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Results for “Proliferation”

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PubMed1996

[Stages of cell proliferation in an experimental model of vitreoretinal proliferation following injection of platelet-rich plasma].

PURPOSE: To understand the pathophysiogenesis of the proliferative retinopathies, with a simple and valuable tool, for pathophysiologic and therapeutic assays. METHODS: We prepared a 10 million platelet concentrate from the same donor in 30 microliters, directly injected into the right eye of 46 pigmented and 14 albino rabbits. Animals were sacrificed at days 7, 14, 21 and one month after injection. Before histopathological analysis, all animals were followed clinically to evaluate the vitreoretinal proliferation, scored according to a 6 grade classification. RESULTS: Vitreoretinal proliferation started at day 5 or 8 after injection and increased during the 3 following weeks. Eighty per cent of the eyes showed at the end of the first month a tractional retinal detachment. histopathology revealed intense cell migration and proliferation close to ciliary body appearing from the 7th day, then further increasing rapidly. Immunostaining showed cell infiltrates expressing vimentin and cytokeratin. Overexpression of vimentin was also found in ciliary and retinal epithelia, and in Müller cells. CONCLUSION: This simple and valuable model can reproduce some characteristics of human vitreoretinal proliferations, such as the involvement of the ciliary body and the retinal pigment epithelium, inflammatory mechanisms occurring together with cell proliferation, and significant disturbances of cytoskeleton within deep ocular structures. Furthermore, this study is a first step on the way of antiproliferative assays, and for a better understanding of pathogenesis of intraocular proliferative disorders.

Animals↗

PubMed1998

Fibroblast growth factor 2 uses PLC-gamma1 for cell proliferation and PI3-kinase for alteration of cell shape and cell proliferation in corneal endothelial cells.

PURPOSE: Fibroblast growth factor 2 (FGF-2) induces endothelial-mesenchymal modulation in corneal endothelial cells, including stimulation of cell proliferation and cell shape change and induction of fibrillar collagen. In the present study, we investigated whether FGF-2 uses distinct signaling pathways for individual biological activities. METHODS: Specific metabolic inhibitors were used to block cell proliferation, while reversion of cellular morphology (modulated with FGF-2) was determined using specific antibodies and inhibitors. Immunocytochemical analysis was performed to identify any changes observed in the cytoskeleton in relation to cell shape. Association of cytoskeleton molecules with phosphatidylinositol 3-kinase was determined using co-precipitation. Cell proliferation was assayed using a colorimetric method for determining the number of viable cells. RESULTS: The fibroblastic morphology induced by FGF-2 reverted to a polygonal shape in cells treated with anti-FGF-2 antibody, anti-phosphatidylinositol 3-kinase antibody, LY294002, and genistein, while anti-phospholipase C gamma1 antibody did not to reverse the modulated cell morphology. Cell proliferation mediated by FGF-2 was blocked by metabolic inhibitors (genistein, LY294002 and wortmannin); genistein inhibited FGF-mediated cell proliferation in a dose-response manner and had a maximum inhibition of 80% at 100 microM, while inhibitors of phosphatidylinositol 3-kinase had less inhibitory effect than did genistein. When cytoskeleton proteins were examined, the characteristic punctated staining profiles of vinculin observed in normal cells were maintained in fibroblastic corneal endothelial cells treated with FGF-2. The inhibitors that cause reversion of cell shape also demonstrated the punctated staining potential. Likewise, the staining profiles of alpha-actinin and smooth muscle alpha-actin were not altered, regardless of cell shape. Filamentous actin and alpha-actinin were co-localized to the cytoskeleton and phosphatidylinositol 3-kinase was associated with the cytoskeleton, regardless of cell shape. CONCLUSIONS: These findings indicate that FGF-2 uses distinct and/or dual signaling pathways for individual biological activities.

Androstadienes↗

PubMed2005

[Inhibition of osteosarcoma cell proliferation by a short hairpin RNA targeting proliferation cell nuclear antigen].

