Browsing by Subject "Oral cancer"
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- PublicationOpen AccessE-cadherin in oral SCC: An analysis of the confusing literature and new insights related to its immunohistochemical expression(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Vered, Marilena; Allon, Irit; Buchner, Amos; Dayan, DanE-cadherin plays a crucial structural role in cell-cell contacts in epithelial tissues, and a functional role in signaling pathways that regulate cell proliferation, differentiation, and survival. Reduced immunoexpression of E-cadherin adhesions is largely considered as being equivalent to defective functionality and malignancy, and has been used as a prognostic parameter. A critical analysis of studies on E-cadherin immunoexpression in oral carcinomas revealed a wide range of both technical and interpretational aspects. This paper highlights biological characteristics of E-cadherin with respect to its expression in normal and neoplastic epithelial cells and to its interrelations with the tumor microenvironment that can have an impact on immunohistochemical results and their application in the clinical setting
- PublicationOpen AccessE-cadherin, β-catenin, and α2β1 and α3β1 integrin expression in primary oral squamous cell carcinoma and its regional metastasi(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Quirino Silveira Soares, Mariana; Andrade Mendonça, Juliana; Oliveira Morais, Marília; Rodrigues Leles, Claudio; Carvalho Batista, Aline; Mendonça, Elismauro Francisco. To investigate E-cadherin, β-catenin, and α2β1 and α3β1 integrins in 40 samples of nonmetastatic and metastatic oral squamous cell carcinoma (OSCC) with positive cervical lymph nodes (LN). Immunohistochemistry was used to evaluate expression in the lesion center (LC) and invasive tumor front (ITF) of non-metastatic (n=18) and metastatic (n=22) OSCC and in the LN on the metastatic neoplastic cells (MNC; n=22). In metastatic OSCC, E-cadherin and β-catenin presented significantly lower cytoplasmic membrane expression in the ITF and MNC when compared to the LC and lower cytoplasmic expression in MNC when compared to the LC and ITF (p<0.05). Integrins α2β1 and α3β1 showed high cytoplasmic expression in the LC, ITF and MNC (p>0.05). A positive correlation was observed between E-cadherin cytoplasmic expression and α2β1 (ρ=0.860) and α3β1 (ρ=0.975) expression. When comparing the primary sites of metastatic and non-metastatic disease, β-catenin presented lower cytoplasmic membrane (p=0.013) expression in metastatic OSCC. E-cadherin presented low expression and the integrins high expression in both groups. Abnormal expression of β-catenin and E-cadherin associated with high expression of α2β1 and α3β1 integrins contribute to LN metastasis in OSCC.
- PublicationOpen AccessEmerging histopathological parameters in the prognosis of oral squamous cell carcinomas(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Freitas de Morais, Everton; Almangush, Alhadi; Salo, Tuula; Silva da, Sabrina Daniela; Kujan, Omar; Coletta, Ricardo D.Oral squamous cell carcinoma (OSCC) is the most common oral malignancy, representing 90% of all malignant neoplasms in the head and neck region. Patients with this aggressive tumor have an overall 5year survival rate of approximately 50%, which drops to less than 30% when tumors are diagnosed at advanced clinical stages. Over decades, several studies provided high-level evidence of the impact of histopathological features on treatment guidelines and prognosis of OSCC. The 8th American Joint Committee on Cancer (AJCC) TNM staging system recognized the importance of depth of invasion to the T category and extranodal extension to the N category for OSCC. This review provides the current knowledge on emerging histopathological parameters identified as potential biomarkers for OSCC, such as depth of invasion, tumor thickness, the pattern of invasion, inflammatory profile, and tumor-stroma ratio, evaluating their clinical relevance on patient outcomes. Analysis, limitations, and potential biological mechanisms are highlighted and discussed. Assessing and reporting these markers are cost-effective and can be incorporated into daily practice.
- PublicationEmbargoInfluence of years of professional experience in relation to the diagnostic skill of general dental practitioners (GDPs) in identifying oral cancer and precancerous lesions(FDI/World Dental Press, 2008-06) López Jornet, Pia; Camacho Alonso, Fabio; Martínez Beneyto, Yolanda; Dermatología, Estomatología, Radiología y Medicina FísicaObjective: To evaluate skill in diagnosing cancer and oral precancerous lesions among general dentists in the Autonomous Community of Murcia (Spain). Material and method: Twenty randomly distributed clinical images were used, of which 45% corresponded to benign lesions, 35% to oral precancerous lesions, and 20% to oral cancer. Each case was accompanied by a summarised clinical history. The study sample comprised 150 general dentists divided into two groups: group I (60 recently graduated dentists without professional experience) and group II (90 dentists with established professional activity). Results: In group I, the sensitivity of oral cancer diagnosis was 61.3% versus 85.5% in group II (p<0.001), while the sensitivity of precancerous lesion diagnosis was 71.7% in group I versus 80.7% in group II (p=0.004). Conclusions: The results obtained show that junior dentists and general dentists with public or private practice need more training and more experience in diagnosing cancer and oral precancerous lesions.
