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61.
Luiz Sergio Azevedo Lígia Camera Pierrotti Edson Abdala Silvia Figueiredo Costa Tania Mara Varej?o Strabelli Silvia Vidal Campos Jéssica Fernandes Ramos Acram Zahredine Abdul Latif Nadia Litvinov Natalya Zaidan Maluf Helio Hehl Caiaffa Filho Claudio Sergio Pannuti Marta Heloisa Lopes Vera Aparecida dos Santos Camila da Cruz Gouveia Linardi Maria Aparecida Shikanai Yasuda Heloisa Helena de Sousa Marques 《Clinics (S?o Paulo, Brazil)》2015,70(7):515-523
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Jing Li SongTao Xiang QiouHong Zhang JingJing Wu Qing Tang JianFu Zhou LiJun Yang ZhiQiang Chen Swei Sunny Hann 《Journal of experimental & clinical cancer research : CR》2015,34(1)
Background
Prostate cancer is one of the most common malignancies in men. The mucin 1 (MUC1) heterodimeric oncoprotein is overexpressed in human prostate cancers with aggressive pathologic and clinical features, resulting in a poor outcome. However, the functional role for MUC1 C-terminal domain (MUC1-C) in androgen-independent prostate cancer occurrence and development has remained unclear.Methods
Cell viability was measured by MTT assays. Western blot analysis was performed to measure the phosphorylation and protein expression of SAPK/JNK and ERK1/2, and MUC1-C, NF-κB subunit p65 and p50. Exogenous expression of MUC1-C, NF-κB subunit p65 was carried out by transient and electroporated transfection assays.Results
We showed that curcumin inhibited the growth of androgen-independent prostate cancer cells and a synergy was observed in the presence of curcumin and bicalutamide, the androgen receptor antagonist. To further explore the potential mechanism underlining this, we found that curcumin increased the phosphorylation of ERK1/2 and SAPK/JNK, which was enhanced by bicalutamide. In addition, curcumin reduced the protein expression of MUC1-C and NF-κB subunit p65, which were abrogated in the presence of the inhibitors of MEK/ERK1/2 (PD98059) and SAPK/JNK (SP60015). A further reduction was observed in the combination of curcumin with bicalutamide. Moreover, while exogenous expression of MUC1-C had little effect on curcumin-reduced p65, the overexpression of p65 reversed the effect of curcumin on MUC1-C protein expression suggesting that p65 is upstream of MUC1-C. Intriguingly, we showed that exogenous expression of MUC1-C feedback diminished the effect of curcumin on phosphorylation of ERK1/2 and SAPK/JNK, and antagonized the effect of curcumin on cell growth.Conclusion
Our results show that curcumin inhibits the growth of androgen-independent prostate cancer cells through ERK1/2- and SAPK/JNK-mediated inhibition of p65, followed by reducing expression of MUC1-C protein. More importantly, there are synergistic effects of curcumin and bicalutamide. The negative feedback regulatory loop of MUC1-C to ERK1/2 and SAPK/JNK further demonstrates the role of MUC1-C that contributes to the overall responses of curcumin. This study unveils the potential molecular mechanism by which combination of curcumin with bicalutamide enhances the growth inhibition of androgen-independent prostate cancer cells. 相似文献64.
Min Zhong Wan-ling Song Ye-chun Xu Yang Ye Lin-yin Feng 《Acta pharmacologica Sinica》2015,36(3):298-310
Aim:
Paeoniflorin from Chinese herb Paeoniae Radix has been shown to ameliorate middle cerebral artery occlusion-induced ischemia in rats. The aim of this study was to investigate the mechanisms underlying the neuroprotective action of PF in cultured rat cortical neurons.Methods:
Primary cultured cortical neurons of rats were subjected to oxygen-glucose deprivation and reoxygenation (OGD/R) insult. Cell survival was determined using MTT assay. HEK293 cells stably transfected with A1R (HEK293/A1R) were used for detailed analysis. Phosphorylation of the signaling proteins was evaluated by Western blot or immunoprecipitation. Receptor interactions were identified using co-immunoprecipitation and immunofluorescence staining.Results:
Paeoniflorin (10 nmol/L to 1 μmol/L) increased the survival of neurons subjected to OGD/R. Furthermore, paeoniflorin increased the phosphorylation of Akt and ERK1/2 in these neurons. These effects were blocked by PI3K inhibitor wortmannin or MEK inhibitor U0126. Paeoniflorin also increased the phosphorylation of Akt and ERK1/2 in HEK293/A1R cells. Both A1R antagonist DPCPX and EGFR inhibitor AG1478 not only blocked paeoniflorin-induced phosphorylation of ERK1/2 and Akt in HEK293/A1R cells, but also paeoniflorin-increased survival of neurons subjected to OGD/R. In addition, paeoniflorin increased the phosphorylation of Src kinase and activation of MMP-2 in HEK293/A1R cells. Both Src inhibitor PP2 and MMP-2/MMP-9 inhibitor BiPs not only blocked paeoniflorin-induced phosphorylation of ERK1/2 (and Akt) in HEK293/A1R cells, but also paeoniflorin-increased survival of neurons subjected to OGD/R.Conclusion:
Paeoniflorin promotes the survival of cultured cortical neurons by increasing Akt and ERK1/2 phosphorylation via A1R-mediated transactivation of EGFR. 相似文献65.
