Novel therapeutic approaches in chondrosarcoma.

Chondrosarcoma is a malignant tumor of bones, characterized by the production of cartilage matrix. Due to lack of effective treatment for advanced disease, the clinical management of chondrosarcomas is exceptionally challenging. Current research focuses on elucidating the molecular events underlying the pathogenesis of this rare bone malignancy, with the goal of developing new molecularly targeted therapies. Signaling pathways suggested to have a role in chondrosarcoma include Hedgehog, Src, PI3k-Akt-mTOR and angiogenesis. Mutations in IDH1/2, present in more than 50% of primary conventional chondrosarcomas, make the development of IDH inhibitors a promising treatment option. The present review discusses the preclinical and early clinical data on novel targeted therapeutic approaches in chondrosarcoma

Effectiveness of myAirCoach: A mHealth Self-Management System in Asthma

Background: Self-management programs have beneficial effects on asthma control, but their implementation in clinical practice is poor. Mobile health (mHealth) could play an important role in enhancing self-management. Objective: To assess the clinical effectiveness and technology acceptance of myAirCoach-supported self-management on top of usual care in patients with asthma using inhalation medication. Methods: Patients were recruited in 2 separate studies. The myAirCoach system consisted of an inhaler adapter, an indoor air-quality monitor, a physical activity tracker, a portable spirometer, a fraction exhaled nitric oxide device, and an app. The primary outcome was asthma control; secondary outcomes were exacerbations, quality of life, and technology acceptance. In study 1, 30 participants were randomized to either usual care or myAirCoach support for 3 to 6 months; in study 2, 12 participants were provided with the myAirCoach system in a 3-month before-after study. Results: In study 1, asthma control improved in the intervention group compared with controls (Asthma Control Questionnaire difference, 0.70; P = .006). A total of 6 exacerbations occurred in the intervention group compared with 12 in the control group (hazard ratio, 0.31; P = .06). Asthma-related quality of life improved (mini Asthma-related Quality of Life Questionnaire difference, 0.53; P = .04), but forced expiratory volume in 1 second was unchanged. In study 2, asthma control improved by 0.86 compared with baseline (P = .007) and quality of life by 0.16 (P = .64). Participants reported positive attitudes toward the system. Discussion: Using the myAirCoach support system improves asthma control and quality of life, with a reduction in severe asthma exacerbations. Well-validated mHealth technologies should therefore be further studied

HER2 and TOP2A in high-risk early breast cancer patients treated with adjuvant epirubicin-based dose-dense sequential chemotherapy

<p>Abstract</p> <p>Background</p> <p>HER2 and TOP2A parameters (gene status, mRNA and protein expression) have individually been associated with the outcome of patients treated with anthracyclines. The aim of this study was to comprehensively evaluate the prognostic/predictive significance of the above parameters in early, high-risk breast cancer patients treated with epirubicin-based, dose-dense sequential adjuvant chemotherapy.</p> <p>Methods</p> <p>In a series of 352 breast carcinoma tissues from patients that had been post-operatively treated with epirubicin-CMF with or without paclitaxel, we assessed HER2 and TOP2A gene status (chromogenic in situ hybridization), mRNA expression (quantitative reverse transcription PCR), as well as HER2 and TopoIIa protein expression (immunohistochemistry).</p> <p>Results</p> <p>HER2 and TOP2A amplification did not share the same effects on their downstream molecules, with consistent patterns observed in HER2 mRNA and protein expression according to HER2 amplification (all parameters strongly inter-related, p values < 0.001), but inconsistent patterns in the case of TOP2A. TOP2A gene amplification (7% of all cases) was not related to TOP2A mRNA and TopoIIa protein expression, while TOP2A mRNA and TopoIIa protein were strongly related to each other (p < 0.001). Hence, TOP2A amplified tumors did not correspond to tumors with high TOP2A mRNA or TopoIIa protein expression, while the latter were characterized by high Ki67 scores (p = 0.003 and p < 0.001, respectively). Multivariate analysis adjusted for nodal involvement, hormone receptor status, Ki67 score and HER2/TOP2A parameters revealed HER2/TOP2A co-amplification (21.2% of HER2 amplified tumors) as an independent favorable prognostic factor for DFS (HR = 0.13, 95% CI: 0.02-0.96, p = 0.046); in contrast, increased HER2/TOP2A mRNA co-expression was identified as an independent adverse prognostic factor for both DFS (HR = 2.41, 95% CI: 1.31-4.42, p = 0.005) and OS (HR = 2.83, 95% CI: 1.42-5.63, p = 0.003), while high TOP2A mRNA expression was an independent adverse prognostic factor for OS (HR = 2.06, 95% CI: 1.23-3.46, p = 0.006). None of the parameters tested was associated with response to paclitaxel.</p> <p>Conclusions</p> <p>This study confirms the favorable prognostic value of HER2/TOP2A co-amplification and the adverse prognostic value of high TOP2A mRNA expression extending it to the adjuvant treatment setting in early high-risk breast cancer. The strong adverse prognostic impact of high HER2/TOP2A mRNA co-expression needs further validation in studies designed to evaluate markers predictive for anthracyclines.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry <a href="http://www.anzctr.org.au/ACTRN12611000506998">ACTRN12611000506998</a>.</p

Farnesylated Nuclear Proteins Kugelkern and Lamin Dm0 Affect Nuclear Morphology by Directly Interacting with the Nuclear Membrane

Nuclear shape changes are observed during a variety of developmental processes, pathological conditions and ageing. Here, the molecular mechanism is analyzed how the farnesylated nuclear proteins interact with the nuclear envelope and deform the phospholipid bilayer

