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2.
Clinics ; 76: e2498, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1153964

RESUMO

OBJECTIVES: To evaluate the efficacy and safety of sorafenib in elderly patients with advanced hepatocellular carcinoma (HCC). METHODS: We analyzed data from a cohort of patients with advanced HCC treated using systemic treatment according to the local institutional protocol. Patients were divided into two groups, Group A, individuals <70 years of age, and Group B, individuals 70 years of age or older at the time of treatment initiation. Efficacy, measured based on overall survival (OS) and time to treatment failure (TTF), and toxicity were compared between groups. RESULTS: A total of 238 patients with advanced HCC who received sorafenib between 2007 and 2018 were evaluated. The median age for Group A was 59.1 years and that for Group B 73.6 years. The major prognostic characteristics were balanced between the groups. There were no significant differences in OS between Group A (8.0 months, 95%CI 6.34-9.3) and Group B (9.0 months, 95%CI 5.38-12.62), p=0.433, or in TTF between Group A (3.0 months, 95%CI 2.39-3.60) and Group B (3.0 months, 95%CI 1.68-4.32), p=0.936. There were no significant differences between Groups A and B with respect to the incidence of adverse events or treatment discontinuation because of toxicity. CONCLUSION: Efficacy and safety of sorafenib did not differ significantly between younger and older patients with HCC. Our data suggest that age alone should not restrict clinical decision-making for patients with advanced HCC.


Assuntos
Humanos , Pessoa de Meia-Idade , Idoso , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Antineoplásicos/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Prognóstico , Niacinamida/efeitos adversos , Sorafenibe/efeitos adversos
3.
Rev. bras. parasitol. vet ; 30(1): e025220, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1156219

RESUMO

Abstract Southern cattle tick resistance to pour-on and injectable acaricides has yet to be evaluated on a broader scope, and the paucity of information on the subject may hinder efforts to control this parasite. The objective of this study was to evaluate the resistance profile of ten populations of Rhipicephalus microplus to the acaricides fluazuron, fipronil and ivermectin in cattle herds in Mato Grosso do Sul, Brazil. The larval immersion test (LIT) was used to evaluate susceptibility to ivermectin and fipronil and the adult immersion test (AIT) was performed to evaluate fluazuron. Samples were randomly obtained in ten farms, and in general, we found resistance in five samples to fluazuron and in four samples to ivermectin and fipronil. Six samples showed incipient resistance to ivermectin and fipronil. Five of the ten evaluated samples showed resistance and/or incipient resistance to all the active ingredients, and the other five to two active ingredients. Among the samples classified as resistant, the average resistance ratio for ivermectin was 2.75 and 3.26 for fipronil. These results demonstrate the advanced status of resistance to the most modern chemical groups for the control of R. microplus in the state of Mato Grosso do Sul.


Resumo A resistência do carrapato-do-boi a acaricidas com modo de aplicação "pour-on" e injetáveis é pouco avaliada em estudos mais abrangentes, e essa escassez de informação pode resultar falhas no seu controle. Este estudo teve como objetivo avaliar o perfil de resistência em dez populações de Rhipicephalus microplus aos acaricidas fluazuron, fipronil e ivermectina, em rebanhos bovinos em Mato Grosso do Sul, Brasil. A caracterização fenotípica da resistência foi realizada por meio do teste de imersão de adultos (AIT) para o fluazuron, e teste de imersão de larvas (LIT) para fipronil e ivermectina. As amostras foram obtidas aleatoriamente em dez fazendas, sendo diagnosticada resistência em cinco amostras ao fluazuron e em quatro amostras à ivermectina e fipronil. Seis amostras apresentaram resistência incipiente à ivermectina e fipronil. Cinco das dez amostras avaliadas apresentaram resistência e / ou resistência incipiente a todos os princípios ativos, e as outras cinco a dois princípios ativos. Entre as amostras classificadas como resistentes, a média do fator de resistência para ivermectina foi de 2,75 e de 3,26 para fipronil. Esses resultados demonstram o avançado estado de resistência aos mais modernos grupos químicos para o controle de R. microplus em Mato Grosso do Sul.


Assuntos
Animais , Infestações por Carrapato/parasitologia , Infestações por Carrapato/veterinária , Resistência a Medicamentos , Doenças dos Bovinos/parasitologia , Rhipicephalus/efeitos dos fármacos , Acaricidas/farmacologia , Compostos de Fenilureia/farmacologia , Pirazóis/farmacologia , Ivermectina/farmacologia , Brasil , Bovinos
4.
Salud pública Méx ; 62(4): 424-431, jul.-ago. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1377334

RESUMO

Abstract: Objective: To compare the efficacy of three modern larvicides with the organophosphate temephos for control of Aedes aegypti in water tanks in Chiapas. Materials and methods: Trials were performed to compare the efficacy of pyriproxyfen, novaluron, two formulations of spinosad (granules and tablets) and temephos in oviposition traps and domestic water tanks. Results: Pyriproxyfen and temephos provided 2-3 weeks of complete control of larvae in oviposition traps, whereas spinosad granules and novaluron provided 7-12 weeks of control. Treatment of water tanks resulted in a significant reduction in oviposition by Ae. aegypt in houses (p<0.001). Higher numbers of larvae were present in temephos and pyriproxyfen-treated water tanks compared to novaluron and spinosad tablet treatments during most of the study. Conclusion: Spinosad formulations and novaluron were effective larvicides in this region. The poor performance of temephos may be indicative of reduced susceptibility in Ae. aegypti populations in Chiapas.


