Pleomorphic Adenoma of Minor Salivary Glands: a Rare Case Report.

Pleomorphic adenoma is a non-cancerous neoplasm that develops in the salivary glands. Originating from minor salivary glands, it is extremely uncommon and primarily affects females. The peak incidence is observed between 40 and 60 years of age. It usually presents as a slowly growing, painless, solid tumor that does not cause ulcers on the overlying mucosa. Here, a 47-year-old woman experienced repeated swelling on the buccal mucosa following surgical extraction of a pleomorphic adenoma three years ago. The swelling was solid with clearly defined boundaries. An excisional biopsy was conducted under general anesthesia, resulting in total mass removal. The histological evaluation revealed the existence of a recurring pleomorphic adenoma. This instance emphasizes the significance of addressing this entity as a potential etiology for persistent painless and intraoral swellings.

Clinical Impact of C-myc Oncogenic Diversity on Solid and Lymphoid Malignancies.

INTRODUCTION: Onset and progression of malignant tumors is a multistep process including a variety of gross chromosomal and specific genes' deregulation. Among oncogenes that are frequently altered in solid and also in hematological malignancies, the C-myc (gene locus: 8q24.21) plays a pivotal role. C-myc is a proto-oncogene encoding for a nuclear phosphoprotein implicated in cell cycle progression, apoptosis and cellular differentiation and transformation. OBJECTIVE: The purpose of the current molecular review was to explore the differences of C-myc oncogenic activity in solid and lymphoid malignancies that modify its clinical impact on them. MATERIAL AND METHOD: A systematic review of the literature in the international database PubMed was carried out. The year 2010 was set as a prominent time limit for the publication date of articles in the majority of them, whereas specific references of great importance and historical value in the field of C-myc gene discovery and analysis were also included. The following keywords were used: C-myc, oncogene, signaling pathway, malignancies, carcinoma, lymphoma. A pool of 43 important articles were selected for the present study at the basis of combining molecular knowledge with new targeted therapeutic strategies. RESULTS: C-myc oncogene demonstrates two different mechanisms of deregulation: amplification, mutation and translocation patterns. These particular aspects of gene alteration are unique for solid and non-solid (hematological) malignancies, respectively. CONCLUSIONS: C-myc is characterized by diversity regarding its deregulation mechanisms in malignancies derived from different tissues. C-myc translocation is sporadically combined with amplification ("complicon" formation) or mutations creating exotic genetic signatures. This "bi-phasic" C-myc deregulation model in the corresponding malignant tumor categories clinically affects the corresponding patients, also modifying the targeted therapeutic strategies on them.

C-Jun Transcription Factor Oncogenic Activation in Oral Carcinoma.

INTRODUCTION: Oral carcinogenetic is based on a variety of genomic imbalances (gross chromosome or specific gene alterations) that drive the normal oral mucosa to its neoplastic/dysplastic epithelial form and finally to a totally malignant tissue transformation. In this multi-step procedure, down-regulation of suppressor genes combined with overactivation of oncogenes are two crucial and partially early genetic events involved in the onset and progression of neoplastic/malignant epithelia transformation. More specifically, deregulation of strong transcription factors negatively affects the normal expression of a broad spectrum of genes that are involved in cell proliferation and signalling transduction to the nucleus. OBJECTIVE: The purpose of the current molecular review was to explore the c-Jun (chromosome location: 1p32-p31) transcription factor transformation mechanisms to oncogene in oral squamous cell carcinoma (OSCC). MATERIAL AND METHOD: A systematic review of the literature was carried out by searching in PubMed international database. The year 2010 was set as a prominent time limit for the publication date of the articles in the majority of them, whereas specific references of great importance and historical value in the field of the c-Jun gene discovery and analysis were also included. The following keywords were used: c-Jun, oncogene, signaling pathway, oral, carcinoma, transcription. A pool of 45 important articles were selected for the present study at the basis of combining molecular knowledge with new targeted therapeutic strategies. RESULTS: C-Jun - as a part of the c-Jun/c-Fos transcription factors' complex -critically regulates the expression levels in a variety of genes inside the cellular microenvironment. A broad spectrum of malignancies, including OSCC, demonstrate c-Jun alterations driving the gene to its oncogenic phenotype. Interestingly, c-Jun oncogenic activation is mediated by high-risk human papilloma virus (HR-HPV) persistent infection in significant subsets of these malignancies. CONCLUSIONS: C-Jun was the first oncogene - acting as a strong transcription factor - that was discovered and cloned 35 years ago. C-Jun is the living history of oncogenes and its discovery marks a significant step in the evolution of molecular biology.

