The application of surface-enhanced Raman spectroscopy (SERS) in biological and biomedical detection schemes is feasible due to its excellent molecular specificity and high sensitivity as well as the ...capability of SERS to be performed in complex biological compositions. SERS-based investigation of cells, which are the basic structure and functional unit of organisms, represents the starting point of this review. It is demonstrated that SERS provides a deep understanding of living cells as well as their microenvironment which is needed to assess the development of diseases. The clinical relevance of SERS is proved by its application for the detection of cancer cells and tumour margins under in vivo conditions and examples for theranostic approaches are discussed. This review article provides a comprehensive overview of the recent progress within the last 3 years.
Normal computed tomography abdominal imagewithout significant periaortic collection at day 1 of symptoms A new CT scan of the abdomen was performed, revealing an anterior pre- and para-vertebral soft ...tissue mass with focal hypodensities surrounding the aorta at the T12-L1 level (Fig 2). Other micro-organisms commonly implicated include Enterococcus species, Streptococcus pneumoniae, Salmonella species, Mycobacterium tuberculosis, and in the more distant past, syphilis.1 Rare case reports have featured the radiological evolution of infectious aortitis while on conservative treatment, and these often illustrate peri-aortic soft tissue masses progressing to aneurysmal formation from S aureus or Salmonella species infection.1 2 3 4 5 Prompt antimicrobial therapy is crucial along with endovascular or surgical intervention.5 Our patient demonstrated radiological normality to pathology within a week of symptom onset and subsequent improvement while on conservative therapy alone, followed by full radiological resolut
The comparison between relatively intact nanoscale extracellular vesicle-derived DNA (nEV-DNA) and fragmented circulating cell-free DNA (cfDNA) in mutation detection among patients with ...non-small-cell lung cancer (NSCLC) has not been carried out yet, and thus deserves investigation.
Both nEV-DNA and cfDNA was obtained from 377 NSCLC patients with known EGFR mutation status and 69 controls. The respective EGFRE19del/T790M/L858R mutation status was interrogated with amplification-refractory-mutation-system-based PCR assays (ARMS-PCR).
Neither nEV-DNA nor cfDNA levels show a strong correlation with tumor volumes. There is no correlation between cfDNA and nEV-DNA levels either. The detection sensitivity of nEV-DNA and cfDNA using ARMS-PCR in early-stage NSCLC was 25.7% and 14.2%, respectively, with 96.6% and 91.7% specificity, respectively. In late-stage NSCLC, both nEV-DNA and cfDNA show ∼80% sensitivity and over 95% specificity.
nEV-DNA is superior to cfDNA for mutation detection in early-stage NSCLC using ARMS-PCR. However, the advantages vanish in late-stage NSCLC.
Transcript fusions as a result of chromosomal rearrangements have been a focus of attention in cancer as they provide attractive therapeutic targets. To identify novel fusion transcripts with the ...potential to be exploited therapeutically, we analyzed RNA sequencing, DNA copy number and gene mutation data from 4366 primary tumor samples. To avoid false positives, we implemented stringent quality criteria that included filtering of fusions detected in RNAseq data from 364 normal tissue samples. Our analysis identified 7887 high confidence fusion transcripts across 13 tumor types. Our fusion prediction was validated by evidence of a genomic rearrangement for 78 of 79 fusions in 48 glioma samples where whole-genome sequencing data were available. Cancers with higher levels of genomic instability showed a corresponding increase in fusion transcript frequency, whereas tumor samples harboring fusions contained statistically significantly fewer driver gene mutations, suggesting an important role for tumorigenesis. We identified at least one in-frame protein kinase fusion in 324 of 4366 samples (7.4%). Potentially druggable kinase fusions involving ALK, ROS, RET, NTRK and FGFR gene families were detected in bladder carcinoma (3.3%), glioblastoma (4.4%), head and neck cancer (1.0%), low-grade glioma (1.5%), lung adenocarcinoma (1.6%), lung squamous cell carcinoma (2.3%) and thyroid carcinoma (8.7%), suggesting a potential for application of kinase inhibitors across tumor types. In-frame fusion transcripts involving histone methyltransferase or histone demethylase genes were detected in 111 samples (2.5%) and may additionally be considered as therapeutic targets. In summary, we described the landscape of transcript fusions detected across a large number of tumor samples and revealed fusion events with clinical relevance that have not been previously recognized. Our results support the concept of basket clinical trials where patients are matched with experimental therapies based on their genomic profile rather than the tissue where the tumor originated.
Family history is a significant risk factor for prostate cancer, although the molecular basis for this association is poorly understood. Linkage studies have implicated chromosome 17q21-22 as a ...possible location of a prostate-cancer susceptibility gene.
We screened more than 200 genes in the 17q21-22 region by sequencing germline DNA from 94 unrelated patients with prostate cancer from families selected for linkage to the candidate region. We tested family members, additional case subjects, and control subjects to characterize the frequency of the identified mutations.
