PubMed Health⌕ Search

Biomedical subjects

F L Meyskens

Publications and source records attributed to F L Meyskens.

At least 91 records · Page 5Linked to original sources
PubMed1990

Relation of cytogenetic abnormalities and clinical outcome in metastatic melanoma.

The value of chromosomal analysis is well established in human hematologic neoplasms. In contrast, the relation between chromosomal abnormalities and clinical outcome in solid tumors in humans has received little study. We undertook this study to determine whether chromosomal abnormalities could provide information on the survival of patients with malignant melanoma. Chromosome-banding analysis was performed on tumor-biopsy samples from 62 patients with metastatic melanoma, and recurring cytogenetic abnormalities were correlated with survival. Patients with structural abnormalities of chromosome 7 or 11 had significantly shorter survival than patients without these abnormalities. We conclude that cytogenetic analysis may provide useful prognostic information about patients with metastatic melanoma.

Chromosome Aberrations↗
PubMed1990

Phase II study of fenretinide (N-[4-hydroxyphenyl]retinamide) in advanced breast cancer and melanoma.

Retinoids, the natural and synthetic analogs of vitamin A, are growth-inhibiting and differentiation-inducing agents and show clinical promise as chemopreventive and antineoplastic agents. Fenretinide, a new synthetic retinoid, has antitumor activity in certain in vitro and in vivo model systems and was relatively nontoxic in phase I trials. Based on these data, we designed a phase II study of Fenretinide involving 31 patients with advanced breast cancer [15] and melanoma [16], two cancers shown to be responsive to this agent in preclinical models. Fenretinide was inactive in patients with advanced disease. Toxicity was mild, and reversible. Mucocutaneous side effects occurred in 16 (52%) patients. Nyctalopia developed in three patients one of whom developed decreased B-wave amplitude of the scotopic electroretinogram. The minimal toxicity and significant activity in preclinical studies make this an attractive agent for future breast cancer chemoprevention studies.

Adult↗
PubMed1990

Polyamine biosynthesis inhibitors combined with systemic hyperthermia in cancer therapy.

A Phase I clinical trial has been initiated at the University of Arizona Cancer Center which combines escalating oral doses of the polyamine biosynthesis inhibitor alpha-difluoromethylornithine (DFMO), with systemic hyperthermia (approximately 41.5 degrees C) in the treatment of metastatic melanoma. The rationale for the combination of hyperthermia and polyamine biosynthesis inhibitors in the treatment of human cancers includes studies which show that depletion of endogenous polyamines, as a result of treatment with DFMO, sensitizes both rodent and human tumor cells to the cytotoxic effects of hyperthermia. Heat shock induces the first enzyme in polyamine catabolism, spermidine/spermine N1-acetyltransferase (N1-SAT). The consequently acetylated forms of spermidine and spermine are then constitutively oxidized by the enzyme polyamine oxidase (PAO). Both CHO and human A549 lung cancer cells exhibit heat-inducible polyamine acetylation, display potent heat sensitization after polyamine depletion, and ultimately reveal prolonged expression of thermotolerance. Conversely, HeLa cells do not demonstrate heat-inducible polyamine catabolism, are not sensitized to heat with DFMO, and display more rapid kinetics of thermotolerance decay. These laboratory studies suggest that enhancement of the cytotoxic action of hyperthermia by DFMO occurs as a consequence of the inhibition of polyamine catabolism, a heat-inducible process that affords some form of protection to cells undergoing heat stress. Human melanoma cultures demonstrate heat-inducible polyamine catabolism and are sensitized to hyperthermic cytotoxicity by DFMO. To date, 24 systemic hyperthermia treatments have been delivered to nine patients with metastatic melanoma in conjunction with oral DFMO under this Phase I clinical trial.

Acetylation↗
PubMed1990

Radiosensitivity of murine and human melanoma cells: a comparative study with different models.

The in vitro radiosensitivity of one murine melanoma cell line (Cloudman S91 CCL 53.1) and three human melanoma cell strains (C8146C, C8161, and R83-4) were studied. Cells were irradiated by single dose X-rays and plated either in agar or on plastic. The survival curves were fitted by the single-hit multitarget, two-hit multitarget, and quadratic models. Multiple comparisons of the residual sum of squares suggested that the two-hit model was clearly inferior to the single-hit and quadratic models. No statistically significant difference was suggested for either the single-hit or quadratic models. Furthermore, on examination of the differences in correlations between the observed and predicted values, the residual plots (observed minus predicted over dose) failed to suggest a clear advantage of either the single-hit multitarget or the quadratic models. Either model could be recommended for analysis of in vitro radiation data.

Animals↗
PubMed1990

Response of oral leukoplakia to beta-carotene.

