Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.810
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 , Vincristina/efeitos adversos
2.
Anticancer Res ; 39(8): 4379-4383, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366533

RESUMO

BACKGROUND/AIM: Dose-dense doxorubicin and cyclophosphamide (ddAC) followed by dose-dense paclitaxel (ddP) (ddAC-P) has improved disease-free survival of patients with breast cancer. The aim of this study was to evaluate the safety and relative dose intensity (RDI) of ddAC-P administered together with pegfilgrastim. PATIENTS AND METHODS: Between May 2015 and Aug 2017, 44 patients were retrospectively reviewed; they were administered 4 cycles of ddAC, followed by 4 cycles of ddP. Pegfilgrastim (3.6 mg) was administered in every cycle. RESULTS: The mean RDIs for ddAC-P, ddAC, and ddP were 95.0%, 94.5%, and 93.3%, respectively. The prevalence of high RDIs (≥85%) for ddAC-P, ddAC, and ddP was 90.9%, 84.1%, and 88.6%, respectively. Seven of the 10 patients with low RDIs experienced grade 1 or 2 fever. CONCLUSION: DdAC-P administered together with pegfilgrastim (3.6 mg) appears to be feasible and maintains RDI in most of Japanese patients with breast cancer. Rapid evaluation and proper management of fever may prevent low RDI.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Paclitaxel/administração & dosagem , Adulto , Idoso , Neoplasias da Mama/patologia , Ciclofosfamida/efeitos adversos , Relação Dose-Resposta a Droga , Doxorrubicina/efeitos adversos , Feminino , Filgrastim/administração & dosagem , Humanos , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Polietilenoglicóis/administração & dosagem
3.
N Engl J Med ; 381(5): 432-443, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31365801

RESUMO

BACKGROUND: Data regarding the efficacy of treatment with ibrutinib-rituximab, as compared with standard chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab, in patients with previously untreated chronic lymphocytic leukemia (CLL) have been limited. METHODS: In a phase 3 trial, we randomly assigned (in a 2:1 ratio) patients 70 years of age or younger with previously untreated CLL to receive either ibrutinib and rituximab for six cycles (after a single cycle of ibrutinib alone), followed by ibrutinib until disease progression, or six cycles of chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab. The primary end point was progression-free survival, and overall survival was a secondary end point. We report the results of a planned interim analysis. RESULTS: A total of 529 patients underwent randomization (354 patients to the ibrutinib-rituximab group, and 175 to the chemoimmunotherapy group). At a median follow-up of 33.6 months, the results of the analysis of progression-free survival favored ibrutinib-rituximab over chemoimmunotherapy (89.4% vs. 72.9% at 3 years; hazard ratio for progression or death, 0.35; 95% confidence interval [CI], 0.22 to 0.56; P<0.001), and the results met the protocol-defined efficacy threshold for the interim analysis. The results of the analysis of overall survival also favored ibrutinib-rituximab over chemoimmunotherapy (98.8% vs. 91.5% at 3 years; hazard ratio for death, 0.17; 95% CI, 0.05 to 0.54; P<0.001). In a subgroup analysis involving patients without immunoglobulin heavy-chain variable region (IGHV) mutation, ibrutinib-rituximab resulted in better progression-free survival than chemoimmunotherapy (90.7% vs. 62.5% at 3 years; hazard ratio for progression or death, 0.26; 95% CI, 0.14 to 0.50). The 3-year progression-free survival among patients with IGHV mutation was 87.7% in the ibrutinib-rituximab group and 88.0% in the chemoimmunotherapy group (hazard ratio for progression or death, 0.44; 95% CI, 0.14 to 1.36). The incidence of adverse events of grade 3 or higher (regardless of attribution) was similar in the two groups (in 282 of 352 patients [80.1%] who received ibrutinib-rituximab and in 126 of 158 [79.7%] who received chemoimmunotherapy), whereas infectious complications of grade 3 or higher were less common with ibrutinib-rituximab than with chemoimmunotherapy (in 37 patients [10.5%] vs. 32 [20.3%], P<0.001). CONCLUSIONS: The ibrutinib-rituximab regimen resulted in progression-free survival and overall survival that were superior to those with a standard chemoimmunotherapy regimen among patients 70 years of age or younger with previously untreated CLL. (Funded by the National Cancer Institute and Pharmacyclics; E1912 ClinicalTrials.gov number, NCT02048813.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imunoterapia , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem , Rituximab/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Feminino , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos , Rituximab/efeitos adversos , Vidarabina/administração & dosagem , Vidarabina/efeitos adversos , Vidarabina/análogos & derivados
4.
Environ Sci Pollut Res Int ; 26(26): 26664-26673, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31292874

