Biology and Hemodynamics of Aneurysm Rupture.

Predicting rupture risk in intracranial aneurysms is among one of the most critical questions in vascular surgery. The processes that govern an aneurysm growth are multifaceted and complex, but may be summarized into three components: hemodynamics, biology, and mechanics. We review and connect the literature in the three disciplines, identifying considerable strides in recent history and current gaps in research. Taken together, the findings from each field elucidate how and why certain aneurysms rupture, whereas others remain stable. These parameters could eventually inform a translatable predictive model that optimizes risk evaluation and physician's decision-making in treatment options for aneurysms.

Breast tumor cell hybrids form spontaneously in vivo and contribute to breast tumor metastases.

Cancer cell fusion was suggested as a mechanism of metastasis about a century ago. Since then, many additional modes of material transfer (i.e., tunneling nanotubes, and exosomes) to generate cell hybrids have been identified. However, studies documenting spontaneous tumor hybrid formation in vivo as a mechanism that enables metastasis are still lacking. Here, we tested whether spontaneous hybrid formation in vivo contributes to bona fide metastatic tumors. We first used single cell RNASeq to analyze the gene expression profile of spontaneously formed cancer cell-stromal hybrids, and results revealed that hybrids exhibit a clustering pattern that is distinct from either parental cell and suggestive of substantial diversity of individual hybrids. Despite the newly gained diversity, hybrids can retain expression of critical genes of each parental cell. To assess the biological impact of cancer cell hybrids in vivo, we transfected murine mammary tumor cells, isolated from FVB/N-Tg(MMTV-PyVT)634Mul/J mice (PyVT) with Cre recombinase prior to injection to the murine fat pad of FVB.129S6(B6)-Gt(ROSA)26Sortm 1(Luc)Kael /J mice such that luciferase expression is induced with hybrid formation; luciferase expression was tracked for up to four months. We observed that hybrid formation occurs spontaneously in vivo and that a significantly higher number of hybrids reside in metastases compared to the primary tumor, supporting the possibility that hybrids can emerge from the primary tumor and proliferate to help create a new tumor at a distant site. Additional studies are now warranted to delineate the mechanisms of cancer cell hybrid transit to metastases since drugs to inhibit hybrid formation might prevent metastatic spread.