Interleukin-1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment

The tumor microenvironment consists of tumor, immune, stromal, and inflammatory cells which produce cytokines, growth factors, and adhesion molecules that promote tumor progression and metastasis. Of particular interest in this setting is interleukin-1 (IL-1), a pleiotropic cytokine with numerous roles in both physiological and pathological states. It is known to be up regulated in many tumor types and has been implicated as a factor in tumor progression via the expression of metastatic and angiogenic genes and growth factors. A number of studies have reported that high IL-1 concentrations within the tumor microenvironment are associated with a more virulent tumor phenotype. Solid tumors in which IL-1 has been shown to be up regulated include breast, colon, lung, head and neck cancers, and melanomas, and patients with IL-1 producing tumors have generally bad prognoses. The exact mechanisms by which IL-1 promotes tumor growth remain unclear, though the protein is believed to act via induction of pro-metastatic genes such as matrix metalloproteinases and through the stimulation of adjacent cells to produce angiogenic proteins and growth factors such as VEGF, IL-8, IL-6, TNFα, and TGFβ. The IL-1 receptor antagonist (IL-1ra) is a naturally occurring inhibitor to IL-1 and acts by binding to the IL-1 receptor without activating it. The protein has been shown to decrease tumor growth, angiogenesis, and metastases in murine xenograft models. Our focus in this review is to summarize the known data on the role of IL-1 in tumor progression and metastasis and the use of IL-1 inhibition as a novel therapeutic approach in the treatment of solid organ malignancies.     

Patient satisfaction on AIDS and oncology special care units and integrated units: a pilot study

The authors assessed patients' satisfaction with their nursing care in seven hospitals. Five of the hospitals utilized the special care unit (SCU) method of delivering care to AIDS or oncology patients; three had SCUs for AIDS patients. All seven of the hospitals had integrated units (IUs) where general medical, oncology, and/or AIDS patients were received in various proportions. Satisfaction with nursing care was measured with the Risser Patient Satisfaction Instrument. Patient satisfaction with nursing care was shown to be a function of delivery method; AIDS and oncology patients on SCUs expressed greater satisfaction with their care than medical, oncology, or AIDS patients on IUs (p less than .001). Patient satisfaction with nursing care was greater among whites than nonwhites. Also, some major sociodemographic and case mix variables, such as age, employment status, and diagnosis, were not associated with patient satisfaction directly; in other instances, the associations initially seen did not hold when delivery method (SCU vs. IU) and race were controlled for in a linear regression analysis.     

Factors associated with hypertension in Nigerian civil servants

BACKGROUND. Study of hypertension in segments of West African populations in transition toward Westernization may lead to better understanding of the high risk for hypertension among Westernized blacks. METHODS. Five hundred fifty-nine urban civil servants, ages 25-54, were recruited from six ministries of Bendel State, Nigeria. Blood pressure, physical measurements, urinary protein and glucose, fasting blood glucose, and demographic data were collected at the workplace. Subjects were classified as senior staff (professionals or administrators) or junior staff (non-administrators). RESULTS. Among 172 male senior staff, the age-adjusted rate of hypertension (diastolic blood pressure > or = 90 mm Hg, systolic blood pressure > or = 140 mm Hg, or on an antihypertensive medication) was 43% and occurrence rose dramatically from 21 to 63% across age groups 25-34 to 45-54, respectively. Among 266 male junior staff, the age-adjusted rate of hypertension was 23%, and occurrence did not rise with age. Logistic regression showed that body mass index (kg/m2), age, alcohol drinking, and being senior staff were all independently related to hypertension in men. On the other hand, the age-adjusted rate of hypertension in 121 women was 20% and was significantly related only to body mass index. CONCLUSION. Male urban civil servants appeared to have a risk for hypertension similar to that of U.S. black males. Age, body mass index, alcohol drinking, and other unidentified factors related to higher socioeconomic status were strong determinants of hypertension in this population.     

An analysis of panel data. The impact of a psychiatric consultation letter on the expenditures and outcomes of care for patients with somatization disorder.

In this study, the cost and health outcomes of a psychiatric consultation letter to primary care physicians caring for a sample of patients diagnosed with somatization disorder, a psychiatric condition associated with multiple, unexplained medical complaints, was assessed. To accommodate the small sample size of 73 patients, outcome effects were calculated using panel analysis. Study patients were randomized to a consultation or noconsultation group, and were repeatedly assessed at equal time intervals. Data were analyzed using parsimonious regression models derived from economic theory. During the 1-year follow-up period, a psychiatric consultation letter was associated with a 12% reduction in health care costs ($455 per patient within first year), with no evidence of deterioration in physical, mental, or general health. Less powerful t-test comparisons between treated and control groups lead to different conclusions. Reasons for these differences are discussed.     

Prospective evaluation of complications in an endoscopy unit: use of the A/S/G/E quality care guidelines.

In 1989, the American Society for Gastrointestinal Endoscopy released a quality assurance monograph in which a procedure review process was outlined. The major elements of the program for quality assurance in gastrointestinal endoscopy included: (1) procedure reports, (2) an endoscopic unit record, and (3) a procedure review. This study was designed to use the procedure review process to determine the incidence of complications, to identify quality assurance issues, and to determine whether audits and/or studies would result from this process. To make a meaningful interpretation as to what constitutes an important complication, a classification to define potential problems was established. Using this classification, a complication was identified in 64 of 3287 procedures (1.9%). These complications were discussed in a monthly morbidity and mortality conference. Additionally, 21 quality assurance issues were identified that led to four studies addressing these quality assurance issues.     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.