Biomedical subjects

C Cordon-Cardo

Publications and source records attributed to C Cordon-Cardo.

255 records · Page 15Linked to original sources

PubMedDate not supplied

Tobacco smoking, occupation, and p53 nuclear overexpression in early stage bladder cancer.

Epidemiological studies show an increased risk of bladder cancer associated with tobacco smoking and occupational exposures. Certain carcinogens in tobacco and occupational exposures cause DNA damage and may produce specific mutations. TP53 is considered a common target for carcinogenic agents, and mutations of this gene are reported to be the most frequent nuclear abnormalities in human cancer. In order to investigate the relationship between tobacco smoking, occupations, and altered patterns of p53 expression, we have analyzed a group of 109 incident patients with superficial transitional cell carcinoma of the bladder. We assessed p53 nuclear overexpression by the use of anti-p53 antibody PAb1801 and immunohistochemistry, and identified 45 of 109 patients (41%) displaying p53-positive phenotype. We observed a significant association between the number of cigarettes smoked per day and p53 nuclear overexpression (p = 0.02). The odds ratios were 2.3 for those smoking 1-2 packs per day and 8.4 for smoking more than 2 packs per day. Similar estimates were obtained after controlling for age, sex, and race. Elevated odds ratios were also observed for dye-/ink-related (odds ratio = 2.0; 95% CI, 0.4-9.4) and cooking-related occupations (1.8, 0.6-5.0), although those were not statistically significant. These data support the hypothesis that certain carcinogens derived from cigarette smoking and occupations may induce TP53 mutations, which in turn are involved in early steps of bladder carcinogenesis.

Aged↗

PubMedDate not supplied

Expression of the retinoblastoma gene product in renal tumors.

BACKGROUND: Alterations in the retinoblastoma (Rb) gene and its protein product have been detected in numerous solid tumor malignancies. Loss of Rb function is believed to contribute to neoplastic transformation or to the development of metastases. To define the role of Rb in renal cancer, we analyzed renal tumor specimens for molecular alterations in the Rb gene and for lack of Rb protein expression, and correlated the results to clinicopathological characteristics. MATERIALS AND METHODS: Thirteen renal cancer cell lines, 62 primary renal tumors, and 5 metastatic renal cancers were studied by Southern blot analysis for defects in the Rb gene, and by immunohistochemistry for Rb protein expression. Results were correlated with histopathological parameters and patient survival. RESULTS: Structural alterations in the Rb gene were not detects in any of the renal cancer cell line or primary renal tumors studied. A rearranged Rb gene was observed in 1/5 metastatic tumor specimens. Western blot analyses revealed a truncated Rb protein in one of 13 renal cancer cell lines; immunohistochemical analysis revealed Rb protein in all papillary and oncocytic tumors, and in 39/44 non-papillary tumors. Rb expression patterns did not correlate with pathological stage, histological grade or the development of metastatic disease. CONCLUSION: Molecular alterations of the Rb gene are infrequent (<2%) in renal cancers, and Rb protein is present in the majority of primary (92%) and metastatic (100%) renal tumors. Loss of Rb expression does not appear to significantly contribute to malignant transformation or progression of renal cancers.

Adenocarcinoma↗

PubMedDate not supplied

Intravenous basic fibroblast growth factor protects the lung but not mediastinal organs against radiation-induced apoptosis in vivo.

PURPOSE: We evaluated the therapeutic potential of intravenously injected basic fibroblast growth factor against the lethal syndromes associated with irradiation of intrathoracic organs and assessed whether such protection might be associated with inhibition of programmed cell death (apoptosis) in the exposed tissues. MATERIALS AND METHODS: C3H/HeJ and C3H/scid mice received either whole-chest, mediastinal, or bilateral lung irradiation. Human recombinant basic fibroblast growth factor was injected intravenously at doses of 400 ng immediately before and after irradiation, and then at 1 hour and 2 hours later. Time-adjusted survival was calculated from the date of irradiation by the product-limit Kaplan-Meier method. Detection of apoptotic changes in paraffin sections was performed by the DNA terminal transferase nick-end translation method. RESULTS: Basic fibroblast growth factor protected the lungs but not other intrathoracic organs against radiation-induced damage. When radiation was restricted to the lungs, the LD50/180 from radiation pneumonitis was 20.75 Gy and increased to 23.0 Gy in basic fibroblast growth factor-treated mice. When the whole thorax was irradiated, basic fibroblast growth factor partially protected against pneumonitis at the low range of radiation doses (< or = LD50/180), but failed to confer protection at higher doses, nor did it protect against lethal radiation esophagitis. Staining for the presence of apoptotic nuclei revealed time- and radiation dose-dependent development of apoptosis in endothelial cells of the pulmonary capillary network, endocardium, and mesothelial cells of the pleura and pericardium. Although basic fibroblast growth factor inhibited apoptosis in the microvascular endothelium and the endocardium, it had no effect on apoptosis in the serosal mesothelium of the pleura and pericardium. CONCLUSIONS: Intravenous basic fibroblast growth factor protects against the apoptotic microvascular component of early-phase radiation pneumonitis but may have no effect on other elements of the primary damage produced by radiation in the lungs and other intrathoracic organs. Understanding the patterns and temporal evolution of radiation-induced apoptosis and basic fibroblast growth factor-mediated antiapoptotic effects in thoracic organs and tumors may offer opportunities for pharmacologic intervention in the radiotherapeutic management of primary and metastatic lung tumors.

Animals↗