Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 30
Filtrar
1.
Anal Chem ; 93(36): 12329-12336, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34474564

RESUMO

"On-demand" accurate imaging of multiple intracellular miRNAs will significantly improve the detection reliability and accuracy. However, the "always-active" design of traditional multicomponent detection probes enables them to passively recognize and output signals as soon as they encounter targets, which will inevitably impair the detection accuracy and, inevitably, result in false-positive signals. To address this scientific problem, in this work, we developed a near-infrared (NIR) light-activated multicomponent detection intelligent nanoprobe for spatially and temporally controlled on-demand accurate imaging of multiple intracellular miRNAs. The proposed intelligent nanoprobe is composed of a rationally designed UV light-responsive triangular DNA nano sucker (TDS) and upconversion nanoparticles (UCNPs), named UCNPs@TDS (UTDS), which can enter cells autonomously through endocytosis and enable remote regulation of on-demand accurate imaging for multiple intracellular miRNAs using NIR light illumination at a chosen time and place. It is worth noting that the most important highlight of the UTDS we designed in this work is that it can resist nonspecific activation as well as effectively avoid false-positive signals and improve the accuracy of imaging of multiple intracellular miRNAs. Moreover, distinguishing different kinds of cell lines with different miRNA expressions levels can be also achieved through this NIR light-activated intelligent UTDS, showing feasible prospects in precise imaging and disease diagnosis.


Assuntos
MicroRNAs , Nanopartículas , DNA , Raios Infravermelhos , Reprodutibilidade dos Testes
2.
Cancer Biol Med ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33755379

RESUMO

OBJECTIVE: To assess the efficacy and safety of the novel histone deacetylase inhibitor, chidamide, in combination with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (Chi-CHOEP) for untreated peripheral T-cell lymphoma (PTCL). METHODS: A prospective, multicenter, single arm, phase 1b/2 study was conducted. A total of 128 patients with untreated PTCL (18-70 years of age) were enrolled between March 2016 and November 2019, and treated with up to 6 cycles with the Chi-CHOEP regimen. In the phase 1b study, 3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximum-tolerated dose and recommended phase 2 dose (RP2D). The primary endpoint of the phase 2 study was 2-year progression-free survival (PFS). RESULTS: Fifteen patients were enrolled in the phase 1b study and the RP2D for chidamide was determined to be 20 mg, twice a week. A total of 113 patients were treated at the RP2D in the phase 2 study, and the overall response rate was 60.2%, with a complete response rate of 40.7%. At a median follow-up of 36 months, the median PFS was 10.7 months, with 1-, 2-, and 3-year PFS rates of 49.9%, 38.0%, and 32.8%, respectively. The Chi-CHOEP regimen was well-tolerated, with grade 3/4 neutropenia occurring in approximately two-thirds of the patients. No unexpected adverse events (AEs) were reported and the observed AEs were manageable. CONCLUSIONS: This large cohort phase 1b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.

3.
Anal Chem ; 93(4): 2480-2489, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33410672

RESUMO

Plasmon-enhanced fluorescence (PEF) is considered to be a powerful signal amplification technology to overcome intrinsic shortcomings of photobleaching and brightness of the traditional fluorescent dyes. Nevertheless, exploitation of PEF-based probes for bioimaging application is still at a very early stage. In this work, a simple but powerful gold nanostar (Au NST)@SiO2-based PEF probe with 20 symmetric "hot spots" was developed for highly sensitive "lighting up" in situ imaging of intracellular microRNAs (miRNAs). By regulating the thickness of the silica shell, the distance between Au NSTs and fluorescent dyes was controlled, and the optimum fluorescence enhancement (21-fold) was obtained with the silica shell thickness of approximately 22 nm. Thanks to the 20 more powerful "hot spots" that can produce stronger localized electric fields, the Au NST-based PEF probe exhibits stronger PEF effects than the traditional plasmonic nanostructures such as gold nanorods (Au NRs), gold nanobipyramids (Au NBPs), and triangular gold nanoprisms (Au NPRs), resulting in high sensitivity and improved detection limit (LOD) of 0.21 pM for miRNA-21 analysis. Moreover, not only cancer cells (MCF-7 and Hela) and normal cells (L02) with distinct miRNA-21 expression levels can be discriminated but also tumor cells in co-cultured mixtures can be recognized, indicating its promising potential in clinical diagnosis.

