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1.
Oncol Lett ; 23(1): 7, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34820006

RESUMO

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is triggered by breakpoint cluster region-abelson leukemia virus (BCR/ABL) kinase. Targeting BCR/ABL kinase with tyrosine kinase inhibitors combined with chemotherapy is the standard first-line therapy for Ph+ ALL. Imatinib and dasatinib are the preferred agents for the treatment of Ph+ ALL. Dasatinib treatment can induce a faster and deeper remission than imatinib treatment; however, the side effects of dasatinib, especially the cardiovascular side effects, are markedly greater than those of imatinib. Patients will benefit from treatments that improve the efficacy of imatinib without increasing its side effects. The present study revealed that tanshinone IIA markedly potentiated the cytotoxic and apoptotic induction effects of imatinib by regulating the AKT-MDM2-P53 signaling pathway and inhibiting the anti-apoptotic proteins BCL2 and MCL1 apoptosis regulator, BCL2 family member in Ph+ ALL cell lines. In vitro studies, MTT assay, flow cytometry, western blotting and reverse transcription-quantitative PCR were performed in the present study to detect cell viability, cell apoptosis, protein expression and gene expression, respectively. In a Ph+ ALL mouse model, imatinib combined with tanshinone IIA also exhibited a synergistic effect on the reduction in leukemia burden without increasing the toxic side effects of imatinib. These results demonstrated that imatinib combined with tanshinone IIA might be a promising treatment strategy for patients with Ph+ ALL.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1071-1079, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362484

RESUMO

OBJECTIVE: To compare the efficacy and safety of different doses of daunorubicin combined with a standard dose of cytarabine as induction chemotherapy in newly diagnosed primary acute myeloid leukemia (AML) patients. METHODS: The clinical data and outcome were retrospectively analyzed in 86 newly diagnosed primary AML patients who were under 65 years old and treated with daunorubicin combined with cytarabine (DA regimen) at West China Hospital of Sichuan University from January 2017 to June 2019. Patients were divided into 2 groups based on the dose of daunorubicin they received, 35 cases in the escalated-dose group ï¼»75 mg/(m2·d)ï¼½ and 51 cases in the standard-dose group ï¼»60 mg/(m2·d)ï¼½. And then the effects of different doses of daunorubicin on complete remission (CR) rate, minimal residual disease (MRD)-negative CR rate, relapse-free survival (RFS), overall survival (OS), and adverse events were analyzed. RESULTS: Median follow-up time of all the patients was 15 months. The CR rate and MRD- CR rate of the escalated-dose group was 88.5% and 71.4%, respectively, which were higher than 64.7% and 41.2% of the standard-dose group (P=0.029, P=0.008). The estimated 2-year RFS of the escalated-dose group was 68.4%, which was higher than 38.5% of the standard-dose group (P=0.015), but estimated 2-year OS showed no statistically significant difference (77.1% vs 66.7%, P=0.059), as well as grade 3-4 adverse events. The escalated dose of daunorubicin had prolonged RFS (13 months vs not reached, P=0.022) and OS (23 months vs not reached, P=0.029) in the FLT3-ITD- AML patients. CONCLUSION: The escalated dose of daunorubicin can induce higher complete remission rate, deeper remission and longer duration of remission without increasing adverse events in newly diagnosed primary AML patients.


Assuntos
Daunorrubicina , Leucemia Mieloide Aguda , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Citarabina/uso terapêutico , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Indução de Remissão , Estudos Retrospectivos
3.
J Cancer ; 10(20): 4947-4953, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31598167

