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  1 / 1825 MEDLINE  
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[PMID]:28934712
[Au] Autor:Stuchlíková LR; Skálová L; Szotáková B; Syslová E; Vokrál I; Vanek T; Podlipná R
[Ad] Endereço:Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic. Electronic address: lucie.raisova@faf.cuni.cz.
[Ti] Título:Biotransformation of flubendazole and fenbendazole and their effects in the ribwort plantain (Plantago lanceolata).
[So] Source:Ecotoxicol Environ Saf;147:681-687, 2018 Jan.
[Is] ISSN:1090-2414
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Although veterinary anthelmintics represent an important source of environmental pollution, the fate of anthelmintics and their effects in plants has not yet been studied sufficiently. The aim of our work was to identify metabolic pathways of the two benzimidazole anthelmintics fenbendazole (FBZ) and flubendazole (FLU) in the ribwort plantain (Plantago lanceolata L.). Plants cultivated as in vitro regenerants were used for this purpose. The effects of anthelmintics and their biotransformation products on plant oxidative stress parameters were also studied. The obtained results showed that the enzymatic system of the ribwort plantain was able to uptake FLU and FBZ, translocate them in leaves and transform them into several metabolites, particularly glycosides. Overall, 12 FLU and 22 FBZ metabolites were identified in the root, leaf base and leaf top of the plant. Concerning the effects of FLU and FBZ, both anthelmintics in the ribwort plantain cells caused significant increase of proline concentration (up to twice), a well-known stress marker, and significant decrease of superoxide dismutase activity (by 50%). In addition, the activities of four other antioxidant enzymes were significantly changed after either FLU or FBZ exposition. This could indicate a certain risk of oxidative damage in plants influenced by anthelmintics, particularly when they are under other stress conditions.
[Mh] Termos MeSH primário: Anti-Helmínticos/toxicidade
Fenbendazol/toxicidade
Mebendazol/análogos & derivados
Plantago/efeitos dos fármacos
Drogas Veterinárias/toxicidade
[Mh] Termos MeSH secundário: Animais
Anti-Helmínticos/metabolismo
Biotransformação
Fenbendazol/metabolismo
Mebendazol/metabolismo
Mebendazol/toxicidade
Redes e Vias Metabólicas/efeitos dos fármacos
Estresse Oxidativo/efeitos dos fármacos
Plantago/enzimologia
Plantago/crescimento & desenvolvimento
Drogas Veterinárias/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthelmintics); 0 (Veterinary Drugs); 621BVT9M36 (Fenbendazole); 81G6I5V05I (Mebendazole); R8M46911LR (flubendazole)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE


  2 / 1825 MEDLINE  
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[PMID]:29329288
[Au] Autor:Pabalan N; Singian E; Tabangay L; Jarjanazi H; Boivin MJ; Ezeamama AE
[Ad] Endereço:Center for Research and Development, Angeles University Foundation, Angeles City, Philippines.
[Ti] Título:Soil-transmitted helminth infection, loss of education and cognitive impairment in school-aged children: A systematic review and meta-analysis.
