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At least 757 records · Page 42Linked to original sources
PubMed1999

Down-regulation of the expression of O-acetyl-GD3 by the O-acetylesterase cDNA in hamster melanoma cells: effects on cellular proliferation, differentiation, and melanogenesis.

The composition of the gangliosides of hamster melanoma cells is closely related to their cellular growth and degree of differentiation, with slow-growing, highly differentiated melanotic melanoma MI cells expressing GM3 and fast-growing, undifferentiated amelanotic Ab melanoma cells having a preponderance of GD3 and O-acetyl-GD3. To study the putative function of O-acetyl-GD3, we established stably transfected AbC-1 amelanotic hamster melanoma cells with O-acetylesterase gene from influenza C virus to hydrolyze the O-acetyl group from O-acetyl-GD3. The content of O-acetyl-GD3 in the transfected cells expressing O-acetylesterase gene was reduced by >90%. These O-acetyl-GD3-depleted cells differed from the parental ones in their cellular morphology, growth behavior, and melanogenesis activity. The absence of O-acetyl-GD3 in the transfected cells was accompanied by increased thick dendrite formation with an enlarged cell body, which is in striking contrast to the control cells, which were rounded and flattened, with few processes. Their growth was significantly slower than that of the control cells. They also demonstrated significantly lower tyrosinase activity and melanogenic potential. We suggest that the enhanced expression of melanoma-associated O-acetyl-GD3 ganglioside may stimulate cellular growth and suppress certain differentiated phenotypes such as dendrite formation but not melanogenesis.

Acetylesterase↗
PubMed1995

Synthesis, structure-affinity relationships, and biological activities of ligands binding to retinoic acid receptor subtypes.

The retinoic acid receptors (RARs) transduce retinoid dependant gene regulation, and many biological effects of retinoids are mediated through binding and activation of three closely related receptor subtypes (RAR alpha, RAR beta, and RAR gamma). In order to investigate the role of receptor subtypes, we have carried out a chemical synthesis program to seek selective retinoids for these receptors. We measured receptor binding affinity using recombinant RAR alpha, -beta, and -gamma proteins and assessed cellular differentiating activity in F9 murine teratocarcinoma cells (F9 cells). This research has identified the 4-substituted-3-(1-adamantyl)phenyl moiety as a new pharmacophore which can replace the beta-cyclogeranylidene ring of the naturally occurring all-trans-retinoic acid. Two chemical series derived from the general structures 6-(3-tertioalkylphenyl)-2-naphthoic acid (series I) and 4-[(E)-2-(3-tertioalkylphenyl)propenyl]benzoic acid (series II) were developed. In particular, we have obtained the RAR gamma selective derivatives 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthoic acid (7) [Ki(RAR alpha) = 6500 nM, Ki(RAR beta) = 2480 nM, Ki(RAR gamma) = 77 nM] and 4-[(E)-2-[3-(1-adamantyl)-4-hydroxyphenyl]propenyl]benzoic acid (19) [Ki(RAR alpha) = 1,144 nM, Ki(RAR beta) = 1245 nM, Ki(RAR gamma) = 53 nM]. In series I, the presence of a phenol group, irrespective of the nature of tertioalkyl group, imparted at least partial RAR gamma selectivity, whereas in series II, the presence of both adamantyl and phenol groups is needed to confer RAR gamma selectivity. The RAR gamma selective ligands induce differentiation in F9 cells (7, AC50 = 33 nM; 19, AC50 = 66 nM). From series I, a mixed RAR beta-gamma agonist with potent cellular differentiating activity was selected for development as a topical antiacne agent, 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid (5, CD 271) [Ki(RAR alpha) = 1100 nM, Ki-(RAR beta) = 34 nM, Ki(RAR gamma) = 130 nM, AC50(F9) = 37 nM]. Finally, from series II, we have obtained a weak antagonist in the F9 cellular differentiation assay, 4-[(E)-2-(3-tert-butyl-4-hydroxyphenyl)propenyl]benzoic acid (15, IC50 = 700 nM).

