Telehealth is an aspect of healthcare whose potential scope and impact have yet to be determined. However, we are beginning to see more programs experiment and validate various implementations of telehealth with promising results.
Objective: Oral Anticoagulation Treatment (OAT) resumption is a therapeutic dilemma in Intracerebral Hemorrhage (ICH) care, particularly for lobar hemorrhages related to amyloid angiopathy. We sought to determine whether OAT resumption after ICH is associated with long-term outcome, accounting for ICH location (i.e. lobar vs. non-lobar).
Methods: We meta-analyzed individual patient data from: 1) the multi-center RETRACE study (n=542); 2) a US-based single-center ICH study (n=261); 3) the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study (n=209). We determined whether, within one year from ICH, OAT resumption was associated with: 1) mortality; 2) favorable functional outcome (modified Rankin Scale [mRS] 0-3); stroke incidence. We separately analyzed non-lobar and lobar ICH cases using propensity score matching and Cox regression models.
Results: We included 1012 OAT-related ICH survivors (633 non-lobar and 379 lobar). Among non-lobar ICH survivors 178/633 (28%) resumed OAT, while 86/379 (23%) lobar ICH survivors did. In multivariable analyses OAT resumption after non-lobar ICH was associated with decreased mortality (Hazard Ratio [HR]=0.25, 95% Confidence Interval [CI]=0.14-0.44, p<0.0001) and improved functional outcome (HR=4.22, 95% CI=2.57-6.94, p<0.0001). OAT resumption after lobar ICH was also associated with decreased mortality (HR=0.29, 95% CI=0.17-0.45, p<0.0001) and favorable functional outcome (HR=4.08, 95% CI=2.48-6.72, p<0.0001). Furthermore, OAT resumption was associated with decreased all-cause stroke incidence in both lobar and non-lobar ICH (both p<0.01).
Interpretation: These results suggest novel evidence of an association between OAT resumption and outcome following ICH, regardless of hematoma location. These findings support conducting randomized trials to explore risks and benefits of OAT resumption after ICH. This article is protected by copyright. All rights reserved.
Cancers, Vol. 9, Pages 136: Radiation-Induced Changes of microRNA Expression Profiles in Radiosensitive and Radioresistant Leukemia Cell Lines with Different Levels of Chromosome Abnormalities
Cancers doi: 10.3390/cancers9100136
Authors: Daria Liamina Wladimir Sibirnyj Anna Khokhlova Viacheslav Saenko Eugenia Rastorgueva Aleksandr Fomin Yury Saenko
In our study, we estimate an effect from chromosome aberrations and genome mutations on changes in microRNA expression profiles in cancer cell lines demonstrating different radiosensitivity. Here, cell viability and microRNA spectrum have been estimated 1, 4, and 24 h after irradiation. MiSeq high-throughput sequencing system (Illumina, San Diego, CA, USA) is employed to perform microRNA spectrum estimation. In the K562 cell line, the number of expressed microRNAs in chromosomes demonstrates a more pronounced variation. An analysis of microRNA effects on signaling pathway activity demonstrates differences in post-transcriptional regulation of the expression of genes included into 40 signaling pathways. In the K562 cell line, microRNA dynamics analyzed for their dependence on chromosome localization show a wider scattering of microRNA expression values for a pair of chromosomes compared to the HL-60 cell line. An analysis of microRNAs expression in the K562 and HL-60 cell lines after irradiation has shown that chromosome abnormalities can affect microRNA expression changes. A study of radiation-induced changes of microRNA expression profiles in the K562 and HL-60 cell lines has revealed a dependence of microRNA expression changes on the number of chromosome aberrations and genome mutations.