Graphene oxide and oxidized carbon nanodiscs as biomedical scaffolds for the targeted delivery of quercetin to cancer cells.

Targeting cancer cells without affecting normal cells poses a particular challenge. Nevertheless, the utilization of innovative nanomaterials in targeted cancer therapy has witnessed significant growth in recent years. In this study, we examined two layered carbon nanomaterials, graphene and carbon nanodiscs (CNDs), both of which possess extraordinary physicochemical and structural properties alongside their nano-scale dimensions, and explored their potential as nanocarriers for quercetin, a bioactive flavonoid known for its potent anticancer properties. Within both graphitic allotropes, oxidation results in heightened hydrophilicity and the incorporation of oxygen functionalities. These factors are of great significance for drug delivery purposes. The successful oxidation and interaction of quercetin with both graphene (GO) and CNDs (oxCNDs) have been confirmed through a range of characterization techniques, including FTIR, Raman, and XPS spectroscopy, as well as XRD and AFM. In vitro anticancer tests were conducted on both normal (NIH/3T3) and glioblastoma (U87) cells. The results revealed that the bonding of quercetin with GO and oxCNDs enhances its cytotoxic effect on cancer cells. GO-Quercetin and oxCNDs-Quercetin induced G0/G1 cell cycle arrest in U87 cells, whereas oxCNDs caused G2/M arrest, indicating a distinct mode of action. In long-term survival studies, cancer cells exhibited significantly lower viability than normal cells at all corresponding doses of GO-Quercetin and oxCNDs-Quercetin. This work leads us to conclude that the conjugation of quercetin to GO and oxCNDs shows promising potential for targeted anticancer activity. However, further research at the molecular level is necessary to substantiate our preliminary findings.

Solitary Fibrous Tumor of the Masticator Space with Unusual Extension: a Case Report.

Background: We present the case of a patient with solitary fibrous tumor of the masticator space with unusual extension. Case presentation: A 43-year-old woman presented with a painless mass with intraoral extension on the right cheek. The B-scan sonograph and magnetic resonance imaging revealed the extension of the tumor. The biopsy performed under local anesthesia raised the suspicion of a solitary fibrous tumor. Tumor excision included a preoperative tumor embolization. The surgical removal of the tumor included a partial parotidectomy on the right side, insertion of masseteric and temporalis muscle, resection of the middle part of the zygomatic bone and stabilization of the bone with a plate, mobilization of the tumor from the maxillary sinus and the pterygopalatine fossa through an endoscopic approach and an approach via partial resection of the anterior wall of the maxillary sinus after identifying and sparing the infraorbital nerve. Ôhe histological findings confirmed the diagnosis of solitary fibrous tumor. The patient's treatment completed with radiation therapy, and 2.5 years later, there was recurrence in the right temporal area. Conclusion:To our knowledge, this is the second reported case of solitary fibrous tumor arising in the masticator space and the only case with extension intraorally and in the paranasal sinuses. Tumor embolization and complete surgical excision are the most frequently recommended treatments.

PTEN Deregulation Mechanisms in Salivary Gland Carcinomas.

Among the tumour suppressor genes that affect critically cell functions and homeostasis, phosphatase and tensin homolog deleted in chromosome 10 (PTEN- gene locus: 10q21) regulates the PI3K/Akt/mTOR signalling pathway. PTEN is deleted, mutated or epigenetically hyper-methylated in a variety of human solid malignancies. Salivary gland carcinomas (SGCs) belong to the head and neck carcinomas (HNCs) super category of solid malignancies. Histo-pathologically, they demonstrate a significant diversity due to a variety of distinct and mixed subtypes. Genetically, they are characterized by a broad spectrum of gene and chromosomal imbalances. Referring specifically to suppressor genes, PTEN deregulation plays a critical role in signaling transduction in the corresponding SGC pre- and malignant epithelia modifying the response rates to potential targeted therapeutic strategies. In the current review, we explored the role of PTEN deregulation mechanisms that are involved in the onset and progression of SGCs.