Resumen: Objetivo: Comparar la eficacia de tres larvicidas modernos para el control de Aedes aegypti en tanques de agua doméstica en Chiapas. Material y métodos: Se comparó la eficacia de piriproxifeno, novalurón, dos formulaciones de spinosad (gránulos y tabletas) y temefos en ovitrampas y tanques domésticos de agua. Resultados: El piriproxifeno y el temefos proporcionaron de 2 a 3 semanas de control de larvas en ovitrampas, mientras que los gránulos de spinosad y novaluron proporcionaron de 7 a12 semanas. Los tanques de agua tratados produjeron una reducción significativa en la oviposición por Ae. aegypti en las casas (p<0.001). Se encontró gran cantidad de larvas en los tanques tratados con temefos y piriproxifeno en comparación con los tratados con novaluron y tabletas de spinosad durante la mayor parte del estudio. Conclusión: Las formulaciones de spinosad en tabletas y novaluron fueron larvicidas efectivos en esta región. El bajo desempeño de temefos puede indicar una susceptibilidad reducida en poblaciones de Ae. aegypti en Chiapas.


Assuntos
Animais , Feminino , Compostos de Fenilureia , Piridinas , Temefós , Macrolídeos , Aedes , Inseticidas , Oviposição , Água/parasitologia , Controle de Mosquitos/métodos , Aedes/anatomia & histologia , Combinação de Medicamentos , Habitação , Larva , México
5.
Electron. j. biotechnol ; 40: 45-51, July. 2019. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1053457

RESUMO

Background: This research is intended to determine suitable types and concentrations of plant growth regulators (PGRs) to induce callus on stem and leaf sections of 4 species of the genus Garcinia, namely, Garcinia mangostana, Garcinia schomburgkiana, Garcinia cowa, and Garcinia celebica. The base medium was MS medium containing 30 g l -1 sucrose, 0.5 g l-1 polyvinylpyrrolidone (PVP), and 7 g l-1 agar, and for the different treatments, PGRs were added to the medium as follows: thidiazuron (TDZ) at concentrations of 0, 0.1, 0.5, 1, and 2 mg l-1; 6-(3- hydroxybenzylamino) purine (meta-topolin) at concentrations of 0, 0.5, 2.5, and 5 mg l-1; 4-amino-3,5,6- trichloro-2-pyridinecarboxylic acid (picloram) at concentrations of 0, 0.5, 2.5, and 5 mg l-1; and 2,4- dichlorophenoxyacetic acid (2,4-D) at concentrations of 0, 0.5, 1, 2, and 4 mg l-1. The occurrence of callus was observed after 4 weeks. Results: A maximum of 100% and 93% of G. mangostana leaf explants formed callus in the 0.5 mg l-1 and 1 mg l-1 TDZ treatments, respectively, while 100% of G. schomburgkiana stem explants formed callus in the 1 mg l-1 TDZ treatment and 89% of G. schomburgkiana leaf explants formed callus in the 0.5 mg l-1 picloram treatment. The highest callus induction rate for G. cowa was 62% in the 1 mg l-1 TDZ treatment and for G. celebica was 56% in the 0.5 mg l-1•mT-1 treatment. Conclusions: For all 4 species, the greatest amount of large nodular callus was observed in the TDZ treatments. White, friable callus was observed on most of the 2,4-D and picloram treatment groups. Most meta-topolin treatments resulted in minimal callus formation.


Assuntos
Reguladores de Crescimento de Plantas/metabolismo , Garcinia/crescimento & desenvolvimento , Compostos Fitoquímicos/metabolismo , Compostos de Fenilureia , Tiadiazóis , Fatores de Tempo , Transformação Genética , Clusiaceae/crescimento & desenvolvimento , Garcinia/fisiologia , Técnicas de Cultura de Tecidos
6.
Biol. Res ; 52: 3, 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1011433

RESUMO

BACKGROUND: Gymnema sylvestre is a medicinal woody perennial vine known for its sweetening properties and antidiabetic therapeutic uses in the modern and traditional medicines. Its over-exploitation for the therapeutic uses and to meet the demand of pharmaceutical industry in raw materials supply for the production of anti-diabetic drugs has led to considerable decline in its natural population. RESULTS: An efficient system of shoot bud sprouting from nodal segment explants and indirect plant regeneration from apical meristem-induced callus cultures of G. sylvestre have been developed on Murashige and Skoog (MS) medium amended with concentrations of cytokinins. Of the three growth regulators tested, N6-benzylaminopurine (BAP) was the most efficient and 2.0 mg L-1 gave the best shoot formation efficiency. This was followed by thidiazuron (TDZ) and kinetin (Kin) but, most of the TDZ-induced micro shoots showed stunted growth. Multiple shoot formation was observed on medium amended with BAP or TDZ at higher concentrations. The produced micro shoots were rooted on half strength MS medium amended with auxins and rooted plantlets acclimatized with 87% survival of the regenerates. CONCLUSIONS: The developed regeneration system can be exploited for genetic transformation studies, particularly when aimed at producing its high yielding cell lines for the anti-diabetic phytochemicals. It also offers opportunities for exploring the expression of totipotency in the anti-diabetic perennial vine.


