The involvement of epidermal growth factor receptor/protein kinase B signaling in the tumor intrinsic PD-L1-induced malignant potential of oral squamous cell carcinoma.

Background: Various antigen-presenting cells and tumor cells-expressing PD-L1 inhibits antitumor immune responses in the tumor microenvironment. Recently, numerous studies have shown that tumor cell intrinsic PD-L1 also plays important roles in tumor growth and progression. On the other hand, oral squamous cell carcinoma (OSCC) cells overexpress epidermal growth factor receptor (EGFR) and EGFR signal pathway exacerbates tumor progression.

Detection of Merkel cell polyomavirus in multiple primary oral squamous cell carcinomas.

Oral microbiome studies have mainly focussed on bacteria, with the relationship between viruses and oral cancers remaining poorly understood. Oral cancers can develop even in the absence of any history of daily smoking or drinking. Oral cancer patients frequently have multiple primary cancers in the oral cavity and other organs, such as the upper gastrointestinal tract.

Gene therapy with SOCS1 induces potent preclinical antitumor activities in oral squamous cell carcinoma.

Background: Constitutive activation of STAT3 promotes oncogenesis and growth of oral squamous cell carcinoma (OSCC). We investigated the mechanism of action of suppressor of cytokine signaling 1 (SOCS1), an endogenous inhibitor of JAK, as gene therapy for OSCC.

Methods: Antitumor effect of SOCS1 was compared to JAK inhibitor I by cell proliferation assay, cell cycle analysis, and apoptosis analysis in vitro.

Epidermal growth factor/epidermal growth factor receptor signaling blockage inhibits tumor cell-derived exosome uptake by oral squamous cell carcinoma through macropinocytosis.

Various cell types secrete exosomes into their surrounding extracellular space, which consequently affect the function and activity of recipient cells. Numerous studies have showed that tumor cell-derived exosomes play important roles in tumor growth and progression. Although a variety of endocytic pathways are reportedly involved in the cellular uptake of exosomes, detailed mechanisms remain unknown.

Vertebral fracture and splenomegaly in a head and neck cancer producing granulocyte colony-stimulating factor: A case report of systemic complications associated with a cytokine-producing solid tumor.

Granulocyte colony-stimulating factor (G-CSF)-producing tumors are rare and are associated with a poor prognosis when they occur in the lungs and the head and neck region. Positron emission tomography/computed tomography has been reported to show systemic specific accumulation of fluorodeoxyglucose in these cases, but the systemic complications associated with the cytokines produced are not well known. We herein present the case of a G-CSF-producing maxillary sinus squamous cell carcinoma in a 73-year-old Japanese woman with a vertebral fracture and splenomegaly.

Current Trends and Future Prospects of Molecular Targeted Therapy in Head and Neck Squamous Cell Carcinoma.

In recent years, advances in drug therapy for head and neck squamous cell carcinoma (HNSCC) have progressed rapidly. In addition to cytotoxic anti-cancer agents such as platinum-based drug (cisplatin and carboplatin) and taxane-based drugs (docetaxel and paclitaxel), epidermal growth factor receptor-tyrosine kinase inhibitors (cetuximab) and immune checkpoint inhibitors such as anti-programmed cell death-1 (PD-1) antibodies (nivolumab and pembrolizumab) have come to be used. The importance of anti-cancer drug therapy is increasing year by year.

Macrophage‑derived exosomes attenuate the susceptibility of oral squamous cell carcinoma cells to chemotherapeutic drugs through the AKT/GSK‑3β pathway.

Although chemotherapy is initially effective in debulking tumor mass in a number of different types of malignancy, tumor cells gradually acquire chemoresistance and frequently progress to advanced clinical stage. Accumulating evidence has indicated that the tumor sensitivity to several chemotherapeutic drugs is regulated by tumor stromal cells including macrophages. However, the role of macrophages in the efficacy of chemotherapeutics on oral squamous cell carcinoma (OSCC) cells is poorly understood.

Characterization of two newly isolated Staphylococcus aureus bacteriophages from Japan belonging to the genus Silviavirus.