Impact of Amplified Oncogenes on Salivary Gland Carcinomas.

In normal epithelia, proto-oncogenes regulate critical intra- or intercellular functions, including cell growth and proliferation, apoptosis, and signaling transduction from the cell periphery (extracellular space) to the nucleus mediated by different pathways. Oncogenes are the mutated or amplified forms of the corresponding proto-oncogenes that are crucially involved in cell neoplastic and malignant transformation during carcinogenesis. Salivary gland carcinomas (SGCs) demonstrate a variety of histogenetic types. They are characterized by a broad spectrum of chromosomal and gene alterations. In particular, amplifications in specific genes [human epidermal growth factor receptor 2 (HER2), human epidermal growth factor receptor 4 (HER4), epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), Mouse double minute 2 homolog (MDM2), androgen receptor (AR), programmed death (ligand 1 (PD-L1), neurogenic differentiation factor 2 (NEUROD2), phosphatidylinositol 3,4,5-trisphosphate-dependent RAC exchanger 1 protein (PREX1), cyclin-dependent kinase4/6 (CDK4/6), proline-rich acidic protein 1 (PRAP1), kell antigen system (KEL), glutamate receptor subunit epsilon 2 (GRIN2D), Ewing sarcoma RNA-binding protein 1 (EWSR1), MYC proto-oncogene (MYC)] combined or not with chromosomal numerical imbalances (aneuploidy/ polysomy/monosomy) form different genetic signatures affecting the response to monoclonal antibody-based, oncologicaly targeted regimens. Different SGC histotypes demonstrate specific combinations of mutated/amplified genes that modify their clinicohistological features. In the current molecular review, we present the most important amplified oncogenes and their impact on the biological behavior of SGCS.

Mutational Signatures in Salivary Gland Carcinomas.

Salivary gland carcinomas belong to the head and neck carcinoma super category of malignancies. They are characterized by histopathological diversity and comprise a variety of entities and subtypes. Mucoepidermoid, adenoid cystic and salivary duct carcinomas represent the most prominent malignancies. Concerning their corresponding genetic background, a broad spectrum of gene and chromosomal imbalances has been detected. Point mutations and deletions, amplifications and translocations, combined or not with chromosomal aneuploidy/polysomy/monosomy, create a landscape of specific genetic signatures that affect the biological behavior of these tumors and modify response rates to potential targeted therapeutic strategies. In the current molecular review, we focused on the categorization and description of the most important mutational signatures in salivary gland carcinomas.

Brain Perfusion Changes in a Patient with Facial Trauma.

A 69-year-old male was admitted to our hospital because of left facial trauma with bone fractures, including the maxillary sinus, zygomatic arch, and ethmoid and sphenoid bones. Brain computed tomography was unremarkable but regional cerebral blood flow with hexamethyl-propylene-amine oxime single-photon emission computed tomography (SPECT) showed hypoperfusion of the left hemisphere, which was reversible since a repeat SPECT 4 months later was substantially improved. Brain perfusion SPECT may provide information on cerebrovascular status in some cases of facial injury.

Anti-EGFR/BRAF-Tyrosine Kinase Inhibitors in Thyroid Carcinoma.

Alterations in significant genes located on chromosome 7 - including epidermal growth factor receptor (EGFR) and also v-Raf murine sarcoma viral oncogene homolog B (BRAF) as a mitogen-activated protein kinase (MAPK)  - combined or not with numerical imbalances of the whole chromosome (aneuploidy-polysomy) are crucial genetic events involved in the development and progression of malignancies. Identification of EGFR/BRAF-dependent specific somatic mutations and other mechanisms of deregulation (i.e., amplification) is critical for applying targeted therapeutic approaches [tyrosine kinase inhibitors (TKIs] or monoclonal antibodies (mAbs). Thyroid carcinoma is a specific pathological entity characterized by a variety of histological sub-types. Follicular thyroid carcinoma (FTC), papillary thyroid carcinoma (PTC), medullary thyroid carcinoma (MTC), and anaplastic thyroid carcinoma (ATC) represent its main sub-types. In the current review, we explore the role of EGFR/BRAF alterations in thyroid carcinoma in conjunction with the corresponding anti-EGFR/BRAF TKI-based novel therapeutic strategies for patients with specific genetic signatures.

