Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.049
Filtrar
1.
Rinsho Ketsueki ; 60(8): 929-931, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31484892

RESUMO

A 51-year-old man was diagnosed with stage IV mantle cell lymphoma based on terminal ileum biopsy and treated with the R-CHOP regimen. Abdominal CT to assess continuous fever after three courses of R-CHOP revealed three low-density areas in the liver. PCR of the fluid obtained by percutaneous drainage revealed Entamoeba histolytica positivity, although the cultures were negative. Metronidazole treatment achieved cure. The patient was not a homosexual but had an 8-month stay in Lesotho 21 years ago, leading to the possibility that E. histolytica infection at the time continued as an asymptomatic colonization until the initiation of corticosteroid-containing chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Entamoeba histolytica , Abscesso Hepático Amebiano , Linfoma de Célula do Manto , Anticorpos Monoclonais Murinos/efeitos adversos , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Humanos , Abscesso Hepático Amebiano/induzido quimicamente , Linfoma de Célula do Manto/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prednisona/efeitos adversos , Rituximab , Vincristina/efeitos adversos
2.
BMC Cancer ; 19(1): 693, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307410

RESUMO

BACKGROUND: To evaluate the safety and efficacy of intra-arterial chemotherapy (IAC) for the primary or secondary treatment of infants diagnosed with advanced retinoblastoma before 3 months of age. METHODS: This single-center retrospective study included 39 infants (42 eyes) aged ≤3 months who were diagnosed with unilateral or bilateral advanced intraocular retinoblastoma (group D and E eyes) and received IAC as primary or secondary treatment between June 2012 and February 2017. Based on each patient's therapeutic history and response to chemotherapeutic drugs, melphalan, topotecan, and/or carboplatin were used for IAC. The main outcomes included the technical success rate for IAC, survival rates, and adverse events. RESULTS: In total, 29 and 13 eyes received IAC as primary and secondary treatments, respectively. Catheterization was successful in 136 of 137 procedures. All eyes in the secondary IAC group had previously received intravenous chemotherapy. The mean number of IAC sessions for each eye was 3 (range, 2-6). The 2-year ocular survival rates were 80.7% (95% confidence interval [CI], 58.9-91.7) in the primary IAC group and 91.7% (95% CI, 53.9-98.8) in the secondary IAC group. During the follow-up period, 1 patient with unilateral disease (group E) developed extraocular disease and died. The 2-year recurrence-free survival rates in the primary and secondary IAC groups were 71.9% (95% CI, 49.4-85.7) and 75.0% (95% CI, 40.8-91.2), respectively. During each catheterization procedure, the main complications included eyelid erythema (2.4%), fundus hemorrhage (11.9%), myelosuppression (7.7%), transient vomiting and hair loss (2.6%), and transient pancytopenia (2.6%). Prolonged complications included phthisis bulbi (19.0%), vision loss (19.0%), poor vision (9.5%), and cataract (2.4%). There was no case of stroke, neurological impairment, secondary malignant tumor, or metastasis. CONCLUSIONS: Our findings suggest that IAC, whether primary or secondary, is effective and fairly safe for the management of advanced retinoblastoma in infants aged < 3 months. However, adverse events related to intra-arterial injection and the visual outcomes cannot be neglected and require further investigation.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Carboplatina/uso terapêutico , Etoposídeo/uso terapêutico , Infusões Intra-Arteriais/efeitos adversos , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Vincristina/uso terapêutico , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/efeitos adversos , Cateterismo/efeitos adversos , Pré-Escolar , Etoposídeo/efeitos adversos , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias da Retina/mortalidade , Retinoblastoma/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/efeitos adversos
3.
J Clin Pathol ; 72(9): 630-635, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31189540

RESUMO

AIMS: Heightened B-cell receptor (BCR) activity in diffuse large B-cell lymphoma (DLBCL) is well established, and a subset of patients with relapsed DLBCL can benefit from BCR-targeted therapies. Universal outreach of such emerging therapies mandates forming a global landscape of BCR molecular signalling in DLBCL, including Southeast Asia. METHODS: 79 patients with DLBCL (nodal, 59% and extranodal, 41%) treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy were selected. Expression levels of BCR and linked signalling pathway molecules were inter-related with Lymph2Cx-based cell of origin (COO) types and overall survival (OS). RESULTS: Activated B-cell (ABC) type DLBCL constituted 49% (39/79) compared with germinal centre B-cell (GCB) type DLBCL (29/79; 37%) and revealed poor prognosis (p=0.013). In ABC-DLBCL, high BTK expression exerted poor response to R-CHOP, while OS in ABC-DLBCL with low BTK expression was similar to GCB-DLBCL subtype (p=0.004). High LYN expression coupled with a poor OS for ABC-DLBCL as well as GCB-DLBCL subtypes (p=0.001). Furthermore, high coexpression of BTK/LYN (BTK high/LYN high) showed poor OS (p=0.019), which linked with upregulation of several genes associated with BCR repertoire and nuclear factor-kappa B pathway (p<0.01). In multivariate analysis, high BTK and LYN expression retained prognostic significance against established clinical predictive factors such as age, International Prognostic Index and COO (p<0.05). CONCLUSIONS: Our data provide a clear association between high BCR activity in DLBCL and response to therapy in a distinct population. Molecular data provided here will pave the pathway for the provision of promising novel-targeted therapies to patients with DLBCL in Southeast Asia.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Medicina de Precisão/métodos , Receptores de Antígenos de Linfócitos B/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores Tumorais/imunologia , Tomada de Decisão Clínica , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/etnologia , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Prevalência , Receptores de Antígenos de Linfócitos B/imunologia , Sistema de Registros , Rituximab , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico
4.
Int J Pediatr Otorhinolaryngol ; 123: 1-4, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31048222

RESUMO

OBJECTIVES: To describe three new cases of vincristine-induced vocal cord paresis or paralysis (VIVCPP) in children and to review the diagnosis and management of this neuropathy. METHODS: Retrospective case series. Diagnosis of VIVCPP was confirmed by laryngoscopy in all children. RESULTS: Less than 20 cases of VIVCPP in children have been previously documented in the literature. Of the three children in our case series, one had unilateral vincristine-induced vocal cord paresis and two had bilateral VIVCPP. The first two patients each had two separate episodes of paresis, lasting 4 months and 1 month respectively. In the last patient, whose medical course was complicated by many additional factors, vocal cord paralysis persisted for over three years. CONCLUSIONS: Clinicians must evaluate children with suspected VIVCPP for concomitant symptoms and signs of vincristine neuropathies and examine the vocal cords via laryngoscopy. The effects of vincristine neurotoxicity can be waxing and waning, demonstrate delayed onset and persist well beyond drug cessation. Further studies are needed to identify effective neuroprotectants and delineate appropriate vincristine dosing in patients with vincristine neurotoxicity and cancer.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Vincristina/efeitos adversos , Paralisia das Pregas Vocais/induzido quimicamente , Adolescente , Pré-Escolar , Feminino , Humanos , Laringoscopia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estudos Retrospectivos , Paralisia das Pregas Vocais/diagnóstico por imagem , Prega Vocal/diagnóstico por imagem
5.
BMC Cancer ; 19(1): 471, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31109313

