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1.
J Fish Dis ; 44(3): 249-262, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33314157

RESUMO

Takifugu rubripes and Dicentrarchus labrax are important commercial fish in China that are under serious threat from Cryptocaryon irritans. C. irritans is a ciliated obligate parasite that causes marine white spot disease and leads to heavy economic losses. We analysed the transcriptome in the gills of T. rubripes and D. labrax to compare differentially expressed genes (DEGs) and pathways during infection with C. irritans. In total, we identified 6,901 and 35,736 DEGs from T. rubripes and D. labrax, respectively. All DEGs were annotated into GO terms; 6,901 DEGs from T. rubripes were assigned into 991 sub-categories, and 35,736 DEGs from D. labrax were assigned into 8,517 sub-categories. We mapped DEGs to the KEGG database and obtained 153 and 350 KEGG signalling pathways from T. rubripes and D. labrax, respectively. Immune-related categories included Toll-like receptors, MAPK, lysosome, C-type lectin receptor and NOD-like receptor signalling pathways were significantly enriched pathways. In immune-related signalling pathways, we found that AP-1, P38, IL-1ß, HSP90 and PLA were significantly up-regulated DEGs in T. rubripes, but P38 and PLA were significantly down-regulated in D. labrax. In this study, transcriptome was used to analyse the difference between scaly and non-scaly fish infection by C. irritans, which not only provided a theoretical basis for the infection mechanism of C. irritans, but also laid a foundation for effectively inhibiting the occurrence of this disease. Our work provides further insight into the immune response of host resistance to C. irritans.

3.
Acta Pharmacol Sin ; 39(3): 482-491, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29047460

RESUMO

In drug design and discovery, binding affinity and selectivity are two basic properties of a drug candidate. Opioid receptors (ORs) are the main targets of strong analgesics. Like some other class A members of G-protein-coupled receptors (GPCRs), ORs exhibit complex selectivity on their ligands. The diversity of binding activity and selectivity among opioids has deeply attracted researchers for a long time. To investigate the subtype selectivity of µ, δ and κ ORs in detail, using the κ-selective antagonist JDTic as a probe, we performed a series of computational simulations, including molecular dynamics and metadynamics, on JDTic-µ/δ/κ-OR complexes. From the simulations, we found that the decisive factor of JDTic selectivity on the µ-subtype was the 2.63 position, which affected the efficacy of JDTic through changing the dynamics of the Q2.60 residue. In addition to the 2.63-position residue, the 7.35 position was the other crucial aspect of JDTic selectivity for the δ-subtype. Based on the results, we suggest a new concept, the "message-address-efficacy" hypothesis, to explain the relationships among the affinity, selectivity and function between ORs and opioids. Thus, all the detailed dynamics of JDTic-bound ORs might be helpful to deeply understand the subtype selectivity and binding mechanisms of other GPCRs.


Assuntos
Simulação de Acoplamento Molecular , Piperidinas/farmacologia , Receptores Opioides/metabolismo , Tetra-Hidroisoquinolinas/farmacologia , Estrutura Molecular , Piperidinas/química , Relação Estrutura-Atividade , Tetra-Hidroisoquinolinas/química
4.
Acta Pharmacol Sin ; 39(1): 154-164, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29188799

RESUMO

The µ opioid receptor (OR), a member of the class A subfamily of G-protein coupled receptors (GPCRs), is a major target for the treatment of pain. G-protein biased µ-OR agonists promise to be developed as analgesics. Thus, TRV130, the first representative µ-OR ligand with G-protein bias, has entered into phase III clinical trials. To identify the detailed G-protein-biased activation and inactivation mechanisms of the µ-OR, we constructed five µ-OR systems that were in complexes with the G-protein-biased agonists TRV130 and BU72, the antagonists ß-FNA and naltrexone, as well as the free receptor. We performed a series of conventional molecular dynamics simulations and analyses of G-protein-biased activation and inactivation mechanisms of µ-OR. Our results, together with previously reported mutation results, revealed the operating mode of the activation switch composed of residues W6.48 and Y7.43 (Ballesteros/Weinstein numbering), the activity of which was responsible for down- and up-regulation, respectively, of the ß-arrestin signaling, which in turn affected G-protein-biased activation of µ-OR. TRV130 was found to stabilize W6.48 by interacting with Y7.43. In addition, we obtained useful information regarding µ-OR-biased activation, such as strong stabilization of W7.35 through a hydrophobic ring interaction in the TRV130 system. These findings may facilitate understanding of µ-OR biased activation and the design of new biased ligands for GPCRs.


