27,742 research outputs found
Advances in the design and development of oncolytic measles viruses.
A successful oncolytic virus is one that selectively propagates and destroys cancerous tissue without causing excessive damage to the normal surrounding tissue. Oncolytic measles virus (MV) is one such virus that exhibits this characteristic and thus has rapidly emerged as a potentially useful anticancer modality. Derivatives of the Edmonston MV vaccine strain possess a remarkable safety record in humans. Promising results in preclinical animal models and evidence of biological activity in early phase trials contribute to the enthusiasm. Genetic modifications have enabled MV to evolve from a vaccine agent to a potential anticancer therapy. Specifically, alterations of the MV genome have led to improved tumor selectivity and delivery, therapeutic potency, and immune system modulation. In this article, we will review the advancements that have been made in the design and development of MV that have led to its use as a cancer therapy. In addition, we will discuss the evidence supporting its use, as well as the challenges associated with MV as a potential cancer therapeutic
Radiotherapy planning for glioblastoma based on a tumor growth model: Improving target volume delineation
Glioblastoma are known to infiltrate the brain parenchyma instead of forming
a solid tumor mass with a defined boundary. Only the part of the tumor with
high tumor cell density can be localized through imaging directly. In contrast,
brain tissue infiltrated by tumor cells at low density appears normal on
current imaging modalities. In clinical practice, a uniform margin is applied
to account for microscopic spread of disease.
The current treatment planning procedure can potentially be improved by
accounting for the anisotropy of tumor growth: Anatomical barriers such as the
falx cerebri represent boundaries for migrating tumor cells. In addition, tumor
cells primarily spread in white matter and infiltrate gray matter at lower
rate. We investigate the use of a phenomenological tumor growth model for
treatment planning. The model is based on the Fisher-Kolmogorov equation, which
formalizes these growth characteristics and estimates the spatial distribution
of tumor cells in normal appearing regions of the brain. The target volume for
radiotherapy planning can be defined as an isoline of the simulated tumor cell
density.
A retrospective study involving 10 glioblastoma patients has been performed.
To illustrate the main findings of the study, a detailed case study is
presented for a glioblastoma located close to the falx. In this situation, the
falx represents a boundary for migrating tumor cells, whereas the corpus
callosum provides a route for the tumor to spread to the contralateral
hemisphere. We further discuss the sensitivity of the model with respect to the
input parameters. Correct segmentation of the brain appears to be the most
crucial model input.
We conclude that the tumor growth model provides a method to account for
anisotropic growth patterns of glioblastoma, and may therefore provide a tool
to make target delineation more objective and automated
Tumor growth instability and the onset of invasion
Motivated by experimental observations, we develop a mathematical model of
chemotactically directed tumor growth. We present an analytical study of the
model as well as a numerical one. The mathematical analysis shows that: (i)
tumor cell proliferation by itself cannot generate the invasive branching
behaviour observed experimentally, (ii) heterotype chemotaxis provides an
instability mechanism that leads to the onset of tumor invasion and (iii)
homotype chemotaxis does not provide such an instability mechanism but enhances
the mean speed of the tumor surface. The numerical results not only support the
assumptions needed to perform the mathematical analysis but they also provide
evidence of (i), (ii) and (iii). Finally, both the analytical study and the
numerical work agree with the experimental phenomena.Comment: 12 pages, 8 figures, revtex
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