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1.
Arch Microbiol ; 206(6): 248, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713383

RESUMO

Describing the microbial community within the tumour has been a key aspect in understanding the pathophysiology of the tumour microenvironment. In head and neck cancer (HNC), most studies on tissue samples have only performed 16S rRNA short-read sequencing (SRS) on V3-V5 region. SRS is mostly limited to genus level identification. In this study, we compared full-length 16S rRNA long-read sequencing (FL-ONT) from Oxford Nanopore Technology (ONT) to V3-V4 Illumina SRS (V3V4-Illumina) in 26 HNC tumour tissues. Further validation was also performed using culture-based methods in 16 bacterial isolates obtained from 4 patients using MALDI-TOF MS. We observed similar alpha diversity indexes between FL-ONT and V3V4-Illumina. However, beta-diversity was significantly different between techniques (PERMANOVA - R2 = 0.131, p < 0.0001). At higher taxonomic levels (Phylum to Family), all metrics were more similar among sequencing techniques, while lower taxonomy displayed more discrepancies. At higher taxonomic levels, correlation in relative abundance from FL-ONT and V3V4-Illumina were higher, while this correlation decreased at lower levels. Finally, FL-ONT was able to identify more isolates at the species level that were identified using MALDI-TOF MS (75% vs. 18.8%). FL-ONT was able to identify lower taxonomic levels at a better resolution as compared to V3V4-Illumina 16S rRNA sequencing.


Assuntos
Bactérias , Neoplasias de Cabeça e Pescoço , Sequenciamento por Nanoporos , RNA Ribossômico 16S , Humanos , RNA Ribossômico 16S/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/microbiologia , Sequenciamento por Nanoporos/métodos , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Microbiota/genética , Sequenciamento de Nucleotídeos em Larga Escala , Pessoa de Meia-Idade , Análise de Sequência de DNA , Masculino , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Feminino , Idoso , Adulto , Filogenia
2.
Cancer Biol Ther ; 25(1): 2350249, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38722731

RESUMO

Head and Neck Squamous Cell Carcinoma (HNSCC) comprises a diverse group of tumors with variable treatment response and prognosis. The tumor microenvironment (TME), which includes microbiome and immune cells, can impact outcomes. Here, we sought to relate the presence of specific microbes, gene expression, and tumor immune infiltration using tumor transcriptomics from The Cancer Genome Atlas (TCGA) and associate these with overall survival (OS). RNA sequencing (RNAseq) from HNSCC tumors in TCGA was processed through the exogenous sequences in tumors and immune cells (exotic) pipeline to identify and quantify low-abundance microbes. The detection of the Papillomaviridae family of viruses assessed HPV status. All statistical analyses were performed using R. A total of 499 RNAseq samples from TCGA were analyzed. HPV was detected in 111 samples (22%), most commonly Alphapapillomavirus 9 (90.1%). The presence of Alphapapillomavirus 9 was associated with improved OS [HR = 0.60 (95%CI: 0.40-0.89, p = .01)]. Among other microbes, Yersinia pseudotuberculosis was associated with the worst survival (HR = 3.88; p = .008), while Pseudomonas viridiflava had the best survival (HR = 0.05; p = .036). Microbial species found more abundant in HPV- tumors included several gram-negative anaerobes. HPV- tumors had a significantly higher abundance of M0 (p < .001) and M2 macrophages (p = .035), while HPV+ tumors had more T regulatory cells (p < .001) and CD8+ T-cells (p < .001). We identified microbes in HNSCC tumor samples significantly associated with survival. A greater abundance of certain anaerobic microbes was seen in HPV tumors and pro-tumorigenic macrophages. These findings suggest that TME can be used to predict patient outcomes and may help identify mechanisms of resistance to systemic therapies.


Assuntos
Neoplasias de Cabeça e Pescoço , Microbiota , Infecções por Papillomavirus , Carcinoma de Células Escamosas de Cabeça e Pescoço , Microambiente Tumoral , Humanos , Neoplasias de Cabeça e Pescoço/virologia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/microbiologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/genética , Feminino , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/complicações , Masculino , Microbiota/genética , Microambiente Tumoral/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Prognóstico , Pessoa de Meia-Idade , Papillomaviridae/genética , Idoso
3.
Microbiol Spectr ; 12(5): e0426023, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38587390