The peptides N-tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (BOC2) and BOC-Met-Leu-Phe (BOC1) are widely used antagonists of formyl peptide receptors (FPRs), BOC2 acting as an FPR1/FPR2 antagonist whereas BOC1 inhibits FPR1 only. Extensive investigations have been performed by using these FPR antagonists as a tool to assess the role of FPRs in physiological and pathological conditions. Based on previous observations from our laboratory, we assessed the possibility that BOC2 may exert also a direct inhibitory effect on the angiogenic activity of vascular endothelial growth factor-A (VEGF-A). Our data demonstrate that BOC2, but not BOC1, inhibits the angiogenic activity of heparin-binding VEGF-A165 with no effect on the activity of the non-heparin-binding VEGF-A121 isoform. Endothelial cell-based bioassays, surface plasmon resonance analysis, and computer modeling indicate that BOC2 may interact with the heparin-binding domain of VEGF-A165, thus competing for heparin interaction and preventing the binding of VEGF-A165 to tyrosine kinase receptor VEGFR2, its phosphorylation and downstream signaling. In addition, BOC2 inhibits the interaction of a variety of heparin-binding angiogenic growth factors with heparin, including fibroblast growth factor 2 (FGF2) whose angiogenic activity is blocked by the compound. Accordingly, BOC2 suppresses the angiogenic potential of human tumor cell lines that co-express VEGF-A and FGF2. Thus, BOC2 appears to act as a novel multi-heparin-binding growth factor antagonist. These findings caution about the interpretation of FPR-focusing experimental data obtained with this compound and set the basis for the design of novel BOC2-derived, FPR independent multi-target angiogenesis inhibitors.
Q fever caused by Coxiella burnetii usually presents asymptomatically or as an undifferentiated febrile disease and rarely as rash or other cutaneous manifestations of the disease. Here we present a 41 year old male complaining of body aches, fevers, nausea, malaise, bilateral knee pain, and vomiting. Clinical examination revealed a notable erythematous blanching rash all over his body. Workup revealed positive serologic testing for C burnetii and skin biopsy of the rash revealed leukocytoclastic vasculitis.
Intensive trimodality therapy is needed for locally advanced esophageal squamous cell carcinoma (ESCC). However, some patients develop recurrence and die of cancer even after trimodality therapy.
We evaluated prognostic factors based on data from 125 patients with ESCC who underwent neoadjuvant chemoradiotherapy (NCRT) comprising concurrent chemotherapy and 40 Gy of radiation, followed by curative-intent esophagectomy.
Thirty-four (27.2%) patients achieved a pathological complete response (pCR) after NCRT. The 5-year recurrence-free (RFS) and overall survival (OS) rates of all patients were 49.2 and 52.9%, respectively, and were significantly better for patients with pCR than without pCR (p = 0.01 and 0.02, respectively). Univariate and multivariate analyses selected performance status [PS 0 vs. 1: hazard ratio (HR) 2.05; 95% confidence interval (CI) 1.30–4.84; p = 0.01] and ypN (0 vs. 1: HR 2.33; 95% CI 1.12–4.84; p = 0.02; 0 vs. 2/3: HR 3.73; 95% CI 1.68–8.28; p = 0.001) as independent covariates for RFS. Furthermore, PS (0 vs. 1; HR 2.94; 95% CI 1.51–5.72; p = 0.002) and ypN (0 vs. 1; HR 2.26; 95% CI 1.09–4.69; p = 0.03; 0 vs. 2/3: HR 3.90; 95% CI 1.79–8.48; p = 0.001) were also independent covariates for OS.
Performance status 1 and ypN+ were significantly associated with a poor prognosis after trimodality therapy for ESCC.
To explore the effects and mechanisms of anti-tumor necrosis factor-α (TNF-α) antibody on insulin resistance (IR) in rats with sepsis-induced stress hyperglycemia.
The sepsis-induced stress hyperglycemic rat model was constructed by cecal ligation and puncture combined with the intraperitoneal injection of lipopolysaccharide. The rats were randomly divided into six groups: normal control (NC) group, surgical rats (Cntl) group, high-dose anti-TNF-α antibody therapy (TNF, 6 mg/kg) group, low-dose anti-TNF-α antibody therapy (Tnf, 3 mg/kg) group, insulin therapy (INS) group, and INS + Tnf group. The blood glucose and serum insulin concentrations were detected, followed by analysis of intraperitoneal glucose tolerance test (IPGTT) and hyperinsulinemic–euglycemic clamp. Finally, the expression levels of phospho-Akt (p-Akt), Akt, p-mTOR, mTOR, nuclear factor-κB (NFκB), I kappa beta kinase (IKKβ), and suppressor of cytokine signaling (SOCS-3) were detected by western blotting.
There was no significant difference in blood glucose concentrations among these groups, while the serum insulin concentration in TNF and Tnf groups was lower than that in the Cntl group at postoperative 6 h (P < 0.05). IPGTT analysis revealed that blood glucose level was lower in the TNF group than that in the Cntl group (P < 0.05). The glucose infusion rate in the Cntl group was lower than that in the Tnf and TNF groups (P < 0.05). The p-Akt/Akt, p-mTOR/mTOR ratio, and expression levels of NFκB, IKKβ and SOCS-3 were lower in the drug intervention than that in the Cntl group (P < 0.05).