RESUMO

Cyclophosphamide (CYP) is a common anticancer drug used in the treatment of various malignancies. Naringin (NG) is a natural bioflavonoid that have been reported to have many medicinal and pharmacological properties. Acetylcholinesterase (AChE), butyrylcholinesterase (BChE), carbonic anhydrase (CA), α-glycosidase (α-Gly), and aldose reductase (AR) enzymes are the essential biological molecules needed for metabolic processes in all living cells. In the present study, the aim was to investigate the effect of NG against CYP-induced liver, brain, kidney, heart, and testis toxicities on some metabolic enzyme activities such as AChE, BChE, CA, α-Gly, and AR. Thirty-five male Wistar rats were randomly divided into five groups with each group consisting of seven rats. The rats were subjected to oral treatment of NG (50 and 100 mg/kg body weight) for 7 days before administering a single dose of CYP (200 mg/kg body weight, i.p) on the seventh day. Treatment with NG in all tissues regulated these enzyme activities in CYP-induced rats. The results of this study showed that NG regulates abnormal increases and decreases in CYP-induced metabolic enzyme activities in all tissues.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Ciclofosfamida/antagonistas & inibidores , Flavanonas/farmacologia , Acetilcolinesterase/metabolismo , Aldeído Redutase/metabolismo , Animais , Antineoplásicos Alquilantes/efeitos adversos , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Butirilcolinesterase/metabolismo , Anidrases Carbônicas/metabolismo , Ciclofosfamida/efeitos adversos , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/enzimologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Miocárdio , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Testículo/efeitos dos fármacos , Testículo/enzimologia
5.
J Cancer Res Clin Oncol ; 145(9): 2343-2355, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31280348

RESUMO

PURPOSE: Combinations of bortezomib (Velcade), cyclophosphamide and dexamethasone have shown significant efficacy and safety for patients of newly diagnosed multiple myeloma (NDMM). In this study, we compared the efficacy and safety of modified VCD regimens with novel changes in bortezomib dose and schedule for NDMM. METHODS: Eighty-five NDMM patients from multiple centers were randomly assigned to a high-dose (1.6 mg/m2) (group A) or a low-dose (1.3 mg/m2) (group B) bortezomib, administrated on days 1, 6, 11, and 16 subcutaneously in a 4-week cycle for nine cycles, combined with 40 mg dexamethasone on bortezomib days and cyclophosphamide 300 mg/m2 on days 1-3 intravenously. RESULTS: After four cycles, complete response (CR) or better in group A (43.6%) was higher than that in group B (12.8%) (P = 0.002). During induction, for patients with R-ISS stage III, the CR or better rate in group A was superior to that in group B (P = 0.01). Of patients < 65, the CR or better rate of group A was superior to that of group B (P = 0.004). Rapid onset of CR occurred in group A (P < 0.01). Meanwhile, rate of 3-4 diarrhea was higher in group A (P = 0.03), which caused higher rate of dose reduction for patients ≥ 65 (P = 0.041). No significant difference between the two groups in PFS and OS. CONCLUSIONS: The studied high-dose VCD as induction regimen had an improved CR rate, especially in patients < 65 or with R-ISS stage III, and is feasible for young and high-risk patients. Trial registration ClinicalTrials.gov: NCT02086942.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bortezomib/administração & dosagem , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bortezomib/efeitos adversos , Ciclofosfamida/efeitos adversos , Dexametasona/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Teniposídeo/administração & dosagem , Resultado do Tratamento
6.
Lancet Haematol ; 6(8): e419-e428, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31208944