Leukoplakia is associated with increased risk of oral cancer and is considered a premalignant lesion. Retinoids, particularly 13-cis retinoic acid, can frequently reverse leukoplakia. However, these drugs have considerable toxicity and are not suitable for large-scale use in the prevention of oral cancer. Beta-carotene is a naturally occurring, nontoxic carotenoid with biologic properties that suggest that it might be efficacious against oral leukoplakia. In 1986, we began a randomized study of 13-cis retinoic acid (1 mg/kg/d) versus beta-carotene (30 mg/d) in leukoplakia. However, owing to the marked differences in toxicity between the two compounds outlined in the consent form, 11 of the initial 16 eligible patients refused to participate unless they were "guaranteed" beta-carotene. Therefore, the study design was changed to a phase II trial of beta-carotene in which the compound was given daily for 3 months. Responding patients were continued for another 3 months of treatment. All lesions were examined histologically at entry. Responses were monitored by bidimensional measurements and photography done at entry, then monthly while on treatment and at study completion. Twenty-four evaluable patients were treated, and 17 had major responses (two complete, 15 partial), a response rate of 71% (95% confidence limits, 53% to 89%). There was no significant toxicity requiring drug discontinuation or dose reduction. These results indicate that beta-carotene has substantial activity in oral premalignancy. Because of its lack of toxicity, it is an excellent candidate for a preventive agent for oral cancer.

Aged↗
PubMed1990

Development of a contingency recruitment plan for a phase III chemoprevention trial of cervical dysplasia.

Development of contingency recruitment plans in cancer chemoprevention research is as important as formulation of the initial plan. We found that requesting recruitment information from our initial CTCD subjects provided a framework for our contingency plan. The revised recruitment plan consisted of: 1) calling and sending letters to community gynecologists in private practice or affiliated with HMO's to explain the study and ask for referrals; 2) continued personal contact by the principal investigator with referring physicians; 3) sending thank you and follow-up letters to every physician who referred patients to the study; 4) soliciting Papanicolaou smear reports from HMO's if physicians of women with abnormal Papanicolaou smears gave permission to pathologists to release this information; 5) utilizing free media such as feature articles on the CTCD in local papers, public service announcements, and television "spots;" 6) continued use of brochures and posters printed for the initial recruitment effort; and 7) continued presentations to local professional physician and nurse groups about the study. Our contingency plan to date has provided us with 100% of our projected accrual. Thus, our recruitment methods have proved to be effective in accruing subjects for this cancer chemoprevention trial.

Double-Blind Method↗
PubMed1989

Surviving adult cancers. Part 2: Psychosocial implications.

PURPOSE: To address the psychosocial implications of surviving adult cancers by a comprehensive review of the literature. DATA IDENTIFICATION: An English-language literature search using MEDLINE (1970 to 1988). Index Medicus (1970 to 1988), and bibliographic reviews of textbooks and review articles. STUDY SELECTION: Of 103 originally identified articles, 58 that specifically addressed the stated purpose were selected. DATA EXTRACTION: Four authors reviewed and critiqued the literature extrapolating the major themes on this topic. RESULTS OF DATA SYNTHESIS: There is little information on the many psychosocial variables that affect an adult's long-term cancer survival trajectory. Collation of data identified the following significant psychosocial themes: fear of recurrence and death, relationships with the health care team, adjustment to physical compromise, alterations in customary social support, isolationism, psychosocial reorientation, and employment and insurance problems. CONCLUSIONS: The continuation of a rehabilitation effort begun around the initial diagnosis of cancer would be instrumental in providing post-therapy evaluation and guidance needed by adult long-term survivors of cancer. Education, research, and support interventions need to be mobilized for this population of adults with a history of cancer.

Adaptation, Psychological↗
PubMed1989

Surviving adult cancers. Part 1: Physiologic effects.

PURPOSE: To provide an overview of the physiologic long-term and late effects of adult cancers and cancer treatments by a review of the medical and nursing literature. DATA IDENTIFICATION: Primarily from an English-language literature search using MEDLINE (1980 to 1988) and Index Medicus (1980 to 1988). STUDY SELECTION: After a consensus review by four observers, 285 articles were selected that addressed the stated purpose. DATA EXTRACTION: Four observers assessed the literature using predetermined criteria for eliciting information about long-term and late effects. RESULTS AND DATA SYNTHESIS: Much has been written about the acute phases of cancer and cancer treatments. In comparison, relatively few data are available that define physiologic long-term: and late effects of cancer treatments in adult survivors. Review of the existing data showed that these sequelae may affect virtually any body system months or years after treatment ends. In addition, few prospective studies dealing with physiologic survivorship issues have been done. CONCLUSIONS: Health care providers need to be aware of long-term or late complications that may affect the increasing number of adult cancer survivors. Attention to treatment regimens in the acute cancer phase and careful follow-up once the disease is eradicated may help to prevent or manage these complications. More prospective research should be done in this area.

