Emergence of sequence type 252 Enterobacter cloacae producing GES-5 carbapenemase in a Czech hospital

ST252 Enterobacter cloacae, producing GES-5 carbapenemase, was isolated in a Czech hospital. bla_GES-5 was part of a novel class 1 integron, In1406, which also included a new allele of the aadA15 gene cassette. In1406 was located on a ColE2-like plasmid, pEcl-35771cz (6953 bp).     

Role of local therapy in the management of patients with metastatic anal squamous cell carcinoma: a National Cancer Database study

BackgroundAbout 10–20% of patients with anal squamous cell carcinoma (SCCa) present with metastatic disease and are usually treated with systemic chemotherapy. However, primary tumor control is crucial as local failure is associated with significant morbidity. Using the largest cohort to date, we report the impact of local therapy on survival among patients with metastatic anal SCCa.MethodsData were collected from US hospitals that contributed to the National Cancer Database (NCDB) between 2004 and 2015. Patients who did not receive palliative systemic chemotherapy were excluded from analysis. Univariate (UVA) and multivariable analyses (MVA) were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to evaluate the association between tumor/patient characteristics and overall survival (OS).ResultsA total of 1,160 patients were identified over the 12 years of study. Median age was 57 years. Majority were female (64.9%), non-Hispanic Whites (79.1%) and had Charlson-Deyo Score of 0 (83.6%). Most common metastatic sites were liver (25.9%), lung (11.6%) and bone (8.5%). More than 79% of the patients had received radiation to the primary site, and 10.4% underwent surgical resection for local control. Use of local therapy correlated closely with OS on MVA (HR 0.66; 0.55–0.79; P<0.001), with a 12-month and 5-year OS rates of 72.8% and 25.7% respectively, compared with 61.1% and 14.6% for patients treated with chemotherapy only. Poor prognostic factors included male gender (HR 1.44; 1.24–1.67; P<0.001), age >70 years (HR 1.28; 1.02–1.62; P=0.034), lack of health insurance (HR 1.32; 1.02–1.71; P=0.034), and cloacogenic zone location (HR 4.02; 1.43–11.30; P=0.008). There was no benefit from abdominoperineal resection (mOS =19.7 months; HR 1.05; 0.48–2.29; P=0.909), but both local resection of the primary (mOS =24.8 months, HR 0.48; 0.29–0.80; P=0.005) and palliative radiation (mOS =22.6 months; HR 0.66; 0.55–0.79; P<0.001) were associated with improved OS.ConclusionsIn addition to systemic therapy, resection of the primary tumor or palliative radiation improved OS in patients with anal SCCa. Patients unlikely to benefit from local control were those >70 years of age, male, lack of health insurance and cloacogenic carcinoma.     

AKT2 is frequently upregulated in HER-2/neu-positive breast cancers and may contribute to tumor aggressiveness by enhancing cell survival

Amplification or overexpression of the HER-2/neu gene in breast cancers is associated with aggressive behavior and resistance to therapeutic regimens. The molecular mechanisms that contribute to therapeutic resistance/survival of HER-2/neu-overexpressing tumor cells have not been well defined. To determine if phosphatidylinositol 3-kinase/AKT signaling contributes to cell survival in HER-2/neu-positive breast cancers, we performed immunohistochemical analyses to evaluate expression of HER-2/neu and AKT in a series of 52 breast carcinomas. Elevated expression of HER-2/neu was found to correlate with overexpression of AKT2 protein and activation of AKT kinase. HER-2/neu-overexpressing breast cancer cell lines were resistant to apoptosis induced by UV treatment and hypoxia, which was suppressed in the presence of the phosphatidylinositol 3-kinase inhibitors LY294002 and wortmannin, indicating a link between AKT activation and stress resistance in HER-2/neu-overexpressing cells. These observations suggest that AKT signaling augments resistance to stress-induced apoptosis in breast cancer cells overexpressing HER-2/neu.     

Inhibition of intracellular Ca2+ signalling, cytotoxicity and antitumor activity of the herbicide oryzalin and its analogues

