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Programmed cell death, also known as apoptosis, is a normal physiologic process which occurs during embryonic development as well as in maintenance of tissue homeostasis. Increasing evidence suggests that alterations in cell death contribute to the pathogenesis of a number of human diseases, including cancer, viral infections, autoimmune diseases and acquired immunodeficiency syndrome (AIDS). The extraordinary research activity of the past few years has resulted in the characterization of the principal proteins involved in the apoptosis machinery. An area of particular interest has been the induction of apoptosis by two death receptor/ligand pairs, Fas/Fas Ligand and DR4-DR5/TRAIL. The identification of these molecules with the recruited signaling pathways could clarify their physiopathological implications, having a significant impact upon potential therapeutic interventions in diseases associated with cell survival alterations.

Background: After the liver, the lungs represent the most frequent site of metastasis from primary tumours. Surgical treatment of lung secondary neoplasms leads to a significant improvement in survival., Methods: Between 1960-1997, 178 patients with lung metastases underwent surgery at the Thoracic Surgery Department of Turin University in a total of 193 operations. A retrospective study was made in order to identify the prognostic factors which influenced final survival in this population., Results: Overall survival was 47% after 2 years and 20% after five years. Prognosis was not influenced by the size of metastases, the type of surgery, adjuvant therapy and the number of operations on the same patient. On the other hand, useful prognostic factors were found to be the histological type of the primary tumour, the original site of the neoplasm, the number of metastases and, above all, the disease-free interval (DFI)., Conclusions: Lung metastasectomy is an important therapeutic aid in selected patients, whereas the preoperative evaluation of the above prognostic factors enables a reasonably precise prognosis to be made in most patients.

Background: Pancreatic adenocarcinomas are among the most aggressive types of cancer with an extremely poor diagnosis. Since this type of cancer is not well amenable to chemo- and radiotherapy or immunotherapy, surgical resection remains the only feasible treatment to date. Transforming Growth Factor (TGF)-beta and Interleukin (IL)-10 are potent immunomodulators that have been shown to suppress several aspects of the immune response. Vascular Endothelial Growth Factor (VEGF) is a powerful angiogenic factor, recently thought to be involved in neoangiogenesis and metastasis spreading. Therefore the three cytokines may contribute, by different pathways, to immune escape and growth of tumor. This study was conducted to determine the possible significance of TGF-beta1, IL-10 and VEGF as markers for monitoring the clinical course of pancreatic adenocarcinoma patients., Methods: Cytokine serum levels were measured in 30 pancreatic cancer patients and in 30 age and sex-matched healthy subjects., Results: In comparison to serum concentrations in controls, TGF-beta1, IL-10 and VEGF levels were significantly elevated in all patients. Where the patients were divided by groups on the basis of the clinical stage of the disease, no differences were observed in TGF-beta1 levels among the groups. On the contrary, IL-10 and VEGF were more represented in stage IV patients than in stage II and III patients. In addition, the 14 patients who underwent surgical resection had postoperative cytokine serum levels markedly lower than those observed at diagnosis., Conclusions: Overall, the results suggest the importance of these markers in predicting the biological activity of the disease and suggest new targets for future rational therapies.

There is increasing evidence to support the concept that growth and metastasis of solid tumors, including those of gastrointestinal tract, is facilitated by neoangiogenesis. Vascular Endothelial Growth Factor (VEGF) is one of the most powerful known inducer of endothelial cell growth. Therefore, VEGF is likely to contribute to tumor growth by promoting angiogenesis and stroma formation both directly, through its neovascularization inducing activity, and indirectly, by increasing vascular permeability. In addition, VEGF facilitates tumor diffusion favouring metastatic spread of cancer cells. In view of these implications, it is important to understand the physiopathological role played by this factor. In this review the authors present the accumulating body of data on the biological and functional properties of VEGF, paying special reference to new evidence on its contribution in tumor immune escape, through a marked inhibition of differentiation and activity of the professional antigen presenting cells (APC), namely dendritic cells (DC). As the molecular and cellular events that underlie the functional role of VEGF in tumor angiogenesis and immune suppression become better defined, rational pharmacological and/or gene therapies can be derived in order to treat those neoplasms, such as pancreatic adenocarcinoma, not well amenable to chemo- and radiotherapy or immunotherapy.