ABSTRACT
Prostate cancer is one of the most common tumors in males and its incidence is steadily increasing worldwide. Serotonin or 5-hydroxytryptamine (5-HT) is a well-known neurotransmitter that mediates a wide variety of physiological effects. An increase in the number of 5-HT-releasing neuroendocrine (NE) cells has been correlated with tumor progression. However, it is particularly unclear whether released 5-HT or the release of 5-HT has a role in tumor cell growth. We hypothesized that 5-HT synthesis and metabolism in NE cells regulate the growth of prostate cancer cells. In the present study, 5-HT was found to play a role as a cell growth factor in prostate cancer cells. Moreover, the pharmacological inhibition of 5-HT synthesis and metabolism interrupted the growth of prostate cancer cells. To confirm the existence of 5-HT in prostate cancer cells, we performed ELISA, HPLC, RT-PCR and immunohistochemical analyses. A high expression of tryptophan hydroxylase (TPH-1), dopa decarboxylase (DDC) and monoamine oxidase A (MAO-A) was noted in the prostate cancer cells when compared with normal prostate cells. Previous studies showed that 5-HT stimulated the proliferation of prostate cancer cells mediated by 5-HT receptors 5-HTR1A and R1B. However, cell proliferation was significantly inhibited when siRNA for both DDC and TPH-1 was transfected to the cells. Consequently, we propose that the secretion system of prostate NE cells capable of 5-HT synthesis and metabolism plays a significant role in prostate tumor generation and progression. These findings provide crucial clues for the development of potential pharmacotherapeutics to slow prostate tumor progression.
ABSTRACT
The purpose of this study was to investigate the effect of an increase in laser power on the transmitted laser signals from vital and non-vital teeth, in the hope of achieving a better assessment of human pulp vitality with the transmitted laser-light flowmeter. The experiments were carried out on total of 61 vital teeth with no restoration (19 upper central incisors, 16 upper lateral incisors, 16 upper canines, and 10 first premolars) and five non-vital upper central incisors (the root canals of which were filled with gutta-percha) in 15 subjects aged 22-28 years. For use with transmitted laser light, the fibers within the probe of a conventional laser Doppler flowmeter (LDF) apparatus were used, one for transmitting light onto the labial surface, the other for receiving it at the palatal surface of the same tooth, as reported previously. Laser output power was set at the original 2 mW and also at 5, 7, and 10 mW. The number of vital teeth displaying a blood flow (BF) signal at each laser power setting was: 1) 12/19 central incisors at 2 mW, 19/19 at 5, 7, and 10 mW, 2) 19/19 lateral incisors at 2, 5, 7, and 10 mW, 3) 0/16 canines at 2 mW, but eight, 12, and 14 at 5, 7, and 10 mW, 4) 0/10 first premolars at 2, 5, 7, and 10 mW. Thus, an increase in laser power increased BF detection from the thicker teeth (but not from premolars). In addition, clearer BF signals synchronized with heart rate, and greater passive BF changes secondary to blood pressure (BP) changes were observed at higher laser settings. In non-vital teeth, no signals synchronized with heart rate or BP changes were observed, indicating that no BF signal of non-pulpal origin was ever monitored with this ballistic light even when the laser power was increased. These results indicate that high-powered transmitted laser light could be a useful tool both for monitoring pulpal BF and for the assessment of tooth-pulp vitality.