarray was performed to identify the differentially expressed miRNAs in hUCB-MSC derived exosomes involving in liver regeneration after PH. We demonstrated that hUCB-MSC derived exosomal miR-124 could promote liver regeneration and prevent against liver injury after PH in rats. Inhibition of miR-124 abrogated the protective role of hUCB-MSC derived exosome in rat liver regeneration after PH. In addition, we identified that transcription factor Foxg1 was a direct target of miR-124 and miR-124 promoted rat liver cell proliferation via suppressing Foxg1 expression. Furthermore, we demonstrated that hUCB-MSC derived exosomal miR-124 enhanced liver regeneration via inhibiting Foxg1 in rats after PH. In summary, our findings suggest that hUCB-MSC-derived exosomal miR-124 could promote rat liver regeneration after PH via downregulating Foxg1.

5.
Neoplasma ; 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33350850

RESUMO

It is generally believed that the existence of cancer stem cells (CSCs) is related to tumor recurrence and metastasis of hepatocellular carcinoma (HCC). Neuropilin1 (NRP1) is involved in numerous pathophysiological processes of tumor progression, however, whether NRP1 is involved in the regulation of liver CSCs and metastasis of HCC is still unknown. In the present study, we examined the effect of NRP1 on the population of liver CSCs and the metastasis mechanism of HCC. In NRP1 small hairpin RNA (shRNA)-transduced HCC cells, liver CSCs surface markers (CD133+/ EpCAM+/CD13+/CD44+) expressing cells, which imply the CSCs population, were decreased. Transwell assay and nude mouse liver orthotopic transplantation model confirmed that NRP1 knockdown inhibited HCC cells migration and lung metastasis. Our data showed that the expression of NRP1 was upregulated in 5 independent cohorts of HCC patients, consequently, high levels of NRP1 correlated with recurrence and poor prognosis in HCC. Mechanism research showed that NRP1 promotes cell spreading through the epithelial-mesenchymal transition (EMT) signaling pathway. In summary, NRP1 enhanced the population of liver CSCs and migration of HCC via EMT, indicating that NRP1 might be a novel target for HCC treatments.

6.
World J Gastroenterol ; 26(44): 7061-7075, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33311950

RESUMO

BACKGROUND: Uric acid is the end product of purine metabolism. Previous studies have found that serum uric acid (SUA) levels are associated with the total cancer risk. However, due to the dual effect of uric acid on cancer, the relationship between the SUA levels and most specific-site cancer remains unclear. AIM: To investigate the associations between the SUA levels and incidence of hepatobiliary-pancreatic cancer. METHODS: In this prospective cohort study, 444462 participants free of cancer from the UK Biobank were included. The SUA levels were measured at baseline, and the incidence of hepatobiliary-pancreatic cancer was determined by contacting the cancer registry. The hazard ratios (HRs) and 95% confidence intervals (CIs) between the SUA levels and hepatobiliary-pancreatic cancer were investigated using multiple adjusted Cox regression models adjusted for potential confounders. RESULTS: In total, 920 participants developed liver, gallbladder, biliary tract or pancreatic cancer during a median of 6.6 yrs of follow-up. We found that the HR of pancreatic cancer in the highest SUA group was 1.77 (95%CI: 1.29-2.42) compared with that in the lowest group. After stratifying by gender, we further found that SUA was associated with an increased risk of pancreatic cancer only among the females (highest quartile vs lowest quartile HR 2.04, 95%CI: 1.35-3.08). Among the males, the SUA levels were positively associated with the gallbladder cancer risk (highest quartile vs lowest quartile HR 3.09, 95%CI: 1.28-7.46), but a U-shaped association with the liver cancer risk was observed (P-nonlinear = 0.03). CONCLUSION: SUA is likely to have gender-specific effects on hepatobiliary-pancreatic cancer. High SUA levels are a risk factor for pancreatic cancer in females and gallbladder cancer in males. A U-shaped association with the liver cancer risk was identified.

