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1.
Nat Cell Biol ; 14(12): 1282-94, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23178882

ABSTRACT

Basal cell carcinoma, the most frequent human skin cancer, arises from activating hedgehog (HH) pathway mutations; however, little is known about the temporal changes that occur in tumour-initiating cells from the first oncogenic hit to the development of invasive cancer. Using an inducible mouse model enabling the expression of a constitutively active Smoothened mutant (SmoM2) in the adult epidermis, we carried out transcriptional profiling of SmoM2-expressing cells at different times during cancer initiation. We found that tumour-initiating cells are massively reprogrammed into a fate resembling that of embryonic hair follicle progenitors (EHFPs). Wnt/ ß-catenin signalling was very rapidly activated following SmoM2 expression in adult epidermis and coincided with the expression of EHFP markers. Deletion of ß-catenin in adult SmoM2-expressing cells prevents EHFP reprogramming and tumour initiation. Finally, human basal cell carcinomas also express genes of the Wnt signalling and EHFP signatures.


Subject(s)
Carcinoma, Basal Cell/pathology , Hair Follicle/cytology , Neoplastic Stem Cells/cytology , Animals , Carcinoma, Basal Cell/metabolism , Flow Cytometry , Hair Follicle/metabolism , Immunohistochemistry , Keratinocytes/cytology , Keratinocytes/metabolism , Mice , Mice, Transgenic , Neoplastic Stem Cells/metabolism , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , beta Catenin/metabolism
2.
Plast Reconstr Surg ; 111(7): 2192-9; discussion 2200-2, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12794459

ABSTRACT

Since 1989, superior pedicle vertical scar mammaplasty as described by Lejour has been used in the authors' department as the only technique for breast reduction. From 1991 through 1994, a series of 170 consecutive patients (330 breasts) underwent an operation. In these patients, minor complications were observed in 30 percent of the patients and major complications in 15 percent. Surgical revision for scar or volume corrections was necessary in 28 percent of the breasts, which seemed unacceptable. Therefore, the original technique was modified by decreasing the skin undermining and avoiding liposuction in the breast. Primary skin excision was performed in the submammary fold at the end of the operation if the skin could not be puckered adequately. This modified technique was used from 1996 through 1999 in 138 consecutive patients (227 breasts). In the second series, minor complications were observed in 15 percent of the patients and major complications in 5 percent. However, the technical modifications did not significantly change the rate of secondary scar and volume corrections, which were still necessary in 22 percent of the breasts. In large breasts, the addition of a horizontal scar at the end of the operation did not change the rate of secondary revision, which however compares favorably with the figures obtained with the inverted T, superior pedicle mammaplasty.


Subject(s)
Cicatrix/etiology , Mammaplasty/methods , Postoperative Complications/etiology , Adolescent , Adult , Aged , Cicatrix/surgery , Esthetics , Female , Humans , Lipectomy/methods , Middle Aged , Outcome and Process Assessment, Health Care , Postoperative Complications/surgery , Reoperation/methods , Suture Techniques
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