The influence of cervical lymph node number of neck dissection on the prognosis of the early oral cancer patients.

BACKGROUND/PURPOSE: The status of neck lymph nodes (LNs) plays an important role in survival of oral cavity cancer. Early stage oral cancer patients are still at a risk for locoregional metastasis. We aimed to determine the number of LNs that needs to be retrieved for adequate diagnosis and treatment of the neck tumor. MATERIALS AND METHODS: We conducted a retrospective study of 126 oral cavity cancer patients who underwent wide excision and 3 types of neck dissection at MacKay Memorial Hospital, Taiwan. Data from the operative and pathology reports were collected and analyzed. The significant difference was defined as p < 0.05 by SPSS 21.0 and Prizm 5 software. RESULTS: There was a significant difference between the total retrieved LNs and tumor differentiation and nerve invasion on multivariate analysis. Receiveroperating characteristic (ROC) curve showed significant difference in the total number of neck LNs between the survival and expired groups. The cut-off point was 36.5 nodes. However, there was no difference in survival between supraomohyoid and modified radical neck dissection. CONCLUSION: Retrieval of adequate LNs can improve oral cancer survival rates. If total number of neck nodes examined is <37 with poor differentiation and/or nerve invasion, early oral cancer patients with neck dissection have a lower survival rate and are candidates for adjuvant therapy.

BI2536 induces mitotic catastrophe and radiosensitization in human oral cancer cells.

BI2536 has been developed as a potential therapeutic agent for various cancers but not in oral cancer cells. Since BI2536 exhibits mitosis-regulating activity which are the most radiosensitive, we hypothesized that BI2536 might modulate the radiosensitivity of oral cancer cells. Human normal fibroblasts, oral cancer SAS, and OECM1 cells were treated with BI2536 (0-50 nM) and/or radiation (0-4 Gy). MTT assay, Liu's staining, flow cytometry, clonogenic assay, Annexin V/propidium iodide (PI) staining, western blot analysis, and small interfering RNA knockdown experiments were used to assess cell viability, morphology, cell cycle progression, radiation survival, and expression of regulatory proteins in vitro. Male BALB/c nude mice implanted with SAS cells were used to examine the effects of BI2536 in vivo. Treatment with BI2536 preferentially inhibited the viability of SAS and OECM1 cells, but not the normal fibroblasts. Morphological examination and Annexin V/PI staining of BI2536-treated oral cancer cells showed mitotic catastrophe and apoptosis. A DNA histogram revealed BI2536 induced G2/M and upregulation of phosphorylated H3 indicating accumulation in the M phase. BI2536 modulated the expression of PLK1, cell division control protein (Cdc)2, Cdc20, Cdc25c, adenomatous polyposis coli 3, and cyclin B1. At 10 nM, BI2536 exhibited low cytotoxicity, effectively induced mitotic catastrophe, and more importantly, sensitized oral cancer cells to radiotherapy. The animal study showed that BI2536 (10 mg/kg) + radiation (2 Gy) resulted in stronger tumor inhibition than that associated with radiation alone. Our findings showed that BI2536 could be an effective radiosensitizer both in vitro and in vivo.

Plasma miR-187* is a potential biomarker for oral carcinoma.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is prevalent worldwide, and survival in OSCC has not improved significantly in the past decades. MicroRNAs (miRNAs) have an important regulatory role in oral carcinogenesis. This study investigated the functional and clinical implications of miR-187* in OSCC pathogenesis. MATERIALS AND METHODS: Expression of miR-187* in OSCC tissues and patient plasma was assayed using quantitative RT-PCR. The diagnostic power was specified using receiver operator curve analysis. The phenotypic influence of miR-187* in OSCC cells was delineated using exogenous expression. RESULTS: miR-187* was upregulated in OSCC tissue relative to control mucosa. Overexpression of miR-187* enhanced the oncogenic phenotype of OSCC cells, including cell migration and anchorage-independent colony formation. Plasma miR-187* levels could be used to distinguish patients from controls with a separating power of 0.73. Patients showing a reduction in plasma miR-187* after tumor resection had a better prognosis. CONCLUSION: miR-187* plays oncogenic roles in oral carcinogenesis. Plasma miR-187* could be validated as a marker of OSCC for diagnostic uses. CLINICAL RELEVANCE: This research implied that plasma miR-187* was a diagnostic marker for patients with OSCC, and plasma miR-187* level could be a prognostic factor for OSCC patients who received ablation surgery.

EGF and EGFR genetic polymorphisms predict prognosis in locally advanced pharyngolaryngeal squamous cell carcinoma patients receiving postoperative concurrent chemoradiotherapy.

BACKGROUND: Epidermal growth factor (EGF) and its receptor (EGFR) are part of an important signaling pathway that is involved in the pathogenesis of squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that EGF/EGFR genetic polymorphisms might have a prognostic impact on disease-free survival and overall survival (OS) in locally advanced SCCHN. MATERIALS AND METHODS: The patient group included a consecutive cohort of 180 patients with locally advanced SCCHN who underwent postoperative concurrent chemoradiotherapy between 2002 and 2010. DNA from formalin-fixed, paraffin-embedded tumor tissues was genotyped for the single nucleotide polymorphism (SNP) of EGF A61G A>G, EGFR R521K G>A and G-216T. The log-rank test was applied to evaluate the impact of SNPs on the outcomes. Survival was estimated using the Kaplan-Meier statistical method. RESULTS: We demonstrated that EGF/EGFR SNPs might predict prognosis in patients with primary pharyngolaryngeal tumors, but not in those with oral cavity tumors. In pharyngolaryngeal tumor subgroup, EGF61 G/G genotype led to worse 5 year OS rate when compared to G/A or A/A genotypes (13.3% versus 34.3% versus 50.0%, P=0.017). The 5 year OS of patients with EGFR R521K G/G (11.1%) and G/A (15.9%) were lower than the A/A (62.5%) genotype (P=0.054). Patients carrying one or two unfavorable alleles had worse 5 year OS than those without unfavorable allele (not available versus 20% versus 71.4%, P=0.002). Multivariate analysis revealed that the highest risk of death was associated with the coexistence of two unfavorable genotypes (hazard ratio 25.7, 95% confidence interval =3.4-193.4; P=0.002). CONCLUSION: In this study, we were able to demonstrate that the EGF A61G and EGFR R521K genetic polymorphisms might be important prognostic factors in patients with locally advanced primary pharyngolaryngeal squamous cell carcinoma who underwent postoperative concurrent chemoradiotherapy.

The traditional Chinese medicine prescription patterns of Sjögren׳s patients in Taiwan: a population-based study.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicines (TCM), when given for symptom relief, have gained widespread popularity among Sjögren׳s patients. The aim of this study was to analyze the utilization of TCM among Sjögren׳s patients in Taiwan. MATERIALS AND METHODS: The usage, frequency of service, and the Chinese herbal products prescribed among Sjögren׳s patients were evaluated in a cohort of 1,000,000 beneficiaries recruited from the National Health Insurance Research Database. The logistic regression method was employed to estimate the odds ratios (ORs) for utilization of a TCM. RESULTS: More than 90% of Sjögren׳s patients received TCM out-patient services at least once during the study period. Patients with secondary Sjögren׳s syndrome were more likely to seek TCM treatment than those with primary Sjögren׳s syndrome. The aOR for those suffering from at least one rheumatologic disease was 1.56 (95% CI: 1.26-1.93), those with two rheumatologic diseases was 1.98 (95% CI: 1.29-3.04), while those with three or more rheumatologic diseases was 7.86 (95% CI: 1.09-56.58). Compared to Sjögren׳s patients who used no medical treatment, the aOR for those who took one type of conventional medication was 1.55 (95% CI: 1.25-1.92), those who took two types was 1.98 (95% CI: 1.60-2.47) while those who took three or more types was 2.91 (95% CI: 2.20-3.84). Qi-Ju-Di-Huang-Wan (Lycium Berry, Chrysanthemum, and Rehmannia Pill) was the most frequently prescribed formula among Sjögren׳s patients. CONCLUSION: Qi-Ju-Di-Huang-Wan is the most commonly prescribed Chinese herbal formula for Sjögren׳s syndrome and its effects should be taken into account by healthcare providers.

Areca nut extract-treated gingival fibroblasts modulate the invasiveness of polymorphonuclear leukocytes via the production of MMP-2.

BACKGROUND: Areca nut chewing is associated with an increase in the incidence of oral neoplastic or inflammatory diseases. Aberrations in matrix metalloprotease (MMP) expression are associated with the pathogenesis of oral diseases. This study investigated the potential effects of areca nut extract (ANE) on human gingival fibroblasts and the consequential impacts on inflammatory pathogenesis. METHODS: Analyses of senescence marker, cell viability, changes of the cell cycle, and cell granularity in gingival fibroblasts together with an assessment of the invasiveness of polymorphonuclear (PMN) leukocytes after treatment with the supernatant of ANE-treated gingival fibroblasts were performed to characterize the phenotypic impacts. Western blotting and gelatin zymography were used to assay the expression and activity of MMP-2. RESULTS: Chronic subtoxic (<10 microg/ml) ANE treatment resulted in premature growth arrest, appearance of senescence-associated beta-galactosidase activity and various other senescence-associated phenotypes in gingival fibroblasts. Gingival fibroblasts established from older individuals had a higher propensity to become ANE-induced senescent gingival fibroblasts. An activation of MMP-2 was identified in senescent cells. PMN leukocytes treated with the supernatant of ANE-induced senescent cells exhibited a significant increase in invasiveness, which was abrogated by both a MMP-2 blocker and a MMP-2 nullifying antibody. CONCLUSIONS: This study provides evidence whereby MMP-2 secreted from ANE-induced senescent gingival fibroblasts would facilitate the invasiveness of PMN leukocytes, which could be associated with the oral inflammatory process in areca chewers.

Vascular endothelial growth factor 936 C/T polymorphism is associated with vascular invasion in oral squamous cell carcinoma.

OBJECTIVE: The objective of this study was to analyze the relation of VEGF 936 C/T polymorphisms in progression of oral squamous cell carcinoma (OSCC) patients and healthy subjects in Taiwan. STUDY DESIGN: We genotyped 218 patients with OSCC, comparing the genotypes and gene frequencies with those of 121 control subjects. VEGF 936 C/T polymorphisms were determined by using polymerase chain reaction and restriction fragment length polymorphism. RESULTS: There were no significant differences in genotype, phenotype, or gene frequency between the OSCC and control groups. Among patients with OSCC, there were also no significant differences in the polymorphism between those with and without cervical lymph node metastases or in survival. However, 21 of the 218 patients had vascular invasion by their OSCC, and these patients were significantly more likely to have a C/C (P = .033) or C/T genotype (P = .026) than were those without vascular invasion. CONCLUSIONS: This study suggests that the VEGF 936 C allele is associated with vascular invasion in OSCC.

Association of pretreatment thrombocytosis with disease progression and survival in oral squamous cell carcinoma.

The objective of this study was to review the prevalence and prognostic impact of pretreatment thrombocytosis in patients with oral squamous cell carcinoma (OSCC). Medical records of 253 patients with OSCC were retrospectively reviewed. The relationship between the platelet count, TNM stage, histologic differentiation, recurrence rate, metastasis, and survival were analyzed. Pretreatment thrombocytosis was found in 61 (24.1%) of 253 patients and was associated with aggressive tumour growth (p=0.015), lymph node metastasis (p=0.009), and distant metastasis (p=0.001). Association with tumour recurrence fell just short of statistical significance (p=0.058). Patients with preoperative thrombocytosis had a poorer survival than those with normal platelet counts (p=0.004). Multivariate analysis using Cox's proportional hazards model indicated that thrombocytosis was an independent predictor of shorter survival (RR 2.48, 95% CI 1.30- 4.73, p=0.006).