RESUMO

Streptococcus pyogenes causes a variety of human infections, and hospital outbreaks with this pathogen have also been reported. The purpose of this study is to describe the clinical characteristics of an outbreak of S. pyogenes involving 15 patients and four healthcare workers (HCWs), as well as the molecular characteristics of the causative isolates. The course and response to the outbreak were reviewed, and information on the characteristics of the patients was extracted retrospectively from the medical records. Whole-genome sequencing of the 16 causative isolates (14 from patients and two from HCWs) was also performed. All 15 patients were postoperative of head and neck cancer with tracheotomy, and 12 had invasive infections, primarily surgical site infections, all of which resolved without causing serious illness. All but the first case was detected more than 7 days after admission. S. pyogenes was detected in two patients after empiric antimicrobial administration was performed on all inpatients and HCWs, and the outbreak was finally contained in approximately 2 months. All isolates detected in patients and HCWs belonged to emm89/clade 3, a hypervirulent clone that has emerged worldwide and was classified as sequence type 646. These isolates had single nucleotide polymorphism (SNP) differences of zero to one, indicating clonal transmission. This study demonstrated an outbreak of S. pyogenes emm89/clade 3 in a ward of patients with head and neck cancer. The global emergence of hypervirulent isolates may increase the risk of outbreaks among high-risk patients. IMPORTANCE: This study describes an outbreak of Streptococcus pyogenes that occurred in a ward caring for patients with head and neck cancer and tracheostomies. Many cases of invasive infections occurred in a short period, and extensive empiric antimicrobial administration on patients and healthcare workers was performed to control the outbreak. Whole-genome sequencing analysis of the causative strains confirmed that it was a monoclonal transmission of strains belonging to emm89/clade 3. The epidemiology and clinical characteristics of S. pyogenes infections have changed with the replacement of the prevalent clones worldwide. In the 1980s, there was a reemergence of S. pyogenes infections in high-income countries due to the spread of hypervirulent emm1 strains. emm89/clade 3 has recently been spreading worldwide and shares common features with emm1, including increased production of two toxins, NADase, and streptolysin O. The outbreak reported here may reflect the high spreading potential and virulence of emm89/clade 3.


Assuntos
Infecção Hospitalar , Surtos de Doenças , Neoplasias de Cabeça e Pescoço , Infecções Estreptocócicas , Streptococcus pyogenes , Humanos , Streptococcus pyogenes/genética , Streptococcus pyogenes/isolamento & purificação , Streptococcus pyogenes/classificação , Streptococcus pyogenes/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/microbiologia , Neoplasias de Cabeça e Pescoço/cirurgia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Estudos Retrospectivos , Sequenciamento Completo do Genoma , Adulto , Polimorfismo de Nucleotídeo Único , Infecção da Ferida Cirúrgica/microbiologia , Infecção da Ferida Cirúrgica/epidemiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Idoso de 80 Anos ou mais , Pessoal de Saúde/estatística & dados numéricos
4.
J Cell Mol Med ; 28(4)2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38363001

RESUMO

Periodontal disease is a risk factor for head and neck squamous cell carcinoma (HNSCC), and Porphyromonas gingivalis, a major periodontal pathogen, has been identified as a specific and potentially independent microbial factor that increases the risk of cancer mortality. Gene expression in HNSCC due to P. gingivalis infection and how changes in gene expression affect the prognosis of HNSCC patients are not clarified. When P. gingivalis was cultured with HNSCC cells, it efficiently adhered to these cells and enhanced their invasive ability. A transcriptome analysis of P. gingivalis -infected HNSCC cells showed that genes related to migration, including CCL20, CITED2, CTGF, C8orf44-SGK3, DUSP10, EGR3, FUZ, HBEGF, IL1B, IL24, JUN, PLAU, PTGS2, P2RY1, SEMA7A, SGK1 and SIX2, were highly up- or down-regulated. The expression of up-regulated genes was examined using the expression data of HNSCC patients obtained from The Cancer Genome Atlas (TCGA) database, and the expression of 5 genes, including PLAU, was found to be higher in cancer tissue than in solid normal tissue. An analysis of protein-protein interactions revealed that these 5 genes formed a dense network. A Cox regression analysis showed that high PLAU expression levels were associated with a poor prognosis in patients with TCGA-HNSCC. Furthermore, the prognostic impact correlated with tumour size and the presence or absence of lymph node metastasis. Collectively, these results suggest the potential of PLAU as a molecular prognostic marker in HNSCC patients. Further in vivo and in vitro studies are needed to verify the findings of this study.