Adult↗
PubMed1989

Quality of life end points in cancer clinical trials: review and recommendations.

In this presentation, issues that influenced the development of policies for inclusion of quality of life end points in certain Southwest Oncology Group clinical trials are reviewed. The key policies recommended by us and adopted by the Cancer Control Research Committee of the Southwest Oncology Group are as follows: (a) Begin assessment of quality of life in specific types of phase III protocols. (b) Always measure physical functioning, emotional functioning, symptoms (general and protocol specific), and global quality of life separately. (c) Include measures of social functioning and additional protocol-specific measures if resources permit. (d) Use patient-based questionnaires with psychometric properties that have been documented in published studies. In this review, we also recommend specific questionnaires. Our recommendations may prove useful for other cancer clinical trials groups and for multi-institution trials of treatment for chronic diseases.

Clinical Trials as Topic↗
PubMed1989

Cutaneous malignant melanoma. II. The natural history and prognostic factors influencing the development of stage II disease.

The survival history of 259 patients with Stage I cutaneous malignant melanoma who were at risk for developing regional nodal metastases (Stage II) were studied. Eighty-seven of 377 Stage I patients (23%) developed regional nodal metastases (Stage IIB) with 40% 5-year survival. Fifty patients had regional nodal metastases at presentation, with or without a known primary (Stages IIA or IIC, respectively), with a 42% 5-year survival. A step-down multivariate analysis using the Cox regression model revealed four risk factors as being highly significant for predicting a more favorable survival outcome: (1) thinner Breslow thickness (P = 0.0001), (2) pathologic Stage I disease (P = 0.004), (3) no clinical ulceration (P = 0.0004), and (4) being a woman younger than 50 years of age (P = 0.029). These results are discussed in reference to other series.

Age Factors↗
PubMed1989

Pharmacokinetics of N-4-hydroxyphenyl-retinamide and the effect of its oral administration on plasma retinol concentrations in cancer patients.

Concurrent with a phase-II trial of 4HPR in patients with various cancers, we studied the plasma pharmacokinetics of both 4HPR and its major metabolite 4MPR as well as the effect of 4HPR administration on plasma retinol concentrations using a simple, specific and sensitive HPLC procedure. Initial estimates of plasma pharmacokinetic parameters after oral administration of 4HPR (300 mg/day) [corrected] in 3 cancer patients were the following: 4HPR, t beta 1/2 = 13.7 hr, AUC = 3.49 micrograms.hr/ml, CL = 56.57 L/hr/m2; 4MPR, t beta 1/2 = 23.0 hr, AUC = 1.15 micrograms.hr/ml, CL = 239.29 L/hr/m2. We also found that oral administration of 4HPR resulted in a rapid, profound and significant reduction in plasma retinol concentrations. The mean plasma retinol concentrations for 9 patients decreased 60% from baseline to below 200 ng/ml within 1-2 weeks of 4HPR dosing initiation. In addition, there was a concurrent, significant reduction in plasma retinol-binding protein levels in these patients. The mechanism whereby 4HPR reduces plasma retinol levels in vivo has not been determined. The addition of 4HPR to pooled human plasma at 37 degrees C in vitro did not reduce endogenous retinol levels, suggesting no direct chemical interaction between these 2 retinoids.

Administration, Oral↗
PubMed1989

Identification of a recurring translocation site involving chromosome 6 in human malignant melanoma.

The recognition of recurring sites of chromosome change in human cancers has pinpointed the location in the genome of several important growth-regulatory sequences (e.g., cellular oncogenes). This report details the finding of a recurring translocation site involving the long arm of chromosome 6 (6q) in malignant melanoma. We have observed a translocation (t) between chromosomes 1 and 6 in five different cases of malignant metastatic melanoma. All five melanomas evidencing t(1;6) involved band regions 6q11-13, while two different regions of chromosome 1 (p22, q12-q21) were shown to be translocated to 6q. In reviewing previously published cases of melanoma, an additional two cases of t(1;6) and 13 cases of other translocations to 6q11-13 have been identified. Chromosome 6q contains several biologically important gene sequences including the proto-oncogenes ros, myb, and mas1. However, based on current mapping studies, the breakpoint of this translocation (6q11-13) is not within the region encoding these sequences. By analogy to other systems, molecular analysis of the translocation breakpoints may identify a gene(s) which plays a role in melanoma tumorigenesis.

Chromosome Banding↗
PubMed1989

Immunohistochemical and ultrastructural study of human melanoma colonies grown in soft agar.