RESUMO

BACKGROUND: Transformation of chronic lymphocytic leukaemia (CLL) to diffuse large B-cell lymphoma (DLCBL) type Richter's syndrome (RS) carries a dismal prognosis. Standard-of-care chemoimmunotherapy for de novo RS is inadequate with median survival of less than one year. Patients are frequently elderly or have co-morbidities limiting dose-intense chemotherapy. Treatment of relapsed/refractory (R/R) RS and RS emerging after CLL-directed therapy represent urgent unmet clinical needs. Agents targeting Bruton's tyrosine kinase (BTK) deliver improved outcomes for patients with high-risk CLL and expand effective treatments to frailer patients. Acalabrutinib is an oral, second-generation BTK inhibitor with a favourable toxicity profile and demonstrated activity in CLL and B-cell lymphomas. Combination of acalabrutinib with standard-of-care CHOP-R chemoimmunotherapy offers a sound rationale to test in a prospective trial for de novo RS. METHODS: The prospective multicentre STELLAR study is designed in two elements, consisting of a randomised study to evaluate the safety and activity of CHOP-R chemoimmunotherapy in combination with acalabrutinib in newly diagnosed RS and single-arm studies of novel agents for other RS patient cohorts. Eligible patients with newly diagnosed DLBCL-type RS are randomised between six cycles of CHOP-R therapy and six cycles CHOP-R plus acalabrutinib, followed by acalabrutinib maintenance. The primary endpoint of the randomised component is progression free survival (PFS). Cohort 1 enrols RS patients with progressive disease following chemoimmunotherapy for acalabrutinib monotherapy. Patients with RS diagnosed while on ibrutinib may enrol in Cohort 2, a single-arm study of CHOP-R plus acalabrutinib. The primary endpoint for the single-arm studies is overall response rate (ORR). Secondary endpoints for all cohorts are overall survival (OS), quality of life and proportion of patients proceeding to stem cell transplantation. The study will be accompanied by exploratory analysis of the mutational landscape of RS and the relationship between dynamic changes in sequential circulating tumour DNA samples and clinical outcomes. DISCUSSION: The STELLAR randomised trial evaluates the role of CHOP-R plus acalabrutinib in newly diagnosed RS patients. The single-arm platform studies enable the incorporation of promising novel therapies into the protocol. The STELLAR study has potential to identify novel biomarkers of treatment response in this high-risk malignancy. TRIAL REGISTRATION: EudraCT: 2017-004401-40 , registered on the 31-Oct-2017. IRSCTN: https://www.isrctn.com/ISRCTN52839057 , registered on the 04-Mar-2019. ClinicalTrials.gov : NCT03899337 , registered on 02-April-2019.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Benzamidas/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Pirazinas/administração & dosagem , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzamidas/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Estudos Prospectivos , Pirazinas/efeitos adversos , Recidiva , Projetos de Pesquisa , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Adulto Jovem
6.
Blood ; 134(3): 252-262, 2019 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-31118164

RESUMO

Patients with primary central nervous system lymphoma (PCNSL) are treated with high-dose methotrexate-based chemotherapy, which requires hospitalization and extensive expertise to manage related toxicity. The use of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) could overcome these difficulties, but blood-brain barrier (BBB) penetration of related drugs is poor. Tumor necrosis factor-α coupled with NGR (NGR-hTNF), a peptide targeting CD13+ vessels, induces endothelial permeabilization and improves tumor access of cytostatics. We tested the hypothesis that NGR-hTNF can break the BBB, thereby improving penetration and activity of R-CHOP in patients with relapsed/refractory PCNSL (NCT03536039). Patients received six R-CHOP21 courses, alone at the first course and preceded by NGR-hTNF (0.8 µg/m2) afterward. This trial included 2 phases: an "explorative phase" addressing the effect of NGR-hTNF on drug pharmacokinetic parameters and on vessel permeability, assessed by dynamic contrast-enhanced magnetic resonance imaging and 99mTc-diethylene-triamine-pentacetic acid-single-photon emission computed tomography, and the expression of CD13 on tumor tissue; and an "expansion phase" with overall response rate as the primary end point, in which the 2-stage Simon Minimax design was used. At the first stage, if ≥4 responses were observed among 12 patients, the study accrual would have continued (sample size, 28). Herein, we report results of the explorative phase and the first-stage analysis (n = 12). CD13 was expressed in tumor vessels of all cases. NGR-hTNF selectively increased vascular permeability in tumoral/peritumoral areas, without interfering with drug plasma/cerebrospinal fluid concentrations. The NGR-hTNF/R-CHOP combination was well tolerated: there were only 2 serious adverse events, and grade 4 toxicity was almost exclusively hematological, which were resolved without dose reductions or interruptions. NGR-hTNF/R-CHOP was active, with 9 confirmed responses (75%; 95% confidence interval, 51-99), 8 of which were complete. In conclusion, NGR-hTNF/R-CHOP was safe in these heavily pretreated patients. NGR-hTNF enhanced vascular permeability specifically in tumoral/peritumoral areas, which resulted in fast and sustained responses.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Barreira Hematoencefálica/efeitos dos fármacos , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Proteínas Recombinantes de Fusão/farmacocinética , Fator de Necrose Tumoral alfa/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores , Barreira Hematoencefálica/diagnóstico por imagem , Antígenos CD13/metabolismo , Permeabilidade da Membrana Celular , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/metabolismo , Neoplasias do Sistema Nervoso Central/mortalidade , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Imuno-Histoquímica , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/metabolismo , Linfoma não Hodgkin/mortalidade , Masculino , Neuroimagem/métodos , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Proteínas Recombinantes de Fusão/administração & dosagem , Projetos de Pesquisa , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Tomografia Computadorizada de Emissão de Fóton Único , Resultado do Tratamento , Fator de Necrose Tumoral alfa/administração & dosagem , Vincristina/efeitos adversos , Vincristina/uso terapêutico
7.
Oncol Res Treat ; 42(7-8): 375-381, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31132772