Probands from four families were discovered to have a rare but recurrent mutation (G84E) in HOXB13 (rs138213197), a homeobox transcription factor gene that is important in prostate development. All 18 men with prostate cancer and available DNA in these four families carried the mutation. The carrier rate of the G84E mutation was increased by a factor of approximately 20 in 5083 unrelated subjects of European descent who had prostate cancer, with the mutation found in 72 subjects (1.4%), as compared with 1 in 1401 control subjects (0.1%) (P=8.5x10(-7)). The mutation was significantly more common in men with early-onset, familial prostate cancer (3.1%) than in those with late-onset, nonfamilial prostate cancer (0.6%) (P=2.0x10(-6)).
The novel HOXB13 G84E variant is associated with a significantly increased risk of hereditary prostate cancer. Although the variant accounts for a small fraction of all prostate cancers, this finding has implications for prostate-cancer risk assessment and may provide new mechanistic insights into this common cancer. (Funded by the National Institutes of Health and others.).
Aim
Recent studies have shown that sarcopenia is associated with negative postoperative outcomes. However, none of these studies analysed muscle strength or physical performance, which are also ...important components of sarcopenia. The present study aimed to investigate whether sarcopenia itself, as defined by low muscle mass, strength and physical performance, would predict complications after surgery for colorectal cancer.
Method
We conducted a prospective study of patients who underwent surgery for colorectal cancer at our department between August 2014 and February 2015. Sarcopenia was diagnosed by a combination of third lumbar vertebra muscle index (L3 MI), handgrip strength and 6‐m usual gait speed. Univariate and multivariate analyses evaluating the risk factors for postoperative complications were performed. Only complications classified as Grade II or above according to the Clavien–Dindo classification were analysed in this study.
Results
A total of 142 patients were included in the study, and 17 patients were diagnosed as having sarcopenia. Postoperative complications of Grade II or above occurred in 40 patients, including 10 with sarcopenia and 30 without sarcopenia. Multivariate analysis showed that sarcopenia and previous abdominal surgery were independent risk factors for postoperative complications. Patients with sarcopenia also had an obvious tendency to a higher incidence of infectious complications. By comparing two logistic regression models, sarcopenia showed a better predictive power for postoperative complications than did low muscle mass.
Conclusion
Sarcopenia and previous abdominal surgery are independent risk factors for complications after surgery for colorectal cancer. Including a functional aspect to the definition of sarcopenia may result in a better prediction of postoperative complications.
Superoxide dismutase 1 (Sod1) has been known for nearly half a century for catalysis of superoxide to hydrogen peroxide. Here we report a new Sod1 function in oxidative signalling: in response to ...elevated endogenous and exogenous reactive oxygen species (ROS), Sod1 rapidly relocates into the nucleus, which is important for maintaining genomic stability. Interestingly, H2O2 is sufficient to promote Sod1 nuclear localization, indicating that it is responding to general ROS rather than Sod1 substrate superoxide. ROS signalling is mediated by Mec1/ATM and its effector Dun1/Cds1 kinase, through Dun1 interaction with Sod1 and regulation of Sod1 by phosphorylation at S60, 99. In the nucleus, Sod1 binds to promoters and regulates the expression of oxidative resistance and repair genes. Altogether, our study unravels an unorthodox function of Sod1 as a transcription factor and elucidates the regulatory mechanism for its localization.
Alternative splicing is a fundamental regulatory process of gene expression. Defects in alternative splicing can lead to various diseases, and modification of disease-causing splicing events presents ...great therapeutic promise. Splicing outcome is commonly affected by extracellular stimuli and signaling cascades that converge on RNA-binding splicing regulators. These trans-acting factors recognize cis-elements in pre-mRNA transcripts to affect spliceosome assembly and splice site choices. Identification of these splicing regulators and/or upstream modulators has been difficult and traditionally done by piecemeal. High-throughput screening strategies to find multiple regulators of exon splicing have great potential to accelerate the discovery process, but typically confront low sensitivity and low specificity of screening assays. Here we describe a unique screening strategy, IRAS (identifying regulators of alternative splicing), using a pair of dual-output minigene reporters to allow for sensitive detection of exon splicing changes. Each dual-output reporter produces green fluorescent protein (GFP) and red fluorescent protein (RFP) fluorescent signals to assay the two spliced isoforms exclusively. The two complementary minigene reporters alter GFP/RFP output ratios in the opposite direction in response to splicing change. Applying IRAS in cell-based high-throughput screens allows sensitive and specific identification of splicing regulators and modulators for any alternative exons of interest. In comparison to previous high-throughput screening methods, IRAS substantially enhances the specificity of the screening assay. This strategy significantly eliminates false positives without sacrificing sensitive identification of true regulators of splicing.
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