Assuntos
Reguladores de Crescimento de Plantas/farmacologia , Regeneração/efeitos dos fármacos , Brotos de Planta/crescimento & desenvolvimento , Gymnema sylvestre/crescimento & desenvolvimento , Morfogênese/efeitos dos fármacos , Compostos de Fenilureia/farmacologia , Purinas/farmacologia , Tiadiazóis/farmacologia , Compostos de Benzil/farmacologia , Brotos de Planta/efeitos dos fármacos , Gymnema sylvestre/efeitos dos fármacos , Cinetina/farmacologia
7.
Arch. endocrinol. metab. (Online) ; 62(6): 636-640, Dec. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-983805

RESUMO

ABSTRACT Objective: The advent of multikinase inhibitor (MKI) therapy has led to a radical change in the treatment of patients with advanced thyroid carcinoma. The aim of this manuscript is to communicate rare adverse events that occurred in less than 5% of patients in clinical trials in a subset of patients treated in our hospital. Subjects and methods: Out of 760 patients with thyroid cancer followed up with in our Division of Endocrinology, 29 (3.8%) received treatment with MKIs. The median age at diagnosis of these patients was 53 years (range 20-70), and 75.9% of them were women. Sorafenib was prescribed as first-line treatment to 23 patients with differentiated thyroid cancer and as second-line treatment to one patient with advanced medullary thyroid cancer (MTC). Vandetanib was indicated as first-line treatment in 6 patients with MTC and lenvatinib as second-line treatment in two patients with progressive disease under sorafenib treatment. Results: During the follow-up of treatment (mean 13.7 ± 7 months, median 12 months, range 6-32), 5/29 (17.2%) patients presented rare adverse events. These rare adverse effects were: heart failure, thrombocytopenia, and squamous cell carcinoma during sorafenib therapy and squamous cell carcinoma and oophoritis with intestinal perforation during vandetanib treatment. Conclusions: About 3 to 5 years after the approval of MKI therapy, we learned that MKIs usually lead to adverse effects in the majority of patients. Although most of them are manageable, we still need to be aware of potentially serious and rare or unreported adverse effects that can be life-threatening.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Piperidinas/efeitos adversos , Quinazolinas/efeitos adversos , Carcinoma/tratamento farmacológico , Carcinoma Medular/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Antineoplásicos/efeitos adversos , Ooforite/induzido quimicamente , Compostos de Fenilureia/efeitos adversos , Quinolinas/efeitos adversos , Trombocitopenia/induzido quimicamente , Fatores de Tempo , Neoplasias da Glândula Tireoide/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , Seguimentos , Estimativa de Kaplan-Meier , Sorafenibe/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Perfuração Intestinal/induzido quimicamente
8.
Arch. endocrinol. metab. (Online) ; 62(3): 370-375, May-June 2018. graf
Artigo em Inglês | LILACS | ID: biblio-950060

RESUMO

Summary Total thyroidectomy, radioiodine (RAI) therapy, and TSH suppression are the mainstay treatment for differentiated thyroid carcinomas (DTCs). Treatments for metastatic disease include surgery, external-beam radiotherapy, RAI, and kinase inhibitors for progressive iodine-refractory disease. Unresectable locoregional disease remains a challenge, as standard therapy with RAI becomes unfeasible. We report a case of a young patient who presented with unresectable papillary thyroid carcinoma (PTC), and treatment with sorafenib allowed total thyroidectomy and RAI therapy. A 20-year-old male presented with severe respiratory distress due to an enlarging cervical mass. Imaging studies revealed an enlarged multinodular thyroid gland, extensive cervical adenopathy, severe tracheal stenosis, and pulmonary micronodules. He required an urgent surgical intervention and underwent tracheostomy and partial left neck dissection, as the disease was deemed unresectable; pathology revealed PTC. Treatment with sorafenib was initiated, resulting in significant tumor reduction allowing near total thyroidectomy and bilateral neck dissection. Postoperatively, the patient underwent radiotherapy for residual tracheal lesion, followed by RAI therapy for avid cervical and pulmonary disease. The patient's disease remains stable 4 years after diagnosis. Sorafenib has been approved for progressive RAI-refractory metastatic DTCs. In this case report, we describe a patient with locally advanced PTC in whom treatment with sorafenib provided sufficient tumor reduction to allow thyroidectomy and RAI therapy, suggesting a potential role of sorafenib as an induction therapy of unresectable DTC.