Animals↗
PubMed1984

Regional variations in proliferation rate and degree of differentiation in B16 melanomas.

The relationship between proliferation rate and degree of differentiation has been studied in different regions of transplantable B16 melanomas. The regions studied were peripheral parts of the tumours and the inner (perivascular) and outer (external) zones of so-called corded structures. The highest proliferation rates and the poorest cellular differentiation (estimated by volume densities of premelanosomes and melanosomes) occurred in the perivascular zones of corded structures. Conversely, the lowest proliferation rates and the best cellular differentiation was encountered in the external zones of corded structures. Proliferation rates and cellular differentiation in the peripheral parts of the tumours were intermediate between the values obtained in the perivascular or external regions of corded structures. The results in corded structures indicate an inverse relationship between proliferation rate and degree of differentiation, and a positive correlation between proliferative capacity and blood vessel proximity. The intermediate values in the peripheral parts of tumours may reflect the presence of a mixed population of cells which vary in their proximity to the nearest blood vessel.

Animals↗
PubMed2005

Arginine methylation provides epigenetic transcription memory for retinoid-induced differentiation in myeloid cells.

Cellular differentiation is governed by changes in gene expression, but at the same time, a cell's identity needs to be maintained through multiple cell divisions during maturation. In myeloid cell lines, retinoids induce gene expression and a well-characterized two-step lineage-specific differentiation. To identify mechanisms that contribute to cellular transcriptional memory, we analyzed the epigenetic changes taking place on regulatory regions of tissue transglutaminase, a gene whose expression is tightly linked to retinoid-induced differentiation. Here we report that the induction of an intermediary or "primed" state of myeloid differentiation is associated with increased H4 arginine 3 and decreased H3 lysine 4 methylation. These modifications occur before transcription and appear to prime the chromatin for subsequent hormone-regulated transcription. Moreover, inhibition of methyltransferase activity, pre-acetylation, or activation of the enzyme PAD4 attenuated retinoid-regulated gene expression, while overexpression of PRMT1, a methyltransferase, enhanced retinoid responsiveness. Taken together, our results suggest that H4 arginine 3 methylation is a bona fide positive epigenetic marker and regulator of transcriptional responsiveness as well as a signal integration mechanism during cell differentiation and, as such, may provide epigenetic memory.

Acetylation↗
PubMed1998

Modulation of osteogenic differentiation in human skeletal cells in Vitro by 5-azacytidine.

Cellular differentiation is controlled by a variety of factors including gene methylation, which represses particular genes as cell fate is determined. The incorporation of 5-azacytidine (5azaC) into DNA in vitro prevents methylation and thus can alter cellular differentiation pathways. Human bone marrow fibroblasts and MG63 cells treated with 5azaC were used as models of osteogenic progenitors and of a more mature osteoblast phenotype, respectively. The capacity for differentiation of these cells following treatment with glucocorticoids was investigated. 5azaC treatment led to significant expression of the osteoblastic marker alkaline phosphatase in MG63 osteosarcoma cells, which was further augmented by glucocorticoids; however, in human marrow fibroblasts alkaline phosphatase activity was only observed in glucocorticoid-treated cultures. MG63 cells represent a phenotype late in the osteogenic lineage in which demethylation is sufficient to induce alkaline phosphatase activity. Marrow fibroblasts are at an earlier stage of differentiation and require stimulation with glucocorticoids. In contrast, the expression of osteocalcin, an osteoblastic marker, was unaffected by 5azaC treatment, suggesting that regulation of expression of the osteocalcin gene does not involve methylation. These models provide novel approaches to the study of the control of differentiation in the marrow fibroblastic system.

Alkaline Phosphatase↗
PubMed2001

Differentiation, proliferation and apoptosis in primary and recurrent primitive neuroectodermal tumors of childhood.

