1.Novel hormone therapies for advanced prostate cancer: Understanding and countering drug resistance.
Zhipeng WANG ; Jie WANG ; Dengxiong LI ; Ruicheng WU ; Jianlin HUANG ; Luxia YE ; Zhouting TUO ; Qingxin YU ; Fanglin SHAO ; Dilinaer WUSIMAN ; William C CHO ; Siang Boon KOH ; Wei XIONG ; Dechao FENG
Journal of Pharmaceutical Analysis 2025;15(9):101232-101232
Prostate cancer is the most prevalent malignant tumor among men, ranking first in incidence and second in mortality globally. Novel hormone therapies (NHT) targeting the androgen receptor (AR) pathway have become the standard of care for metastatic prostate cancer. This review offers a comprehensive overview of NHT, including abiraterone, enzalutamide, apalutamide, darolutamide, and rezvilutamide, which have demonstrated efficacy in delaying disease progression and improving patient survival and quality of life. Nevertheless, resistance to NHT remains a critical challenge. The mechanisms underlying resistance are complex, involving AR gene amplification, mutations, splice variants, increased intratumoral androgens, and AR-independent pathways such as the glucocorticoid receptor, neuroendocrine differentiation, DNA repair defects, autophagy, immune evasion, and activation of alternative signaling pathways. This review discusses these resistance mechanisms and examines strategies to counteract them, including sequential treatment with novel AR-targeted drugs, chemotherapy, poly ADP-ribose polymerase inhibitors, radionuclide therapy, bipolar androgen therapy, and approaches targeting specific resistance pathways. Future research should prioritize elucidating the molecular basis of NHT resistance, optimizing existing therapeutic strategies, and developing more effective combination regimens. Additionally, advanced sequencing technologies and resistance research models should be leveraged to identify novel therapeutic targets and improve drug delivery efficiencies. These advancements hold the potential to overcome NHT resistance and significantly enhance the management and prognosis of patients with advanced prostate cancer.
2.Utility of Radiographic Parameter in Assessing Bone Density and Subsequent Fractures in Patients With Osteoporotic Vertebral Compression Fracture
Yunsheng WANG ; Mei DONG ; Jiali ZHANG ; Dechao MIAO ; Feng WANG ; Tong TONG ; Linfeng WANG
Neurospine 2024;21(3):966-972
Objective:
To investigate the ability of radiological parameter canal bone ratio (CBR) to assess bone mineral density and to differentiate between patients with primary and multiple osteoporotic vertebral compression fracture (OVCF).
Methods:
A retrospective analysis was conducted on OVCF patients treated at our hospital. CBR was measured through full-spine x-rays. Patients were categorized into primary and multiple fracture groups. Receiver operating characteristic curve analysis and area under the curve (AUC) calculation were used to assess the ability of parameters to predict osteoporosis and multiple fractures. Predictors of T values were analyzed by multiple linear regression, and independent risk factors for multiple fractures were determined by multiple logistic regression analysis.
Results:
CBR showed a moderate negative correlation with dual-energy x-ray absorptiometry T values (r = -0.642, p < 0.01). Higher CBR (odds ratio [OR], -6.483; 95% confidence interval [CI], -8.234 to -4.732; p < 0.01) and lower body mass index (OR, 0.054; 95% CI, 0.023–0.086; p < 0.01) were independent risk factors for osteoporosis. Patients with multiple fractures had lower T values (mean ± standard deviation [SD]: -3.76 ± 0.73 vs. -2.83 ± 0.75, p < 0.01) and higher CBR (mean ± SD: 0.54 ± 0.07 vs. 0.46 ± 0.06, p < 0.01). CBR had an AUC of 0.819 in predicting multiple fractures with a threshold of 0.53. T values prediction had an AUC of 0.816 with a threshold of -3.45. CBR > 0.53 was an independent risk factor for multiple fractures (OR, 14.66; 95% CI, 4.97–43.22; p < 0.01).
