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1.
Cell Biochem Funct ; 33(7): 495-502, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26486443

RESUMO

Gastric cancer remains one of the most prevalent and lethal malignancies in the world. Despite new advances in treatment and diagnosis, patients with advanced gastric cancer are still difficult to cure resulting in a high mortality rate and poor prognosis. Signal transducer and activator of transcription 3 (Stat3) is observed aberrant in multiple tumours, including gastric cancer. Stat3 overexpression was confirmed performing a vital role in tumorigenesis. In the present study, we constructed a pSi-Stat3 plasmid to silence Stat3 and investigated the effect of pSi-Stat3 on cell proliferation, apoptosis and cell cycle progression in gastric cancer cell line SGC-7901 and mice xenograft model. Downstream proteins of Stat3, including Cyclin-D1, Survivin and Bcl-2, were detected as well for the underlying mechanism exploration. It showed that pSi-Stat3 can effectively silence the expression of Stat3 and inhibits the growth of gastric tumour both in vitro and in vivo significantly via cell apoptosis and cell cycle shift induction. The findings suggest that Stat3 signal pathway might be a promising therapeutic target for tumour treatment, including gastric cancer.


Assuntos
Antineoplásicos/farmacologia , RNA Interferente Pequeno/farmacologia , Fator de Transcrição STAT3/antagonistas & inibidores , Neoplasias Gástricas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular , Linhagem Celular Tumoral , Ciclina D1/metabolismo , Feminino , Genes bcl-2 , Xenoenxertos , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Mensageiro/antagonistas & inibidores , Fator de Transcrição STAT3/genética , Neoplasias Gástricas/metabolismo , Survivina
2.
Oncol Rep ; 32(2): 573-80, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24899100

RESUMO

It has been shown that overexpression of signal transducer and activator of transcription 3 (Stat3) contribute to the progression and metastasis of various solid tumors and that silencing Stat3 inhibits tumor growth in several types of cancer. Gene associated with retinoid-IFN-induced mortality 19 (GRIM-19), a Stat3-inhibitory protein, was identified as a potential tumor suppressor associated with growth inhibition and cell apoptosis by targeting the transcription factor Stat3 for inhibition. However, little is known about Stat3 and GRIM-19 roles in the tumor growth of thyroid carcinoma cells. In the present study, we developed a dual expression plasmid that co-expressed Stat3-specific siRNA and GRIM-19 (pSi-Stat3-GRIM-19) and transfected it into SW579 cells (thyroid carcinoma cell line) to evaluate its effects on cell proliferation, cell apoptosis, cell migration and cell invasion in vitro and tumor growth in vivo. Simultaneous expression of pSi-Stat3-GRIM-19 in SW579 cancer cells was found to significantly suppress the proliferation, migration and invasion in vitro and tumor growth in vivo, when compared to the controls either Stat3-specific siRNA or GRIM-19 alone. In conclusion, our data demonstrated that a combined strategy of co-expressed Stat3-specific siRNA and GRIM19 synergistically and more effectively suppressed thyroid tumor growth, and have therapeutic potential for the treatment of thyroid cancer.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , NADH NADPH Oxirredutases/metabolismo , RNA Interferente Pequeno/metabolismo , Fator de Transcrição STAT3/antagonistas & inibidores , Neoplasias da Glândula Tireoide/patologia , Animais , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos BALB C , NADH NADPH Oxirredutases/genética , Plasmídeos/genética , Fator de Transcrição STAT3/genética , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Int J Clin Exp Pathol ; 6(10): 2071-81, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24133585