RESUMO

Radiotherapy for liver cancer can affect the level of autophagy in cells, and effective autophagy regulation can increase the radiosensitivity of liver cancer cells.Saikosaponin-d (SSd) is an effective active ingredient extracted from traditional Chinese medicine Bupleurum. We have confirmed previously in vitro and in vitro experiments that SSd can significantly induce apoptosis of liver cancer cells, increase the radiosensitivity of liver cancer cells.This study explored the role of autophagy in SSd-mediated radiosensitivity of liver cancer cells. MTT and clone formation experiments showed that radiation can inhibit the proliferation of hepatoma cells and reduce the colony formation of hepatoma cells. After the addition of SSd, the inhibitory effect of radiation on the proliferation and clonal formation of hepatoma cells was further enhanced. However, the addition of the autophagy inhibitor chloroquine or mTOR agonist can partially reverse the inhibitory effect of the combined treatment of SSd with radiation on the proliferation of hepatoma cells. Similarly, transmission electron microscopy and laser confocal microscopy showed that after the addition of SSd, the number of radiation-induced autophagosomes increased significantly in hepatoma cells and the intervention of mTOR agonist can reduce the formation of autophagosomes in hepatoma cells.In addition,Western blot analysis presented that radiation significantly increased LC3-II levels. Especially when SSd is added, LC3-II levels is further increased. Our data indicate that SSd can inhibit the growth of liver cancer cells and enhance cell radiosensitivity by inducing autophagy formation.

4.
Int J Biochem Cell Biol ; 106: 8-20, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30389549

RESUMO

P53 dysfunction has been associated with various malignant tumors, including acute leukemia. The overexpression of mouse double minute 2 (MDM2) causes the inactivation of p53 in acute leukemia. MDM2 inhibitors that activate p53 and induce apoptosis are currently being developed for potential treatment of acute leukemia. However, MDM2 inhibitors alone have limited efficacy in acute leukemia therapeutics. Combining other drugs to enhance the efficacy of MDM2 inhibitors is the thus considered as a potential treatment scheme. Here, we report that the combination of Nutlin-3 and Tanshinone IIA synergistically induces cytotoxicity, cell cycle arrest, apoptosis, and autophagic cell death, thereby imparting anti-leukemia effect in an acute leukemia cell line with wild-type p53 by effectively activating p53, inhibiting the AKT/mTOR pathway, and activating the RAF/MEK pathway. Using primary samples from acute leukemia patients, we show that the combination of Nutlin-3 plus Tanshinone IIA synergistically induces cytotoxicity by activating p53 and inhibiting the AKT/mTOR pathway. This specific combination of Nutlin-3 and Tanshinone IIA is also effective in preventing the recurrence of refractory leukemia, such as Ph+ ALL with the ABL kinase T315I mutation and AML with the FLT3-ITD mutation. Taken together, the results of this study demonstrate that the Nutlin-3 plus Tanshinone IIA combination exerts synergistic anti-leukemia effects by regulating the p53 and AKT/mTOR pathways, although further investigation is warranted. Small-molecule MDM2 antagonists plus Tanshinone IIA may thus be a promising strategy for the treatment of acute leukemia.


Assuntos
Benzofuranos/farmacologia , Citotoxinas/farmacologia , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Imidazóis/farmacologia , Leucemia/tratamento farmacológico , Piperazinas/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/biossíntese , Serina-Treonina Quinases TOR/metabolismo , Proteína Supressora de Tumor p53/biossíntese , Doença Aguda , Adolescente , Adulto , Idoso de 80 Anos ou mais , Benzofuranos/agonistas , Citotoxinas/agonistas , Sinergismo Farmacológico , Feminino , Células HL-60 , Humanos , Imidazóis/agonistas , Leucemia/genética , Leucemia/metabolismo , Leucemia/patologia , Masculino , Pessoa de Meia-Idade , Piperazinas/agonistas , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-mdm2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-mdm2/genética , Serina-Treonina Quinases TOR/genética , Proteína Supressora de Tumor p53/genética
5.
Biochem J ; 474(24): 4153-4170, 2017 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-29046392

RESUMO

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is triggered by BCR/ABL kinase. Recent efforts focused on the development of more potent tyrosine kinase inhibitors (TKIs) that also inhibit mutant tyrosine kinases such as nilotinib and dasatinib. Although major advances in the treatment of this aggressive disease with potent inhibitors of the BCR/ABL kinases, patients in remission frequently relapse due to drug resistance possibly mediated, at least in part, by compensatory activation of growth-signaling pathways and protective feedback signaling of leukemia cells in response to TKI treatment. Continuous activation of AKT/mTOR signaling and inactivation of p53 pathway were two mechanisms of TKI resistance. Here, we reported that nutlin-3 plus tanshinone IIA significantly potentiated the cytotoxic and apoptotic induction effects of imatinib by down-regulation of the AKT/mTOR pathway and reactivating the p53 pathway deeply in Ph+ ALL cell line. In primary samples from Ph+ ALL patients, nutlin-3 plus tanshinone IIA also exhibited synergetic cytotoxic effects with imatinib. Of note, three samples from Ph+ ALL patients harboring T315I mutation also showed sensitivity to the combined treatment of imatinib, nutlin-3 plus tanshinone IIA. In Ph+ ALL mouse models, imatinib combined with nutlin-3 plus tanshinone IIA also exhibited synergetic effects on reduction in leukemia burden. These results demonstrated that nutlin-3 plus tanshinone IIA combined TKI might be a promising treatment strategy for Ph+ ALL patients.


