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D L Morris

Publications and source records attributed to D L Morris.

443 records · Page 25Linked to original sources

Multicenter evaluation of the performance and clinical utility in longitudinal monitoring of the Bayer Immuno 1 complexed PSA assay.

We conducted a multicenter evaluation of the analytical and clinical performance of the automated Bayer Immuno 1 complexed PSA (cPSA) assay, and compared assay performance to the Bayer Immuno 1 PSA assay. We sought to determine whether measurements of cPSA could be of clinical utility in the management of patients with prostate cancer. Results of the 10-day imprecision across three evaluation sites produced total CV < 2.50% and an analytical sensitivity of 0.02 microgram/L. There was an increased trend in clinical sensitivity for prostate cancer with increasing stage of disease (71-86%). Clinical specificity for patients with benign urogenital disease was 74.8%, and for other nonprostate diseases ranged from 91.1-100%. Retrospective serial monitoring of 155 patients with prostate cancer demonstrated concordance of cPSA measurements to clinical status for 97% of the patients analyzed. Results from the clinical studies using the Bayer Immuno 1 cPSA assay were comparable to results obtained with the Bayer Immuno 1 PSA assay. The Bayer Immuno 1 cPSA assay demonstrates analytical performance and clinical effectiveness in the management of prostate cancer patients during the course of disease and therapy.

Adolescent↗

1,25-dihydroxyvitamin D3 dissolved in lipiodol produces a sustained antiproliferative effect in the human hepatoblastoma cell line HepG2.

The steroid hormone 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has potential to be used as an anti-tumor agent, but its clinical application has been restricted by the strong systemic calcemic activity. Regional administration of the drug dissolved in lipiodol, might be a way of selectively delivering high concentrations of the drug to lipiodol avid tumor cells without causing systemic side effects. In acute (1 day treatment) and chronic (5 days treatment) experiments, efficacy of the drug dissolved in ethanol (control) or lipiodol and subsequently diluted in the culture medium was tested in vitro against the hepatoblastoma cell line HepG2. Using [3H]thymidine incorporation and cell count, antiproliferative effects of 1,25-(OH)2D3 dissolved in the two different solvents was compared. Microscopic examination of cells exposed to the lipiodol containing media revealed intra-cellular presence of the oil in abundance. Chronic treatment of cells with either formulation of 1,25-(OH)2D3 resulted in profound inhibition of cell proliferation. However, exposure of cells to 1,25-(OH)2D3 in lipiodol was followed by significantly greater and lasting inhibition of cell proliferation in both acute and chronic studies. These results indicate that, 1,25-(OH)2D3 dissolved in lipiodol probably acts as a sustained release drug depot formulation, in which case it could have some potential for the regional treatment of liver tumors.

Antineoplastic Agents↗

The use of lipiodol and medium chain triglyceride as delivery agents for hepatic arterial administration of 1, 25-dihydroxyvitamin D3--a potential new treatment for hepatocellular carcinoma.

It is well established that 1, 25 dihydroxyvitamin D3 is capable of inhibiting the proliferation of a number of human cancer cell lines, including hepatoma cell lines. However, clinical usage in the treatment of cancers has been limited by its hypercalaemic effects. We hypothesised that by delivering 1, 25 dihydroxyvitamin D3 dissolved in a lipid based carrier agent as a hepatic arterial infusion it would be possible to achieve high local concentrations within hepatomas for prolonged periods, whilst avoiding high systemic concentrations and hypercalcaemia. We examined this hypothesis by administering a hepatic arterial infusion of 1, 25 dihydroxyvitamin D3 in either Lipiodol, Medium Chain Triglyceride (MCT), or saline to hepatoma bearing rats. Assay of serum and tissue concentrations revealed that this approach using lipiodol or triglyceride results in selective distribution of 1, 25-dihydroxyvitamin D3 into, and retention within hepatoma tissue and low initial systemic serum levels. Lipiodol was more effective in these respects than MCT. This method of administration has potential in the treatment of hepatoma.

Animals↗

Hepatic intra-arterial injection of lipiodol-1,25-dihydroxyvitamin D3 for hepatocellular carcinoma in rats.

BACKGROUND: 1,25-(OH)2 D3 has an in vitro growth regulator effect on different cancers. Unfortunately, dose-limiting toxicity (hypercalcemia) limits its use in anticancer therapy. For primary liver tumors, loco-regional delivery of 1,25-(OH)2 D3 in lipiodol might avoid high systemic concentrations and development of hypercalcemia. MATERIALS AND METHODS: 1,25-(OH)2 D3 alone or mixed in lipiodol, was delivered at different concentrations into the hepatic artery of rats bearing a primary liver tumor. Calcium levels, tumor volume and proliferation index were assessed after treatment. RESULTS: Serum calcium values were significantly lower when the drug was mixed into lipiodol. Treatment with 10 micrograms of 1,25-(OH)2 D3 in ethanol resulted in a decrease in proliferation index within the tumor. CONCLUSIONS: The delivery of 1,25-(OH)2 D3 mixed in lipiodol reduces the subsequent elevation of serum calcium. Locoregional treatment with 1,25-(OH)2 D3 was shown for the first time to be effective on primary liver tumor growth in vivo.

Animals↗

In vitro antiproliferative activity of a medium-chain triglyceride solution of 1,25-dihydroxyvitamin D3 in HepG2 cells.

BACKGROUND: Successful targeted delivery of 1,25-dihydroxyvitamin D3 [1,25-D3] for the treatment of liver cancer would necessitate the use of an appropriate delivery agent. MATERIALS AND METHODS: Using liver cancer cell line HepG2 in culture, we examined, the possibility of using medium-chain triglyceride (MCT) as a solvent for targeted delivery of 1,25-D3. The drug was made up in either the medium or first dissolved in MCT and subsequently diluted in the medium. Cells were exposed for 1 (acute) or 5 days (chronic) to the 2 different formulations of the drug and cell proliferation was measured by [3H]thymidine and cell count methods. RESULTS: In chronic experiments, exposure of cells to the MCT containing formulation of 1,25-D3 led to significantly greater inhibition of cell proliferation. In the acute experiments where, 1 day 1,25-D3 treatment was followed by 4 days of incubation with normal medium (no drug, no MCT), inhibition of proliferation was more than 2 fold greater in cells exposed to the 1,25-D3/MCT preparation. CONCLUSION: These results indicate that, 1,25-D3 dissolved in MCT probably accumulates and then acts as a sustained release drug depot formulation, in which case it may have potential for the regional treatment of liver tumors.

Calcitriol↗

Lipiodol avid liver metastases from adrenocortical carcinoma; prospects for therapy?

A young lady with liver metastases from adrenocortical carcinoma was given a tracer dose of lipiodol into the hepatic artery and her liver metastases were shown to be extremely lipiodol avid. A therapeutic dose of lipiodol I131 was then given. There was not, however, any evidence of response to this treatment.

Adrenal Cortex Neoplasms↗

Hepatic cryotherapy for metastatic liver tumours.

Liver resection is the treatment of choice for resectable hepatic metastases; however, most patients have unresectable disease when diagnosed. Hepatic cryotherapy has been advocated to treat unresectable tumours in the liver although its precise role is still being evaluated. This article discusses mechanisms of action, technical considerations, current indications and the early results of cryotherapy in treating metastatic liver disease.

Colorectal Neoplasms↗