Assuntos
Humanos , Masculino , Adulto Jovem , Compostos de Fenilureia/administração & dosagem , Neoplasias da Glândula Tireoide/terapia , Carcinoma Papilar/terapia , Niacinamida/análogos & derivados , Radioisótopos do Iodo/administração & dosagem , Antineoplásicos/administração & dosagem , Tireoidectomia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Carcinoma Papilar/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Niacinamida/administração & dosagem , Terapia Neoadjuvante , Sorafenibe , Câncer Papilífero da Tireoide
9.
Medicina (B.Aires) ; 78(1): 29-32, feb. 2018. tab
Artigo em Inglês | LILACS | ID: biblio-894543

RESUMO

Hepatocellular carcinoma (HCC) is the second cause of cancer-related death in the world and is the main cause of death in cirrhotic patients. Unfortunately, the incidence of HCC has grown significantly in the last decade. Curative treatments such as surgery, liver transplantation or percutaneous ablation can only be applied in less than 30% of cases. The multikinase inhibitor sorafenib is the first line therapy for advanced HCC. Regorafenib is the standard of care for second-line patients. However, novel and more specific potent therapeutic approaches for advanced HCC are still needed. The liver constitutes a unique immunological microenvironment, although anti-tumor immunity seems to be feasible with the use of checkpoint inhibitors such as nivolumab. Efficacy may be further increased by combining checkpoint inhibitors or by applying loco-regional treatments. The success of immune checkpoint blockade has renewed interest in immunotherapy in HCC.


El hepatocarcinoma (HCC) es la segunda causa de muerte relacionada con el cáncer en el mundo y es la principal causa de muerte en pacientes cirróticos. Desafortunadamente, la incidencia de HCC ha crecido significativamente en la última década. Los tratamientos curativos como la cirugía, el trasplante de hígado o la ablación solo pueden aplicarse en menos del 30% de los casos. El sorafenib es el tratamiento de primera línea para el HCC avanzado, mientras que el regorafenib se reserva como segunda línea. Sin embargo, todavía son necesarios nuevos enfoques terapéuticos potentes y más específicos para el HCC avanzado. El hígado constituye un microambiente inmunológico único, aunque la inmunidad antitumoral parece ser factible mediante el uso de inhibidores de punto de control como nivolumab. La eficacia puede aumentarse adicionalmente combinando inhibidores de puntos de control inmunitario o aplicando tratamientos loco-regionales. En este sentido, el éxito del uso de anticuerpos monoclonales, que bloquean el control inmunitario, ha renovado el interés en la inmunoterapia para el HCC.


Assuntos
Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Antineoplásicos Imunológicos/uso terapêutico , Imunoterapia/métodos , Neoplasias Hepáticas/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Piridinas/uso terapêutico , Ensaios Clínicos como Assunto , Sorafenibe/uso terapêutico , Nivolumabe/uso terapêutico
10.
An. acad. bras. ciênc ; 89(4): 3103-3110, Oct.-Dec. 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-886869

RESUMO

ABSTRACT The low fruit set is one of the main factors leading to poor yield of pear orchards in Brazil. The exogenous application of thidiazuron (TDZ) and aminoethoxyvinilglycine (AVG) has shown promising results in some pear cultivars and other temperate fruit trees. The objective of this study was to evaluate the effect of TDZ and AVG on fruit set, yield, and fruit quality of 'Hosui' and 'Packham's Triumph' pears. The study was performed in a commercial orchard located in São Joaquim, SC. Plant material consisted of 'Hosui' and 'Packham's Triumph' pear trees grafted on Pyrus calleryana. Treatments consisted on different rates of TDZ (0 mg L-1, 20 mg L-1, 40 mg L-1 and 60 mg L-1) sprayed at full bloom for both cultivars. An additional treatment of AVG 60 mg L-1 was sprayed one week after full bloom in 'Hosui'. The fruit set, number of fruit per tree, yield, fruit weight, seed number, and fruit quality attributes were assessed. Fruit set and yield of both cultivars are consistently increased by TDZ, within the rates of 20 to 60 mg L-1. Besides, its application increased fruit size of 'Hosui' and did not negatively affect fruit quality attributes of both cultivars.


Assuntos
Compostos de Fenilureia/farmacologia , Tiadiazóis/farmacologia , Pyrus/efeitos dos fármacos , Glicina/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Tiadiazóis/administração & dosagem , Pyrus/crescimento & desenvolvimento , Produção Agrícola , Glicina/administração & dosagem , Glicina/farmacologia
11.
Einstein (Säo Paulo) ; 15(3): 355-358, July-Sept. 2017.
Artigo em Inglês | LILACS | ID: biblio-891404

RESUMO

ABSTRACT Acute myeloid leukemia is a hematopoietic stem cell neoplastic disease associated with high morbidity and mortality. The presence of FLT3 internal tandem duplication mutations leads to high rates of relapse and decreased overall survival. Patients with FLT3 internal tandem duplication are normally treated with hematopoietic stem cell transplantation in first complete remission. Nevertheless, the incidence of post-transplant relapse is considerable in this group of patients, and the management of this clinical condition is challenging. The report describes the outcomes of patients with FLT3 internal tandem duplication positive acute myeloid leukemia who relapsed after allogeneic hematopoietic stem cell transplantation and were treated with the combination of re-induction chemotherapy, donor lymphocyte infusion, sorafenib and azacitidine. Three cases are described and all patients achieved prolonged complete remission with the combined therapy. The combination of induction chemotherapy followed by donor lymphocyte infusion, and the maintenance with azacitidine and sorafenib can be effective approaches in the treatment of post-hematopoietic stem cell transplant and relapsed FLT3 internal tandem duplication positive acute myeloid leukemia patients. This strategy should be further explored in the context of clinical trials.