RESUMO

BACKGROUND: It is known that chemotherapeutic agents cause myocardial cell damage leading to left ventricular dysfunction and heart failure. Fragmented QRS is an indication of fibrosis developing as a result of myocardial cell damage. The aim of this study is to assess whether there is a relationship between the chemotherapeutic treatment and the development of the fragmented QRS complex in electrocardiography (ECG). PATIENTS AND METHODS: Among 130 patients who were diagnosed with non-Hodgkin lymphoma and received an R-CHOP treatment regimen, the potential emergence of fragmented QRS on ECG as well as the changes in the left ventricular ejection fraction (LVEF) (on transthoracic echocardiography) in response to various chemotherapeutic regimens were sought. RESULTS: New development of a fragmented QRS pattern was observed in 53 of the 130 patients (40.8%). These patients were found to have lower LVEF values along with higher numbers of chemotherapy courses and cumulative doses. In the logistic regression analysis, age (OR = 1.042; 95% CI 1.009-1.076; p = 0.012) and number of courses (OR = 1.848; 95% CI 1.409-2.423; p < 0.001) were found to be the most important predictors of fragmented QRS development. In subjects with a fragmented QRS pattern, there was a significant difference between the initial and repeat LVEF values (p < 0.001). Importantly the emergence of a fragmentation pattern occurred much earlier compared to the drop in LVEF values (10.62 ± 4.04 vs. 15.24 ± 7.49 months). CONCLUSION: Development of a fragmented QRS pattern in response to cancer therapy emerges as a new parameter potentially predictive of chemotherapy-induced cardiotoxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cardiotoxicidade/diagnóstico por imagem , Linfoma não Hodgkin/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Eletrocardiografia , Feminino , Humanos , Modelos Logísticos , Linfoma não Hodgkin/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prednisona/efeitos adversos , Estudos Retrospectivos , Rituximab/efeitos adversos , Função Ventricular Esquerda , Vincristina/efeitos adversos
8.
Acta Oncol ; 58(8): 1170-1177, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31131659

RESUMO

Background: Patients with certain autoimmune diseases (AID) have an increased risk of developing diffuse large B-cell lymphoma (DLBCL). However, the occurrence of AID in patients with DLBCL as well as the impact of AID on outcome has not been extensively studied. The main purpose of this study was to establish the occurrence of AIDs in a population-based cohort of DLBCL patients and to compare outcomes in patients with or without AID treated with rituximab(R)-CHOP/CHOP-like treatment. We also aimed to analyse gender differences and the potential role of different AIDs on outcome and the frequency of treatment-associated neutropenic fever. Patients and methods: All adult patients treated 2000-2013 with R-CHOP/CHOP-like treatment for DLBCL in four counties of Sweden were included (n = 612). Lymphoma characteristics, outcome and the presence of AID were obtained through medical records. Results: The number of patients with AID was 106 (17.3%). Thyroid disease dominated (n = 33, 31.1%) followed by rheumatoid arthritis (RA) (n = 24, 22.6%). The proportion of AID was significantly higher in females (59/254, 23.2%) vs. in males (47/358, 13.1%) (p = .001). In the whole cohort there was no difference in event free survival (EFS) or overall survival (OS) between patients with or without AID. However, patients with an AID primarily mediated by B-cell responses (thyroid disorders excluded) had a worse OS (p = .037), which seemed to affect only women. The AID group more often had neutropenic fever after first treatment (16.0% vs 8.7%, p = .034) and those with neutropenic fever had a worse OS (p = .026) in Kaplan-Meier analyses. Conclusion: There is a high prevalence of AID among patients with DLBCL. AIDs categorized as primarily B-cell mediated (in this study mainly RA, systemic lupus erythematosus and Sjögren's syndrome) may be associated with inferior OS. AID patients may be more prone to neutropenic fever compared to patients without concomitant AID.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doenças Autoimunes/epidemiologia , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Linfoma Difuso de Grandes Células B/complicações , Rituximab/administração & dosagem , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doenças Autoimunes/etiologia , Linfócitos B/imunologia , Neutropenia Febril Induzida por Quimioterapia/etiologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Prevalência , Estudos Retrospectivos , Rituximab/efeitos adversos , Fatores Sexuais , Análise de Sobrevida , Suécia/epidemiologia , Linfócitos T/imunologia , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Adulto Jovem
11.
Cell Mol Neurobiol ; 39(6): 799-808, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31011938