Two Staphylococcus aureus bacteriophages, KSAP7 and KSAP11, were isolated from sewage and characterized. Based on morphology and DNA sequences, they were assigned to the genus Silviavirus, subfamily Twortvirinae, family Herelleviridae, whose members are hypothesized to be suitable for bacteriophage therapy. The KSAP7 and KSAP11 genomes were 137,950 and 138,307 bp in size, respectively.

Metal nanoparticles-induced activation of NLRP3 inflammasome in human oral keratinocytes is a possible mechanism of oral lichenoid lesions.

The NLRP3 inflammasome has been implicated in the pathogenesis of various inflammatory diseases and is activated by particulate stimulants. Oral epithelial keratinocytes are frequently exposed to metal nanoparticles. In this study, we examined the effects of gold, silver, and palladium nanoparticles, which are frequently used for dental metal alloys on cell proliferation, cytotoxicity, autophagy, lysosomal functions, and NLRP3 inflammasome activation using the immortalized human oral keratinocyte cell line RT-7.

Ephrin-B2 reverse signaling regulates progression and lymph node metastasis of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and neck and frequently metastasizes to cervical lymph nodes. Aggressive local invasion and metastasis of OSCC are significant factors for poor prognosis. In this study, we investigated whether ephrin-B2 expressed in OSCC contributed to tumor progression and lymph node metastasis.

Application of a Persistent Heparin Treatment Inhibits the Malignant Potential of Oral Squamous Carcinoma Cells Induced by Tumor Cell-Derived Exosomes.

Exosomes are 30-100 nm-sized membranous vesicles, secreted from a variety of cell types into their surrounding extracellular space. Various exosome components including lipids, proteins, and nucleic acids are transferred to recipient cells and affect their function and activity. Numerous studies have showed that tumor cell-derived exosomes play important roles in tumor growth and progression.

Complete remission of Merkel cell carcinoma on the upper lip treated with radiation monotherapy and a literature review of Japanese cases.

Merkel cell carcinoma is a rare and aggressive neuroendocrine-derived skin cancer arising most commonly on the sun-exposed head and neck skin of elderly and immunocompromised patients. Although a combination of wide excision and adjuvant radiotherapy is the optimal therapeutic approach for Merkel cell carcinoma, radiation monotherapy has recently been recommended for unresectable tumors. We report here a case of Merkel cell carcinoma treated with radiation monotherapy and reviewed Merkel cell carcinoma cases treated with radiotherapy alone in Japan.

SPARC is associated with carcinogenesis of oral squamous epithelium and consistent with cell competition.

The matricellular protein, secreted protein acidic and rich in cysteine (SPARC) is thought to be involved in cell competition. The objective of this study is to investigate the role of SPARC in cancerization of oral squamous epithelium. Clinical specimens from 57 pre- and early cancerous lesion, 66 invasive squamous cell carcinoma (SCC) and controls were immunostained with SPARC.

Mucinous Cystadenoma in the Upper Lip: Report of Two Cases.

Mucinous cystadenoma of the salivary gland is a very rare disease, and only a few cases have been reported. We report here 2 cases of mucinous cystadenoma in the upper lip. The first case was a 57-year-old man and the second was a 42-year-old woman.

TCDD disrupts posterior palatogenesis and causes cleft palate.

Dioxins (e.g. 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD) cause cleft palate at a high rate.

Low-grade myofibroblastic sarcoma of the palate.

Low-grade myofibroblastic sarcoma (LGMS) is a rare, malignant tumor with myofibroblastic differentiation. Despite it being classified as a distinct entity by the World Health Organization, a few cases were reported in the oral and maxillofacial region. Here, a LGMS developed on the palate of a 73-year-old man who presented with a 1-cm tumor on the posterior border of the palate.

Correlation of metabolism/hypoxia markers and fluorodeoxyglucose uptake in oral squamous cell carcinomas.

Objective: The objective of this study was to analyze the relationship between the uptake of (18)F-2-fluoro-2-deoxy-d-glucose (FDG) by positron emission tomography-computerized tomography (PET-CT) and glucose metabolism/hypoxia markers in oral squamous cell carcinoma (OSCC).

