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Differential resistance to platinum‐based drugs and 5‐fluorouracil in p22phox‐overexpressing oral squamous cell carcinoma: Implications of alternative treatment strategies
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Pei‐Yu Chu PhD Yu‐Jen Wu PhD Chang‐Shen Lin PhD Chih‐Jen Huang MD PhD Leong‐Perng Chan MD Yen‐Yun Wang PhD Shyng‐Shiou F. Yuan MD PhD Tzyh‐Chyuan Hour PhD Jeff Yi‐Fu Chen PhD 《Head & neck》2017,39(8):1621-1630
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Regulatory effect of microRNA‐34a on osteogenesis and angiogenesis in glucocorticoid‐induced osteonecrosis of the femoral head
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《Journal of orthopaedic research》2018,36(1):417-424
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To evaluate the value of seminal plasma miR‐210‐3p as a novel and non‐invasive biomarker for screening dyszoospermia caused by varicocele. Semen samples from patients with varicocele and healthy males were collected for semen analysis and quantitative real‐time polymerase chain reaction. Cox univariate and multivariate analysis and receiver operating characteristic curve analysis were used to assess the relationship between the level of seminal plasma miR‐210‐3p and impaired spermatogenic function. Our results showed that the level of seminal plasma miR‐210‐3p in the varicocele patients was 2.18 times that of the control group (p < 0.001), and its expression increased significantly with the severity of varicocele. Compared with preoperative, the expression of seminal plasma miR‐210‐3p declined significantly at 3 months after surgery. Cox univariate and multivariate analysis showed that seminal plasma miR‐210‐3p (p = 0.02), bilateral varicocele (p = 0.04) and the grade 3 varicocele (p = 0.03) were significantly and independently associated with dyszoospermia caused by varicocele. Our results suggest that seminal plasma miR‐210‐3p is a useful clinical biomarker for screening dyszoospermia caused by varicocele, and this is the key to deciding early effective treatment and protecting the fertility of the patients. 相似文献
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Taku Ukai Masato Sato Hidenori Akutsu Akihiro Umezawa Joji Mochida 《Journal of orthopaedic research》2012,30(12):1915-1922
MicroRNAs (miRNAs) are small RNAs of ~22 base pairs that regulate gene expression. We harvested cartilage tissue from patients with polydactylism, anterior cruciate ligament injury, and osteoarthritis undergoing total knee arthroplasty and used microarrays to identify miRNAs whose expression is upregulated or downregulated with age. The results were assessed by real‐time PCR and MTT assay in a mimic group, in which synthetic double‐stranded RNA from the isolated miRNA was transfected to upregulate expression, and in an inhibitor group, in which the miRNA was bound specifically to downregulate expression. The expression of two miRNAs (miR‐199a‐3p and miR‐193b) was upregulated with age and that of one miRNA (miR‐320c) was downregulated with age. A real‐time PCR assay showed that type 2 collagen, aggrecan, and SOX9 expression were downregulated in the miR‐199a‐3p mimic group but was upregulated in the inhibitor group. Similar results were observed for miR‐193b. By contrast, ADAMTS5 expression was downregulated in the miR‐320c mimic group and upregulated in the inhibitor group. Cell proliferative activity was upregulated significantly in the miR‐193b inhibitor group compared with the control group. We believe that miR‐199a‐3p and miR‐193b are involved in the senescence of chondrocytes, and miR‐320c is involved in the juvenile properties of chondrocytes. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1915–1922, 2012 相似文献
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Yoshiyuki Matsui Jun Watanabe Sentai Ding Koji Nishizawa Yoichiro Kajita Kentaro Ichioka Ryoichi Saito Takashi Kobayashi Osamu Ogawa Hiroyuki Nishiyama 《BJU international》2010,105(4):558-564
OBJECTIVE
To investigate the effectiveness of a combined treatment of 3–30‐methylene‐bis[4‐hydroxycoumarin] (dicoumarol) with doxorubicin for the treatment of urothelial cancer, as doxorubicin is a common chemotherapeutic agent but its therapeutic efficacy is limited.MATERIALS AND METHODS
The synergistic effect of dicoumarol with chemotherapeutic agents such as cisplatin, doxorubicin and paclitaxel was evaluated in RT112 urothelial cancer cells. Then, dicoumarol‐mediated enhancement of doxorubicin‐induced cytotoxicity was screened in urothelial cancer cell lines with different p53 statuses or RT112 stable transfectants with a dominant‐negative mutant of p53 (p53DN). To clarify the importance of the modification of p53 function by dicoumarol to enhance doxorubicin toxicity, the change in the p53‐p21 pathway and mitogen‐activated protein kinase (MAPK)‐mitochondria pathway by the combined treatment were elucidated by Western blot analysis. Finally, the effect of p21 knockdown in the susceptibility to doxorubicin was examined with RT112 stable transfectants with short hairpin RNA (shRNA) of p21.RESULTS
Dicoumarol significantly increased the susceptibility of RT112 cells to cisplatin and doxorubicin, but not to paclitaxel in RT112 cells. Dicoumarol (100 µm ) also enhanced the cytotoxicity of doxorubicin in other bladder cancer cell lines with wild‐type p53 (wt‐p53; three times in 253J and 13 times in KK47), but not in those with mutant‐type p53 (TCCsup, J82 and EJ) or in RT112 p53DN. The combined treatment with dicoumarol suppressed p53/p21 induction by doxorubicin and resulted in sequential p38 MAPK activation, myeloid cell leukaemia 1 suppression and caspase cleavage. The synergistic effect of doxorubicin/dicoumarol was suppressed by the p38 MAPK inhibitor SB202190 and, furthermore, p21 knockdown with shRNA transfection made RT112 cells six times more susceptible to doxorubicin with p38 MAPK activation.CONCLUSION
These results suggest that concomitant use of dicoumarol could enhance the cytotoxicity of doxorubicin in urothelial cancer cells with wt‐p53 through the p53/p21/p38 MAPK pathways. This combined treatment may provide a new therapeutic option to overcome chemoresistance in bladder cancer. 相似文献11.
