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The prognostic factors of effective ketoconazole treatment for metastatic castration-resistant prostate cancer： who can benefit from ketoconazole therapy？

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Asian Journal of Andrology 2012年第5期14卷 732-737页

作者： Guo-Wen Lin Xu-Dong Yao Ding-Wei Ye Yao Zhu Shi-Lin Zhang Bo Dai Hai-Liang Zhang Yi-Jun Shen chun-guang ma Department of Urology Fudan University Shanghai Cancer CenterShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China

We investigated the prognostic value of some variables of effective ketoconazole treatment for metastatic castration-resistant prostate cancer （mCRPC）. In total, 163 patients with mCRPC were eligible, receiving ketoconazole 200-400 mg three times daily with replacement doses of prednisone. Progression-free survival （PFS） was calculated from the beginning of the ketoconazole therapy to the onset of disease progression. The prognostic value of different variables for PFS was assessed by Cox regression analysis. The median PFS was 2.6 months （0.5-8.6 months） for these patients. The serum testosterone level changed during therapy, which decreased when the prostate-specific antigen （PSA） declined; the serum testosterone level increased as the levels of PSA relapsed. The median PFS values for patients associated with different factors were the following： 1.4 and 3.5 months for a nadir PSA of ≥ 0.2 and 〈0.2 ng ml- 1, respectively （hazard rate （HR）=4.767, P〈0.001）; 3.1 and 1.6 months for a baseline testosterone of ≥0.1 and 〈0.1 ng m1-1, respectively （HR=2.865, P=0.012）; 2.8 and 1.9 months for a baseline haemoglobin of ≥ 120 and 〈120 g 1-1, respectively （HR= 1.605, P〈0.001）; and 3.0 and 1.9 months for a PSA doubling time （PSADT） of ≥ 2.0 and 〈2.0 months, respectively （HR= 1.454, P=-0.017）. A risk model was constructed according to the four factors that divided patients into three subgroups of low risk （0-1 factors）, moderate risk （2 factors） and high risk （3-4 factors） with PFS values of 3.6, 3.0 and 1.4 months, respectively （HR=1.619, P〈0.001）. A nadir PSA of ≥0.2 ng m1-1, a baseline testosterone of 〈0.1 ng m1-1, a baseline haemoglobin of 〈 120 g I- 1 and a PSADT of 〈2 months were associated with a poor PFS. This risk model could provide evidence to predict the survival benefit of ketoconazole therapy.

关键词： castration-resistant prostate cancer ketoconazole therapy predictor progression-free survival

Prognostic factors in Chinese patients with metastatic castration-resistant prostate cancer treated with docetaxel-based chemotherapy

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Asian Journal of Andrology 2013年第1期15卷 110-115页

作者： Yuan-Yuan Qu Bo Dai Yun-Yi Kong Ding-Wei Ye Xu-Dong Yao Shi-Lin Zhang Hai-Liang Zhang chun-guang ma Wei-Yi Yang Department of Urology Fudan University Shanghai Cancer Center Shanghai 200032 China Department of Oncology Fudan University Shanghai Medical College Shanghai 200032 China Department of Pathology Fudan University Shanghai Cancer Center Shanghai 200032 China

This study aims to evaluate the potential value of patient characteristics in predicting overall survival （OS） in patients with metastatic castration-resistant prostate cancer （mCRPC） treated with docetaxel-based thermotherapy. A total of 115 patients with mCRPC undergoing a docetaxel q3w regimen were enrolled in this study. A survival analysis was performed using the Kaplan-Meier method. Cox proportional hazards models were used to evaluate the prognostic value of all covariates for OS. OS was also analysed after stratifying patients according to the results of multivariate analysis. The median OS for the entire cohort was 17.0 months. The multivariate analysis showed that the prostate-specific antigen doubling time （PSADT）, baseline haemoglobin （Hb） concentration, alkaline phosphatase （ALP） concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS. According to the presence of PSADT 〈46.3 days and baseline ALP/〉 110 IU 1-1, all patients were divided into three risk groups： low-risk group （no risk factors）, intermediate-risk group （one risk factor） and high-risk group （two risk factors）. Median OSs for patients in low-, intermediate- and high-risk groups were 28.0 months （95% Ch 23.8-32.2）, 21.0 months （95% Ch 18.9-23.1） and 11.0 months （95% Ch 7.6-14.4）, respectively （P〈O.O01）. In conclusion, PSADT, baseline Hb concentration, ALP concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS in Chinese patients with mCRPC treated with docetaxel. PSADT combined with the baseline ALP concentration could be a useful risk stratification parameter for evaluating survival outcomes.

