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Biomedical subjects

F L Meyskens

Publications and source records attributed to F L Meyskens.

At least 73 records · Page 4Linked to original sources
PubMed1992

Coexpression of vimentin and keratins by human melanoma tumor cells: correlation with invasive and metastatic potential.

BACKGROUND: Several protein markers, including vimentin, have been used to diagnose human melanoma. Because melanoma often has metastasized by the time of diagnosis, early markers prognostic for metastatic potential need to be identified. Commonly, vimentin is found in mesenchymal cells, and keratins are present in epithelial cells, but recent studies report coexpression of vimentin and keratin(s) in epithelial and nonepithelial neoplasms, including some melanomas. PURPOSE: Our purpose was to determine whether coexpression of vimentin and keratin(s) is correlated with tumor cell invasion and metastatic behavior. METHODS: We evaluated nine human melanoma cell lines expressing vimentin and other markers of aggressive tumor behavior (HMB-45, S-100, HLA-ABC class I and HLA-DR class II histocompatibility antigens, and K8 and K18 keratins). Levels of K8 and K18 keratins were determined in the highly metastatic C8161 cell line, the poorly metastatic A375P line, and the moderately metastatic A375M line. To determine whether the presence of keratin affects migratory ability, we altered the conformational structure of keratin filaments in C8161 cells by transfection with a mutant K18 complementary DNA. We also determined messenger RNA levels of human type IV collagenase, an enzyme marker for invasion and metastasis. RESULTS: In A375P cells, two-dimensional electrophoresis with Coomassie-stained gels, immunoblotting, and immunofluorescence staining showed no detectable levels of K8 or K18. A375M cells showed low levels of K8 and K18 by Western and Northern blotting, with a distinctive fluorescent subpopulation of cells. In comparison, K8 and K18 levels in C8161 cells were high in all cells. Type IV collagenase messenger RNA levels were lowest in A375P cells and highest in C8161 cells, correlating with invasive ability in vitro and metastatic potential in athymic nude mice. The transfectant clones C1070-10 and C1070-14 derived from the C8161 parent line showed dramatic morphological changes, disrupted keratin filaments, and decreased invasive and metastatic potential directly correlated with a reduction in migratory activity. CONCLUSION: These findings show a correlation between the coexpression of vimentin with K8 and K18 keratins and the invasive and metastatic behavior of three representative human melanoma cell lines.

Animals↗
PubMed1992

A quantitatively scored cancer-risk assessment tool: its development and use.

Achievement of NIH and ACS goals for reduction in cancer mortality will require increased efforts directed at risk reduction and early detection in the general population. Primary care providers will play a major role. This paper describes the development and use of a quantitative cancer-risk appraisal tool designed to promote cancer prevention and screening and provide a framework for advancing education on these critical issues at all levels of medical training, to assist physicians in risk identification and patient counseling. The risk assessment questionnaire is close-ended and easily completed by the patient within 10 to 15 minutes. The IBM-compatible format permits easy quantitation by laser scanning and computer analysis. This program quantitates risks arising from interacting independent factors and estimates the effects of primary prevention interventions. Program output includes age- and sex-specific ACS screening guidelines and discussion of intensified screening measures in high-risk subjects.

Breast Neoplasms↗
PubMed1992

Phase I study of low-dose cyclophosphamide and recombinant interleukin-2 for the treatment of advanced cancer.