Purpose: Studies were conducted on oryzalin (3,5-dinitro-N,N-di(n-propyl)sulfanilamide), a widely used dinitroaniline sulfonamide herbicide, which was identified from plant extracts as an inhibitor of mitogen- and growth factor-mediated intracellular free Ca²⁺ ([Ca²⁺]_i) signalling in mammalian cells. Methods and Results: Oryzalin inhibited vasopressin, bradykinin and platelet-derived growth factor [Ca²⁺]_i signalling in Swiss 3T3 fibroblasts with IC₅₀ values of 14, 16 and 18 μM, respectively. ⁴⁵Ca²⁺ uptake into nonmitochondrial stores of saponin-permeabilized Swiss 3T3 cells was inhibited by oryzalin with an IC₅₀ of 34 μM. Oryzalin inhibited colony formation of HT-29 colon carcinoma cells with an IC₅₀ of 8 μM and inhibited the growth of a number of other cancer cell lines and primary human tumors in vitro with IC₅₀ values in the range 3 to 22 μM. A number of oryzalin analogues were studied and an association was found between the ability to inhibit [Ca²⁺]_i signalling and inhibition of the growth of HT-29 human colon cancer cells (P=0.001) and of CCRF-CEM human leukemia cells (P=0.016). Oryzalin at doses up to 600 mg/kg administered orally or subcutaneously daily to mice for 3 to 10 days beginning a day after tumor inoculation inhibited the growth of murine B16 melanoma by 63% but showed no appreciable activity when administered subcutaneously or intraperitoneally to mice beginning a number of days after tumor inoculation against a variety of human tumor xenografts. The peak plasma concentration of oryzalin following repeated subcutaneous administration of oryzalin at 600 mg/kg per day to mice was 37 μM and of its major metabolite N-depropyl oryzalin was 53 μM. Conclusion: It is unlikely that the absence of significant antitumor activity of oryzalin is a result of the inability to achieve adequate plasma concentrations. Received: 24 December 1996 / Accepted: 20 March 1997     

How reliable is MRCP with an SS-FSE sequence at 3.0 T: comparison between SS-FSE BH and 3D-FSE BH ASSET sequences

PurposeThe purpose of the present study was to evaluate the visibility and the image quality of the biliary and pancreatic duct system on magnetic resonance cholangiopancreatography (MRCP) images based on two breath-hold (BH) methods using array spatial sensitivity technique: a single-shot fast spin-echo (SS-FSE) sequence and a three-dimensional single slab fast spin-echo (3D-FSE) sequence.Materials and methodsIn the present prospective comparative study, 47 patients (22 male and 25 female, mean age=50 years, age range=22–82 years) that were referred for MRCP during a 12-month period are included. All of them were referred with suspected pancreaticobiliary disease. All patients underwent MRCP with both a SS-FSE BH sequence and a 3D-FSE BH sequence. Qualitative evaluation regarding the depiction of three segments of the pancreaticobiliary tree and the frequency of artifacts was performed. Two radiologists graded each sequence of the obtained studies in a blinded fashion. Quantitative evaluation including calculation of relative signal intensity (rSI) and relative contrast (RC) ratios at seven segments of the pancreaticobiliary tree between fluid-filled ductal structures and organ parenchyma at the same ductal segments was performed. In order to evaluate the parameters' differences of the two sequences, either in qualitative or in quantitative analysis, the Wilcoxon paired signed-rank test was performed.ResultsOn quantitative evaluation, both rSI and RC ratios of all segments of the pancreaticobiliary tree at SS-FSE BH sequence were higher than those at 3D-FSE BH sequences. This finding was statistically significant (P< .01). On qualitative evaluation, the two radiologists found intrahepatic ducts and pancreatic ducts to be better visualized with SS-FSE BH than with 3D-FSE BH sequence. This finding was statistically significant (P< .02). One of them found extrahepatic ducts to be significantly better visualized with SS-FSE BH sequence. Moreover, the frequency of artifacts was lower in the SS-FSE sequence, a finding that was of statistical significance. Interobserver agreement analysis found at least substantial agreement (κ>0.60) between the two radiologists.ConclusionThe SS-FSE sequence is performed faster and significantly improves image quality; thus, it should be included into the routine MRCP sequence protocol at 3.0 T. Furthermore, we recommended SS-FSE BH MRCP examination to be applied to uncooperative patients or patients in emergency because of its short acquisition time (1 s).     

First episode of shellfish contamination by palytoxin-like compounds from Ostreopsis species (Aegean Sea, Greece).

In order to investigate the toxicity of Ostreopsis species present in Greek coastal waters, cultures of Ostreopsis sp. and Ostreopsis ovata, mixed Ostreopsis field populations and shellfish collected from coastal waters of North Aegean Sea during late summer and autumn periods of 2004, 2005 and 2006 were examined by both mouse bioassay (MBA) and hemolysis neutralization assay (HNA). MBA testing was based on two different extraction protocols, while HNA also included the use of ouabain, a known palytoxin (PLT) antagonist. Results indicated the presence of a compound in both Ostreopsis cells and shellfish tissues, which was strongly toxic to mice. This compound exhibited characteristic symptomatology in mice (death, numbness, waddling gait and blindness) to that of PLT, as well as delayed hemolytic activity, which was neutralized by ouabain. HNA indicated that Ostreopsis cells contained a PLT-like compound (putative PLT, p-PLT) at concentrations ranging between 0.4 and 0.9 pg/cell, whereas concentration in shellfish tissues was estimated to range from about 33.3 to 97.0 microg p-PLT/kg tissue. To our knowledge, this is the first report of p-PLT contamination of shellfish by natural Ostreopsis species populations in European coastal waters and possibly globally, and also the first evidence on Ostreopsis cells' toxicity in the Eastern Mediterranean Sea.