Sequence uniqueness and sequence variability as modulating factors of human anti-HCV humoral immune response.

We recently compared the HCV polyprotein to the human proteome in order to test whether amino acid sequences unique to the virus could represent immunodominant epitopic determinants of the human humoral immune response against HCV. We identified a relatively limited number of HCV fragments with no/low similarity to the human host that represented exclusive HCV motifs. In this study, the peptides corresponding to low/zero similarity sequences were synthesized and assayed with HCV-infected sera. With different patterns, the synthetic HCV peptides corresponding to low/zero similarity sequences were found to be immunoreactive. In particular, the HCV E1 (315-323) HRMAWDMMM, HCV E2/NS1 (547-555) NWFGCTWMN, and HCV NS5 (2638-2646) YDTRCFDST sequences were immunodominant in the HCV-infected cohort under study. These three peptides correspond to sequences that are endowed with low-similarity to the human proteome, are highly conserved among various HCV strains, and have, potentially, a scarce susceptibility to proteolytic attacks. These data may be of help in defining the multiple factors which concur in the modulation of the human immune response against HCV, eventually providing information for the design of effective anti-HCV vaccines.

Gene therapy in cancer: the missing point.

Over the last century cancer research has produced data leading to a composite picture where gene mutations and epigenetic phenomena strictly relate and overlap. This complexity has repercussions on the anti-cancer therapeutical strategies. The therapeutic pathway paved by the kochian one-cause/one disease principle fails in front of a multigenic multiphenomena disease like cancer. We still do not know what target(s) to hit/modify in order to prevent/stop the carcinogenic progression. On the light of cancer statistics 2005, we discuss the need of exactly defining the cancer targets in order to exploit the high potential of gene therapy.

Cancer prevention and therapy: strategies and problems.

During the next years, molecular diagnostic science and the pharmaceutical industry will face increasing demand for personalized medicine. Therapeutic treatments should be tailored to the needs of individual patient. Patients will inquire for information about potential tumor detection at an early stage when disease can be more likely to be arrested or cured with specific regimens of drug therapy. To respond to this demand, science and industry need to modulate therapeutic approaches to the continuous development of cancer. Now more than ever, it is necessary to fill the knowledge hiatus between the "beginning" and the "end" of cancer development, i.e we need to critically analyze the extensive multi-step process of cancer development that still remains poorly understood.

Cell death: apoptosis versus necrosis (review).

Cell death and the subsequent post-mortem changes, called necrosis, are integral parts of normal development and maturation cycle. Despite the importance of this process, the mechanisms underlying cell death are still poorly understood. In the recent literature, cell death is said to occur by two alternative, opposite modes: apoptosis, a programmed, managed form of cell death, and necrosis, an unordered and accidental form of cellular dying. The incorrect consequence is the overlapping of: a) the process whereby cells die, cell death; and b) the changes that the cells and tissues undergo after the cells die. Only the latter process can be referred to as necrosis and represents a process in cell life. In this review, we discuss the excellent basic research developed in this field during last decades and problems that remain to be resolved in defining both experimentally and mechanicistically the events that lead to and characterize cell death.