- PublicationOpen AccessMolecules of cell adhesion and extracellular matrix proteolysis in oral squamous cell carcinoma(Murcia : F. Hernández, 2010) Shi, Zonggao; Stack, M. SharonOral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity with a poor 5-year survival rate, due in large part to the presence of metastatic disease at initial diagnosis. In recent years, a number of studies have examined the oral tumor microenvironment to asses the potential dynamic balance between extracellular matrix deposition and proteolytic degradation as well as the cellular adhesion molecules that mediate adhesion to matrix and regulate tissue cohesion. The objective of this review is to provide a brief overview of the major matrix components, adhesion molecules and proteolytic enzymes in the oral tumor microenvironment and to summarize recent findings regarding the role of these complex molecular players in oral tumor progression.
- PublicationOpen AccessMultiple kallikrein (KLK 5, 7, 8, and 10) expression in squamous cell carcinoma of the oral cavity(Murcia : F. Hernández, 2009) Pettus, Jason R.; Johnson, Jeffrey J.; Shi, Zonggao; Davis, J.Wade; Koblinski, Jennifer; Ghosh, Supurna; Liu, Yueying; Ravosa, Matthew J.; Frazier, Shellaine; Stack, M. SharonOral squamous cell carcinoma (OSCC) represents 3% of all cancer deaths in the U.S. and is ranked one of the top 10 cancers worldwide. The 5-year survival rate has remained at a low 50% for the past several decades, necessitating discovery of novel biomarkers of aggressive disease and therapeutic targets. As overexpression of urinary type plasminogen activator and receptor (uPA/R) in OSCC is associated with malignant progression and poor outcome, cell lines were generated with either overexpression (SCC25-uPAR+) or silencing (SCC25-uPAR-KD) of uPAR. As SCC25- uPAR+ tumors behaved more aggressively both in vitro and in vivo, comparative cDNA microarray analysis was used to identify additional genes that may be associated with aggressive tumors. Four members of the human tissue kallikrein family (KLK 5, 7, 8, and 10) were identified and real-time RT-PCR (qPCR) was used to verify and quantify gene expression. qPCR analysis revealed 2.8-, 5.3-, 4.0-, and 3.5-fold increases in gene expression for KLK5, 7, 8, and 10, respectively, in SCC25-uPAR+ versus SCC25-uPAR-KD. Immunohistochemical analysis demonstrated strong reactivity for KLKs 5, 7, 8 and 10 in both orthotopic murine tumors and human OSCC tissues. Control experiments show lack of reactivity against KLK3 (prostate specific antigen). These results demonstrate that kallikreins 5, 7, 8, and 10 are abundantly expressed in human OSCC and may be implicated in malignant progression.
- PublicationEmbargoPremalignant nature of oral lichen planus. A retrospective study of 550 oral lichen planus patients from south-eastern Spain(Elsevier, 2009-04-09) Bermejo Fenoll, A.; Sanchez-Piles, M.; López Jornet, Pía; Camacho Alonso, Fabio; Salazar Sánchez, N.; Dermatología, Estomatología, Radiología y Medicina FísicaThe most important complication of oral lichen planus (OLP) is the development of squamous cell carcinoma (SCC) – this being an association that remains subject to controversy. This study aims to examine the incidence and clinical presentation of oral malignancies associated with OLP. A retrospective study was made of 550 patients diagnosed with OLP according to the criteria of the World Health Organization, in the period between 1991 and 2007, in south-eastern Spain 128 males (23.3%) and 422 females (76.7%). A clinical protocol was applied in all cases (sociodemographic data, habits and hepatitis C markers), with histological confirmation of the disease. Five of the 550 patients (0.9%) developed SCC. The mean duration of follow-up was 24 ± 20.83 months. The tongue was the most common location. The exact incidence of malignant transformation of OLP is difficult to establish, due to the possible contribution of external risk factors that may be of relevance in oral malignancy.