RESUMO

Vincristine is a toxic chemotherapeutic agent which often triggers neuropathic pain through inflammation. Morin isolated from figs (Ficus carica) exerts anti-inflammatory and neuroprotective activities. We investigated whether morin ameliorates vincristine-induced neuropathic pain and the underlying mechanism. Vincristine was injected i.p. for 10 days (day 1-5 and day 8-12). Morin was orally administered every other day from day 1 to 21. The pain behaviors were determined by measuring paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). The axons of sciatic nerves were stained with toluidine blue to study the histological abnormality. Function deficit of sciatic nerves was evaluated by sciatic functional index and the sciatic nerve conduction velocity. Neuronal excitability was assessed electrophysiologically and inflammatory mediators were detected using western blotting in dorsal root ganglia. The vincristine-induced reduction in PWT, PWL, and body weight gain was attenuated by morin. Morin restored the sciatic nerve deficits both histologically and functionally in vincristine-injected rats. The vincristine-induced neuronal hyperexcitability and increase in the expression of IL-6, NF-κB, and pNF-κB were abolished after morin administration. This study suggests that morin treatment suppressed vincristine-induced neuropathic pain by protecting the sciatic nerve and inhibiting inflammation through NF-κB pathway.


Assuntos
Flavonoides/uso terapêutico , NF-kappa B/metabolismo , Neuralgia/induzido quimicamente , Neuralgia/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Nervo Isquiático/patologia , Transdução de Sinais , Vincristina/efeitos adversos , Animais , Flavonoides/farmacologia , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/patologia , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Masculino , Fármacos Neuroprotetores/farmacologia , Ratos Sprague-Dawley , Nervo Isquiático/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
13.
Int J Cancer ; 145(9): 2459-2467, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30973963

RESUMO

Erythropoiesis-stimulating agents (ESAs), such as erythropoietin (EPO) and darbepoetin, may alleviate anemia in diffuse large B-cell lymphoma (DLBCL) patients. However, many cancer cells express EPO receptors (EPOR), through which exogenously administered ESAs potentially promote cancer cell growth. We conducted preclinical/phase II studies to investigate the safety and efficacy of ESAs for managing chemotherapy-related anemia in DLBCL patients. We examined EPOR expression in germinal center B-cell (GCB)- and activated B-cell (ABC)-DLBCL cell lines, and investigated the effects of ESAs on cell proliferation, and rituximab-mediated complement-dependent cytotoxicity (CDC). The clinical study enrolled 50 histologically confirmed DLBCL patients receiving rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone (R-CHOP) who had hemoglobin levels <10.0 g/dl after a maximum of three R-CHOP cycles and received ≥4 doses of fixed-dose darbepoetin (360 µg) once every 3 weeks. EPOR mRNA was detected in all GCB-DLBCL cell lines, but little/none was detected in ABC-DLBCL cell lines. GCB-DLBCL and ABC-DLBCL cell proliferation was unaffected by EPO or darbepoetin. Rituximab-mediated CDC of DLBCL cell lines with/without EPOR expression was not affected adversely by EPO. In the clinical study, baseline mean hemoglobin was 9.19 g/dl; the overall mean change in hemoglobin was 1.59 ± 1.3 g/dl (16 weeks). Forty-eight percent of enrolled patients achieved a hematopoietic response. Our study shows that ESAs do not affect the growth of DLBCL cells or rituximab-mediated CDC under the experimental conditions that we used, and the appropriate use of ESAs may be effective and safe for DLBCL patients with anemia after R-CHOP.