4.
J Hematol Oncol ; 14(1): 12, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436023

RESUMO

BACKGROUND: Peripheral T cell lymphoma (PTCL) is a rare disease and recent approved drugs for relapsed/refractory (r/r) PTCL provided limited clinical benefit. We conducted this study to evaluate the efficacy and safety of geptanolimab (GB226), an anti-PD-1 antibody, in r/r PTCL patients. METHODS: We did this single-arm, multicenter phase 2 study across 41 sites in China. Eligible patients with r/r PTCL received geptanolimab 3 mg/kg intravenously every 2 weeks until disease progression or intolerable toxicity. All patients who received at least one dose of geptanolimab and histological confirmed PTCL entered full analysis set (FAS). The primary endpoint was objective response rate (ORR) in FAS assessed by the independent radiological review committee (IRRC) per Lugano 2014 criteria. RESULTS: Between July 12, 2018, and August 15, 2019, 102 patients were enrolled and received at least one dose of geptanolimab. At the data cutoff date (August 15, 2020), the median follow-up was 4.06 (range 0.30-22.9) months. For 89 patients in FAS, 36 achieved objective response (40.4%, 95% CI 30.2-51.4), of which 13 (14.6%) were complete response and 23 (25.8%) had partial response assessed by IRRC. The median duration of response (DOR) was 11.4 (95% CI 4.8 to not reached) months per IRRC. Patients with PD-L1 expression ≥ 50% derived more benefit from geptanolimab treatment compared to < 50% ones (ORR, 53.3% vs. 25.0%, p = 0.013; median PFS 6.2 vs. 1.5 months, p = 0.002). Grade ≥ 3 treatment-related adverse events occurred in 26 (25.5%) patients, and the most commonly observed were lymphocyte count decreased (n = 4) and platelet count decreased (n = 3). Serious adverse events were observed in 45 (44.1%) patients and 19 (18.6%) were treatment related. CONCLUSIONS: In this study, geptanolimab showed promising activity and manageable safety profile in patients with r/r PTCL. Anti-PD-1 antibody could be a new treatment approach for this patient population. TRIAL REGISTRATION: This clinical trial was registered at the ClinicalTrials.gov (NCT03502629) on April 18, 2018.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Linfoma de Células T Periférico/tratamento farmacológico , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Resultado do Tratamento
5.
Minerva Med ; 112(2): 310-312, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-31317691
6.
Anal Chem ; 92(22): 15169-15178, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33125850

RESUMO

Versatile all-in-one nanoplatforms that inherently possess both diagnostic imaging and therapeutic capabilities are highly desirable for efficient tumor diagnosis and treatment. Herein, we have developed a novel core-shell multifunctional nanomaterial-based all-in-one nanoplatform composed of gold nanobipyramids@polydopamine (Au NBPs@PDA) and gold nanoclusters (Au NCs) for simultaneous in situ multilayer imaging of dual types of tumor biomarkers (using a single-wavelength excitation) with different intracellular spatial distributions and fluorescence-guided photothermal therapy. The competitive combination between target transmembrane glycoprotein mucin1 (MUC1) and its aptamer caused Au NCs (620 nm) labeled with MUC1 aptamer to detach from the surface of Au NBPs@PDA, turning on the red fluorescence. Meanwhile, the hybridization between microRNA-21 (miRNA-21) and its complementary single-stranded DNA triggered the green fluorescence of Au NCs (515 nm). Based on this, simultaneous in situ multilayer imaging of dual types of tumor biomarkers with different intracellular spatial distributions was achieved. In addition, the potential of Au NBPs@PDA/Au NCs was also confirmed by simultaneous multilayer in situ imaging within not only three cell lines (MCF-7, HepG2, and L02 cells) with different expression levels of MUC1 and miRNA-21 but also cancer cells treated with different inhibitors. Moreover, the remarkable photothermal properties of Au NBPs@PDA resulted in the more efficient killing of cancer cells, demonstrating the great promise of the all-in-one nanoplatform for accurate diagnosis and tumor therapy.


