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Results for “cellular proliferation”

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PubMed1997

Expression of the SIL gene is correlated with growth induction and cellular proliferation.

The SIL gene was discovered at the site of a cancer-associated interstitial deletion in which its promoter assumed the regulation of a second gene, SCL. The human SIL gene encodes a 1287-amino acid cytosolic protein that has been found to be highly conserved in the mouse. SIL is expressed in proliferating cells and is down-regulated when cellular proliferation ceases because of serum starvation, contact inhibition, or induction of terminal differentiation. SIL is induced within 1 h of stimulation by 20% serum in growth-arrested 3T3 cells. This induction is independent of protein synthesis because "superinduction" is observed in the presence of the protein synthesis inhibitor cyclohexamide. Thus, SIL is an immediate-early gene. Upon release from serum starvation of 3T3 fibroblasts, SIL mRNA and protein levels display a biphasic pattern during the first cell cycle. In contrast, in exponentially growing EL4 lymphoblasts, SIL mRNA is stable throughout the cell cycle, whereas SIL protein accumulates into G2 phase and then falls precipitously at the completion of the cell cycle. This pattern of cell cycle expression suggests that SIL may play an important role in cellular growth and proliferation.

Animals↗

PubMed1997

Inhibition of cellular proliferation by cyclosporin A during compensatory renal growth: flow cytometric analysis.

Cell cycle analysis using flow cytometer (FCMX) was performed to evaluate the influence of cyclosporin A (CsA) on cellular proliferation during compensatory renal growth (CRG) in uninephrectomized (Ux) rats. CsA (50 mg/kg/day) was administered subcutaneously for 7 days and animals were scarificed 0, 12, 24, 48, 72, 120 and 168 h after Ux. The percent changes in the S (DNA synthesis) and G2M (DNA replication) phases in the contralateral kidney were analyzed. The cortical cells entering the S and G2M phases showed significant differences between CsA and vehicle groups (p = 0.0001, p = 0.001, respectively), but the medullary cells entering the S and G2M phases showed no significant differences between the 2 groups (p = 1.000, respectively). In the cortex, the CsA group showed a significant decrease in the S (at 12, 72 and 120 h) and G2M phases (at 24, 72 and 120 h) compared to the vehicle group (p < 0.05, respectively), but there was no significant difference in the medulla. In conclusion, cellular proliferation is suppressed in cortical cells by CsA.

Animals↗

PubMed2000

Cellular proliferation and macrophage populations associated with implanted expanded polytetrafluoroethylene and polyethyleneterephthalate.

The chronic inflammatory response associated with the abluminal surface of polymeric vascular grafts has been suggested to affect adversely graft neovascularization, the cellular response at the luminal surface of vascular grafts, and overall graft patency. To better understand the source for this chronic inflammation, this study examined two types of macrophages and the amount of cellular proliferation around two widely used graft materials, expanded polytetrafluoroethylene (ePTFE) and polyethyleneterephthalate (PET or Dacron) implanted in the rat for 3 and 5 weeks. Serial sections of explants were analyzed for recruited macrophages (ED1), resident macrophages (ED2), and proliferating cells (PCNA). Results show that Dacron is more inflammatory than ePTFE and that there is a segregated macrophage response; the first 54 micrometer of perigraft tissue were composed predominantly of recruited macrophages (ED1+) while the more distal tissue consisted of resident macrophages (ED2+). Proliferating cells were located predominantly in this same 54 micrometer perigraft region. In subcutaneous tissue they accounted for 23% of all cells present around Dacron after 3 weeks of implantation and 8% after 5 weeks. Conversely, cellular proliferation around ePTFE increased from 4% at 3 weeks to 21% at 5 weeks. In adipose tissue, proliferation levels around the implanted polymers were lower and more similar after 3 and 5 weeks. Serial sections revealed the coordinate expression of PCNA and ED1 antigens by the same individual cells, suggesting that proliferation is a mechanism used to perpetuate the chronic inflammatory response. These results suggest a new target for designing treatments to alter inflammation and improve the healing associated with these biomaterials.

Adipose Tissue↗

PubMed1990

Cellular proliferation at the site of organ allografts and the influence of immunosuppressive therapy.

In this study we investigated cellular proliferation of T cells and macrophages at the site of rat cardiac allografts and determined the influence of immunosuppressive therapy on the proliferative characteristics of these cell types. A bromodeoxyuridine-labeling technique was used that allowed both the accurate detection of proliferative activity and the phenotypic characterization of cellular infiltrates within grafted tissues. In untreated recipients (BN----Lewis), T cytotoxic/suppressor cells as well as T helper cells showed proliferative activity at the site of the graft. The percentage of OX8-positive cells within the graft that showed proliferation ranged from 15% to 37%. The percentage of W3/25-positive cells within the graft that showed proliferation ranged from 25% to 30%. In contrast, macrophages hardly showed proliferative activity within the graft; only 1-4% of the macrophages stained positive for bromodeoxyuridine. From these observations it is concluded that the graft serves as a nonlymphoid tissue site, wherein lymphocytes can freely proliferate and expand. To study the influence of immunosuppressive therapy on cellular proliferation, the steroid budesonide, 120 micrograms/kg/day, was administered for 13 days (MST, 20 days). During effective immunosuppressive therapy, still a remarkable amount of infiltrating cells was present within the grafts. Moreover, immunosuppressive treatment did not primarily appear to affect the proliferative capacity of the individual cell types. OX8-positive cells as well as W3/25-positive cells clearly showed proliferative activity within the treated grafts. However, despite the presence of these proliferative cells, signs of graft destruction were absent during immunosuppressive therapy. This finding may shed new light on the effect of steroids at the site of the graft and their role in the prevention of tissue destruction.

Animals↗

PubMed1990

Influence of angiotensin converting enzyme inhibitor (captopril) on kidney epithelial cells in vitro: studies on potassium (86Rb) influx and cellular proliferation.

The effects of captopril on potassium influx and cellular proliferation in a dog kidney epithelial cell line (Madin-Darby canine kidney cells, MDCK) were studied. Na+K(+)-ATPase activity and the loop diuretic sensitive Na/K/2Cl- cotransport were measured using 86Rb as tracer substance. Cells were incubated with various concentrations of captopril (1-10 mmol/l). The furosemide sensitive Na/K/2Cl- cotransport was significantly decreased from 1 mmol/l onwards. Na+/K(+)-ATPase activity was lowered only when high amounts (10 mmol/l) of the drug were used. Cell proliferation was measured via [3H]thymidine incorporation. After incubation with 1 mmol/l captopril proliferation was strongly decreased (greater than 50%). Higher amounts (5-10 mmol/l) did not further suppress cell proliferation. The data suggest that natriuresis following ACE inhibition in vivo does not involve a direct effect of captopril on Na+K(+)-ATPase. However, the effect on cell proliferation may be of clinical relevance in respect to a possible mitogenic effect of angiotensin II.

Animals↗

PubMed1982

Acute lethal graft-versus-host disease stimulates cellular proliferation in the adult rat liver.

The present investigation was designed to analyse the effects of acute lethal graft-versus-host disease (GVHD) in adult (DA x LEW)F1 rats on cellular proliferation within the liver. The influence of the host thymus on GVHD-induced proliferation was also assessed. From 1-28 days after initiation of GVHD [3H]thymidine ([3H]-TdR) was injected i.v. and rats were killed one hour later. Percentage labelled cells (LI) of periportal infiltrating cells (PIC), hepatocytes (H), and sinusoidal lining cells (SC) were counted. Mean values for control rats were 0.3 +/- 0.1% (H), 0.4 +/- 0.1% (SC) and 0.2 +/- 0.1% (PIC). GVHD rats demonstrated a significant increase in LI of PIC (days 1-21), SC (days 2-17) and H (days 2-17). Most labelled cells in PIC were large lymphocytes. Peak LI values were 7.0 +/- 1.0% PIC (day 17), 6.8 +/- 0.9% SC (day 17), and 5.2 +/- 0.9% H (day 7), with all cellular compartments returning to near normal LI values by day 28. Stimulation of cellular proliferation occurred in all three liver cell compartments in neonatally thymectomized (TXM) rats. The intensity of GVHD-induced cell proliferation was significantly decreased at day 7 in all compartments and PIC was dramatically decreased at day 21 in TXM-GVHD rats as compared to non-TXM-GVHD rats. It is hypothesized that the general stimulation of hepatocyte cell proliferation in GVHD is related to the secretion of lymphokines by primarily donor and secondarily host T cells in the periportal infiltrate.

Animals↗

PubMedDate not supplied

Tumour necrosis factor alpha and cellular proliferation in primary biliary cirrhosis.

AIMS: 1) To evaluate serum levels and tissue expression of Tumour necrosis factor alpha in primary biliary cirrhosis: 2) to correlate serum tumour necrosis factor alpha levels and cellular proliferation with the severity and prognosis of liver disease. METHODS: Twenty-nine primary biliary cirrhosis patients (6 stage I, 8 II, 8 III, and 7 IV) entered the study. Serum tumour necrosis factor alpha was measured by EIA (Innogenetics, Antwerp, Belgium). Tissue tumour necrosis factor alpha and Ki-67 were tested by indirect immunoperoxidase staining on liver sections. RESULTS: Serum tumour necrosis factor alpha increased with the severity of histological stage (from 10.8 +/- 11 pg/ml in stage II to 17.1 +/- 10 in stage III and 22.8 +/- 8.7 in stage IV, p < 0.036). A positive correlation was also found between tumour necrosis factor alpha serum levels and the Mayo score (p < 0.05). A weak and sporadic expression of tumour necrosis factor alpha was observed in the inflammatory infiltrate around the bile ducts. Tissue Ki-67 (expressed as the labelling index in the hepatocellular nuclei) was evaluated in all stages of the disease (1.09 +/- 0.6% in stage I, 1.14 +/- 0.6% in stage II, 2.11 +/- 1.9% in stage III, and 2.67 +/- 2.8% in stage IV; the labelling index was significantly lower in early stages (I/II) than in late stages (III/IV), p < 0.05. A strong correlation between Ki-67 and the Mayo score was observed (p < 0.0005). CONCLUSIONS: 1) tumour necrosis factor alpha production seems related to the severity and the prognosis of primary biliary cirrhosis; 2) liver mononuclear cells in the inflammatory infiltrate do not seem to be the major site of tumour necrosis factor alpha release; 3) cellular proliferation is correlated with the severity of liver disease.

Adult↗

PubMed2006

Activation of transferrin receptor 1 by c-Myc enhances cellular proliferation and tumorigenesis.

Overexpression of transferrin receptor 1 (TFRC1), a major mediator of iron uptake in mammalian cells, is a common feature of human malignancies. Therapeutic strategies designed to interfere with tumor iron metabolism have targeted TFRC1. The c-Myc oncogenic transcription factor stimulates proliferation and growth by activating thousands of target genes. Here we demonstrate that TFRC1 is a critical downstream target of c-Myc. Using in vitro and in vivo models of B-cell lymphoma, we show that TFRC1 expression is activated by c-Myc. Chromatin immunoprecipitation experiments reveal that c-Myc directly binds a conserved region of TFRC1. In light of these findings, we sought to determine whether TFRC1 is required for c-Myc-mediated cellular proliferation and cell size control. TFRC1 inhibition decreases cellular proliferation and results in G1 arrest without affecting cell size. Consistent with these findings, expression profiling reveals that TFRC1 depletion alters expression of genes that regulate the cell cycle. Furthermore, enforced TFRC1 expression confers a growth advantage to cells and significantly enhances the rate of c-Myc-mediated tumor formation in vivo. These findings provide a molecular basis for increased TFRC1 expression in human tumors, illuminate the role of TFRC1 in the c-Myc target gene network, and support strategies that target TFRC1 for cancer therapy.

Animals↗

PubMed2003

Increased expression and processing of the Alzheimer amyloid precursor protein in pancreatic cancer may influence cellular proliferation.

Abnormal cleavage of amyloid precursor protein (APP) in the central nervous system has been linked to the development of Alzheimer's disease. Recent work has identified additional roles for APP in peripheral tissue, such as cellular proliferation and motility. APP undergoes proteolytic processing to release a soluble NH(2)-terminal ectodomain fragment (sAPP), an Abeta or p3 peptide, and cytosolic COOH-terminal fragments. We have identified the up-regulation of APP expression in pancreatic cancer cells both in vitro and in vivo. APP undergoes high levels of proteolytic processing in pancreatic cancer cells, and sAPP can be detected in collected medium in vitro. Inhibition of sAPP signaling reduces pancreatic cancer cell number via a reduction in cellular proliferation. We propose that APP may function to promote growth in pancreatic cancer cells via signaling through sAPP and may therefore represent a novel therapeutic target in pancreatic cancer.

Amyloid beta-Protein Precursor↗

PubMed1977

Effects of antiinflammatory agents on mouse skin tumor promotion, epidermal DNA synthesis, phorbol ester-induced cellular proliferation, and production of plasminogen activator.

The antinflammatory ateroids fluocinoine acetonide, fluocinonide, and fluclorolone acetonide were found to be very effectiveinhibitory agents of mouse skin tumor promotion. These steroids also drastically inhibited epidermal DNA synthesis and epidermal cellular proliferation induced by a phorbal ester tumor promoter. In addition, these compounds were potent inhibitors, of plasminogen activator production in tumor cell cultures. The clinically used non-steroidal antiinflammatory agents oxyphenbutazone, indomethacin, and Seclazone also inhibite tumor promotion but were much less effective. Although these agents are useful against inflammatory disorders in general when given p.o., in our studies they had little effect on inflammation and epidermal cellular proliferation induced by a phorbol ester tumor promoter when given topically. The afore mentioned nonsteroidal antiinflammatory agents also had little effect on epidermal DNA synthesis. Oxyphenbutazone and indomethacin were less potent inhibitors of plasminogen activator production in tumor cells than were the antiinflammatory steroids, and Seclazone produced a negligible inhibition. There is, therefore, a general correlation in the potencies of a series of steroidal antiinflammatory agents for inhibition of tumor promotion and their ability to inhibit plasminogen activator production by tumor cell cultures and epidermal DNA synthesis.

Animals↗

PubMedDate not supplied

Induction of vascular endothelial phenotype and cellular proliferation from human cord blood stem cells cultured in simulated microgravity.

Recent studies have demonstrated that stem cells derived from adult hematopoietic tissues are capable of trans-differentiation into non-hematopoietic cells, and that the culture in microgravity (microg) may modulate the proliferation and differentiation. We investigated the application of microg to human umbilical cord blood stem cells (CBSC) in the induction of vascular endothelial phenotype expression and cellular proliferation. CD34+ mononuclear cells were isolated from waste human umbilical cord blood samples and cultured in simulated microg for 14 days. The cells were seeded in rotary wall vessels (RWV) with or without microcarrier beads (MCB) and vascular endothelial growth factor was added during culture. Controls consisted of culture in 1 G. The cell cultures in RWV were examined by inverted microscopy. Cell counts, endothelial cell and leukocyte markers performed by flow cytometry and FACS scan were assayed at days 1, 4, 7 and at the termination of the experiments. Culture in RWV revealed significantly increased cellular proliferation with three-dimensional (3D) tissue-like aggregates. At day 4, CD34+ cells cultured in RWV bioreactor without MCB developed vascular tubular assemblies and exhibited endothelial phenotypic markers. These data suggest that CD34+ human umbilical cord blood progenitors are capable of trans-differentiation into vascular endothelial cell phenotype and assemble into 3D tissue structures. Culture of CBSC in simulated microg may be potentially beneficial in the fields of stem cell biology and somatic cell therapy.

Antigens, CD34↗

PubMedDate not supplied

Proteic expression of p53 and cellular proliferation in oral leukoplakias.

OBJECTIVES: We intend to know the protein expression of genetic alterations that take place in the early stages in the field cancerization of oral cavity in our means as well as to study the cellular proliferation by means of Ki-67 and the protein product expression of p53 to value if the alterations in the protein products expression of these markers happen in a sequential pathway through the different stages in the field cancerization of oral cavity. MATERIALS AND METHODS: A study was made by immunohistochemistry on 53 patients that presented lesions of oral leukoplaquia, assisted by the ENT service at University Hospital of Salamanca, from 1.990 up to 2000. 11 samples of normal epithelium, 15 mild to moderate dysplasias, 15 in situ carcinomas and 12 microinvasive carcinomas are included in the study. RESULTS: we find an increased cellular proliferation and p53 over-expression as we advance in the grade of severity histopathologic of these lesions. The most early alterations are a significant increase of cell proliferation in mild and moderate dysplasias and an increased p53 over-expression. CONCLUSIONS: Oral leukoplaquia is a precancerous stage that constitutes a cancerisable lesion due to the genetic alterations that mediate in the evolution of lesion. Routine Immunohistochemical and molecular study of these lesions allow us to know the protein expression of genetic alterations that can help in the early diagnosis and treatment of this pathology, having special relevance the study of Ki-67 in early stages and p53 in advanced lesions.

Adult↗

PubMed1981

Interrelationships between cellular proliferation, DNA alkylation and age as determinants of ethylnitrosourea-induced neoplasia.

Thirty-day-old Sprague--Dawley rats were used to study the persistence of DNA lesions (e.g., O6-alkylguanine) induced by various doses of ethylnitrosourea (ENU). Cellular proliferation was measured as an increment of DNA content per organ at 7 days post-treatment. We observed that the persistence of O6-EtGua was not affected by the various dose levels. Comparing the 3 organs, the persistence of O6-EtGua ranked in the order of brain greater than kidney greater than liver, while the percent increase in DNA content was measured as liver greater than kidney greater than brain. When the target specificity of ENU carcinogenesis in 30-day-old rats was compared to that following transplacental exposure in terms of its relationship to the persistence of DNA lesions and the rate of target cellular proliferation, it permitted the conclusion that induction of neoplasia in target cells is not only determined by persistent DNA lesions but also by the rate of proliferation of target cells at the time of exposure.

Age Factors↗

PubMed1997

Regulatory roles of high-density and low-density lipoproteins in cellular proliferation and secretion of progesterone and insulin-like growth factor I by enriched cultures of bovine small and large luteal cells.

We tested the hypotheses that bovine high-density (HDL) and low-density (LDL) lipoproteins differentially influence cellular proliferation and progesterone and IGF-I production by bovine small and large luteal cells. Unit gravity sedimentation was used to produce enriched cultures of small (> 95% pure) and large (75 to 90% pure) luteal cells from corpora lutea (CL) on d 4 and 10 of the estrous cycle. Addition of LDL, HDL, or both resulted in the maintenance of higher (P < .05) numbers of 3beta-hydroxysteroid dehydrogenase (HSD)-positive small and large cells in culture and produced a marked proliferation of 3beta-HSD-negative small luteal cells compared to control medium. Low-density lipoprotein and HDL each stimulated greater (P < .01) progesterone secretion in enriched large cell cultures on both days of the cycle, and by small luteal cells on d 10, compared to the control. Together, LDL and HDL maximized this response. Lipoproteins markedly stimulated (P < .01) the secretion of IGF-I by bovine large luteal cells, and secretion was greater (P < .05) by cells from d 10 CL compared to d 4 CL. Results suggest that the actions of lipoproteins in bovine luteal cells extend beyond their widely recognized roles in steroidogenesis and include remarkable effects on cellular proliferation and IGF-I secretion. Type of lipoprotein (LDL vs HDL) did not have differential effects on any of the variables measured.

3-Hydroxysteroid Dehydrogenases↗

PubMed2003

Variations in the cellular proliferation of prolactin cells from late pregnancy to lactation in rats.

Lactation is a physiological process associated with hyperactivity of hypophyseal prolactin-producing cells. It is known that the percentage of these cells is increased during lactation, although there are discrepancies in the reports regarding the mechanisms responsible for increasing the number of prolactin cells. In order to analyse whether this increase is a result of previous proliferation, variations in the proliferation rate of prolactin-positive cells were determined from late pregnancy to lactation in adult female rats by means of observation of the immunohistochemical expression of PCNA as a marker of cellular proliferation. During late pregnancy, a very significant increase in the percentage of proliferating prolactin cells was observed in comparison to non-pregnant females in the proestrus phase (p < 0.01). Although the percentage of prolactin-positive cells after one week of lactation was higher than in non-lactating or in pregnant females (p < 0.01), the proliferation rate was lower than in the other groups studied. In sum, our results suggest that late pregnancy constitutes a preliminary proliferative phase preparatory to the ensuing lactation phase and that endocrine changes in late pregnancy involve the cellular proliferation of hypophyseal prolactin cells in order to prepare the gland for later demands and to prevent proliferative changes from occurring during lactation.

Animals↗

PubMed1968

The kinetics of cellular proliferation in regenerating liver.

The study concerns the kinetics of cellular proliferation in the different cell populations of the normal and regenerating rat liver. A detailed analysis is presented, which includes techniques of in vivo labeling of DNA with tritiated thymidine and high-resolution radioautography, of the temporal and spatial patterns of DNA synthesis and cell division in the parenchymal cells, littoral cells, bile duct epithelium, and other cellular components in the liver during the first 64 hr of regeneration after partial hepatectomy. The analysis of cell population kinetics indicates that (a) the rate of entry of parenchymal cells into synthesis, after an initial burst of proliferative activity, was an orderly progression at 3-4%/hr; (b) most cells divided once and a few twice, a large proportion of the cell deficit being replaced by 72 hr after the onset of proliferation; (c) T(s) was approximately 8.0 hr; T(gg2+m/2), 3.0 hr; and M, approximately 1.0 hr. Littoral cell proliferation began about 24 hr after the onset of parenchymal cell proliferation; the rate of entry of littoral cells into synthesis was greater than 4%/hr. Interlobular bile duct cell proliferation lagged well behind the parenchymal and littoral cell populations both in time and extent of proliferation.

Animals↗

PubMed1998

Cellular proliferation in bovine luteal tissues of different reproductive states as demonstrated by Ki-67 immunocytochemistry.

Luteal tissue specimens of corpora lutea of oestrous cycle and pregnancy, post partum corpora lutea, and of luteinised follicular cysts of cows were harvested at slaughter. Cellular proliferation was examined employing Ki-67 immunocytochemistry. Ki-67 immunoreactivities could mainly be demonstrated within the nuclei of the theca interna and theca externa derived cell populations of cyclic corpora lutea. These cells obviously differentiated into vascular cells, connective tissue cells and small luteal cells. Proliferative activity was strongest in young corpora lutea and markedly reduced in the mature ones. During involution of corpora lutea of oestrous cycle Ki-67-positive cells were mainly found in vascular walls and connective tissue districts. Luteinised follicular cysts closely resembled cyclic corpora lutea. Corpora lutea of pregnancy exhibited foci of immunopositive cells close to blood vessels and connective tissue septae during whole gestation. Post partal luteal involution was characterised by Ki-67-positive cells within vascular walls and the surrounding stroma. Results suggest that luteal cellular proliferation is restricted mainly to theca interna-derived cells, which may differentiate to stromal cells and parenchymal cells.

Animals↗

PubMed2000

Inhibition of cellular proliferation by drug targeting of cyclin-dependent kinases.

Abnormal cellular proliferation is associated with the pathology of several diseases, including cancer, atherosclerosis and restenosis post-angioplasty. Therefore, antiproliferative therapies may be a suitable approach to treat these disorders. Candidate targets for such strategies include specific components of the cell cycle machinery. Progression through the cell cycle in mammalian cells requires the activation of several cyclin-dependent protein kinases (CDKs) through their association with regulatory subunits called cyclins. Active CDK/cyclin holoenzymes phosphorylate cellular proteins including the retinoblastoma susceptibility gene product (pRb) and the related pocket proteins p107 and p130. Several compounds have been described that directly or indirectly inhibit the activity of CDKs, which results in a suppression of cell growth. In this review, we will discuss the use of drugs targeting CDKs and their therapeutic application in animal models and clinical trials.

Animals↗