The complexity of cancer survivorship: a case for personalized medicine. Report of the 2014 Grandangolo conference

This article reviews the Grandangolo conference on cancer survivorship and highlights the major findings. These include the improvement in survivorship, and the emergence of survivorship related syndromes, such as new neoplasms, cardiomyopathy, neutorpathy fatigue and memory loss. Emotional disorders may include the Lazarus’ Syndrome and the post-traumatic stress disorder. An open question is whether we should have specialists of survivorship or primary care physicians or oncologists could fulfill this role.     

Antiangiogenic evaluation of ZnWO4 nanoparticles synthesised through microwave-assisted hydrothermal method

Angiogenesis, the complex process of formation of new blood vessels from pre-existing blood vessels, which involves the participation of several pro- and anti-angiogenic factors, is implicated in many physiological and pathological conditions. Nanoparticle-based anti-angiogenic activity at the tumour tissue, harnessed by the Enhanced Permeability and Retention Effect (EPR effect), could potentially become a breakthrough therapy to halt tumour progression. Herein, we evaluate the anti-angiogenic effect of ZnWO₄ nanoparticles (NPs). The nanoparticles were obtained by microwave-assisted hydrothermal synthesis (MAHS) at 120?°C for 60?min and were structurally characterised by X-ray diffraction (XRD) and micro-Raman (MR) spectroscopy. The mean size and polydispersity index were estimated by Zeta potential analysis. The XRD analysis revealed structural organisation at a long-range order, with an average crystallite size of around 3.67?nm, while MR revealed short-range order for ZnWO₄. The anti-angiogenic potential of zinc tungstate nanoparticles was investigated through the chorioallantoic membrane assay (CAM) using fertilised chicken eggs. We demonstrate, in an unprecedented way, that nanocrystalline ZnWO₄ NPs obtained by MAHS, at low reaction temperatures, showed excellent anti-angiogenic properties even at low concentrations. The ZnWO₄ NPs were further evaluated for its cytotoxicity in vitro.     

Peripheral administration of an angiotensin II AT(1) receptor antagonist decreases the hypothalamic-pituitary-adrenal response to isolation Stress

Angiotensin II, which stimulates AT(1) receptors, is a brain and peripheral stress hormone. We pretreated rats with the AT(1) receptor antagonist candesartan for 13 d via sc-implanted osmotic minipumps, followed by 24-h isolation in individual metabolic cages. We measured angiotensin II receptor-type binding and mRNAs and tyrosine hydroxylase mRNA by quantitative autoradiography and in situ hybridization, catecholamines by HPLC, and hormones by RIA. Isolation increased AT(1) receptor binding in hypothalamic paraventricular nucleus as well as anterior pituitary ACTH, and decreased posterior pituitary AVP. Isolation stress also increased AT(1) receptor binding and AT(1B) mRNA in zona glomerulosa and AT(2) binding in adrenal medulla, adrenal catecholamines, tyrosine hydroxylase mRNA, aldosterone, and corticosterone. Candesartan blocked AT(1) binding in paraventricular nucleus and adrenal gland; prevented the isolation-induced alterations in pituitary ACTH and AVP and in adrenal corticosterone, aldosterone, and catecholamines; abolished the increase in AT(2) binding in adrenal medulla; and substantially decreased urinary AVP, corticosterone, aldosterone, and catecholamines during isolation. Peripheral pretreatment with an AT(1) receptor antagonist blocks brain and peripheral AT(1) receptors and inhibits the hypothalamic-pituitary-adrenal response to stress, suggesting a physiological role for peripheral and brain AT(1) receptors during stress and a possible beneficial effect of AT(1) antagonism in stress-related disorders.     

Follicular lymphoma international prognostic index

The prognosis of follicular lymphomas (FL) is heterogeneous and numerous treatments may be proposed. A validated prognostic index (PI) would help in evaluating and choosing these treatments. Characteristics at diagnosis were collected from 4167 patients with FL diagnosed between 1985 and 1992. Univariate and multivariate analyses were used to propose a PI. This index was then tested on 919 patients. Five adverse prognostic factors were selected: age (> 60 years vs 60 years), Ann Arbor stage (III-IV vs I-II), hemoglobin level (< 120 g/L vs 120 g/L), number of nodal areas (> 4 vs 4), and serum LDH level (above normal vs normal or below). Three risk groups were defined: low risk (0-1 adverse factor, 36% of patients), intermediate risk (2 factors, 37% of patients, hazard ratio [HR] of 2.3), and poor risk ( 3 adverse factors, 27% of patients, HR = 4.3). This Follicular Lymphoma International Prognostic Index (FLIPI) appeared more discriminant than the International Prognostic Index proposed for aggressive non-Hodgkin lymphomas. Results were very similar in the confirmation group. The FLIPI may be used for improving treatment choices, comparing clinical trials, and designing studies to evaluate new treatments.      

Improving the role of echocardiography in studying the right ventricle of repaired tetralogy of Fallot patients: comparison with cardiac magnetic resonance

Right ventricular (RV) evaluation represents one of the major clinical tasks in the follow-up of repaired tetralogy of Fallot patients (rToF) with pulmonary valve regurgitation, as both severe RV dilatation and dysfunction are key factors in defining the need of pulmonary valve replacement. The aim of our study was to report the diagnostic accuracy of echocardiography in the identification of rToF patients with severely dilated and/or depressed RV as compared to cardiac magnetic resonance (CMR). Among our patients with rToF, a subgroup of 95 (17.6?±?6.8 years; 60% male), who underwent right ventricular qualitative and quantitative evaluation with CMR following echocardiographic suspicion of severe dilation/dysfunction, were included in the analysis. When comparing echocardiographic RV functional parameters to CMR findings, we found no association between CMR-ejection fraction (EF) and either tricuspid annulus plane systolic excursion (TAPSe) nor tissue Doppler systolic tricuspid excursion velocity (all p?=?ns). In contrast RVFAC was strongly associated with CMR-EF (r?=?0.44; p?<?0.01) as well as to longitudinal components of RV mechanics including tissue Doppler s′ (r?=?0.40; p?<?0.01) and TAPSE (r?=?0.36; p?<?0.01). When comparing echocardiographic and CMR structural parameters of the RV, we found that CMR RV volume was strongly related to echocardiographic measurements of RV end diastolic area (from the 4 chamber apical view) and with proximal parasternal short axis right ventricle outflow-dimension. Accordingly a regression model was derived from multiple regression analysis, which allows a more accurate estimate of CMR RV volume from echocardiography (r²?=?0.59, p?<?0.001). Our study demonstrates a significant, although imperfect, correlation between echocardiographic and CMR RV functional and geometrical parameters. Combining echocardiographic measures of RV inflow and RV outflow, we deliver a simple formula to estimate CMR-RV volume, improving the echocardiographic accuracy in RV volume quantification.