RESUMO
BACKGROUND: Studies have shown that the ideal dose of epidural dexmedetomidine is 0.4â µgâ mL-1 for epidural labor analgesia. However, the appropriate dose of ropivacaine when combined with 0.4â µgâ mL-1 of dexmedetomidine for epidural labor analgesia is still unknown. Therefore, we aimed to determine the dose-response of ropivacaine when using 0.4â µgâ mL-1 of dexmedetomidine as epidural adjuvant for labor analgesia. METHODS: One hundred of nulliparous singleton pregnant patients were randomized allocated into 1 of 5 groups with epidural ropivacaine concentration of 0.05%, 0.0625%, 0.075%, 0.0875%, and 0.1%. Labor analgesia was initialed with 12 mL of the mixed study solution. Effective analgesia was defined as a visual analogue scale <10 mm 30 minutes after the initial epidural bolus. The EC50 and EC95 for epidural ropivacaine was calculated by probit regression. RESULTS: Ninety-three of parturients were involved into the final analysis. Totals of 63.2% (12/19), 73.7% (14/19), 88.9% (16/18), 94.7% (18/19), and 100% (18/18) of parturients in group 0.05, 0.0625, 0.075, 0.0875, and 0.1 received effective epidural labor analgesia. The calculated EC50 and EC95 of epidural ropivacaine were 0.046% (95% CI 0.028-0.054%) and 0.086% (95% CI 0.074-0.137%), respectively. CONCLUSIONS: Under the condition of the study, a bolus of 12 mL ropivacaine 0.086% and dexmedetomidine 0.4â µgâ mL-1 could afford 95% of nulliparous singleton pregnant patients without suffering labor pain after a test dose of lidocaine 45 mg.
Assuntos
Analgesia Epidural , Analgesia Obstétrica , Anestésicos Locais , Dexmedetomidina , Relação Dose-Resposta a Droga , Ropivacaina , Humanos , Feminino , Ropivacaina/administração & dosagem , Gravidez , Dexmedetomidina/administração & dosagem , Método Duplo-Cego , Adulto , Analgesia Epidural/métodos , Anestésicos Locais/administração & dosagem , Estudos Prospectivos , Analgesia Obstétrica/métodos , Analgésicos não Narcóticos/administração & dosagem , Medição da Dor , Dor do Parto/tratamento farmacológico , Adulto JovemRESUMO
Malignant melanoma is an invasive and highly aggressive skin cancer that-if diagnosed-poses a serious threat to the patient's health and life. In this work, a novel purified cell-wall polysaccharide (termed Abwp) was obtained from the discarded stipe of Agaricus bisporus (A. bisporus) and characterized to be a novel homogeneous polysaccharide consisted of a ß-(1 â 4)- glucosyl backbone with ß-(1 â 2) and (1 â 6)-d-glucosyl side-chains. The anti-melanoma effects of Abwp and its associated mechanisms in mice were then explored using in vitro and in vivo approaches. In vitro results showed that Abwp inhibited B16 melanoma cell proliferation and promoted their apoptosis in both time- and dose-dependent manners. In B16 cells induced with tumor necrosis factor (TNF-α), Abwp significantly decreased the protein expression of inflammatory-related signaling pathway (e.g., p38 MAPK and NF-κB) in time-, concentration-, and dose-dependent manners. Moreover, Abwp blocked nuclear entry of NF-κB-p65. In an in vivo mouse model featuring neoplasm transplantation with B16 melanoma cells, Abwp significantly inhibited the growth and proliferation of mouse melanoma. Hematoxylin staining showed that the invasion of melanoma cells into the lung tissue of the Abwp-treated group was significantly reduced. Immunohistochemical analysis showed that the expression of proliferation cell nuclear antigen (PCNA), N-cadherin, MMP-9, and Snail in the lung of mouse was significantly inhibited. Immunofluorescence showed that Abwp significantly interfered with the nuclear transcription of NF-κB-p65 in a dose-dependent manner. Collectively, these results showed that Abwp mediated p38 MAPK and NF-κB signaling pathways to inhibit the inflammatory response and malignant proliferation and metastasis of melanoma in mice.
Assuntos
Melanoma Experimental , NF-kappa B , Animais , Camundongos , NF-kappa B/metabolismo , Melanoma Experimental/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Proliferação de Células , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Linhagem Celular TumoralRESUMO
Lentinan (LNT) isolated from Lentinus edodes is a vital host defense potentiator previously utilized as an adjuvant in cancer therapy. The present study investigated the effect of LNT on the mouse hepatocellular carcinoma (HCC) cell line Hepa16 and its possible mechanism. Mouse HCC apoptosis and its potential associated mechanism were then explored using in vitro and in vivo approaches. For in vitro approaches, the effect of LNT on the proliferation of Hepa16 cells was investigated by Cell Counting Kit8 assay. Annexin VFITC staining and flow cytometry were applied to explore HCC apoptosis. Western blotting was used to analyze related proteins, such as EGR1, phosphatase and tensin homolog (PTEN), phosphorylated protein kinase B (pAkt), protein kinase B (Akt), B lymphocyte2 (Bcl2), Bcl2 familyassociated X protein (Bax), etc. Cellular immunofluorescence staining was employed to assess the localization and expression of EGR1 and PTEN in nuclear and cytoplasmic fractions of Hepa16 cells. The association between EGR1 and PTEN was explored by EGR1 overexpression in cell lines. For in vivo methods, a mouse model of diethylnitrosamine (DEN)induced primary liver cancer was established using C57BL/6 mice to investigate the inhibitory effect of LNT on liver cancer. Histopathology of liver tissue from mice was detected by hematoxylineosin staining and immunohistochemical assay. In vitro and in vivo results showed that LNT can inhibit the proliferation and promote the apoptosis of mouse HCC cells. Besides, LNT increased the expression of EGR1 in Hepa16 cells, which is translocated to the nucleus to function as a transcriptional factor. EGR1 then activates the expression of the tumor suppressor PTEN, thereby inhibiting the activation of the AKT signaling pathway. These data revealed a novel antitumor mechanism by which LNT can induce apoptosis to inhibit mouse HCC progression through the EGR1/PTEN/AKT axis. These results provide a scientific basis for the potential use of LNT in drug development and clinical applications associated with primary liver cancer.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Lentinano/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Transdução de Sinais , Apoptose , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Proliferação de Células , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismoRESUMO
Glutaredoxin 3 (GLRX3) is antioxidant enzyme, maintaining a low level of ROS, thus contributing to the survival and metastasis of several types of cancer. However, the expression and functions of GLRX3 have not been addressed in nasopharyngeal carcinoma (NPC). In this study, we found that GLRX3 was overexpressed in NPC. Knockdown of GLRX3 in NPC cell lines inhibited proliferation in vitro, tumorignesis in vivo, and colony formation. In addition, GLRX3 knockdown decreased the migration and invasion capacity of NPC cells by reversing the epithelial-mesenchymal transition (EMT). Furthermore, stabilization of GLRX3 was positively related to with epidermal growth factor receptor (EGFR) expression and negatively with ROS generation. Phosphorylation of Akt, a key downstream effector, was induced by EGFR signaling but did not rely on increasing ROS level in NPC cells. GLRX3 might be an oncoprotein in NPC, playing important roles in increasing redox reaction and activating EGFR/ Akt signals, so it may be a therapeutic target for NPC.