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PubMedDate not supplied

Antineoplastic effects of gallium nitrate on human medulloblastoma in vivo.

Gallium nitrate possesses antineoplastic activity against certain solid tumors and has been demonstrated to be an effective agent in reducing cell proliferation and DNA synthesis in the medulloblastoma Daoy cell line in vitro. In prior studies, gallium inhibited the cellular uptake of 59Fe by brain tumor cells; however, this block in 59Fe uptake was variable and closely paralleled the inhibitory effects of gallium on cell growth. In vivo trials now have been conducted and have yielded some promising results. Nude mice received intradermal injections of medulloblastoma Daoy and then allowed to grow tumors. When the mice had developed at least one tumor between 9 to 10 mm in diameter, a 10-day course of intraperitoneal gallium nitrate injections was initiated. Gallium nitrate treatment reduced overall tumor growth rate and reduced actual tumor size. Nephrotoxicity was severe, but may be preventable by continuous gallium infusion and use of diuretics and hyperhydration.

Animals↗
PubMed2006

Preclinical characterization of anticancer gallium(III) complexes: solubility, stability, lipophilicity and binding to serum proteins.

The discovery and development of gallium(III) complexes capable of inhibiting tumor growth is an emerging area of anticancer drug research. A range of novel gallium coordination compounds with established cytotoxic efficacy have been characterized in terms of desirable chemical and biochemical properties and compared with tris(8-quinolinolato)gallium(III) (KP46), a lead anticancer gallium-based candidate that successfully finished phase I clinical trials (under the name FFC11), showing activity against renal cell cancer. In view of probable oral administration, drug-like parameters, such as solubility in water, saline and 0.5% dimethyl sulfoxide, stability against hydrolysis, measured as the rate constant of hydrolytic degradation in water or physiological buffer using a capillary zone electrophoresis (CZE) assay, and the octanol-water partition coefficient (logP) providing a rational estimate of a drug's lipophilicity, have been evaluated and compared. The differences in bioavailability characteristics between different complexes were discussed within the formalism of structure-activity relationships. The reactivity toward major serum transport proteins, albumin and transferrin, was also assayed in order to elucidate the drug's distribution pathway after intestinal absorption. According to the values of apparent binding rate constants determined by CZE, both KP46 and bis(2-acetylpyridine-4,4-dimethyl-3-thiosemicarbazonato-N,N,S)gallium(III) tetrachlorogallate(III) (KP1089) bind to transferrin faster than to albumin. This implies that transferrin would rather mediate the accumulation of gallium antineoplastic agents in solid tumors. A tendency of being faster converted into the protein-bound form found for KP1089 (due possibly to non-covalent binding) seems complementary to its greater in vitro antiproliferative activity.

Antineoplastic Agents↗
PubMed2004

Selective removal of gallium (III) from aqueous solutions containing zinc or aluminum using sodium di-(n-octyl) phosphinate.

Gallium was removed selectively from aqueous solutions containing zinc or aluminum using sodium di-(n-octyl) phosphinate as a ligand (NaL). At low pH or low mole ratios, the gallium was removed by complexation with the ligand as GaL(3(S)), while the zinc or the aluminum remained in the solution. Nearly complete separation of gallium was obtained. By increasing the amount of ligand or by increasing the pH, the zinc or aluminum remaining in the solution was then removed as a solid complex: ZnL(2(S)) or AlL(3(S)), respectively. At a pH between 1.5 and 2 and a mole ratio ligand to total metals of 0.75 for zinc solutions and 1.0 for aluminum solutions, more than 98% of the gallium was selectively removed with a high molar selectivity, alpha(Ga/Zn) and alpha(Ga/Al), respectively. Over 95% of gallium was recovered from the solid GaL(3(S)) complex by treatment of the complex with a 3M NaOH solution and diethyl ether. The gallium was concentrated in the aqueous solution to 4 times its initial concentration and the ligand was extracted into the ether phase. After evaporation of the ether, 95% of the ligand was regenerated in its sodium form as a solid.

Aluminum↗
PubMed1995

Effects of the antihypercalcemic drugs gallium nitrate and pamidronate on hormone release of pathologic human parathyroid cells.

