Exosomes: Mediators of cellular communication in potentially malignant oral lesions and head and neck cancers.

Exosomes are a unique type of extracellular vesicles that contain a plethora of biological cargo such as miRNA, mRNA, long non-coding RNA, DNA, proteins and lipids. Exosomes serve as very effective means of intercellular communication. Due the presence of a lipid bilayer membrane, exosomes are resistant to degradation and are highly stable. This makes them easily identifiable in blood and other bodily fluids such as saliva. The exosomes that are secreted from a parent cell directly release their contents into the cytoplasm of a recipient cell and influence their cellular activity and function. Exosomes can also transfer their content between cancer cells and normal cells and regulate the tumor microenvironment. Exosomes play a vital role in tumor growth, tumor invasion and metastasis. Exosomes provide a multitude of molecular and genetic information and have become valuable indicators of disease activity at the cellular level. This review explores the molecular characteristics of exosomes and the role that exosomes play in the tumorigenesis pathway of potentially malignant oral lesions and head and neck cancers The application of exosomes in the treatment of oral cancers is also envisioned. Exosomes are very small and can easily pass through various biological barriers, making them very good delivery vectors for therapeutic drugs as well as to selectively induce DNA's mRNA and miRNAs into targeted cancer cells.

Inhaled corticosteroids and adverse outcomes among chronic obstructive pulmonary disease patients with community-acquired pneumonia: a population-based cohort study.

Introduction: While inhaled corticosteroids (ICS) may increase pneumonia risk in patients with chronic obstructive pulmonary disease (COPD), the impact of ICS on pneumonia outcomes is debated. We examined whether ICS use is associated with adverse outcomes among COPD patients with community-acquired pneumonia (CAP). Materials and methods: Population-based cohort study of all COPD patients with an incident hospitalization for CAP between 1997 and 2013 in Northern Denmark. Information on medications, COPD severity, comorbidities, complications, and death was obtained from medical databases. Adjusted risk ratios (aRRs) for pleuropulmonary complications, intensive care unit (ICU) admissions, and 30-day mortality in current and former ICS users were compared with those in non-users, using regression analyzes to handle confounding. Results: Of 11,368 COPD patients with CAP, 6,073 (53.4%) were current ICS users and 1,733 (15.2%) were former users. Current users had a non-significantly decreased risk of pleuropulmonary complications [2.6%; aRR = 0.82 (0.59-1.12)] compared to non-users (3.2%). This was also observed among former users [2.5%; aRR = 0.77 (0.53-1.12)]. Similarly, decreased risks of ICU admission were observed among current users [aRR = 0.77 (0.57-1.04)] and among former users [aRR = 0.81 (0.58-1.13)]. Current ICS users had significantly decreased 30-day mortality [9.1%; aRR = 0.72 (0.62-0.85)] compared to non-users (12.6%), with a stronger association observed among patients with frequent exacerbations [0.58 (0.39-0.86)]. No significant association was observed among former ICS users [0.89 (0.75-1.05)]. Conclusion: Our results suggest a decreased risk of death with ICS use among COPD patients admitted for CAP.

"Giant cell fibroma of buccal mucosa -an unusual lesion of unusual size": A case report.

Giant cell fibroma is a benign oral fibrous tumour. The clinical appearance of majority of non-neoplastic fibrous growths is similar, but unique histopathological features of giant cell fibroma aid in its final diagnosis. It usually manifests as an asymptomatic, sessile or pedunculated mass usually less than 1 cm in diameter. In this case report, we highlight a case of giant cell fibroma in a 58-year-old male patient, which had an unusual size with associated pain. Although giant cell fibromas are benign lesions, it is important for dentists to be aware of this lesion based on its frequency of occurrence and need for its accurate diagnosis.

Orofacial granulomatosis: A case report and a proposal of a diagnostic algorithm for oral granulomatous lesions.

Orofacial granulomatosis (OFG) is an uncommon chronic inflammatory disorder with multifactorial etiology and pathogenesis affecting the orofacial region which appears usually as a persistent and/or recurrent swelling that may involve one or both the lips and/or recurrent ulcers along with other orofacial features. The diagnosis of OFG is challenging and it should be ruled out from other conditions characterized by granulomatous inflammation. This article describes a case of a 30-year-old female patient with upper lip swelling as the main manifestation without any systemic involvement and we have also laid down a proposal of a diagnostic algorithm for differential diagnoses and treatment modalities for OFG which could be helpful for the clinician and dentists alike to rule out other granulomatous disorders thus in effective management of OFG.

Elucidating the role of excision repair cross-complement group 1 in oral epithelial dysplasia and early invasive squamous cell carcinoma: An immunohistochemical study.