Conclusion
CBR is negatively correlated with bone mineral density (BMD) and can be a novel opportunistic BMD assessment method. It is a simple and effective measurement index for predicting multiple fractures, with predictive performance not inferior to T values.
3.Utility of Radiographic Parameter in Assessing Bone Density and Subsequent Fractures in Patients With Osteoporotic Vertebral Compression Fracture
Yunsheng WANG ; Mei DONG ; Jiali ZHANG ; Dechao MIAO ; Feng WANG ; Tong TONG ; Linfeng WANG
Neurospine 2024;21(3):966-972
Objective:
To investigate the ability of radiological parameter canal bone ratio (CBR) to assess bone mineral density and to differentiate between patients with primary and multiple osteoporotic vertebral compression fracture (OVCF).
Methods:
A retrospective analysis was conducted on OVCF patients treated at our hospital. CBR was measured through full-spine x-rays. Patients were categorized into primary and multiple fracture groups. Receiver operating characteristic curve analysis and area under the curve (AUC) calculation were used to assess the ability of parameters to predict osteoporosis and multiple fractures. Predictors of T values were analyzed by multiple linear regression, and independent risk factors for multiple fractures were determined by multiple logistic regression analysis.
Results:
CBR showed a moderate negative correlation with dual-energy x-ray absorptiometry T values (r = -0.642, p < 0.01). Higher CBR (odds ratio [OR], -6.483; 95% confidence interval [CI], -8.234 to -4.732; p < 0.01) and lower body mass index (OR, 0.054; 95% CI, 0.023–0.086; p < 0.01) were independent risk factors for osteoporosis. Patients with multiple fractures had lower T values (mean ± standard deviation [SD]: -3.76 ± 0.73 vs. -2.83 ± 0.75, p < 0.01) and higher CBR (mean ± SD: 0.54 ± 0.07 vs. 0.46 ± 0.06, p < 0.01). CBR had an AUC of 0.819 in predicting multiple fractures with a threshold of 0.53. T values prediction had an AUC of 0.816 with a threshold of -3.45. CBR > 0.53 was an independent risk factor for multiple fractures (OR, 14.66; 95% CI, 4.97–43.22; p < 0.01).
Conclusion
CBR is negatively correlated with bone mineral density (BMD) and can be a novel opportunistic BMD assessment method. It is a simple and effective measurement index for predicting multiple fractures, with predictive performance not inferior to T values.
4.Utility of Radiographic Parameter in Assessing Bone Density and Subsequent Fractures in Patients With Osteoporotic Vertebral Compression Fracture
Yunsheng WANG ; Mei DONG ; Jiali ZHANG ; Dechao MIAO ; Feng WANG ; Tong TONG ; Linfeng WANG
Neurospine 2024;21(3):966-972
Objective:
To investigate the ability of radiological parameter canal bone ratio (CBR) to assess bone mineral density and to differentiate between patients with primary and multiple osteoporotic vertebral compression fracture (OVCF).
Methods:
A retrospective analysis was conducted on OVCF patients treated at our hospital. CBR was measured through full-spine x-rays. Patients were categorized into primary and multiple fracture groups. Receiver operating characteristic curve analysis and area under the curve (AUC) calculation were used to assess the ability of parameters to predict osteoporosis and multiple fractures. Predictors of T values were analyzed by multiple linear regression, and independent risk factors for multiple fractures were determined by multiple logistic regression analysis.
Results:
CBR showed a moderate negative correlation with dual-energy x-ray absorptiometry T values (r = -0.642, p < 0.01). Higher CBR (odds ratio [OR], -6.483; 95% confidence interval [CI], -8.234 to -4.732; p < 0.01) and lower body mass index (OR, 0.054; 95% CI, 0.023–0.086; p < 0.01) were independent risk factors for osteoporosis. Patients with multiple fractures had lower T values (mean ± standard deviation [SD]: -3.76 ± 0.73 vs. -2.83 ± 0.75, p < 0.01) and higher CBR (mean ± SD: 0.54 ± 0.07 vs. 0.46 ± 0.06, p < 0.01). CBR had an AUC of 0.819 in predicting multiple fractures with a threshold of 0.53. T values prediction had an AUC of 0.816 with a threshold of -3.45. CBR > 0.53 was an independent risk factor for multiple fractures (OR, 14.66; 95% CI, 4.97–43.22; p < 0.01).