Primitive neuroectodermal tumors (PNETs) of the CNS are a group of embryonal tumors composed of small undifferentiated or poorly differentiated cells. Infratentorially located PNETs are a synonym for medulloblastomas. In this study 31 PNETs, including 5 recurrent tumors, were examined. All children underwent neurosurgery and chemotherapy according to the HIT and HIT-SKK protocols. The specimens were investigated both for their expression of nine immunohistochemical markers for neuronal, astrocytic, mesenchymal and epithelial differentiation and for their proliferation. Results regarding cellular differentiation were confirmed ultrastructurally. Apoptosis was detected by labeling the 3'OH ends generated by DNA fragmentation and by electron microscopy. Glial differentiation was shown to have a prognostic relevance, with an elevated (twofold) risk of recurrence. Neuronal differentiation also indicated a tendency to poor prognosis. Those tumors that recurred later showed an increased proliferation rate (69%) compared with nonrecurrent tumors (58%). Apoptosis was identified in all tumors examined. The proportion of apoptotic cells could not be related to the effect of therapy. These results indicate that cellular differentiation may be a useful predicative factor for the prognosis of cerebral PNETs.

Adolescent↗
PubMed2005

New perspectives on eye development and the evolution of eyes and photoreceptors.

Recent experiments on the genetic control of eye development have opened up a completely new perspective on eye evolution. The demonstration that targeted expression of one and the same master control gene, that is, Pax6 can induce the formation of ectopic eyes in both insects and vertebrates, necessitates a reconsideration of the dogma of a polyphyletic origin of the various eye types in all the animal phyla. The involvement of Pax6 and six1 and six3 genes, which encode highly conserved transcription factors, in the genetic control of eye development in organisms ranging from planarians to humans argues strongly for a monophyletic origin of the eye. Because transcription factors can control the expression of any target gene provided it contains the appropriate gene regulatory elements, the conservation of the genetic control of eye development by Pax6 among all bilaterian animals is not due to functional constraints but a consequence of its evolutionary history. The prototypic eyes postulated by Darwin to consist of two cells only, a photoreceptor and a pigment cell, were accidentally controlled by Pax6 and the subsequent evolution of the various eye types occurred by building onto this original genetic program. A hypothesis of intercalary evolution is proposed that assumes that the eye morphogenetic pathway is progressively modified by intercalation of genes between the master control genes on the top of the hierarchy and the structural genes like rhodopsin at the bottom. The recruitment of novel genes into the eye morphogenetic pathway can be due to at least two different genetic mechanisms, gene duplication and enhancer fusion.In tracing back the evolution of eyes beyond bilaterians, we find highly developed eyes in some box-jellyfish as well as in some Hydrozoans. In Hydrozoans the same orthologous six genes (six1 and six3) are required for eye regeneration as in planarians, and in the box jellyfish Tripedalia a pax B gene, which may be a precursor of Pax6, was found to be expressed in the eyes. In contrast to the adults, which have highly evolved eyes, the Planula larva of Tripedalia has single- celled photoreceptors similar to some unicellular protists. For the origin of photoreceptor cells in metazoa, I propose two hypotheses, one based on cellular differentiation and a more speculative one based on symbiosis. The former assumes that photoreceptor cells originated from a colonial protist in which all the cells were photosensitive and subsequent cellular differentiation to give rise to photoreceptor cells. The symbiont hypothesis, which I call the Russian doll model, assumes that photosensitivity arose first in photosynthetic cyanobacteria that were subsequently taken up into red algae as primary chloroplasts. The red algae in turn were taken up by dinoflagellates as secondary chloroplasts and in some species evolved into the most sophisticated eye organelles, as found, for example, in some dinoflagellates like Erythropsis and Warnovia, which lack chloroplasts. Because dinoflagellates are commonly found as symbionts in cnidarians, the dinoflagellates may have transferred their photoreceptor genes to cnidarians. In cnidarians such as Tripedalia the step from photoreceptor organelles to multicellular eyes has occurred. These two hypotheses, the cellular differentiation and the symbiont hypothesis, are not mutually exclusive and are the subject of further investigations.

Animals↗
PubMed1995

The control of asymmetric gene expression during Caulobacter cell differentiation.

