Salivary microbiome changes distinguish response to chemoradiotherapy in patients with oral cancer.

Background: Oral squamous cell carcinoma (SCC) is associated with oral microbial dysbiosis. In this unique study, we compared pre- to post-treatment salivary microbiome in patients with SCC by 16S rRNA gene sequencing and examined how microbiome changes correlated with the expression of an anti-microbial protein.

Results: Treatment of SCC was associated with a reduction in overall bacterial richness and diversity.

Galanin mediates tumor-induced immunosuppression in head and neck squamous cell carcinoma.

Purpose: Galanin receptor 2 (GALR2) plays a significant role in the progression of head and neck squamous cell carcinomas (HNSCC). Since there is virtually no information on immunomodulation mediated by its ligand in the tumor microenvironment, we assessed the effects of galanin on peripheral blood mononuclear cells (PBMCs).

Methods: After verification of GALR2 expression and it activity in PBMCs we evaluated the effect of galanin and conditioned media from HNSCC cell lines silenced for galanin or antibody-depleted, on proliferation, apoptosis, cytokine expression and activation/differentiation of immune cells.

Cancer-associated keratinocytes: new members of the microenvironment in head and neck cancer.

The tumor microenvironment is a complex ecosystem of malignant and nonmalignant cells and extracellular proteins that work together to enhance tumor progression. We identified a mechanism in which adjacent nonmalignant epithelium enhances invasion of squamous cell carcinoma, thereby expanding the tumor microenvironment to include cancer-associated keratinocytes.

Squamous cell carcinoma subverts adjacent histologically normal epithelium to promote lateral invasion.

Recurrent and new tumors, attributed in part to lateral invasion, are frequent in squamous cell carcinomas and lead to poor survival. We identified a mechanism by which cancer subverts adjacent histologically normal epithelium to enable small clusters of cancer cells to burrow undetected under adjacent histologically normal epithelium. We show that suppression of DMBT1 within cancer promotes aggressive invasion and metastasis in vivo and is associated with metastasis in patients.

5-Hydroxymethylation highlights the heterogeneity in keratinization and cell junctions in head and neck cancers.

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide, with human papillomavirus (HPV)-related HNSCC rising to concerning levels. Extensive clinical, genetic and epigenetic differences exist between HPV-associated HNSCC and HPV-negative HNSCC, which is often linked to tobacco use. However, 5-hydroxymethylation (5hmC), an oxidative derivative of DNA methylation and its heterogeneity among HNSCC subtypes, has not been studied.

Silencing matrix metalloproteinase-13 (Mmp-13) reduces inflammatory bone resorption associated with LPS-induced periodontal disease in vivo.

Objectives: The aim of this study was to evaluate the effect of specific inhibition of MMP-13 on inflammation and inflammatory bone resorption in a murine model of lipopolysaccharide (LPS)-induced periodontitis.

Materials And Methods: Periodontitis was induced in mice by micro-injections of LPS into the gingival tissues adjacent to the palatal surfaces of maxillary molars twice a week for 15 days. Matrix metalloproteinase-13 (Mmp-13) shRNA or a specific biochemical inhibitor were also injected into the same sites in alternating days with the LPS injections.

Activin A triggers angiogenesis via regulation of VEGFA and its overexpression is associated with poor prognosis of oral squamous cell carcinoma.

Poor prognosis associated with the dysregulated expression of activin A in a number of malignancies has been related to with numerous aspects of tumorigenesis, including angiogenesis. The present study investigated the prognostic significance of activin A immunoexpression in blood vessels and cancer cells in a number of oral squamous cell carcinoma (OSCC) cases and applied in vitro strategies to determine the impact of activin A on angiogenesis. In a cohort of 95 patients with OSCC, immunoexpression of activin A in both blood vessels and tumor cells was quantified and the association with clinicopathological parameters and survival was analyzed.

Systemic administration of curcumin or piperine enhances the periodontal repair: a preliminary study in rats.

Objectives: Studies have documented the anti-inflammatory effects of spices, which may be related to treatment of chronic diseases. The purpose of this study was to evaluate the influence of curcumin and piperine and their association on experimental periodontal repair in rats.