Conclusion
CBR is negatively correlated with bone mineral density (BMD) and can be a novel opportunistic BMD assessment method. It is a simple and effective measurement index for predicting multiple fractures, with predictive performance not inferior to T values.
5.Utility of Radiographic Parameter in Assessing Bone Density and Subsequent Fractures in Patients With Osteoporotic Vertebral Compression Fracture
Yunsheng WANG ; Mei DONG ; Jiali ZHANG ; Dechao MIAO ; Feng WANG ; Tong TONG ; Linfeng WANG
Neurospine 2024;21(3):966-972
Objective:
To investigate the ability of radiological parameter canal bone ratio (CBR) to assess bone mineral density and to differentiate between patients with primary and multiple osteoporotic vertebral compression fracture (OVCF).
Methods:
A retrospective analysis was conducted on OVCF patients treated at our hospital. CBR was measured through full-spine x-rays. Patients were categorized into primary and multiple fracture groups. Receiver operating characteristic curve analysis and area under the curve (AUC) calculation were used to assess the ability of parameters to predict osteoporosis and multiple fractures. Predictors of T values were analyzed by multiple linear regression, and independent risk factors for multiple fractures were determined by multiple logistic regression analysis.
Results:
CBR showed a moderate negative correlation with dual-energy x-ray absorptiometry T values (r = -0.642, p < 0.01). Higher CBR (odds ratio [OR], -6.483; 95% confidence interval [CI], -8.234 to -4.732; p < 0.01) and lower body mass index (OR, 0.054; 95% CI, 0.023–0.086; p < 0.01) were independent risk factors for osteoporosis. Patients with multiple fractures had lower T values (mean ± standard deviation [SD]: -3.76 ± 0.73 vs. -2.83 ± 0.75, p < 0.01) and higher CBR (mean ± SD: 0.54 ± 0.07 vs. 0.46 ± 0.06, p < 0.01). CBR had an AUC of 0.819 in predicting multiple fractures with a threshold of 0.53. T values prediction had an AUC of 0.816 with a threshold of -3.45. CBR > 0.53 was an independent risk factor for multiple fractures (OR, 14.66; 95% CI, 4.97–43.22; p < 0.01).
Conclusion
CBR is negatively correlated with bone mineral density (BMD) and can be a novel opportunistic BMD assessment method. It is a simple and effective measurement index for predicting multiple fractures, with predictive performance not inferior to T values.
6.Utility of Radiographic Parameter in Assessing Bone Density and Subsequent Fractures in Patients With Osteoporotic Vertebral Compression Fracture
Yunsheng WANG ; Mei DONG ; Jiali ZHANG ; Dechao MIAO ; Feng WANG ; Tong TONG ; Linfeng WANG
Neurospine 2024;21(3):966-972
Objective:
To investigate the ability of radiological parameter canal bone ratio (CBR) to assess bone mineral density and to differentiate between patients with primary and multiple osteoporotic vertebral compression fracture (OVCF).
Methods:
A retrospective analysis was conducted on OVCF patients treated at our hospital. CBR was measured through full-spine x-rays. Patients were categorized into primary and multiple fracture groups. Receiver operating characteristic curve analysis and area under the curve (AUC) calculation were used to assess the ability of parameters to predict osteoporosis and multiple fractures. Predictors of T values were analyzed by multiple linear regression, and independent risk factors for multiple fractures were determined by multiple logistic regression analysis.