Obsessed with healthy eating: a systematic review of observational studies assessing orthorexia nervosa in patients with diabetes mellitus

Orthorexia nervosa (ON) is an unspecified feeding or eating disorder (USFED) characterized by an exaggerated, unhealthy obsession with healthy eating. Typical eating disorders (EDs) and USFEDs are common among patients with diabetes mellitus (DM), which complicates metabolic control and disease outcomes. The present systematic review summarizes the evidence on the prevalence of ON symptomatology among patients with DM. PubMed, Web of Science, Scopus, and grey literature were searched, and relevant observational studies were screened using the Rayyan software. The quality of the studies was assessed using the appraisal tool for cross-sectional studies (AXIS) and the Newcastle–Ottawa scale (NOS). Out of 4642 studies, 6 fulfilled the predefined criteria and were included in the qualitative synthesis. Most studies relied on the ORTO-15 or its adaptations to identify ON among patients with DM. No apparent sex or age differences exist regarding the prevalence of ON symptoms. None of the studies compared the prevalence of ON in patients with type 1 and type 2 DM. Most of the research was of average to good methodological quality. In conclusion, patients with DM often exhibit ON tendencies, although research is still limited regarding the etiology or mechanistic drivers behind ON and the characteristics of patients with a dual ON–DM diagnosis

Obsessed with healthy eating: A systematic review of observational studies assessing orthorexia nervosa in patients with diabetes mellitus

Orthorexia nervosa (ON) is an unspecified feeding or eating disorder (USFED) characterized by an exaggerated, unhealthy obsession with healthy eating. Typical eating disorders (EDs) and USFEDs are common among patients with diabetes mellitus (DM), which complicates metabolic control and disease outcomes. The present systematic review summarizes the evidence on the prevalence of ON symptomatology among patients with DM. PubMed, Web of Science, Scopus, and grey literature were searched, and relevant observational studies were screened using the Rayyan software. The quality of the studies was assessed using the appraisal tool for cross-sectional studies (AXIS) and the Newcastle–Ottawa scale (NOS). Out of 4642 studies, 6 fulfilled the predefined criteria and were included in the qualitative synthesis. Most studies relied on the ORTO-15 or its adaptations to identify ON among patients with DM. No apparent sex or age differences exist regarding the prevalence of ON symptoms. None of the studies compared the prevalence of ON in patients with type 1 and type 2 DM. Most of the research was of average to good methodological quality. In conclusion, patients with DM often exhibit ON tendencies, although research is still limited regarding the etiology or mechanistic drivers behind ON and the characteristics of patients with a dual ON–DM diagnosis. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Obsessed with Healthy Eating: A Systematic Review of Observational Studies Assessing Orthorexia Nervosa in Patients with Diabetes Mellitus

Orthorexia nervosa (ON) is an unspecified feeding or eating disorder (USFED) characterized by an exaggerated, unhealthy obsession with healthy eating. Τypical eating disorders (EDs) and USFEDs are common among patients with diabetes mellitus (DM), which complicates metabolic control and disease outcomes. The present systematic review summarizes the evidence on the prevalence of ON symptomatology among patients with DM. PubMed, Web of Science, Scopus, and grey literature were searched, and relevant observational studies were screened using the Rayyan software. The quality of the studies was assessed using the appraisal tool for cross-sectional studies (AXIS) and the Newcastle–Ottawa scale (NOS). Out of 4642 studies, 6 fulfilled the predefined criteria and were included in the qualitative synthesis. Most studies relied on the ORTO-15 or its adaptations to identify ON among patients with DM. No apparent sex or age differences exist regarding the prevalence of ON symptoms. None of the studies compared the prevalence of ON in patients with type 1 and type 2 DM. Most of the research was of average to good methodological quality. In conclusion, patients with DM often exhibit ON tendencies, although research is still limited regarding the etiology or mechanistic drivers behind ON and the characteristics of patients with a dual ON–DM diagnosis

Prognostic significance of RACGAP1 mRNA expression in high-risk early breast cancer: a study in primary tumors of breast cancer patients participating in a randomized Hellenic Cooperative Oncology Group trial

RACGAP1 is a Rac GTPase-activating protein involved in cell growth regulation, cell transformation and metastasis. The aim of the present study was to explore the prognostic and/or predictive significance of RACGAP1 mRNA expression on disease-free survival (DFS) and overall survival (OS) in high-risk early breast cancer patients and compare it to that of Ki67 protein expression and to the Nottingham prognostic index (NPI). A total of 595 high-risk breast cancer patients were treated in a two-arm trial evaluating postoperative dose-dense sequential chemotherapy with epirubicin followed by CMF with or without paclitaxel. RNA was extracted from 314 formalin-fixed paraffin-embedded primary tumor tissue samples followed by one-step quantitative RT-PCR for assessing RACGAP1 mRNA expression. High RACGAP1 mRNA expression (above the median) was associated with poor DFS (log-rank, p = 0.002) and OS (p &lt; 0.001). High histological grade, as well as high Ki67 protein expression, was more frequent in the high-expression group of RACGAP1. Results of the Cox multivariate regression analysis revealed that high RACGAP1 mRNA expression independently predicted poor overall survival (Wald’s p = 0.008). High Ki67 protein expression was also an adverse prognostic factor for death (p = 0.016), while high NPI score values were not. High RACGAP1 mRNA expression, as assessed by qRT-PCR, was found to be of adverse prognostic significance in high-risk early breast cancer patients treated with dose-dense sequential chemotherapy. The utility of RACGAP1 mRNA expression in patient selection for treatment with aggressive chemotherapy regimens should be further explored and validated in larger cohorts