Assuntos
Abietanos/administração & dosagem , Mesilato de Imatinib/administração & dosagem , Imidazóis/administração & dosagem , Proteína Oncogênica v-akt/antagonistas & inibidores , Piperazinas/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Feminino , Genes p53/efeitos dos fármacos , Genes p53/fisiologia , Humanos , Células K562 , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Proteína Oncogênica v-akt/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/metabolismo , Resultado do Tratamento
6.
Mol Cell Biochem ; 422(1-2): 161-170, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27644195

RESUMO

microRNAs (miRNAs) act as a major regulator of acquired chemo-resistance in various types of cancer therapeutics. This study investigated the contribution of miRNAs in influencing multiple drug resistance in esophageal squamous cell carcinoma (ESCC). The sensitivity of four ESCC cell lines (EC109, EC9706, TE-1 and KYSE-150) to 5-fluorouracil (5-FU) and oxaliplatin (OX) was determined by MTT assay. A 5-FU and OX-resistant subline, EC9706R, was established by continuous exposure to stepwise increasing concentration of 5-FU and OX. Microarray technology was used to compare the differential expression of miRNAs between resistant cells and parental cells. Chemo-sensitivity assay was performed to evaluate drug response in EC9706R cells transfected with miRNA mimic or inhibitor. The direct targets of miRNA were identified by employing pathway analysis and then confirmed with luciferase assay. Sixty ESCC tissue samples and their paired adjacent normal tissues were collected to validate the expression of identified miRNA. Mouse models were further utilized to investigate the function of miRNA on acquired chemo-resistance. MicroRNA panel results indicated that a total of 12 miRNAs were differentially expressed and miR-141-3p was highly over expressed in resistant cells. Inhibition of miR-141-3p reversed acquired chemo-resistance in EC9706R cells by stimulating apoptosis. The expression of miR-141-3p was significantly increased in ESCC tissue samples compared to their matched distant normal tissues. In addition, the elevated miR-141-3p expression was found to be associated with ESCC differentiation status and TNM stage. Moreover, Phosphatase and tensin homolog (PTEN) was identified as direct target of miR-141-3p. Western blot exhibited altered protein levels of PTEN, Akt, and PI3k with miR-141-3p inhibitor. An inverse correlation between PTEN expression and miR-141-3p expression was also observed in tissue samples. EC9706R xenograft mouse model became sensitized to 5-FU and OX treatment following miR-141-3p inhibitor transfection in vivo. Our study demonstrated that miR-141-3p contributed to an acquired chemo-resistance through PTEN modulation both in vitro and in vivo.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias Esofágicas/metabolismo , Fluoruracila/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/biossíntese , Proteínas de Neoplasias/biossíntese , Compostos Organoplatínicos/farmacologia , PTEN Fosfo-Hidrolase/biossíntese , RNA Neoplásico/biossíntese , Animais , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Camundongos , MicroRNAs/genética , Proteínas de Neoplasias/genética , Oxaliplatina , PTEN Fosfo-Hidrolase/genética , RNA Neoplásico/genética , Ensaios Antitumorais Modelo de Xenoenxerto
7.
J Radiat Res ; 57(5): 468-476, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27422937