Assuntos
Proteínas de Ligação ao GTP/metabolismo , Morfinanos/metabolismo , Pirróis/metabolismo , Receptores Opioides mu/metabolismo , Compostos de Espiro/metabolismo , Tiofenos/metabolismo , Animais , Proteínas de Ligação ao GTP/química , Ligantes , Camundongos , Simulação de Dinâmica Molecular , Morfinanos/química , Naltrexona/análogos & derivados , Naltrexona/química , Naltrexona/metabolismo , Ligação Proteica , Conformação Proteica , Pirróis/química , Receptores Opioides mu/agonistas , Receptores Opioides mu/antagonistas & inibidores , Receptores Opioides mu/química , Compostos de Espiro/química , Tiofenos/química , Ureia/análogos & derivados , Ureia/química , Ureia/metabolismo , Água/química
5.
Clin Exp Pharmacol Physiol ; 44(1): 79-87, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27658187

RESUMO

In clinical practice, human ovarian cancer shows considerable resistance to chemotherapy. This study aimed to investigate the role of c-Met in the chemoresistance of ovarian cancer. Ovarian cancer cell line SKOV3 and OVCAR-3 were pretreated with c-Met inhibitor INCB28060, and then treated with paclitaxel. Cell survival, cell cycle and apoptosis were analyzed by MTT assay, flow cytometry analysis and TUNEL assay, respectively. The activation of c-Met signalling was detected by western blot analysis. INCB28060 inhibited the survival of SKOV3 and OVCAR-3 cells and enhanced the chemosensitivity of SKOV3 and OVCAR-3 cells to paclitaxel. INCB28060 inhibited c-Met signalling, caused mitochondrial membrane depolarization and DNA repair, and induced the apoptosis of SKOV3 and OVCAR-3 cells. c-Met plays an important role in mediating the chemoresistance of ovarian cancer. The combination of c-Met inhibitor and chemotherapy is a promising strategy to human ovarian cancer.


Assuntos
Benzamidas/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Neoplasias Ovarianas/metabolismo , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-met/metabolismo , Benzamidas/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/fisiologia , Feminino , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/fisiologia , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico
6.
Int J Clin Exp Med ; 8(11): 20829-36, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26885007

RESUMO

The acute myocardial infarction (AMI) model in Chinese miniswine was built by percutaneous coronary artery occlusion. Pathological observation of AMI was performed, and the expression of tumor necrosis factor alpha (TNF-α) in the infarct sites was detected at different days after modeling in Chinese miniswine. The experimental findings may be used as the basis for blood flow reconstruction and intervention after AMI. Seven experimental Chinese miniswine were subjected to general anesthesia and Seldinger right femoral artery puncture. After coronary angiography, the gelfoam was injected via the microtube to occlude the obtuse marginal branch (OM branch). At 1 d, 3 d, 5 d, 7 d, 10 d, 14 d and 17 d after modeling, hetatoxylin-eosin (HE) staining was performed to observe the pathological changes and to detect the expression of TNF-α in the myocardial tissues. Cytoplasmic acidophilia of the necrotic myocardial tissues at 1 d after modeling was enhanced, and cytoplasmic granules were formed; at 3 d, the margins of the necrotic myocardial tissues were infiltrated by a large number of inflammatory cells; at 5 d, the nuclei of the necrotic myocardial cells were fragmented; at 7 d, extensive granulation tissues were formed at the margin of the necrotic myocardial tissues; at 10 d, part of the granulation tissues were replaced by fibrous scar tissues; at 14-17 d, all granulation tissues were replaced by fibrous scar tissues. Immunohistochemical detection indicated that no TNF-α expression in normal myocardial tissues. The TNF-α expression was first detected at 3 d in the necrotic myocardial tissues and then increased at 5 d and 7 d. After reaching the peak at 10 d, the expression began to decrease at 14 d and the decrease continued at 17 d. Coronary angiography showed the disappearance of blood flow at the distal end of OM branch occluded by gelfoam, indicating that AMI model was constructed successfully. The repair of the infarcted myocardium began at 10-17 d after modeling with safe blood flow reconstruction. TNF-α expression in the infarcted myocardium was the highest at 10 d, which can be explained by inflammation and repair of the infarcted myocardium.