[So] Source:PLoS Negl Trop Dis;12(1):e0005523, 2018 01.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Evidence of an adverse influence of soil transmitted helminth (STH) infections on cognitive function and educational loss is equivocal. Prior meta-analyses have focused on randomized controlled trials only and have not sufficiently explored the potential for disparate influence of STH infection by cognitive domain. We re-examine the hypothesis that STH infection is associated with cognitive deficit and educational loss using data from all primary epidemiologic studies published between 1992 and 2016. METHODS: Medline, Biosis and Web of Science were searched for original studies published in the English language. Cognitive function was defined in four domains (learning, memory, reaction time and innate intelligence) and educational loss in two domains (attendance and scholastic achievement). Pooled effect across studies were calculated as standardized mean differences (SMD) to compare cognitive and educational measures for STH infected/non-dewormed children versus STH uninfected /dewormed children using Review Manager 5.3. Sub-group analyses were implemented by study design, risk of bias (ROB) and co-prevalence of Schistosoma species infection. Influential studies were excluded in sensitivity analysis to examine stability of pooled estimates. FINDINGS: We included 36 studies of 12,920 children. STH infected/non-dewormed children had small to moderate deficits in three domains-learning, memory and intelligence (SMD: -0.44 to -0.27, P<0.01-0.03) compared to STH-uninfected/dewormed children. There were no differences by infection/treatment status for reaction time, school attendance and scholastic achievement (SMD: -0.26 to -0.16, P = 0.06-0.19). Heterogeneity of the pooled effects in all six domains was high (P<0.01; I2 = 66-99%). Application of outlier treatment reduced heterogeneity in learning domain (P = 0.12; I2 = 33%) and strengthened STH-related associations in all domains but intelligence (SMD: -0.20, P = 0.09). Results varied by study design and ROB. Among experimental intervention studies, there was no association between STH treatment and educational loss/performance in tests of memory, reaction time and innate intelligence (SMD: -0.27 to 0.17, P = 0.18-0.69). Infection-related deficits in learning persisted within design/ROB levels (SMD: -0.37 to -52, P<0.01) except for pre-vs post intervention design (n = 3 studies, SMD = -0.43, P = 0.47). Deficits in memory, reaction time and innate intelligence persisted within observational studies (SMD: -0.23 to -0.38, all P<0.01) and high ROB strata (SMD:-0.37 to -0.83, P = 0.07 to <0.01). Further, in Schistosoma infection co-prevalent settings, associations were generally stronger and statistically robust for STH-related deficits in learning, memory and reaction time tests(SMD:-0.36 to -0.55, P = 0.003-0.02). STH-related deficits in school attendance and scholastic achievement was noted in low (SMD:-0.57, P = 0.05) and high ROB strata respectively. INTERPRETATION: We provide evidence of superior performance in five of six educational and cognitive domains assessed for STH uninfected/dewormed versus STH infected/not-dewormed school-aged children from helminth endemic regions. Cautious interpretation is warranted due to high ROB in some of the primary literature and high between study variability in most domains. Notwithstanding, this synthesis provides empirical support for a cognitive and educational benefit of deworming. The benefit of deworming will be enhanced by strategically employing, integrated interventions. Thus, multi-pronged inter-sectoral strategies that holistically address the environmental and structural roots of child cognitive impairment and educational loss in the developing world may be needed to fully realize the benefit of mass deworming programs.
[Mh] Termos MeSH primário: Disfunção Cognitiva/parasitologia
Testes de Memória e Aprendizagem
Esquistossomose/patologia
Esquistossomose/transmissão
Solo/parasitologia
[Mh] Termos MeSH secundário: Adolescente
Albendazol/uso terapêutico
Animais
Anti-Helmínticos/uso terapêutico
Criança
Pré-Escolar
Cognição/fisiologia
Avaliação Educacional
Função Executiva/fisiologia
Seres Humanos
Mebendazol/uso terapêutico
Schistosoma/isolamento & purificação
Esquistossomose/tratamento farmacológico
Esquistossomose/parasitologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Anthelmintics); 0 (Soil); 81G6I5V05I (Mebendazole); F4216019LN (Albendazole)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180210
[Lr] Data última revisão:
180210
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005523


  3 / 1825 MEDLINE  
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[PMID]:29218962
[Ti] Título:Schistosomiasis and soil-transmitted helminthiases: number of people treated in 2016.
[Ti] Título:Schistosomiase et géohelminthiases: nombre de personnes traitées en 2016..
[So] Source:Wkly Epidemiol Rec;92(49):749-60, 2017 Dec 08.
