Three-cycle fentanyl patch system contributes to stable control of plasma fentanyl concentration in gynecologic cancer pain patients.

OBJECTIVE: Pain affects many cancer patients in advancing stages, lowering the level of their quality of life. Morphine has long been the "gold standard" for the treatment of cancer pain; however, its side effects, particularly sedation and cognitive impairment at high doses, have encouraged the use of "opioid rotation". The transdermal fentanyl patch has advantages over oral morphine, with reduced side effects and increased convenience in practical usage. The side effects were reduced in patients who changed to the fentanyl patch, but rescue analgesia was often needed because of the decrease of fentanyl release from the patch, especially on patch replacement day. To maintain a stable fentanyl plasma level before patch replacement, we have established a three-cycle fentanyl patch system and reported that it provided appropriate pain control. The objective of this study was to investigate the individual variability of plasma fentanyl concentration in a three-cycle fentanyl patch system. CASE REPORT: The gynecologic cancer patients were treated using the three-cycle fentanyl patch system. Blood samples were taken from the patients and plasma fentanyl concentration was analyzed. A stable plasma fentanyl level was observed, and good pain control was achieved in each patient using the three-cycle fentanyl patch system. A stable plasma fentanyl level was maintained the day before the conventional patch replacement day. DISCUSSION: The three-cycle fentanyl patch system provided a stable plasma fentanyl concentration and excellent pain relief and should be considered for pain control in cancer patients.

Three-cycle fentanyl patch system significantly improves pain control in gynecologic cancer.

Pain affects many cancer patients, and in advanced stages of the disease it can significantly affect the quality of their lives. Morphine has long been the 'gold standard' for the treatment of cancer pain. However, its side-effects, particularly sedation and cognitive impairment at high doses, have encouraged the use of 'opioid rotation'. The transdermal fentanyl patch has advantages over oral morphine, with reduced side-effects and increased convenience in practical usage. The side-effects were reduced in patients who changed to the fentanyl patch, but rescue analgesia was often needed because of the decrease of fentanyl release from the patch, especially on the patch replacement day. We have developed a three-cycle fentanyl patch system that provided an appropriate pain control, and this system should be considered for pain relief in cancer patients.

Increased expression of calcium-binding protein S100 in human uterine smooth muscle tumours.

S100 proteins belong to the EF-hand Ca(2+ )-binding protein family and regulate a variety of cellular processes via interaction with different target proteins. Several diseases, including cancer and melanoma, are related to the abnormal expression of S100 proteins, which are expressed in cell- and tissue-specific manners. We investigated the expression of S100 family members in human uterine smooth muscle tumours. Expression of six members of the S100 protein family: S100A1, A4, A6, A7, A10 and A11, was found in human uterine leiomyoma and myometrium tissue, but expression of other members was not detected by RT-PCR. Real-time PCR showed that S100A11 expression was significantly increased in leiomyoma compared with myometrium. Suppression of S100A11 by small interfering RNA (siRNA) led to apoptosis, and the overexpression of S100A11 inhibited apoptosis in human uterine smooth muscle tumour cells. These findings suggest that S100A11 has an anti-apoptotic function and is related to the process of growth of human uterine leiomyoma.

PEP-19 overexpression in human uterine leiomyoma.

Although uterine leiomyomas represent one of the most common neoplasms in adult women, their pathogenesis remains poorly understood. A cDNA microarray analysis was performed to search for candidate genes expressed to a greater degree in leiomyoma compared with matched myometrium. A total of 15 candidate genes was obtained; neuron-specific protein PEP-19 (Purkinje cell protein 4; PCP 4) exhibited a striking difference in expression between leiomyoma and myometrium. Although PEP-19 expression has been reported exclusively in the central nervous system, the present study demonstrated that PEP-19 is also expressed in other human organs, including prostate, kidney and uterus. To clarify the role of PEP-19 in the pathogenesis of leiomyomas, PEP-19 expression was investigated for a series of human leiomyoma, as well as normal myometrium and leiomyosarcoma. PEP-19 mRNA and protein expression were much stronger in leiomyomas compared with normal myometrium, suggesting that PEP-19 might be involved in leiomyoma pathogenesis.

Tranilast inhibits the proliferation of uterine leiomyoma cells in vitro through G1 arrest associated with the induction of p21(waf1) and p53.

Uterine leiomyoma is a mesenchymal tumor composed of smooth muscle cells with fibrous tissues and many mast cells. Tranilast is known to suppress fibrosis or to work as a mast cell stabilizer and is reported to inhibit proliferation of vascular smooth muscle cells. In this study, we examined the effects of tranilast on cultured human leiomyoma cells in vitro to evaluate whether this agent has the potential to inhibit the growth of uterine leiomyomas. Tranilast inhibited the proliferation of cultured leiomyoma cells in a dose-dependent manner without any cytotoxic effect or induction of apoptosis. In association with the inhibitory effect, tranilast induced the cyclin-dependent kinase (CDK) inhibitor p21(waf1) and tumor suppressor gene p53 and decreased CDK2 activity. These results suggest that tranilast arrests the proliferation of uterine leiomyoma cells at the G0/G1 phase, through the suppression of CDK2 activity via an induction of p21(waf1) and p53. Tranilast was concluded to be a potent agent to inhibit proliferative activity of uterine leiomyoma cells.

Secreted frizzled related protein 1 is overexpressed in uterine leiomyomas, associated with a high estrogenic environment and unrelated to proliferative activity.

Secreted frizzled related protein 1 (sFRP1) is a modulator of Wnt signaling. Recently, aberrations of Wnt signaling were reported to be involved in the pathology of various human neoplasms. We investigated the expression and function of sFRP1 in uterine leiomyomas. Secreted FRP1 expression was increased in leiomyomas, compared with normal myometrium using Northern and Western blot analyses. Expression was strongest in the late follicular phase (high estrogenic milieu) of the menstrual cycle. Interestingly, expression was negligible in leiomyomas treated with GnRH agonist. Expression was also prominent in cells during E2 treatment, serum deprivation, and hypoxia. Moreover, induction of apoptosis by serum deprivation in a leiomyosarcoma cell line was enhanced by antisense inhibition of sFRP1. These results suggest that sFRP1 expression was associated with uterine leiomyomas, particularly under high estrogenic conditions. Secreted FRP1 expression was not associated with cell proliferation but rather occurred during cell protection against apoptosis in vitro. Strong sFRP1 expression under high estrogenic conditions seems to contribute to the development of uterine leiomyomas through the antiapoptotic effect of sFRP1, which appear to be independent of cell proliferation.