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2.
Ann Surg Oncol ; 31(6): 3819-3829, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38245646

RESUMO

BACKGROUND: The impact of changes in skeletal muscle and sarcopenia on outcomes during neoadjuvant chemoradiotherapy (NACR) for patients with esophageal cancer remains controversial. PATIENTS AND METHODS: We retrospectively analyzed the data of patients with locally advanced esophageal squamous cell cancer who received NACR followed by esophagectomy between June 2013 and December 2021. The images at third lumbar vertebra were analyzed to measure the cross-sectional area and calculate skeletal muscle index (SMI) before and after NACR. SMI less than 52.4 cm2/m2 for men and less than 38.5 cm2/m2 for women were defined as sarcopenia. The nonlinearity of the effect of percent changes in SMI (ΔSMI%) to survival outcomes was assessed by restricted cubic splines. RESULTS: Overall, data of 367 patients were analyzed. The survival outcomes between sarcopenia and non-sarcopenia groups had no significant differences before NACR. However, patients in post-NACR sarcopenia group showed poor overall survival (OS) benefit (P = 0.016) and poor disease-free survival (DFS) (P = 0.043). Severe postoperative complication rates were 11.9% in post-NACR sarcopenia group and 5.0% in post-NACR non-sarcopenia group (P = 0.019). There was a significant non-linear relationship between ΔSMI% and survival outcomes (P < 0.05 for non-linear). On the multivariable analysis of OS, ΔSMI% > 12% was the independent prognostic factor (HR 1.76, 95% CI 1.03-2.99, P = 0.039) and significant difference was also found on DFS analysis (P = 0.025). CONCLUSIONS: Patients with post-neoadjuvant chemoradiotherapy sarcopenia have worse survival and adverse short-term outcomes. Moreover, greater loss in SMI is associated with increased risks of death and disease progression during neoadjuvant chemoradiotherapy, with maximum impact noted with SMI loss greater than 12%.


Assuntos
Neoplasias Esofágicas , Esofagectomia , Músculo Esquelético , Terapia Neoadjuvante , Sarcopenia , Humanos , Sarcopenia/etiologia , Sarcopenia/patologia , Masculino , Feminino , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/complicações , Terapia Neoadjuvante/mortalidade , Estudos Retrospectivos , Pessoa de Meia-Idade , Taxa de Sobrevida , Músculo Esquelético/patologia , Prognóstico , Idoso , Seguimentos , Quimiorradioterapia/mortalidade , Quimiorradioterapia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Quimiorradioterapia Adjuvante
4.
Signal Transduct Target Ther ; 7(1): 317, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-36097006

RESUMO

Finely tuned mitogen-activated protein kinase (MAPK) signaling is important for cancer cell survival. Perturbations that push cells out of the MAPK fitness zone result in cell death. Previously, in a screen of the North China Pharmaceutical Group Corporation's pure compound library of microbial origin, we identified elaiophylin as an autophagy inhibitor. Here, we demonstrated a new role for elaiophylin in inducing excessive endoplasmic reticulum (ER) stress, ER-derived cytoplasmic vacuolization, and consequent paraptosis by hyperactivating the MAPK pathway in multiple cancer cells. Genome-wide CRISPR/Cas9 knockout library screening identified SHP2, an upstream intermediary of the MAPK pathway, as a critical target in elaiophylin-induced paraptosis. The cellular thermal shift assay (CETSA) and surface plasmon resonance (SPR) assay further confirmed the direct binding between the SHP2 and elaiophylin. Inhibition of the SHP2/SOS1/MAPK pathway through SHP2 knockdown or pharmacological inhibitors distinctly attenuated elaiophylin-induced paraptosis and autophagy inhibition. Interestingly, elaiophylin markedly increased the already-elevated MAPK levels and preferentially killed drug-resistant cells with enhanced basal MAPK levels. Elaiophylin overcame drug resistance by triggering paraptosis in multiple tumor-bearing mouse models resistant to platinum, taxane, or PARPi, suggesting that elaiophylin might offer a reasonable therapeutic strategy for refractory ovarian cancer.