The dimorphic bacterium Caulobacter crescentus provides a simple model for cellular differentiation. Each cell division produces two distinct cell types: a swarmer cell and a stalked cell. These cells possess distinct functional morphologies and differential programs of transcription and DNA replication. The synthesis of a single polar flagellum is restricted to the swarmer pole of the predivisional cell by a genetic hierarchy comprising at least 50 genes whose transcription is regulated by novel and ubiquitous promoters, cognate sigma factors, and auxiliary transcriptional regulators. Chromosome replication is restricted to the stalked cell by a unique chromosome origin of replication that may be regulated by a novel cell-specific transcriptional control system. Phosphorylation signals, DNA methylation, differential chromosome structures, protein targeting, and selective protein degradation are also involved in establishing and maintaining cellular asymmetry. The molecular details of these universal cellular processes in C. crescentus will provide paradigms applicable to many general aspects of cellular differentiation.

Bacterial Proteins↗
PubMed1990

Progestin binds to the glucocorticoid receptor and mediates antiglucocorticoid effect in rat adipose precursor cells.

The binding of progestin and glucocorticoid hormones was examined in the cytosol of rat adipose precursor cells. Progestin binding sites of high affinity and limited capacity were present in the cytosol of adipose precursor cells from female rats, but not from male rats, by using [3H]R5020 as radioligand. Glucocorticoid binding sites of high affinity and limited capacity were present in the cytosol of these cells from both male and female rats by using [3H]dexamethasone and [3H]triamcinolone acetonide as radioligands. The dissociation constants were in the physiological concentration range. Studies of competitive binding showed that progestin could compete with glucocorticoids at glucocorticoid binding sites. In a serum free medium glucocorticoid effect on cellular differentiation, monitored by glycerophosphate dehydrogenase (GPDH), was effectively counteracted by progesterone which by itself had no effect. These results demonstrate that progestin receptor exists only in rat adipose precursor cells from female rats, while glucocorticoid receptor exists in rat adipose precursor cells of both sexes. Glucocorticoid effects on cellular differentiation in these cells are mediated by the glucocorticoid receptor. Progestin binds to the glucocorticoid receptor and antagonizes glucocorticoid effect on cellular differentiation in these cells.

Adipose Tissue↗
PubMed1989

Phylogenetic diversity of cellular organization in the cardia of muscoid flies (Diptera: Schizophora).

In each of 30 dipteran species, representing 13 acalyptrate and 7 calyptrate families, the cardia is formed from specialized cells at the junction between foregut and midgut. Foregut epithelium forms the stomodeal valve; midgut epithelium envelops the valve to form the cardia's outer wall. Cytological characteristics within these epithelia differ from region to region and from species to species. Since the cardia secretes the peritrophic membrane, cardias with diverse patterns of cellular differentiation may be expected to produce peritrophic membranes with similarly diverse properties. Close relatives often share more details of cardia structure than do distantly related taxa. Within the monophyletic Calyptratae, a common pattern of cellular differentiation includes three distinct zones of columnar midgut cells enclosing a flanged stomodeal valve. Among species in the paraphyletic Acalyptratae, midgut typically includes a single zone of tall columnar cells, while the valve may be spheroidal, cylindrical, conical, or flanged. The correlation of phylogenetic distance with divergence in cardia organization implies a strong influence of ancestry upon current structure, regardless of current diet. However, at least some of the observed diversity in cardia structure is associated with dietary divergence. Calyptrate flies with derived blood-feeding behavior display cellular differentiation that is simplified from that seen in calyptrate relatives with less specialized feeding habits. This evolutionary modification suggests that cardia organization and hence peritrophic membrane structure can adapt to dietary changes, with possible significance for the spatial organization of digestive processes and interactions with ingested microorganisms.

Animals↗
PubMed2004

Three-dimensional in vitro tissue culture models of breast cancer-- a review.

