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1.
We previously reported that increased DNA methylation was an important mechanism of silencing the p27 gene in some pituitary
tumor cell lines [1]. DNA methylation correlated inversely with p27 gene expression. The p27 and cyclin D2 genes are located
in the same region of mouse chromosome 6, rat chromosome 4, and human chromosome 12p13. Because both genes are located in
the same gene cluster, we investigated whether methylation was a principal mechanism regulating cyclin D2 as well as p27 expression
in rodent pituitary cell lines. Bisulfite genomic sequencing showed that the normally unmethylated cytosines of the p27 gene
in normal pituitary (NP) were extensively methylated in GH3 and GHRH-CL1 cells, but not in AtT 20, αT3-1 and LβT2 cells; but cyclin D2 was extensively inactivated in various pituitary tumor cell lines by increased DNA methylation. These abnormalities of methylation in p27 and cyclin
D2 genes occurred with different frequencies in five pituitary tumor cell lines with 100% (5/5) methylation of the cyclin
D2 gene and 40% (2/5) methylation of the p27 gene. Treatment with the methyl transferase inhibitor 5′-aza-2′-deoxycytidine
(AZAdC) increased expression of cyclin D2 and p27 in GH3 and GHRH-CL1 pituitary tumor cells. There was a correlation between
hypermethylation and gene expression. GH3 tumors implanted into Wistar-Furth rats in vivo did not change the methylation status of the p27 and cyclin D2 genes. These
data indicate a coordinately reduced expression of these two linked genes in most rodent pituitary tumor cell lines and suggest
that methylation of cyclin D2 and p27 might occur in a “hot spot” in this gene-rich cluster.
Supported in part by NIH CA 37231 and CA 42951 相似文献
2.
The effects of estradiol 17β (E2) on the regulation of estrogen receptor (ER) mRNA amounts in normal and neoplastic rat pituitary tissues were analyzed by
in situ hybridization with an oligonucleotide probe. E2 treatment produced a significant increase in ER mRNA amounts in two transplantable pituitary tumors (MtT/Wl5 and MtT/F4)
and in the GH3 cell line. ER mRNA amounts were also increased In normal pituitaries after 6 weeks of E2 treatment, but the differences were not significant. Biochemical assay of ER proteins confirmed the presence of ER protein
in MtT/Wl 5 and MtT/F4 tumors. “Cytoplasmic” ER proteins were decreased by E2 in the MtT/Wl5 tumor.These results indicate that ER mRNA is present in normal pituitaries and in pituitary tumors and can
be regulated by estrogen treatment in vivo and in vitro. The inhibitory effects of high estrogen concentration on proliferation
of transplantable pituitary tumors in vivo and GH3 cells in vitro is not explained by the absence of ER mRNAs in these tumors. 相似文献
3.
DNA Methylation Regulates p27Kip1 Expression in Rodent Pituitary Cell Lines 总被引:11,自引:0,他引:11
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Xiang Qian Long Jin Elzbieta Kulig Ricardo V. Lloyd 《The American journal of pathology》1998,153(5):1475-1482
We previously reported loss of expression of p27Kip1 (p27) protein in rat GH3 and mouse GHRH-CL1 pituitary tumor cells compared with normal pituitary (NP). The molecular basis for the loss of expression of p27 protein in GH3 and GHRH-CL1 cells is unknown. To determine the role of p27 gene methylation in the regulation of the expression of this cell cycle protein, the methylation patterns of p27 in normal and neoplastic pituitary cells was analyzed. Inhibition of DNA methyltransferase (DNA-MTase) with 5-aza-2′-deoxycytidine (AZAdC) induced expression of both p27 protein and mRNA when GH3 and GHRH-CL1 cells were treated for 7 days in vitro. DNA methylation correlated inversely with the expression of p27 gene products in NP and pituitary tumor cell lines. Bisulfite genomic sequencing analysis showed that the normally unmethylated cytosines in exon 1 in NP and AtT20 cells were extensively methylated in GH3 and GHRH-CL1 cells. After treatment of GH3 and GHRH-CL1 cells with 10 μmol/L AZAdC, there were decreased numbers of methylated cytosines (by 60% to 90%) with variable methylation patterns observed by bisulfite genomic sequencing. Analysis of genomic DNA with methylation-sensitive enzymes showed that all SmaI, HhaI, and AvaI enzyme sites of the p27 gene in exon 1 were methylated in GH3 cells but not in NP, confirming the bisulfite genomic sequencing results. AtT20 cells and a human pituitary null cell adenoma cell line (HP75), which expressed abundant p27, had a methylation pattern similar to the NP. DNA-MTase activity was elevated fourfold in GH3 cells and twofold in GHRH-CL1 cells compared with DNA-MTase activity in NP and AtT20 cells. These results suggest that increased DNA methylation is another mechanism of silencing of the p27 gene in some pituitary tumors and possibly in other types of neoplasms. 相似文献
4.
