[A fatal case of meningeal carcinomatosis in a Stage IV gastric cancer patient who responded to multi-line chemotherapy].

A 60-year-old man was diagnosed with Stage IV gastric cancer with pyloric stenosis, peritoneal dissemination and multiple bone metastasis. One course of low dose CDDP and 5-FU, and 3 courses of S-1 and CDDP were carried out. Although a partial response was obtained, a large amount of ascites appeared again. As a third-line chemotherapy for this patient, PTX (60-100 mg/body) was administered to the peritoneal cavity on day 1 and 14, and S-1 (80 mg/body/ day) was given orally for 2 weeks followed by a 14-day rest period. The ascites had completely disappeared after 1 course of the combined chemotherapy. As a fourth-line chemotherapy, combination chemotherapy of biweekly infused PTX and daily oral S-1 was started, because the primary gastric lesion was increased. Subsequently, various neurological symptoms rapidly appeared, including dizziness, hypertension, and convulsion. Meningeal carcinomatosis was diagnosed by an examination of cerebrospinal fluid, and he died of disease rapid progression.

Effects of leptin on gonadotropin secretion in juvenile female rat pituitary cells.

OBJECTIVE: Leptin is an adipocyte-derived hormone, which is the product of the obese gene and it is thought to play important roles in pubertal development and maintenance of reproductive function in the female. In a study using adult male or female rats, it was found that leptin stimulated the secretion of gonadotropin directly from the pituitary in a dose-related manner. However, there is no study in juvenile female rats before puberty. METHODS: In this study, we cultured pituitary cells from 4-, 6- and 8-week-old female Wistar rats with leptin (0-10(-7)mol/l) and gonadotropin-releasing hormone (GnRH) (0 or 10(-8) mol/l). Basal or GnRH-stimulated secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and their synthesis within cells were determined by radioimmunoassay (RIA). RESULTS: Leptin induced bell-shaped dose--response curves of basal LH and FSH secretion from cultured cells of every age-group of rats studied. The most effective concentration of leptin on the basal secretion of LH and FSH from 6- and 8-week-old cultured pituitary cells was 10(-10) mol/l. This leptin concentration was consistent with circulating physiological serum leptin levels at each age. As for juvenile 4-week-old pituitary cells, the most effective concentration was 10(-11) mol/l which was lower than that of 6- and 8-week-old rats. It was consistent with the circulating serum leptin levels of 4-week-old rats. Also, the synthesis and the GnRH-stimulated secretion of LH and FSH were effectively controlled by leptin at concentrations similar to the serum leptin levels of given ages. CONCLUSIONS: Leptin induced pituitary cells to synthesize and secrete both LH and FSH regardless of the presence or absence of GnRH. The concentration of leptin that induced the greatest synthesis and secretion of gonadotropins from pituitary cells changed around the pubertal period. The most effective leptin concentrations in each experiment were similar to the physiological serum leptin level at each animal age. These results indicate that leptin stimulates gonadotrophs not only in the pubertal and the mature period but also in the juvenile period before puberty. It is also conceivable that leptin may modulate the sensitivity of gonadotrophs until the appearance of GnRH stimulation, and may be the factor that brings about puberty onset.

The obesity in bilateral ovariectomized rats is related to a decrease in the expression of leptin receptors in the brain.

We investigated the expression levels of leptin receptors in the brain of ovariectomized (OVX) rats. The mean expression level of ob mRNA in adipose tissues of OVX rats was significantly (P < 0.01) lower than that in the SHAM operation group rats, and the mean body weight of OVX rats was significantly (P < 0.01) greater than that in the SHAM group rats. However, there were no differences between serum leptin concentrations in these two groups. The mean level of leptin receptor (OB-R) mRNA expression in the brain tissue and the mean level of long form type OB-R (OB-RL) mRNA expression in the hypothalamus of the OVX rats were significantly (P < 0.05) lower than those in the SHAM group rats. These changes were cancelled by supplementation with 17 beta-estradiol in OVX rats. These results suggested that not only changes in the expression level of ob mRNA in adipose tissue and the serum leptin concentration but also changes in the OB-R mRNA in the brain are involved in the body weight increase in OVX rats and that a decrease in OB-R makes transmission of signals to suppress the amount of food intake difficult, thus leading to an increase in body weight.