The predictive value of CTCs characterization for time to castration resistance of high-volume metastatic castration sensitive prostate cancer / 中华泌尿外科杂志

Objective@#To explore the predictive value of circulating tumor cells (CTCs) characterization for time to castration resistance of newly diagnosed high volume metastatic castration sensitive prostate cancer (mCSPC) patients.@*Methods@#Newly diagnosed high volume mCSPC patients were prospectively enrolled in this study from September 2015 to February 2017. The inclusion criteria include that the patients' age should be between 18 to 85 years old. The Prostate cancer should be diagnosed by biopsy or cytopathology. No endocrinological therapy, radiative therapy or chemotherapy was used before the study. High-volume metastatic lesion was confirmed by imaging. Those patients who accepted previous endocrinological therapy, radiative therapy or chemotherapy were excluded in this study. Those patients combined with concomitant tumor were also excluded. The health males were enrolled in the control group. All patients received androgen deprivation therapy (ADT) with goserelin plus bicalutamide (goserelin 3.6 mg subcutaneous injection, once a month plus bicalutamide 50mg orally, once a day). CanPatrol system was used to count CTCs in peripheral blood of patients and characterize CTCs based on expressions of epithelial markers(EpCAM and CK8/18/19) and mesenchymal markers(vimentin and twist). Primary endpoint was time to castration resistance. Survival analysis was conducted using Kaplan-Meier method and log-rank test was used to assess the difference of survival between groups, and univariate and multivariate analyses of prognostic factors were conducted using the Cox proportional hazards model.@*Results@#A total of 108 newly diagnosed high volume mCSPC patients were enrolled in this study. The median age of enrolled patients was 68 years old (ranging 51-85 years old), and median PSA was 196.2 ng/ml(ranging 5.8-5 011.9 ng/ml). The median level of hemoglobin was 32 g/L(ranging 9-172 g/L). The median level of LDH was 179 U/L(ranging 49-630 U/L). The ECOG scores was 0-1 score in 94 cases(87.0%), 2 scores in 14 cases (13.0%). The Gleason scores was 6-7 in 20 cases (18.5%) and more than 8 in 88 cases (81.5%). All patients had bone metastatic lesions, among which 41 (38.0%) patients had more than 10 metastatic lesions and 6 (5.6%) patients with visceral metastasis, 30(27.8%) patients with limb bone metastasis. The median CTCs count was four, and ranging 0-35. Mesenchymal CTCs positive and negative (negative included CTCs negative, epithelial CTCs positive and biophenotypic CTCs positive) patients were 58(53.7%) and 50, respectively. There was no correlation between CTCs characterization with age, baseline PSA, Gleason score, ALP and other clinical parameters (P>0.05). In control group, the mean age was 26 years old (ranging 20-31 years old). No CTCs were detected among those people. After a median follow-up of 24 months (ranging 18-32 months), 90 patients (83.3%) progressed to castration resistant prostate cancer (CRPC). The median time to CRPC for patients of mesenchymal CTCs positive and negative was (10.5±1.4) and (14.0±3.4) months, respectively(P<0.001). Univariate analysis revealed CTCs characterization(HR=1.647, P=0.003), the number of metastatic lesions (HR=1.624, P=0.025)and limb bone metastasis(HR=1.706, P=0.019) were prognostic factors of time to CRPC; further multivariate analysis showed that only baseline mesenchymal CTCs positive (HR=1.562, P=0.008) was independent prognostic factors of unfavorable time to CRPC.@*Conclusions@#CTCs characterization can predict time to CRPC of newly diagnosed high volume mCSPC patients receiving ADT, and patients of baseline mesenchymal CTCs positive are more likely to progress to CRPC.