RESUMO

BACKGROUND: Fludarabine, cyclophosphamide, and rituximab (FCR) can improve disease-free survival for younger (age ≤65 years) fit patients with chronic lymphocytic leukaemia with mutated IGHV. However, patients with unmutated IGHV rarely have durable responses. Ibrutinib is active for patients with chronic lymphocytic leukaemia irrespective of IGHV mutation status but requires continuous treatment. We postulated that time-limited ibrutinib plus FCR would induce durable responses in younger fit patients with chronic lymphocytic leukaemia. METHODS: We did a multicentre, open-label, non-randomised, single-arm phase 2 trial at seven sites in the USA. We enrolled patients aged 65 years or younger with previously untreated chronic lymphocytic leukaemia. Our initial cohort (original cohort) was not restricted by prognostic marker status and included patients who had del(17p) or TP53 aberrations. After a protocol amendment (on March 21, 2017), we enrolled an additional cohort (expansion cohort) that included patients without del(17p). Ibrutinib was given orally (420 mg/day) for 7 days, then up to six 28-day cycles were administered intravenously of fludarabine (25 mg/m2, days 1-3), cyclophosphamide (250 mg/m2, days 1-3), and rituximab (375 mg/m2 day 1 of cycle 1; 500 mg/m2 day 1 of cycles 2-6) with continuous oral ibrutinib (420 mg/day). Responders continued on ibrutinib maintenance for up to 2 years, and patients with undetectable minimal residual disease in bone marrow after 2 years were able to discontinue treatment. The primary endpoint was the proportion of patients who achieved a complete response with undetectable minimal residual disease in bone marrow 2 months after the last cycle of ibrutinib plus FCR. Analyses were done per-protocol in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov (NCT02251548) and is ongoing. FINDINGS: Between Oct 23, 2014, and April 23, 2018, 85 patients with chronic lymphocytic leukaemia were enrolled. del(17p) was detected in four (5%) of 83 patients and TP53 mutations were noted in three (4%) of 81 patients; two patients had both del(17p) and TP53 mutations. Median patients' age was 55 years (IQR 50-58). At data cutoff, median follow-up was 16·5 months (IQR 10·6-34·1). A complete response and undetectable minimal residual disease in bone marrow 2 months after the last cycle of ibrutinib plus FCR was achieved by 28 (33%, 95% CI 0·23-0·44) of 85 patients (p=0·0035 compared with a 20% historical value with FCR alone). A best response of undetectable minimal residual disease in bone marrow was achieved by 71 (84%) of 85 patients during the study. One patient had disease progression and one patient died (sudden cardiac death after 17 months of ibrutinib maintenance, assessed as possibly related to ibrutinib). The most common all-grade toxic effects were haematological, including thrombocytopenia in 63 (74%) patients, neutropenia in 53 (62%), and anaemia in 41 (49%). Grade 3 or 4 non-haematological serious adverse events included grade 3 atrial fibrillation in three (4%) patients and grade 3 Pneumocystis jirovecii pneumonia in two (2%). INTERPRETATION: The proportion of patients who achieved undetectable minimal residual disease in bone marrow with ibrutinib plus FCR is, to our knowledge, the highest ever published in patients with chronic lymphocytic leukaemia unrestricted by prognostic marker status. Ibrutinib plus FCR is promising as a time-limited combination regimen for frontline chronic lymphocytic leukaemia treatment in younger fit patients. FUNDING: Pharmacyclics and the Leukemia & Lymphoma Society.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem , Rituximab/administração & dosagem , Vidarabina/análogos & derivados , Administração Oral , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/efeitos adversos , Esquema de Medicação , Feminino , Doenças Hematológicas/etiologia , Doenças Hematológicas/patologia , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Masculino , Pessoa de Meia-Idade , Mutação , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos , Indução de Remissão , Rituximab/efeitos adversos , Resultado do Tratamento , Proteína Supressora de Tumor p53/genética , Vidarabina/administração & dosagem , Vidarabina/efeitos adversos
7.
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 , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico
9.
Food Funct ; 10(6): 3262-3271, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31089650