7.
Nan Fang Yi Ke Da Xue Xue Bao ; 31(5): 903-7, 2011 May.
Artigo em Chinês | MEDLINE | ID: mdl-21602155

RESUMO

OBJECTIVE: To study the inhibitory effect of human umbilical cord mesenchymal stem cells (UC-MSCs) infected by a adenoviral vector containing interleukin 12 (IL-12) gene on the proliferation of ovarian carcinoma SKOV3 in vitro and the growth of tumor explants in nude mice. METHODS: Cultured human UC-MSCs were infected with the recombinant adenovirus vector harboring IL-12 gene to establish the IL-12-expressing cell line AdIL-12-MSCs. Western blotting and RT-PCR were used to detect IL-12 expressions in AdIL-12-MSCs at the protein and mRNA levels, respectively. ELISA were used to detect IL-12 content in the supernatant of AdIL-12-MSCs, whose effect on the proliferation and apoptosis of ovarian carcinoma SKOV3 cells was evaluated with MTT assay and flow cytometry, respectively. In a nude mouse model bearing subcutaneous SKOV3 tumor explants, AdIL-12-MSCs were infused via the tail vein and the inhibitory effect on the tumor growth was observed. RESULTS: The exogenous IL-12 gene was successfully transduced into UC-MSCs by the recombinant adenovirus vector, resulting in efficient IL-12 expression in the cell at both the protein and mRNA levels. The supernatant of AdIL-12-MSCs significantly inhibited the proliferation of SKOV3 cells and induced cellular apoptosis in vitro as compared with UC-MSC supernatant. In the tumor-bearing nude mouse model, the transplantation of AdIL-12-MSCs significantly inhibited the growth of SKOV3 tumor explants (P<0.05). CONCLUSION: Human UC-MSCs with IL-12 gene transduction, which express IL-12 at protein and mRNA levels, can inhibit the proliferation and induce apoptosis of ovarian carcinoma SKOV3 cells in vitro, and suppress the growth of ovarian cancer explants in nude mice.


Assuntos
Interleucina-12/genética , Células-Tronco Mesenquimais/citologia , Neoplasias Ovarianas/terapia , Cordão Umbilical/citologia , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Terapia Genética , Vetores Genéticos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Transfecção
8.
Int J Oncol ; 38(5): 1319-27, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21399867

RESUMO

Ganoderma lucidum is a herbal mushroom known to have many health benefits, including the inhibition of tumor cell growth. However, the effect of Ganoderma lucidum on epithelial ovarian cancer (EOC), the most fatal gynecological malignancy, has not yet been reported. In this study, we determined whether Ganoderma lucidum regulates EOC cell activity. Using several cell lines derived from EOC, we found that Ganoderma lucidum strongly decreased cell numbers in a dose-dependent manner. Ganoderma lucidum also inhibited colony formation, cell migration and spheroid formation. In particular, Ganoderma lucidum was effective in inhibiting cell growth in both chemosensitive and chemoresistant cells and the treatment with Ganoderma lucidum significantly enhanced the effect of cisplatin on EOC cells. Furthermore, Ganoderma lucidum induced cell cycle arrest at the G2/M phase and also induced apoptosis by activating caspase 3. Finally, Ganoderma lucidum increased p53 but inhibited Akt expression. Taken together, these findings suggest that Ganoderma lucidum exerts multiple anti-tumor effects on ovarian cancer cells and can enhance the sensitivity of EOC cells to cisplatin.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Reishi , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Humanos , Neoplasias Ovarianas/patologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores
9.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 40(4): 639-43, 2009 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-19764562