Assuntos
Neoplasias de Cabeça e Pescoço , Proteínas de Membrana , Porphyromonas gingivalis , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Biomarcadores Tumorais/genética , Fosfatases de Especificidade Dupla/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/microbiologia , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Porphyromonas gingivalis/isolamento & purificação , Prognóstico , Proteínas Repressoras/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Transativadores/genética , Proteínas de Membrana/genética
5.
Sci Rep ; 11(1): 23176, 2021 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-34848792

RESUMO

Oral microbiota can alter cancer susceptibility and progression by modulating metabolism and inflammation. We assessed the association between the oral microbiome and lymph node (LN) metastasis in oral squamous cell carcinoma (OSCC). We collected a total of 54 saliva samples from patients with OSCC before surgery. LN metastasis was assessed based on postoperative pathological examination. We used QIIME2, linear discriminant analysis effect size (LEfSe), and PICRUSt2 methods to analyze microbial dysbiosis. A random forest classifier was used to assess whether the oral microbiome could predict LN metastasis. Among the 54 OSCC samples, 20 had LN metastasis, and 34 had no evidence of metastasis. There was a significant difference in ß-diversity between the metastasis and no metastasis groups. Through LEfSe analysis, the metastasis group was enriched in the genera Prevotella, Stomatobaculum, Bifidobacterium, Peptostreptococcaceae, Shuttleworthia and Finegoldia. Pathways related to signal peptidase II were predominant in the no metastasis group. The RF model showed a modestly high accuracy for predicting metastasis. Differences in microbial community composition and functions were observed in the oral microbiome of patients with OSCC with and without LN metastasis. However, the finding that specific taxa may be associated with LN metastasis should be verified in a further prospective study.


Assuntos
Neoplasias de Cabeça e Pescoço/microbiologia , Microbiota , Neoplasias Bucais/microbiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Idoso , Bactérias , Bifidobacterium , Biomarcadores Tumorais , Biologia Computacional , Análise Discriminante , Suscetibilidade a Doenças , Disbiose/microbiologia , Feminino , Humanos , Modelos Lineares , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prevotella , Estudos Prospectivos , RNA Ribossômico 16S/metabolismo
6.
Biochem Biophys Res Commun ; 576: 80-85, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34482027

RESUMO

Epidemiological data have shown that periodontal bacterial infection, periodontitis, and oral squamous cell carcinoma have close relationship on the disease progress and risk. However, the specific role of periodontal microbes and their mechanism in the development of oral squamous cell carcinoma is not yet clear. In our previous work, metagenomic Illumina Mi-seq analysis was used to identify tstructure and abundance of periodontital microbiome. Accoding to the results, we used Porphyromonas.spp. and Fusobacterium.spp. as the periodontitis positive microbiota; Neisseria.spp and Corynebacterium.spp as periodontitis negative microbiota (their average relative abundance were >5%). These representative strains of the above genus were used to infect OSCC cells to explore their effect on tumor cell biology behavior, and detect the expression level of the gene in related to inflammation, migration, invasion and cell cycle. We find that periodontitis positive correlated microbiota had a promoting effect on the development of oral squamous cell carcinoma in vitro by regulating mRNA and protein expression of IL-6, IL-8, MMP-9 and Cyclin-D1. Periodontitis negative correlated microbiota had suppression effect on the development of oral squamous cell carcinoma in vitro analysis.


Assuntos
Neoplasias de Cabeça e Pescoço/microbiologia , Microbiota , Periodontite/microbiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Infecções por Bacteroidaceae/complicações , Infecções por Bacteroidaceae/microbiologia , Infecções por Bacteroidaceae/patologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Corynebacterium/genética , Corynebacterium/isolamento & purificação , Infecções por Fusobacterium/complicações , Infecções por Fusobacterium/microbiologia , Infecções por Fusobacterium/patologia , Fusobacterium nucleatum/genética , Fusobacterium nucleatum/isolamento & purificação , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neisseria sicca/genética , Neisseria sicca/isolamento & purificação , Infecções por Neisseriaceae/complicações , Infecções por Neisseriaceae/microbiologia , Infecções por Neisseriaceae/patologia , Porphyromonas gingivalis/genética , Porphyromonas gingivalis/isolamento & purificação , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
7.
Tohoku J Exp Med ; 253(4): 249-259, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33840648