OBJECTIVES: Oral epithelial dysplasia (OED) is characterized by cellular alterations which have the proclivity of progressing to squamous cell carcinoma. Excision repair cross-complement group 1 (ERCC1) is one of the key proteins involved in nucleotide excision repair (NER) pathway. The expression of ERCC1 has been studied in colorectal, esophageal, ovarian and oral squamous cell carcinoma; but, very few studies have been done to apprehend the expression of ERCC1 in OED and early invasive squamous cell carcinoma (EISCC). The goal of this study is to evaluate the role of ERCC1 in OED and EISCC. MATERIALS AND METHODS: Histopathologically diagnosed cases of moderate dysplasia (n = 10), severe dysplasia (n = 10) and EISCC (n = 10) were retrieved. 4 µ thick sections were cut from the formalin-fixed paraffin-embedded tissue blocks. The sections were immunohistochemically stained for ERCC1 following standard protocols. The expression of ERCC1 was evaluated semiquantitatively. Statistical analysis was carried out using Fischer's exact t-test. RESULTS: The expression of ERCC1 was found to be strong (+3) in EISCC, moderate (+2) in severe dysplasia and mild (+1) in moderate dysplasia. Thus, the results were statistically significant between the three groups (P < 0.001). CONCLUSION: Disruption in the mechanisms that regulate cell cycle checkpoints and DNA repair mechanism results in genomic instability; these alterations might contribute to carcinoma. ERCC1 is essential to repair the DNA damage induced by various carcinogens. The present study shows significant difference in the expression of ERCC1 between EISCC and OED, which suggests ERCC1 could be used as one of the predictive markers.

Spalt-like transcription factor 4 expression in oral epithelial dysplasia and oral squamous cell carcinoma: An immunohistochemical appraisal.

BACKGROUND: Spalt-like transcription factor 4 (SALL4) is a stem cell marker that plays a critical role in maintaining the pluripotency and self-renewal of embryonic and hematopoietic stem cells. Only a few studies have been done to apprehend the expression of SALL4 in the potentially malignant oral lesion (leukoplakia with dysplasia) and oral squamous cell carcinoma (OSCC). AIM: The aim of this study is to evaluate the expression of SALL4 in leukoplakia with dysplasia and OSCC and to correlate the expression of the marker (SALL4) with the various clinicopathological parameters and patient outcome. MATERIALS AND METHODS: Immunohistochemistry for SALL4 protein was performed on 140 cases: those histopathologically confirmed cases of leukoplakia with dysplasia (n = 30) and OSCC (n = 110). Ten cases of nonepithelial neoplasm (fibroepithelial hyperplasia and excised tissue surrounding impacted third molars) were taken as control. Statistical analyses were applied to evaluate correlations between SALL4 overexpression and clinicopathological features of leukoplakia and OSCC. Survival rates were analyzed using Kaplan-Meier method. RESULTS: SALL4 positivity was observed to be higher (P = 0.001) in the tumor cells of OSCC with Immuno Reactive Score (IRS) ranging from 0 to 9. Poorly differentiated squamous cell carcinoma (SCC) had paramount higher expression with a median IRS of 6. Similar IRS and above (IRS, 6-9) was observed in Stage I (five cases), which recurred and well-differentiated cases with metastasis (four cases) while in leukoplakia with dysplasia the SALL4 expression was weak with a range of 2-4. CONCLUSIONS: SALL4 being one of the cancer stem cell molecules plays an important role in the progression of oral cancer, which was evident in this study. This could also account for aggressive clinical behavior. Follow-up of these patients would relate this molecule could be responsible for cancer relapse. Patients diagnosed to have oral epithelial dysplasia had a low expression of SALL4, are under follow-up, although seven cases did transform to SCC. Thus, we conclude, SALL4 may be of prognostic relevance, but in oral epithelial dysplasia, it requires further investigations.

Kapetansky-Juri Technique to Correct the Whistlers Lip in the Multiple Operated Cleft Patient.

PURPOSE: One of the common sequels of a cleft lip repair may be "whistling lip deformity" but other deformities are also seen particularly in failed or multiple resurgery cases. This retrospective study was carried out to evaluate the usefulness of "Kapetansky-Juri" advancement flap technique to correct such deformities. METHODS: Ten patients of bilateral cleft lip with history of minimum five failed cleft lip surgeries and having residual lip deformity were operated using "Kapetansky-Juri" advancement flap technique and were followed up to minimum 36 months. RESULTS: All patients showed good tissue fullness and complete correction of the deformity. There was no contracture of surrounding skin or vermilion during follow-up period. In eight patients minimal scar formation was seen while two showed midline scar formation. CONCLUSION: No tissue loss due to vascular insufficiency was observed. The technique gives good tissue distribution and minimal surface scar formation.

