Jason Tasoulas

Salivaomics for oral diseases biomarkers detection

ABSTRACT The variation of saliva composition in different physiological and pathological states is well demonstrated. Several saliva constituents (enzymes, hormones, antibodies, cytokines etc.) are up- or down-regulated in respect to benign, premalignant and malignant conditions in the oral cavity, and several patterns of deregulation are associated with specific disorders. Omics technologies have contributed significantly in the identification of alterations in gene expression, transcription, protein coding and small molecules concentration, in biologic systems. In this aspect, salivaomics integrate these technologies in saliva analysis and represent a novel and holistic approach in oral disease management including diagnosis, prognosis and monitoring. This review summarizes the current research in the discovery of biomarkers and molecular signatures with diagnostic or prognostic utility for oral diseases in saliva. The review also focuses on the emerging issues of the salivaomics technology and saliva diagnostics and the translational potential.

Evaluation of cannabinoid CB1 and CB2 receptors expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients’ survival

Cannabinoid receptors (CB1R and CB2R) constitute essential members of the endocannabinoid system (ECS) which participates in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to assess the clinical significance of CB1R and CB2R protein expression in mobile tongue squamous cell carcinoma (SCC). CB1R and CB2R expression was assessed immunohistochemically on 28 mobile tongue SCC tissue samples and was analyzed in relation with clinicopathological characteristics and overall and disease-free patients’ survival. CB1R, CB2R, and concomitant CB1R/CB2R expression was significantly increased in older compared to younger mobile tongue SCC patients (p = 0.0243, p = 0.0079, and p = 0.0366, respectively). Enhanced CB2R and concomitant CB1R/CB2R expression was significantly more frequently observed in female compared to male mobile tongue SCC patients (p = 0.0025 and p = 0.0016, respectively). Elevated CB2R expression was significantly more frequently observed in mobile tongue SCC patients presenting well-defined tumor shape compared to those with diffuse (p = 0.0430). Mobile tongue SCC patients presenting enhanced CB1R, CB2R, or concomitant CB1R/CB2R expression showed significantly longer overall (log-rank test, p = 0.004, p = 0.011, p = 0.018, respectively) and disease-free (log-rank test, p = 0.003, p = 0.007, p = 0.027, respectively) survival times compared to those with low expression. In multivariate analysis, CB1R was identified as an independent prognostic factor for disease-free patients’ survival (Cox-regression analysis, p = 0.032). The present study provides evidence that CB1R and CB2R may play a role in the pathophysiological aspects of the mobile tongue SCC and even each molecule may constitute a potential target for the development of novel anti-cancer drugs for this type of malignancy.

Mandibulofacial dysostosis (Treacher-Collins syndrome) in the fetus: Novel association with pectus carinatum in a molecularly confirmed case and review of the fetal phenotype

BACKGROUND Treacher Collins syndrome is the most common mandibulofacial dysostosis of autosomal dominant or, rarely, recessive inheritance. Affected fetuses may be identified by prenatal ultrasound or diagnosed at autopsy in case of perinatal death or pregnancy termination. METHODS We describe the ultrasonographic, autopsy, and molecular findings in a 25-week-gestation affected fetus, and review the clinical, prenatal, and postmortem findings in 15 previously reported fetal and perinatal cases. RESULTS A nearly complete spectrum of the typical facial characteristics can be present by the early second trimester of gestation, including subtle defects such as lower eyelid colobomas. Mandibular hypoplasia and bilateral auricle defects were constant findings in the affected fetal population. Downslanting palpebral fissures were the second more common feature, followed by midface hypoplasia, polyhydramnios, and ocular defects. Association with Pierre Robin sequence was common (38%) in the reviewed series. Previously unreported pectus carinatum was noted in our case bearing a heterozygous TCOF1 mutation. Other unique reported findings include salivary gland hyperplasia, single umbilical artery, and tracheo-esophageal fistula, all in molecularly unconfirmed cases. CONCLUSION Treacher Collins syndrome can be prenatally detected by ultrasound and should be included in the wide range of genetic syndromes that can be diagnosed at perinatal autopsy. Affected fetuses tend to have a more severe phenotype than living patients. The reported association of Treacher Collins syndrome type 1 with pectus carinatum expands the phenotype, provides information on genotype-phenotype correlation, and suggests possible pathogenetic interactions between neural crest cell disorders and the formation of the sternum that merit investigation.

Ossifying Fibromyxoid Tumor of the Retromolar Trigone: A Case Report and Systematic Review of the Literature

Ossifying fibromyxoid tumor (OFMT) is a mesenchymal neoplasm of uncertain lineage and intermediate biologic behavior. Involvement of the head and neck area is infrequent (10% to 15%) and intraoral presentation is very rare. An OFMT developing in the retromolar trigone of a 13-year-old male is presented, along with a comprehensive review of oral OFMT cases. Among 12 oral OFMTs (including the present case), most patients were male (72.7%), with a mean age of 30.3 (13-67) years. The tumors generally appeared as painless masses of firm or hard consistency (mean diameter 27.7 mm), most commonly located in the soft tissues of the mandible (50%). Common microscopic features included ossification, lack of atypia or high mitotic activity, and immunohistochemical positivity for S100 (5/7), vimentin (6/6), GFAP (3/6), and SMA (2/6). Recurrence was reported only in one case. Further characterization of this rare entity is needed to increase our understanding of its distinct clinical and histopathologic features.

