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Biomedical subjects

F L Meyskens

Publications and source records attributed to F L Meyskens.

At least 163 records · Page 9Linked to original sources
PubMed1983

Treatment of cutaneous T-cell lymphoma (mycosis fungoides) with 13-cis-retinoic acid.

Four patients with refractory cutaneous T-cell lymphoma (mycosis fungoides) were treated with 13-cis-retinoic acid. Near complete clearing of extensive tumours and plaques was seen in one patient, who remains in partial remission with continued improvement after fifteen months. Two patients showed improvement in pruritus and 50% reduction in plaques by four and six weeks, respectively. The fourth patient had improvement in pruritus and clearing of plaques, but dryness and scaling necessitated reduction and eventually withdrawal of the treatment.

Adult↗
PubMed1983

Diagnostic electron microscopy for amelanotic melanoma: correlation of patient biopsy, soft agar assay, and xenograft.

In an attempt to diagnose a suspected amelanotic melanoma tumour, we examined a variety of tissue and cell samples from one patient at the ultrastructural level, which consisted of single cell suspensions of tumour cells with and without DOPA treatment, tumour cells after culture in agar with and without DOPA treatment, and single tumour cells hetero-transplanted into a nude mouse. Premalanosomes were not observed in sections of the amelanotic tumour with routine electron microscopy. Osmophilic-dense bodies, suggestive of melanosomes, were noted in the single cells in suspension treated with DOPA and cells grown in agar without DOPA treatment. Definitive premelanosomes, with an identifiable striated matrix, were only observed in cells grown into colonies in agar and treated with DOPA. Positive L-DOPA reaction products were noted in the golgi complex, endoplasmic reticulum closely related to the golgi (GERL), and in vacuoles from cells grown in agar. As controls, Cloudman S91 53.1 melanoma cells were evaluated as single cells in suspension or as colonies after culture in agar, both with and without DOPA treatment. Premelanosomes were always observed in this established melanoma cell line while DOPA-treated cells contained positive L-DOPA reaction products. The overall findings identified the tumour as amelanotic melanoma and indicated that both DOPA treatment and culture in agar were needed for the demonstration of premelanosomes.

Adult↗
PubMed1983

In vitro modulation of human and murine melanoma growth by prostanoid analogues.

The inhibitory effect of various prostaglandin analogues on the anchorage independent growth of murine and human melanoma cells was measured. PGA analogues (which were modified at C-16 and C-18) did not demonstrate any major improvement in activity over PGA alone. These included 16,16-dimethyl PGA1, 16,16-dimethyl-PGA2, 16,16-dimethyl-18-oxa-PGA2 and trans-delta-2-15-alpha acetoxy-16,16-dimethyl-18-oxa-11-deoxy-PGE1-methylester. The thromboxane synthetase inhibitor, U51605, demonstrated weak anti-proliferative activity. PGD2 (with a ketone at C-11 versus C-9 for PGA and PGE) was the most potent prostaglandin tested. Cells from melanoma lines displayed species differences in their sensitivities. PGA1 and PGE1 were the most potent inhibitors of the anchorage independent growth of murine melanoma cells. On human melanoma cells PGD2 was the most active prostaglandin, 2-3 times more potent than PGA1; PGE1 was a very weak inhibitor.

Alprostadil↗
PubMed1983

Chromosome 6q involvement in human malignant melanoma.

Chromosome banding analysis was performed on five cases of human malignant melanoma. Results demonstrated a variety of chromosome alterations, including deletion or translocation of chromosome 6q, in four of five cases. A comparison of our results with previously published studies suggests that chromosome 6q may represent a specific site of chromosome aberration in malignant melanoma.

Chromosome Aberrations↗
PubMed1983

Vitamin A: evidence for its preventive role in human cancer.

Both the provitamin beta-carotene and natural vitamin A and its derivatives (the retinoids) are being proposed as potential chemopreventive agents. The biochemistry and pharmacology of vitamin A suggest a number of mechanisms whereby carcinogenesis can be affected. Epidemiologic studies have consistently demonstrated an increased relative risk of cancer for people with low vitamin A intake or low-to-normal serum retinol values. Chemoprevention trials in humans are only now beginning. In the interim, daily consumption of vitamin-A-containing foods may be a "prescription" worth following.

Carotenoids↗
PubMed1983

Phase I trial of retinol in cancer patients.

