Randomized phase II placebo controlled study of codrituzumab in previously treated patients with advanced hepatocellular carcinoma.

Background & Aims: Codrituzumab, a humanized monoclonal antibody against Glypican-3 (GPC3) that is expressed in hepatocellular carcinoma (HCC), interacts with CD16/FcγRIIIa and triggers antibody-dependent cytotoxicity. Codrituzumab was studied vs. placebo in a randomized phase II trial in advanced HCC patients who had failed prior systemic therapy.

An integrated approach to quantitative modelling in angiogenesis research.

Angiogenesis, the process by which new vessels form from existing ones, plays an important role in many developmental processes and pathological conditions. We study angiogenesis in the context of a highly controllable experimental environment: the cornea micropocket assay. Using a multidisciplinary approach that combines experiments, image processing and analysis, and mathematical modelling, we aim to provide mechanistic insight into the action of two angiogenic factors, vascular endothelial growth factor A (VEGF-A) and basic fibroblast growth factor (bFGF).

Semantically linking in silico cancer models.

Multiscale models are commonplace in cancer modeling, where individual models acting on different biological scales are combined within a single, cohesive modeling framework. However, model composition gives rise to challenges in understanding interfaces and interactions between them. Based on specific domain expertise, typically these computational models are developed by separate research groups using different methodologies, programming languages, and parameters.

Differences in the biologic activity of 2 novel MEK inhibitors revealed by 18F-FDG PET: analysis of imaging data from 2 phase I trials.

Unlabelled: Two mitogen-activated protein kinase kinase (MAPK2, also known as MEK) inhibitors were assessed with (18)F-FDG PET in separate phase I clinical studies, clearly illustrating the potential of metabolic imaging for dose, dosing regimen, and compound selection in early-phase trials and utility for predicting nonresponding patients.

Methods: (18)F-FDG PET data were collected during 2 independent, phase I, dose-escalation trials of 2 novel MEK inhibitors (RO5126766 and RO4987655). PET acquisition procedures were standardized between the 2 trials, and PET images were analyzed centrally.

Evidence for bistable bacteria-neutrophil interaction and its clinical implications.

Neutropenia, which may develop as a consequence of chemotherapy, increases the risk of bacterial infection. Similarly, increased risk of bacterial infection appears in disorders of phagocytic functions, such as the genetic disorder chronic granulomatous disease. To elucidate the organizing principles behind these distinct immunodeficiency conditions, we investigated the interaction between in vitro bacteria and human neutrophils by experiments and mathematical modeling.

Bistability and bacterial infections.

Bacterial infections occur when the natural host defenses are overwhelmed by invading bacteria. The main component of the host defense is impaired when neutrophil count or function is too low, putting the host at great risk of developing an acute infection. In people with intact immune systems, neutrophil count increases during bacterial infection.

Novel strategies for granulocyte colony-stimulating factor treatment of severe prolonged neutropenia suggested by mathematical modeling.

Purpose: To improve the effectiveness of granulocyte colony-stimulating factor (G-CSF) treatment in high-risk neutropenic patients.

Experimental Design: We study G-CSF effects on chemotherapy-induced neutropenia by expanding a simple mathematical model of neutrophil dynamics in the blood. The final model is fitted and validated using published clinical data of neutrophil response to chemotherapy and standard s.

Mathematical model of BCG immunotherapy in superficial bladder cancer.

Immunotherapy with Bacillus Calmette-Guérin (BCG)-an attenuated strain of Mycobacterium bovis (M. bovis) used for anti tuberculosis immunization-is a clinically established procedure for the treatment of superficial bladder cancer. However, the mode of action has not yet been fully elucidated, despite much extensive biological experience.

Human haematopoiesis in steady state and following intense perturbations.

Haematopoiesis is comprised of multiple stages, originating from pluripotent stem cells through intermediate progenitors to mature differentiated cells. Consequently, during the development of blood cells numerous sites are potentially exposed to the intense perturbations induced by anticancer chemotherapy. However, little is known about human haematopoietic stem cell kinetics in health and following cytotoxic perturbations.