De Jong, S.

De Vries, E. G.E.

Richie, Jerome P.

Spierings, D. C.J.

Stel, A. J.

Te Rietstap, N.

Vellenga, E.

English

Dissertations of the University of Groningen

   University of GroningenLow p21Waf1/Cip1 Protein Level Sensitizes Testicular Germ Cell Tumor Cells to Fas-Mediated ApoptosisSpierings, D. C.J.; De Vries, E. G.E.; Stel, A. J.; Te Rietstap, N.; Vellenga, E.; De Jong, S.;Richie, Jerome P.Published in:Journal of UrologyIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2005Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Spierings, D. C. J., De Vries, E. G. E., Stel, A. J., Te Rietstap, N., Vellenga, E., De Jong, S., & Richie, J. P.(2005). Low p21Waf1/Cip1 Protein Level Sensitizes Testicular Germ Cell Tumor Cells to Fas-MediatedApoptosis. Journal of Urology, 173(4), 1171-1172. https://www.scopus.com/record/display.uri?eid=2-s2.0-15044353659&origin=inward&txGid=eb37b8c4e979e200b50407d47001206aCopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.(odds ratio (OR): 0.70, 95% confidence interval (CI): 0.46–1.1). Most of the screening tests were DREs,and it was not possible to assess the separate influence of PSA screening.Conclusions: The results of this study suggest that men who have been screened for prostate cancer havea reduced risk of dying as a result of this disease.Editorial Comment: This study, which was carried out in the pre-PSA era, demonstrates thatpatients who underwent a digital rectal examination had a 40% reduction in prostate cancermortality (OR 0.60, 95% CI 0.38 to 0.93).Patrick C. Walsh, M.D.Delayed Intraoperative Hydration Limits Blood Loss During Radical Retropubic ProstatectomyB. J. DAVIES, S. Y. CHUNG AND J. B. NELSON, Department of Urology, University of Pittsburgh School ofMedicine, Pittsburgh, PennsylvaniaUrology, 64: 712–716, 2004Objectives. To evaluate the effects of limiting hydration during prostate mobilization on intraoperativeblood loss.Methods. The patient records of 519 consecutive men undergoing radical retropubic prostatectomy bya single surgeon from January 2000 through April 2003 were reviewed. In the initial 328 cases,intravenous fluids were not limited throughout the case (constant hydration group). In the next 189cases, intravenous fluids were limited to a target of 1500 mL during prostate dissection (delayedhydration group). After the prostate was removed, hydration was brisk for an additional target of 3500mL. The patient characteristics, perioperative events, and postoperative recovery were evaluated.Results. Delayed hydration resulted in a statistically significant reduction in estimated blood losscompared with the constant hydration group, averaging 700 mL versus 965 mL, respectively. Theimmediate postoperative hematocrit values were also significantly greater in the delayed hydrationgroup (31.5%) than in the constant hydration group (30.2%). Furthermore, the delayed hydration grouphad significantly fewer cases of blood loss greater than 1500 mL and fewer patients needed intraoper-ative transfusions. No statistically significant difference was found in total intravenous fluids given andno increased morbidity occurred with delayed hydration.Conclusions. Delayed hydration appears to reduce blood loss during radical retropubic prostatectomy. Inthe hemodynamically stable patient, limiting intravenous fluids before complete dissection of the prostateis feasible without increasing morbidity.Editorial Comment: For a number of years I have instructed our anesthesiologists to limitthe amount of crystalloids administered to patients prior to removal of the prostate. Thisstudy proves the wisdom of that approach. These authors were able to reduce blood loss byalmost 30% by limiting the replacement of crystalloids to 1,500 ml prior to removal of theprostate followed by brisk rehydration. They point out in their discussion that this approachhas been successful both in liver transplantation and in the critical care setting wherehydration is limited until there is control of significant hemorrhage.Patrick C. Walsh, M.D.UROLOGICAL ONCOLOGY: TESTIS CANCER AND ADVANCES IN ONCOLOGICALTHERAPYLow p21Waf1/Cip1 Protein Level Sensitizes Testicular Germ Cell Tumor Cells to Fas-MediatedApoptosisD. C. J. SPIERINGS, E. G. E. DE VRIES, A. J. STEL, N. TE RIETSTAP, E. VELLENGA AND S. DE JONG Departments ofMedical Oncology and Hematology, University Hospital Groningen, Groningen, The NetherlandsOncogene, 23: 4862–4872, 2004In the present study, we investigated the relation between p21 expression and the sensitivity oftesticular germ cell tumor (TGCT) cells to apoptotic stimuli. Despite similar cisplatin-induced wild-typeTESTIS CANCER AND ADVANCES IN ONCOLOGICAL