The Immune Landscape of Cancer

We performed an extensive immunogenomic anal-ysis of more than 10,000 tumors comprising 33diverse cancer types by utilizing data compiled byTCGA. Across cancer types, we identified six im-mune subtypes\u2014wound healing, IFN-gdominant,inflammatory, lymphocyte depleted, immunologi-cally quiet, and TGF-bdominant\u2014characterized bydifferences in macrophage or lymphocyte signa-tures, Th1:Th2 cell ratio, extent of intratumoral het-erogeneity, aneuploidy, extent of neoantigen load,overall cell proliferation, expression of immunomod-ulatory genes, and prognosis. Specific drivermutations correlated with lower (CTNNB1,NRAS,orIDH1) or higher (BRAF,TP53,orCASP8) leukocytelevels across all cancers. Multiple control modalitiesof the intracellular and extracellular networks (tran-scription, microRNAs, copy number, and epigeneticprocesses) were involved in tumor-immune cell inter-actions, both across and within immune subtypes.Our immunogenomics pipeline to characterize theseheterogeneous tumors and the resulting data areintended to serve as a resource for future targetedstudies to further advance the field

Molecular analysis of sentinel lymph nodes and search for molecular signatures of the metastatic potential of breast cancer

Molecular assays are a new and invaluable tool in the assessment of axillary lymph node status and metastatic potential of breast cancer. Many protocols for assessing the sentinel lymph node (SLN) status have been developed based on cytology and/or histology, showing that the rate of detection of metastasis increases with the number of histologic sections examined and with use of immunohistochemical staining in addition to conventional Hematoxylin & Eosin staining. However, full standardization of protocols for this procedure has not been achieved. Further attempts to increase sensitivity and specificity of sentinel node analysis include molecular biology-based techniques such as the real-time polymerase chain reaction (RT-PCR) and, more recently, one step nucleic acid amplification (OSNA). The latter technique, that has sensitivity close to 100% and extremely high specificity along with good reproducibility, allows analysis of the SLN in full with an intraoperative procedure in approximately 30 minutes. This highly standardized method permits to compare results between groups and predicts the probability of involvement of the remaining axillary lymph nodes based on the total tumor load of the SLN(s). Results of multicenter clinical trials suggest that OSNA allows a better personalization of patients' care based on the results of SLN analysis, because it offers criteria to select patient with metastatic SLN who will not receive additional benefit from axillary clearance. Due to the current controversy on the best treatment of the axilla after a positive SLN, the SLN copy number of CK19 mRNA can have a high impact on therapeutic decisions in this group of patients. Breast cancer is a highly heterogeneous group of diseases, characterized by remarkable differences in the histopathological features, response to treatment and clinical outcome. Most of the clinical and translational research efforts during the last decades aimed at identifying markers that would allow to predict the metastatic potential of early breast cancer, and hence to assess accurately its prognosis and to inform the choice of adjuvant systemic treatments. It is now clear that neoplastic transformation, tumor progression and response to treatment are driven and accompanied by the deregulated expression of hundred or thousand genes, whose status cannot be assessed by the currently established histopathological and immunohistochemical approach. The new molecular assays have elicited a great deal of expectations, and for the most part they have been enthusiastically welcomed as potentially offering new chances for a better and more personalized care of the patients. Many, however, are still reluctant to consider these assays ready for use in the clinical practice, and keep waiting for a confirmatory evidence of their utility when the results of ongoing clinical trials will be mature

Forage type and transportation stress effects on gut microbial counts and meat quality in goats

An experiment was conducted to determine the effects of feeding highly condensed tannin legume (sericea lespedeza, SL; Lespedeza cuneata) forage on gastrointestinal tract microbial counts and meat quality in goats. Intact male Spanish kids were kept in 0.40 ha paddocks of SL, bermudagrass (BG; Cynodon dactylon; control), or a combination of SL + BG (n = 10 goats per treatment group) for 8 wk. All goats were supplemented with a commercial feed pellet at 0.45 kg·head−1·d−1 for the first 4 wk and 0.23 kg·head−1·d−1 for the final 4 wk of the trial. At the end of the experiment, half the goats from each paddock were subjected to 3 h transportation stress, then all animals were humanely slaughtered. Diet or stress did not have a significant effect on skin Escherichia coli, coliform, or aerobic plate counts, and carcass, rumen, and fecal bacterial counts. Muscle pH at 24 h postmortem tended (P = 0.06) to be higher in transported compared with non-transported goats. The results indicate that SL consumption by goats for 8 wk did not significantly affect gastrointestinal tract, skin, and carcass microbial counts or meat quality, although preslaughter stress could influence meat quality due to changes in the course of postmortem pH decline.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Embalmed or not embalmed? New set of analyses on the Frankish queen Arnugundis

