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ABSTRACT: We investigated taurolidine (TRD) against various human bladder cell lines and the AY-27 rat bladder carcinoma cells. In vitro we tested the effect of TRD in ascending concentrations depending on different incubation times on cell proliferation by the XTT-test. Taurolidine had an inhibitory effect on all tested cell lines. Increasing concentrations and longer incubation times decreased the proliferation depending on the primary quantities of cells. For in vivo studies, an orthotopic rat bladder carcinoma was used. The animals were treated intravenously or intravesically and the tumors were harvested and weighted after the study. In contrast to other authors we could not find any anti-proliferative effect, we actually showed that instillation into the rat urinary bladder enhanced tumor growth.
Oncology Reports 09/2009; 22(2):409-14. · 1.84 Impact Factor
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ABSTRACT: To quantify independent pharmacokinetic parameters for differentiation of prostate pathology.
Twenty-seven patients with biopsy-proven prostate cancer (PSA: 1.4-16.1 ng/mL) underwent magnetic resonance imaging with a new dynamic contrast-enhanced, inversion-prepared dual-contrast gradient echo sequence (T1/T2*-weighted, 1.65 seconds temporal resolution) using a combined endorectal/body phased-array coil at 1.5 Tesla. Perfusion, blood volume, mean transit time, delay, and dispersion were calculated using a sequential 3-compartment model. Twenty-three patients underwent prostatectomy. For histologic correlation a pathologist mapped areas of normal prostate tissue, chronic prostatitis, and prostate cancer (total of 63 areas) on histologic sections corresponding to the magnetic resonance imaging planes.
Compared with normal prostate tissue, low-grade cancer (Gleason score <or=6) only showed higher perfusion (1.01 mL/cm/min vs. 0.26 mL/cm/min, P = 0.050), whereas high-grade cancer showed higher perfusion (1.21 mL/cm/min vs. 0.26 mL/cm/min, P <or= 0.001), higher blood volume (1.44% vs. 0.95%, P = 0.005), shorter mean transit time (3.55 seconds vs. 4.40 seconds, P = 0.019), shorter delay (10.15 seconds vs. 13.36 seconds, P = 0.015), and smaller dispersion (8.56 seconds vs. 12.11 seconds, P = 0.020). High-grade cancer showed higher perfusion than chronic prostatitis (1.21 mL/cm/min vs. 0.90 mL/cm/min, P = 0.041). Chronic prostatitis showed higher perfusion (0.90 mL/cm/min vs. 0.26 mL/cm/min, P = 0.006), higher blood volume (1.53% vs. 0.95%, P = 0.046), shorter delay (11.42 seconds vs. 13.36 seconds, P = 0.015), and smaller dispersion (10.49 seconds vs. 12.11 seconds, P = 0.020) than normal prostate tissue. There were no statistically significant differences between low-grade and high-grade cancer or between low-grade cancer and chronic prostatitis.
The pharmacokinetic parameters investigated, especially perfusion, allow statistically significant in situ differentiation of normal prostate tissue from cancer and chronic prostatitis and of high-grade cancer from chronic prostatitis.
