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1.
Front Med (Lausanne) ; 10: 1212851, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37601787

RESUMO

Objective: To analyze and evaluate the role of the High-throughput Drug Sensitivity (HDS) screening strategy in identifying highly sensitive drugs against esophageal squamous cell carcinoma (ESCC). Methods: A total of 80 patients with progressive ESCC were randomly divided into the observation (40 cases) and the control groups (40 cases). In the observation group, primary ESCC cells were isolated from the tumor tissues with a gastroscope, and drug sensitivity screening was performed on cells derived from the 40 ESCC cases using the HDS method, followed by verification in a patient-derived tumor xenograft (PDX) mouse model. Finally, the differences in the therapeutic efficacy (levels of CEA, CYFRA21-1, SCCA after chemotherapy and the rates of overall survival, local progression, and distant metastasis at 12 months and 18 months time points after chemotherapy) were compared between the observation group (Screened drug-treated) and the control group (Paclitaxel combined with cisplatin regimen-treated). Results: Forty ESCC patients were screened for nine different high-sensitive chemotherapeutics, with the majority showing sensitivity to Bortezomib. Experiments on animal models revealed that the tumor tissue mass of PDX mice treated with the HDS-screened drug was significantly lower than that of the Paclitaxel-treated mice (p < 0.05), and the therapeutic efficacy of the observation group was better than the control group (p < 0.05). Conclusion: HDS screening technology can be beneficial in screening high-efficacy anticancer drugs for advanced-stage ESCC patients, thereby minimizing adverse drug toxicity in critically ill patients. Moreover, this study provides a new avenue for treating advanced ESCC patients with improved outcomes.

2.
Am J Transl Res ; 14(3): 1714-1720, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35422918

RESUMO

OBJECTIVE: To compare the clinical efficacy, safety, and prognosis of full-threaded headless cannulated compression screws (HCCSs) and anatomical plates (APs) in the treatment of triplane fractures of the distal tibia. METHODS: In this retrospective study, 74 patients with triplane fractures of the distal tibia treated in our hospital from April 2017 to March 2019 were selected as the research subjects. Among them, 38 patients receiving full-threaded HCCSs were assigned to the research group (RG), and the remaining 36 patients receiving APs were assigned to the control group (CG). The general indices, including operation, fracture healing, and ambulation times, efficacy, and complications were recorded and compared between the two groups. Visual analogue scale (VAS) was applied to assess pain, and a quality of life (QOL) survey was conducted at 6 months after surgery. RESULTS: Compared with the CG, the operation time, fracture healing time, and ambulation time of the RG were significantly shortened (P<0.05). The proportion of patients with excellent and good outcomes and Mazur Scores in the RG were higher than those in the CG (P<0.05). The frequency of complications in the RG was lower than that in the CG (P<0.05). The preoperative VAS score did not exhibit significant differences between the two groups (P<0.05), but the scores in the RG at T1 and T2 were significantly lower than those in the CG (P<0.001). The QOL score in the RG (76.17±8.57) was also significantly higher than in the CG (71.54±8.02) (P<0.05). CONCLUSION: Full-threaded HCCSs are more effective and safer than APs and can effectively improve the prognosis of patients with triplane fractures of the distal tibia.

3.
Aging (Albany NY) ; 13(23): 25365-25376, 2021 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-34890366

RESUMO

Currently, 5-Fluorouracil (5-FU) based chemotherapy is the primary option for colorectal cancer after surgery, whereas chemotherapy resistance related mortality is observed in a large proportion of patients. Anemoside B4 (AB4) is a triterpene saponin, which exhibits a considerable activity in oncotherapy. In this study, we explored the efficacy of AB4 in FU-based chemotherapy in colorectal cancer cells and the underlying molecular mechanisms. Our results indicated a significant synergistic activity of AB4 in 5-FU treated colorectal cancer cells. Furthermore, AB4 treatment eliminated colorectal cancer stem cells by promoting apoptotic cell death in 5-FU resistant colorectal cancer cells. Mechanically, AB4 activated caspase-9 pathway in 5-FU resistant colorectal cancer cells. Elevated Src activity induced cell apoptosis and cancer stem cells elimination effects in AB4 treated colorectal cancer cells. In conclusion, AB4 showed promising sensitization effect in the FU-based chemotherapy of colorectal cancer. Our study may pave a way to ameliorate FU-based chemotherapeutic efficiency in colorectal cancer.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/uso terapêutico , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Saponinas/uso terapêutico , Animais , Caspase 9/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Células HCT116/efeitos dos fármacos , Humanos , Camundongos Nus , Transplante de Neoplasias , Células-Tronco Neoplásicas/efeitos dos fármacos
4.
Zhonghua Bing Li Xue Za Zhi ; 43(9): 583-7, 2014 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-25471497