7.
Toxicol Lett ; 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33338565

RESUMO

Toxicity caused by the heavy metal Cadmium leads to liver diseases; this finding has generated interest among researchers. We detected DNA methylation using Whole Genome Bisulfite Sequencing (WGBS) to study the relationship between Cadmium exposure and liver damage. Forty-eight Sprague-Dawley rats were randomly divided into six groups, and given normal saline or 2.5, 5, 10, 20, and 40 mg/kg body weight per day CdCl2 by gavage. Twelve weeks later, their liver tissues were collected for pathological examination and DNA extraction. Increased exposure to Cadmium led to a reduction in the amount of weight gain as well as pathological degeneration and necrosis of liver cells of the rats. Using WGBS, we found that DNA methylation changes in the high-dose exposure group were more remarkable, and most of the changes occurred in the gene promoter region. GO enrichment analysis showed that the genes were enriched in the biological process of "response to stimulus." KEGG analysis revealed that metabolic pathways, like MAPK, PI3K-Akt and cAMP, had the largest number of enriched genes. Using Integrative Genomics Viewer (IGV), the demethylation of F2rl3 after Cadmium poisoning was established. This finding may explain why there are changes in liver metabolism after Cadmium poisoning.

8.
J Appl Toxicol ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33197057

RESUMO

Beryllium and its compounds are systemic toxicants that mainly accumulate in the lungs. As a regulator of gene expression, microRNAs (miRNAs) were involved in some lung diseases. This study aimed to analyze the levels of some inflammatory cytokine and the differential expressions of miRNAs in human bronchial epithelial cells (16HBE) induced by beryllium sulfate (BeSO4 ) and to further explore the biological functions of differentially expressed miRNAs. The profile of miRNAs in 16HBE cells was detected using the high-throughput sequencing between the control groups (n = 3) and the 150 µmol/L of BeSO4 -treated groups (n = 3). Bioinformatics analysis of differentially expressed miRNAs was performed, including the prediction of target genes, Gene Ontology (GO) analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to verify some damage-related miRNAs. We found that BeSO4 can increase the levels of some inflammatory cytokine such as interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), interferon-γ (IFN-γ), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). And BeSO4 altered miRNAs expression of 16HBE cells and a total of 179 differentially expressed miRNAs were identified, including 88 upregulated miRNAs and 91 downregulated miRNAs. The target genes predicted by 28 dysregulated miRNAs were mainly involved in the transcription regulation, signal transduction, MAPK, and VEGF signaling pathway. The qRT-PCR verification results were consistent with the sequencing results. miRNA expression profiling in 16HBE cells exposed to BeSO4 provides new insights into the toxicity mechanism of beryllium exposure.

10.
Eye (Lond) ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33188291

RESUMO

BACKGROUND: To investigate trends in the prevalence of reduced visual acuity (VA), a proxy measure for myopia, in an urban district in China. METHODS: Data were extracted from the dataset of the 2002 and 2018 Annual Survey on Students' Constitution and Health from Yuhua District, Changsha City, China. Children aged 6-15 years were included in the study. VA was measured using a LogMAR tumbling E chart. The prevalence of reduced VA was calculated by age and gender. The chi-square test was used to compare the differences between groups. RESULTS: The final VA analysis included 26217 children in 2002 and 45510 children in 2018. The overall prevalence of reduced VA increased from 28.3% in 2002 to 46.5% in 2018 (P < 0.001). The prevalence of reduced VA started to increase markedly from the age of 14 years in 2002, while in 2018 it started to increase markedly from the age of 9 years. The prevalence of severely reduced VA increased in all age groups from 2002 to 2018 and increased with age (all P < 0.001). In 2002, over 50% of children in all age groups had normal VA. By 2018, the prevalence of normal VA decreased from 61.4% in those aged 6 years to 31.9% in those aged 15 years. CONCLUSIONS: The prevalence of reduced VA among children aged 6-15 years in Yuhua District has become more common with age, and there has been a marked increase in the prevalence of reduced VA from 2002 to 2018. The remarkable epidemic of reduced VA started 5 years earlier in 2018 than in 2002. Evidence from the present study suggests that interventions should be launched before the age of 9 years.