Investigative radiology 07/2008; 43(7):481-7. · 4.85 Impact Factor
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Siam Oottamasathien,
Karin Williams,
Omar E Franco,
John C Thomas,
Katrina Saba,
Neil A Bhowmick, Andrea Staack,
Romano T Demarco,
John W Brock,
Simon W Hayward,
John C Pope
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ABSTRACT: Tissue recombination is a powerful method to evaluate the paracrine-signaling events that orchestrate the development of organs using the in vivo environment of a host rodent. Studies have reported the successful generation of primary cultures of rodent bladder urothelium, but none have reported their use to recapitulate bladder tissue with tissue recombination. We propose that primary cultured bladder urothelium, when recombined with inductive embryonic bladder mesenchyme, will form bladder tissue in a recombination model. Adult rat bladders were isolated and urothelium obtained. Sheets of bladder urothelium were re-suspended in collagen and maintained in tissue culture. After expansion (>20 passages), the urothelium was recombined with embryonic day-14 mouse bladder mesenchyme, then grafted beneath the renal capsule of immunocompromised mouse hosts. Grafts were harvested after 28 days. Control grafts were performed with bladder mesenchyme alone, cultured bladder urothelium alone, and collagen matrix alone. Final tissues were evaluated with staining and immunohistochemistry (H&E, Gomori's trichrome, broad-spectrum uroplakin, and smooth muscle actin alpha and gamma). Immunocytochemistry on cultured urothelium for broad-spectrum keratin, vimentin, and broad-spectrum uroplakin confirmed pure populations, void of mesenchymal contaminants. Staining of recombinant grafts demonstrated bladder tissue with mature urothelium and stromal differentiation. Control tissues were void of bladder tissue formation. We have successfully demonstrated that a chimeric bladder is formed from primary cultured bladder urothelium recombined with embryonic bladder mesenchyme. This is a powerful new tool for investigating the molecular mechanisms of bladder development and disease. Future applications may include the in vitro genetic manipulation of urothelium and examining those effects on growth and development in an in vivo environment.
Developmental Dynamics 11/2006; 235(10):2795-801. · 2.54 Impact Factor
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ABSTRACT: We assessed the diagnostic accuracy of bone markers in the serum of patients with renal cell carcinoma to detect bone metastases and evaluate the prognostic potential concerning renal cell carcinoma caused mortality.
The bone formation markers total and bone specific alkaline phosphatase, the bone resorption markers cross-linked N-terminal and tartrate-resistant acid phosphatase isoenzyme 5b, and the osteoclastogenesis markers osteoprotegerin and ligand of the receptor activator of nuclear factor-kappaB, were measured in the serum of 72 patients with renal cell carcinoma, including 28 with pN0M0, 8 with pN1M0 and 36 with M1, and in 32 female and 36 male controls by enzyme-linked immunosorbent assay techniques. Data were evaluated by receiver operating characteristics and survival analysis.
Bone specific alkaline phosphatase, tartrate-resistant acid phosphatase isoenzyme 5b and ligand of the receptor activator of nuclear factor-kappaB did not significantly differ between patients with renal cell carcinoma and controls. Compared with controls tartrate-resistant acid phosphatase isoenzyme 5b, cross-linked N-terminal and osteoprotegerin showed increased concentrations in patients with nonbone metastases but not in those with bone metastases. No bone turnover marker led to differentiation between patients with nonbone and bone metastases. Increased osteoprotegerin above the upper 95% cutoff limit, tumor stage and distant metastatic spread were associated with renal cell carcinoma related survival on Kaplan-Meier analyses. A multivariate Cox proportional hazards regression model revealed that these 3 variables were independent prognostic factors for cancer related death.
Bone turnover markers are hardly useful to diagnose bone metastases in patients with renal cell carcinoma. However, osteoprotegerin together with clinicopathological characteristics may be helpful as prognosticator of cancer specific death.