RESUMO

OBJECTIVE: To explore the serum levels of IGFBP-2, -3 and their proper roles in the regulation of IGF-II bioavailability in patients with ovarian tumor, and to investigate the correlation between the expressions of IGFBP-2 and IGFBP-3 in ovarian tumor tissues and related clinicopathological characteristics. METHODS: Serum levels of IGFBP-2, -3 and big/mature IGF-II were measured by Western ligand blot (WLB) and Western blot (WB) in patients with ovarian tumor (10 cases of benign tumor, 6 cases of borderline tumor and 10 cases of malignant tumor) and 10 cases of normal control. The expressions of IGFBP-2 and IGFBP-3 were examined in 39 specimens of ovarian tumor (8 cases of benign tumor, 8 cases of borderline tumor and 23 cases of malignant tumor) and 4 cases of normal ovarian tissues by immunohistochemical staining. RESULTS: The serum levels of both big and mature IGF-II in epithelial ovarian cancer (ovarian cancer) patients were significantly decreased compared with those of normal control and benign and borderline tumor (P<0.001 or P<0.01). The increased serum level of IGFBP-2 and decreased IGFBP-3 level were observed in patients with malignant ovarian tumors by comparing with those of patients with normal controls, benign and borderline tumor (P<0.001 or P<0.01). The expression of IGFBP-2 was significantly higher in malignant ovarian tumor tissues than those in normal control and benign ovarian tumors tissues (P<0.0001, P<0.001, and the expression of IGFBP-3 decreased significantly in lower differentiated ovarian cancer tissues compared with that in high and moderate differentiated ovarian cancer tissues (P<0. 05). CONCLUION: IGFBP-2 predominantly presents in the circulation of malignant patients in contrast to IGFBP-3, which may result in altered bioavailability of IGF-II in ovarian cancer, leading to the progress of tumor. The serum levels of both IGFBP-2 and IGFBP-3 and their expressions in tumor tissues are correlated with the clinicopathological characteristics of ovarian cancer patients. Our findings suggest that the presence of new mechanisms in the regulation of IGF-II bioavailability, and provide the evidence for the possibility to use IGFBP-2/IGFBP-3 as biological markers in diagnosis and prognosis of ovarian cancer.


Assuntos
Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like II/análise , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Imunoquímica , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Pessoa de Meia-Idade
10.
Artigo em Chinês | MEDLINE | ID: mdl-18724891

RESUMO

OBJECTIVE: To observe the effects of prenatal exposure to low level lead on the protein and mRNA expression of growth-associated protein (GAP-43) in hippocampus of rat's offspring, and to explore the molecular mechanisms of lead on learning and memory. METHODS: The pregnant rats were randomizedly divided into 4 groups and provided with doubly evaporated water in control group and 125, 250, 500 mg/L lead acetate solution via drinking water in treatment groups respectively during pregnancy. When the rat's offspring was 1, 21, 60 days old, the lead content in hippocampus was measured by hydride generation atomic absorption spectrometry, and the GFAP protein and mRNA expression at hippocampal CA1 region were observed by immunohistochemistry and in situ hybridization. RESULTS: The content of lead in the hippocampus was (1.64 +/- 0.32), (2.33 +/- 0.42) and (3.28 +/- 0.58) microg/L, and (0.94 +/- 0.18), (1.27 +/- 0.26) and (1.79 +/- 0.42) microg/L respectively in the low, middle and high lead dosage group when the rat's offspring was one day and 21 day old. When the rat's offspring was 1, 21 days old, the content of lead in hippocampus in treatment groups was significant higher than that of control (P < 0.05), the integral optical density of GAP-43 protein and mRNA expression (except low dosage treatment at 21 d) were significantly decreased compared with the control (P < 0.01, P < 0.05), but there was no significant difference at 60-day old offsprings for the parameters above. CONCLUSION: Exposure to low level lead during pregnancy could inhibit the GAP-43 protein and mRNA expression in hippocampus of rat's offspring, which may be one of the molecular mechanisms of lead on learning and memory.


Assuntos
Exposição Ambiental/efeitos adversos , Proteína GAP-43/metabolismo , Hipocampo/efeitos dos fármacos , Chumbo/toxicidade , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Animais , Feminino , Proteína GAP-43/genética , Hipocampo/metabolismo , Gravidez , RNA Mensageiro/genética , Ratos , Ratos Wistar
11.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 24(6): 577-80, 2008 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-18538088

RESUMO

AIM: To investigate the effects of IL-18 gene transfection on proliferation, apoptosis and tumorigenesis of mouse ovarian cancer cell line OVHM. METHODS: OVHM were transfected with retrovirus encoding IL-18 gene (OVHM/IL-18). The wild OVHM and OVHM transfected with vector without IL-18 gene (OVHM/LXSN) were enrolled as the controls. The proliferation, cell cycle and apoptosis were measured by MTT and FCM respectively. The nude mice were subcutaneously inoculated with the three different cells respectively. The observation of transplanted tumor's growth and calculation of tumorigenesis ratio was made. The expression of IL-18 mRNA in tumor tissues was detected by RT-PCR, and the apoptosis of tumor cell in tissue was analyzed by electron microscope and FCM. RESULTS: The three cells cultured in vitro showed no apoptotic peaks, and no differences in proliferation and cell cycle (All P>0.05). Following inoculation, the ratios of tumorigenesis were similar in all the three groups. But in OVHM/IL-18 group, the latent period of tumorigenesis was longer with slower tumor growth rate and positive expression of IL-18 mRNA in tumor tissue. It was also observed that in the tumor cells from nude mice inoculated by OVHM/IL-18, the cells in phase of G0/G1 increased with typical morphology of apoptosis, and those in S phase decreased with decreased proliferation index and increased apoptosis index (All P<0h01). CONCLUSION: Although IL-18 gene has no cytotoxic effects in vitro, its inhibiting effects on tumorigenesis of OVHM in vivo were exerted by interdicting cell cycle and accelerating apoptosis of tumor cells.