THERAPY 1171p53 accumulation, the TGCT cell lines Tera and Scha expressed low p21 protein and mRNA levels incomparison to A2780 ovarian cancer cells. Inhibition of the proteasome complex with MG-132 increasedp21 protein levels in TGCT cells but much more in A2780 cells, whereas cisplatin had no additionaleffect on p21 protein levels. Inhibition of caspase-3 activity in TGCT cells with the broad-spectrumcaspase inhibitor zVAD-fmk had no effect on p21 levels and also not upon cisplatin treatment. A similarinduction of p53 irradiation, in contrast to cisplatin, substantially increased both p21 mRNA andprotein expression in Tera cells. Cisplatin-treated Tera cells expressing low p21 protein levels wereFas-sensitive, while irradiation-induced p21, which was mainly localized in the cytosol, renderedirradiated Tera cells resistant to Fas-induced apoptosis. Sensitivity of irradiated Tera cells to Fas-induced apoptosis was restored by short interfering RNA-specific suppression of p21 expression. Theseresults strongly indicate that the low p21 protein levels are caused by reduced p21 gene transcriptionand sensitize cisplatin-treated TGCT cells to the Fas death pathway.Editorial Comment: The tumor suppressor protein p53 has been shown to be important inthe response of cancer cells to DNA damage. However, p53 mutations rarely occur in humantesticular germ cell tumors. Previous studies by the authors have demonstrated that sensi-tivity of testicular germ cell tumors to cisplatin is related to the presence of a functional p53as well as a Fas dependent death pathway or apoptosis. Most testicular germ cell tumors lackp21 protein expression as well, a downstream factor related to p53. Decreased p21 expressionin testicular germ cell tumors may fail to prevent rapid apoptosis that occurs with DNAdamage, and may be a partial explanation for the sensitivity of testicular germ cell tumorsto apoptotic stimuli.The authors studied the relationship of p21 expression and sensitivity of testicular germcell tumors to apoptotic stimuli. They evaluated potential mechanisms involved in thedecreased p21 protein levels. Low p21 protein expression on cisplatin exposure relates to adecreased p21 gene transcription rather than an increased caspase mediated breakdown.Testicular germ cell tumor cells treated with cisplatin and expressing low p21 protein tendto be Fas sensitive. However, in irradiated testicular germ cell tumors increased p21 proteinlevels tend to make these cells more resistant to Fas induced apoptosis. This interestingarticle may help explain why some patients who have undergone radiation therapy tend tobe locally resistant to chemotherapeutic treatments.Jerome P. Richie, M.D.UROLOGICAL ONCOLOGY: BLADDER, PENIS AND URETHRAL CANCER, ANDBASIC PRINCIPLES OF ONCOLOGYHistologic Grading of Noninvasive Papillary Urothelial Tumors. Validation of the 1998 WHO/ISUP System by Immunophenotyping and Follow-UpH. YIN AND A. S.-Y. LEONG, Division of Anatomical Pathology, Hunter Area Pathology Service, Newcastle,New South Wales, AustraliaAm J Clin Pathol, 121: 679–687, 2004Cytokeratin (CK) 20, Ki-67, and p53 were applied to 84 noninvasive papillary urothelial tumorsgraded by the 1973 World Health Organization (WHO) and 1998 WHO/International Society of Uro-logical Pathology (ISUP) systems. In the WHO/ISUP classification, all benign lesions showed normalCK20 staining and all carcinomas showed abnormal staining. The Ki-67 index was significantlydifferent between benign and malignant lesions (P .05) and between low- and high-grade carcinomas(P .001). p53 was negative in all benign lesions, with a significant difference between low- andhigh-grade carcinomas (P .001). Tumor recurrence was significantly different between low- andhigh-grade carcinomas (no recurrences among the papillary urothelial neoplasms of low malignantpotential). By the 1973 WHO classification, normal CK20 staining was present both in benign lesionsand in carcinomas. Ki-67 staining did not distinguish between grade 2 and grade 3 carcinomas (P .05),and there was no difference in p53 staining in grades 1 and 2 carcinomas (P .05). Recurrences werenot different between grades 1, 2, and 3 carcinomas. All biologic markers studied and tumor recurrencesBLADDER, PENIS AND URETHRAL CANCER, AND BASIC PRINCIPLES OF ONCOLOGY1172

Low p21Waf1/Cip1 Protein Level Sensitizes Testicular Germ Cell Tumor Cells to Fas-Mediated Apoptosis

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Low p21Waf1/Cip1 Protein Level Sensitizes Testicular Germ Cell Tumor Cells to Fas-Mediated Apoptosis

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Dissertations of the University of Groningen