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1.
Sci Rep ; 13(1): 5460, 2023 04 04.
Article in English | MEDLINE | ID: mdl-37015965

ABSTRACT

Pericytes are perivascular cells related to vessel structure and angiogenesis that can interact with neoplastic cells, interfering with cancer progression and outcomes. This study focused on the characterization of pericytes in oral squamous cell carcinoma (OSCC) using clinical samples and a transgenic mouse model of oral carcinogenesis. Nestin-/NG2+ (type-1) and nestin+/NG2+ (type-2) pericytes were analyzed by direct fluorescence after induction of oral carcinogenesis (4-nitroquinoline-1-oxide). Gene expression of neuron glial antigen-2 (NG2), platelet-derived growth factor receptor beta (PDGFR-ß), and cluster of differentiation 31 (CD31) was examined in human OSCC tissues. The protein expression of von Willebrand factor and NG2 was assessed in oral leukoplakia (i.e., oral potentially malignant disorders) and OSCC samples. Additionally, clinicopathological aspects and survival data were correlated and validated by bioinformatics using The Cancer Genome Atlas (TCGA). Induction of carcinogenesis in mice produced an increase in both NG2+ pericyte subsets. In human OSCC, advanced-stage tumors showed a significant reduction in CD31 mRNA and von Willebrand factor-positive vessels. Low PDGFR-ß expression was related to a shorter disease-free survival time, while NG2 mRNA overexpression was associated with a reduction in overall survival, consistent with the TCGA data. Herein, oral carcinogenesis resulted in an increase in NG2+ pericytes, which negatively affected survival outcomes.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Mice , Humans , Animals , Pericytes/metabolism , Carcinoma, Squamous Cell/metabolism , Nestin/metabolism , Mouth Neoplasms/metabolism , Squamous Cell Carcinoma of Head and Neck/pathology , von Willebrand Factor/genetics , von Willebrand Factor/metabolism , Mice, Transgenic , Receptor, Platelet-Derived Growth Factor beta/genetics , Receptor, Platelet-Derived Growth Factor beta/metabolism , Carcinogenesis/pathology , Head and Neck Neoplasms/pathology , RNA, Messenger/metabolism
2.
Arch Oral Biol ; 134: 105344, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34990927

ABSTRACT

OBJECTIVE: Undifferentiated cells play pivotal roles in sustaining tissue homeostasis during physiological turnovers and after tissue impairment. Nestin and Neuron-glial antigen 2 (NG2) are markers frequently deployed to distinguish progenitor populations. In the salivary gland scenario, these markers remain largely unknown. Particularly for a double-labeled group of progenitor cells (NG2+Nestin+), their phenotype and distribution have never been explored in freshly isolated tissues. Herein, we analyzed a subset of plastic cells that express Nestin and NG2 near the ducts and in the periacinar region of the major salivary glands of murine samples. DESIGN: The major salivary glands tissues of Nestin-GFP/NG2-DsRed mice were analyzed under a fluorescence microscope. The cells marked by GFP and DsRed were counted in the merged image component of random representative images obtained for each gland sample at × 20 magnification. RESULTS: In the parotid, submandibular, and sublingual glands, the population of cells exclusively expressing Nestin was more abundant. There was a predominance of Nestin, NG2, and double-labeled cells in the submandibular gland compared to the parotid gland, mainly near the ductal system. Of note, the sublingual and parotid glands had similar populations of Nestin+ and NG2+, especially in acini, and some positive cells were observed surrounding ducts. CONCLUSIONS: Collectively, our study revealed differential expression patterns of Nestin and NG2, alone or in combination, in the salivary gland subset during homeostasis.


Subject(s)
Salivary Glands , Sublingual Gland , Animals , Mice , Nestin/genetics , Neurons , Parotid Gland , Submandibular Gland , Transgenes
3.
Head Neck Pathol ; 15(4): 1127-1136, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33840043

ABSTRACT

To evaluate molecular epithelial changes, we investigated whether a profile of survivin, cyclin dependent kinase inhibitor 2A (CDKN2A), epidermal growth factor receptor (EGFR), polo like kinase 1 (PLK1), p63, p40 (Δnp63 isoform), cyclin D1 (CCND1) and BCL2 apoptosis regulator (BCL2) proteins could predict malignant transformation. Different tissue segments (tumor adjacent epithelium; dysplasia and tumor) from a total of 109 patients were analyzed by immunohistochemistry. An increased expression of survivin (p < 0.001), PLK1 (p = 0.001), and p63 (p < 0.001) in parallel to reduced immunostaining of p40 (p < 0.001) and BCL2 (p = 0.029) was observed among the tissue segments analyzed. Our study revealed that survivin, PLK1, p63, p40 and BCL2 play a role in oral tumorigenesis and represent promising biomarkers able to recognize mesenchymal phenotype induction in the transition from nonmalignant cells to tumor cells. These results reveals critical interaction between survivin, PLK1, p63, p40 promising proteins during invasive carcinoma development.