RESUMO

OBJECTIVE: To investigate the inhibitory effect of plasmid-based survivin-specific short hairpin RNA and GRIM-19 on the growth of Hep-2 laryngeal cancer cells. METHODS: The plasmid expressing survivin-specific short hairpin RNA (shRNA) and GRIM-19 (p-siRNA survivin/GRIM-19) was prepared and transfected into Hep-2 cells with Lipofectamine 2000. The mRNA and protein expression of surviving and GRIM-19 were measured with RT-PCR and western blot assay, respectively. MTT assay was employed to detect the proliferation of Hep-2 cells, and flow cytometry and AO/EB assay were done to determine the apoptosis of Hep-2 cells. RESULTS: In the p-siRNA survivin/GRIM-19, the mRNA and protein expression of survivin was markedly reduced by 54.4% and 42.2%, and the reduction in protein expression of surviving was more obvious than that in the p-siRNA survivin group (37%) (P<0.05). The protein expression of GRIM-19 was markedly enhanced when compared with the control group (P<0.01). MTT assay revealed the proliferation of Hep-2 cells undergoing transfection with p-siRNA survivin/GRIM-19 was markedly inhibited, and the inhibition rate was as high as 79%, which was higher than that in the psi-survivin group (45%) and p-GRIM-19 group (35%). AO/EB assay and flow cytometry indicated that the apoptotic cells in the p-siRNA survivin/GRIM-19 group were dramatically increased as compared to the psi-survivin group and p-GRIM-19 group. CONCLUSION: The p-siRNA survivin/GRIM-19 has marked decrease in survivin expression and dramatic increase in GRIM-19 expression. Moreover, silencing of survivin and over-expression of GRIM-19 can significantly inhibit the growth and induce the apoptosis of Hep-2 in vitro and in vivo.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Proliferação de Células , Proteínas Inibidoras de Apoptose/genética , Neoplasias Laríngeas/genética , NADH NADPH Oxirredutases/genética , Animais , Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Terapia Genética , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Masculino , Camundongos , Camundongos Nus , NADH NADPH Oxirredutases/metabolismo , Interferência de RNA , RNA Interferente Pequeno , Survivina
4.
Asian J Androl ; 15(2): 218-20, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23334201

RESUMO

The PSA screening for 25 years in America is the biggest cohort study in a field of public health.27 We should realize not only the significance of the early diagnosis and treatment of PCa, but also the dramatic decrease in PCaMR from 2002 to 2008. The data from the IARC were especially noteworthy.Moreover, the patients with highly aggressive PCa, who account for more than 30% of all PCa patients, could only be diagnosed earlier by PSA screening. The patients would thus gain the opportunity for earlier treatment and would have a prolonged, higher quality life-span. However, the complications of interventional treatments, including biopsy,radical prostatectomy and/or radiation therapy,will become more avoidable in the near future.According to the supporting evidence for the decrease in PCa mortality in PSA screening, we strongly hope that the USPSTF changes the 'D' recommendation for PSA screening.


Assuntos
Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Asiático , Biomarcadores Tumorais/sangue , Biópsia/efeitos adversos , Humanos , Incidência , Masculino , Programas de Rastreamento , Gradação de Tumores , Neoplasias da Próstata/sangue , Neoplasias da Próstata/mortalidade , Estados Unidos/epidemiologia
5.
Asian J Androl ; 14(4): 536-45, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22580637

RESUMO

Persistent activation of Survivin and its overexpression contribute to the formation, progression and metastasis of several different tumor types. Therefore, Survivin is an ideal target for RNA interference mediated-growth inhibition. Blockade of Survivin using specific short hairpin RNAs (shRNA) can significantly reduce prostate tumor growth. RNA interference does not fully ablate target gene expression, owing to the idiosyncrasies associated with shRNAs and their targets. To enhance the therapeutic efficacy of Survivin-specific shRNA, we employed a combinatorial expression of Survivin-specific shRNA and gene associated with retinoid-interferon-induced mortality-19 (GRIM-19). Then, the GRIM-19 coding sequences and Survivin-specific shRNAs were used to create a dual expression plasmid vector and were carried by an attenuated strain of Salmonella enteric serovar typhimurium (S. typhimurium) to treat prostate cancer in vitro and in vivo. We found that the co-expressed Survivin-specific shRNA and GRIM-19 synergistically and more effectively inhibited prostate tumor proliferation and survival, when compared with treatment with either single agent alone in vitro and in vivo. This study has provided a novel cancer gene therapeutic approach for prostate cancer.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma/terapia , Terapia Genética , Proteínas Inibidoras de Apoptose/metabolismo , NADH NADPH Oxirredutases/metabolismo , Neoplasias da Próstata/terapia , RNA Interferente Pequeno/uso terapêutico , Animais , Apoptose , Proteínas Reguladoras de Apoptose/genética , Carcinoma/metabolismo , Caspase 3/metabolismo , Linhagem Celular Tumoral , Ciclina D1/metabolismo , Expressão Gênica , Humanos , Proteínas Inibidoras de Apoptose/genética , Antígeno Ki-67/metabolismo , Masculino , Camundongos , NADH NADPH Oxirredutases/genética , Plasmídeos , Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Interferente Pequeno/metabolismo , Fator de Transcrição STAT3/metabolismo , Salmonella typhimurium , Survivina , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteína bcl-X/metabolismo
6.
Asian J Androl ; 13(5): 698-701, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21765437

