Cornelius F.J. Jansen

Complex cadherin expression in human prostate cancer cells

Changes in cell‐cell interactions are critical in the process of cancer progression. Likewise, it has been shown that loss of expression of the cell adhesion molecule E‐cadherin is associated with grade, stage, and prognosis in many carcinomas, including prostate cancer. Impaired E‐cadherin‐mediated interactions result in an invasive phenotype; however, the mere loss of cell‐cell contact and communication is not the sole explanation for the observed correlation between loss of E‐cadherin‐mediated adhesion and poor clinical outcome. Using a degenerate cloning strategy for sequences that are highly conserved between the various cadherins, we found several other cadherins (N‐ and P‐cadherin and cadherin‐4, ‐6, and ‐11) to be expressed in human prostate cancer cells. Our data suggest that besides loss of E‐cadherin function, also (upregulation of) expression of other cadherins is involved in the acquisition of an invasive and/or metastatic phenotype. Especially, changes in the expression of N‐cadherin and cadherin‐11 may play an important role in prostate cancer progression. Int. J. Cancer 85:446–450, 2000. ©2000 Wiley‐Liss, Inc.

Detailed analysis of histopathological parameters in radical prostatectomy specimens and PCA3 urine test results

Due to the drawbacks of serum prostate‐specific antigen, there is an ongoing search for new diagnostic and prognostic prostate cancer (PCa) markers. PCA3 has proven to be of value in the diagnosis of PCa. However, so far few attempts have been made to investigate the prognostic value of PCA3. Our objective was to further investigate the prognostic value of PCA3.

Pharmacokinetics and toxicity of intravesical TMX-101: a preclinical study in pigs.

• To study the pharmacokinetic and toxicity profile of intravesically administered TMX‐101, with its active ingredient R‐837, a synthetic Toll‐like receptor (TLR)‐7 agonist, in a pig model.

Antitumor Effects of cis-Urocanic Acid on Experimental Urothelial Cell Carcinoma of the Bladder

PURPOSE We determined the effect of protodynamic therapy against bladder cancer cells in vitro and in vivo. We investigated cis-urocanic acid in rat bladder cancer cell cultures and in an orthotopic rat urothelial carcinoma model to assess its safety and antiproliferative activity. MATERIALS AND METHODS The rat bladder cancer cell line AY-27 was exposed to cis-urocanic acid (BioCis Pharma, Turku, Finland) at pH 6.5 or 7.4 for 2 hours. Cell viability was measured by colorimetric assay at 24 and 48 hours. For in vivo experiments AY-27 cells were instilled into the acid treated bladder of 17 rats. After 4, 7 and 10 days 14 rats were treated intravesically with cis-urocanic acid 6% (weight per volume) or vehicle. Rats were sacrificed on day 12 and the bladders were dissected. Immunohistochemical staining was done to assess apoptosis (caspase-3) and cell proliferation (Ki-67) in vivo. RESULTS Cis-urocanic acid caused dose dependent, pH dependent inhibition of AY-27 cell proliferation, showing the protodynamic action at concentrations of 0.5% and 1%. At higher cis-urocanic acid doses complete cell death was observed. All tumors detected in animals treated with vehicle were muscle invasive (stage T2 or greater) but only 43% of tumors were muscle invasive in the cis-urocanic acid treated group (p=0.049). There was no difference in the percent of apoptotic or proliferating tumor cells between treatment groups. No signs of toxicity were observed. CONCLUSIONS Cis-urocanic acid showed direct antiproliferative activity against rat bladder cancer cells in vitro and antitumor effects in vivo. It may have therapeutic potential as an intravesical agent for nonmuscle invasive bladder cancer.