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Case Review: Genitourinary Imaging
792
BOOK REVIEW
Editorial Comment: Survivin is an anti-apoptotic protein that is expressed in cancer cells of several histological types, including bladder carcinoma. This expression provides the basis for targeting survivin as a urinary marker for bladder cancer detection. The authors tested 158 patients for positive urinary survivin, including 17 healthy volunteers, 30 with nonneoplastic urinary tract disease, 30 with genitourinary cancer other than bladder cancer, 46 with new onset or recurrent bladder cancer and 35 with bladder cancer that had been treated. The spectrum of patients provides an excellent initial population for assessing the potential of survivin to detect transitional cell carcinoma of the bladder. The sensitivity and specificity of tumor detection in this initial study were excellent. Included in the study were 13 patients with grade II cancer, which is traditionally difficult to detect by urinary assays, including cytology. This test holds promise but must be further evaluated in larger populations in a multiinstitutional study. Timothy L. Ratliff, Ph.D.
A Small Composite Probasin Promoter Confers High Levels of Prostate-Specific Gene Expression Through Regulation by Androgens and Glucocorticoids in Vitro and in Vivo J. ZHANG, T. Z. THOMAS, S. KASPER AND R. J. MATUSIK, Department of Urologic Surgery, Vanderbilt Prostate Cancer Center, Nashville, Tennessee Endocrinology, 141: 4698 – 4710, 2000 Transient transfection studies have shown that the probasin (PB) promoter confers androgen selectivity over other steroid hormones, and transgenic animal studies have demonstrated that the PB promoter will target androgen, but not glucocorticoid, regulation in a prostate-specific manner. Previous PB promoters either targeted low levels of transgene expression or became too large to be conveniently used. The goal was to design a PB promoter that would be small, yet target high levels of prostate-specific transgene expression. Thus, a composite probasin promoter (ARR2PB) coupled to the bacterial chloramphenicol acetyltransferase reporter (ARR2PBCAT) was generated and tested in prostatic and nonprostatic cell lines and in a transgenic mouse model. In PC-3, LNCaP, and DU145 prostate cancer cell lines, the ARR2PB promoter gave basal expression and was induced in response to androgen and glucocorticoid treatment after cotransfection with the respective steroid receptor. Basal expression of ARR2PBCAT in the nonprostatic COS-1, MCF-7, ZR-75-1, and PANC-1 cell lines was very low; however, CAT activity could be induced in response to androgens and glucocorticoids when cells were cotransfected with either the AR or GR. In contrast to the transfection studies, ARR2PBCAT transgene expression remained highly specific for prostatic epithelium in transgenic mice. CAT activity decreased after castration, and could be induced by androgens and, in addition, glucocorticoids. This demonstrates that the necessary sequences required to target prostatespecific epithelial expression are contained within the composite ARR2PB minimal promoter, and that high transgene expression can now be regulated by both androgens and glucocorticoids. The ARR2PB promoter represents a novel glucocorticoid inducible promoter that can be used for the generation of transgenic mouse models and in viral gene therapy vectors for the treatment of prostate cancer in humans. Editorial Comment: The authors report the development of a composite promoter derived from the probasin promoter, which exhibits prostate specificity. Probasin promoter constructs have been reported but when used in gene transfer, weak expression of transgene products was observed. The newly developed composite promoter, which retains prostate specificity, exhibited higher expression levels of transferred genes. This composite promoter, AAR2PB, contains 2 antigen response elements and remains responsive to glucocorticoids. The findings demonstrate exquisite prostate specificity, high level of gene expression, and show potential for the use of this promoter to generate genetically modified animals and target prostate specific tissue in gene therapy. Timothy L. Ratliff, Ph.D.
BOOK REVIEW Case Review: Genitourinary Imaging G. A. TUNG, R. J. ZAGORIA
AND
W. W. MAYO-SMITH, St. Louis: Mosby, Inc., 259 pages, 2000
This book is a case review designed to prepare radiology residents and fellows. This book would also be excellent preparation for urology residents and fellows, although there are a few gynecological cases that may not be applicable to urologists.
BOOK REVIEW
The text is divided into 3 sections based on the degree of case difficulty. There are 66, 67 and 67 cases in the easy, moderate and challenging sections, respectively. Each case includes a few detailed images and 4 pertinent questions. Of these questions some specifically relate to the imaging diagnosis in question, and others relate to anatomy, differential diagnosis, significance, and treatment and followup. The images are of excellent quality, and there is a good range of conventional urography, ultrasound, computerized tomography and magnetic resonance imaging. The case presentation and questions are followed by the answers to the questions with references as well as a comment section containing 3 to 4 paragraphs of information on the pathological condition in question. Also included in the comment section are references to recent radiological articles and observations with references. The references are correlated to Genitourinary Radiology: The Requisites, to which this review is a nice complement. I learned several interesting facts in the comment sections of this text. I highly recommend this excellent book and am sure that this text will be beneficial to radiologists and urologists. Cary Lynn Siegel, M.D. Department of Radiology Mallinckrodt Institute of Radiology Washington University Medical Center St. Louis, Missouri
793
BOOK REVIEW
Editorial Comment: Survivin is an anti-apoptotic protein that is expressed in cancer cells of several histological types, including bladder carcinoma. This expression provides the basis for targeting survivin as a urinary marker for bladder cancer detection. The authors tested 158 patients for positive urinary survivin, including 17 healthy volunteers, 30 with nonneoplastic urinary tract disease, 30 with genitourinary cancer other than bladder cancer, 46 with new onset or recurrent bladder cancer and 35 with bladder cancer that had been treated. The spectrum of patients provides an excellent initial population for assessing the potential of survivin to detect transitional cell carcinoma of the bladder. The sensitivity and specificity of tumor detection in this initial study were excellent. Included in the study were 13 patients with grade II cancer, which is traditionally difficult to detect by urinary assays, including cytology. This test holds promise but must be further evaluated in larger populations in a multiinstitutional study. Timothy L. Ratliff, Ph.D.