RESUMO

The potential association between xenotropic murine leukaemia virus-related gammaretrovirus (XMRV) and prostate cancer (PCa) has been documented since 2006. It is important for furthering our understanding of the biological mechanisms of PCa to ascertain whether this association is causal. To summarize the available information on the epidemiological and laboratory findings of the association, we conducted a literature search of the PubMed electronic database (from March 2006 to February 2011) to identify relevant published studies that examined the association between XMRV and PCa. Although several studies showed the positive association between XMRV and PCa, more recent studies did not support this conclusion. The positive findings might be due to contamination of human samples. Further studies are needed to clarify this association.


Assuntos
Neoplasias da Próstata/virologia , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/patogenicidade , Síndrome de Fadiga Crônica/virologia , Humanos , Masculino
7.
Asian J Androl ; 13(4): 574-8, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21552284

RESUMO

The aim of this study was to determine and examine the possible reasons for the difference in prostate cancer incidence between Asian men and North American men by literature review. Data regarding cancer incidence and mortality were obtained from the database of the International Agency for Research on Cancer (IARC). A literature review was conducted by studying related articles published in peer-reviewed journals such as the The New England Journal of Medicine, Journal of Clinical Oncology, A Cancer Journal for Clinicians and Asian Journal of Andrology. To evaluate the early diagnosis and survival rates, the mortality-to-incidence rate ratio (MR/IR) was calculated from the IARC data. By comparing prostate cancer data between Asian men and North American men, we found that differences in the incidence rate and MR/IR could be attributed largely to a lack of annual prostate cancer screening with serum prostate-specific antigen (PSA) in most Asian countries. It is likely that PSA screening also contributes significantly to the differences in prostate cancer mortality rates. Prostate cancer has the highest incidence rate among five common malignancies in Asian Americans. However, the MR/IR ratio of prostate cancer is the lowest among cancers. These data seem to further support the usefulness of PSA screening, even though the percentage of low risk cancers is greater in prostate cancer than in other cancers. The low incidence rate of prostate cancer does not reflect the actual statistics of this disease in Asia. The data from limited institutions in many Asian countries seem to bias the true incidence and mortality rates. To improve this situation, incorporating PSA screening for prostate cancer, as well as constructing a nationwide cancer registration system, will be helpful.


Assuntos
Neoplasias da Próstata/epidemiologia , Idoso , Ásia/epidemiologia , Asiático/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , América do Norte/epidemiologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/mortalidade , População Branca/estatística & dados numéricos
8.
Zhonghua Nan Ke Xue ; 17(1): 21-6, 2011 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-21351527

RESUMO

OBJECTIVE: To investigate the expressions of survivin and GRIM-19 in prostatic cancer tissue and their clinical implications. METHODS: We detected the expressions of survivin and GRIM-19 in the tissues of normal prostate (NP), benign prostate hyperplasia (BPH) and prostate cancer (PCa) using immunohistochemical staining, RT-PCR and Western blot, and processed the data by SPSS12. RESULTS: The positive rates of survivin expression were 6.25% , 18.18% and 90.62% in NP, BPH and PCa (P < 0.01), while those of GRIM-19 were 87.50%, 81.82% and 9.37% , respectively (P < 0.01). Semiquantitative RT-PCR and immunohistochemical staining showed that both survivin mRNA and survivin expressions were highly positive in PCa but negative in NP and BPH. Western blot exhibited that the survivin protein was expressed strongly in PCa but weakly in NP and BPH, while the GRIM-19 protein was expressed just contrariwise (P < 0.01). CONCLUSION: The expressions of survivin and GRIM-19 may be closely correlated with the pathogenesis of prostate cancer.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , NADH NADPH Oxirredutases/metabolismo , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Estudos de Casos e Controles , Humanos , Masculino , Próstata/patologia , Neoplasias da Próstata/patologia , Survivina
9.
J Pharmacol Exp Ther ; 338(1): 173-83, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21444629

