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1.
Pharmaceutics ; 13(12)2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34959268

RESUMO

The anticancer properties of fucoidan have been widely studied in cancer research. However, the lack of safety information on the parenteral administration of fucoidan and its rapid clearance from the system have limited its application. Herein, we assessed the therapeutic efficacy and safety of fucoidan and developed fucoidan nanoparticles (FuNPs) to enhance their therapeutic effect in the mouse model of breast cancer. FuNPs were synthesized through the emulsion method, and the stable colloid has an average size of 216.3 nm. FuNPs were efficiently internalized into breast cancer cells in vitro, demonstrating an enhanced antitumor activity in comparison with free form fucoidan. After the treatment of FuNPs, the tumor progression was significantly inhibited in viv. The tumor volume was reduced by 2.49-fold compared with the control group. Moreover, the inhibition of the invasion of tumor cells into the lungs revealed the antimetastatic properties of the FuNPs. FuNPs, as naturally marine polysaccharide-based nanoparticles, have shown their broader therapeutic window and enhanced antimetastatic ability, opening an avenue to the development of the inherently therapeutic nanomedicines.

2.
Sci Rep ; 10(1): 20319, 2020 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230218

RESUMO

Pancreatic cancer is one of the most lethal and chemo-resistant cancers worldwide. Growing evidence supports the theory that the gut microbiota plays an essential role in modulating the host response to anti-cancer therapy. The present study aimed to explore the effect of probiotics as an adjuvant during chemotherapy for pancreatic cancer. An LSL-KrasG12D/--Pdx-1-Cre mouse model of pancreatic ductal adenocarcinoma (PDAC) was created to study the effects of using four-week multi-strain probiotics (Lactobacillus paracasei GMNL-133 and Lactobacillus reuteri GMNL-89) as an adjuvant therapy for controlling cancer progression. At 12 weeks of age, pancreatitis was induced in the mice by two intraperitoneal injection with caerulein (25 µg/kg 2 days apart). Over the next 4 weeks the mice were treated with intraperitoneal injections of gemcitabine in combination with the oral administration of probiotics. The pancreas was then harvested for analysis. Following caerulein treatment, the pancreases of the LSL-KrasG12D/--Pdx-1-Cre transgenic mice exhibited more extensive pancreatic intraepithelial neoplasia (PanIN) formation. Combined treatment with gemcitabine and probiotics revealed a lower grade of PanIN formation and a decrease in the expression of vimentin and Ki-67. Mice that received gemcitabine in combination with probiotics had lower aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Notably, the use of high-dose probiotics alone without gemcitabine also had an inhibitory effect on PanIN changes and serum liver enzyme elevation. These findings suggest that probiotics are able to make standard chemotherapy more effective and could help improve the patient's tolerance of chemotherapy.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Carcinoma Ductal Pancreático/dietoterapia , Carcinoma Ductal Pancreático/tratamento farmacológico , Desoxicitidina/análogos & derivados , Lactobacillus , Neoplasias Pancreáticas/dietoterapia , Neoplasias Pancreáticas/tratamento farmacológico , Probióticos/administração & dosagem , Administração Oral , Animais , Carcinoma Ductal Pancreático/induzido quimicamente , Carcinoma Ductal Pancreático/microbiologia , Ceruletídeo/efeitos adversos , Desoxicitidina/administração & dosagem , Modelos Animais de Doenças , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neoplasias Pancreáticas/induzido quimicamente , Neoplasias Pancreáticas/microbiologia , Resultado do Tratamento , Gencitabina
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