Anti-TNF-α antibody could reduce IR by inhibiting AKt/mTOR signaling pathway and the expression levels of NFκB, IKKβ, and SOCS-3 in rats with sepsis-induced stress hyperglycemia.
The aim of our study was to investigate Internet and eHealth usage, with respect to eHealth literacy, by cancer patients and their relatives.
Using a standardized questionnaire we asked patients who attended lectures on complementary medicine in 2016.
We received 142 questionnaires. The frequency of general Internet usage was directly associated with younger age and better Internet connection. Younger participants were not only more confident in allocating health-related Internet information into reliable or unreliable facts, but also more confident and capable of gaining medical knowledge through eHealth services. A regular use of eHealth services facilitated the decision-making process. Reading ability was associated with a better understanding regarding eHealth offers.
In a modern health care system, emphasis should be on skills contributing to eHealth literacy among patients to improve their ability to profit from eHealth offers and improve health care.
The presence of disseminated tumor cells (DTC) in the bone marrow of endometrial carcinoma patients has been demonstrated previously. In contrast to breast cancer, no prognostic significance or association with clinicopathological features was revealed for endometrial carcinoma so far. The aim of this study was to investigate DTC in a large patient cohort with in-depth pathology review data available and to study DTC occurrence in the context of L1CAM and long-term disease specific follow-up.
Patients treated for endometrial carcinoma at the Tuebingen University Women's hospital between 2003 and 2013 were identified. Cases with previous expert central pathology review including L1CAM immunohistochemistry and bone marrow aspirates available were selected. The presence of DTC and L1CAM expression was studied immunohistochemically.
In 395 cases with a confirmed diagnosis of endometrial carcinoma, bone marrow aspirates were available. DTC were detected in 17.2%. The presence of DTC was independent from tumor histology, grade, lymphovascular space involvement (LVSI), FIGO stage, myoinvasion, L1CAM immunoreactivity, and nodal metastasis. DTC occurred less frequently in cases with a microcystic elongated and fragmented (MELF) pattern of invasion (2.2 vs. 21.8%, p = 0.0003). Disease progression was distributed equally among patients with and without DTC present.
We were able to confirm previous findings of DTC presence in a large well-characterized cohort of endometrial carcinoma patients. DTC are detectable in almost one-fifth of endometrial carcinoma and occur less frequently with a MELF pattern of invasion. Further studies investigating the role of DTC in endometrial carcinoma are warranted.
Esophageal squamous cell carcinoma (ESCC) is a heterogeneous disease in the sense that the biological behavior is regulated by the activation of various signaling pathways. The aim of this study was to investigate the relationships between the expressions of various targetable proteins and the clinicopathological characteristics of ESCC patients.
A total of 286 patients with ESCC who had undergone curative surgical resection without neoadjuvant therapy were enrolled in this study. The protein expressions of EGFR, HER2, MET, IGF1R, FGFR2, p53, and PD-L1 were immunohistochemically evaluated in a tissue microarray analysis. The relationships between the expression statuses of each of the above molecules, and the PD-L1 expression status as well as the clinicopathological characteristics, including the survival outcome were assessed.
The expression frequencies of EGFR, HER2, MET, IGF1R, FGFR2, p53, and PD-L1 were as follows: 90.9, 1.0, 2.4, 71.0, 16.1, 62.9 and 23.4%. The overlapping expressions of two or more receptor tyrosine kinases were observed in 72.0%. MET expression was the only poor prognostic factor of recurrence-free survival [hazard ratio (HR) 1.89, 95% confidence interval (CI) 1.15–3.11]; in contrast, PD-L1 was the only favorable prognostic factor for both recurrence-free survival (HR 0.57, 95% CI 0.38–0.87) and overall survival (HR 0.56, 95% CI 0.35–0.89). No correlation was observed between the expressions of PD-L1 and the other molecules.
This large cohort study demonstrated that multiple molecules were co-expressed in most of the ESCC cases, suggesting that combining molecular targeted agents for these co-expressed molecules should be considered.
Intracellular antioxidant enzymes are commonly upregulated in various cancer types and are associated with treatment outcomes. Because the relationship has rarely been examined in oral squamous cell carcinoma (OSCC), we aimed to evaluate the association between the levels of glutathione peroxidase (GPX)1, GPX4, and thioredoxin reductase (TrxR)1 expression and prognosis in patients with OSCC who underwent curative surgical resection.
