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1.
JCI Insight ; 3(6)2018 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-29563330

RESUMO

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are a population of immature immune cells with several protumorigenic functions. CD38 is a transmembrane receptor-ectoenzyme expressed by MDSCs in murine models of esophageal cancer. We hypothesized that CD38 could be expressed on MDSCs in human colorectal cancer (CRC), which might allow for a new perspective on therapeutic targeting of human MDSCs with anti-CD38 monoclonal antibodies in this cancer. METHODS: Blood samples were collected from 41 CRC patients and 8 healthy donors, followed by peripheral blood mononuclear cell (PBMC) separation. Polymorphonuclear (PMN-) and monocytic (M-) MDSCs and CD38 expression levels were quantified by flow cytometry. The immunosuppressive capacity of M-MDSCs from 10 CRC patients was validated in a mixed lymphocyte reaction (MLR) assay. RESULTS: A significant expansion of CD38+ M-MDSCs and a trend of expansion of CD38+ PMN-MDSCs (accompanied by a trend of increased CD38 expression on both M- and PMN-MDSCs) were observed in PBMCs of CRC patients when compared with healthy donors. The CD38+ M-MDSCs from CRC patients were found to be immunosuppressive when compared with mature monocytes. CD38+ M- and PMN-MDSC frequencies were significantly higher in CRC patients who previously received treatment when compared with treatment-naive patients. CONCLUSIONS: This study provides a rationale for an attempt to target M-MDSCs with an anti-CD38 monoclonal antibody in metastatic CRC patients. FUNDING: NCI P01-CA14305603, the American Cancer Society, Scott and Suzi Lustgarten Family Colon Cancer Research Fund, Hansen Foundation, and Janssen Research and Development.


Assuntos
ADP-Ribosil Ciclase 1/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Esofágicas/metabolismo , Leucócitos Mononucleares/metabolismo , Glicoproteínas de Membrana/metabolismo , Células Supressoras Mieloides/metabolismo , Neutrófilos/metabolismo , ADP-Ribosil Ciclase 1/imunologia , Adulto , Idoso , Animais , Anticorpos Monoclonais , Neoplasias Colorretais/imunologia , Neoplasias Esofágicas/imunologia , Feminino , Humanos , Imunossupressores/farmacologia , Linfócitos , Masculino , Glicoproteínas de Membrana/imunologia , Camundongos , Pessoa de Meia-Idade , Monócitos , Pennsylvania
2.
Colloids Surf B Biointerfaces ; 140: 421-429, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26784658

RESUMO

Bacterial cellulose (BC) films modified by the in situ method with the addition of alginate (Alg) during the microbial cultivation of Gluconacetobacter hansenii under static conditions increased the loading of doxorubicin by at least three times. Biophysical analysis of BC-Alg films by scanning electron microscopy, thermogravimetry, X-ray diffraction and FTIR showed a highly homogeneous interpenetrated network scaffold without changes in the BC crystalline structure but with an increased amorphous phase. The main molecular interactions determined by FTIR between both biopolymers clearly suggest high compatibility. These results indicate that alginate plays a key role in the biophysical properties of the hybrid BC matrix. BC-Alg scaffold analysis by nitrogen adsorption isotherms revealed by the Brunauer-Emmett-Teller (BET) method an increase in surface area of about 84% and in pore volume of more than 200%. The Barrett-Joyner-Halenda (BJH) model also showed an increase of about 25% in the pore size compared to the BC film. Loading BC-Alg scaffolds with different amounts of doxorubicin decreased the cell viability of HT-29 human colorectal adenocarcinoma cell line compared to the free Dox from around 95-53% after 24h and from 63% to 37% after 48 h. Dox kinetic release from the BC-Alg nanocomposite displayed hyperbolic curves related to the different amounts of drug payload and was stable for at least 14 days. The results of the BC-Alg nanocomposites show a promissory potential for anticancer therapies of solid tumors.


Assuntos
Alginatos/química , Celulose/química , Doxorrubicina/farmacologia , Gluconacetobacter/química , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Celulose/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Liberação Controlada de Fármacos , Ácido Glucurônico/química , Células HT29 , Ácidos Hexurônicos/química , Humanos , Microscopia Eletrônica de Varredura , Nanocompostos/química , Nanocompostos/ultraestrutura , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Alicerces Teciduais/química , Difração de Raios X
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