RESUMO

Polysaccharides are closely associated with immune regulation. In this study, the aim was to investigate the effect of polysaccharides from Cordyceps gunnii mycelia (PPS) in cyclophosphamide (CTX)-induced immunodeficient mice. Compared with the CTX-induced immunosuppressed mice, the spleen and thymus indexes in mice with orally administered PPS were significantly increased, body weight loss was alleviated, and the natural killer (NK) cytotoxicity and proliferative activities of the lymphocytes were elevated. The recovery of peripheral white blood cells, red blood cells, hemoglobins and platelets was accelerated. Furthermore, the results from ELISA showed that PPS could up-regulate the serum levels of IL-2, IL-12, IFN-γ and IgG, and reduce the level of TGF-ß. Histopathological analysis of the spleen revealed the protective effect of PPS against CTX-induced immunosuppression. Western blotting results showed that PPS possessed immunomodulatory activity via TLR4/TRAF6/NF-κB signalling pathways. Finally, the intestinal absorption of PPS was poor, as detected in the Caco-2 transwell system. Taken together, these findings suggest that PPS plays a crucial role in protection against immunosuppression in cyclophosphamide-treated mice and could be a potential candidate for use in immune therapy regimens.


Assuntos
Cordyceps/química , Doenças do Sistema Imunitário/prevenção & controle , Fatores Imunológicos/administração & dosagem , Polissacarídeos/administração & dosagem , Fator 6 Associado a Receptor de TNF/imunologia , Receptor 4 Toll-Like/imunologia , Animais , Ciclofosfamida/efeitos adversos , Feminino , Humanos , Doenças do Sistema Imunitário/induzido quimicamente , Doenças do Sistema Imunitário/imunologia , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Imunossupressão , Camundongos , Camundongos Endogâmicos BALB C , Micélio/química , NF-kappa B/genética , NF-kappa B/imunologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Fator 6 Associado a Receptor de TNF/genética , Receptor 4 Toll-Like/genética
10.
Cell Prolif ; 52(3): e12608, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30932251

RESUMO

OBJECTIVES: We performed histological, cellular and behavioural analyses of the effects of cyclophosphamide (CTX), a chemotherapeutic drug, in the developing cerebellum and aimed to provide valuable insights into clinical application of CTX in children. MATERIALS AND METHODS: C57BL/6 mice and Math1-dependent GFP expression transgenic mice were used in the research. H&E staining was performed to analyse histological effects of CTX in the cerebellum. Staining for EdU and TUNEL was used to estimate the cell proliferation and apoptosis. Rotarod test and hanging wire test were used to evaluate the behavioural functions. Immunofluorescent staining was used to identify the cell types. The differentiation markers and genes related to Sonic Hedgehog (SHH) signalling were measured via quantitative real-time PCR or immunoblotting. RESULTS: We found that while CTX induced a significant reduction in cell proliferation and increased apoptosis in the EGL in 48 hours, the behavioural functions and the multilayer laminar structure of cerebella were largely restored when the mice grew to adults. Mechanistically, granule neuron progenitors, driven by the SHH signalling, enhanced the capability of proliferation quickly after CTX administration was stopped, which allowed the developing cerebellum to catch up and to gradually replenish the injury. CONCLUSION: The chemotherapeutic agent CTX induces an immediate damage to the developing cerebellum, but the cerebellar multilayer laminar structure and motor function can be largely restored if the agent is stopped shortly after use.