RESUMO

Our objective was to evaluate cell growth and death effects by inhibiting Murine Double Minute 2 (MDM2) expression in human prostate cancer cells overexpressing the wild-type (WT) p53 gene. Prostate PC-3 tumor cells were transfected with a plasmid containing either mdm2 small interfering (Si-mdm2) or the WT p53 gene (Pp53) alone, or both (Pmp53), using Lipofectamine in vitro and attenuated Salmonella enterica serovar Typhi vaccine strain Ty21a (Salmonella Typhi Ty21a) in vivo. Cell growth, apoptosis, and the expression of related genes and proteins were examined in vitro and in vivo by flow cytometry and Western blot assays. We demonstrated that human prostate tumors had increased expression of MDM2 and mutant p53 proteins. Transfection of the PC-3 cells with the Pmp53 plasmid in vitro offered significant inhibition of cell growth and an increase in apoptotic cell death compared with that of the Si-mdm2 or Pp53 group. These effects were associated with up-regulation of p21 and down-regulation of hypoxia-inducible factor 1α expression in Pmp53-transfected cells. To validate the in vitro findings, the nude mice implanted with PC-3 cells were treated with attenuated Salmonella Typhi Ty21a carrying the plasmids, which showed that the Pmp53 plasmid significantly inhibited the tumor growth rate in vivo compared with that of the Si-mdm2 or Pp53 plasmid alone. Tumor tissues from mice treated with the Pmp53 plasmid showed increased expression of p21 and decreased expression of hypoxia-inducible factor 1α proteins, with an increased apoptotic effect. These results suggest that knockdown of mdm2 expression by its specific small interfering RNA with overexpression of the WT p53 gene offers synergistic inhibition of prostate cancer cell growth in vitro and in vivo.


Assuntos
Regulação Neoplásica da Expressão Gênica , Genes p53/fisiologia , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/biossíntese , Proteínas Proto-Oncogênicas c-mdm2/genética , RNA Interferente Pequeno/biossíntese , RNA Interferente Pequeno/genética , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Camundongos Nus , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Distribuição Aleatória , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
10.
Asian J Androl ; 13(3): 481-6, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21297658

RESUMO

DNA vector-based Stat3-specific RNA interference (si-Stat3) blocks Stat3 signalling and inhibits prostate tumour growth. However, the antitumour activity depends on the efficient delivery of si-Stat3. The effects on the growth of mouse prostate cancer cells of si-Stat3 delivered by hydroxyapatite were determined in this study. RM-1 tumour blocks were transplanted into C57BL/6 mice. CaCl2-modified hydroxyapatite carrying si-Stat3 plasmids were injected into tumours, and tumour growth and histology were determined. The expression levels of Stat3, pTyr-Stat3, Bcl-2, Bax, Caspase3, VEGF and cyclin D1 were measured by western blot analysis. Amounts of apoptosis in cancer cells were analysed with immunohistochemistry and the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) assay. The results showed that hydroxyapatite-delivered si-Stat3 significantly suppressed tumour growth up to 74% (P < 0.01). Stat3 expression was dramatically downregulated in the tumours. The immunohistochemistry and TUNEL results showed that si-Stat3-induced apoptosis (up to 42%, P < 0.01). The Stat3 downstream genes Bcl-2, VEGF and cyclin D1 were also strongly downregulated in the tumour tissues that also displayed significant increases in Bax expression and Caspase3 activity. These results suggest that hydroxyapatite can be used for the in vivo delivery of plasmid-based siRNAs into tumours.