Assuntos
Antineoplásicos , Neoplasias Ovarianas , Animais , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Feminino , Humanos , Macrolídeos , Camundongos , Proteínas Quinases Ativadas por Mitógeno , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética
5.
Eur J Cardiothorac Surg ; 62(1)2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35695773

RESUMO

OBJECTIVES: The aim of this study was to evaluate the short-term outcomes of neoadjuvant chemoimmunotherapy (NACI) followed by oesophagectomy for locally advanced oesophageal squamous carcinoma. METHODS: Patients receiving NACI or chemoradiotherapy between September 2019 and September 2021 were identified. The primary outcomes were tumour response and survival. Secondary outcomes were toxic effects and postoperative complications. The propensity score matching for enrolled patients was performed. RESULTS: Data of 149 patients with clinical stage II-IV oesophageal squamous cancer, including 55 receiving NACI and 94 receiving neoadjuvant chemoradiotherapy (NACR), were analysed after propensity score matching. With regard to tumour response score, 24 (43.6%) and 59 (62.8%) patients were scored 0/1 in the NACI and NACR groups, respectively (P = 0.023). Of note, 17 (30.9%) patients in the NACI group achieved pathological complete response (CR) (ypT0N0), while 48 (51.1%) patients in NACR group achieved pathological CR (P = 0.026). NACR was associated with the higher risk of postoperative pneumonia (P = 0.034) and less lymph nodes and stations dissected (P ≤ 0.001). The 1-year cumulative overall survival rate was 94.5% and 86.2% in the NACI and NACR groups, respectively (P = 0.170). CONCLUSIONS: We found that NACI compared with NACR was associated with lower pneumonia rate and was safe and feasible for locally advanced oesophageal squamous cancer. However, the tumour regression score and the pathological CR rate of patients treated with neoadjuvant immunotherapy were lower than those of patients treated with NACR. The short-term follow-up results were comparable between 2 treatment modalities.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Quimiorradioterapia/métodos , Carcinoma de Células Escamosas do Esôfago/terapia , Esofagectomia/métodos , Humanos , Imunoterapia , Terapia Neoadjuvante , Estudos Retrospectivos
6.
Stem Cell Res Ther ; 13(1): 281, 2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35765072

RESUMO

Non-traumatic intracerebral hemorrhage is a highly destructive intracranial disease with high mortality and morbidity rates. The main risk factors for cerebral hemorrhage include hypertension, amyloidosis, vasculitis, drug abuse, coagulation dysfunction, and genetic factors. Clinically, surviving patients with intracerebral hemorrhage exhibit different degrees of neurological deficits after discharge. In recent years, with the development of regenerative medicine, an increasing number of researchers have begun to pay attention to stem cell and exosome therapy as a new method for the treatment of intracerebral hemorrhage, owing to their intrinsic potential in neuroprotection and neurorestoration. Many animal studies have shown that stem cells can directly or indirectly participate in the treatment of intracerebral hemorrhage through regeneration, differentiation, or secretion. However, considering the uncertainty of its safety and efficacy, clinical studies are still lacking. This article reviews the treatment of intracerebral hemorrhage using stem cells and exosomes from both preclinical and clinical studies and summarizes the possible mechanisms of stem cell therapy. This review aims to provide a reference for future research and new strategies for clinical treatment.


Assuntos
Exossomos , Animais , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/terapia , Fatores de Risco , Transplante de Células-Tronco/efeitos adversos
7.
Medicine (Baltimore) ; 100(46): e27898, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797341

