58 research outputs found

    Expression of phosphorylated eIF4E-binding protein 1, but not of eIF4E itself, predicts survival in male breast cancer

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    Background: Male breast cancer is rare and treatment is based on data from females. High expression/activity of eukaryotic initiation factor 4E (eIF4E) denotes a poor prognosis in female breast cancer, and the eIF4E pathway has been targeted therapeutically. eIF4E activity in female breast cancer is deregulated by eIF4E over-expression and by phosphorylation of its binding protein, 4E-BP1, which relieves inhibitory association between eIF4E and 4E-BP1. The relevance of the eIF4E pathway in male breast cancer is unknown. Methods: We have assessed expression levels of eIF4E, 4E-BP1, 4E-BP2 and phosphorylated 4E-BP1 (p4E-BP1) using immunohistochemistry in a large cohort of male breast cancers (n=337) and have examined correlations with prognostic factors and survival. Results: Neither eIF4E expression or estimated eIF4E activity were associated with prognosis. However, a highly significant correlation was found between p4E-BP1 expression and disease-free survival, linking any detectable p4E-BP1 with poor survival (univariate log rank p=0.001; multivariate HR 8.8, p=0.0001). Conclusions: Our data provide no support for direct therapeutic targeting of eIF4E in male breast cancer, unlike in females. However, as p4E-BP1 gives powerful prognostic insights that are unrelated to eIF4E function, p4E-BP1 may identify male breast cancers potentially suitable for therapies directed at the upstream kinase, mTOR

    Imaging findings in craniofacial childhood rhabdomyosarcoma

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    Rhabdomyosarcoma (RMS) is the commonest paediatric soft-tissue sarcoma constituting 3–5% of all malignancies in childhood. RMS has a predilection for the head and neck area and tumours in this location account for 40% of all childhood RMS cases. In this review we address the clinical and imaging presentations of craniofacial RMS, discuss the most appropriate imaging techniques, present characteristic imaging features and offer an overview of differential diagnostic considerations. Post-treatment changes will be briefly addressed

    Non-Rhabdomyosarcoma Soft Tissue Sarcomas

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    Colonic neuroendocrine carcinoma in a child

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    Body Mindsets are Associated With Pain and Threat-Related Risk Factors for Pain in Survivors of Childhood Cancer.

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    Pain is a common consequence of childhood cancer. While most research has examined biomedical predictors of post-cancer pain, biopsychosocial conceptualisations such as the cancer threat interpretation (CTI) model hold promise for guiding comprehensive pain management strategies. Guided by the CTI model, this cross-sectional study evaluated correlates of post-cancer pain in childhood cancer survivors including threat-related risk factors (bodily threat monitoring, fear of cancer recurrence, help-seeking) and mindsets about the body. In the preceding three months, 21.8% of the survivors reported chronic pain (>3 months), and 14.3% experienced pain most days. Greater bodily threat monitoring, more fear of cancer recurrence, and more help-seeking were associated with more pain. There was heterogeneity in the mindsets that survivors of childhood cancer hold about their bodies. Holding the mindset that the 'body is an adversary' was associated with more pain, greater bodily threat monitoring, and more fear of cancer recurrence. Holding the mindset that the 'body is responsive' was associated with less bodily threat monitoring, while the mindset that the 'body is capable' was associated with greater help-seeking. A path model demonstrated a significant combined indirect effect of the 'body is an adversary' mindset on pain through bodily threat monitoring and fear of cancer recurrence. Overall, this study supported that a sub-group of childhood cancer survivors experience persistent and interfering pain and provided cross-sectional support for threat-related correlates for pain aligning with the CTI model. Body mindsets were associated with pain and threat-related correlates and may represent a novel target to support survivors with pain. PERSPECTIVE: This article presents associations of body mindsets, threat-related risk factors, and pain in survivors of childhood cancer (aged 11-25), guided by the Cancer Threat Interpretation model. The study indicates that body mindsets may be novel targets to embed in comprehensive post-cancer pain management approaches to support young survivors with pain

    Measurement of glomerular filtration rate by dynamic contrast-enhanced magnetic resonance imaging using a subject-specific two-compartment model

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    Measuring glomerular filtration rate (GFR) by dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) as part of standard of care clinical MRI exams (e.g., in pediatric solid tumor patients) has the potential to reduce diagnostic burden. However, enthusiasm for this relatively new GFR test may be curbed by the limited amount of cross-calibration studies with reference GFR techniques and the vast variety of MR tracer model algorithms causing confusion on the choice of model. To advance MRI-based GFR quantification via improved GFR modeling and comparison with associated 99mTc-DTPA-GFR, 29 long-term Wilms' tumor survivors (19.0-43.3 years, [median 32.0 ± 6.0 years]) treated with nephrectomy, nonnephrotoxic chemotherapy ± radiotherapy underwent MRI with Gd-DTPA administration and a 99mTc-DTPA GFR test. For DCE-MRI-based GFR estimation, a subject-specific two-compartment (SS-2C) model was developed that uses individual hematocrit values, automatically defines subject-specific uptake intervals, and fits tracer-uptake curves by incorporating these measures. The association between reference 99mTc-DTPA GFR and MR-GFRs obtained by SS-2C, three published 2C uptake, and inflow-outflow models was investigated via linear regression analysis. Uptake intervals varied from 64 sec to 141 sec [96 sec ± 21 sec] and hematocrit values ranged from 30% to 49% [41% ± 4%]; these parameters can therefore not be assumed as constants in 2C modeling. Our MR-GFR estimates using the SS-2C model showed accordingly the highest correlation with 99mTc-DTPA-GFRs (R2 = 0.76, P < 0.001) compared with other models (R2-range: 0.36-0.66). In conclusion, SS-2C modeling of DCE-MRI data improved the association between GFR obtained by 99mTc-DTPA and Gd-DTPA DCE-MRI to such a degree that this approach could turn into a viable, diagnostic GFR assay without radiation exposure to the patient
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