The Landscape of Single Nucleotide Polymorphisms in Papillary Thyroid Carcinoma.

Thyroid carcinoma represents a leading malignancy among those derived from human endocrine systems. It comprises a variety of different histological subtypes, including mainly papillary carcinoma, follicular carcinoma, anaplastic carcinoma, and medullar carcinoma. A broad spectrum of genetic imbalances, comprising gross chromosomal (polysomy/aneuploidy) and specific gene (mutations, amplifications, deletions) alterations, has been reported. Interestingly, the role of isolated, specific gene polymorphisms, especially of the single nucleotide polymorphism (SNP) type, in thyroid carcinoma is under investigation. SNPs are the most common genetic variations in the genome. The current molecular review focuses on the impact of specific SNPs on the biological behavior of papillary thyroid carcinoma in their carriers.

Unilateral Nasal Mass Mimicking Tumor in a Young Patient: The Value of Differential Diagnosis.

Nasal masses are a clinical entity with great diversity. They present with various symptoms such as nasal obstruction, facial pain, discomfort, epistaxis, headache, anosmia and visual disturbances. Especially unilateral nasal masses are very suspicious and must be differentiated between benign and malignant lesions. Nasal endoscopy is a weapon in the quiver of otorhinolaryngologists. It is an innovative, quick, direct and inexpensive examination that can be performed even at the otorhinolaryngologist's office. Immediate imaging of lesions within the nasal cavity allows rapid initiation of treatment. This article highlights the importance of correct differential diagnosis of a unilateral nasal mass in a 37-year-old female patient.

c-FOS Expression Analysis in Pterygia Cell Spot Arrays.

BACKGROUND/AIM: Mechanisms of c-FOS activation in the onset and progression of pterygia remain under investigation. This study aimed to comparatively analyze c-FOS proto-oncogene expression levels in neoplastic pterygia and normal epithelia. MATERIALS AND METHODS: We used a liquid-based cytology assay on thirty (n=30) pterygia cell populations and normal epithelia (n=10) extracted by a smooth scraping of conjunctiva epithelia. Applying a cell spot-based technique, we constructed five (n=5) slides, each containing eight (n=8) cell spots. A modified immune-cytochemistry (ICC) assay for c-FOS protein was used. Additionally, digital image analysis was implemented to calculate c-FOS immunostaining intensity levels. RESULTS: High staining intensity levels of c-FOS were detected in 12/30 (40%), whereas the rest 18/30 (60%) demonstrated moderate expression. c-FOS levels were statistically significantly higher in the pterygia compared to control tissues (p=0.001). c-FOS levels in the pterygia were not associated with the sex of patients (p=0.678), the presence of recurrent lesion (p=0.390) or the location of the lesion (p=0.158). The levels of c-FOS, however, were marginally significantly affected by the morphology of the pterygia (p=0.005). More precisely, the c-FOS levels were significantly higher in pterygia with a fleshy morphology. CONCLUSION: c-FOS over-expression is observed frequently in pterygia. It seems to be critically involved in the molecular mechanism of the lesion by its over-expression affecting partially their morphological features. Cell spot liquid - based array analysis is an innovative, easy to implement technique for simultaneously evaluating a broad spectrum of molecules in multiple specimens on the same slide.

P53 Suppressor Gene Tissue Microarray-based Protein Expression Analysis in Meningiomas.

BACKGROUND/AIM: Meningiomas represent the main intracranial primary central nervous system (CNS) tumour in adults worldwide. Oncogenes' over-activation combined with suppressor genes' silencing affect negatively the biological behavior of these neoplasms. This study aimed to explore the impact of p53 suppressor gene expression in meningiomas' clinic-pathological features based on a combination of sophisticated techniques. MATERIALS AND METHODS: Fifty (n=50) meningiomas were included in the study, comprising a broad spectrum of histopathological subtypes. An immunohistochemistry assay was applied on tissue microarray cores followed by digital image analysis. RESULTS: p53 protein over-expression (high staining intensity levels) was observed in 27/50 (54%) cases, whereas the rest (23/50-/46%) demonstrated moderate to low levels of the protein. p53 over-expression was statistically significantly correlated to the mitotic index of the examined cases (p-value=0.001). Interestingly, the atypical/anaplastic group of histotypes demonstrated the strongest p53 expression rates compared to the others (p-value=0.001). CONCLUSION: p53 overexpression is observed in a broad spectrum of meningiomas. High expression levels lead to an aggressive biological behavior of the malignancy (combined with increased mitotic rates), especially in atypical and anaplastic sub-types that also have a high recurrence rate.