Assuntos
Anemia/induzido quimicamente , Anemia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Hematínicos/farmacologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Idoso , Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Linhagem Celular Tumoral , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Centro Germinativo/efeitos dos fármacos , Centro Germinativo/metabolismo , Hemoglobinas/metabolismo , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Masculino , Pessoa de Meia-Idade , Prednisolona/efeitos adversos , Prednisolona/uso terapêutico , Estudos Prospectivos , Rituximab/uso terapêutico , Vincristina/efeitos adversos , Vincristina/uso terapêutico
14.
Neurosci Lett ; 705: 14-19, 2019 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-30936034

RESUMO

Loss of the sense of touch or numbness in fingertips and toes is one of the earliest sensory dysfunctions in patients receiving chemotherapy with anti-cancer drugs such as vincristine. However, mechanisms underlying this chemotherapy-induced sensory dysfunction is poorly understood. Whisker hair follicles are tactile organs in non-primate mammals which are functionally equivalent to human fingertips. Here we used mouse whisker hair follicles as a model system to explore how vincristine treatment induces the loss of the sense of touch. We show that chronic treatment of mice with vincristine impaired in vivo whisker tactile behavioral responses. In vitro electrophysiological recordings made from whisker hair follicle afferent nerves showed that mechanically evoked whisker afferent impulses were significantly reduced following vincristine treatment. Furthermore, patch-clamp recordings from Merkel cells of whisker hair follicles revealed a significant reduction of mechanically activated currents via Piezo2 channels in Merkel cells. Collectively, our results suggest that Piezo2 channel dysfunction in Merkel cells contribute to the loss of the sense of touch following the chemotherapy treatment regimen with vincristine.


Assuntos
Folículo Piloso/efeitos dos fármacos , Canais Iônicos/metabolismo , Células de Merkel/efeitos dos fármacos , Tato/efeitos dos fármacos , Vincristina/efeitos adversos , Animais , Folículo Piloso/fisiologia , Técnicas In Vitro , Células de Merkel/fisiologia , Camundongos , Tato/fisiologia , Vibrissas/fisiologia
15.
J Toxicol Sci ; 44(4): 273-282, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30944280

RESUMO

Previously, we reported that the frequency of micronucleated reticulocytes (MNRETs) in the peripheral blood of male C3H/He mice intraperitoneally administered ethylnitrosourea (ENU) (25 mg/kg body weight) in the dark period (zeitgeber time, ZT15) was higher than in the light period (ZT3). In this study, to clarify the mechanism underlying this phenomenon, we investigated the differences in micronucleus (MN) induction observed between ZT3 and ZT15 using five chemicals, methylnitrosourea (MNU), ethylmethane sulfonate (EMS), mitomycin C, cyclophosphamide and vincristin. MNU and EMS, monofunctional alkylating agents, showed higher frequencies of MNRETs in the ZT15 than the ZT3 treatment similar to ENU. However, no differences were observed for the other chemicals. In the comet assay, more DNA damage was induced by ENU in the ZT15 than the ZT3 treatment. Furthermore, the plasma erythropoietin (EPO) level, a known effector of MN induction with anti-apoptotic activity mediated by Bcl-xL expression, was higher in the dark than in the light period. EPO did not increase the frequency of MNRETs. However, in the ENU treatment group at ZT3 following EPO injection a significant increase of MNRETs was observed similar to the ZT15 treatment. Higher expression of apoptosis-related genes such as Bcl-xL was induced in bone marrow cells from mice treated with ENU at ZT15 compared with ZT3. From these results, it was speculated that the differences in MN induction in the peripheral blood of mice exposed to monofunctional alkylating agents such as ENU depend on apoptotic or anti-apoptotic conditions related to the circadian rhythms of EPO in bone marrow.


