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1.
Zhongguo Zhong Yao Za Zhi ; 46(7): 1696-1700, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33982471

RESUMO

At present, the issues regarding multi-center clinical trials of new drugs of traditional Chinese medicine(TCM) remain: the lack of agreement on the content and scope of the ethical review among the ethics committee members of the center and the participating units results in repeated review, which leads to a time-consuming ethical review process. Moreover, the review capabilities of the ethics committees of various research centers are uneven, which is not necessarily beneficial to the protection of subjects' rights and safety. In view of the existing problems, to improve the efficiency of ethical review of multi-center clinical trials of new drugs of TCM and avoid repeated reviews, the TCM Clinical Evaluation Professional Committee of Chinese Pharmaceutical Association organized experts to formulate the "Consensus on collaborative ethical review of multi-center clinical trials of new drugs of TCM(version 1.0)"(hereinafter referred to as "Consensus"). The "Consensus" is formulated in accordance with the requirements of relevant documents such as but not limited to "the opinions on deepening the reform of the evaluation and approval system to encourage the innovation of pharmaceutical medical devices", "the regulations of ethical review of biomedical research involving human subjects". The "Consensus" covers the scope of application, formulation principles, conditions for the ethics committee of the center, sharing of ethical review resources, scope and procedure of collaborative review, rights and obligations, etc. The aims of the "Consensus" is to preliminarily explore and establish a scientific and operable ethical review procedure. Additionally, on the basis of fully protecting the rights and interests of the subjects, a collaborative ethical review agreement needs to be signed to clarify the ethical review responsibilities of all parties, to avoid repeated review, and to improve the efficiency and quality of ethical review in multi-center clinical trials of new drugs of TCM.


Assuntos
Pesquisa Biomédica , Medicamentos de Ervas Chinesas , Preparações Farmacêuticas , Ensaios Clínicos como Assunto , Consenso , Revisão Ética , Humanos , Medicina Tradicional Chinesa , Estudos Multicêntricos como Assunto
2.
Biochem Cell Biol ; 98(2): 99-105, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31018104

RESUMO

This study investigated the role of miR-628-5p and interferon-induced protein 44-like (IFI44L) in osteosarcoma (OS) and determined whether miR-628-5p modulated OS growth by regulating IFI44L. Based on the data downloaded from Gene Expression Omnibus (GEO) database, we revealed that the expression of IFI44L was downregulated in OS and low expression of IFI44L was correlated with better prognosis of patients with OS. Biological prediction of its upstream regulatory miRNAs on the miRWalk website found that miR-628-5p is a possible upstream regulatory miRNA of IFI44L. Luciferase activity assay demonstrated that miR-628-5p could bind to the 3' untranslated region (UTR) of IFI44L, which proved the above prediction. The expression of miR-628-5p is upregulated in OS and high expression of miR-628-5p is correlated with poor prognosis of patients with OS. The results of RT-qPCR showed that the expression of miR-628-5p in MG-63, U2OS, Saos-2, and SW1353 cells was significantly higher than that in the hFOB1.19 cells. Downregulation of miR-628-5p by miR-628-5p inhibitor significantly inhibited the proliferation, migration, and invasion of MG-63 cells. By rescue assay, we found that knockdown of IFI44L rescued the proliferation and motility of miR-628-5p depleted MG-63 cells. Collectively, our present data illustrated that miR-628-5p promoted the growth and motility of OS at least partly by targeting IFI44L. Moreover, miR-628-5p and IFI44L might be proposed as promising biomarkers in OS diagnosis and treatment.


Assuntos
Neoplasias Ósseas/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Osteossarcoma/genética , Proteínas Supressoras de Tumor/metabolismo , Regiões 3' não Traduzidas , Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Osteossarcoma/metabolismo , Prognóstico , Cicatrização
3.
Zhong Xi Yi Jie He Xue Bao ; 10(6): 695-700, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22704420