RESUMO A leucemia mieloide aguda é uma doença neoplásica de células-tronco hematopoiéticas com alta morbimortalidade. A presença de mutações de duplicação em tandem de FLT3 leva a altas taxas de recorrência e a menor sobrevida global. Os pacientes com duplicação em tandem de FLT3 são normalmente tratados com transplante de células-tronco hematopoiéticas na primeira remissão completa. No entanto, a incidência de recidiva pós-transplante é considerável neste grupo de pacientes, e a conduta, nestes casos, é um desafio. O relato descreve os resultados do tratamento de pacientes com leucemia mieloide aguda positiva e duplicação em tandem de FLT3 que recidivaram depois do transplante alogênico de células-tronco hematopoiéticas e que foram tratados com combinação de quimioterapia de reindução, infusão de linfócitos de doador, sorafenib e azacitidina. São descritos três casos, e todos os pacientes apresentaram remissão completa prolongada com a terapia combinada. A combinação de quimioterapia de indução, seguida de infusão de linfócitos do doador, e a manutenção com azacitidina e sorafenib podem ser abordagens eficazes no tratamento da recorrência pós-transplante em pacientes com leucemia mieloide aguda e duplicação em tandem de FLT3. Essa estratégia deve ser mais explorada no contexto de ensaios clínicos.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Compostos de Fenilureia/administração & dosagem , Azacitidina/administração & dosagem , Leucemia Mieloide Aguda/terapia , Niacinamida/análogos & derivados , Transfusão de Linfócitos , Tirosina Quinase 3 Semelhante a fms/genética , Quimioterapia de Indução , Antineoplásicos/administração & dosagem , Recidiva , Leucemia Mieloide Aguda/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento , Niacinamida/administração & dosagem , Terapia Combinada/métodos , Recidiva Local de Neoplasia/terapia
13.
Ann. hepatol ; 16(2): 263-268, Mar.-Apr. 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-887231

RESUMO

ABSTRACT Background and Aims. The presence of dermatologic reaction as an adverse event to sorafenib treatment in patients with unresectable hepatocellular carcinoma has been indicated as a prognostic factor for survival in a recent prospective analysis. To date, this is the only clinical predictor of treatment response, which can be evaluated earlier in the treatment and, therefore, contribute to a better and more individualized patient management. Material and methods. This retrospective study included 127 patients treated with sorafenib under real-life practice conditions in two hepatology reference centers in Brazil. Demographic data, disease/medical history and time of sorafenib administration as well as adverse events related to the medication were recorded in a database. Results. Cirrhosis was present in 94% of patients, 85.6% were Child-Pugh A, 80.3%BCLC-C, 81% had vascular invasion and/or extrahepatic spread and 95% had a performance status 0 to 1.The median duration of treatment was 10.1 months (range: 0.1-47 months).The most common adverse event within the first 60 days of treatment were diarrhea (62.2%) and dermatological reaction (42%).The median overall survival for the cohort was 20 months, and it was higher for patients who developed dermatological reactions within the first 60 days compared to those who did not present this adverse event. Conclusion. This retrospective analysis showed the use of sorafenib in patients selected according to BCLC staging, and it is the first external validation of early dermatologic adverse events as a predictor of overall survival in patients with advanced hepatocellular carcinoma.


Assuntos
Humanos , Compostos de Fenilureia/efeitos adversos , Niacinamida/análogos & derivados , Erupção por Droga/etiologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Antineoplásicos/efeitos adversos , Fatores de Tempo , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Niacinamida/efeitos adversos , Erupção por Droga/diagnóstico , Erupção por Droga/mortalidade , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Estimativa de Kaplan-Meier , Sorafenibe , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Estadiamento de Neoplasias
14.
Ann. hepatol ; 16(2): 255-262, Mar.-Apr. 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-887230

RESUMO

ABSTRACT Background. Hepatocellular carcinoma (HCC) is the most common malignancy that develops in cirrhotic livers. Its clinical and epidemiological characteristics and mortality rates vary according to geographical region. The objective of this study was to evaluate the clinical profile, epidemiological characteristics, laboratory parameters, treatment and survival of patients with HCC. Material and methods. Patients with HCC seen between 2000 and 2012 were studied. The Kaplan-Meier method was used for survival analysis according to variables in question. Results. The study included 247 patients with a mean age of 60 ± 10 years. There was a predominance of males (74%). The main etiologies of HCC were HCV infection (55%), excessive alcohol consumption (12%), and HBV infection (8%). Liver cirrhosis was present in 92% of cases. The mean tumor number and diameter were 2 and 5 cm, respectively. Patients meeting the Milan criteria corresponded to 43% of the sample. Liver transplantation was performed in 22.4% of patients of the Milan subset and in 10% of the whole sample. The overall mean survival was 60 months, with a 1-, 3- and 5-year survival probability of 74%, 40% and 29%, respectively. Lower survival was observed among patients with alcoholic etiology. Survival was higher among patients submitted to liver transplantation (P < 0.001), TACE (P < 0.001), or any kind of treatment (P < 0.001). However, no difference was found for surgical resection (P = 0.1) or sorafenib (P = 0.1). Conclusion. Patients with HCC were mainly older men diagnosed at an advanced stage. Treatment was associated with better overall survival, but few patients survived to be treated.