RESUMO

Although radiation resistance is a common challenge in the clinical treatment of esophageal squamous cell carcinoma (ESCC), an effective treatment strategy has yet to be developed. Aberrant expression of microRNAs (miRNAs) is responsible for cancer sensitivity to radiation. In this study, we aimed to identify the miRNAs that are associated with radioresistance in ESCC. We used a miRNA microarray to perform a comparison of miRNA expression in both ESCC parental and acquired radioresistance cell lines. qRT-PCR was used to confirm the alterations. Cell radiosensitivity was determined with a survival fraction assay. Functional analyses of the identified miRNA in ESCC cells with regard to metastasis and apoptosis were performed by transwell assays and flow cytometry. The miRNA targets were identified with pathway analysis and confirmed with a luciferase assay. miR-98 was recognized as the most downregulated miRNA in established radioresistant cell line. AmiR-98 mimic enforced the expression of miRNA-98 and made ESCC cells sensitive to radiotherapy, while anti-miR-98 reversed this process. Optimal results were achieved by decreasing cellular proliferation, decreasing cell migration and inducing apoptosis. The luciferase target gene analysis results showed that the overexpression of miRNA-98 inhibited tumor growth and resistance tolerance by directly binding to the BCL-2 gene. Our study indicated that increasing miRNA-98 expression can be used as a potential radiosensitive therapeutic strategy for treating esophageal cancer cells.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Tolerância a Radiação/genética , Regulação para Cima/genética , Apoptose/genética , Apoptose/efeitos da radiação , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/genética , Movimento Celular/efeitos da radiação , Carcinoma de Células Escamosas do Esôfago , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , MicroRNAs/metabolismo , Ligação Proteica/efeitos da radiação , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Tolerância a Radiação/efeitos da radiação , Regulação para Cima/efeitos da radiação , Raios X
8.
Jpn J Clin Oncol ; 45(2): 169-75, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25416813

RESUMO

OBJECTIVE: Esophageal squamous cell carcinoma is increasingly treated with trimodality therapy. The objective of this Phase I/II clinical study is to assess the efficacy and safety of neoadjuvant radiochemotherapy with docetaxel and cisplatin and radiotherapy in patients with esophagectomy for locally advanced squamous cell carcinoma of the esophagus with neoadjuvant chemoradiotherapy. METHODS: Patients with esophageal squamous cell carcinoma received radiochemotherapy (50 Gy/25 fractions during Weeks 1-5) using a three-dimensional conformal radiation therapy or intensity-modulated radiation therapy technique together with weekly docetaxel (20 mg/m(2) at dose levels 1 and 2, 25 mg/m(2) at dose level 3 on Weeks 1-5) and cisplatin (30 mg/m(2) at dose level 1, 40 mg/m(2) at dose levels 2 and 3 on Weeks 1-5) from January 2009 to December 2011. The dose-limiting toxicities and maximum tolerated dose were the primary endpoints and overall response rate and progression-free survival were the secondary endpoints. RESULTS: Over this timeframe, a total of 49 patients completed trimodality therapy. Thirteen patients were treated at dose level 1, 21 patients at dose level 2 and 15 patients at dose level 3.The maximum tolerated dose for docetaxel was 20 mg/m(2) and cisplatin 40 mg/m(2). The complete response or partial response was observed in 26.5% (13/49) of patients. Thirty-four patients (69.4%) were treated with neoadjuvant radiochemotherapy followed by surgical resection. The median progression-free survival and median overall survival for all patients (n = 49) were 8 and 17.2 months, respectively. The median overall survival was 27.5 months for patients treated at dose level 2. CONCLUSION: Neoadjuvant radiochemotherapy with docetaxel 20 mg/m(2) and cisplatin 40 mg/m(2) was effective and tolerable induction regimen in patients with esophageal tumors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Esofagectomia , Terapia Neoadjuvante/métodos , Radioterapia Conformacional , Adulto , Idoso , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Quimiorradioterapia , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Docetaxel , Relação Dose-Resposta a Droga , Esquema de Medicação , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Radioterapia de Intensidade Modulada , Taxoides/administração & dosagem , Resultado do Tratamento
9.
Asian Pac J Trop Med ; 7(10): 772-5, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25129458

