Technical aspects of ultrasound imaging guidewires.

In many interventional catheterization laboratories around the world the use of intravascular ultrasound (IVUS) has become a routine addition to the catheter-based interventional procedures. IVUS catheters, for coronary use, typically of a size around 3 French, provide images that assist in diagnosing the coronary obstructive disease, choosing the most appropriate recanalization method, monitoring the recanalization process and evaluating the end result. The downside of the use of IVUS, apart from additional cost to the procedure, is the additional exchange of catheters during the procedure. Several designs of hybrid catheters have been proposed, combining IVUS imaging with a therapeutic de-obstruction method in one catheter. A more modular approach is to equip the guidewire with imaging capability. Such a guidewire would provide an image of the stenotic region as well as guide the recanalization catheter to its location. It will, however, require further miniaturization of the ultrasound imaging technology, which already is scaled down considerably to enable coronary imaging. In addition, the ultrasound imaging guidewire (UIG) would have to possess specific qualities in bending and torque to act as a true guidewire. A first step to modularity is the separately used 'imaging core', which is advanced into the guidewire lumen of a therapeutic catheter, but cannot guide this catheter to the desired location. The combination of both imaging and mechanical requirements would yield a true UIG, but constitutes major technical challenges.

Rat prostate cancer cells contain functional receptors for transforming growth factor-beta.

Clonally derived C-, D-, and T-family AXC/SSh rat prostate cancer cell lines contain transforming growth factor-beta (TGF beta) receptors. The content in C3, D1, T1, and T5 cells, respectively, was 8,560 +/- 1,450, 13,160 +/- 1,240, 2,425 +/- 490, and 10,540 +/- 1,025 sites/cell (mean +/- SEM). Respective Kd values were 160 +/- 48, 200 +/- 53, 24 +/- 3, and 115 +/- 15 pM (mean +/- SEM). T1 cell TGF beta receptor site content and Kd differed significantly from those of other prostate cancer cell lines (P less than 0.05). TGF beta is a bifunctional concentration-dependent modulator of T1 and T5 cell thymidine incorporation. At low concentrations, thymidine incorporation was inhibited, whereas as the medium TGF beta content was increased, T1 and T5 cell thymidine incorporation was stimulated. The concentrations of TGF beta causing half-maximum inhibition of T1 or T5 cell thymidine incorporation, respectively, were 0.11 and 0.24 pM, whereas the respective TGF beta concentrations causing half-maximum stimulation of thymidine incorporation were 14.4 and 134 pM. These findings establish that rat prostate cancer cell sensitivity to TGF beta inhibition of function is at least 2 orders of magnitude greater than that of most other mammalian cells. In contrast, the sensitivity of rat prostate cancer cells to TGF beta enhancement of function is comparable to that of other mammalian cells. TGF beta inhibited basic fibroblast growth factor (bFGF) stimulation of T1 and T5 cell thymidine incorporation. Because the concentration of bFGF required for half-maximum increase of T5 cell thymidine incorporation was independent of medium TGF beta content, the effect of TGF beta is distal to the T5 cell bFGF receptor. In contrast, the concentration of bFGF required for half-maximum increase in T1 cell thymidine incorporation increased 5-fold as the medium TGF beta content was increased; suggesting that the effect of TGF beta in T1 cells is proximal to the T1 cell bFGF receptor. Our studies establish that rat prostate cancer cells contain functional TGF beta receptors, imply the presence of functional bFGF receptors, and demonstrate that mitogen modulation of prostate cancer cell function is multifactorial. The finding that TGF beta is a bifunctional effector of prostate cancer cell DNA synthesis provides some insight into the potential complexity of mitogen modulation of prostate cancer cell proliferation. The mechanism by which these mitogens interact is unknown; however, our studies suggest that some interactive effects may be cell line specific.

Differences in responsiveness of clonally derived AXC/SSh rat prostate cancer cells to secreted or prototypic mitogens.

AXC/SSh rat prostate cancer cells elaborate heat-sensitive, heparin-binding mitogens which include members of the fibroblast growth factor (FGF)-like family of growth factors. The quantity of FGF-like growth factors, relative to total growth factor production, was cell line specific as was prostate cancer cell response to secreted or the prototypic mitogens basic FGF (bFGF), acidic FGF (aFGF), or epidermal growth factor (EGF). C3 cell proliferation, assayed either by cell counting or thymidine incorporation, was not affected by mitogens secreted by C3, D1, T1, or T5 prostate cancer cells or by bFGF, aFGF, or EGF. In contrast, C3, D1, T1, or T5 cell-secreted mitogens enhanced proliferation of T1 and T5 cells, and proliferation of D1, T1, and T5 cells was enhanced by bFGF, aFGF, and EGF. D1 cell response to prototypic mitogens was 3- to 12-fold less than that of T1 or T5 cells. By comparison, the NRKF cell response to prototypic mitogens was qualitatively comparable but quantitatively greater than that of rat prostate cancer cells. The relative and absolute bFGF or aFGF concentrations necessary for half-maximum stimulation of prostate cancer or normal rat kidney fibroblast cell thymidine incorporation were comparable to that known to effect half-maximum increase in proliferation of mesoderm-derived cells. Similarly, the EGF concentration required for half-maximum prostate cancer or normal rat kidney fibroblast cell thymidine incorporation was comparable to that known to effect half-maximum fibroblast thymidine incorporation or granulosa cell proliferation. Our data establish that prostate cancer cell response to prototypic mitogens is representative of that of nonneoplastic cells and imply that C3 cell insensitivity to prostate cancer cell or prototypic mitogens represents defects in cellular response mechanisms. The basis for C3 cell unresponsiveness or D1 cell-diminished responsiveness remains to be elaborated.