42 research outputs found
Palliative sedation and time to death in home palliative care. Retrospective analysis
No full textObjectivesWe described time to death and rates of palliative sedation during home palliative care leveraging a retrospective cohort of patients with advanced cancer. MethodsThe cohort consists of 143 patients with solid or haematological malignancies admitted to home palliative care in the Tuscany region in central Italy. Only patients for whom a date of death was available were included. The outcome measures were time from admission to home palliative care to death and receipt of palliative sedation. Results143 patients were included in this report. Lower Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores were significantly associated with anticancer treatment at admission, as was younger age. Increasing ECOG PS scores were associated with lower survival time. Women and patients on anticancer treatment had longer survival time. Thirty-eight per cent of patients underwent palliative sedation at home; palliative sedation was more frequent among younger patients and among patients with brain or lung cancer. The most common reasons for palliative sedation were delirium and dyspnoea. ConclusionsECOG PS, sex and anticancer treatment had a significant impact on survival time. Thirty-eight per cent of patients in our cohort underwent home palliative sedation for refractory symptoms, most often delirium and dyspnoea
Association between MICA Gene Variants and the Risk of Hepatitis C Virus-Induced Hepatocellular Cancer in a Sicilian Population Sample
No full textThere are currently no biomarkers that predict hepatocellular carcinoma (HCC) risk in patients with hepatitis C virus (HCV)-related cirrhosis. We investigated the relationships among major histocompatibility complex (MHC) class I chain-related gene A (MICA) polymorphisms, plasma levels of soluble MICA (sMICA), and HCC risk in patients with HCV-related HCC. One hundred fifty-four HCV-related HCC patients, 93 HCV-related liver cirrhosis (LC) cases, and 244 healthy controls, all sampled from the native Sicilian population, were genotyped using the KASPTMsingle-nucleotide polymorphism genotyping method. The MICA rs2596542 polymorphism showed that the G/G genotype was significantly more frequent in HCC than control subjects and LC patients (p < 0.005). For MICA rs2596538 polymorphism, the C allele and C/C genotype were significantly more frequent in HCC than in controls and LC cases (p < 0.005), after controlling for potential confounders. These results demonstrate that MICA rs2596542G/G, and particularly the rs2596538C/C polymorphism, are associated with the risk of developing HCV-related HCC in a Sicilian population sample. Importantly, using a machine learning classifier, we found that "age" and either rs2596542 or rs2596538 were important discriminating factors for patients with LC and HCC. Finally, sMICA levels significantly increased during HCV-related liver disease progression, while a significant relationship between both rs2596542 and rs2596538 genotypes and sMICA plasma levels was identified in patients with LC and HCC. In summary, the MICA rs2596538 and rs2596542 variants warrant further research for their clinical validity and utility in relationship to the risk of developing HCV-related HCC in independent populations
Effect of Detector and Electronics Fault on PET Reconstructed Image Acquired with the Full Ring HR+
No full textTRIM8-driven transcriptomic profile of neural stem cells identified glioma-related nodal genes and pathways
No full textBACKGROUND: We recently reported TRIM8, encoding an E3 ubiquitin ligase, as a gene aberrantly expressed in glioblastoma whose expression suppresses cell growth and induces a significant reduction of clonogenic potential in glioblastoma cell lines.
METHODS: we provided novel insights on TRIM8 functions by profiling the transcriptome of TRIM8-expressing primary mouse embryonal neural stem cells by RNA-sequencing and bioinformatic analysis. Functional analysis including luciferase assay, western blot, PCR arrays, Real time quantitative PCR were performed to validate the transcriptomic data.
RESULTS: Our study identified enriched pathways related to the neurotransmission and to the central nervous system (CNS) functions, including axonal guidance, GABA receptor, Ephrin B, synaptic long-term potentiation/depression, and glutamate receptor signalling pathways. Finally, we provided additional evidence about the existence of a functional interactive crosstalk between TRIM8 and STAT3.
CONCLUSIONS: Our results substantiate the role of TRIM8 in the brain functions through the dysregulation of genes involved in different CNS-related pathways, including JAK-STAT.