RESUMO

OBJECTIVE: To investigate the mutation rate and types of KRAS gene in colorectal carcinoma of Chinese patients, and to document the regional distribution of the mutation. METHODS: A total of 6 364 colorectal carcinoma tumor specimens were obtained from 27 provinces and autonomous regions in China from 2009 to 2013. Pyrosequencing was used to detect mutations in codons 12 and 13 of KRAS gene. The mutation types of KRAS and the difference of regional distribution were statistically analyzed. RESULTS: KRAS mutation rate in Chinese colorectal carcinoma patients was 37.43 % (2 382/6 364). Ten types of single-base mutations of KRAS codons 12 and 13 were detected, including six common types: 12GGT > GAT (14.77%), 13GGC > GAC (8.19%), 12GGT > GTT (7.89%), 12GGT > TGT (2.20%), 12GGT > AGT (2.00%), and 12GGT > GCT (1.48%). Other four less occurring mutation types (<1%) included 12GGT > CGT, 13GGC > TGC, 13GGC > CGC, and 13GGC > AGC. In addition, 8 other mutation types were identified in 13 tumor samples. The rates of KRAS mutation in patients from different regions were between 35.68% and 38.04% and no significant differences were observed (P > 0.05). CONCLUSIONS: Abundant mutation types of KRAS gene exist in colorectal cancers among Chinese patients. The six common mutation types occur with a frequency of not less than 1%. There are no significant differences of KRAS mutation rate among Chinese patients from various areas. Pyrosequencing provides a rapid and accurate method of KRAS mutation detection for clinical application.


Assuntos
Códon , Neoplasias Colorretais/genética , Genes ras , Mutação , Idoso , Povo Asiático , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Mutação
5.
Neurosci Lett ; 505(2): 165-70, 2011 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-22019984

RESUMO

The axons of the adult mammalian brain and spinal cord fail to regenerate after injury, and it has been suggested that Nogo-66 could prevent CNS axon repair. However, the mechanism of Nogo-66 inhibiting neurite outgrowth remains unknown. Our previous results indicated that protein kinase B (PKB) is involved in the inhibition of the neurite outgrowth by Nogo-66. Glycogen synthase kinase-3ß (GSK-3ß) is implicated in many processes in the nervous system, including differentiation, specification, polarity, plasticity and axon growth. In addition, GSK-3ß is one of the most important molecules downstream of PKB. In the present study, we report on the role of GSK-3ß signaling on Nogo-66-treated mouse neuroblastoma N2a cells. Nogo-66 reduced the phosphorylation of GSK-3ß at Ser9 in N2a cells. In contrast, pretreatment with SB216763, a specific inhibitor of GSK-3ß, resulted in an amelioration of neurite outgrowth by Nogo-66, compared with the Nogo-66 alone group (P<0.05). Moreover, we performed RNA interference experiments to knock down GSK-3ß expression levels in N2a cells via transient transfection of shRNA plasmids. The inhibition of neurite outgrowth by Nogo-66 was subdued in shRNA cells, compared to the non-RNAi cells (P<0.05). Taken together, these data suggest that GSK-3ß is involved in the inhibition by Nogo-66 of neurite outgrowth in N2a cells.


Assuntos
Quinase 3 da Glicogênio Sintase/metabolismo , Proteínas da Mielina/fisiologia , Regeneração Nervosa/fisiologia , Inibição Neural/genética , Neuritos/metabolismo , Neurogênese/fisiologia , Receptores de Superfície Celular/fisiologia , Animais , Linhagem Celular Tumoral , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/genética , Proteínas Ligadas por GPI/fisiologia , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Quinase 3 da Glicogênio Sintase/genética , Glicogênio Sintase Quinase 3 beta , Indóis/farmacologia , Maleimidas/farmacologia , Camundongos , Regeneração Nervosa/efeitos dos fármacos , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Neuritos/patologia , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Neurogênese/efeitos dos fármacos , Receptor Nogo 1 , Fosforilação/efeitos dos fármacos , Fosforilação/genética , Interferência de RNA/efeitos dos fármacos , RNA Interferente Pequeno/genética
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