Caspase 8 Expression Patterns in Meningiomas: A Tissue Microarray Digital Image Analysis.

BACKGROUND: Caspases (cysteine-aspartic proteases) represent a family of enzymes that critically influence cell homeostasis by being involved in inflammation and apoptosis mechanisms. Meningiomas demonstrate the most common intracranial primary central nervous system tumors in adults worldwide. AIM: Our purpose was to explore the role of caspase 8 expression in meningiomas' pathological features. MATERIALS AND METHODS: A total of 50 meningioma cases were included in the study, comprising a broad spectrum of histopathological sub-types. An immunohistochemistry assay was applied on tissue microarray cores followed by digital image analysis. RESULTS: Overexpression of caspase 8 protein was observed in 21/50 (42%) cases, whereas the rest of them (29/50, 58%) demonstrated moderate to low levels of the molecule. Caspase 8 overall expression was statistically significantly correlated to grade of the examined tumors and to mitotic index (p=0.001,p=0.002, respectively). CONCLUSIONS: Caspase 8 aberrant expression is observed in meningiomas associated with their differentiation grade and mitotic activity. Targeted therapeutic strategies focused on enhancing caspase 8 expression and also inducing the overall apoptotic activity should be a very promising approach in rationally handling sub-groups of meningioma patients.

Impact of Ubiquitination Signaling Pathway Modifications on Oral Carcinoma.

Among intra-cellular homeostasis mechanisms, ubiquitination plays a critical role in protein metabolism regulation by degrading proteins via activating a broad spectrum of ubiquitin chains. In fact, ubiquitination and sumoylation signaling pathways are characterized by increased complexity regarding the molecules and their interactions. The Ubiquitin-Proteasome System (Ub-PS) recognizes and targets a broad spectrum of protein substrates. Ubiquitin conjugation modifies each substrate protein determining its biochemical fate (degradation). A major functional activity of Ub-PS is autophagy mechanism regulation. Interestingly, Ub-PS promotes all stages of bulk autophagy (initiation, execution, and termination). Autophagy is a crucial catabolic process that provides protein degradation and for this reason the interaction with Ub-PS is crucial. Furthermore, ubiquitination controls and regulates specific types of protein targets. Ub-PS is also involved in oxidative cellular stress and DNA damage response. Additionally, the functional role of Ub-PS in ribosome machinery regulation seems to be crucial. Concerning carcinogenesis, Ub-PS is involved in malignant disease development and progression by negatively affecting the corresponding TGF-B-, MEEK/MAPK/ERK-JNK- dependent signaling pathways. In the current review article, we describe the role of Ub-PS biochemical modifications and alterations in oral squamous cell carcinoma (OSCC).

ALK Protein Expression Patterns in Squamous Cell Carcinoma of the Oral Cavity.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is characterized by a broad spectrum of genomic imbalances, including gross chromosomal (polysomy/aneuploidy) ones as well as specific gene alterations. Aberrant expression of anaplastic lymphoma kinase (ALK) seems to be a useful molecular marker for discriminating patients based on genetic signatures in a variety of solid malignancies, such as lung carcinoma. Our aim was to analyze ALK protein expression patterns in a series of OSCCs. MATERIALS AND METHODS: Fifty (n=50) OSCC tissue sections were analyzed by implementing an ALK-based immunohistochemistry protocol. Digital image analysis was performed for measuring the corresponding protein expression levels. RESULTS: ALK overexpression was observed in 14/50 (28%) OSCC tissue sections, whereas the rest 36/50 (72%) demonstrated low expression levels. ALK expression was negatively associated with grade (p=0.027) and stage (p=0.0028) of the examined cases. CONCLUSION: Abnormal ALK expression in subsets of patients with OSCC seems to be related to an aggressive phenotype (advanced stage/progressive dedifferentiation). ALK protein overexpression may be used as a significant marker for applying targeted therapeutic regimens.