Subject(s)
Carcinoma, Squamous Cell/metabolism , Mouth Mucosa/metabolism , Mouth Neoplasms/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/pathology , Cell Cycle Proteins/metabolism , Cell Transformation, Neoplastic/pathology , Cyclin D1/metabolism , Cyclin-Dependent Kinase Inhibitor p16/metabolism , ErbB Receptors/metabolism , Female , Humans , Immunohistochemistry , Male , Middle Aged , Mouth Neoplasms/pathology , Protein Isoforms , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Survivin/metabolism , Transcription Factors/metabolism , Polo-Like Kinase 1
5.
Spec Care Dentist ; 41(1): 20-31, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33125723

ABSTRACT

Myiasis is an infection caused by the deposition of fly larvae in tissues, and its involvement in the human oral cavity is uncommon. Herein, we have performed a data analysis of published cases of oral myiasis. A search was performed in PubMed, Ovid, Web of Science, Scopus, and LILACS. Geographic distribution, demographic data, associated factors, clinical features, fly types, treatment, and presence of sequelae were analyzed. A total of 122 articles reported the cases of 157 infected individuals. The most affected countries were India (41%) and Brazil (29.5%). Male predominance (67.5%) and a mean of 41.9 years of age were observed. The gingiva (29%) was the most affected site, followed by palate (25%) and lip (21%). There were different forms and combinations of treatments: manual removal of larvae and surgical debridement, application of asphyxiating substances, antibiotic therapy, and use of ivermectin. The condition predominantly affects individuals with neurological and/or locomotor disabilities, of low socioeconomic status, with poor oral hygiene and chemical dependence and individuals with previous injuries or with the absence of lip sealing. The establishment of a standard treatment protocol, enabling comparison in future studies and providing uniformity in treatment strategies offered by health services is strongly recommended.


Subject(s)
Myiasis , Adult , Brazil/epidemiology , Humans , India/epidemiology , Ivermectin , Male , Mouth , Myiasis/therapy
6.
Sci Rep ; 10(1): 19257, 2020 11 06.
Article in English | MEDLINE | ID: mdl-33159113

ABSTRACT

Photobiomodulation is being widely applied for improving dermal or mucosal wound healing. However, the underlying cellular and molecular processes that directly contribute to its effects remain poorly understood. Pericytes are relevant cells involved in the wound microenvironment and could be one of the main targets of photobiomodulation due to their plasticity and perivascular localization. Herein, we investigate tissue repair under the photobiomodulation stimulus using a pericyte labeled (or reporter) transgenic mice. Using a model of two contralateral back wounds, one the control and the other photoactivated daily (660 nm, 20 mW, 0.71 W/cm2, 5 J/cm2, 7 s, 0.14 J), we showed an overall influx of immune and undifferentiated cells and higher mobilization of a potent pericyte subpopulation (Type-2 pericytes) in the photoactivated wounds in comparison to the controls. Doppler analysis showed a significant increase in the blood flow in the photoactivated wounds, while marked vascular supply was observed histologically. Histochemical analysis has indicated more advanced stages of tissue repair after photoactivation. These data suggest that photobiomodulation significantly accelerates tissue repair through its vascular effects with direct recruitment of pericytes to the injury site.


Subject(s)
Low-Level Light Therapy , Pericytes/metabolism , Skin/injuries , Skin/metabolism , Wound Healing , Animals , Mice , Mice, Transgenic , Pericytes/pathology , Skin/pathology
7.
BMC Cancer ; 18(1): 324, 2018 03 27.
Article in English | MEDLINE | ID: mdl-29580212

ABSTRACT

BACKGROUND: The prevalence of high-risk human papillomavirus (HPV) DNA in cases of oral cavity squamous cell carcinoma (SCC) varies widely. The aim of this study is to investigate the frequency of high-risk HPV DNA in a large Brazilian cohort of patients with oral cavity SCC. METHODS: Biopsy and resected frozen and formalin-fixed paraffin-embedded specimens of oral cavity SCC were available from 101 patients who were recruited at two Brazilian centres. Stringent measures with respect to case selection and prevention of sample contamination were adopted to ensure reliability of the data. Nested PCR using MY09/MY11 and GP5+/GP6+ as well as PGMY09/11 L1 consensus primers were performed to investigate the presence of HPV DNA in the tumours. HPV-positive cases were subjected to direct sequencing. Shapiro-Wilk and Student t test were used to evaluate data normality and to compare the means, respectively. Qualitative variables were analysed by logistic regression. RESULTS: Our results demonstrate that the frequency of high-risk HPV types in oral cavity SCC is very low and is less than 4%. All HPV-positive cases were HPV16. In addition, our results do not show a significant association between the tumour clinical features and the risk factors (tobacco, alcohol and HPV) for oral cavity SCC. CONCLUSION: In the current study, we observed an overlapping pattern of risk factors that are related to tumour development. This, along with a low frequency of high-risk HPV DNA, supports the findings that HPV is not involved in the genesis of oral cavity SCC in Brazilian population.


Subject(s)
Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/etiology , Mouth Neoplasms/epidemiology , Mouth Neoplasms/etiology , Papillomaviridae , Papillomavirus Infections/complications , Papillomavirus Infections/epidemiology , Adult , Aged , Aged, 80 and over , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Odds Ratio , Papillomavirus Infections/virology , Prevalence , Risk Factors
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