A Small Composite Probasin Promoter Confers High Levels of Prostate-Specific Gene Expression Through Regulation by Androgens and Glucocorticoids in Vitro and in Vivo J. ZHANG, T. Z. THOMAS, S. KASPER AND R. J. MATUSIK, Department of Urologic Surgery, Vanderbilt Prostate Cancer Center, Nashville, Tennessee Endocrinology, 141: 4698 – 4710, 2000 Transient transfection studies have shown that the probasin (PB) promoter confers androgen selectivity over other steroid hormones, and transgenic animal studies have demonstrated that the PB promoter will target androgen, but not glucocorticoid, regulation in a prostate-specific manner. Previous PB promoters either targeted low levels of transgene expression or became too large to be conveniently used. The goal was to design a PB promoter that would be small, yet target high levels of prostate-specific transgene expression. Thus, a composite probasin promoter (ARR2PB) coupled to the bacterial chloramphenicol acetyltransferase reporter (ARR2PBCAT) was generated and tested in prostatic and nonprostatic cell lines and in a transgenic mouse model. In PC-3, LNCaP, and DU145 prostate cancer cell lines, the ARR2PB promoter gave basal expression and was induced in response to androgen and glucocorticoid treatment after cotransfection with the respective steroid receptor. Basal expression of ARR2PBCAT in the nonprostatic COS-1, MCF-7, ZR-75-1, and PANC-1 cell lines was very low; however, CAT activity could be induced in response to androgens and glucocorticoids when cells were cotransfected with either the AR or GR. In contrast to the transfection studies, ARR2PBCAT transgene expression remained highly specific for prostatic epithelium in transgenic mice. CAT activity decreased after castration, and could be induced by androgens and, in addition, glucocorticoids. This demonstrates that the necessary sequences required to target prostatespecific epithelial expression are contained within the composite ARR2PB minimal promoter, and that high transgene expression can now be regulated by both androgens and glucocorticoids. The ARR2PB promoter represents a novel glucocorticoid inducible promoter that can be used for the generation of transgenic mouse models and in viral gene therapy vectors for the treatment of prostate cancer in humans. Editorial Comment: The authors report the development of a composite promoter derived from the probasin promoter, which exhibits prostate specificity. Probasin promoter constructs have been reported but when used in gene transfer, weak expression of transgene products was observed. The newly developed composite promoter, which retains prostate specificity, exhibited higher expression levels of transferred genes. This composite promoter, AAR2PB, contains 2 antigen response elements and remains responsive to glucocorticoids. The findings demonstrate exquisite prostate specificity, high level of gene expression, and show potential for the use of this promoter to generate genetically modified animals and target prostate specific tissue in gene therapy. Timothy L. Ratliff, Ph.D.
BOOK REVIEW Case Review: Genitourinary Imaging G. A. TUNG, R. J. ZAGORIA
AND
W. W. MAYO-SMITH, St. Louis: Mosby, Inc., 259 pages, 2000
This book is a case review designed to prepare radiology residents and fellows. This book would also be excellent preparation for urology residents and fellows, although there are a few gynecological cases that may not be applicable to urologists.
BOOK REVIEW
The text is divided into 3 sections based on the degree of case difficulty. There are 66, 67 and 67 cases in the easy, moderate and challenging sections, respectively. Each case includes a few detailed images and 4 pertinent questions. Of these questions some specifically relate to the imaging diagnosis in question, and others relate to anatomy, differential diagnosis, significance, and treatment and followup. The images are of excellent quality, and there is a good range of conventional urography, ultrasound, computerized tomography and magnetic resonance imaging. The case presentation and questions are followed by the answers to the questions with references as well as a comment section containing 3 to 4 paragraphs of information on the pathological condition in question. Also included in the comment section are references to recent radiological articles and observations with references. The references are correlated to Genitourinary Radiology: The Requisites, to which this review is a nice complement. I learned several interesting facts in the comment sections of this text. I highly recommend this excellent book and am sure that this text will be beneficial to radiologists and urologists. Cary Lynn Siegel, M.D. Department of Radiology Mallinckrodt Institute of Radiology Washington University Medical Center St. Louis, Missouri
793