Marina Gallottini

A review of oral toxicity associated with mTOR inhibitor therapy in cancer patients

Aphthous-like stomatitis has been identified as one of the most common dose-limiting toxicities associated with mTOR inhibitor therapy in cancer patients. The objective of this study was to summarize the cumulative oral toxicities associated with mTOR inhibitors in published oncology trials with respect to dose, schedule, and need for dose modifications. A review of all oncology-related clinical trials of mTOR inhibitors was conducted and standardized data was abstracted from each study. 44 studies were included in the analysis with a total of 2822 patients treated with temsirolimus (19 studies), everolimus (20 studies), and ridaforolimus (five studies) for a wide range of malignancies. At least one adverse event (AE) occurred in 74.4% of patients. Mucositis was the most frequent AE overall (73.4%), the third most frequent severe AE (20.7%), accounting for 27.3% dose reductions and 13.1% of discontinuations, and the most frequent dose limiting toxicity (52.5%). Mucositis typically occurred during the first cycle of therapy and was graded as mild to moderate in approximately 90% of the patients; severe mucositis generally occurred at higher doses. There were no clear differences in mucositis among the three agents and in most cases lesions resolved spontaneously. Oral mucositis is a frequent complication of mTOR inhibitor therapy and a significant cause of dose reductions and discontinuations in oncology trials. Prevention and management strategies should be investigated to improve tolerability and better permit effective long-term regimens.

Medical problems and oral care of patients with Down syndrome: a literature review.

When planning the dental treatment of patients with Down syndrome (DS), dental practitioners should always consider their general health, in order to achieve a holistic and interdisciplinary approach. This article presents a literature review of the primary medical conditions in patients with DS that may affect their general health care and the appropriate clinical delivery of oral health care.

Assessment and management of oral health in liver transplant candidates

Liver transplantation has become a standard treatment for end-stage liver disease and the number of recipients has grown rapidly in the last few years. Dental care during pre-transplant workup is important to reduce potential sources of infection in the drug-induced immunosuppression phase of liver transplantation. Objectives The objectives of this study were to document the prevalence of oral abnormalities in patients on a liver transplant waiting list presenting to an urban dental school clinic, discuss the appropriate dental treatment according their systemic conditions and compare their oral manifestations with those of healthy individuals. Material and Methods A pilot study was conducted involving 16 end-stage liver disease individuals (study group- SG) attending the Special Care Dentistry Center of the University of São Paulo and 16 control individuals (control group- CG) with no liver diseases, receiving dental care at the Dental School of the University of São Paulo. These individuals were assessed for their dental status (presence of oral disease or abnormalities), coagulation status, and dental treatment indications. Results The patients from SG exhibited a greater incidence of oral manifestations compared with CG (p=0.0327) and were diagnosed with at least one oral disease or condition that required treatment. Coagulation abnormalities reflecting an increased risk of bleeding were found in 93.75% of the patients. However, no bleeding complications occurred after dental treatment. Conclusions The patients with chronic liver diseases evaluated in this study exhibited a higher incidence of oral manifestations compared with the control group and had at least one oral disease or abnormality which required dental treatment prior to liver transplantation. Careful oral examination and evaluation of the patient, including laboratory tests, will ensure correct oral preparation and control of oral disease prior to liver transplantation.

PI3K-AKT-mTOR pathway proteins are differently expressed in oral carcinogenesis.

BACKGROUND PI3K-AKT-mTOR signaling pathway is associated with several cellular functions and is frequently changed in several malignancies. The aim of this study was to characterize the immunohistochemical expression pattern of components in PI3K-AKT-mTOR signaling pathway in oral epithelial dysplasia (OED), comparing to oral squamous cell carcinoma (OSCC) and non-dysplastic oral tissues (NDOT). METHODS A total of 186 cases of NDOT, OED and OSCC were retrieved. Nuclear staining and cytoplasmic staining of the keratinocytes were considered positive, and the percentage of positive cells was calculated. RESULTS Increased immunoreactivity from NDOT to OED and OSCC was seen for all proteins. In NDOT cases, positivity was found only for pS6 (52.9%) and p4EBP1 (13.5%). In OED, immunoreactivity was observed for pAKT (62.2%), pmTOR (28.6%), pS6 (70.8%), and p4EBP1 (42.9%). In OSCC cases, immunoreactivity was found for pAKT (83.3%), pmTOR (50%), pS6 (77.4%), and p4EBP1 (50%). The pAKT and pmTOR expression was higher in OED (<0.001, Fishers exact test) and OSCC (<0.001, Fishers exact test). CONCLUSION Our study demonstrated higher pAKT and pmTOR expression during carcinogenesis of oral mucosa, differing considerably among OED and OSCC specimens when compared to NDOT. These proteins can be considered potential diagnostic markers for early detection of cancer.

