Asbestos-induced cellular and molecular alteration of immunocompetent cells and their relationship with chronic inflammation and carcinogenesis.

Asbestos causes lung fibrosis known as asbestosis as well as cancers such as malignant mesothelioma and lung cancer. Asbestos is a mineral silicate containing iron, magnesium, and calcium with a core of SiO(2). The immunological effect of silica, SiO(2), involves the dysregulation of autoimmunity because of the complications of autoimmune diseases found in silicosis. Asbestos can therefore cause alteration of immunocompetent cells to result in a decline of tumor immunity. Additionally, due to its physical characteristics, asbestos fibers remain in the lung, regional lymph nodes, and the pleural cavity, particularly at the opening sites of lymphatic vessels. Asbestos can induce chronic inflammation in these areas due to the production of reactive oxygen/nitrogen species. As a consequence, immunocompetent cells can have their cellular and molecular features altered by chronic and recurrent encounters with asbestos fibers, and there may be modification by the surrounding inflammation, all of which eventually lead to decreased tumor immunity. In this paper, the brief results of our investigation regarding reduction of tumor immunity of immunocompetent cells exposed to asbestos in vitro are discussed, as are our findings concerned with an investigation of chronic inflammation and analyses of peripheral blood samples derived from patients with pleural plaque and mesothelioma that have been exposed to asbestos.

Renal cell carcinoma (RCC) and telomerase activity: relationship to stage.

Limited information is available on the correlation of telomerase activity and the clinical and pathological characteristics, in patients with renal cell carcinoma (RCC). Telomerase repeat amplification protocol (TRAP) was used to measure telomerase activity in frozen RCC specimens from partial/radical nephrectomies performed between 1987 and 1991. Presence of tumor tissue was verified by a pathologist using hematoxylin and eosin stained sections. RNA was measured to ensure the presence of intact protein necessary for telomerase expression. Data on demographics, tumor type, and stage at presentation, local recurrence, distant metastasis, disease-free survival (DFS), and overall survival (OS) was collected, and telomerase activity was correlated with each of these variables. Forty-nine of 67 patients (73%) were telomerase positive (+ve). Gender and stage were the only variables that appeared to be associated with telomerase positivity. Tumors were telomerase +ve in 12/21 females (57 %) vs. 37/46 males (80%) (P = 0.07). Tumors were telomerase +ve in 85% of Stage IV, 76% of Stage III, and 70% of Stage I/II patients (P = 0.12). Five-year survival was 0% for Stage IV, 57% for Stage III, and 77% for Stage I/II patients (P < 0.001), DFS 54% for stage III and 84% for Stage I/II patients (P = 0.05). Telomerase activity, however, was not related to survival in either univariate or multivariate analysis. In patients with telomerase +ve tumors 5-year survival was 55%, and with telomerase -ve tumors 58% (P = 0.56). Stage was the only variable associated with OS or DFS in clear cell RCC patients. In patients with advanced disease, there is a high incidence of telomerase positivity was found, within this limited sample, however, no correlation with survival was found.

Telomerase activity in stage II colorectal carcinoma.

BACKGROUND: Telomerase is a ribonucleoprotein polymerase that adds telomeric repeats to chromosome ends. This enzyme is deficient in the majority of normal somatic cells, but often is reactivated during tumorigenesis. In the current study, the authors examined telomerase activity in human American Joint Committee on Cancer Stage II colorectal carcinomas and correlated it with traditional prognostic indicators and disease outcome. METHODS: The telomerase repeat amplification protocol (TRAP) was employed to determine telomerase activity in 122 surgical specimens (from 77 male and 45 female patients) of human Stage II colorectal carcinoma. The primary site of the tumor was the colon in 52 cases and the rectum in 70 cases. Telomerase activity was correlated with traditional prognostic indicators such as gender, age, T classification, tumor size, tumor grade, and disease outcome (overall survival and disease-free survival). The Median follow-up for patients who still were alive was 5.8 years. RESULTS: Telomerase activity was detected in 80% of the tumors (98 of 122 tumors). Telomerase-positive patients differed from telomerase-negative patients in that they tended to be female (41% vs. 21%; P = 0.1), presented with primary tumors of the colon more frequently (49% vs. 17%; P = 0.01), and had a higher T classification (T(4)) (62% vs. 38%; P = 0.04). Univariate and multivariate analyses demonstrated a correlation between telomerase activity and disease-free survival (P = 0.05). CONCLUSIONS: Although a large percentage of Stage II colorectal carcinoma samples were positive for telomerase activity, the prognosis for patients with telomerase-negative tumors was found to be worse than that for patients with telomerase-positive tumors.