Modeling tumor growth

A natural progression from using CA to model bacterial growth is to model tumor growth and the development of abnormal cells. There has been considerable work on this topic. Features such as cell mutation, adhesion, layered growth, and chemotaxis can readily be incorporated into a CA model.5 Deutsch and Dormann s book provides a useful introduction to this area.6... 

Conceptual description of an avascular tumor growth model. Tumor growth is represented as a layered structure consisting of an outer proliferating rim, quiescent band, and necrotic core. The model treats the proliferating, quiescent, and necrotic cells as a continuum under the influence of environmental factors such as nutrient/growth factors from underl)dng tissues, and cell movement in terms of migration and contact inhibition. 

Wn et al. demonstrates that a lipid-polymer hybrid drug delivery systan loaded with doxorubicin is effective for tnmor treatment in a well-established animal model. Tumor growth delay and tnmor necrosis were observed in tnmors treated with the lipid-polymer hybrid formulation of doxorubicin. It was fonnd that these lipid-polymer hybrids carrying anticancer agents were useful for loco-regional treatment of breast cancer with an improved therapeutic index. 

Electrochemistry of adhesion and spreading of hpid vesicles on electrodes Bio-Electrochemistry and chalcogens Nanoplasmonics in medicine Extravascular hemoglobin aging contusions Modeling tumor growth and response to radiation... 

Preclinical Model Tumor Growth Inhibition Efficacy and... 

While the obvious value of in vivo animal models is clear, there also are instances—especially in cases of inflammatory arthritis, behavior, and tumor growth—where they have failed to be predictive of useful clinical activity in humans [51], For example, leukotriene (LTB4) antagonists showed activity in animal models of inflammatory arthritis yet failed to be useful in rheumatoid arthritis [52]. Similarly, dopamine D4 antagonists showed activity in animal behavior models previously predictive of dopamine D2 antagonists in schizophrenia. However, testing of dopamine D4 antagonists showed no efficacy in humans [53]. 

One further question that has a substantial impact on the application of modeling techniques to biomedical problems is the choice of the design. Suppose that in our Gompertz tumor growth example we wanted to decide, given the results of some pilot experiments, when it is most useful to observe the tumor volume. In other words, we wish to choose the time points at which we obtain tumor volume observations in order to maximize the precision of the resulting parameter estimates. 

Keane MP, Belperio JA, Xue YY, Burdick MD, Strieter RM. Depletion of CXCR2 inhibits tumor growth and angiogenesis in a murine model of lung cancer. J Immunol 2004 172(5) 2853-2860. 

To evaluate PARP inhibition in a realistic setting, olaparib (7) was tested in a BrcflI / p53 / mouse breast cancer model. Treatment with olaparib caused tumor growth inhibition without generating signs of toxicity [14]. Interestingly, upon cessation of treatment and tumor... 

Hu-Lieskovan S, Heidel JD, Bartlett DW, Davis ME, Triche TJ (2005) Sequence-specific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic Ewing s sarcoma. Cancer Res 65 8984—8992... 

In many cases the hypothesis that PTK inhibitors provide an effective block to proliferative disease or tumor growth in vivo has in fact been proven in pre-clinical animal models. Such cases are listed below. 

ARRY-142886 (AZD6244) is another potent, selective and ATP non-competitive MEK1/2 inhibitor with IC50 = 12 nM. This compound inhibited cellular pERK with an ICYn < 10 nM and tumor growth in a number of xenograft models and is reported to be in Phase II clinical trials in cancer patients [25]. 

Owing to the favorable activity profile of 66, which acts as a prodrug of the active species 62, additional studies were conducted on 66 to establish its cell-based profile. It was determined that 66 potentiated chlorambucil (74) toxicity in cell lines expressing GST Pl-1, namely HT-29, HT4-1, SK OV-3, and SK VLB. Also, while 66 alone did not prevent tumor growth in the HT4-1 xenograph model, 66 increased by 56% the tumor growth inhibitory effect of melphalan (75). 

T. C. Stover, A. Sharma, G. P. Robertson, and M. Kester. Systemic delivery of liposomal short-chain ceramide limits solid tumor growth in murine models of breast adenocarcinoma. Clin. Cancer Res. 11 3465-3474 (2005). 

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