RESUMO

Bacterial infection contributes to tumor development and malignant progression. Fusobacterium nucleatum (F. nucleatum) is reported to promote oral squamous cell carcinoma. However, molecular bases of F. nucleatum regulating oral cancer cells have not been fully elucidated. We report here that F. nucleatum down-regulates p53 and E-cadherin via the Wnt/NFAT pathway to promote cisplatin-resistance and migration in oral squamous carcinoma cells. We pretreated Cal-27 and HSC-3 cells with F. nucleatum and the survival rates against cysplatin (Cis-diamminedichloroplatinum, CDDP) were significantly higher in treated cells. The expressions of migration and apoptosis-related proteins like E-cadherin and p53 were lower in western blot analysis. We observed that F. nucleatum was an activator of the Wnt/NFAT pathway. The expression levels of the Wnt pathway gene wnt5a and Nuclear factors of activated T cells 3 (NFATc3) were notably higher in treated cells. With the inhibition effect of NFAT-inhibitory peptide VIVIT, the expressions of E-cadherin and p53 in response to F. nucleatum infection were up-regulated reversely. We concluded that F. nucleatum might promote cisplatin-resistance and migration of oral squamous cell carcinoma cells through the Wnt/NFAT pathway.


Assuntos
Movimento Celular , Cisplatino/farmacologia , Fusobacterium nucleatum/fisiologia , Neoplasias de Cabeça e Pescoço/genética , Fatores de Transcrição NFATC/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Regulação para Cima/genética , Proteína Wnt-5a/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Fusobacterium nucleatum/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/microbiologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Fatores de Transcrição NFATC/metabolismo , Oligopeptídeos/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Proteína Wnt-5a/metabolismo
8.
Oral Oncol ; 117: 105305, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33905914

RESUMO

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) has now surpassed cervical cancer as the most common site of HPV-related cancer in the United States. HPV-positive OPSCCs behave differently from HPV-negative tumors and often present with early lymph node involvement. The bacterial microbiome of HPV-associated OPSCC may contribute to carcinogenesis, and certain bacteria may influence the spread of cancer from the primary site to regional lymphatics. OBJECTIVE: To determine the bacterial microbiome in patients with HPV-associated, early tonsil SCC and compare them to benign tonsil specimens. METHOD: The microbiome of primary tumor specimens and lymph nodes was compared to benign tonsillectomy specimens with pan-pathogen microarray (PathoChip). RESULTS: A total of 114 patients were enrolled in the study. Patients with OPSCC had a microbiome that shifted towards more gram-negative. Numerous signatures of bacterial family and species were associated with the primary tumors and lymph nodes of cancer patients, including the urogenital pathogens Proteus mirabilis and Chlamydia trachomatis, Neisseria gonorrhoeae, Shigella dysenteriae, and Orientia tsutsugamushi. CONCLUSION: Our results suggest that detection of urogenital pathogens is associated with lymph node metastasis for patients with HPV-positive OPSCCs. Additional studies are necessary to determine the effects of the OPSCC microbiome on disease progression and clinical outcomes.


Assuntos
Neoplasias de Cabeça e Pescoço , Microbiota , Neoplasias Orofaríngeas , Papillomaviridae , Infecções por Papillomavirus , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias de Cabeça e Pescoço/microbiologia , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Neoplasias Orofaríngeas/microbiologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/microbiologia , Infecções por Papillomavirus/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia
9.
Sci Rep ; 11(1): 7870, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846399

RESUMO

Changes in the oral microbiome, particularly Fusobacterium nucleatum, are associated with oral squamous cell carcinoma (OSCC). F. nucleatum has been reported to modulate local immunity in cancers. We aimed to assess the association between intratumoral F. nucleatum and clinico-pathological features, relapse, and overall survival (OS) in two independent cohorts of patients with OSCC, and to explore the interplay with immune-related genes. We retrospectively analyzed tissue samples from a first cohort of 122 patients with head and neck squamous cell carcinoma, including 61 OSCC (cohort #1), and a second cohort of 90 additional OSCC (cohort #2). We then performed a sensitivity analysis on the merged cohort of OSCC patients (N = 151). F. nucleatum 16S rRNA gene sequences were quantified using real-time quantitative PCR. The presence of gram-negative bacteria and macrophages was confirmed by LPS and CD163 immunostainings, respectively. F. nucleatum positivity was associated with older age, less alcohol and combined alcohol plus tobacco consumption, and less frequent lymph node invasion. There was a trend for a lower recurrence rate in F. nucleatum-positive cases, with less metastatic relapses compared to F. nucleatum-negative tumors, and significantly longer OS, relapse-free and metastasis-free survival. F. nucleatum status was independently associated with OS in multivariate analysis. Immune-related gene and immunohistochemistry analyses showed that gram-negative bacteria load inversely correlated with M2 macrophages. F. nucleatum-associated OSCC has a specific immune microenvironment, is more frequent in older, non-drinking patients, and associated with a favorable prognosis.


Assuntos
Fusobacterium nucleatum/isolamento & purificação , Microbioma Gastrointestinal , Regulação Neoplásica da Expressão Gênica/imunologia , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Microambiente Tumoral , Feminino , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia
10.
Sci Rep ; 11(1): 6229, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737604

RESUMO

It remained inconclusive whether patients with peptic ulcer disease had a higher risk of head and neck cancer (HNC). Therefore, we enrolled 109,360 patients with peptic ulcer disease and matched for age and sex with 218,720 controls from the Taiwan National Health Insurance Research Database between January 1, 1997 and December 31, 2013.The HNC incidence rate was 1.33-fold higher in the peptic ulcer group than in the control group (7.52 vs. 5.68 per 100,00 person-years; crude relative risk: 1.33; 95% confidence interval [CI]: 1.08-1.63) after > 6 years of follow-up. However, in the peptic ulcer subgroup with H. pylori treatment, HNC risk was not significantly different from that of the control group (crude relative risk: 1.12; 95% CI: 0.86-1.46). Moreover, the population with peptic ulcers had the highest risk of laryngeal and hypopharyngeal cancer (adjusted HR: 2.27 [95% CI: 1.16-4.44] and 2.00 [95% CI, 1.13-3.55]), respectively. This observational study suggested that peptic ulcer disease is associated with an increased incidence of laryngeal and hypopharyngeal cancer and H. pylori treatment may have a role in preventing HNC in patients with peptic ulcer disease.


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/patogenicidade , Úlcera Péptica/diagnóstico , Adulto , Idoso , Feminino , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias de Cabeça e Pescoço/microbiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/crescimento & desenvolvimento , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/complicações , Úlcera Péptica/epidemiologia , Úlcera Péptica/microbiologia , Fatores de Risco , Taiwan/epidemiologia
11.
Arch Microbiol ; 203(1): 137-152, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32783067

RESUMO

Advanced combinatorial treatments of surgery, chemotherapy, and radiotherapy do not have any effect on the enhancement of a 5-year survival rate of oral squamous cell carcinoma (OSCC). The discovery of early diagnostic non-invasive biomarkers is required to improve the survival rate of OSCC patients. Recently, it has been reported that oral microbiome has a significant contribution to the development of OSCC. Oral microbiome induces inflammatory response through the production of cytokines and chemokines that enhances tumor cell proliferation and survival. The study aims to develop saliva-based oral microbiome and cytokine biomarker panel that screen OSCC patients based on the level of the microbiome and cytokine differences. We compared the oral microbiome signatures and cytokine level in the saliva of OSCC patients and healthy individuals by 16S rRNA gene sequencing targeting the V3/V4 region using the MiSeq platform and cytokine assay, respectively. The higher abundance of Prevotella melaninogenica, Fusobacterium sp., Veillonella parvula, Porphyromonas endodontalis, Prevotella pallens, Dialister, Streptococcus anginosus, Prevotella nigrescens, Campylobacter ureolyticus, Prevotella nanceiensis, Peptostreptococcus anaerobius and significant elevation of IL-8, IL-6, TNF-α, GM-CSF, and IFN-γ in the saliva of patients having OSCC. Oncobacteria such as S. anginosus, V. parvula, P. endodontalis, and P. anaerobius may contribute to the development of OSCC by increasing inflammation via increased expression of inflammatory cytokines such as IL-6, IL-8, TNF-α, IFN-γ, and GM-CSF. These oncobacteria and cytokines panels could potentially be used as a non-invasive biomarker in clinical practice for more efficient screening and early detection of OSCC patients.


Assuntos
Fenômenos Fisiológicos Bacterianos/imunologia , Citocinas/genética , Disbiose/complicações , Neoplasias de Cabeça e Pescoço/microbiologia , Neoplasias Bucais/microbiologia , Saliva/microbiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/imunologia , Citocinas/imunologia , Disbiose/imunologia , Disbiose/microbiologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/imunologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Inflamação/microbiologia , Masculino , Microbiota/imunologia , Pessoa de Meia-Idade , Neoplasias Bucais/imunologia , Neoplasias Bucais/patologia , RNA Ribossômico 16S/genética , Saliva/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia
13.
Sci Rep ; 10(1): 16582, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024215

RESUMO

Squamous cell carcinoma is the most common type of throat cancer. Treatment options comprise surgery, radiotherapy, and/or chemo(immuno)therapy. The salivary microbiome is shaped by the disease, and likely by the treatment, resulting in side effects caused by chemoradiation that severely impair patients' well-being. High-throughput amplicon sequencing of the 16S rRNA gene provides an opportunity to investigate changes in the salivary microbiome in health and disease. In this preliminary study, we investigated alterations in the bacterial, fungal, and archaeal components of the salivary microbiome between healthy subjects and patients with head and neck squamous cell carcinoma before and close to the end point of chemoradiation ("after"). We enrolled 31 patients and 11 healthy controls, with 11 patients providing samples both before and after chemoradiation. Analysis revealed an effect on the bacterial and fungal microbiome, with a partial antagonistic reaction but no effects on the archaeal microbial community. Specifically, we observed an individual increase in Candida signatures following chemoradiation, whereas the overall diversity of the microbial and fungal signatures decreased significantly after therapy. Thus, our study indicates that the patient microbiome reacts individually to chemoradiation but has potential for future optimization of disease diagnostics and personalized treatments.


Assuntos
Quimiorradioterapia , Neoplasias de Cabeça e Pescoço/microbiologia , Neoplasias de Cabeça e Pescoço/terapia , Microbiota/efeitos dos fármacos , Microbiota/efeitos da radiação , Saliva/microbiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adulto , Idoso , Candida/genética , Candida/isolamento & purificação , Feminino , Voluntários Saudáveis , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Microbiota/genética , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética
14.
Sci Rep ; 10(1): 15010, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929151

RESUMO

Exhaled breath compounds can non-invasively detect head and neck squamous cell carcinoma (HNSCC). Here we investigated exhaled compounds related to intestinal bacterial carbohydrate fermentation. Fasting breath samples were collected into 3 litre FlexFoil PLUS bags from patients awaiting a biopsy procedure for suspected HNSCC. Samples were analysed using a Syft selected ion flow-tube mass spectrometer and a Quintron BreathTracker. Two tailed non-parametric significance testing was conducted with corrections for multiple imputations. 74 patients were diagnosed (histological) with HNSCC and 61 patients were benign (controls). The methane to hydrogen ratio was significantly different between cancer and non-cancer controls (p = 0.0440). This ratio increased with tumour stage with a significant difference between T1 and T4 tumours (p = 0.0259). Hydrogen levels were significantly higher in controls who were smokers (p = 0.0129), with no smoking dependent methane changes. There were no differences in short chain fatty acids between groups. Exhaled compounds of intestinal carbohydrate fermentation can detect HNSCC patients. These findings suggest a modified carbohydrate fermentation profile in HNSCC patients that is tumour stage and smoking status dependent.


Assuntos
Disbiose/diagnóstico , Neoplasias de Cabeça e Pescoço/microbiologia , Hidrogênio/análise , Metano/análise , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Testes Respiratórios/métodos , Metabolismo dos Carboidratos , Estudos de Casos e Controles , Jejum , Ácidos Graxos Voláteis/análise , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
15.
Cancer ; 126(23): 5124-5136, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32888342

RESUMO

BACKGROUND: Oral mucositis (OM) is a debilitating sequela for patients treated for squamous cell carcinoma of the head and neck (HNSCC). This study investigated whether oral microbial features before treatment or during treatment are associated with the time to onset of severe OM in patients with HNSCC. METHODS: This was a cohort study of newly diagnosed patients with locoregional HNSCC who received chemotherapy with or without radiotherapy from April 2016 to September 2017. OM was based on the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. The oral microbiome was characterized on the basis of the 16S ribosomal RNA V4 region with the Illumina platform. A mixture cure model was used to generate hazard ratios for the onset of severe OM. RESULTS: Eighty-six percent of the patients developed OM (n = 57 [33 nonsevere cases and 24 severe cases]) with a median time to onset of OM of 21 days. With adjustments for age, sex, and smoking status, genera abundance was associated with the hazard for the onset of severe OM as follows: 1) at the baseline (n = 66), Cardiobacterium (P = .03) and Granulicatella (P = .04); 2) immediately before the development of OM (n = 57), Prevotella (P = .03), Fusobacterium (P = .03), and Streptococcus (P = .01); and 3) immediately before the development of severe OM (n = 24), Megasphaera (P = .0001) and Cardiobacterium (P = .03). There were no differences in α-diversity between the baseline samples and Human Microbiome Project data. CONCLUSIONS: Changes in the abundance of genera over the course of treatment were associated with the onset of severe OM. The mechanism and therapeutic implications of these findings need to be investigated in future studies.