The Journal of Urology 11/2006; 176(4 Pt 1):1326-31. · 3.75 Impact Factor
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Siam Oottamasathien,
Karin Williams,
Omar E. Franco,
John C. Thomas,
Katrina Saba,
Neil A. Bhowmick, Andrea Staack,
Romano T. Demarco,
John W. Brock III,
Simon W. Hayward,
John C. Pope IV
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ABSTRACT: Tissue recombination is a powerful method to evaluate the paracrine-signaling events that orchestrate the development of organs using the in vivo environment of a host rodent. Studies have reported the successful generation of primary cultures of rodent bladder urothelium, but none have reported their use to recapitulate bladder tissue with tissue recombination. We propose that primary cultured bladder urothelium, when recombined with inductive embryonic bladder mesenchyme, will form bladder tissue in a recombination model. Adult rat bladders were isolated and urothelium obtained. Sheets of bladder urothelium were re-suspended in collagen and maintained in tissue culture. After expansion (>20 passages), the urothelium was recombined with embryonic day-14 mouse bladder mesenchyme, then grafted beneath the renal capsule of immunocompromised mouse hosts. Grafts were harvested after 28 days. Control grafts were performed with bladder mesenchyme alone, cultured bladder urothelium alone, and collagen matrix alone. Final tissues were evaluated with staining and immunohistochemistry (H&E, Gomori's trichrome, broad-spectrum uroplakin, and smooth muscle actin α and γ). Immunocytochemistry on cultured urothelium for broad-spectrum keratin, vimentin, and broad-spectrum uroplakin confirmed pure populations, void of mesenchymal contaminants. Staining of recombinant grafts demonstrated bladder tissue with mature urothelium and stromal differentiation. Control tissues were void of bladder tissue formation. We have successfully demonstrated that a chimeric bladder is formed from primary cultured bladder urothelium recombined with embryonic bladder mesenchyme. This is a powerful new tool for investigating the molecular mechanisms of bladder development and disease. Future applications may include the in vitro genetic manipulation of urothelium and examining those effects on growth and development in an in vivo environment. Developmental Dynamics 235:2795–2801, 2006. © 2006 Wiley-Liss, Inc.
Developmental Dynamics 09/2006; 235(10):2795 - 2801. · 2.54 Impact Factor
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ABSTRACT: Leukoplakia has been found to be precancerous in organs covered with squamous epithelium. The present study was conducted to determine whether leukoplakia described in the female bladder is also a premalignant lesion.
Between 1973 and 1996, 77 female patients were diagnosed with vesical leukoplakia by cystoscopy and cytology and were followed-up until 2004 (mean follow-up time: 8.3 years). A survey was conducted to analyze exposure to cocarcinogens. Additionally, DNA was isolated from 36 urine sediments and analyzed for TP53 mutations. The results were compared to the mutation frequency of TP53 in urine sediments from patients diagnosed with transitional cell carcinoma (TCC) of the bladder and healthy controls.
The whitish lesion was mostly located at the trigone and varied in size and location during the follow-up years. TP53 mutations were detected in 6 out of 36 urine samples in exons 5, 6 and 7 (mutation frequency: 16.7%). Among control patients with no leukoplakia or TCC of the bladder (n = 70), the spontaneous mutation frequency was similar (14.3%). In contrast, the mutation frequency in patients with TCC of the bladder (n = 148) revealed 39.9% in exons 5, 6, 7 and 8. The present study did not show any statistically significant correlations between chronic inflammations, TP53 mutations, exposure to carcinogens and vesical leukoplakia.
Our data suggest that vesical leukoplakia does not necessarily hold neoplastic potential and needs to be clearly distinguished from leukoplakia in other localizations. Therefore, we suggest that a biopsy can be omitted, if follow-up controls by cystoscopy are performed regularly.
International Journal of Urology 09/2006; 13(8):1092-7. · 1.75 Impact Factor
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ABSTRACT: Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play a major role in the maintenance of extracellular matrix homeostasis. Alterations of MMP and TIMP expressions have been found in several malignant tumour entities. In this study the expression pattern of MMP1, MMP2, MMP3, MMP9, and their inhibitors TIMP1, and TIMP2 were investigated at mRNA and protein levels in human renal cell carcinoma (RCC). Formalin fixed paraffin embedded tumour samples of 10 patients and adjacent non-malignant controls were analysed by radioactive labelled riboprobe in situ hybridisation (isH) and immunohistochemistry. The slides were evaluated semiquantitatively. MMP1-antigen was strongly expressed in tumour epithelium with moderate stroma expression in one case. The gelatinases MMP2 and MMP9 showed moderate to strong signals in tumour epithelial cells at the mRNA and protein level, while the expression in tumour stroma was moderate. MMP3-mRNA and -antigen were expressed moderately to strong in tumour epithelium and focally in stroma cells. mRNA or TIMP1- and TIMP2-mRNA and -antigen were also predominantly expressed in tumour epithelium; only few samples showed positive expression in stroma cells. mRNA expression could be generally correlated to the protein expression in our study group, except for MMP1 (mRNA expression was only expressed in two cases). We found a pronounced expression for the gelatinases MMP2 and MMP9 and for MMP3 in RCC at the mRNA and protein level. The expression of TIMP1 and TIMP2 appears also to be relevant in RCC. Due to the small sample size further investigations need to be done to prove a statistical significant correlation between the MMP/TIMP expression and clinicopathological parameters.