关键词： castration-resistant docetaxel metastatic overall survival prognostic factor prostate cancer

The effectiveness of the TAX 327 nomogram in predicting overall survival in Chinese patients with metastatic castration-resistant prostate cancer

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Asian Journal of Andrology 2013年第5期15卷 679-684页

作者： Xiao-Jie Bian Yao Zhu Yi-Jun Shen Jin-You Wang chun-guang ma Hai-Liang Zhan Bo Dai Shi-Lin Zhang Xu-Dong Yao Ding-Wei Ye Department of Urology Fudan University Shanghai Cancer Center Shanghai 200032 China Department of Oncology Shanghai Medical College Fudan University Shanghai 200032 China

Based on the results of TAX 327, a nomogram was developed to predict the overall survival of metastatic castration-resistant prostate cancer （mCRPC） after first-line chemotherapy. The nomogram, however, has not been validated in an independent dataset, especially in a series out of clinical trials. Thus, the objective of the current study was to validate the TAX 327 nomogram in a community setting in China. A total of 146 patients with mCRPC who received first-line chemotherapy （docetaxel or mitoxantrone） were identified. Because clinical trials are limited in China's mainland, those patients did not receive investigational treatment after the failure of first-line chemotherapy. The predicted overall survival rate was calculated from the TAX 327 nomogram. The validity of the model was assessed with discrimination, calibration and decision curve analysis. The median survival of the cohort was 21 months （docetaxel） and 19 months （mitoxantrone） at last follow-up. The predictive c-index of the TAX 327 nomogram was 0.66 （95% CI： 0.54-0.70）. The calibration plot demonstrated that the 2-year survival rate was underestimated by the nomogram. Decision curve analysis showed a net benefit of the nomogram at a threshold probability greater than 30%. In conclusion, the present validation study did not confirm the predictive value of the TAX 327 nomogram in a contemporary community series of men in China, and further studies with a large sample size to develop or validate nomograms for predicting survival and selecting therapies in advanced prostate cancer are necessary.

关键词： castration-resistant chemotherapy nomogram prostate cancer validation studies

External validation of the Prostate Cancer Prevention Trial and the European Randomized Study of Screening for Prostate Cancer risk calculators in a Chinese cohort

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Asian Journal of Andrology 2012年第5期14卷 738-744页

作者： Yao Zhu Jin-You Wang Yi-Jun Shen Bo Dai chun-guang ma Wen-Jun Xiao Guo-Wen Lin Xu-Dong Yao Shi-Lin Zhang Ding-Wei Ye Department of Urology Fudan University Shanghai Cancer Center Shanghai 200032 China Department of Oncology Shanghai Medical College Fudan University Shanghai 200032 China

Several prediction models have been developed to estimate the outcomes of prostate biopsies. Most of these tools were designed for use with Western populations and have not been validated across different ethnic groups. Therefore, we evaluated the predictive value of the Prostate Cancer Prevention Trial （PCPT） and the European Randomized Study of Screening for Prostate Cancer （ERSPC） risk calculators in a Chinese cohort. Clinicopathological information was obtained from 495 Chinese men who had undergone extended prostate biopsies between January 2009 and march 2011. The estimated probabilities of prostate cancer and high-grade disease （Gleason 〉6） were calculated using the PCPT and ERSPC risk calculators. Overall measures, discrimination, calibration and clinical usefulness were assessed for the model evaluation. Of these patients, 28.7% were diagnosed with prostate cancer and 19.4% had high-grade disease. Compared to the PCPT model and the prostate-specific antigen （PSA） threshold of 4 ng m1-1, the ERSPC risk calculator exhibited better discriminative ability for predicting positive biopsies and high-grade disease （the area under the curve was 0.831 and 0.852, respectively, P〈O.01 for both）. Decision curve analysis also suggested the favourable clinical utility of the ERSPC calculator in the validation dataset. Both prediction models demonstrated miscalibration： the risk of prostate cancer and high-grade disease was overestimated by approximately 20% for a wide range of predicted probabilities. In conclusion, the ERSPC risk calculator outperformed both the PCPT model and the PSA threshold of 4 ng ml- z in predicting prostate cancer and high-grade disease in Chinese patients. However, the prediction tools derived from Western men significantly overestimated the probability of prostate cancer and high-grade disease compared to the outcomes of biopsies in a Chinese cohort.

关键词： European Randomized Study of Screening for Prostate Cancer (ERSPC) predictive value of tests prostate cancer prostate-specific antigen (PSA) Prostate Cancer Prevention Trial (PCPT)

Prostate-specific antigen half-life： a new predictor of progression- free survival and overall survival in Chinese prostate cancer patients

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Asian Journal of Andrology 2009年第4期11卷 443-450页

作者： Guo-Wen Lin Xu-Dong Yao Shi-Lin Zhang Bo Dai chun-guang ma Hai-Liang Zhang Yi-Jun Shen Yao Zhu Yi-Ping Zhu Guo-Hai Shi Xiao-Jian Qin Ding-Wei Ye Department of Urology Cancer Hospital Fudan University Shanghai 200032 China Department of Oncology Shanghai Medical College Fudan University Shanghai 200032 China

We investigated the potential value of prostate-specific antigen half-life （PSAHL） and decreasing velocity （PSAVd） to predict progression-free survival （PFS） and overall survival （OS） in Chinese patients with prostate cancer. A total of 153 patients treated with hormonal therapy were included in the study. Of these, 78 patients progressed to hormone- refractory prostate cancer （HRPC） and 24 patients died by the end of follow-up. PSAHL was defined as the time during which prostate-specific antigen （PSA） concentration became half of the initial value during the first hormonal therapy. PSAVd reflected the decreasing velocity of PSA during the first hormonal therapy. PFS was defined as the interval from the beginning of hormonal therapy to HRPC. Cox proportional hazards regression analysis was used to evaluate whether PSAHL and PSAVd were significantly associated with PFS and OS. The median PSAHL and PSAVd were 0.50 months and 33.8 ng mL^-1 per month. The median PFS and OS were 22.7 months （95% confidence interval [CI], 22.0-29.6 months） and 43.5 months （95% CI, 37.9-48.4 months）, respectively. On univariate and multivariate analysis, long PSAHL （〉 0.5 months）, metastatic disease, high biopsy Gleason scores （〉 8） and high nadir PSA （〉 0.4 ng mL^-1） were all found to be significantly associated with short PFS. Long PSAHL, high nadir PSA and short PSA doubling time （PSADT 〈 2.0 months） were significantly associated with short OS. There were no significant relationships between PSAVd and either PFS or OS. Thus, PSAHL is a promising new independent predictor of survival. Patients with long PSAHL were identified as those at high risk for a relatively short PFS and OS.

关键词： predictor prognosis prostate cancer prostate-specific antigen decreasing velocity prostate-specific antigen half-life

Human epidermal growth factor receptor type 2 protein expression in Chinese metastatic prostate cancer patients correlates with cancer specific survival and increases after exposure to hormonal therapy

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Asian Journal of Andrology 2008年第5期10卷 701-709页

作者： Bo Dai Yun-Yi Kong Ding-Wei Ye chun-guang ma Xiao-Yan Zhou Xu-Dong Yao Department of Urology Cancer Hospital Fudan University Shanghai 200032 China Department of Pathology Cancer Hospital Fudan University Shanghai 200032 China Department of Oncology Shanghai Medical College Fudan University Shanghai 200032 China

Aim： To investigate human epidermal growth factor receptor type 2 （HER2） protein expression and gene amplification in Chinese metastatic prostate cancer patients and their potential value as prognostic factors. Methods： Immunohistochemistry （IHC） was performed to investigate HER2 protein expression in prostate biopsy specimens from 104 Chinese metastatic prostate cancer patients. After 3-11 months of hormonal therapy, 12 patients underwent transurethral resection of the prostate （TURP）. HER2 protein expression of TURP specimens was compared with that of the original biopsy specimens. Of these, 10 biopsy and 4 TURP specimens with HER2 IHC staining scores ≥ 2＋ were investigated for HER2 gene amplification status by fluorescent in situ hybridization （FISH）. Results： Of the 104 prostate biopsy specimens, HER2 protein expression was 0, 1＋, 2＋ and 3＋ in 49 （47.1%）, 45 （43.3%）, 8 （7.7%） and 2 （1.9%） cases, respectively. There was a significant association between HER2 expression and Gleason score （P = 0.026）. HER2 protein expression of prostate cancer tissues increased in 33.3% of patients after hormonal therapy. None of the 14 specimens with HER2 IHC scores 〉 2＋ showed HER2 gene amplification. Patients with HER2 scores 〉 2＋ had a significantly higher chance of dying from prostate cancer than those with HER2 scores of 0 （P = 0.004） and 1＋（P = 0.034）. Multivariate Cox regression analysis showed that HER2 protein expression intensity was an independent predictor of cancer-related death （P = 0.039）. Conclusion： An HER2 IHC score 〉 2＋ should be defined as HER2 protein overexpression in prostate cancer. Overexpression of HER2 protein in cancer tissue might suggest an increased risk of dying from prostate cancer. HER2 protein expression increases in some individual patients after hormonal therapy.