11.
Bioorg Med Chem ; : 115868, 2020 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-33191085

RESUMO

Unlike other DNA topoisomerase II (topo II) inhibitors, our recently identified acridone derivative E17 exerted strong cytotoxic activity by inhibiting topo II without causing topo II degradation and DNA damage, which promoted us to explore more analogues of E17 by expanding its chemical diversification and enrich the structure-activity relationship (SAR) outcomes of acridone-oriented chemotypes. To achieve this goal, 42 novel acridone derivatives were synthesized and evaluated for their antiproliferative efficacies. SAR investigations revealed that orientation and spatial topology of R3 substituents make greater contributions to the bioactivity, exemplified by compounds E24, E25 and E27, which has provided valuable information for guiding further development of acridone derivatives as promising drug candidates.

12.
J Clin Neurosci ; 81: 448-454, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33222961

RESUMO

OBJECTIVE: To compare the clinical symptoms, brain copper deposition changes of Meso-2,3-dimercaptosuccinic acid (DMSA) and penicillamine therapy in patients with Wilson disease (WD) within 2 years. METHODS: 68 drug-naive patients with WD were enrolled. 10 WD patients treated with zinc gluconate alone were used as the control group. Neurological symptoms were scored using the modified Young Scale. Liver function tests, copper indices and sensitive weighted imaging (SWI) examination were collected. The values of corrected phase (CP) were collected. WD patients were treated with DPA (group 1) or DMSA (group 2) for two years, and followed up every 2 months. RESULTS: The ratio of neurological improvement in group 2 was higher than that in group 1 (P = 0.029). Higher rate of neurologic worsening was noticed in patients treated with DPA vs DMSA (P = 0.039). The post-treatment neurological score of DMSA group was lower than that of Zn group (P = 0.037). Hepatic function in 63.3% of patients was stable, while 16.7% was improved, and 20% was deteriorated, after DMSA therapy. Urinary copper levels were lower 1 month (p = 0.032), 4 months (p = 0.041), 12 months (p = 0.037) after initiation of treatment in group 2 than in group 1. At the first year of treatment, the CP values in globus pallidus and substantia nigra in group 2 were higher than those in group 1 (P = 0.034,0.039). At the second year of treatment, the CP values of substantia nigra in group 2 were higher (P = 0.041). Discontinuation was more common in patients on DPA therapy (P = 0 0.032). CONCLUSIONS: DMSA could remove metal from brain tissue faster than DPA. DMSA is effective for neurologic symptoms, while the outcome for hepatic symptoms is not entirely satisfactory. DMSA therapy is better tolerated than DPA.

13.
Eng Life Sci ; 20(11): 476-484, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33204234

RESUMO

At present, AIDS drugs are typical inhibitors that cannot achieve permanent effects. Therefore, the research of blocking HIV infection is essential. Especially for people in the high-risk environment, long-term prevention is important, because HIV can easily infect cells once the drug is interrupted. However, there is still no long-acting AIDS prevention drug approved. Hence, the purpose of this study is to prepare a fusion inhibitor loaded poly(d, l-lactic-co-glycolic acid) (PLGA) microspheres as a sustained-release system for long-term AIDS prevention. As the HIV membrane fusion inhibitor (LP-98) used in this research is amphiphilic lipopeptide, W1/O/W2 double-emulsion method was chosen, and premix membrane emulsification technique was used for controlling the uniformity of particle size. Several process parameters that can impact drug loading efficiency were summarized: the concentration of LP-98 and PLGA, and the preparation condition of primary emulsion. Finally, the microspheres with high loading efficiency (>8%) and encapsulation efficiency (>90%) were successfully prepared under optimum conditions. Pharmacokinetic studies showed that LP-98-loaded microspheres were capable to continuously release for 24 days in rats. This research can promote the application of sustained-release microspheres in AIDS prevention, and the embedding technique used in this study can also provide references for the loading of other amphipathic drugs.