Jinhua Wang Wei Hua Sharon K. Huang Kun Fan Ling Takeshima Ying Mao Dave S.B. Hoon 《Oncotarget》2015,6(30):30165-30177
Our group previously demonstrated that the RASSF1 gene has a significant tumor suppressor role in cutaneous melanoma. The RASSF8 gene is a member of the N-terminal RASSF gene family. Previously, we identified RASSF8 (HOJ1, NCBI Gene ID:11228) expression in cutaneous melanoma; however the functional role of RASSF8 in melanoma is not known. RASSF8 expression was assessed in melanoma cell lines and tumors of different AJCC stages. Results indicated that RASSF8 expression was low in metastatic melanoma lines and decreased with melanoma progression. We then explored the mechanism of RASSF8 downregulation in melanoma by assessing methylation of RASSF8 and demonstrated that methylation of RASSF8 gene promoter was higher in advanced than in early stages melanomas. Functional activity of RASSF8 in melanoma lines by knockdown and overexpression of RASSF8 demonstrated that RASSF8 expression significantly inhibited cell growth, cell migration and invasion, whereas knockdown of RASSF8 expression significantly increased cell growth, cell migration and invasion of melanoma cells by increasing expression of P65 and its downstream target IL-6. Moreover RASSF8 was found to induce apoptosis in melanoma cells by activating the P53-P21 pathway, and also in vivo studies demonstrated that inhibiting RASSF8 increases the tumorigenic properties of human melanoma xenografts. These results suggest that RASSF8 plays a significant role in suppressing the progression of cutaneous melanoma. 相似文献
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目的:通过评价HSP65抗原表达在结核病血清诊断中的效果,分析其应用前景。方法取活动期结核病患者63例纳入观察组,选取体检健康志愿者60例纳入对照组,就HSP65分别与38 kDa、16 kDa、LAM联合检测诊断对照组与观察组结核病。结果Western-blot结果显示,表达产物在相对分子量65 kμ处有一条表达带,在健康人血清阴性中则无表达带;特异度、敏感度与38 kPa基本一致,差异无统计学意义(P>0.05)。结论 HSP65在结核病血清诊断中可作为备选标志物,反应强度与38kDa基本相当,联合诊断有助于提高诊断符合率;HSP65对结核病X线空洞影敏感度较高。 相似文献
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Vladimir Tsuprun Nevra Keskin Mark R. Schleiss Pat Schachern Sebahattin Cureoglu 《American journal of otolaryngology》2019,40(6):102270
ObjectivePublications on histopathology of human temporal bones with cytomegalovirus (CMV) infection are limited. We aim to determine histopathology of the inner ears and the middle ears in human temporal bones with congenital and acquired CMV infections.MethodsTemporal bones from 2 infants with congenital and 2 adults with acquired CMV infection were evaluated by light microscopy.ResultsTwo infants with congenital CMV infection showed striking pathological changes in the inner ear. There was a hypervascularization of the stria vascularis in the cochlea of the first infant, but no obvious loss of outer and inner hair cells was seen in the organ of Corti. However, cytomegalic cells and a loss of outer hair cells were found in the cochlea of the second infant. The vestibular organs of both infants showed cytomegalic cells, mostly located on dark cells. There was a loss of type I and type II hair cells in the macula of the saccule and utricle. Loss of hair cells and degeneration of nerve fibers was also seen in the semicircular canals. Both infants with congenital infection showed abundant inflammatory cells and fibrous structures in the middle ear cavity. No evidence of cytomegalic cells and hair cell loss was found in the cochlea or vestibular labyrinth in acquired CMV infection.ConclusionsIn two infants with congenital CMV infection, the cochlea, vestibule, and middle ear were highly affected. Temporal bones of adult donors with acquired viral infection showed histological findings similar to donors of the same age without ear disease. 相似文献