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Head and neck squamous cell carcinoma of the (HNSCC) represents approximately 5% of malignant tumours in Italy. HNSCC are commonly treated with surgery or radiotherapy, or a combination of such therapies. The objectives of treatment are maximum cure rate balanced with organ preservation, restoration of form and function, reduction of morbidities and improvement or maintenance of the patient's quality of life. Immediate reconstructive surgery: local, regional or free flaps are now widely advised in the treatment of these patients. Microsurgical transfer requires expertise, is time and resource consuming, and as a whole requires substantial costs. These considerations introduce some concerns about the wide or indiscriminate use of free flap reconstructive surgery. When considering cost-benefit outcomes of such treatment, the main objective is undoubtedly, survival. This data is underreported in the current literature, whereas functional outcomes of free flaps have been largely diffused and accepted. This study collects data from 1178 patients treated with free flap reconstructive surgery following ablation of HNSCC in a group of Italian tertiary hospitals, all members of the HeadNeck Group affiliated with the Italian Society of Microsurgery. According to many authors, free flap surgery for HNSCC seems to be a beneficial option for treatment even in terms of survival.I tumori spinocellulari del distretto Cervico Facciale rappresentano circa il 5% dei tumori maligni in Italia. Essi sono comunemente trattati con chirurgia o radioterapia, o entrambi le terapie. La ricostruzione rappresenta un momento fondamentale della terapia nel rispetto della qualità di vita di questi pazienti. La microchirurgia ricostruttiva rappresenta la tecnica che offre i migliori risultati funzionali ma è oggetto di discussione in un rapporto costo-benefici. In questo lavoro sono raccolti ed analizzati i dati di 1178 pazienti provenienti dai membri del gruppo testa e collo, affiliato alla società Italiana di Microchirurgia, e i cui dati sono rapportati primariamente alla sopravvivenza.

It is widely believed that the inflammatory events mediated by microglialactivation contribute to several neurodegenerative processes. Alzheimer'sdisease, for example, is characterized by an accumulation of beta-amyloidprotein (Abeta) in neuritic plaques that are infiltrated by reactive microgliaand astrocytes. Although Abeta and its fragment 25-35 exert a direct toxiceffect on neurons, they also activate microglia. Microglial activation isaccompanied by morphological changes, cell proliferation, and release of variouscytokines and growth factors. A number of scientific reports suggest that theincreased proliferation of microglial cells is dependent on ionic membranecurrents and in particular on chloride conductances. An unusual chloride ionchannel known to be associated with macrophage activation is the chlorideintracellular channel-1 (CLIC1). Here we show that Abeta stimulation of neonatalrat microglia specifically leads to the increase in CLIC1 protein and to thefunctional expression of CLIC1 chloride conductance, both barely detectable onthe plasma membrane of quiescent cells. CLIC1 protein expression in microgliaincreases after 24 hr of incubation with Abeta, simultaneously with theproduction of reactive nitrogen intermediates and of tumor necrosis factor-alpha(TNF-alpha). We demonstrate that reducing CLIC1 chloride conductance by aspecific blocker [IAA-94(R(+)-[(6,7-dichloro-2-cyclopentyl-2,3-dihydro-2-methyl-1-oxo-1H-inden-5yl)-oxy]acetic acid)] prevents neuronal apoptosis in neurons cocultured withAbeta-treated microglia. Furthermore, we show that small interfering RNAs usedto knock down CLIC1 expression prevent TNF-alpha release induced by Abetastimulation. These results provide a direct link between Abeta-inducedmicroglial activation and CLIC1 functional expression.

Curcumin, a phenolic compound extracted from the rhizome of Curcuma longa, was found to attenuate NMDA-induced excitotoxicity in primary retinal cultures. This study was conducted to further characterize curcumin neuroprotective ability and analyze its effects on NMDA receptor (NMDAr). METHODS: NMDAr modifications were analyzed in primary retinal cell cultures using immunocytochemistry, whole-cell patch-clamp recording and western blot analysis. Cell death was evaluated with the TUNEL assay in primary retinal and hippocampal cultures. Optical fluorometric recordings with Fura 2-AM were used to monitor [Ca(2+)](i). RESULTS: Curcumin dose- and time-dependently protected both retinal and hippocampal neurons against NMDA-induced cell death, confirming its anti-excitotoxic property. In primary retinal cultures, in line with the observed reduction of NMDA-induced [Ca(2+)](i) rise, whole-cell patch-clamp experiments showed that a higher percentage of retinal neurons responded to NMDA with low amplitude current after curcumin treatment. In parallel, curcumin induced an increase in NMDAr subunit type 2A (NR2A) level, with kinetics closely correlated to time-course of neuroprotection and decrease in [Ca(2+)](i). The relation between neuroprotection and NR2A level increase was also in line with the observation that curcumin neuroprotection required protein synthesis. Electrophysiology confirmed an increased activity of NR2A-containing NMDAr at the plasma membrane level.

Pancreatic acinar cell carcinoma (PAC) is a rare pancreatic tumor for which no information about chromosomal anomalies is available. We examined six primary PACs by comparative genomic hybridization (CGH). All cases showed chromosomal changes. A total of 106 gains and 48 losses was detected. Consensus regions of gain were identified on chromosomes 1, 12, and X: 1q21 in four cases, 1q42 in three cases, 12p11.2 in four cases, and Xq12-21 in three cases. Recurrent losses were found at 16p13.2-p13.1 in three cases and at 16q23 in three cases. To verify these chromosomal imbalances, microsatellite analysis of matched normal and tumor DNA was performed using PCR-amplified markers for chromosomes 1, 12, and 16 in the regions showing nonrandom gains or losses. This analysis showed allelic imbalances in tumor DNA consistent with the CGH profiles. Our CGH study suggests that PAC shows a characteristic pattern of chromosomal alterations, involving gain at 1q, 12p, and Xq and loss of sequences at 16p and 16q. This pattern appears unique among solid tumors and is markedly different from that detected in pancreatic ductal carcinomas by the same technique. This suggests that PAC tumorigenesis involves different molecular pathways than those involved in the more common pancreatic ductal tumors. Genes Chromosomes Cancer 28:294-299, 2000.