BACKGROUND: Gallium nitrate and the bisphosphonates pamidronate and its dimethylated derivative comprise antihypercalcemic drugs with actions on bone. This study examines the in vitro effects of these compounds on human parathyroid cells. METHODS: Parathyroid hormone (PTH) release and the concentration of cytoplasmic calcium ion (Ca2+) of dispersed cells from parathyroid glands of 27 patients with sporadic primary or uremic hyperparathyroidism was measured. RESULTS: In 1.25 mmol/L external Ca2+, 200 mumol/L gallium nitrate inhibited PTH release from preparations of primary and uremic hyperparathyroidism by 14% and 22%, respectively. Similar reductions were evident also in 0.5 and 3.0 mmol/L Ca2+. The gallium nitrate-induced suppression of PTH release was dose dependent in the 2 to 200 mumol/L range. Cytoplasmic Ca2+ concentration displayed a biphasic rise on elevation of external Ca2+ and remained unaffected by gallium nitrate. None of the bisphosphonates altered PTH release of pathologic human or normal bovine parathyroid cells. CONCLUSIONS: The results support clinical usefulness of gallium nitrate through its dual actions on bone and the parathyroid. The findings substantiate that gallium may reduce PTH release by stabilization of the plasma membrane rather than by interference with the surface cation receptor mediating Ca2+ regulation of the secretion.

Adult↗
PubMed2000

Reproducibility and applicability of gallium replication as evaluated by biological specimen use.

Structures of biological surfaces pressed on to a pure liquid gallium surface were successfully traced on to the gallium surface by quick-freezing below the melting point (28.78 degrees C) in air or water for replication in scanning electron microscopy. Gallium's high surface tension (approximately 700 mN m(-1) at 30 degrees C) deteriorates the spatial resolution of replicas and destroys some types of specimens. Five different biological surfaces were replicated on to gallium surfaces to evaluate spatial resolution and specimen resistance, i.e. reproducibility and applicability. Gallium replication of jewel beetle wing and human hair demonstrated submicron spatial resolution in the horizontal direction at least. Trials of protozoa, bacteria, and culture cell replication showed that protozoa are suited to replication because the cell membrane has characteristic structures with sufficient resistance to the gallium surface.

Animals↗
PubMed2003

A high-fibre diet in combination with bisacodyl for bowel preparation in gallium renal scintigraphy.

Bowel accumulation of gallium-67 frequently complicates the interpretation of gallium-67 scintigrams. This is a drawback, especially when reading gallium renal images. In this study, we evaluated the value of a high-fibre diet in bowel preparation for improving the quality of gallium renal imaging in lupus nephritis. Group A, consisting of 86 patients, was on a regular diet and received bisacodyl the night before imaging. Group B, consisting of 77 patients, was on a high-fibre diet for three consecutive days before imaging and received bisacodyl the night before imaging. Gallium bowel activity was rated on a scale of 0 to III on the basis of anterior and posterior views of delayed 48 h images. Our data revealed that there was a significant difference in image quality between groups A and B. Fifty per cent of group A patients had obvious bowel activity. The percentage decreased significantly to 25% in group B. In conclusion, the application of a high-fibre diet significantly improves the efficacy of bowel preparation for gallium renal scintigraphy in the evaluation of lupus nephritis.

Adult↗
PubMed1995

Marginal leakage of Gallium Alloy root-end fillings: an in-vitro assessment.

The sealing ability of amalgam and Gallium Alloy Gallium Filling (GF) root-end fillings was evaluated in vitro using a highly uniform collection of sheep incisor roots. Following ultrasonic canal debridement and orthograde obturation with gutta-percha and sealer, root-end cavities were prepared in 100 roots and filled with amalgam (50 teeth) or Gallium Alloy GF (50 teeth), Twenty-five teeth from each group were subjected to immediate dye leakage assessment under vacuum conditions with methylene blue dye (2%), pH 7. Linear dye penetration was measured following longitudinal splitting. The other 25 teeth from each group were incubated in Ringer's solution for 12 weeks before leakage assessment by the same method. Control teeth were included in each component of the study. Mean linear dye penetration was: amalgam--5.17 mm at baseline, 2.33 mm after 12 week's incubation; Gallium Alloy GF--2.21 mm at baseline, 1.41 mm after 12 week's incubation. The apical marginal seal of both materials improved significantly following storage in Ringer's solution (P<0.001). Gallium Alloy GF provided a better apical seal than amalgam, both at baseline and following storage (P<0.001). Subjective evaluation of the general handling characteristics of Gallium Alloy GF revealed that it was a more difficult material to manipulate than amalgam, largely because of its wetting ability and consequent adhesion to dental instruments.

Alloys↗
PubMed1989

Gallium scanning in the management of mediastinal Hodgkin's disease.