Vitamin A (all-trans-retinol) and its analogues are undergoing evaluation as antineoplastic and chemoprevention agents. Because its toxicity and activity are poorly defined, we have completed a phase I trial of retinol. Retinol was administered to 13 cancer patients in daily doses ranging from 100,000 units/m2 to 350,000 units/m2. Neuropsychiatric changes were the earliest dose-limiting symptomatic toxicities, noted in 3 of 5 patients receiving more than 240,000 U/m2 for 3-4 months. Two patients receiving more than 270,000 U/m2 developed hepatomegaly after 3 and 4 months. Liver biopsies were consistent with vitamin A toxicity. Three patients receiving 200,000 U/m2 developed an increase in serum triglycerides concentration. Mild skin and mucous membrane dryness occurred in most patients receiving more than 150,000 U/m2. A mixed response was seen in one patient with melanoma. Because of neuropsychiatric and hepatic toxicity a retinol dose of 200,000 U/m2/day is recommended for future phase II trials.

Adult↗
PubMed1983

Improvement of human melanoma colony formation in soft agar using boiled instead of autoclaved agar.

The effect of agar sterilized by either boiling or autoclaving on human melanoma colony formation in soft agar was compared using cells from 17 biopsies of metastatic malignant melanoma. The frequency of colony formation was significantly increased for cells grown in boiled agar in 8 samples (47%), unchanged in 8 samples (47%), and decreased in only one sample (6%). There were increases in both cluster and colony formation for the melanomas which had augmented colony formation when grown in boiled agar. There was also qualitative morphological improvement, including rounder, smoother cells and less extracellular debris surrounding the colonies. These data suggest that melanoma colony formation is enhanced when cells are grown in agar which has been sterilized by boiling rather than autoclaving.

Agar↗
PubMed1983

Inhibition of human malignant melanoma colony-forming cells in vitro by prostaglandin A1.

The direct effect of continuous exposure to prostaglandins on the cloning efficiency and proliferative capacity of human malignant melanoma colony-forming cells in soft agar was evaluated. Prostaglandin A1 (PGA1) and prostaglandin E1 (PGE1) effected a dose-dependent inhibition of colony formation and proliferative capacity. PGA1 at a concentration of 5 microgram/ml reduced colony formation of cells from human melanoma cell strains C8054, C8130, and C822 by at least 85%. PGA1 also inhibited colony formation of cells obtained directly from biopsies of melanoma tissues from eight patients by greater than 70% at a concentration of 5 microgram/ml. A steep dose-response curve was evident by the little effect of PGA1 on colony formation at a concentration of 0.5 microgram/ml. The mean 50% inhibitory doses for PGA1 and PGE1 were 1.25 and 4.25 microgram/ml, respectively. Prostaglandin A2 was much less effective than PGA1 in inhibiting melanoma colony formation. The related prostaglandins (prostaglandin B1, prostaglandin F1 alpha, and prostaglandin E2 alpha) had little or no effect on colony formation. Overall, these results suggested that the presence of a carbonyl group at position 9 of the cyclopentane ring may be required for inhibitory activity as prostaglandins of the A and E series inhibited human melanoma cell growth. PGA1 and PGE1 did not effect a rise in cyclic adenosine 3':5'-monophosphate levels in C8054 and C8130 cells. However, while alpha-melanocyte-stimulating hormone and prostaglandin F2 alpha did generate a rise in adenosine 3':5'-monophosphate levels in C8054 cells, these hormones had no effect on colony formation. These results are consistent with the notion that the PGA1 and PGE1 inhibition of melanoma colony-forming cells occurs via a noncyclic nucleotide mechanism.

Alprostadil↗
PubMed1983

A phase I trial of beta-all-trans-retinoic acid delivered via a collagen sponge and a cervical cap for mild or moderate intraepithelial cervical neoplasia.

A phase I trial was conducted of the vitamin A derivative beta-all-trans-retinoic acid (vitamin A acid; TRA), delivered via a collagen sponge and cervical cap for mild or moderate intraepithelial cervical neoplasia. On the basis of known skin and mucosal membrane toxicity, a concentration of 0.05% TRA in a cream-based vehicle was selected as the starting dose and was escalated later with the use of a modified Fibonacchi scale. The delivery device and the TRA were changed daily for 4 days, and side effects were assessed on days 1, 2, 3, 4, 8, and 30 by clinical and colposcopic examination. Vaginal, cervical, and systemic toxicity were evaluated in 35 patients. No dose-related systemic effects were found; mild cervical inflammation increased in many patients at higher doses. Unacceptably high vaginal toxicity was reached at a TRA concentration of 0.484%. A concentration of 0.372% TRA is recommended for use in phase II trials in mild and moderate cervical intraepithelial neoplasia.