Assuntos
Biomarcadores Tumorais/metabolismo , Imagem Molecular/métodos , Nanoestruturas/química , Fototerapia , Nanomedicina Teranóstica/métodos , Linhagem Celular Tumoral , Humanos
7.
Technol Cancer Res Treat ; 19: 1533033820964231, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33073702

RESUMO

In this study we aimed to identify a set of prognostic factors for angioimmunoblastic T-cell lymphoma (AITL) and establish a novel prognostic model. The clinical data of 64 AITL patients enrolled to the Fourth Hospital of Hebei Medical University (from 2012 Jan to 2017 May) were retrospectively analyzed. The estimated 5-year overall survival and progression-free survival of this cohort of patients were 45.8% and 30.8%, respectively. Univariate analysis showed that age > 60 years, performance status ≥2, Ann Arbor stage III/IV, lactate dehydrogenase > 250 U/L, serum albumin (ALB) < 30 g/l, Coombs test positive, and Ki-67 rate ≥ 70% were significantly associated with poor prognosis. Multivariate analysis demonstrated that age > 60 years, ALB < 30 g/l, Ki-67 rate ≥ 70%, and Coombs test positive were independent prognosis factors for AITL. Here a new prognostic model, named as AITLI, was constructed using the top 5 significant prognostic factors for AITL prognostic prediction. The AITL patients were stratified into 3 risk groups: low, intermediate, and high risk groups. The new prognostic model AITLI showed better performance in predicting prognosis than the International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT) that were wisely used to predict the outcome for patients with other subtypes of lymphoma.

8.
Chem Commun (Camb) ; 56(89): 13828-13831, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33079123

RESUMO

Based on the distinct fingerprint-like fluorescence responses generated by different electrostatic and hydrophobic interactions between three kinds of self-designed water-soluble aggregation-induced emission (AIE) fluorogens (AIEgens) and proteins, a fast responsive (10 min) and one-step "lighting up" fluorescent sensor array for rapid protein discrimination was developed.


Assuntos
Proteínas/química , Técnicas Biossensoriais , Fluorescência , Corantes Fluorescentes/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Solubilidade , Espectrometria de Fluorescência , Água
9.
EBioMedicine ; 54: 102731, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32304999

RESUMO

BACKGROUND: Blood-based biomarker such as circulating tumor DNA (ctDNA) has emerged as a promising tool for assessment of response to immunotherapy in solid tumors; But in hematological malignances, evidences are still lacking to support its clinical utility. In current study the feasibility of ctDNA for prediction and monitoring of response to anti-PD-1 therapy in Chinese patients with relapsed or refractory classical Hodgkin lymphoma (r/r cHL) was assessed. METHODS: A total of 192 plasma samples from 75 patients with r/r cHL were collected at baseline and upon therapeutic evaluation. ctDNA were sequenced by targeting panels capturing frequently mutated genes in cHL and other hematological malignancies and then quantified. Analysis on: 1) Gene mutation profile and association of the gene mutations with progression-free survival; 2) Association of pre- and post-treatment ctDNA variant allelic frequencies with clinical outcome; (3) Correlation of the mutated genes with treatment resistance; were performed. FINDINGS: Somatic mutations were detected in 50 out of 61 patients by ctDNA genotyping. The mutations of CHD8 was significantly higher in patients with PFS ≥ 12 months. Baseline ctDNA was significantly higher in responders and a decrease of ctDNA ≥ 40% from baseline indicated superior clinical outcome. Strong agreement between ctDNA dynamic and radiographic response change during therapy was observed in majority of the patients. Furthermore, the mutations of B2M, TNFRSF14 and KDM2B were found to be associated with acquired resistance. INTERPRETATION: ctDNA could be an informative biomarker for anti-PD-1 immunotherapy in r/r cHL. FUNDING: This work was supported by Innovent Biologics, Eli Lilly and Companyhttps://doi.org/10.13039/501100002852, China National New Drug Innovation Program (2014ZX09201041-001 and 2017ZX09304015), Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-001) and National Key Scientific Program Precision Medicine Research Fund of China (2017YFC0909801). The funders had no role in study design, data collection, data analysis, interpretation or writing.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Doença de Hodgkin/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Adulto , Idoso , Proteínas de Ligação a DNA/genética , Resistencia a Medicamentos Antineoplásicos , Proteínas F-Box/genética , Feminino , Doença de Hodgkin/sangue , Doença de Hodgkin/tratamento farmacológico , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Masculino , Pessoa de Meia-Idade , Mutação , Membro 14 de Receptores do Fator de Necrose Tumoral/genética , Fatores de Transcrição/genética , Microglobulina beta-2/genética
10.
Chem Commun (Camb) ; 56(29): 4074-4077, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32159543

RESUMO

In this study, three kinds of CDs with blue, yellow and red emissions were prepared and their luminescence mechanisms through theoretical calculations together with experimental data were further investigated in depth. Afterwards, a sensor array was constructed by using three kinds of CD-metal ions for rapid discrimination of different types of sulfur-containing species.

