Ena-DATASET-JHU-29-06-2015-20:17:30:536-212 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001001421 | EGA |
REPOSITORIES: EGA
Publications
Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients.
Sausen Mark M Phallen Jillian J Adleff Vilmos V Jones Siân S Leary Rebecca J RJ Barrett Michael T MT Anagnostou Valsamo V Parpart-Li Sonya S Murphy Derek D Kay Li Qing Q Hruban Carolyn A CA Scharpf Rob R White James R JR O'Dwyer Peter J PJ Allen Peter J PJ Eshleman James R JR Thompson Craig B CB Klimstra David S DS Linehan David C DC Maitra Anirban A Hruban Ralph H RH Diaz Luis A LA Von Hoff Daniel D DD Johansen Julia S JS Drebin Jeffrey A JA Velculescu Victor E VE
Nature communications 20150707
Pancreatic adenocarcinoma has the worst mortality of any solid cancer. In this study, to evaluate the clinical implications of genomic alterations in this tumour type, we perform whole-exome analyses of 24 tumours, targeted genomic analyses of 77 tumours, and use non-invasive approaches to examine tumour-specific mutations in the circulation of these patients. These analyses reveal somatic mutations in chromatin-regulating genes MLL, MLL2, MLL3 and ARID1A in 20% of patients that are associated w ...[more]
Similar Datasets
Project description:The genome sequence of human papillomavirus type 20 (HPV-20; family Papillomaviridae, genus Betapapillomavirus, species Betapapillomavirus 1, type 20) was assembled by deep sequencing from nasopharyngeal swabs. The assembled genome is 0.37% divergent over its full length from the single complete genome of HPV-20 in GenBank (U31778). We named the strain HPV-20/Lancaster/2015.
| S-EPMC5543637 | biostudies-literature
Project description:The crosstalk between tumor and immune cells has important implications for cancer treatment, in particular for immunotherapies. Pancreatic ductal adenocarcinoma (PDAC) generally displays a chemoresistant phenotype and is refractory to immune-based therapies. Highly tumorigenic and stem-like cells known as cancer stem cells (CSCs) within PDAC tumors have been demonstrated to contribute to its aggressiveness, metastatic capacity and chemoresistance. Here, we show that CSCs could be also relevant to establish an immunosuppresive environment. Using genetically engineered mouse models (GEMMs) of PDAC we isolated a triple positive (EpCAM+, Sca-1+ and CD133+) population of tumor cells, functionally validated these cells as bona fide CSCs and probed their transcriptional profile by microarray analysis. In addition to stem pathways, signatures related to tumor immune evasion, immune modulation, invasiveness, and innate immune response were enriched in this population. Peptidoglycan recognition protein 1 (Pglyrp1), an innate immune response anti-bacterial protein expressed primarily by neutrophils, was highly expressed in this triple-positive population and in CSC-enriched spheres from human cell lines. Interestingly, modulation of Pglyrp1 expression in murine PDAC primary cultures affected their immune evasive properties, specifically their ability to escape macrophage- and T-cell-mediated killing in vitro and to establish tumors in immunocompetent hosts. Pglyrp1 expression in tumor cells seemed to interfere with TNFα-mediated killing by T cells and to promote activated T-cell cytotoxicity. Importantly, these results could be validated in CSCs from human patient-derived xenografts, and PGLYRP1 protein levels were also significantly higher in PDAC patient samples versus healthy controls. Thus, our study demonstrates a hierarchical organization of cancer cells in a murine model of PDAC, validating the CSC concept, and identifies Pglyrp1 as a putative PDAC biomarker that confers immune privilege properties to CSCs which could have important therapeutic implications.
