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1.
Arch Otolaryngol Head Neck Surg ; 136(10): 958-64, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20956740

ABSTRACT

OBJECTIVE: To demonstrate that the 3 reconstructive advantages of the thoracodorsal artery scapular tip transplant (Tdast), a long pedicle, independently mobile tissue components, and the 3-dimensional nature of the scapular tip, will improve the quality and success of complex reconstructions by avoiding vein grafting, preventing the need for 2 separate transplants, and facilitating bony inset. DESIGN: Prospective case series. SETTING: Tertiary care academic medical center. PATIENTS: Twenty-one patients (male to female ratio, 16:5; mean age, 52 years) underwent reconstruction of the upper, middle, and lower face from 2001 through 2006. Indications for reconstruction were tumor ablation in 11 patients, secondary reconstruction in 4 patients, osteoradionecrosis in 4, and posttraumatic reconstruction in 2. Seventeen patients underwent radiation. INTERVENTIONS: All patients underwent harvest of an autogenous transplant of scapular tip bone and latissimus dorsi soft tissue based on the thoracodorsal artery. The mean bone length was 5.2 cm (range, 2.5-9.0 cm), and the mean cutaneous surface area was 68 cm² (range, 20-250 cm²). MAIN OUTCOME MEASURES: Reduction of vein grafting, avoidance of 2 transplants, use of the triangular shape of the scapular tip in reconstruction, complications, and shoulder function. RESULTS: The success rate of transplantation was 100%. The use of this transplant avoided vein grafting in 16 patients and the need for 2 separate transplants in 11 patients, and the 3-dimensional nature of the scapular tip facilitated inset in 13 patients. In 14 patients, more than 1 of these reconstructive advantages was achieved. In 6 patients, all 3 were accomplished. Eleven patients experienced a complication. The major complication rate was 33%, and the minor complication rate was 33%. The mean Constant-Murley test of shoulder function score was 87 of 100 (range, 74-100). CONCLUSIONS: The Tdast is an excellent choice for reconstruction in the head and neck as an alternative to procedures requiring vein grafting and multiple free tissue transplants, or in which the 3-dimensional contour of the scapular tip aids in reconstruction. The complication rate should be assessed in the context of the risk factors of the patient population and the outcome with respect to stable employment, increasing body mass index, and maintenance of shoulder function.


Subject(s)
Plastic Surgery Procedures/methods , Scapula/transplantation , Surgical Flaps/blood supply , Adolescent , Adult , Aged , Child , Child, Preschool , Facial Injuries/surgery , Facial Neoplasms/surgery , Female , Graft Survival , Humans , Male , Middle Aged , Postoperative Complications , Prospective Studies , Treatment Outcome , Young Adult
2.
Am J Pathol ; 168(2): 585-96, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16436672

ABSTRACT

Rap1, a growth regulatory protein that is strongly expressed in human squamous cell carcinoma (SCC), is inactivated by rap1GAP. Recent evidence in normal rat cells suggests that rap1GAP regulates proliferation. The objective of the current study was to investigate whether rap1GAP functions as a tumor suppressor in SCC. Using a pull-down assay, active GTP-bound rap1 was up-regulated in SCC compared to normal or immortalized keratinocytes. Because both rap1A and rap1B isoforms of rap1 are expressed in SCC, the rap1GAP inactivation of both rap1 isoforms was verified using cells transfected with EGFP-rap1A or EGFP-rap1B or co-transfected with FLAG-tagged rap1GAP. The results demonstrate that expression of rap1GAP in oropharyngeal SCC down-regulated active rap1, ERK activation, and proliferation. Incubation of stably transfected SCC cells with nocodazole, an inhibitor of mitosis, caused a slower accumulation of rap1GAP-transfected cells in the G2 phase, in comparison to the vector control, indicating that rap1GAP-transfected cells have slower progression through the cell cycle. This was supported by down-regulation of cyclin D1, cdk4, and cdk6 in rap1GAP-transfected SCC cells. Furthermore, SCC cells transfected with rap1GAP produced significantly smaller tumors in nude mice as compared to controls (P < 0.01). These novel findings suggest that rap1GAP acts as a tumor suppressor protein in SCC.


Subject(s)
Carcinoma, Squamous Cell/enzymology , Carcinoma, Squamous Cell/prevention & control , GTPase-Activating Proteins/metabolism , Oropharyngeal Neoplasms/enzymology , Oropharyngeal Neoplasms/prevention & control , Animals , Antineoplastic Agents/pharmacology , Cell Proliferation , Cells, Cultured , Cyclin D1/metabolism , Cyclin-Dependent Kinase 4/metabolism , Cyclin-Dependent Kinase 6/metabolism , G2 Phase/drug effects , GTPase-Activating Proteins/genetics , Green Fluorescent Proteins , Humans , Keratinocytes/cytology , Keratinocytes/enzymology , Kidney/metabolism , Mice , Mice, Nude , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Mitosis/drug effects , Nocodazole/pharmacology , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , Transfection , rap GTP-Binding Proteins/genetics , rap GTP-Binding Proteins/metabolism , rap1 GTP-Binding Proteins/genetics , rap1 GTP-Binding Proteins/metabolism
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