11.
ACS Appl Mater Interfaces ; 12(1): 373-379, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31840494

RESUMO

A simple and label-free sensing platform with low background based on the chain-displacement triggered self-assembly of Ag NCs was developed for ratiometric visual analysis of intracellular miRNA-21. Based on this sensitively ratiometric sensing approach, a picomole limit detection for miRNA-21 can be obtained. Most importantly, compared with the traditional single base mismatch detection method, our proposed method can realize single base mismatch detection according to the remarkable fluorescence color conversion, rather than simple fluorescence intensity change, which can obviously improve the accuracy and reliability. In addition, successful multicolor real-time monitoring of intracellular miRNA-21 makes the probe a potential candidate for miRNA-21 inhibiting drug screening. Furthermore, MCF-7, HeLa, and normal L02 cells can also be visually differentiated according to the fluorescence color by using the label-free sensing platform, showing its potential prospect in target visual analysis.


Assuntos
Nanopartículas Metálicas/química , Nanoestruturas/química , Ácidos Nucleicos/química , Prata/química , Técnicas Biossensoriais/métodos , Células HeLa , Humanos , Células MCF-7 , Nanopartículas Metálicas/ultraestrutura , Microscopia Eletrônica de Transmissão
12.
Lancet Haematol ; 6(1): e12-e19, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30612710

RESUMO

BACKGROUND: Sintilimab (Innovent Biologics, Suzhou, China), a highly selective, fully humanised, monoclonal antibody, blocks the interaction between PD-1 and its ligands. We aimed to assess the activity and safety profile of sintilimab in Chinese patients with relapsed or refractory classical Hodgkin lymphoma. METHODS: In this ongoing, single-arm, phase 2 study, we recruited patients with histopathologically diagnosed classical Hodgkin lymphoma that was relapsed or refractory after two or more lines of therapy from 18 hospitals in China. Patients were given intravenous sintilimab (200 mg, once every 3 weeks) until progression, death, unacceptable toxicity, or withdrawal of consent. The primary outcome was the proportion of patients in the full analysis set (ie, those with classical Hodgkin lymphoma confirmed by the central pathology laboratory) who had an objective response, as assessed by an independent radiological review committee (IRRC), by 24 weeks after enrolment of the last patient. Tumour response was assessed by enhanced CT scan or MRI at baseline, at weeks 6, 15, and 24, every 12 weeks from weeks 24 to 48, and every 16 weeks beyond week 48. Safety was assessed in all treated patients. This study is registered with ClinicalTrials.gov, number NCT03114683, and is ongoing. FINDINGS: Between April 19, 2017, and Nov 1, 2017, 96 patients were enrolled and commenced treatment. Four patients, whose diagnosis was not subsequently confirmed by the central pathology laboratory, were excluded from the full analysis set. Ten patients discontinued treatment. Median duration of follow-up was 10·5 months. In the full analysis set (n=92), 74 patients (80·4%; 95% CI 70·9-88·0) had an IRRC-assessed objective response before the analysis cutoff date of April 16, 2018. 89 (93%) of 96 patients had treatment-related adverse events, and 17 patients (18%) had grade 3 or 4 treatment-related adverse events, the most common being pyrexia (three [3%] patients). 14 (15%) patients had serious adverse events of any cause. No patient died during the study. INTERPRETATION: Sintilimab could be a new treatment option for patients with relapsed or refractory classical Hodgkin lymphoma in China. FUNDING: Innovent Biologics, Eli Lilly and Company, National New Drug Innovation Programme, and the National Key Scientific Programme Precision Medicine Research Fund of China.