RESUMO

OBJECTIVES: To study the effect of arsenic trioxide (As2O3) combined with ginsenosides Rg3 on inhibiting the NCI-H1299 lung cancer cells and subsistence in nude mice bearing hepatoma. METHODS: MTT method was used to measure the inhibition effect of As2O3 combined Rg3 on NCI-H1299 cells, and the proliferation inhibiting effect was observed via establishing the transplanted tumor model in vitro. A total of 40 tumor-bearing nude mice were randomly divided into normal saline group, As2O3, Rg3 and As2O3+Rg3 group. Transplantation tumor model of lung cancer in nude mice was constructed, followed by injection of certain concentrations of normal saline, As2O3, ginseng saponin Rg3 and As2O3+Rg3 every day. The survival duration and the tumors size of the mice were recorded and the Kaplan-Meier curve was made; microscopic observation of apoptosis of tumor cells in vivo was done using TUNEL staining. RESULTS: After 72 h of injection, inhibition rate of tumor cell in normal saline group, As2O3 group, Rg3 group and As2O3+Rg3 group was (5.66±0.31)%, (65.58±4.75)%, (44.69±3.32)% and (82.67±5.43)%, respectively. Inhibition rate of tumor cell in As2O3 group, Rg3 group and As2O3+Rg3 group was significantly higher than that of normal saline group (P<0.01); inhibition rate of tumor cells of As2O3+Rg3 group was significantly higher than that of the two groups given As2O3 or Rg3 alone (P<0.01). The tumor volume of As2O3 group, Rg3 group and As2O3+Rg3 group shrank to (65.38±3.25)%, (77.68±3.43)% and (42.65±3.55)% of the original, tumor volume of saline group was 1.21 times of the original size (P<0.01); Median survival of saline group, Rg3 group, As2O3 group were significantly shorter than that of As2O3+Rg3 group (P<0.01); co-ordinated intervention ability of As2O3+Rg3 on NCI-H1299 cell was significantly higher than that of As2O3 or Rg3, separately. CONCLUSIONS: As2O3 combined with Rg3 can significantly inhibit proliferation of NCI-H1299 cells in lung cancer, prolong survival of tumor-bearing nude mice, and promote tumor cell apoptosis, and have significant effect on lung cancer treatment.

10.
Med Sci Monit ; 20: 1340-4, 2014 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-25080219

RESUMO

BACKGROUND: The aim of this study was to investigate the effects of Saikosaponin-d (SSd) combined with radiotherapy on SMMC-7721 hepatoma cell lines and its mechanism. MATERIAL/METHODS: SMMC-7721 hepatoma cell lines are selected in our research. With MTT (methylthiazolyldiphenyl-tetrazolium-bromide) method, the effects of SSd and radiation on inhibiting SMMC-7721 cell growth were investigated. We also used transmission electron microscopy (TEM) to observe ultrastructural changes of cells. Colorimetry methods were used to measure content changes of glutathione (GSH) and malondialdehyde (MDA) in cells. RESULTS: Both SSd and radiation inhibited the growth of SMMC-7721 cells. The combination of SSd and radiotherapy had a time-dependent synergistic effect. Radiation caused ultrastructural damage to cells, and the damage was enhanced in combination with SSd. Radiation decreased the GSH content and increased the MDA content in cells, and this effect was suppressed after the intervention of SSd. CONCLUSIONS: SSd can inhibit the growth of SMMC-7721 hepatoma cell lines in vitro. Additionally, it significantly enhances the effects of radiation on inhibiting the growth of SMMC-7721 hepatoma cell lines, and up-regulates the antioxidant level after the radiotherapy. Thus, SSd could be an ideal radiotherapy sensitizer for the treatment of liver cancer.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/radioterapia , Ácido Oleanólico/análogos & derivados , Radiossensibilizantes/farmacologia , Saponinas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Humanos , Técnicas In Vitro , Microscopia Eletrônica de Transmissão , Ácido Oleanólico/farmacologia , Sais de Tetrazólio , Tiazóis
11.
Indian J Hematol Blood Transfus ; 30(2): 97-104, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24839363

