Combination of antibodies directed against different ErbB3 surface epitopes prevents the establishment of resistance to BRAF/MEK inhibitors in melanoma

Patients with metastatic melanoma bearing V600 mutations in BRAF oncogene clinically benefit from the treatment with BRAF inhibitors alone or in combination with MEK inhibitors. However, a limitation to such treatment is the occurrence of resistance. Tackling the adaptive changes helping cells survive from drug treatment may offer new therapeutic opportunities. Very recently the ErbB3 receptor has been shown to act as a central node promoting survival of BRAF mutated melanoma. In this paper we first demonstrate that ErbB3/AKT hyperphosphorylation occurs in BRAF mutated melanoma cell lines following exposure to BRAF and/or MEK inhibitors. This strongly correlates with increased transcriptional activation of its ligand neuregulin. Anti-ErbB3 antibodies impair the establishment of de novo cell resistance to BRAF inhibition in vitro. In order to more potently ablate ErbB3 activity we used a combination of two anti-ErbB3 antibodies directed against distinct epitopes of its extracellular domain. These two antibodies in combo with BRAF/MEK inhibitors potently inhibit in vitro cell growth and tumor regrowth after drug withdrawal in an in vivo xenograft model. Importantly, residual tumor masses from mice treated by the antibodies and BRAF/ERK inhibitors combo are characterized almost exclusively by large necrotic areas with limited residual areas of tumor growth. Taken together, our findings support the concept that triple therapy directed against BRAF/MEK/ErbB3 may be able to provide durable control of BRAF mutated metastatic melanoma

Underwater archaeological surveys in Salento waters: results and methods

This paper is related to the survey carried out in several coastal sites of Puglia in 2020, within the project UnderwaterMuse. The core of the activities took place at the Torre S. Sabina site, on the Adriatic Sea, where an integrated topographic and photogrammetric survey has been conducted on the late-imperial Roman shipwreck. Another activity, always on the Adriatic Sea, are been conducted in the “Le Cesine” Natural Reserve how led to the identification of a big pier from the Augustan period. On the Ionian Sea, furthermore, in Porto Cesareo Marine Protected Area, new evidence has been added to the numerous ones already known, such as some spectacular formations composed uniquely by cemented sherds of Tripolitanian amphorae (2nd cent. AD). This evidence seems to be significant markers of sea-level changes and the evolution of the seascape

Roca archaeological survey : inquadramento e primissimi risultati

Mobility and interaction have been primarily analysed from the vantage point of the archaeological sites representing the main hubs of interaction. However, such hubs were always immersed in a continuous landscape which had a considerable effect on interaction dynamics. An effect that has started to be taken in due consideration only recently. The Roca Archaeological Survey, of which we here present the first preliminary results, tries to integrate our detailed knowledge based on excavations of the site of Roca Vecchia in Apulia, with a systematic multi-period surface investigation able to assess whether and to what extent the surrounding landscape has affected dynamics of interaction recognised in the main site from the bronze age to modern times

Roca Archaeological Survey: Inquadramento e primissimi risultati

Mobility and interaction have been primarily analysed from the vantage point of the archaeological sites representing the main hubs of interaction. However, such hubs were always immersed in a continuous landscape which had a considerable effect on interaction dynamics. An effect that has started to be taken in due consideration only recently.The Roca Archaeological Survey, of which we here present the first preliminary results, tries to integrate our detailed knowledge based on excavations of the site of Roca Vecchia in Apulia, with a systematic multi-period surface investigation able to assess whether and to what extent the surrounding landscape has affected dynamics of interaction recognised in the main site from the bronze age to modern time

Shipwrecks stories in a “trap bay”: Research and valorization in Torre S. Sabina (Brindisi, Italy)

The 2020 underwater archaeological research in the inlet of Torre Santa Sabina - Baia dei Camerini (Municipality of Carovigno, Brindisi, Italy ) represented the first phase of the pilot intervention of the Interreg Italia-Croatia UnderwaterMuse project, which aims to enhance and make accessible the huge underwater heritage of the areas involved through the creation of submerged archaeological parks and the narrative and communicative use of the virtual reality. The Puglia Region - Department of Tourism, Economics of Culture and Valorization of the Territory, partner of the UnderwaterMuse project, launching these researches aimed at valorisation, has involved the three regional Universities thanks to an agreement. The fruitful synergy between the various actors involved and the support of the territory and the community have allowed the achievement of the objectives of this campaign, preliminary to the broader and more articulated intervention foreseen for the next year. Thanks to the collaboration with the Polytechnic of Turin, the entire stretch of coast was mapped with drone flights, in order to reconstruct the coastal landscape in the various phases, starting from the Bronze Age. Targeted interventions were carried out on the Roman wreck of the imperial age, beached and abandoned at the ancient shore and now submerged due to the relative rise in sea level, and on the remains of on-board equipment of a ship of the Serenissima, the Galea Magna (1598). Another important focus was represented by the stratigraphy of cargos resulting from the various shipwreck episodes, accumulated at the foot of the western cliff

