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Biomedical subjects

Ulrich Frey

Publications and source records attributed to Ulrich Frey.

7 recordsLinked to original sources

Expression analysis and potential functional role of the CXCR4 chemokine receptor in bladder cancer.

OBJECTIVE: Recent analysis gave evidence for the fact that the chemokine receptor CXCR4 is of functional significance in the multistep procedure of metastasis directing tumor cells to their metastatic target organs. In our study we investigated the expression of the CXCR4 receptor on bladder cancer cells and the functional activation of the CXCR4 receptor in bladder cancer cell lines regarding signal transduction pathways, which are involved in metastasis. METHODS: Receptor transcript expression was analysed and quantified by reverse transcription PCR with RNA extracted from different samples of native human bladder cancer tissue, normal urothelium and the bladder cancer cell lines J82 and T24. Measurement of intracellular [Ca(++)](i) and analysis of intracellular stress fiber formation, chemotaxis, Matrigel invasion and proliferation were performed in the bladder cancer cell lines J82 and T24 upon stimulation with the specific agonist SDF-1. RESULTS: Specific CXCR4 receptor transcripts were detected in normal urothelium, the bladder cancer cell lines J82 and T24 and in all bladder carcinoma specimens. We did not observe a quantitative correlation of transcript expression and tumor stage. While SDF-1 did not evoke increases in [Ca(++)](i) in bladder cancer cell lines, we observed a distinct rise in intracellular stress fiber formation, chemotactic activity, invasion through Matrigel coated membranes and cell growth upon stimulation with SDF-1, which was blocked in the presence of a specific CXCR4 receptor antibody. CONCLUSION: Our results support that the chemokine receptor CXCR4 is an interesting candidate for the future investigation of metastasis of bladder cancer in vivo.

Chemokine CXCL12↗

How harmful is contralateral testicular biopsy?--an analysis of serial imaging studies and a prospective evaluation of surgical complications.

OBJECTIVE: Testicular biopsy has recently gained a role in early detection of testicular cancer. However, its use is still limited mainly because of the fear of untoward consequences. There is a paucity of data regarding unfavourable effects of testicular biopsy. Therefore, we systematically looked to the consequences of the procedure by using clinical observational methods and by modern imaging techniques, respectively. PATIENTS, METHODS: 1874 patients with testicular cancer enrolled in a nation-wide contralateral biopsy study were prospectively analyzed in regard to surgical complications. Serial scrotal imaging was performed by scrotal sonography (7.5 Mhz) in 55 patients and by magnetic resonance tomography (1.5 Tesla machine, surface coil, contrast media) in 60 patients, respectively. Imaging examinations were done preoperatively and again at 1 week, 6 months, 12 months, and 18 months respectively. Imaging results were tabulated according to an abnormality score and analyzed by descriptive statistics. RESULTS: 52 patients (2.78%; 95% confidence intervals 2.05-3.60) experienced surgical complications. Forty minor complications were managed conservatively. Twelve patients (0.64%) required repeat surgery; 1 testicle was ultimately lost following a sequence of unfortunate events. No pre-existing clinical parameter was associated with complications. One week after surgery, abnormalities were detected in 33% by sonography and in 45% by MRI, respectively. Importantly, the abnormalities resolved in 96% of the cases, as found in both of the imaging modalities in the serial scans. CONCLUSIONS: Testicular biopsy is associated with a low burden of clinically significant complications. However, scrotal imaging discloses intratesticular abnormalities in a high proportion of cases one week after the biopsy. These changes represent focal haematoma, oedema or circumscript injury to vascular supply. Most of these lesions resolve with time and are thus not significant, clinically. Evidently, testicular biopsy is a safe procedure provided the vascular anatomy of the testis is respected upon surgery.

Adolescent↗

The human G protein beta4 subunit: gene structure, expression, Ggamma and effector interaction.

The aim of this study was the characterization of the human Gbeta4 subunit of heterotrimeric G proteins. Human Gbeta4 is widely expressed. Its gene is located on chromosome 3 with a genomic structure indistinguishable from that of the genes of Gbeta1 to Gbeta3, but entirely different from Gbeta5. In vitro translation co-precipitation analyses revealed that Gbeta4 can form stable dimers with Ggamma1, Ggamma2, Ggamma3, Ggamma4, Ggamma5, Ggamma7, Ggamma10, Ggamma11, Ggamma12, and Ggamma13, dimers which were also able to stimulate phospholipase beta2.

Amino Acid Sequence↗

Testicular microlithiasis--one case and four points to note.

A 38-year-old man with non-specific scrotal complaints was found to have bilateral testicular microlithiasis (TM) sonographically. MRI of the testes failed to depict microlithiasis. Bilateral double biopsies of the testes revealed testicular intraepithelial neoplasia (TIN; carcinoma in situ of the testis) in only one of the two biopsies from the right testis. At the request of the patient the biopsies were repeated, with the same histological result. A right-sided orchiectomy was performed. Histology disclosed TIN in only some tubules of the lower pole of the testis. This case highlights four interesting points: (i) TM may be associated with testicular malignancy; (ii) MRI does not depict TM; (iii) TIN is arranged focally within the testis; and (iv) a two-site biopsy may increase the sensitivity of the diagnosis of TIN.

Adult↗

The CC genotype of the C825T polymorphism of the G protein beta3 gene (GNB3) is associated with a high relapse rate in patients with chronic lymphocytic leukaemia.

A C825T polymorphism has been described in the GNB3 gene which encodes the Gbeta3 subunit of heterotrimeric G proteins. The GNB3 825T allele is predictive of enhanced Gi protein activation. This study was performed to correlate genotypes of the C825T polymorphism with various clinical aspects of chronic lymphocytic leukaemia (B-CLL). The GNB3 genotype distribution in B-CLL patients was similar to that in other Caucasian populations, arguing against a role of the polymorphism in the susceptibility to develop B-CLL. No statistically significant differences were observed at diagnosis between patients with the CC genotype and homozygous or heterozygous T allele carriers with respect to age at disease onset, sex distribution, proportion of patients with CD38+ leukaemia or patients in Binet stage A, blood cell counts, degree of bone marrow infiltration or serum levels of lactate dehydrogenase, thymidine kinase or beta2-microglobulin. In a subgroup of 44 patients requiring chemotherapy, the median interval between diagnosis and first treatment and the response to treatment were similar in patients with CC or CT/TT genotypes. A statistically significant difference, however, was found in the proportion of patients relapsing and requiring second line chemotherapy (CC: 95%; CT/TT: 52%; p = 0.0043). The GNB3 genotype (p = 0.024) and age (p = 0.042) were identified as independent prognostic factors for a second therapy. Thus, the long-term success of the treatment appears to be correlated with the GNB3 genotype.

Aged↗