RESUMO

Recent data indicates that nucleoside/nucleotide analogue (NUC) is effective in preventing and controlling hepatitis B virus (HBV) reactivation in HBV-carrying cancer patients who undergo chemotherapy, but the ideal antiviral agent and optimal application protocol still needs to be determined. Meanwhile, it is uncertain whether those with past HBV infection require antiviral prophylaxis during chemotherapy. This report retrospectively analyzed non-Hodgkin's lymphoma (NHL) patients seen from January, 2004 to June, 2009 in West China Hospital. We found that the prevalence of chronic HBV infection in our NHL patients was 20.7 % while that of past HBV infection was 21.05 %. Compared with the high rate (25.6 %) of HBV reactivation in patients with chronic HBV infection, none of those with past HBV infection in fact had occult HBV infection thus none experienced reactivation. Of the 82 patients with chronic HBV infection who received chemotherapy, antiviral prophylaxis could significantly reduce the incidence of HBV reactivation (5.0 vs. 45.2 % in the control group) and the incidence of liver function damage (32.5 vs. 73.8 % in the control group). The results of the current study confirmed previous reports that prophylactic NUCs administration can effectively prevent HBV reactivation and significantly reduce the incidence of HBV reactivation especially for patients receiving rituximab-containing regimens. Due to the fact that none of individuals who had past HBV infection developed HBV reactivation reported in our study, antiviral prophylaxis may not be required for patients with past HBV infection. Close observation of alanine aminotransferase and HBV-DNA contributes to early diagnosis and timely treatment of HBV reactivation.

12.
Asian Pac J Trop Med ; 7(4): 276-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24507675

RESUMO

OBJECTIVE: To investigate the effect of sevoflurane on tissue permeability of lung ischemia-reperfusion injury (LIRI) in rats. METHODS: A total of 45 wistar rats were randomly divided into 3 groups I, II, III. Modified Eppinger method was adopted to establish the rat lung ischemia-reperfusion injury model. Group I served as the control group, group III as ischemia reperfusion group, group III as sevoflurane ischemia-reperfusion group. Blood gas index, lung permeability index (LPI) change, lung tissue pathology change and lung water content were observed and compared between groups of rats at different time points. RESULTS: During ischemia reperfusion, all rats kept balance of the MAP during different time points, SPO2 of group II and III decreased significantly than I group (P<0.05); after reperfusion lung permeability index in Group II and III was higher than the control group significantly (P<0.05), 120 min after reperfusion LPI change and injury of group III was significantly lower than II group (P<0.05); interstitial and alveolar cavity effusion in of group III were lower than that of group II. CONCLUSIONS: Sevoflurane pretreatment can reduce the lung tissue permeability, and LIRI plays a protective role in LIRI.


Assuntos
Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Éteres Metílicos/farmacologia , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/metabolismo , Animais , Pulmão/metabolismo , Masculino , Permeabilidade/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar , Traumatismo por Reperfusão/tratamento farmacológico , Sevoflurano
13.
World J Gastroenterol ; 20(1): 193-203, 2014 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-24415872

RESUMO

AIM: To investigate the effects of diallyl trisulfide (DATS), a garlic-derived organosulfur compound, in pancreatic cancer cells. METHODS: Human pancreatic cancer cells with wild-type p53 gene (Capan-2) and normal pancreatic epithelial cells (H6C7) were cultured in RPMI1640. DATS was prepared at a concentration of 100 µmol/L. Cell viability was determined via the methyl thiazolyl tetrazolium assay. Apoptotic cells were detected by TUNEL assay. Cell cycle analysis was performed using flow cytometry. Protein expression was determined by Western blot. Bax and Bcl-2 expression was detected by immunofluorescence. Apoptosis genes and cell cycle were assessed by quantitative real-time polymerase chain reaction. RESULTS: DATS suppressed the viability of cultured human pancreatic cancer cells (Capan-2) by increasing the proportion of cells in the G2/M phase and induced apoptotic cell death. Western blot analysis indicated that DATS enhanced the expression of Fas, p21, p53 and cyclin B1, but downregulated the expression of Akt, cyclin D1, MDM2 and Bcl-2. DATS induced cell cycle inhibition which was correlated with elevated levels of cyclin B1 and p21, and reduced levels of cyclin D1 in Capan-2 cells and H6C7 cells. DATS-induced apoptosis was markedly elevated in Capan-2 cells compared with H6C7 cells, and this was correlated with elevated levels of cyclin B1 and p53, and reduced levels of Bcl-2. DATS-induced apoptosis was correlated with down-regulation of Bcl-2, Akt and cyclin D1 protein levels, and up-regulation of Bax, Fas, p53 and cyclin B protein levels in Capan-2 cells. CONCLUSION: DATS induces apoptosis of pancreatic cancer cells (Capan-2) and non-tumorigenic pancreatic ductal epithelial cells (H6C7).


