Patient-derived xenografts and in vitro model show rationale for imatinib mesylate repurposing in HEY1-NCoA2-driven mesenchymal chondrosarcoma.

Mesenchymal chondrosarcoma (MCS) is a high-grade malignancy that represents 2-9% of chondrosarcomas and mostly affects children and young adults. HEY1-NCoA2 gene fusion is considered to be a driver of tumorigenesis and it has been identified in 80% of MCS tumors. The shortage of MCS samples and biological models creates a challenge for the development of effective therapeutic strategies to improve the low survival rate of MCS patients. Previous molecular studies using immunohistochemical staining of patient samples suggest that activation of PDGFR signaling could be involved in MCS tumorigenesis. This work presents the development of two independent in vitro and in vivo models of HEY1-NCoA2-driven MCS and their application in a drug repurposing strategy. The in vitro model was characterized by RNA sequencing at the single-cell level and successfully recapitulated relevant MCS features. Imatinib, as well as specific inhibitors of ABL and PDGFR, demonstrated a highly selective cytotoxic effect targeting the HEY1-NCoA2 fusion-driven cellular model. In addition, patient-derived xenograft (PDX) models of MCS harboring the HEY1-NCoA2 fusion were developed from a primary tumor and its distant metastasis. In concordance with in vitro observations, imatinib was able to significantly reduce tumor growth in MCS-PDX models. The conclusions of this study serve as preclinical results to revisit the clinical efficacy of imatinib in the treatment of HEY1-NCoA2-driven MCS.

Quantum steering ellipsoids.

The quantum steering ellipsoid of a two-qubit state is the set of Bloch vectors that Bob can collapse Alice's qubit to, considering all possible measurements on his qubit. We provide an elementary construction of the ellipsoid for arbitrary states, calculate its volume, and explain how this geometric representation can be made faithful. The representation provides a range of new results, and uncovers new features, such as the existence of "incomplete steering" in separable states. We show that entanglement can be analyzed in terms of three geometric features of the ellipsoid and prove that a state is separable if and only if it obeys a "nested tetrahedron" condition.

Maximally and minimally correlated states attainable within a closed evolving system.

The amount of correlation attainable between the components of a quantum system is constrained if the system is closed. We provide some examples, largely from the field of quantum thermodynamics, where knowing the maximal possible variation in correlations is useful. The optimization problem it raises requires us to search for the maximally and minimally correlated states on a unitary orbit, with and without energy conservation. This is fully solvable for the smallest system of two qubits. For larger systems, the problem is reduced to a manageable, classical optimization.

Exchange fluctuation theorem for correlated quantum systems.

We extend the exchange fluctuation theorem for energy exchange between thermal quantum systems beyond the assumption of molecular chaos, and describe the nonequilibrium exchange dynamics of correlated quantum states. The relation quantifies how the tendency for systems to equilibrate is modified in high-correlation environments. In addition, a more abstract approach leads us to a "correlation fluctuation theorem". Our results elucidate the role of measurement disturbance for such scenarios. We show a simple application by finding a semiclassical maximum work theorem in the presence of correlations. We also present a toy example of qubit-qudit heat exchange, and find that non-classical behaviour such as deterministic energy transfer and anomalous heat flow are reflected in our exchange fluctuation theorem.