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- Stephenson, Andrew J, et al.
(författare)
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Defining biochemical recurrence of prostate cancer after radical prostatectomy: a proposal for a standardized definition
- 2006
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 24:24, s. 3973-3978
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Prostate-specific antigen (PSA) defined biochemical recurrence (BCR) of prostate cancer is widely used for reporting the outcome of radical prostatectomy (RP). A standardized BCR definition is lacking, and overall progression-free probability and risk of subsequent metastatic disease progression may vary greatly depending on the PSA criterion used. Ten definitions of BCR were evaluated to identify the one that best explains metastatic progression. METHODS: Of 3,125 patients who underwent RP at our institution since 1985, 75 developed distant metastasis during a median follow-up of 49 months. To predict metastasis progression, we modeled the clinical information using multivariable Cox regression analysis. BCR was included in the model as a time-dependent covariate, and separate models were developed for each definition. A goodness-of-fit (R2) statistic was used to determine the Cox model (and thereby the BCR definition) that best explained metastatic progression. RESULTS: The 10-year progression-free probability ranged from 63% to 79%, depending on the BCR definition. The model containing BCR defined as a PSA of at least 0.4 ng/mL followed by another increase best explained metastatic progression (R2 = 0.21). This definition was also associated with a high probability of subsequent secondary therapy, continued PSA progression, and rapid PSA doubling time. CONCLUSION: BCR defined as a PSA value of at least 0.4 ng/mL followed by another increase best explains the development of distant metastasis among 10 candidate definitions, after controlling for clinical variables and the use of secondary therapy. On the basis of this evidence, we propose that this definition be adopted as the standard for reporting the outcome of RP.
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| 2. |
- Chung, J S, et al.
(författare)
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Identification and developmental expression of mRNAs encoding crustacean cardioactive peptide (CCAP) in decapod crustaceans.
- 2006
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Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 0022-0949 .- 1477-9145. ; 209:Pt 19, s. 3862-72
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Tidskriftsartikel (refereegranskat)abstract
- Full-length cDNAs encoding crustacean cardioactive peptide (CCAP) were isolated from several decapod (brachyuran and astacuran) crustaceans: the blue crab Callinectes sapidus, green shore crab Carcinus maenas, European lobster Homarus gamarus and calico crayfish Orconectes immunis. The cDNAs encode open reading frames of 143 (brachyurans) and 139-140 (astacurans) amino acids. Apart from the predicted signal peptides (30-32 amino acids), the conceptually translated precursor codes for a single copy of CCAP and four other peptides that are extremely similar in terms of amino acid sequence within these species, but which clearly show divergence into brachyuran and astacuran groups. Expression patterns of CCAP mRNA and peptide were determined during embryonic development in Carcinus using quantitative RT-PCR and immunohistochemistry with whole-mount confocal microscopy, and showed that significant mRNA expression (at 50% embryonic development) preceded detectable levels of CCAP in the developing central nervous system (CNS; at 70% development). Subsequent CCAP gene expression dramatically increased during the late stages of embryogenesis (80-100%), coincident with developing immunopositive structures. In adult crabs, CCAP gene expression was detected exclusively in the eyestalk, brain and in particular the thoracic ganglia, in accord with the predominance of CCAP-containing cells in this tissue. Measurement of expression patterns of CCAP mRNA in Carcinus and Callinectes thoracic ganglia throughout the moult cycle revealed only modest changes, indicating that previously observed increases in CCAP peptide levels during premoult were not transcriptionally coupled. Severe hypoxic conditions resulted in rapid downregulation of CCAP transcription in the eyestalk, but not the thoracic ganglia in Callinectes, and thermal challenge did not change CCAP mRNA levels. These results offer the first tantalising glimpses of involvement of CCAP in environmental adaptation to extreme, yet biologically relevant stressors, and perhaps suggest that the CCAP-containing neurones in the eyestalk might be involved in adaptation to environmental stressors.
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