Assuntos
Humanos , Transplante de Fígado , Quimioembolização Terapêutica , Carcinoma Hepatocelular/terapia , Técnicas de Ablação , Hepatectomia , Neoplasias Hepáticas/terapia , Antineoplásicos/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Fatores de Tempo , Brasil/epidemiologia , Fatores de Risco , Resultado do Tratamento , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/mortalidade , Niacinamida/análogos & derivados , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carga Tumoral , Estimativa de Kaplan-Meier , Centros de Atenção Terciária , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Neoplasias Hepáticas/etiologia , Estadiamento de Neoplasias , Antineoplásicos/efeitos adversos
15.
Ann. hepatol ; 16(2): 247-254, Mar.-Apr. 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-887229

RESUMO

ABSTRACT Background & Aim. Transarterial chemoembolization (TACE) or sorafenib is recommended for hepatocellular carcinoma BCLC stages B and C respectively. We studied the role of combination of TACE and sorafenib in BCLC stages B/C. Material and methods. We undertook an observational study on a cohort of cirrhotics with HCC from August 2010 through October 2014. Patients in BCLC stages B/C who had received TACE and/or sorafenib were included. mRECIST criteria were used to assess tumor response. The primary end point was overall survival. Results. Out of 124 patients, 47.6% were in BCLC-B and 52.4% in BCLCC. Baseline characteristics were comparable. The predominant etiology was cryptogenic (37.2% and 38.5%, p = NS). 49.1% in BCLC-B and 56.9% in BCLC-C had received TACE+sorafenib. In BCLC-B, the overall survival improved from 9 months (95% CI 6.3-11.7) using TACE only to 16 months (95% CI 12.9-19.1) using TACE+sorafenib (p < 0.05). In BCLC-C, addition of TACE to sorafenib improved the overall survival from 4 months (95%CI 3-5) to 9 months (95%CI 6.8-11.2) (p < 0.0001). As per mRECIST criteria, patients on TACE+sorafenib had reduced progressive disease (37.8% vs. 83.3%), improved partial response (43.2% vs. 3.3%) and one had complete response compared to those on sorafenib alone (p < 0.0001) in BCLC-C but not in BCLC-B group. Hand foot syndrome was noted in 27.7% patients on sorafenib and post TACE syndrome in 80.2% patients, but both were reversible. No major adverse events were noted. Conclusion. TACE+sorafenib was more effective than TACE or sorafenib alone in HCC BCLC stages B or C with a significant survival benefit and improved tumour regression especially in BCLC-C patients.


Assuntos
Humanos , Compostos de Fenilureia/uso terapêutico , Niacinamida/análogos & derivados , Carcinoma Hepatocelular/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias Hepáticas/terapia , Antineoplásicos/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/mortalidade , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Inibidores de Proteínas Quinases/efeitos adversos , Carga Tumoral , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Estadiamento de Neoplasias , Antineoplásicos/efeitos adversos
16.
Braz. j. med. biol. res ; 50(8): e6207, 2017. graf
Artigo em Inglês | LILACS | ID: biblio-888978

RESUMO

Both sorafenib and interleukin-27 (IL-27) are antineoplastic drugs. This study aimed to investigate the synergistic effect of these two drugs on bladder cancer cells. HTB-9 and T24 cells were stimulated with IL-27 (50 ng/mL), sorafenib (2 μM) or the synergistic action of these two drugs. The cells without treatment acted as control. Cell proliferation, apoptosis and invasion were measured by bromodeoxyuridine assay, flow cytometry and modified Boyden chamber, respectively. Simultaneously, both modified Boyden chamber and scratch assay were used to assess cell migration. Finally, the phosphorylation levels of key kinases in the Akt/mechanistic target of rapamycin (mTOR)/mitogen-activated protein kinase (MAPK) pathway, and expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 were detected by western blot analysis. Stimulation with IL-27 or sorafenib repressed proliferation, migration and invasion but promoted apoptosis, and the effects were all enhanced by the combination of these two drugs in HTB-9 cells. The effect of the combined treatment on bladder cancer cells was verified in T24 cells. Additionally, the phosphorylation levels of AKT, mTOR and MAPK as well as the expression levels of MMP-2 and MMP-9 were all decreased by a single treatment of IL-27 or sorafenib, and further decreased by the combined treatment of these two drugs. The combination of IL-27 and sorafenib inhibited proliferation, migration and invasion and promoted apoptosis of bladder cancer cells compared with mono-drug treatment. Additionally, the AKT/mTOR/MAPK pathway might be implicated in the functional effects by down-regulations of MMP-2 and MMP-9.