Assuntos
Doença de Hodgkin/tratamento farmacológico , Rituximab/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Rituximab/farmacologia
13.
Cancer Sci ; 109(12): 3943-3952, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30302857

RESUMO

Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare subtype of DLBCL with limited data on patterns of failure. This multicenter study aimed to define the optimum treatment strategy and patterns of failure for PB-DLBCL patients. We retrospectively reviewed data on 108 PB-DLBCL patients from 21 Chinese medical centers. Only patients with localized disease (involvement of breast and localized lymph nodes) were included. After a median follow-up of 3.2 years, 32% of patients developed progression or relapse. A continuous pattern of relapse was observed, characterized by frequent late relapses in the contralateral breast and central nervous system (CNS). Although rituximab significantly reduced the overall cumulative risk of progression or relapse (5-year cumulative risk 57% vs 24%, P = .029), it had limited effect on the reduction of breast relapse (P = .46). Consolidative radiotherapy significantly decreased the risk of breast relapse, even in the subgroup of patients treated with rituximab (5-year cumulative risk 21.2% vs 0%, P = .012). A continuous risk of CNS progression or relapse up to 8.2 years from diagnosis was observed (10-year cumulative risk 28.3%), with a median time to CNS relapse of 3.1 years. Neither rituximab nor prophylactic intrathecal chemotherapy significantly decreased the risk of CNS relapse. In summary, our study indicates that PB-DLBCL has a continuous pattern of relapse, especially with frequent late relapses in the CNS and contralateral breast. Rituximab and RT confer complementary benefit in the reduction of relapse. However, neither the addition of rituximab nor prophylactic intrathecal chemotherapy could effectively prevent CNS relapse for PB-DLBCL patients.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Rituximab/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/radioterapia , Progressão da Doença , Feminino , Humanos , Linfoma Difuso de Grandes Células B/radioterapia , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
14.
BMC Cancer ; 18(1): 910, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30241515

RESUMO

BACKGROUND: The combination of chemotherapy and L-asparaginase (L-ASP) treatment significantly increased survival rate in an adult patient with extranodal natural killer (NK)/T-cell lymphoma (NKTCL). However, hypersensitivity reactions of L-ASP in some patients limited its application. Polyethylene glycol-conjugated asparaginase (PEG-ASP) has a lower immunogenicity and longer circulating half-life than unconjugated L-ASP, and has been reported to be effective and well-tolerated in children with acute lymphoblastic leukemia. Cyclophosphamide, hydroxydaunorubicin (doxorubicin), oncovin (vincristine), and prednisolone (CHOP) is the most common chemotherapy for non-Hodgkin lymphoma. In this report, we sought to study the efficacy and safety of PEG-L- CHOP in NKTCL in adult Chinese patients. METHODS: Our study is a prospective, multi-center, open-label clinical trial. Patients with newly diagnosed adult NKTCL and an ECOG performance status of 0 to 2 were eligible for enrollment. Treatment included six cycles of PEG-L-CHOP regimen. Radiotherapy was scheduled after 2-4 cycles of PEG-L-CHOP regimen, depending on the stage and primary anatomic site. RESULTS: We enrolled a total of 33 eligible patients. All 33 patients completed 170 cycles of chemotherapy combined with radical radiotherapy. The overall response rate was 96.9% (32/33) with 75.8% (25/33) achieving complete responses and 21.2% (7/33) achieving partial responses. The overall survival (OS) at 1, 2, 3-year were 100, 90.61 and 80.54%, respectively. The major adverse effects were bone marrow suppression, reduction of fibrinogen level, liver dysfunction, and digestive tract toxicities. No allergic reaction and no treatment-related mortality or severe complications were recorded. CONCLUSIONS: PEG-L-CHOP chemotherapy in combination radiotherapy is safe and durably effective treatment for adult extranodal NK/T-cell lymphoma with fewer allergic reactions. This study was approved by the Peking University Beijing Cancer Hospital Ethics Review Committee (reference number: 2011101104). The clinical trial registration number ChiCTR1800016940 was registered on July 07, 2018 at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/index.aspx ). The clinical trial was registered retrospectively.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Asparaginase/administração & dosagem , Biomarcadores , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Humanos , Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma Extranodal de Células T-NK/radioterapia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Polietilenoglicóis/administração & dosagem , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico
15.
Chin Med J (Engl) ; 131(15): 1767-1775, 2018 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-30058572

