Protease-Activated Receptor 1 (PAR1) Expression Contributes to HPV-Associated Oropharyngeal Cancer Prognosis.

BACKGROUND: Human papillomavirus (HPV)-associated oropharyngeal cancer occasionally has a poor prognosis, making prognostic risk stratification crucial. Protease-activated receptor-1 (PAR1) is involved in carcinogenesis, and its expression is regulated by alpha-arrestin domain-containing protein 3 (ARRDC3). It is also involved in the tumor microenvironment. We sought to evaluate the predictive ability of PAR1, ARRDC3, and tumor-infiltrating lymphocyte (TIL) scores in patients with oropharyngeal, hypopharyngeal, and uterine cervical cancers, serving as comparators for HPV-associated oropharyngeal cancer. METHODS: Immunohistochemical analysis of p16, ARRDC3, and PAR1 expression was performed on 79 oropharyngeal, 44 hypopharyngeal, and 42 uterine cervical cancer samples. The TIL scores were assessed and classified into the following groups based on invasion: low: 0-10%, medium: 20-40%, and high: > 50%. For prognostic analysis, the three groups were evaluated by dividing them into low, medium, and high categories, or alternatively into two groups using the median value as the cutoff. RESULTS: p16 was expressed in 44 (56%) oropharyngeal, 8 (18%) hypopharyngeal, and all uterine cervical cancer samples. ARRDC3 was detected in 39 (49%) oropharyngeal, 25 (57%) hypopharyngeal, and 23 (55%) uterine cervical cancer samples. PAR1 was expressed in 45 (57%) oropharyngeal, 22 (50%) hypopharyngeal, and 22 (50%) uterine cervical cancer samples. Patients diagnosed with p16-positive oropharyngeal cancer had a substantially improved prognosis compared to those diagnosed with p16-negative cancer. The PAR1-negative cases had a considerably improved prognosis compared to the positive cases (disease-specific survival [DSS] and -negative cases (disease-free survival [DFS]). Multivariate analysis revealed that ARRDC3-positive cases had an appreciably better DSS prognosis than patients with p16-negative oropharyngeal cancers. PAR1-positive patients among patients with p16-positive oropharyngeal cancer had a poor prognosis. With respect to DFS, patients with PAR1-positive and p16-negative oropharyngeal cancer had a 35-fold higher recurrence rate than those with PAR1-negative and p16-negative oropharyngeal cancer. CONCLUSION: Our results suggest that PAR1 expression affects the prognosis and recurrence rate of HPV-associated oropharyngeal cancer.

Descending necrotizing mediastinitis in a healthy young adult.

A 26-year-old man with right lower mandibular and chest pain, fever, and respiratory distress was urgently transported to our hospital. CT images revealed gas collection and an abscess from the neck to the mediastinum with bilateral pleural effusion. Descending necrotizing mediastinitis (DNM) induced by an odontogenic infection of a right mandibular molar abscess was diagnosed. The cervical and mediastinal areas were drained, extensive debridement was performed, necrotic tissue was excised, and broad-spectrum antibiotics were administered immediately. Prompt diagnosis and intensive care were necessary for managing the DNM, and the patient was discharged with no comorbidities.

Uptake of microparticles into the epithelium of human nasopharyngeal lymphoid tissue.

The M cells of nasopharyngeal lymphoid tissue (NALT) have been considered to play an important role for vaccine delivery systems in humans. A number of investigations have reported particle uptake data in NALT of rodents. However, there have been no reports indicating any involvement of the nasopharyngeal lymphoid tissue in human vaccination. In the present study, we investigated whether the epithelium of human adenoid tissues might incorporate fluorescent microparticles using electron and fluorescent microscopy. The dissected adenoid tissues were incubated with various sizes and concentrations of fluorescent microparticles for 120 min at 37 degrees C. Furthermore, the effect of surface coatings of microparticles with cations on the uptake into the epithelium of adenoid tissues was investigated. Transmission electron microscopy revealed that microparticles were taken up by the M cells of human nasopharyngeal lymphoid tissues. The NALT-M cells showed greater uptake of the smallest particles, 0.2 microm in diameter, than those of 0.5, 1.0, or 2.0 microm diameter. It was also revealed that surface coatings with poly-L: -lysin or chitosan resulted in efficient uptake into the NALT. These results indicate that nasal administration of antigenic microparticles, which were coated with cationic materials, probably leads to a useful method of transnasal vaccination against respiratory and intestinal infections in humans.

The role of M cells of human nasopharyngeal lymphoid tissue in influenza virus sampling.

Little is known about the role of the M cells of human nasopharyngeal lymphoid tissue in the sampling of viruses that cause respiratory infections. To clarify whether M cells could function as a gateway for influenza virus into human nasopharyngeal lymphoid tissue, excised adenoid tissue was incubated in media containing influenza A virus for 30, 60, and 90 min, respectively. Transmission electron microscopic observation revealed that many influenza viruses adhered to M cell surfaces and were taken up into the cytoplasmic vesicles of M cells after 30 min incubation; the viruses had been transported into enfolded lymphoid cells after 60 min incubation. By staining M cells with Sambucus nigra lectin, which specifically recognizes the NeuAcalpha2,6 Gal linkage of sialoprotein, it was also found that abundant receptors for the human influenza virus are present on the M cell surface. Our findings indicated that M cells of human nasopharyngeal tonsils function as a major port for influenza A virus entry and that the virus could be efficiently transferred to enfolded macrophages and lymphoid cells by M cells. The transport of influenza viruses to lymphoid cells by M cells may promote antigen delivery to the immune system, and these findings may be important for systemic delivery of those influenza viruses that have the capacity to productively infect cells outside of the respiratory tract.

[A case of advanced hypopharyngeal carcinoma successfully treated with superselective intra-arterial infusion of docetaxel].

Docetaxel is an excellent agent with a high antitumor effect for advanced/recurrent head and neck cancer. A 67-year-old male with advanced hypopharyngeal cancer (T3N2bM1: Stage IV) underwent two courses of superselective intra-arterial infusion of docetaxel and intravenous administration of CDDP and 5-FU. Using a coaxial technique, a microcatheter was placed in the feeding artery. Using imaging techniques docetaxel (60 mg/body and 30 mg/body) was infused into the vessels. During chemotherapy the patient received concomitant radiotherapy (50 Gy). MRI after chemoradiation showed a complete response for the primary tumor and a partial response for the neck metastasis. Grade 4 leukopenia and neutropenia and grade 3 pharyngitis/esophagitis were observed during chemoradiotherapy, but these adverse effects abated immediately and were not critical. We conclude that this superselective intra-arterial infusion of docetaxel will be useful and safe for head and neck cancer.

Participation of Fas-mediated apoptotic pathway in KB, a human head and neck squamous cell carcinoma cell line, after irradiation.

In head and neck clinical oncology, recurrent cancer after initial irradiation therapy is no longer sensitive to irradiation. To explore the irradiation resistance in head and neck squamous cell carcinoma, a human cell line, KB, derived from the floor of the oral cavity was used. The participation of the Fas-mediated apoptotic pathway was suggested by the upregulation of the surface Fas molecule, the reduction of the apoptotic cell fraction after inhibition of caspase 8 which is a Fas-related initiator caspase, and the changes in Fas-related genes after irradiation. Therefore, it is suggested that disruption of the Fas-mediated apoptotic pathway participates in the acquisition of irradiation-resistance in HNSCC.