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1.
Oncol Rep ; 41(5): 2615-2624, 2019 May.
Article in English | MEDLINE | ID: mdl-30896830

ABSTRACT

Head and neck squamous cell carcinoma (HNSCC) is the sixth most commonly diagnosed cancer worldwide. It has poor clinical outcome due to intrinsic or acquired drug resistance. Deregulation of both apoptosis and autophagy contributes to chemotherapy resistance and disease progression. A new member of the inhibitors of apoptosis protein (IAP) family, namely survivin, is selectively overexpressed in tumors, including HNSCC, but not in normal tissues. Thus, it is considered a tumor biomarker. Here, we reviewed survivin expression and function in tumor progression focusing on its nodal role in the regulation of cell apoptosis and autophagy. Based on literature data, survivin targeting may be envisaged as a novel therapeutic strategy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Biomarkers, Tumor/metabolism , Head and Neck Neoplasms/drug therapy , Squamous Cell Carcinoma of Head and Neck/drug therapy , Survivin/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Apoptosis/drug effects , Autophagy/drug effects , Biomarkers, Tumor/antagonists & inhibitors , Cell Cycle/drug effects , Clinical Trials as Topic , Disease Progression , Drug Resistance, Neoplasm/drug effects , Head and Neck Neoplasms/pathology , Humans , Molecular Targeted Therapy/methods , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/prevention & control , Squamous Cell Carcinoma of Head and Neck/pathology , Survivin/antagonists & inhibitors , Treatment Outcome
2.
Int J Immunopathol Pharmacol ; 22(2): 485-92, 2009.
Article in English | MEDLINE | ID: mdl-19505400

ABSTRACT

Fibroblasts play a key role in tissue healing by producing the majority of extracellular matrix components, favouring granulation tissue formation, and stimulating re-epithelialization. Hyaluronan is a component of ECM and its anti-inflammatory effects and properties in enhancing wound closure are well known. In this study, we examined the effects of Aminogam gel, a new pharmacological preparation suggested to improve wound healing, composed of hyaluronic acid, proline, lysine, glycine and leucine, on human fibroblasts. Results show that fibroblasts treated with hyaluronic acid plus aminoacid solution increased their proliferative activity, collagen I and III, and fibronectin synthesis. Moreover, HA plus aminoacid solution increased the expression of transforming growth factor beta, connective tissue growth factor, interleukin-6 and -8, assayed by RT-PCR. These results suggested that Aminogam gel, involved in several stages of wound healing, as fibroblast proliferation, granulation tissue formation, ECM component deposition, and production of cytokines, may be a useful device to favour and accelerate wound closure.


Subject(s)
Amino Acids/pharmacology , Cell Proliferation/drug effects , Collagen Type III/biosynthesis , Collagen Type I/biosynthesis , Fibroblasts/drug effects , Hyaluronic Acid/pharmacology , Intercellular Signaling Peptides and Proteins/metabolism , Wound Healing/drug effects , Cell Cycle/drug effects , Cells, Cultured , Collagen Type I/genetics , Collagen Type III/genetics , Connective Tissue Growth Factor/metabolism , Drug Combinations , Fibroblasts/metabolism , Fibronectins/biosynthesis , Humans , Intercellular Signaling Peptides and Proteins/genetics , Interleukin-6/metabolism , Interleukin-8/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Time Factors , Transforming Growth Factor beta/metabolism
3.
Int J Immunopathol Pharmacol ; 18(3 Suppl): 33-8, 2005.
Article in English | MEDLINE | ID: mdl-16848985

ABSTRACT

The molecular mechanisms involved in the development of oral squamous cell carcinomas (OSCC) are not yet well understood. Evidence of recent studies suggests that aberrant beta-catenin signalling may participate in the neoplastic transformation and that it is implicated in the development of several tumours. Beta-catenin is a component of the catenin family and plays a crucial role in cadherin mediated cell adhesion. However, it has recently been shown that beta-catenin is also involved in other functions such as intracellular signalling and the regulation of gene transcription. The aim of this study is to evaluate the presence of mutation in exon 3 of the beta-catenin gene in 20 OSCC cell lines. DNA was extracted using Qiagen Qiamp DNA minikit and a region encompassing the exon 3 of beta-catenin gene was amplified using a single PCR assay. The PCR products were analysed by SSCP and direct sequencing to detect any mutation of the gene. Most of the cell lines examined showed, by immunofluorescence, a beta-catenin delocalization. SSCP and sequence analysis of the PCR products did not show any mutation of the beta-catenin gene in any of the cell lines. In conclusion, although aberrant expressions or abnormal localization of beta-catenin have been detected in several OSCC cells, it appears that this finding has no relationship with beta-catenin gene mutations.


Subject(s)
Carcinoma, Squamous Cell/genetics , Mouth Neoplasms/genetics , Mutation , beta Catenin/genetics , Cell Line, Tumor , Exons , Humans
4.
Histol Histopathol ; 19(1): 119-28, 2004 01.
Article in English | MEDLINE | ID: mdl-14702179

ABSTRACT

UNLABELLED: HSP27 belongs to the Heat shock protein (HSP) family, which plays essential functions in cells under physiological conditions and prevents stress-induced cellular damage. The aim of this study was to investigate the biological role of HSP27 in oral tumorigenesis. MATERIALS AND METHODS: Seventy-nine cases of oral squamous cell carcinoma and 10 cases of normal mucosa were analysed for HSP27 expression by immunohistochemistry. Moreover, the western blot analysis was performed on two cases of normal mucosa and five cases of OSCC. RESULTS: Normal oral mucosa showed a suprabasal expression of HSP27. Twenty-four cases of SCC (30.7%) showed a diffuse staining for HSP27, and 48 cases (60.3%) showed instead a decrease in staining, which was diffuse, homogeneous, or with alternation of positive and negative areas in a single tumor ("mosaic" pattern). Only 7 cases of OSCC (7.5%) were completely negative for HSP27. Frequency of lymph node metastases was higher in HSP27-negative tumours (3/7, 42.8%) than in HSP-reduced (16/48, 33.3%) or positive ones (5/26, 19.2%). Regard staging, stages I and II had a higher score than stages III and IV (stage I > stage II > stage III > stage IV). There was also a statistically significant correlation between HSP27 expression and grade: HSP27 expression was reduced in poorly differentiated tumours (P < 0.05). When analysed for prognostic significance, patients with negative/reduced HSP27 expression had poorer survival rates than the group with positive HSP27 expression (P < 0.05). The statistical analysis of these findings showed no significant correlation between HSP27 expression, sex, and tumour size. CONCLUSION: Cases with reduced expression were more aggressive and poorly differentiated. These data suggest that HSP27 expression may be useful in order to identify cases of oral squamous cell carcinoma with more aggressive and invasive phenotype providing novel diagnostic and prognostic information on individual patient survival with oral cancers.


Subject(s)
Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , Heat-Shock Proteins , Mouth Neoplasms/diagnosis , Mouth Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Blotting, Western , Carcinoma, Squamous Cell/mortality , Female , Humans , Immunohistochemistry , Italy , Lymphatic Metastasis , Male , Middle Aged , Mouth Neoplasms/mortality , Neoplasm Staging , Prognosis , Survival Rate
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