High Expression of Human Uroplakin Ia in Urinary Bladder Transitional Cell Carcinoma

Kageyama, Susumu; Tokura, Y.; Isono, Takahiro; Tanaka, Tsutomu; Kim, Choi Jang; Yuasa, Takeshi; Okada, Yusaku

doi:10.1111/j.1349-7006.2002.tb01287.x

Cited by 24 publications

(16 citation statements)

References 19 publications

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“…We could detect cancer cells in the peripheral blood of urothelial cancer patients by nested reverse transcription-PCR and suggested molecular staging for micrometastasis (22)(23)(24). We also produced anti-human uroplakin Ia antibody and showed its usefulness as a specific histologic marker because of its stable expression even in metastatic lesions (25 ). However, in spite of much effort we could not establish a diagnostic method using uroplakins in sera or urine from patients.…”

Section: Discussionmentioning

confidence: 99%

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Identification by Proteomic Analysis of Calreticulin as a Marker for Bladder Cancer and Evaluation of the Diagnostic Accuracy of Its Detection in Urine

Kageyama¹,

Isono²,

Iwaki³

et al. 2004

Clinical Chemistry

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128

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Background: New methods for detection of bladder cancer are needed because cystoscopy is both invasive and expensive and urine cytology has low sensitivity. We screened proteins as tumor markers for bladder cancer by proteomic analysis of cancerous and healthy tissues and investigated the diagnostic accuracy of one such marker in urine. Methods: Three specimens of bladder cancer and healthy urothelium, respectively, were used for proteome differential display using narrow-pH-range twodimensional electrophoresis. To evaluate the presence of calreticulin (CRT) as detected by Western blotting, we obtained 22 cancerous and 10 noncancerous surgical specimens from transurethral resection or radical cystectomy. To evaluate urinary CRT, we collected 70 and 181 urine samples from patients with and without bladder cancer, respectively. Anti-CRT COOH-terminus antibody was used to detect CRT in tissue and urine. Results: Proteomic analysis revealed increased CRT (55 kDa; pI 4.3) in cancer tissue. Quantitative Western blot analysis showed that CRT was increased in cancer tissue (P ‫؍‬ 0.0003). Urinary CRT had a sensitivity of 73% (95% confidence interval, 62-83%) at a specificity of 86% (80 -91%) for bladder cancer in the samples tested. Conclusions: Proteomic analysis is useful in searching for candidate proteins as biomarkers and led to the

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Section: Discussionmentioning

confidence: 99%

“…Previously we investigated the urothelium-specific proteins, uroplakins, and their clinical application (22)(23)(24)(25). We could detect cancer cells in the peripheral blood of urothelial cancer patients by nested reverse transcription-PCR and suggested molecular staging for micrometastasis (22)(23)(24).…”

Section: Discussionmentioning

confidence: 99%

Identification by Proteomic Analysis of Calreticulin as a Marker for Bladder Cancer and Evaluation of the Diagnostic Accuracy of Its Detection in Urine

Kageyama¹,

Isono²,

Iwaki³

et al. 2004

Clinical Chemistry

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128

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“…Immunohistochemical staining was performed by the conventional avidin-biotin-peroxidase complex method (VECTASTAIN Elite ABC kit; Vector Laboratories Inc.), as described previously (26). Anti-human PLK-1 mAb (Transduction Laboratories) with a 1:100 dilution was used as the primary antibody.…”

Section: Methodsmentioning

confidence: 99%

“…Informed consent was provided according to the World Medical Association Declaration of Helsinki. Clinical and pathological data were obtained by retrospective chart review, as previously described (26).…”

Section: Methodsmentioning

confidence: 99%

Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer

Nogawa¹,

Yuasa²,

Kimura³

et al. 2005

J. Clin. Invest.

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The mainstay in the management of invasive bladder cancer continues to be radical cystectomy. With regard to improvement of quality of life, however, therapies that preserve the bladder are desirable. We investigated the use of intravesical PLK-1 small interfering RNA (siRNA) against bladder cancer. Patients with bladder cancers expressing high levels of PLK-1 have a poor prognosis compared with patients with low expression. Using siRNA/cationic liposomes, the expression of endogenous PLK-1 could be suppressed in bladder cancer cells in a time-and dose-dependent manner. As a consequence, PLK-1 functions were disrupted. Inhibition of bipolar spindle formation, accumulation of cyclin B1, reduced cell proliferation, and induction of apoptosis were observed. In order to determine the efficacy of the siRNA/liposomes in vivo, we established an orthotopic mouse model using a LUC-labeled bladder cancer cell line, UM-UC-3 LUC . PLK-1 siRNA was successfully transfected into the cells, reduced PLK-1 expression, and prevented the growth of bladder cancer in this mouse model. This is the first demonstration, to our knowledge, of inhibition of cancer growth in the murine bladder by intravesical siRNA/cationic liposomes. We believe intravesical siRNA instillation against bladder cancer will be useful as a therapeutic tool.

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“…8,9 Also, we have demonstrated that UPII and UPIII are cross-linked to UPIa and UPIb, respectively, suggesting the existence of 2 types of heterodimers, consisting of UPIa/UPII and UPIb/UPIII. 10,11 As UPs have been shown to be markers of urothelial differentiation by several independent investigators, [12][13][14][15][16] their level of expression might be low in poorly differentiated tumors. Nevertheless, we have shown previously that UPs are decreased at the protein level in such tumors; however, evidence indicates that even very poorly differentiated urothelial cells continue to express UPs at the mRNA level.…”

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confidence: 99%

Detection of circulating cancer cells expressing uroplakins and epidermal growth factor receptor in bladder cancer patients

Osman

Kang

Lee

et al. 2004

Intl Journal of Cancer

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Our purpose was to determine the clinical relevance of the detection of circulating tumor cells (CTCs) expressing urothelial and epithelial markers in bladder cancer patients. Sixty-two patients who presented to Memorial Sloan-Kettering Cancer Center between July 2000 and September 2001 were studied. Peripheral blood was tested by nested RT-PCR assay for uroplakins (UPs) Ia, Ib, II and III as well as for epidermal growth factor receptor (EGFR). We determined the sensitivity and specificity of each individual marker and the combinations of UPIa/UPII and UPIb/UPIII. The latter strategy was based on our data, which showed that UPIa and UPIb form heterodimers with UPII and UPIII, respectively. Forty patients had clinically advanced bladder cancer and 22 had no evidence of disease at the time of assay. Eight of the 22 patients recurred during the follow-up period. All 8 patients were positive at presentation for UPIa/UPII. The combination of UPIa/UPII provided the best sensitivity (75%) of detecting CTCs, with a specificity of 50%. The combination of UPIb/UPIII was the most specific (79%) but had modest sensitivity (31%). Detection of EGFR-positive cells alone and in combination with UPs was inferior to that for UPIa/UPII. Combinations of urothelial markers are superior to single urothelial or epithelial markers in detecting CTCs in bladder cancer patients. Further efforts are under way to confirm the potential predictive value of these markers in a prospectively designed study of a larger cohort of patients.

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High Expression of Human Uroplakin Ia in Urinary Bladder Transitional Cell Carcinoma

Cited by 24 publications

References 19 publications

Identification by Proteomic Analysis of Calreticulin as a Marker for Bladder Cancer and Evaluation of the Diagnostic Accuracy of Its Detection in Urine

Identification by Proteomic Analysis of Calreticulin as a Marker for Bladder Cancer and Evaluation of the Diagnostic Accuracy of Its Detection in Urine

Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer

Detection of circulating cancer cells expressing uroplakins and epidermal growth factor receptor in bladder cancer patients

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