2024-09-30 | GSE222985 | GEO
Project description:For the uropathogenic Escherichia coli strain 536 (O6:K15:H31), the DNA sequences of three pathogenicity islands (PAIs) (PAI I(536) to PAI III(536)) and their flanking regions (about 270 kb) were determined to further characterize the virulence potential of this strain. PAI I(536) to PAI III(536) exhibit features typical of PAIs, such as (i) association with tRNA-encoding genes; (ii) G+C content differing from that of the host genome; (iii) flanking repeat structures; (iv) a mosaic-like structure comprising a multitude of functional, truncated, and nonfunctional putative open reading frames (ORFs) with known or unknown functions; and (v) the presence of many fragments of mobile genetic elements. PAI I(536) to PAI III(536) range between 68 and 102 kb in size. Although these islands contain several ORFs and known virulence determinants described for PAIs of other extraintestinal pathogenic E. coli (ExPEC) isolates, they also consist of as-yet-unidentified ORFs encoding putative virulence factors. The genetic structure of PAI IV(536), which represents the core element of the so-called high-pathogenicity island encoding a siderophore system initially identified in pathogenic yersiniae, was further characterized by sample sequencing. For the first time, multiple PAI sequences (PAI I(536) to PAI IV(536)) in uropathogenic E. coli were studied and their presence in several wild-type E. coli isolates was extensively investigated. The results obtained suggest that these PAIs or at least large fragments thereof are detectable in other pathogenic E. coli isolates. These results support our view that the acquisition of large DNA regions, such as PAIs, by horizontal gene transfer is an important factor for the evolution of bacterial pathogens.
| S-EPMC130402 | biostudies-literature
Project description:Bacillus cereus strain:JHU | isolate:JHU Genome sequencing and assembly
| PRJNA591929 | ENA
Project description:The title compound, C(29)H(37)NO(2), crystallized with two independent mol-ecules in an asymmetric unit in which the conformation of the cyclo-hexyl ring of the pregnene moiety bonded to the 3?-(1,3-dioxoisoindolin-2-yl)- ring system differs: in one mol-ecule it is in a chair conformation, while in the other it exhibits a half-chair conformation. The other six-membered rings in the pregnene moiety are in chair conformations and the five-membered rings are in envelope forms in both mol-ecules. In both mol-ecules, the 3?-(1,3-dioxoisoindolin-2-yl)- ring systems are individually approximately planar, with r.m.s. devtaions 0.0148 and 0.0264?Å. The structure is consolidated by inter-molecular C-H?O hydrogen-bonding inter-actions involving the carbonyl O atoms and methyl, methyl-ene and methyl-idyne groups, resulting in a two-dimensional structure.
| S-EPMC3213511 | biostudies-literature
Project description:In the pregnene fragment of the title compound, C27H38ClN, the three six-membered rings exhibit chair conformations and the five-membered ring has a distorted envelope form with the fused C atom not bearing a methyl group as the flap atom. The amino group is involved in the formation of an intra-molecular N-H?Cl hydrogen bond. The crystal packing exhibits no short inter-molecular contacts.
| S-EPMC3647836 | biostudies-other
Project description:The transition of patients with ?20% <30% bone marrow (BM) blast from the FAB category of myelodysplasia to the family of acute myeloid leukemia (AML) according to the recent WHO classification has not resolved the argument as to whether the natural history and responsiveness to therapy of these diseases is comparable to that of AML with > 30% BM blast. These controversies are even more manifest when it comes to elderly patients in whom concern for intensive chemotherapy (IC) related toxicity is the critical determinant for the therapeutic choice. In fact, due to concerns of treatment-related morbidity and mortality associated with delivery of IC, approximately only 30% of all patients ?65 years are considered eligible for this approach. Therefore, a great deal of attention has been dedicated to alternative agents such as hypomethylators (azacitidine and decitabine). Actually, these agents have shown efficacy with reduced toxicity when administered to elderly patients with 20-30% BM blasts and not eligible for IC. In the present review, we will discuss the clinical results achieved in the treatment of elderly patients with 20%-30% BM blasts AML using intensive chemotherapy (IC) or hypomethylating agents. Overall, our survey of the literature suggests that only controlled, randomized, clinical trials will answer the question as to whether hypomethylating agents has the potential to substitute for IC even in elderly patients with an optimal functional status.
