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- W4361943140 abstract "<div>Abstract<p><b>Purpose:</b> Nonmelanoma skin cancer incidence is enhanced >50-fold in patients taking antirejection drugs (ARD) following organ transplantation. Preclinical studies suggest that ARD treatment increases transforming growth factor-β1 (TGF-β1) levels, which contribute to enhanced tumor susceptibility independent of the immunosuppressive effects of ARDs. This study investigates whether TGF-β signaling is elevated in transplant patients.</p><p><b>Experimental Design:</b> Immunohistochemical tissue microarray analysis was used to determine the levels of TGF-β1, TGF-β2, TGF-β3, TβRII, and activated P-Smad2/3 and P-Smad1/5/8, which are phosphorylated directly by distinct TGF-β/BMP receptor complexes. We analyzed >200 cutaneous lesions and adjacent nonlesional skin samples from 87 organ transplant recipients, and 184 cutaneous lesions and adjacent skin samples from 184 individuals who had never received ARDs.</p><p><b>Results:</b> We found significantly higher levels of P-Smad2 in both nonlesional and lesional tissue from transplant recipients compared with those not exposed to ARDs (<i>P</i> ≤ 0.001). In contrast, P-Smad1/5/8, a marker of activation of the bone morphogenetic protein signaling pathway, was generally not expressed at higher levels in patients taking ARDs, including analysis of nonlesional skin, actinic keratoses, carcinoma <i>in situ</i>, or squamous cell carcinoma but was differentially expressed between keratoacanthoma from transplant recipients compared with those from non–transplant recipients (<i>P</i> ≤ 0.005).</p><p><b>Conclusions:</b> Observation of elevated P-Smad2 levels in transplant recipients is consistent with the notion that elevated TGF-β signaling may contribute to malignancy in organ transplant recipients. Disparate P-Smad1/5/8 expression levels between keratoacanthoma from the two patient groups might reflect the distinct BMP-responsive cell of origin for this hair follicle–derived lesion. (Clin Cancer Res 2009;15(16):5101–7)</p></div>" @default.
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- W4361943140 date "2023-03-31" @default.
- W4361943140 modified "2023-10-14" @default.
- W4361943140 title "Data from Elevated Cutaneous Smad Activation Associates with Enhanced Skin Tumor Susceptibility in Organ Transplant Recipients" @default.
- W4361943140 doi "https://doi.org/10.1158/1078-0432.c.6517639" @default.
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