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1.
Medicina (Kaunas) ; 57(8)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34441007

RESUMO

Background and Objectives: Seasonal climatic changes may affect the development of the rash that is characteristic of treatment with anti-epidermal growth factor receptor (EGFR) antibodies. We evaluated the association between seasons and rash incidence among patients with cancer. Materials and Methods: Data from patients with colorectal or head and neck cancer treated with cetuximab or panitumumab during summer (S group; n = 34) or winter (W group; n = 37) between June 2014 and February 2019 were collected to retrospectively examine patient characteristics and rash incidence ≤ 8 weeks after treatment initiation. Results: Rashes were observed in 73.5% (n = 25) and 78.4% (n = 29) and grade 3 rashes were observed in 17.6% (n = 6) and 2.7% (n = 1) of the patients in the S and W groups, respectively. The incidence of grade ≥ 2 rashes in males in the S group was higher than that in the rest of the patient groups (p < 0.01). Conclusions: The higher incidence of skin rashes in males during summer might be attributed to the effects of ultraviolet light, lack of skincare, male hormones, and secretion of anti-EGFR antibodies in sweat. These findings highlight the need for research on preventive measures for such rashes.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Exantema , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Cetuximab/efeitos adversos , Mudança Climática , Neoplasias Colorretais/tratamento farmacológico , Receptores ErbB , Exantema/induzido quimicamente , Exantema/epidemiologia , Humanos , Incidência , Masculino , Estudos Retrospectivos , Estações do Ano
2.
Biochem Pharmacol ; 90(2): 159-65, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-24821112

RESUMO

Liver microsomal flavin-containing monooxygenases (FMO, EC 1.14.13.8) 1 and 3 were functionally characterized in terms of expression levels and molecular catalytic capacities in human, cynomolgus monkey, rat, and minipig livers. Liver microsomal FMO3 in humans and monkeys and FMO1 and FMO3 in rats and minipigs could be determined immunochemically with commercially available anti-human FMO3 peptide antibodies or rat FMO1 peptide antibodies. With respect to FMO-dependent N-oxygenation of benzydamine and tozasertib and S-oxygenation of methimazole and sulindac sulfide activities, rat and minipig liver microsomes had high maximum velocity values (Vmax) and high catalytic efficiency (Vmax/Km, Michaelis constant) compared with those for human or monkey liver microsomes. Apparent Km values for recombinantly expressed rat FMO3-mediated N- and S-oxygenations were approximately 10-100-fold those of rat FMO1, although these enzymes had similar Vmax values. The mean catalytic efficiencies (Vmax/Km, 1.4 and 0.4 min(-1)µM(-1), respectively) of recombinant human and monkey FMO3 were higher than those of FMO1, whereas Vmax/Km values for rat and minipig FMO3 were low compared with those of FMO1. Minipig liver microsomal FMO1 efficiently catalyzed N- and S-oxygenation reactions; in addition, the minipig liver microsomal FMO1 concentration was higher than the levels in rats, humans, and monkeys. These results suggest that liver microsomal FMO1 could contribute to the relatively high FMO-mediated drug N- and S-oxygenation activities in rat and minipig liver microsomes and that lower expression of FMO1 in human and monkey livers could be a determinant factor for species differences in liver drug N- and S-oxygenation activities between experimental animals and humans.


Assuntos
Benzidamina/metabolismo , Metimazol/metabolismo , Microssomos Hepáticos/enzimologia , Oxigenases/metabolismo , Piperazinas/metabolismo , Sulindaco/análogos & derivados , Sequência de Aminoácidos , Animais , Humanos , Inativação Metabólica , Cinética , Fígado/enzimologia , Macaca fascicularis , Masculino , Dados de Sequência Molecular , Oxigenases/classificação , Oxigenases/genética , Filogenia , Ratos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Especificidade da Espécie , Sulindaco/metabolismo , Suínos , Porco Miniatura
3.
Sci Rep ; 4: 4513, 2014 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-24675426

RESUMO

The CRISPR/Cas system, in which the Cas9 endonuclease and a guide RNA complementary to the target are sufficient for RNA-guided cleavage of the target DNA, is a powerful new approach recently developed for targeted gene disruption in various animal models. However, there is little verification of microinjection methods for generating knockout mice using this approach. Here, we report the verification of microinjection methods of the CRISPR/Cas system. We compared three methods for injection: (1) injection of DNA into the pronucleus, (2) injection of RNA into the pronucleus, and (3) injection of RNA into the cytoplasm. We found that injection of RNA into the cytoplasm was the most efficient method in terms of the numbers of viable blastocyst stage embryos and full-term pups generated. This method also showed the best overall knockout efficiency.


