Expression of glucose transporter protein-1 (Glut-1) in ocular surface squamous neoplasia
ABSTRACT To examine the expression of glucose transporter protein-1 (GLUT-1) in ocular surface squamous neoplasia and to study its relationship with degree of neoplasia and cell proliferation index (Ki-67 labeling index).
Twelve cases diagnosed as ocular surface squamous neoplasia (4 invasive and 8 intraepithelial tumors) at Inonu University Faculty of Medicine, Department of Pathology, were included in this study. There were 3 squamous cell carcinomas, 1 basosquamous cell carcinoma, and 8 conjunctival intraepithelial neoplasms. Immunohistochemically, GLUT-1 and Ki-67 antibody staining were performed.
GLUT-1 membranous immunoreactivity was seen in all tumors except in 1 case. GLUT-1 immunostaining was observed in all layers of the neoplastic epithelium of squamous cell carcinoma. Intense staining for GLUT-1 was determined in the upper two thirds of the severe dysplastic squamous epithelium. Although immunoreactivity for Ki-67 nuclear antigen was present throughout the epithelium, it was higher in the lower two thirds. Ki-67 labeling index ranged between 6% and 80%, and the mean value was 35% for invasive tumors and 20% for intraepithelial tumors.
Marked GLUT-1 and Ki-67 immunoreactive cells throughout the neoplastic epithelium of ocular surface squamous neoplasia were observed. In most cases, it was observed that GLUT-1 expression was severe in cases having >10% Ki-67 labeling index. These findings indicate that glucose uptake was increased in dysplastic cells, especially by GLUT-1. To our knowledge, this is the first study on the subject in the literature, and further studies with more cases are needed with GLUT-1 and other GLUT members.
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ABSTRACT: Poor bioavailability of topically instilled drug is the major concern in the field of ocular drug delivery. Efflux transporters, static and dynamic ocular barriers often possess rate limiting factors for ocular drug therapy. Different formulation strategies like suspension, ointment, gels, nanoparticles, implants, dendrimers and liposomes have been employed in order to improve drug permeation and retention by evading rate limiting factors at the site of absorption. Chemical modification such as prodrug targeting various nutrient transporters (amino acids, peptide and vitamin) has evolved a great deal of interest to improve ocular drug delivery. In this review, we have discussed various prodrug strategies which have been widely applied for enhancing therapeutic efficacy of ophthalmic drugs. The purpose of this review is to provide an update on the utilization of prodrug concept in ocular drug delivery. In addition, this review will highlight ongoing academic and industrial research and development in terms of ocular prodrug design and delivery.Medicinal chemistry (Shāriqah (United Arab Emirates)) 04/2012; 8(4):753-68. DOI:10.2174/157340612801216283 · 1.36 Impact Factor
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ABSTRACT: Purpose: To examine the novel application of a commercially available optical coherence tomography (OCT) system toward molecular histopathology using gold nanorod (GNR) linked antibodies as a functionalized contrast agent to evaluate ocular surface squamous neoplasia (OSSN). Methods: GNRs were synthesized and covalently attached to anti-glucose transporter-1 (GLUT-1) antibodies via carbodiimide chemistry. Three specimens from each of three distinct categories of human conjunctival tissue were selected for analysis, including conjunctiva without epithelial atypia (controls); conjunctival intraepithelial neoplasia, carcinoma in situ (CIS); and conjunctival squamous cell carcinoma (SCC). Tissue sections were incubated initially with GNR tagged anti-GLUT-1 antibodies and then with a fluorescent-tagged secondary antibody. Immunofluorescence and OCT imaging of the tissue was performed and the results were correlated to the light microscopic findings on traditional hemotoxyin and eosin stained sections. Results: No binding of the functionalized GNRs was observed within the epithelium of three normal conjunctiva controls. While immunofluorescence disclosed variable binding of the functionalized GNRs to atypical epithelial cells in all six cases of OSSN, the enhancement of the OCT signal in three cases of CIS was insufficient to distinguish these specimens from normal controls. In two of three cases of SCC, binding of functionalized GNRs was sufficient to produce an increased scattering effect on OCT in areas correlating to atypical epithelial cells which stained intensely on immunofluorescence imaging. Binding of functionalized GNRs was sufficient to produce an increased scattering effect on OCT in areas correlating to regions of erythrocytes and hemorrhage which stained intensely on immunofluorescence imaging within all nine tested samples. Conclusions: We have demonstrated the use of OCT for molecular histopathology using functionalized gold nanorods in the setting of OSSN. Our results suggest a threshold concentration of functionalized GNRs within tissue is required to achieve a detectable enhancement in scattering of the OCT signal.Investigative ophthalmology & visual science 01/2013; 54(2). DOI:10.1167/iovs.12-10794 · 3.40 Impact Factor