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OBJECTIVE: Anaplastic lymphoma kinase (ALK) gene has been demonstrated to be rearranged, mutated or amplified in several haematological and solid tumors. Moreover, the use of ALK inhibitors has recently revolutionized the treatment of ALK-rearranged patients affected by non-small cell lung carcinoma. Herein we review the genetic alterations of ALK in melanocytic neoplasms described in literature, focusing on their potential diagnostic and predictive role. MATERIALS AND METHODS: The Authors reviewed the pertinent literature through research on PubMed server was performed typing the terms "ALK", "Anaplastic lymphoma kinase", "ALKATI", "Melanoma", "Spitz", "Spitzoid". RESULTS: ALK translocations were demonstrated in melanocytic neoplasms, particularly in acral melanoma and spitzoid tumors. ALKATI was described in primary and metastatic melanoma, indicating its early occurrence in oncogenesis, with varying immunohistochemical expression of the protein. CONCLUSIONS: The identification of the specific type of ALK mutations could be interesting for planning biologic therapy of melanoma patients. Further studies are needed to evaluate the possibility to introduce an ALK-targeted therapy in patients affected by malignant melanoma.

We have only now noticed that in Fig. 3a, the immunohistochemical analysis of IL-4Rα on paraffin-embedded sections from breast is incorrect: IL-4 from breast was duplicated and used for the IL-4Rα staining. The correct Fig. 3a is given below.

This review presents a multidisciplinary framework for integrating the ecological, regulatory, procedural and technical aspects of forest management for fires prevention under Mediterranean environments. The aims are to: i) provide a foreground of wildfire scenario; ii) illustrate the theoretical background of forest fuel management; iii) describe the available fuel management techniques and mechanical operations for fire prevention in forest and wildland-urban interfaces, with exemplification of case-studies; iv) allocate fire prevention activities under the hierarchy of forest planning. The review is conceived as an outline commentary discussion targeted to professionals, technicians and government personnel involved in forestry and environmental management.

Il lavoro esamina le relazioni tra pianificazione forestale a livello regionale e locale(PFR e piani di assestamento forestale) e la relativa pianificazione antincendio. in particolare si evidenzia l'importanza della relazione con il livello locale nella programmazione di azioni selvicolturali volte a diminuire il livello di rischio e gestire il combustibile, nella possibilità di aumentare la resilienza dei sistemi.

I dati relativi agli ultimi anni e le previsioni per i prossimi decenni di quasi tutti i modelli climatici a livello globale e regionale evidenziano un aumento della frequenza di eventi estremi come intense precipitazioni, alluvioni, colate di fango e frane. Con questa prospettiva è di prioritaria importanza la valutazione del ruolo, attuale e futuro, svolto dai popolamenti forestali nel prevenire e mitigare alcuni pericoli naturali e nel difendere il suolo nei confronti dell’erosione. Effetti dell’abbandono degli spazi rurali ed espansione del bosco, processi idrologici e pericoli naturali, a scala di popolamento forestale ed a scala di bacino, sono oggetto di studio in Italia da diversi decenni. In questi ultimi anni le conoscenze di questi processi e del ruolo dei sistemi forestali nella prevenzione e mitigazione dei pericoli naturali sono migliorate sia perché è aumentata la disponibilità di studi e di dati quantitativi, sia perché sono stati utilizzati alcuni innovativi approcci modellistici. I dati sperimentali raccolti e gli scenari prodotti dai modelli costituiscono un importante supporto alla gestione dei popolamenti forestali ed alle scelte di pianificazione del territorio montano. In questo lavoro viene discusso lo stato dell’arte della ricerca italiana in questo settore e vengono presentati alcuni casi di studio significativi in riferimento all’applicazione di modelli.

