Impact of miR-21, miR-126 and miR-221 as prognostic factors of clear cell renal cell carcinoma with tumor thrombus of the inferior vena cava

Clear cell renal cell carcinoma (ccRCC) characterized by a tumor thrombus (TT) extending into the inferior vena cava (IVC) generally indicates poor prognosis. Nevertheless, the risk for tumor recurrence after nephrectomy and thrombectomy varies. An applicable and accurate prediction system to select ccRCC patients with TT of the IVC (ccRCC/TT) at high risk after nephrectomy is urgently needed, but has not been established up to now. To our knowledge, a possible role of microRNAs (miRs) for the development of ccRCC/TT or their impact as prognostic markers in ccRCC/TT has not been explored yet. Therefore, we analyzed the expression of the previously described onco-miRs miR-200c, miR-210, miR-126, miR-221, let-7b, miR-21, miR-143 and miR-141 in a study collective of 74 ccRCC patients. Using the expression profiles of these eight miRs we developed classification systems that accurately differentiate ccRCC from non-cancerous renal tissue and ccRCC/TT from tumors without TT. In the subgroup of 37 ccRCC/TT cases we found that miR-21, miR-126, and miR-221 predicted cancer related death (CRD) accurately and independently from other clinico-pathological features. Furthermore, a combined risk score based on the expression of miR-21, miR-126 and miR-221 was developed and showed high sensitivity and specificity to predict cancer specific survival (CSS) in ccRCC/TT. Using the combined risk score we were able to classify ccRCC/TT patients correctly into high and low risk cases. The risk stratification by the combined risk score (CRS) will benefit from further cohort validation and might have potential for clinical application as a molecular prediction system to identify high- risk ccRCC/TT patients.

Combination of expression levels of miR-21 and miR-126 is associated with cancer-specific survival in clear-cell renal cell carcinoma

BACKGROUND Renal cell carcinoma (RCC) is marked by high mortality rate. To date, no robust risk stratification by clinical or molecular prognosticators of cancer-specific survival (CSS) has been established for early stages. Transcriptional profiling of small non-coding RNA gene products (miRNAs) seems promising for prognostic stratification. The expression of miR-21 and miR-126 was analysed in a large cohort of RCC patients; a combined risk score (CRS)-model was constructed based on expression levels of both miRNAs. METHODS Expression of miR-21 and miR-126 was evaluated by qRT-PCR in tumour and adjacent non-neoplastic tissue in n = 139 clear cell RCC patients. Relation of miR-21 and miR-126 expression with various clinical parameters was assessed. Parameters were analysed by uni- and multivariate COX regression. A factor derived from the z-score resulting from the COX model was determined for both miRs separately and a combined risk score (CRS) was calculated multiplying the relative expression of miR-21 and miR-126 by this factor. The best fitting COX model was selected by relative goodness-of-fit with the Akaike information criterion (AIC). RESULTS RCC with and without miR-21 up- and miR-126 downregulation differed significantly in synchronous metastatic status and CSS. Upregulation of miR-21 and downregulation of miR-126 were independently prognostic. A combined risk score (CRS) based on the expression of both miRs showed high sensitivity and specificity in predicting CSS and prediction was independent from any other clinico-pathological parameter. Association of CRS with CSS was successfully validated in a testing cohort containing patients with high and low risk for progressive disease. CONCLUSIONS A combined expression level of miR-21 and miR-126 accurately predicted CSS in two independent RCC cohorts and seems feasible for clinical application in assessing prognosis.

