Role of biology and prevention in aerodigestive tract cancers.

Primary prevention aimed at smoking control and chemoprevention for high-risk persons or patients at risk for a second cancer provide strong potential for cancer prevention and control of aerodigestive cancers. The National Cancer Institute (NCI) has a major effort to build this area of research. The Third Upper Aerodigestive Tract Cancer Task Force Workshop, held in 1989 under the auspices of the National Cancer Institute's Organ System Program, reviewed the opportunities for chemoprevention research on aerodigestive epithelial cancers such as the regulation of growth and differentiation in normal and malignant cells. The chemoprevention program's drug development effort is evaluating several promising candidate agents for future clinical testing and the NCI clinical intervention program is supporting several trials of selected chemoprevention agents with demonstrated potential for inhibiting cancers of the lung, bronchus, oral cavity, and esophagus. Of special interest to this program is the assessment of beta-carotene, retinol and related synthetic retinoids, and several vitamin and mineral combinations under study in high-risk international populations. Chemoprevention in the medical setting is a major focus of NCI's Community Oncology Program (CCOP), a network designed not only to increase accrual of patients to trials but also to speed adoption of state-of-the-art therapies. Public health strategies are directed toward control of exposure to tobacco. The focal point for these activities is NCI's Smoking, Tobacco, and Cancer Program (STCP). STCP smoking cessation efforts are targeted at specific populations that are at greater risk for developing cancer including youth, minority and ethnic groups, women, smokeless tobacco users, and heavy smokers. Two of the world's largest controlled intervention trials conducted by the STCP are underway: the Community Intervention Trial for Smoking Cessation (COMMITT), which focuses on 6.5 million heavy smokers in 11 pairs of matched communities in North America, and the American Stop Smoking Intervention Study (ASSIST), a coalition model designed to reach millions of Americans through existing health promoting systems.     

Assessment of 5α-reductase activity in hirsute women: comparison of serum androstanediol glucuronide with urinary androsterone and aetiocholanolone excretion

OBJECTIVE Recent evidence suggests that androstanediol glucuronide (AG), a metabolite of dihydrotestosterone (DHT) formed in skin, is frequently elevated in hirsute women, presumably reflecting enhanced 5a-reductase activity. An alternative method of demonstrating 5a-reductase activity is the androsterone (A)/aetiocholano-lone (E) ratio in urine. A and E are the 5α- and 5β- reduced metabolites, respectively, of androstenedione, which is the principal metabolite of dehydroepiandrosterone (D). Although serum AG and the urinary A/E ratio have both been considered valid methods for assessing 5α-reductase activity, the two have not been previously compared in hirsute women. The present study was undertaken to assess 5a-reductase activity in hirsute patients as determined by these two different methods. PATIENTS AND MEASUREMENTS We surveyed 47 untreated women (ages 17–33) with various degrees of hirsutism. Serum testosterone, bioavailable testosterone, dehydroepiandrosterone sulphate, and AG were determined. Additionally, A, E and D were measured in 24-hour collections of urine. RESULTS For the 47 women, 37 had elevated blood levels of AG (17.4 ± 2.2, mean±SEM; normal <8 nmol/l), but only 18 of these had an increased urinary A/E ratio (> 1.5). All but one of the remainder had elevated urinary and/or serum androgen levels. Overall, no significant correlation between AG and A/E was observed. There was a highly significant correlation between AG in serum and A in urine (r= 0.82, P<0 001). AG was also positively related to dehydroepiandrosterone sulphate (r= 0.64; P< 0.005), bioavailable testosterone (r= 0.6; P<0001), aetiocholanolone (r= 0.58; P<0 001) and total testosterone (r= 0.52; P& 0.01). In contrast, A/E was not significantly related to androgen production. CONCLUSIONS There is a poor correlation between AG and the A/E ratio in hirsute women. Although AG may be raised by increased 5α-reductase activity, it is probably also affected by the presence of elevated androgens regardless of 5α-reductase activity.     

The expression of 5T4 antigen in colorectal and gastric carcinoma.

The expression of 5T4, an oncotrophoblast cell surface antigen was examined in 72 colorectal and 27 gastric carcinomas, with immunoperoxidase technique, on frozen sections. Highly significant association was found between 5T4 expression in the malignant cells and metastatic spread. The results suggest that the appearance of 5T4 molecules in cancer cells reflects a change which may contribute to the development of metastatic potential.     

Immunomodulation during prolonged treatment with combined interleukin-2 and interferon-alpha in patients with advanced malignancy.

Treatment with combined IL-2 and alpha-IFN has resulted in synergistic antitumour efficacy in animal studies. The mechanisms responsible for this synergy remain unclear. In this study, several immune parameters which might be involved in mediating antitumour activity have been monitored serially in 15 patients with advanced malignant melanoma or renal cell cancer during treatment with concurrent IL-2 and alpha-IFN. Both drugs were given subcutaneously in low to moderate (outpatient) dosages but for a prolonged duration. This treatment resulted in remarkable immunomodulation. In vivo induction of cytotoxicity against K562 and Daudi target cells was consistently seen, and percentages of peripheral blood cells expressing CD 25 (IL-2 receptor) and CD 56 (Leu-19) increased. In vitro proliferation of lymphocytes in response to IL-2 was enhanced during the treatment periods, whereas spontaneous proliferation was inhibited. Moreover, correlations between immune parameters and subsequent clinical responses were present in the early phase of the study. Cytotoxicity levels generated in vivo as well as the percentage of CD 56+ lymphocytes were higher in patients who responded to treatment than in non-responders. In contrast, responders had lower levels of CD 25+ cells. These findings indicate that it might be possible to select patients who are likely to benefit from prolonged immunotherapy.     

Computed tomographic (CT) demonstration of calcification of the ligamenta flava of the lumbosacral spine associated with protrusion of the intervertebral disc

Axial computed tomographic (CT) scan of the lumbosacral region was performed in 220 patients. The patient population was divided into three groups. The control group included 40 elderly patients without calcification of the ligamenta flava. The second group included 150 patients with posterior protrusion of the intervertebral discs. The third group included 30 patients with spinal stenosis. More than 80% of the patients of the second and the third group had calcification of the ligamenta flava. The diagnostic and practical importance of these findings is discussed.     

Prematurity Stereotyping by Mothers of Premature Infants

Previous research has experimentally documented a prematuritystereotype in college students and mothers of full-term infants.The present investigation extends the scope of earlier studiesto mothers of premature infants. Thirty-two mothers of prematureinfants viewed four videotapes of 9-month-old full-term infants,each labeled either full-term or premature and either male orfemale. When infants were labeled premature the mothers perceivedthem as littler, finer featured, weaker, more passive, and slowerthan infants labeled full-term. The mothers also perceived labeledboys as bigger than labeled girls. Differences in stereotypingbetween the mothers in this study and both mothers of full-terminfants and college students are identified and discussed. Resultssuggest that mothers of premature infants expect deficits inpremature infants' physical development but not in prematureinfants' mental or social development. The likely sources andpossible self-fulfilling nature of these biased perceptionsare considered