RESUMO

RATIONALE: Thrombotic thrombocytopenic purpura (TTP) is a critical thrombotic microangiopathy involving multiple organs. To the best of our knowledge, there are no reports of TTP complicated by acute aortic dissection. PATIENT CONCERNS: We herein described a 53-year-old male with TTP who did not have a significant medical history. After immediate plasma exchange and glucocorticoid therapy, the patient's clinical condition improved. However, the patient suddenly experienced chest pain with elevated blood pressure. DIAGNOSES: Computed tomography angiography suggested acute type B aortic dissection. INTERVENTIONS: The patient was immediately transferred to the cardiac aortic surgery department for thoracic aortic endovascular repair. OUTCOMES: The patient was discharged after successful thoracic aortic endovascular repair. Unfortunately, 3 months later, the patient experienced chest and back pain at home and died suddenly, possibly due to the recurrence of aortic dissection. LESSONS: Even if patients have no identifiable risk factors, physicians should be aware of this rare and life-threatening acute complication of TTP, which may have multiple causes, including preexisting connective tissue disease, abnormal blood pressure fluctuations, and increased risk of hemorrhage. Early identification and timely treatment of acute aortic dissection are critical for improving prognosis.


Assuntos
Dissecção Aórtica/etiologia , Púrpura Trombocitopênica Trombótica/complicações , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares , Humanos , Masculino , Pessoa de Meia-Idade , Troca Plasmática , Púrpura Trombocitopênica Trombótica/diagnóstico , Resultado do Tratamento
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1601-1605, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627447

RESUMO

OBJECTIVE: To analyze the clinical efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH), and preliminarily explore the role of an improved post-transplantation cyclophosphamide (PTCy) based conditioning regimen in PNH patients receiving transplantation. METHODS: Clinical related data of PNH sufferers receiving allo-HSCT in Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were collected, and hematopoietic reconstitution, chimerism, PNH cloning, graft-versus-host disease (GVHD), infection, and survival were analyzed. RESULTS: Totally five PNH patients receiving allo-HSCT were enrolled, including 1 case with classic PNH, 3 cases with aplastic anemia-PNH syndrome, 1 case with myelodysplastic syndrome, three of them (case 1-3) received the improved PTCy based conditioning regimen before HSCT. All sufferers engrafted successfully within 28 days, the median time of neutrophil and platelet engraftment was 11 days and 12 days, respectively, no patient occurred acute or chronic GVHD, after a median follow-up of 16 months, all recipients survived and completely eliminated PNH cloning. CONCLUSION: Allo-HSCT can completely clear PNH cloning and restore hematopoietic function with controllable complications, and the improved PTCy based conditioning regimen is proved to be effective in PNH transplantation.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Hemoglobinúria Paroxística , Anemia Aplástica/terapia , Hemoglobinúria Paroxística/terapia , Humanos , Condicionamento Pré-Transplante
10.
Biomed Res Int ; 2021: 8569921, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34327238

RESUMO

Doxorubicin is a cornerstone chemotherapeutic drug widely used to treat various cancers; its dose-dependent cardiomyopathy, however, is one of the leading causes of treatment-associated mortality in cancer survivors. Patients' threshold doses leading to doxorubicin-induced cardiomyopathy (DIC) and heart failure are highly variable, mostly due to genetic variations in individuals' genomes. However, genetic susceptibility to DIC remains largely unidentified. Here, we combined a genetic approach in the zebrafish (Danio rerio) animal model with a genome-wide association study (GWAS) in humans to identify genetic susceptibility to DIC and heart failure. We firstly reported the cardiac and skeletal muscle-specific expression and sarcomeric localization of the microtubule-associated protein 7 domain-containing protein 1b (Map7d1b) in zebrafish, followed by expression validation in mice. We then revealed that disruption of the map7d1b gene function exaggerated DIC effects in adult zebrafish. Mechanistically, the exacerbated DIC are likely conveyed by impaired autophagic degradation and elevated protein aggregation. Lastly, we identified 2 MAP7D1 gene variants associated with cardiac functional decline and heart failure in cancer patients who received doxorubicin therapy. Together, this study identifies MAP7D1 as a clinically relevant susceptibility gene to DIC and heart failure, providing useful information to stratify cancer patients with a high risk of incurring severe cardiomyopathy and heart failure after receiving chemotherapy.