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Comportamento Animal/efeitos dos fármacos , Cerebelo/efeitos dos fármacos , Ciclofosfamida/efeitos adversos , Animais , Animais Recém-Nascidos , Antineoplásicos Alquilantes/administração & dosagem , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cerebelo/crescimento & desenvolvimento , Cerebelo/patologia , Criança , Ciclofosfamida/administração & dosagem , Proteínas Hedgehog/metabolismo , Humanos , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Modelos Animais , Neurogênese/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
11.
Mol Cell Biochem ; 458(1-2): 185-195, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31004308

RESUMO

In this study, we aimed to evaluate whether the encapsulation of ellagic acid (EA) into nanoliposomes would improve its potential in preventing cyclophosphamide-induced liver damage. Stability and antioxidative potential of free and encapsulated EA were determined. Experimental study conducted in vivo included ten groups of rats treated with cyclophosphamide and ellagic acid in its free and encapsulated form during 5 days. The protective effect of EA in its free and encapsulated form was determined based on serum liver function, liver tissue antioxidative capacities, and oxidative tissue damage parameters. Also, tissue morphological changes following cyclophosphamide administration were studied using standard histopathological and immunohistochemical analyses. The encapsulation of EA significantly prevented its degradation and improved its antioxidant properties in in vitro conditions. In in vivo experiments in both forms of EA were found to prevent rat liver damage induced by cyclophosphamide estimated through the changes in serum liver-damage parameters and tissue antioxidant capacities, as well as based on oxidatively modified lipids and proteins. Also, changes in morphology of liver cells and the expressions of Bcl-2, HIF-1α, and CD15 molecules in livers of animals of different experimental groups are in accordance with the obtained biochemical parameters. Thus, the encapsulation process might be effective in preventing EA from different environmental influences and could significantly increase its hepatoprotective potential. The encapsulation could prevent ellagic acid degradation and might deliver this potent compound to its target tissue in significantly larger quantities than when it is administered in its free form.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Ciclofosfamida/efeitos adversos , Ácido Elágico/farmacologia , Fígado/metabolismo , Nanopartículas , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Ciclofosfamida/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Antígenos CD15/biossíntese , Lipossomos , Fígado/lesões , Fígado/patologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Ratos , Ratos Wistar
12.
Breast Cancer Res Treat ; 175(3): 659-666, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30937656

RESUMO

PURPOSE: To evaluate and compare the efficacy and safety of the taxane plus anthracycline (TA) regimen vs. the taxane plus anthracycline plus cyclophosphamide (TAC) regimen as adjuvant chemotherapy in Chinese patients with node-positive breast cancer (BCa). METHODS: Patients with BCa (n = 640) were recruited between January 2010 and June 2012. All patients were randomized to receive six cycles of adjuvant therapy with the TA or TAC regimen. The primary endpoint was disease-free survival (DFS). The secondary endpoints were overall survival (OS), quality of life (QoL), and chemotherapy-related toxicity. Finally, 630 patients were evaluable, with a median follow-up of 70 months. RESULTS: There were no differences in the 70-month median DFS and OS between the two groups (DFS: TA 79.7% vs. TAC 75.6%, P = 0.371; OS: TA vs. TAC, 85.1% vs. 87.6%, P = 0.271). The TA group had lower frequencies grade III/IV vomiting (TA vs. TAC, 11.7% vs. 18.1%, P = 0.025) and nausea (13.0% vs. 19.4%, P = 0.031). The health-related QoL score was higher in the TA group (74.1 ± 5.3 vs. 67.9 ± 4.4, P = 0.001 vs. TAC). CONCLUSIONS: In the adjuvant setting, compared with the TAC regimen, the TA regimen exhibits no significant difference with respect to DFS and OS in Chinese patients with node-positive BCa. On the other hand, TA is associated with less severe adverse events, lower economic burden, and better QoL.