We conducted a phase I study of low-dose cyclophosphamide and recombinant interleukin-2 (rIL-2) in 66 patients with advanced cancer resistant to standard therapy. All patients were evaluable for toxicity and 46 patients were evaluable for antitumor response. Patients evaluable for antitumor response included 23 with malignant melanoma, 10 with renal cell carcinoma, 4 with colon cancer, and 9 with various other solid tumors. All patients received i.v. cyclophosphamide (350 mg/m2) on day 1 followed by rIL-2 via 15 min i.v. infusion on days 4-8 and 11-15. The doses of rIL-2 ranged from 6.0 to 36.0 x 10(6) IU/m2. Each treatment cycle consisted of 21 days and a total of 113 cycles was administered. The number of treatment cycles administered per patient ranged from 1 to 8. The dose-limiting toxicities associated with rIL-2 included altered mental status, arthralgias, diarrhea, fatigue, fever, hypotension, nausea/vomiting, and peripheral edema. Twelve patients (18%) were removed from the study secondary to toxicity. Among the evaluable patients, 2 (4%) (malignant melanoma, renal cell carcinoma) developed a partial remission, 13 (29%) maintained stable disease, and 31 (67%) developed progressive disease. We conclude that the combination of low-dose cyclophosphamide and rIL-2 is tolerable in most patients but our data do not suggest an improved response rate for the combination vs. rIL-2 alone.

Adolescent↗
PubMed1992

Comparison of calmodulin gene expression in human neonatal melanocytes and metastatic melanoma cell lines.

The qualitative and quantitative expression of three calmodulin genes (CAM I, CAM II and CAM III) was characterized in human neonatal melanocytes and metastatic melanoma cell lines in the absence and presence of serum, other growth modulators, and/or 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Results indicated that the qualitative expression in melanocytes was the same as that of melanomas, that is, CAM I gene expressed two transcripts, 4.4 kb and 2.1 kb, whereas CAM II and CAM III expressed one transcript each, 1.95 kb and 2.37 kb, respectively. Differential quantitative expression was seen particularly with CAM I. The average levels of both CAM I transcripts in melanomas were less than one-half those of melanocytes. Serum and other growth modulators (including Ca++, isobutyl methyl xanthine, bovine pituitary extract, and insulin) enhanced CAM I and CAM II gene expression in melanocytes; in contrast, the net effect of serum in melanomas was to decrease expression of CAM I and CAM III. This effect was most prominent in melanoma C81-46C. TPA markedly inhibited expression of all three CaM genes in melanocytes; however, in melanomas the net effect of TPA was to increase their expression. CAM I in melanoma C81-46C was the most sensitive to TPA stimulation.

Culture Media, Serum-Free↗
PubMed1992

Biomarker intermediate endpoints and cancer prevention.

Detection of cancer is the definitive endpoint in the conduct of chemoprevention trials. There are, however, several reasons why cancer as the endpoint may not be feasible or ethical: 1) the usage of patients with easily followable preneoplasias may preclude the development of cancer, and 2) the time to a cancer event may be long or the incidence uncommon, even in individuals at high risk. Two major types of biomarker intermediate endpoints should be considered: 1) those that identify individuals at high risk and 2) those that serve as a surrogate for cancer. Various epidemiologic features, including family history, have been used to estimate relative risk. This approach, however, only slightly decreases the size of populations needed for chemoprevention trials and only little addresses the question of individual risk. Advances in understanding the genetic basis for cancer will lead to the development of probes that will help assess risk for many cancers. Innumerable biomarker intermediate endpoints can be identified as associated with cancer formation, including genetic, epigenetic, and histologic features. The challenge is not in identifying potential biomarker intermediate endpoints but in showing that they are relevant. Carcinogenesis has been shown to be carcinogen, inhibitor, dose, tissue, and species specific; it is likely that relevant biomarker intermediate endpoints will need to be identified, studied, and verified in human models. The upper aerodigestive system should be a rich source for biomarker intermediate endpoint studies, as tissue is readily available, the carcinogenic process can be monitored, and there are currently available reasonable compounds to use in biomarker intermediate endpoint modulation and chemoprevention trials.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗
PubMed1992

Strategies for prevention of cancer in humans.

A substantial amount of epidemiologic and laboratory data indicates that the majority of human cancers should be preventable. In this article, the biologic basis of cancer prevention is presented and the major factors contributing to the initiation, promotion, and progression of cancer in humans detailed. These include tobacco, ultraviolet and ionizing (radon) radiation, certain chemicals (asbestos, aniline dyes), and viruses--both sexually transmitted and endemic. Dietary factors both enhance and inhibit carcinogenesis in humans. In this article, the roles of fat, fiber, and beta-carotene are reviewed with respect to the genesis of breast, colon, prostate, lung, and oral cancers. A large number of prevention trials involving most common malignancies are being conducted in the United States and abroad. This article considers the major strategies and methodology of prevention trials and outlines the major trials now in progress.

