RESUMEN
BACKGROUND: Chemotherapy-induced adverse effects (CIAEs) remain a challenging problem due to their high incidences and negative impacts on treatment in Chinese colorectal cancer (CRC) patients. We aimed to identify risk factors and predictive markers for CIAEs using food/nutrition data in CRC patients receiving post-operative capecitabine-based chemotherapy. METHODS: Food/nutrition data from 130 Chinese CRC patients were analyzed. Univariate and multivariate analyses were used to identify CIAE-related food/nutrition factors. Prediction models were constructed based on the combination of these factors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the discrimination ability of models. RESULTS: A total of 20 food/nutrition factors associated with CIAEs were identified in the univariate analysis after adjustments for total energy and potential confounding factors. Based on multivariate analysis, we found that, among these factors, dessert, eggs, poultry, and milk were associated with several CIAEs. Most importantly, poultry was an overall protective factor; milk and egg were risk factors for hand-foot syndrome (HFS) and bone marrow suppression (BMS), respectively. Developed multivariate models in predicting grade 1 to 3 CIAEs and grade 2/3 CIAEs both had good discrimination (AUROC values from 0.671 to 0.778, 0.750 to 0.946 respectively), which had potential clinical application value in the early prediction of CIAEs, especially for more severe CIAEs. CONCLUSIONS: Our findings suggest that patients with high milk and egg intakes should be clinically instructed to control their corresponding dietary intake to reduce the likelihood of developing HFS and BMS during capecitabine-based chemotherapy, respectively. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03030508.
Asunto(s)
Antimetabolitos Antineoplásicos , Capecitabina , Neoplasias Colorrectales , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Animales , Antimetabolitos Antineoplásicos/efectos adversos , Capecitabina/efectos adversos , China/epidemiología , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/tratamiento farmacológico , Huevos , Fluorouracilo/efectos adversos , Síndrome Mano-Pie/tratamiento farmacológico , Síndrome Mano-Pie/etiología , Humanos , Leche , Factores de RiesgoRESUMEN
Ligand fishing is a widely used approach for screening active compounds from natural products. Recently, cell membrane (CM) as affinity ligand has been applied in ligand fishing, including cell membrane chromatography (CMC) and CM-coated magnetic bead. However, these methods possess many weaknesses, including complicated preparation processes and time-consuming operation. In this study, cheap and easily available cellulose filter paper (CFP) was selected as carrier of CM and used to fabricate a novel CM-coated CFP (CMCFP) for the first time. The type of CFP was optimized according to the amount of immobilized protein, and the immobilization of CM onto CFP by the insertion and self-fusion process was verified by confocal imaging. The CMCFP exhibited good selectivity and stability and was used for fishing potentially active compounds from extracts of Angelica dahurica. Three potentially active compounds, including bergapten, pabulenol, and imperatorin, were fished out and identified. The traditional Chinese medicine systems pharmacology database and analysis platform was used to build an active compound-target protein network, and accordingly, the gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1) was deduced as potential target of CM for the active compounds of Angelica dahurica. Molecular docking was performed to evaluate the interaction between active compounds and GABRA1, and bergapten was speculated as a new potentially active compound. Compared with other methods, the fishing assay based on CMCFP was more effective, simpler, and cheaper.
Asunto(s)
Productos Biológicos/aislamiento & purificación , Productos Biológicos/farmacología , Celulosa/química , Descubrimiento de Drogas/instrumentación , Membrana Eritrocítica/metabolismo , Filtración/instrumentación , Angelica/química , Animales , Productos Biológicos/química , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Papel , Conejos , Receptores de GABA-A/metabolismoRESUMEN
OBJECTIVE: To study the preparation technique of 5-fluorouracil and the release characteristic of 5-fluorouracil-loaded chitosan microspheres for the intranasal administration. METHODS: 5-fluorouracil-loaded chitosan microspheres were prepared by emulsion chemical cross-link technique. The orthogonal experimental design was used to optimize the preparation procedure. Dynamic dialysis method was applied to determine the release characteristic of microspheres in vitro and its influencing factors. Swelling behavior was expressed by swelling ratio. The degree of mucoadhesion was investigated by determining the mucociliary transport rate(MTR) of the microparticle across a frog palate. RESULTS: Microspheres with a good shape and narrow size distribution were prepared. The average diameter was 43±4 µm. The drug loading was (38.5±1.0) %. The entrapment efficiency was (79.0±1.8) %. The drug release profile in vitro could be described by Higuichi eqution as Q=0.1035t1/2+0.0284 (r=0.9965). Chitosan had good mucoadhesive property and caused a significant reduction in MTR(P<0.01). CONCLUSION: The optimized technique has a good reproducibility and a high entrapment efficiency, so it could be used to prepare 5-fluorouracil-loaded chitosan microspheres for the intranasal administration.Chitosan is a good material for nasal preparation and has prospective development in the pharmaceutical field.