Assuntos
Cardiomiopatias/induzido quimicamente , Cardiomiopatias/genética , Doxorrubicina/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/genética , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Animais , Apoptose , Autofagia , Elementos de DNA Transponíveis/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Insuficiência Cardíaca/fisiopatologia , Modelos Biológicos , Músculo Esquelético/metabolismo , Mutação/genética , Miocárdio/metabolismo , Miócitos Cardíacos/patologia , Polimorfismo de Nucleotídeo Único/genética , Agregados Proteicos , Fatores de Risco , Estresse Fisiológico
11.
Curr Med Sci ; 41(3): 474-481, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34169427

RESUMO

Anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy is effective and well-tolerated for refractory or relapsed multiple myeloma (RRMM). The purpose of the present study was to analyze efficacy in RRMM patients with renal impairment treated by anti-BCMA CAR-T cell therapy. A total of 59 RRMM patients were selected, and divided into impaired renal function (IRF) group [baseline estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 (n=18)] and normal renal function (NRF) group (baseline eGFR ≥ 90 mL/min/1.73 m2, n=41). For patients with IRF, eGFR at the 6th month post-CAR-T cells infusion was significantly higher than the baseline (P<0.05). The multivariate analysis showed that light chain type and beta-2 micro-globulin (beta-2M) were associated factors with the decrease of serum creatinine. Median progression-free survival (PFS) in the NRF group and IRF group was 266 days and 181 days respectively. Overall survival (OS) in the NRF group and IRF group was 877 days and 238 days respectively. There was no significant difference in the objective response rate (ORR) between the IRF group and the NRF group. It is suggested that CAR-T cells therapy could improve the renal function during the treatment of RRMM. The renal function could be more significantly improved in RRMM patients with light chain type than with other types.


Assuntos
Antígeno de Maturação de Linfócitos B/genética , Imunoterapia Adotiva , Nefropatias/terapia , Mieloma Múltiplo/terapia , Adulto , Antígeno de Maturação de Linfócitos B/antagonistas & inibidores , Terapia Baseada em Transplante de Células e Tecidos/tendências , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Nefropatias/complicações , Nefropatias/genética , Nefropatias/patologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/uso terapêutico
12.
Curr Med Sci ; 41(3): 482-490, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34170459

RESUMO

Epstein-Barr virus (EBV) T/NK-cell lymphoproliferative diseases are characterized by clonal expansion of EBV-infected T or NK cells, including chronic active EBV infection of T/NK-cell type (CAEBV+T/NK), EBV-associated hemophagocytic lymphohistiocytosis (EBV+HLH), extranodal NK/T-cell lymphoma of nasal type (ENKTL), and aggressive NK-cell leukemia (ANKL). However, the role of inherited genetic variants to EBV+T/NK-LPDs susceptibility is still unknown. A total of 171 nonimmunosuppressed patients with EBV+T/NK-LPDs and 104 healthy donors were retrospectively collected and a targeted sequencing study covering 15 genes associated with lymphocyte cytotoxicity was performed. The 94 gene variants, mostly located in UNC13D, LYST, ITK, and PRF1 genes were detected, and mutations covered 28/50 (56.00%) of CAEBV-T/NK, 31/51 (60.78%) of EBV+HLH, 13/28 (46.42%) of ENKTL, and 13/48 (27.09%) of ANKL. Most mutations represented monoallelic and missense. Three-year overall survival rate of patients with CAEBV-T/NK and EBV+HLH was significantly lower in patients with germline mutations than in those without germline mutations (P=0.0284, P=0.0137). Our study provided novel insights into understanding a spectrum of nonimmunosuppressed EBV+T/NK-LPDs with respect to genetic defects associated with lymphocyte cytotoxicity and reminded us that the gene sequencing may be an auxiliary test for diagnosis and risk stratification of EBV+T/NK-LPDs.


