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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.
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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.
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Background and purpose:It has been demonstrated that radical prostatectomy for patients with oligometastatic prostate cancer may contribute to improving local control of prostate cancer and overall survival by several retrospective studies. Perioperative complications play an important role in determining whether radical prostatectomy is appropriate for patients with oligometastatic prostate cancer. This study aimed to discuss the recurrence rate and the sever-ity of perioperative complications, and the primary curative effect of radical prostatectomy on oligometastatic prostate can-cer patients.Methods:A total number of 247 patients who received radical prostatectomy were recruited in the study from Jul. 2015 to Jan. 2016, including 25 patients with oligometastatic prostate cancer and 222 patients with localized prostate cancer. Patients with perioperative complications in both groups were graded with the Clavien-Dindo grading system. The proportion of PSA decline and the rates and severity of perioperative complications were analyzed in both groups.Results:The cases of prostate specific antigen (PSA) decline in the oligometastatic group were 21 (84.0%), lower than the localized group with 212 cases (95.5%). There were 6 cases (24.0%) with postoperative complications in the oligometastatic group, including serious complications (Ⅲ or above) 1 case (4.0%), and 49 cases (22.1%) with postoperative complications in the localized group, including serious complications (Ⅲ or above) 7 cases (3.2%). The differences between the groups reached no statistical significance (P>0.05).Conclusion:Radical prostatectomy for patients with oligometastatic prostate cancer could be safe, effective, and appropriate, the risk of perioperative complications should not be one of the limiting factors.
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Objective To investigate the stability of lumbar single?level dynamicly fixed by socket track pedicle screws after decompression. Methods Socket track pedicle screws are made of titanium?alloy, swing like universal screw within the scope of 18° in the sagittal plane and 8° in the horizontal plane. Motion constraints were due to the hole which the screw goes through. Six pig spines (L1-5) were tested by applying a pure moment of 4.018 Nm in 3 directions of loading. The range of motion (ROM) of the following groups underwent different surgical procedures was measured:(1) intact;(2) dynamic fixation 1 (decompres?sion by total laminectomy and instrumentation with socket track pedicle screws); (3) dynamic fixation 2 (decompression by total laminectomy and bilateral facetectomy while instrumentation with socket track pedicle screws);( 4) instability resulted from decom?pression (decompression by total laminectomy plus bilateral facetectomy without any rod);(5) hybrid fixation (decompression by to?tal laminectomy and bilateral facetectomy while instrumentation with 2 socket track pedicle screws connected with 2 unilateral pedicle screws ). Results Compared with the intact specimens (in flexion, extension, lateral bending and rotation, corresponding angular displacements were 1.84°±0.75°, 1.55°±0.34°, 2.2°±1.07°, 2.06°±0.76° respectively), the ROM of segment L3, 4 of each group were significantly restricted except for axial rotation. In flexion, extension and lateral bending, the ROM was reduced to 0.71°±0.39°, 0.46°±0.18°, 0.85°±0.66° in dynamic fixation 1 group;0.79°±0.43°, 0.71°±0.20°, 1.17°±0.48° in dynamic fixation 2 group and 0.63°±0.50°, 0.37°±0.19°, 0.54°±0.60° in hybrid fixation group. The rotation ROM of dynamic fixation 1 group and hy?brid fixation group were decreased to 1.50°±0.64° and 1.22°±0.36°, whereas the ROM of dynamic fixation 2 had a non?significant reduction to 1.85°±0.67°. The extension and rotation ROM of dynamic fixation 2 increased significantly comparing to dynamic fixa?tion 1 group; the extension, lateral bending and axial rotation ROM of hybrid fixation group were reduced comparing to the state of dynamic fixation 2 group. Conclusion The dynamic instrumentation of single?level lumbar spine with socket track pedicle screws could offer stability in all directions. The flexion, extension, lateral bending and rotation ROM of spine with dynamic instru?mentation after total laminectomy and bilateral facetectomy could be reduced.
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Enzyme engineering is an important part of the modern biotechnology. Industrial biocatalysis is considered the third wave of biotechnology following pharmaceutical and agricultural waves. In 25 years, China has made a mighty advances in enzyme engineering research. This review focuses on enzyme genomics, enzyme proteomics, biosynthesis, microbial conversion and biosensors in the Chinese enzyme engineering symposiums and advances in enzyme preparation industry in China.
Subject(s)
Agriculture , Biocatalysis , Biosensing Techniques , Biotechnology , China , Enzymes , Industrial Microbiology , Protein Engineering , ProteomicsABSTRACT
From air bacteria capable of decomposing creatinine, three single independent strains K9510、K9511 and K9512 have been isolated. The highest creatinine amidohydrolase (EC 3.5.2.10; creatininase) producing strain K9510 was screened out. The strain K9510 was identified as Pseudomonas sp. The results of culture condition for creatininase formation by strain K9510 were obtained as follows: creatinine and creatine were found to be the effective inducers for enzyme formation; the solution of mixed metallic salts could stimulate cell growth and enzyme formation. The suitable medium for creatininase formation was consisted of 0.9% creatinine、 0. 15% yeast extract、 0. 09% malt extract、0.05% NH4C1 and some amount of the solution of mixed metallic salts at pH5. 5. When the bacterium was grown in 250mL conic flask containing 50mL of the medium mentioned above on the rotary shaker(250r/min) at 35℃ for 33 h, about 50 u creatininase was obtained.