Colon cancer comprises a small population of cancer stem cells (CSC) that is responsible for tumor maintenance and resistant to cancer therapies, possibly allowing for tumor recapitulation once treatment stops. We previously demonstrated that such chemoresistance is mediated by autocrine production of IL-4 through the up-regulation of antiapoptotic proteins. Several innate and adaptive immune effector cells allow for the recognition and destruction of cancer precursors before they constitute the tumor mass. However, cellular immune-based therapies have not been experimented yet in the population of CSCs. Here, we show that the bisphosphonate zoledronate sensitizes colon CSCs to Vgamma9Vdelta2 T cell cytotoxicity. Proliferation and production of cytokines (TNF-alpha and IFN-gamma) and cytotoxic and apoptotic molecules (TRAIL and granzymes) were also induced after exposure of Vgamma9Vdelta2 T cells to sensitized targets. Vgamma9Vdelta2 T cell cytotoxicity was mediated by the granule exocytosis pathway and was highly dependent on isoprenoid production by of tumor cells. Moreover, CSCs recognition and killing was mainly TCR mediated, whereas NKG2D played a role only when tumor targets expressed several NKG2D ligands. We conclude that intentional activation of Vgamma9Vdelta2 T cells by zoledronate may substantially increase antitumor activities and represent a novel strategy for colon cancer immunotherapy.

To date, few studies of preoperative chemotherapy or chemoradiotherapy (crt) in gastroesophageal junction (gej) cancer have been statistically powered, indeed, gej tumours have thus far been grouped with esophageal or gastric cancer in phase iii trials, thereby generating conflicting results. We studied 41 patients affected by locally advanced Siewert type i and ii gej adenocarcinoma who were treated with a neoadjuvant crt regimen [folfox4 (leucovorin&ndash, 5-fluorouracil&ndash, oxaliplatin) for 4 cycles, and concurrent computed tomography&ndash, based three-dimensional conformal radiotherapy delivered using 5 daily fractions of 1.8 Gy per week for a total dose of 45 Gy], followed by surgery. Completeness of tumour resection (performed approximately 6 weeks after completion of crt), clinical and pathologic response rates, and safety and outcome of the treatment were the main endpoints of the study. All 41 patients completed preoperative treatment. Combined therapy was well tolerated, with no treatment-related deaths. Dose reduction was necessary in 8 patients (19.5%). After crt, 78% of the patients showed a partial clinical response, 17% were stable, and 5% experienced disease progression. Pathology examination of surgical specimens demonstrated a 10% complete response rate. The median and mean survival times were 26 and 36 months respectively (95% confidence interval: 14 to 37 months and 30 to 41 months respectively). On multivariate analysis, TNM staging and clinical response were demonstrated to be the only independent variables related to long-term survival. In our experience, preoperative chemoradiotherapy with folfox4 is feasible in locally advanced gej adenocarcinoma, but shows mild efficacy, as suggested by the low rate of pathologic complete response.

We investigated the mechanisms involved in the resistance to cell death observed in epithelial cancers. Here, we identify that primary epithelial cancer cells from colon, breast and lung carcinomas express high levels of the antiapoptotic proteins PED, cFLIP, Bcl-xL and Bcl-2. These cancer cells produced interleukin-4 (IL-4), which amplified the expression levels of these antiapoptotic proteins and prevented cell death induced upon exposure to TRAIL or other drug agents. IL-4 blockade resulted in a significant decrease in the growth rate of epithelial cancer cells and sensitized them, both in vitro and in vivo, to apoptosis induction by TRAIL and chemotherapy via downregulation of the antiapoptotic factors PED, cFLIP, Bcl-xL and Bcl-2. Furthermore, we provide evidence that exogenous IL-4 was able to upregulate the expression levels of these antiapoptotic proteins and potently stabilized the growth of normal epithelial cells rendering them apoptosis resistant. In conclusion, IL-4 acts as an autocrine survival factor in epithelial cells. Our results indicate that inhibition of IL-4/IL-4R signaling may serve as a novel treatment for epithelial cancers.

