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  • 1
    ISSN: 1432-2307
    Keywords: Key words Apoptosis ; Gastric carcinoma ; Intratumoral microvessel density ; Thymidine phosphorylase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Thymidine phosphorylase (dThdPase) / platelet- derived endothelial cell growth factor (PD-ECGF) is expressed at higher levels in a variety of human carcinomas than in adjacent normal tissue. The higher expression is associated with an increase in intratumoral microvessel density (IMVD) and an unfavorable patient prognosis. This study examined the role of dThdPase in apoptosis, IMVD and p53 expression in human gastric carcinomas. dThdPase expression was noted in 12 (35.3%) of 34 early carcinomas, and in 20 (55.6%) of 36 advanced carcinomas. At least 10 areas consisting of carcinoma cells with diffuse dThdPase expression from the 32 dThdPase-positive tumors (category I), and 10 areas without dThdPase expression from the 38 negative tumors (category II) were selected from each case. For early gastric carcinoma, the mean IMVD was 88.8±19.4 in category I and 61.4±17.3 in category II carcinomas, while for advanced gastric carcinoma, the mean IMVD was 98.8±21.0 in category I and 76.0±27.1 in category II carcinomas. The mean IMVD was significantly higher in category I than in category II tumors (P〈0.05). The mean apoptotic index (AI: percentage of apoptotic cells) was 1.95±1.30 in category I, and 3.76±1.49 in category II carcinomas for early gastric carcinoma, and 1.51±0.98 in category I and 2.14±0.66 in category II carcinomas for advanced gastric carcinoma, the value of the mean AI being significantly (P〈0.05) higher in dThdPase- negative tumors (category II) than in the positive tu-mors (category I), regardless of tumor stage or histological type. There was a significant inverse correlation (P〈0.001) between AI and IMVD. These results indicate that dThdPase expression is associated with both an increase in intratumoral microvessels and a decrease in apoptosis in human gastric carcinomas.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Key words Serotonin receptor ; 5HT2A ; M100907 ; [11C]M100907 ; Positron emission tomography ; PET ; Human brain ; Schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Selective drugs are required to test the hypothesis whether antipsychotic effects may be induced or modulated by 5HT2A receptor antagonism. M100907 (previously known as MDL 100,907) is a highly selective 5HT2A antagonist in clinical development. Objective: To test if the suggested clinical dose of 20 mg M100907 daily induces high 5HT2A receptor occupancy in patients with schizophrenia. Methods: The 5HT2A receptor occupancy was determined in two patients with schizophrenia treated with M100907, 20 mg once a day. Positron emission tomography (PET) with 11C-labeled M100907, was performed prestudy and under steady state conditions. Clinical ratings were performed weekly. Results: Clinical treatment with M100907, 20 mg daily induced a very high 5HT2A receptor occupancy in the frontal cortex of both patients (〉90%). M100907 was well tolerated. One patient improved minimally and one patient became minimally worse during treatment. Conclusions: The results confirm that an oral dose of 20 mg per day ensures adequate 5HT2A receptor occupancy for clinical proof of concept. The sample is too small to allow conclusions about the clinical effect.
    Type of Medium: Electronic Resource
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