The expression of p53 protein in primary head and neck squamous cell carcinoma was significantly predictive of shorter survival because of its association with earlier development of both tumor recurrence and second primary tumors. Thus, p53 expression may be a valuable marker for identifying individuals at high risk of developing a recurrence of primary disease and second primary tumors who may benefit from adjuvant therapy and chemoprevention after definitive local therapy.
The incidence of atherosclerosis is higher among patients with systemic lupus erythematosus (SLE); however, the mechanism by which an atherogenic environment affects autoimmunity remains unclear. We found that reconstitution of atherosclerosis-prone Apoe and Ldlr mice with bone marrow from lupus-prone BXD2 mice resulted in increased autoantibody production and glomerulonephritis. This enhanced disease was associated with an increase in CXCR3 follicular helper T cells (T cells). T cells isolated from Apoe mice had higher expression of genes associated with inflammatory responses and SLE and were more potent in inducing production of the immunoglobulin IgG2c. Mechanistically, the atherogenic environment induced the cytokine IL-27 from dendritic cells in a Toll-like receptor 4 (TLR4)-dependent manner, which in turn triggered the differentiation of CXCR3 T cells while inhibiting the differentiation of follicular regulatory T cells. Blockade of IL-27 signals diminished the increased T cell responses in atherogenic mice. Thus, atherogenic dyslipidemia augments autoimmune T cell responses and subsequent IgG2c production in a TLR4- and IL-27-dependent manner.
For successful infection of their hosts, pathogenic bacteria recognize host-derived signals that induce the expression of virulence factors in a spatiotemporal manner. The fulminating food-borne pathogen Vibrio vulnificus produces a cytolysin/hemolysin protein encoded by the vvhBA operon, which is a virulence factor preferentially expressed upon exposure to murine blood and macrophages. The Fe-S cluster containing transcriptional regulator IscR activates the vvhBA operon in response to nitrosative stress and iron starvation, during which the cellular IscR protein level increases. Here, electrophoretic mobility shift and DNase I protection assays revealed that IscR directly binds downstream of the vvhBA promoter PvvhBA, which is unusual for a positive regulator. We found that in addition to IscR, the transcriptional regulator HlyU activates vvhBA transcription by directly binding upstream of PvvhBA, whereas the histone-like nucleoid-structuring protein (H-NS) represses vvhBA by extensively binding to both downstream and upstream regions of its promoter. Of note, the binding sites of IscR and HlyU overlapped with those of H-NS. We further substantiated that IscR and HlyU outcompete H-NS for binding to the PvvhBA regulatory region, resulting in the release of H-NS repression and vvhBA induction. We conclude that concurrent antirepression by IscR and HlyU at regions both downstream and upstream of PvvhBA provides V. vulnificus with the means of integrating host-derived signal(s) such as nitrosative stress and iron starvation for precise regulation of vvhBA transcription, thereby enabling successful host infection.
As the age distribution in Korean society has gotten gradually older, the morbidity of cancer in Korea has increased accordingly. This also derives from the increase of smoking, drinking, and air pollution. Since the 1980s, in spite of the substantial expansion of surgical aspect and radiotherapy, significant number of people has still been suffering from cancer, which often ends up with death. The data of cancer registry reports the current status of nationwide cancers under the guidance of central committee of the Korean Cancer Registry in the Ministry of Health and Welfare. However, this implies several limitations because it is focused too much on the diagnosis itself. Thus, in our epidemiologic survey, we intend to develop various items to add, such as classification of anatomical primary site, staging of head and neck cancers, correlation between smoking or drinking and head and neck cancer, double primary cancers, and treatment modality by site and stage. We further expect to accomplish the accuracy and the completion of the survey data by allowing otolaryngologists let input the data, who are in charge of head and neck cancers. We truly hope that we could understand head and neck cancers of Korea systematically and precisely through this data. This understanding could hopefully make analysis of survival rate, and treatment result possible. Finally, we expect that this data could serve as an important sour- Epidemiologic Survey of Head and Neck Cancers in KoreaHead and neck cancers have never been systematically studied for clinical purposes yet in Korea. This epidemiological survey on head and neck cancer patients was undertaken from January to December 2001 in 79 otorhinolaryngology resident-training hospitals nationwide. The number of head and neck cancer patients was 1,063 cases in the year. The largest proportion of cases arose in the larynx, as many as 488 cases, which accounted for 45.9%. It was followed by, in order of frequency, oral cavity (16.5%), oropharynx (10.0%), and hypopharynx (9.5%). The male:female ratio was 5:1, and the mean age was 60.3 yr. Surgery was the predominant treatment modality in head and neck cancers: 204 (21.5%) cases were treated with only surgery, 198 (20.8%) cases were treated with surgery and radiotherapy, 207 cases (21.8%) were treated with combined therapy of surgery, radiotherapy, and chemotherapy. Larynx and hypopharynx cancers had a stronger relationship with smoking and alcohol drinking than other primary site cancers. Of them, 21 cases were found to be metastasized at the time of diagnosis into the lung, gastrointestinal tract, bone, or brain. Coexisting second primary malignancies were found in 23 cases. At the time of diagnosis, a total of 354 cases had cervical lymph node metastasis accounting for 42.0%.
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