G. Toffoli

HLA DR‐DQ combination associated with the increased risk of developing human HCV positive non‐Hodgkin's lymphoma is related to the type II mixed cryoglobulinemia

This investigation was focused on the contribution of individual human leukocyte antigen (HLA)-DR and -DQ alleles to the human hepatitis C virus (HCV)(+) non-Hodgkins lymphoma (NHL), with and without mixed cryoglobulinemia (MC), to study whether individual HLA class II alleles are expressed preferentially or equally in human HCV-specific NHL. For this purpose, peripheral blood mononuclear cells were obtained from two groups of patients with HCV(+) NHL and with or without MC (70 and 71 cases, respectively), and from 4575 blood donors. Eighty-three subjects with HCV infection only, and 118 patients with MC, only without lymphoma, were added as additional control groups. Individual HLA-DR and -DQ alleles were determined using high-resolution sequence-based typing and then data were collected by considering the HLA-DRB1 and DQB1 supertypes on the basis of common structural and functional features, proposed by in silico Bioinformatic studies. From the data, it is evidenced that the DR5-DQ3 HLA combination was strongly associated with the HCV (+) MC (+) NHL group of patients compared with bone marrow donor population (P<or= 0.001, RR = 2.498), while the contribution of DR1-DQ1 was higher in HCV (+) NHL without MC (P<or= 0.001, RR = 2.519). Thus, cryoglobulinemia clinical manifestation was found to be correlated with the preferential use of HLA DR-DQ combination in HCV-associated NHL. These data provide new insight into HCV-associated lymphoproliferative pathogenesis.

p53 expression in human soft tissue sarcomas. Correlation with biological aggressiveness

The p53 gene located at chromosome 17 p13 encodes a MW 53,000 nuclear phosphoprotein which is frequently mutated in many human cancers [1]. The mutant p53 protein has a much longer half-life than the wild-type protein ; the result is a large amount of mutant proteins in transformed cells and tumours. The exact function of p53 protein expression abnormalities in tumour cells has not been completely clarified yet. Several studies have shown that reintroduction of a wild-type p53 gene into p53 deficient cells leads to suppression of the neoplastic phenotype [2]. This suppressor activity may be exerted through the transcriptional control of the proliferation-related genes [3] and/or regulation of DNA replication through wild-type p53 association with DNA replication complexes [4, 5]. It has been supposed that p53 mutations might have a predisposing effect in carcinogenesis and be a favourable event in progression of human tumours. Abnormalities of p53 have been related to the development of various cancers including bladder [6], lung [7], breast [8], colorectal [9] and brain [10] cancer. In this study we investigated p53 expression in human soft tissue sarcomas [HSTS]. The aim was to compare p53 expression with the tumour behaviour of HSTS.

Functional activity of P-glycoprotein localized in subcellular structures and reversal of multidrug resistance (MDR)

The multidrug resistant (MDR) phenotype in human cells is thought to be primarily consequent to the increased expression of the mdrl gene which encodes for a glycoprotein of 170 KD (P-gp) [1]. P-gp causes a reduced intracellular drug accumulation through an energy-dependent active drug efflux [1]. However variations in drug-transmembrane equilibria due to P-gp activity cannot completely explain the MDR phenotype since MDR cells can tolerate intracellular drug concentrations higher than those tolerated by their drug-sensitive parent cells [2].