Assuntos
Predisposição Genética para Doença , Herpesvirus Humano 4/patogenicidade , Transtornos Linfoproliferativos/genética , Proteínas de Neoplasias/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Herpesvirus Humano 4/genética , Humanos , Lactente , Células Matadoras Naturais/patologia , Células Matadoras Naturais/virologia , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/virologia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Linfócitos T/patologia , Linfócitos T/virologia , Adulto Jovem
13.
14.
Proc Natl Acad Sci U S A ; 118(6)2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33495363

RESUMO

As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO-based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA-anthracycline for low-/intermediate-risk patients, or ATRA-ATO-anthracycline versus ATRA-anthracycline-cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of -5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI -0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan-Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA-chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Trióxido de Arsênio/administração & dosagem , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Trióxido de Arsênio/efeitos adversos , Quimioterapia de Consolidação/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Resultado do Tratamento , Tretinoína/efeitos adversos
15.
Front Oncol ; 11: 777686, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34993139

RESUMO

BACKGROUND: The published evidence from several randomized controlled clinical trials of immunotherapy for advanced esophageal squamous cell carcinoma has shown promising results. This study aimed to investigate the efficacy and safety of immune checkpoint inhibitor treatment in esophageal squamous cell carcinoma. METHODS: PubMed, Web of Science, Cochrane Library, and Embase databases were searched for relevant articles published before December 30, 2020. The data for efficacy and safety of immune checkpoint inhibitor treatment were subjected to meta-analysis. RESULTS: Seven clinical trials comprising 1733 patients were included. The results showed that immune checkpoint inhibitor treatment as second- or later-line treatment was associated with an increased risk of the objective response rate (relative risk: 1.82, 95% confidence interval: 0.82-4.04; P=0.002) and median overall survival (hazard ratio: 0.75, 95% confidence interval: 0.67-0.85; P<0.001) compared with chemotherapy in locally advanced or metastatic esophageal squamous cell carcinoma. Moreover, immune checkpoint inhibitor treatment was associated with significant improvement in median overall survival (hazard ratio: 0.61, 95% confidence interval: 0.48-0.77, P<0.001) compared with chemotherapy in the programmed death-ligand 1 (PD-L1)-positive population. However, immune checkpoint inhibitor treatment was also effective in all patients independent of PD-L1 expression. The most common grade ≥3 treatment-related adverse events with immune checkpoint inhibitor therapy were anemia, asthenia, rash, fatigue, decreased appetite, diarrhea, pneumonia, decreased neutrophil count, and vomiting. Patients undergoing immune checkpoint inhibitor therapy was associated with a decreased risk of treatment-related adverse events (relative risk: 0.82, 95% confidence interval: 0.62-1.08; P<0.001) and grade ≥3 treatment-related adverse events (relative risk: 0.50, 95% confidence interval: 0.42-0.60; P<0.001) compared with those undergoing chemotherapy. CONCLUSIONS: Immune checkpoint inhibitors as second- or later-line therapy may improve overall response rate and overall survival but not all oncological outcomes for patients with locally advanced or metastatic esophageal squamous cell carcinoma. Patients treated with immune checkpoint inhibitors might experience fewer treatment-related adverse events of any grade, but specifically grade ≥3, compared with those treated with chemotherapy.

16.
BMC Cancer ; 20(1): 714, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736575

RESUMO

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a spectrum of disease comprising more than 30% of non-Hodgkin lymphomas. Although studies have identified several molecular subgroups, the heterogeneous genetic background of DLBCL remains ambiguous. In this study we aimed to develop a novel approach and to provide a distinctive classification system to unravel its molecular features. METHOD: A cohort of 342 patient samples diagnosed with DLBCL in our hospital were retrospectively enrolled in this study. A total of 46 genes were included in next-generation sequencing panel. Non-mutually exclusive genetic signatures for the factorization of complex genomic patterns were generated by random forest algorithm. RESULTS: A total of four non-mutually exclusive signatures were generated, including those with MYC-translocation (MYC-trans) (n = 62), with BCL2-translocation (BCL2-trans) (n = 69), with BCL6-translocation (BCL6-trans) (n = 108), and those with MYD88 and/or CD79B mutations (MC) signatures (n = 115). Comparison analysis between our model and traditional mutually exclusive Schmitz's model demonstrated consistent classification pattern. And prognostic heterogeneity existed within EZB subgroup of de novo DLBCL patients. As for prognostic impact, MYC-trans signature was an independent unfavorable prognostic factor. Furthermore, tumors carrying three different signature markers exhibited significantly inferior prognoses compared with their counterparts with no genetic signature. CONCLUSION: Compared with traditional mutually exclusive molecular sub-classification, non-mutually exclusive genetic fingerprint model generated from our study provided novel insight into not only the complex genetic features, but also the prognostic heterogeneity of DLBCL patients.