Assuntos
Neoplasias da Próstata/tratamento farmacológico , RNA Interferente Pequeno/farmacologia , Fator de Transcrição STAT3/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Durapatita/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas , Plasmídeos , Neoplasias da Próstata/genética , Interferência de RNA , Fator de Transcrição STAT3/biossíntese , Fator de Transcrição STAT3/genética
11.
Radiol Oncol ; 45(3): 196-203, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22933956

RESUMO

BACKGROUND: The aim of the study was to investigate the suppressive effects of pSilencer2.1-U6-siRNA-stat3 recombinant plasmids on the growth of ovarian cancer in vitro. MATERIAL AND METHODS.: Three pairs of DNA template (stat3-1, stat3-2, stat3-3) specific for different target sites on stat3 mRNA were synthesized to reconstruct pSilencer2.1-U6-siRNA-stat3s, which were transfected into SKOV3 cells. The expressions of STAT3, BcL-2, cyclin D1 and C-myc in these cells were detected by Western blot and Northern blot. The cell cycle and the growth were determined by flow cytometry (FCM) and MTT assay, respectively. Cell apoptosis was determined by TUNEL staining. RESULTS: Of the three siRNAs, only siRNA targeting stat3-3 markedly suppressed the protein expression of stat3 in SKOV3 cells; MTT assay and FCM showed that transfection of stat3-3 siRNA could significantly suppress the growth of SKOV3 cells and arrest the cell cycle in vitro. TUNEL staining also showed massive apoptosis in SKOV3 cells transfected with stat3-3 siRNA. CONCLUSIONS: pSilencer2.1-U6-siRNA-stat3-3 can significantly inhibit the STAT3 expression in human ovarian cancer cells resulting in the inhibition of the cancer growth and the increase of apoptosis of cancer cells.

12.
Artigo em Chinês | MEDLINE | ID: mdl-21055246

RESUMO

OBJECTIVE: To study the effect of silencing survivin on the growth of Hep-2 human laryngeal cancer cells in vitro and in vivo. METHODS: Hep-2 cells were transfected with pGCsilencer-siRNA-survivin (psi-survivin)by Lipofectamine 2000. The mRNA and protein expressions of survivin were detected by semi-quantitative RT-PCR and Western blot, respectively. Cell proliferation activity was measured by MTT assay. Apoptosis was assessed by flow cytometry. The implanted tumors were formed from injected Hep-2 cells in nude mice. After the tumor formation, psi-survivin was injected into peritumor tissues. The growth of tumor were observed. The tumor volume was calculated and the tumor growth curve was plotted. The expression of survivin in tumor tissues was detected by Western blot. The tumor cell apoptosis was observed by Tunel staining. RESULTS: The sequence-specific siRNA of survivin inhibited the expressions of survivin mRNA and protein. The inhibition rates of survivin mRNA and protein expression were 54.4% and 37.0% respectively. Also the growth of Hep-2 cells was inhibited significantly, with a decrease by 71.7%. By the day 32 of tumor growth, the mean tumor volumes were (1443.9 ± 230.5) mm(3) (x(-) ± s) in saline control group, (1348.5 ± 198.4) mm(3) in plasmid-negative control group, and (624.6 ± 188.4) mm(3) in psi-survivin group, respectively (t = -5.917, P < 0.01). In the implanted tumors injected with psi-survivin, survivin protein expression was down-regulated significantly, with a inhibition rate of 41.8%. Tunel staining showed the apoptosis occurred in the implanted tumors. CONCLUSION: Silencing survivin could significantly inhibit the growth of Hep-2 human laryngeal cancer cells in vitro and in vivo.


Assuntos
Proliferação de Células , Inativação Gênica , Proteínas Inibidoras de Apoptose/genética , Animais , Apoptose , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Laríngeas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Survivina , Transfecção , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Asian J Androl ; 11(1): 9-13, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19050685

RESUMO

We have analysed the reasons for the low reported incidence of prostate cancer in China and argue for early diagnosis and treatment of this disease. According to the 2002 database of the International Agency for Research on Cancer (IARC), the age-standardized incidence of prostate cancer in China is 1.6/10(5) person years (PY), with a mortality rate of 1.0/10(5) PY and mortality-to-incidence rate ratio (MR/IR) = 0.63. The MR/IR ratio of prostate cancer in China was found to be higher than the average in Asia (MR/IR = 0.57) and much higher than that in North America (MR/IR = 0.13). These data indicate that in China most prostate cancers were in the advanced stages at the time of diagnosis, and that patients had a short survival time thereafter. In 2004, Stamey et al. reported a retrospective American study of prostate cancer for the years 1983-2003. It was shown that most cases of prostate cancer detected by prostate-specific antigen (PSA) screening were in the advanced stage at the start of this 20-year period. These early follow-up data are quite similar to the results obtained from mass PSA screening of elderly men in Changchun, China. However, after the American programmes for early diagnosis and treatment of prostate cancer were accepted, tumours were diagnosed at earlier stages. On the basis of these findings, mass screening should be performed in the whole of China using serum PSA to facilitate early diagnosis and treatment of prostate cancer.