OBJECTIVE: To construct a plasmid vector expressing the short hairpin RNA (shRNA) targeting proliferation cell nuclear antigen (PCNA), and to investigate its effect in vitro on the expression of PCNA, proliferation and apoptosis of human osteosarcoma cells. METHODS: A plasmid vector expressing the short hairpin RNA targeting at PCNA was constructed and transfected into human osteosarcoma cell line MG-63 by dosper liposomal method. PCNA mRNA and protein expressions were examined using RT-PCR and immunohistochemical staining, respectively. Inhibition of the cell proliferation was studied by MTT method and colony forming assay. DNA synthesis was analyzed by (3)H-TdR incorporation and the cell cycle was determined by flow cytometry. The apoptotic cells were stained with acridine orange. RESULTS: Expression of PCNA mRNA after the transfection was markedly inhibited by 80.51% with a PI value of 25.68% of that of the control group. PCNA shRNA inhibited MG-63 cell growth detected by using MTT method, with an inhibition rate of 61.78% at 48 h. DNA synthesis rate also decreased in the (3)H-TdR incorporation test. Flow cytometry analysis showed an increase of the percentage of G(0)/G(1) phase cells, along with a decrease of cell population in the S phase. The apoptosis rate of cells transfected with the plasmid vector was 16.54%. CONCLUSIONS: PCNA shRNA significantly suppresses the expression of PCNA at both mRNA and protein levels, corresponding to an inhibition of the proliferation of MG-63 cell and an increase of the cellular apoptosis.

Apoptosis↗

PubMed1992

A study of cell proliferation in formalin-fixed, wax-embedded bone marrow trephine biopsies using the monoclonal antibody PC10, reactive with proliferating cell nuclear antigen (PCNA).

We have investigated proliferation in bone marrow trephine biopsies from 32 patients with normal or abnormal haemopoiesis, using the monoclonal antibody PC10, which detects proliferating cell nuclear antigen (PCNA), together with immunohistochemical markers of haemopoietic cell lineage. PCNA immunostaining revealed the pattern of proliferation within individual haemopoietic lineages in normal marrow. Two unexpected observations were made: of erythroid cells, only pro-erythroblasts and occasional early normoblasts reacted, and positivity of megakaryocytes was unrelated to nuclear lobulation or CD61 expression. The pathological cases represented conditions in which haemopoiesis is increased (reactive hyperplasia, chronic granulocytic leukaemia, myeloproliferative and myelodysplastic syndromes, megaloblastic anaemia). Increases in the number, and disturbances of the spatial organization, of PCNA-expressing cells were present to a variable extent in all cases. Sheets of PCNA-positive megaloblastoid erythrocytes were frequently found in myelodysplastic and myeloproliferative tissue, associated with marked disturbances in the spatial organization of all haemopoietic lineages. Cases of megaloblastic anaemia due to vitamin B12/folate deficiency also demonstrated greatly increased erythroid PCNA expression, with positivity in some giant metamyelocytes. In addition to reflecting increased proliferation, elevated PCNA expression in some bone marrow pathologies may be due to altered kinetics of the protein induced by disturbances in growth factor production.

Autoantigens↗

PubMed1993

Immunohistochemical evidence for the expression of proliferating cell nuclear antigen (PCNA) by non-proliferating hepatocytes adjacent to metastatic tumours and in inflammatory conditions.

The possibility that proliferating cell nuclear antigen (PCNA) is expressed by non-proliferating liver cells was investigated. Liver biopsies from 107 patients were investigated, which included histologically normal liver, metastatic tumour, and inflammatory lesions. PCNA was detected using immunohistochemical staining with the monoclonal antibody PC10. This was compared with the proportion of proliferating cells as assessed by immunostaining for the Ki-67 antigen using the monoclonal antibody MIB 1. Most cases of histologically normal liver showed few PC10-positive cells. PCNA-positive hepatocytes far outnumbered those positive with MIB 1 in specimens showing metastatic tumour or an inflammatory cell infiltrate. There was no relation between the degree of PCNA overexpression and the type of tumour present or the nature of the inflammatory lesion. Other cell types, including the biliary epithelium, did not show this large difference between the proportions of PC10- and MIB 1-positive cells. It is concluded that non-proliferating hepatocytes increase their levels of PCNA in a wide variety of pathological conditions. This may be mediated by cytokines released by tumour cells or inflammatory cells.

Antibodies, Monoclonal↗

PubMed1995

Proliferating cell nuclear antigen (PCNA) detection of cellular proliferation in hypothyroid and hyperthyroid rat hearts.

Immunocytochemical techniques examining the expression of cell proliferation-related markers such as proliferating cell nuclear antigen (PCNA), may be employed to provide visual and quantitative evidence of cell proliferation. The efficacy of this method in frozen samples was tested on sections of 2-day-old rat heart. Mouse monoclonal anti-PCNA and goat anti-mouse IgG2a peroxidase-conjugated antibodies were applied to tissue cross-sections. PCNA positive (PCNA+) cells were evident in these sections as intensely stained, dark brown nuclei. This method was then applied to the hearts of four groups of adult rats (1) 1 month hyperthyroid, (2) 1 month hypothyroid, (3) 6 days hyperthyroid following 1 month hypothyroidism, or (4) euthyroid, in order to assess the ability of identifying and quantifying PCNA+cell types (myocyte, endothelial, or remaining, "other" cells). Serial cross-sections were prepared, half of the sections processed using the PCNA technique, while corresponding sections were stained with hematoxylin and eosin. Identification of PCNA+cell types was made by comparison of PCNA with H&E sections. PCNA labeling indices for a given cell type were expressed as the proportion of PCNA+nuclei per 1000 nuclei. No PCNA+myocyte nuclei were observed in any of the adult hearts. Only hypothyroid/hyperthyroid demonstrated significantly higher PCNA labeling of endothelial and "other" nuclei compared to euthyroid. This finding agrees with previous morphometric data which suggested capillary growth in these hearts. Results demonstrate that quantitation of PCNA expression on frozen heart tissue is possible, and can be used to provide direct, discernible evidence for cell proliferation.

Animals↗

PubMed2005

Ultrasound stimulation of tendon cell proliferation and upregulation of proliferating cell nuclear antigen.

Therapeutic ultrasound has been widely used in sports-related tendon injuries. However, previous research has not examined the molecular mechanism of this therapeutic effect on tendon cell proliferation. This study was designed to determine the in vitro effect of ultrasound on the proliferation of tendon cells intrinsic to rat Achilles tendon. Furthermore, the existence of a correlation between this effect and the expression of the proliferating cell nuclear antigen (PCNA) was also examined. Using cultured tendon cells, cell viability was evaluated by MTT assay. The expression of PCNA protein in cells was evaluated by immunocytochemistry. The mRNA expression of PCNA was determined by reverse transcription-polymerase chain reaction (RT-PCR). A dose-dependent increase in the cellularity of tendon cells by either pulsed or continuous mode ultrasound was demonstrated by MTT assay (p=0.044 for the pulsed mode; p=0.004 for the continuous mode). Ten minutes of treatment achieved maximum cellularity compared to 5 min of treatment time (p=0.010 for pulsed ultrasound; p=0.004 for continuous ultrasound). Immunocyto-chemical staining revealed that ultrasound treated tendon cells were stained more strongly for PCNA than were control cells. Upregulation of PCNA at the mRNA level was also confirmed by RT-PCR. In conclusion, ultrasound stimulates tendon cell proliferation in a process that is probably mediated by the upregulation of PCNA.

Achilles Tendon↗

PubMed2004

The proliferation inhibitory proteins p27(Kip1) and retinoblastoma are involved in the control of equine lymphocyte proliferation.

Observations in early equine pregnancy clearly reveal maternal immune recognition of and response to the presence of the conceptus. Nevertheless, both maternal cellular and humoral responses appear ineffective in destroying the developing placenta and fetus in early pregnancy. Our previous studies had shown that the pre-conditioned medium generated from the culture of equine invasive trophoblast inhibited mitogen-induced lymphocyte proliferation and the expression of cytokine messenger RNA in vitro. Those findings also suggested that lymphocytes might have been halted in the G0/G1 phase of the cell cycle. To characterize the cell cycle and the intracellular mechanisms involved in the inhibition of lymphocyte proliferation, equine peripheral blood lymphocytes were cultured in the presence or absence of pokeweed mitogen (PWM) in fresh medium, or in medium pre-conditioned through cell culture of invasive trophoblast cells or fetal fibroblasts. Two-color flow cytometric analysis for bromodeoxyuridine (BrdU) incorporation by stimulated lymphocytes, and concomitant DNA staining with 7-amino-actinomycin D (7-AAD), indicated that a greater proportion of lymphocytes were found in the G0/G1 phase of the cell cycle when cultured in the invasive trophoblast cell pre-conditioned medium compared to controls. Analysis using carboxyfluorescein diacetate succinimidyl ester (CFSE) fluorescence intensity demonstrated that lymphocytes cultured in the presence of invasive trophoblast cell pre-conditioned medium had fewer cells going through division, but that those fewer cells sustained similar numbers of cell divisions as in control cultures. Hypophosphorylated retinoblastoma (Rb) protein expression was increased and p27Kip1 expression was maintained at higher levels in lymphocytes cultured in invasive trophoblast pre-conditioned medium compared to fresh medium. In agreement with these data, flow cytometric measurement of the Ki-67 protein expression in lymphocytes cultured in invasive trophoblast pre-conditioned medium was lower in comparison to controls. These findings suggest that the equine lymphocyte proliferation is at least partially regulated by the expression of proliferation inhibitory proteins such as p27Kip1 and hypophosphorylated Rb. These proteins seem to be important regulators of cell cycle transition between G1 and S phase in equine lymphocytes.

Animals↗

PubMed2003

The relationship between liver peroxisome proliferation and adipose tissue atrophy induced by peroxisome proliferator exposure and withdrawal in mice.

We have previously demonstrated that severe adipose tissue atrophy occurs upon dietary treatment of mice with potent peroxisome proliferators (PPs). This atrophy occurs subsequent to peroxisome proliferation in the liver and may represent a novel addition to the pleiotropic effects exerted by PPs. In the present study we have characterized the recovery of mice from such atrophy following cessation of exposure. Following termination of treatment with perfluorooctanoic acid (PFOA) for 7 days, the adipose tissue atrophy was rapidly reversed, beginning on 2-5 days of recovery and being complete within 10 days. In contrast, hepatic peroxisome proliferation recovered much more slowly, indicating that these processes are not strictly coordinated. Analysis of lipoprotein lipase and hormone-sensitive lipase activities in adipose tissue revealed that the decrease and increase in these activities, respectively, caused by PFOA were both reversed within 10 days of recovery. Overall, these data provide further support for our previous conclusion that the adipose tissue atrophy induced by PFOA is caused, at least in part, by changes in the activities of lipoprotein lipase and hormone-sensitive lipase. The serum level of cholesterol, which increased after termination of PFOA treatment, returned to normal with a time-course similar to the recovery of adipose tissue weight, although hepatic peroxisome proliferation was still present. The possible relationship between the reduction in serum cholesterol and/or in its availability to peripheral tissues and the associated atrophy of adipose tissues caused by PPs is discussed.

Adipose Tissue↗

PubMed2001

Studies of early hepatocellular proliferation and peroxisomal proliferation in Wistar rats treated with herbicide diclofop.