RESUMO

OBJECTIVE: To study the effect of Feiyanning Decoction (FYN), a compound traditional Chinese medicine, on expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) activated by tumor necrosis factor-α (TNF-α) in human lung adenocarcinoma epithelial cell line (A549). METHODS: A549 cells were incubated with rat serum containing FYN for 24 h. Gene expressions of iNOS and COX-2 were determined by quantitative real-time polymerase chain reaction and Western blot. The iNOS-dependent luciferase reporter was transfected for 24 h and the cells were treated with the reagents for 24 h, then the transcriptional activity of iNOS promoter was detected by luciferase assay. The production of NO was determined by diaminofluorescein-2. RESULTS: FYN significantly inhibited TNF-α-induced expression of iNOS and COX-2 compared with the control group in A549 cells (P<0.01, P<0.01). Also, FYN inhibited the transcriptional activity of the iNOS promoter and reduced NO production compared with the control group (P<0.01, P<0.01). CONCLUSION: These results suggest that FYN inhibits iNOS and COX-2 activation induced by TNF-α, therefore, it is expected to develop a new strategy to treat lung cancer.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma de Pulmão , Animais , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/metabolismo , Ratos , Soro , Fator de Necrose Tumoral alfa/efeitos adversos
4.
Zhong Xi Yi Jie He Xue Bao ; 10(5): 584-90, 2012 May.
Artigo em Chinês | MEDLINE | ID: mdl-22587982

RESUMO

OBJECTIVE: To study the effects of Feiyanning Decoction, a compound traditional Chinese herbal medicine, on the ratio of CD4(+)CD25(+) regulatory T cells and expression of transcription factor Foxp3 in mice with Lewis lung cancer. METHODS: Thirty-two male wild-type C57BL/6 mice aging from 6 to 8 weeks were inoculated with Lewis lung cancer cells to establish the tumor-bearing model of Lewis lung carcinoma and were randomly divided into model group, Chinese medicine group, chemotherapy group and Chinese medicine combined with chemotherapy group. After intervention for 14 d with corresponding drugs, behaviors, physical signs and changes of feed consumption of the mice were observed. All mice were sacrificed after drug treatment, and tumors and organs were removed to weigh and calculate organ indexes (lung index, spleen index and thymus index). The percentages of CD4(+)CD25(+) regulatory T cells in the thymus, spleen and tumor were determined by flow cytometry. The expression of Foxp3 mRNA in the thymus, spleen and tumor tissues was detected by quantitative real-time polymerase chain reaction. RESULTS: Compared with those in the model group, the mice in the Chinese medicine group showed significant reductions in spleen and thymus indexes and tumor weight, and elevation in the body weight without tumor (P<0.05). The numbers of CD4(+)CD25(+) regulatory T cells in spleen, thymus and tumor were lower in the Chinese medicine group than in the model group (P<0.05). The expression of Foxp3 mRNA in spleen, thymus and tumor was significantly down-regulated in the Chinese medicine group compared with the model group (P<0.05). There were no significant differences in CD4(+)CD25(+) regulatory T cell ratio and Foxp3 mRNA expression between the Chinese medicine combined with chemotherapy group and the chemotherapy group. CONCLUSION: Feiyanning Decoction can enhance the antitumor immune response and thus play a role in antitumor therapy by reducing the ratio of CD4(+)CD25(+) regulatory T cells and down-regulating the expression of Foxp3 mRNA.


Assuntos
Carcinoma Pulmonar de Lewis/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Fatores de Transcrição Forkhead/metabolismo , Linfócitos T Reguladores/metabolismo , Animais , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL
5.
Zhong Xi Yi Jie He Xue Bao ; 10(4): 448-53, 2012 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-22500719

