scholarly journals Anastrozole and celecoxib for endometriosis treatment, good to keep them apart?

Reproduction ◽  
2013 ◽  
Vol 145 (2) ◽  
pp. 119-126 ◽  
Author(s):  
Carla N Olivares ◽  
Mariela A Bilotas ◽  
Analía G Ricci ◽  
Rosa Inés Barañao ◽  
Gabriela F Meresman
Keyword(s):  
Cell Proliferation ◽  
Nuclear Antigen ◽  
Gynecological Disease ◽  
Cox 2 ◽  
Benign Gynecological Disease ◽  
Surgically Induced ◽  
Free Women ◽  
Proliferating Cell

Endometriosis is a benign gynecological disease. Cyclooxygenase-2 (COX-2) and aromatase proteins have been shown to be overexpressed in eutopic endometrium from women suffering from this disease compared to disease-free women. Furthermore, inhibition of these molecules individually was demonstrated to have antiproliferative and proapoptotic effects both in vitro and in vivo in several models. In this study, the effect of combining celecoxib, a selective COX-2 inhibitor, and anastrozole, an aromatase inhibitor, on the implantation and growth of endometriotic like lesions in a murine model of endometriosis was evaluated. Endometriosis was surgically induced in female BALB/c mice. After 28 days of treatment with celecoxib, anastrozole, or their combination, animals were killed and lesions were counted, measured, excised, and fixed. Immunohistochemistry for proliferating cell nuclear antigen and CD34 was performed for assessment of cell proliferation and vascularization. TUNEL technique was performed for apoptosis evaluation. Celecoxib was the only treatment to significantly reduce the number of lesions established per mouse, their size and vascularized area. In addition, cell proliferation was significantly diminished and apoptosis was significantly enhanced by both individual treatments. When the therapies were combined, they reversed their effects. These results confirm that celecoxib and anastrozole separately decrease endometriotic growth, but when combined they might have antagonizing effects.

Involvement of proliferating cell nuclear antigen (cyclin) in DNA replication in living cells

1989 ◽  
Vol 9 (1) ◽  
pp. 57-66
Author(s):  
M Zuber ◽  
E M Tan ◽  
M Ryoji
Keyword(s):  
Dna Polymerase ◽  
Proliferating Cell Nuclear Antigen ◽  
Living Cells ◽  
Nuclear Antigen ◽  
Plasmid Replication ◽  
Dna Polymerase Delta ◽  
Dna Polymerase Alpha ◽  
Proliferating Cell

Proliferating cell nuclear antigen (PCNA) (also called cyclin) is known to stimulate the activity of DNA polymerase delta but not the other DNA polymerases in vitro. We injected a human autoimmune antibody against PCNA into unfertilized eggs of Xenopus laevis and examined the effects of this antibody on the replication of injected plasmid DNA as well as egg chromosomes. The anti-PCNA antibody inhibited plasmid replication by up to 67%, demonstrating that PCNA is involved in plasmid replication in living cells. This result further implies that DNA polymerase delta is necessary for plasmid replication in vivo. Anti-PCNA antibody alone did not block plasmid replication completely, but the residual replication was abolished by coinjection of a monoclonal antibody against DNA polymerase alpha. Anti-DNA polymerase alpha alone inhibited plasmid replication by 63%. Thus, DNA polymerase alpha is also required for plasmid replication in this system. In similar studies on the replication of egg chromosomes, the inhibition by anti-PCNA antibody was only 30%, while anti-DNA polymerase alpha antibody blocked 73% of replication. We concluded that the replication machineries of chromosomes and plasmid differ in their relative content of DNA polymerase delta. In addition, we obtained evidence through the use of phenylbutyl deoxyguanosine, an inhibitor of DNA polymerase alpha, that the structure of DNA polymerase alpha holoenzyme for chromosome replication is significantly different from that for plasmid replication.

scholarly journals A Novel Gold Calreticulin Nanocomposite Based on Chitosan for Wound Healing in a Diabetic Mice Model

Nanomaterials ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 75 ◽  
Author(s):  
Sara Paola Hernández Martínez ◽  
Teodoro Iván Rivera González ◽  
Moisés Armides Franco Molina ◽  
Juan José Bollain y Goytia ◽  
Juan José Martínez Sanmiguel ◽  
...  
Keyword(s):  
Wound Healing ◽  
Topical Administration ◽  
Nuclear Antigen ◽  
Histological Evaluation ◽  
Mice Model ◽  
Fibroblast Migration ◽  
And Migration ◽  
Proliferating Cell

The development of new nanomaterials to promote wound healing is rising, because of their topical administration and easy functionalization with molecules that can improve and accelerate the process of healing. A nanocomposite of gold nanoparticles (AuNPs) functionalized with calreticulin was synthetized and evaluated. The ability of the nanocomposite to promote proliferation and migration was determined in vitro, and in vivo wound healing was evaluated using a mice model of diabetes established with streptozotocin (STZ). In vitro, the nanocomposite not affect the cell viability and the expression of proliferating cell nuclear antigen (PCNA). Moreover, the nanocomposite promotes the clonogenicity of keratinocytes, endothelial cells, and fibroblasts, and accelerates fibroblast migration. In vivo, mice treated with the nanocomposite presented significantly faster wound healing. The histological evaluation showed re-epithelization and the formation of granular tissue, as well as an increase of collagen deposition. Therefore, these results confirm the utility of AuNPs–calreticulin nanocomposites as potential treatment for wound healing of diabetic ulcers.

Identification of the functional domain of p21WAF1/CIP1 that protects cells from cisplatin cytotoxicity

2005 ◽  
Vol 289 (3) ◽  
pp. F514-F520 ◽  
Author(s):  
Fang Yu ◽  
Judit Megyesi ◽  
Robert L. Safirstein ◽  
Peter M. Price
Keyword(s):  
Dominant Negative ◽  
Nuclear Antigen ◽  
Functional Domain ◽  
Binding Domains ◽  
Cdk2 Activity ◽  
Localization Signal ◽  
Induced Apoptosis ◽  
Proliferating Cell

The p21 cyclin-dependent kinase (cdk) inhibitor protects cells from cisplatin cytotoxicity in vivo and in vitro. However, the mechanism of protection is not known. Separate p21 domains are known to interact with several different proteins having proapoptotic functions. To investigate the mechanism of protection by p21, we have constructed adenoviruses encoding the different domains of p21. We were able to localize the protective activity to a region of 54 amino acids containing the cyclin-cdk interacting moiety. Other protein binding domains of p21, including the NH2-terminal procaspase-3 interactive region and the COOH-terminal region containing the proliferating cell nuclear antigen binding domain and the nuclear localization signal, had little protective effect on cisplatin cytotoxicity. The dependence of cisplatin cytotoxicity on cdk2 activity was also demonstrated because 1) cisplatin caused a marked increase in cdk2 activity, which was prevented by the p21 expression adenovirus, and 2) a cdk2 dominant-negative adenovirus also protected cells from cisplatin-induced apoptosis. Thus the data suggest that the mechanism of p21 protection is by direct inhibition of cdk2 activity and that cisplatin-induced apoptosis is caused by a cdk2-dependent pathway.

Proliferation and repair of guinea pig tracheal epithelium after neuropeptide depletion and injury in vivo

1997 ◽  
Vol 273 (6) ◽  
pp. L1235-L1241 ◽  
Author(s):  
John S. Kim ◽  
Valerie S. McKinnis ◽  
Kimberly Adams ◽  
Steven R. White
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Mucosal Injury ◽  
Nuclear Antigen ◽  
Airway Epithelial ◽  
Epithelial Cell Proliferation ◽  
Injury Site ◽  
And Migration

Neuropeptides stimulate airway epithelial cell proliferation and migration in vitro, but the role of neuropeptides in the repair of the epithelium after injury in vivo is not clear. We studied epithelial proliferation and repair in 83 male Hartley guinea pigs. Animals received capsaicin weekly for 3 wk to deplete airway neuropeptides. One week later, the dorsal aspect of the trachea was injured with a metal stylette. Animals were killed 1 h to 1 wk later, after which epithelial cell proliferation was assessed for the presence of proliferating cell nuclear antigen (PCNA). PCNA labeling was <3% in noninjured animals. PCNA labeling increased substantially in the first 72 h after injury in control animals but was significantly decreased in capsaicin-treated animals within and adjacent to the site of injury. PCNA labeling increased opposite to the injury site in both control and capsaicin animals over the first 72 h. We conclude that neuropeptide depletion significantly attenuates both epithelial cell proliferation and repair in the first 72 h after mechanical injury to the trachea. However, neuropeptide depletion did not slow the ultimate repair of tracheal mucosal injury. Proliferation of epithelial cells in response to injury occurs throughout the airway, even away from the injury site.

scholarly journals 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

1994 ◽  
Vol 6 (4) ◽  
pp. 453-457 ◽  
Author(s):  
Alain Pierre Théon ◽  
Loretta Metzger ◽  
Stephen Griffey
Keyword(s):  
Cell Proliferation ◽  
Proliferating Cell Nuclear Antigen ◽  
Cellular Proliferation ◽  
Nuclear Antigen ◽  
Brdu Incorporation ◽  
Immunohistochemical Detection ◽  
Proliferating Cells ◽  
Proliferating Cell

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.