From delta to Omicron: S1-RBD/S2 mutation/deletion equilibrium in SARS-CoV-2 defined variants.

Coronavirus-related Severe Acute Respiratory Syndrome (SARS-CoV) in 2002/2003, Middle-East Respiratory Syndrome (MERS-CoV) in 2012/2013, and especially the current 2019/2021 Severe Acute Respiratory Syndrome-2 (SARS-CoV-2) affected negatively the national health systems' endurance worldwide. SARS-Cov-2 virus belongs to lineage b of beta-CoVs demonstrating a strong phylogenetic similarity with BatCoVRaTG13 type. Spike (S) glycoprotein projections -consisting of two subunits S1/S2- provide a unique crown-like formation (corona) on virion's surface. Concerning their functional role, S1 represents the main receptor-binding domain (RBD), whereas S2 is involved in the virus-cell membrane fusion mechanism. On Nov 26th 2021, WHO designated the new SARS-CoV-2 strain - named Omicron, from letter ''όµÎ¹κρον'' in the Greek alphabet - as a variant of concern (B.1.1529 variant). Potentially this new variant is associated with high transmissibility leading to elevated infectivity and probably increased re-infection rates. Its impact on morbidity/mortality remains under investigation. In the current paper, analyzing and comparing the alterations of SARS-CoV-2 S RNA sequences in the defined variants (Alpha to Omicron), we observed some interesting findings regarding the S1-RBD/S2 mutation/deletion equilibrium that maybe affect and modify its activity.

Impact of SARS-CoV-2 infection on oral carcinoma patients.

Coronavirus-related Severe Acute Respiratory Syndrome (SARS-CoV) in 2002/2003, Middle-East Respiratory Syndrome (MERS-Cov) in 2012/2013, and especially the current 2019/2020 Severe Acute Respiratory Syndrome-2 (SARS-CoV-2) tested the national health systems' endurance worldwide. In order to fight this emergency situation, a variety of pharmaceutical companies focused on the design and development of efficient vaccines that are considered necessary for providing a level of normalization in totally affected human social-economical activity worldwide. COVID-19 led to an increased uncertainty in the field of oncological patients' management disrupting the normal conditions of therapeutic and monitoring procedures. In the current article, we explored the impact of SARS-CoV-2 infection on oral carcinoma patients. We observed COVD-19 pandemic negatively affects the normality regarding early diagnosis and optimal management (surgical operation, post-operational follow up/monitoring) in HNSCC/OSCC patients. Understanding the involvement of SARS-CoV-2 in the progression of malignancies is the first critical step for targeting the virus by efficient monoclonal antibodies and vaccines.

Topoisomerase IIa protein expression analysis in oral squamous cell carcinoma.

PURPOSE: Topoisomerases represent a super-family of nucleic enzymes involved in the DNA replication, transcription, recombination, and also chromosome topological formation. Topoisomerase II alpha (Topo IIa-gene location 17q21) is a critical gene associated with response to chemotherapeutic agents such as anthracyclines especially in breast adenocarcinoma. Our aim was to investigate the role of aberrant Topo IIa protein expression in oral squamous cell carcinoma (OSCC). METHODS: Fifty formalin-fixed, paraffin-embedded primary OSCCs tissue sections were used. Immunohistochemistry was performed using an anti- Topo IIa antibody. Digital image analysis was implemented for evaluating objectively the protein expression levels on the corresponding stained nuclei. RESULTS: Topo IIa protein overexpression (moderate to high immunostaining intensity values) was observed in 29/50 (58%) tissue cores, whereas low expression rates were detected in the remaining cases (21/50;42%). Topo IIa overall expression was strongly associated with the differentiation grade of the examined tumors (p=0.037) and also with human papillomavirus (HPV) positivity (p=0.029). No other statistical correlations were identified. CONCLUSIONS: Topo IIa overexpression is observed in significant subsets of OSCCs correlated with the grade of differentiation. Additionally, HPV persistent infection is associated with increased Topo IIa protein expression levels. Topo IIa expression analysis should be critical for identifying patients eligible for applying specific chemotherapeutic strategies based on anti-Topo IIa agents.