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Biomedical subjects

P Ferroni

Publications and source records attributed to P Ferroni.

At least 109 records · Page 6Linked to original sources

Anti-envelope antibodies in anti-hepatitis C virus (HCV) positive patients with and without liver disease.

Our aim was to verify whether the presence of antibodies to HCV envelope protein might mark the occurrence of liver damage, as recently suggested in the literature. Sera from 104 patients (62 male, 42 female) were tested: 84 were positive and 20 were negative to a second generation enzyme immunoassay for anti-HCV antibodies; 51 patients had mild chronic liver disease (44 chronic hepatitis, seven steatosis), 43 had liver cirrhosis (superimposed by hepatocellular carcinoma in 18) and ten were asymptomatic anti-HCV positive subjects with normal liver function tests. Besides, all sera were tested by means of an enzyme immunoassay for the presence of serum antibodies to the synthetic peptide S24A (SIYPGHVSGH RMAWDMMMNW SPTA) derived from amino acids 307-330 of HCV polyprotein. Anti-S24A antibodies were detected in 40/84 sera positive and 1/20 negative at anti-HCV testing (Pearson chi 2 12.29; p = 0.005). Among anti-HCV positive sera, no significant difference existed in anti-S24A status with regard to clinical evidence of liver disease, ALT concentration or HCV RNA positivity. Thus, anti-S24A antibodies are detectable in approximately half of HCV-positive sera, but they do not seem to add significant clinical information to existing tests or to be useful as putative markers of viraemia.

Adult↗

Prevalence of HBeAg, anti-HBe and Dane particle-associated DNA polymerase activity in asymptomatic carriers of HBsAg.

HBeAg/anti-HBe and Dane particle-associated DNA polymerase activity were detected in serum samples from 358 HBsAg asymptomatic carriers found during normal routine screening of 11,200 blood donors (HBsAg prevalence 3.1%). Since virus specific DNA polymerase activity and HBeAg seem to be associated in some way with hepatitis B virus infectivity and liver damage, 5% of the HBsAg carriers examined, as detected by the presence of HBeAg, and 9.5%, as shown by DNA polymerase activity, can be expected to have liver damage and a potential risk of transmitting hepatitis B to contacts. On the other hand, 48% of subjects were theoretically healthy and non-infective because of the presence of anti-HBe in their blood. The differentiation of groups of asymptomatic HBsAg carriers, on the basis of these serological markers, may have important clinical and epidemiological implications.

Antibodies, Viral↗

Anti-LAV/HTLV-III antibodies in groups of individuals at high risk for infection in Italy.

We have studied anti-LAV/HTLV-III antibody prevalence in individuals at high risk for infection, such as intravenous drug addicts, hemophiliacs and homosexual men. Among intravenous drug addicts, LAV/HTLV-III infection was first recognized in 1981 and positive serum reactions for anti-LAV/HTLV-III antibody rose in successive years to 53%. Anti-LAV/HTLV-III antibody prevalence was 13.5% in the group of homosexual men, while in hemophiliacs treated with commercial concentrates it was 37% in 1984 and had increased to 45% in 1985. There was a significant correlation between antibody status and concentrate consumption in these patients. Results of studies of anti-LAV/HTLV-III antibody patterns with the Western blot technique suggest that antibodies against core proteins (mainly p25 and p18) and the envelope protein gp40 are always present in asymptomatic individuals and in patients with the lymphadenopathy syndrome, but usually not in patients with full-blown AIDS. These last patients have typical positive reactions only against the envelope proteins gp110 and gp40.

Acquired Immunodeficiency Syndrome↗

Effects of isolated limb perfusion with tumor necrosis factor-alpha on circulating levels of proinflammatory cytokines.

Hyperthermic isolated limb perfusion (ILP) with tumor necrosis factor-a (TNFalpha) and cytotoxic drugs is currently used for treatment of melanoma and sarcoma of the limbs. Tumor necrosis factor-alpha is involved in the systemic inflammatory response syndrome as a result of activation of inflammatory cells and production of bioactive substances. The goal of this study was to determine the circulating levels of proinflammatory cytokines and soluble adhesion molecules in 19 patients with limb melanoma or sarcoma undergoing ILP with (n = 9) or without TNFalpha (n = 10). The results obtained demonstrated that ILP with TNFalpha was responsible for a leakage of TNFalpha in the systemic circulation, followed by a rise in interleukin (IL)-6 and IL-8 levels within I h. Elevated soluble (s)P-selectin levels were found 1-3 h after ILP. Plasma sE-selectin peaked 6-9 h after ILP, and soluble vascular cell adhesion molecule (sVCAM) levels reached a maximum after 24 h. Significant correlations were observed among these variables, confirming the interdependence of all changes observed. On the other hand, ILP with cytotoxic drugs alone induced only a modest release of TNFalpha, which was not followed by an immediate rise in IL-6 and IL-8. Four of the 9 patients undergoing ILP with TNF had severe systemic toxicity. No association was found between systemic TNF levels and the clinical outcome, whereas elevated TNF perfusion levels as well as systemic IL-6 and IL-8 levels were constantly elevated in patients with severe toxicity. These results are suggestive of an important role of TNFalpha levels in the perfusion system (more than leakage of perfusate) in causing postoperative toxicity, although other ILP-related factors should not be excluded.

