Cancer-associated cells release citrate to support tumour metastatic progression.

Citrate is important for lipid synthesis and epigenetic regulation in addition to ATP production. We have previously reported that cancer cells import extracellular citrate via the pmCiC transporter to support their metabolism. Here, we show for the first time that citrate is supplied to cancer by cancer-associated stroma (CAS) and also that citrate synthesis and release is one of the latter's major metabolic tasks. Citrate release from CAS is controlled by cancer cells through cross-cellular communication. The availability of citrate from CAS regulated the cytokine profile, metabolism and features of cellular invasion. Moreover, citrate released by CAS is involved in inducing cancer progression especially enhancing invasiveness and organ colonisation. In line with the in vitro observations, we show that depriving cancer cells of citrate using gluconate, a specific inhibitor of pmCiC, significantly reduced the growth and metastatic spread of human pancreatic cancer cells in vivo and muted stromal activation and angiogenesis. We conclude that citrate is supplied to tumour cells by CAS and citrate uptake plays a significant role in cancer metastatic progression.

Modeling and simulation of the cardiovascular system: a review of applications, methods, and potentials.

Proper function of the cardiovascular system is indispensible to human survival. However, this system is dominated by complex interactions between different physiological processes and control mechanisms. A structured analysis and a mathematical description of this system can provide more insight, and a computer-based simulation of dynamic processes in the cardiovascular system could be applied in numerous tasks. This article gives a review of different approaches to cardio-circulatory modeling and discusses methodological aspects and fields of application for several classes of models.

Methods of design, simulation, and control for the development of new VAD/TAH concepts.

Cardiovascular diseases are a major cause of death worldwide. If medical treatments fail to restore adequate blood flow in a patient, mechanical support is needed. To date, many different types of blood pumps have been developed, but only few are clinically available. This review article describes the challenges involved in this field of research and gives an overview of the development process. Past developments as well as current and new technologies and approaches applied are summarized. Finally, a perspective for improved devices is discussed.

Use of the Body Composition Monitor for Fluid Status Measurements in Subjects with High Body Mass Index.

BACKGROUND: Fluid management is a central aspect of haemodialysis (HD). Body composition monitor (BCM)-measured overhydration (OH) can improve fluid management strategies, but there remains uncertainty about its use in subjects with high body mass index (BMI). This study explored whether the observed tendency for HD patients with high BMI to complete dialysis fluid depleted according to BCM is associated with an artefact in the BCM models, or with systematic differences in the prescription and delivery of treatment. METHODS: To isolate the effect of BMI from effects relating to treatment, BCM measurements were made on 20 healthy subjects with high BMI. Mean OH was compared with a previously reported cohort of healthy subjects with normal BMI. To further explore BCM-measured OH in HD patients, measurements were made pre- and post-dialysis on 10 patients with high BMI alongside relative blood volume monitoring. Body shape was classified to assess associations between shape and OH. RESULTS: The mean OH for healthy subjects with high BMI was -0.1 litres, which was not different from that of healthy subjects with normal BMI. Median BCM-measured OH for HD patients was 1.8 and -1.8 litres pre- and post-dialysis respectively, while blood volume and blood pressure were maintained. Body shape correlated with OH in control subjects but not HD patients. CONCLUSIONS: We found no evidence of systematic bias in BCM-measured OH with high BMI in healthy subjects. BCM-measured post-dialysis fluid depletion in asymptomatic patients with high BMI appears to result from greater tolerance of ultrafiltration and ability to maintain blood volume.

Modeling a healthy and a person with heart failure conditions using the object-oriented modeling environment Dymola.

Several mathematical models of different physiological systems are spread through literature. They serve as tools which improve the understanding of (patho-) physiological processes, may help to meet clinical decisions and can even enhance medical therapies. These models are typically implemented in a signal-flow-oriented simulation environment and focus on the behavior of one specific subsystem. Neglecting other physiological subsystems and using a technical description of the physiology hinders the exchange with and acceptance of clinicians. By contrast, this paper presents a new model implemented in a physical, object-oriented modeling environment which includes the cardiovascular, respiratory and thermoregulatory system. Simulation results for a healthy subject at rest and at the onset of exercise are given, showing the validity of the model. Finally, simulation results showing the interaction of the cardiovascular system with a ventricular assist device in case of heart failure are presented showing the flexibility and mightiness of the model and the simulation environment. Thus, we present a new model including three important physiological systems and one medical device implemented in an innovative simulation environment.