Assuntos
Compostos Alílicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Pancreáticas/patologia , Sulfetos/farmacologia , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Ductos Pancreáticos/efeitos dos fármacos , Ductos Pancreáticos/metabolismo , Ductos Pancreáticos/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
14.
BMC Complement Altern Med ; 13: 263, 2013 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-24119370

RESUMO

BACKGROUND: Saikosaponin-d (SSd), a monomer terpenoid purified from the Chinese herbal drug Radix bupleuri, has multiple effects, including anticancer properties. However, the effect of SSd on tumors exposed to radiation is largely unknown. To investigate the radiosensitizing effect of SSd and its possible mechanism, we combined SSd with radiation therapy to treat SMMC-7721 hepatocellular carcinoma cells under oxia and hypoxia. METHODS: Cell growth, apoptosis, and cell cycle distribution were examined after treatment with SSd alone, radiation alone, and their combinations under oxia and hypoxia. The protein and mRNA levels of p53, Bcl2, and BAX were measured using western blot analysis and RT-PCR, respectively. RESULTS: Treatment with SSd alone and radiation alone inhibited cell growth and increased apoptosis rate at the concentration used. These effects were enhanced when SSd was combined with radiation. Moreover, SSd potentiated the effects of radiation to induce G0/G1 arrest in SMMC-7721 cells, and reduced the G2/M-phase population under hypoxia. However, under oxia, SSd only potentiated the effects of radiation to induce G0/G1 arrest, but not G2/M-phase arrest. These effects of SSd alone, radiation alone, and their combination, were accompanied by upregulated expression of p53 and BAX and downregulation of Bcl2 expression under oxia and hypoxia. CONCLUSION: SSd potentiates the effects of radiation on SMMC-7721 cells; thus, it is a promising radiosensitizer. The radiosensitizing effect of SSd may contribute to its effect on the G0/G1 and G2/M checkpoints of the cell cycle.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/radioterapia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/radioterapia , Ácido Oleanólico/análogos & derivados , Radiossensibilizantes/farmacologia , Saponinas/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Carcinoma Hepatocelular/patologia , Pontos de Checagem do Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/patologia , Ácido Oleanólico/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Raios X , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
15.
Drug Des Devel Ther ; 7: 149-59, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23662044

RESUMO

The mammalian target of rapamycin (mTOR) is a protein kinase that regulates protein translation, cell growth, and apoptosis. Rapamycin (RPM), a specific inhibitor of mTOR, exhibits potent and broad in vitro and in vivo antitumor activity against leukemia, breast cancer, and melanoma. Recent studies showing that RPM sensitizes cancers to chemotherapy and radiation therapy have attracted considerable attention. This study aimed to examine the radiosensitizing effect of RPM in vitro, as well as its mechanism of action. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay showed that 10 nmol/L to 15 nmol/L of RPM had a radiosensitizing effects on pancreatic carcinoma cells in vitro. Furthermore, a low dose of RPM induced autophagy and reduced the number of S-phase cells. When radiation treatment was combined with RPM, the PC-2 cell cycle arrested in the G2/M phase of the cell cycle. Complementary DNA (cDNA) microarray and reverse transcription polymerase chain reaction (RT-PCR) revealed that the expression of DDB1, RAD51, and XRCC5 were downregulated, whereas the expression of PCNA and ABCC4 were upregulated in PC-2 cells. The results demonstrated that RPM effectively enhanced the radiosensitivity of pancreatic carcinoma cells.