The predictive value of CTCs characterization for time to castration resistance of high-volume metastatic castration sensitive prostate cancer / 中华泌尿外科杂志

Objective To explore the predictive value of circulating tumor cells (CTCs) characterization for time to castration resistance of newly diagnosed high volume metastatic castration sensitive prostate cancer (mCSPC) patients.Methods Newly diagnosed high volume mCSPC patients were prospectively enrolled in this study from September 2015 to February 2017.The inclusion criteria include that the patients'age should be between 18 to 85 years old.The Prostate cancer should be diagnosed by biopsy or cytopathology.No endocrinological therapy,radiative therapy or chemotherapy was used before the study.High-volume metastatic lesion was confirmed by imaging.Those patients who accepted previous endocrinological therapy,radiative therapy or chemotherapy were excluded in this study.Those patients combined with concomitant tumor were also excluded.The health males were enrolled in the control group.All patients received androgen deprivation therapy (ADT) with goserelin plus bicalutamide (goserelin 3.6 mg subcutaneous injection,once a month plus bicalutamide 50mg orally,once a day).CanPatrol system was used to count CTCs in peripheral blood of patients and characterize CTCs based on expressions of epithelial markers(EpCAM and CK8/18/19) and mesenchymal markers (vimentin and twist).Primary endpoint was time to castration resistance.Survival analysis was conducted using Kaplan-Meier method and log-rank test was used to assess the difference of survival between groups,and univariate and multivariate analyses of prognostic factors were conducted using the Cox proportional hazards model.Results A total of 108 newly diagnosed high volume mCSPC patients were enrolled in this study.The median age of enrolled patients was 68 years old (ranging 51-85 years old),and median PSA was 196.2 ng/ml (ranging 5.8-5 011.9 ng/ml) . The median level of hemoglobin was 32 g/L(ranging 9-172 g/L).The median level of LDH was 179 U/L(ranging 49-630 U/L).The ECOG scores was 0-1 score in 94 cases(87.0％),2 scores in 14 cases (13.0％).The Gleason scores was 6-7 in 20 cases (18.5％) and more than 8 in 88 cases (81.5％).All patients had bone metastatic lesions,among which 41 (38.0％) patients had more than 10 metastatic lesions and 6 (5.6％) patients with visceral metastasis,30 (27.8％) patients with limb bone metastasis.The median CTCs count was four,and ranging 0-35.Mesenchymal CTCs positive and negative (negative included CTCs negative,epithelial CTCs positive and biophenotypic CTCs positive) patients were 58 (53.7％) and 50,respectively.There was no correlation between CTCs characterization with age,baseline PSA,Gleason score,ALP and other clinical parameters (P ＞ 0.05).In control group,the mean age was 26 years old (ranging 20-31 years old).No CTCs were detected among those people.After a median follow-up of 24 months (ranging 18-32 months),90 patients (83.3％) progressed to castration resistant prostate cancer (CRPC).The median time to CRPC for patients of mesenchymal CTCs positive and negative was (10.5 ± 1.4) and (14.0 ± 3.4) months,respectively (P ＜ 0.001).Univariate analysis revealed CTCs characterization(HR =1.647,P =0.003),the number of metastatic lesions (HR =1.624,P =0.025) and limb bone metastasis(HR =1.706,P =0.019) were prognostic factors of time to CRPC;further multivariate analysis showed that only baseline mesenchymal CTCs positive (HR =1.562,P =0.008) was independent prognostic factors of unfavorable time to CRPC.Conclusions CTCs characterization can predict time to CRPC of newly diagnosed high volume mCSPC patients receiving ADT,and patients of baseline mesenchymal CTCs positive are more likely to progress to CRPC.