Gallium-67 scanning was performed pre- and post-therapy in 25 patients with Hodgkin's disease and a mediastinal mass. At restaging after therapy, radiographs (or CT scans) did not predict the presence of active disease whereas gallium scans did with a high degree of accuracy. Gallium-67 determined disease activity in those patients who had a residual mediastinal mass predicting outcome in 11 out of 12 patients; one had a late relapse at 7 years. In patients without a residual mass gallium scanning was again accurate, predicting outcome in 11 of 13 patients. Two patients with negative gallium scans but subsequent active disease were scanned too soon after chemotherapy. The results suggest that gallium scanning has an important role in the management of mediastinal Hodgkin's disease and is superior to all current methods of assessing disease activity irrespective of the presence of a residual mediastinal mass.

Adolescent↗
PubMed1981

Immunosuppressive therapy in patients with congestive cardiomyopathy and myocardial uptake of gallium-67.

Thirty-nine patients with idiopathic congestive cardiomyopathy underwent gallium-67 scintigraphy. Twenty had no evidence of myocardial uptake (group I) and 19 had demonstrable myocardial gallium-67 activity (group II). There was no significant difference in age, sex, duration of symptoms, antecedent viral illness, left ventricular end-diastolic pressure, pulmonary artery systolic pressure, or ejection fraction between the two groups. Fifteen patients in group II were treated with prednisone and azathioprine for a minimum of 8 months. Nine of 15 patients were clinically unchanged and gallium-67 scans remained positive (group IIa). Six patients had significant improvement and resolution of myocardial gallium-67 uptake (group IIb). The mean change in ejection fraction was +0.2% in group I, -4.8% in Group IIa, and +13.8% in group IIb. There were five deaths in group I (25% mortality), three in group IIa (33% mortality), and no deaths in group IIb. The only significant difference between patients in group IIa and those in group IIb was a greater left ventricular posterior wall thickness in group IIa patients. Twenty control patients without cardiac disease had negative gallium-67 scans. We conclude that gallium-67 myocardial scintigraphy may be a useful test for predicting the response to prednisone and azathioprine therapy.

Adolescent↗
PubMed1994

Effects of humoral hypercalcemia of malignancy and gallium nitrate on thyroid C cells in nude mice: immunohistochemical and ultrastructural investigations.

Immunohistochemical and ultrastructural investigations of thyroid C cells were conducted in male nude (athymic) mice bearing a serially transplantable canine adenocarcinoma (CAC-8) model of humoral hypercalcemia of malignancy following subcutaneous administration of gallium nitrate. The following four groups were investigated: 1) vehicle-treated non-tumor-bearing control mice; 2) non-tumor-bearing mice treated with gallium nitrate; 3) vehicle-treated hypercalcemic mice bearing CAC-8; and 4) CAC-8 tumor-bearing mice treated with gallium nitrate. Gallium nitrate-treated tumor-bearing mice had a significant decrease in serum calcium as compared with tumor-bearing controls. C cells of non-tumor-bearing mice stained intensely for calcitonin and calcitonin gene-related peptide and weakly for chromogranin A and neuron-specific enolase. In C cells of both vehicle- and gallium-treated tumor-bearing mice, immunoreactive staining was decreased for calcitonin, calcitonin gene-related peptide, and chromogranin A, whereas there was a moderate increase in staining for neuron-specific enolase. Ultrastructurally, thyroid C cells in hypercalcemic tumor-bearing control and gallium-treated mice were hypertrophic and markedly degranulated as compared with those of non-tumor-bearing controls. Hypertrophic C cells contained few mature secretory granules, a well-developed Golgi apparatus, and lamellar arrays of rough endoplasmic reticulum. There was no evidence of C-cell hyperplasia. Immunohistochemical and ultrastructural findings revealed that C cells in mice with cancer-associated hypercalcemia were primarily in the actively synthesizing phase of the secretory cycle and had diminished immunoreactivity for calcitonin, calcitonin gene-related peptide, and chromogranin A.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1999

Strength and microstructure of gallium alloys.