Oncology Reports 06/2006; 15(5):1379-84. · 1.84 Impact Factor
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ABSTRACT: Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play a major role in the maintenance of extracellular matrix homeostasis and are involved in the process of tumour invasion and metastasis in several malignant tumour entities. The goal of this study is to evaluate the diagnostic value of various circulating MMPs and TIMPs in blood plasma for a non-invasive detection of transitional cell carcinoma of the bladder (TCC).
In this study the concentrations of MMP1, MMP2, MMP3, MMP9, their inhibitors TIMP1, TIMP2, and the MMP1/TIMP1-complex (MTC1) were quantified in blood plasma with the sandwich enzyme-linked immunosorbent assay (ELISA). Blood plasma samples were investigated from 68 patients (non-metastasized, n = 57 and metastasized, n = 11) with TCC of the bladder and from 79 healthy controls. The mROC program was used to calculate the best two- and three- marker combinations. The diagnostic values for all single markers and the marker combinations were estimated both by the overall diagnostic performance index area under the ROC curve (AUC) and the sensitivity and specificity at cutoff limits with the highest diagnostic accuracy and at the 90% and 95% limits of sensitivity and specificity, respectively.
The median MMP2 concentration was elevated in blood plasma in all patient groups with TCC in comparison to the controls (p < 0.001). The concentrations of TIMP1, TIMP2, and MTC1 in plasma probes were significantly lower from patients with non-metastasized TCC compared to the controls. MMP2 tested alone reached the highest sensitivity and specificity at 75%, respectively. The sensitivity and specificity increased when tested in combination with MMP9 and TIMP1 (97%, 94%, respectively). The combination of MMP9 and TIMP1 also showed an improved sensitivity (80%) and specificity (99%) than tested alone.
MMP2 is a statistically significant marker in blood plasma for bladder cancer detection with an increased diagnostic value in combination with MMP9 and TIMP1. This study showed that the highest sensitivities and specificities are not obtained by testing each marker alone. As shown by the best two-marker combination, which includes MMP9 and TIMP1, the optimized combination does not always include the best single markers.
BMC Urology 01/2006; 6:19. · 1.45 Impact Factor
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Venugopal Bhuvarahamurthy,
Joerg Schroeder,
Glen Kristiansen,
Jan Roigas,
Carsten Denkert,
Manfred Johannsen,
Michael Lein,
Stefan A Loening,
Dietmar Schnorr,
Klaus Jung, Andrea Staack
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ABSTRACT: The urokinase-type plasminogen activator (uPA) system plays a central role in extracellular matrix degradation, cell migration, and invasion. uPA belongs to the family of serine proteases. It has been shown that its proteolytic activity is involved in the metastatic process by activation and binding to its receptor (uPAR). Previous studies in several organ systems have elucidated a higher uPA expression in malignant tissue in comparison to normal tissue. In this study uPA and uPAR gene expression were investigated in 18 human renal cell carcinoma (RCC) specimens in comparison with adjacent non-malignant renal tissues. mRNA in situ hybridisation and immunohistochemical staining were performed. mRNA of uPA and uPAR was significantly higher expressed in 56% (10/18) and 72% (13/18) of the RCC specimens in comparison to the adjacent non-malignant renal tissue (p<0.0001), respectively. uPA-mRNA and uPAR-mRNA were expressed predominantly in malignant renal cells and in very few surrounding stromal cells. The elevated expression of uPAR-protein in RCC reached statistical significance compared to adjacent normal tissue (p=0.007). uPAR genes were higher expressed in comparison to uPA alone. There was a statistical trend that higher expression of uPA and uPAR corresponded with TNM tumour stage and grade in RCC. Further investigations need to be done with larger sample sizes to prove a correlation of expression between uPA and uPAR to a more aggressive phenotype. We conclude that uPA- and uPAR are overexpressed in RCC and could function as tumour markers.
