High‐risk neuroblastoma is a rapidly growing tumor with a survival rate below 50%. A new treatment strategy is to administer chemotherapeutic drugs metronomically, i.e., at lower doses and frequent intervals. The aim of the study was to investigate the effects of GMX1777, a chemotherapeutic drug affecting cellular energy metabolism, in a mouse model for high‐risk neuroblastoma. Female SCID mice were injected s.c. with MYCN‐amplified human neuroblastoma cells and randomized to either treatment with GMX1777 or vehicle. In some animals, treatment was discontinued allowing tumor relapse. Treatment response was evaluated using the pediatric preclinical testing program (PPTP). Immunohistochemistry and qRT‐PCR was performed on tumor cryosections to investigate the microscopic and molecular changes in tumors in response to GMX1777. Despite an increase in vessel density, tumor regression and a high group response score according to PPTP criteria was induced by GMX1777 without inducing drug resistance. Treatment resulted in inhibition of tumor cell proliferation, vessel maturation, reduced hypoxia, increased infiltration of MHC class II negative macrophages and expansion of the nonvascular stromal compartment. Decreased stromal VEGF‐A and PDGF‐B mRNA in response to treatment together with the structural data suggest a “deactivation” or “silencing” of the tumor stroma as a paracrine entity. In conclusion, GMX1777 was highly efficient against high‐risk neuroblastoma xenografts through modulation of both the tumor cell and stromal compartment.

Appropriate cardiovascular animal models are urgently needed to investigate genetic, molecular, and therapeutic approaches, yet the translation of results from the currently used species is difficult due to their genetic distance as well as their anatomical or physiological differences. Animal species that are closer to the human situation might help to bridge this translational gap. The common marmoset (Callithrix jacchus) is an interesting candidate to investigate certain heart diseases and cardiovascular comorbidities, yet a basic functional characterization of its hemodynamic system is still missing. Therefore, cardiac functional analyses were performed by utilizing the invasive intracardiac pressure–volume loops (PV loop) system in seven animals, magnetic resonance imaging (MRI) in six animals, and echocardiography in five young adult male common marmosets. For a direct comparison between the three methods, only data from animals for which all three datasets could be acquired were selected. All three modalities were suitable for characterizing cardiac function, though with some systemic variations. In addition, vena cava occlusions were performed to investigate the load-independent parameters collected with the PV loop system, which allowed for a deeper analysis of the cardiac function and for a more sensitive detection of the alterations in a disease state, such as heart failure or certain cardiovascular comorbidities.

Background: Previous studies have shown cardiac abnormalities in acute liver injury, suggesting a potential role in the associated high mortality. Methods: We designed an experimental study exploring the short-term effects of acute cholestasis-induced liver injury on cardiac function and structure in a rodent bile duct ligation (BDL) model to elucidate the potential interplay. Thirty-seven male Sprague-Dawley rats were subjected to BDL surgery (n = 28) or served as sham-operated (n = 9) controls. Transthoracic echocardiography, Doppler evaluation of the left anterior descending coronary artery, and myocardial contrast echocardiography were performed at rest and during adenosine and dobutamine stress 5 days after BDL. Immunohistochemical staining of myocardial tissue samples for hypoxia and inflammation as well as serum analysis were performed. Results: BDL animals exhibited acute liver injury with elevated transaminases, bilirubin, and total circulating bile acids (TBA) 5 days after BDL (TBA control: 0.81 ± 2.54 µmol/L vs. BDL: 127.52 ± 57.03 µmol/L; p < 0.001). Concurrently, cardiac function was significantly impaired, characterized by reduced cardiac output (CO) and global longitudinal strain (GLS) in the echocardiography at rest and under pharmacological stress (CO rest control: 120.6 ± 24.3 mL/min vs. BDL 102.5 ± 16.6 mL/min, p = 0.041; GLS rest control: −24.05 ± 3.8% vs. BDL: −18.5 ± 5.1%, p = 0.01). Myocardial perfusion analysis revealed a reduced myocardial blood flow at rest and a decreased coronary flow velocity reserve (CFVR) under dobutamine stress in the BDL animals (CFVR control: 2.1 ± 0.6 vs. BDL: 1.7 ± 0.5 p = 0.047). Immunofluorescence staining indicated myocardial hypoxia and increased neutrophil infiltration. Conclusions: In summary, acute cholestasis-induced liver injury can lead to impaired cardiac function mediated by coronary microvascular dysfunction, suggesting that major adverse cardiac events may contribute to the mortality of acute liver failure. This may be due to endothelial dysfunction and direct bile acid signaling.

The chorioallantoic membrane (CAM) model resembles a preclinical in vivo platform for the engraftment of different tumors and is especially well‐suited for the development and evaluation of novel cancer therapies. Due to the CAM′s extensive vascular network, it can sustain engrafted human tumor tissue, which can be used for therapy testing and analysis throughout the experimental process. Although numerous studies have demonstrated successful tumor engraftment and vascular integration into the CAM′s blood vessel network, the accurate and sequential measurement of tumor volume remains a significant challenge. Current imaging modalities, such as positron emission tomography/computed tomography, magnetic resonance imaging or three‐dimensional (3D) digital microscopy are limited by cost, complexity, and potential harm due to injected agents or radiation. This study introduces an innovative imaging approach by utilizing ultrahigh frequency (UHF) ultrasound combined with 3D ultrasound reconstruction of pancreatic ductal adenocarcinoma (PDAC) on the CAM. By utilizing ultrasound frequencies of up to 71 MHz, two‐dimensional (2D) imaging of PDAC tumors was transformed into comprehensive 3D reconstructions. This innovative approach provides a more detailed tissue resolution and enables noninvasive, longitudinal volumetric monitoring of tumor growth in vivo, and in principle provides a platform for future studies assessing angiogenesis and therapy response. In this study the accuracy of 3D UHF ultrasound was tested by comparing it with established imaging techniques such as 3D digital microscopy. In summary, the 3D ultrasound reconstruction resembles a more versatile noninvasive alternative for in vivo tumor volume measurement. This advanced imaging approach adds a valuable methodology for the investigation of tumor biology in the CAM model by providing noninvasive volumetric and morphological characterization of engrafted tumor tissue, thereby linking preclinical research and clinical applications.