RESUMO

Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. Methods: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. Results: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. Conclusions: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment. Trial Registration: ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Rituximab/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , China , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Vincristina/administração & dosagem
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(4): 1053-1057, 2017 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-28823267

RESUMO

OBJECTIVE: To evaluate the correlation of single nucleotide polymorphisms (SNP) of Gemin 3(rs197412) in the miRNA biosynthesis with NHL cancer risk and overall prognosis. METHODS: miR-SNP were genotyped using PCR-ligase detection reaction(LAR, LCR) in NHL group of 230 non-Hodgkin lymphoma (NHL) patients and in control group of 120 healthy persons. The survival curves were drawn using the Kaplan-Meier method, and comparisons between the curves were made using the log-rank test. Multivariate survival analysis was performed by using a Cox proportional hazards model. RESULTS: The rs197412 genotype distribution difference was not statistically significant, in NHL and control group; the survival time of patients carrying the rs197412 TT genotype was significantly longer than that of the patients carrying the CC+CT genotype (P=0.007). In addition, rs197412 was independent from the survival of NHL patients by multivariate analysis (RR: 2.138,95% CI: 1.303-3.508, P<0.01). CONCLUSION: The single nucleotide polymorphisms of Gemin 3 (rs197412) in the miRNA processing are not related with NHL risk, but that may affect NHL survival.


Assuntos
Linfoma não Hodgkin , Polimorfismo de Nucleotídeo Único , Genótipo , Humanos , MicroRNAs , Prognóstico
17.
J Hematol Oncol ; 10(1): 69, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28298231

RESUMO

The efficacy and safety of chidamide, a new subtype-selective histone deacetylase (HDAC) inhibitor, have been demonstrated in a pivotal phase II clinical trial, and chidamide has been approved by the China Food and Drug Administration (CFDA) as a treatment for relapsed or refractory peripheral T cell lymphoma (PTCL). This study sought to further evaluate the real-world utilization of chidamide in 383 relapsed or refractory PTCL patients from April 2015 to February 2016 in mainland China. For patients receiving chidamide monotherapy (n = 256), the overall response rate (ORR) and disease control rate (DCR) were 39.06 and 64.45%, respectively. The ORR and DCR were 51.18 and 74.02%, respectively, for patients receiving chidamide combined with chemotherapy (n = 127). For patients receiving chidamide monotherapy and chidamide combined with chemotherapy, the median progression-free survival (PFS) was 129 (95% CI 82 to 194) days for the monotherapy group and 152 (95% CI 93 to 201) days for the combined therapy group (P = 0.3266). Most adverse events (AEs) were of grade 1 to 2. AEs of grade 3 or higher that occurred in ≥5% of patients receiving chidamide monotherapy included thrombocytopenia (10.2%) and neutropenia (6.2%). For patients receiving chidamide combined with chemotherapy, grade 3 to 4 AEs that occurred in ≥5% of patients included thrombocytopenia (18.1%), neutropenia (12.6%), anemia (7.1%), and fatigue (5.5%). This large real-world study demonstrates that chidamide has a favorable efficacy and an acceptable safety profile for refractory and relapsed PTCL patients. Chidamide combined with chemotherapy may be a new treatment choice for refractory and relapsed PTCL patients but requires further investigation.


Assuntos
Aminopiridinas/administração & dosagem , Benzamidas/administração & dosagem , Linfoma de Células T Periférico/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminopiridinas/efeitos adversos , Aminopiridinas/uso terapêutico , Anemia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzamidas/efeitos adversos , Benzamidas/uso terapêutico , China , Intervalo Livre de Doença , Fadiga/induzido quimicamente , Feminino , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Linfoma de Células T Periférico/complicações , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Recidiva , Indução de Remissão/métodos , Terapia de Salvação/efeitos adversos , Terapia de Salvação/métodos , Trombocitopenia/induzido quimicamente , Adulto Jovem
18.
BMC Cancer ; 16: 537, 2016 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-27460571