A study was performed to determine whether diclofop (2-(4-(2,4-dichlorophenoxy) phenoxy)propionic acid), introduced as a herbicide, exhibits the properties of peroxisome proliferators (PPs). Diclofop was administered orally at 7-56 mg/kg body weight per day to male Wistar rats for 2, 4, 7 or 14 consecutive days and some effects regarded as early hepatic markers of PPs were studied. The early changes in rat liver, produced by short-term treatment with diclofop consisted of mitogenesis and, time- and dose-related increase in liver weight. Hepatomegaly was typically associated with proliferation of smooth endoplasmic reticulum (SER) and peroxisomes. The parallel biochemical measurements showed that there was a dose-dependent increase in peroxisomal palmitoyl-CoA oxidation and catalase activity in treated rats. Markers of hepatocellular proliferation (S- and M-phase) indicated that mitogenesis was transient and declined despite continuation of diclofop treatment. The threshold exposure level for the palmitoyl-CoA oxidation (one of the peroxisome proliferation markers) was approximately the same (14 mg/kg body weightxper day) as for the stimulation of mitogenesis in Wistar rats. However, for hepatomegaly and catalase activity the threshold exposure level was 7 mg/kg body weightxper day. The results presented here demonstrate clearly that diclofop belongs to a class of rodent PPs.

Animals↗

PubMed1994

Quantification of hepatocytic proliferation in the laboratory mouse. A comparative study using immunohistochemical detection of bromodeoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) expression.

The proliferation rate in livers of 120 mice (60 males and 60 females) was analyzed by immunohistochemical detection of bromodeoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) expression on ethanol-fixed/paraffin-embedded specimens. Mice were divided into three groups, with 20 males and 20 females in each group: mice in the first group served as controls, while mice in the second and third groups were treated with a low and a high dose, respectively, of a non-genotoxic drug candidate for 2 weeks. A dose-related increase of the proliferating hepatocyte fraction was disclosed by both immunohistochemical methods, reaching statistical significance already in the low-dose male group for BrdU incorporation and in both male and female low-dose groups for PCNA expression. A good correlation between the degree of BrdU and PCNA labeling was observed and, as expected, the percentage of PCNA expressing cells was generally higher than the percentage of BrdU-positive cells. We concluded that the detection of PCNA expression represents a reliable method for the quantification of the hepatocytic proliferating fraction in rodents and allows the use of archival material for cell kinetic investigations in toxicologic pathology.

Animals↗

PubMed1999

Proliferation indices in spontaneous canine lung cancer: proliferating cell nuclear antigen (PCNA), Ki-67 (MIB1) and mitotic counts.

Proliferation indices were measured for specimens from 55 spontaneous canine lung tumours, collected by surgical biopsy from clinical patients and archived in paraffin wax blocks. These indices were then related to the mitotic index and histological type of the tumour. Proliferating cell nuclear antigen (PCNA) and Ki-67 (MIB1) proteins were detected immunohistochemically with a biotin-streptavidin amplified detection system on a representative tissue section from each tumour. Five adjacent, non-overlapping fields were selected at random, and 200 cells per field were examined in each section. For PCNA, cells were classified subjectively into negative, weak or strong reactivity groups, based on nuclear staining. MIB1 cells were classified as negative or positive, based on nuclear staining. Mitotic figures were counted in anti-PCNA-labelled and anti-MIB1-labelled sections, in the same tumour areas as those in which indices were established. Mitotic counts were also done on haematoxylin and eosin-stained tissue sections. Linear regression analysis showed that all PCNA, MIB1 and mitotic indices had highly significant positive correlations (P<0.0001) with each other. Adenosquamous and squamous cell carcinomas differed from other histological tumour types in having significantly higher proliferation indices. These data suggest that growth rates for lung tumours in the dog vary according to histological type. On the basis of differences in proliferation indices and the distribution of immunoreactivity between histological subtypes in this study, it would seem that immunohistochemical detection of PCNA and MIB/1 reactivity and analysis of mitotic figures in routinely processed tissues may be useful in the diagnosis of lung tumours. 1999 W.B. Saunders and Company Ltd.

Adenocarcinoma↗

PubMed2005

Inhibitory activity on matrix metalloproteinases and cell-proliferating activity of tissue inhibitor of metalloproteinases-1 (TIMP-1)-contrastive difference between human and bovine TIMP-1s on mouse cell proliferation.