RESUMO

OBJECTIVE: Malignant tumor cells were found with an abnormal cell cycle. Previous in vivo experiment had confirmed the Feiyanning's intervention effect on checkpoint signaling of G1/S in the cell cycle. This study was to further observe the expressions of nucleosome conformation-regulating factors intervened by Feiyanning decoction in S phase. METHODS: Lewis lung carcinoma models of C57BL/6 mice were established. Sixty mice were randomly divided into four groups: normal control group, model control group, Feiyanning group, and cisplatin group. There were 15 mice in each group. Tumor weight and tumor inhibition rate were observed. In addition, the cell cycle distribution was detected by flow cytometry and the proliferation index was calculated. Furthermore, mRNA and protein expressions of H3-K56, regulator of Ty1 transposition 109 (Rtt109), antisilencing function 1 (Asf1) and E2F1 were analyzed by real-time polymerase chain reaction and Western blot methods, respectively. RESULTS: The tumor weights of mice in the Feiyanning group and the cisplatin group were lower than those in the model group (P<0.01), with tumor inhibition rates of 27.92% and 42.50%, respectively. Cancer cell proliferation index and proportion of cancer cell population in S phase in the Feiyanning group were significantly lower than those in the cisplatin group (P<0.01). The mRNA and protein levels of H3-K56, Rtt109, Asf1, E2F1 in the Feiyanning group were lower than those in the model group (P<0.05). CONCLUSION: Feiyanning plays a role in intervening in the abnormal cell cycle by nucleosome conformation-regulating factors and thus inhibits the lung cancer cell proliferation.


Assuntos
Carcinoma Pulmonar de Lewis/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Pulmonares/metabolismo , Nucleossomos , Animais , Carcinoma Pulmonar de Lewis/patologia , Ciclo Celular/efeitos dos fármacos , Divisão Celular , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais
6.
Oncol Rep ; 27(5): 1619-24, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22267101

RESUMO

The aim of the present study was to investigate the effects of cinobufocini on nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2) and the production of cytokines induced by tumor necrosis factor-α (TNF-α) in the A549 cell line. A549 cells were incubated with cinobufocini at different concentrations for 24, 48 or 72 h. Cell proliferation was examined by the WST-8 assay. The expression of NF-κB, COX-2 and inhibitor κBα (IκBα) was studied by western blotting. The NF-κB-dependent luciferase rporter (3xκB-luc) was transfected for 24 h, the cells were treated with the reagents for 24 h, and the transcriptional activity of the NF-κB promoter was detected by a luciferase assay. The levels of IL-6 and IL-8 mRNA were detected by reverse transcription-polymerase chain reaction. We found that cinobufocini inhibited NF-κB p65 expression and the transcriptional activity of the NF-κB promoter induced by TNF-α compared with the control in the nuclei of A549 cells. Moreover, induced COX-2 expression was blocked by cinobufocini and was correlated with a reduction in the activated p65 subunit of NF-κB. Additionally, the levels of IL-6 and IL-8 mRNA induced by TNF-α were significantly suppressed by the addition of cinobufocini. In conclusion, these results suggest that the anti-inflammatory effects of cinobufocini are dependent on the NF-κB/COX-2 pathway in A549 cells, thereby providing a possible anticancer mechanism for the compound.


Assuntos
Adenocarcinoma/metabolismo , Venenos de Anfíbios/farmacologia , Antineoplásicos/farmacologia , Ciclo-Oxigenase 2/metabolismo , Neoplasias Pulmonares/metabolismo , NF-kappa B/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo , Adenocarcinoma de Pulmão , Venenos de Anfíbios/química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-6/genética , Interleucina-8/genética , Medicina Tradicional Chinesa , NF-kappa B/genética , Regiões Promotoras Genéticas , Transcrição Genética/efeitos dos fármacos
7.
Zhong Xi Yi Jie He Xue Bao ; 9(2): 129-34, 2011 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-21288445

RESUMO

Pain is one of the common symptoms of cancer which seriously affects the quality of life of the patients. Cancer pain is mainly treated with the three-step method, biological therapy or nerve block therapy based on antitumor therapy. However, up to 50 percent of patients with cancer-related pain do not receive adequate pain relief, affecting their physical and psychological well-being, and leading to a lower quality of life for the patient after conventional treatment. Clinical observation suggests that traditional Chinese medicine may alleviate cancer-related pain either by oral administration, topical administration, acupuncture or other means with continuing non-addictive and non-drug-resistant qualities. However, scientific evaluation of the efficacy of herbs in the treatment of pain is insufficient; the underlying mechanisms are unclear and, safety and toxicity remain a concern.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Dor/tratamento farmacológico , Humanos , Medicina Tradicional Chinesa , Neoplasias/complicações , Dor/etiologia
8.
Exp Ther Med ; 1(2): 277-283, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22993540