关键词： prostatic neoplasms human epidermal growth factor receptor type 2 immunohistochemistry gene amplification prostate cancer prognosis

The Citron homology domain of maP4Ks improves outcomes of traumatic brain injury

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Neural Regeneration Research 2025年第11期20卷 3233-3244页

作者： Xiaoling Zhong Wenjiao Tai Meng-Lu Liu Shuaipeng ma Tianjin Shen Yuhua Zou chun-Li Zhang Department of Molecular Biology University of Texas Southwestern Medical CenterDallasTXUSA Hamon Center for Regenerative Science and Medicine University of Texas Southwestern Medical CenterDallasTXUSA Peter O’Donnell Jr.Brain Institute University of Texas Southwestern Medical CenterDallasTXUSA

The mitogen-activated protein kinase kinase kinase kinases(maP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following *** targeting this pathway is beneficial to brain injury remains *** this study,we showed that adeno-associated virus-delivery of the Citron homology domain of maP4Ks effectively reduces traumatic brain injury-induced reactive gliosis,tauopathy,lesion size,and behavioral *** inhibition of maP4Ks replicated the ameliorative effects observed with expression of the Citron homology ***,the Citron homology domain acted as a dominant-negative mutant,impeding maP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin *** findings implicate a therapeutic potential of targeting maP4Ks to alleviate the detrimental effects of traumatic brain injury.

关键词： adeno-associated virus Citron homology Citron homology domain gene therapy mitogen-activated protein kinase kinase kinase kinases traumatic brain injury

Catalytic atroposelective synthesis of indolyl quinazolinones bearing N-N/C-C diaxes

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Science China Chemistry 2025年

作者： Ning-Yi Wang Shuo Gao Zhu-Di Shu Bei-Bei Cheng chun ma Yu-Chen Zhang Feng Shi Research Center of Chiral Functional Heterocycles School of Chemistry and Materials Science Jiangsu Normal University School of Petrochemical Engineering Changzhou University School of Chemistry and Chemical Engineering Henan Normal University

The first catalytic atroposelective synthesis of indole derivatives bearing N-N/C-C diaxes has been established by the strategy of de novo ring formation. By this strategy, various indolyl quinazolinones bearing vicinal N-N/C-C diaxes were synthesized in high yields with overall good diastereoselectivities and excellent enantioselectivities via chiral phosphoric acid-catalyzed onepot asymmetric formal (5+1) cycloaddition/oxidation reaction. Moreover, such indolyl quinazolinones bearing vicinal N-N/CC diaxes have good configurational stability and could be converted into new chiral ligands with applications in asymmetric catalysis. Therefore, this work not only offered a new member for the family of diaxial atropisomers, but also provided a powerful strategy for catalytic asymmetric synthesis of atropisomers bearing N-N/C-C diaxes.

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Cryptanalysis and security enhancement of a remote user authentication scheme using smart cards

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The Journal of China Universities of Posts and Telecommunications 2012年第5期19卷 104-114页

作者： WANG Ding ma chun-guang College of Computer Science and Technology Harbin Engineering University Harbin 150001 China Automobile management Institute of PLA Bengbu 233011 China

With the broad implementations of the electronic business and government applications, robust system security and strong privacy protection have become essential requirements for remote user authentication schemes. Recently, Chen et al. pointed out that Wang et al.＇s scheme is vulnerable to the user impersonation attack and parallel session attack, and proposed an enhanced version to overcome the identified security flaws. In this paper, however, we show that Chen et al.＇s scheme still cannot achieve the claimed security goals and report its following problems：（1） It suffers from the offline password guessing attack, key compromise impersonation attack and known key attack; （2） It fails to provide forward secrecy; （3） It is not easily repairable. As our main contribution, a robust dynamic ID-based scheme based on non-tamper resistance assumption of the smart cards is presented to cope with the aforementioned defects, while preserving the merits of different related schemes. The analysis demonstrates that our scheme meets all the proposed criteria and eliminates several grave security threats that are difficult to be tackled at the same time in previous scholarship.

关键词： cryptanalysis authentication protocol smart card non-tamper resistant forward secrecy