Saliva--a pivotal player in the pathogenesis of oropharyngeal cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Reznick AZ
PROVIDER: S-EPMC2364762 | biostudies-other | 2004 Jul
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Cerebral Cavernous Malformation (CCM) is a major cerebrovascular disease of proven genetic origin affecting 0.3-0.5% of the general population. It is characterized by abnormally enlarged and leaky capillaries, which predispose to seizures, focal neurological deficits and intracerebral hemorrhage. Causative loss-of-function mutations have been identified in 3 genes, KRIT1 (CCM1), CCM2 and PDCD10 (CCM3). While providing new options for the development of pharmacological therapies, recent advances in knowledge of the functions of these genes have clearly indicated that they exert pleiotropic effects on several biological pathways. Recently, we found that defective autophagy is a common feature of loss-of-function mutations of the 3 known CCM genes, and underlies major phenotypic signatures of CCM disease, including endothelial-to-mesenchymal transition and enhanced ROS production, suggesting a unifying pathogenetic mechanism and reconciling the distinct therapeutic approaches proposed so far. In this invited review, we discuss autophagy as a possible unifying mechanism in CCM disease pathogenesis, and new perspectives and avenues of research for disease prevention and treatment, including novel potential drug repurposing and combination strategies, and identification of genetic risk factors as basis for development of personalized medicine approaches.
| S-EPMC4838318 | biostudies-literature
Project description:Periodontitis is a prevalent chronic inflammatory disease due to the host response (IL-1?, IL-6, TNF-? and IL-17A) to oral bacteria such as Porphyromonas gingivalis. The newer members of the IL-1 family, IL-36s (IL-36?/IL-36?/IL-36?/IL-36Ra/IL-38) are known to be involved in host defense against P. gingivalis in oral epithelial cells (OECs) and are considered as key inflammatory mediators in chronic diseases. The aim of this study was to investigate the potential role of IL-36s in periodontitis. We showed here that IL-36? mRNA gingival expression is higher in periodontitis patients, whereas IL-36? and IL-36Ra mRNA expression are lower compared to healthy controls. Interestingly, the elevated IL-36? expression in patients is positively correlated with the RANKL/OPG ratio, an index of bone resorption. In vitro, IL-36? expression was induced through TLR2 activation in primary OECs infected with P. gingivalis but not in gingival fibroblasts, the most widespread cell type in gingival connective tissue. In OECs, recombinant IL-36? enhanced the expression of inflammatory cytokines (IL-1?, IL-6, TNF-? and IL-36?), of TLR2 and importantly, the RANKL/OPG ratio. These findings suggest that IL-36? could be a pivotal inflammatory player in periodontitis by perpetuating gingival inflammation and its associated alveolar bone resorption and could be a relevant therapeutic target.
| S-EPMC6917751 | biostudies-literature
Project description:BACKGROUND:The coronavirus disease-2019 (COVID-19) pandemic has put tremendous pressure on the healthcare system worldwide. Diagnostic testing remained one of the limiting factors for early identification and isolation of infected patients. This study aimed to evaluate posterior oropharyngeal saliva (POPS) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection among patients with confirmed or suspected COVID-19. METHODS:The laboratory information system was searched retrospectively for all respiratory specimens and POPS requested for SARS-CoV-2 RNA detection between Feb 1, 2020 and Apr 15, 2020. The agreement and diagnostic performance of POPS against NPsp were evaluated. RESULTS:A total of 13772 specimens were identified during the study period, including 2130 POPS and 8438 NPsp. Two hundred and twenty-nine same-day POPS-NPsp paired were identified with POPS and NPsp positivity of 61.5% (95% CI [55.1-67.6%]) and 53.3% (95% CI [46.8-59.6%]). The overall, negative and positive percent agreement were 76.0% (95% CI [70.2-80.9%]), 65.4% (95% CI [55.5-74.2%]), 85.2% (95% CI [77.4-90.8%]). Better positive percent agreement was observed in POPS-NPsp obtained within seven days (96.6%, 95% CI [87.3-99.4%]) compared with after seven days of symptom onset (75.0%, 95% CI [61.4-85.2%)). Among the 104 positive pairs, the mean difference in Cp value was 0.26 (range: 12.63 to -14.74), with an overall higher Cp value in NPsp (Pearson coefficient 0.579). No significant temporal variation was noted between the two specimen types. CONCLUSIONS:POPS is an acceptable alternative specimen to nasopharyngeal specimen for the detection of SARS-CoV-2.
