Objective To explore the correlation between IT-GA6 gene ( rs12621278, G ) , MSMB gene ( rs10993994,T) ,chromosome 8q24 9 ( rs10086908, T) and prostate cancer ( PCa) in Beijing residents,and to explore the correlation...Objective To explore the correlation between IT-GA6 gene ( rs12621278, G ) , MSMB gene ( rs10993994,T) ,chromosome 8q24 9 ( rs10086908, T) and prostate cancer ( PCa) in Beijing residents,and to explore the correlation between genotype and pheno-展开更多
Objective: Prostate secretory protein of 94 amino acids(PSP94) is a target gene of the EZH2 transcriptional repressor and is often downregulated in prostate cancer;however, its prognostic value is disputed.Methods: Im...Objective: Prostate secretory protein of 94 amino acids(PSP94) is a target gene of the EZH2 transcriptional repressor and is often downregulated in prostate cancer;however, its prognostic value is disputed.Methods: Immunohistochemical analysis of a tissue microarray of 12, 432 prostate cancer specimens was performed to evaluate PSP94 expression. Correlation of PSP94 expression with tumor phenotype, patient prognosis, TMPRSS2:ERG fusion status, EZH2 expression and PTEN deletion was studied.Results: PSP94 expression was increased in benign prostatic hyperplasia;however, it was downregulated in 48% and negative in42% of the 9, 881 interpretable prostate cancer specimens. The loss of PSP94 expression was inversely correlated to EZH2 expression(P < 0.0001) and largely unrelated to the ERG status, but strongly correlated with high Gleason grade, advanced tumor stage, and nodal metastasis(P <0.0001 each). The fraction of PSP94-negative cancer specimens increased from 40% in pT2 to 52%in pT3 b-pT4(P < 0.0001) and from 40% in Gleason 3+3 = 6 to 46% in Gleason 4+3 = 7 and 60% in Gleason ≥4+4 = 8(P <0.0001). Loss of PSP94 was linked to early prostate-specific antigen recurrence, but with little absolute effect(P < 0.0001).However, it provided additional prognostic impact in cancer specimens with PTEN deletion. Loss of PSP94 deteriorated prognosis of cancer patients with PTEN deletion by more than 10%(P < 0.0001). The combination of PTEN deletion and PSP94 loss provided independent prognostic information that was observed in several subgroups defined by classical and quantitative Gleason grade.Conclusions: The results of our study suggest that combined PSP94/PTEN analysis can be potentially used in the clinical prognosis of prostate cancer.展开更多
FK228 is an FDA-approved anticancer drug naturally produced by Chromobacterium violaceum No.968 up to 19 mg/L in a pilot industry-scale batch fermentation.Here we report a genomics-guided discovery of Burkholderia tha...FK228 is an FDA-approved anticancer drug naturally produced by Chromobacterium violaceum No.968 up to 19 mg/L in a pilot industry-scale batch fermentation.Here we report a genomics-guided discovery of Burkholderia thailandensis MSMB43 as a new and significantly better source of FK228.The genome of B.thailandensis MSMB43 was found to contain a functional biosynthetic gene cluster highly homologous to that of FK228 in C.violaceum No.968,and the bacterium indeed produces authentic FK228.By simple fermentation in shaking flasks in a preferred M8 medium,B.thailandensis MSMB43 produced FK228 up to 67.7 mg/L;by fedbatch fermentation in a 20-L fermentor in M8 medium,B.thailandensis MSMB43 produced FK228 up to 115.9 mg/L,which is 95 fold higher than that of C.violaceum No.968 under the same laboratory fermentation conditions.RT-PCR analysis indicated that the high FK228 yield of B.thailandensis MSMB43 was due to high expression of biosynthetic genes,represented by Bth_depA,during the fermentation process.Further genetic manipulation resulted in a recombinant strain,B.thailandensis MSMB43/pBMTL3-tdpR,which harbors a broad host-range vector expressing the thailandepsin biosynthetic pathway regulatory gene tdpR.This engineered strain produced up to 168.5 mg/L of FK228 in fed-batch fermentation in a 20-L fermentor in M8 medium.Therefore,the wild-type B.thailandensis MSMB43 or its engineered derivative could potentially be a good starting point for an industrial process to improve FK228 production for its expanding use in therapy.展开更多
