Collective radioresistance of T47D breast carcinoma cells is mediated by a Syncytin-1 homologous protein

It is generally accepted that radiotherapy must target clonogenic cells, i.e., those cells in a tumour that have self-renewing potential. Focussing on isolated clonogenic cells, however, may lead to an underestimate or even to an outright neglect of the importance of biological mechanisms that regulate tumour cell sensitivity to radiation. We develop a new statistical and experimental approach to quantify the effects of radiation on cell populations as a whole. In our experiments, we change the proximity relationships of the cells by culturing them in wells with different shapes, and we find that the radiosensitivity of T47D human breast carcinoma cells in tight clusters is different from that of isolated cells. Molecular analyses show that T47D cells express a Syncytin-1 homologous protein (SyHP). We observe that SyHP translocates to the external surface of the plasma membrane of cells killed by radiation treatment. The data support the fundamental role of SyHP in the formation of intercellular cytoplasmic bridges and in the enhanced radioresistance of surviving cells. We conclude that complex and unexpected biological mechanisms of tumour radioresistance take place at the cell population level. These mechanisms may significantly bias our estimates of the radiosensitivity of breast carcinomas in vivo and thereby affect treatment plans, and they call for further investigations

c-Abl and Src-family kinases cross-talk in regulation of myeloid cell migration

AbstractCytoskeleton dynamics are regulated by Src-family tyrosine kinases (SFKs) and c-Abl. We found that the SFK members Hck and c-Fgr regulate tyrosine phosphorylation of c-Abl and c-Abl associates with β1 integrin-bound Hck or c-Fgr in murine macrophages. Studies with selective inhibitors and cells from SFK-deficient mice showed that c-Abl and SFK regulate migration and activation of the small GTPases Cdc42 and Rac in macrophages. Additionally, human neutrophil chemotactic activity was reduced by c-Abl inhibitors, and neutrophils from chronic myeloid leukaemia patients displayed an increased chemotactic ability. Hence, Src-family kinase and c-Abl cross-talk in the regulation of myeloid cell migration.Structured summaryMINT-7296608: Integrin beta-1 (uniprotkb:P09055) physically interacts (MI:0914) with Hck (uniprotkb:P08103), Abl (uniprotkb:P00520) and Fgr (uniprotkb:P14234) by anti bait coimmunoprecipitation (MI:0006) MINT-7296596: Integrin beta-1 (uniprotkb:P09055) physically interacts (MI:0914) with Fgr (uniprotkb:P14234) and Abl (uniprotkb:P00520) by anti bait coimmunoprecipitation (MI:0006

Genomic Characterization of Arcobacter butzleri Isolated From Shellfish: Novel Insight Into Antibiotic Resistance and Virulence Determinants

Arcobacter (A.) butzleri is an emerging pathogenic microorganism, whose taxonomy has been recently suggested to be emended to the Aliarcobacter (Al.) butzleri comb. nov. Despite extensive taxonomic analysis, only few fragmented studies have investigated the occurrence and the prevalence of virulence and antibiotic resistance determinants of this species in strains isolated from shellfish. Herein we report for the first time the whole genome sequencing and genomic characterization of two A. butzleri strains isolated from shellfish, with particular reference to the antibiotic, heavy metals and virulence determinants. This study supported the taxonomic assignment of these strains to the Al. butzleri species, and allowed us to identify antibiotic and metal resistance along with virulence determinants, also additional to those previously reported for the only two A. butzleri strains from different environments genomically characterized. Moreover, both strains showed resistance to β-lactams, vanocomycin, tetracycline and erythromycin and susceptibility to aminoglycosides and ciprofloxacin. Beside enlarging the availability of genomic data to perform comparative studies aimed at correlating phenotypic differences associated with ecological niche and geographic distribution with the genetic diversity of A. butzleri spp., this study reports the endowment of antibiotic and heavy metal resistance and virulence determinants of these shellfish-isolated strains. This leads to hypothesize a relatively high virulence of A. butzleri isolated from shellfish and prompt the need for a wider genomic analysis and for in vitro and in vivo studies of more strains isolated from this and other ecological niches, to unravel the mechanism of pathogenicity of this species, and the potential risk associated to their consumption

Pattern of care and effectiveness of treatment for glioblastoma patients in the real world: Results from a prospective population-based registry. Could survival differ in a high-volume center?