Adult↗

Prognostic value of serum and tumor tissue CA 72-4 content in gastric cancer.

To date no general agreement has been reached regarding the prognostic significance of CEA, CA 19-9 and CA 72-4 as serum markers in gastric cancer, and only scattered information is available on the predictive value of marker expression in tumor tissue. Therefore, a longitudinal study was designed to analyze the presurgical serum and tumor tissue content of CA 72-4, CEA and CA 19-9 in 166 patients at different stages of gastric cancer, and to evaluate the possible correlation with clinicopathological features in respect to prognostic information on relapse-free survival. The results obtained showed that 48.4% of patients with tumor recurrence had positive presurgical CA 72-4 levels compared to approximately 24% of patients who remained free of disease. Furthermore, the median presurgical serum CA 72-4 levels were significantly elevated in relapsing patients. Serosa and lymph node involvement as well as positive presurgical serum CA 72-4 levels had independent prognostic value in predicting recurrence. A significant association between disease-free survival and lymph node involvement, depth of invasion and tumor tissue content of CA 72-4 was also demonstrated. We may therefore conclude that CA 72-4 antigen can be considered the marker of choice in the follow-up of gastric cancer patients and may be used as a prognostic indicator of relapse.

Adult↗

Potential for artifacts in monitoring for the detection of tumor associated antigens (TAG-72 and CEA) in serum from patients undergoing MAb-based diagnostic and therapeutic protocols.

The administration of murine monoclonal antibodies (MAbs) induces, in many patients, an immunological response represented by the development of human anti-mouse antibodies (HAMA). HAMA have been previously shown to interfere in some assays for the detection of CEA, as well as other non tumor related analytes. The present study was performed to determine whether the CA 72-4 assay is affected by the presence of HAMA, and to establish conditions capable of overcoming this artifact. Serum samples obtained from 8/9 patients entered into a therapeutic protocol using 131I-labeled MAb B72.3 showed the development of apparently high levels of TAG-72 during the clinical follow-up concurrent with the appearance of elevated titers of HAMA. Heat treatment at 90 degrees C at pH 5.0 sodium acetate, previously reported as a method of abolishing HAMA interference without affecting CEA levels, resulted in a considerable loss of detectable TAG-72. However, treatment of these samples at 90 degrees C in pH 6.5 Bis Tris abolished the artifact due to HAMA and resulted in the reversion of reported TAG-72 levels to those observed prior to any MAb administration. As the use of murine MAbs, for both diagnostic and therapeutic applications continues to expand, the identification of this artifactual increase in reported antigen levels due to the development of HAMA has become an important factor in the use of tumor markers, e.g. TAG-72 and CEA, in the follow-up of carcinoma patients.

Animals↗

Soluble selectin levels in patients with lung cancer.

Increased expression of selectins has been found on endothelial cells of venules and capillaries in the tumor stroma of non-small cell lung cancer, suggesting their functional role in the process of chemotaxis for tumor cells. The present study was aimed at analyzing the role of both soluble (s)P-selectin and sE-selectin levels in association with clinico-pathological variables in 116 patients with lung cancer, 38 patients with benign diseases and 59 healthy donors. The results obtained showed that sP-selectin and sE-selectin levels were higher in patients with lung cancer compared to normal donors (p<0.02 and p<0.005, respectively). No differences were observed among patients with various benign diseases for both selectins. Increased levels of sP-selectin and sE-selectin were significantly associated with squamous lung cancer at late stages (p<0.05), but not adenocarcinoma. Both sP- and sE-selectin were independently related to the stage of squamous lung cancer by stepwise regression analysis (p<0.02 and p<0.03, respectively), while only sE-selectin was independently related to the presence of distant metastasis in the same histotype (p<0.02). These results suggest that measurement of plasma soluble selectins might represent a useful laboratory parameter in the management of patients with squamous lung cancer.

Adenocarcinoma↗

Evaluation of the CA 242 tumor antigen as a potential serum marker for colorectal cancer.

