Cyclin D1 protein expression and gene polymorphism in colorectal cancer. Aberdeen Colorectal Initiative.

Cyclin D1 is a key cell cycle regulatory protein, the expression and subcellular localization of which is often altered in human tumor cells. A common A/G single nucleotide polymorphism (A870G) in exon 4 of the cyclin D1 gene, CCND1, is associated with the presence of 2 distinct mRNA transcripts for this G1/S regulatory protein, and CCND1 genotype has been related to prognosis in lung cancer and head and neck carcinoma. We have investigated both the expression of cyclin D1 protein and the CCND1 A870G polymorphism in 100 colorectal cancer patients. Immunohistochemistry demonstrated cyclin D1 protein expression in 55% of tumors, and while the absence of cyclin D1 protein was not associated with outcome (p=0.81), high levels of protein expression (>50% of tumor cells expressing cyclin D1) correlated with significantly shortened overall survival (p=0.01). Using polymerase chain reaction restriction fragment length polymorphism analysis, we determined the frequency of each genotype and found that CCND1 genotype was not related to overall survival (p>0.05). In addition, genotype was unrelated to the level of expression and localization of cyclin D1 protein, as well as other key G1/S checkpoint proteins (p21, p27, p53, retinoblastoma) and tumor proliferation markers (proliferating cell nuclear antigen). However, higher levels of p27, and to a lesser extent p21, were associated with reduced cytoplasmic cyclin D1 protein (p=0.029 and p=0.054, respectively). In conclusion, we have demonstrated that high levels of cyclin D1 protein expression are related to outcome in colorectal cancer; however, the CCND1 A870G polymorphism is unrelated to either cyclin D1 protein expression or patient survival.

Expression of cell cycle control proteins in primary colorectal tumors does not always predict expression in lymph node metastases.

Analysis of tumor markers focuses on expression in primary tumors with the assumption that this is representative of metastatic tumor, against which treatment is targeted. Few studies have compared the expression of such markers in primary and secondary tumors. In this study, several key genes involved in cell cycle regulation were investigated in colorectal tumors and corresponding lymph node metastases. The cell cycle regulators p53, cyclin D1, p21, p27, retinoblastoma protein (Rb), and proliferating cell nuclear antigen (PCNA) were examined in a series of 42 paired samples of primary colorectal and secondary lymph node tumors by immunohistochemistry. Expression of p53, p27, and Rb was similar in virtually all paired samples (p53, 38 of 42; p27, 39 of 42; Rb, 40 of 42), indicating that the pattern of these proteins in colorectal tumors may be used to predict that in lymph node tumors. It also suggests a lack of direct involvement in the metastatic process. A lower concordance for p21 and cyclin D1 staining was observed between primary and secondary tumors (p21, 19 of 42; cyclin D1, 22 of 42). p21 expression was more often observed in primary colorectal cancers, whereas cyclin D1 expression was more frequently seen in lymph node metastases, in keeping with the contrasting roles of these proteins as a cell cycle inhibitor (p21) and activator (cyclin D1). The PCNA-labeling index was found to vary considerably in a number of cases, thus limiting the ability to predict expression of this protein in lymph node metastases from the primary tumor. In addition, PCNA-labeling indices between paired samples were neither consistently higher nor lower, suggesting that the proliferative capacity of tumor cells is not directly related to their ability to metastasize.

Evidence of normal emotional responsiveness in alcoholic Korsakoff's syndrome in the presence of profound memory impairment.

Memory and likeability ratings for emotion-laden and neutral stimuli were investigated in Korsakoff amnesics, former heavy drinkers and light drinkers. Tasks were recall of self-generated paired-associates, primed recognition and likeability ratings for faces previously paired with emotional or neutral descriptors, and ratings of the emotionality of items in a 64-word list. The Profile of Mood States and Geriatric Depression Scale were also administered. Despite severely impaired recall in Korsakoff's amnesics, the effects of emotional versus neutral material were not distinguishable among the three groups. These findings indicate a need to re-examine the notion that flattening of emotional responsiveness is a central characteristics of Korsakoff's Syndrome.

Treatment-related change in sex roles of addicted men and women.

To investigate differences in sex-role self-concept and self-esteem for men and women substance misusers and to examine sex-role change during treatment, pretreatment and posttreatment PRF Andro Scale scores were obtained from 108 inpatients at an addiction treatment center. Significant sex differences occurred in masculinity and femininity, with significant change during treatment in masculinity and self-esteem. Change during treatment was toward a more balanced self-perception, with addicted men being more atypical than women. Comparisons are made with recently published related data and it is suggested that addicted men may experience more role conflict than do addicted women.

Laboratory validation and field verification of a new passive air monitoring badge for sampling ethylene oxide in air.

A new diffusion colorimetric air monitoring badge for sampling ethylene oxide is described. The Du Pont Pro-Tek C-70 badge has been laboratory validated over the range of 4-375 ppm-hours (0.5-47 ppm on an 8-hour TWA) using standard spectrophotometer readout in 1 centimeter (10 mm) cells. The lower range can be extended to 2 ppm-hours (0.25 ppm) by using 4 cm (40 mm) cells. The badge has an overall sampling and analytical method accuracy of +/- 13.5%. It meets NIOSH accuracy criteria and has a mean coefficient of variation CVT = 0.059. The badge has no temperature, pressure, relative humidity or face velocity effects over practical ranges. The response time is adequate to sample peak concentrations over short time periods. The badge may be used to determine ambient formaldehyde levels if suspected to be present along with ethylene oxide. Badges are shown to agree very well with the industry accepted and proposed ASTM pump/charcoal tube method in three extensive plant field tests. Badges were more precise than the charcoal tube/pump method in all field tests conducted.