Better Oral Hygiene Habits Are Associated With a Lower Incidence of Peritoneal Dialysis-Related Peritonitis.

Some peritoneal dialysis (PD)-related peritonitis cases are thought to be caused by the pathogens in the oral cavity; however, the relationship between peritonitis and oral hygiene habits is unclear. In this study, we retrospectively examined the relationship between oral hygiene habits and peritonitis in patients who agreed to a questionnaire survey. Of the 75 patients, 37 patients developed PD-related peritonitis during the observation period. Peritonitis-free survival was significantly higher in patients who spent more time on oral hygiene daily and in patients who replaced their toothbrush more frequently (P < 0.05). According to multivariable analysis, increased daily oral hygiene duration and more frequent toothbrush replacement were associated with a significantly (P < 0.01) lower risk for peritonitis (hazard ratio [HR] 0.37 [95% CI, 0.18-0.77] and HR 0.35 [95% CI, 0.17-0.70], respectively). In conclusion, PD patients with superior oral hygiene habits showed a lower risk for PD-related peritonitis.

Anti-tumor effect of radiation response by combined treatment with angiogenesis inhibitor, TNP-470, in oral squamous cell carcinoma.

Blocking angiogenesis may enhance conventional anticancer treatments such as radiation therapy. In this study, we examined the effects of the angiogenesis inhibitor TNP-470 on human OSCC cell lines HSC2 and KB, with combining radiation therapy in the nude mouse. We evaluated cell-induced neovascularization with dorsal air sac assay, and selected two cells (HSC2: low, KB: high) with different level of cell-induced angiogenesis. The angiogenesis inhibitor TNP-470 was given 30 mg/kg s.c. daily on day 1-5, and irradiation, 8 Gy x 1, was administered on day 1 each week for 3 weeks. Significant inhibition of tumor growth relative to untreated controls was achieved in KB cells showing high induced angiogenesis with both TNP-470 (P < 0.01) and radiation (P < 0.01) and combining TNP-470 and radiation (P < 0.01). We saw little effect of TNP-470 either alone or in addition to the effect of radiation on the HSC2 cells showing low induced angiogenesis. These results suggested that TNP-470 significantly enhanced the effect of radiation on the cells with high neovascularization. These findings indicated that individual evaluation of each tumor neovascularization potential will be important before deciding the anti-angiogenesis treatment.

Overexpression of cyclooxygenase-2 is associated with radioresistance in oral squamous cell carcinoma.

Cyclooxygenase-2 (COX-2), an inducible isoform of cyclooxygenase, is overexpressed in many types of malignant tumors, which in turn may stimulate tumor growth and protect against damage by irradiation or cytotoxic agents. The purpose of this study is to investigate the relationship between the radiation sensitivity and elevated level of COX-2. Radiation sensitivity of the eight oral SCC cell lines differed greatly in their response to radiation. Further, the level of the COX-2 expression correlated inversely with increased tumor radiation sensitivity. The similar significant association between the response to preoperative radiation therapy and COX-2 overexpression was observed in the oral SCC patients. In addition, treatment with a COX-2 selective inhibitor enhanced the radioresponse of HSC-2 cell, which constitutively expressed COX-2. These results suggested that COX-2 expression level correlates to radiation tolerance and the COX-2 selective inhibitor may be a potent enhancer for tumor radioresponse in oral SCC.

Gefitinib ('Iressa', ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, up-regulates p27KIP1 and induces G1 arrest in oral squamous cell carcinoma cell lines.

High expression of epidermal growth factor receptor (EGFR) is frequently observed in many solid tumor types including oral squamous cell carcinomas (OSCC). Recently, the results of preclinical studies and early clinical trials targeting the EGFR have shown evidence of the activity. In this study, gefitinib ('Iressa', ZD1839), an EGFR-tyrosine kinase inhibitor, inhibited cell proliferation and upregulated p27KIP1 in OSCC cells. Growth inhibition was observed in OSCC xenografts when mice were treated with gefitinib in vivo. A flow cytometric analysis demonstrated that treatment with gefitinib induced accumulation in G1 phase, accompanied by a decrease in the percentage of cells in S phase. Apoptosis was not seen in this study. Cell growth was inhibited by an increase of the cell cycle inhibitor p27KIP1 and a decrease of its ubiquitin ligase subunit Skp2.

Enhancement of tumor radioresponse by combined treatment with gefitinib (Iressa, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, is accompanied by inhibition of DNA damage repair and cell growth in oral cancer.