OBJECTIVE: The present study was designed to define the performance of serum CA 242 as a marker in colorectal cancer patients. PATIENTS AND METHODS: Serum samples from 1,013 subjects (440 healthy volunteers, 384 patients with primary or recurrent colorectal carcinoma and 189 with benign colorectal diseases) were evaluated. RESULTS: The measurement of serum CA 242 levels in the population of healthy subjects demonstrated the presence of positive levels in approximately 5% of the cases. Interestingly, similar results (5.8%) were obtained in patients with benign colorectal disease, demonstrating the high specificity of CA 242. When serum samples from colorectal cancer patients were analyzed, a sensitivity of 34.9% was observed. Moreover, 18.6% Stage A and B patients had positive CA 242 levels, compared to 33.3% and 58.8% of Stage C and D patients, respectively, indicating a correlation with the stage of disease. A comparison between preoperative and immediate postoperative CA 242 levels showed a consistent relationship between the efficacy of surgery and the reduction in serum CA 242 levels; further, elevated CA 242 levels were present in the immediate postsurgical follow-up of patients undergoing palliative surgery. A longitudinal evaluation of serum CA 242 levels demonstrated that this marker was indicative of the status of disease. CONCLUSIONS: The results obtained suggest the possible utility of CA 242 in monitoring the disease status, providing a rationale for future studies focusing on the longitudinal monitoring of colorectal cancer patients.

Adenocarcinoma↗

CA 19-9 monosialoganglioside content of human colorectal tumor cells correlates with tumor cell-induced platelet aggregation.

BACKGROUND: Gangliosides are involved in tumor cell-induced platelet aggregation (TCIPA). CA 19-9 is a monosialoganglioside detected in colon carcinoma cells. Therefore, this study was designed to evaluate whether there was any correlation between the CA 19-9 monosialoganglioside content and TCIPA. MATERIALS AND METHODS: The CA 19-9 content was determined on gangliosidic extracts of human colorectal tumor cells (GEO, WiDr, DLD-1, MIP) in comparison with the degree of TCIPA. RESULTS: CA 19-9 was detected in all cell lines, except MIP. The mean CA 19-9 content was 10.2, 30.2 and 82.6 U/microgram of sialic acid for GEO, DLD-1 and WiDr, respectively. CA 19-9 content directly correlated with TCIPA (p < 0.0001). Furthermore, incorporation of exogenous gangliosides in GEO cells resulted in an increase of CA 19-9 content, paralleled by a concomitant increase of TCIPA. CONCLUSIONS: The CA 19-9 monosialoganglioside may be involved in platelet/tumor cell interactions, thus playing an important role in the haematogenous metastases of colorectal cancer.

CA-19-9 Antigen↗

Comparative analysis of CA 242 and CA 19-9 serum tumor markers in colorectal cancer patients. A longitudinal evaluation.

OBJECTIVE: Following the encouraging results obtained on CA 242 as an adjunctive marker for colorectal cancer this study was designed to compare the clinical behavior of CA 242 to that of its related marker CA 19-9. PATIENTS AND METHODS: Sera from 630 patients with benign (n = 201) or malignant (n = 429) colorectal diseases were evaluated. Moreover, 50 patients with colorectal cancer were longitudinally monitored during. post-surgical follow-up for either a minimum of 5 years or until time of recurrence. Serum CEA, CA 19-9 and CA 242 levels were determined before treatment and at each scheduled follow-up. RESULTS: The distribution of CA 242 levels in colorectal cancer patients demonstrated a similar positivity rate (32.9%) compared to that of CA 19-9 (29.8%), although both sensitivities were lower than that of CEA (43.8%). Moreover, elevated CA 242 serum levels were found in metastatic disease (58.2%). A longitudinal evaluation demonstrated that serum CEA, CA 19-9 and CA 242 levels were elevated in 63.9%, 63.9% and 66.7% of recurrences. Combined evaluation of CEA, CA 19-9 and CA 242 serum levels in the overall population demonstrated a complementarity of CEA with the latter two markers. Conversely, a highly significant correlation was observed, suggesting that the two assays might recognize the same macromolecular complex. CONCLUSION: CA 242 determination does not seem to offer a particular advantage over CA 19-9, while CEA remains the marker of choice in monitoring colorectal cancer patients.

Adult↗

Sporadic cases associated with non polio enteroviruses studied in Lombardy between 1965 and 1972.

The results of virological investigations on 492 sporadic cases with a clinical diagnosis compatible with an enterovirus etiology studied in Lombardy between 1965 and 1972 are reported. A recent infection with non polio enteroviruses was established in 54 patients, mostly children under 4 years of age. Coxsackie viruses group A were prevalent being associated with 38 cases; echoviruses were involved in 13 cases, Coxsackie B viruses only in 3 instances. The frequency of isolation was highest from patients with paralytic illnesses either spinal or facial palsy than from patients with other diagnosis.

