Analysis of αv integrin protein expression in human eyelid and periorbital squamous cell carcinomas.

BACKGROUND: Alpha v integrins are receptors for many extracellular matrix (ECM) protein ligands, including latent transforming growth factor betas (TGFßs). Various studies in mice have shown that ablation of genes encoding αv integrin or TGFß signaling pathway components leads to spontaneous squamous cell carcinomas (SCCs) in the conjunctiva and periocular skin. Here, we have analyzed patterns of αv integrin protein expression and TGFß signaling in human eyelid and periorbital SCC samples. METHODS: An anti-αv integrin antibody was used to immunostain 19 eyelid and periorbital SCC samples. Additionally, tissue lysates from resected normal eyelid and SCC samples were analyzed by immunoblotting for αv integrin protein. Tumor sections were also immunostained with an antibody directed against Smad2, an intracellular signaling protein that is phosphorylated by TGFß receptors. RESULTS: Alpha v integrin protein was highly expressed in the invasive and less-differentiated components of human SCCs. Lower levels of αv integrin protein were detected in more differentiated components of tumors, as well as in SCC in situ. Patterns of phosphorylated Smad2 immunoreactivity correlated with levels αv integrin expression. CONCLUSIONS: Alpha v integrin was expressed at robust levels in tumor cells representing less differentiated, more invasive components of SCC; by contrast, well-differentiated cells as well as SCC in situ expressed low levels of αv integrin protein.

Acellular dermal graft (AlloDerm) for upper eyelid reconstruction after cancer removal.

PURPOSE: To report the use of AlloDerm for reconstruction of large upper eyelid defects in cancer patients. METHODS: The clinical records of all patients who had AlloDerm as part of their upper eyelid reconstruction between July 2005 and July 2006 at a single institution were reviewed. Functional and cosmetic outcomes and postoperative complications were assessed. RESULTS: Two patients had recurrent sebaceous gland carcinoma, 2 had melanoma, and 1 had squamous cell carcinoma. The upper eyelid defect involved the full thickness and entire width of the upper eyelid in 4 patients and full thickness and two thirds of the upper eye eyelid in 1 patient. The reconstructive procedure included a modified Cutler-Beard procedure using AlloDerm as the posterior lamellar sandwich graft in all 5 patients. One patient had early postoperative adjuvant radiation therapy to the upper eyelid. Three patients had excellent functional and cosmetic outcome; 2 patients had satisfactory outcomes. Two patients had residual exposure keratopathy. Allergic reaction to AlloDerm, infectious transmission, and immunologic rejection were not encountered at the time of this report (mean follow-up time = 13 months). CONCLUSIONS: AlloDerm can be used as an alternative sandwich graft material to replace the tarsus for reconstruction of large upper eyelid defects using a modified Cutler-Beard procedure.

Postoperative adjuvant external-beam radiation therapy for cancers of the eyelid and conjunctiva.

PURPOSE: To outline the indications for and our experience with postoperative adjuvant external-beam radiotherapy (EBRT) in patients with eyelid or conjunctival cancers. METHODS: Twenty consecutive patients with primary eyelid or conjunctival cancer treated with surgical resection followed by postoperative EBRT between January 2000 and September 2006 were included. The indications for postoperative EBRT, type and dose of EBRT, oculoplastic reconstructive procedures, timing of EBRT in relation to reconstructive procedures, and the ocular side effects of EBRT were recorded. RESULTS: Sixteen women and 4 men ranged in age from 44 to 86 years (median, 64 years). The oculoplastic procedures included local flaps or direct closure of eyelid defect (12), tarsoconjunctival flap (6), full-thickness skin grafts (6), amniotic membrane grafts (2), other conjunctival reconstruction (2), tarsoconjunctival graft (1), and lacrimal stenting (1). The total radiation dose ranged from 26 to 63 Gy (median, 60 Gy). The indications for postoperative EBRT included aggressive histology, recurrent tumor, microscopic perineural invasion, advanced-stage disease, and microscopically positive or "close" margins. EBRT started 5 to 12 weeks (median, 7 weeks) after reconstructive procedures. The follow-up time ranged from 7 to 50 months (mean, 24 months). Thirteen patients experienced dry eye syndrome; 3 keratinization of conjunctiva; and 1 each blepharitis, trichiasis, radiation retinopathy/optic neuropathy, and exposure keratopathy. CONCLUSIONS: Postoperative EBRT can be used as adjuvant therapy after surgical resection of eyelid or conjunctival cancers and may obviate more radical surgery such as orbital exenteration in some patients. The ocular side effects from EBRT were relatively minor in most patients.

The Saccharomyces cerevisiae COQ6 gene encodes a mitochondrial flavin-dependent monooxygenase required for coenzyme Q biosynthesis.

Coenzyme Q (Q) is a lipid that functions as an electron carrier in the mitochondrial respiratory chain in eukaryotes. There are eight complementation groups of Q-deficient Saccharomyces cerevisiae mutants, designated coq1-coq8. Here we have isolated the COQ6 gene by functional complementation and, in contrast to a previous report, find it is not an essential gene. coq6 mutants are unable to grow on nonfermentable carbon sources and do not synthesize Q but instead accumulate the Q biosynthetic intermediate 3-hexaprenyl-4-hydroxybenzoic acid. The Coq6 polypeptide is imported into the mitochondria in a membrane potential-dependent manner. Coq6p is a peripheral membrane protein that localizes to the matrix side of the inner mitochondrial membrane. Based on sequence homology to known proteins, we suggest that COQ6 encodes a flavin-dependent monooxygenase required for one or more steps in Q biosynthesis.