Biomedical subjects

Rainer Kuefer

Publications and source records attributed to Rainer Kuefer.

23 records · Page 2Linked to original sources

PubMed2002

The role of calpain in the proteolytic cleavage of E-cadherin in prostate and mammary epithelial cells.

The E-cadherin protein mediates Ca(2+)-dependent interepithelial adhesion. Association of E-cadherin with the catenin family of proteins is critical for the maintenance of a functional adhesive complex. We have identified a novel truncated E-cadherin species of 100-kDa (E-cad(100)) in prostate and mammary epithelial cells. E-cad(100) was generated by treatment of cells with ionomycin or TPA. Cell-permeable calpain inhibitors prevented E-cad(100) induction by ionomycin. Immunoblotting for spectrin and mu-calpain confirmed calpain activation in response to ionomycin treatment. Both the mu- and m-isoforms of calpain efficiently generated E-cad(100) in vitro. The E-cad(100) fragment was unable to bind to beta-catenin, gamma-catenin, and p120, suggesting that this cleavage event would disrupt the E-cadherin adhesion complex. Mutational analysis localized the calpain cleavage site to the cytosolic domain upstream of the beta- and gamma-catenin binding motifs of E-cadherin. Because E-cadherin is inactivated in many adenocarcinomas we hypothesized that calpain may play a role in prostate tumorigenesis. A prostate cDNA microarray data base was analyzed for calpain expression in which it was found that m-calpain was up-regulated in localized prostate cancer, and to an even higher degree in metastatic prostate cancer compared with normal prostate tissue. Furthermore, we examined the cleavage of E-cadherin in prostate cancer specimens and found that E-cad(100) accumulated in both localized and metastatic prostate tumors, supporting the cDNA microarray data. These findings demonstrate a novel mechanism by which E-cadherin is functionally inactivated through calpain-mediated proteolysis and suggests that E-cadherin is targeted by calpain during the tumorigenic progression of prostate cancer.

Amino Acid Sequence↗

PubMed2002

alpha-Methylacyl-CoA racemase: expression levels of this novel cancer biomarker depend on tumor differentiation.

alpha-Methylacyl-CoA racemase (AMACR) has previously been shown to be a highly sensitive marker for colorectal and clinically localized prostate cancer (PCa). However, AMACR expression was down-regulated at the transcript and protein level in hormone-refractory metastatic PCa, suggesting a hormone-dependent expression of AMACR. To further explore the hypothesis that AMACR is hormone regulated and plays a role in PCa progression AMACR protein expression was characterized in a broad range of PCa samples treated with variable amounts and lengths of exogenous anti-androgens. Analysis included standard slides and high-density tissue microarrays. AMACR protein expression was significantly increased in localized hormone-naive PCa as compared to benign (P < 0.001). Mean AMACR expression was lower in tissue samples from patients who had received neoadjuvant hormone treatment but still higher compared to hormone-refractory metastases. The hormone-sensitive tumor cell line, LNCaP, demonstrated stronger AMACR expression by Western blot analysis than the poorly differentiated cell lines DU-145 and PC-3. AMACR protein expression in cells after exposure to anti-androgen treatment was unchanged, whereas prostate-specific antigen, known to be androgen-regulated, demonstrated decreased protein expression. Surprisingly, this data suggests that AMACR expression is not regulated by androgens. Examination of colorectal cancer, which is not hormone regulated, demonstrated high levels of AMACR expression in well to moderately differentiated tumors and weak expression in anaplastic colorectal cancers. Taken together, these data suggest that AMACR expression is not hormone-dependent but may in fact be a marker of tumor differentiation.

Biomarkers, Tumor↗

PubMed2002

Visualization of urinary stones by 3-D ultrasound with surface rendering.

The purpose of this study was to evaluate the diagnostic value of 3-D ultrasound with surface rendering in stones located in different parts of the urinary tract. A total of 55 patients with urinary stones were examined by transabdominal 3-D ultrasound (US) with surface rendering of the stone. In calculi of the prevesical ureter, bladder and prostatic urethra, transrectal 3-D endosonography was performed as well. The radiographic shape and the chemical analysis of the stone were correlated to the sonographic findings. The localization of the stone was: renal 23, ureteral 26, vesical 5 and urethral 1. All stones could be identified by 3-D US. Surface rendering produced useful results in stones > 2 cm with a 3.5-MHz transabdominal scanning probe, and in all stones that were accessible with a 7.5-MHz transrectal scanning probe. In stones < 1 cm, endoUS with surface rendering provides more information on the structure of the stone than plain radiography, but there is no correlation between surface and chemical analysis.

Endosonography↗

PubMed2002

High-flow priapism: a combined interventional approach with angiography and colour Doppler.

Traumatic high-flow priapism caused by a pathologic influx from lacerated arteries to the cavernous bodies is usually treated by transcatheter arterial embolisation. The purpose of this study was to evaluate a combined interventional approach with intraoperative perineal colour Doppler ultrasound (US) while performing the embolisation procedure. Our aim was to reduce radiation exposure and application of iodinised contrast media. To achieve an optimal position of the angiography catheter directly before or in the fistula, instead of several x-ray examinations with contrast media, a perineal colour Doppler US examination was performed while saline or US contrast media were injected through the catheter. The flow pattern allows the assessment of the occlusion of the fistula and the intact flow in the arteries that were not damaged. In four patients (unilateral fistula: 1, bilateral fistulas: 3) with traumatic high-flow priapism, this technique was performed combined with a conventional angiographic control of the embolisation. Seven embolisation sessions were performed. Only in one case, a dislocation of a microcoil required a second session. In all cases, the priapism disappeared immediately after the final session, leading to a restored erectile function. This combined approach may reduce the exposure to radiation and contrast media, especially in children, who often suffer from multiple fistulas and need more than one session. The procedure also prevents an occlusion of intact arteries that affects the penile perfusion and increases the risk of erectile dysfunction.

Adult↗

PubMed2002

Evaluation of disintegration in prevesical ureteral calculi by 3-dimensional endo-ultrasound with surface rendering.

PURPOSE: Lower ureteral calculi are accessible by transrectal endo-ultrasound, including 3-dimensional image processing with surface rendering. We analyzed the efficiency of this innovative technology compared with that of standard radiographic examinations with respect to the outcome of extracorporeal shock wave lithotripsy (ESWL) (Dornier Medical Systems, Marietta, Georgia). MATERIALS AND METHODS: In patients with prevesical or intramural calculi we performed excretory urography and transrectal endo-ultrasound using a Combison 530 device (Kretz Technik, Zipf, Austria) with integrated optional 3-dimensional image processing and surface rendering. A total of 102 ESWL cases (108 radiopaque stones, 145 ESWL sessions) were included in the study. One day after ESWL an evaluation was independently performed by a radiologist (plain x-ray) and a urologist (transrectal endo-ultrasound). Results were compared to the outcome determined during further followup. RESULTS: All stones were evaluable by endo-ultrasound with surface rendering, whereas in 27 cases the stone was hidden by extraureteral processes on followup radiography. Immediately after endo-ultrasound 8 calculi were passed. In 7 of the remaining 110 cases (6.4%) radiographic examination did not confirm sonographic findings. In these cases evaluation by surface rendering proved to be correct on followup. CONCLUSIONS: Endo-ultrasound with surface rendering proved to be highly effective for evaluating ESWL success in cases of prevesical ureteral stones. This technique is independent from bowel gas or other factors that impede radiological imaging. It is safe, easy to learn, well tolerated by patients and does not expose them to radiation.

Adult↗