Assuntos
Administração Metronômica , Alquilantes/administração & dosagem , Alquilantes/efeitos adversos , Nucléolo Celular/efeitos dos fármacos , Nucléolo Celular/patologia , Ritmo Circadiano/fisiologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/farmacologia , Eritropoetina/fisiologia , Metanossulfonato de Etila/farmacologia , Metilnitrosoureia/administração & dosagem , Metilnitrosoureia/efeitos adversos , Mitomicina/administração & dosagem , Mitomicina/efeitos adversos , Reticulócitos/citologia , Reticulócitos/efeitos dos fármacos , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/patologia , Nucléolo Celular/genética , Dano ao DNA/efeitos dos fármacos , Escuridão , Eritropoetina/metabolismo , Eritropoetina/farmacologia , Metanossulfonato de Etila/administração & dosagem , Luz , Masculino , Camundongos Endogâmicos C3H , Tempo , Proteína bcl-X/metabolismo
17.
Eur J Haematol ; 102(6): 457-464, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30834564

RESUMO

PURPOSE: Sinonasal tract diffuse large B-cell lymphoma (SNT-DLBCL), a rare extranodal lymphoma, is not well characterized. We performed a population-based study to determine cell-of-origin, clinical presentation and impact of rituximab (R) and central nervous system (CNS) directed chemotherapy on survival. PATIENTS AND METHODS: Patients with SNT-DLBCL were identified from pathology databases. Clinical information was collected and outcomes between different treatment modalities evaluated. RESULTS: Thirty-two percent of the patients had germinal centre B-cell phenotype. Forty-six patients were treated with curative intent using CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CHOP-like chemotherapy, 21 (46%) before and 25 (54%) in the R-era. Additionally, 24 (52%) received CNS-directed chemotherapy. Addition of R to chemotherapy reduced the risk of progression (RR = 0.368, 95% CI 0.138-0.976, P = 0.045) and death (RR = 0.245, 95% CI 0.068-0.883, P = 0.032), and translated into better survival (5-year PFS, 67% vs 38%, P = 0.037; 5-year OS, 81% vs 48%, P = 0.020). CNS-directed chemotherapy reduced the risk of progression (RR = 0.404, 95% CI 0.159-1.029, P = 0.057) and death (RR = 0.298, 95% CI 0.093-0.950, P = 0.041), and translated into favorable survival (5-year PFS, 67% vs 32%, P = 0.050; 5-year OS 82% vs 43%, P = 0.030). CONCLUSION: Patients with SNT-DLBCL benefit from rituximab and CNS-directed chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Neoplasias Nasais/diagnóstico , Neoplasias Nasais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Progressão da Doença , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Nasais/mortalidade , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Prognóstico , Modelos de Riscos Proporcionais , Avaliação de Sintomas , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico
18.
J Clin Pathol ; 72(4): 316-321, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30755497