Oncology Reports 10/2005; 14(3):777-82. · 1.84 Impact Factor
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Claudia Abramjuk,
Klaus Jung,
Hans-Willi Krell,
Rolf Juchem,
Robert Peters,
Kasra Taymoorian, Andrea Staack,
Carsten Stephan,
Joerg Schnorr,
Stefan A Loening,
Michael Lein
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ABSTRACT: Therapeutic efficacy of the novel matrix metalloproteinase (MMP) inhibitor, Ro 28-2653 (5-biphenyl-4-yl-5-[4-(-nitro-phenyl)-piperazin-1-yl]-pyrimidine-2,4,6-trione), has been shown in various models of different tumor entities. The tumor growth-reducing effect has been demonstrated in the orthotopic rat prostate Dunning model (subline MatLyLu). Based on these results we investigated Ro 28-2653 in combination with estramustine on the G subline of the Dunning tumor. This subline is characterized by a low metastatic ability and androgen sensitivity. Efficacy was determined by recording tumor growth in vivo by magnetic resonance imaging (MRI). Tumor cells were injected into the prostates of 81 Copenhagen rats. MRI was performed at day 100 and at day 126 after tumor cell injection. The duration of therapy was 17 days with daily oral application of Ro 28-2653 (100 mg/kg) and four i.p. injections of estramustine (7.5 mg/kg). Histological evaluations were conducted to provide further information about the effects on tumor morphology. Orthotopic tumor induction was successful in 100% of the animals. Tumor volume calculations with MRI showed a significant difference between the control groups, the animals treated with Ro 28-2653, and the animals treated with the combination of Ro 28-2653 and estramustine. The new MMP inhibitor Ro 28-2653 reduces tumor growth and provides a compatible therapeutic alternative for patients with prostate cancer.
Anti-Cancer Drugs 10/2005; 16(8):855-61. · 2.41 Impact Factor
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ABSTRACT: We investigated the efficacy and toxicity of a first-line combination chemotherapy using weekly paclitaxel and carboplatin in patients with metastatic transitional cell cancer (TCC).
Thirty-three patients with advanced measurable TCC of the urothelium were entered onto this trial. Patients were treated once weekly with a combination therapy of paclitaxel (100mg/m(2)) and carboplatin (AUC 2, according to the Calvert formula). Therapy courses were administered for six consecutive weeks. After two cycles, a re-staging was carried out to evaluate response.
Objective response rate was 57.6% with 6 complete (18.2%) and 13 partial remissions (39.4%). Seven patients had stable disease (21.2%) and 7 patients had progressed at the first evaluation of response (21.2%). Median progression-free interval and median survival was 6.5 (1-35) and 12 (2.5-58) months, respectively. Toxicity was moderate and manageable with grade 3 and 4 neutropenia in 8 patients (24%), but no case of neutropenic fever. Other hematological grade 3 toxicities occurred in 9 patients (27%) and grade 3 peripheral neuropathy in 2 patients (6%). There was no treatment-related death. Dose reduction or short delay of treatment was necessary in 3 patients.
Combination therapy using weekly paclitaxel and carboplatin was active in patients with advanced TCC and adverse prognostic features. The weekly dosing used in this trial warrants further investigation as an alternative first-line approach in patients with poor renal reserve and/or performance status or as a second-line management of advanced TCC.