Assuntos
Neoplasias Pancreáticas/radioterapia , Tolerância a Radiação/efeitos dos fármacos , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Autofagia/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Citometria de Fluxo , Perfilação da Expressão Gênica , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
16.
17.
Am Surg ; 78(12): 1329-35, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23265121

RESUMO

The aim of this study was to discuss the new methods of clinical classification and staging of patients with myasthenia gravis (MG) proposed by our group and to summarize the experiences of surgical treatment of MG with a novel incision by cutting the sternum cross-sectionally at the second intercostal level. A retrospective analysis was made for the clinical data from the patients with MG who underwent thymectomy from July 1988 to May 2009. The surgical procedures were designed into three groups, a group with Osserman classification and median incision of the sternum (Group 1), a group with MGFA typing (Myasthenia Gravis Foundation of America) and a small transverse sternal incision at the second intercostal level (Group 2), and a group with new typing and a smaller transverse sternal incision at the second intercostal level (Group 3). Observation of the clinical typing and staging was made in the patients with myasthenia crisis. The parameters such as procedure duration in Group 2 and 3 was significantly lower than those in Group 1 (P < 0.05). The incidence of myasthenia crisis in Group 3 was significantly lower than that in Groups 2 and 3 (P < 0.05). The procedure with a smaller transverse sternal incision at the second intercostal level (Group 3) is a safer method for patients with MG. The combination of this procedure with the new typing and staging methods proposed by our group could facilitate the selection of operation indications and opportunity, resulting in the lower incidence of myasthenia crisis and mortality. Our new procedure is well deserved to be a preferential selection by other hospitals.


Assuntos
Miastenia Gravis/classificação , Miastenia Gravis/cirurgia , Esterno/cirurgia , Timectomia/métodos , Adolescente , Adulto , Perda Sanguínea Cirúrgica , Estudos de Coortes , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Miastenia Gravis/diagnóstico , Duração da Cirurgia , Cuidados Pós-Operatórios/métodos , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Medição de Risco , Timoma/cirurgia , Neoplasias do Timo/cirurgia , Resultado do Tratamento , Adulto Jovem
19.
Int J Hematol ; 94(5): 491-4, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22020400

RESUMO

Mast cell sarcoma is a rare disease characterized by localized, but destructive and rapid, growth of the tumor, high risk of distant metastasis, possibility of a leukemic phase, and poor prognosis. We report successful treatment of uterine mast cell sarcoma with imatinib in a 39-year-old woman who presented with abdominal distention and massive ascites. Routine treatment, such as combined chemotherapy, had little effect. We administered imatinib to the patient and achieved a good response in the absence of c-kit mutation, BCR/ABL, and FIP1L1-PDGFRα. Our results indicate that imatinib is of potential use in the treatment of mast cell sarcoma.


Assuntos
Antineoplásicos/administração & dosagem , Sarcoma de Mastócitos/tratamento farmacológico , Sarcoma de Mastócitos/genética , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/genética , Adulto , Benzamidas , Feminino , Genes abl , Humanos , Mesilato de Imatinib , Mutação , Proteínas de Fusão Oncogênica , Proteínas Proto-Oncogênicas c-kit/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas , Resultado do Tratamento , Fatores de Poliadenilação e Clivagem de mRNA
20.
Immunol Res ; 51(1): 80-96, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21814860

RESUMO

In the murine splenocytes, CD8α+ dendritic cells (abbreviated as 8+DC) and CD8α- dendritic cells (abbreviated as 8-DC) are identified with some vague features for each of them. 8+DCs but not 8-DCs cross-prime cytotoxic T cells in vivo. We aim to distinguish the two subtypes of DC based on gene expression profiling. Suppressive subtractive hybridization was undertaken to get differentially expressed genes from such subtracted cDNA library specific to 8+DC. A total of 114 sequences from the subtracted cDNA library specific to 8+DC library were analyzed. Most of them are known proteins, but some of them were novel, either totally novel genes or homologs to known genes, but with novel exon. About 55 probably novel exons were discovered, and 11 exons had longer length than those in gene bank. The clones 12, 44, 79, and 110 have no match with known sequences in gene bank. Then, semi-quantitative PCR was done to compare the expression of the enriched sequences between 8+DC and 8-DC. About 14 genes are differentially expressed in 8+DC. Therefore, SSH is an effective method to clone differentially expressed genes for 8+DC compared to 8-DC.


Assuntos
Antígenos CD8 , Células Dendríticas/imunologia , Regulação da Expressão Gênica/imunologia , Baço/imunologia , Animais , Células Dendríticas/citologia , Feminino , Perfilação da Expressão Gênica , Masculino , Camundongos , Baço/citologia
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