Diet↗
PubMed1991

A community-based feasibility study using wheat bran fiber supplementation to lower colon cancer risk.

METHODS: In this feasibility study, free-living older adults (n = 180; means = 67.5 years old) were randomly assigned to one of three levels of a 3-month standardized compliance enhancement program. RESULTS: Regarding subject compliance with the 18 g/day wheat bran fiber supplement, the high compliance enhancement group had a superior regimen compliance rate (88%) versus the medium and low groups, (66 and 29%, respectively) (P = 0.01), with similar attrition rates. CONCLUSION: No significant gastrointestinal side effects and changes in body weight were reported. For similar efficacy, the comprehensive compliance enhancement group had the greatest cost effectiveness.

Adult↗
PubMed1991

The differential expression of protein kinase C genes in normal human neonatal melanocytes and metastatic melanomas.

Expression of protein kinase C (PKC) genes (alpha, beta, gamma and epsilon) was measured in cultured normal human neonatal melanocytes and metastatic melanoma cell strains. Three of the PKC isotypes (alpha, beta and epsilon) were constitutively expressed in neonatal melanocytes. Protein kinase C beta RNA transcripts were induced in neonatal melanocytes cultivated in medium with serum and 12-O-tetradecanoylphorbol-13-acetate (TPA). In contrast, PKC alpha and epsilon RNA transcripts were detected in melanocytes cultivated in medium without serum and TPA, but were repressed in melanocytes cultivated in medium with serum and TPA. Only PKC alpha and epsilon RNA transcripts were detected in the melanoma cell strains and the PKC RNA transcript expression levels varied among the five metastatic melanomas. In four metastatic melanoma cell strains, PKC alpha and epsilon RNA transcript expression levels were repressed by serum, but in one melanoma cell strain, PKC alpha and epsilon RNA transcript expression levels were induced by serum. Protein kinase C gamma RNA transcripts were not detected in either the melanocytes or melanoma cell strains. These data suggest an alteration of PKC isotype gene expression in the progression of primary melanocytes to metastatic melanoma. The absence of the PKC beta RNA transcripts and altered expression of PKC alpha and epsilon isotypes in particular may be a feature in the transformation of human primary melanocytes.

Gene Expression↗
PubMed1991

Dose-related alpha-difluoromethylornithine ototoxicity.

We assessed the ototoxicity associated with oral alpha-difluoromethylornithine (DFMO) administration in 58 patients with metastatic malignant melanoma. One hundred seventy-nine sequential audiograms obtained from patients treated with DFMO alone (16 patients) or in combination with alpha 2b-interferon (42 patients) were evaluated. DFMO doses ranged from 2 to 12 g/m2/d and were given over periods of 2 to 50 weeks. Total doses ranging from 60 g/m2 to 1390 g/m2 were correlated with clinical effects and pure tone audiometric changes. By regression analysis cumulative DFMO dose showed a consistent and statistically significant positive relationship to hearing loss at multiple frequencies (500, 1000, 2000, 4000, and 8000 Hz). Patients with normal (threshold less than 30 db) baseline audiograms demonstrated more hearing loss than those with abnormal (threshold greater than or equal to 30 db) baseline audiograms at the higher frequency levels. Of the patients with normal prestudy hearing thresholds 10% or less developed a demonstrable hearing deficit at cumulative DFMO doses below 150 g/m2. Conversely, up to 75% of the patients who received more than 250 g/m2 developed a clinically demonstrable hearing loss. Other factors which adversely affected hearing included age, male gender, and the concomitant use of alpha 2b-interferon. In summary, the risk of clinically significant hearing loss in patients treated with DFMO was primarily related to dose and the presence of a pre-existing hearing deficit.