Effect of estrogen or progesterone combined with paclitaxel on human ovarian cancer cell growth and Drosha expression / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effect of estrogen (E2), progesterone(P4), and paclitaxel (taxol) on the growth of primary human ovarian cancer cells in vitro and the expression of Drosha.</p><p><b>METHODS</b>Human ovarian cancer cells were treated with estrogen, progesterone or in combination with paclitaxel in vitro. The inhibition rate of ovarian cancer cells was assessed by methyl thiazolyl tetrazolium (MTT) assay. Apoptosis rate and cell cycle were determined by FACS analysis. The relative abundence of Drosha expression was detected by real-time quantitative PCR (qRT-PCR) and Western blotting.</p><p><b>RESULTS</b>The inhibition rate of the estrogen group, progesterone group, paclitaxel group, E2(+)Taxol group, P4(+)Taxol group was (31.53 ± 8.21)%, (25.22 ± 15.50)%, (46.71 ± 4.25)%, (69.46 ± 3.71)%, and (47.35 ± 39.02)%, respectively, significantly higher than that of the control group (0%, P<0.05 for all). Relative to the ER (-) in ovarian cancer cells,Drosha mRNA expression level of estrogen group, progesterone group, paclitaxel group, E2(+) Taxol group,and P4(+)Taxol group was 1.62 ± 0.10,1.60 ± 0.10,1.75 ± 0.16,1.95 ± 0.20, and 1.53 ± 0.06, respectively, significantly higher than that of the control group (1.00, P<0.05 for all). Relative to the ER (+)in ovarian cancer cells,the Drosha mRNA expression level of estrogen group, progesterone group, paclitaxel group, E2(+)taxol group, and P4(+)Taxol group was 1.03 ± 0.14, 1.60 ± 0.09, 1.75 ± 0.16, 1.60 ± 0.10, 1.53 ± 0.06, respectively except estrogen group, significantly higher than that of the control group (1.00, P<0.05). Relative to the ER (-) in ovarian cancer cells, the Drosha protein expression levels of the control group, estrogen group, progesterone group, paclitaxel group, E2(+) taxol group, and P4(+) Taxol group were 0.25 ± 0.05, 0.87 ± 0.30, 0.85 ± 0.38, 1.30 ± 0.21, 1.75 ± 0.83, 1.62 ± 0.82, respectively, with a significant difference between the experimental groups and the control group (P<0.05). Relative to the ER(+)ovarian cancer cells, the Drosha protein expression levels in the estrogen group, progesterone group, paclitaxel group, E2(+) taxol group, and P4(+) taxol group, were 0.28 ± 0.16, 0.85 ± 0.38, 1.30 ± 0.21, 0.94 ± 0.18, and 1.62 ± 0.82, respectively except estrogen group, significantly higher than that of the control group (0.25 ± 0.05, P<0.05 for all).</p><p><b>CONCLUSIONS</b>Estrogen and progesterone in combination with paclitaxel can inhibit the growth of human ovarian cancer cells in vitro, and affect the cell apoptosis rate. Estrogen and taxol can alter the cell cycle. Estrogen and progesterone combined with paclitaxel show tumor suppressing or sensitizing effect through upregulated Drosha expression, and are associated with the estrogen receptor expression.</p>

Analysis the effect of pelvic floor muscle rehabilitation treatment of 435 cases of urinary incontinence / 中国基层医药

Objective To explore the clinical effect of pelvic floor muscle rehabilitation therapy to recover pelvic floor dysfunction.Methods 435 cases of 6-8 weeks postpartum urinary incontinence patients were chosen.The urinary incontinence questionnaire ( ICI-QSF) ,and Female Sexual Function Index questionnaire ( FSFI questionnaire) were used to detect maternal urinary incontinence (UI) investigation,pelvic organ prolapse (POP-Q) degree and quality of sexual life questionnaire.Ⅰ muscle,Ⅱ muscle strength and fatigue, vaginal and the change of dynamic pressure for pelvic floor functional change before and after Pelvic floor rehabilitation were compared.Pelvic floor mus-cle rehabilitation treatment included:imitation bioelectricity stimulus,biofeedback,scene reflection training and Kegel exercises.Results After pelvic floor muscle rehabilitation,pelvic floor function improved significantly,pelvic floor muscle strength increase, decrease fatigue, vaginal dynamic pressure rose significant difference:Electrical values (μV) before treatment (5.6 ±1.8),after treatment(15.1 ±4.6),t =3.6,P <0.05;Vaginal dynamic pressure (cmH2O) before treatment(48.7 ±11.0),after treatment (86.3 ±5.1)cmH2O(t=7.2,P<0.01);Fatigue obvi-ously improved,(P<0.01),the effect of Urinary incontinence treatment is very obvious (t=5.6,P<0.05)and pelvic organ prolapse improved significantly:Before treatment vaginal wall prolapse II degrees 63 people,after treat-ment 14 people,remission rate 82%,and Before treatment uterine prolapse 172 people,after treatment uterine pro-lapse 39 people,the response rate of 77.3% (P <0.01),sexual function improved significantly:before treatment score is (78.00 ±20.45) and after treatment scores is (100.00 ±25.36),t=8.6 (P<0.01).Conclusion Pelvic floor muscle rehabilitation effectively improve postpartum women pelvic floor function,can achieve the purpose of the treatment of urinary incontinence,improve pelvic organ prolapse and the quality of sex life.