AKT and PERP Show Higher Expression in Precancerous than in Malignant Skin Neoplasms: Profiling in an Animal Model of Sequential Skin Carcinogenesis.

The primary aim of this study was to evaluate the activation of the PERP and Akt oncogenes in the induction of skin cancer in FVB/N mice by a stepwise chemical process. Forty four-week-old female FVB/N mice were randomly divided into a control group (n = 8) and two experimental groups (group A: n = 16, group B: n = 16). In the study, the groups were subjected to a two-stage carcinogenesis procedure.

FGFR2 and NOTCH1 Expression Inversely Correlated in Progressive Cutaneous Carcinogenesis in an Experimental Mouse Model.

Cutaneous squamous cell carcinoma (cSCC) is a common and increasingly prevalent form of skin cancer, posing significant health challenges. Understanding the molecular mechanisms involved in cSCC progression is crucial for developing effective treatments. The primary aim of this research was to evaluate the activation of NOTCH1 and FGFR2 oncogenes in inducing skin cancer in FVB/N mice through a stepwise chemical process.

Identification of Stage-Specific microRNAs that Govern the Early Stages of Sequential Oral Oncogenesis by Strategically Bridging Human Genetics with Epigenetics and Utilizing an Animal Model.

Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy, with mortality rates reaching 60%, mainly due to its excessive diagnostic delay. MiRNAs, a class of crucial epigenetic gene-expression regulators, have emerged as potential diagnostic biomarkers, with >200 molecules exhibiting expressional dysregulation in OSCC. We had previously established an in silico methodology for the identification of the most disease-specific molecules by bridging genetics and epigenetics.

Genetic Variations Related to Angiotensin II Production and Risk for Basal Cell Carcinoma.

Basal cell carcinoma (BCC) is the most prevalent human neoplasm, with constantly increasing annual incidence. Despite its slow growth, BCC is locally invasive and, if left untreated, can cause severe complications, including metastasis and death. The renin-angiotensin system (RAS) plays a key role in electrolyte balance, atrial pressure, tissue development, homeostasis, and inflammation, but also in cancer development.

EGFR and HER-2 oncogenes expression in an experimental model of two-stage chemically induced carcinogenesis in mouse skin.

The aim of the study was to investigate the expression of EGFR and HER-2 oncogenes using an experimental two stage chemically induced carcinogenesis protocol on the dorsal skin in FVB/N mice. Forty female FVB/N mice 4 weeks old, were grouped into one control (n = 8) and two experimental groups (Group A: n = 16, Group B: n = 16) following a randomization process. Two-stage carcinogenesis protocol, was implicated, including an initial treatment with 97.

Review of Disease-Specific microRNAs by Strategically Bridging Genetics and Epigenetics in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most prevalent human malignancies and a global health concern with a poor prognosis despite some therapeutic advances, highlighting the need for a better understanding of its molecular etiology. The genomic landscape of OSCC is well-established and recent research has focused on miRNAs, which regulate gene expression and may be useful non-invasive biomarkers or therapeutic targets. A plethora of findings regarding miRNA expression have been generated, posing challenges for the interpretation and identification of disease-specific molecules.

Angiotensinogen, Angiotensin-Converting Enzyme, and Chymase Gene Polymorphisms as Biomarkers for Basal Cell Carcinoma Susceptibility.

Introduction: The intake of angiotensin-converting enzyme (ACE) inhibitors and specific antagonists of angiotensin II receptors, widely used as antihypertensive drugs, significantly reduces the risk of developing basal cell carcinoma (BCC), highlighting the possible tumorigenic role of angiotensin II (AngII). We present here the investigated genetic association between the development of BCC and functional DNA polymorphisms M235T, I/D, and A1903G in the genes of angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and chymase (CMA1), which mediate AngII production levels.

Methods: DNA samples of 203 unrelated Greeks were studied, including 100 patients with BCC and 103 matched healthy controls.

Molecular Mechanisms Involved in Craniosynostosis.

Craniosynostosis refers to the early fusion of one or many cranial sutures, causing craniofacial abnormalities observed in 1:2,500 births worldwide. In most cases (85%), craniosynostosis is presented as sporadic anomaly (non-syndromic craniosynostosis), while in other cases (15%) as part of syndromes (syndromic craniosynostosis). Patients with syndromic disorder usually have more severe symptoms compared to those with single suture synostosis.

Association Between a High Gene Expression Variant of Chymase and Increased Risk for Basal Cell Carcinoma.

Background/aim: Previous studies have associated certain variations in genes encoding factors of renin-angiotensin system (RAS), indirectly leading to higher angiotensin II (AngII) levels, with greater risk for basal cell carcinoma (BCC) development. Chymase (CMA1) is the main regulator of the RAS-independent AngII generation pathway and numerous studies have shown its oncogenic potential in several cancer types including BCC. In this study, we investigated the possible association between BCC pathogenesis and the functional DNA polymorphism A1903G (rs1800875) that affects expression of the CMA1 gene.

Lack of Association Between the G8790A Gene Variation and Risk for Basal Cell Carcinoma.

Background/aim: The G8790A (rs2285666) functional polymorphism of the angiotensin-converting enzyme 2 (ACE2) gene influences alternative mRNA splicing and quantitatively affects the enzyme's production. Specifically, the presence of the A allele has been associated with higher ACE2 plasma levels. In this study, we investigated the possible association of the functional polymorphism ACE2-G8790A with the pathogenesis of basal cell carcinoma (BCC).

Association study indicates combined effect of interleukin-10 and angiotensin-converting enzyme in basal cell carcinoma development.

Cytokines involved in inflammatory and immune response have been associated with risk for development of basal cell carcinoma (BCC). In this study, three functional DNA polymorphisms affecting gene expression were investigated in 54 BCC patients and 111 healthy controls: interleukin-1b (IL-1b) +3953C/T, interleukin-10 (IL-10) - 1082G/A and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphisms. Significant increase of the variant alleles was observed in IL-10 - 1082G (P = 0.

The Hamster Model of Sequential Oral Carcinogenesis: An Update.

Animal models are valuable tools for studying human cancer as well as for preclinical trials. The hamster model of chemically induced sequential oral carcinogenesis was developed by our group a decade ago in order to study the multistep process of alterations in gene expression during carcinogenesis. The purpose of this review was to discuss the utility of the hamster model of sequential oral carcinogenesis regarding the deciphering of the main pathways altered.

Association of Polymorphisms in the Genes of Angiotensinogen and Angiotensin Receptors With Risk for Basal Cell Carcinoma.

Background/aim: Basal cell carcinoma (BCC) has been genetically associated with an increased expression of angiotensin-converting enzyme (ACE), an important factor of the renin-angiotensin system which produces vasoconstrictor angiotensin II. Other factors of this system include angiotensinogen (AGT) and angiotensin receptors AGTR1, AGTR2. We investigated the possible association of BCC with genetic variability in the AGT, AGTR1 and AGTR2 genes.

Gene Variant Causing High Blood Pressure May Be Associated With Medication-related Jaw Osteonecrosis.

The association of the high blood pressure D variant of the angiotensin-converting enzyme (ACE) gene with medication-related jaw osteonecrosis (MRONJ) is described in two Greek patients. The first patient, a 73-year-old man, took zolendronate, 4 mg/100 ml IV once per month for two years for prostate cancer and bone metastases. Three months after drug discontinuation, extraction of the first premolar was performed.

Effect of Olmesartan on the Level of Oral Cancer Risk Factor PAI1.

Aim: To study if the angiotensin receptor blocker olmesartan reduces levels of plasminogen activator inhibitor 1 (PAI1), a risk factor for oral cancer, in a mouse model and therefore whether it could be used in the treatment of this malignancy.

Materials And Methods: Twelve transgenic PAI1 mice aged 16-20 weeks were divided in two groups each containing six animals. One group was given olmesartan every day for 30 days in drinking water in an amount corresponding to their weight, 0.

Proliferating fibroblasts and HeLa cells co-cultured in vitro reciprocally influence growth patterns, protein expression, chromatin features and cell survival.

Aim: to identify biological interactions between proliferating fibroblasts and HeLa cells in vitro.

Materials And Methods: Fibroblasts were isolated from both normal and tumour human tissues. Coverslip co-cultures of HeLa and fibroblasts in various ratios with medium replacement every 48 h were studied using fixed cell staining with dyes such as Giemsa and silver staining, with immunochemistry for Ki-67 and E-cadherin, with dihydrofolate reductase (DHFR) enzyme reaction, as well as live cell staining for non-specific esterases and lipids.

Effect of thrombosis-related gene polymorphisms upon oral cancer: a regression analysis.

It is well-known that there is an interplay between hemostasis, thrombosis and cancer. Functional DNA polymorphisms in genes encoding factors related to thrombosis have been associated with increased risk for oral squamous cell carcinoma (OSCC). The present study investigated the possible combinatory effect of 10 such polymorphisms as primary risk predictors for OSCC in a European population.

Association of polymorphisms in Tumor Necrosis Factor Alpha and Beta genes with increased risk for oral cancer.

Background: In light of the recently found contribution of inflammation-related factors to oral oncogenesis, the possible correlation of tumor necrosis factor alpha and beta genes (TNF-alpha and TNF-beta) with risk of oral cancer was investigated.

Materials And Methods: DNA samples of 160 German and Greek patients with oral squamous cell carcinoma and 153 healthy controls of equivalent age, gender and ethnicity were studied. The functional polymorphisms TNF-alpha (-308 G/A) and TNF-beta (252 G/A), which affect gene expression, were investigated by restriction fragment length polymorphism analysis.

Diabetes enhances the expression of H-ras and suppresses the expression of EGFR leading to increased cell proliferation.

EGFR kinase activity triggers numerous signaling pathways, such as the Ras/Raf/MAPK cascade, leading to the activation of various mitogen activated protein kinases, which are implicated in cell proliferation through induction of several genes, including c-fos. The possible effect of diabetes on the expression of the oncogenes EGFR, H-ras and c-fos was investigated in an experimental model of chemically induced oral oncogenesis in normal and diabetic (type I) Sprague-Dawley rats. Thirteen diabetic and twelve normal rats developed cancer after 4NQO treatment, while six diabetic and six normal animals were used as controls.

Orbital cellulitis, orbital subperiosteal and intraorbital abscess: report of three cases and review of the literature.

Introduction: Orbital cellulitis is usually a complication of paranasal sinus infection. Either the infection may dissect under the periosteum and lead to subperiosteal abscess (SPA) or intraorbital abscess may be formed secondary to a progressive and localized cellulitis. Without appropriate treatment orbital infection may lead to serious complications, even death.

H-ras and c-fos exhibit similar expression patterns during most stages of oral oncogenesis.

Background: H-ras and c-fos oncogenes interact in signalling pathways but their level and time course of expression during oral cancer development are unclear. The present study used an animal model for the simultaneous investigation of H-Ras and c-Fos expression in sequential stages of oral oncogenesis.

Materials And Methods: Three experimental groups of Syrian golden hamsters (A, B and C; 10 animals each) and one control group (7 animals) were used.

Angiotensinogen polymorphism is associated with risk for malignancy but not for oral cancer.

Background: In light of the recently found contribution of angiogenic and inflammation-related factors to malignancies, this study investigated the possible association of the angiotensinogen gene (AGT) with increased risk of oral cancer.

Materials And Methods: The M235T polymorphism, which influences AGT gene expression, was evaluated by restriction fragment length polymorphism analysis in the DNA samples of 163 German and Greek patients with oral squamous cell carcinoma (OSCC) and 124 healthy controls of equivalent gender, ethnicity and age.

Results: No significant difference of the mutant (235T) allele, which results in higher AGT gene expression, was observed in the whole patient group in comparison with the normal controls.