scholarly journals Glucocorticoid effects on chondrogenesis, differentiation and apoptosis in the murine ATDC5 chondrocyte cell line

2002 ◽  
Vol 175 (3) ◽  
pp. 705-713 ◽  
Author(s):  
T Mushtaq ◽  
C Farquharson ◽  
E Seawright ◽  
SF Ahmed
Keyword(s):  
Cell Line ◽  
Bone Growth ◽  
Apoptotic Cell ◽  
Recovery Period ◽  
Terminal Differentiation ◽  
Cell Number ◽  
Proteoglycan Synthesis ◽  
Alp Activity ◽  
Significant Impairment

Glucocorticoids (GC) are used extensively in children and may cause growth retardation, which is in part due to the direct effects of GC on the growth plate. We characterised the ATDC5 chondrocyte cell line, which mimics the in vivo process of longitudinal bone growth, to examine the effects of dexamethasone (Dex) and prednisolone (Pred) during two key time points in the chondrocyte life cycle - chondrogenesis and terminal differentiation. Additionally, we studied the potential for recovery following Dex exposure. During chondrogenesis, Dex and Pred exposure at 10(-8) M, 10(-7) M and 10(-6) M resulted in a significant mean reduction in cell number (28% vs 20%), cell proliferation (27% vs 24%) and proteoglycan synthesis (47% vs 43%) and increased alkaline phosphatase (ALP) activity (106% vs 62%), whereas the incidence of apoptosis was unaltered. Minimal effects were noted during terminal differentiation with both GC although all concentrations of Dex lowered apoptotic cell number. To assess catch-up growth the cells were incubated for a total of 14 days which included 1, 3, 7, 10 or 14 days exposure to 10(-6) M Dex, prior to the recovery period. Recovery of proteoglycan synthesis was irreversibly impaired following just one day exposure to Dex. Although cell number showed a similar pattern, significant impairment was only achieved following 14 days exposure. Irreversible changes in ALP activity were only noticed following 10 days exposure to Dex. In conclusion, GC have maximal effects during chondrogenesis; Dex is more potent than Pred and cells exposed to Dex recover but this may be restricted due to differential effects of GC on specific chondrocyte phenotypes.

scholarly journals Bioinformatic and experimental findings to indicate anti-cancer targets and mechanisms of calycosin against nasopharyngeal carcinoma

2020 ◽  
Author(s):  
Fangxian Liu ◽  
Qijin Pan ◽  
Liangliang Wang ◽  
Shijiang Yi ◽  
Peng Liu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Cell Number ◽  
Network Pharmacology ◽  
Tunel Staining ◽  
Pharmacological Targets ◽  
Experimental Findings

Abstract Background: Calycosin is a naturally-occurring phytoestrogen that reportedly exerts anti- nasopharyngeal carcinoma (NPC) effects. Nevertheless, the molecular mechanisms for anti-NPC using calycosin remain unrevealed. Methods: Thus, a network pharmacology was used to uncover anti-NPC pharmacological targets and mechanisms of calycosin. Additionally, validated experiments were conducted to validate the bioinformatic findings of calycosin for treating NPC. Results: As results, bioinformatic assays showed that the predictive pharmacological targets of calycosin against NPC were TP53, MAPK14, CASP8, MAPK3, CASP3, RIPK1, JUN, ESR1, respectively. And the top 20 biological processes and pharmacological mechanisms of calycosin against NPC were identified accordingly. In clinical data, NPC samples showed positive expression of MAPK14, reduced TP53, CASP8 expressions. In studies in vitro and in vivo, calycosin-dosed NPC cells resulted in reduced cell proliferation, promoted cell apoptosis. In TUNEL staining, calycosin exhibited elevated apoptotic cell number. And immunostaining assays resulted in increased TP53, CASP8 positive cells, and reduced MAPK14 expressions in calycosin-dosed NPC cells and tumor-bearing nude mice. Conclusion: Altogether, these bioinformatic findings reveal optimal pharmacological targets and mechanisms of calycosin against NPC, following with representative identification of human and preclinical experiments. Notably, some of original biotargets may be potentially used to treat NPC.

scholarly journals Long-Term Exposure to Urban Particulate Matter on the Ocular Surface and the Incidence of Deleterious Changes in the Cornea, Conjunctiva and Retina in Rats

2020 ◽  
Vol 21 (14) ◽  
pp. 4976
Author(s):  
Wan Seok Kang ◽  
Hakjoon Choi ◽  
Goeun Jang ◽  
Ki Hoon Lee ◽  
Eun Kim ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Apoptotic Cell ◽  
Tear Film ◽  
Cell Number ◽  
Corneal Epithelial Cell ◽  
Urban Particulate Matter ◽  
Epithelium Thickness ◽  
The Right

We investigated the time-dependent deleterious ocular changes induced by urban particulate matter (UPM) in vitro and in vivo. UPM treatment decreased human corneal epithelial cell migration and survival. Fluorescein scores were consistently increased by UPM application for 16 weeks. One week of rest at 2 or 4 weeks led to a recovery trend, whereas two weeks of rest at 8 weeks induced no change. UPM treatment decreased the tear film break-up time at 2 weeks, which was thereafter maintained until 16 weeks. No changes were found after periods of rest. UPM-treated eyes exhibited greater corneal epithelium thickness than normal eyes at 2 weeks, which recovered to normal at 4 and 8 weeks and was significantly decreased at 16 weeks. Apoptotic cell number in the epithelium was increased at 2 weeks, which remained constant except at 8 weeks. IL-6 expression in the cornea of the right eye continually increased for 16 weeks, and significant recovery was only observed at 8 weeks after 2 weeks of rest. Ocular pressure was significantly increased in the right eye at 12 and 16 weeks. Topical UPM application to the eye induced deleterious changes to various closely related parts of the eye.

scholarly journals Involvement of the gp130 cytokine transducer in MtT/S pituitary somatotroph tumour development in an autocrine-paracrine model

2004 ◽  
pp. 595-604 ◽  
Author(s):  
M Graciarena ◽  
A Carbia-Nagashima ◽  
C Onofri ◽  
C Perez-Castro ◽  
D Giacomini ◽  
...  
Keyword(s):  
Cell Line ◽  
Growth Regulation ◽  
Functional Characterization ◽  
Cell Number ◽  
Pituitary Cells ◽  
Tumour Development ◽  
Low Concentrations ◽  
High Concentrations ◽  
And Control

OBJECTIVE: gp130 cytokines are placed as auto-paracrine regulators of pituitary function, since they, as well as their receptors, have been shown to be expressed in and to act in normal and tumoral anterior pituitary cells. The objective of this work was to study their involvement in a model that shows the interaction between different cellular types that participate in a tumorigenic process. DESIGN: The dependence of a pituitary somatotrophic cell line (MtT/S) on a gp130 cytokine-producing folliculostellate (FS) cell line (TtT/GF) for tumorigenesis in vivo has been described. In order to study the participation of gp130 cytokines in the auto-paracrine stimulation of MtT/S growth, we generated MtT/S gp130 sense (gp130-S) and gp130 antisense (gp130-AS) clones stably transfected with pcDNA3/gp130 sense and pcDNA3/gp130 antisense vectors respectively. METHODS AND RESULTS: Functional characterization studies revealed that gp130-AS clones have an inhibited gp130 signalling, and proliferation studies showed that they have an impaired response to gp130 cytokines but respond normally to other independent stimuli. When injected into nude mice, MtT/S clones respond differently depending on cell number; at high concentrations MtT/S clones alone generated tumours equivalent in size to tumours derived from MtT/S plus TtT/GF cells. At low concentrations, MtT/S sense and control clones generated tumours of smaller size than tumours derived from these same clones plus TtT/GF cells, showing a dependence on FS cells. In both cases MtT/S gp130-AS clones had impaired tumour development. Furthermore, vessel density was significantly lower in tumours derived from gp130-AS plus TtT/GF cells. CONCLUSIONS: This study underlines the importance of gp130 cytokines in proliferation and establishes its role in auto-paracrine pituitary growth regulation.

scholarly journals Anticancer Activity of Tetrandrine by Inducing Apoptosis in Human Breast Cancer Cell Line MDA-MB-231 In Vivo

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Chun-hui Wang ◽  
Jia-min Yang ◽  
Yu-bo Guo ◽  
Jing Shen ◽  
Xiao-hua Pei
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Anticancer Activity ◽  
Cell Line ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
Cancer Cell Line ◽  
B Cell Lymphoma

Tetrandrine (TET) is an alkaloid extracted from a traditional Chinese medicinal plant. It exerts remarkable anticancer activity and induces apoptotic cell death in various human cancer cells. The present study aimed to investigate the effects of TET on the inhibition of tumor growth and the induction of apoptosis in MDA-MB-231 breast cancer in xenograft mice. Tumor weight and volume were measured. The histopathological changes in the tumor tissue were observed. Immunohistochemistry analysis of Bcl-2-associated X protein (Bax) and B-cell lymphoma/leukemia-2 (Bcl-2) was carried out. The expression of apoptosis-associated genes and proteins, such as cysteine aspartic acid-specific protease-3 (Caspase-3), Survivin, Bax, Bcl-2, BH3-interacting domain death agonist (Bid), and poly ADP-ribose polymerase (PARP), was measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. TET inhibited tumor growth and induced apoptosis in TNBC cell line MDA-MB-231. The mechanism underlying this effect might be mediated by TET-upregulated Caspase-3, Bax, and Bid and downregulated by Bcl-2, Survivin, and PARP. Taken together, this study supported the fact that TET is a promising therapeutic agent for the treatment of TNBC, thereby providing experimental evidence for its use in the treatment of breast cancer.

scholarly journals The restricted potential for recovery of growth plate chondrogenesis and longitudinal bone growth following exposure to pro-inflammatory cytokines

2006 ◽  
Vol 189 (2) ◽  
pp. 319-328 ◽  
Author(s):  
V E MacRae ◽  
C Farquharson ◽  
S F Ahmed
Keyword(s):  
Bone Growth ◽  
Recovery Period ◽  
Normal Growth ◽  
Chronic Inflammatory Disease ◽  
Proteoglycan Synthesis ◽  
Growth Trajectories ◽  
Inhibitory Effects ◽  
Factor Α ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines

Childhood chronic inflammatory disease can be associated with transient and permanent growth retardation. This study examined the potential for spontaneous growth recovery following pro-inflammatory cytokine exposure. Murine ATDC5 chondrogenic cells and postnatal metatarsals were exposed to interleukin (IL)-1β, IL-6 and tumour necrosis factor-α (TNFα), and their growth and proliferative capacity were determined following recovery. TNFα and IL-1β reduced chondrocyte proliferation and aggrecan and collagen types II and X expression at minimum concentrations of 10 ng/ml and 0.1 ng/ml respectively. TNFα but not IL-1β exposure led to increased caspase-3 activity and altered cellular morphology, consistent with reduced viability. Cytokine exposure particularly inhibited proteoglycan synthesis. This effect was dose and duration dependent. Compared with the control, IL-1β and TNFα led to a 71% and 45% reduction in metatarsal growth after 8 days of exposure respectively (P < 0.05). An additive effect of IL-1β combined with TNFα was observed (110% decrease; P < 0.05). Metatarsals exposed to IL-1β or TNFα individually for a 2-day period, and allowed to recover spontaneously in the absence of cytokines for a further 6 days, showed normal growth trajectories. In combination, growth was 59% lower (P < 0.01) compared with control metatarsals at the end of the recovery period. Exposure to the combination for 4 days followed by a 4-day recovery period resulted in 87% decrement compared with controls (P < 0.05). IL-6 did not alter any parameter studied. IL-1β and TNFα exert diverse inhibitory effects on ATDC5 chondrocyte dynamics and metatarsal growth. The extent of recovery following cytokine exposure depends on the duration of exposure, and may be incomplete following longer periods of exposure.

Total inhibition of involucrin synthesis by a novel two-step antisense procedure. Further examination of the relationship between differentiation and malignancy in hybrid cells

1992 ◽  
Vol 102 (4) ◽  
pp. 799-805 ◽  
Author(s):  
E.F. Griffin ◽  
H. Harris
Keyword(s):  
Cell Line ◽  
Target Genes ◽  
Hybrid Cell ◽  
Terminal Differentiation ◽  
Complete Inactivation ◽  
Total Inhibition ◽  
Antisense Constructs ◽  
Progressive Growth ◽  
Normal Human

A novel procedure involving the sequential use of two different antisense constructs has been used to inhibit the synthesis of involucrin in a hybrid cell line formed by the fusion of a human cervical carcinoma cell with a normal human keratinocyte (ESH100P6). In this cell line, and other similar hybrids, malignancy, as measured by progressive growth in vivo, is suppressed; and it has been shown that the keratinocyte imposes its own programme of terminal differentiation on the non-malignant hybrid cell. In particular, involucrin, a precursor of one of the major components of the cornified envelope of mature keratinocytes, continues to be produced. When, however, malignant segregants arise in the hybrid cell population, the terminal differentiation programme of the keratinocyte is not expressed and involucrin ceases to be made. It seemed possible that if the synthesis of involucrin, a critical marker of keratinocyte terminal differentiation, could be completely inhibited, this differentiation programme might be disrupted, and the malignant phenotype might then reappear in the non-malignant hybrids. This question was investigated further in the present paper. Total, and specific, inhibition of involucrin synthesis was indeed achieved by a sequential two-step antisense procedure, which might provide a systematic general method for the complete inactivation of other selected target genes.

scholarly journals Overexpression of miR-155 causes expansion, arrest in terminal differentiation and functional activation of mouse natural killer cells

Blood ◽  
2013 ◽  
Vol 121 (16) ◽  
pp. 3126-3134 ◽  
Author(s):  
Rossana Trotta ◽  
Li Chen ◽  
Stefan Costinean ◽  
Srirama Josyula ◽  
Bethany L. Mundy-Bosse ◽  
...  
Keyword(s):  
Natural Killer Cells ◽  
Cell Survival ◽  
Nk Cells ◽  
Nk Cell ◽  
Terminal Differentiation ◽  
Interferon Γ ◽  
Cell Number ◽  
Erk Activation ◽  
Key Points

Key Points miR-155 tg mice have increased NK-cell number, enhanced NK-cell survival, excess immature CD11blowCD27high NK cells, and an activated phenotype. miR-155 tg NK cells exhibit enhanced expansion, interferon-γ production, AKT and ERK activation, and killing of lymphoma in vivo.

Irinotecan: a potential new chemotherapeutic agent for atypical or malignant meningiomas

2007 ◽  
Vol 106 (3) ◽  
pp. 455-462 ◽  
Author(s):  
Vinay Gupta ◽  
Yuzhuang S. Su ◽  
Christian G. Samuelson ◽  
Leonard F. Liebes ◽  
Marc C. Chamberlain ◽  
...  
Keyword(s):  
Cell Line ◽  
Topoisomerase I ◽  
Cellular Proliferation ◽  
Apoptotic Cell ◽  
Tumor Model ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Malignant Meningioma ◽  
Meningioma Cell

Object There is currently no effective chemotherapy for meningiomas. Although most meningiomas are treated surgically, atypical or malignant meningiomas and surgically inaccessible meningiomas may not be removed completely. The authors have investigated the effects of the topoisomerase I inhibitor irinotecan (CPT-11) on primary meningioma cultures and a malignant meningioma cell line in vitro and in vivo. Methods The effects of irinotecan on cellular proliferation in primary meningioma cultures and the IOMM-Lee malignant meningioma cell line were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide assay and flow cytometry. Apoptosis following drug treatment was evaluated by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and the DNA laddering assays. The effects of irinotecan in vivo on a meningioma model were determined with a subcutaneous murine tumor model using the IOMM-Lee cell line. Irinotecan induced a dose-dependent antiproliferative effect with subsequent apoptosis in the primary meningioma cultures (at doses up to 100 μM) as well as in the IOMM-Lee human malignant meningioma cell line (at doses up to 20 μM) irinotecan. In the animal model, irinotecan treatment led to a statistically significant decrease in tumor growth that was accompanied by a decrease in Bcl-2 and survivin levels and an increase in apoptotic cell death. Conclusions Irinotecan demonstrated growth-inhibitory effects in meningiomas both in vitro and in vivo. Irinotecan was much more effective against the malignant meningioma cell line than against primary meningioma cultures. Therefore, this drug may have an important therapeutic role in the treatment of atypical or malignant meningiomas and should be evaluated further for this purpose.

Ultrastructural Study of a differentiating human colon carcinoma cell line

1990 ◽  
Vol 48 (3) ◽  
pp. 208-209
Author(s):  
Sylvie Polak-Charcon ◽  
Mehrdad Hekmati ◽  
Yehuda Ben Shaul
Keyword(s):  
Cell Line ◽  
Morphological Changes ◽  
Secretory Granules ◽  
Human Colon ◽  
Cell Types ◽  
Culture Conditions ◽  
Morphological Evidence ◽  
Human Colon Carcinoma Cell ◽  
Colon Cell

The epithelium of normal human colon mucosa “in vivo” exhibits a gradual pattern of differentiation as undifferentiated stem cells from the base of the crypt of “lieberkuhn” rapidly divide, differentiate and migrate toward the free surface. The major differentiated cell type of the intestine observed are: absorptive cells displaying brush border, goblet cells containing mucous granules, Paneth and endocrine cells containing dense secretory granules. These different cell types are also found in the intestine of the 13-14 week old embryo.We present here morphological evidence showing that HT29, an adenocarcinoma of the human colon cell line, can differentiate into various cell types by changing the growth and culture conditions and mimic morphological changes found during development of the intestine in the human embryo.HT29 cells grown in tissue-culture dishes in DMEM and 10% FCS form at late confluence a multilayer of morphologically undifferentiated cell culture covered with irregular microvilli, and devoid of tight junctions (Figs 1-3).

Intense Static Magnetic Field Induced Bone Growth in Vivo

1984 ◽  
Vol 3 (1) ◽  
pp. 223-234
Author(s):  
Frank Papatheofanis ◽  
Bill Fapatheofanls ◽  
Robert Ray
Keyword(s):  
Magnetic Field ◽  
Static Magnetic Field ◽  
Bone Growth
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