Three-dimensional (3D) in vitro breast tumour models have an invaluable role in tumour biology today providing some very important insights into breast cancer. As well as increasing our understanding of homeostasis, cellular differentiation and tissue organization they provide a well defined environment for cancer research in contrast to the complex host environment of an in vivo model. With the recent availability of relevant stromal elements together with the vast array of extracellular matrix constituents available, in vivo like microenvironments can be recreated. These tissue like structures more realistically model the structural architecture and differentiated function of breast cancer than a cellular monolayer providing in vivo like responses to therapeutic agents. Three dimensional in vitro models allow the study of cell-cell and cell-extracellular matrix interactions, in addition to the influence of the microenvironment on cellular differentiation, proliferation, apoptosis and gene expression. Due to their enormous potential 3D cultures are currently being exploited by many other branches of biomedical science with therapeutically orientated studies becoming the major focus of research. In return great progress in 3D culture techniques have been made, largely due to this greater interaction. At present they are being used in studies ranging from investigating the role of adhesion molecules (e.g., E-cadherin) in invasion/metastasis; VEGF and angiogenesis, to tissue modelling and remodelling. Progress in the development of complex 3D culture systems is more productive than ever, however further research is vital.

Breast Neoplasms↗
PubMed1990

The physiology and biochemistry of retinoic acid.

The ability of the fat soluble Vitamin A to modulate cellular differentiation has been known for over 60 years. Numerous studies have shown that Vitamin A and its 2 major metabolites play a key role in vision (retinal) and cell differentiation (retinoic acid, RA). The control of cellular differentiation may be exercised on a variety of tissues including simple and stratified epithelia, the latter will be the focal point of this article, with emphasis being given to the skin. In the development of the limb bud, RA has been proposed as a morphogen controlling development via a concentration gradient established by a mechanism thought to involve specific nuclear receptors and a cytosolic binding protein (CRABP). In the hemopoietic system, RA is known to modulate several functions of polymorphonuclear leucocytes (PMN) in vitro and the differentiation of granulocyte macrophage-precursors. Moreover it has been shown to exert immunomodulatory properties.

Adjuvants, Immunologic↗
PubMed2004

FoxOs at the crossroads of cellular metabolism, differentiation, and transformation.

Forkhead transcription factors of the FoxO subfamily are emerging as a shared component among pathways regulating diverse cellular functions, such as differentiation, metabolism, proliferation, and survival. Their transcriptional output is controlled via a two-tiered mechanism of phosphorylation and acetylation. Modest alterations of this balance can result in profound effects. The gamut of phenotypes runs from protection against diabetes and predisposition to neoplasia, conferred by FoxO loss of function, to increased cellular survival and a marked catabolic response associated with gain of function.

Acetylation↗
PubMed1988

Quantification of cells recovered by bronchoalveolar lavage. Comparison of cytocentrifuge preparations with the filter method.

Controversy exists as to the appropriate methods to use in the processing of bronchoalveolar lavage (BAL) fluid for total cell numbers and cellular differential analysis. It has been shown that cell losses (primarily lymphocytes) occur by the most commonly employed methods. Therefore, we examined the total cell and differential counts obtained by several methods of cytocentrifuge preparation and by the filter preparation in 46 consecutive patients with interstitial lung disease and 29 healthy volunteers undergoing bronchoalveolar lavage. The retrieved lavage fluid was pooled, and an aliquot was used to determine the total cell count, cell viability, and the differential cell count by the filter and cytocentrifuge techniques. The remaining fluid was centrifuged (800 g for 10 min), and the cell pellet was resuspended in Hank's balanced salt solution without Ca2+ and Mg2+. An aliquot of these centrifuged and resuspended cells was used for repeat determination of the cell viability, total cell count, and cellular differential by cytocentrifuge technique. Autologous serum was added to another aliquot of these centrifuged and resuspended cells to arrive at a 10% protein solution, and the cellular differential obtained by cytocentrifuged preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Contaminant effect on cellular metabolic differential pressure curves.

