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1.
Pharm Biol ; 62(1): 676-690, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39345207

RESUMO

CONTEXT: Epigallocatechin-3-gallate (EGCG), the predominant catechin in green tea, has shown the potential to combat various types of cancer cells through its ability to modulate multiple signaling pathways. However, its low bioavailability and rapid degradation hinder its clinical application. OBJECTIVE: This review explores the potential of nanoencapsulation to enhance the stability, bioavailability, and therapeutic efficacy of EGCG in cancer treatment. METHODS: We searched the PubMed database from 2019 to the present, using 'epigallocatechin gallate', 'EGCG', and 'nanoparticles' as search terms to identify pertinent literature. This review examines recent nano-engineering technology advancements that encapsulate EGCG within various nanocarriers. The focus was on evaluating the types of nanoparticles used, their synthesis methods, and the technologies applied to optimize drug delivery, diagnostic capabilities, and therapeutic outcomes. RESULTS: Nanoparticles improve the physicochemical stability and pharmacokinetics of EGCG, leading to enhanced therapeutic outcomes in cancer treatment. Nanoencapsulation allows for targeted drug delivery, controlled release, enhanced cellular uptake, and reduced premature degradation of EGCG. The studies highlighted include those where EGCG-loaded nanoparticles significantly inhibited tumor growth in various models, demonstrating enhanced penetration and efficacy through active targeting mechanisms. CONCLUSIONS: Nanoencapsulation of EGCG represents a promising approach in oncology, offering multiple therapeutic benefits over its unencapsulated form. Although the results so far are promising, further research is necessary to fully optimize the design of these nanosystems to ensure their safety, efficacy, and clinical viability.


Assuntos
Catequina , Nanopartículas , Neoplasias , Catequina/análogos & derivados , Catequina/administração & dosagem , Catequina/química , Catequina/farmacologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Animais , Disponibilidade Biológica , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Chá/química
2.
J Asian Nat Prod Res ; 22(4): 346-352, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30924356

RESUMO

Two new compounds 7-hydroxy-4'-methoxy-3'-(7''-hydroxy-3'',7''-dimethyl-octa-2'',5''-dienyl)-isoflavone (1) and 7-hydroxy-4'-methoxy-3'-(6''-hydroxy-3'',7''-dimethyl-octa-2'',7''-dienyl)-isoflavone (2), together with five known compounds (3-7), were isolated from EtOAc-soluble extract of the seeds of Psoralea corylifolia. Their structures were elucidated on the basis of detailed spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against diacylglycerol acyltransferase (DGAT). And compounds 1-7 displayed significant inhibitory activity on DGAT1 with IC50 values ranging from 51.2 ± 1.1 to 116.4 ± 1.3 µM.


Assuntos
Isoflavonas , Psoralea , Diacilglicerol O-Aciltransferase , Estrutura Molecular , Sementes
3.
Biomed Chromatogr ; 33(5): e4511, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30773664

RESUMO

The purpose of this study was to develop and validate an LC-MS/MS method for simultaneous determination of idelalisib and GS-563117 in dog plasma. The analytes were extracted using ethyl acetate and then separated on a Waters Acquity UPLC BEH C18 column (50 × 2.1 mm, i. d., 1.7 µm) using 0.1% formic acid in water and acetonitrile as mobile phase at a flow rate of 0.3 mL/min in gradient elution mode. The analytes were quantified using selected reaction monitoring with precursor-to-product transitions at m/z 416.2 → 176.1, m/z 432.2 → 192.1 and m/z 421.2 → 176.1 for idelalisib, GS-563117 and [2 H5 ]-idelalisib (internal standard). The assay showed good linearity (r > 0.9992) over the tested concentration range of 0.1-600 ng/mL for idelalisib and 0.1-300 ng/mL for GS-563117. The intra- and inter-day RSD values for idelalisib and GS-563117 were <8.84 and 12.41%, respectively. The intra- and inter-day RE values were within the range of -7.21-8.52%, and -6.44-14.23%, respectively. The extraction recovery was found to be >84.59% and no matrix effects were observed. The validated LC-MS/MS method has been successfully applied for the simultaneous determination of idelalisib and GS-563117 in a pharmacokinetic study in dogs. Our results suggested that idelalisib was rapidly metabolized into its metabolite GS-563117 in dog and the in vivo exposure of GS-563117 was 17.59% of that of idelalisib.


