Giulio Tarro

Early Diagnosis of Lung Cancer by Detection of Tumor Liberated Protein

Tumor liberated protein (TLP) is a protein that can be used to reveal the early development of a tumor. Besides being formed in the tumor, TLP is released in the blood when a patient starts producing cancer cells, which in turn enables the physician to intervene at a stage when the cancer is operable. To date, the available studies of tumor markers in lung cancer patients are CEA, NSE, TPA, Chromogranine, CA125, CA19‐9, and Cyfra 21‐1. The sensitivity and specificity for serum markers ranges between 50 and 90%, depending on the study and the clinical samples analyzed. Most of these markers show an increased rate of positivity as the stage advances. There are very limited data on TLP to draw any firm conclusion regarding the diagnostic value of this marker. TLP has been detected in 53.1% of non‐small cell lung cancer (NSCLC) patients (N = 534) with 75% being positive in the early stage (stage I) and dropping to 45% in the late stage (stage IV). However, 7.6% blood donor sera and 17.4% chronic lung disease sera have also tested positive. In a confirmation study, the specificity was 89.94% and the sensibility was 63.63% from stage III to IV NSCLC patients. In an initial study of TLP as a marker for early detection in stage I, NSCLC patients showed a sensitivity of 66.7% and a specificity of 80% for TLP compared to a sensitivity of 33.3% for CA19‐9, 11.1% for Cyfra 21‐1 and CA125, and 0% for CEA; the specificity for all four of the latter markers was 100%. Using immunohistochemical analysis with peroxidase anti‐peroxidase (PAP), we observed that NSCLC cells were positive; we used the specific rabbit antiserum to TLP, which turned out negative in the presence of 1 mg/ml of the synthetized peptide. The pre‐serum was also negative. The same reactivity was found early in the modified epithelial cells of interstitial lung fibrosis and might be a predictive marker of cell transformation. The site of the peroxidase positivity was cytoplasmic, of diffuse and/or granular type.

Mass spectrometry‐based proteomics: The road to lung cancer biomarker discovery

Lung cancer is the leading cause of cancer death in men and women in Western nations, and is among the deadliest cancers with a 5-year survival rate of 15%. The high mortality caused by lung cancer is attributable to a late-stage diagnosis and the lack of effective treatments. So, it is crucial to identify new biomarkers that could function not only to detect lung cancer at an early stage but also to shed light on the molecular mechanisms that underlie cancer development and serve as the basis for the development of novel therapeutic strategies. Considering that DNA-based biomarkers for lung cancer showed inadequate sensitivity, specificity, and reproducibility, proteomics could represent a better tool for the identification of useful biomarkers and therapeutic targets for this cancer type. Among the proteomics technologies, the most powerful tool is mass spectrometry. In this review, we describe studies that use mass spectrometry-based proteomics technologies to analyze tumor proteins and peptides, which might represent new diagnostic, prognostic, and predictive markers for lung cancer. We focus in particular on those findings that hold promise to impact significantly on the clinical management of this disease.

Human Tumor Antigens Inducing in vivo Delayed Hypersensitivity and in vitro Mitogenic Activity

Significant immunogenic properties were observed with an antigen extracted from tumor-liberated particles (TLP). Several different tumors were used to obtain antigens by such cell analysis and purification procedures as: gel filtration on Sephadex G-100, ion-exchange chromatography, affinity chromatography, and gel filtration on Sephadex G-200. The molecular weight determined on SDS-PAGE was about 214,000 daltons. In vivo, TLP yields delayed hypersensitivity reactions both in autologous and homologous hosts. TLP does not seem to have any nonspecific mitogenic activity, but it does have specific mitogenic activity, since lymphocyte blastogenesis (TLP-induced in presensitized patients) could mean its ability when intradermally inoculated to sensitize a lymphocytic clone.

Purification of herpes simplex virus tumor associated antigen from human kidney carcinoma

In the present studies, we attempted to purify herpes simplex virus (HSV) tumor associated antigen(s) (TAA) extracted from human kidney carcinoma. Trypsinized human tumor cells were sonicated for 9 minutes and clarified at 100.000 × g for 1 hour; the supernate yielded 70% of detectable TAA as determined by means of quantitative absorption with specific antisera. The supernate used as source of soluble HSV‐TAA was concentrated and the pellet was resuspended in 0.02 M tris, pH 7.2, and purified by means of filtration on Sephadex G‐100 followed by chromatography on DEAE Sephadex A‐50 and then affinity chromatography on concanavalin A (Con A) sepharose. The TAA bound to Con A sepharose was eluted by 0.5 M of α‐CH3D‐mannoside (α‐MM) and behaved as a glycoprotein. The molecular weight determined on SDS‐PAGE was about 70,000 daltons in relation to standard marker proteins. This antigen reacted in complement fixing tests with hyperimmune guinea pig sera as well as with certain human squamous cancer sera. As a control we used a human kidney carcinoma which showed no complement fixing activity in any of the procedural steps, and as control sera, guinea pig sera prepared by inoculation of uninfected guinea pig cells.

Tracking the 2009 H1N1 influenza virus in the Italian region Campania

A novel swine‐origin influenza A (H1N1) virus affecting humans was detected in April 2009 in Mexico, Canada, and USA. The S‐OIV infection caused a mild to severe febrile respiratory disease throughout the world. Here, we briefly review the main features of influenza A viruses, which caused also other pandemics in the past, and focus in particular on the epidemiology data of the H1N1 influenza in the Italian region Campania, which resulted the most affected by the S‐OIV and the one with more lethal cases. In Campania, the peak of influenza preceded of about 2 weeks the incidence peak at the national level. Moreover, the percentage of H1N1‐positive patients was much higher in the main town Naples, compared to the other Campania provinces. The age group from 7 months to 17 years was the most affected by the H1N1 infection (43.45%), similarly to what reported at the national level. Here, we discuss the possible reasons of the high H1N1 incidence in Campania and the implications that these findings could have on the future prevention campaigns. J. Cell. Physiol. 227: 2813–2817, 2012.

Serological and virological investigations of young children with acute respiratory syndrome associated with respiratory syncytial virus

From January 1979 to March 1979, 341 young children from the metropolitan area of Naples, Italy, were hospitalized with respiratory virus disease. Diagnosis of patients made from virus isolation and seroconversion indicate that the respiratory syncytial virus was a primary cause of this acute respiratory syndrome.