OBJECTIVE: To determine whether prolongation of the inflammatory reaction in patients with Behçet's disease (BD) is related to apoptosis resistance and is associated with the up-regulation of antiapoptotic factors. METHODS: The percentage of cell death was evaluated by flow cytometry in peripheral blood mononuclear cells from 35 patients with BD and 30 healthy volunteers. The expression levels of antiapoptotic factors and NF-kappaB regulatory proteins were measured using Western blotting and immunohistochemical analyses. To down-regulate NF-kappaB nuclear translocation, BD T lymphocytes were exposed in vitro to thalidomide and subjected to transfection with NF-kappaB small interfering RNA. RESULTS: Although CD95 is highly expressed in BD T cells, the absence of sensitivity to CD95-induced apoptosis observed may be attributable to the inhibitory action of antiapoptotic genes. Immunoblot analysis for major antiapoptotic proteins showed considerable up-regulation of the short form of cellular FLIP (cFLIP) and Bcl-x(L) in BD activated T cells, while levels of Bcl-2, caspase 3, and caspase 8 in activated T cells from patients with BD were comparable with those in activated T cells from normal donors. Moreover, expression of IKK and IkappaB was up-regulated, whereas NF-kappaB translocated to the nucleus in BD T cells, suggesting that NF-kappaB activation may modulate the expression of antiapoptotic genes. Interestingly, thalidomide and NF-kappaB small interfering RNA down-regulated cFLIP and Bcl-x(L) expression levels and sensitized BD activated T cells to CD95-induced apoptosis. CONCLUSION: Taken together, these results indicate that NF-kappaB contributes to the regulation of the apoptosis-related factors and death receptors leading to apoptosis resistance in BD T cell subsets. Our results suggest that NF-kappaB plays a crucial role in the pathogenesis of BD, and that its pharmacologic control could represent a key strategy in modulating specific immune-mediated disease.

La presenza di lembi di foreste con caratteri di vetustà assume particolare valenza poiché il loro studio consente di interpretare meglio i dinamismi naturali in assenza di interventi antropici da lunghi periodi. Nel lavoro viene preso in esame un bosco vetusto di pino laricio nel quale è presente una pineta pura a cui si affianca una pineta in evoluzione. Al suo interno sono state discriminate e studiate separatamente tre situazioni: pineta pura, pineta a maggiore densità con presenza di latifoglie, pineta a minore densità con presenza di latifoglie. Per ognuna è stata eseguita la caratterizzazione strutturale anche attraverso l'applicazione del sistema di indici del gruppo NBSI e dell'indice di Latham. Inoltre, è stata stimata la necromassa censendo separatamente gli alberi morti in piedi, gli alberi morti a terra, i frammenti legnosi e le ceppaie, effettuando la classificazione del grado di decomposizione secondo il sistema proposto da Hunter (1990). Le relazioni evidenziate tra variazioni dei parametri strutturali e ingresso di specie diverse dal pino apportano da un lato un contributo di conoscenze sulle dinamiche dei boschi in assenza di interventi antropici da lungo periodo, dall'altro consentono di confermare come il trattamento codificato da CianCio et al. (2006) nel "taglio a scelta a piccoli gruppi" rappresenti l'approccio selvicolturale che consente la conservazione delle pinete, anche dove ci sono condizioni pedoclimatiche favorevoli per un ingresso di specie diverse, quali in questo caso, il cerro.

Lymphoepithelial carcinoma is an undifferentiated nasopharyngeal carcinoma with lymphoid stroma and non-keratinizing squamous cells with distinctive clinical, epidemiological and etiological features. Conversely, lymphoepithelioma-like carcinomas (LELCs) are carcinomas that arise outside the nasopharynx but resemble a lymphoepithelioma histologically. In this case study, LELC presentation in connective tissue (left sternocleidomastoid muscle) is peculiar and unusual, but its diagnosis is supported by histological findings and clinical history, especially long disease free survival and no primary lesions in nasopharynx and lung district. We also discuss the pathogenesis, hypothesizing an embryological theory. To our knowledge, it could be the first reported case of a primary connective tissue LELC to the neck.