The possibility of a pressure monitoring system by differential pressure sensors to detect contaminant effects on cellular cultures metabolic activity is discussed using Saccharomyces cerevisiae, lymphocyte, and AHH1 cell cultures. Metabolic (aerobic and anaerobic) processes in cells are accompanied by CO(2) production that induces changes in pressure values when cells are cultured in sealed vessels. These values are subsequently converted in voltage units and plotted pressure dynamics versus time. This procedure leads to a standard curve, typical of the cellular line, which characterizes cellular metabolism when all parameters are controlled, such as temperature and nutrients. Different phases appear in the S. cerevisiae differential pressure curve: an initial growth up to a maximum, followed by a decrement that leads to a typical "depression" (pressure values inside the test-tubes are lower than the initial one) after about 35 h from the beginning. The S. cerevisiae differential pressure curve is successfully used to test the effects of chemical (Amuchina, trieline) and physical (UV radiation, blue light, magnetic fields) contaminants. The same technique is applied to lymphocytes and AHH1 cultures to investigate the effects generated by a 72-h exposure to a 50-Hz, 60-microT electromagnetic field. Lymphocyte samples, cultured in a PHA medium, grow less than control ones, but exhibit a greater metabolic activity: changes in the exposure system configuration influence neither sample growth differences nor metabolic response variations between control and irradiated samples, while all the other irradiation parameters remain constant. Control and irradiated lymphocyte samples, without PHA in culture medium, show the same behavior both during irradiation and metabolic test. AHH1 control and irradiated samples show no difference both in growth percentage during irradiation and in metabolic activity. Different cell cultures respond to the same stimulus in different manners.

Biosensing Techniques↗
PubMedDate not supplied

Differentiation can convey resistance to transformation by activated ras oncogene.

Nonterminal cellular differentiation has recently been shown to induce transformed cells to revert to a benign state and to become resistant to retransformation by chemical and physical carcinogens without limiting their proliferative potential. Nonterminal differentiation also induces native 3T3 T mesenchymal stem cells to become resistant to transformation induced by numerous chemical and physical carcinogens. This characteristic has been designated anticancer activity. In the current study, experiments show that cells expressing differentiation-associated anticancer activity are also resistant to transformation by the activated ras (EJras) oncogene. Resistance to EJras transformation is shown not to result from a reduced efficiency of DNA transfection nor from reduced integration of EJras into the genome. Moreover, the results show that the EJras oncogene product can be expressed in cells demonstrating anticancer activity. Nonterminal cellular differentiation, therefore, induces resistance to transformation caused by activated ras oncogene as well as to numerous physical and chemical carcinogens.

Animals↗
PubMed2000

Distinct radiochemotherapy protocols differentially influence cellular proliferation and expression of p53 and Bcl-2 in glioblastoma multiforme relapses in vivo.

Several protocols for the adjuvant treatment of glioblastoma multiforme (GBM) are currently being evaluated. In this context, little is known about the influence of radiochemotherapy on apoptosis and the expression of apoptosis-related proteins in vivo. We have analyzed the incidence of apoptosis using in situ nick translation (ISNT) and expression of Ki-67 (MIB- 1), p53 (DO-1 and DO-7), Bcl-2 and transglutaminase II (TGase II) by immunohistochemistry in 41 patients with GBM and their matched relapses. Sixteen patients received radiochemotherapy, 18 irradiation and 7 no treatment. Radiochemotherapy resulted in an increase in Bcl-2+ cells (p = 0.013). Irradiation caused the reduction of MIB-1+ (p = 0.0015), DO-7+ (p = 0.0043) and the increase of Bcl-2+ cells (p = 0.016). We calculated a positive correlation between high TGase II scores in patients preceding radiochemotherapy (p = 0.0186) and no treatment (p = 0.0158), low ISNT scores (p = 0.0018) and high DO-1 scores (p = 0.0233) in patients preceding irradiation and short time to progression. These data show that distinct postsurgical radiochemotherapy protocols differentially alter cellular proliferation and expression of p53 and Bcl-2 in GBM relapses. Furthermore, we show that ISNT, DO-I and TGase II labeling scores are therapy-specific predictors of time to progression in GBM patients.

Adult↗