Assuntos
Algoritmos , Genes Neoplásicos/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Linfoma Difuso de Grandes Células B/genética , Transcriptoma/genética , Adulto , Idoso , Inteligência Artificial , Antígenos CD79/genética , China , Estudos de Coortes , Análise Mutacional de DNA/métodos , Feminino , Genes bcl-2 , Genes myc , Humanos , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/classificação , Masculino , Pessoa de Meia-Idade , Fator 88 de Diferenciação Mieloide/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Estudos Retrospectivos , Translocação Genética
17.
J Clin Oncol ; 38(29): 3367-3376, 2020 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-32650683

RESUMO

PURPOSE: The role of antithymocyte globulin (ATG) in preventing acute graft-versus-host disease (aGVHD) after HLA-matched sibling donor transplantation (MSDT) is still controversial. PATIENTS AND METHODS: We performed a prospective, multicenter, open-label, randomized controlled trial (RCT) across 23 transplantation centers in China. Patients ages 40-60 years with standard-risk hematologic malignancies with an HLA-matched sibling donor were randomly assigned to an ATG group (4.5 mg/kg thymoglobulin plus cyclosporine [CsA], methotrexate [MTX], and mycophenolate mofetil [MMF]) and a control group (CsA, MTX, and MMF). The primary end point of this study was grade 2-4 aGVHD on day 100. RESULTS: From November 2013 to April 2018, 263 patients were enrolled. The cumulative incidence rate of grade 2-4 aGVHD was significantly reduced in the ATG group (13.7%; 95% CI, 13.5% to 13.9%) compared with the control group (27.0%; 95% CI, 26.7% to 27.3%; P = .007). The ATG group had significantly lower incidences of 2-year overall chronic GVHD (27.9% [95% CI, 27.6% to 28.2%] v 52.5% [95% CI, 52.1% to 52.9%]; P < .001) and 2-year extensive chronic GVHD (8.5% [95% CI, 8.4% to 8.6%] v 23.2% [95% CI, 22.9% to 23.5%]; P = .029) than the control group. There were no differences between the ATG and control groups with regard to cytomegalovirus reactivation, Epstein-Barr virus reactivation, 3-year nonrelapse mortality (NRM), 3-year cumulative incidence of relapse (CIR), 3-year overall survival, or 3-year leukemia-free survival. Three-year GVHD relapse-free survival was significantly improved in the ATG group (38.7%; 95% CI, 29.9% to 47.5%) compared with the control group (24.5%; 95% CI, 16.9% to 32.1%; P = .003). CONCLUSION: Our study is the first prospective RCT in our knowledge to demonstrate that ATG can effectively decrease the incidence of aGVHD after MSDT in the CsA era without affecting the CIR or NRM.


Assuntos
Soro Antilinfocitário/administração & dosagem , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Adulto , Ciclosporina/administração & dosagem , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Antígenos HLA/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Irmãos , Doadores de Tecidos
18.
Curr Med Sci ; 39(6): 874-882, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31845217

RESUMO

As a rapidly progressing field in oncology, the adoptive transfer of T cells that have been genetically modified with chimeric antigen receptors (CARs) has shown striking efficacy in the management of hematological malignancies and has been reported in a number of clinical trials. Of note, CAR T cell therapy has shown extraordinary potential, especially in relapsed/refractory patients. However, there are still challenges regarding the further development of this strategy, spanning from engineering and manufacturing issues, to limited applications, to accompanying toxicities. In this review, we will summarize the general knowledge of this novel method, including receptor composition, applications, adverse events and challenges. Additionally, we will propose several comprehensive recommendations.