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Yu‐Jen Chiu Mann‐Jen Hour Chi‐Cheng Lu Jing‐Gung Chung Sheng‐Chu Kuo Wen‐Wen Huang Hui‐Jye Chen Yi‐An Jin Jai‐Sing Yang 《Journal of orthopaedic research》2011,29(9):1448-1456
Human osteogenic sarcoma is the most common primary bone tumor. Despite of the success of frontline therapy, about 40% of patients have disease progression and further therapy is palliative and toxic. In this study, we developed a novel quinazoline HMJ‐30 to investigate the cell growth inhibition and apoptotic responses in U‐2 OS human osteogenic sarcoma cells. Our results demonstrated that HMJ‐30 significantly reduced cell viabilities of U‐2 OS, HOS, and 143B cells in a dose‐dependent manner, but it exhibited low cytotoxicity in normal hFOB cells. HMJ‐30 induced DNA damage and apoptosis in U‐2 OS cells as revealed by morphologic changes, comet assay and DAPI staining. Immuno‐staining, colorimetric assays, and Western blotting analyses indicated that activities of caspase‐8, caspase‐9, and caspase‐3 and the levels of Bcl‐2 family‐related proteins (Bcl‐2, Mcl‐1, Bax, BAD, and t‐Bid) were altered in HMJ‐30‐treated U‐2 OS cells. Pretreatment of cells with caspase‐8, ‐9, and ‐3 specific inhibitors significantly reduced the cell growth inhibition. HMJ‐30‐induced apoptosis was mediated through both death‐receptor and mitochondria‐dependent apoptotic pathways in U‐2 OS cells. HMJ‐30 induced early phosphorylation of p53Ser18 was through the activation of ataxia telangiectasia mutated (ATM) in U‐2 OS cells. The cell growth inhibition by HMJ‐30 was substantially attenuated either by the pre‐incubation of U‐2 OS cells with N‐acetylcysteine (NAC, an antioxidant) and caffeine (an ATM kinase inhibitor) or by p53 knockdown via RNAi. In conclusion, ROS dependent‐ATM/p53 signaling pathway is involved in HMJ‐30‐induced apoptosis in U‐2 OS cells. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1448–1456, 2011 相似文献
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Prevalence of human papillomavirus in oral epithelial dysplasia: Systematic review and meta‐analysis
Cecilie Dovey de la Cour Cecilie Dyg Sperling Federica Belmonte Stina Syrjnen Freija Verdoodt Susanne Krüger Kjaer 《Head & neck》2020,42(10):2975-2984
The purpose of this systematic review and meta‐analysis was to estimate the overall and type‐specific prevalence of human papillomavirus (HPV) DNA in oral epithelial dysplasia and assess p16INK4a overexpression in relation to HPV‐status. A systematic literature search identified 31 eligible studies (832 cases) evaluating the presence of HPV DNA in oral epithelial dysplasia cases by PCR. Of these, six studies evaluated p16INK4a overexpression in relation to HPV‐status. The overall pooled prevalence of HPV DNA in oral epithelial dysplasia was 27.2% (95% CI: 17.6‐38.1). We observed substantial interstudy heterogeneity, which could not be explained by differences in continent, tissue type, or severity of epithelial dysplasia. HPV16 was the predominant genotype detected. Moreover, 62.2% of HPV positive and 17.8% of HPV negative oral epithelial dysplasia samples stained intensively positive for p16INK4a. This meta‐analysis found that 27% of oral epithelial dysplasia harbor HPV DNA. Whether this represents a transient infection or has a carcinogenic role is unknown. 相似文献
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Prognostic value of p16 expression in Epstein‐Barr virus–positive nasopharyngeal carcinomas
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Wen Jiang MD PhD Paul D. Chamberlain BS Adam S. Garden MD Betty Y. S. Kim MD PhD Dominic Ma BS Emily J. Lo MD Diana Bell MD G. Brandon Gunn MD Clifton D. Fuller MD PhD David I. Rosenthal MD Beth M. Beadle MD PhD Steven J. Frank MD William H. Morrison MD Adel K. El‐Naggar MD Bonnie S. Glisson MD Erich M. Sturgis MD PhD Jack Phan MD PhD 《Head & neck》2016,38(Z1):E1459-E1466
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Prognostic value of pretreatment 18F‐fluorodeoxyglucose positron emission tomography/CT volume‐based parameters in patients with oropharyngeal squamous cell carcinoma with known p16 and p53 status
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Shogo Shinohara MD PhD Yu Usami DDS PhD Yukihiro Imai MD PhD Megumu Hino MD PhD Kyo Itoh MD PhD Risa Tona MD Yuji Kanazawa MD Ippei Kishimoto MD Hiroyuki Harada MD Yasushi Naito MD PhD 《Head & neck》2015,37(10):1524-1531