5.
P. Selvaraj S. Prabhu Anand M. Harishankar K. Alagarasu 《Journal of clinical immunology》2009,29(4):470-478
Introduction Vitamin D3, which exerts its effect through vitamin D receptor (VDR), is known for its potent immunomodulatory activities. Associations
between low serum vitamin D3 levels and increased risk of tuberculosis have been reported.
Study Subjects and Methods Plasma 1,25 dihydroxy vitamin D3 levels (1,25(OH)2 D3) and ex vivo levels of VDR protein from peripheral blood mononuclear cells were studied in 65 pulmonary tuberculosis (PTB)
patients and 60 normal healthy subjects (NHS) using enzyme-linked immunosorbent assay-based methods. Using real-time polymerase
chain reaction (PCR), induction of VDR, cathelicidin, and CYP27B1 mRNA were studied in live Mycobacterium tuberculosis-stimulated macrophage cultures treated with or without 1,25 dihydroxy vitamin D3. VDR and CYP27B1 (-1077 A/T) gene polymorphisms were studied using PCR-based methods.
Results 1,25(OH)2 D3 were significantly increased (p = 0.0004), while ex vivo levels of VDR protein were significantly decreased in PTB patients (p = 0.017) as compared to NHS. 1,25(OH)2 D3 levels were not different between variant genotypes of CYP27B1. A trend towards decreased levels of VDR protein was observed
among NHS with BsmI BB and TaqI tt genotypes compared to NHS with other genotypes. Relative quantification of mRNA using real-time PCR revealed increased
VDR mRNA expression in live M. tuberculosis-stimulated culture in PTB patients (p < 0.01) than normal healthy subjects. Cathelicidin mRNA expression was significantly increased in vitamin D3-treated cultures compared to unstimulated and M. tuberculosis-stimulated culture in both patients (p < 0.001) and NHS (p < 0.05).
Conclusions The present study suggests that PTB patients may have increased 1,25(OH)2 D3 levels, and this might lead to downregulation of VDR expression. Decreased VDR levels could result in defective VDR signaling.
Moreover, addition of 1,25(OH)2 D3 might lead to increased expression of cathelicidin which could enhance the immunity against tuberculosis. 相似文献
6.
TNF-α is postulated to play a significant role in regulating TGF-β1 expression. In lung fibroblasts, for example, TNF-α is supposed to induce TGF-β1 via AP-1 activation. TNF-α receptor, knock-out mice are resistant to induced fibrosis and over-expression of TNF-α causes
increased TGF-β1 production in mice. Therefore, we investigated whether TNF-α mRNA levels are associated with the TGF-β1 mRNA levels of blood leucocytes in humans. Quantitative real-time PCR of TNF-α and TGF-β1 was performed in 118 Germans. Calculations of expression were made with the 2−ΔΔCT method. When the investigated population was divided in two groups (TNF-α low and TNF-α high) by the median of the determined
TNF-α expression, highly significant (p < 0.0001) differences of TGF-β1 mRNA expression were revealed. Additionally, dividing the investigated population into quartiles
of the determined TNF-α expression showed significantly different TGF-β1 mRNA expressions. Comparing the determined CT-values
of TNF-α in context with these of TGF-β1, a coefficient of determination R
2 = 0.4635 was calculated. In this study we demonstrated in vivo a significant association of the relative TNF-α/B2M mRNA expression and the relative TGF-β1/B2M mRNA expression in 118 Germans. 相似文献
7.
Luis?Carretero Francisco?Barros Pablo?Miranda Jorge?Fernández-Trillo Angeles?Machín Pilar?de la?Pe?a Pedro?Domínguez
While the thyrotropin-releasing hormone (TRH) effect of raising intracellular Ca2+ levels has been shown to rely on Gq/11 and PLC activation, the molecular mechanisms involved in the regulation of ERG K+ channels by TRH are still partially unknown. We have analysed the effects of βγ scavengers, Akt/PKB inactivation, and TRH
receptor (TRH-R) overexpression on such regulation in native and heterologous expression cell systems. In native rat pituitary
GH3 cells β-ARK/CT, Gαt, and phosducin significantly reduced TRH inhibition of rERG currents, whereas in HEK-H36/T1 cells permanently expressing
TRH-R and hERG, neither of the βγ scavengers affected the TRH-induced shift in V
1/2. Use of specific siRNAs to knock Akt/PKB expression down abolished the TRH effect on HEK-H36/T1 cell hERG, but not on rERG
from GH3 cells. Indeed, wortmannin or long insulin pretreatment also blocked TRH regulation of ERG currents in HEK-H36/T1 but not
in GH3 cells. To determine whether these differences could be related to the amount of TRH-Rs in the cell, we studied the TRH concentration
dependence of the Ca2+ and ERG responses in GH3 cells overexpressing the receptors. The data indicated that independent of the receptor number additional cellular factor(s)
contribute differently to couple the TRH-R to hERG channel modulation in HEK-H36/T1 cells. We conclude that regulation of
ERG currents by TRH and its receptor is transduced in GH3 and HEK-H36/T1 cell systems through common and different elements, and hence that the cell type influences the signalling
pathways involved in the TRH-evoked responses. 相似文献
8.
Long Jin MD Elzbieta Kulig PhD Xiang Qian MD Bernd W. Scheithauer MD Norman L. Eberhardt PhD Ricardo V. Lloyd MD PhD 《Endocrine pathology》1998,9(2):169-184
Human pituitary cells proliferate very slowly in vitro. Only a few cell lines have been established, and these have been used
mainly for short-term studies. To obtain immortalized cell lines of human pituitary adenomas for in vitro studies, we infected
adenoma cells with a replication-defective recombinant human adenovirus, which contains an SV40 early large T-antigen. One
of the cell lines (HP75), which has been studied in culture during 60 passages, has been extensively characterized. It expressed
the large T-antigen protein and its mRNA, as well as the genes for FSH-β, LH-β and α-subunit (α-SU) of gonadotropin hormone.
The HP75 cell line also expressed the genes of various members of the chromogranin (Cg)/secretogranin (Sg) family, including
CgA as well as the prohormone convertases PC1/3 and PC2. CgA was processed to pancreastatin in vitro, which was secreted into
the culture medium. Treatment with phorbol 12-myristate 13-acetate (PMA), TGF-β1, and forskolin increased CgA expression in
the cells and stimulated pancreastatin secretion into the medium while inhibiting cell growth. The HP75 cell line also expressed
TGF-β mRNA isoforms (β1, β2, β3) and the mRNAs for the receptors for TGF-β (RI, RII, and RIII). The cells responded to TGF-β1
in vitro by increasing CgA protein expression and pancreastatin secretion. TGF-β-RII protein and mRNA expression were both
increased by PMA.
Ultrastructural studies showed that the HP75 cells had very few dense-core secretory granules and a poorly developed Golgi
complex. After treatment with TGF-β1 and PMA, there was an increase in the development of rough endoplasmic reticulum and
the Golgi complex.
This is the first report of the development of an immortalized human pituitary cell line that retains some differentiated
functions. HP75 can be used to study TGF-β and CgA functions in pituitary cells. Replication-defective recombinant human adenovirus
with an SV40 large T-antigen insert can be used to generate other immortalized human pituitary cell lines for in vitro studies. 相似文献
9.
Cyclins are prime cell-cycle regulators central to the control of cell proliferation in eukaryotic cells. The formation of
cyclin/cyclin-dependent kinases (CDK) complexes activates the kinases and initiates a cascade of events, which directs cells
through the cell cycle. CDK inhibitors (CDKIs) such as p27kip1 inhibit cyclin-CDK complexes and function as negative regulators of the cell cycle. Previous studies have shown that p27kip1 is decreased in malignant relative to benign thyroid tumors, but its role and interaction with other cell cycle regulatory
proteins have not been well established in oncocytic lesions of the thyroid. We studied the expression of p27kip1, cyclins D1 and E, and Ki67 in 20 cases of oncocytic adenoma (AD), 6 cases of oncocytic carcinoma (CA), 8 cases of Hashimoto’s
thyroiditis (HT), and 9 cases of nodular goiter with oncocytic change (NG) by immunohistochemistry. In the latter two lesions
only oncocytic cells were evaluated. The positive staining was stratified into four groups. Statistical analysis was done
using the Kruskal-Wallis one-way analysis of variance test, and, when significant, the Dunn multiple-comparisons procedure
was used to determine pairwise differences. All 20 AD were p27kip1 positive, 10 were 4+, 2 were 3+, and the remaining 8 were 1+. In contrast all 6 CA showed 4+ p27kip1 staining, of the 8 HT, 2 were 4+, two 3+, three 1+, and 1 was negative. All 9 NG were p27 positive, 7 showed 4+, one 3+,
and one 1+ staining. On pairwise comparison differences in p27kip1 staining between AD and CA and between HT and CA were statistically significant (p=0.0243 and p=0.0142, respectively). In all but one case Ki67 expression was either very low (<3%) or negative. No significant differences
were seen in the expression of cyclin D1 or cyclin E among the groups observed. In conclusion, the increased p27kip1 expression in malignant oncocytic tumors relative to benign oncocytic lesions is unlike any other malignant progression reported
in the thyroid and other organ systems in the body. This may reflect on the biologic nature of the oncocytic cells of the
thyroid and the significance of this finding remains to be established. Proliferative activity as studied by Ki67 immunostaining
was not helpful in distinguishing benign from malignant oncocytic tumors. 相似文献
10.
Di-8-ANEPPS (4-{2-[6-(dibutylamino)-2-naphthalenyl]-ethenyl}-1-(3-sulfopropyl)pyridinium inner salt) has been used as a fast-response
voltage-sensitive styrylpyridinium probe. However, little is known regarding the mechanism of di-8-ANEPPS actions on ion currents.
In this study, the effects of this dye on ion currents were investigated in pituitary GH3 cells. In whole-cell configuration, di-8-ANEPPS (10 μM) reversibly increased the amplitude of Ca2+-activated K+ current. In inside-out configuration, di-8-ANEPPS (10 μM) applied to the intracellular surface of the membrane caused no
change in single-channel conductance; however, it did enhance the activity of large-conductance Ca2+-activated K+ (BKCa) channels with an EC50 value of 7.5 μM. This compound caused a left shift in the activation curve of BKCa channels with no change in the gating charge of these channels. A decrease in mean closed time of the channels was seen in
the presence of this dye. In the cell-attached mode, di-8-ANEPPS applied on the extracellular side of the membrane also activated
BKCa channels. However, neither voltage-gated K+ nor ether-à-go-go-related gene (erg)-mediated K+ currents in GH3 cells were affected by di-8-APPNES. Under current-clamp configuration, di-8-ANEPPS (10 μM) decreased the firing of action
potentials in GH3 cells. In pancreatic βTC-6 cells, di-8-APPNES (10 μM) also increased BKCa-channel activity. Taken together, this study suggests that during the exposure to di-8-ANEPPS, the stimulatory effects on
BKCa channels could be one of potential mechanisms through which it may affect cell excitability. 相似文献
11.
Mycophenolate mofetil and roscovitine decrease cyclin expression and increase p27(kip1) expression in anti Thy1 mesangial proliferative nephritis 总被引:1,自引:0,他引:1
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Chiara M Menegatti E Di Simone D Davit A Bellis D Sferch D De Rosa G Giachino O Sena LM Roccatello D 《Clinical and experimental immunology》2005,139(2):225-235
The response of mesangial cells to a phlogistic challenge includes cell proliferation and mesangial matrix expansion. Cell proliferation is a highly regulated process which includes enhancing factors such as cyclins, cyclin dependent kinases, and inhibitory proteins, such as p27(kip1). The aim of the study was to evaluate the effects of Mycophenolate mofetil (MMF), and roscovitine (R), on the cell cycle regulatory system when administered in the florid phase of the experimental model of mesangial proliferative nephritis induced by the anti Thy-1 antigen monoclonal antibody. Three days after nephritis induction, different groups were given MMF and R. Rats treated with MMF or R showed a slight decrease in mesangial proliferation and matrix expansion. Samples of cortical tissue were tested by 'real time' RT-PCR in order to study gene expression of cyclins B, D1, D2, D3, E, and the cyclin inhibitor p27(kip1). Localization of mRNA was evaluated by in situ hybridization. Real time RT-PCR analysis showed a significant decrease in cyclins B, D1, D2, and D3 in rats treated with either MMF or R as compared to controls. Both MMF and R treatment induced a significant increase in p27(kip1) mRNA expression. In situ hybridization showed a mesangial-endothelial expression pattern in glomeruli. The number of labelled cells per glomerulus, the number of positive glomeruli in each examined slide as well as cyclin D2 and D3 signal intensity was significantly lower in rats treated with MMF or R as compared to controls, whereas MMF or R treatment up-regulated p27(kip1) mRNA expression. Immunohistochemical evaluation of p27(kip1) aimed to examine the influence of MMF or R on protein expression confirmed up-regulation. 相似文献
12.
Watanabe Y Kinoshita A Yamada T Ohta T Kishino T Matsumoto N Ishikawa M Niikawa N Yoshiura K 《Journal of human genetics》2002,47(9):478-483
Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine that is produced in the platelet, bone, placenta, and
other tissues. It acts as a growth inhibitor in many types of cells, and also mediates extracellular matrix production and
immunosuppression. Mutations in the specific domain of its gene (TGFB1) cause Camurati-Engelmann disease, a bone-sclerosing disorder, and those in other domains may be associated with osteoporosis.
We identified 106 single-nucleotide polymorphisms and 11 other types of variations in TGFB1 and six other genes. These genes were TGF-β type I receptor gene (TGFBR1), TGF-β type II receptor gene (TGFBR2), SMAD2 gene (SMAD2), SMAD3 gene (SMAD3), SMAD4 gene (SMAD4), and SMAD7 gene (SMAD7), all of which compose the TGF-β1 signaling pathway. We also estimated allele frequencies of these DNA polymorphisms among
48 Japanese individuals. Our data will provide a useful resource for the study of disease susceptibility.
Received: May 9, 2002 / Accepted: June 4, 2002 相似文献
13.
14.
Katsuko S. Furukawa PhD Takashi Ushida PhD Yasuyuki Sakai PhD Kaiko Kunii MS Motoyuki Suzuki PhD Junzo Tanaka PhD Tetsuya Tateishi PhD 《Journal of artificial organs》2001,4(4):353-356
Higher-density inoculation of fibroblasts into a three-dimensional scaffold should accelerate wound healing after skin implantation.
This study attempted to develop tissue-engineered skin with a higher density of fibroblasts. We first attempted to fabricate
three-dimensional high-cell-density aggregates (spheroids) of normal human fibroblasts for application to tissue-engineered
skin. Our method consisted of rotational shaking with nontreated dishes, decreasing fibroblast-meterial interactions, and
augmenting cell-cell interaction. To prompt aggregate formation, the medium was supplemented with insulin, dexamethasone,
ascorbic acid, and basic fibroblast growth factors that potentiate secretion of extracellular matrices. Under such improved
conditions, fibroblasts were able to form spheroidal aggregates within 24 to 36h of rotational culture. Although the formed
aggregates were irregular in shape and were composed of only several cells after 12h, they became almost spheroidal after
24h. The aggregates grew even more round after 36h, and their surfaces became smooth. After 36h of rotational culture, the
fibroblast aggregates were collected and reinoculated onto a biodegradable mesh composed of polyglycolic acid coated with
collagen. The aggregates were trapped in the material and became attached after 24h. Finally, because transforming growth
factor-β3 (TGF-β3) is known to accelerate wound healing, we conducted a semiquantitative analysis of TGF-β3 mRNA in both the fibroblast monolayers (two-dimensional culture) and the aggregates (three-dimensional culture). Analysis
of TGF-β3 mRNA expression showed that mRNA expression was greater in the fibroblasts of aggregates than in a monolayer. Therefore,
our newly developed dermal graft is expected to accelerate wound healing faster than conventional grafts. 相似文献
15.
H. Yoshimura K. Nakahama O. Safronova N. Tanaka T. Muneta I. Morita 《Inflammation research》2006,55(12):543-549
Objective and Design: Transforming growth factor- β (TGF-β) has not only a fibrogenic role, but also monocyte/ macrophage chemotactic properties
in a synovial joint. However, little is known about the effects of TGF-β on monocyte chemoattractant protein-1 (MCP-1) expression
in human synovial cells under inflammatory status. The aim of this study was to determine whether TGF-modulates MCP-1 production
under the chronic inflammation, and to elucidate the cell signaling mechanism involved.
Materials and methods: Human synovial cells were exposed to IL-1β, which mimics the environment of chronic inflammation. Production of MCP-1 protein
and expression of MCP-1 mRNA were determined by ELISA and real-time PCR.
Results: TGF-β upregulated the expression of MCP-1 mRNA and protein with or without IL-1β. TGF-β and IL-1β synergistically enhanced
MCP-1 gene expression, and an AP-1 binding site was involved in the signal transduction. In addition, MEK inhibitor completely
suppressed TGF-β-induced MCP-1 production.
Conclusions: TGF-β and IL-1β synergistically enhance MCP-1 gene expression through the activation of the MEK/ERK1/2 pathways, which leads
to AP-1 activation. The impairment of MCP-1 regulation by TGF-β in resident synovial cells might represent an important mechanism
of chronic inflammation and tissue fibrosis in a synovial joint. MCP-1 should be considered a valid target for therapeutic
intervention.
Received 22 September 2005; returned for revision 3 February 2006; accepted by J. Skotnicki 29 May 2006 相似文献
16.
Immunohistochemical analysis of p27 (Kip1) in human pituitary glands and in various types of pituitary adenomas 总被引:3,自引:0,他引:3
Komatsubara K Tahara S Umeoka K Sanno N Teramoto A Osamura RY 《Endocrine pathology》2001,12(2):181-188
p27 (Kip1) plays regulatory roles in the cell cycle by inhibiting the activity of cyclin dependent kinases (CDKs). This immunohistochemical
study is aimed at elucidating the expression of p27 in human pituitary and in various types of pituitary adenomas in order
to clarify its role in the regulation of proliferation.
Sixteen normal pituitary glands and 179 human pituitary adenomas were used for immunohistochemical studies. The tissues were
fixed in 10% formalin and embedded in paraffin. Indirect peroxidase method was performed after heat-induced antigen retrieval
using a monoclonal antibody against p27 protein. p27 protein was expressed in the nuclei of all 16 normal human pituitary
glands. p27 protein was also expressed in 128 of 179 cases of pituitary adenomas (71.5%).
A marked decrease of p27 expression was noted in ACTH-secreting adenomas, 8/20 (40.0%), compared with other types of pituitary
adenomas—GH-secreting adenomas, 35/46 (76.1%); PRL-secreting adenomas, 22/33 (66.7%); TSH-secreting adenomas, 8/11 (72.7%);
and nonfunctioning adenomas, 55/69 (79.7%).
These results suggest that p27 may play some role in the regulation of proliferation in all types of pituitary adenomas. The
lower levels of p27 in ACTH-secreting adenoma is of particular interest with respect to the intermediate lobe-derived pituitary
tumor developed in p27 knockout mice. 相似文献
17.
Overexpression of p21, cyclin E and decreased expression of p27 in DMBA (7, 12-dimethylbenzanthracene)-induced rat ovarian carcinogenesis 总被引:1,自引:0,他引:1
Ovarian cancer is a common gynecological malignancy and a leading cause of death in women. Inactivation of the tumor suppressor gene and deregulation of cyclin E are frequent in human ovarian cancer. The objective of this study was to investigate the expressions and roles of cyclin E, p21 and p27 in 7, 12-dimethylbenzanthracene (DMBA)-induced ovarian tumors in rats. The expressions of cyclin E, p21 and p27 were evaluated by immunohistochemistry and western blot analysis. The expressions of cyclin E and p21 in ovarian tumors was higher than that in normal ovarian surface epithelium. In contrast, the expression of p27 in ovarian tumors was lower than that in normal ovarian surface epithelium. But there were no differences among the cancer types. Positive correlation was present between cyclin E and p21. p27 was negatively correlated with cyclin E and p21. These results suggest that the increased expression of cyclin E and p21, and the decreased expression of p27, occur in DMBA-induced rat ovarian carcinogenesis and result in tumor progression. 相似文献
18.
K. Koike Z. X. Zhang Y. Sakamoto A. Miyake M. Inoue 《American journal of reproductive immunology (New York, N.Y. : 1989)》1998,39(3):217-222
PROBLEM: Cytokine-induced neutrophil chemoattractant (CINC) was reported to influence anterior pituitary hormone release. We recently found that Unkei-to, one of the Japanese Kampo medicines, stimulated CINC secretion by rat anterior pituitary cells and the pituitary folliculo-stellate (FS)-like cell line (TtT/GF). Therefore, the effect of Unkei-to on growth hormone (GH) secretion by rat anterior pituitary cells was investigated. METHOD OF STUDY: Dispersed normal anterior pituitary cells, the folliculo-stellate-like cell line TtT/GF, and the GH3 cell were used to test the effect of Unkei-to on GH secretion. In reconstitutive coculture experiments, TtT/GF cells were mixed with GH3 cells at a ratio (TtT/GF cells: GH3 cells) of 1:99. From this mixture, cells were seeded onto plates at a density of 104 cells/well and were cultured for 5 days. The cells were then used in the experiments. RESULTS: Unkei-to at 20 μg/ml significantly inhibited GH secretion by normal anterior ptuitary cells within 12 hr of incubation. In contrast Unkei-to stimulated GH secretion by GH3 cells in a time- and dose-dependent manner, suggesting that an accessory cell type was involved. To assess the contribution of CINC as a paracrine factor, an experiment using a reconstitutive coculture system was performed, and Unkei-to was found to inhibit GH secretion when GH3 cells were cocultured with TtT/GF cells. The addition of anti-CINC antibody to the reconstitutive coculture system antagonized Unkei-to-inhibited GH secretion. CONCLUSION: CINC, which was secreted from FS cells by Unkei-to, may be responsible for mediating the inhibitory effect of Unkei-to on GH secretion by rat anterior pituitary cells. 相似文献
19.
Li H Yu JP Cao S Wei F Zhang P An XM Huang ZT Ren XB 《Journal of clinical immunology》2007,27(3):317-326
CD4
+CD25
+ regulatory T cells (Tregs) have been shown to inhibit cytotoxic lymphocytes-mediated immune responses. Cytokine-induced killer
(CIK) cells exert high impact on adoptive immunotherapeutic approaches. Therefore, the purpose of this report was to determine
the effect of Tregs on CIK cell growth and CIK-induced cytotoxicity for inhibition of tumor growth in vivo as well as in vitro. After depletion of CD4
+CD25
+ cells before culture, the proliferation and cytotoxicity of CIK cells, which indicated in bromodeoxyuridine (BrdU) and lactic
dehydrogenase (LDH) assays, were significantly increased. Depletion of CD4
+CD25
+ cells preculture also enhanced the suppression effect on the lung cancer cells inoculated in experimental animals. Blockage
of glucocorticoid-induced tumor necrosis factor receptor (GITR) and transforming growth factor β1 (TGF-β1) by antibodies partially
abrogated the suppressive effect of CD4
+CD25
+ cells on CIK. These results indicated that Tregs could inhibit the antitumor activity of CIK cells. The molecules TGF-β and
GITR may contribute to the suppressive function of CD4
+CD25
+ cells. 相似文献
20.
Cheryl E. Gillett Paul Smith Gordon Peters Xin Lu Diana M. Barnes 《The Journal of pathology》1999,187(2):200-206
p27, cyclin D1, and retinoblastoma (Rb) protein have been demonstrated using immunohistochemistry in 189 cases of primary breast carcinoma with long-term follow-up. There was a statistically significant association between the expression of p27 and both cyclin D1 and the retinoblastoma gene product (pRb), corresponding to their close interactions in regulating the G1/S transition in the cell cycle. Low levels of p27 were seen in high-grade, rapidly proliferating, oestrogen receptor-negative tumours. In univariate analysis, low p27 expression was associated with a reduced relapse-free and overall survival. In multivariate analysis, p27 was not an independent predictor of survival when either histological grade or proliferative activity (S-phase fraction) was included in the model. When the combined expression of p27 and cyclin D1 was related to survival, patients with high levels of p27, regardless of their cyclin D1 status, did well, whilst those with low p27 had a poor outcome. The only exception, in the latter group, was patients with tumours expressing high levels of cyclin D1, who did as well as the high p27 group. We have shown that in clinical material p27 expression is associated with proliferative activity and while univariate analysis shows it to be a significant indicator of prognosis, this significance is lost in multivariate analysis when traditional prognostic factors are included in the model. The interest in p27 expression in mammary carcinoma lies in its behaviour when examined in combination with other G1 cell cycle regulators. Copyright © 1999 John Wiley & Sons, Ltd. 相似文献