Assuntos
Neoplasias Hematológicas/terapia , Imunoterapia Adotiva/métodos , Ensaios Clínicos como Assunto , Neoplasias Hematológicas/imunologia , Humanos , Imunoterapia Adotiva/efeitos adversos , Engenharia de Proteínas , Receptores de Antígenos Quiméricos/imunologia , Resultado do Tratamento
19.
Front Oncol ; 9: 1133, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31709191

RESUMO

Background: DNA methyltransferase 3A (DNMT3A) plays a unique role in hematopoiesis and acute myeloid leukemia (AML) pathogenesis. While the influences of DNMT3A mutation subtypes are still under debate. Purpose: Exploration of the clinical and molecular differences between AML patients carrying DNMT3A R882 mutations and DNMT3A frameshift mutations. Methods: Next generation of sequencing (NGS) and clinical data of 118 AML patients in our center were analyzed and compared. NGS, mRNA and miRNA profiling and clinical data from 12 patients in TCGA database were integrative analyzed. Results: Among all patients enrolled, 113 patients were positive for the variants of interest. Overall, a total of 295 variants were discovered, among which 24 DNMT3A mutations were detected, including 1 non-sense, 20 missense, 3 frameshift mutations. And 7 DNMT3A R882 mutations (3 R882H, 2 R882C, and 2 R882P) were found. Clinical analysis from our cohort and TCGA database indicated that patients carrying DNMT3A R882 mutation exhibited significantly higher levels of peripheral blood hemoglobin and non-significantly inferior prognosis compared with patients with DNMT3A frameshift mutations. Integrative analysis indicated that miR-10b, miR-143, and miR-30a were significantly decreased in the DNMT3A R882 group. High miR-143 expression is significantly associated with better prognosis in AML patients with DNMT3A mutations. Conclusion: Different molecular and clinical characteristics existed between patients with DNMT3A variant subtypes. The distinct microRNA expression pattern for DNMT3A R882 AML patients might not only act as markers to predict disease prognosis, but also could be further investigated to develop novel therapeutic targets for patients with DNMT3A mutations.

20.
Chin J Dent Res ; 22(3): 181-188, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31508606

RESUMO

OBJECTIVE: To evaluate the effect of provisional restorations using ovate pontics on the hard and soft tissues of the alveolar ridge after tooth extraction. METHODS: Patients with intact buccal bone after extraction of a maxillary incisor underwent a series of treatments. The protocol included tooth extraction and provisional restoration using ovate pontics. The outcomes were assessed 1, 3 and 6 months after the procedure, regarding changes in bone volume and soft tissue dimension. RESULTS: A total of 11 patients (6 female and 5 male) were treated using an ovate pontic provisional restoration after tooth extraction. After 6 months, bone loss at level 1, 3 and 5 mm below the most coronal section of the bone crest was 2.28 ± 0.53 mm, 1.51 ± 0.30 mm and 1.46 ± 0.41 mm, respectively. Changes in bone volume of these three levels were significantly lower (P < 0.01) than changes previously reported in the literature. The mesial and distal papillae recessed 0.47 ± 0.24 mm and 0.88 ± 0.57 mm, respectively, whereas the midfacial shrinkage was 0.86 ± 0.44 mm. The dimension of the ridge contour around the socket reduced mostly at 3 and 5 mm below the coronal section and the gingival mucosa, with values of 1.68 ± 0.48 mm and 1.61 ± 0.48 mm, respectively. CONCLUSION: Using a provisional restoration with ovate pontics after tooth extraction may preserve the alveolar ridge by sustaining the soft tissue, in particular the gingival papilla.


Assuntos
Perda do Osso Alveolar , Prótese Parcial Fixa , Processo Alveolar , Feminino , Gengiva , Humanos , Masculino , Maxila , Extração Dentária
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