RESUMO

To investigate the in vivo and in vitro inhibitory effects of deuterium-depleted water (DDW) on human lung cancer and the possible mechanisms underlying these effects, we cultured and treated human lung carcinoma cell line A549 and human embryonic lung fibroblasts HLF-1 with various concentrations of DDW from 2 to 72 h. Cellular growth inhibition rates were determined using the 3-(4, 5-dimethyldiazol-2-yl)-2, 5-diphenyltetrazolium-bromide) (MTT) proliferation assay. A549 cells were treated with 50±5 ppm DDW, and the morphology and structure of cells were observed by scanning electron microscopy (SEM). We observed alterations in the cellular skeleton by transmission electron microscopy (TEM) and changes in cell cycle by flow cytometry. Our data showed that DDW significantly inhibited the proliferation of A549 cells at a specific time point, and cells demonstrated the characteristic morphological changes of apoptosis under SEM and TEM. The length of the S phase increased significantly in cells treated with 50 ppm DDW, whereas the G0 to G1 phase and G2 to M phase were decreased. We observed DDW-induced cellular apoptosis using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and DNA fragment analyses. In addition, we established a tumor transplantion model by injecting H460 tumor cells into subcutaneous tissue of BALB/c mice treated with DDW for 60 days. We determined the tumor inhibition rate of treated and control groups and found that the tumor weight was significantly decreased and the tumor inhibition rate was approximately 30% in the DDW group. We conclude that DDW is a promising new anticancer agent with potential for future clinical application.

9.
Zhong Xi Yi Jie He Xue Bao ; 7(8): 741-5, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19671412

RESUMO

OBJECTIVE: To study the effects of Feiyanning Decoction, a compound traditional Chinese herbal medicine, on proliferation of lung adenocarcinoma cell line A549 cells and their production of interleukin-6 (IL-6) and IL-8 induced by tumor necrosis factor-alpha (TNF-alpha). METHODS: A549 cells were incubated with rat serum containing Feiyanning Decoction at 15% for 24, 48 and 72 h respectively. The cell proliferation was examined by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium, monosodium salt assay (WST-8). The production of IL-6 and IL-8 was tested by enzyme-linked immunosorbent assay after 48-hour treatment of reagents, and the expressions of IL-6 and IL-8 mRNAs were detected by reverse transcription-polymerase chain reaction. RESULTS: Serum containing Feiyanning Decoction had obvious inhibitive functions in A549 cell proliferation after 48- and 72-treatment. TNF-alpha (1 microg/L) strongly induced the production of IL-6 and IL-8 as compared with the control serum in A549 cells, and the induced cytokine production was significantly suppressed by 15% serum containing Feiyanning Decoction (P<0.01). In addition, serum containing Feiyanning Decoction could inhibit the mRNA expressions of IL-6 and IL-8 (P<0.01). CONCLUSION: Feiyanning Decoction can inhibit IL-6 and IL-8 production induced by TNF-alpha. It is therefore expected to be a new strategy for treating lung cancer.


Assuntos
Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Neoplasias Pulmonares/patologia , Fator de Necrose Tumoral alfa/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Humanos , Interleucina-6/genética , Interleucina-8/genética , Neoplasias Pulmonares/metabolismo , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Soro
11.
Zhong Xi Yi Jie He Xue Bao ; 7(3): 249-54, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19284955