- PublicationOpen AccessQuantitative cell-cycle protein expression in oral cancer assessed by computer-assisted system(Murcia : F. Hernández, 2006) Soares, C.P.; Zuanon, J.A.S.; Teresa, D.B.; Fregonezi, P.A.; Neto, C.B.; Oliveira, M.R.B.; Donadi, E.A.; Martinelli-Kläy, C.P.; Soares, E.G.The knowledge of cell-cycle control has shown that the capacity of malignant growth is acquired by the stepwise accumulation of defects in specific genes regulating cell growth. Histologic diagnosis might be improved by a quantitative evaluation of more specific diagnosis biomarkers, which could help to precisely identify pre-malignant and malignant oral lesions. The aim of the present study is to evaluate whether computer-based quantitative assessment of p53, PCNA and Ki-67 immunohistochemical expression, could be used clinically to foresee the risk of oral malignant transformation. This retrospective study was carried out in ninety-five oral biopsies, 27 were classified as fibrous inflammatory hyperplasia, 40 as leukoplakia and 28 as oral squamous cell carcinoma. Sixteen out of the 40 leukoplakia were diagnosed as non-dysplastic leukoplakia, the other 24 being dysplastic leukoplakia, of which 50.0% were classified as moderate to severe dysplasia. Comparison of the four groups of oral tissues showed significant rises in p53 and Ki-67 positivity index, which increased steadily in the order benign, premalignant, and malignant. In contrast, it was not possible to relate higher PCNA levels with pre-malignant and malignant oral lesions. We therefore conclude that PCNA immunohistochemistry expression is probably an inappropriate marker to identify oral carcinogenesis, whereas joint quantitative evaluation of p53 and Ki-67, appears to be useful as a tumor marker, providing a prediagnostic estimate of the potential for cell-cycle deregulation of the oral proliferate status.
- PublicationOpen AccessTargeting eIF5A2 reduces invasion and reverses chemoresistance in SCC-9 cells in vitro(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Gao, Jinbo; Li, PengBackground and Aims. Eukaryotic translation initiation factor 5A2 (EIF5A2) has been reported to be involved in metastasis and chemotherapy resistance in many human cancers. However, the effect and mechanism of EIF5A2 in oral cancer cells are unknown. Here, we investigated the effects of targeting EIF5A2 on chemotherapy resistance in oral cancer cells in vitro. Methods. By using a lentiviral system, we investigated the effects of targeting EIF5A2 on the invasion, migration, growth, and chemosensitivity of SCC-9 cells to CDDP in vitro. Through the method of gene intervention, we explore the role of pro-apoptotic Bim and epithelial and mesenchymal marker E-cadherin protein in this process and the regulation of EIF5A2 on Bim and E-cadherin. Results. Targeting EIF5A2 reduces invasion and migration in SCC-9 cells partly through upregulation of E-cadherin expression; Targeting EIF5A2 promotes cell apoptosis and inhibits cell survival as well as increasing chemosensitivity in SCC-9 cells through upregulation of Bim expression. Conclusion. EIF5A2 may be a novel potential therapeutic target for oral cancer by upregulation of Bim and E-cadherin
- PublicationOpen AccessThe receptor for advanced glycation end products is dispensable in a mouse model of oral and esophageal carcinogenesis(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Mark, Regina; Lorenzo Bermejo, Justo; Bierhaus, Angelika; Plinker, Peter K; Angel, Peter; Hess, JochenAberrant expression of the receptor for advanced glycation end products (RAGE) and its ligands, such as S100/Calgranulins, has been demonstrated in squamous cell carcinomas of the upper aerodigestive tract. However, the question whether RAGE signaling is causally linked with neoplastic transformation of keratinocytes in mucosal epithelia has not been addressed so far. We used the well-established mouse model of 4-nitroquinoline-1-oxide (4-NQO) induced tumorigenesis to investigate tumor development in control and RAGE-deficient (Rage-/- ) animals. Although 4-NQO induced lesions of the tongue and the esophagus showed strong induction of the RAGE ligands S100a8 and S100a9, we did not observe any significant difference in tumor incidence or multiplicity between control and Rage-/- mice. Furthermore, detailed analysis of tumor sections by histological and immunohistochemical staining revealed no difference in either the size or histological architecture of dysplastic lesions, tumor cell proliferation, or the number of inflammatory immune cells in the tumor microenvironment. Finally, we detected induced transcript and protein levels of the Toll-like receptor 4 (Tlr4) in 4-NQO induced lesions, suggesting that signaling via the S100- Tlr4 axis may compensate for the lack of RAGE in early stages of tumor development.