BACKGROUND: As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. METHODS: Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. RESULTS: Two hundred sixty-seven GBM patients (median age, 64 y; range, 29-84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2-12.4). The 139 patients 64aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0-18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248-0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388-0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328-0.986; P = .0446). CONCLUSIONS: The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged 6470 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor

Meccanismi di regolazione del movimento cellulare: ruolo di tirosin chinasi della famiglia SRC e ABL

Il movimento direzionato è un processo cellulare fondamentale, essenziale per vari fenomeni biologici e patologici, quali ad esempio l’embriogenesi, la risposta infiammatoria, la riparazione e lo sviluppo tissutale ed i tumori. È generalmente accettato che la forza guida per il movimento cellulare è data dalla riorganizzazione dinamica del citoscheletro di actina, che guida le protrusioni al fronte della cellula e la ritrazione alla coda, ma è tuttavia noto che un’efficiente migrazione richiede variazioni ordinate in molte altre attività cellulari, come la secrezione direzionata, che fornisce nuovi componenti alle membrane, il “turnover” delle interazioni fra cellula e matrice, che controlla l’adesione, e variazioni nella trascrizione genica. Perché avvenga quindi un effettivo spostamento della cellula è necessaria l’integrazione spazio-temporale di numerosi processi, che coinvolgono il riarrangiamento del citoscheletro di actina e varie proteine accessorie ad esso associate. Un’efficace migrazione direzionata richiede in particolare l’acquisizione ed il mantenimento da parte della cellula di un’asimmetria spaziale, che si manifesta in una morfologia polarizzata, che porta ad una netta distinzione fra il fronte e la coda della cellula stessa. [...]not availabl

Influence of Cold Storage on Pear Physico-Chemical Traits and Antioxidant Systems in Relation to Superficial Scald Development

Superficial scald is the most common physiological disorder in apples and pears and causes huge economic losses worldwide. The aim of this study is to determine the different scald susceptibilities of seven pear cultivars/selections during five months of cold storage (CS). Four advanced pear selections and three commercial cultivars were harvested from an orchard located in Emilia-Romagna region, and cold stored at −1 °C and 85% relative humidity (RH).After 90, 120, and 150 days, fruits of each cultivar and selection were removed for ripening for 4 d, after which scald damage, physico-chemical and nutraceutical traits, and enzymatic antioxidant systems were evaluated on peel and pulp. ‘Abbé Fétel’, ‘Falstaff’, and ‘CREA 171’ did not showed superficial scald symptoms after 90 days, while ‘Doyenne du Comice’ and ‘CREA 264’ showed the highest susceptibility. After 90 days, CS ‘Falstaff’ and ‘CREA 179’ showed the highest total polyphenol content (TPH) in peel, followed by ‘Doyenne du Comice’ and ‘AbbéFétel’; lowest TPH was detected in ‘CREA 264’. After 120 and 150 days of CS, ‘Abbé Fétel’ and ‘CREA 171’ showed the highest peel TPH. ‘CREA 264’ and ‘CREA 125’ reached the lowest values of TPH during the three CS time periods. Superoxide dismutase and catalase activities were higher in the peel of scald-resistant than that in scald-susceptible pear cultivars/advanced selections. Superficial scald induced an increase in polyphenoloxidase, and guaiacol peroxidase activities involved in fruit-browning during CS. Furthermore, we observed an increase in lipoxygenase activity and consequent membrane damage in both the peel and flesh of the fruit. This study indicates that pear cultivars/advanced selections have different superficial scald susceptibilities that enable them to induce the activity of several antioxidant enzymes, following CS