Chronic Powder Diet After Weaning Induces Sleep, Behavioral, Neuroanatomical, and Neurophysiological Changes in Mice.

The purpose of this study is to clarify the effects of chronic powder diet feeding on sleep patterns and other physiological/anatomical changes in mice. C57BL/6 male mice were divided into two groups from weaning: a group fed with solid food (SD) and a group fed with powder food (PD), and sleep and physiological and anatomical changes were compared between the groups. PD exhibited less cranial bone structure development and a significant weight gain. Furthermore, these PD mice showed reduced number of neurogenesis in the hippocampus. Sleep analysis showed that PD induced attenuated diurnal sleep/wake rhythm, characterized by increased sleep during active period and decreased sleep during rest period. With food deprivation (FD), PD showed less enhancement of wake/locomotor activity compared to SD, indicating reduced food-seeking behavior during FD. These results suggest that powder feeding in mice results in a cluster of detrimental symptoms caused by abnormal energy metabolism and anatomical/neurological changes.

Clinical relevance of thymidylate synthase (TS) activity for S-1-based chemotherapy in squamous cell carcinoma of the oral cavity.

S-1 is a newly developed oral fluoropyrimidine derivative that is now widely used as a chemotherapeutic agent in the treatment of oral squamous cell carcinoma (SCC). Thymidylate synthase (TS) is the rate-limiting enzyme in the de novo DNA biosynthetic pathway, and improves clinical response to chemotherapy with fluoropyrimidines. We have retrospectively evaluated the predictive value of thymidylate synthase activity in 75 patients with oral SCC with an enzyme-linked immunosorbent assay (ELISA). Mean (SD) activity (pmol/mg) in the specimens was 0.078 (0.080) (median 0.059). The median value was taken as the cut-off value based on which the patients were divided into high and low activity groups. Both the clinical and histopathological responses to chemotherapy and radiochemotherapy were higher in the group with low TS activity. The group with low TS activity also differed significantly in their clinical response to S-1-based chemotherapy (p<0.05). However, there was no significant difference in cause-specific survival. Measurement of TS activity may aid in predicting the clinical response to chemotherapy including S-1 for oral SCC.

[Clinical evaluation of palliative chemotherapy with S-1 for oral cancer patients].

The purpose of this study was to investigate the effectiveness and safety of palliative chemotherapy using S-1. We treated 19 advanced oral SCC patients including 8 men and 11 women with S-1. Of the 19 patients studied, two patients were classified as UICC Stage II, two patients as Stage III, 14 patients as Stage IV A, and one patient was classified as StageIV C. The ages varied from 54 to 9 1 years (mean ages; 78.3 years-old). The patients received this chemotherapy (80-120 mg/day) consisting of 2 weeks' administration including 5-days' administration and 2-days' termination (named 'Weekday-on/Weekend-off administration schedule' ) following 1 week rest. After this treatment, 7 CR and 4 PR were achieved, but the toxicities were only anorexia, leukopenia, thrombocytopenia, and uritication of NCI-CTC grade 1. The prognosis of 19 cases was 7 terminal by primary disease, 3 terminal by other disease, 7 lives with tumor bearing, and 2 lives without tumor bearing. We concluded that our novel S-1 administration method was extremely effective for oral SCC, including lymph node metastasis, providing high potential without any severe adverse effects for palliative therapy.