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Biomedical subjects

M Reiss

Publications and source records attributed to M Reiss.

At least 199 records · Page 11Linked to original sources
PubMed1989

Prognostic factors in primary breast cancer.

Approximately 25% of women with node-negative breast cancer treated with surgery alone eventually experience a relapse of their disease. Survival in this group of patients correlates with the level of estrogen-receptors and inversely with the size of the primary tumor. Moreover, the rate of tumor growth, as determined either clinically or by using in vitro techniques, such as thymidine-labeling and flow cytometric measurements of DNA content, can be used to identify patients with node-negative breast cancer who have a high probability of recurrence. Based on such an analysis, the subset of patients with slow growing cancers may be spared adjuvant cytotoxic therapy. On the other hand, a rapid tumor growth rate predicts for a higher than usual chance of relapse among patients with node-positive breast cancer. Therefore, this subset of women may benefit from more prolonged and/or intensive adjuvant chemotherapy than is currently recommended. Finally, ongoing studies of structural or functional disturbances of proto-oncogenes in breast cancer can be expected to provide practitioners with additional prognostic indicators that will lead to further improvements in the management of this group of diseases in the near future.

Breast Neoplasms↗
PubMed1988

Reinitiation of DNA synthesis in quiescent mouse keratinocytes; regulation by polypeptide hormones, cholera toxin, dexamethasone, and retinoic acid.

Cloned mouse keratinocytes (MK-1 cells) display density-dependent growth arrest when reaching confluency in a serum-free medium with a calcium concentration less than 0.1 mM, supplemented only with insulin and transferrin. In this quiescent state, greater than 95% of the cell population is in the Go/1 phase of the cell cycle. Treatment of quiescent MK-1 cells with 1 to 10 ng/ml epidermal growth factor (EGF) resulted in a sharp burst of DNA synthetic activity. Both insulin and cholera toxin potentiated the mitogenic effect of EGF, but neither agent was necessary or sufficient to induce thymidine incorporation into DNA. Dexamethasone abolished the effect of insulin, but not the mitogenic effect of EGF alone. In contrast, retinoic acid (RA) did not possess any mitogenic effect for quiescent MK-1 cells, nor did it modulate the actions of EGF or dexamethasone. A number of commercially available crude extracts of bovine brain and pituitary were also capable of initiating DNA synthesis in resting MK-1 cells. Finally, transforming growth factor type beta (TGF beta) proved to be a potent inhibitor of the mitogen-induced DNA synthesis in MK-1 cells (IC50:10 pM). This defined culture system is eminently suited to study the regulation of DNA synthesis of epidermal cells. In addition, it can be used as a sensitive bioassay for the detection of epidermal mitogens, as well as inhibitors of DNA synthesis such as TGF beta.

Animals↗
PubMed1988

Down-regulation of glucocorticoid binding sites by retinoic acid in squamous carcinoma cells resistant to the induction of keratinization by hydrocortisone.

Physiologic concentrations of retinoic acid strongly inhibit the in vitro maturation of human squamous carcinoma cells in serum-free medium. Differentiation, as measured by the capacity to synthesize cornified cell envelopes, could be induced by hydrocortisone in retinoic acid-treated SqCC/Y1 and CE-81T cells. However, two other cell lines (C4-1 and A431) were less competent to spontaneously form cornified cell envelopes and resistant to the induction of envelope competence by hydrocortisone in the presence of retinoic acid. To investigate the mechanism underlying the resistance of these two lines to hydrocortisone, the characteristics of glucocorticoid receptors were analyzed. Whole cell dexamethasone binding sites ranged from 1300 to 9000 sites per cell for the four cell lines. The binding affinity for dexamethasone was similar in all four squamous carcinoma cell lines (1.32 to 4.75 nM). During retinoic acid-treatment, the binding of dexamethasone by intact SqCC/Y1 and CE-81T cells increased 1.5- to 3.0-fold over 48 h. In contrast, the number of dexamethasone binding sites were decreased by 80% in retinoic acid-treated A431 and C4-1 cells. In each case, the regulation of dexamethasone binding was dependent on the concentration of retinoic acid, with maximal effects being observed at 10(-6) M. Thus, the manner in which retinoic acid regulates the availability of dexamethasone binding sites might explain, in part, the effects of glucocorticoids on differentiation of retinoic acid-treated squamous carcinoma cell lines.

