Human primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and show similar properties to embryonic stem cells. Here we report the successful establishment of human adult germline stem cells derived from spermatogonial cells of adult human testis. Cellular and molecular characterization of these cells revealed many similarities to human embryonic stem cells, and the germline stem cells produced teratomas after transplantation into immunodeficient mice. The human adult germline stem cells differentiated into various types of somatic cells of all three germ layers when grown under conditions used to induce the differentiation of human embryonic stem cells. We conclude that the generation of human adult germline stem cells from testicular biopsies may provide simple and non-controversial access to individual cell-based therapy without the ethical and immunological problems associated with human embryonic stem cells.
Study Type – Prognosis (case series)
Level of Evidence 4
What’s known on the subject? and What does the study add?
There is increasing evidence for a prognostic significance of pretherapeutically elevated serum C‐reactive protein levels in various cancers. However, little is known about its significance in patients with invasive bladder cancer. This study shows that serum CRP is an independent predictor for cancer‐specific survival in bladder cancer, and its incorporation into a new outcome model (TNR‐C Score) encompassing major pathological determinants for survival, increases significantly its predictive accuracy.
OBJECTIVE
• To assess the predictive value of preoperative C‐reactive protein (CRP) in patients undergoing radical cystectomy (RC) for carcinoma invading the bladder in light of recent data showing it to be an independent indicator of adverse oncological outcome in other malignancies.
PATIENTS AND METHODS
• A contemporary, consecutive series of 246 patients undergoing RC and bilateral pelvic lymphadenectomy for bladder cancer between 1999 and 2009.
• Elevated CRP was defined as >0.5 mg/dL and was consistent during the study period. The median (range) follow‐up was 30 (6–116) months.
• Kaplan–Meier analysis was used to estimate cancer‐specific survival (CSS) using a log‐rank test and Cox regression analysis for multivariate analysis of risk factors.
• Based on regression estimates of significant parameters in multivariate analysis, a new CRP‐based scoring model was developed to predict cancer‐specific outcomes. The predictive accuracy of the model was evaluated using the concordance index.
RESULTS
• The 3‐year CSS was 74.0% in patients with normal and 44.0% with elevated CRP (P < 0.001).
• In multivariate analysis, CRP (P < 0.001; used as a continuous variable), tumour stage (P= 0.001), lymph‐node density ≥0.09 (P= 0.02) and resection margin status (P < 0.001) were independent predictors of CSS.
• The 3‐year CSS in patients with a score in the ranges 0–2, 3–6 and 7–10 was 80.5%, 44.9% and 7.1%, respectively (P < 0.001). Consideration of CRP in the final model increased its predictive accuracy by 4.9% with a concordance index of 0.788 (P= 0.01).
CONCLUSIONS
• This is the largest, contemporary series to date indicating that preoperative serum CRP is an independent risk factor for CSS.
• CRP may be a useful parameter to include in predictive bladder cancer nomograms.
Es wird mit Hilfe yon Gedankenexperimenten gezeigt, dal3 es entgegen verbreiteter Auffassung sehr wohl Mel~vorg~nge gibt, die keineflei Rfickwirkung auf das Mef3-objekt austiben. Diese ,,negativen" Messungen bestehen in experimenteller Featstellung des Ausbleibens von mit bestimmter Wahrscheinlichkeit zu erwartenden Ereignissen, Feststellungen, die --Kennzeichen ,,echter" lVfessungen --neue Prognosen fiber das Mel3objekt vermitteln, somit ,,Reduktion de:~ Wellenfunktion" ganz ebenso verursachen wie die normalen, ,,positiven", das Mel3Objekt st6renden Beobachtungen. Daraus folgt zwingend, dab die vielfach iibliehe ansehauliche ]3egrtindung der Unbestimmtheits-t~elation rnit angeblich prinzipiell unvermeidlicher Rfickwirkung jedes Mef3vorgangs auf das Mel3objekt unzul~ssig ist, dab sie vielmehr ihre wirklich tragende Begriindullg in der Einwirkung hat, die alle Materie der n~heren und ferneren Umgebung eines Teilchens ununterbrochen auf dieses austibt, unabhXngig davon, ob sie einer Mef3apparatul ~ angeh6rt oder nicht.
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