| S-EPMC7337706 | biostudies-literature
Project description:A disintegrin and metalloproteinase 9 (ADAM9) is a member of the transmembrane ADAM family. It is expressed in different types of solid cancer and promotes tumor invasiveness. To the best of our knowledge, the present study was the first to examine ADAM9 expression in vestibular schwannomas (VS) from patients with and without neurofibromatosis type 2 (NF2) and to associate the data with clinical parameters of the patients. The aim of the present study was to evaluate if ADAM9 could be used as prognostic marker or therapeutic target. ADAM9 mRNA and protein levels were measured in VS samples (n=60). A total of 30 of them were from patients with neurofibromatosis. Healthy peripheral nerves from autopsies (n=10) served as controls. ADAM9 mRNA levels were measured by PCR, and protein levels were determined by immunohistochemistry (IHC) and western blotting (WB). The Hannover Classification was used to categorize tumor extension and hearing loss. ADAM9 mRNA levels were 8.8-fold higher in VS compared with in controls. The levels were 5.6-fold higher in patients with NF2 and 12-fold higher in patients with sporadic VS. WB revealed two mature isoforms of the protein, and according to IHC ADAM9 was mainly expressed by S100-positive Schwann cells. There was a strong correlation between ADAM9 mRNA expression and the level of functional impairment (r~1, p=0.01). Particularly, the secreted isoform of ADAM9 was expressed in patients with higher hearing impairment. ADAM9 mRNA was overexpressed in the tumor samples relative to healthy vestibular nerves, and there was an association between higher ADAM9 expression levels and greater hearing impairment. Therefore, ADAM9 may be a prognostic marker for VS, and ADAM9 inhibition might have the potential as a systemic approach for the treatment of VS.
| S-EPMC7039135 | biostudies-literature
Project description:RNases perform indispensable functions in regulating gene expression in many bacterial pathogens by processing and/or degrading RNAs. Despite the pivotal role of RNases in regulating bacterial virulence factors, the functions of RNases have not yet been studied in the major human respiratory pathogen Streptococcus pneumoniae (pneumococcus). Here, we sought to determine the impact of two conserved RNases, the endoribonuclease RNase Y and exoribonuclease polynucleotide phosphorylase (PNPase), on the physiology and virulence of S. pneumoniae serotype 2 strain D39. We report that RNase Y and PNPase are essential for pneumococcal pathogenesis, as both deletion mutants showed strong attenuation of virulence in murine models of invasive pneumonia. Genome-wide transcriptomic analysis revealed that the abundances of nearly 200 mRNA transcripts were significantly increased, whereas those of several pneumococcal small regulatory RNAs (sRNAs), including the Ccn (CiaR-controlled noncoding RNA) sRNAs, were altered in the Δrny mutant relative to the wild-type strain. Additionally, lack of RNase Y resulted in pleiotropic phenotypes that included defects in pneumococcal cell morphology and growth in vitro. In contrast, Δpnp mutants showed no growth defect in vitro but differentially expressed a total of 40 transcripts, including the tryptophan biosynthesis operon genes and numerous 5' cis-acting regulatory RNAs, a majority of which were previously shown to impact pneumococcal disease progression in mice using the serotype 4 strain TIGR4. Together, our data suggest that RNase Y exerts a global impact on pneumococcal physiology, while PNPase mediates virulence phenotypes, likely through sRNA regulation. IMPORTANCE Streptococcus pneumoniae is a notorious human pathogen that adapts to conditions in distinct host tissues and responds to host cell interactions by adjusting gene expression. RNases are key players that modulate gene expression by mediating the turnover of regulatory and protein-coding transcripts. Here, we characterized two highly conserved RNases, RNase Y and PNPase, and evaluated their impact on the S. pneumoniae transcriptome for the first time. We show that PNPase influences the levels of a narrow set of mRNAs but a large number of regulatory RNAs primarily implicated in virulence control, whereas RNase Y has a more sweeping effect on gene expression, altering levels of transcripts involved in diverse cellular processes, including cell division, metabolism, stress response, and virulence. This study further reveals that RNase Y regulates expression of genes governing competence by mediating the turnover of CiaR-controlled noncoding (Ccn) sRNAs.
| S-EPMC8546594 | biostudies-literature
Project description:OBJECTIVE:Gastric cancer (GC) is a leading cause of cancer death, occurs predominantly in older age, with increasing incidence in young patients. The Cancer Genome Atlas indicates four subtypes for GC among which Epstein-Barr virus (EBV) subtype is estimated at 8.7%. We aim to determine the prevalence of EBV subtype in young GC patients (?45?years) compared with an average-onset cohort (?55?years) and characterize the clinicopathologic pattern of young-onset GC. METHODS:Gastric cancer samples of patients of both cohorts were screened for EBV by qPCR. Additional staining was done for Human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI) status and Programmed death-ligand 1 (PD-L1). Demographics and clinical data were retrieved from the medical records. RESULTS:Thirty-nine young-onset and 35 average-onset GC patients were reviewed. There was no apparent difference in tumor location, family history, histology and HER2 status between the cohorts. More young-onset patients were diagnosed with metastatic disease (27% vs 9%, p?=?0.0498). EBV was significantly more prevalent in the young-onset cohort (33% vs 11%, p?=?0.025). 15/17 EBV positive patients were under the median age of diagnosis for GC in the US (68?years). MSI-H was found only in the average-onset cohort [0% vs 27%, p?=?0.001). PD-L1 positivity was higher in the young-onset cohort (31% vs 3%, p?=?0.002). CONCLUSION:Our study indicates that EBV subtype is more prevalent in young-onset GC and may play a key role in the pathogenesis. Higher rate of PD-L1 positivity in young-onset GC could change treatment strategies. We are currently evaluating these findings in a prospective trial.