This study included 233 patients who underwent curative surgery for previously untreated OSCC between 2000 and 2012. Tumour GPX1, GPX4, and TrxR1 expression was evaluated by immunohistochemistry and was dichotomised to low and high values according to defined expression levels. The association between GPX1, GPX4, and TrxR1 expression and clinicopathological results was analysed. Univariate and multivariate analyses using the Cox proportional hazards model were conducted to assess the significance of differences in recurrence or survival outcomes between variables.
High GPX1, GPX4, and TrxR1 expression was observed in 99 (42.5%), 133 (57.1%), and 46 (19.7%) patients, respectively. GPX1 overexpression was significantly correlated with nodal metastasis, advanced overall stage, depth of invasion of >10 mm, high grade and perineural invasion (P < 0.05). High GPX4 expression was also related to nodal metastasis, overall advanced stage and high grade (P < 0.05). Univariate and multivariate analyses showed that increased GPX1 expression was significantly associated with poor disease-free, cancer-specific and overall survival (all P < 0.05), while increased GPX4 or TrxR1 expression was not (all P > 0.1).
Tumour GPX1 expression is a useful biomarker predictive of recurrence and survival in OSCC patients.
In clinical practice, most patients with hepatocellular carcinoma require subsequent treatments for remaining, progressing, or recurring tumors. We investigated all-treatment array and outcomes in an HCC cohort from initial diagnosis to death.
We enrolled 1687 consecutive patients with HCC who underwent initial diagnosis and treatment at the National Cancer Center, Korea, from January 2004 to December 2009.
In total, 1357 patients (80.4%) showed RPRTs during median 20.4-month follow-up. Initial transplantation resulted in the least rate (32.3%) of RPRTs. Median treatment frequency was 3.0 times (range 1–20) and 382 patients (27.3%) received treatments ≥6 times. The median treatment frequency was different based on four factors (p < 0.05): age, tumor stage, tumor type and initial treatment modality. Patients with Barcelona Clinic Liver Cancer stage 0 received less frequent treatments. As the stage progressed from 0 to B, the median treatment frequency increased. Radiofrequency ablation as initial treatment was associated with the longest median treatment interval at 19.0 weeks, followed by resection at 14.1 weeks. The median treatment interval was significantly shorter as the stage progressed (p < 0.01). TACE was most frequently performed for RPRTs; the median number of subsequent TACE was 3 (range 1–19). Subsequent treatment array was very heterogeneous, and no certain pattern was found.
Our findings suggest that the survival outcome of patients with HCC is based on the results of cumulative multiple treatments rather than an initial treatment. It is time to consider prospective studies evaluating sequential treatment array of HCC.
To identify the unmonitored use of herbal medicine by female patients with breast cancer, examining the impact of an integrative physician (IP) consultation on this practice.
The files of 269 female patients with breast cancer following an IP consultation were surveyed retrospectively for use of herbal medicine for cancer-related goals. Expectations from the IP consultation and adherence to the IP-guided treatments were examined as well.
Among the cohort, 111 (41.3%) reported using herbal medicine for cancer-related goals, unmonitored by their oncology healthcare professional. Factors predicting herbal medicine use were the adoption of dietary changes (odds ratio = 13.6, p < 0.001, CI 7.16–26.0) and the expectation that the IP consultation and treatments would address cancer-related goals (odds ratio = 3.29, p = 0.001, CI 1.64–6.6). Patients with metastatic disease were more likely to be using herbal medicine than non-users (34.5 vs. 22.8%; p = 0.088), as were those who had consulted with a complementary/alternative medicine practitioner (54.9 vs. 20.8%; p = 0.005). The IP advised 17 patients (15.3%) to stop taking specific herbal products due to safety-related concerns; and 10 patients to take dietary supplements for relief of specific symptoms. Herbal medicine users were less likely than non-users to adhere to the IP-recommended treatment program (34.7 vs. 48.3%; p = 0.037).
Unmonitored use of herbal medicine by patients with breast cancer is more frequent among those adopting dietary changes for cancer-related goals. Integrative physicians provide evidence-based guidance on the safe and effective use of herbal products, and reframe patient expectations from cancer-related goals to reducing symptoms and improving quality of life.