Results:
CBR showed a moderate negative correlation with dual-energy x-ray absorptiometry T values (r = -0.642, p < 0.01). Higher CBR (odds ratio [OR], -6.483; 95% confidence interval [CI], -8.234 to -4.732; p < 0.01) and lower body mass index (OR, 0.054; 95% CI, 0.023–0.086; p < 0.01) were independent risk factors for osteoporosis. Patients with multiple fractures had lower T values (mean ± standard deviation [SD]: -3.76 ± 0.73 vs. -2.83 ± 0.75, p < 0.01) and higher CBR (mean ± SD: 0.54 ± 0.07 vs. 0.46 ± 0.06, p < 0.01). CBR had an AUC of 0.819 in predicting multiple fractures with a threshold of 0.53. T values prediction had an AUC of 0.816 with a threshold of -3.45. CBR > 0.53 was an independent risk factor for multiple fractures (OR, 14.66; 95% CI, 4.97–43.22; p < 0.01).
Conclusion
CBR is negatively correlated with bone mineral density (BMD) and can be a novel opportunistic BMD assessment method. It is a simple and effective measurement index for predicting multiple fractures, with predictive performance not inferior to T values.
7.Chitosan hydrogel composite with adipose-derived stem cells for repair of rabbit articular cartilage defect
Tao LIN ; Zhu CHEN ; Dechao YUAN ; Kang LIU ; Xiaocong XIANG ; Yuchuan ZHOU ; Gang FENG
Chinese Journal of Trauma 2016;32(4):357-362
Objective To fabricate a novel tissue-engineered cartilage with adipose-derived stem cells (ADSCs) seeded on the chitosan hydrogel scaffold to repair articular cartilage defect.Methods Adipose tissue and costal cartilage were harvested from New Zealand rabbits,and ADSCs in passage one and chondrocytes were obtained after the samples were digested and cultured in vitro.ADSCs were digested,suspended,seeded onto the sterile chitosan gel,and cultured in vitro for 1 week to fabricate the tissue-engineered cartilage.The defects were respectively filled with the tissue-engineered cartilage (composite group),chondrocyte suspension (cell group),chitosan gel (material group) and nothing at all (control group).At postoperative 12 weeks,cartilage repair was evaluated using the gross examination,histological staining,immunohistochemical staining and international cartilage repair society (ICRS) histological score.Results Effect of cartilage repair in composite group was significantly better compared to other groups.The regenerated tissue in composite group seemed tightly bound in normal tissue,with similar structure and extracellular matrix secretion.ICRS histological score in composite group was (13.89 ± 0.14) points,which differed significantly from (7.06 ± 0.19) points in control group,(7.14 ± 0.22) points in cell group and (7.46 ± 0.26) points in material group (P <0.01).Conclusion The tissue-engineered cartilage with ADSCs seeded onto the chitosan hydrogel is effective for repair of articular cartilage defect.
8.Preliminary construction of a novel tissue-engineered BMG/PBST biphasic scaffold for annulus fibrosus in vitro
Dechao YUAN ; Zhu CHEN ; Xiaocong XIANG ; Kang LIU ; Gang FENG
Chinese Journal of Orthopaedics 2016;(1):35-42
Objective To construct a novel tissue?engineered bone matrix gelatin (BMG)/poly[butylene succinate?co?tere?phthalate] (PBST) biphasic scaffold for annulus fibrosus. Methods The PBST spinning fibers were prepared by electrospinning and the porosity and water absorption rate were tested. Rabbit annulus fibrosus cells were isolated, cultured and identified through SafraninOstaining, and collagenⅡimmunohistochemical staining in vitro. And then annulus fibrosus cells were implanted on the PBST fiber, whose growth situation was observed by scanning electron microscope (SEM). Then the BMG/PBST biphasic scaf?fold was constructed by BMG as the outer annular fibrosus and PBST fiber as the inner annular fibrosus. The annulus fibrosus cells were implanted on the biphasic scafflod and cultured for 3, 7 and 21 days in vitro. The biomechanical and biological property was observed at the predetermined time point. Results The porosity of the fiber was 61.83%±7.33%and its water absorption rate was 297.34%± 57.13%. The identified result of annulus fibrosus cells were positive, suggesting that the cells have still kept their annulus fibrosus cells characteristics. The cells growth could be observed through SEM at 3rd and 7th day after implanted on the fi?bers. After cultured on the BMG/PBST scaffold, HE staining proved that the cells could ingress into the inner of fiber with time. SafraninOstaining and collagenⅡimmunohistochemical staining proved that the cells can secreted abundant proteoglycan and collagenⅡ, the special annulus fibrosus cell extracellular matrix. Compared with the BMG/PBST scaffold without cells, the elastic modulus of biphasic scaffold was increased from 14.83±1.02 MPa to 17.56±1.47 MPa after cultured with cells for 21 days in vitro. Conclusion The novel tissue?engineered biphasic scaffold for annulus fibrosus constructed with BMG and PBST fiber spinning has good cytocompatibility and biomechanical characteristics, which provide a basis for the complete tissue engineered interverte?bral disc.
