Macrovascular infiltration and spikes in circulating tumor cells in cancer patients approaching end of life
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1254684 | ENA |
REPOSITORIES: ENA
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Project description:End-of-life neoplastic events related to carcinoma lethality are poorly characterized. With the purpose of exploring biological events in cancer patients nearing death, we conducted an observational, prospective, case-control study enrolling 21 patients with solid tumors and 10 patients without known malignancy, complemented by a retrospective validation cohort of 1,250 cancer patients. In our prospective cohort, we observed remarkable spikes in circulating tumor cell (CTC) counts immediately before death (P < 0.0001), as well as pathological evidence of macrovascular infiltration and large-vessel occlusion obtained through rapid autopsy. In the validation cohort, radiological evidence of macrovascular infiltration emerged as the strongest predictor of poor survival – independent of clinical metastasis – in treatment-homogenous patients with colorectal, lung, ovarian, hepatocellular, or pancreatic cancer (hazard ratio range: 4.0 - 22.4). These findings suggest that spikes in CTC formation and consequent macrovascular failure could be pivotal end-of-life events associated with cancer lethality, providing a rationale for future clinical trials aimed at curbing tumor infiltration into large vessels.
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Project description:Phytohormones are key regulators of plant growth, development, and signalling networks involved in responses to diverse biotic and abiotic stresses. Transcriptional reference maps of hormone responses have been reported for several model plant species such as Arabidopsis thaliana, Oryza sativa, and Brachypodium distachyon. However, because of species differences and the complexity of the wheat genome, these transcriptome data are not appropriate reference material for wheat studies. We comprehensively analysed the transcriptomic responses in wheat spikes to seven phytohormones, including indole acetic acid (IAA), gibberellic acid (GA), abscisic acid (ABA), ethylene (ET), cytokinin (CK), salicylic acid (SA), and methyl jasmonic acid (MeJA). A total of 3386 genes were differentially expressed at 24 h after the hormone treatments. Furthermore, 22.7% of these genes exhibited overlapping transcriptional responses for at least two hormones, implying there is crosstalk among phytohormones. We subsequently identified genes with expression levels that were significantly and differentially induced by a specific phytohormone (i.e., hormone-specific responses). The data for these hormone-responsive genes were then compared with the transcriptome data for wheat spikes exposed to biotic (Fusarium head blight) and abiotic (water deficit) stresses. Our data were used to develop a transcriptional reference map of hormone responses in wheat spikes.
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Project description:Objectives:
The primary objective of the research project is to investigate how declining health status influences the end-of-life (EOL) treatment preferences in Latino Medicare beneficiaries with cancer and to examine if and how these preferences are modified by predisposing characteristics (i.e., acculturation, education, medical mistrust, perceived racism) and/or provider-related characteristics (i.e., ethnicity, language used, provision of interpreters, or patient navigators). The specific aims are:
1. To determine if declining functional status influences the end-of-life treatment preferences of older Latino Medicare beneficiaries with cancer.
2. To determine if predisposing characteristics (i.e., acculturation, age, education, medical mistrust, perceived racism) and/or provider-related characteristics (i.e., ethnicity, language used, provision of interpreters, or patient navigators) modify the association between end-of-life treatment preferences and declining health status in older Latino Medicare beneficiaries with cancer.
3. To identify if the end-of-life treatment preferences of Latino Medicare beneficiaries with cancer differ from those of older Medicare beneficiaries without cancer.
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Project description:Our previous study identified 8 risk and 9 protective plasma miRNAs associated with progression to end-stage kidney disease (ESKD) in diabetes. This study aimed to elucidate pre-analytical factors that influence the quantification of circulating miRNAs. Using the EdgeSeq platform, which quantifies 2,002 miRNAs in plasma, including ESKD-associated miRNAs, we compared miRNA profiles in whole plasma vs. miRNAs profiles in RNA extracted from the same plasma specimens. Less than half of the miRNAs were detected in standard RNA extracted methods from plasma. Detection of individual and concentrations of miRNAs were much lower when RNA extracted from plasma was quantified by RNA sequencing (RNASeq) or RT-qPCR platforms compared to EdgeSeq. Plasma profiles of miRNAs determined by the EdgeSeq platform had excellent reproducibility in assessment, and had no variation with age, sex, HbA1c, BMI, and cryostorage time. The risk ESKD-associated miRNAs were detected and measured accurately only in whole plasma and using the EdgeSeq platform. Protective ESKD-associated miRNAs were detected by all platforms except RT-qPCR, however, correlations among concentrations obtained with different platforms were weak or non-existent. In conclusion, pre-analytical factors have a profound effect on detection and quantification of circulating miRNAs in ESKD in diabetes. Quantification of miRNAs in whole plasma and using the EdgeSeq platform may be the preferable method to study profiles of circulating cell-free miRNAs associated with ESKD, and possibly other diseases.
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Project description:Organ specific microarray analysis were performed to identify genes responding to Fusarium graminearum inoculation in specific organs of wheat spikes.
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