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Capecitabine plus oxaliplatin(CapeOX)is widely used as postoperative adjuvant chemotherapy for gastric cancer. The CapeOX regimen often causes digestive symptoms, such as nausea and vomiting under postoperative conditions, and oxaliplatin- induced neurological symptoms, for which supportive intervention is needed. The pharmaceutical outpatient clinic of Jichi Medical University provides pharmaceutical intervention for cancer patients. This study evaluated the usefulness of the pharmaceutical outpatient clinic for gastric cancer patients receiving postoperative adjuvant chemotherapy. The primary endpoint was defined as the effect of the number of outpatient pharmacist interventions on the relative dose intensity of the CapeOX regimen. The secondary endpoint was the correlation between the number of outpatient pharmacist interventions and the worst grade of each side effect. It was observed that patients who received at least 5 outpatient pharmacist interventions had significantly higher dose intensities(p=0.019). Outpatient pharmaceutical interventions were associated with the reduction of side effect symptoms that could be managed with preventive and supportive care. These results showed that continuous intervention by outpatient pharmacists contribute to the optimization of dose intensity and reduction of side effects in gastric cancer patients receiving CapeOX as postoperative adjuvant chemotherapy.

For achieving retrograde gene transfer, we have so far developed two types of lentiviral vectors pseudotyped with fusion envelope glycoprotein, termed HiRet vector and NeuRet vector, consisting of distinct combinations of rabies virus and vesicular stomatitis virus glycoproteins. In the present study, we compared the patterns of retrograde transgene expression for the HiRet vs. NeuRet vectors by testing the cortical input system. These vectors were injected into the motor cortex in rats, marmosets, and macaques, and the distributions of retrograde labels were investigated in the cortex and thalamus. Our histological analysis revealed that the NeuRet vector generally exhibits a higher efficiency of retrograde gene transfer than the HiRet vector, though its capacity of retrograde transgene expression in the macaque brain is unexpectedly low, especially in terms of the intracortical connections, as compared to the rat and marmoset brains. It was also demonstrated that the NeuRet but not the HiRet vector displays sufficiently high neuron specificity and causes no marked inflammatory/immune responses at the vector injection sites in the primate (marmoset and macaque) brains. The present results indicate that the retrograde transgene efficiency of the NeuRet vector varies depending not only on the species but also on the input projections.

Protein S, a nonenzymatic cofactor to activated protein C, presents in two forms in plasma, free form and in a complex with C4b-binding protein. The aim of this study was to determine the association of plasma protein S levels with the variables related to cardiovascular disease risk. The relationships between plasma protein S levels with lipids, inflammation markers, and adiposity were first examined on middle-aged obese women (n = 62), then on young nonobese women (n = 160) to verify the findings in the obese women. Total and free protein S antigen levels in middle-aged obese women, approximately half being in a postmenopausal state and suffered from dyslipidemia, correlated negatively with estradiol and positively with triglycerides, total cholesterol, LDL cholesterol, apoA-II, apoB, apoC-II, apoC-III, apoE, hemoglobin A1c, and protein C, whereas there was no correlation with HDL cholesterol, apoA-I, BMI, visceral fat area, blood pressure, or factor VII activity. Multiple linear regression analyses revealed that protein C, apoC-II, and fibrinogen were significant predictors of total protein S antigen levels, accounting for 51.9% of variance, and apoC-II as a singular significant predictor for free protein S antigen levels (12.3% of variance). In young nonobese women, most being normolipidemic, apoC-II was also selected as a significant predictor of total protein S antigen levels, but not of free protein S antigen levels. The positive relationship between plasma protein S levels and apoC-II, a key regulator of triglycerides hydrolysis, may contribute to the pathogenesis of increased concentrations of plasma protein S.

Objective To investigate the localization and expression of steroid sulfatase (STS) in cumulus cells obtained from subjects with and without endometriosis. Design Case-control study. Setting In vitro fertilization program at the Showa University School of Medicine. Patient(s) Cumulus cells (142 samples) were obtained from 49 patients for whom IVF was indicated. Some of these samples were taken from cases complicated by endometriosis (35 samples), polycystic ovary syndrome (PCOS; 16 samples), or latent hyperprolactinemia (16 samples). Intervention(s) Immunohistochemical staining for STS. Measurement of STS mRNA expression by real-time polymerase chain reaction (PCR). Main Outcome Measure(s) Expression of STS mRNA and localization of STS. Result(s) Steroid sulfatase was localized in the cytoplasm of the cumulus cells, and expression of STS mRNA was observed. The expression level of STS mRNA from patients with endometriosis was significantly higher (11.8-fold) than that of patients without endometriosis. Conclusion(s) These results suggest a local steroidal regulation mechanism in cumulus cells. Although the physiological role of STS in cumulus cells remains unclear, STS may be involved in the quality of eggs in patients with endometriosis.

Background It has been reported that the progesterone receptor (PR) level is transiently increased within the follicle by LH stimulation and controls cumulus cells in follicles and oocyte maturation. The purpose of this study was to predict developmental competence of human oocytes during IVF via analysis of PR in cumulus cells surrounding mature oocytes. Methods Prior to oocyte retrieval, the follicular diameter was measured and follicular fluid was collected from each mature follicle. Cumulus cells were manually separated from the oocyte-cumulus complex under a microscope. PR and PR mRNA were assessed by immunohistochemistry and real-time quantitative polymerase chain reaction (RT-PCR) measurement in human cumulus cells. Results Immunoreactive PR-A was mainly localized in the cytoplasm and PR-B was localized in the nuclei. There was no significant relationship between PR expression and follicular diameter, follicular fluid concentration of steroids, or LH. There was no significant relationship between expression of PRs and fertilization or cleavage rate. However, PR expression was lower in the good morphology group (blastomeres > or =7 cells with fragmentation > or =5% on day 3) when compared to the other groups (P Conclusions These results suggest that follicular LH or steroids do not affect PR expression, and full reduction of total PR expression on cumulus cells at the time of oocyte collection is associated with good morphology in human oocytes.

Objective To use microdissection and DNA microarray technology to demonstrate differences in gene expression between epithelial and stromal areas in the proliferative human endometrium. Design Pilot study. Setting University hospital. Patient(s) Patients with normal menstrual cycles and at least one previous intrauterine pregnancy. Intervention(s) Uterine endometrial biopsy. Main Outcome Measure(s) Gene expression. Result(s) From a total of 1,200 genes, 14 were strongly expressed in epithelial areas and 12 were strongly expressed in stromal areas. Among the genes strongly expressed in the stroma, expressions of decorin and discoidin domain receptor were confirmed by real-time polymerase chain reaction. Decorin was localized in the stromal areas by immunohistochemical staining. To confirm the effects of estrogen on gene expression, stromal cells were cultured. When E 2 was added to the culture media, expression of decorin mRNA was increased. Conclusion(s) The data demonstrated in this study help to understand the physiology of human endometrium. Decorin was strongly expressed in the stromal areas and was regulated by estrogen, and therefore it may be involved in restoration of the endometrium.