Either human or bovine TIMP-1 inhibited matrix metalloproteinase (MMP) activities, such as collagenolytic, gelatinolytic and caseinolytic, expressed by mouse cells as well as those expressed by human cells. Bovine TIMP-1 stimulated the proliferation of both human and mouse cells, but human TIMP-1 only proliferate human cells and not mouse cells indicating that the cell-proliferating activity has more strict species specificity than MMP inhibitory activity. All the results from [(3)H]thymidine incorporation, the phosphorylation of tyrosine-containing cellular proteins and extracellular-signal-regulated protein kinases supported the cell-proliferating properties of both human and bovine TIMP-1s. Human TIMP-1 seems not to bind to TIMP-1 receptors on mouse cells.

Animals↗

PubMed2000

Peroxisome proliferator-activated receptor alpha is restricted to hepatic parenchymal cells, not Kupffer cells: implications for the mechanism of action of peroxisome proliferators in hepatocarcinogenesis.

Peroxisome proliferators increase hepatocyte proliferation and cause liver tumors in rodents, yet the mechanism of action is not understood. Based on studies with null mice it is known that peroxisome proliferator-activated receptor-alpha (PPARalpha) is involved. There is also evidence that Kupffer cells play a central role in peroxisome proliferator-induced carcinogenesis, most likely via mechanisms involving increases in superoxide, activation of nuclear factor kappaB and production of tumor necrosis factor-alpha (TNFalpha). However, it is not known whether PPARalpha is constitutively expressed in Kupffer cells. Therefore, the expression of PPAR isoforms in rat Kupffer and parenchymal cells was examined. Kupffer cells and hepatocytes of >99% purity were isolated from rats fed either a control diet or one containing 0.1% WY-14,643 for 1 week. Protein and RNA were obtained and PPAR expression was analyzed using northern and western blots. PPARalpha, PPARbeta and PPARgamma mRNA was detected in purified hepatocytes. In Kupffer cells, mRNA encoding PPARgamma was present while transcripts for PPARalpha and PPARbeta were not detected. Immunoblots were consistent with the results found by northern analysis. Moreover, when Kupffer cells from wild-type or PPARalpha-null mice were treated with WY-14,643 in vitro, superoxide production was similar. Combined, these results show that PPARalpha is expressed in rat parenchymal cells but not in Kupffer cells. These data are consistent with the hypothesis that parenchymal cells respond to Kupffer cell-derived TNFalpha via mechanisms dependent on PPARalpha within the parenchymal cells.

Animals↗

PubMed1994

Immunohistochemical localization of proliferating cell nuclear antigen as a tool to study cell proliferation in rodent and primate testes.

The immunohistochemical localization of proliferating cell nuclear antigen (PCNA) has become a widely used method for the detection of proliferating cells in cancerous tissues. PCNA expression is maximal around the S phase of the cell cycle. This study has evaluated the applicability of PCNA localization for the analysis of germ cell proliferation in rats, Djungarian hamsters, rhesus and cynomolgus monkeys and men, using Bouin's-fixed, paraplast-embedded tissue. In addition, involuted testes from photoinhibited hamsters, testes from immature rhesus monkeys and from GnRH antagonist-treated rats and cynomolgus monkeys were included. Monoclonal mouse anti-PCNA antibody (clone: PC10) was used for detection of the antigen. Visualization was performed by immunogold-silver staining or avidin-biotin staining. PCNA labelling was confined to the nuclei of spermatogonia and early spermatocytes within the seminiferous epithelium of all species. The distribution of PCNA among the different types of A-spermatogonia in primates is in good agreement with the previously described proliferation pattern of these cells. No staining was observed in resting A-dark spermatogonia, while differentiating A-pale spermatogonia were positive at distinct stages of the seminiferous epithelium cycle. In the rodent species the pattern of labelled A-spermatogonia was stage-specific, but agreed only partly with the previously described pattern of mitotic figures of A-spermatogonia. Hormonal withdrawal induced a decrease in the number of PCNA-positive cells in adult rats, hamsters and monkeys. In immature testes from rhesus monkeys positive staining was present in spermatogonia but also in some Sertoli cells, indicating proliferative activity of Sertoli cells in the prepubertal stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1992

Proliferating cell nuclear antigen (PCNA) in common epidermal lesions. An immunohistochemical study of proliferating cell populations.