Assuntos
Neoplasias de Cabeça e Pescoço/terapia , Microbiota , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Estomatite/etiologia , Idoso , Feminino , Neoplasias de Cabeça e Pescoço/microbiologia , Humanos , Masculino , Microbiota/efeitos dos fármacos , Microbiota/efeitos da radiação , Pessoa de Meia-Idade , RNA Ribossômico 16S , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Estomatite/microbiologia , Fatores de Tempo
16.
Sci Rep ; 10(1): 13201, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32764634

RESUMO

Xerostomia detrimentally affects the oral health of many head and neck cancer patients who undergo radiotherapy. Its sequelae become an ongoing burden for patients that often manifest as periodontal disease and dental decay. Bacteria play a major role in the pathogenesis of these conditions and here we explore the use of an oral probiotic to beneficially modulate the oral bacterial community post-radiotherapy. In this pilot study, a four-week intervention with oral probiotic lozenges containing Streptococcus salivarius M18 was trialled in seven patients. Post-intervention changes in oral health and in the composition of the plaque and saliva bacterial communities were compared with six patients in a placebo group. An improvement in periodontal screening and plaque index scores was observed in both groups after the intervention period. The oral probiotic lozenges did not significantly impact bacterial community composition or diversity, nor did the probiotic lozenges increase the relative sequence abundance of ZOTU_1 (the probiotic-associated sequence assigned to S. salivarius) detected in the samples. Network analyses suggest negative interactions occurred between ZOTU_1 and species from the periopathogenic genera Campylobacter, Fretibacterium, Selenomonas and Treponema but further investigation is required to more fully understand the beneficial properties of this oral probiotic.


Assuntos
Neoplasias de Cabeça e Pescoço/microbiologia , Neoplasias de Cabeça e Pescoço/radioterapia , Probióticos/farmacologia , Streptococcus salivarius/fisiologia , Administração Oral , Biodiversidade , Estudos de Coortes , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Probióticos/administração & dosagem
17.
Cancer Prev Res (Phila) ; 13(5): 463-474, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32071121

RESUMO

While smoking is inextricably linked to oral/head and neck cancer (HNSCC), only a small fraction of smokers develop HNSCC. Thus, we have sought to identify other factors, which may influence the development of HNSCC in smokers including microbiology. To determine microbial associations with HNSCC among tobacco users, we characterized oral microbiome composition in smokers with and without HNSCC. 16S rRNA MiSeq sequencing was used to examine the oral mucosa microbiome of 27 smokers with (cases) and 24 without HNSCC (controls). In addition, we correlated previously reported levels of DNA damage with the microbiome data. Smokers with HNSCC showed lower microbiome richness compared with controls (q = 0.012). Beta-diversity analyses, assessed as UniFrac (weighted and unweighted) and Bray-Curtis distances, showed significant differences in oral mucosal microbiome signatures between cases and controls (r 2 = 0.03; P = 0.03) and higher interindividual microbiome heterogeneity in the former (q ≤ 0.01). Higher relative abundance of Stenotrophomonas and Comamonadaceae and predicted bacterial pathways mainly involved in xenobiotic and amine degradation were found in cases compared with controls. The latter, in contrast, exhibited higher abundance of common oral commensals and predicted sugar degradation pathways. Finally, levels of DNA damage in the oral cavity were correlated with the microbiome profiles above. Oral microbiome traits differ in smokers with and without HNSCC, potentially informing the risk of eventual HNSCC and shedding light into possible microbially mediated mechanisms of disease. These findings present data that may be useful in screening efforts for HNSCC among smokers who are unable to quit.


Assuntos
Bactérias/classificação , Neoplasias de Cabeça e Pescoço/microbiologia , Mucosa Bucal/microbiologia , Fumantes/estatística & dados numéricos , Fumar/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Bactérias/genética , Bactérias/isolamento & purificação , Estudos de Casos e Controles , DNA Bacteriano/análise , DNA Bacteriano/genética , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
18.
Arch Oral Biol ; 112: 104669, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32028171

RESUMO

AIMS: This systematic review aimed to analyse: a) the presence and the abundance of Fusobacterium; b) the Fusobacterium species most often found, and c) the most common methods used for their identification in oral/head and neck cancer samples. DESIGN: A protocol was registered on PROSPERO database. This review was conducted following PRISMA guidelines. Literature search was performed on five electronic biomedical databases, namely Pubmed, Scopus, Web of Science, Embase, and Cochrane from their start dates to 30 August 2018. Two reviewers independently assessed the eligibility for inclusion; extracted the data; and evaluated the risk of bias. RESULTS: From 118 unique abstract records, 88 full-text articles were assessed for eligibility. According to inclusion and exclusion criteria, 17 publications were included in this review. Meta-analysis showed an increased prevalence of 6 % (95 % CI, 3-9) of Fusobacterium in tumour lesions than in non-tumour lesions (Fusobacterium prevalence of 16 % in tumour lesions and of 10 % in non-tumour lesions), and a 2.93 higher chance of Fusobacterium being present in tumour lesions (95 % CI, 1.47-5.81). The most common detection methods were based on molecular evidence (64.70 %) (95 % CI, 37.7-84.7). F. nucleatum was the most prevalent species (47.06 %) (95 % CI, 23.5-72). CONCLUSION: In conclusion, Fusobacterium is present and in higher abundance in oral/head and neck cancer samples when compared to non-cancer samples, suggesting that Fusobacterium may contribute to oral/head and neck cancer development.


Assuntos
Fusobacterium/isolamento & purificação , Neoplasias de Cabeça e Pescoço/microbiologia , Humanos
19.
Eur Ann Otorhinolaryngol Head Neck Dis ; 137(1): 69-71, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31186167

RESUMO

INTRODUCTION: Beside HPV infection, there is currently no evidence of association between head and neck squamous cell carcinomas and microbial infections. We report the case of a cervical squamous cell carcinoma by Mycoplasma hominis. CASE SUMMARY: A 20-year-old woman, consulted for a swelling on the left cervical side. Clinical examination found a large fixed mass. Biological tests found no evidence of infection. Biopsies of the cervical lesion diagnosed an HPV negative squamous cell carcinoma. Microbiological tests of 16sRNA identification showed the presence of Mycoplasma hominis in the 3 specimens. The patient was treated by induction chemotherapy associated to antibiotherapy, followed by chemo-radiotherapy. DISCUSSION: The present case suggests that oropharyngeal infection by Mycoplasma hominis might be more frequent than expected, that 16sRNA is an efficient technique to isolate this pathogen and finally that further studies are required to document its potential oncogenic role in head and neck squamous cell carcinomas.


Assuntos
Neoplasias de Cabeça e Pescoço/microbiologia , Infecções por Mycoplasma/complicações , Mycoplasma hominis/isolamento & purificação , Neoplasias Primárias Desconhecidas/microbiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Feminino , Humanos , Adulto Jovem
20.
Int J Cancer ; 147(3): 856-865, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31808149

RESUMO

While reductions in breast cancer mortality have been evident since the introduction of population-based breast screening in women aged 50-74 years, participation in cancer screening programs can be influenced by several factors, including health system and those related to the individual. In our study, we compared cancer incidence and mortality for several cancer types other than breast cancer, noncancer mortality and patterns of treatment amongst women who did and did not participate in mammography screening. All women aged 50-65 years enrolled on the Queensland Electoral Roll in 2000 were included. The study population was then linked to records from the population-based breast screening program and private fee-for-service screening options to establish screened and unscreened cohorts. Diagnostic details for selected cancers and cause of death were obtained from the Queensland Oncology Repository. We calculated incidence rate ratios and hazard ratios comparing screened and unscreened cohorts. Among screened compared to unscreened women, we found a lower incidence of cancers of the lung, cervix, head and neck and esophagus and an increase in colorectal cancers. Cancer mortality (excluding breast cancer) was 35% lower among screened compared to unscreened women and they were also about 23% less likely to be diagnosed with distant disease. Screened compared to unscreened women were more likely to receive surgery and less likely to receive no treatment. Our study adds further to the population data examining outcomes among women participating in mammography screening.


Assuntos
Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer/estatística & dados numéricos , Neoplasias Esofágicas/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias Pulmonares/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/mortalidade , Neoplasias Colorretais/mortalidade , Detecção Precoce de Câncer/economia , Neoplasias Esofágicas/microbiologia , Planos de Pagamento por Serviço Prestado , Feminino , Neoplasias de Cabeça e Pescoço/microbiologia , Humanos , Incidência , Neoplasias Pulmonares/mortalidade , Programas de Rastreamento/economia , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Mortalidade/tendências , Modelos de Riscos Proporcionais , Queensland/epidemiologia , Neoplasias do Colo do Útero/mortalidade
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