Study Design: Thirty-six patients with OSCC (tongue [n = 23], buccal mucosa [n = 7], and floor of the mouth [n = 6]) were assessed and underwent incisional biopsy and subsequently received FDG-PET-CT. Expressions of hypoxia-inducible factor 1α (HIF-1α), glucose transporter protein 1 (GLUT-1), hexokinase-II (HK-II), and glucose-6-phosphatase (G6Pase) were immunohistochemically quantified, and FDG uptake was evaluated by the maximum standardized uptake values (SUV(max)) at the primary tumor site.

Enhanced expression of Toll-like receptor 2 in lesional tissues and peripheral blood monocytes of patients with oral lichen planus.

Some members of the Toll-like receptor (TLR) family, which plays key roles in both innate and adaptive immune responses, are involved in the pathogenesis of autoimmune, chronic inflammatory and infectious diseases. However, the role of TLR in the pathogenesis of oral lichen planus (OLP) has not been investigated. The aim of this study was to understand the roles of TLR in OLP.

[Effects of concurrent enteral hyperalimentation with chemo-radiotherapy in patients with oral cancer].

We compared the nutritional condition, immunological function, and frequency of adverse effects during concurrent chemoradiotherapy for oral cancer between patients simultaneously receiving enteral hyperalimentation (Racol) (n=20; EHA group) and patients receiving peripheral vein nutrition (n=20; PVN group). Although there was no significant difference in the change of body weight between the two groups, the decrease of plasma albumin values in the EHA group appeared later than in the PVN group. In the PVN group, the number of lymphocytes and lymphocyte blastogenesis significantly decreased on and after day 14.

Reactive oxygen species produced by the knockdown of manganese-superoxide dismutase up-regulate hypoxia-inducible factor-1alpha expression in oral squamous cell carcinoma cells.

Hypoxia-inducible factor-1alpha (HIF-1alpha) is a central regulator that controls the hypoxic response of mammalian cells through the induction of various target genes, and its expression contributes to the development and malignant progression of many tumors. We previously reported that some chemotherapeutic drugs and gamma-rays induce HIF-1alpha expression through increased production of reactive oxygen species (ROS) in oral squamous cell carcinoma (OSCC) cells. However, the mechanism by which intracellular ROS activate HIF-1alpha expression is poorly understood.

Enhancement of apoptotic damage of squamous cell carcinoma cells by inhibition of the mitochondrial DNA repairing system.

Mitochondrial DNA (mtDNA) repair systems are thought to be associated with the susceptibility of cancer cells to anticancer agents. The present study investigated the relationship between the susceptibility to gamma-rays and the mtDNA repair ability of oral squamous cell carcinoma (OSC) cell lines. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and mtDNA common deletion in both nuclear and mitochondrial DNA of OSC-2, OSC-3 and OSC-6 cells (radio-sensitive cell lines) after gamma-ray-irradiation were higher than those of OSC-1, OSC-4 and OSC-5 cells (radio-resistant cell lines).

Ionizing irradiation induces apoptotic damage of salivary gland acinar cells via NADPH oxidase 1-dependent superoxide generation.

Reactive oxygen species (ROS) have important roles in various physiological processes. Recently, several novel homologues of the phagocytic NADPH oxidase have been discovered and this protein family is now designated as the Nox family. We investigated the involvement of Nox family proteins in ionizing irradiation-induced ROS generation and impairment in immortalized salivary gland acinar cells (NS-SV-AC), which are radiosensitive, and immortalized ductal cells (NS-SV-DC), which are radioresistant.

The involvement of hypoxia-inducible factor-1alpha in the susceptibility to gamma-rays and chemotherapeutic drugs of oral squamous cell carcinoma cells.

The transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha) is the key regulator that controls the hypoxic response of mammalian cells. The overexpression of HIF-1alpha has been demonstrated in many human tumors. However, the role of HIF-1alpha in the therapeutic efficacy of chemotherapy and radiotherapy in cancer cells is poorly understood.

Concomitant chemo-radio-immunotherapy has a lethal therapeutic effect on tongue carcinomas independent of the clinical stage and histological characteristics of the tumor.

We examined the effect of concomitant chemo-radio-immunotherapy on 80 patients with tongue carcinoma. Disappearance of the tumor without recurrence was observed in 21 patients (38.9%) in intravenous infusion chemotherapy group (A) and in 20 patients (76.