Adolescent↗

Biological effects of a software-controlled voltage pulse generator (PhyBack PBK-2C) on the release of vascular endothelial growth factor (VEGF).

BACKGROUND: Electrical stimulation (ES) may induce vascular permeability and physiological angiogenesis. ES of rat muscles significantly increases the microvessel density and vascular endothelial growth factor (VEGF) protein levels. Thus, a pilot study was designed to analyze the effects of low-voltage electric impulses on VEGF levels in patients with dystrophic ulcers. MATERIALS AND METHODS: Circulating VEGF levels were analyzed in 9 patients undergoing an ES session with low voltage software-controlled impulses applied through topical transducers (1-9 micros width, 1-420-Hz frequency and 30-120 V strength-100 microA max). RESULTS: The session was accompanied by a peak of circulating VEGF (3-10 min from start) in all 9 patients, which was preceded by a rise of TNF-alpha (2-min) and was independently associated with soluble E-selectin levels. Nitric oxide generation was significantly improved on the day after treatment. No hemostatic activation or sustained inflammatory reaction were observed. CONCLUSION: ES may represent a safe method for augmenting VEGF-mediated vascular protection, either directly or by induction of NO.

Aged↗

Clinical evaluation of the new tumor marker TAG-72.

Tumor-associated glycoprotein-72 (TAG-72) is a high molecular weight glycoprotein found in the sera of patients diagnosed with gastrointestinal and other malignancies. TAG-72 was detected in the serum of a significant percentage of patients whose CEA levels were negative which underscores the possibility of exploiting the complementarity of the two tumor markers in the diagnosis of gastrointestinal (G.I.) carcinoma. Moreover, the measurement of TAG-72 may also be clinically useful in discriminating malignant from benign effusions. Serum TAG-72 and CEA levels were evaluated longitudinally in a series of patients following resection of primary G.I. carcinomas. A consistent relationship between efficacy of the surgery and serum TAG-72 clearance was observed, and TAG-72 alone or in combination with CEA accurately predicted recurrence of malignant disease in greater than 90% of the patients. The results indicate that TAG-72 is a new human serum tumor marker which, measured alone or in combination with other well established markers, may improve the diagnosis and/or clinical management of malignant disease.

Adenocarcinoma↗

Effects on platelet function by human interferon-beta in carcinoma patients.

The effects of a therapeutic course of human interferon-beta (Hu IFN-beta) on platelet function were evaluated in 10 patients with neoplastic disorders. Each patient received, by intramuscular route, 6 x 10(6) IU of Hu IFN-beta every other day for 2 weeks. Platelet count, packed platelet volume, platelet size and in vitro aggregation tests were evaluated before IFN treatment and weekly during the treatment. An overall increase of in vitro platelet aggregation was present in all patients after the first week, and persisted after the second week of treatment. This effect was most pronounced when ADP and collagen were used as aggregation inducers. No significant differences were observed in IFN-gamma, IL-6, IL-1 beta and GM-CSF serum levels before and after IFN-beta treatment; nevertheless a parallel rise in IL-1 beta and/or GM-CSF and platelet count was noticed. The results obtained indicate that the effects of IFN-beta on platelet function are most likely due to a direct influence on bone marrow.

Adenosine Diphosphate↗

Correlation between positive CA 72-4 serum levels and lymph node involvement in patients with gastric carcinoma.

CA 72-4 serum marker has been shown to be one of the most specific and sensitive markers for monitoring gastric cancer. In the present study we evaluated the correlation between CA 72-4, CA 19-9 and CEA serum levels, and tumor size and lymph node involvement in gastric carcinoma patients. One-hundred sixty-one patients with primary or recurrent gastric carcinoma were studied. Elevated CA 72-4, CA 19-9, and CEA serum levels were found in 42.2%, 32.3% and 24.2%, respectively. As previously shown, the combination of CA 72-4 and CA 19-9 increased positive samples to 56.5%, while the addition of CEA did not further improve this percentage. Unlike what has been previously published, none of the markers showed a significant correlation with serosal involvement. In fact, elevated serum levels were observed for the three markers in a very low percentage of cases either in T1-T2N0 or T3-T4N0 patients. In contrast, CA 72-4 showed a highly significant correlation with lymph node involvement: T1-T4N0 patients had positive CA 72-4 levels in 5 out of 37 (13.5%), while T1-T4N1 in 12 out of 32 (37.5%), and T1-T4N2 in 20 out of 40 (50%) (p < 0.003). CA 19-9 and CEA serum levels were not significantly correlated. Since the presence of lymph node metastases is considered a negative prognostic factor, these results suggest that the measurement of CA 72-4 serum levels may be an important parameter in the diagnosis and clinical follow-up of patients with gastric carcinoma.

Adult↗

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↗

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↗