Biomedical subjects

F Guadagni

Publications and source records attributed to F Guadagni.

77 records · Page 5Linked to original sources

PubMedDate not supplied

Intraoperative radioimmunolocalization of an anti-CEA MAb F(Ab')2 (FO23C5) in CEA serum-negative colorectal cancer patients.

Serum positivity to an antigen recognized by the monoclonal antibody (MAb) which will be administered is frequently being used as a predictive criterion for positive MAb tumor localization. In the present study, which is based on our previous data that clearly showed no correlation between quantitative levels of CEA in sera and in carcinoma tissues, we selected a population of 12 primary colorectal carcinoma patients which were serum CEA-negative. The main purpose was to assess the potential diagnostic use of Radioimmunoguided Surgery (RIGS) with an anti-CEA FO23C5 F(Ab')2 MAb and its clinical value in this series of patients. In all RIGS patients, the MAb localized to histologically confirmed tumor; this included 96% of primary tumor tissues, 29% of lymph nodes and one occult liver metastasis. Thus, serum CEA positivity should not be a criterion for the use of anti-CEA MAbs for the diagnosis of colon cancer, since the serum CEA level is not indicative of CEA expression in tumors.

Aged↗

PubMedDate not supplied

Novel approaches to tumor detection and therapy using a combination of monoclonal antibody and cytokine.

Cytokine-based tumor antigen augmentation is one of the approaches researchers and clinicians are using to improve the effectiveness of MAb-directed tumor diagnosis and therapy. Other efforts encompass the use of dose-fractionation for multiple administrations of radioimmunoconjugates, exploitation of genetic engineering to construct antibody molecules with specific biological properties (i.e., altered pharmacokinetics, activation of cellular immune responses, etc.) and use of MAb-directed conjugates that can enhance tumor MAb uptake by altering tumor perfusion. The studies summarized here as well as those from other laboratories have served as the framework for clinical investigations designed to determine the effectiveness of the interferons and other differentiation-inducing agents to alter the tumor antigen phenotype in patients. In an earlier study, patients given IFN-alpha had improved tumor uptake of an antimelanoma MAb. Subsequently, we reported that i.p. IFN-gamma administration substantially upregulated TAG-72 and CEA on the surface of human tumor cells isolated from malignant ascites. A seminal investigation showed significant increase of TAG-72 and CEA levels in tumor biopsies from patients diagnosed with colorectal carcinoma and given systemic IFN-alpha. Those studies led to a clinical trial in which late stage breast cancer patients were administered interferon in combination with therapeutic doses of CC49. Some clinical responses were observed, however, the cytokine and MAb combination may have also enhanced marrow toxicity. Future studies will continue to evaluate the ability to enhance tumor antigen expression in the context of genetically engineered MAbs designed to minimize normal organ toxicity.

Antibodies, Monoclonal↗

PubMedDate not supplied

TAG-72 expression and its role in the biological evaluation of human colorectal cancer.

Immunohistochemical studies showed that TAG-72 is expressed in more than 80% of colorectal carcinomas, but is rarely expressed in normal epithelium and benign diseases. TAG-72 can also be found in the body fluids of patients with adenocarcinomas, and its direct measurement can be used in conjunction with immunocytochemical analysis to help in discriminating benign from malignant effusions. The evaluation of TAG-72 in serum of colorectal carcinoma patients showed a sensitivity of approximately 40%, comparable to that of the widely used CEA. TAG-72 serum levels correlate with the stage of disease, suggesting its utility in discriminating between early-stage versus late-stage colon carcinoma. Longitudinal studies demonstrated that TAG-72 serum levels may be used as a predictive marker of recurrences. Moreover, the simultaneous measurement of TAG-72 and CEA serum markers improves the monitoring of recurrent disease. Therefore, these data suggest that TAG-72 is a well suitable marker for colorectal cancer.

Antigens, Neoplasm↗

PubMedDate not supplied

Tumor markers as targets for selective diagnostic and therapeutic procedures.

Monoclonal antibodies (MAbs) that are reactive with tumor associated antigens (TAAs) have led to many of the recent advances made in tumor immunology. At the present time, many of these MAbs have already been used in various aspects of patient management and in better understanding the biology of carcinoma cell populations. Because of their diversity, specificity and biological activity, these MAbs are potentially ideal agents for a variety of applications in malignant disorders such as, clinical diagnosis using serum assays, immunocytopathological analyses of effusions or fine-needle aspiration specimens, immunoscintigraphy, radioimmunoguided surgery and, with additional development, site directed immunotherapy. Nevertheless, their clinical application shows advantages and limitations. Optimization of their clinical use is actually under evaluation in several Institutions, including our Department. Many innovations have been developed over the last decade which may enhance their clinical efficacy. In this view, an optimal tumor targeting for diagnostic or therapeutic applications may require a better choice of radiotracer, generation of new molecules and the characterization of TAAs at the target level.

Antibodies, Monoclonal↗

PubMedDate not supplied

Clinical utility of CA 72-4 serum marker in the staging and immediate post-surgical management of gastric cancer patients.

CA 72-4 is a high molecular weight, pancarcinoma human tumor mucin which may play an important role in the identification (i.e., staging) and clinical management of patients with gastric carcinoma. In the present study of 242 patients with primary or recurrent gastric cancer, a higher percentage of these patients had measurable serum CA 72-4 levels when compared with either CA 19.9 or CEA. Moreover, the presence of positive serum CA 72-4 levels correlated with the presence of lymph node involvement and with the identification of patients with a poor prognosis due to the presence of an advanced stage of gastric cancer. Post-operative monitoring of serum CA 72-4 revealed that the disappearance of CA 72-4 often indicated curative surgery which correlated with a longer disease-free interval. Additional clinical studies are needed to better evaluate the role of CA 72-4 as a serum marker for human gastric carcinoma. Concomitant studies should also focus on what role CA 72-4 may play in the initiation and/or progression of the gastric carcinoma phenotype.

Adult↗