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1.
Anticancer Agents Med Chem ; 11(6): 585-90, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21554205

ABSTRACT

Gallium is antiproliferative to many types of cancer, due primarily to its ability to act as a non-functional mimic of ferric iron (Fe(3+)). Because Fe(3+) is needed for ribonucleotide reductase activity--and thus DNA synthesis--gallium can inhibit DNA production and cell division. Diagnostic gallium scans have shown that hepatocellular carcinoma (HCC) is commonly avid for gallium. Furthermore, in vitro studies have found that gallium nitrate, and particularly gallium maltolate (GaM), have dose-dependent antiproliferative activity against HCC cell lines. Rationale thus exists to use GaM, an orally active compound that has been well tolerated in Phase I clinical trials, to treat patients whose HCC is gallium-avid in a gallium scan. Because gallium absorbed from orally administered GaM is bound predominately to serum transferrin, which travels to all tissues in the body, GaM has the potential to treat even distant metastases. A patient with advanced HCC (20 × 10 cm primary tumor, ascites around liver and spleen, resistant to Nexavar(®) (sorafenib)), whose cancer was highly gallium-avid in a (67)Ga-scan, was treated with oral gallium maltolate at 1500 mg/day q.d. After four weeks of treatment, the patient had a large reduction in pain, with greatly increased mobility and quality of life, and significantly lowered serum bilirubin and inflammation-related liver enzymes. At eight weeks, CT scans showed apparent necrosis of the tumor.


Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/drug therapy , Gallium Radioisotopes , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/drug therapy , Organometallic Compounds/therapeutic use , Pyrones/therapeutic use , Administration, Oral , Aged , Cell Division/drug effects , DNA Replication/drug effects , Female , Humans , Radionuclide Imaging , Radiopharmaceuticals
2.
J Rheumatol ; 31(5): 896-901, 2004 May.
Article in English | MEDLINE | ID: mdl-15124247

ABSTRACT

OBJECTIVE: In a retrospective study we evaluated the effect, duration of effect, and safety of radiosynoviorthesis of the ankle in patients with persistent synovitis, refractory to disease modifying antirheumatic drugs (DMARD) and intraarticular glucocorticoid injections. We estimated leakage and dose to target and non-target organs. METHODS: Radiation synovectomy was performed by injection of 75 MBq 186rhenium colloid and 20 mg triamcinolone-hexacetonide mixed in a volume of about 1.5 ml. About 24 hours after injection, leakage of the radionuclide was measured with a single-head gamma camera, with views of the ankle joint, regional (inguinal) lymph nodes, and liver. Leakage was expressed as counts in the target region of interest corrected for background relative to total counts corresponding with percentage of injected dose. The effect of radiosynoviorthesis was scored into 3 categories: (1) No effect, i.e., persistent synovitis or only minimal reduction of swelling and/or pain, or the need of intraarticular glucocorticoid injection within 3 months or arthrodesis of the treated joint within 6 months. (2) Moderate effect, i.e., significant reduction of swelling, pain, and improvement of function. (3) Good effect, i.e., complete or almost complete remission of synovitis. RESULTS: The mean age of patients (28 women, 12 men) at the time of treatment was 58 years (range 33-76); 54 consecutive procedures in ankles of the 40 patients were evaluated. No effect was found in 12 of 54 (22%) treated joints; moderate effect in 12 (22%), with a mean duration of effect of 34 months (range 12-49); and good effect in 30 (56%), with a mean duration of effect of 41 months (range 21-75). Mean effect-duration did not differ significantly between the moderate and good effect groups. Mean leakage did not differ significantly between the effect groups. CONCLUSION: Radiation synovectomy of the ankle is a safe and effective treatment in persistent synovitis, although all patients eventually experienced recurrence of arthritis.


Subject(s)
Ankle Joint/surgery , Chlorides/therapeutic use , Radioisotopes/therapeutic use , Rhenium/therapeutic use , Synovectomy , Synovitis/surgery , Adult , Aged , Ankle Joint/pathology , Ankle Joint/radiation effects , Body Burden , Colloids , Female , Humans , Male , Middle Aged , Radiation Dosage , Recurrence , Retrospective Studies , Sulfides , Synovial Membrane/pathology , Synovial Membrane/radiation effects , Synovitis/pathology , Synovitis/radiotherapy , Treatment Outcome
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