15.
Opt Lett ; 45(21): 5917-5920, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33137031

RESUMO

Strong magneto-optical effect with low external magnetic field is of great importance to achieve high-performance isolators in modern optics. Here, we experimentally demonstrate a significant enhancement of the magneto-optical effect and nonreciprocal chiral transmission in low-biased gyrotropic media. A designer magneto-optical metasurface consists of a gyrotropy-near-zero slab doped with magnetic resonant inclusions. The immersed magnetic dopants enable efficient nonreciprocal light-matter interactions at the subwavelength scale, providing a giant macroscopic nonreciprocity and strong robustness against the bias disturbance. Microwave measurements reveal that the metasurface can act as a chiral isolator for circular polarization, with extremely weak intrinsic gyromagnetic activity. We also demonstrate its capability of signal isolation for circularly polarized antennas. Our findings provide an experimental verification of nonreciprocal photonic doping with low static magnetic fields.

16.
Surg Endosc ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33140156

RESUMO

BACKGROUND: Malignant biliary obstruction secondary to metastatic cancer is associated with poor prognosis. To the best of our knowledge, no previous study has investigated long-term survival and associated prognostic factors after biliary endoscopic retrograde cholangiopancreatography (ERCP) drainage for obstruction jaundice secondary to various types of metastatic cancer. METHODS: This retrospective study included 60 patients who underwent biliary ERCP drainage for obstructive jaundice secondary to metastatic cancer at two hospitals during the period from November 2012 to December 2019. Multivariate analysis was conducted to identify independent prognostic factors. RESULTS: Biliary drainage was successfully achieved in 55 (91.7%) patients, 37 of whom received subsequent treatment. Overall median survival time was 133 days after stent placement. The overall survival (OS) rates after ERCP drainage were significantly better in the post-drainage treatment group than in the post-drainage untreated group (239 days vs. 45 days, p < 0.001). Good ECOG performance status before drainage, albumin level ≥ 35 g/L, successful drainage, absence of ascites, and post-drainage treatment were identified as factors of improved survival in univariate analysis. ECOG performance status and post-drainage treatment were independent predictors of OS in multivariate analysis. CONCLUSIONS: We showed that stent placement with ERCP was a safe and effective treatment method for patients with malignant biliary obstruction caused by metastatic cancer and may be preferred over percutaneous transhepatic biliary drainage. Post-drainage treatment and a good ECOG performance status were predictors of better prognosis.

17.
J Am Chem Soc ; 142(43): 18687-18697, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33064473

RESUMO

Incorporating hidden length into polymer chains can improve their mechanical properties, because release of the hidden length under mechanical loads enables localized strain relief without chain fracture. To date, the design of hidden length has focused primarily on the choice of the sacrificial bonds holding the hidden length together. Here we demonstrate the advantages of adding mechanochemical reactivity to hidden length itself, using a new mechanophore that integrates (Z)-2,3-diphenylcyclobutene-1,4-dicarboxylate, with hitherto unknown mechanochemistry, into macrocyclic cinnamate dimers. Stretching a polymer of this mechanophore more than doubles the chain contour length without fracture. DFT calculations indicate that the sequential dissociation of the dimer, followed by cyclobutene isomerization at higher forces yields a chain fracture energy 11 times that of a simple polyester of the same initial contour length and preserves high energy-dissipating capacity up to ∼3 nN. In sonicated solutions cyclobutene isomerizes to two distinct products by competing reaction paths, validating the computed mechanochemical mechanism and suggesting an experimental approach to quantifying the distribution of single-chain forces under diverse loading scenarios.