Assuntos
Antraciclinas/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Ciclofosfamida/administração & dosagem , Taxoides/administração & dosagem , Adulto , Idoso , Antraciclinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , China , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Taxoides/efeitos adversos , Resultado do Tratamento
14.
Dev Period Med ; 23(1): 39-44, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30954980

RESUMO

OBJECTIVE: Background: Patients with Ewing sarcoma have a dismal outcome. Maintenance treatment with trofosfamide has been proposed as an effective regimen for some paediatric malignancies. Aim: We sought to evaluate the schedule of trofosfamide for patients with high-risk primary bone Ewing sarcoma. PATIENTS AND METHODS: Materials and methods: Fifteen patients with primary bone Ewing sarcoma received treatment with trofosfamide (150 mg/m2 p.o. days 1-10) every 28 days. All patients had standard tumour imaging and laboratory evaluation. All toxicities were documented. RESULTS: Results: A total of 90 cycles (median 5 cycles/patient) were administered. A complete response was maintained in nine patients, while six patients had disease progression during treatment. Median time to progression was 1.9 months (range 1.8 to 4.6). Eleven patients (73.3%) are alive including nine with no evidence of disease with a median follow-up of 3.9 years (range 1.4 to 7.6). All patients with active disease at the start of the trofosfamide treatment died. There were no significant toxicities. CONCLUSION: Conclusions: Treatment with trofosfamide is well-tolerated and could have a role to maintain response in patients with primary bone Ewing sarcoma. Further studies are needed to better define the use of this regimen in the upfront management of those patients.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Ciclofosfamida/análogos & derivados , Sarcoma de Ewing/tratamento farmacológico , Adolescente , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/diagnóstico por imagem , Criança , Pré-Escolar , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Masculino , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/diagnóstico por imagem , Resultado do Tratamento , Adulto Jovem
15.
Oncol Res Treat ; 42(5): 269-274, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943501

RESUMO

BACKGROUND: Pegylated liposomal doxorubicin (PEG-LD) has a comparable efficacy but a distinct toxicological profile compared with free doxorubicin. The use of PEG-LD and cyclophosphamide followed by docetaxel regimen as neoadjuvant chemotherapy has not been well established. OBJECTIVES: We aimed to assess the maximum tolerated dose (MTD) and toxicity of this regimen in patients with locally advanced breast cancer. METHODS: A total of 19 patients were enrolled in this trial. In the initial treatment plan, patients were given PEG-LD at 35, 40, 45, or 50 mg/m2 on day 1 during the first four cycles, and cyclophosphamide was administered at a dose of 600 mg/m2. During the last four cycles, docetaxel was administered at 75 mg/m2 on day 1 of a 21-day scheme. RESULTS: The MTD was 40 mg/m2 PEG-LD and 600 mg/m2 cyclophosphamide administered on day 1 of a 21-day cycle. Dose-limiting toxicity, grade 3 hand-foot syndrome, was observed in one patient during level 2 and three patients during level 3. Other side effects included neutropenia, anemia, stomatitis, rash, nausea/vomiting, alopecia, transaminase elevation, and cardiotoxicity. The pathological complete response rate was 21.1%. CONCLUSIONS: Our study demonstrated that combination of 40 mg/m2 PEG-LD and 600 mg/m2 cyclophosphamide, followed by 75 mg/m2 docetaxel on day 1 of a 21-day scheme, was an efficacious and well-tolerated neoadjuvant regimen for patients with locally advanced breast cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Docetaxel/uso terapêutico , Doxorrubicina/análogos & derivados , Adulto , Idoso , Alopecia/induzido quimicamente , Anemia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/efeitos adversos , Docetaxel/efeitos adversos , Relação Dose-Resposta a Droga , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Terapia Neoadjuvante , Neutropenia/induzido quimicamente , Projetos Piloto , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/uso terapêutico , Estomatite/induzido quimicamente , Resultado do Tratamento
18.
Best Pract Res Clin Haematol ; 32(1): 74-88, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30927978