Assuntos
Sistemas CRISPR-Cas , Marcação de Genes/métodos , Genoma , Microinjeções , Animais , Sequência de Bases , Blastocisto/metabolismo , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Feminino , Masculino , Camundongos , Camundongos Knockout , Dados de Sequência Molecular , Mutação , Reprodutibilidade dos Testes , Alinhamento de Sequência
4.
Biol Pharm Bull ; 28(7): 1229-33, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15997104

RESUMO

Melanogenesis stimulation activities of seven ethanolic extracts obtained from Umbelliferae plants used as Chinese crude drugs, namely the roots of Angelica dahurica BENTH. et HOOK., A. biserrata SHEN et YUAN, Notopterygium incisum TING, Heracleum lanatum MICHX., and H. candicans WALL., and the fruits of Cinidium monnieri (L.) CUSSON and C. formosanum YABE, were examined by using cultured murine B16 melanoma cells. Among them, the extract (5, 25 microg/ml) of H. lanatum showed a potent stimulatory effect on melanogenesis with significant enhancement of cell proliferation in a dose-dependent manner. The melanogenesis stimulatory effects of sixteen coumarins (1-16) isolated from the seven Umbelliferae crude drugs were also examined. Among them, linear-furocoumarins [psoralen (1), xanthotoxin (2), bergapten (3), and isopimpinellin (4)] and angular-furocoumarin [sphondin (13)] exhibited potent melanogenesis stimulation activity. From the view point of structure-activity relationships, it may be assumed that a linear-furocoumarin ring having a hydrogen and/or methoxyl group at 5 and 8 positions such as 1, 2, 3 and 4 was preferable for the melanogenesis stimulation activity. The introduction of a prenyl group into the furocoumarin ring was disadvantageous. Coumarin derivatives having a simple coumarin ring were inactive.


Assuntos
Apiaceae/química , Cumarínicos/farmacologia , Melaninas/biossíntese , Melanoma Experimental/metabolismo , Extratos Vegetais/farmacologia , Animais , Linhagem Celular Tumoral , Melanoma Experimental/patologia , Camundongos
5.
Biol Pharm Bull ; 27(10): 1611-6, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15467205

RESUMO

A methanolic extract from the leaves of Piper nigrum L. showed a significant stimulatory effect on melanogenesis in cultured murine B16 melanoma cells. Activity-guided fractionation of the methanolic extract led to the isolation of two known lignans, (-)-cubebin (1) and (-)-3,4-dimethoxy-3,4-desmethylenedioxycubebin (2), together with a new lignan, (-)-3-desmethoxycubebinin (3). Among these lignans, 1 and 2 showed a significant stimulatory activity of melanogenesis without any significant effects on cell proliferation.


Assuntos
Lignanas/farmacologia , Melaninas/biossíntese , Piper nigrum , Animais , Proliferação de Células/efeitos dos fármacos , Lignanas/química , Lignanas/isolamento & purificação , Melanoma Experimental , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta , Células Tumorais Cultivadas
6.
Phytother Res ; 17(7): 797-800, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12916080

RESUMO

A 70% methanol extract from red ginseng (steamed and dried roots of Panax ginseng C. A. Meyer, a kind of Ginseng Radix) had superior activity to that of white ginseng (peeled and dried root of P. ginseng, another kind of Ginseng Radix) in a hair growth promoting assay using mouse vibrissal follicles in organ culture. Of the major constituents of P. ginseng, ginsenoside-Rb(1) (G-Rb(1)) exhibited activity, but ginsenoside-Rg(1) (G-Rg(1)) and -Ro (G-Ro) were ineffective. Additionally, 20(S)-ginsenoside-Rg(3) (20(S)-G-Rg(3)) formed by the processing of red ginseng from the crude root of P. ginseng also showed hair growth promoting activity. These results indicate that Ginseng Radix possesses hair growth promoting activity, and its bioactive components are partially attributable to the ginseng saponin components mentioned above.


Assuntos
Folículo Piloso/efeitos dos fármacos , Panax , Fitoterapia , Extratos Vegetais/farmacologia , Animais , Relação Dose-Resposta a Droga , Camundongos , Camundongos Endogâmicos , Técnicas de Cultura de Órgãos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Raízes de Plantas
7.
Biol Pharm Bull ; 25(5): 622-6, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-12033503

RESUMO

The aqueous ethanol extract of Lygodii Spora (spore of Lygodium japonicum (Thunb.) Sw.) showed in vitro testosterone 5alpha-reductase inhibitory activity and in vivo anti-androgenic activity using growth of flank organ in castrated Syrian hamsters and hair regrowth after shaving in testosterone-treated C57Black/6CrSlc mice. From the lipophilic constituents of Lygodii Spora, oleic, linoleic and palmitic acids were identified as the main active principles inhibiting testosterone 5alpha-reductase.


Assuntos
Inibidores de 5-alfa Redutase , Antagonistas de Androgênios/farmacologia , Inibidores Enzimáticos/farmacologia , Gleiquênias/química , Cabelo/crescimento & desenvolvimento , Nandrolona/análogos & derivados , Esporos/química , Animais , Cricetinae , Ácidos Graxos/farmacologia , Cabelo/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nandrolona/farmacologia , Testosterona/farmacologia
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