18.
Biomed Res Int ; 2020: 9259742, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029532

RESUMO

Physical activity participation in children declines with age. It is not clear yet whether the age-related trends vary by weight status. This study is aimed at investigating the association between physical activity participation and age among children with healthy weight, overweight, or obesity, using data from the 2016-2017 National Survey of Children's Health (NSCH). Physical activity participation was evaluated by days participated in physical activity for at least 60 minutes out of 7 days. Weight status was categorized from body mass index (BMI) percentiles. Data were analyzed on 33,056 US children age 10-17 years. The percentages of been active 0 day out of 7 days in BMI5th < 85th (healthy weight), 85th < 95th (overweight), and ≥95th percentile (obese) groups were 8.9%, 11.5%, and 18.2%, respectively. Among all groups, been active 0 day out of 7 days was positively associated with age, while the strongest associations were observed in the BMI85th < 95th group (age 17 years vs. age 10 years: OR = 7.48, p < 0.0001). Older age was significantly associated with been active less than 4 days out of 7 days in the BMI5th < 85th and 85th < 95th groups, but those associations were attenuated in the BMI ≥ 95th group. This study found that physical activity participation was inversely associated with age among children with healthy weight, overweight, or obese, and the association was strongest among children with overweight and weakest among children with obesity. Interventions aimed at promoting physical activity among children should take these patterns of association into account.

19.
Sci Rep ; 10(1): 16265, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004957

RESUMO

Pyroptosis is a kind of necrotic and inflammatory programmed cell death induced by inflammatory caspases. SENP7 is a SUMO-specific protease, which mainly acts on deconjugation of SUMOs from substrate proteins. We evaluated the effect of SENP7 knockdown on pyroptosis, NF-κB signaling pathway, and NLRP3 inflammasome in Raw 264.7 cells. The results showed that the GSDMD protein mainly expressed in the cytoplasm nearby nuclei of Raw 264.7 cells. It migrated to cytomembrane with the numbers of Raw 264.7 cell decreased when LPS + ATP were administrated. Which was inhibited by SENP7 knockdown. In addition, not only the pyroptosis of Raw 264.7 cells was inhibited, the activation of NF-κB signaling pathway and NLRP3 inflammasome were also attenuated by SENP7 knockdown. The mechanism may be associated with the over SUMOylation of proteins induced by SENP7 knockdown.


Assuntos
Endopeptidases/metabolismo , Inflamassomos/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Transdução de Sinais , Animais , Western Blotting , Citocinas/metabolismo , Técnicas de Silenciamento de Genes , Camundongos , Células RAW 264.7/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1551-1557, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067953

RESUMO

OBJECTIVE: To investigate the clinical characteristics of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and the factors affecting overall survival (OS) time. METHODS: The clinical data of 14 R/R DLBCL patients admitted to the Hainan Hospital of Chinese PLA General Hospital from April 2012 to March 2019 were analyzed retrospectively and the overall response rate (ORR) after the end of different treatments was estimated. Kaplan-Meier method was used to describe the survival curve, and Log-rank test was used to compare whether different survival curves showed statistically different. RESULTS: There were 8 males and 6 females with a median age of 51 (26-75) years old and the median course of treatment before R/R was 7 (4-13). Finally, 11 patients achieved remission, 6 patients of which showed complete remission, and 5 patients showed partial remission, with the median ORR duration at 2.5 (0-51) months. All patients in the group of ibrutinib combined with second-line chemotherapy achieved remission (4/4), it was equivalent to the high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDC-AHSCT) group (4/4), which was significantly higher than that of the other second-line group (3/6). The median OS time of patients was 17 (6-76) months. The survival of patients receiving ibrutinib combined with second-line chemotherapy and HDC-AHSCT was significantly better than that of patients not receiving ibrutinib combined with second-line chemotherapy and HDC-AHSCT. Normal lactate dehydrogenase, IPI score<3 at diagnosis, and CR/PR after treatment could improve the survival time of patients. CONCLUSION: The duration of remission for R/R DLBCL patients is short and the prognosis is very poor. The survival time of patients with high level of lactate dehydrogenase, IPI score≥3 at diagnosis and SD/PD after treatment is significantly shortened. Ibrutinib combined second-line chemotherapy and HDC-AHSCT can improve the efficacy and survival of R/R DLBCL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Transplante Autólogo
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