Carcinoma, Squamous Cell↗
PubMed1987

Regulation of growth and differentiation of human keratinocytes by type beta transforming growth factor and epidermal growth factor.

The role of type beta transforming growth factor (TGF beta) and epidermal growth factor (EGF) as regulators of the growth and differentiation of cultured human neonatal epidermal cells and squamous carcinoma cells was investigated in postconfluent cultures. Neither cell proliferation nor DNA synthesis was affected by treatment with TGF beta alone; however, EGF significantly stimulated cell growth, and this process was specifically antagonized by TGF beta. In addition, TGF beta inhibited the maturation of human foreskin-derived epidermal cells, as measured by their competence to synthesize involucrin and to form cornified cell envelopes, in a dose-dependent manner. Although treatment with EGF did not affect the maturation of human foreskin-derived epidermal cells, the combination of a low concentration of TGF beta with EGF resulted in significant enhancement of the maturation of these normal keratinocytes. Growth of three of four squamous carcinomas in the presence of EGF was not inhibited by TGF beta. In addition, all four carcinomas were either totally or partially resistant to the induction of maturation by the combination of TGF beta and EGF. This resistance of squamous carcinomas to TGF beta was paralleled by an increased sensitivity to the antikeratinizing effects of EGF. Thus, TGF beta inhibited the mitogenic stimulation of keratinocytes by EGF and induces cell maturation.

Cell Differentiation↗
PubMed1986

DNA-mediated gene transfer into epidermal cells using electroporation.

A reliable method for the introduction of foreign DNA into epidermal cells is described. Electroporation of murine BALB/c MK-1 epidermal cells with pSV2-CAT resulted in the transient expression of chloramphenicol-acetyltransferase (0.03 to 0.05 nmoles acetylchloramphenicol per mg protein per min) in the transfected cells. Transfection of MK-1 cells with pSV2-neo led to the appearance of approximately eight G418 resistant clones per 10(-6) cells per microgram of plasmid DNA. Distinct patterns of integration of SV2-neo were detected in three different resistant clones.

Acetyltransferases↗
PubMed1986

Mechanisms involved in the induction of malignant cell differentiation.

Cancer appears to be a disease of altered maturation, with changes in genetic expression leading to a situation in which the physiological regulation of cellular proliferation and maturation are altered. Environmental factors as well as defined chemical agents have been demonstrated to have the capacity to convert neoplastic cells to end-stage forms with a finite life span through a process characteristic of cellular maturation. The correction of genetic defects by these inducers of differentiation does not appear to be required; the critical feature is that the differentiated cells assume a state in which they no longer possess the capability for continued cellular replication. The extrapolation of these advances, accomplished in experimental systems, to clinical practice should yield significant decreases in the neoplastic cell burden without the degree of morbidity produced by aggressive therapy with cytodestructive agents, especially when employed in multidrug combinations. The ultimate introduction of differentiation as a therapeutic approach to cancer treatment if attained, however, will require a variety of principles to be established, so that optimum efficacy may be obtained from each agent, the fabrication of new agents with major changes in the ratio of the concentrations required to produce cytotoxicity relative to those necessary to initiate maturation is attained, and the elucidation of non-antagonistic combinations of differentiation inducing agents with or without cytotoxic drugs is achieved to combat the problem of tumor cell heterogeneity.

Animals↗
PubMed1986

Modulation of cell shedding and glycosaminoglycan synthesis of human malignant keratinocytes by all-trans-retinoic acid and hydrocortisone in vitro.

