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APF, HB-EGF, and EGF biomarkers in patients with ulcerative vs. non-ulcerative interstitial cystitis.

Zhang CO, Li ZL, Kong CZ - BMC Urol (2005)

Bottom Line: APF activity (inhibition of thymidine incorporation) was significantly greater in all IC patient urine specimens than in normal control specimens or in specimens from patients with bacterial cystitis or bladder cancer (p < 0.0001 for each comparison).Urine HB-EGF levels were also significantly lower and EGF levels significantly higher in both groups of IC patients than in the three control groups (p < 0.0001 for each comparison).Although APF and HB-EGF levels were similar in ulcerative and nonulcerative IC patients, EGF levels were significantly higher in IC patients with vs. without ulcers (p < 0.004).

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Infectious Diseases, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. czhan001@umaryland.edu

ABSTRACT

Background: Interstitial cystitis (IC) is a chronic bladder disorder, with symptoms including pelvic and or perineal pain, urinary frequency, and urgency. The etiology of IC is unknown, but sensitive and specific biomarkers have been described, including antiproliferative factor (APF), heparin-binding epidermal growth factor-like growth factor (HB-EGF), and epidermal growth factor (EGF). However, the relative sensitivity of these biomarkers in ulcerative vs. nonulcerative IC is unknown, and these markers have yet to be validated in another laboratory. We therefore measured these markers in urine from patients with or without Hunner's ulcer, as well as normal controls, patients with bladder cancer, and patients with bacterial cystitis, at the First Hospital of China Medical University.

Methods: Urine specimens were collected from two groups of Chinese IC patients (38 IC patients with Hunner's ulcers, 26 IC patients without Hunner's ulcers), 30 normal controls, 10 bacterial cystitis patients and 10 bladder cancer patients. APF activity was determined by measuring 3H-thymidine incorporation in vitro, and HB-EGF and EGF levels were determined by ELISA.

Results: APF activity (inhibition of thymidine incorporation) was significantly greater in all IC patient urine specimens than in normal control specimens or in specimens from patients with bacterial cystitis or bladder cancer (p < 0.0001 for each comparison). Urine HB-EGF levels were also significantly lower and EGF levels significantly higher in both groups of IC patients than in the three control groups (p < 0.0001 for each comparison). Although APF and HB-EGF levels were similar in ulcerative and nonulcerative IC patients, EGF levels were significantly higher in IC patients with vs. without ulcers (p < 0.004).

Conclusion: These findings indicate that APF, HB-EGF and EGF are good biomarkers for both ulcerative and nonulcerative IC and validate their measurement as biomarkers for IC in Chinese patients.

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APF activity in urine from Chinese interstitial cystitis patients with Hunner's ulcers (IC-U), Chinese interstitial cystitis patients without Hunner's ulcers (IC-N), normal controls (Ctr), and patients with bacterial cystitis (BC), or bladder cancer (BCa). APF activity was measured as inhibition of 3H-thymidine incorporation in normal bladder epithelial cells. Each data point indicates the mean change in incorporation, with each specimen tested in triplicate. Horizontal line indicates value of mean; vertical line indicates standard error of the mean for each group.
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Figure 1: APF activity in urine from Chinese interstitial cystitis patients with Hunner's ulcers (IC-U), Chinese interstitial cystitis patients without Hunner's ulcers (IC-N), normal controls (Ctr), and patients with bacterial cystitis (BC), or bladder cancer (BCa). APF activity was measured as inhibition of 3H-thymidine incorporation in normal bladder epithelial cells. Each data point indicates the mean change in incorporation, with each specimen tested in triplicate. Horizontal line indicates value of mean; vertical line indicates standard error of the mean for each group.

Mentions: HBE cells exposed to urine from the 38 Chinese IC patients with Hunner's ulcers had significantly less 3H-thymidine incorporation than cells incubated with urine from normal controls (-82.1 ± 2.2% vs. 1.6 ± 3.5%, p < 0.000001) (Figure 1), and cells exposed to urine from the 26 Chinese IC patients without Hunner's ulcers also had significantly less 3H-thymidine incorporation than cells incubated with urine from normal controls (-78.5 ± 2.8% vs. 1.6 ± 3.5%, p < 0.000001). The two groups of IC patients did not differ significantly from each other (p = 0.13). In comparison, HBE cells exposed to urine from bacterial cystitis or bladder cancer patients did not differ significantly from cells incubated with urine from normal controls (-8.4 ± 6.5%, and -8.5 ± 5.3% vs. 1.6 ± 3.5%), but each differed significantly from cells cultured with IC patients urine (p < 0.0001). When inhibition of thymidine incorporation greater than 2 standard deviations from the mean of cell controls was used as the definition for APF activity, 59/64 (92%) of IC patients had evidence for APF activity vs. only 1/30 (3%) of normal controls. None of the samples from bacterial cystitis or bladder cancer patients had any evidence for APF activity.