European Urology 09/2005; 48(2):246-51. · 8.49 Impact Factor
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ABSTRACT: Urinary bladder malfunction and disorders are caused by congenital diseases, trauma, inflammation, radiation, and nerve injuries. Loss of normal bladder function results in urinary tract infection, incontinence, renal failure, and end-stage renal dysfunction. In severe cases, bladder augmentation is required using segments of the gastrointestinal tract. However, use of gastrointestinal mucosa can result in complications such as electrolyte imbalance, stone formation, urinary tract infection, mucous production, and malignancy. Recent tissue engineering techniques use acellular grafts, cultured cells combined with biodegradable scaffolds, and cell sheets. These techniques are not all currently applicable for human bladder reconstruction. However, new avenues for bladder reconstruction maybe facilitated by a better understanding of urogenital development, the cellular and molecular biology of urothelium, and cell-cell interactions, which modulate tissue repair, homeostasis, and disease progression.
Differentiation 05/2005; 73(4):121-33. · 2.81 Impact Factor
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ABSTRACT: The urokinase-type plasminogen activator (uPA) system plays a central role in the blood clot dissolution and tissue plasticity. uPA is a serine protease that is also involved in the metastatic process upon activation and binding to its receptor (uPAR). Studies have shown that levels of uPA in malignant tumors are higher than in the corresponding normal tissue or in benign tumors of the same tissue. We investigated uPA and uPAR gene expression in 20 human transitional cell carcinomas (TCC) of the bladder (n=19) and the renal pelvis (n=1) in comparison with adjacent non-malignant tissues. We performed mRNA in situ hybridization (isH) and immunohistochemical staining. uPA-mRNA and uPAR-mRNA were present in 95% (19/20) and 85% (17/20) of the TCC samples, respectively and significantly higher expressed than in the adjacent normal tissue. uPA-mRNA was expressed only in malignant urothelial cells, whereas uPAR-mRNA was localized in malignant urothelial cells as well as in surrounding stromal cells. There was a statistically significant lower expression of uPA/uPAR-protein in adjacent normal tissue. Strong uPAR-protein signal intensity was related to a marked protein expression as semi-quantitatively determined by immunohistochemistry. For uPA-protein this observation was less frequent. There was a statistical trend that higher expression of uPA and uPAR corresponded with tumor stage and grade of TCC. Statistical significance was reached for uPAR-antigen compared to tumor stage (p=0.025). We conclude that higher expression of uPA and uPAR could indicate a more aggressive phenotype of TCC.
Oncology Reports 11/2004; 12(4):909-13. · 1.84 Impact Factor
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ABSTRACT: It has been shown that the expression of the lysosomal proteolytic enzymes cathepsin B, H, and L (CB, CH, and CL, respectively) correlate with tumor progression in various neoplasms. However, no data are available in cell lysates and supernatants of differently differentiated human bladder cell lines or in noncancerous and cancerous bladder tissue.
Using spectrofluorometric assays, catalytic activities of CB, CH, CL, and their inhibitor (CIP) were measured both in differently differentiated human bladder cell lines (HCV29, normal; RT4, well differentiated; J82, poorly differentiated) and in noncancerous and cancerous tissue samples (n = 20) of transitional cell carcinoma obtained from transurethral resections of the bladder or cystectomies. Enzyme activities were related to the protein content in tissue samples or to the cell count in cell lines.
In comparison to the intracellular activities of CB, CH, and CL in the poorly differentiated cell line J82, the intracellular activities in the normal cell line HCV29 were significantly greater (P <0.05), independent of stage or grade. In contrast, the portion of cathepsins released from cell line J82 into the supernatant revealed higher values than that from cell line HCV29. In cancerous bladder tissue, CB and CH were significantly greater than in the matched normal tissue (P <0.05). CL and CIP did not show any statistically significant differences.