RESUMO

Autoimmune diseases (ADs) are associated with an increased risk not only of lymphoproliferative disorders but also of myeloid malignancies. The excess risk of myelodysplastic syndromes and/or acute myeloid leukemia is observed across several AD types, including systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disorders, multiple sclerosis, among others. The risk of developing myeloid neoplasms (MNs) is dependent on several variables, including the specific AD type, chronicity and severity of the AD, type and duration of exposure of disease modifying anti-rheumatic drugs or cytotoxics/immunosuppressives, and genetic predisposition risk. Putative triggering factors linking AD to elevated MN risk include AD-directed medications, shared genetic susceptibilities between the two disease entities, and chronic immune stimulation or bone marrow infiltration by the AD. Molecular mechanisms underpinning leukemogenesis remain largely speculative and warrant further investigation. Leukemias arising in patients with AD are not always 'therapy-related' in that MNs may develop in certain AD subtypes even among patients with no prior therapy exposure. Only a few studies have attempted to determine factors associated with MN development in AD but failed to demonstrate consistent characteristic clinical or paraclinical features. These reports have failed to demonstrate a clear correlation between individual agent exposure and subsequent leukemia development due to the low rates of therapy exposure compounded by the rarity of MN occurrence. Notwithstanding, the leukemogenic potential is best documented with agents such as azathioprine, cyclophosphamide, and mitoxantrone; this risk of MN development does not appear to be shared by biologic approaches such as anti-tumor necrosis factors-alpha inhibitors. In this article, we discuss plausible biologic mechanisms underlying MN pathogenesis in AD and review the data available on the development of MNs in patients with AD.


Assuntos
Artrite Reumatoide , Ciclofosfamida/efeitos adversos , Predisposição Genética para Doença , Imunossupressores/efeitos adversos , Leucemia Mieloide Aguda , Lúpus Eritematoso Sistêmico , Mitoxantrona/efeitos adversos , Síndromes Mielodisplásicas , Segunda Neoplasia Primária , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Ciclofosfamida/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Leucemia Mieloide Aguda/induzido quimicamente , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Mitoxantrona/uso terapêutico , Síndromes Mielodisplásicas/induzido quimicamente , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/patologia , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/metabolismo , Segunda Neoplasia Primária/patologia
19.
Int Immunopharmacol ; 72: 98-111, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30974284

RESUMO

Ginsenoside Rg3 (Rg3), which comprises Panax ginseng, is commonly used to improve the immunocompetence of cancer patients undergoing chemotherapy. This study was designed to elucidate the immunoenhancement effects of Rg3 in immunosuppressed mice induced by cyclophosphamide (CTX) treatment. Balb/c mice were administered Rg3 intragastrically once daily for 19 consecutive days and were intraperitoneally administered CTX (80 mg/kg) on days 15-19. Weight and immune organ indices were recorded. Hematological tests and cytokines were assessed using ELISA. We measured the activity of LDH and ACP, performed pathological and immunohistochemical staining of immune organs, and evaluated cytokines and transcription factors using RT-PCR. Immunosuppressed mice showed weight loss, decreased thymus and spleen indices and severe pathological damage. CTX attenuated macrophage phagocytosis by decreasing activity of LDH and ACP and decreased the release of related immune factors, IgG, IL-2 and G-CSF. Subsequently, we observed T lymphocyte expression on the surface of the thymus and spleen, which inhibited T cell activity. Further mechanistic analysis showed that CTX decreased the expression of T-bet and IFN-γ and increased the expression of GATA-3 and IL-4 in the thymus and spleen, which affected the Th1/Th2 balance. However, Rg3 treatment reversed CTX-induced immunosuppression. In summary, all the results suggest that Rg3 has protective effects on CTX-induced immunosuppression, which could be partially related to macrophages, T cells and Th1/Th2 balance. Although deeper studies of its mechanism are needed, these findings support the hypothesis that Rg3 can improve the reduced immunocompetence after CTX injury.


Assuntos
Ciclofosfamida/efeitos adversos , Ginsenosídeos/farmacologia , Fatores Imunológicos/farmacologia , Imunossupressão , Animais , Fator Estimulador de Colônias de Granulócitos/sangue , Imunoglobulina G/sangue , Fatores Imunológicos/efeitos adversos , Interleucina-2/sangue , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos Endogâmicos BALB C , Fagocitose/efeitos dos fármacos , Baço/efeitos dos fármacos , Baço/imunologia , Baço/patologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Timo/efeitos dos fármacos , Timo/imunologia , Timo/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA