bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of rabbit articular chondrocyte (RAC) proliferation by TGF‐β isoforms
Authors: Boumediene K. , Vivien D. , Macro M. , Bogdanowicz P. , Lebrun E. , Pujol J‐P. 
Published: May 2008

AbstractWe have previously shown that TGF‐β1 exerts a bifunctional effect on RAC proliferation. Added to quiescent cultures, it inhibits the entry of G0/G1 cells into S phase whereas in S phase synchronized populations, it stimulates the DNA replication rate with a delayed G2+ M phase and a subsequent transient increase of cell number. As TGF‐β2 and β3 isoforms are also expressed in bone and cartilage tissues, it was of interest to study their effect on RAC proliferation, in comparison to that of TGF‐β1.Using cell counting and tritiated thymidine incorporation, we found that all the TGF‐βs used here induced an increase of RAC proliferation rate occurring between 24 and 48 h of exposure. TGF‐β2 appeared as the most efficient form as judged from the maximum of thymidine labelling. However, TGF‐β3 induced an increase of cell number slightly higher than both TGF‐β1 and TGF‐β2 (+30% versus 20% for TGF‐β1 and β2). TGF‐β2 and β3 were able to stimulate the DNA replication rate as previously demonstrated for TGF‐β1. However, the effect occurred later for TGF‐β2 and β3 (12 h) than for TGF‐β1 (6 h). This was confirmed by flow cytometric analysis of DNA content. In addition, immunodetection by flow cytometry demonstrated that all TGF‐β isoforms enhanced endogenous expression of TGF‐β‐related peptides. The effect was shown to be associated with the cell cycle S phase and was greater for TGF‐β3 than for TGF‐β1 and β2. These findings suggest that TGF‐βs could act on RAC functions via autocrine and paracrine ways.Taken together, these data indicate that TGF‐βs may modulate proliferation of articular chondrocytes and therefore could play a role in the activation of these cells in the early stages of osteoarthritis.
Different growth patterns of a cancer cell population as a function of its starting growth characteristics: analysis by mathematical modelling
Authors: Solyanik G. I. , Berezetskaya N. M. , Bulkiewicz R. I. , Kulik G. I. 
Published: May 2008

AbstractThe growth kinetics of a cancer cell population as a function of the total number of cells and the proportion of proliferating and resting cells at the beginning of the growth has been analysed by a mathematical model. The model takes into account the processes of cell division, death and transition from proliferation to rest and backwards. It is shown that a single cell population growing under the same environmental conditions has an extremely broad spectrum of growth patterns. The whole multiplicity of possible growth patterns has been determined by the inherent cellular growth characteristics of the population, while the growth pattern actually realized of the variety of growth curves depends on the total number of cells and the proportion of proliferating and resting cells at the initial moment of growth. The model is shown to provide a good prediction of experimentally measured kinetics of regrowth of tumour cells subcultured after various times of the growth in unfed cultures, and the kinetics of tumour cell growth after severe hypoxia. The role of cell transitions between proliferating and resting stages in the problem of growth control is discussed.
Effect of ebrotidine on the density of antral G‐cells in the gastric mucosa in the rat
Authors: Romero A. , Gömez F. , Villamayor F. , Sacristán A. , Ortíz J‐A. 
Published: May 2008

AbstractTwo groups of male rats were treated orally for 60 days with ebrotidine and cimetidine, used as reference standard, respectively. The dose used of both drugs was 500mg/kg. A third group, used as control, received 10 ml/kg of an aqueous agar suspension. After receiving the last dose, the animals were killed by inhalation of CO2 in a sealed chamber and the stomachs were removed for histological preparation.The purpose of this study was to count antral G‐cells throughout the gastric mucosa by light microscope. A PAP system‐associated antigastrin immunohistochemical method was used for cell identification. Cell density, with respect to their location in the gastric mucosa and the treatments given, was calculated using image analysis techniques.The results showed that ebrotidine did not cause any significant differences in the density of the population of these cells compared with the control group, while cimetidine induced a significant proliferation of antral G‐cells.
Differential effects of nitrogen mustardin vivoon the cancer and host cells in MCa‐11 tumours
Authors: Bose K. K. , Zahurak M. L. , Allison D. C. 
Published: May 2008

AbstractWe analysed the effects of nitrogen mustard (HN2) on the growth, cell cycle distributions, and ratios of tumour cells to host cells for MCa‐11 tumours grownin vivo.Treatment of tumour‐bearing BALB/c mice with 3 mg/kg of HN2produced a significant slowing of MCa‐11 tumour growth. Seventy‐two hours after treatmentin vivowith either 3 or 4 mg/kg of HN2, the host cells in the treated tumours showed a significantly decreased G0/G1peak and an increased G2/M peak (P< 0.01), whereas the cancer cells in the treated tumours showed significant increases in the G0/G1peak coupled with relatively decreased proportions of S and G2/M tumour cells (P< 0.001). The ratio of the total number of cancer cells to the total number of host cells in the tumours was significantly increased 72 h after HN2administration (P<0.01). Thirty‐two days after treatment with HN2, the cell cycle distributions of the host and tumour cells in the treatment and control tumours had returned to being identical, but the ratio of the total number of cancer cells to the total number of host cells remained increased in the treated tumours (P<0.01). These results show that the administrationin vivoof HN2can lead to entirely different cell cycle effects for the host and cancer cells in the same tumour, and that the partial growth arrest of MCa‐11 tumours from HN2treatment may be due in part to the preferential destruction of host cells rather than solely to a direct cytotoxic effect on the cancer cells.
Hormone gradients and cartilage cell kinetics
Authors: Vogl C. , Atchley W. R. 
Published: May 2008

AbstractWe present a model of growth control in mammalian cartilage growth plates by hormones. The model is based on the distribution of insulin‐like growth factors I and II (IGF‐I and IGF‐II) and their receptors, and assumes that a hormone‐receptor complex of IGF controls cells proliferation. A system of differential equations is derived and solved with simplifications in extreme cases, for the one‐dimensional time independent case. Even if opposite extremes, such as proliferation control by factors extrinsic to the cell versus intrinsic to the cell, are assumed, similar distributions of hormones and proliferating cells are produced. Hence, choice between alternative models of growth control must be based on empirical observations. On the positive side, similarities between our model for cartilage growth and other models for differentiation and proliferation are evident and might be exploited for unifying these systems on an abstract level.
Argyrophilic nucleolar organizer regions and bromodeoxyuridine and 3[H]‐thymidine labelling indices in colorectal cancer
Authors: Losi L. , Gregorio C. Di , Fante R. , Migaldi M. , Roncucci L. , Pedroni M. , De Leon M. Ponz , Trentini G. Paolo 
Published: May 2008

AbstractThe count of argyrophilic nucleolar organizer regions (AgNORs) has been proposed as a useful method for evaluating cell replication in human tumours. The current study was undertaken to compare AgNOR values in colorectal cancers with two better established methods for investigating cell proliferation such as bromodeoxyuridine (BrdUrd) and 3[H]‐thymidine (3[H]dT) labelling indices (LIs).Because some concern still exists regarding accuracy and reproducibility of AgNOR quantifying methods, we carried out a control study by independently repeating the same measurements (number, area and area per silver‐stained NOR particle) in two centres with different operators and computer‐assisted image analysers on 40 colorectal carcinomas. AgNOR values recorded in the two centres were strictly correlated (r= 0.75; P < 0.001 for number; r= 0.62, P < 0.01 for area; r= 0.63, P < 0.001 for area per silver‐stained NOR particle) and the range of values were almost identical. Then, AgNOR values were compared with BrdUrd and 3[H]dT LIs, respectively obtained by in vivo incorporation and in vitro incubation in the same series of colorectal carcinomas. No correlation was found between AgNOR values and BrdUrd or 3[H]dT LIs. BrdUrd and 3[H]dT LIs were instead reciprocally significantly correlated. No evident correlation was seen between LIs or AgNOR values and clinico‐pathological parameters of the tumour. In conclusion, in colorectal neoplasms, AgNOR values did not appear to relate with more direct parameters of cell proliferation. It follows that AgNOR reliability as a biomarker of cell proliferation remains questionable.
Pluripotential liver stem cells: facultative stem cells located in the biliary tree
Authors: Alison M. R. , Golding M. H. C. , Sarraf C. E. 
Published: May 2008

Abstract. The ability of the liver to regenerate after parenchymal damage is usually accomplished by the ephemeral entry of normally proliferatively quiescent (G0) hepatocytes into the cell cycle. However, when hepatocyte regeneration is defective, arborizing ductules which are continuous with the biliary tree, proliferate and migrate into the surrounding parenchyma. In man these biliary cells have variously been referred to as ductular structures, neoductules and neocholangioles, and have been observed in many forms of chronic liver disease, including cancer. In experimental animals similar ductal cells are usually called oval cells, and their association with defective regeneration has led to the belief that these cells represent a progenitor cell population. Oval cells are thought to take over the burden of regenerative growth after substantial hepatocyte loss, suggesting that they are the progeny of facultative stem cells. The liver is not, however, generally considered as a stem cellfed hierarchy, although this is disputed by others. Despite this, the subject of oval cells has aroused intense interest as these cells may represent a target population for hepatic carcinogens, and they may be useful vehicles for ex vivo gene therapy.This review proposes that the liver does harbour stem cells which are located throughout the biliary epithelium, and that oval cells represent the progeny of these stem cells and function as an amplification compartment for the generation of ‘new’hepatocytes. This is a conditional process which only occurs when the regenerative capacity of hepatocytes is overwhelmed and thus, unlike the intestinal epithelium, the liver is not behaving as a classical continually renewing stem cell‐fed lineage. We focus on the biliary network, not merely as a conduit for bile, but also as a cell compartment with the potential to proliferate under appropriate conditions and give rise to fully differentiated hepatocytes and other cell types.
Monoclonal antibodies Ki‐S3 and Ki‐S5 yield new data on the ‘Ki‐67’proteins
Authors: Heidebrecht H. J. , Buck F. , Haas K. , Wacker H. H. , Parwaresch R. 
Published: May 2008

Abstract. The monoclonal antibody (mab) Ki‐67 has been used for about 10 years, mainly in tissue sections, to monitor proliferating cells, but so far only very little is known about the proteins it recognizes. The new mabs Ki‐S3 and Ki‐S5 detect proliferating cells in frozen and paraffin‐embedded tissues. They recognize proteins with the same molecular mass as Ki‐67 in Western blot and for the first time also in immunoprecipitation experiments. With these mabs we were able to enrich and purify the Ki‐67 proteins. Protein sequencing of four peptides of the digested proteins corresponded to the cDNA‐deduced amino acid sequence already published for the Ki‐67 proteins.Since we were able to immunoprecipitate the Ki‐67 proteins, we performed various immunoprecipitation experiments to obtain more information about the nature of these proteins. After radiolabelling L428 cells with [35S]‐methionine we were able to immunoprecipitate the Ki‐67 proteins after only 5 min of labelling time. In turnover experiments the Ki‐67 proteins could not be detected 3 h after the end of labelling. These data indicate a halt‐life of the Ki‐67 proteins of about 90 min.Labelling experiments with [32P]‐orthophosphate revealed that the Ki‐67 proteins are phosphorylated. After dephosphorylation was blocked with okadaic acid or cell growth was arrested by means of Colcemid, the phosphorylation of the Ki‐67 proteins was greatly increased, indicating that the Ki‐67 proteins are phosphorylated via serine and threonine, and that the phosphorylation of the Ki‐67 proteins increases in cycling cells. Labelling experiments with [3H]‐mannose and [3H]‐glucose revealed that the protein is weakly N‐glycosylated.
The antiproliferative activity of the tetrapeptide Acetyl‐N‐SerAspLysPro, an inhibitor of haematopoietic stem cell proliferation, is not mediated by a thymosin β4‐like effect on actin assembly
Authors: Cheviron N. , Grillon C. , Carlier M.‐F. , Wdzieczak‐Bakala J. 
Published: May 2008

Abstract. Acetyl‐N‐SerAspLysPro (AcSDKP), known as a negative regulator of haematopoiesis, has been principally reported as an inhibitor of haematopoietic pluripotent stem cell proliferation. The tetrapeptide sequence is identical to the N‐terminus of thymosin β4 (Tβ4), from which it has been suggested that it may be derived. Recently, evidence was shown that Tβ4 plays a role as a negative regulator of actin polymerization leading to the sequestration of its monomeric form. The structural similarity between the N‐terminus of Tβ4 and AcSDKP has raised the possibility that AcSDKP may also participate in intracellular events leading to actin sequestration.The effect of Tβ4 on the proliferation of haematopoietic cells was compared to that of AcSDKP. The results revealed that Tβ4, like AcSDKP, exerts an inhibitory effect on the entry of murine primitive bone marrow cells into cell cycle in vitro. Qualitative electrophoretic analysis and quantitative polymerization assays were used to investigate the role of AcSDKP in actin polymerization. AcSDKP does not affect actin assembly at concentrations up to 50 μM, and does not compete with Tβ4 for binding to G‐actin. These results suggest that AcSDKP is not involved in cell cycle regulation via an effect on the process of actin polymerization.
Cloning of intestinal phospholipase A2 from intestinal epithelial RNA by differential display PCR
Authors: Keshav S. , McKnight A. J. , Arora R. , Gordon S. 
Published: May 2008

AbstractDifferential display polymerase chain reaction (DD‐PCR) is a powerful technique for comparing gene expression between cell types, or between stages of development or differentiation. Differentially expressed genes may be cloned and analysed further. Here we extend the use of DD‐PCR to analyse differences in gene expression between two complex epithelia: that of the small intestine and of the large intestine. The aim of this study was to identify genes expressed preferentially in Paneth cells. Paneth cells are secretory epithelial cells putatively involved in host defense and regulation of crypt cell proliferation and are found at the base of the small intestinal crypts adjacent to the stem cell zone. Of 34 clones that were analysed, partial sequencing identified two clones related to known Paneth cell products: a homologue of secretory phospholipase A2 (clone B1) and a homologue of a neutrophil defensin (clone C5). B1 was strongly expressed in Paneth cells, as demonstrated by in‐situ hybridization. B1 was also expressed at a lower level in the large intestinal epithelium. A full length B1 cDNA clone was isolated and sequenced, and shown to be highly homologous to type II secretory phospholipase A2 genes, and almost identical to the enhancing factor gene and the putative gene for the MOM‐1 locus. B1 expression is limited to the intestinal tract, and we propose that it be designated intestinal phospholipase A2, or i‐PLA2. The method we describe is well suited to the rapid identification of genes expressed exclusively or predominantly in Paneth cells.
Unbalanced growth in mouse cells with amplified dhfr genes
Authors: Snapka R. M. , Ge S. , Trask J. , Robertson F. 
Published: May 2008

AbstractWhen grown in the absence of methotrexate, cells carrying unstably amplified dihydrofolate reductase (dhfr) genes have a growth disadvantage that is a function of their level of gene amplification. Although this growth disadvantage is thought to drive the loss of unstably amplified dhfr genes in the absence of methotrexate, its mechanism is not understood. The present studies of murine cell lines with different levels of dhfr gene amplification demonstrate that such cells experience increased unbalanced growth (excess RNA and protein content relative to DNA content) with increased levels of dhfr gene amplification. Stathmokinetic analysis of a cell line with unstably amplified dhfr genes showed that the unbalanced growth was associated with a very low rate of G1/S transit, which suggests that amplified DNA sequences may activate a cell cycle checkpoint at the G1/S boundary. Hydroxyurea, which is known to induce rapid elimination of amplified genes at sub‐cytotoxic concentrations, also inhibits the cell cycle at the G1/S transition and causes unbalanced growth. Earlier work has shown that hydroxyurea selectively targets those cells within the heterogeneous drug resistant cell populations which have the highest amplified gene dosage. The finding that unstable gene amplification and hydroxyurea have similar effects on the cell suggests that hydroxyurea may achieve this selective targeting by pushing those cells with the highest levels of gene amplification over a critical stress threshold to cause growth arrest or cell death.
Immunoreactivity to MIB‐1 in breast cancer: methodological assessment and comparison with other proliferation indices
Authors: Benini E. , Rao S. , Daidone M. Grazia , Pilotti S. , Silvestrini R. 
Published: May 2008

AbstractThe recent availability of the monoclonal antibody MIB‐1 (which is able to detect the human nuclear cell proliferation‐associated antigen Ki‐67 even on formalin‐fixed, paraffin‐embedded sections, microwave‐treated and routinely processed for immunohistochemistry) could open new avenues for validation of the clinical role of tumour cell proliferation on large, consecutive and unselected series of human tumours. However, the routine use of such a marker requires a methodological standardization as well as the comparative assessment of some technical and biological aspects. The MIB‐1 index was determined in parallel samples from 50 consecutive invasive breast carcinomas processed with different fixatives for different times. The median values of MIB‐1 indices following 2, 6 and 24 h of formalin fixation were similar (29.4%, 30.6% and 29.7%, respectively) and consistent with those reported in the literature; squared linear regression coefficients were 0.99. The median values of MIB‐1 indices were markedly lower in Bouin‐fixed, paraffin‐embedded, and in frozen samples (20.0% and 19.8%, respectively), with a poor correlation coefficient with the values detected following formalin fixation (R2=0.456). Moderate and poor correlations were observed between Ki‐67 index and MIB‐1 detected on frozen (rs, 0.78) or formalin‐fixed, paraffin‐embedded samples (rs, 0.47) and a minimal concordance was observed between TLI and MIB‐1 or Ki‐67 (rs, 0.25 and 0.22, respectively). Our results indicate interference of the fixative type on immunoreactivity to MIB‐1 and also suggest that Ki‐67 and MIB‐1 reacted with different epitopes of the same antigen.
3H‐Thymidine labelling index (TLI) as a marker of tumour growth heterogeneity: evaluation in human solid carcinomas
Authors: Becciolini A. , Balzi M. , Barbarisi M. , Faraoni P. , Biggeri A. , Potten C. S. 
Published: May 2008