A commercially available antibody to proliferating cell nuclear antigen was used to characterize and compare proliferating cell populations in paraffin sections of benign, premalignant, and malignant lesions of human epidermis using routine immunohistochemical techniques. Three patterns emerged. An ordered pattern was found in prurigo nodularis and keratoacanthoma, wherein moderately and strongly positive nuclei were distributed in a continuous, basal-suprabasal layer of relatively uniform thickness. There was graded loss and ultimate extinction of PCNA staining in progressively more superficial epidermal cells. A basal dysplastic pattern was found in actinic keratosis and squamous cell carcinoma. Nuclei of essentially all dysplastic cells of both categories expressed PCNA, with a preponderance of strongly positive nuclei. These were localized to basal-suprabasal zones that were often expanded. Loss of PCNA reactivity toward the surface was often abrupt. Bowen's disease exhibited a diffuse dysplastic pattern, wherein large numbers of moderately and strongly positive nuclei, in random array, were present in essentially full thickness distribution. In many fields, however, a layer of cytologically bland basal cells, with faint or no nuclear staining, was interposed between dysplastic epithelium and dermis. This study has demonstrated that proliferating cell populations in epidermal lesions can be assessed with simple, inexpensive methods. There were consistent differences between the proliferating cell populations of the various entities studied, differences that can be reasonably correlated with other known clinical, microscopic, and biologic features of the lesions. This technique should provide an interesting new avenue for study of diverse cutaneous diseases.

Antigens, Neoplasm↗

PubMed1994

In situ analysis of cellular proliferation in canine, feline and equine tumors by immunohistochemistry: a comparison of bromodeoxyuridine, proliferating cell nuclear antigen, and interchromatin-associated antigen immunostaining techniques.

Cell proliferation in canine, feline, and equine tumors was evaluated using immunohistochemical detection of in vitro 5-bromodeoxyuridine (BrdU) incorporation, proliferating cell nuclear antigen (PCNA), and interchromatin-associated antigen (p105). Ten tumors in each species were analyzed. The tumor proliferative fraction (PF) was defined as the percentage of labeled nuclei for 5,000 tumor nuclei counted. Immunoreactivity was observed with all techniques in all species. A good correlation was observed between the proliferative fractions measured with the BrdU (PFBrdU) and PCNA (PFPCNA) techniques (rs = 0.523, P = 0.0026). There was no correlation between the PFs measured with the BrdU (PFBrdU) and p105 (PFP105) techniques. Using the median values obtained from the different approaches as cutoff points to define slowly and rapidly proliferating tumors, there was an 80% agreement (P = 0.009) between PFBrdU and PFPCNA and no agreement between PFBrdU and PFP105. The results of this study indicate that both BrdU and PCNA labeling methods can be used reliably for identifying proliferating cells in animal tumors. In addition, PCNA could be used to replace the BrdU method to assess tumor proliferative fraction because it does not require pretreatment of tissues.

Animals↗

PubMed2005

OX40 signals during priming on dendritic cells inhibit CD4 T cell proliferation: IL-4 switches off OX40 signals enabling rapid proliferation of Th2 effectors.

In this study we examined the role and regulation of OX40 signals during CD4 T cell priming on dendritic cells (DCs). Contrary to expectation, OX40-deficient cells proliferated more rapidly than their normal counterparts, particularly when stimulated with peptide in the absence of added cytokines. This proliferative advantage was not apparent for Th2-differentiated cells. When the reasons for this were investigated, we found that the cytokine IL-4 specifically down-regulated expression of OX40 ligand on T, B, and DCs, but not on the CD4(+)CD3(-) cells linked with selection of Th2 cells into the memory compartment. OX40 ligand expression was also down-regulated on rapidly proliferating Th1 effectors. These data are compatible with OX40 signals acting during priming as a check on naive T cell proliferation while T cells integrate additional DC signals. This would serve to limit inappropriate T cell responses. In contrast, OX40 signals from CD4(+)CD3(-) cells located in the outer T zone select proliferating Th2 effectors into the memory T cell pool.

Animals↗