Assuntos
Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , China/epidemiologia , Saúde Global , Humanos , Incidência , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/etnologia , Estados Unidos
14.
Zhonghua Yi Xue Za Zhi ; 88(10): 661-4, 2008 Mar 11.
Artigo em Chinês | MEDLINE | ID: mdl-18642764

RESUMO

OBJECTIVE: To study the effects of idarubicin (IDA) combined with 3, 3-diindolylmethane (DIM) on the growth inhibition of human prostate cancer cells. METHODS: Human prostate cancer cells of the line PC-3M were cultured and then divided into the following groups: control group with solvent added into the culture fluid; IDA groups, with IDA of the terminal concentrations of 0.5, 1 or 5 mg/L added into the culture fluid; DIM groups, with DIM of the terminal concentrations of 30, 60 or 100 micromol/L added into the culture fluid; and DIM + IDA groups, with 0. 5 mg/L IDA and DIM 30, 60 or 100 micromol/L added into the culture fluid. 48 h later the cell growth inhibition rate was detected by MTT assay. Flow cytometry and acridine orange staining were used to detect the cell cycle and apoptosis. RT-PCR and Western blotting were used to detect the mRNA and protein expression of caspase 9, an apoptosis gene. RESULTS: Both IDA and DIM dose-dependently inhibited the growth of the PC-3M cells. The growth inhibition rate of the 60 micromol/L DIM + 0.5 mg/L IDA group was 69.9%, almost 10 times as that of the 0.5 mg/L IDA group. The apoptosis rate of the 60 micromol/L DIM + 0. 5 mg/L IDA group was 47.0%, significantly higher than that of the 0.5 mg/L IDA group (3.2%, P < 0.05). RT-PCR and Western blotting showed that the combination of DIM and IDA significantly enhanced the mRNA and protein expression of caspase 9. CONCLUSION: DIM enhances the growth inhibition effect of IDA on human prostate cancer cells by the mechanism of induction of apoptosis.


Assuntos
Proliferação de Células/efeitos dos fármacos , Idarubicina/farmacologia , Indóis/farmacologia , Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
Zhonghua Yi Xue Za Zhi ; 88(9): 641-4, 2008 Mar 04.
Artigo em Chinês | MEDLINE | ID: mdl-18646723

RESUMO

OBJECTIVE: To investigate the STEAP1 gene function of the newly discovered gene six transmembrAne epithelial antigen of the prostate-1 (STEAP1). METHODS: Total RNA was obtained from human prostate cancer tissue and underwent PCR amplification. The full length of STEAP1 gene thus obtained was cloned. Mammalian expression vector pcDNA3. 1-STEAP1 was constructed and stably transfected into the human thyroid epithelial cells of the line FRTAP2320. A growth curve of the transfected cells was drawn. The intracellular reactive oxygen species (ROS) level was determined by flow cytometry (FC) with dichlorodihydrofluorescein diacetate (DCFHDA). RESULTS: The growth curve showed that the STEAP1 transfected cells grew faster than the control cells. FC showed that the fluorescence intensity of he intracellular ROS of the STEAP1 transfected cells was 42.13 +/- 1.13, significantly higher than those of the cell transfected with blank plasmid (10.02 +/- 1.42) and un-transfected cells (13.02 +/- 2.42, both P < 0.01). CONCLUSION: STEAP1 promotes the cell growth through inducing the intracellular ROS level.