International audienceEtudes multidisciplinaires et internationales des restes organiques (poumon et cheveux) de la reine Arégonde (VIe siècle

Homogeneous photoconversion of seawater uranium using copper and iron mixed-oxide semiconductor electrodes

Sunlight-driven conversion of hexavalent uranium (U(VI)) in seawater is achieved with mixed p-type CuO and CuFeO2 (CuO/CuFeO2) photocatalyst film electrodes synthesized via electrodeposition (ED) of Cu(II) and Fe(III), followed by annealing in air. The mixed photocatalysts exhibit a double-layer configuration with crystalline structures of CuO and CuFeO2. On irradiation of the CuO/CuFeO2 electrodes (held at −0.5 V vs. SCE) with solar simulated light (air mass 1.5; 100 mW cm−2), the U(VI) concentration decreases with time, while the total amount of uranium in solution does not change. This indicates that virtually all conversion reactions of U(VI) occur in the bulk solution, while surface reactions are limited due to insignificant adsorption of U(VI). U(VI) conversion leads to the mixed production of lower oxidation states U4+, U14/3+, and U16/3+ at a ratio of 42:28:30, with an overall Faradaic efficiency of ∼98%. The kinetics and induction time for U(VI) conversion are significantly influenced by the conditions of photocatalyst synthesis (CuO/CuFeO2, CuO, and CuFeO2; ED times of 2–4 h), the applied potential value (−0.4, −0.5, and −0.6 V vs. SCE), and the seawater condition (air-equilibrated vs. N2-purged; pH 3–10.4). Based on the obtained results, O2 is proposed to play a key role in shuttling photogenerated electrons between the electrodes and U(VI). In addition, the existence of an induction time is discussed in terms of material and reaction pathway. © 2017 Elsevier B.V.

Quantitative analysis of methylation of genomic loci in early-stage rectal cancer predicts distant recurrence.

Contains fulltext : 71286.pdf (publisher's version ) (Open Access)PURPOSE: There are no accurate prognostic biomarkers specific for rectal cancer. Epigenetic aberrations, in the form of DNA methylation, accumulate early during rectal tumor formation. In a preliminary study, we investigated absolute quantitative methylation changes associated with tumor progression of rectal tissue at multiple genomic methylated-in-tumor (MINT) loci sequences. We then explored in a different clinical patient group whether these epigenetic changes could be correlated with clinical outcome. PATIENTS AND METHODS: Absolute quantitative assessment of methylated alleles was used to assay methylation changes at MINT 1, 2, 3, 12, 17, 25, and 31 in sets of normal, adenomatous, and malignant tissues from 46 patients with rectal cancer. Methylation levels of these biomarkers were then assessed in operative specimens of 251 patients who underwent total mesorectal excision (TME) without neoadjuvant radiotherapy in a multicenter clinical trial. RESULTS: Methylation at MINT 2, 3, and 31 increased 11-fold (P = .005), 15-fold (P < .001), and two-fold (P = .02), respectively, during adenomatous transformation in normal rectal epithelium. Unsupervised grouping analyses of quantitative MINT methylation data of TME trial patients demonstrated two prognostic subclasses. In multivariate analysis of node-negative patients, this subclassification was the only predictor for distant recurrence (hazard ratio [HR], 4.17; 95% CI, 1.72 to 10.10; P = .002), cancer-specific survival (HR, 3.74; 95% CI, 1.4 to 9.43; P = .003), and overall survival (HR, 2.68; 95% CI, 1.41 to 5.11; P = .005). CONCLUSION: Methylation levels of specific MINT loci can be used as prognostic variables in patients with American Joint Committee on Cancer stage I and II rectal cancer. Quantitative epigenetic classification of rectal cancer merits evaluation as a stratification factor for adjuvant treatment in early disease