Background: The aim of this study was to compare the outcomes of postoperative adjuvant concomitant chemoradiotherapy using two different schedules of cisplatin for patients with high-risk oral squamous cell carcinoma (OSCC).Methods: From Feb. 2008 to Aug. 2010, 55 patients with high-risk OSCC were included in this study. Patients were randomized into treatment groups that either received 100 mg/m2cisplatin once every 3 weeks (arm A) or 40 mg/m2cisplatin once per week (arm B). All patients were irradiated with 66 Gy in 33 fractions.Results: Of the 50 eligible patients, 26 were assigned to arm A, and 24 were assigned to arm B. Both groups of patients received the same mean doses of radiotherapy and cisplatin. However, 88.5% of patients in arm A and 62.5% of those in arm B (p = 0.047) received ≥ 200 mg/m2of cisplatin in total. The overall toxicity was significantly greater in arm B (p = 0.020), and all of the grade 4 toxicities occurred in patients in arm B.Conclusions: Three-weekly high-dose cisplatin treatment showed higher compliance, and lower acute toxicity compared to weekly low-dose cisplatin treatment.
Raman spectroscopy (RS) is widely used as a non-invasive technique in screening for the diagnosis of oral cancer. The potential of this optical technique for several biomedical applications has been proved. This work studies the efficacy of RS in detecting oral cancer using sub-site-wise differentiation. A total of 80 samples (44 tumor and 36 normal) were cryopreserved from three different sub-sites: The tongue, the buccal mucosa, and the gingiva of the oral mucosa during surgery. Linear discriminant analysis (LDA) and quadratic discriminant analysis (QDA) were used with principal component analysis (PCA) to classify the samples and the classifications were validated by leave-one-out-cross-validation (LOOCV) and k-fold cross-validation methods. The normal and tumor tissues were differentiated under the PCA-LDA model with an accuracy of 81.25% (sensitivity: 77.27%, specificity: 86.11%). The PCA-QDA classifier model differentiated these tissues with an accuracy of 87.5% (sensitivity: 90.90%, specificity: 83.33%). The PCA-QDA classifier model outperformed the PCA-LDA-based classifier. The model studies revealed that protein, amino acid, and beta-carotene variations are the main biomolecular difference markers for detecting oral cancer.
MicroRNA-196 (miR-196), which is highly up-regulated in oral cancer cells, has been reported to be aberrantly expressed in several cancers; however, the significance of miR-196 in oral cancer has not yet been addressed. Cellular functions in response to miR-196 modulation were examined, including cell growth, migration, invasion and radio/chemosensitivity. Algorithm-based studies were used to identify the regulatory target of miR-196. The miR-196 target gene and downstream molecular mechanisms were confirmed by RT-qPCR, western blot, luciferase reporter and confocal microscopy analyses. miR-196 expression was determined in paired cancer and adjacent normal tissues from oral cancer patients. Both miR-196a and miR-196b were highly over-expressed in the cancer tissue and correlated with lymph node metastasis (P = 0.001 and P = 0.006, respectively). Functionally, miR-196 actively promoted cell migration and invasion without affecting cell growth. Mechanistically, miR-196 performed it's their function by inhibiting NME4 expression and further activating p-JNK, suppressing TIMP1, and augmenting MMP1/9. miR-196 contributes to oral cancer by promoting cell migration and invasion. Clinically, miR-196a/b was significantly over-expressed in the cancer tissues and correlated with lymph node metastasis. Thus, our findings provide new knowledge of the underlying mechanism of cancer metastasis. miR-196 may serve as a promising marker for better oral cancer management.
Background: Cyclin D1 gene regulates cell cycle and plays an important role in the tumorigenesis of human cancers. The association between cyclin D1, clinicopathologic parameters and prognosis in oral cavity squamous cell carcinoma (OSCC) is inconclusive. Methods: A total of 264 male OSCCs were examined for cyclin D1 protein expression using immunohistochemistry (IHC). The expression levels of cyclin D1 were defined as overexpression when more than 10% of tumor cells displayed nuclear staining with moderate to strong intensity. Results: Overexpression of cyclin D1 was found in 97 (36.7%) OSCCs. Cyclin D1 protein overexpression was significantly associated with lymph node metastasis (P = 0.002), tumor cell differentiation (P = 0.031) and tumor stage (P = 0.051), but not associated with age onset, cigarette smoking, alcohol drinking, or areca quid chewing. Overexpression of cyclin D1 was also significantly associated with poor clinical outcomes in terms of disease-free survival (DFS, P = 0.002) and overall survival (OS, P < 0.001). The effects of cyclin D1 protein overexpression on DFS (hazard ratio (HR) = 1.540; 95% confidence interval (CI), 1.068 - 2.222) and OS (HR = 1.702; 95% CI, 1.168 - 2.480) were still existed after adjusting for clinicopathological paremeters (such as age, primary tumor status, tumor cell differentiation, and lymph node metastasis) using logistic multivariate analysis. Conclusion: Cyclin D1 protein worked as an independent prognostic factor and can be as a biomarker for the aggressiveness of OSCC.