This study investigated the physical and mechanical properties and the microstructure of four different gallium alloys. For all gallium alloys, the compressive strengths measured at one hour (86-223 MPa) and 24 hours (265-286 MPa) after specimen preparation were found to be well within the range exhibited by many high-copper amalgams. The creep values and dimensional change of the gallium alloys were comparable to those of leading amalgams, except for the dimensional change value of one alloy. The set gallium alloys consisted of a multi-phase structure including beta-Sn, CuGa2, In4Ag9, Ag72Ga28, and Ga5Pd (except for one product that did not contain Pd) that was more complicated than the structure of dental amalgams. Although the gallium alloys had physical and mechanical properties comparable to those of high-copper amalgams, the microstructure, coupled with the instability of the element gallium itself, could make these materials more prone to corrosive attack compared to amalgams.

Analysis of Variance↗
PubMed1979

Angiotensin-I-converting enzyme and gallium scan in noninvasive evaluation of sarcoidosis.

Angiotensin-converting enzyme assays and gallium-scan results were obtained from 27 patients with biopsy-proven, clinically active sarcoidosis. Twenty-three of these patients had elevated converting enzyme levels, and 22 had positive gallium-scan results. Three of four patients with normal or borderline-elevated levels of angiotensin-converting enzyme also had positive gallium-scan results. Of 156 nonsarcoid patients (pulmonary and other diseases), 27 were found to have elevated serum converting enzyme levels, and 25 of these had negative gallium-scan results. These results indicate that the combination of an assay of angiotensin-converting enzyme and gallium scan increases diagnostic specificity from 83% to 99% without sacrificing sensitivity. We conclude that the concurrent use of angiotensin-converting enzyme assay and gallium scan is of value in the diagnosis of sarcoidosis.

Clinical Enzyme Tests↗
PubMed1999

Direct-placement gallium restorative alloy: a 3-year clinical evaluation.

OBJECTIVE: A pilot clinical study on a direct-placement gallium restorative alloy was initiated with nine patients who signed a consent form. METHOD AND MATERIALS: Thirty Class I restorations were placed and assessed over a 3-year period. The cavity preparations and surface of the restorations were sealed to prevent oral fluids from contacting the gallium alloy during placement and early setting of the gallium restorative material. RESULTS: The initial 18-month clinical results were encouraging. But at 21 months, one tooth had fractured, and within another year two molars were diagnosed with cracked-tooth syndrome (incomplete tooth fracture). These three fractured teeth were restored with amalgam and are symptomless at this time. There was little fracture at the margins of the gallium restorative, but tarnish and a rough surface were noted on many of the gallium restorations. The direct-placement gallium restorative alloys must be further assessed in the laboratory to correct dimensional instability. CONCLUSION: Results suggested that Galloy, used with either of two sealing resins, is not a suitable restorative material.

Dental Alloys↗
PubMed1975

Gallium gallbladder scanning in cholecystitis.

Gallium has been shown to accumulate in metabolically active tissue including sites of infection. The purpose of this study was to evaluate gallium scanning in cholecystitis. Ten patients with cholecystitis were studied using conventional gallium scanning techniques. Five patients with acute cholecystitis showed intense gallium accumulation in the gallbladder area. One of five patients with chronic cholecystitis showed significant accumulation in the gallbladder. The limitations of this method are mainly the need for serial scanning to rule out gallium accumulation in the hepatic flexure of the colon and also the failure to detect consistently a chronically diseased fibrotic gallbladder. We conclude that gallium scanning of the gallbladder is an important adjunctive study in the evaluation of cholecystitis.

Adult↗
PubMed2006

Effect of gallium nitrate on tamoxifen induced hypercalcemia in rats bearing mammary tumor.

AIM: To study the effect of gallium nitrate in the treatment of flare hypercalcemia in rats, bearing mammary tumor with bone metastasis. MATERIALS AND METHODS: Female Sprague-Dawley albino rats were used in the study. Animals were divided into 5 groups: normal control; hypercalcemic rats bearing DMBA-induced mammary tumors; flare hypercalcemic animals bearing DMBA-induced mammary tumors (hypercalcemic rats, treated with tamoxifen at the dose of 10 mg/kg); flare hypercalcemic rat bearing DMBA-induced mammary tumors, treated with gallium nitrate at the dose of 2.5 mg/kg; control rats, treated with gallium nitrate at the dose of 2.5 mg/kg. Eligibility criteria - serum calcium levels were 11.0 mg% or above. Biochemical parameters were measured, using standard methods. Urinary excretion of calcium, creatinine ratio, urinary bone marker were also evaluated by using standard method. RESULTS: All flare hypercalcemic rats were treated with gallium nitrate and developed normocalcemia. Biochemical parameters were measured in hypercalcemic and flare hypercalcemic animals. Calcium level in blood serum, alkaline phosphatase were significantly higher in flare hypercalcemia than in hypercalcemic rats. Urinary pyridinoline, deoxypyridinoline and hydroxyproline were also elevated in flare hypercalcemic rats. In contrast, intact parathyroid hormone and albumin levels were lowered in flare as well as hypercalcemic groups when compared with normal control groups. After gallium nitrate treatment all the above parameters returned to normal level. CONCLUSIONS: Administration of gallium nitrate in vivo is highly effective in treatment of flare hypercalcemia.