Physiologic concentrations (5 X 10(-8) M) of all-trans-retinoic acid (RA) caused a 2- to 3-fold increase in the rate of cell desquamation of a malignant keratinocyte line (SqCC/Y1) grown in serum-free medium. Measurement of the incorporation of [35S]sulfate and [3H]glucosamine into cetylpyridinium chloride-precipitable glycosaminoglycans (GAGS) demonstrated that RA treatment did not alter total GAG production. In addition, compartmental distribution was not affected by RA, with 50-70% of GAGS being recovered from the medium, 25% from the pericellular matrix, and the remainder from the cells. Relatively small amounts of GAGS were associated with shed cells in RA-treated cultures, presumably reflecting a relatively short association of these cells with the monolayer before desquamation. Chondroitin sulfate (Ch-S), heparin/heparan sulfate (Hep-S), and hyaluronic acid (HA) were the GAG species identified in SqCC/Y1 cultures by gel-exclusion chromatography. RA reduced the relative amount of HA in the trypsin-sensitive pericellular compartment by 50%. Since the proportions of Ch-S and Hep-S were not affected by RA, the findings suggest that the altered ratio of HA to sulfated GAGS in this fraction may contribute to the increased cell desquamation. Hydrocortisone (10(-6) M) reversed the effect of RA on cell shedding, and increased the proportion of pericellular HA relative to that found in cultures exposed to RA alone. These findings support the concept that the relative proportion of HA to sulfated GAGS may be important in the intercellular cohesion of keratinocytes. In addition, the relative decrease in HA and the predominance of Ch-S over Hep-S in SqCC/Y1 cultures differed from results reported with normal keratinocytes, indicating that this property may be associated with the malignant phenotype.

Carcinoma, Squamous Cell↗
PubMed1985

Comparison of intramuscular and intravenous recombinant alpha-2 interferon in melanoma and other cancers.

In two phase I-II trials, 33 patients were given recombinant interferon alpha-2 daily at dosages of 3, 10, 30, 50, or 100 MU/d for up to 4 weeks by intramuscular or intravenous routes. Dose-limiting toxicities, including neutropenia, elevated hepatocellular enzyme levels, fatigue, and disturbed mentation, correlated with differing serum pharmacokinetics of interferon in the two trials. In the intramuscular study, dose-limiting toxicity occurred at all dosages greater than 10 MU/d, at a median of 6 to 9 days of treatment. In the intravenous dose-study, limiting toxicity was seen only at dosages of 100 MU/d, at a median of day 8. Twenty-three patients had metastatic melanoma and 4 had objective partial or complete responses at dosages of 10 to 50 MU/d in the first month. Two patients with complete responses are free of tumor after 2.5 years of follow-up. A fifth patient had delayed complete regression, requiring 1 year to achieve maximum response, but remains free of disease at 26 months since entry to the trial. Interferon had antitumor activity against melanoma by both routes tested, at dosages of 10 to 50 MU/d.

Adult↗
PubMed1985

A facility-wide approach to recreation programming for adults who are severely and profoundly retarded.

A facility-wide recreation program was designed and implemented in order to increase staff and client participation in daily leisure activities at an intermediate care facility for severely and profoundly mentally retarded adults. The baseline phase of the study consisted of having recreational materials available during scheduled recreation periods. The treatment was a package program consisting of (1) providing the staff with preplanned materials and activities, (2) assigning staff to specific roles, and (3) monitoring staff and providing feedback by supervisors. The treatment was implemented on the two living units of the Liberty Intermediate Care Facility. Treatment effects were similar on both units. Client participation increased from a baseline average of less than 10% to nearly 50% and staff participation increased from less than 10% to an average of 60% during program implementation.

Adult↗
PubMed1985

Reversible effects of retinoic acid on glycosaminoglycan synthesis during differentiation of HL-60 leukemia cells.

Glycosaminoglycans (GAGs) play an important role in cell-cell and cell-substratum interactions, and undergo specific changes during neutrophil development. Previous studies (Luikart, S.D., Maniglia, C. A., and Sartorelli, A. C. Cancer Res., 44: 2907-2912, 1984) have shown that both dimethyl sulfoxide and 4-beta-phorbol-12-beta-myristate-13-alpha-acetate decreased GAG production by a hypoxanthine-guanine phosphoribosyl transferase-deficient clone of HL-60 promyelocytic leukemia cells prior to the appearance of a mature myeloid or monocytoid phenotype. To expand these investigations further, GAGs were analyzed by cetylpyridinium chloride precipitation and DEAE-Sephacel ion-exchange chromatography after labeling of parental HL-60 cultures with [35S]sulfate and D-[3H]glucosamine for 6 h, following treatment with 1 microM all-trans retinoic acid (RA). Chondroitin sulfate represented the major GAG species produced, although endo-beta-galactosidase-sensitive undersulfated macromolecules which possibly might be keratan sulfate, were also identified. GAG production decreased over a time period of 144 h in culture. RA treatment reduced the amount of radiolabeled cell-associated GAGs by 50% after 48, 96, and 144 h of exposure. In contrast, commitment to myelocytic maturation of the majority (i.e., approximately 60%) of the cells occurred between 72 and 96 h of RA treatment. Concurrently with the appearance of mature granulocytic cells, two-thirds of the radiolabeled GAGs were recovered from the medium, compared to one-third in untreated cultures, a phenomenon that resulted in an overall alteration in the distribution of GAGs. When RA was removed by washing after either 48 h (i.e., precommitment to differentiation) or 96 h (i.e., postcommitment to differentiation), a 1.5- to 3.5-fold increase in GAG production was noted 48 h later; this increase was unrelated to the medium change or to alterations in cell cycle distribution. The amounts of endo-beta-galactosidase-sensitive macromolecules were unaltered. Thus, although 1 microM RA inhibited the synthesis of chondroitin sulfate by HL-60 leukemia cells, this inhibition was reversible by removal of the drug and appeared to be unrelated to the commitment to myelocytic maturation.

