The effect of tyrosine kinase inhibitors, tyrphostins: AG1024 and SU1498, on autocrine growth of prostate cancer cells (DU145).

It is well established that autocrine growth of human prostate cancer cell line DU145 is dependent on TGF (EGF)/EGFR loop. However, the participation of several other growth factors in proliferation of DU145 cells has been also proposed. We employed two selective tyrosine kinase inhibitors (tyrphostins): AG1024 (an IGFIR inhibitor) and SU1498 (a VEGFR2 inhibitor) for growth regulation of DU145 cells, cultured in chemically defined DMEM/F12 medium. Both the tested compounds inhibited autocrine growth of DU145 cells at similar concentration values (IC50 approximately 2.5 microM). The tyrphostins arrested cell growth of DU145 in G1 phase, similarly as inhibitors of EGFR. However, in contrast to selective inhibitors of EGFR, neither AG1024, nor SU1498 (at concentration < or =10 microM) decreased the viability of the investigated cells. These results strongly suggest that autocrine growth of DU145 cells is stimulated by, at least, three autocrine loops: TGFalpha(EGF)/EGFR, IGFII/IGFIr and VEGF/VEGFR2(VEGFR1). These data support the hypothesis of multi-loops growth regulation of metastatic prostate cancer cell lines

The effect of tyrosine kinase inhibitors, tyrphostins: AG1024 and SU1498, on autocrine growth of prostate cancer cells (DU145).

It is well established that autocrine growth of human prostate cancer cell line DU145 is dependent on TGF (EGF)/EGFR loop. However, the participation of several other growth factors in proliferation of DU145 cells has been also proposed. We employed two selective tyrosine kinase inhibitors (tyrphostins): AG1024 (an IGFIR inhibitor) and SU1498 (a VEGFR2 inhibitor) for growth regulation of DU145 cells, cultured in chemically defined DMEM/F12 medium. Both the tested compounds inhibited autocrine growth of DU145 cells at similar concentration values (IC50 approximately 2.5 microM). The tyrphostins arrested cell growth of DU145 in G1 phase, similarly as inhibitors of EGFR. However, in contrast to selective inhibitors of EGFR, neither AG1024, nor SU1498 (at concentration < or =10 microM) decreased the viability of the investigated cells. These results strongly suggest that autocrine growth of DU145 cells is stimulated by, at least, three autocrine loops: TGFalpha(EGF)/EGFR, IGFII/IGFIr and VEGF/VEGFR2(VEGFR1). These data support the hypothesis of multi-loops growth regulation of metastatic prostate cancer cell lines

Apical defect — the essence of cystocele pathogenesis?

Objectives: Lack of standardization causes misunderstandings in planning of cystocele treatment and the evaluation of surgical method effectiveness. The POP-Q System and DeLancey’s three levels of pelvic support do not account for the phenomenon of cystocele caused by an apical defect. We aimed to evaluate the impact of level I defect on the formation of cystocele. Material and methods: Women reporting complaints related to bladder prolapse (cystocele) were subjected to a urogynecological examination. For this purpose, a simple and standardized method was used, based on the POP-Q System and DeLancey’s three levels of pelvic support. Furthermore, it was expanded by evaluating the impact of level I defect (apical defect) on prolapse at level II of the anterior compartment. Results: In total, contribution of an apical defect to the pathogenesis of cystocele was founded in 72.2% of 302 female patients included in this study. In 30.8% the cystocele was caused exclusively by an apical defect. In turn, in 41.4% of patients, it resulted from concomitant apical and level II defect of the anterior compartment (lateral or central). Conclusions: The results of this study indicate that an apical defect may play a significant role in the development of a cystocele. Hence, it could be essential to take the influence of an apical defect on level II in anterior compartment into account when planning a surgical procedure. The authors suggest that lack of such procedures potentially exposes some cystocele patients to ineffective treatment

Sodium orthovanadate affects growth of some human epithelial cancer cells

KLEIN A., HOLKO P., LIGEZA J.