Adolescent↗
PubMed1991

Expression of c-jun, jun-B, and c-fos proto-oncogenes in human primary melanocytes and metastatic melanomas.

Analysis of the regulation of c-jun, jun-B, and c-fos RNA transcript expression was performed in human primary melanocytes and metastatic melanoma cell strains. The medium requirements for human melanocyte in vitro growth are phorbol esters, agents that elevate intracellular cAMP levels, hormones, and growth factors. Cellular jun, jun-B, and c-fos gene expression are known to be affected by growth promoting agents. In primary melanocytes, the expression of c-jun, jun-B, and c-fos RNA transcripts was dependent on the growth-promoting agents present in the medium. Uniformly high c-jun, jun-B, and c-fos RNA transcript levels were observed in melanocytes cultivated in complete medium. Higher levels of c-jun RNA transcripts and low levels of c-fos RNA transcripts were observed in melanocytes cultivated in plain medium. In contrast, a range of c-jun, jun-B, and c-fos RNA transcript levels was detected in metastatic melanoma cell strains cultivated in medium with or without serum. In general, an increase in jun-B and c-fos RNA transcript expression and a decrease in c-jun RNA transcript expression was observed in metastatic melanomas compared to neonatal melanocytes. These data suggest a potential role for c-jun, jun-B, and c-fos genes in the transformation of melanocytes to malignant melanoma.

Blotting, Northern↗
PubMed1991

An exploratory study of attitudes, beliefs and practices related to the interim dietary guidelines for reducing cancer in the elderly.

In this pilot study, a self-administered questionnaire was used to assess the health attitudes, beliefs and practices related to each of the Interim Dietary Guidelines for Reducing Cancer Risk (I.D.G.R.C.R.) in a convenience sample of elderly Caucasian subjects (N = 30) over 60 years old. The questionnaire items included personal efficacy, perceived motivators and barriers, and current practices related to the compliance of each of the dietary guidelines. The distributions of responses to the questionnaire items show variations in the subjects' attitudes, beliefs and current dietary practices related to each of the dietary guidelines. Most subjects reported current practice of most guidelines except the guideline of a low fat diet. Most of the time, the subjects perceived one or more motivations to comply with the guidelines of eating fruits and vegetables high in vitamin C, and eating dark green or deep yellow vegetables. Taste and health benefits were shown to be important factors among motivators influencing the compliance to the dietary guidelines. The findings of this exploratory study have direct implications for planning nutrition intervention programs for cancer risk reduction in the elderly.

Aged↗
PubMed1991

Chemoprevention of cancer.

Chemoprevention is a relatively new area of clinical cancer research. In this article we have presented a general overview of the concepts as well as the status of ongoing clinical trials using the most promising agents in selected populations. The reader is referred to recent excellent reviews presenting more detailed discussions of the various topics discussed, such as the selection process for new agents, in vitro and animal model screening procedures, epidemiologic studies, and other agents now being screened and tested for potential clinical study. Increased understanding of the biology of carcinogenesis will undoubtedly lead to new ideas and approaches. Pathways for conversion of proto-oncogenes to tumor-supporting oncogenes, the mechanisms of action of tumor suppressor genes, and the involvement of abnormal growth factor responses in producing "field cancerization" are some examples of future targets for chemopreventive intervention. Long-term goals of this effort will include application of the results of early promising prevention studies, such as those in oral premalignant lesions, to the design of carefully controlled trials to demonstrate actual inhibition of cancer occurrence. In the laboratory, basic studies need to be conducted to increase our understanding of the molecular events underlying carcinogenesis, in order to identify additional targets for new agents to enhance the clinical efforts. Some of the most exciting developments in the control of cancer over the next decade will very likely result from this chemopreventive approach, with application not only to prevention of the first or primary malignancy, especially in high risk populations, but also to clinical situations traditionally considered to be in the domain of chemotherapeutic strategies, such as adjuvant treatment after definitive therapy of a primary cancer.

Carotenoids↗