Assuntos
Humanos , Antineoplásicos/farmacologia , Interleucina-27/farmacologia , Niacinamida/análogos & derivados , Compostos de Fenilureia/farmacologia , Neoplasias da Bexiga Urinária/patologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Niacinamida/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico
17.
Rev. bras. parasitol. vet ; 25(1): 54-60, Jan.-Mar. 2016. graf
Artigo em Inglês | LILACS | ID: lil-777530

RESUMO

Abstract Aiming to characterize the potential off-target effects of fluazuron on ticks, biochemical analyses were conducted to evaluate changes in the carbohydrate metabolism of Rhipicephalus (Boophilus) microplus ticks after exposure to fluazuron. Hemolymph and fat body were collected from female ticks before and after (4, 8 and 15 days) exposure to fluazuron. Spectrophotometric analyses were done to quantify glucose concentration and lactate dehydrogenase (LDH) activity in the hemolymph and the concentration of glycogen in the tick’s fat body. High Performance Liquid Chromatography (HPLC) was employed to determine the concentration of carboxylic acids in the hemolymph and to evaluate changes in intermediary metabolic processes requiring oxygen consumption. Increases in the levels of LDH activity and lactic acid concentration indicated that fluazuron enhanced fermentative metabolism in ticks. Exposure to fluazuron was also found to increase glucose concentrations in the hemolymph over time, although no significant differences were noted daily. In addition to expanding the body of knowledge about the mode of action of fluazuron, investigations into these mechanisms may also be useful in discovering new and as yet unexplored secondary effects.


Resumo Com o objetivo de caracterizar os efeitos não-alvo da ação do fluazuron, foram realizados testes bioquímicos para analisar possíveis alterações no metabolismo de carboidratos em carrapatos Rhipicephalus (Boophilus) microplus após sua exposição ao composto. Foram coletados hemolinfa e corpo gorduroso de fêmeas ingurgitadas antes e após (4, 8 e 15 dias) a exposição ao fluazuron. Análises espectrofotométricas foram usadas para quantificar a concentração de glicose e a atividade da lactato desidrogenase (LDH) na hemolinfa e concentração de glicogênio no corpo gorduroso. Cromatografia Líquida de Alta Eficiência (CLAE) foi usada para determinação das concentrações de ácidos carboxílicos na hemolinfa e avaliar possíveis alterações em metabolismo intermediário em relação ao consumo de oxigênio. Aumento na atividade de LDH e concentração de ácido lático indicaram que o fluazuron pode regular o metabolismo fermentativo em carrapatos. A exposição ao fluazuron também aumentou a concentração de glicose na hemolinfa, apesar de não ter havido diferença significativa na comparação entre as médias no mesmo dia de avaliação. Além de aumentar o conhecimento sobre o modo de ação do fluazuron, investigações sobre tais mecanismos também são úteis no descobrimento de novos efeitos secundários ainda não explorados.


Assuntos
Animais , Feminino , Compostos de Fenilureia/farmacologia , Corpo Adiposo/efeitos dos fármacos , Hemolinfa/efeitos dos fármacos , Rhipicephalus/efeitos dos fármacos , Corpo Adiposo/química , Hemolinfa/química , Rhipicephalus/metabolismo
18.
Gastroenterol. latinoam ; 27(2): 106-113, 2016. tab
Artigo em Espanhol | LILACS | ID: biblio-907622

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide. Most cases occur in patients with chronic liver disease who are diagnosed at an advanced stage, and their prognosis is poor. Because HCC is resistant to conventional systemic therapies, molecular therapies have emerged and been established as the standard for advanced forms of the disease. Since the publication of phase III clinical studies on sorafenib, research has searched for new molecular targets. Thus, multiple clinical studies that inhibit relevant molecular pathways have been performed with numerous patients. Many of these trials have had unexpectedly negative results, not only due to patient complexity and the difficulty in evaluating a therapeutic response, quality of life and the survival rate but also because phase II clinical studies, without the selection of molecular targets, have continued on to poor results in phase III studies. This review article aims to evaluate different phase II and phase III clinical studies to understand the clinically relevant molecular pathways and to improve the future management of HCC patients.


El carcinoma hepatocelular (CHC) es uno de los tumores más comunes a nivel mundial. La mayoría de los casos ocurre en pacientes con enfermedad hepática crónica, quienes son diagnosticados en un estado avanzado con muy pobre pronóstico. Terapias moleculares orientadas al tratamiento del CHC han sido destacadas; estas pueden afectar la proliferación celular del tumor, diferenciación celular, angiogénesis, invasión y metástasis, entre otros procesos críticos al desarrollo del tumor. El estándar para el CHC avanzado es la terapia target usando Sorafenib, sin embargo, nuevas moléculas han sido testeadas en estudios fase III de primera línea, tales como sunitinib, brivanib, erlotinib y linifanib, sin superioridad sobre sorafenib. La investigación de nuevos tratamientos es un desafío para investigadores, hepatólogos y oncólogos. Las principales vías moleculares de CHC con relevancia en estudios clínicos fase II y III son: MAP-kinase (MAPK), PI3K/AKT/mTOR, (HGF)/c-Met, cromatina y regulación epigenética, mantenimiento de telómeros, Notch, Hedgehog, Hippo y vía señalizante Jak/STAT. Las terapias futuras en CHC pueden ser orientadas rutinariamente usando sólo objetivos adecuados para terapias moleculares y seleccionando subgrupos de pacientes sobre la base de la expresión de targets moleculares o basados en nuevas clasificaciones definidas por estudios genómicos.