RESUMO

OBJECTIVE: To study the effects of Feiyanning Decoction, a compound traditional Chinese herbal medicine, on gene expression of nuclear factor-kappaB (NF-kappaB) activated by tumor necrosis factor-alpha (TNF-alpha) in lung adenocarcinoma cell line (A549). METHODS: A549 cells were incubated with rat serum containing Feiyanning at different concentrations for 24 and 48 h, respectively. Morphology of cells was observed by an inverted microscope after treatment with reagents. The cell proliferation was examined by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-8) assay. The expressions of NF-kappaB and inhibitor kappaBalpha (IkappaBalpha) were studied by Western blotting. NF-kappaB-dependent luciferase reporter (3 x kappaB-luc) was transfected for 24 h, and the cells were treated with the reagents for 24 h, and then the transcriptional activity of NF-kappaB promoter was detected by luciferase assay. RESULTS: TNF-alpha (1 microg/L) strongly induced the expression of NF-kappaB by approximately 1.76-fold compared with the control in the nuclei of A549 cells, and the induced NF-kappaB expression was significantly suppressed by addition of Feiyanning (P < 0.01). In addition, Feiyanning inhibited the transcriptional activity of the NF-kappaB promoter. However, we observed no significant changes in IkappaBalpha expression (P > 0.05). CONCLUSION: Feiyanning Decoction can markedly inhibit human lung cancer A549 cell proliferation, which may be partly due to inhibition of NF-kappaB activation induced by TNF-alpha. It is therefore expected to be a new strategy for treating lung cancer.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Pulmonares/genética , NF-kappa B/genética , Animais , Linhagem Celular Tumoral , Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , NF-kappa B/metabolismo , Ratos , Fator de Necrose Tumoral alfa/efeitos adversos
12.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 29(11): 1018-22, 2009 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-20329615

RESUMO

OBJECTIVE: To observe the effect of Feiyanning Granule (FYN) on tumor growth and cell cycle distribution in mice with Lewis lung cancer, as well as its influence on G1/S cell cycle checkpoint dominating signaling RB-E2F1 bio-axis. METHODS: Modeled C57BL/6 mice were randomly divided into 6 groups: the model group (A), the DDP treated group (B) peritoneally injected with cisplatin 0.1 mg on d1, d3 and d5 after modeling, and the 4 FYN treated groups (C-F), administered via gastrogavage with FYN Decoction, and FYN Granule in small-, median- and high- dose respectively for 14 days. The tumour inhibiting rate, tumour weight, and body weight of mice were observed after treatment; cell cycle distribution was detected by flow cytometry (FCM), RB-E2F1mRNA expressions in tumour tissue were analyzed by RT-PCR, and their protein expressions by Western blot. RESULTS: Tumour weight in the 5 treated groups was lower than that in the model group (P < 0.05, P < 0.01). Body weight in group E was significantly higher than that in group A and B (P < 0.05, P < 0.01). FCM analysis showed the proportion of G0/G1 phase was higher in group E than in group A, B and C (P < 0.01), and cancer cell proliferation index (PI) in group E was lower than in group B (P < 0.05, P < 0.01). RT-PCR showed mRNA level of E2F1 was lower, but that of RB was significantly higher in group E than those in group A, B and C respectively (P < 0.01). Westem blot analysis showed the protein expression of E2F1 was lower in group E and B than that in group A (P < 0.05), while the protein expression of Rb in group E was higher than that in group A, B and C (P < 0.05). CONCLUSION: The effect of FYN in inhibiting Lewis lung cancer growth was related to its intervention on cancer cell cycle distribution which blocks most tumor cells in G0/G1 phase. Moreover, FYN can reduce MDM2 expression, enhance P53 expression to influence cell cycle G1/S checkpoint dominating signaling, so as to achieve the effect of antagonizing lung cancer cell proliferation.


Assuntos
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Animais , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patologia , Linhagem Celular Tumoral , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos
13.
Zhong Xi Yi Jie He Xue Bao ; 5(3): 298-301, 2007 May.
Artigo em Chinês | MEDLINE | ID: mdl-17498490

RESUMO

OBJECTIVE: To study the apoptosis of human hepatocellular carcinoma cell line HepG 2 induced by pitavastatin (NK-104) and to investigate the change of caspase-3 activity. METHODS: HepG 2 cells were treated with NK-104 for 48 hours and observed under a microscope by using Hoechst 33258 staining. The proliferation of the cells was detected with WST-8 method. The apoptosis peaks were examined by flow cytometry. The caspase-3 activity was detected with caspase-3 colorimetric protease assay. RESULTS: The treatment of HepG 2 with 10 micromol/L NK-104 could inhibit the proliferation, and induce HepG 2 apoptosis and up-regulate the caspase-3 activity. CONCLUSION: NK-104 at 10 micromol/L induces apoptosis of HepG 2 cells. It is dependent on caspase-3 pathway in human hepatocellular carcinoma cells.


Assuntos
Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Quinolinas/farmacologia , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citometria de Fluxo , Humanos , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologia
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