[Is] ISSN:0049-8114
[Cp] País de publicação:Switzerland
[La] Idioma:eng; fre
[Mh] Termos MeSH primário: Anti-Helmínticos/uso terapêutico
Helmintíase/tratamento farmacológico
Helmintíase/epidemiologia
Mebendazol/uso terapêutico
Esquistossomose/tratamento farmacológico
Esquistossomose/epidemiologia
Solo/parasitologia
[Mh] Termos MeSH secundário: Adulto
África/epidemiologia
Albendazol/uso terapêutico
Américas/epidemiologia
Ásia/epidemiologia
Criança
Pré-Escolar
Feminino
Helmintíase/transmissão
Seres Humanos
Lactente
Masculino
Região do Mediterrâneo/epidemiologia
Praziquantel/uso terapêutico
Esquistossomose/transmissão
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthelmintics); 0 (Soil); 6490C9U457 (Praziquantel); 81G6I5V05I (Mebendazole); F4216019LN (Albendazole)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171208
[Lr] Data última revisão:
171208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE


  4 / 1825 MEDLINE  
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[PMID]:29080749
[Au] Autor:Kim YJ; Sung D; Oh E; Cho Y; Cho TM; Farrand L; Seo JH; Kim JY
[Ad] Endereço:Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Department of Biomedical Research Center and Rare Diseases Institute, Korea University Guro Hospital, Korea University, Seoul 152-703, Republic of
[Ti] Título:Flubendazole overcomes trastuzumab resistance by targeting cancer stem-like properties and HER2 signaling in HER2-positive breast cancer.
[So] Source:Cancer Lett;412:118-130, 2018 Jan 01.
[Is] ISSN:1872-7980
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Although trastuzumab provides significant clinical benefit for HER2-positive breast cancers, responses are limited by the emergence of resistance. Trastuzumab resistance is a multi-factorial phenomenon thought to arise from the presence of cancer stem cells and interactions between truncated p95HER2 and HER family members. Flubendazole (FLU) is a potent anthelmintic agent with an exceptional safety profile. Evidence also suggests that it can act as an anticancer agent in several cancer cell types. We sought to investigate the effect of FLU on apoptosis, HER2/Akt signaling, breast cancer stem cell (BCSC)-like properties and trastuzumab resistance in HER2-positive breast cancer cells. FLU treatment induced apoptosis, associated with a significant downregulation of truncated p95HER2, phospho-HER2, phospho-HER3 and phospho-Akt levels, as well as suppression of HER2/HER3 hetero-dimerization in both trastuzumab-sensitive and -resistant lines. FLU effectively targeted BCSC-like properties including aldehyde dehydrogenase 1 (ALDH1) expression and the CD44 /CD24 phenotype, concomitant with a suppression of mammosphere-forming ability. FLU administration also caused significant tumor suppression in trastuzumab-resistant xenografts, coinciding with the downregulation of BCSC-related markers and intracellular HER2. These findings highlight the mechanisms of action of FLU in overcoming trastuzumab resistance in breast cancer.
[Mh] Termos MeSH primário: Antineoplásicos Imunológicos/farmacologia
Neoplasias da Mama/tratamento farmacológico
Mebendazol/análogos & derivados
Células-Tronco Neoplásicas/efeitos dos fármacos
Receptor ErbB-2/fisiologia
Transdução de Sinais/efeitos dos fármacos
Trastuzumab/farmacologia
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Neoplasias da Mama/química
Neoplasias da Mama/patologia
Caspases/metabolismo
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Resistência a Medicamentos Antineoplásicos
Feminino
Seres Humanos
Mebendazol/farmacologia
Camundongos
Camundongos Endogâmicos BALB C
Receptor ErbB-2/análise
Transdução de Sinais/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Immunological); 81G6I5V05I (Mebendazole); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, ErbB-2); EC 3.4.22.- (Caspases); P188ANX8CK (Trastuzumab); R8M46911LR (flubendazole)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171205
[Lr] Data última revisão:
171205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171030
[St] Status:MEDLINE


  5 / 1825 MEDLINE  
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[PMID]:28945752
[Au] Autor:Yang CA; Liang C; Lin CL; Hsiao CT; Peng CT; Lin HC; Chang JG
[Ad] Endereço:Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan.
[Ti] Título:Impact of Enterobius vermicularis infection and mebendazole treatment on intestinal microbiota and host immune response.