APF, HB-EGF, and EGF biomarkers in patients with ulcerative vs. non-ulcerative interstitial cystitis.

Zhang CO, Li ZL, Kong CZ - BMC Urol (2005)

APF activity in urine from Chinese interstitial cystitis patients with Hunner's ulcers (IC-U), Chinese interstitial cystitis patients without Hunner's ulcers (IC-N), normal controls (Ctr), and patients with bacterial cystitis (BC), or bladder cancer (BCa). APF activity was measured as inhibition of 3H-thymidine incorporation in normal bladder epithelial cells. Each data point indicates the mean change in incorporation, with each specimen tested in triplicate. Horizontal line indicates value of mean; vertical line indicates standard error of the mean for each group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1131910&req=5

Figure 1: APF activity in urine from Chinese interstitial cystitis patients with Hunner's ulcers (IC-U), Chinese interstitial cystitis patients without Hunner's ulcers (IC-N), normal controls (Ctr), and patients with bacterial cystitis (BC), or bladder cancer (BCa). APF activity was measured as inhibition of 3H-thymidine incorporation in normal bladder epithelial cells. Each data point indicates the mean change in incorporation, with each specimen tested in triplicate. Horizontal line indicates value of mean; vertical line indicates standard error of the mean for each group.
Mentions: HBE cells exposed to urine from the 38 Chinese IC patients with Hunner's ulcers had significantly less 3H-thymidine incorporation than cells incubated with urine from normal controls (-82.1 ± 2.2% vs. 1.6 ± 3.5%, p < 0.000001) (Figure 1), and cells exposed to urine from the 26 Chinese IC patients without Hunner's ulcers also had significantly less 3H-thymidine incorporation than cells incubated with urine from normal controls (-78.5 ± 2.8% vs. 1.6 ± 3.5%, p < 0.000001). The two groups of IC patients did not differ significantly from each other (p = 0.13). In comparison, HBE cells exposed to urine from bacterial cystitis or bladder cancer patients did not differ significantly from cells incubated with urine from normal controls (-8.4 ± 6.5%, and -8.5 ± 5.3% vs. 1.6 ± 3.5%), but each differed significantly from cells cultured with IC patients urine (p < 0.0001). When inhibition of thymidine incorporation greater than 2 standard deviations from the mean of cell controls was used as the definition for APF activity, 59/64 (92%) of IC patients had evidence for APF activity vs. only 1/30 (3%) of normal controls. None of the samples from bacterial cystitis or bladder cancer patients had any evidence for APF activity.

Bottom Line: APF activity (inhibition of thymidine incorporation) was significantly greater in all IC patient urine specimens than in normal control specimens or in specimens from patients with bacterial cystitis or bladder cancer (p < 0.0001 for each comparison).Urine HB-EGF levels were also significantly lower and EGF levels significantly higher in both groups of IC patients than in the three control groups (p < 0.0001 for each comparison).Although APF and HB-EGF levels were similar in ulcerative and nonulcerative IC patients, EGF levels were significantly higher in IC patients with vs. without ulcers (p < 0.004).

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Infectious Diseases, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. czhan001@umaryland.edu

ABSTRACT

Background: Interstitial cystitis (IC) is a chronic bladder disorder, with symptoms including pelvic and or perineal pain, urinary frequency, and urgency. The etiology of IC is unknown, but sensitive and specific biomarkers have been described, including antiproliferative factor (APF), heparin-binding epidermal growth factor-like growth factor (HB-EGF), and epidermal growth factor (EGF). However, the relative sensitivity of these biomarkers in ulcerative vs. nonulcerative IC is unknown, and these markers have yet to be validated in another laboratory. We therefore measured these markers in urine from patients with or without Hunner's ulcer, as well as normal controls, patients with bladder cancer, and patients with bacterial cystitis, at the First Hospital of China Medical University.

Methods: Urine specimens were collected from two groups of Chinese IC patients (38 IC patients with Hunner's ulcers, 26 IC patients without Hunner's ulcers), 30 normal controls, 10 bacterial cystitis patients and 10 bladder cancer patients. APF activity was determined by measuring 3H-thymidine incorporation in vitro, and HB-EGF and EGF levels were determined by ELISA.

Results: APF activity (inhibition of thymidine incorporation) was significantly greater in all IC patient urine specimens than in normal control specimens or in specimens from patients with bacterial cystitis or bladder cancer (p < 0.0001 for each comparison). Urine HB-EGF levels were also significantly lower and EGF levels significantly higher in both groups of IC patients than in the three control groups (p < 0.0001 for each comparison). Although APF and HB-EGF levels were similar in ulcerative and nonulcerative IC patients, EGF levels were significantly higher in IC patients with vs. without ulcers (p < 0.004).

Conclusion: These findings indicate that APF, HB-EGF and EGF are good biomarkers for both ulcerative and nonulcerative IC and validate their measurement as biomarkers for IC in Chinese patients.

Show MeSH
Related in: MedlinePlus