RESUMO

BACKGROUND: The efficacy and safety of rituximab-based chemotherapy (R-chemo), the standard regimen for patients with diffuse large B-cell lymphoma (DLBCL), which is more common in Asia than in Western countries, are well confirmed in randomized controlled trials (RCTs). However, the safety and effectiveness of R-chemo in patients who are largely excluded from RCTs have not been well characterized. This real-world study investigated the safety and effectiveness of R-chemo as first-line treatment in Chinese patients with DLBCL. METHODS: Treatment-naive DLBCL patients who were CD20 positive and eligible to receive R-chemo were enrolled with no specific exclusion criteria. Data collected at baseline included age, gender, disease stage, international prognostic index (IPI), B symptoms, extranodal involvement, performance status, and medical history. In the present study, data on safety, treatment effectiveness, and HBV infection management were collected 120 days after the last R-chemo administration. RESULTS: Overall, R-chemo was well tolerated. The safety profile of R-chemo in patients with a history of heart or liver disease was well described without any additional unexpected safety concerns. The overall response rate (ORR) in the Chinese patients from this study was 94.2 % (complete response [CR], 55.0 %; CR unconfirmed [CRu] 18.2 %; and partial response [PR], 20.9 %). Compared to patients with no history of disease, the CR and PR rates of patients with a history of heart or liver disease were lower and higher, respectively; this tendency could be in part explained by treatment interruptions in patients with heart or liver diseases. HBsAg positivity and a maximum tumor diameter of ≥7.5 cm negatively correlated with CR + CRu, whereas age and HBsAg positivity negatively correlated with CR. CONCLUSIONS: This study further validated the safety and effectiveness of R-chemo in Chinese patients with DLBCL. Patients with a history of heart or liver disease may further benefit from R-chemo if preventive measures are taken to reduce hepatic and cardiovascular toxicity. In addition to IPI and tumor diameter, HBsAg positivity could also be a poor prognostic factor for CR in Chinese patients with DLBCL. TRIAL REGISTRATION: ClinicalTrials.gov # NCT01340443 , April 20, 2011.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Ensaios Clínicos Pragmáticos como Assunto , Rituximab/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD20/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , China/epidemiologia , Intervalo Livre de Doença , Cardiopatias/complicações , Antígenos de Superfície da Hepatite B/sangue , Humanos , Hepatopatias/complicações , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/mortalidade , Pessoa de Meia-Idade , Estudos Prospectivos , Rituximab/efeitos adversos , Resultado do Tratamento , Adulto Jovem
19.
Biosci Biotechnol Biochem ; 80(10): 1883-6, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27296359

RESUMO

The inhibitory effect of 13 taxanes isolated from the Chinese yew (Taxus chinensis var. mairei) on the proliferation of human cervical cancer HeLa cells were examined using an MTT assay. Four compounds having a hydrophobic cinnamate side chain showed antiproliferative activity, which may be due to increased cell permeability.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Hidrocarbonetos Aromáticos com Pontes/química , Diterpenos/química , Diterpenos/farmacologia , Taxoides/química , Taxus/química , Neoplasias do Colo do Útero/patologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Interações Hidrofóbicas e Hidrofílicas
20.
Onco Targets Ther ; 8: 1735-41, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26203264

RESUMO

OBJECTIVE: microRNA (miRNA)-related single nucleotide polymorphisms (miR-SNPs) in miRNA-processing machinery genes can affect cancer risk, treatment efficacy, and patients' prognosis by mediating the expression of targeted genes. Five miR-SNPs in miRNA processing machinery genes, including XPO5 (rs11077), RAN (rs14035), TNRC6B (rs9623117), GEMIN3 (rs197412), and GEMIN4 (rs2740348), in 168 non-Hodgkin's lymphoma (NHL) patients were evaluated for their association with the cancer risk and outcomes associated with NHL. MATERIALS AND METHODS: miR-SNPs were genotyped using polymerase chain reaction-ligase detection reaction. The survival curves were calculated using the Kaplan-Meier method, and comparisons between the curves were made using the log-rank test. Multivariate survival analysis was performed using a Cox proportional hazards model. RESULTS: Among the five SNPs, only rs197412 located in the coding region of the GEMIN3 gene was identified; it was independently associated with overall survival in NHL patients, as determined by multivariate analysis (relative risk: 1.649; 95% confidence interval: 1.110-2.449; P=0.013). The prognostic value of this miR-SNP in patient outcomes was also observed in the diffuse large B-cell lymphoma and T-cell lymphoma NHL subtypes. CONCLUSION: Our results suggested that the specific genetic variants observed in the miRNA machinery genes may affect NHL survival.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...