Management of Late Post-traumatic Facial Artery Pseudoaneurysmal Cyst: Review of Literature.

Pseudoaneurysms of the branches of the external carotid artery as a result of trauma are rare in oral and maxillofacial surgery practice. The most affected branches are the superficial temporal artery, internal maxillary artery and distal part of facial artery, usually where they pass over the bone. Very few cases of facial artery pseudoaneurysms of proximal parts (from external carotid artery up to the lower border of the mandible) are reported in the literature. We present a review of literature for management of late post-traumatic pseudoaneurysmal cyst and a case report involving proximal part of facial artery in the submandibular region following open reduction and rigid fixation of the condylar fracture in a 25-year-old male. To our knowledge this is the fourth reported case of proximal facial artery pseudoaneurysm.

Lingual guttering technique for removal of impacted mandibular third molars.

BACKGROUND: To assess the clinical feasibility of lingual bone guttering technique for surgical extraction of mandibular third molars. MATERIALS AND METHODS: 20 patients with thick lingual cortical plate were included in the study. Surgical extraction of mandibular third molars by lingual bone guttering technique was performed in all the subjects. These subjects were evaluated for integrity of lingual cortical plate and sensation of lingual nerve postoperatively. RESULTS: All extractions done by lingual bone guttering technique were clinically feasible to perform and no complications were seen. CONCLUSION: Lingual bone guttering technique can be used safely in extraction of mandibular third molars with thick lingual cortical plate.

Preparation and evaluation of lipid vesicles of camptothecin as targeted drug delivery system.

Site-specific delivery of anticancer based therapy of human cancers has led to several remarkable outcomes, particularly in the therapy of breast cancer and lymphoma. Camptothecin, a plant secondary metabolite is widely used in the treatment of metastatic breast cancer and lymphoma. However its side effect profile often results in cessation of therapy. In this study the principle of both active as well as passive targeting using camptothecin loaded stealth liposomes as per the magic gun approach was followed. Stealth liposomes of camtothecin were prepared by thin film hydration method using a PEGylated phospholipid like DSPE-MPEG 2000. Similarly conventional liposomes were prepared using phospholipids like DPPC, DSPC. Conventional liposomes were coated with a hydrophilic biocompatible polymer like chitosan. It was found that chitosan coating of the conventional liposomes increased the physical stability of the liposomal suspension. Further, chitosan coated conventional liposomes and the PEGylated liposomes released the drug for a prolonged period of time, compared to the uncoated conventional liposomes. In vivo screening of the formulations for their antitumor efficacy was carried out in rats. Breast cancer was induced in female Sprague-Dawley rats using an indirectly acting chemical carcinogen DMBA (7, 12 dimethyl benz(a)anthracene). It was found that there was significant decrease (P>0.01) in tumor volume in the rat group treated with test 2 formulation and test 1 formulation compared to standard free CPT. However the chitosan coated liposomal formulation showed a better antitumor efficacy than that of the PEGylated liposomal formulation.

Evaluation of Calretinin expression in Ameloblastoma and Non-Neoplastic Odontogenic Cysts - An immunohistochemical study.

BACKGROUND: Calretinin a 29-kDa calcium binding protein is expressed widely in normal human tissue and tumours including amelobastoma. The objective of this study was to determine calretinin expression in heamatoxylin and eosin diagnosed cases of ameloblastoma and non-neoplastic odontogenic cysts. MATERIALS & METHODS: The lining epithelium in 3 cases of radicular cysts, 5 cases of odontogenic keratocysts, 5 cases of dentigerous cysts and 11 cases of ameloblastomas were examined for expression of calretinin. RESULTS: No positive epithelial staining was observed in radicular and dentigerous cysts. In comparison, however 100% of cases of ameloblastomas and 40% of cases of odontogenic karatocysts showed positive calretinin expression. CONCLUSION: Calretinin may be a specific immunohistochemical marker for ameloblastoma. If there is any possible relation between calretinin expression and neural origin of the odontogenic epithelium and its neoplastic transformation and if calretinin could be used as an early marker to predict the tendency of neoplastic change of odontogenic epithelium could be answered through further researches. How to cite this article: D'Silva S, Sumathi MK, Balaji N, Shetty NK, Pramod KM, Cheeramelil J. Evaluation of Calretinin expression in Ameloblastoma and Non-Neoplastic Odontogenic Cysts - An immunohistochemical study. J Int Oral Health 2013; 5(6):42-8 .