Animals↗
PubMed1988

Early recognition of recurrent hepatocellular carcinoma utilizing gallium-67 citrate scintigraphy.

Gallium-67 scintigraphy is a valuable test together with other screening tests such as alpha feto-protein (AFP) and other imaging modalities in following up recurrent hepatocellular carcinoma (HCC). Three patients were followed in our institution for intervals varying from 2-24 mo after successful resection of uninodular localized hepatomas. In the first patient, gallium scan showed abnormal localized activity while the computed tomography (CT) scan and the magnetic resonance imaging were negative. Liver function tests and AFP were also normal and the patient was operated upon only on the basis of the gallium scan. The second patient had a follow-up gallium scan 2 mo after the first operation that showed an area of increased activity along the inferior aspect of the right lobe. A CT scan done after that showed no evidence of recurrence, but subsequently became positive when repeated 4 mo later. The third patient had abnormal simultaneous gallium scan and CT scan demonstrating a recurrence in the left adrenal gland while both AFP and carcinoembryonic antigen were normal. This has led us to consider every patient a candidate for a baseline and follow-up gallium scan for evaluation for recurrence following HCC.

Adrenal Gland Neoplasms↗
PubMed1986

Sequential technetium-99m HMDP-gallium-67 citrate imaging for the evaluation of infection in the painful prosthesis.

In order to evaluate the clinical utility of sequential technetium-99m HMDP-gallium-67 scanning in patients with painful orthopedic prosthesis, a retrospective review was made of 154 sequential scans performed in 130 patients. Criteria for a positive study included spatially incongruent gallium-technetium uptake or gallium uptake that was congruent but more intense than technetium. Images were interpreted as negative if gallium was congruent and less intense than technetium. Sixty-six patients underwent surgery (31 infected, 35 aseptic), and 64 were evaluated clinically (3 infected, 61 aseptic). The combined results of the surgical and nonsurgical patients yielded a sensitivity of 66%, a specificity of 81%, and an accuracy of 77%. In this series, the technetium-gallium scan combination has proven to be helpful but more recent techniques such as indium-111-labeled leukocytes may prove to be superior to sequential technetium-gallium imaging.

Adult↗
PubMed1986

Gallium nitrate for acute treatment of cancer-related hypercalcemia: clinicopharmacological and dose response analysis.

Current treatment of cancer-related hypercalcemia is limited by agents of limited effectiveness or excessive toxicity. Gallium nitrate is a new drug which both inhibits bone resorption and increases calcium content of bone. We have now treated 39 episodes of hypercalcemia with gallium nitrate administered as a continuous i.v. infusion for 5-7 days at 3 daily dose levels (100 and 200 mg/m2, and 50 mg/m2 by brief infusion followed by 150 mg/m2). Nadir calcium values were significantly lower (9.2 +/- 1.5 mg/dl) for patients who received the highest dose relative to patients who received the lowest dose (10.5 +/- 1.6 mg/dl, P less than 0.001). While the actual percentage of patients who achieved normocalcemia was higher at the highest dose relative to the lowest dose (86 versus 60%), this difference was not statistically significant. Mean serum concentration of inorganic phosphorous declined significantly for all patients from 2.9 +/- 0.86 mg/dl at base line to 1.8 +/- 0.66 mg/dl (P less than 0.001). Pharmacokinetic studies suggested that a threshold plasma gallium concentration of approximately 1 microgram/ml must be attained to achieve acute normalization of elevated serum calcium levels. Steady-state plasma gallium levels were attained after 48 h; there was no evidence of drug accumulation in plasma after 2 days. Effects on serum creatinine concentration were negligible, and there were no other toxic reactions. These data confirm preclinical experiments which suggested that inhibition of bone resorption by gallium nitrate is dependent upon the dose and duration of drug exposure. We conclude that gallium nitrate is effective treatment for cancer-related hypercalcemia. The drug is now being evaluated against standard treatment in a randomized, double-blind trial.

Adult↗