RESUMO

AIMS: Oxidative stress markers and antioxidant enzymes have previously been shown to have prognostic value and associate with adverse outcome in patients with diffuse large B cell lymphoma (DLBCL). Nuclear factor erythroid 2-related factor 1 (Nrf1) and factor 2 (Nrf2) are among the principal inducers of antioxidant enzyme production. Kelch ECH associating protein 1 (Keap1) is a negative regulator of Nrf2, and BTB (BR-C, ttk and bab) domain and CNC homolog 1 (Bach1) represses the function of both factors. Their significance in DLBCL prognosis is unknown. METHODS: Diagnostic biopsy samples of 76 patients with high-risk DLBCL were retrospectively stained with immunohistochemistry for Nrf1, Nrf2, Keap1 and Bach1, and correlated with clinical data and outcome. RESULTS: Nuclear Nrf2 and nuclear Bach1 expression were associated with adverse clinical features (anaemia, advanced stage, high IPI, high risk of neutropaenic infections), whereas cytoplasmic Nrf1 and Nrf2 were associated with favourable clinical presentation (normal haemoglobin level, no B symptoms, limited stage). None of the evaluated factors could predict survival alone. However, when two of the following parameters were combined: high nuclear score of Nrf2, low nuclear score of Nrf1, high cytoplasmic score of Nrf1 and low cytoplasmic score of Keap1 were associated with significantly worse overall survival. CONCLUSIONS: Nrf1 and Nrf2 are relevant in disease presentation and overall survival in high-risk DLBCL. Low nuclear expression of Nrf1, high cytoplasmic expression of Nrf1, high nuclear expression of Nrf2 and low cytoplasmic expression of Keap1 are associated with adverse outcome in this patient group.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/análise , Linfoma Difuso de Grandes Células B/química , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Fator 1 Relacionado a NF-E2/análise , Fator 2 Relacionado a NF-E2/análise , Rituximab/administração & dosagem , Adulto , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fatores de Transcrição de Zíper de Leucina Básica/análise , Núcleo Celular/química , Núcleo Celular/patologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citoplasma/química , Citoplasma/patologia , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Imuno-Histoquímica , Proteína 1 Associada a ECH Semelhante a Kelch/análise , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Rituximab/efeitos adversos , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Adulto Jovem
19.
Nephrology (Carlton) ; 24(2): 272, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30697886

Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Ósseas , Neutropenia Febril Induzida por Quimioterapia , Glomerulonefrite por IGA/complicações , Falência Renal Crônica , Neoplasias Renais , Transplante de Rim , Linfoma Difuso de Grandes Células B , Complicações Pós-Operatórias , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Neutropenia Febril Induzida por Quimioterapia/diagnóstico , Neutropenia Febril Induzida por Quimioterapia/tratamento farmacológico , Neutropenia Febril Induzida por Quimioterapia/etiologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Evolução Fatal , Humanos , Imunossupressão/métodos , Rim/diagnóstico por imagem , Falência Renal Crônica/etiologia , Falência Renal Crônica/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/fisiopatologia , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/fisiopatologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Reoperação/métodos , Rituximab , Vincristina/administração & dosagem , Vincristina/efeitos adversos
20.
Int J Cardiovasc Imaging ; 35(5): 771-779, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30684081

RESUMO

Chemotherapy contained anthracycline inevitably cause declines of cardiac function. This study evaluated the deterioration of left ventricular segmental systolic function in patients with lymphoma received anthracycline chemotherapy detected by echocardiographic three dimensional speckle tracking imaging (3D-STI). Sixty patients with newly diagnosed diffuse large B-cell lymphoma who received R-CHOP chemotherapy were enrolled. Three dimensional left ventricular global longitudinal strain (3D-GLS), three dimensional left ventricular global circumferential strain (3D-GCS) and three dimensional left ventricular longitudinal strain of different left ventricular segments (3D-LS) were measured by 3D-STI at baseline, after the completion of two cycles and four cycles of the regimen respectively. Compared with baseline, 3D-GLS reduced significantly after four cycles of anthracycline therapy (P < 0.001), while 3D-GCS showed no significant variation during the whole procedure (all P > 0.05). For individual segment, LS of apical anterior and septal walls decreased significantly after two cycles of chemotherapy (all P < 0.05). After four cycles of treatment, 3D-LS of the mid-ventricular level (all P < 0.05), apical level (all P < 0.05) and apex (P < 0.05) worsened. Serum hs-cTnT levels increased after anthracycline exposure (P < 0.05) and Serum hs-cTnT levels were correlated with 3D-GLS at the end of four cycles (r = 0.12, P = 0.03). Mean values of involved segmental 3D-LS of two and four cycles were both correlated with serum hs-cTnT levels at the end of both two and four cycles (r = 0.368, P = 0.041; r = 0.79, p < 0.001). 3D-STI evaluation of the LV provides an understanding of the segmental impairment of LV wall and the possible process of LV impairment in lymphoma patients after anthracycline chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ecocardiografia Tridimensional , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda/efeitos dos fármacos , Adulto , Idoso , Anticorpos Monoclonais Murinos/efeitos adversos , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prednisona/efeitos adversos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Rituximab , Sístole/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/fisiopatologia , Vincristina/efeitos adversos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA