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<h2>Replication Study: The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors</h2> <p><br> <strong>Abstract:</strong></p> <p>In 2015, as part of the <a href="https://osf.io/e81xl/wiki/home/" rel="nofollow">Reproducibility Project: Cancer Biology</a>, we published a Registered Report (<a href="http://elifesciences.org/content/4/e04586v1" rel="nofollow">Chroscinski et al., 2015</a>), 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“ (<a href="http://www.pnas.org/content/109/17/6662" rel="nofollow">Willingham et al., 2012</a>). 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; <a href="http://www.pnas.org/content/109/17/6662" rel="nofollow">Willingham et al., 2012</a>). 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; <a href="http://www.pnas.org/content/109/17/6662" rel="nofollow">Willingham et al., 2012</a>). Additionally, the excised tumors were scored for inflammatory cell infiltrates. Both IgG and anti-CD47 treated tumors resulted in minimal to moderate lymphocytic infiltrate, while neutrophilic infiltration was slightly increased in anti-CD47 treated tumors, while the original study observed sparse lymphocytic infiltrate in IgG-treated tumors and increased inflammatory cell infiltrates in anti-CD47 treated tumors (Figure 6C; <a href="http://www.pnas.org/content/109/17/6662" rel="nofollow">Willingham et al., 2012</a>). Finally, we report a meta-analysis of the result.</p> <hr> <h3>Contents</h3> <p><strong>Reports:</strong> Read the <a href="http://dx.doi.org/10.7554/eLife.18173" rel="nofollow">Replication Study</a>, or view the <a href="https://osf.io/hfk42/" rel="nofollow">preprint versions</a>. </p> <p>To reproduce the Replication Study manuscript text run this in <a href="https://www.rstudio.com" rel="nofollow">R Studio</a> (note: downloads <a href="https://osf.io/bsefc/" rel="nofollow">R markdown file</a> directly from <a href="http://osf.io" rel="nofollow">osf.io</a>):</p> <pre class="highlight"><code>library(httr) library(rmarkdown) GET(&quot;<a href="https://osf.io/bsefc/?action=download" rel="nofollow">https://osf.io/bsefc/?action=download</a>&quot;, write_disk(&quot;Replication_Study_39.Rmd&quot;, overwrite = T)) render(&quot;Replication_Study_39.Rmd&quot;, output_format = &quot;word_document&quot;)</code></pre> <p><br> Also, explore the <a href="https://elifesciences.org/content/4/e04586" rel="nofollow">Registered Report</a> and materials related to the Registered Report <a href="https://osf.io/tbr62/wiki/home/" rel="nofollow">here</a>.</p> <p><br> <strong>Experiments replicated:</strong> Reproduce and explore the figures, analyses, data, and methods generated in this replication attempt.</p> <ul> <li><a href="https://osf.io/g57ch/wiki/home/" rel="nofollow">Engraftment of mouse breast cancer cells and treatment with CD47 targeted antibodies</a></li> <li>Replication of Figures 6A-C and Table S4 in Willingham et al., 2012.</li> </ul> <p><br> <strong>Meta-analyses:</strong> As a measure of evaluating reproducibility a meta-analysis of each effect was performed. The forest plots, analyses, and data are available <a href="https://osf.io/ha2bx/wiki/home/" rel="nofollow">here</a>.</p> <p><br> Questions about the project can be directed to <a href="mailto:contact+rpcb@cos.io">contact+rpcb@cos.io</a>.</p>
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