Cell Differentiation↗
PubMed1985

Modulation of the terminal differentiation of human squamous carcinoma cells in vitro by all-trans-retinoic acid.

A malignant human cell line (SqCC/Y1) derived from a squamous carcinoma of the buccal mucosa is described. It formed a stratified cellular structure with ultrastructural characteristics of a fully differentiated stratified squamous epithelium when cultured in equal parts of Dulbecco's modified Eagle medium and Ham's medium F12, supplemented only with insulin, transferrin, and selenium. After 14 days in culture in this defined medium, 30% of the cells became keratinized (insoluble in detergent), and 75% of the cells were capable of being induced to form cornified cell envelopes. Involucrin, the precursor protein of the cornified cell envelope, could be detected by immunofluorescence only in suprabasal cells. Treatment of SqCC/Y1 cultures with 5 X 10(-8) M all-trans-retinoic acid (RA) completely inhibited stratification and markedly increased cell desquamation. In the presence of RA, less than 10% of the cells became keratinized, and only 15-20% of the cells acquired envelope-forming competence. The fraction of colony-forming cells in RA-treated cultures was tenfold higher than in fully mature cultures. Thus RA appears to be an effective inhibitor of terminal differentiation of SqCC/Y1 cells.

Carcinoma, Squamous Cell↗
PubMed1978

Differences in oxygen metabolism of phagocytosing monocytes and neutrophils.

The oxidative metabolism of monocytes and polymorphonuclear leukocytes from human peripheral blood was studied in resting and phagocytosing cells. Monocytes, like neutrophils, showed an increase in oxygen consumption during phagocytosis with a concurrent release of superoxide anions and hydrogen peroxide. Both oxygen products are highly reactive agents with potential bactericidal activity. Neutrophils consumed two and a half times as much oxygen, generated about twice as much superoxide, and released five times as much hydrogen peroxide as monocytes did. Monocytes generated superoxide and hydrogen peroxide at equivalent rates.Antimycin A, a specific mitochondrial respiratory chain inhibitor, depressed the oxygen consumption of monocytes by congruent with70% but had no effect on neutrophil respiration. Therefore, the oxygen consumed by phagocytosing monocytes appeared to be metabolized in two distinct processes: congruent with30% of the oxygen is converted to hydrogen peroxide, whereas the remaining 70% is metabolized via the mitochondrial respiratory chain. The release of superoxide and hydrogen peroxide was unaffected by antimycin in either cell type. Phagocytosis of zymosan particles by monocytes was nearly abolished by antimycin, whereas no effect was noted with neutrophils. Thus, phagocytosis appears to be highly dependent on oxidative phosphorylation in monocytes but not in polymorphonuclear leukocytes. Moreover, in monocytes treated with antimycin, an addition of opsonized zymosan particles induced stimulation of the oxidative metabolism without occurrence of ingestion.

Antimetabolites↗
PubMed1977

[Peptone-stimulated gastric secretion and antacids. Effect of antacids with various content of calcium, magnesium and aluminiumions on the peptone-induced secretion of gastric juice, double-blind study].

A double-blind-trial was performed to prove the effect of antacids containing Mg (OH)2, Al (OH)3 and CaCO3 on peptone-stimulated gastric secretion (intragastric titration). A high efficacy of antacids given after meals was demonstrated. After application of antacids no significant rise in serum gastrin levels during intragastric titration was found. Serum calcium and magnesium levels remained unchanged. Peptone-stimulated gastric secretion was not influenced by application of different antacids within a period of 2 hours.

Aluminum↗