| S-EPMC3684350 | biostudies-literature
Project description:Recent reports suggest that human genogroup II genotype 17 (GII.17) noroviruses are increasing in prevalence. We analyzed the evolutionary changes of three GII.17 capsid protruding (P) domains. We found that the GII.17 P domains had little cross-reactivity with antisera raised against the dominant GII.4 strains. X-ray structural analysis of GII.17 P domains from 2002 to 2014 and 2015 suggested that surface-exposed substitutions on the uppermost part of the P domain might have generated a novel 2014-2015 GII.17 variant.
| S-EPMC4810701 | biostudies-literature
Project description:Using data from 23,313 patients, we assessed whether two blood culture sets of three bottles per set would detect more pathogens than two sets of two bottles per set and achieve similar sensitivity to collecting three sets of two bottles per set. We also compared the yield of aerobic and anaerobic bottles. Thirty milliliters of blood was distributed to one anaerobic and two aerobic bottles. Among 26,855 collections of ≥ 60 ml within 30 min, 1,379 (5.1%) were positive for a pathogen not requiring detection in more than one set to be considered a pathogen, with 72 additional distinct pathogens detected using two 30-ml compared to two 20-ml sets of one aerobic and one anaerobic bottle (increased yield, 7.9%; 95% confidence interval [CI], 6.2 to 9.8%). For conditional pathogens requiring detection in at least two positive blood cultures for classification as pathogens (i.e., otherwise classified as contaminants), there were 162 positive detections with two 30-ml sets, of which 16 would not have been detected by two 20-ml sets (increased yield, 11.0% [95% CI, 6.4 to 17.2%]). Among 134 subjects who had three sets of 30 ml each within a 30-min interval, there was complete concordance between 60 ml of blood drawn in the first two sets of 30 ml and three 20-ml sets (P = 1.0). One aerobic bottle plus one anaerobic bottle yielded more pathogens than two aerobic bottles for organisms requiring a single (P < 0.001) and two (P = 0.04) positive sets to be defined as pathogens. In conclusion, we showed that collection of two aerobic and one anaerobic blood culture bottles per set results in improved yield compared to two bottles per set. We also confirmed that an anaerobic bottle should be included in blood culture sets.
| S-EPMC3232938 | biostudies-literature
Project description:IL-17 cytokines, in particular IL-17A, are critical effectors in psoriasis. Antibodies that block IL-17A are highly efficacious in treating psoriasis. Likewise, disruption of IL-17 cytokines signaling, such as via the loss of the adaptor CIKS/Act1, ameliorates inflammation in mouse models of psoriasis. IL-17A promotes a cascade of effects, including the robust production of IL-19 in both humans and mice. IL-19, along with IL-20 and IL-24, signal via IL-20 receptors and comprise a subgroup within the IL-10 cytokine family. The role of these three cytokines in psoriasis is unresolved. They have been linked to inflammatory processes, including psoriatic pathology, but these cytokines have also been reported to suppress inflammation in other contexts. In this study, we demonstrate that signaling via IL-20 receptors, including in response to IL-19, delimited aspects of imiquimod-induced psoriatic inflammation. IL-20 receptor signaling suppressed the dermal production of the CCL2 chemokine and thereby reduced CCL-2-driven infiltration of inflammatory cells into the dermis, including IL-17A-producing γδT cells. This constitutes a negative feedback, since IL-17A strongly induces IL-19 in keratinocytes. The effects of IL-17 cytokines in this inflammatory setting are dynamic; they are central to the development of both dermal and epidermal hallmarks of psoriasis but also initiate a path to mitigate inflammatory damage.
| S-EPMC6926146 | biostudies-literature