9.How to build a tissue-engineered intervertebral disc annulus fibrosus that is more close to the natural one?
Dechao YUAN ; Zhu CHEN ; Daxiong FENG ; Gang FENG
Chinese Journal of Tissue Engineering Research 2015;(42):6832-6837
BACKGROUND:Tissue-engineered intervertebral disc has provided a new biological therapeutic approach for intervertebral disc degeneration. Tissue-engineered annulus fibrosus is one key step of constructing a complete tissue-engineered intervertebral disc. OBJECTIVE:To sum up the research progress of tissue-engineered annulus fibrosus from the folowing aspects: structural features, scaffold materials, seed cels. METHODS:PubMed database and Wanfang database (2000-2015) were retrieved by the key words of “tissue engineering, intervertebral disc, annulus fibrosus, seed cel, scaffold, construction” in Chinese and in English, respectively. According to inclusion and exclusion criteria, 48 literatures were involved for summarization. RESULTS AND CONCLUSION: Previous studies about tissue-engineered annulus fibrosus only focused on cel adhesion, proliferation and extracelular matrix secretion on the scaffold. Currently, tissue-engineered annulus fibrosus exhibit similar features to the natural annulus fibrosus in the folowing aspects: cel function, tissue structure and mechanical features, and relevant animal experiments have achieved certain results in animal experiments. However, it is stil difficult to build a tissue-engineered annulus fibrosus entirely similar to the natural one, and we need to further improve scaffold materials, culture conditions, colection of seed cels. The current strategies of annulus fibrosus construction stil focus on single phase of scaffold, and the biphasic scaffold and complete intervertebral disc scaffold wil be the trend of the researches. Technology of induced differentiation of stem cels provides a broach source of seed cels for tissue-engineered annulus fibrosus.
10.The impact of collagenaseⅡdigestion time on the biological characteristics of rabbit chondrocytes
Dechao YUAN ; Zhu CHEN ; Shang DENG ; Gang FENG
Chongqing Medicine 2015;(32):4553-4555,4559
Objective To investigate the best digestion time for rabbit rib cartilage cells separation by collagenase Ⅱ diges‐tion method .Methods Rabbit cartilage tissue was taken from 3‐month‐old New Zealand white rabbits ,and then digested in 0 .2%collagenase Ⅱ solution for 4 ,8 ,12 ,16 and 20 h under vibration at 37 ℃ ,respectively .The corresponding experiments were named as group A ,B ,C ,D ,and E .The obtained primary cells were cultured and passaged after counting .The cell morphology ,proliferation rate ,secretion of extracellular matrix of passage 2 cells were compared to chose the best digestion time .Results The primary chon‐drocytes obtained in group C ,D and E were more than the other two group A and B .The chondrocytes cytoactive in group C and D were better than the other three group A ,B and E .The passage 2 chondrocytes in group C ,D had better secretion of extracellular matrix capability than the other three groups .Conclusion The best collagenase Ⅱ digestion time is 12 to 16 h ,at this digestion time period ,more primary chondrocytes with high cytoactive and strong proliferation capability can be obtained ,and the phenotype of their passage 2 cells is quite good .

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