Uno sguardo dall\u2019esterno. Attivit\ue0 marinare e interazione nelle periferie nord occidentali e nord orientali del mondo egeo durante la tarda et\ue0 del Bronzo

Le due aree periferiche prese in esame in questo articolo, Salento e Lemnos, si collocano grosso modo alla stessa distanza dalla Grecia continentale, ma questo non significa, ovviamente, che i processi di interazione verificatisi nel corso della tarda eta\u300 del Bronzo tra queste realta\u300 debbano aver seguito linee di sviluppo affini. Da un lato il differente grado di influenza esercitato dalle civilta\u300 stanziate a ridosso dei cardini del sistema geo-politico del Mediterraneo (regni anatoli- ci, micenei e realta\u300 protourbane dell\u2019Italia meridionale), e dall\u2019altro il condizionamento fisico dei distretti marittimi che ne realizzano i collegamenti, creano, infatti, differenze sostanziali. Le evidenze archeologiche piu\u300 rappresentative offerte dai due siti, inoltre, sembrerebbero indiziare l\u2019appartenenza a due orizzonti cronologici successivi e distinti. Efestia, integrata nel ko\u300smos Egeo fin dalla media eta\u300 del Bronzo, soprattutto in seguito al processo di minoicizzazione di alcune isole del Nord, sembra manifestare una certa congruenza con le realta\u300 della Grecia continentale almeno fino al tracollo della struttura palaziale, quando la presenza micenea sull\u2019isola scompare e viene soppiantata, almeno per cio\u300 che riguarda la produzione materiale, da nuovi apporti di origine tracia o balcanica. L\u2019acme della presenza di materiale miceneo a Roca, invece, viene raggiunta all\u2019indomani del collasso del sistema palaziale, in un contesto di forte fermento economico e sociale che puo\u300 aver direttamente coinvolto le comunita\u300 indigene, in associazione ad altre compagini di provenienza orientale (gruppi fenici e ciprioti), in un processo di conquista di ambiti territoriali e commerciali prima di allora preclusi e probabilmente gestiti di- rettamente dai regni micenei. E\u300 questo il momento delle partecipazioni occidentali alla rete dei traffici condotti nell\u2019Egeo e nel Mediterraneo orientale, come attestano i sempre piu\u300 cospicui ritrovamenti di vasellame (Handmade Burnished Ware e ceramica grigia tornita) e prodotti metallurgici di origine italica

Roca e il mondo egeo tra il XVI e l\u2019XI sec. a.C.: una messa a punto

Roca e il mondo egeo tra il XVi e l\u2019Xi sec. a.c.: una messa a punto - il contributo contiene tre brevi note degli autori su temi attinenti ai rapporti con l\u2019egeo e oggetto di ricerche in corso. nella prima si propone un aggior- namento e una breve sintesi sulla documentazione riguardante le fasi piu\u300 antiche di occupazione. nella seconda e\u300 esposto uno studio quantitativo dei materiali di tipo egeo dal sas X per ricostruire le dinamiche diacroniche dei rapporti. nella terza viene presentata un\u2019analisi delle innovazioni architettoniche registrabili nella fase subappenninica delle mura di for- tificazione

Roca e il mondo egeo tra il XVI e l\u2019XI sec. a.C.: una messa a punto

Roca e il mondo egeo tra il XVi e l\u2019Xi sec. a.c.: una messa a punto - il contributo contiene tre brevi note degli autori su temi attinenti ai rapporti con l\u2019egeo e oggetto di ricerche in corso. nella prima si propone un aggior- namento e una breve sintesi sulla documentazione riguardante le fasi piu\u300 antiche di occupazione. nella seconda e\u300 esposto uno studio quantitativo dei materiali di tipo egeo dal sas X per ricostruire le dinamiche diacroniche dei rapporti. nella terza viene presentata un\u2019analisi delle innovazioni architettoniche registrabili nella fase subappenninica delle mura di for- tificazione