AbstractMany studies deal with the analysis of cell kinetic, cytogenetic, biochemical and molecular cell biology parameters to identify prognostic factors relating to tumour growth but all methods use only a small part of the total tumour mass. This study is devoted to the analysis of the heterogeneity of the growth of human solid tumours assaying proliferative activity by means of 3H‐thymidine labelling index (TLI) in a fixed number of samples collected in different areas of the lesion (larynx and colon cancers), or in different lesions of the same subject (breast and bladder cancers). Each sample (at the macroscopic level) was divided into small fragments (at the microscopic level) and proliferative activity was determined. The analysis of variance for hierarchical designs demonstrated that in all cases a high component of the variance is attributable to the subjects and to the fragments whereas the variance attributable to the different areas is very low. The heterogeneity of proliferative activity displays a higher focal variability among the fragments (microscopic level) compared with that among areas (macroscopic level) within subjects, provided an adequate number of fragments and cells are counted. In multiple synchronous carcinoma of the bladder the wide variability of proliferation among the single lesions demonstrated that it is necessary to analyse all the tumours in a subject because each one is characterized by a different cell growth potential.
Laser scanning cytometry (LCS) allows detailed analysis of the cell cycle in PI stained human fibroblasts (TIG‐7)
Authors: Kawasaki M. , Sasaki K. , Satoh T. , Kurose A. , Kamada T. , Furuya T. , Murakami T. , Todoroki T. 
Published: May 2008

AbstractWe have demonstrated a method for the in situ determination of the cell cycle phases of TIG‐7 fibroblasts using a laser scanning cytometer (LSC) which has not only a function equivalent to flow cytometry (FCM) but also has a capability unique in itself. LSC allows a more detailed analysis of the cell cycle in cells stained with propidium iodide (PI) than FCM. With LSC it is possible to discriminate between mitotic cells and G2 cells, between post‐mitotic cells and G1 cells, and between quiescent cells and cycling cells in a PI fluorescence peak (chromatin condensation) vs. fluorescence value (DNA content) cytogram for cells stained with PI. These were amply confirmed by experiments using colcemid and adriamycin. We were able to identify at least six cell subpopulations for PI stained cells using LSC; namely G1, S, G2, M, postmitotic and quiescent cell populations. LSC analysis facilitates the monitoring of effects of drugs on the cell cycle.
Effect of sodium butyrate on human breast cancer cell lines
Authors: Coradini D. , Biffi A. , Costa A. , Pellizzaro C. , Pirronello E. , Di Fronzo G. 
Published: May 2008

AbstractWe have investigated the effects exerted by sodium butyrate (NaBu) on the growth and cell cycle perturbations of four human breast cancer cell lines (MCF7, T47D, MDA‐MB231 and BT20) with different steroid receptor profiles. Moreover, since one of the supposed mechanisms of action for NaBu activity involves the induction of apoptosis, we have studied the effects of NaBu on DNA fragmentation by agarose gel electrophoresis and flow cytometry. In all investigated cell lines, NaBu exerted a time‐ and dose‐dependent inhibition of growth and caused a maximum inhibitory effect (85% to 90%) at the concentration of 2.5 mm. The inhibition was already evident after 3 days of treatment. The antiproliferative effect of NaBu was associated with a persistent block of cells in the G2M phase. The block was associated with apoptosis only in oestrogen‐receptor positive cell lines. The inhibiting effect of NaBu in hormone‐dependent and independent cell lines and its ability to induce apoptosis through a cell cycle perturbation in hormone‐dependent cell lines may have important implications in the treatment of human tumours including breast cancer.