[So] Source:PLoS Negl Trop Dis;11(9):e0005963, 2017 Sep.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Previous studies on the association of enterobiasis and chronic inflammatory diseases have revealed contradictory results. The interaction of Enterobius vermicularis infection in particular with gut microbiota and induced immune responses has never been thoroughly examined. METHODOLOGY/FINDINGS: In order to answer the question of whether exposure to pinworm and mebendazole can shift the intestinal microbial composition and immune responses, we recruited 109 (30 pinworm-negative, 79 pinworm-infected) first and fourth grade primary school children in Taichung, Taiwan, for a gut microbiome study and an intestinal cytokine and SIgA analysis. In the pinworm-infected individuals, fecal samples were collected again at 2 weeks after administration of 100 mg mebendazole. Gut microbiota diversity increased after Enterobius infection, and it peaked after administration of mebendazole. At the phylum level, pinworm infection and mebendazole deworming were associated with a decreased relative abundance of Fusobacteria and an increased proportion of Actinobacteria. At the genus level, the relative abundance of the probiotic Bifidobacterium increased after enterobiasis and mebendazole treatment. The intestinal SIgA level was found to be lower in the pinworm-infected group, and was elevated in half of the mebendazole-treated group. A higher proportion of pre-treatment Salmonella spp. was associated with a non-increase in SIgA after mebendazole deworming treatment. CONCLUSIONS/SIGNIFICANCE: Childhood exposure to pinworm plus mebendazole is associated with increased bacterial diversity, an increased abundance of Actinobacteria including the probiotic Bifidobacterium, and a decreased proportion of Fusobacteria. The gut SIgA level was lower in the pinworm-infected group, and was increased in half of the individuals after mebendazole deworming treatment.
[Mh] Termos MeSH primário: Citocinas/imunologia
Enterobíase/tratamento farmacológico
Enterobíase/imunologia
Enterobius/efeitos dos fármacos
Microbioma Gastrointestinal/efeitos dos fármacos
Mebendazol/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Bifidobacterium/efeitos dos fármacos
Bifidobacterium/genética
Bifidobacterium/crescimento & desenvolvimento
Bifidobacterium/isolamento & purificação
Criança
Pré-Escolar
Biologia Computacional
Citocinas/biossíntese
Enterobíase/microbiologia
Enterobíase/parasitologia
Enterobius/genética
Enterobius/imunologia
Fezes/parasitologia
Feminino
Fusobactérias/efeitos dos fármacos
Fusobactérias/genética
Fusobactérias/crescimento & desenvolvimento
Fusobactérias/isolamento & purificação
Microbioma Gastrointestinal/genética
Seres Humanos
Imunidade/efeitos dos fármacos
Imunoglobulina A Secretora/análise
Imunoglobulina A Secretora/imunologia
Intestinos/efeitos dos fármacos
Intestinos/imunologia
Intestinos/microbiologia
Intestinos/parasitologia
Masculino
Mebendazol/administração & dosagem
Salmonella/efeitos dos fármacos
Salmonella/genética
Salmonella/crescimento & desenvolvimento
Salmonella/isolamento & purificação
Taiwan/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (Immunoglobulin A, Secretory); 81G6I5V05I (Mebendazole)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170926
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005963


  6 / 1825 MEDLINE  
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[PMID]:28842127
[Au] Autor:Arbildi P; Turell L; López V; Alvarez B; Fernández V
[Ad] Endereço:Cátedra de Inmunología/DEPBIO, Facultad de Química, Universidad de la República, Montevideo, 11600, Uruguay.
[Ti] Título:Mechanistic insights into EgGST1, a Mu class glutathione S-transferase from the cestode parasite Echinococcus granulosus.
[So] Source:Arch Biochem Biophys;633:15-22, 2017 Nov 01.
[Is] ISSN:1096-0384
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glutathione transferases (GSTs) comprise a major detoxification system in helminth parasites, displaying both catalytic and non-catalytic activities. The kinetic mechanism of these enzymes is complex and depends on the isoenzyme which is being analyzed. Here, we characterized the kinetic mechanism of rEgGST1, a recombinant form of a cytosolic GST from Echinococcus granulosus (EgGST1), which is related to the Mu-class of mammalian enzymes, using the canonical substrates glutathione (GSH) and 1-chloro-2,4-dinitrobenzene (CDNB). Initial rate and product inhibition studies were consistent with a steady-state random sequential mechanism, where both substrates are bound to the enzyme before the products are released. Kinetic constants were also determined (pH 6.5 and 30 °C). Moreover, rEgGST1 lowered the pK of GSH from 8.71 ± 0.07 to 6.77 ± 0.08, and enzyme-bound GSH reacted with CDNB 1 × 10 times faster than free GSH at pH 7.4. Finally, the dissociation of the enzyme-GSH complex was studied by means of intrinsic fluorescence, as well as that of the complex with the anthelminth drug mebendazole. This is the first report on mechanistic issues related to a helminth parasitic GST.