Assuntos
Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Progressão da Doença , Niacinamida/análogos & derivados , Análise de Sobrevida
19.
Arch. endocrinol. metab. (Online) ; 59(4): 347-350, Aug. 2015. tab, ilus
Artigo em Inglês | LILACS | ID: lil-757374

RESUMO

Advanced radioactive refractory and progressive or symptomatic differentiated thyroid carcinoma (DTC) is a rare condition. Sorafenib was recently approved for the treatment of these patients. We present the case of a 67 year old woman diagnosed with DTC who underwent a total thyroidectomy with central, lateral-compartment neck dissection and shaving of the trachea and esophagus due to tumor infiltration. A local recurrence was detected 14 months later requiring, additionally, two tracheal rings resection. The patient received a cumulative 131I dose of 650 mCi and developed dysphagia and dyspnea 63 months after initial surgery. A 18FGD-PET/CT showed progression of the local mass associated to hypermetabolic pulmonary nodules. Sorafenib 800 mg/day was then prescribed. A dose reduction to 400 mg/day was necessary due to grade 3 thrombocytopenia that appeared four months after drug prescription. Platelet count went to normal after this dose reduction. Five months after initiation of sorafenib, a partial response of the local mass with significant intra-tumoral necrosis was observed. We conclude that sorafenib is a valid option for locally advanced DTC and that the platelet count should be evaluated regularly because it seems that thrombocytopenia might be more frequently observed in DTC than in other types of tumors.


Assuntos
Humanos , Feminino , Idoso , Compostos de Fenilureia/uso terapêutico , Trombocitopenia/induzido quimicamente , Neoplasias da Glândula Tireoide/terapia , Niacinamida/análogos & derivados , Recidiva Local de Neoplasia/terapia , Antineoplásicos/uso terapêutico , Compostos de Fenilureia/administração & dosagem , Tireoidectomia , Neoplasias da Glândula Tireoide/complicações , Niacinamida/administração & dosagem , Niacinamida/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Sorafenibe , Estadiamento de Neoplasias , Antineoplásicos/administração & dosagem
20.
Arq. bras. endocrinol. metab ; 58(1): 37-41, 02/2014. tab, graf
Artigo em Inglês | LILACS | ID: lil-705238

RESUMO

Objective: To investigate the efficacy of sorafenib in progressive radioiodine resistant metastatic thyroid carcinoma.Subjects and methods: Off-label observational study. Sorafenib 400 mg twice daily was evaluated. Therapy duration was 12 ± 3 months (range 6-16 months).Results: Eight patients were included (seven papillary, one insular variant). The eight patients meeting study criteria received sorafenib 400 mg orally twice a day until disease progression or unacceptable toxicity developed. One patient showed a partial response with tumor regression of -35%, six months after the beginning of the treatment; five patients exhibited stable disease and two patients had progressive disease and died. Thyroglobulin decreased within 4 weeks in all patients by 50% ± 23%.Adverse events: one patient had heart failure, and recovered after sorafenib withdrawal. However, she died five months later of sudden death.Conclusion: These data suggest a possible role for sorafenib in the treatment of progressive metastatic DTC. Adverse event are usually manageable, but severe ones may appear and these patients should be strictly controlled.


Objetivo: Investigar a eficácia do sorafenibe no carcinoma de tireoide metastático progressivo e refratário à iodoterapia.Sujeitos e métodos: Estudo observacional do efeito do sorafenibe off-label administrado 400 mg duas vezes ao dia. A duração da terapia foi de 12 ± 3 meses (variação de 6-16 meses).Resultados: Oito pacientes foram incluídos (sete com variante papilífera e um com variante insular). Os oito pacientes que preencheram os critérios do estudo receberam o sorafenibe 400 mg por via oral duas vezes por dia até progressão da doença ou toxicidade inaceitável. Um paciente apresentou uma resposta parcial com regressão tumoral da lesão alvo de 35% seis meses após o início do tratamento; cinco pacientes apresentaram doença estável e dois pacientes progrediram e morreram. A tireoglobulina diminuiu 50% ± 23% em 4 semanas em todos os pacientes.Eventos adversos: um paciente teve insuficiência cardíaca e morreu por morte súbita cinco meses após a retirada do sorafenibe.Conclusão: Esses dados sugerem um possível papel para sorafenibe para o tratamento do CDT metastático progressivo.


Assuntos
Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antineoplásicos/uso terapêutico , Carcinoma Papilar/tratamento farmacológico , Carcinoma Papilar/patologia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Antineoplásicos/efeitos adversos , Neoplasias Ósseas/secundário , Ensaios de Uso Compassivo , Carcinoma Papilar/radioterapia , Carcinoma Papilar/secundário , Seguimentos , Insuficiência Cardíaca/induzido quimicamente , Radioisótopos do Iodo/uso terapêutico , Neoplasias Pulmonares/secundário , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Critérios de Avaliação de Resposta em Tumores Sólidos , Resultado do Tratamento , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia
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