Alan Roger Santos-Silva

Osteonecrosis of the mandible associated with bevacizumab therapy

Bevacizumab is a humanized antibody that blocks vascular endothelial growth factor and is of great value for the treatment of advanced cancer. Several adverse effects following its administration have been reported. To date, only 8 cases of osteonecrosis of the jaws associated with bevacizumab (without any association with bisphosphonates) have been reported. The aim of this article was to describe an original case of bevacizumab-related osteonecrosis of the jaw. A 61-year-old man diagnosed with advanced renal cell carcinoma was undergoing treatment with intravenous bevacizumab and temsirolimus when he spontaneously developed mandible osteonecrosis, which resolved after 3 months of conservative management. The present case reinforces recent speculation that the anti-angiogenic properties of bevacizumab may represent a potential new source of osteonecrosis of the jaws in patients undergoing cancer treatment. Multidisciplinary teams in cancer care should be aware of the possible association between osteonecrosis of the jaw and bevacizumab therapy.

Clinicopathological prognostic factors of oral tongue squamous cell carcinoma: A retrospective study of 202 cases

Although several histopathological parameters and grading systems have been described as predictive of the treatment response and outcome of oral squamous cell carcinoma (OSCC), none is universally accepted. A new scoring system, the histological risk model, was recently described to be a powerful predictive tool for recurrence and overall survival in OSCC. The aim of this study was to verify the predictive role of the histological risk model in a cohort of 202 patients at all stages of oral/mobile tongue squamous cell carcinoma (OTSCC). Demographic and clinical data were collected from the medical records and the tumours were evaluated using the histological risk model. Statistical analyses were performed using the χ(2) test, the Kaplan-Meier method, and the Cox regression model. The histological risk model showed no statistical correlation with demographic or clinical parameters and did not Predict the outcome of the OTSCC patients. However, multivariate regression analysis revealed a significant correlation of the clinical disease stage with the disease outcome. Despite major efforts to identify new predictive parameters and histological systems, clinical features are still the most reliable prognostic factors for patients with OTSCC.

High incidences of DNA ploidy abnormalities in tongue squamous cell carcinoma of young patients: an international collaborative study

Santos‐Silva A R, Ribeiro A C P, Soubhia A M P, Miyahara G I, Carlos R, Speight P M, Hunter K D, Torres‐Rendon A, Vargas P A & Lopes M A (2011) Histopathology 58, 1127–1135
High incidences of DNA ploidy abnormalities in tongue squamous cell carcinoma of young patients: an international collaborative study

Osteonecrosis after administration of intravitreous bevacizumab.

Bevacizumab is a recombinant humanized monoclonal immunoglobulin G1 antibody (149 kDa) that binds to and inhibits the biologic activity of all isoforms of human vascular endothelial growth factor. It has been used for the treatment of a myriad of malignancies, including metastatic colon and nonsmall cell lung cancers. Retinal afflictions and neovascular diseases are currently being treated with this medication, a therapy performed as an off-label use based on its short-term safety and low cost, turning bevacizumab into a widely used medication in ophthalmology. Its antineoplastic use has been related to a series of adverse effects such as hypertension, proteinuria; mild to moderate hemorrhage, wound-healing complications, thromboembolic events, and impaired wound healing. Adverse effects after intravitreal dministration have also been described and consist f local ocular events such as subconjunctival hemorhage and systemic effects such as increased blood ressure. Cases of osteonecrosis of the jaw (ONJ) related to chemotherapy using bevacizumab were first described in 2008. To the best of the present investigators’ knowledge, there are only 4 reports published in the medical literature reporting jaw bone osteonecrosis related to bevacizumab (Table 1). No cases f ONJ after intravitreal administration of bevacizumab or treatment of ocular ailments have been reported n the literature. A case of ONJ occurring after intraitreal bevacizumab therapy is presented.

Agrin and perlecan mediate tumorigenic processes in oral squamous cell carcinoma.

Oral squamous cell carcinoma is the most common type of cancer in the oral cavity, representing more than 90% of all oral cancers. The characterization of altered molecules in oral cancer is essential to understand molecular mechanisms underlying tumor progression as well as to contribute to cancer biomarker and therapeutic target discovery. Proteoglycans are key molecular effectors of cell surface and pericellular microenvironments, performing multiple functions in cancer. Two of the major basement membrane proteoglycans, agrin and perlecan, were investigated in this study regarding their role in oral cancer. Using real time quantitative PCR (qRT-PCR), we showed that agrin and perlecan are highly expressed in oral squamous cell carcinoma. Interestingly, cell lines originated from distinct sites showed different expression of agrin and perlecan. Enzymatically targeting chondroitin sulfate modification by chondroitinase, oral squamous carcinoma cell line had a reduced ability to adhere to extracellular matrix proteins and increased sensibility to cisplatin. Additionally, knockdown of agrin and perlecan promoted a decrease on cell migration and adhesion, and on resistance of cells to cisplatin. Our study showed, for the first time, a negative regulation on oral cancer-associated events by either targeting chondroitin sulfate content or agrin and perlecan levels.