[Mh] Termos MeSH primário: Echinococcus granulosus/química
Glutationa Transferase/metabolismo
Glutationa/metabolismo
Proteínas de Helminto/metabolismo
Proteínas Recombinantes de Fusão/metabolismo
[Mh] Termos MeSH secundário: Animais
Anti-Helmínticos/farmacologia
Clonagem Molecular
Dinitroclorobenzeno/metabolismo
Echinococcus granulosus/enzimologia
Escherichia coli/genética
Escherichia coli/metabolismo
Expressão Gênica
Glutationa Transferase/antagonistas & inibidores
Glutationa Transferase/genética
Proteínas de Helminto/antagonistas & inibidores
Proteínas de Helminto/genética
Concentração de Íons de Hidrogênio
Inativação Metabólica/genética
Isoenzimas/genética
Isoenzimas/metabolismo
Cinética
Mebendazol/farmacologia
Ligação Proteica
Proteínas Recombinantes de Fusão/genética
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthelmintics); 0 (Helminth Proteins); 0 (Isoenzymes); 0 (Recombinant Fusion Proteins); 81G6I5V05I (Mebendazole); EC 2.5.1.18 (Glutathione Transferase); GAN16C9B8O (Glutathione); GE3IBT7BMN (Dinitrochlorobenzene)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170827
[St] Status:MEDLINE


  7 / 1825 MEDLINE  
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[PMID]:28590167
[Au] Autor:Zhao J; Han Q; Liao C; Wang J; Wu L; Liu Q; Lindsay DS
[Ad] Endereço:Laboratory of Tropical Veterinary Medicine and Vector Biology, Hainan Key Laboratory of Sustainable Utilization of Tropical Bioresources, and Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou, Hainan 570228, China. Correspondence should be sent to Qi
[Ti] Título:Effects of In Vivo and In Vitro Treatment of Ascaris suum Eggs with Anthelmintic Agents on Embryonation and Infectivity for Mice.
[So] Source:J Parasitol;103(5):598-601, 2017 Oct.
[Is] ISSN:1937-2345
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ascaris suum is an important intestinal nematode causing economic losses in swine. Anthelminthic treatment is used to control A. suum infections and is part of normal production practices. Treatment with anthelminthic agents results in expulsion of adult worms from the intestinal tract and ends further contamination of the environment with eggs. The present study was conducted to determine the effects of drug treatment on the embryonation of A. suum eggs collected from worms obtained from pigs treated with 4 different commercially available anthelmintics. The effects of treatment with abamectin, doramectin, ivermectin, flubendazole, or no treatment on embryonation of A. suum eggs collected from female A. suum expelled in the feces was determined. The embryonation of eggs obtained from pigs treated with abamectin, doramectin, and ivermectin was not significantly (P > 0.05) different from eggs from non-treated control pigs. In contrast, the embryonation of A. suum eggs collected from worms from pigs treated with flubendazole demonstrated inhibited development, and most eggs remained in the 1-cell stage (85.5%) and only 6.3% of eggs developed larvae. In another experiment, we examined the direct effects of doramectin and flubendazole added to solutions of A. suum eggs collected from non-treated control pigs. Egg cultures were exposed to direct in vitro treatment with 0.04-parts per million (ppm) doramectin or 1.0-ppm flubendazole for 24 hr (highest concentrations [C ] of drugs in serum) and then embryonation and infectivity for mice was determined. Treatment of eggs in vitro did not significantly effect (P > 0.05) larval development or oral infectivity for mice. Our study demonstrates that flubendazole fed to pigs results in inhibited embryonation of A. suum eggs. However, direct treatment of A. suum eggs in culture for 24 hr with flubendazole did not inhibit embryonation or oral infectivity of in vitro treated eggs. Anthelmintic treatment of pigs in vivo with abamectin, doramectin, and ivermectin had no significant (P > 0.05) effect on embryonation of A. suum eggs, and 24 hr treatment with doramectin in vitro had no direct effects (P > 0.05) on embryonation or oral infectivity of A. suum eggs.
[Mh] Termos MeSH primário: Anti-Helmínticos/farmacologia
Ascaríase/tratamento farmacológico
Ascaris suum/efeitos dos fármacos
Doenças dos Suínos/parasitologia
[Mh] Termos MeSH secundário: Administração Oral
Ração Animal
Animais
Anti-Helmínticos/administração & dosagem
Anti-Helmínticos/uso terapêutico
Ascaríase/parasitologia
Fezes/parasitologia
Feminino
Injeções Subcutâneas
Ivermectina/administração & dosagem
Ivermectina/análogos & derivados
Ivermectina/farmacologia
Ivermectina/uso terapêutico
Mebendazol/administração & dosagem
Mebendazol/análogos & derivados
Mebendazol/farmacologia
Mebendazol/uso terapêutico
Camundongos
Óvulo/efeitos dos fármacos
Contagem de Ovos de Parasitas/veterinária
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthelmintics); 5U8924T11H (abamectin); 70288-86-7 (Ivermectin); 81G6I5V05I (Mebendazole); KGD7A54H5P (doramectin); R8M46911LR (flubendazole)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170608
[St] Status:MEDLINE
[do] DOI:10.1645/17-21


  8 / 1825 MEDLINE  
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[PMID]:28399389
[Au] Autor:Cánová K; Rozkydalová L; Rudolf E
[Ad] Endereço:Charles University, Faculty of Medicine in Hradec Králové, Department of Medical Biology and Genetics, Hradec Králové, Czech Republic.
[Ti] Título:Anthelmintic Flubendazole and Its Potential Use in Anticancer Therapy.
[So] Source:Acta Medica (Hradec Kralove);60(1):5-11, 2017.
[Is] ISSN:1211-4286
[Cp] País de publicação:Czech Republic
[La] Idioma:eng
[Ab] Resumo:Flubendazole is a widely used anthelmintic drug belonging to benzimidazole group. The molecular mechanism of action of flubendazole is based on its specific binding to tubulin, which results in disruption of microtubule structure and function, and in the interference with the microtubule-mediated transport of secretory vesicles in absorptive tissues of helminths. The microtubule-disrupting properties of benzimidazole derivatives raised recently interest in these compounds as possible anti-cancer agents. In this minireview flubendazole effects towards selected human malignant cells including myeloma, leukemia, neuroblastoma, breast cancer, colorectal cancer and melanoma are discussed along with basic data on its pharmacokinetics, metabolism and toxicity.
[Mh] Termos MeSH primário: Senescência Celular/efeitos dos fármacos
Leucemia/tratamento farmacológico
Mebendazol/análogos & derivados
Microtúbulos/metabolismo
Mieloma Múltiplo/tratamento farmacológico
[Mh] Termos MeSH secundário: Sobrevivência Celular
Relação Dose-Resposta a Droga
Seres Humanos
Mebendazol/uso terapêutico
Tubulina (Proteína)/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Tubulin); 81G6I5V05I (Mebendazole); R8M46911LR (flubendazole)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170412
[St] Status:MEDLINE
[do] DOI:10.14712/18059694.2017.44


  9 / 1825 MEDLINE  
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[PMID]:28274133
[Au] Autor:Vigh T; Démuth B; Balogh A; Galata DL; Van Assche I; Mackie C; Vialpando M; Van Hove B; Psathas P; Borbás E; Pataki H; Boeykens P; Marosi G; Verreck G; Nagy ZK
[Ad] Endereço:a Department of Organic Chemistry and Technology , Budapest University of Technology and Economics , Budapest , Hungary.
[Ti] Título:Oral bioavailability enhancement of flubendazole by developing nanofibrous solid dosage forms.
[So] Source:Drug Dev Ind Pharm;43(7):1126-1133, 2017 Jul.
[Is] ISSN:1520-5762
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The bioavailability of the anthelminthic flubendazole was remarkably enhanced in comparison with the pure crystalline drug by developing completely amorphous electrospun nanofibres with a matrix consisting of hydroxypropyl-ß-cyclodextrin and polyvinylpyrrolidone. The thus produced formulations can potentially be active against macrofilariae parasites causing tropical diseases, for example, river blindness and elephantiasis, which affect altogether more than a hundred million people worldwide. The bioavailability enhancement was based on the considerably improved dissolution. The release of a dose of 40 mg could be achieved within 15 min. Accordingly, administration of the nanofibrous system ensured an increased plasma concentration profile in rats in contrast to the practically non-absorbable crystalline flubendazole. Furthermore, easy-to-grind fibers could be developed, which enabled compression of easily administrable immediate release tablets.
[Mh] Termos MeSH primário: Mebendazol/análogos & derivados
Nanofibras/química
Povidona/química
Comprimidos/química
beta-Ciclodextrinas/química
[Mh] Termos MeSH secundário: 2-Hidroxipropil-beta-Ciclodextrina
Administração Oral
Animais
Disponibilidade Biológica
Química Farmacêutica
Cristalização
Mebendazol/administração & dosagem
Mebendazol/química
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Tablets); 0 (beta-Cyclodextrins); 1I96OHX6EK (2-Hydroxypropyl-beta-cyclodextrin); 81G6I5V05I (Mebendazole); FZ989GH94E (Povidone); R8M46911LR (flubendazole)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170310
[St] Status:MEDLINE
[do] DOI:10.1080/03639045.2017.1298121


  10 / 1825 MEDLINE  
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[PMID]:28157711
[Au] Autor:Simbulan-Rosenthal CM; Dakshanamurthy S; Gaur A; Chen YS; Fang HB; Abdussamad M; Zhou H; Zapas J; Calvert V; Petricoin EF; Atkins MB; Byers SW; Rosenthal DS
[Ad] Endereço:Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC, USA.
[Ti] Título:The repurposed anthelmintic mebendazole in combination with trametinib suppresses refractory NRASQ61K melanoma.
[So] Source:Oncotarget;8(8):12576-12595, 2017 Feb 21.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Structure-based drug repositioning in addition to random chemical screening is now a viable route to rapid drug development. Proteochemometric computational methods coupled with kinase assays showed that mebendazole (MBZ) binds and inhibits kinases important in cancer, especially both BRAFWT and BRAFV600E. We find that MBZ synergizes with the MEK inhibitor trametinib to inhibit growth of BRAFWT-NRASQ61K melanoma cells in culture and in xenografts, and markedly decreased MEK and ERK phosphorylation. Reverse Phase Protein Array (RPPA) and immunoblot analyses show that both trametinib and MBZ inhibit the MAPK pathway, and cluster analysis revealed a protein cluster showing strong MBZ+trametinib - inhibited phosphorylation of MEK and ERK within 10 minutes, and its direct and indirect downstream targets related to stress response and translation, including ElK1 and RSKs within 30 minutes. Downstream ERK targets for cell cycle, including cMYC, were down-regulated, consistent with S- phase suppression by MBZ+trametinib, while apoptosis markers, including cleaved caspase-3, cleaved PARP and a sub-G1 population, were all increased with time. These data suggest that MBZ, a well-tolerated off-patent approved drug, should be considered as a therapeutic option in combination with trametinib, for patients with NRASQ61mut or other non-V600E BRAF mutant melanomas.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Proliferação Celular/efeitos dos fármacos
Mebendazol/farmacologia
Melanoma/patologia
Piridonas/farmacologia
Pirimidinonas/farmacologia
[Mh] Termos MeSH secundário: Animais
Antinematódeos/farmacologia
Linhagem Celular Tumoral
GTP Fosfo-Hidrolases
Seres Humanos
Immunoblotting
Melanoma/genética
Proteínas de Membrana
Camundongos
Análise Serial de Proteínas
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antinematodal Agents); 0 (Membrane Proteins); 0 (Pyridones); 0 (Pyrimidinones); 33E86K87QN (trametinib); 81G6I5V05I (Mebendazole); EC 3.6.1.- (GTP Phosphohydrolases); EC 3.6.1.- (NRAS protein, human)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170204
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.14990



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