Assuntos
Proliferação de Células , Interleucina-18/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/fisiopatologia , Transfecção , Animais , Apoptose , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-18/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Processos Neoplásicos , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Distribuição Aleatória , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Zhonghua Zhong Liu Za Zhi ; 30(12): 905-9, 2008 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-19173990

RESUMO

OBJECTIVE: To investigate the variation in expression of ARHI, STAT3 and E2F1 and the correlation among them during carcinogenesis of ovarian serous carcinoma. METHODS: Immunohistochemical staining was used to detect the expression of ARHI, STAT3 and E2F1 in samples of 25 normal ovaries, 35 ovarian serous cystadenomas, 18 borderline serous cystadenomas and 56 ovarian serous carcinomas. The variation in expression of the three genes and relationship among them were analyzed. RESULTS: ARHI expression was detected in 22 of 25 (88.0%) normal ovaries and 30 of 35 (85.7%) cystadenomas, but only in 10 of 18 (55.6%) borderline serous cystadenomas and 22 of 56 (39.3%) ovarian serous carcinomas, significantly lower than that in the normal ovaries and ovarian serous cystadenomas (P < 0.05). STAT3 expression was found in 14 of 18 (77.8%) borderline serous cystadenomas and 49 of 56 (87.5%) ovarian serous carcinomas, significantly higher than that in the normal ovaries and ovarian serous cystadenomas (P < 0.05). To compare with E2F1 expression in the normal ovaries, serous cystadenomas and borderline serous cystadenomas, E2F1 expression in 46 of 56 (82.1%) ovarian serous carcinomas was significantly higher (P < 0.05). It was found that the expression of ARHI was inversely correlated with that of STAT3 and E2F1. CONCLUSION: Our findings indicate that ARHI expression is down-regulated, but STAT3 and E2F1 expressions are up-regulated, with an inverse correlation between ARHI and STAT3 in the carcinogenesis of ovarian serous carcinoma.


Assuntos
Cistadenocarcinoma Seroso/metabolismo , Fator de Transcrição E2F1/metabolismo , Neoplasias Ovarianas/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Adulto , Idoso , Cistadenocarcinoma Seroso/patologia , Cistadenoma Seroso/metabolismo , Cistadenoma Seroso/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Ovário/metabolismo , Ovário/patologia
13.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 23(12): 1167-9, 2007 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-18062892

RESUMO

AIM: To investigate the functional mechanism of CIK cells or ovarian carcinoma cell lines SKOV3/CDDP. METHODS: The changes of ultramicrostructure, cell cycle, apoptosis, expression of multidrug resistance-associated protein (MDR1, Topo-IIbeta) and other molecules (hB7-1, hB7-2, MHCIb, HLA-DR) of SKOV3/CDDP cells treated with or without CIK cells were detected by electron microscope, MTT and FCM. The changes of cytokine (IL-2, TNF-alpha, IFN-gamma, GM-CSF) in sera of SCID mice bearing SKOV3/CDDP cells were detected by radioimmunit and ELISA. RESULTS: CIK cells could induce apoptosis of the SKOV3/CDDP cells by electronmicroscopic observations. The apoptosis rate in CIK group was 9.07%, and its cell cycle was arrested at S and G2/M phase (P<0.05). Compared with NS Group, the co-expression of MDR-1 and Topo-IIbeta were decreased significantly in the CIK treated group(P<0.05), and the expression of MHCIb, HLA-DR, hB7-1 and hB7-2 antigen were increased significantly (P<0.01). Compared with NS Group, the contents of IL-2, TNF-alpha, INF-gamma, GM-CSF were increased significantly (P<0.01) in SCID mice of CIK group. CONCLUSION: CIK cells have several important biological effects on the ovarian carcinoma cell line SKOV3/CDDP, which may lay the foundation for further research on anti-tumor therapy.


