PPARδ is pro-tumorigenic in a mouse model of COX-2-induced mammary cancer

Optical coherence tomography (OCT) is a high-resolution, nondestructive imaging modality that enables time-serial assessment of adenoma development in the mouse model of colorectal cancer. In this study, OCT was utilized to evaluate the effectiveness of interventions with the experimental antitumor agent α-difluoromethylornithine (DFMO) and a nonsteroidal anti-inflammatory drug sulindac during early [chemoprevention (CP)] and late stages [chemotherapy (CT)] of colon tumorigenesis. Biological endpoints for drug interventions included OCT-generated tumor number and tumor burden. Immunochistochemistry was used to evaluate biochemical endpoints [Ki-67, cleaved caspase-3, cyclooxygenase (COX)-2, β-catenin]. K-Ras codon 12 mutations were studied with polymerase chain reaction-based technique. We demonstrated that OCT imaging significantly correlated with histological analysis of both tumor number and tumor burden for all experimental groups ( P < 0.0001), but allows more accurate and full characterization of tumor number and burden growth rate because of its time-serial, nondestructive nature. DFMO alone or in combination with sulindac suppressed both the tumor number and tumor burden growth rate in the CP setting because of DFMO-mediated decrease in cell proliferation (Ki-67, P < 0.001) and K-RAS mutations frequency ( P = 0.04). In the CT setting, sulindac alone and DFMO/sulindac combination were effective in reducing tumor number, but not tumor burden growth rate. A decrease in COX-2 staining in DFMO/sulindac CT groups (COX-2, P < 0.01) confirmed the treatment effect. Use of nondestructive OCT enabled repeated, quantitative evaluation of tumor number and burden, allowing changes in these parameters to be measured during CP and as a result of CT. In conclusion, OCT is a robust minimally invasive method for monitoring colorectal cancer disease and effectiveness of therapies in mouse models.

Download Full-text

Prostaglandin EP2 receptor antagonist ameliorates neuroinflammation in a two-hit mouse model of Alzheimer’s disease

Journal of Neuroinflammation ◽

10.1186/s12974-021-02297-7 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Avijit Banik ◽

Radhika Amaradhi ◽

Daniel Lee ◽

Michael Sau ◽

Wenyi Wang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Complete Blood Count ◽

Cardiovascular Effects ◽

Mrna Levels ◽

Proinflammatory Mediators ◽

Model Of Alzheimer’S Disease ◽

Cox 2 ◽

5Xfad Mice

Abstract Background Alzheimer’s disease (AD) causes substantial medical and societal burden with no therapies ameliorating cognitive deficits. Centralized pathologies involving amyloids, neurofibrillary tangles, and neuroinflammatory pathways are being investigated to identify disease-modifying targets for AD. Cyclooxygenase-2 (COX-2) is one of the potential neuroinflammatory agents involved in AD progression. However, chronic use of COX-2 inhibitors in patients produced adverse cardiovascular effects. We asked whether inhibition of EP2 receptors, downstream of the COX-2 signaling pathway, can ameliorate neuroinflammation in AD brains in presence or absence of a secondary inflammatory stimuli. Methods We treated 5xFAD mice and their non-transgenic (nTg) littermates in presence or absence of lipopolysaccharide (LPS) with an EP2 antagonist (TG11-77.HCl). In cohort 1, nTg (no-hit) or 5xFAD (single-hit—genetic) mice were treated with vehicle or TG11-77.HCl for 12 weeks. In cohort 2, nTg (single-hit—environmental) and 5xFAD mice (two-hit) were administered LPS (0.5 mg/kg/week) and treated with vehicle or TG11-77.HCl for 8 weeks. Results Complete blood count analysis showed that LPS induced anemia of inflammation in both groups in cohort 2. There was no adverse effect of LPS or EP2 antagonist on body weight throughout the treatment. In the neocortex isolated from the two-hit cohort of females, but not males, the elevated mRNA levels of proinflammatory mediators (IL-1β, TNF, IL-6, CCL2, EP2), glial markers (IBA1, GFAP, CD11b, S110B), and glial proteins were significantly reduced by EP2 antagonist treatment. Intriguingly, the EP2 antagonist had no effect on either of the single-hit cohorts. There was a modest increase in amyloid–plaque deposition upon EP2 antagonist treatment in the two-hit female brains, but not in the single-hit genetic female cohort. Conclusion These results reveal a potential neuroinflammatory role for EP2 in the two-hit 5xFAD mouse model. A selective EP2 antagonist reduces inflammation only in female AD mice subjected to a second inflammatory insult.

Download Full-text

Effect of Bee Venom Pharmacopuncture on Inflammation in Mouse Model of Induced Atopic Dermatitis

Journal of Acupuncture Research ◽

10.13045/jar.2020.00122 ◽

2020 ◽

Vol 37 (2) ◽

pp. 123-127

Author(s):

Kyeong Ju Park ◽

Ho-Sueb Song

Keyword(s):

Atopic Dermatitis ◽

Mouse Model ◽

Treated Group ◽

Bee Venom ◽

Related Protein ◽

Griess Reaction ◽

Cox 2 ◽

Dose Dependent Decrease ◽

Dose Dependent ◽

Inflammatory Effect

Background: This study was designed using a mouse model of atopic dermatitis [phthalic anhydride (PA)-treated mice], to investigate the anti-inflammatory effect of bee venom pharmacopuncture (BVP) in keratinocytes.Methods: Western blot analysis was performed to investigate inflammation related protein expression of iNOS, COX-2, phospho-ERK (p-ERK), and ERK, in LPS (1 μg/mL)-activated keratinocytes, following BVP treatment, and in PA-treated mice, after BVP treatment. Griess reaction was performed to investigate NO concentration. Enzyme-linked immunosorbent assays were used to determine the concentrations of interleukin (IL)-4+, IL-17A+, IL-13 and IL-4 in PA-treated mice after BVP treatment. In addition, monocyte, macrophage, neutrophil, and eosinophil counts were measured to observe the changes in white blood cell infiltration.Results: The keratinocytes of the BVP-treated group showed a decreased expression of iNOS, COX-2, ERK at 5 OX-2, ERK E, and p-ERK at 1, 2 and 5 RKRK ERK ERK, and a dose-dependent decrease in NO concentration at 2 and 5 ntrationof s. In the BVP-treated groups (0.1 μ.1-trea μ.1-treated gr), PA-treated mice showed recovery after 4 weeks which was dose-dependent, showing a significant decrease in clinical scores for AD, and a decreased concentration of IL-13 and IL-4 with BV treatment. There was a dose-dependent decrease in the infiltration of eosinophils, neutrophils, monocytes, macrophages, and a decreased thickness of the epidermis due to inflammation, and decreased expressions of iNOS, COX-2, p-ERK, ERK, especially in the 0.1 μ0/mL BVP-treated group,<br>Conclusion: These results suggest that BVP may be an effective alternative treatment for atopic dermatitis.

Download Full-text

Multimodal In Vivo Imaging of Tumorigenesis and Response to Chemotherapy in a Transgenic Mouse Model of Mammary Cancer

Molecular Imaging and Biology ◽

10.1007/s11307-015-0916-7 ◽

2015 ◽

Vol 18 (4) ◽

pp. 617-626 ◽

Cited By ~ 4

Author(s):

Jean-Louis Alberini ◽

Raphaël Boisgard ◽

Stéphanie Guillermet ◽

Karine Siquier ◽

Benoît Jego ◽

...

Keyword(s):

Mouse Model ◽

Transgenic Mouse ◽

In Vivo Imaging ◽

Mammary Cancer ◽

Transgenic Mouse Model ◽

Response To Chemotherapy

Download Full-text

Different role of COX-2 and angiogenesis in canine inflammatory and non-inflammatory mammary cancer

The Veterinary Journal ◽

10.1016/j.tvjl.2013.02.009 ◽

2013 ◽

Vol 197 (2) ◽

pp. 427-432 ◽

Cited By ~ 26

Author(s):

Mónica Clemente ◽

Ana Rodríguez Sánchez-Archidona ◽

David Sardón ◽

Lucía Díez ◽

Asunción Martín-Ruiz ◽

...

Keyword(s):

Mammary Cancer ◽

Cox 2

Download Full-text

Abstract 3244: Combination of COX-2 inhibitor Celebrex with androgen deprivation synergistically inhibits tumor growth in a syngeneic mouse model of prostate cancer

10.1158/1538-7445.am10-3244 ◽

2010 ◽

Author(s):

Parisa Abedinpour ◽

Véronique Baron ◽

John Welsh ◽

Per Borgström

Keyword(s):

Prostate Cancer ◽

Mouse Model ◽

Tumor Growth ◽

Androgen Deprivation ◽

Syngeneic Mouse ◽

Syngeneic Mouse Model ◽

Cox 2

Download Full-text

Are FDA-Approved Sunscreen Components Effective in Preventing Solar UV-Induced Skin Cancer?

Cells ◽

10.3390/cells9071674 ◽

2020 ◽

Vol 9 (7) ◽

pp. 1674

Author(s):

Ann M. Bode ◽

Eunmiri Roh

Keyword(s):

Mouse Model ◽

Mouse Skin ◽

Hairless Mouse ◽

Cutaneous Squamous Cell Carcinoma ◽

Skin Carcinogenesis ◽

Skin Damage ◽

Solar Uv ◽

Keratin 17 ◽

Cox 2 ◽

Solar Ultraviolet

Solar ultraviolet (SUV) exposure is a major risk factor in the etiology of cutaneous squamous cell carcinoma (cSCC). People commonly use sunscreens to prevent SUV-induced skin damage and cancer. Nonetheless, the prevalence of cSCC continues to increase every year, suggesting that commercially available sunscreens might not be used appropriately or are not completely effective. In the current study, a solar simulated light (SSL)-induced cSCC mouse model was used to investigate the efficacy of eight commonly used FDA-approved sunscreen components against skin carcinogenesis. First, we tested FDA-approved sunscreen components for their ability to block UVA or UVB irradiation by using VITRO-SKIN (a model that mimics human skin properties), and then the efficacy of FDA-approved sunscreen components was investigated in an SSL-induced cSCC mouse model. Our results identified which FDA-approved sunscreen components or combinations are effective in preventing cSCC development. Not surprisingly, the results indicated that sunscreen combinations that block both UVA and UVB significantly suppressed the formation of cutaneous papillomas and cSCC development and decreased the activation of oncoproteins and the expression of COX-2, keratin 17, and EGFR in SSL-exposed SKH-1 (Crl:SKH1-Hrhr) hairless mouse skin. Notably, several sunscreen components that were individually purported to block both UVA and UVB were ineffective alone. At least one component had toxic effects that led to a high mortality rate in mice exposed to SSL. Our findings provide new insights into the development of the best sunscreen to prevent chronic SUV-induced cSCC development.

Download Full-text