Molecular blockade of EGFR with either an EGFR MAb or an EGFR TKI enhances the radiosensitivity of human SCCs. In the present study, we investigated whether treatment with the EGFR TKI gefitinib (Iressa, ZD1839) improves the response to radiotherapy in the OSCC cell lines HSC2 and HSC3. We examined potential mechanisms that may contribute to the enhanced radiation response induced by gefitinib. Growth inhibition was observed in vitro with radiation or gefitinib. A cooperative antiproliferative effect was obtained when cancer cells were treated with radiation followed by gefitinib. Cells treated with a combination of radiation and gefitinib arrested in G(1) and G(2)-M phases, with a decrease in the S-phase population. While radiation alone did not significantly affect MEK1/2 and p38 MAPK autophosphorylation, the combination of gefitinib and radiation completely inhibited the downstream signaling of EGFR. Results from DNA damage repair analysis in cultured OSCC cells demonstrated that gefitinib had a strong inhibitory effect on DNA-PKc pathways after radiation. Tumor xenograft studies demonstrated that the combination of gefitinib and radiation caused growth inhibition and tumor regression of well-established OSCC tumors in athymic mice; tumor volume was reduced from 1,008.2 to 231.4 mm(3) in HSC2 cells (p < 0.01) and from 284.2 to 12.4 mm(3) in HSC3 cells (p < 0.01). Immunohistochemical analysis of OSCC xenografts revealed that gefitinib caused a striking decrease in tumor cell proliferation when combined with radiotherapy. Overall, we conclude that gefitinib enhances tumor radioresponse by multiple mechanisms that may involve antiproliferative growth inhibition and effects on DNA repair after exposure to radiation.

[A case of mandibular gingival cancer (T4) responding to concurrent chemoradiotherapy with TS-1].

We report here a patient with advanced oral cancer in which concurrent chemoradiotherapy with TS-1 was performed. The patient was an 82-year-old male who had a 41 x 22 mm tumor mass around the left lower gingiva, whose X-ray showed a bone resorption image reaching the mandibular canal. We carried out concurrent chemoradiotherapy with TS-1. After 4 weeks, severe side effects, i.e., stomatitis and diarrhea, force us to discontinue the treatment. However, the tumor had begun to shrink from the 2nd week of treatment, and had clinically disappeared by the 8th week. The histopathological examination also indicated a complete response (CR). Thus, this treatment was very effective and may be useful for advanced cases.

[A clinical study of neoadjuvant radiochemotherapy with docetaxel and cisplatin for oral cancers].

Docetaxel is classified among the microtubule-inhibiting compounds called taxanes, which are currently used as agents to treat head and neck cancers. To investigate the efficacy and safety of a neoadjuvant radiation therapy combined with docetaxel/cisplatin, we used this combination to treat 6 patients with oral squamous cell carcinoma. The patients received a low-dose fraction of docetaxel (20 mg/m2/week; total dose: 123.0 +/- 35.0 mg) and cisplatin (5 mg/m2/day, 5 days a week; total dose: 160.0 +/- 42.1 mg) combined with simultaneous irradiation of 40 Gy. Of the 6 patients, 5 (83.3%) showed a partial response (PR) and 1 showed no response (NC). Pathological efficacy was revealed in 4 patients (66.7%). All patients experienced stomatitis over grade 2, and 4 experienced neutropenia.

Infiltration of tumor-associated macrophages in human oral squamous cell carcinoma.

Tumor-associated macrophages (TAMs) have been shown to display both positive and negative effects on tumor growth of various cancer. In this study, TAMs were immunohistochemically labeled using CD68 antibody in 82 oral cancer. Macrophage index (MI) were analyzed in association with clinical and pathological factors, intratumoral microvessel density (IMVD) and angiogenic factors including VEGF and TP. Significantly higher number of CD68-positive cells was noted in oral cancer. TAM expressions were significantly associated with stages of invasion, IMVD, and angiogenic factors. These findings suggest that TAMs possibly play a role in angiogenesis during oral cancer progression.

[Non-randomized clinical study comparing chemotherapy plus radiotherapy with radiotherapy alone in neoadjuvant therapy for oral cancer].

Neoadjuvant therapy plays an important role for organ preservation and survival rate in the treatment of oral cancer. We clinically compared the effect of neoadjuvant radiotherapy and chemoradiotherapy in patients with oral cancer. We retrospectively examined 47 patients diagnosed with oral squamous cell carcinoma who underwent neoadjuvant therapy followed by curative surgery in the oral and maxillofacial surgery department of Ehime University Hospital. We divided them into two groups: radiotherapy alone (24 cases) and chemoradiotherapy (23 cases). The patients in the radiotherapy group underwent irradiation of 32.6 +/- 5.0 Gy (mean +/- SD). The patients in the chemoradiotherapy group received a low-dose fraction of cisplatin (8 mg/mm2/day, 5 days a week; total dose: 139.4 +/- 67.1 mg) and 5-fluorouracil (300 mg/mm2/day, 5 days a week; total dose: 5,900 +/- 1,839.8 mg) combined with simultaneous irradiation of 31.0 +/- 3.2 Gy. None of the 24 patients had a complete response to radiotherapy alone and 12 (50%) had a partial response. Six (26%) of the 23 patients had a complete response to chemoradiotherapy and 12 (52%) had a partial response. The primary control rate (82.6%) to chemoradiotherapy was higher than that (67.5%) to radiotherapy alone although no significant difference was found. The 5-year survival rate was 64.3% in the radiotherapy group and 62.8% in the chemoradiotherapy group. The findings of the present study suggest that while the combination of radiation and cisplatin/5-fluorouracil in neoadjuvant therapy for oral cancer may not bring a significant benefit to improve survival rate, the primary local control rate is improved in comparison with radiotherapy alone.