ABSTRACT
Glomus tumors are neoplasms that occur only rarely in the head and neck. These tumors are usually distinguished by benign growth characteristics. We present a case of a large intranasal glomus tumor which, at presentation, had eroded through the ethmoid roof to involve the floor of the anterior cranial fossa. The patient was treated with primary external-beam radiotherapy. To our knowledge, this is the first report of an invasive glomus tumor of the head and neck.
Subject(s)
Glomus Tumor/pathology , Head and Neck Neoplasms/pathology , Aged , Aged, 80 and over , Female , Glomus Tumor/metabolism , Glomus Tumor/radiotherapy , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/radiotherapy , Humans , Immunohistochemistry , Nasal Cavity , Neoplasm InvasivenessABSTRACT
UNLABELLED: In this study we investigated the feasibility of using radionuclide accumulation mediated by the human sodium iodide symporter (hNIS) gene in conjunction with various imaging modalities as a reporter system to noninvasively monitor the expression of transgenes delivered for gene therapy. METHODS: NIS-expressing adenovirus (Ad-hNIS) was delivered in vitro to MB-435 breast carcinoma cells. NIS-mediated accumulation of (125)I(-), (99m)TcO(4)(-), and (76)Br(-) by the cells was visualized using autoradiography, gamma-camera scintigraphy, and PET imaging, respectively. RESULTS: For all imaging modalities, signal intensity generated by the cells correlated linearly both with the amount of Ad-hNIS and with the activity of radionuclide added to the cells. CONCLUSION: hNIS-mediated cellular accumulation of radionuclide was clearly visualized by all 3 imaging modalities tested. This preliminary study demonstrates the feasibility of using hNIS for monitoring the location and magnitude of expression of genes delivered during gene therapy.
Subject(s)
Breast Neoplasms/diagnostic imaging , Breast Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Gene Transfer Techniques , Radiopharmaceuticals/pharmacokinetics , Symporters/pharmacokinetics , Cell Line, Tumor , Feasibility Studies , Genes, Reporter/physiology , Genetic Therapy/methods , Humans , Radionuclide Imaging , Recombinant Fusion Proteins/pharmacokineticsABSTRACT
BACKGROUND: Gene therapy that uses delivery of the sodium-iodide symporter (NIS) gene followed by radioiodide administration has been proposed as a novel form of radiotherapy for nonthyroidal cancers. METHODS: In vitro [(125)I] iodide accumulation and efflux from cells was determined after treatment with an NIS-expressing adenovirus (Ad-NIS). A clonogenic survival assay and tumor growth experiment that used athymic mice were used to demonstrate the in vitro and in vivo cytotoxicity of Ad-NIS treatment and [(131)I] iodide delivery. RESULTS: Head and neck squamous cell carcinoma (HNSCC) cell lines treated with Ad-NIS exhibit significant amounts of radioiodide accumulation and retention. In vitro HNSCC cell survival was significantly diminished after NIS gene delivery followed by administration of [(131)I] iodide. Moreover, NIS gene transfer/[(131)I] iodide administration dramatically attenuated HNSCC tumor formation in athymic mice. CONCLUSIONS: Our data demonstrate the feasibility of genetically targeted radiotherapy by use of the NIS gene as a possible therapeutic intervention in head and neck cancer.
Subject(s)
Carcinoma, Squamous Cell/radiotherapy , Genetic Therapy/methods , Head and Neck Neoplasms/radiotherapy , Symporters/genetics , Adenoviridae/genetics , Animals , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Cell Line, Tumor , Feasibility Studies , Female , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/metabolism , Iodine Radioisotopes/administration & dosage , Mice , Mice, Nude , Symporters/metabolismABSTRACT
NADPH:quinone oxidoreductase (NQO(1)), a homodimeric, ubiquitous, flavoprotein, catalyzes the two-electron reduction of quinones to hydroquinones. This reaction prevents the one-electron reduction of quinones by cytochrome P450 reductase and other flavoproteins that would result in oxidative cycling with generation of superoxide (O(2)(.-)). NQO(1) gene regulation may be up-regulated in some tumors to accommodate the needs of rapidly metabolizing cells to regenerate NAD(+). We hypothesized that pancreatic cancer cells would exhibit high levels of this enzyme, and inhibiting it would suppress the malignant phenotype. Reverse transcription-PCR, Western blots, and activity assays demonstrated that NQO(1) was up-regulated in the pancreatic cancer cell lines tested but present in very low amounts in the normal human pancreas. To determine whether inhibition of NQO(1) would alter the malignant phenotype, MIA PaCa-2 pancreatic cancer cells were treated with a selective inhibitor of NQO(1), dicumarol. Dicumarol increased intracellular production of O(2)(.-), as measured by hydroethidine staining, and inhibited cell growth. Both of these effects were blunted with infection of an adenoviral vector containing the cDNA for manganese superoxide dismutase. Dicumarol also inhibited cell growth, plating efficiency, and growth in soft agar. We conclude that inhibition of NQO(1) increases intracellular O(2)(.-) production and inhibits the in vitro malignant phenotype of pancreatic cancer. These mechanisms suggest that altering the intracellular redox environment of pancreatic cancer cells may inhibit growth and delineate a potential strategy directed against pancreatic cancer.