| S-EPMC6961297 | biostudies-literature
Project description:RNases perform indispensable functions in regulating gene expression in many bacterial pathogens by processing and/or degrading RNAs. Despite the pivotal role of RNases in regulating bacterial virulence factors, the functions of RNases have not yet been studied in the major human respiratory pathogen Streptococcus pneumoniae (pneumococcus). Here, we sought to determine the impact of two conserved RNases, the endoribonuclease RNase Y and exoribonuclease polynucleotide phosphorylase (PNPase), on the physiology and virulence of S. pneumoniae serotype 2 strain D39. We report that RNase Y and PNPase are essential for pneumococcal pathogenesis as both deletion mutants showed strong attenuation of virulence in murine models of invasive pneumonia. Genome-wide transcriptomic analysis revealed that nearly 200 mRNA transcripts were significantly up-regulated, whereas the abundance of several pneumococcal sRNAs, including the Ccn (CiaR Controlled Noncoding RNA) sRNAs, were altered in the ∆rny mutant relative to the wild-type strain. Additionally, lack of RNase Y resulted in pleiotropic phenotypes that included defects in pneumococcal cell morphology and growth in vitro. In contrast, Dpnp mutants showed no growth defect in vitro, but differentially expressed a total of 40 transcripts including the tryptophan biosynthesis operon genes and numerous 5’-cis-acting regulatory RNAs, a majority of which were previously shown to impact pneumococcal disease progression in mice using the serotype 4 strain TIGR4. Altogether our data suggest that RNase Y exerts a global impact on pneumococcal physiology, while PNPase-mediates virulence phenotypes, likely through sRNA regulation.
2021-09-02 | GSE173392 | GEO
Project description:Carriage of Neisseria meningitidis is an accepted endpoint in monitoring meningococcal vaccines effects. We have assessed N. meningitidis and vaccine-type genogroup carriage prevalence in college students at the time of MenACWY vaccine introduction in the Netherlands, and evaluated the feasibility of saliva sampling for the surveillance of carriage. For this, paired saliva and oropharyngeal samples collected from 299 students were cultured for meningococcus. The DNA extracted from all bacterial growth was subjected to qPCRs quantifying meningococcal and genogroup-specific genes presence. Samples negative by culture yet positive for qPCR were cultured again for meningococcus. Altogether 74 (25%) of students were identified as meningococcal carrier by any method. Sixty-one students (20%) were identified as carriers with qPCR. The difference between number of qPCR-positive oropharyngeal (n = 59) and saliva (n = 52) samples was not significant (McNemar's test, p = 0.07). Meningococci were cultured from 72 students (24%), with a significantly higher (p < 0.001) number of oropharyngeal (n = 70) compared with saliva (n = 54) samples. The prevalence of genogroups A, B, C, W, and Y was none, 9%, 1%, 1% and 6%, respectively, and 8% of students carried MenACWY vaccine-type genogroup meningococci. Saliva is easy to collect and when combined with qPCR detection can be considered for meningococcal carriage studies.
| S-EPMC8632920 | biostudies-literature
Project description:Oropharyngeal cancer (OPC) caused by human papillomavirus (HPV) is a rising global concern. Early lesions are small and are often located in difficult to access areas (such as the crypts of the tonsils or base of tongue). Unlike cervical cancer, there is no standard or routine screening program for HPV-driven OPC. HPV DNA from OPC tumors may shed directly into saliva, and this can be used as a biomarker for early diagnosis. In this study, we report the first-ever clinically occult OPC in an asymptomatic patient discovered through a saliva test. This case relied upon serial measurements of HPV-16 DNA in saliva, which fell to undetectable levels following low morbidity, curative treatment.
| S-EPMC7136454 | biostudies-literature
Project description:Oropharyngeal cancer accounts for approximately 2.8% of newly cancer cases. Although classically a tobacco related disease, most cases today are related to infection with human papilloma virus (HPV) and present with locally advanced tumors. HPV related tumors have been recognized as a molecularly distinct entity with higher response rates to therapy, lower rates of relapse, and improved overall survival. Treatment of oropharyngeal cancer entails a multi-disciplinary approach with concomitant chemoradiation. The role of induction chemotherapy in locally advanced tumors continues to be controversial however large studies have demonstrated no difference in survival or time to treatment failure. Surgical approaches may be employed with low volume oropharyngeal cancers and with development new endoscopic tools, more tumors are able to be resected via an endoscopic approach. Given advances in the understanding of HPV related oropharyngeal cancer, ongoing research is looking at ways to minimize toxicities via de-intensification of therapy. Unfortunately, some patients develop recurrent or metastatic disease. Novel therapeutics are currently being investigated for this patient population including immunotherapeutics. This review discusses the current understanding of the pathogenesis of oropharyngeal cancer and treatment. We also discuss emerging areas of research as it pertains to de-intensification as well novel therapeutics for the management of metastatic disease.
| S-EPMC4734935 | biostudies-other