Assuntos
Cromatografia Líquida/métodos , Purinas/sangue , Purinas/metabolismo , Quinazolinonas/sangue , Quinazolinonas/metabolismo , Espectrometria de Massas em Tandem/métodos , Animais , Cães , Estabilidade de Medicamentos , Limite de Detecção , Modelos Lineares , Masculino , Purinas/química , Purinas/farmacocinética , Quinazolinonas/química , Quinazolinonas/farmacocinética , Reprodutibilidade dos Testes
4.
Biomed Chromatogr ; 32(7): e4219, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29470848

RESUMO

A simple and sensitive liquid chromatography tandem mass spectrometry method was validated for simultaneous quantification of evodiamine and its metabolites 10-hydroxyevodiamine (M1), 18-hydroxyevodiamine (M2), 10-hydroxyevodiamine-glucuronide (M3) and 18-hydroxy- evodiamine-glucuronide (M4) in rat plasma for the first time. The analytes were extracted with acetonitrile and separated on a C18 column within 3 min. The detection was achieved in positive selected reaction monitoring mode with precursor-to-product transitions at m/z 304.1 → 161.1 for evodiamine, m/z 320.1 → 134.1 for M1, m/z 320.1 → 150.1 for M2, m/z 496.2 → 134.1 for M3, m/z 496.2 → 171.1 for M4 and m/z 349.2 → 305.1 for camptothecin (internal standard). The linearity was evident over the tested concentration ranges with correlation coefficients >0.9991. The lower limits of quantification for evodiamine, M1, M2, M3 and M4 were 0.1, 0.1, 0.1, 0.25 and 0.25 ng mL-1 , respectively. Extraction recoveries and matrix effects of the analytes were within the ranges of 84.51-97.21 and 90.13-103.30%, respectively. The accuracy (relative error) ranged from -8.14 to 7.23% while the intra- and inter-day precisions (relative standard deviation) were < 9.31%. The validated assay was successfully applied for the pharmacokinetic study of evodiamine, M1, M2, M3 and M4 in rat. The current study will be helpful in understanding the in vivo disposition of evodiamine.


Assuntos
Cromatografia Líquida/métodos , Quinazolinas/sangue , Quinazolinas/farmacocinética , Espectrometria de Massas em Tandem/métodos , Animais , Estabilidade de Medicamentos , Limite de Detecção , Modelos Lineares , Masculino , Quinazolinas/química , Quinazolinas/metabolismo , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes
5.
Immun Inflamm Dis ; 12(9): e70002, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39222064

RESUMO

OBJECTIVE: Hepatocellular carcinoma (HCC) poses a significant challenge to global health. Its pathophysiology involves interconnected processes, including cell proliferation, autophagy, and macrophage polarization. However, the role of Absent in Melanoma 2 (AIM2) in HCC remains elusive. METHODS: The expression of AIM2 in Huh-7 and Hep3B cell lines was manipulated and cell proliferation, autophagy, apoptosis, and migration/invasion, together with the polarization of M2 macrophages, were evaluated. The markers of autophagy pathway, LC3B, Beclin-1, and P62, underwent examination through Western blot analysis. An autophagy inhibitor, 3-MA, was used to measured the role of autophagy in HCC. Finally, the effect of AIM2 overexpression on HCC was further evaluated using a subcutaneous tumor model in nude mice. RESULTS: Our results established that AIM2 overexpression inhibits HCC cell proliferation, migration, and invasion while promoting apoptosis and autophagy. Conversely, knockdown of AIM2 engendered opposite effects. AIM2 overexpression was correlated with reduced M2 macrophage polarization. The autophagy inhibitor substantiated AIM2's role in autophagy and identified its downstream impact on cell proliferation, migration, invasion, and macrophage polarization. In the in vivo model, overexpression of AIM2 led to the inhibition of HCC tumor growth. CONCLUSION: The findings underscore AIM2's crucial function in modulating major biological processes in HCC, pointing to its potential as a therapeutic target. This study inaugurally demonstrated that AIM2 activates autophagy and influences macrophage polarization, playing a role in liver cancer progression.


