がんの科学と治療

Interferons (IFNs) may target cancer cells both through their regulation of the immune response, effect on angiogenesis and through direct effect on cancer cells. Treatment response has been demonstrated in osteosarcoma patients, but tumour resistance to IFN-a is common. Hence, understanding the molecular mechanisms involved in response and resistance is essential for improving therapeutic efficacy. Of five xenografts screened for specific growth delay in response to treatment with unconjugated and PEGylated IFN-a2b, one displayed growth inhibition and tumour shrinkage. Growth inhibition increased on a dosing schedule of PEGylated IFN every third day. Xenografts resistant to PEGylated IFN were similarly resistant to unconjugated IFN. Combination treatment with IFN-a2b and doxorubicin resulted in improved growth control rates. Transcriptional profiling analysis of the one sensitive and two resistant xenografts identified a common set of 79 genes significantly affected by IFN-a2b treatment independent of tumour growth inhibition. All but four of the 79 genes were up-regulated. The majority of these genes were well characterized IFN-stimulated genes and core members of the IFN-a signalling pathway. The expression of a set of 128 unique genes changed only in the sensitive xenograft; 52/128 genes were up-regulated. The specific geneexpression pattern seen in the responsive xenograft identified possible pathways important for the antitumor effect of IFN-a in osteosarcoma, including ssubsets of genes involved in cell adhesion and osteogenic tissue development. The observed improved control rates of combined treatment with IFN and doxorubicin are encouraging and should be further explored.

Background To assess tumor control and survival of the patients with laryngeal cancers who received chemoradiation or radiotherapy alone as definitive treatment. Material and Methods Patients with laryngeal cancers who received organ-saving treatment were enrolled in this trial. Results In 147 cases, chemoradiotherapy was administered in 61 patients. Twelve cases were excluded from the analysis because of the treatment interrupt or death. Fifty eight cases had early-staged disease. In median time of follow up (9.9 months), mean overall survival and mean disease free survival were 51 months and 37 months in early lesions, and 30 months and 17 months in locally advanced tumors, respectively. Local control rate was 60% in early-staged and 43.5% in locally advanced cases. The mean total radiation dose significantly affected the tumor control in chemoradiation group. Conclusion It seems that radiotherapy or chemoradiation can be appropriate alternative to total laryngectomy in laryngeal cancers.

In view of the important oncogenic action of lipoxygenase (LOX) and cycloxygenase (COX) enzymatic activities we investigated, by using real time PCR, their presence in human meningiomas. Results indicated the presence of 5-LOX, 12-LOX, 15-LOX1, 15-LOX2, COX-1, COX-2, prostaglandin E (PGE) synthase, prostacyclin (PGI) synthase and thromboxane (TX) synthase transcripts in meningiomas but without relation to the tumor grade, the subtype of meningiomas, the presence of inflammatory infiltrated cells, of an associated edema, mitosis, brain invasion, vascularisation or necrosis. Similar results were found for BLT1 and BLT2 transcripts (encoding LTB4 receptors) and for prostanoid receptor transcripts (EP1-4 for PGE2, IP for PGI2 and TP for TXA2). In conclusion, genes encoding enzymatic activities implicated in the eicosanoid cascade are expressed in meningiomas. LOX- and COX-derived arachidonic acid metabolites might act on tumor growth not only by acting on cell growth but also by altering the local cytokine and/ or angiogenic networks.