GENERAL SIGNIFICANCE:
This study provides novel insights on the physiological TRIM8 function by profiling for the first time the primary Neural Stem Cell over-expressing TRIM8 by using RNA-Sequencing methodology
EphB2 stem-related and EphA2 progression-related miRNA-based networks in progressive stages of CRC evolution: Clinical significance and potential miRNA drivers 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis
No full textEphB2 and EphA2 control stemness and differentiation in the intestinal mucosa, but the way they cooperate with the complex mechanisms underlying tumor heterogeneity and how they affect the therapeutic outcome in colorectal cancer (CRC) patients, remain unclear. MicroRNA (miRNA) expression profiling along with pathway analysis provide comprehensive information on the dysregulation of multiple crucial pathways in CRC. Through a network-based approach founded on the characterization of progressive miRNAomes centered on EphA2/EphB2 signaling during tumor development in the AOM/DSS murine model, we found a miRNA-dependent orchestration of EphB2-specific stem-like properties in earlier phases of colorectal tumorigenesis and the EphA2-specific control of tumor progression in the latest CRC phases. Furthermore, two transcriptional signatures that are specifically dependent on the EphA2/EphB2 signaling pathways were identified, namely EphA2, miR-423-5p, CREB1, ADAMTS14, and EphB2, miR-31-5p, mir-31-3p, CRK, CXCL12, ARPC5, SRC. EphA2- and EphB2-related signatures were validated for their expression and clinical value in 1663 CRC patients. In multivariate analysis, both signatures were predictive of survival and tumor progression. The early dysregulation of miRs-31, as observed in the murine samples, was also confirmed on 49 human tissue samples including preneoplastic lesions and tumors. In light of these findings, miRs-31 emerged as novel potential drivers of CRC initiation. Our study evidenced a miRNA-dependent orchestration of EphB2 stem-related networks at the onset and EphA2-related cancer-progression networks in advanced stages of CRC evolution, suggesting new predictive biomarkers and potential therapeutic targets
Metabolomic profile in pancreatic cancer patients: a consensus-based approach to identify highly discriminating metabolites
No full textPurpose: pancreatic adenocarcinoma is the fourth leading cause of cancer related deaths due to its aggressive behavior and poor clinical outcome. There is a considerable variability in the frequency of serum tumor markers in cancer’ patients. We performed a metabolomics screening in patients diagnosed with pancreatic cancer.
Experimental Design: Two targeted metabolomic assays were conducted on 40 serum samples of patients diagnosed with pancreatic cancer and 40 healthy controls. Multivariate methods and classification trees were performed.
Materials and Methods: Sparse partial least squares discriminant analysis (SPLS-DA) was used to reduce the high dimensionality of a pancreatic cancer metabolomic dataset, differentiating between pancreatic cancer (PC) patients and healthy subjects. Using Random Forest analysis palmitic acid, 1,2-dioleoyl-sn-glycero-3-phospho-rac-glycerollanosterol, lignoceric acid, 1-monooleoyl-rac-glycerol, cholesterol 5α,6α epoxide, erucic acid and taurolithocholic acid (T-LCA), oleoyl-L-carnitine, oleanolic acid were identified among 206 metabolites as highly discriminating between disease states. Comparison between Receiver Operating Characteristic (ROC) curves for palmitic acid and CA 19-9 showed that the area under the ROC curve (AUC) of palmitic acid (AUC=1.000; 95% confidence interval) is significantly higher than CA 19-9 (AUC=0.963; 95% confidence interval: 0.896-1.000).
Conclusion: Mass spectrometry-based metabolomic profiling of sera from pancreatic cancer patients and normal subjects showed significant alterations in the profiles of the metabolome of PC patients as compared to controls. These findings offer an information-rich matrix for discovering novel candidate biomarkers with diagnostic or prognostic potentials
Usefulness of transesophageal echocardiography in the assessment of aortic dissection
No full textThe acute dissection of the ascending aorta requires prompt and reliable diagnosis to reduce the high risk of mortality; in addition, prognosis is influenced by longterm complications. The aim of this article is to discuss transesophageal echocardiography (TEE) and (1) its diagnostic accuracy in the presurgical evaluation of patients, (2) its role in reducing time of diagnosis and surgery, and (3) its ability to reduce hospital mortality. TEE has also been tested as a screening method in the postsurgical follow-up of these patients. The retrospective investigation concerns a sample of 80 cases of acute dissection of the aorta, submitted for surgical intervention from April 1986 to February 1999. TEE has allowed a precise estimation of aortic diameters and optimal visualization of intimal flap and tear entry with a fine distinction between true and false lumen. A direct comparison of the results of TEE and of transthoracic echocardiography has demonstrated that some elements (visualization of flap and diameters in descending aorta, sites of entry and reentry, direction of let trough intimal tears, phasic intimal flap movement, diastolic collapse of flap on the valvular plane, false lumen thrombosis, coronary involvement, intramural hematoma, and aortic fissuration) were identified only by TEE, whereas other additional diagnostic elements (cardiac tamponade, aortic valve insufficiency, left ventricular function) show a similar pattern of significance. Routine employment of this method has confirmed a reduction of hospitalization time (about 1.5 hours of waiting time), and hospital mortality has changed from 42.8% to 17.3%. In the follow-up of patients operated on for aortic dissection, fundamental information may be obtained from TEE (assessment of the progression of thrombosis in the false lumen with its complete obliteration and modifications in aortic diameter with a consequent, possible worsening of aortic valve insufficiency). In conclusion, our study demonstrated that TEE may provide fast and efficient detection of acute aortic dissection. In the postsurgical follow-up, TEE has confirmed detection of major complications that can influence long-term prognosis and may be proposed as a method with easy access-one that is repeatable and inexpensive for the screening of aortic dissection surgical patients. (C) 2000 by Excerpta Medica, Inc
