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Introduction
Welcome to Head & Neck Oncobiome Group (Salem lab), at the University of Helsinki, Finland.
In our lab, we explore the intricate mechanisms of head and neck carcinogenesis, focusing on the dynamic interplay between tumor cells and oral microbiota. Our research bridges the fields of oncology, microbiology, immunology within dental science, fostering interdisciplinary collaboration, which is essential for comprehensive approaches to complex diseases such as head and neck cancers.
Publications
Publications (61)
Human β-defensin 2 (hBD-2) is a potent antimicrobial peptide that participates in defense against invading bacteria. We recently showed that bacterial components and histamine, through histamine H4 receptor (H4R), are involved in the pathogenesis of the potentially malignant lesion, oral lichen planus (OLP). However, the underlying mechanisms remai...
Head and neck squamous cell carcinoma (HNSCC) is a group of tumours which exhibit low 5 year survival rates. Thus, there is an urgent need to identify biomarkers that may improve the clinical utility of patients with HNSCC. Emerging studies support a role of toll-like receptors (TLRs) in carcinogenesis. Therefore, this systematic review and meta-an...
Lymphatic metastasis represents the main route of tumour cell dissemination in oral squamous cell carcinoma (OSCC). Yet, there are no FDA-approved therapeutics targeting cancer-related lymphangiogenesis to date. The lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE-1), a specific lymphatic marker, is associated with poor survival in OSC...
Tissue vasculature provides the main conduit for metastasis in solid tumours including head and neck squamous cell carcinoma (HNSCC). Vascular mimicry (VM) is an endothelial cell (EC)-independent neovascularization pattern, whereby tumour cells generate a perfusable vessel-like meshwork. Yet, despite its promising clinical utility, there are limite...
Aggregatibacter actinomycetemcomitans is an opportunistic Gram-negative periodontopathogen strongly associated with periodontitis and infective endocarditis. Recent evidence suggests that periodontopathogens can influence the initiation and progression of oral squamous cell carcinoma (OSCC). Herein we aimed to investigate the effect of A. actinomyc...
Oral bacteria naturally secrete extracellular vesicles (EVs), which have attracted attention for their promising biomedical applications including cancer therapeutics. However, our understanding of EV impact on tumor progression is hampered by limited in vivo models. In this study, we propose a facile in vivo platform for assessing the effect of EV...
Background/aim:
Oral squamous cell carcinoma (OSCC) is characterized by early metastasis, clinical resistance and poor prognosis. Recently, we showed that aggressive OSCC cells co-express endothelial cell markers and can form tube-like structures, known as vasculogenic mimicry (VM), a process associated with poor prognosis in head and neck cancers...
Head and neck squamous cell carcinoma (HNSCC) represents frequent yet aggressive tumours that encompass complex ecosystems of stromal and neoplastic components including a dynamic population of cancer stem cells (CSCs). Recently, research in the field of CSCs has gained increased momentum owing in part to their role in tumourigenicity, metastasis,...
Head and neck squamous cell carcinoma (HNSCC) comprises the majority of tumors in head and neck tissues. The prognosis of HNSCC has not significantly improved for decades, signifying the need for new diagnostic and therapeutic targets. Recent evidence suggests that oral microbiota is associated with carcinogenesis. Thus, we conducted a comprehensiv...
This special issue of Frontiers in Oral Health sheds light on recent research regarding the tumor-related angiogenesis in oral cancer, including the present challenges of anticancer therapy targeting angiogenesis. Indeed, angiogenesis is a hallmark of solid tumors and it has important prognostic and therapeutic implications in cancer patients. This...
Lymphangiogenesis is a key process in cancer development and metastasis. The lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) is a widely used marker for lymphatic endothelial cells (LEC), which also mediates immune and cancer cell migration. Recently, LYVE-1+ve tumor cells were shown to acquire LEC-like phenotype and exploit this recept...
Fascin 1 plays important pro-metastatic roles in head and neck carcinoma (HNSCC) migration, invasion, and metastasis. However, limited advancement in targeting metastasis remains a major obstacle in improving HNSCC patients’ survival. Therefore, we assessed the therapeutic potential of fascin 1 targeted inhibition and its potential prognostic value...
Oral tongue squamous cell carcinoma (OTSCC) is one of the most common cancers worldwide and is characterized by early metastasis and poor prognosis. Recently, we reported that extracellular interleukin‐17F (IL‐17F) correlates with better disease‐specific survival in OTSCC patients and has promising anticancer effects in vitro. Vasculogenic mimicry...
Head and neck squamous cell carcinoma (HNSCC) is a group of common cancers characterized by a swift growth pattern, early metastasis, and dismal 5-year survival rates. Despite the recent advances in cancer management, the multimodality approach is not effective in eradicating HNSCC. Moreover, the clinical response to the antiangiogenic therapy rema...
Lymphatic metastasis represents the main route of tumour cell dissemination in oral squamous cell carcinoma (OSCC). Yet, there are no FDA-approved therapeutics targeting cancer-related lymphangiogenesis to date. The lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE-1), a specific lymphatic marker, is associated with poor survival in OSC...