Assuntos
Células Matadoras Induzidas por Citocinas/imunologia , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Animais , Apoptose/imunologia , Ciclo Celular/imunologia , Linhagem Celular Tumoral , Células Matadoras Induzidas por Citocinas/ultraestrutura , Citocinas/sangue , Resistência a Múltiplos Medicamentos/imunologia , Resistencia a Medicamentos Antineoplásicos/imunologia , Feminino , Regulação Neoplásica da Expressão Gênica/imunologia , Antígenos de Histocompatibilidade/metabolismo , Humanos , Camundongos , Camundongos SCID , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia
14.
Zhonghua Fu Chan Ke Za Zhi ; 40(9): 631-5, 2005 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-16202322

RESUMO

OBJECTIVE: To evaluate the effects of 2-methoxyestradiol (2-ME(2)) on human cervical cancer HeLaS3 cells and cervical cancer xenografts. METHODS: Cell proliferation assay and cell cycle analysis were used to measure HeLaS3 cell growth and cell cycle progression after 2-ME(2) treatment. Fluorescent microscopy to observe the cell morphology and DNA electrophoresis to measure apoptosis. In addition, the effect of 2-ME(2) on the expression of inducible nitric oxide synthase (iNOS) was measured by Western blot. Moreover, human cervical cancer model was set up using HeLaS3 cells and 2-ME(2) (75 mg/kg) was orally given for 14 d. Tumor volume was determined and apoptosis was detected by in situ cell death. RESULTS: Newly-formed cell amount in treated group was 81% of that in control group after 1 micromol/L 2-ME(2) treatment for 48 h (P < 0.05), and was 19% of that in control group after 2-ME(2) treatment for 96 h (P < 0.01). G(2)/M phase cells were increased to 55% from 16% of the control (P < 0.01), and apoptotic cells were increased to 16% from 4% of the control, after 5 micromol/L 2-ME(2) treatment for 20 h. Nuclear condensation and abnormal metaphase cells were found by fluorescent microscopy. Typical DNA ladder was found by DNA electrophoresis. And the expression of iNOS was increased by 2-ME(2) in a time- and concentration-dependent manner, in parallel with apoptosis. Moreover, apoptosis was prevented by the iNOS inhibitor 1400W. In vivo, tumor volume was reduced 34% while compared with the control group. In situ cell death detection found more apoptotic and necrotic cells in 2-ME(2)-treated group. CONCLUSIONS: 2-ME(2) inhibits human cervical cancer HeLaS3 cells and tumor growth in cervical cancer xenografts. Thus 2-ME(2) has the therapeutic potential for cervical carcinoma.


Assuntos
Estradiol/análogos & derivados , Neoplasias do Colo do Útero/prevenção & controle , Ensaios Antitumorais Modelo de Xenoenxerto , 2-Metoxiestradiol , Amidinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Benzilaminas/farmacologia , Ciclo Celular/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Relação Dose-Resposta a Droga , Estradiol/farmacologia , Estradiol/uso terapêutico , Feminino , Células HeLa , Humanos , Camundongos , Camundongos SCID , Microscopia de Fluorescência , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/biossíntese , Carga Tumoral , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia
15.
Artigo em Chinês | MEDLINE | ID: mdl-16124901

RESUMO

OBJECTIVE: To analyze the treatment of 42 patients with acute methanol poisoning because of drinking alcohol containing methanol. METHODS: Clinical data of 42 cases of methanol poisoning were collected and analyzed. Methanol concentration in drinking alcohol and blood was determined by gas chromatography (GC). National standard for occupational medicine (GBZ53-2002) was used to diagnose the cases. RESULTS: The methanol concentration in the alcohol was 16% approximately 46%. 42 Patients (40 males, 2 females), at age of 46.1 (22 approximately 80), took 588.1 ml (50 approximately 2,000 ml) of the alcohol. The average methanol concentration in blood was 1.61 mmol/L (0.03 approximately 23.60 mmol/L). According to clinical diagnosis, there were 17 observed cases, 9 mild acute toxication, and 16 severe acute toxication. Among them, 35 (83.3%) patients were recovered, 2 (4.8%) blind, 4 (9.5%) with neuropsychic sequela and 1 (2.4%) dead after adopting 8 cure measures. CONCLUSION: To start using emergency plan for public health events suddenly happened, designate a special treatment hospital, clear blood methanol as soon as possible, correct acidosis, adequately administer folacin and hormone, protect optic nerve and retina, and take comprehensive symptomatic treatment as well as strict monitoring are the keys of clinical cure.


Assuntos
Metanol/envenenamento , Prática de Saúde Pública , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Envenenamento/terapia
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