Ms. hebr. oct. 137 - Sefer totsaʾot ḥayim

Vorbesitzer: Eljāqīm Carmoly; Abraham Merzbacher

Ms. hebr. oct. 126 - Perush masekhet Avot

Vorbesitzer: Eljāqīm Carmoly; Abraham Merzbacher

AMS-C14 analysis of graphite obtained with an Automated Graphitization Equipment (AGE III) from aerosol collected on quartz filters

AMS-14C applications often require the analysis of small samples. Such is the case of atmospheric aerosols where frequently only a small amount of sample is available. The ion beam physics group at the ETH, Zurich, has designed an Automated Graphitization Equipment (AGE III) for routine graphite production for AMS analysis from organic samples of approximately 1 mg. In this study, we explore the potential use of the AGE III for graphitization of particulate carbon collected in quartz filters. In order to test the methodology, samples of reference materials and blanks with different sizes were prepared in the AGE III and the graphite was analyzed in a MICADAS AMS (ETH) system. The graphite samples prepared in the AGE III showed recovery yields higher than 80% and reproducible 14C values for masses ranging from 50 to 300 lg. Also, reproducible radiocarbon values were obtained for aerosol filters of small sizes that had been graphitized in the AGE III. As a study case, the tested methodology was applied to PM10 samples collected in two urban cities in Mexico in order to compare the source apportionment of biomass and fossil fuel combustion. The obtained 14C data showed that carbonaceous aerosols from Mexico City have much lower biogenic signature than the smaller city of Cuernavaca.

Comparative carbon cycle dynamics of the present and last interglacial

Changes in temperature and carbon dioxide during glacial cycles recorded in Antarctic ice cores are tightly coupled. However, this relationship does not hold for interglacials. While climate cooled towards the end of both the last (Eemian) and present (Holocene) interglacials, CO₂ remained stable during the Eemian while rising in the Holocene. We identify and review twelve biogeochemical mechanisms of terrestrial (vegetation dynamics and CO₂ fertilization, land use, wild fire, accumulation of peat, changes in permafrost carbon, subaerial volcanic outgassing) and marine origin (changes in sea surface temperature, carbonate compensation to deglaciation and terrestrial biosphere regrowth, shallow-water carbonate sedimentation, changes in the soft tissue pump, and methane hydrates), which potentially may have contributed to the CO₂ dynamics during interglacials but which remain not well quantified. We use three Earth System Models (ESMs) of intermediate complexity to compare effects of selected mechanisms on the interglacial CO₂ and δ¹³ CO₂ changes, focusing on those with substantial potential impacts: namely carbonate sedimentation in shallow waters, peat growth, and (in the case of the Holocene) human land use. A set of specified carbon cycle forcings could qualitatively explain atmospheric CO₂ dynamics from 8ka BP to the pre-industrial. However, when applied to Eemian boundary conditions from 126 to 115 ka BP, the same set of forcings led to disagreement with the observed direction of CO₂ changes after 122 ka BP. This failure to simulate late-Eemian CO₂ dynamics could be a result of the imposed forcings such as prescribed CaCO₃ accumulation and/or an incorrect response of simulated terrestrial carbon to the surface cooling at the end of the interglacial. These experiments also reveal that key natural processes of interglacial CO₂ dynamics eshallow water CaCO₃ accumulation, peat and permafrost carbon dynamics are not well represented in the current ESMs. Global-scale modeling of these long-term carbon cycle components started only in the last decade, and uncertainty in parameterization of these mechanisms is a main limitation in the successful modeling of interglacial CO₂ dynamics.

Complete Genome Sequence of KPC-3- and CTX-M-15-Producing Klebsiella pneumoniae Sequence Type 307.

Klebsiella pneumoniaesequence type (ST) 307, carryingblaKPC-3,blaCTX-M-15,blaOXA-1,aac(6')-Ib-cr, andqnrB1 genes, is replacing the predominant hyperepidemic ST258 clone in Italy. Whole-genome and complete plasmid sequencing of one ST307 strain was performed and new features were identified.

Ein Sabbathpsalm : Psalm 126

Dolorosa

An den Wassern zu Babel [Musikdruck] : (Psalm 137, Vers I, II)

Hirsch Liwschütz

Psalm 137

E. Simonson