The cyclooxygenase-2 (COX-2) is a potent enzyme that converts arachidonic acid to prostaglandins (PG), including PGE2, a key mediator of inflammation and angiogenesis. Importantly, COX-2 is activated in response to inflammatory stimuli, where it is also believed to promote the development and progression of head and neck cancers (HNC). COX-2 can me...
Oral squamous cell carcinoma (OSCC), the most common oral malignancy, shows an increasing rate of incidence worldwide. In spite of the recent advances in cancer research, OSCC therapy continues to have unfavourable outcomes, and thus patient’s prognosis remains relatively poor. Current research has been devoted to identifying novel therapeutic targ...
Vasculogenic mimicry (VM) is an intratumoral microcirculation pattern formed by aggressive cancer cells, which mediates tumor growth. In this study, we compiled the evidence from studies evaluating whether positive VM status can serve as a prognostic factor to patients with squamous cell carcinoma of the head and neck (HNSCC) or esophagus (ESCC). C...
ABSTRACT
Objective: An association between hypothyroidism (HT) and oral lichen planus (OLP) has been
reported. However, the mechanisms that could explain this association remain unresolved. This study
aimed to evaluate the expression of thyroid-stimulating hormone (TSH) and thyroid-stimulating hormone receptor (TSHR) in healthy oral mucosa and in O...
Background
We reported in recent publication that bacterial lipopolysaccharides (LPS) and mast cells are involved in the pathogenesis of the premalignant lesion, oral lichen planus (OLP). However, the mechanisms beyond such effect remain unknown. We therefore investigated the role of the antimicrobial peptide response, via human β-defensin 2 (hBD-2...
Tongue squamous cell carcinoma (TSCC) has a poor prognosis due to its early metastasis via blood and lymphatic vessels. We performed a systematic review to investigate the prognostic significance of blood microvessel density (MVD) and lymphatic vessel density (LVD) in TSCC patients. We conducted a systematic search in Ovid Medline, Scopus, and Coch...
Tongue squamous cell carcinoma (TSCC) has a poor prognosis due to its early metastasis via blood and lymphatic vessels. We performed a systematic review to investigate the prognostic significance of blood microvessel density (MVD) and lymphatic vessel density (LVD) in TSCC patients. We conducted a systematic search in Ovid Medline, Scopus, and Coch...
Background:
Currently, in vivo model for personalised cancer drug testing is challenging. A zebrafish larvae xenograft model has been applied in recent years to cancer research, particularly for drug testing purposes, showing promising results in drug testing against patient-derived tumour xenografts. Currently, these xenograft models apply imagin...
Objectives
An association between hypothyroidism (HT) and oral lichen planus (OLP) has been reported. However, the mechanisms that could explain this association have not been clarified. This study aimed to evaluate the immunohistochemical expression of thyroid-stimulating hormone (TSH) and thyroid-stimulating hormone receptor (TSHR) in healthy ora...
We recently showed that extracellular interleukin-17F (IL-17F) correlates with better disease-specific survival in oral tongue squamous cell carcinoma (OTSCC) patients. However, the underlying mechanisms of such effect remain obscure. Here, we used qRT-PCR to assess the expression of IL-17F and its receptors (IL-17RA and IL-17RC) in two OTSCC cell...
Background
Oral tongue squamous cell carcinoma (SCC) is characterized by early metastasis and poor prognosis. Interleukin‐17F (IL‐17F) plays a protective role in many tumors. However, IL‐17F expression in oral tongue SCC tissue has not been investigated.
Methods
Immunostaining of 83 oral tongue SCC specimens and blinded‐scoring were used to map IL...
High mobility group box 1 (HMGB1) is an extremely conserved DNA‐binding protein that stabilizes nucleosomes and facilitates gene transcription in mammalian cells. When released extracellularly, HMGB1 becomes an alarmin that can mediate systemic diseases. High mobility group box 1 signals via two main receptors: receptor for advanced glycation end‐p...
Background: Recent reports indicated that histamine and its novel, high-affinity histamine H4 receptor (H4R) play a crucial role in carcinogenesis, and thus H4R signalling has become a focus of Increasing interest in the pathogenesis of many cancers. However, the roles of H4R in oral epithelial dysplasia (OED) and oral tongue squamous cell carcinom...
Objective:
Evidence of increased apoptosis is observed in periodontitis, and may be associated with destruction of the periodontal tissue caused by the increased cell death, with the release of danger signals and subsequent stimulation of the proinflammatory processes. However, the exact mechanisms associated with these processes remain unclear. T...
Purpose:
Recent reports indicate that histamine and its novel, high-affinity histamine H4 receptor (H4R) play a role in carcinogenesis, and thus H4R signalling has become a focus of increasing interest in the pathogenesis of many cancers. The roles of H4R in oral epithelial dysplasia (OED) and oral tongue squamous cell carcinoma (OTSCC) are unknow...