Assuntos
Antígenos de Neoplasias/fisiologia , Proliferação de Células , Oxirredutases/fisiologia , Neoplasias da Próstata/patologia , Espécies Reativas de Oxigênio/metabolismo , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Apoptose , Western Blotting , Linhagem Celular , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Citometria de Fluxo , Expressão Gênica , Humanos , Masculino , Oxirredutases/genética , Oxirredutases/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção
16.
Asian J Androl ; 10(4): 551-60, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18478158

RESUMO

AIM: To investigate possible correlation factors for prostate cancer by a population-based case-control study in China. METHODS: We carried out a mass screening of prostate cancer in Changchun, China, using a prostate-specific antigen assisted by Japan International Cooperation Agency. From June 1998 to December 2000, 3 940 men over 50 years old were screened. Of these, 29 men were diagnosed with prostate cancer. We selected 28 cases and matched them with controls of low prostate-specific antigen value (< 4.1 ng/mL) by 1:10 according to age and place of employment. A case-control study of diet and prostate cancer was then carried out. RESULTS: After adjustment for education, body mass index (BMI), smoking, alcohol consumption, marriage and diet, intake of soybean product was discovered to be inversely related to prostate cancer. Men who consumed soybean product more than twice per week on different days had a multivariate odds ratio (OR) of 0.38 (95% confidence interval [CI], 0.13-1.12). In addition, men who consumed soybean products more than once per day had a multivariate OR of 0.29 (95% CI, 0.11-0.79) compared with men who consumed soybean products less than once per week. The P for trend was 0.02, which showed significant difference. There was no significant difference in P trend for any dairy food. Even when we matched the cases and controls by other criteria, we found that soybean food was the only preventive factor associated with prostate cancer. CONCLUSION: Our study suggests that consumption of soybeans, one of the most popular foods in Asia, would decrease the risk of prostate cancer.


Assuntos
Dieta , Glycine max , Programas de Rastreamento/métodos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , China/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/epidemiologia
17.
Acta Pharmacol Sin ; 27(3): 347-52, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16490172

RESUMO

AIM: To study the effect of pSilencer1.0-U6-siRNA-stat3 on the growth of human laryngeal tumors in nude mice. METHODS: Hep2 cells were transplanted into nude mice, then at the time of tumor formation, growth rates were observed. After the tumor formed, pSilencer1.0-U6-siRNA-stat3 was injected. Tumor volumes were calculated, and growth curves were plotted. Representative histological sections were taken from mice bearing transplantation tumors in both treated and control groups, and stat3, pTyr-stat3, Bcl-2, cyclin D1, and survivin expression were detected by Western blotting. survivin mRNA levels were detected by Northern blotting, hematoxylin and eosin staining and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) assay to confirm the apoptosis of tumors. RESULTS: In nude mice, pSilencer1.0-U6-siRNA-stat3 significantly suppressed the growth of tumors compared with controls (P<0.01). It suppressed stat3 expression, and downregulated BcL2, cyclin D1, and survivin expression within the tumor. This significantly induced apoptosis of the tumors. CONCLUSION: pSilencer1.0-U6-siRNA-stat3 was able to inhibit the growth of transplanted human laryngeal tumors in nude mice and induce apoptosis.


Assuntos
Neoplasias Laríngeas/patologia , Proteínas Associadas aos Microtúbulos/biossíntese , Proteínas de Neoplasias/biossíntese , Interferência de RNA , RNA Interferente Pequeno/biossíntese , Fator de Transcrição STAT3/biossíntese , Animais , Apoptose , Linhagem Celular Tumoral , Ciclina D1/metabolismo , Humanos , Proteínas Inibidoras de Apoptose , Neoplasias Laríngeas/metabolismo , Camundongos , Camundongos Nus , Proteínas Associadas aos Microtúbulos/genética , Proteínas de Neoplasias/genética , Transplante de Neoplasias , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Fator de Transcrição STAT3/genética , Survivina
18.
Asian J Androl ; 8(1): 45-51, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16372118

RESUMO

AIM: To identify the serum biomarkers of prostate cancer (PCa) by protein chip and bioinformatics. METHODS: Serum samples from 83 PCa patients and 95 healthy men were taken from a mass screening in Changchun, China. Protein profiling was carried out using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). The data of spectra were analyzed using two bioinformatics tools. RESULTS: Eighteen serum differential proteins were identified in the PCa group compared with the control group (P < 0.01). There were four proteins at the higher serum level and 14 proteins at the lower serum level in the PCa group. A decision tree classification algorithm that used an eight-protein mass pattern was developed to correctly classify the samples. A sensitivity of 92.0% and a specificity of 96.7% for the study group were obtained by comparing the PCa and control groups. CONCLUSION: We identified new serum biomarkers of PCa. SELDI-TOF MS coupled with a decision tree classification algorithm will provide a highly accurate and innovative approach for the early diagnosis of PCa.


