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The 45th Annual Meeting of the Italian Cancer Society (SIC), held at the Centro Congressi Giovanni XXIII in Bergamo, Italy on 9-12 November, 2003, attracted almost 400 participants. The Scientific Committee chaired by R Giavazzi (Mario Negri Institute, Bergamo) and the board of the Italian Cancer Society produced a packed and varied program. Plenary sessions with keynote speakers (24 lectures) were combined with oral proffered papers (20 selected presentations), providing a platform from laboratory science to clinical interventions. Two hundred and sixty-one abstracts were submitted to the conference and presented in poster and poster discussion sessions, providing a stimulating ground for discussion and a network of interactive collaboration among young investigators. The venue of Bergamo offered exceptional hospitality with social events in the beautiful old town and at the Modern Art Museum. We hope that the following report gives an idea of the event and will encourage the reader to attend the 46th meeting of the SIC, 24-26 October, 2004 in Pisa.

The 45th Annual Meeting of the Italian Cancer Society (SIC), held at the Centro Congressi Giovanni XXIII in Bergamo, Italy on 9-12 November, 2003, attracted almost 400 participants. The Scientific Committee chaired by R Giavazzi (Mario Negri Institute, Bergamo) and the board of the Italian Cancer Society produced a packed and varied program. Plenary sessions with keynote speakers (24 lectures) were combined with oral proffered papers (20 selected presentations), providing a platform from laboratory science to clinical interventions. Two hundred and sixty-one abstracts were submitted to the conference and presented in poster and poster discussion sessions, providing a stimulating ground for discussion and a network of interactive collaboration among young investigators. The venue of Bergamo offered exceptional hospitality with social events in the beautiful old town and at the Modern Art Museum. We hope that the following report gives an idea of the event and will encourage the reader to attend the 46th meeting of the SIC, 24-26 October, 2004 in Pisa.

Here we investigate the mechanism(s) involved in the c-Myc-dependent drug response of melanoma cells. By using three M14-derived c-Myc low-expressing clones, we demonstrate that alkylating agents, cisplatin and melphalan, trigger apoptosis in the c-Myc antisense transfectants, but not in the parental line. On the contrary, topoisomerase inhibitors, adriamycin and camptothecin, induce apoptosis to the same extent regardless of c-Myc expression. Because we previously demonstrated that c-Myc downregulation decreases glutathione (GSH) content, we evaluated the role of GSH in the apoptosis induced by the different drugs. In control cells treated with one of the alkylating agents or the others, GSH depletion achieved by l-buthionine-sulfoximine preincubation opens the apoptotic pathway. The apoptosis proceeded through early Bax relocalization, cytochrome c release, and concomitant caspase-9 activation, whereas reactive oxygen species production and alteration of mitochondria membrane potential were late events. That GSH was determining in the c-Myc-dependent drug-induced apoptosis was demonstrated by altering the intracellular GSH content of the c-Myc low-expressing cells up to the level of controls. Indeed, GSH ethyl ester-mediated increase of GSH abrogated apoptosis induced by cisplatin and melphalan by inhibition of Bax/cytochrome c redistribution. The relationship among c-Myc, GSH content, and the response to alkylating agent has been also evaluated in the M14 Myc overexpressing clones as well as in the melanoma JR8 c-Myc antisense transfectants. All together, these results demonstrate that GSH plays a key role in governing c-Myc-dependent drug-induced apoptosis.

The aim of this study was twofold: to assess the relationship between c-Myb and Bcl-x expression and to evaluate the prognostic significance of their expression in colorectal carcinoma (CRC) patients. Analysis of tumors from 91 CRC patients for expression of c-Myb and Bcl-x revealed a significant relationship between these two proteins. Kaplan-Meier's analysis showed an increased risk of relapse and death in patients whose tumor specimens displayed high c-Myb levels and Bcl-x positivity. Similar results were also observed excluding Dukes' D patients. Molecular analysis using three c-Myb-overexpressing LoVo clones indicated that c-Myb overexpression was accompanied by up-regulation of Bcl-x(L) protein and mRNA. Tumors originating from these clones injected in nude mice were significantly larger than those formed in mice injected with parental or vector-transfected LoVo cells. Moreover, tumors derived from parental and control vector-transfected but not from c-Myb-overexpressing LoVo cells showed high frequency of apoptotic cells. These results provide direct evidence of an association between c-Myb and Bcl-x expression and suggest that expression of both molecules might be a useful prognostic marker in CRC.

Expression of type II receptor of transforming growth factor beta (TbetaRII) is necessary for this factor to inhibit the growth of thyroid epithelial cells. In rat thyroid transformed cells, the resistance to transforming growth factor beta (TGFbeta) is associated with a decreased expression of TbetaRII mRNA and protein. Reduced TbetaRII expression has also been found in human thyroid differentiated and undifferentiated carcinomas. To investigate the role of TbetaRII in modulating the tumorigenic potential of k-ras-transformed thyroid cells, we transfected these cells with an expression vector carrying the human TbetaRII gene, regulated by an inducible promoter. Isolated clones, overexpressing TbetaRII, showed a reduction in the anchorage-dependent and -independent cell growth, compared with control k-ras-transformed cells. When transplanted in athymic nude mice, the transfected clones presented a decrease in tumorigenicity with respect to the highly malignant parental cells. Moreover, the diminished tumorigenic ability of the clones studied was accompanied by a statistically significant reduction in spontaneous and lung artificial metastases. Taken together, our data demonstrate that TbetaRII acts as a potent tumor suppressor gene when overexpressed in malignant thyroid cells.

The modulatory activity of the polar solvent N-methylformamide (NMF) on the effects of hyperhermic treatment was investigated on a human melanoma cell line (M14). Cells treated with NMF alone (1% for 20 h), hyperthermia (Hyp) alone (42.5 degrees C for 2 h) and with the two different sequences of treatment (NMF--Hyp and Hyp--NMF) were analysed by scanning electron microscopy and fluorescence microscopy. Moreover, their clonogenic efficiency and adherence properties were assessed. The results obtained can be summarized as follows. (a) The sequence Hyp--NMF appeared to be more cytotoxic than the reverse sequence or NMF and Hyp given alone. (b) Heat induced cell swelling and detachment from the substrate. The pretreatment with the polar solvent was capable of preventing such alterations. (c) Fluorescence microscopy revealed remarkable changes induced by hyperthermia on actin network, vimentin distribution and vinculin expression. NMF administration proved to be capable of modulating these changes. In particular, the actin and vimentin networks showed a quite normal arrangement in NMF--Hyp treated cells and very altered patterns in cells treated with the reverse sequence. Concerning the effects on the adhesion plaques, revealed by vinculin labeling, a considerable increase in the expression of these structures was observed after NMF treatment. (d) A remarkable increase of the attachment to collagen I and laminin molecules was revealed in NMF treated cells, whereas heat exposure reduced the number of adherent cells. Considered all together, the results obtained indicate that the administration of NMF after hyperthermia enhances the cytotoxic effect and modifies cell adherence properties, responsible for dissemination and metastasis.