Innovative approach to a functional mediastinal paraganglioma with anomalous coronary supply: a case report

Background Mediastinal paragangliomas (PGs) are rare and particularly challenging neuroendocrine tumours. Clinical presentation is heterogeneous and tumour resection can be challenging due to bleeding and the risk of catecholamine surges in functional tumours. Case Summary A 36-year-old man with multiple cardiovascular risk factors was admitted with subacute heart failure. Investigations revealed a large non-metastatic functional mediastinal PG irrigated mainly by a left circumflex coronary anomalous feeder branch. The surgical risk was deemed very high due to patient comorbidities, tumour vascularization, and close relation to major thoracic structures. A multidisciplinary team decided to perform embolization of the anomalous coronary branch followed by peptide-receptor radionuclide therapy with 177-LuDOTATE aiming to decrease tumour size and perioperative risk. Follow-up studies showed a reduction in tumour vascularization, size, and hormonal production. Discussion The innovative strategy of combining embolization of the anomalous feeder branch with radionuclide therapy proved to be a promising approach.

Computational modelling suggests complex interactions between interstitial flow and tumour angiogenesis

Angiogenesis, the growth of capillaries from pre-existing ones, plays a key role in cancer progression. Tumours release tumour angiogenic factors (TAFs) into the extracellular matrix (ECM) that trigger angiogenesis once they reach the vasculature. The neovasculature provides nutrients and oxygen to the tumour. In the ECM, the interstitial fluid moves driven by pressure differences and may affect the distribution of tumour TAFs, and, in turn, tumour vascularization. In this work, we propose a hybrid mathematical model to investigate the influence of fluid flow in tumour angiogenesis. Our model shows the impact of interstitial flow in a time-evolving capillary network using a continuous approach. The flow model is coupled to a model of angiogenesis that includes tip endothelial cells, filopodia, capillaries and TAFs. The TAF transport equation considers not only diffusive mechanisms but also the convective transport produced by interstitial flow. Our simulations predict a significant alteration of the new vascular networks, which tend to grow more prominently against the flow. The model suggests that interstitial flow may produce increased tumour malignancies and hindered treatments.

Hypoxia inducible factor down-regulation, cancer and cancer stem cells (CSCs): ongoing success stories

In cancers, hypoxia inducible factor 1 (HIF-1) is an over-expressed transcription factor, which regulates a large set of genes involved in tumour vascularization, metastases, and cancer stem cells (CSCs) formation and self-renewal.

Registered report: Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of 50 papers in the field of cancer biology published between 2010 and 2012. This Registered report describes the proposed replication plan of key experiments from ‘Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells’ by Ricci-Vitiani and colleagues, published in Nature in 2010 (<xref ref-type="bibr" rid="bib13">Ricci-Vitiani et al., 2010</xref>). The experiments that will be replicated are those reported in Figure 4B and Supplementary Figure 10B (<xref ref-type="bibr" rid="bib13">Ricci-Vitiani et al., 2010</xref>), which demonstrate that glioblastoma stem-like cells can derive into endothelial cells, and can be selectively ablated to reduce tumor progression in vivo, and Supplementary Figures S10C and S10D (<xref ref-type="bibr" rid="bib13">Ricci-Vitiani et al., 2010</xref>), which demonstrate that fully differentiated glioblastoma cells cannot form functionally relevant endothelium. The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife.