Estimating Tumor Growth Rates In Vivo

Talkington, Anne; Durrett, Rick

doi:10.1007/s11538-015-0110-8

Cited by 125 publications

(104 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While tumor growth is exponential under an ideal scenario, factors such as availability of nutrients, oxygen, and space influence and alter the growth of the tumor initially compared to the continued growth of the tumor (Cornelis et al, 2013; Talkington and Durrett, 2015). Simultaneously, other murine immunogenic tumor models are known to spontaneously regress (Penichet et al, 2001; Robinson et al, 2009; Vince et al, 2004), which is a phenomenon known to naturally occur in cancer patients (Jessy, 2011; Saleh et al, 2005; Salman, 2016) .…”

Section: Resultsmentioning

confidence: 99%

Replication Study: The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

Horrigan

2017

eLife

View full text Add to dashboard Cite

In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Chroscinski et al., 2015) that described how we intended to replicate selected experiments from the paper “The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors “(Willingham et al., 2012). Here we report the results of those experiments. We found that treatment of immune competent mice bearing orthotopic breast tumors with anti-mouse CD47 antibodies resulted in short-term anemia compared to controls, consistent with the previously described function of CD47 in normal phagocytosis of aging red blood cells and results reported in the original study (Table S4; Willingham et al., 2012). The weight of tumors after 30 days administration of anti-CD47 antibodies or IgG isotype control were not found to be statistically different, whereas the original study reported inhibition of tumor growth with anti-CD47 treatment (Figure 6A,B; Willingham et al., 2012). However, our efforts to replicate this experiment were confounded because spontaneous regression of tumors occurred in several of the mice. Additionally, the excised tumors were scored for inflammatory cell infiltrates. We found IgG and anti-CD47 treated tumors resulted in minimal to moderate lymphocytic infiltrate, while the original study observed sparse lymphocytic infiltrate in IgG-treated tumors and increased inflammatory cell infiltrates in anti-CD47 treated tumors (Figure 6C; Willingham et al., 2012). Furthermore, we observed neutrophilic infiltration was slightly increased in anti-CD47 treated tumors compared to IgG control. Finally, we report a meta-analysis of the result.DOI: http://dx.doi.org/10.7554/eLife.18173.001

show abstract

Section: Resultsmentioning

confidence: 99%

Replication Study: The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

Horrigan

2017

eLife

View full text Add to dashboard Cite

show abstract

“…Note that the presented study is based on a matrix population model with constant elements, which in principle captures an exponential growing population. Even though there are still uncertainties regarding the growth patterns of cell populations in different contexts (cancer or normal, solid or hematologic tumor, in vivo or in vitro) [7,50] and exponential growth is often considered to be unable to capture the biological processes in reality, exponential-like growth models are widely used as default models to describe growing cell populations, especially in early cancer development [21,[51][52][53]. We followed this idea and used it as a starting point to explore the adaptive significance of de-differentiation.…”

Section: Discussionmentioning

confidence: 99%

The invasion of de-differentiating cancer cells into hierarchical tissues

Zhou

Luo

Dingli

et al. 2019

Preprint

View full text Add to dashboard Cite

Many fast renewing tissues are characterized by a hierarchical cellular architecture, with tissue specific stem cells at the root of the cellular hierarchy and differentiating into a whole range of specialized cells. There is increasing evidence that tumors are structured in a very similar way, mirroring the hierarchical structure of the host tissue. In some tissues, differentiated cells can also revert to the stem cell phenotype, which increases the risk that cells that have already acquired mutations lead to long lasting clones in the tissue. Recently, the modelling community has paid special attention to the consequences of de-differentiation on cellular hierarchies. However, the adaptive significance of de-differentiation is still poorly understood and thus it is unclear under which circumstances de-differentiating cells will invade a tissue. To address this, we developed mathematical models to investigate how de-differentiation could be selected as an adaptive mechanism in the context of cellular hierarchies. We consider the cases of stepwise and jumpwise de-differentiation in this study. Our results show that the emergence of de-differentiation is driven by the combination of the properties of the cellular hierarchy and the de-differentiation pattern and derive thresholds for which de-differentiation is expected to emerge.

show abstract

“…Our model neglects a spatial component of tumor growth (46). This assumption leads to exponential growth in equilibrium, a situation well met in most leukemias (28,47,48).…”

Section: Discussionmentioning

confidence: 99%

The Cancer Stem Cell Fraction in Hierarchically Organized Tumors Can Be Estimated Using Mathematical Modeling and Patient-Specific Treatment Trajectories

et al. 2016

View full text Add to dashboard Cite

Many tumors are hierarchically organized and driven by a sub-population of tumor initiating cells (TICs), or cancer stem cells. TICs are uniquely capable of recapitulating the tumor and are implied to be highly resistant to radio- and chemotherapy. Macroscopic patterns of tumor expansion before treatment and tumor regression during treatment are tied to the dynamics of TICs. Until now, quantitative information about the fraction of TICs from macroscopic tumor burden trajectories could not be inferred. In this study, we generated a quantitative method based on a mathematical model that describes hierarchically organized tumor dynamics and patient-derived tumor burden information. The method identifies two characteristic equilibrium TIC regimes during expansion and regression. We show that tumor expansion and regression curves can be leveraged to infer estimates of the TIC fraction in individual patients at detection and after continued therapy. Furthermore, our method is parameter-free; it solely requires knowledge of a patient’s tumor burden over multiple time points to reveal microscopic properties of the malignancy. We demonstrate proof of concept in the case of chronic myeloid leukemia (CML), wherein our model recapitulated the clinical history of the disease in two independent patient cohorts. Based on patient-specific treatment responses in CML, we predict that after one year of targeted treatment, the fraction of TICs increases 100-fold and continues to increase up to 1000-fold after five years of treatment. Our novel framework may significantly influence the implementation of personalized treatment strategies and has the potential for rapid translation into the clinic.

show abstract

Estimating Tumor Growth Rates In Vivo

Cited by 125 publications

References 39 publications

Replication Study: The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

Replication Study: The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

The invasion of de-differentiating cancer cells into hierarchical tissues

The Cancer Stem Cell Fraction in Hierarchically Organized Tumors Can Be Estimated Using Mathematical Modeling and Patient-Specific Treatment Trajectories

Contact Info

Product

Resources

About