Biopsy↗
PubMed1983

Dexamethasone, prostaglandin A, and retinoic acid modulation of murine and human melanoma cells grown in soft agar.

The cloning efficiencies of a murine melanoma cell line (S91 CCL 53.1) and a human melanoma cell strain (C8146c) were inhibited by dexamethasone (DEX), prostaglandin A1 (PGA1), and beta-all-trans-retinoic acid (RA) in a dose-dependent manner. Murine melanoma tumor colony-forming units (MTCFU) were inhibited more than 99% by DEX (1 X 10(-7) M) and RA (1 X 10(-7) M) with a concentration needed to produce a 50% reduction in colony formation for both hormones of 5 X 10(-9) M. Combinations of DEX and RA effected a synergistic inhibition on colony formation, which was reflected by a 11/2 log reduction in the hormone concentration needed to produce a greater than 99% inhibition of colony formation. When PGA1 was added to DEX and RA, a greater than additive reduction in colony formation was observed. Human MTCFU from cell strain C8146c were inhibited more than 85% at an RA concentration of 1 X 10(-7) M, but they were reduced only to 40% of control at a DEX concentration of 1 X 10(-6) M. DEX-RA produced an additive inhibition of colony formation. Addition of submaximal amounts of PGA1 to DEX-RA combinations or to either hormone alone resulted in synergistic reduction of human MTCFU. These results demonstrated that the proliferative potential of human and murine melanomas can be simultaneously regulated by DEX, PGA1, and RA.

Agar↗
PubMed1983

Scanning and transmission electron microscopic evaluation of human melanoma cells treated with adriamycin and actinomycin D.

A tumorigenic human cell line was derived from a patient with metastatic melanoma. Cells were treated with adriamycin or actinomycin D in order to assess morphological alterations induced by these anticancer agents. Exposure to 0.01 micrograms/ml adriamycin for one hour caused no observable morphological abnormalities as determined by SEM, while 0.1, 1.0 and 10.0 micrograms/ml concentrations of adriamycin produced surface alterations in the form of blebs, filopodia, microvilli and cell rounding. These alterations may be drug-affected changes of the cell surface or may reflect phases of the cell cycle directed by adriamycin action on the nucleus. Cell morphology appeared normal by SEM for 0.01, 0.1, 1.0 and 10.0 micrograms/ml concentrations of adriamycin when the cells were allowed to recover in drug-free media for 24 hours after initial drug incubation. Concentrations of 0.1, 1.0, and 10.0 micrograms/ml actinomycin D for 24 hours created morphological alterations characterized by cell rounding and long, dendritic-like processes. TEM of colonies treated in soft agar for 24 hours with either 1.0 micrograms/ml adriamycin or 1.0 micrograms/ml actinomycin D showed major morphological effects identified by increased cytoplasmic vacuolization and nuclear disintegration.

Cell Line↗
PubMed1983

Phase II trial of the dopaminergic inhibitor pimozide in previously treated melanoma patients.

Pimozide, a potent neuroleptic which inhibits the release of pituitary releasing factors and is an effective dopamine antagonist, was administered to 30 patients with previously treated metastatic melanoma. Six patients were inevaluable because of poor drug tolerance (two), disease progression within 1 week and death within 2 weeks (three), and death from other causes (one). Among the 24 evaluable patients, two had complete response, two had partial response, and two had disease stabilization. Responses were observed in soft tissue, lymph nodes, liver, and lung. Toxic effects consisted of extrapyramidal manifestations in nine patients and malaise in seven. Pimozide has activity in patients with previously treated metastatic melanoma (17% response rate in evaluable patients) and merits consideration of further study in combination regimens.

Adult↗
PubMed1982

Evaluation of topically applied trans-retinoic acid in the treatment of cervical intraepithelial lesions.

The prevention and/or suppression of preneoplastic foci in animals has been convincingly demonstrated with the use of a variety of compounds, including retinoids. We report here a phase I/II trial of beta-trans-retinoic acid delivered via a collagen sponge/diaphragm insert for neoplasia of the cervix. Eighteen patients with biopsy-proved grades 2 and 3 cervical intraepithelial neoplasia underwent four consecutive daily applications of trans-retinoic aicd to the cervix. Conization of the cervix was performed 4 weeks later. Significant vaginal toxicity in 10 of 18 (55%) patients was unrelated to the concentration or carrying media of the drug. A reduction in size of the intraepithelial lesion was noted by colposcopy in six of 18 (33%) patients with complete resolution of disease at conization in two patients. A new delivery system designed to avoid vaginal toxicity while defining the optimal concentration and dosing schedule for these patients is currently under investigation.

Administration, Topical↗