Assuntos
Autofagia , Carcinoma Hepatocelular , Movimento Celular , Proliferação de Células , Neoplasias Hepáticas , Macrófagos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Autofagia/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Animais , Humanos , Camundongos , Macrófagos/metabolismo , Macrófagos/imunologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Apoptose/genética , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto , Ativação de Macrófagos/genética
6.
J Mol Diagn ; 23(2): 223-233, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33271368

RESUMO

RNA sequencing (RNA-seq) is a well-validated tool for detecting gene fusions in fresh-frozen tumors; however, RNA-seq is much more challenging to use with formalin-fixed, paraffin-embedded (FFPE) tumor samples. We evaluated the performance of RNA-seq to detect gene fusions in clinical FFPE tumor samples. Our assay identified all 15 spiked-in NTRK fusions from RNA reference material and six known fusions from five cancer cell lines. Limit of detection for the assay was assessed with a series of dilutions of RNA from the cell line H2228. These fusions can be detected when the dilution is down to 10%. Good intra-assay and interassay reproducibility was observed in three specimens. For clinical validation, the assay detected 10 of 12 fusions initially identified by a DNA panel (covering 23 gene fusions) in clinical specimens (83.3% sensitivity), whereas one fusion (MET fusion) was identified in another 34 fusion-negative tumor specimens as determined by the DNA panel (negative prediction value of 94.3%). This MET fusion was confirmed by RT-PCR and Sanger sequencing, which found that this is a false-negative result for the DNA panel. The assay also identified 26 extra fusions not covered by the DNA panel, 20 (76.9%) of which were validated by RT-PCR and Sanger sequencing. Therefore, this RNA assay has reasonable performance and could complement DNA-based next-generation sequencing assays.


Assuntos
Formaldeído/química , Fusão Gênica , Neoplasias/genética , Inclusão em Parafina , Análise de Sequência de RNA , Fixação de Tecidos , Sequência de Bases , Humanos , Reprodutibilidade dos Testes
7.
Oncol Lett ; 17(1): 1167-1171, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30655879