The crosstalk between immune cells, cancer cells, and extracellular vesicles (EVs) secreted by cancer cells remains poorly understood. We created three-dimensional (3D) cell culture models using human leiomyoma discs and Myogel to study the effects of immune cells on highly (HSC-3) and less (SCC-25) invasive oral tongue squamous cell carcinoma (OTS...
Background and purpose — Although the pathogenesis of osteoarthritis (OA) is not well understood, chondrocyte-mediated inflammatory responses (triggered by the activation of innate immune receptors by damage-associated molecules) are thought to be involved. We examined the relationship between Toll-like receptors (TLRs) and OA in cartilage from 2 j...
Oral lichenoid reactions (OLRs) are chronic inflammatory lesions induced by contact with allergens. Toll-like receptors (TLRs) are members of pattern-recognition receptor superfamily. Once activated, TLRs induce production of cytokines and chemokines, thus leading to inflammatory reaction in host tissue. In the present study, we aimed to investigat...
Background:
Recent reports have indicated that nonimmune cells can produce low concentrations of histamine. This observation, together with the discovery of the high-affinity histamine H4receptor (H4R), has added additional layers of complexity to our understanding of histamine signalling. Human oral keratinocytes (HOKs) possess a uniform H4R patt...
Background: Toll-like receptors (TLRs) are members of pattern-recognition receptors superfamily that recognize both pathogen-associated molecular patterns and damage-associated molecular patterns. Once activated, they lead to cytokines and chemokines production and thus inducing inflammatory responses in host tissue. Oral lichenoid reactions (OLRs)...
Objectives: Evidence of apoptosis is increased in periodontitis and associates with destruction of the periodontal tissue. However, the specific effects regarding these proinflammatory processes remain unclear. The idea was to study the apoptosis in periodontal tissue and its possible role in amplification of the inflammatory process, which could f...
Background: Oral lichen planus is an autoimmune disease affecting oral mucosa. Even though IL-17A is elevated in the oral mucosa and serum of the OLP patients comparing with healthy controls, its sources and regulation are not yet known. Objectives: Due to some pilot experiments, the working hypothesis is that non-Th17 cells, not Th17 cells as was...
Colorectal cancer (CRC) is one of the most common cancers in both genders. Even though interleukin (IL)-17A was shown to play an important role in intestinal tumourigenesis and CRC, other IL-17 family members were not studied well. We therefore studied the expression of IL-17 cytokine family members in CRC. Ten healthy colons and ten CRC mucosa wer...
A recurrent aphthous ulcer (RAU) is a common inflammatory ulcerative lesion affecting oral mucosa. We studied the eventual apoptosis of epithelial cells from the point of view of ulcer and inflammation. RAU lesions and healthy mucosa samples were immunostained for caspase-3 and high-mobility group box 1 (HMGB1). DNA nicks were identified using TUNE...
Apoptosis is involved in the pathogenesis of Sjögren's syndrome (SS), an autoimmune disease affecting exocrine glands. Our recent studies revealed diminished histamine H4 receptor (H4R) expression and impaired histamine transport in the salivary gland epithelial cells in SS. The aim was now to test if nanomolar histamine and high-affinity H4R signa...
Objectives
Oral lichen planus (OLP) is an autoimmune disease characterized by a band-like T-cell infiltrate below apoptotic epithelial cells and degenerated basement membrane. We tested the hypothesis that the high-affinity histamine H4 receptors (H4Rs) are downregulated in OLP by high histamine concentrations and proinflammatory T-cell cytokines.M...
Objectives
It was hypothesized that beta 2 defensin (BD-2) is increased in RAU lesions compared with healthy controls to promote anti-microbial host defence.MethodsRAU and control mucosa samples were subjected to quantitative real-time PCR and immunostained for BD-2, CD68, mast cell tryptase and 4-hydroxynonenal (4HNE). The effect of tumour necrosi...
Objectives: Oral lichen planus (OLP) is an autoimmune disease characterized by a band-like T-cell infiltrate below apoptotic epithelial cells and impaired basement membrane. Here, we tested the hypothesis that the maintenance of the healthy epithelium by non-professional histamine producing cells and high-affinity histamine H4 receptors (H4Rs) is d...
The generation of wear debris is an inevitable result of normal usage of joint replacements. Wear debris particles stimulate local and systemic biological reactions resulting in chronic inflammation, periprosthetic bone destruction, and eventually, implant loosening, and revision surgery. The latter may be indicated in up to 15% patients in the dec...
Recurrent aphthous ulcer (RAU) is an ulcerative disease of non-keratinized oral mucosa. Colon and bronchial epithelial cells produce interleukin-17C (IL-17C) upon stimulation of Toll-like receptor 2 (TLR2), TLR3 and TLR5, which are highly expressed in epithelial cells in RAU lesions. We therefore investigated the eventual presence and function of I...
Objective:
Cartilage degeneration in osteoarthritis (OA) leads to release of potential danger signals. The aim of our study was to profile OA cartilage for the Toll-like receptor (TLR) danger signal receptors.
Methods:
Osteochondral cylinders from total knee replacements were graded using OA Research Society International score and stained for p...