Oral and cervical HPV infection in HIV‐positive and HIV‐negative women attending a sexual health clinic in São Paulo, Brazil

To investigate the prevalence of HPV infections in the oral and cervical mucosa of HIV‐positive and HIV‐negative women attending a sexual health clinic.

Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.

Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells.

Oral hairy leukoplakia diagnosis by Epstein–Barr virus in situ hybridization in liquid‐based cytology

To establish a definitive diagnosis of oral hairy leukoplakia (OHL) by in situ hybridization for Epstein–Barr virus (EBV) detection with liquid‐based cytology (LBC), using the ThinPrep® Pap Test, and to compare its efficacy with the traditional method of performing biopsy.

The effects of zoledronic acid and dexamethasone on osseointegration of endosseous implants: histological and histomorphometrical evaluation in rats

BACKGROUND Bisphosphonates are a widely used class of drugs that prevent bone loss. Several side effects related to bisphosphonate therapy have been reported, including osteonecrosis of the jaws associated with invasive dental procedures and implants placement. OBJECTIVES To evaluate the influence of intravenous nitrogen-containing BPs in combination with or without dexamethasone on osseointegration of titanium implants placed in an animal model. METHODS Twenty-seven male Wistar rats were divided into three groups: group 1 was treated solely with zoledronic acid, group 2 was treated with zoledronic acid and dexamethasone, and group 3 did only receive saline solution injections. Two endosseous implants were placed in each tibia, and three animals from each group were sacrificed at postoperative times of seven, 14, and 28 days. Non-decalcified sections were observed with light microscopy for histological and histomorphometrical analyses. RESULTS Histomorphometrical analysis using the animals and the implants as unit of measurement revealed no statistically significant difference regarding bone-implant contact and bone density among the three groups. Histological observation revealed that zoledronic acid-treated animals in combination with or without dexamethasone showed expressive less bone remodeling activity at 14 and 28 days after implants placement, compared with control specimens. CONCLUSIONS The studied bisphosphonate regimens did not interfere with the osseointegration of the implants, cortical, or medular bone deposition, but a possible lack of bone remodeling of the original cortical bone may affect long-term osseointegration.

Polyomavirus BK and JC in individuals with chronic kidney failure, kidney transplantation, and healthy controls

BACKGROUND New clinical approaches to diagnose and monitor individuals with systemic diseases have been employed through the use of oral fluids. Polyomavirus BK (BKPyV) and JC (JCPyV) infect asymptomatically around 80% of general population worldwide remaining latent in the body. In case of immunosuppression, a replication can occur, leading to diseases. OBJECTIVE The aim of this study was to detect and quantify BKPyV and JCPyV in oral fluids of individuals with chronic kidney failure (CKF), kidney transplantation (KT) and controls compared with their detection in blood and urine, traditionally used for this test. STUDY DESIGN Forty six subjects were included and distributed into 3 groups: 14 with CKF (Group 1), 12 with KT (Group 2) and 20 healthy individuals (Group 3). In a total, 315 samples were collected and analyzed through RT-PCR, being 151 of gingival crevicular fluid, 46 of saliva, 46 of mouthwash, 43 of blood and 29 of urine. RESULTS All subjects from group 1 were positive for BKPyV in at least one collected samples and 14% were positive for JCPyV. In Group 2, 91.7% were positive for BKPyV and 51.7% for JCPyV. Among subjects of Group 3, 80% were positive for BKPyV and 45% for JCPyV. CONCLUSIONS Oral fluids exhibited high prevalence of BKPyV and JCPyV and were equally efficient compared to urine and blood. The use of oral fluids to detect these polyomaviruses enhances positivity in screening, even in cases of absence of viremia and especially in individuals who are not able to urinate.

Salivary parameters and oral health in the Moebius syndrome.

PURPOSE To evaluate salivary characteristics, such as flow rate, buffering capacity and amylase activity, and associate these parameters with oral health in individuals with Moebius syndrome (MS) and controls. METHODS The researchers assessed caries (ICDAS), periodontal disease (PSR), and plaque (Silness Löe) indexes in both groups. Unstimulated, stimulated, and bilateral parotid saliva were also collected. The salivary flow (milliliters/minute) and α-amylase activity were measured in all samples. The α-amylase activity was determined by maltose production. The buffering capacity was measured in stimulated saliva by titration of 0.01N HCl. RESULTS The occurrence of carious lesions, related to cut-off 2, as well as the occurrence of periodontal disease, was significantly higher (p > 0.05) in participants with MS when compared to the control group. Also, MS individuals presented decreased salivary flow, decreased buffering capacity, and amylase activity. CONCLUSIONS MS individuals present salivary alterations, which can be related to higher risk for caries.