文摘Objective To explore the correlation between IT-GA6 gene ( rs12621278, G ) , MSMB gene ( rs10993994,T) ,chromosome 8q24 9 ( rs10086908, T) and prostate cancer ( PCa) in Beijing residents,and to explore the correlation between genotype and pheno-
基金supported by a grant from the Federal Ministry of Education and Research (Grant No.01KU1505B)
文摘Objective: Prostate secretory protein of 94 amino acids(PSP94) is a target gene of the EZH2 transcriptional repressor and is often downregulated in prostate cancer;however, its prognostic value is disputed.Methods: Immunohistochemical analysis of a tissue microarray of 12, 432 prostate cancer specimens was performed to evaluate PSP94 expression. Correlation of PSP94 expression with tumor phenotype, patient prognosis, TMPRSS2:ERG fusion status, EZH2 expression and PTEN deletion was studied.Results: PSP94 expression was increased in benign prostatic hyperplasia;however, it was downregulated in 48% and negative in42% of the 9, 881 interpretable prostate cancer specimens. The loss of PSP94 expression was inversely correlated to EZH2 expression(P < 0.0001) and largely unrelated to the ERG status, but strongly correlated with high Gleason grade, advanced tumor stage, and nodal metastasis(P <0.0001 each). The fraction of PSP94-negative cancer specimens increased from 40% in pT2 to 52%in pT3 b-pT4(P < 0.0001) and from 40% in Gleason 3+3 = 6 to 46% in Gleason 4+3 = 7 and 60% in Gleason ≥4+4 = 8(P <0.0001). Loss of PSP94 was linked to early prostate-specific antigen recurrence, but with little absolute effect(P < 0.0001).However, it provided additional prognostic impact in cancer specimens with PTEN deletion. Loss of PSP94 deteriorated prognosis of cancer patients with PTEN deletion by more than 10%(P < 0.0001). The combination of PTEN deletion and PSP94 loss provided independent prognostic information that was observed in several subgroups defined by classical and quantitative Gleason grade.Conclusions: The results of our study suggest that combined PSP94/PTEN analysis can be potentially used in the clinical prognosis of prostate cancer.
基金the University of Wisconsin-Milwaukee Research Foundation and a Public Health Service grant(CA152212)the National Cancer Institute to YQC,the National Science Foundation of China(31430002,31770055,31570031)+1 种基金the Fundamental Research Funds for the Central Universities(22221818014)the Major Basic Program of the Natural Science Foundation of Shandong Province(ZR2017ZB0206)。
文摘FK228 is an FDA-approved anticancer drug naturally produced by Chromobacterium violaceum No.968 up to 19 mg/L in a pilot industry-scale batch fermentation.Here we report a genomics-guided discovery of Burkholderia thailandensis MSMB43 as a new and significantly better source of FK228.The genome of B.thailandensis MSMB43 was found to contain a functional biosynthetic gene cluster highly homologous to that of FK228 in C.violaceum No.968,and the bacterium indeed produces authentic FK228.By simple fermentation in shaking flasks in a preferred M8 medium,B.thailandensis MSMB43 produced FK228 up to 67.7 mg/L;by fedbatch fermentation in a 20-L fermentor in M8 medium,B.thailandensis MSMB43 produced FK228 up to 115.9 mg/L,which is 95 fold higher than that of C.violaceum No.968 under the same laboratory fermentation conditions.RT-PCR analysis indicated that the high FK228 yield of B.thailandensis MSMB43 was due to high expression of biosynthetic genes,represented by Bth_depA,during the fermentation process.Further genetic manipulation resulted in a recombinant strain,B.thailandensis MSMB43/pBMTL3-tdpR,which harbors a broad host-range vector expressing the thailandepsin biosynthetic pathway regulatory gene tdpR.This engineered strain produced up to 168.5 mg/L of FK228 in fed-batch fermentation in a 20-L fermentor in M8 medium.Therefore,the wild-type B.thailandensis MSMB43 or its engineered derivative could potentially be a good starting point for an industrial process to improve FK228 production for its expanding use in therapy.