Biomedical subjects

N Safi

Publications and source records attributed to N Safi.

At least 19 recordsLinked to original sources

PubMed2000

Assessment of malignancy in pulmonary lesions: FDG dual-head coincidence gamma camera imaging in association with serum tumor marker measurement.

UNLABELLED: The purpose of the study was to evaluate the performance of dual-head coincidence gamma camera imaging using FDG in association with serum marker assays in identifying lung carcinoma in patients with abnormal findings on chest radiography. METHODS: A prospective evaluation of FDG imaging with coincidence detection emission tomography (CDET) using a dual-head gamma camera combined with the assessment of 3 sensitive serum markers of lung cancer (carcinoembryonic antigen, neuron specific enolase, and CYFRA 21-1) was performed on the same day on 58 consecutive patients with known or suspected lung malignancy. RESULTS: Fifty-three patients were proven to have lung cancer, and 5 patients had benign lung disease. Coincidence imaging showed significantly increased FDG uptake in 49 of 53 patients with proven malignancy (sensitivity, 92.5%) and in 3 patients with benign disease. FDG imaging had negative findings in 4 patients with proven malignancy and 2 patients with benign disease. Serum tumor marker levels were elevated in 42 of 53 cancer patients (sensitivity, 79.2%) and normal in 11 patients with proven malignancy. Nine patients with proven malignancy had positive findings on FDG images and negative marker assays. Two patients with proven malignancy had negative findings on FDG images and positive marker assays. The positive predictive value for lung cancer was 94.2% for FDG alone and 97.6% for FDG in association with serum markers. CONCLUSION: In this study, FDG CDET imaging was a powerful tool for evaluating patients with lung lesions suggestive of malignancy. Although the determination of serum marker levels was less accurate than FDG imaging, positive FDG results found in association with positive markers significantly increased the likelihood of lung malignancy.

Adult↗

PubMed1998

Involvement of glutathione in loss of technetium-99m-MIBI accumulation related to membrane MDR protein expression in tumor cells.

UNLABELLED: It was reported recently that 99mTc-hexakis-2-methoxyisobutyl isonitrile (MIBI) uptake is drastically reduced in cancer cells that express the multidrug resistance (MDR) product, Pgp 170 kDa (Pgp), suggesting that 99mTc-MIBI is a transport substrate for this transmembrane glycoprotein. In our study, we explored if another pump, a multidrug resistance-associated protein (MRP), could affect 99mTc-MIBI uptake. In addition, we studied the involvement of intracellular glutathione (GSH) as a modulator of 99mTc-MIBI uptake by both Pgp and MRP proteins. METHODS: MDR1 and MRP gene expression in seven human tumor cell lines was determined on a transcriptional level by reverse transcriptase polymerase chain reaction and on a protein level using immunocytochemistry. Technetium-99m-MIBI uptake was quantified by measuring radioactivity retained in the cells incubated at 37 degrees C in the presence or absence of buthionine sulfoximine (BSO), which depletes cellular GSH. The cellular GSH content was determined with Ellman's reagent. RESULTS: Cell lines were classified according to their phenotypic characteristics: 1/MRP-/Pgp-: breast cancer cells (MCF7), lung carcinoma cells (H69S) and mouth epidermoid tumor cells (KB 3.1), 2/MRP-/Pgp+: MCF7 mdr+, KBA.1; and 3/MRP+/Pgp-: small-cell lung carcinoma (H69 AR and A 549). Technetium-99m-MIBI uptake was significantly lower in cells expressing MRP as well as Pgp compared to MRP/Pgp cells. Depletion of GSH by BSO resulted in an increase of 99mTc-MIBI uptake in multidrug resistant cells overexpressing MRP but not expressing Pgp. CONCLUSION: Technetium-99m-MIBI is extruded by both Pgp and MRP efflux pumps. However, MRP action is indirect and involves intracellular GSH for a presumed interaction with the 99mTc-MIBI before its effLux. Technetium-99m-MIBI seems to be a good candidate for a noninvasive marker to diagnose MDR1 related to Pgp and MRP expression in tumors of different origin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1992

Two antigens detected on human ocular melanomas with the mouse monoclonal antibodies 2/10SN and 10/12SN.

Seven human ocular melanoma cell lines were established in vitro and 3 of these, GU-4, LLN-40 and its subline C17-11, were characterized. Mice were immunized with these ocular melanoma cell lines, and 2 hybridomas producing monoclonal IgG1 antibodies (MAb) were produced. MAb 2/10SN recognizes a 44-kDa monomeric protein, whereas MAb 10/12SN reacts with an 83/65-kDa heterodimeric protein. These melanoma-associated antigens (MAA) are detected at high concentrations in the cytoplasm of ocular melanoma cells. However, cell-surface labelling techniques suggest that these MAA are also associated with the cell-surface membrane. These 2 ocular MAA are also expressed by several skin melanoma cell lines. Immunohistochemical studies have localized these antigens to ocular and skin melanomas, to sweat ducts and basal squamous cells in normal skin, with limited expression in several other normal tissues and some carcinomas. Biodistribution studies in nude mice with human ocular melanomas have demonstrated good localization of 125I-labeled MAb 2/10SN at the tumor sites. Therefore, these 2 MAbs, 2/10SN and 10/12SN, recognize MAA which appear to be unique and may prove useful for imaging purposes.

Animals↗

PubMed1980