Materials And Methods: Periodontitis was induced via the installation of a ligature around the first molar.

Use of a Non-Crosslinked Collagen Membrane During Guided Bone Regeneration Does Not Interfere With the Bone Regenerative Capacity of the Periosteum.

Purpose: To assess whether the use of a non-crosslinked porcine collagen type I and III bi-layered membrane inter-positioned between the periosteum and a bone defect would interfere with the bone regenerative capacity of the periosteum.

Materials And Methods: Sixty rats, each with 1 critical-size calvarial defect (CSD; diameter, 5 mm) in the parietal bone, were randomly allocated to 1 of 3 equal-size groups after CSD creation: 1) the periosteum was excised and the flap was repositioned without interposition of a membrane (no-periosteum [NP] group); 2) the flap including the periosteum was repositioned (periosteum [P] group); and 3) a non-crosslinked collagen membrane was inter-positioned between the flap, including the periosteum, and the bone defect (membrane [M] group). Micro-computed tomography, qualitative histology, immunohistochemistry, and reverse transcription real-time quantitative polymerase chain reaction were performed at 3, 7, 15, and 30 days postoperatively.

Suppressor of cytokine signaling 1 expression during LPS-induced inflammation and bone loss in rats.

This study aimed to characterize the dynamics of suppressor of cytokine signaling (SOCS1) expression in a rat model of lipopolysaccharide-induced periodontitis. Wistar rats in the experimental groups were injected three times/week with LPS from Escherichia coli on the palatal aspect of the first molars, and control animals were injected with vehicle (phosphate-buffered saline). Animals were sacrificed 7, 15, and 30 days after the first injection to analyze inflammation (stereometric analysis), bone loss (macroscopic analysis), gene expression (qRT-PCR), and protein expression/activation (Western blotting).

HNSCC subverts PBMCs to secrete soluble products that promote tumor cell proliferation.

The immune system detects shifts from homeostasis and eliminates altered cells. However, neoplastic cells can modulate the host response to escape immunosurveillance thereby allowing tumor progression. Head and neck squamous cell carcinoma (HNSCC) is one of the most immunosuppressive cancers but its role in co-opting the immune system to actively promote tumor growth has not been investigated.

Functional Haplotypes in Interleukin 4 Gene Associated with Periodontitis.

Chronic periodontitis (CP) is an infectious inflammatory disease that affects tooth-supporting structures and in which dental plaque bacteria, immune mechanisms and genetic predisposition play important roles. Interleukin 4 (IL-4) is a key anti-inflammatory cytokine with relevant action in imbalances in inflamed periodontal tissue. Individuals carrying the TCI/CCI genotype (S-haplotype) of the IL-4 gene are 5 times more susceptible to CP, whereas the CTI/TTD genotype (P-haplotype) confers protection against CP.

Modulation of cell proliferation, survival and gene expression by RAGE and TLR signaling in cells of the innate and adaptive immune response: role of p38 MAPK and NF-KB.

Objective: The aim of this study was to evaluate a possible synergism between AGE-RAGE and TLR4 signaling and the role of p38 MAPK and NF-kB signaling pathways on the modulation of the expression of inflammatory cytokines and proliferation of cells from the innate and adaptive immune response.

Material And Methods: T lymphocyte (JM) and monocyte (U937) cell lines were stimulated with LPS and AGE-BSA independently and associated, both in the presence and absence of p38 MAPK and NF-kB inhibitors. Proliferation was assessed by direct counting and viability was assessed by a biochemical assay of mitochondrial function.

Odontogenic cysts: demographic profile in a Brazilian population over a 38-year period.

Objective: To determine the distribution of odontogenic cysts diagnosed histologically over a period of 38 years in a Brazilian population according to age, gender and site affected and to compare these data with previously reported studies from other countries.

Study Design: A total of 1019 cases of odontogenic cysts diagnosed between 1970 and 2007 were studied. Clinical features obtained from the patient records and microscope slides were reviewed according to the 1992 World Health Organization classification.