Insights into immune responses in oral cancer through proteomic analysis of saliva and salivary extracellular vesicles.

The development and progression of oral cavity squamous cell carcinoma (OSCC) involves complex cellular mechanisms that contribute to the low five-year survival rate of approximately 20% among diagnosed patients. However, the biological processes essential to tumor progression are not completely understood. Therefore, detecting alterations in the salivary proteome may assist in elucidating the cellular mechanisms modulated in OSCC and improve the clinical prognosis of the disease. The proteome of whole saliva and salivary extracellular vesicles (EVs) from patients with OSCC and healthy individuals were analyzed by LC-MS/MS and label-free protein quantification. Proteome data analysis was performed using statistical, machine learning and feature selection methods with additional functional annotation. Biological processes related to immune responses, peptidase inhibitor activity, iron coordination and protease binding were overrepresented in the group of differentially expressed proteins. Proteins related to the inflammatory system, transport of metals and cellular growth and proliferation were identified in the proteome of salivary EVs. The proteomics data were robust and could classify OSCC with 90% accuracy. The saliva proteome analysis revealed that immune processes are related to the presence of OSCC and indicate that proteomics data can contribute to determining OSCC prognosis.

Atypical presentations of simple bone cysts of the mandible: A case series and review of literature

Simple bone cysts are well-defined intraosseous radiolucencies that often extend between the roots and appear clinically like empty cavities. This article aims to provide more information about this lesion with limited prominence in academic literature, to illustrate atypical cases, and to provide a review of the current literature. A series of six atypical cases of simple bone cysts is presented and their clinical, radiographic and microscopic characteristics, differential diagnosis, treatment and follow-up are discussed. Correct diagnosis of this entity is of key importance, since it presents with clinical & radiographic similarities to other bone lesions, some exhibiting more aggressive behaviour.

Bazex Syndrome (Acrokeratosis Paraneoplastica) Diagnosed in a Patient with Oral Persistent Ulcerations

Paraneoplastic syndromes associated with head and neck cancer are rare and have been reported under dermatological, endocrine, hematological, neurological and rheumatological disorders. Bazex syndrome is an intriguing paraneoplasia that can be associated with head and neck squamous cell carcinomas. A range of symmetrical dermatological manifestations, with a clear predilection to extremities, that encompasses erythematous squamous plaques, skin scaling and nail dystrophy can provide a psoriasiform pattern in Bazex syndrome. In addition to these tricky clinical features, the rarity of the disease and the lack of understanding on Bazex syndrome generally make such cases to be mismanaged as psoriasis or lichen planus, causing an important delay in the diagnosis of the underlying malignancy. The authors describe a case of Bazex syndrome that occurred in a patient with a recently diagnosed tongue squamous cell carcinoma. Clinicians should consider paraneoplasia when assessing skin and/or oral persistent lesions.

EEF1D modulates proliferation and epithelial–mesenchymal transition in oral squamous cell carcinoma

EEF1D (eukaryotic translation elongation factor 1δ) is a subunit of the elongation factor 1 complex of proteins that mediates the elongation process during protein synthesis via enzymatic delivery of aminoacyl-tRNAs to the ribosome. Although the functions of EEF1D in the translation process are recognized, EEF1D expression was found to be unbalanced in tumours. In the present study, we demonstrate the overexpression of EEF1D in OSCC (oral squamous cell carcinoma), and revealed that EEF1D and protein interaction partners promote the activation of cyclin D1 and vimentin proteins. EEF1D knockdown in OSCC reduced cell proliferation and induced EMT (epithelial-mesenchymal transition) phenotypes, including cell invasion. Taken together, these results define EEF1D as a critical inducer of OSCC proliferation and EMT.

Micromorphology of the Dental Pulp Is Highly Preserved in Cancer Patients Who Underwent Head and Neck Radiotherapy

INTRODUCTION Teeth are often included in the radiation field during head and neck radiotherapy, and recent clinical evidence suggests that dental pulp is negatively affected by the direct effects of radiation, leading to impaired sensitivity of the dental pulp. Therefore, this study aimed to investigate the direct effects of radiation on the microvasculature, innervation, and extracellular matrix of the dental pulp of patients who have undergone head and neck radiotherapy. METHODS Twenty-three samples of dental pulp from patients who finished head and neck radiotherapy were analyzed. Samples were histologically processed and stained with hematoxylin-eosin for morphologic evaluation of the microvasculature, innervation, and extracellular matrix. Subsequently, immunohistochemical analysis of proteins related to vascularization (CD34 and smooth muscle actin), innervation (S-100, NCAM/CD56, and neurofilament), and extracellular matrix (vimentin) of the dental pulp was performed. RESULTS The morphologic study identified preservation of the microvasculature, nerve bundles, and components of the extracellular matrix in all studied samples. The immunohistochemical analysis confirmed the morphologic findings and showed a normal pattern of expression for the studied proteins in all samples. CONCLUSIONS Direct effects of radiotherapy are not able to generate morphologic changes in the microvasculature, innervation, and extracellular matrix components of the dental pulp in head and neck cancer patients.