Effect of undernutrition on the uterine environment during maternal recognition of pregnancy in sheep

2009 ◽  
Vol 21 (7) ◽  
pp. 869 ◽  
Author(s):  
C. Sosa ◽  
J. A. Abecia ◽  
M. Carriquiry ◽  
M. I. Vázquez ◽  
A. Fernández-Foren ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Types ◽  
Nuclear Antigen ◽  
Igf I ◽  
Uterine Environment ◽  
Cox 2 ◽  
Uterine Secretion ◽  
Maintenance Requirements ◽  
Proliferating Cell

The effects of pregnancy and undernutrition on endometrial gene expression were investigated in ewes fed all or half their maintenance requirements and killed on Day 14 of pregnancy or of the oestrous cycle. The endometrial expression of progesterone, oestrogen, oxytocin and interferon receptors (PR, ERα, OXTR and IFNAR, respectively), cyclo-oxygenase (COX)-2, proliferating cell nuclear antigen (PCNA), insulin-like growth factors (IGF)-I and -II, and IGF-1 receptor (IGF-1R) was studied by immunohistochemistry or real-time reverse transcription–polymerase chain reaction. The luminal epithelium of cyclic control ewes was devoid of PR staining and had relatively high levels of ERα, OXTR, COX-2 and IFNAR2. The presence of a conceptus decreased the in vitro uterine secretion of prostaglandin (PG) F2α and the expression of IFNAR2 in most cell types, and increased the gene expression of IGF-I and IGF-II. Undernutrition tended to increase ERα protein and gene, but decreased in vitro uterine secretion of PGE2 and the gene expression of IFNAR2 in cyclic ewes. There was no effect of undernutrition on pregnancy rates or the number of conceptuses recovered. Consistent with this, undernutrition of pregnant ewes did not have any effect on uterine gene expression. Moreover, in cases where changes were observed in cyclic ewes, these changes were negated when a conceptus was present.

scholarly journals Agmatine Inhibits Cell Proliferation and Improves Renal Function in Anti—Thy-1 Glomerulonephritis

2000 ◽  
Vol 11 (12) ◽  
pp. 2256-2264
Author(s):  
SHUNJI ISHIZUKA ◽  
ROBYN CUNARD ◽  
SIRIA POUCELL-HATTON ◽  
LUCINDA WEAD ◽  
MARK LORTIE ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Proliferation ◽  
Renal Function ◽  
Cellular Proliferation ◽  
Tissue Injury ◽  
Nuclear Antigen ◽  
Polyamine Biosynthesis ◽  
Reduce Cell Proliferation

Abstract. Changes in the expression of alternate arginine metabolic pathways have been implicated in the pathogenesis of experimental glomerulonephritis. Agmatine, decarboxylated arginine, has been shown in vitro to suppress both inducible nitric oxide synthase and the rate-limiting enzyme of polyamine biosynthesis, ornithine decarboxylase (ODC). This study was undertaken to determine whether agmatine administration could reduce tissue injury by decreasing nitric oxide, and reduce cell proliferation, by diminishing ODC activity, in experimental mesangial proliferative glomerulonephritis (Thy-1 nephritis). Agmatine treatment (50 mg/kg per d intraperitoneally) in Thy-1 nephritis rats prevented a reduction in GFR at day 1. Agmatine treatment decreased nitric oxide production in Thy-1 nephritis rats by 23% and 41% at days 1 and 4, respectively. Agmatine treatment also reduced ODC activity and glomerular 3H-thymidine incorporation on days 1, 4, and 7. Histologic evaluation revealed a decline in mesangial cell proliferation and extracellular matrix accumulation associated with agmatine treatment administered before or 24 h after Thy-1 antibody, and this was confirmed by a reduction in the number of cells expressing proliferating cell nuclear antigen on days 4 and 7. These studies provide the first in vivo evidence that agmatine administration can reduce cellular proliferation in Thy-1 nephritis and attenuate the initial reduction in renal function associated with this model.

scholarly journals Using Patient-Derived Xenografts to Explore the Efficacy of Treating Head-and-Neck Squamous Cell Carcinoma With Anlotinib

2021 ◽  
Vol 27 ◽  
Author(s):  
Fangling Hu ◽  
Liang Guo ◽  
Jieqing Yu ◽  
Daofeng Dai ◽  
Yuanping Xiong ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Nuclear Antigen ◽  
Tumor Tissues

Objective: The efficacy of anlotinib as a treatment for head-and-neck squamous cell carcinoma (HNSCC) has been little explored. Here, we used patient-derived xenografts (PDXs) to this end.Methods: Fresh tumor tissues of HNSCC patients were screened in terms of in vitro drug sensitivity using the MTT assay. Patient PDXs were used to confirm the anti-tumor effects of anlotinib in vivo. After the medication regimen was complete, the tumor volume changes in mice were calculated. Apoptosis was measured using the TUNEL assay. The cell proliferation and apoptosis levels of PDXs yielded data on the utility of anlotinib treatment in vivo.Results: Anlotinib suppressed the in vitro proliferation of nine tumor tissues by an average of 51.05 ± 13.74%. Anlotinib also significantly inhibited the growth of three PDXs in mice (tumor growth inhibition 79.02%). The expression levels of Ki-67 and proliferating cell nuclear antigen after anlotinib treatment were significantly lower than those in the controls. The negative and positive controls exhibited no and some apoptosis, respectively, whereas the anlotinib group evidenced extensive apoptosis.Conclusion: Anlotinib suppressed HNSCC growth in vitro and in vivo (by inhibiting cell proliferation and promoting apoptosis), suggesting that anlotinib can potentially treat HNSCC.

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