Increased cathepsin concentrations in the supernatant of the poorly differentiated J82 carcinoma cell culture, as well as in cancerous bladder tissue, are indicative of a proteolytic imbalance and potential indicators of bladder cancer.
Urology 06/2004; 63(6):1089-94. · 2.43 Impact Factor
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ABSTRACT: A detailed knowledge of the developmental anatomy of the embryonic mouse urogenital tract is required to recognize mutant urogenital phenotypes in transgenic and knock-out mice. Accordingly, the purpose of this article is to review urogenital development in the mouse embryo and to give an illustrated methodological protocol for the dissection of urogenital organ rudiments at 12-13 days of gestation (E12-13) to isolate the urogenital ridge and at E16 to isolate the seminal vesicle, Müllerian duct, Wolffian duct, and prostatic rudiment, the urogenital sinus (UGS). The UGS can be cultured and, in the presence of testosterone, prostatic buds form in vitro. Because of the importance of mesenchymal-epithelial interactions in urogenital development, methods for the isolation of epithelium and mesenchyme from the embryonic urogenital sinus are also described. Urogenital sinus mesenchyme (UGM) and urogenital sinus epithelium (UGE) can be used to construct tissue recombinants that can either be grown in vitro or grafted in vivo for the study of epithelial-mesenchymal interactions in prostatic development.
Differentiation 10/2003; 71(7):402-13. · 2.81 Impact Factor
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ABSTRACT: Androgen deprivation induces apoptosis in the prostate. Representative data, quantitating apoptotic activity in human prostatic epithelium following androgen ablation, are lacking.
Human prostatic tissue was grafted beneath the renal capsule of intact male athymic mice and allowed to become established. The mice were castrated and specimens were harvested on post-castration day 0, 1, 2, 3, 4, 5, 7, 8, 9, 10, 14, 17, 18, and 21. Tissue was immediately fixed and apoptotic epithelial nuclei were identified.
The percentage of terminal deoxynucleotidyl-transferase-mediated dUTP nick end-labeling (TUNEL) positive epithelial cells increased from a baseline of 0.026%, peaked on post-castration day 3 (1.54%), and returned to baseline by day 21. Mathematical analysis predicted that the observed apoptotic activity account for the loss of 87% of prostatic epithelial cells in 3 weeks.
Post-castration apoptosis in human prostatic epithelium was low but was sufficient to account for the loss of nearly 90% of epithelial cells.
The Prostate 03/2003; 54(3):212-9. · 3.48 Impact Factor
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ABSTRACT: Cathepsin B, H, and L (CB, CH, CL) are lysosomal proteolytic enzymes that belong to the group of cysteine proteinases. The imbalance between proteinases and their inhibitors is believed to correlate with tumor progression and shortened patient survival. In transitional cell carcinoma (TCC) only limited data have been published.
Using spectrofluorometric assays, catalytic activities of CB, CH, and CL in urine were measured to evaluate the potential diagnostic and prognostic value for patients with TCC of the bladder. Second morning urine was collected and used for measurements. CB, CH, and CL activities were determined for groups of patients with superficial disease (Ta-1, n = 43) and muscle-invasive tumors (T2, n = 18; or greater than T2, n = 9), as well as for different tumor grades (G1, n = 12; G2, n = 26; and G3, n = 31). For comparison, 14 urine samples from patients with bladder inflammation and 43 samples from a control group were also included.
Compared with the control group, patients with superficial Stage Ta-T1 disease and muscle-invasive Stage T2 or greater disease, as well as patients with G3 tumors, revealed significantly higher urinary CL activity. CB and CH did not show any tumor-related activity increase. CB was significantly lower in patients with nonrecurrent tumors.
These results suggest that elevated levels of CL in urine might be indicative of a cellular proteolytic imbalance in TCC of the bladder and may have a prognostic and/or diagnostic value.
Urology 03/2002; 59(2):308-12. · 2.43 Impact Factor
