Neoplastic epithelia may remain dormant and clinically unapparent in human patients for decades. Multiple risk factors including mutations in tumor cells or the stromal cells may affect the switch from dormancy to malignancy. Gene mutations, including p53 mutations, within the stroma of tumors are associated with a worse clinical prognosis; however, it is not known if these stromal mutations can promote tumors in genetically at-risk tissue. To address this question, ApcMin/+ and Apc Min/+ Rag2 −/− mice, which have a predilection to mammary carcinoma (as well as wild-type (wt) mice), received mesenchymal stem cells (MSC) with mutant p53 (p53MSC) transferred via tail vein injection. In the wt mouse, p53MSC circulated in the periphery and homed to the marrow cavity where they could be recovered up to a year later without apparent effect on the health of the mouse. No mammary tumors were found. However, in mice carrying the Apc Min/+ mutation, p53MSC homed to mammary tissue and signifi cantly increased the incidence of mammary carcinoma. Tumor necrosis factor (TNF)-α-dependent factors elaborated from mesenchymal cells converted quiescent epithelia into clinically apparent disease. The increased cancer phenotype was completely preventable with neutralization of TNF-α or by transfer of CD4+ regulatory T cells from immune competent donors, demonstrating that immune competency to regulate infl ammation was suffi cient to maintain neoplastic dormancy even in the presence of oncogenic epithelial and stromal mutations. The signifi cant synergy between host immunity and mesenchymal cells identifi ed here may restructure treatments to restore an anticancer microenvironment.
The results of single-zone annealing of 76 samples of Pb1−xSnxTe are reported, covering the entire composition range from pure PbTe to pure SnTe. Some of the sample preparation work overlapped and improved on the work of others, while some of the results, particularly in the alloy samples, are new. Annealing times, temperatures, source ingot preparation, resulting carrier concentrations, and 77 °K Hall mobilities are reported. The Knight shift of the Pb207 nuclear magnetic resonance and the NMR line shape were used for additional sample characterization. This interesting technique was applied most successfully in the pure PbTe samples with carrier concentrations below 1018 cm−3. It was discovered from NMR studies on powders that strain damage introduced by powdering could completely compensate p-type PbTe. No corresponding effect was noted in n-type PbTe, suggesting the presence of damage-induced levels in the gap.
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