RESUMO

The aim of the study was to investigate the effects of miRNA-101 and miRNA-345 on HBV replication and liver cancer cell growth. qPCR was performed to detect the expression of miRNA-101 and miRNA-345. The expression of HBV RNA was detected by PCR. The expression of HbsAg was detected using ELISA. BEL-7404 cell line proliferation was detected by MTT assay. The expression levels of miR-101 and miR-345 in BEL-7404 pSUPER.neo-miR-101 group and BEL-7404 pSUPER.neo-miR-345 group were significantly higher than those in BEL-7404 pSUPER.neo group (P<0.05). The expression levels of miR-101 and miR-345 in MHCC97-L pSUPER.neo-miR-101 group and MHCC97-L pSUPER.neo-miR-345 group were significantly higher than those in MHCC97-L pSUPER.neo group (P<0.05). The expression of HBV DNA in MHCC97-L pSUPER.neo-miR-101 group was significantly lower than that in MHCC97-L pSUPER.neo group (P<0.05), and the expression of HBV DNA in MHCC97-L pSUPER.neo-miR-345 group was significantly higher than that in MHCC97-L pSUPER.neo group (P<0.05). The expression of HbsAg in MHCC97-L pSUPER.neo-miR-101 group was significantly lower than that in MHCC97-L pSUPER.neo group (P<0.05), and the expression of HbsAg in MHCC97-L pSUPER.neo-miR-345 group was significantly higher than that in MHCC97-L pSUPER.neo group (P<0.05). There was a significant difference in terms of HbsAg expression between the MHCC97-L pSUPER.neo-miR-101 and MHCC97-L pSUPER.neo-miR-345 groups (P<0.05). The proliferation of BEL-7404 cells in the BEL-7404 pSUPER.neo-miR-101 group was significantly lower than that in the BEL-7404 pSUPER.neo group (P<0.05). The proliferation of BEL-7404 cells in the BEL-7404 pSUPER.neo-miR-345 group was significantly higher than that in the BEL-7404 pSUPER.neo group (P<0.05). The proliferation of BEL-7404 cells in BEL-7404 pSUPER.neo-miR-101 group was different from that in BEL-7404 pSUPER.neo-miR-345 group (P<0.05). miR-101 reduced the level of HBV replication, and inhibited the proliferation of liver cancer cells. miR-345 also upregulated the level of HBV replication, and promoted the proliferation of liver cancer cells.

8.
Biomed Pharmacother ; 68(7): 887-92, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25217394

RESUMO

Ganciclovir (GCV) affects the molecular mechanism of cell death and DNA damage by the rAAV (recombinant adeno-associated virus)-mediated Tet-On/HSV-tk/GCV suicide gene system in human breast cancer cell line MCF-7. A rAAV/TRE/Tet-On/HSV-tk combining a Tet-On regulating system and a suicide gene HSV-tk was used to transfect human breast cancer cell line MCF-7, and therapeutic effects on this system were studied. Afterwards, we used RT-PCR, western blotting, and a modified comet-assay to explore the potential mechanism of the HSV-tk/GCV suicide gene system in breast cancer treatments. MTT assay has shown that the cell number of GCV+rAAV+Dox group was significantly decreased compared with that of other groups after treatment and flow cytometric analysis detected that there was a substantial increase of S phase cells in this group, which means the HSV-tk/GCV suicide gene system probably works on the cell cycle. RT-PCR detected the expression level of p21 increased and PCNA had an opposite trend. Western blotting detected the protein expression of p21 and p53 increased and PCNA, CDK1, cyclin B decreased in GCV+rAAV+Dox group. The modified comet-assay shown that the very small extra fragments generated by the GCV+rAAV+Dox group treatment are visible as a small cloud extending from the comet in the direction of electrophoresis. The therapeutic mechanism of the HSV-tk/GCV suicide gene system on human breast cancer cell line MCF-7 is probably by upregulating the expression of p21 through a p53-dependent DNA damage signalling pathway, leading the decrease of protein expression of PCNA, cyclin B, CDK1 in MCF-7 cells and promoting the cell cycle arrest at G1/S phase. In summary, the HSV-tk/GCV suicide gene system arouses the death of MCF-7 cells from blocking the cell cycle and DNA damage.


Assuntos
Morte Celular/genética , Dano ao DNA/genética , Genes Transgênicos Suicidas/genética , Simplexvirus/genética , Antivirais/farmacologia , Proteína Quinase CDC2 , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ciclina B1/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Quinases Ciclina-Dependentes/genética , Dano ao DNA/efeitos dos fármacos , Dependovirus/genética , Fase G1/efeitos dos fármacos , Fase G1/genética , Ganciclovir/farmacologia , Genes Transgênicos Suicidas/efeitos dos fármacos , Vetores Genéticos/genética , Humanos , Células MCF-7 , Antígeno Nuclear de Célula em Proliferação/genética , Fase S/efeitos dos fármacos , Fase S/genética , Proteína Supressora de Tumor p53/genética
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