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10.1172/JCI89820 http://scihub22266oqcxt.onion/10.1172/JCI89820 C5199703!5199703!27869649     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Clin+Invest ä ; 127 (1): 106-16 Nephropedia Template TP {{tp|p=27869649|t=ä. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy |pdf=|usr=}}{{27869649}} gab.com Text Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy JO: J Clin Invest http://www.kidney.de/pget.php?&tw=1&pmid=27869649 #FOAvip BACKGROUND. Actinic keratosis is a precursor to cutaneous squamous cell carcinoma. Long treatment durations and severe side effects have limited the efficacy of current actinic keratosis treatments. Thymic stromal lymphopoietin (TSLP) is an epithelium-derived cytokine that induces a robust antitumor immunity in barrier-defective skin. Here, we investigated the efficacy of calcipotriol, a topical TSLP inducer, in combination with 5-fluorouracil (5-FU) as an immunotherapy for actinic keratosis.METHODS. The mechanism of calcipotriol action against skin carcinogenesis was examined in genetically engineered mouse models. The efficacy and safety of 0.005% calcipotriol ointment combined with 5% 5-FU cream were compared with Vaseline plus 5-FU for the field treatment of actinic keratosis in a randomized, double-blind clinical trial involving 131 participants. The assigned treatment was self-applied to the entirety of the qualified anatomical sites (face, scalp, and upper extremities) twice daily for 4 consecutive days. The percentage of reduction in the number of actinic keratoses (primary outcome), local skin reactions, and immune activation parameters were assessed.RESULTS. Calcipotriol suppressed skin cancer development in mice in a TSLP-dependent manner. Four-day application of calcipotriol plus 5-FU versus Vaseline plus 5-FU led to an 87.8% versus 26.3% mean reduction in the number of actinic keratoses in participants (P < 0.0001). Importantly, calcipotriol plus 5-FU treatment induced TSLP, HLA class II, and natural killer cell group 2D (NKG2D) ligand expression in the lesional keratinocytes associated with a marked CD4+ T cell infiltration, which peaked on days 10?11 after treatment, without pain, crusting, or ulceration.CONCLUSION. Our findings demonstrate the synergistic effects of calcipotriol and 5-FU treatment in optimally activating a CD4+ T cell?mediated immunity against actinic keratoses and, potentially, cancers of the skin and other organs.TRIAL REGISTRATION. ClinicalTrials.gov NCT02019355.FUNDING. Not applicable (investigator-initiated clinical trial). Twit Text FOAVip Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy ????J Clin Invest http://www.kidney.de/pget.php?&tw=1&pmid=27869649 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27869649 #FOAvip English Wikipedia <ref>{{Cite pmid|27869649}}</ref> Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy #MMPMID27869649 Cunningham TJ; Tabacchi M; Eliane JP; Tuchayi SM; Manivasagam S; Mirzaalian H; Turkoz A; Kopan R; Schaffer A; Saavedra AP; Wallendorf M; Cornelius LA; Demehri S J Clin Invest ä[]; 127 (1): 106-16 PMID27869649show ga BACKGROUND. Actinic keratosis is a precursor to cutaneous squamous cell carcinoma. Long treatment durations and severe side effects have limited the efficacy of current actinic keratosis treatments. Thymic stromal lymphopoietin (TSLP) is an epithelium-derived cytokine that induces a robust antitumor immunity in barrier-defective skin. Here, we investigated the efficacy of calcipotriol, a topical TSLP inducer, in combination with 5-fluorouracil (5-FU) as an immunotherapy for actinic keratosis.METHODS. The mechanism of calcipotriol action against skin carcinogenesis was examined in genetically engineered mouse models. The efficacy and safety of 0.005% calcipotriol ointment combined with 5% 5-FU cream were compared with Vaseline plus 5-FU for the field treatment of actinic keratosis in a randomized, double-blind clinical trial involving 131 participants. The assigned treatment was self-applied to the entirety of the qualified anatomical sites (face, scalp, and upper extremities) twice daily for 4 consecutive days. The percentage of reduction in the number of actinic keratoses (primary outcome), local skin reactions, and immune activation parameters were assessed.RESULTS. Calcipotriol suppressed skin cancer development in mice in a TSLP-dependent manner. Four-day application of calcipotriol plus 5-FU versus Vaseline plus 5-FU led to an 87.8% versus 26.3% mean reduction in the number of actinic keratoses in participants (P < 0.0001). Importantly, calcipotriol plus 5-FU treatment induced TSLP, HLA class II, and natural killer cell group 2D (NKG2D) ligand expression in the lesional keratinocytes associated with a marked CD4+ T cell infiltration, which peaked on days 10?11 after treatment, without pain, crusting, or ulceration.CONCLUSION. Our findings demonstrate the synergistic effects of calcipotriol and 5-FU treatment in optimally activating a CD4+ T cell?mediated immunity against actinic keratoses and, potentially, cancers of the skin and other organs.TRIAL REGISTRATION. ClinicalTrials.gov NCT02019355.FUNDING. Not applicable (investigator-initiated clinical trial). äRandomized trial of calcipotriol combined with 5-fluorouracil for skin(epmc).pdf DeepDyve Pubget Overpricing