An immunohistochemical and ultrastructural study of human melanoma colonies grown in soft agar for up to 50 days was performed. Three morphological variants of developing tumor colonies are reported: 1) large light colonies, 2) small dark colonies, and 3) smooth-edged colonies. The large light colony variant is the most frequently observed in the soft agar assay (approximately 70%), followed by the dark colony variant (approximately 27%), and the smooth-edged colony variant (approximately 3%). Major morphological characteristics are associated with each variant, as shown with light microscopy (LM) and transmission electron microscopy (TEM). Both LM and TEM analyses demonstrated that the large light colony variant was hypomelanotic and contained a microfibrillar extracellular matrix (ECM). The small dark colony variant was found to be hypermelanotic and contained a less demonstrable ECM. The smooth-edged variant has an encapsulated periphery, no demonstrable ECM, and tightly packed cells with desmosome-like junctions. In order to characterize further the ECM in the most commonly observed variant, the large light colony, specific antibodies to fibronectin (FN) and collagen types IV and V (COLs IV and V) were applied and observed with immunofluorescence microscopy and immunoperoxidase. In paraffin sections of melanoma colonies, FN was observed associated with both the cell surface and the ECM. However, no specific staining was seen for COLs IV and V. In addition, ruthenium red was used to preserve and selectively bind to glycosaminoglycans (GAGs) and proteoglycans (PGs). TEM studies reveal GAG-like granules stained with ruthenium red in the fibrillar ECM and a dotted, punctate staining of the cell surface. Understanding the biological and architectural composition of developing melanoma tumor colonies in soft agar could contribute to the development of more efficient chemotherapeutic strategies.

Agar↗
PubMed1989

The role of serum and tissue pharmacology studies in the design and interpretation of chemoprevention trials.

The design and interpretation of chemoprevention trials are challenging tasks. Innovative methodological approaches to these investigations are in initial stages of development. Important pharmacologic issues should be addressed as early as possible in these trials to facilitate the optimal design of large, Phase III, randomized trials. These include determining the optimal dose of the compound and the toxicity profile. Other key areas involve the use of serum concentrations to monitor subject compliance, the evaluation of concentration of the chemopreventive agent in the target tissue, adequate assessment of the drug delivery systems, and the evaluation of the relationship between the dose administered and the serum or tissue concentrations achieved. Whenever possible the investigation of the relationship between serum or tissue concentrations of a chemopreventive agent vs its biologic activity should be determined. Specific examples involving the retinoids and carotenoids are presented.

Carotenoids↗
PubMed1989

Retinoids as potential chemopreventive agents in squamous cell carcinoma of the head and neck.

Although newer combined modality approaches, including neoadjuvant cytotoxic chemotherapy, for patients with squamous cell carcinoma (SCCA) of the head and neck have produced high initial complete response rates, they have not improved overall survival for patients with advanced disease. Vitamin A plays an essential role in the normal differentiation of epithelial tissues. Retinoids, analogs of vitamin A, are active in certain premalignant and malignant disorders including SCCA. Six studies, including one recently reported placebo-controlled randomized trial, have demonstrated the efficacy of retinoids in oral leukoplakia. Two studies (totalling 48 patients) have shown significant retinoid activity (67% overall complete response rate) in patients with aggressive, recurrent laryngeal papillomatosis. Two trials (including a randomized phase II trial) of isotretinoin in advanced, refractory SCCA of the head and neck have produced an objective response rate of 16%, which is comparable to that reported in single-agent studies with cytotoxic drugs. There is a need for further study of retinoids in head and neck cancer. The high initial response rates with current therapy and the high subsequent risks of local recurrence and of developing second primary tumors in head and neck cancer patients offer an excellent opportunity to investigate the use of retinoids as adjuvant therapy for this malignancy.

Carcinoma, Squamous Cell↗
PubMed1989

Cloning efficiency of human melanoma cells is modulated after invasion through a reconstituted basement membrane.

Three human malignant melanoma cell strains (C8146A, C8146C, and C83-2CY), three established human melanoma cell lines (A375P, A375M, and C8161), and one selected human melanoma subline (A375P-5) were studied to determine if invasion through a reconstituted basement membrane-coated filter (RBMF), which selects the most aggressively invasive cells, would also modulate the cloning efficiency of these cells in soft agar. With the use of the Membrane Invasion Culture System (MICS), all cell strains tested showed a significant increase in cloning efficiency (1.05-9.3-fold) following transit through the RBMF when compared to unmanipulated populations. The established cell lines (A375P, A375M, and C8161) and the A375P-5 subline showed either a decrease or unaltered status in cloning efficiency after invasion. However, all cells demonstrated a consistent decrease in clonogenicity following transit through an uncoated filter compared with RBMFs, thus suggesting the influence of the extracellular matrix on tumor cell clonogenic properties. In general, the established cell lines were more clonogenic before invasion of the RBMF compared with the cell strains, and no correlation was found between clonogenic potential and invasive or metastatic capability. These data may provide important insight into the underlying mechanisms of tumor cell invasion and the subsequent formation and dissemination of metastases in vivo.

Animals↗