Transforming growth factor-β (TGF-β) induction of epithelial–mesenchymal transition (EMT) in SW480 was established as a system for studies of colon cancer metastasis. However, the epigenetic mechanisms underlying this process remain unknown. In mammal, polycomb repressive complex-2 (PRC2) is a highly conserved histone methyltransferase involved in epigenetic regulations. Enhancer of zeste Homolog 2 (EZH2) is the catalytic subunit of PRC2, which catalyzes methylation of lysine 27 of histone H3 (H3K27).
An inducible EMT system in colorectal cancer was utilized to study its mechanistic and phenotypic changes. Particularly, gene expression analysis was studied after immunoprecipitation.
In this study, we reported that EZH2 is significantly enriched in the promoter region of WNT5A after TGF-β induction in SW480 colon cancer cell line, which in turn silenced the expression of WNT5A. Furthermore, EZH2 inhibitor antagonized the TGF-β-induced morphological conversion associated with epithelial–mesenchymal transition (EMT). Conversely, inhibition of histone H3K27me3 reader CBX does not affect the WNT5A expression level during TGF-β-induced EMT.
Our results indicate that EZH2 was essential for the silencing of WNT5A during TGF-β-induced epithelial–mesenchymal transition of colon cancer cells.
Osteosarcoma (OS) is one of the most prevalent primary malignant bone tumors in adolescent. HOTAIR is highly expressed and associated with the epigenetic modifications, especially DNA methylation, in cancer. However, the regulation mechanism between HOTAIR and DNA methylation and the biological effects of them in the pathogenesis of osteosarcoma remains elusive.
Through RNA-sequencing and computational analysis, followed by a variety of experimental validations, we report a novel interplay between HOTAIR, miR-126, and DNA methylation in OS.
We found that HOTAIR is highly expressed in OS cells and the knockdown of HOTAIR leads to the down-regulation of DNMT1, as well as the decrease of global DNA methylation level. RNA-sequencing analysis of HOTAIR-regulated gene shows that CDKN2A is significantly repressed by HOTAIR. A series of experiments show that HOTAIR represses the expression of CDKN2A through inhibiting the promoter activity of CDKN2A by DNA hypermethylation. Further evidence shows that HOTAIR activates the expression of DNMT1 through repressing miR-126, which is the negative regulator of DNMT1. Functionally, HOTAIR depletion increases the sensibility of OS cells to DNMT1 inhibitor through regulating the viability and apoptosis of OS cells via HOTAIR-miR126-DNMT1-CDKN2A axis.
These results not only enrich our understanding of the regulation relationship between non-coding RNA, DNA methylation, and gene expression, however, also provide a novel direction in developing more sophisticated therapeutic strategies for OS patients.
To explore the biological functions and mechanism of Opa interacting protein 5 (OIP5) in bladder cancer (BC).
We investigated the expression of OIP5 in BC through immunohistochemical staining (IHC) and its correlation with clinicopathologic features of BC patients. Moreover, knockdown of OIP5 was performed in BC cell lines and colony formation capacity, cell growth curve, cell cycle phase and cell apoptosis assay was applied for investigating the roles of OIP5 in BC. Moreover, the expression of OIP5 was validated through the Cancer Genome Atlas (TCGA) database. The diagnosis value of OIP5 was accessed by receiver operating characteristic (ROC) analysis in TCGA database.
The expression of OIP5 in BC tissues was significantly higher than that in adjacent non-tumor tissues and bladder mucosa tissues with chronic cystitis. Higher protein expression level of OIP5 predicted shorter survival time in patients with BC, which was significantly correlated with larger tumor size, high-grade tumor and advanced T classification. The expression of OIP5 was considerably decreased after lentivirus infection both at mRNA and protein levels. Functional assay displayed that silencing of OIP5 inhibited colony formation capacity and cell growth in BC cell lines. Cell cycle assays indicated that suppressed OIP5 disturbed the balance of the cell cycle in BC cell lines, which increased the cell population of the G1 phase and decreased the cell population of the S phase. Furthermore, knockdown of OIP5 expression enhanced cell apoptosis process. The expression of OIP5 was significantly up-regulated in BC compared with adjacent non-tumor tissues based on TCGA database. OIP5 had the potential diagnostic value for BC.
Our work demonstrated that OIP5 might function as an oncogene to promote colony formation capacity and cell growth, arrest cell cycle and suppress cell apoptosis in bladder cancer.
