Cancer, angiogenesis and fractals

Baish, James W.; Jain, Rakesh K.

doi:10.1038/1952

Cited by 160 publications

(155 citation statements)

References 5 publications

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“…Our intention was to characterize the complex geometry of the emerging networks and to identify the basic initial conditions and processes determining the emerging vessel network. There have been attempts to utilize such geometric characteristics of the tumour vasculature (like the fractal dimension) as a diagnostic tools in cancer research (Baish and Jain, 2000), but the purpose of our present work was not to extend these ideas.…”

Section: Discussionmentioning

confidence: 99%

Vascular remodelling of an arterio-venous blood vessel network during solid tumour growth

Welter

Bartha

Rieger

2009

Journal of Theoretical Biology

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d m a n u s c r i p t AbstractWe formulate a theoretical model to analyse the vascular remodelling process of an arterio-venous vessel network during solid tumour growth. The model incorporates a hierarchically organized initial vasculature comprising arteries, veins and capillaries, and involves sprouting angiogenesis, vessel cooption, dilation and regression as well as tumour cell proliferation and death. The emerging tumour vasculature is non-hierarchical, compartmentalized into well characterized zones and transports efficiently an injected drug-bolus. It displays a complex geometry with necrotic zones and "hot spots" of increased vascular density and blood flow of varying size. The corresponding cluster size distribution is algebraic, reminiscent of a self-organized critical state.The intra-tumour vascular-density fluctuations correlate with pressure drops in the initial vasculature suggesting a physical mechanism underlying hot-spot formation.

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Section: Discussionmentioning

confidence: 99%

Vascular remodelling of an arterio-venous blood vessel network during solid tumour growth

Welter

Bartha

Rieger

2009

Journal of Theoretical Biology

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“…The quality of multiscaled analysis can nevertheless suffer from a lack of spatial resolution (Chung and Chung, 2001;Baish and Jain, 2001). Moreover, when considering spatial multiscaled properties, most of the previous studies restricted their investigation to 2D analysis.…”

Section: Introductionmentioning

confidence: 99%

From Homogeneous to Fractal Normal and Tumorous Microvascular Networks in the Brain

Risser

Plouraboué

Steyer

et al. 2006

J Cereb Blood Flow Metab

103

129

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We studied normal and tumorous three-dimensional (3D) microvascular networks in primate and rat brain. Tissues were prepared following a new preparation technique intended for high-resolution synchrotron tomography of microvascular networks. The resulting 3D images with a spatial resolution of less than the minimum capillary diameter permit a complete description of the entire vascular network for volumes as large as tens of cubic millimeters. The structural properties of the vascular networks were investigated by several multiscale methods such as fractal and powerspectrum analysis. These investigations gave a new coherent picture of normal and pathological complex vascular structures. They showed that normal cortical vascular networks have scaleinvariant fractal properties on a small scale from 1.4 lm up to 40 to 65 lm. Above this threshold, vascular networks can be considered as homogeneous. Tumor vascular networks show similar characteristics, but the validity range of the fractal regime extend to much larger spatial dimensions. These 3D results shed new light on previous two dimensional analyses giving for the first time a direct measurement of vascular modules associated with vessel-tissue surface exchange.

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“…The formation of these vessels supplies the rapidly expanding tumour with nutrients and oxygen. However, the vasculature is very chaotic and does not transfer nutrients and oxygen efficiently (Baish and Jain, 1998). This is thought to be a consequence of the number of angiogenic signals coming from the neoplastic cell population, such as VEGF and the angiopoietins.…”

Section: Stem-like Cells In Solid Tumoursmentioning

confidence: 99%

Hypoxia inducible factors in cancer stem cells

et al. 2010

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Oxygen is an essential regulator of cellular metabolism, survival, and proliferation. Cellular responses to oxygen levels are monitored, in part, by the transcriptional activity of the hypoxia inducible factors (HIFs). Under hypoxia, HIFs regulate a variety of pro-angiogenic and pro-glycolysis pathways. In solid cancers, regions of hypoxia are commonly present throughout the tissue because of the chaotic vascular architecture and regions of necrosis. In these regions, the hypoxic state fluctuates in a spatial and temporal manner. Transient hypoxic cycling causes an increase in the activity of the HIF proteins above what is typical for non-pathologic tissue. The extent of hypoxia strongly correlates to poor patient survival, therapeutic resistance and an aggressive tumour phenotype, but the full contribution of hypoxia and the HIFs to tumour biology is an area of active investigation. Recent reports link resistance to conventional therapies and the metastatic potential to a stem-like tumour population, termed cancer stem cells (CSCs). We and others have shown that within brain tumours CSCs reside in two niches, a perivascular location and the surrounding necrotic tissue. Restricted oxygen conditions increase the CSC fraction and promote acquisition of a stem-like state. Cancer stem cells are critically dependant on the HIFs for survival, self-renewal, and tumour growth. These observations and those from normal stem cell biology provide a new mechanistic explanation for the contribution of hypoxia to malignancy. Further, the presence of hypoxia in tumours may present challenges for therapy because of the promotion of CSC phenotypes even upon successful killing of CSCs. The current experimental evidence suggests that CSCs are plastic cell states governed by microenvironmental conditions, such as hypoxia, that may be critical for the development of new therapies targeted to disrupt the microenvironment.

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Cancer, angiogenesis and fractals

Cited by 160 publications

References 5 publications

Vascular remodelling of an arterio-venous blood vessel network during solid tumour growth

Vascular remodelling of an arterio-venous blood vessel network during solid tumour growth

From Homogeneous to Fractal Normal and Tumorous Microvascular Networks in the Brain

Hypoxia inducible factors in cancer stem cells

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