Histone deacetylase inhibitors in oral squamous cell carcinoma treatment

Introduction: The involvement of the histone deacetylases (HDACs) family in tumor development and progression is well demonstrated. HDAC inhibitors (HDACis) constitute a novel, heterogeneous family of highly selective anticancer agents that inhibit HDACs and present significant antitumor activity in several human malignancies, including oral squamous cell carcinoma (OSCC). Areas covered: This review summarizes the current research on the anticancer activity of HDACis against OSCC. The review also presents the molecular mechanisms of HDACis action and the existing studies evaluating their utilization in combined therapies of OSCC. Expert opinion: The currently available data support evidence that HDACis may provide new therapeutic options against OSCC, decreasing treatment side effects and allowing a more conservative therapeutic approach. Future research should be focused on in vivo and clinical evaluation of their utilization as combined therapies or monotherapies. Before HDACis can be brought into clinical practice as treatment options for OSCC, further evaluation is needed to determine their optimal dosage, the appropriate duration of treatment and whether they should be used in combination or as stand-alone therapeutics.

Neovascularization: an attractive but tricky target in thyroid cancer

ABSTRACT Introduction: Neovascularization in carcinogenesis and tumor progression is well-established. Molecular mediators implicated in different modes of vascular remodeling and expansion (e.g. sprouting angiogenesis (SA), vasculogenesis, vascular mimicry) are evaluated as prognostic biomarkers and therapeutic targets in different malignant tumors. Significant progress has been made in the understanding of the complex interplay between thyroid cancer (TC) cells and the tumor microenvironment, thus unraveling the role of angiogenic mediators. Areas covered: This review summarizes current research on neovascularization and TC. Current knowledge on vascular remodeling, in the context of carcinogenesis, is presented. Preclinical and clinical data from TC studies are also discussed. Expert opinion: There is a remarkable effort to pharmacologically target several key molecules of vessel-forming cascades. Despite encouraging preclinical results, clinical outcomes in TC are not optimal, possibly reflecting knowledge gaps in the pathophysiology of neovascularization in thyroid tissue. Increasing amounts of data support the possibility that redundancy of pathways that regulate vascular network remodeling allows tumors to adapt in different conditions. Hypothesizing that alternative forms of neovascularization upregulate when SA is pharmacologically blocked, targeting two or more different pathways of neovascularization could be a promising future strategy. Further research is required to explore molecular mechanisms of neovascularization in TC.

Clinical Significance and Biological Role of HuR in Head and Neck Carcinomas

Background Hu-antigen R (HuR) is a posttranscriptional regulator of several target mRNAs, implicated in carcinogenesis. This review aims to present the current evidence regarding the biological role and potential clinical significance of HuR in head and neck carcinomas. Methods The existing literature concerning HuR expression and function in head and neck carcinomas is critically presented and summarised. Results HuR is expressed in the majority of the examined samples, showing higher cytoplasmic levels in malignant or premalignant cases. Moreover, HuR modulates several genes implicated in biological processes important for malignant transformation, growth, and invasiveness. HuR seems to be an adverse prognosticator in patients with OSCCs, whereas a correlation with a more aggressive phenotype is reported in several types of carcinomas. Conclusions A consistent role of HuR in the carcinogenesis and progression of head and neck carcinomas is suggested; nevertheless, further studies are warranted to expand the present information.

Pure Orbital Trapdoor Fractures in Adults: Tight Entrapment of Perimuscular Tissue Mimicking True Muscle Incarceration with Successful Results from Early Intervention

Orbital trapdoor fractures (OTFs) entail entrapment of intraorbital soft tissues with minimal or no displacement of the affected bones and are almost exclusively seen in children. This article aimed to report the diagnosis and treatment of an OTF of the floor in an adult patient and to critically review the literature regarding the management aspects of this specific subset of orbital blowout fractures in adults. A 29-year-old man presented with limitations of vertical right eye movements owing to blunt orbital trauma. The patient mainly complained of double vision in upper gazes and some episodes of nausea. Neither floor defect nor significant bone displacement found on orbital computed tomography, while edema of inferior rectus muscle was apparent. The patient underwent surgical repair 5 days later; a linear minimally displaced fracture of the floor was recognized and complete release of the entrapped perimuscular tissues was followed. Within the first week postoperatively, full range of ocular motility was restored, without residual diplopia. This case was the only identified pure OTF over a 6-year period in our department (0.6% of 159 orbital fractures in patients >18 years). By reviewing the literature indexed in PubMed, a very limited number of either of isolated case reports or retrospective case series of pure OTFs has been reported in adults. Contrary to the typical white-eyed blowout fractures, the literature indicates that OTFs in adults seem to not always constitute absolute emergency conditions. Although such fractures need to be emergently/ immediately treated in children, in the absence of true muscle incarceration, adults may undergo successful treatment within a wider but either early or urgent frame of time. Adults frequently exhibit vagal manifestations and marked signs of local soft tissues injury.

An Unusual Microscopic Pattern of Foreign Body Reaction as a Complication of Dry Socket Management

Foreign body reactions in the oral cavity are relatively common, frequently resulting from iatrogenic causes. Depending on the nature of the foreign material, various microscopic patterns may be observed, causing diagnostic difficulties. Recognition of the ensuing unusual microscopic pattern, especially for cases in which the possibility of a foreign body reaction is not entertained in the clinical differential diagnosis, necessitates sufficient degree of suspicion, familiarization with the spectrum of microscopic appearances, and careful clinicopathologic correlation. Medicated dressings of various compositions are commonly placed for prevention or management of dry socket (or alveolar osteitis, a common postoperative complication of tooth extraction) and may be a cause of foreign body reaction. Here, we report a foreign body reaction to a medical dressing material in a postextraction socket, with an unusual microscopic pattern bearing resemblance to parasitic infestation.