Objective:Bone metastasis occurs in up to 90%of men with advanced prostate cancer and leads to fractures,severe pain and therapy-resistance.Bone metastases induce a spectrum of types of bone lesions which can respond ...Objective:Bone metastasis occurs in up to 90%of men with advanced prostate cancer and leads to fractures,severe pain and therapy-resistance.Bone metastases induce a spectrum of types of bone lesions which can respond differently to therapy even within individual prostate cancer patients.Thus,the special environment of the bone makes the disease more complicated and incurable.A model in which bone lesions are reproducibly induced that mirrors the complexity seen in patients would be invaluable for pre-clinical testing of novel treatments.The microstructural changes in the femurs of mice implanted with PCSD1,a new patient-derived xenograft from a surgical prostate cancer bone metastasis specimen,were determined.Methods:Quantitative micro-computed tomography(micro-CT)and histological analyses were performed to evaluate the effects of direct injection of PCSD1 cells or media alone(Control)into the right femurs of Rag2/gc/male mice.Results:Bone lesions formed only in femurs of mice injected with PCSD1 cells.Bone volume(BV)was significantly decreased at the proximal and distal ends of the femurs(p<0.01)whereas BV(p<0.05)and bone shaft diameter(p<0.01)were significantly increased along the femur shaft.Conclusion:PCSD1 cells reproducibly induced bone loss leading to osteolytic lesions at the ends of the femur,and,in contrast,induced aberrant bone formation leading to osteoblastic lesions along the femur shaft.Therefore,the interaction of PCSD1 cells with different bone region-specific microenvironments specified the type of bone lesion.Our approach can be used to determine if different bone regions support more therapy resistant tumor growth,thus,requiring novel treatments.展开更多
Only 54% of prostate cancer cases in Korea are localized compared with 82% of cases in the US. Furthermore, half of Korean patients are upgraded after radical prostatectomy （41.6%-50.6%）. We investigated the risk fa...Only 54% of prostate cancer cases in Korea are localized compared with 82% of cases in the US. Furthermore, half of Korean patients are upgraded after radical prostatectomy （41.6%-50.6%）. We investigated the risk factors for upgrading and/or upstaging of low-risk prostate cancer after radical prostatectomy. We retrospectively reviewed the medical records of 1159 patients who underwent radical prostatectomy at five hospitals in Honam Province. Preoperative data on standard clinicopathological parameters were collected. The radical prostatectomy specimens were graded and staged and we defined a ＂worsening prognosis＂ as a Gleason score ≥ 7 or upstaging to ≥ pT3. Multivariate logistic regression models were used to assess factors associated with postoperative pathological upstaging. Among the 1159 patients, 324 were classified into the clinically low-risk group, and 154 （47.5%） patients were either upgraded or upstaged. The multivariable analysis revealed that the preoperative serum prostate-specific antigen level （odds ratio [OR], 1.131; 95% confidence interval [CI], 1.007-1.271; P = 0.037）, percent positive biopsy core （OR： 1.018; 95% CI： 1.002-1.035; P = 0.032）, and small prostate volume （≤30 ml） （OR： 2.280; 95% CI： 1.351-3.848; P = 0.002） were predictive of a worsening prognosis. Overall, 47.5% of patients with low-risk disease were upstaged postoperatively. The current risk stratification criteria may be too relaxed for our study cohort.展开更多
基金We are grateful for the funding support for this work from the Leo and Anne Albert Charitable Foundation and the Phi Beta Psi Sorority.We deeply appreciate the invaluable contributions of Dr.Nissi Varki,Director,and Laarni Gapuz,Manager,Moores Cancer Center Histology Core.
文摘Objective:Bone metastasis occurs in up to 90%of men with advanced prostate cancer and leads to fractures,severe pain and therapy-resistance.Bone metastases induce a spectrum of types of bone lesions which can respond differently to therapy even within individual prostate cancer patients.Thus,the special environment of the bone makes the disease more complicated and incurable.A model in which bone lesions are reproducibly induced that mirrors the complexity seen in patients would be invaluable for pre-clinical testing of novel treatments.The microstructural changes in the femurs of mice implanted with PCSD1,a new patient-derived xenograft from a surgical prostate cancer bone metastasis specimen,were determined.Methods:Quantitative micro-computed tomography(micro-CT)and histological analyses were performed to evaluate the effects of direct injection of PCSD1 cells or media alone(Control)into the right femurs of Rag2/gc/male mice.Results:Bone lesions formed only in femurs of mice injected with PCSD1 cells.Bone volume(BV)was significantly decreased at the proximal and distal ends of the femurs(p<0.01)whereas BV(p<0.05)and bone shaft diameter(p<0.01)were significantly increased along the femur shaft.Conclusion:PCSD1 cells reproducibly induced bone loss leading to osteolytic lesions at the ends of the femur,and,in contrast,induced aberrant bone formation leading to osteoblastic lesions along the femur shaft.Therefore,the interaction of PCSD1 cells with different bone region-specific microenvironments specified the type of bone lesion.Our approach can be used to determine if different bone regions support more therapy resistant tumor growth,thus,requiring novel treatments.
文摘Only 54% of prostate cancer cases in Korea are localized compared with 82% of cases in the US. Furthermore, half of Korean patients are upgraded after radical prostatectomy （41.6%-50.6%）. We investigated the risk factors for upgrading and/or upstaging of low-risk prostate cancer after radical prostatectomy. We retrospectively reviewed the medical records of 1159 patients who underwent radical prostatectomy at five hospitals in Honam Province. Preoperative data on standard clinicopathological parameters were collected. The radical prostatectomy specimens were graded and staged and we defined a ＂worsening prognosis＂ as a Gleason score ≥ 7 or upstaging to ≥ pT3. Multivariate logistic regression models were used to assess factors associated with postoperative pathological upstaging. Among the 1159 patients, 324 were classified into the clinically low-risk group, and 154 （47.5%） patients were either upgraded or upstaged. The multivariable analysis revealed that the preoperative serum prostate-specific antigen level （odds ratio [OR], 1.131; 95% confidence interval [CI], 1.007-1.271; P = 0.037）, percent positive biopsy core （OR： 1.018; 95% CI： 1.002-1.035; P = 0.032）, and small prostate volume （≤30 ml） （OR： 2.280; 95% CI： 1.351-3.848; P = 0.002） were predictive of a worsening prognosis. Overall, 47.5% of patients with low-risk disease were upstaged postoperatively. The current risk stratification criteria may be too relaxed for our study cohort.
