Bioactivity of betulinic acid nanoemulsions on skin carcinogenesis in transgenic mice K14E6

Alternative therapies for cancer treatment have been developed using bioactive compounds such as betulinic acid (BA). The objective of this study was to investigate the bioactivity of BA in its free form and compare it with its nano-encapsulated form under a skin carcinogenesis protocol in a genetically modified murine model. K14E6 and FVB mice were divided into four groups to be treated with free BA and with betulinic acid nanoemulsion (BANE). Lecithin enriched with medium chain fatty acids (MCFAs) was employed as an emulsifier to prepare the nanoemulsions with a mean droplet size of 40 nm. Skin tumors were induced by exposure to DMBA and TPA directly to the transgenic mice. Tumor development was completely inhibited by BANE and by 70% with free BA. This was validated by histological sections and the gene expression of the Cdk4 and Casp8 genes.

Download Full-text

Homozygous K5Cre transgenic mice have wavy hair and accelerated malignant progression in a murine model of skin carcinogenesis

Molecular Carcinogenesis ◽

10.1002/mc.20192 ◽

2006 ◽

Vol 46 (1) ◽

pp. 49-59 ◽

Cited By ~ 5

Author(s):

Edward L. Chan ◽

Belinda E. Peace ◽

Kenya Toney ◽

Sarah A. Kader ◽

Peterson Pathrose ◽

...

Keyword(s):

Transgenic Mice ◽

Murine Model ◽

Skin Carcinogenesis ◽

Malignant Progression

Download Full-text

CYLD Inhibits the Development of Skin Squamous Cell Tumors in Immunocompetent Mice

International Journal of Molecular Sciences ◽

10.3390/ijms22136736 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6736

Author(s):

Josefa P. Alameda ◽

Verónica A. García-García ◽

Silvia López ◽

Ana Hernando ◽

Angustias Page ◽

...

Keyword(s):

Skin Cancer ◽

Tumor Suppressor ◽

Transgenic Mice ◽

Tumor Development ◽

Skin Carcinogenesis ◽

Moderate Increase ◽

Wild Type ◽

Suppressor Activity ◽

Immunocompetent Mice

Cylindromatosis (CYLD) is a deubiquitinase (DUB) enzyme that was initially characterized as a tumor suppressor of adnexal skin tumors in patients with CYLD syndrome. Later, it was also shown that the expression of functionally inactive mutated forms of CYLD promoted tumor development and progression of non-melanoma skin cancer (NMSC). However, the ability of wild-type CYLD to inhibit skin tumorigenesis in vivo in immunocompetent mice has not been proved. Herein, we generated transgenic mice that express the wild type form of CYLD under the control of the keratin 5 (K5) promoter (K5-CYLDwt mice) and analyzed the skin properties of these transgenic mice by WB and immunohistochemistry, studied the survival and proliferating characteristics of primary keratinocytes, and performed chemical skin carcinogenesis experiments. As a result, we found a reduced activation of the nuclear factor kappa B (NF-κB) pathway in the skin of K5-CYLDwt mice in response to tumor necrosis factor-α (TNF-α); accordingly, when subjected to insults, K5-CYLDwt keratinocytes are prone to apoptosis and are protected from excessive hyperproliferation. Skin carcinogenesis assays showed inhibition of tumor development in K5-CYLDwt mice. As a mechanism of this tumor suppressor activity, we found that a moderate increase in CYLD expression levels reduced NF-κB activation, which favored the differentiation of tumor epidermal cells and inhibited its proliferation; moreover, it decreased tumor angiogenesis and inflammation. Altogether, our results suggest that increased levels of CYLD may be useful for anti-skin cancer therapy.

Download Full-text

Retinal abnormalities in transgenic mice overexpressing aberrant human FUS[1-359] gene

Bulletin of Russian State Medical University ◽

10.24075/brsmu.2021.043 ◽

2021 ◽

Author(s):

VO Soldatov ◽

MS Kukharsky ◽

MO Soldatova ◽

OA Puchenkova ◽

YuA Nikitina ◽

...

Keyword(s):

Gene Expression ◽

Amyotrophic Lateral Sclerosis ◽

Transgenic Mice ◽

Western Blot ◽

Murine Model ◽

Retinal Damage ◽

Wild Type ◽

Retinal Examination ◽

Lateral Sclerosis ◽

Fus Protein

Retinal damage is an optional sign in a number of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). The aim of this work was to assess the structural and functional state of the retina in a murine model of ALS caused by overexpression of the aberrant FUS protein [1-359]. The retinal examination was carried out on 12 transgenic and 13 wild-type mice of 2.5–3 months of age. The study revealed not statistically significant higher level of ophthalmoscopic violations in FUS[1-359] mice. Moreover, gene expression assay confirmed an increased expression of the inflammatory genes Vegfa, Il1b, Il6, Icam1, Tnfa. However, despite the detected structural and functional abnormalities, western blot analysis and quantitative PCR did not detect the expression of the protein and mRNA products of the FUS transgene in the retina of FUS[1-359] mice.

Download Full-text

Role of Huntingtin Interacting Protein HIP-1 in Non-Hodgkin’s Lymphoma.

Blood ◽

10.1182/blood.v108.11.2384.2384 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2384-2384

Author(s):

Mitchell R. Smith ◽

Indira Joshi ◽

Fang Jin ◽

Sarah V. Bradley ◽

Theodora S. Ross

Keyword(s):

Gene Expression ◽

B Cells ◽

Transgenic Mice ◽

Cyclin D1 ◽

Murine Model ◽

Actin Binding ◽

Data Set ◽

Interacting Protein ◽

Hodgkin's Lymphomas ◽

Huntingtin Interacting Protein

Abstract We have developed a murine model for mantle cell lymphoma (muMCL) that occurs after pristane injection of Eμ-cyclin D1 transgenic mice that are > 1 year of age (Leukemia 20:891, 2006). Eμ-cyclin D1 transgenic mice are healthy, implying that cyclin D1 may be necessary, but not sufficient, for MCL decvelopment. We are using this model to identify genes that coooperate with cyclin D1 in lymphomagenensis. Comparing gene expression in B cells from spleens of these muMCL with B cells from non-pristane injected age-matched Eμ-cyclin D1 transgenic mice by differential gene expression, we identified up-regulation of RNA for the Huntingtin interacting protein HIP-1 in the muMCL. We confirmed that this translated into up-regulation at the protein level by Western blot. HIP-1 is an inositol lipid, clathrin and actin binding protein that can directly transform fibroblasts. HIP-1, located on 7q, was previously found in a fusion protein with PDGFRβ in a case of CMML with t(5;7), suggsting a role in hematopoietic malignancies. To test the generalizability of the finding of HIP-1 overexpression in lymphoma, we performed immunohistochemistry using the monoclonal anti-HIP-1 antibody 4B10 on a lymphoma tissue microarray (Cybridi). Positive antibody staining was found in 79 of 116 (68.1%) non-Hodgkin’s lymphomas (NHL). Based on: our identification of HIP-1 as a potential cooperating gene in MCL development; overexpression of HIP-1 in many NHL; and that the presence of antibodies to HIP-1 in serum correlates with overexpression of the protein, we tested serum samples from lymphoma patients. We found circulating HIP-1 antibodies in sera from 23 of 39 (59%) lymphoma patients. The highest antibody titer was in serum from a patient with T-ALL in remission during maintenance chemotherapy who had a cytogenetic abnormality of 7q near the site of the HIP-1 gene. Studies are ongoing to expand this data set to see if HIP-1 antibodies correlate with disease type or outcome. In summary, HIP-1 appears to be involved in lymphoma development in a murine model of MCL and is frequently overexpressed in other types of NHL. Its role in lymphomagenesis, and potentially in treatment response and prognosis needs to be further explored.

Download Full-text