HER2 Support Group Forums - Any Mathematicians Here? : Multiparameter Computational Modeling of Tumor Invasion

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Any Mathematicians Here? : Multiparameter Computational Modeling of Tumor Invasion

http://cancerres.aacrjournals.org/co...4493/fd1_1.gif

Taking this in to the next appointment.

Lest anyone be too geeked out, here is the guts of the thing:

"The central finding of this work is that tumor growth and invasion are not erratic or unpredictable, or solely explained through genomic and molecular events, but rather are predictable processes obeying biophysical laws, driven by microenvironmental substrate gradients, and regulated by genotypic, phenotypic, and microenvironmental parameters (e.g., cell adhesion, proliferation, and motility). The model enables quantitative study of invading cell clusters as functional units that move as complex systems. Substrate gradients, e.g., of nutrient, oxygen, growth factors, and metabolites, result from diffusion, cellular activity, and heterogeneous delivery and removal. This leads to local hypoxia, nutrient starvation, acidosis, necrosis, and the pleiomorphic appearance of tumors. The underlying physical mechanism of collective cell migration, i.e., a gross tumor morphologic instability (2, 8–10, 12–14, 40), maximizes cell exposure to substrates by evading a compact, nearly spherical morphology in favor of infiltrating shapes moving up gradients of substrates such as oxygen. Phenotypic changes that increase nutrient uptake and augment cell proliferation (and also increase cell motility and reduce adhesion) have a quantifiable effect on morphology at the tumor scale. In particular, they trigger invasive fingering into host tissue while inducing necrosis and angiogenesis for certain parameter conditions. "

Hopeful

Hmm. If this is dumbed down, I'm dummerer than I figgered ;)

Ah..much better. I found this theory on what drives cancer cells interesting:
"Tumors obtain nutrients and oxygen by harnessing the surrounding blood vessels and making new vessels. Since there typically aren't enough nutrients and oxygen to support tumor cells, an uneven distribution of these substances is created inside and around the tumor mass, Cristini said.

The research of Cristini and colleagues, who worked in collaboration with Elaine L. Bearer, M.D., Ph.D., professor at the Brown School of Medicine, suggests that tumor growth and invasion could be predicted by using biophysical laws that link the effects of the uneven distribution of cell nutrients and oxygen to overall tumor behavior.

For different values of the input parameters, the model consistently reproduced the patterns of tumor invasion observed in experiments and in patient tumors, Cristini said. The patterns were regulated by changes in cellular characteristics, causing more aggressive tumor cells to invade the healthy tissue. As cancer cells invade and replicate themselves, they make the tumor shape unstable and more invasive. The model correctly predicted the different types of invasion under a variety of conditions.

The model further predicted that the different forms of cancer invasion correspond to different stages of tumor progression, Cristini said. In regions of low oxygen, these changes may include a slowdown in cell replication and heightened cell migration, which can result in a "single-cell file" invasion pattern. As cells aggregate in regions that have better access to nutrients and oxygen, migration is lessened and cell replication is resumed. This leads to the formation of wave-like patterns of cell rearrangements at the tumor boundary and the formation of round infiltrative "fingers" that can detach from the tumor as clusters of cells."

Makes me wonder if giving cancer cells the oxygen and nutrients they need would slow down metastasis, at the expense of greater local growth. Depending on location of the tumor and ability to deal with it locally, maybe that would be preferable.

this needs to be applied to the stem cell model as well

Now as herceptin kills stem cells can an approximation be made that shows roughly how long one needs to stay on it once NED to remove all the stem cells left?

It would be nice not to have to stay on it for 10 years if the optimum time is found to be 4 years NED which I am rapidly approaching!
Jackie (down under)