Assuntos
Biomarcadores/sangue , Neoplasias da Próstata/diagnóstico , Proteoma/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Idoso , Idoso de 80 Anos ou mais , Árvores de Decisões , Humanos , Masculino , Informática Médica , Pessoa de Meia-Idade
19.
Asian J Androl ; 7(3): 323-8, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16110361

RESUMO

AIM: To investigate whether the measurement of serum zinc may improve the detection of prostate cancer (PCa) in men who had total prostate-specific antigen (PSA) levels higher than 4.1 ng/mL. METHODS: A mass screening for PCa of 3940 men over 50 years old was undertaken using total serum PSA. Of the 190 men (4.8%) with elevated PSA, 143 (3.6%) underwent a transrectal ultrasonography (TRUS)-guided biopsy of the prostate, and 42 men (1% of total and 29.3% of men undergoing biopsy) were found to have cancer. The areas under the receiver operating characteristic curves (ROC-AUC) were used to compare the diagnostic power of cancer detection by means of serum zinc, and free PSA/total PSA ratio (f/t). RESULTS: The men with levels of serum zinc that ranged from 40 ng/mL-60 ng/mL, had an age-adjusted odds ratios(OR) of 5.0. A cutoff value of 100 microg/mL for serum zinc concentration provided a sensitivity of 90.5% and a specificity of 32.7% in elevated PSA range, and a sensitivity of 93.3% and specificity of 27.1% in gray zone, respectively. In the gray zone ranges of 4.1 ng/mL-10.0 ng/mL, the ROC-AUC for zinc was 73.0% higher than 62.7% of f/t PSA ratio and 56.7% of total PSA. CONCLUSION: PCa displays a lower serum zinc concentration. The measurement of zinc levels improves PCa detection in the gray zone compared with the f/t PSA ratio and total PSA.


Assuntos
Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Zinco/sangue , Área Sob a Curva , Biópsia/métodos , Humanos , Masculino , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Curva ROC , Sensibilidade e Especificidade , Ultrassonografia
20.
Asian J Androl ; 7(2): 159-63, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15897972

RESUMO

AIM: To investigate the pathological features of the prostate biopsy through mass screening for prostate cancer in a Chinese cohort and their association with serum prostate specific antigen (PSA). METHODS: A total of 12027 Chinese men in Changchun were screened for prostate cancer by means of the serum total prostate specific antigen tPSA test (by Elisa assay). Transrectal ultrasound-guided systematic six-sextant biopsies were performed on those whose serum tPSA value was > 4.0 ng/mL and those who had obstructive symptoms (despite their tPSA value) and were subject to subsequent pathological analysis with the aid of the statistic software SPSS 10.0 (SPSS. Inc., Chicago. USA). RESULTS: Of the 12027 cases, 158 (including 137 patients whose serum tPSA values were 4.0 ng/mL and 21 patients [serum tPSA < 4.0 ng/mL] who had obstructive symptoms) undertook prostate biopsy. Of the 158 biopsies, 41 cases of prostatic carcinoma were found (25.9 %, 41/158). The moderately differentiated carcinoma and poorly differentiated carcinoma accounted for 61% and 34%, respectively. A significant linear positive correlation between the serum tPSA and the Gleason scores in the 41 cases of prostatic carcinoma (r = 0.312, P < 0.01) was established. A significant linear positive correlation between the serum tPSA value of the 41 prostatic carcinoma and the positive counts of carcinoma in sextant biopsies was established (r = 0.406, P < 0.01), indicating a significant linear relationship between serum tPSA and the size of tumor. CONCLUSION: This study was the first to conduct mass screening for prostate cancer by testing for serum tPSA values and the first to investigate the pathological features of prostate cancer in a cohort of Chinese men. Our results reveal that the moderately differentiated carcinoma is the most common type of prostate cancer. This study also has shown that the serum tPSA value in prostate cancer is associated with the Gleason score and the size of tumor.


Assuntos
Programas de Rastreamento , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Biópsia/métodos , China , Humanos , Masculino , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Ultrassonografia
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