Targeted screening for prostate cancer in high risk families: early onset is a significant risk factor for disease in first degree relatives

PURPOSE: Targeted screening for prostate cancer in high risk families is generally suggested by ages 40 to 45 years in first degree relatives. We support this concept by reporting higher risk and earlier onset of the disease in these families. MATERIALS AND METHODS: We proposed serum prostate specific antigen (PSA) testing in 40 to 70-year-old first degree relatives of 435 patients with prostate cancer treated between July 1994 and June 1997. A previous systematic genealogical analysis allowed us to define the familial prostate cancer status of each patient as sporadic or familial. RESULTS: Of the 747 potential candidates 442 (59%) accepted into the study have been screened, including 240 who were 40 to 49 years old (mean age 44.8) and 202 who were 50 to 70 years old (mean age 57.4). Two of the 240 subjects (0.8%) had PSA greater than 4 ng./ml. in the 40 to 49-year-old group. Prostate biopsies were negative in 1 relative but diagnostic for prostate cancer in the other. In the 50 to 70-year-old group 25 of 202 subjects (12.4%) had a PSA of greater than 4 ng./ml. Prostate cancer was diagnosed in 9 individuals (4.5%), 9 had negative biopsy results, 1 died before biopsy and 6 refused biopsy. The proportion of relatives with PSA greater than 4 ng./ml. and prostate cancer detection was not different according to familial status (sporadic or familial) but it was significantly higher in first degree relatives with early onset prostate cancer in the family at ages younger than 65 years (p = 0.037 and 0.012, respectively). CONCLUSIONS: Our results emphasize the usefulness of PSA screening in high risk families, including those without obvious hereditary features. Furthermore, early onset prostate cancer is a significant risk factor for prostate cancer in first degree relatives.     

雷公藤红素阻断全反式维甲酸导致的白血病细胞与内皮细胞黏附

目的:全反式维甲酸(all-trans retinoic acid,ATRA)治疗急性早幼粒细胞白血病,引起白血病细胞与内皮细胞之间黏附增加,是发生维甲酸综合征的重要原因。本文观察雷公藤红素对这种黏附增加的影响。方法:用流式细胞术检测雷公藤红素对急性早幼粒细胞白血病细胞系NB4和人脐静脉内皮细胞(humanumbilical vascular endothelial cell,HUVEC)在ATRA刺激下表达黏附分子的影响。用细胞黏附功能实验,检测雷公藤红素对ATRA导致的上述两种细胞之间黏附增加的影响。结果:ATRA能引起NB4细胞表面细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)表达增加,但可被雷公藤红素明显抑制(P<0.01)。NB4细胞上清液能刺激HUVEC表达ICAM-1(P<0.05);而被ATRA处理过的NB4细胞上清液能明显刺激HUVEC表达选择素E(E-selectin)、血管细胞黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)和ICAM-1等黏附分子(P<0.01),雷公藤红素对其抑制率分别达25.3%、42.4%和61.0%。ATRA导致上述两种细胞之间黏附增加,雷公藤红素对其完全抑制。结论:雷公藤红素能抑制ATRA导致的白血病细胞与内皮细胞黏附,有可能用于维甲酸综合征的治疗。     

QUANTITATIVE AUTORADIOGRAPHIC DETERMINATION OF BINDING SITES FOR A PERIPHERAL BENZODIAZEPINE LIGAND ([3H]PK 11195) IN HUMAN IRIS

Specific binding sites of peripheral-type benzodiazepines were investigated in human iris/ciliary body (8 eyes). Examination of color-coded prints and densitometric quantification of autoradiograms were performed on slides (20 micron) labelled with [3H]PK 11195 (1 nM) at 25 degrees C. Nonspecific binding was determined with PK 11211 (5 microM) or Ro 5-4864 (5 microM). Binding sites were present on all the slides, with equivalent density in the 3 regions of the preparation (ciliary body, iris, and pupil margin). The numbers of binding sites in ciliary body, iris, and pupil margin, respectively, were: 42.7 +/- 0.2, 30.1 +/- 0.5, and 37.4 +/- 0.4 femtomol/mg protein. Labelling on the pupil margin seemed to coincide with the iris sphincter muscle. The presence of peripheral benzodiazepine binding sites in iris muscular tissue, and particularly in the pupil margin, suggests that the iris preparation may be a valuable tool to detect putative physiological effects of peripheral benzodiazepines on muscular motility.