Peri-Neural Invasion Is an Important Prognostic Factor of T2N0 Oral Cancer.

Background and objectives: Among patients with pathologically proven T2N0 oral squamous cell carcinoma (OSCC), a notable amount of patients still die from tumor recurrence although they have radical surgery for early stage cancers. In literature, the prognostic indicators of this specific disease entity were rarely reported. This study aims at analyzing the prognostic factors of T2N0 OSCC patients and discussing possible managements to improve the survival. MATERIALS AND METHODS: From January 2012 to December 2017, the data of 166 pathologically proven T2N0 oral cancer patients proved by radical surgery were retrospectively collected. The clinical and pathologic factors including age, gender, tumor differentiation grade, perineural invasion (PNI), angiolymphatic invasion (ALI), margin status, and adjuvant therapy were analyzed by univariate and multivariate analysis to determine their association with disease-specific survival (DSS), and disease-free survival (DFS), which were calculated by Kaplan-Meier method. RESULTS: After median follow up time of 43.5 months, overall 3-year rates of DSS and DFS were 86.1% and 80.1% respectively for our 166 patients. Univariate analysis showed that the 3-year DSS of 90.8% for PNI negative patients was significantly better than DSS of 57.0% for PNI positive patients (p = 0.0006). The 3-year DFS of 84.2% for PNI negative patients was also significantly better than DFS of 54.6% for PNI positive patients (p = 0.001). Further multivariate analysis revealed PNI was the only independent prognostic factor associated with both DSS (Hazard Ratio (HR) = 5.02; 95% Confidence Interval (CI) = 1.99-12.6; p = 0.001), and DFS (HR = 3.92; 95% CI = 1.65-9.32; p = 0.002). Nearly 10% (16) of the 166 patients had adverse pathologic feature of PNI only. In the 11 patients without adjuvant therapy, 5 patients died from OSCC. No patients had recurrence or mortality after they received adjuvant therapy with chemotherapy ± radiotherapy. CONCLUSION: PNI was an independent prognostic factor for T2N0 oral cancer patients. Adjuvant chemotherapy and radiotherapy may benefit the survival of this specific disease entity, but further investigations are needed to elucidate the optimal regimen.

Structure-guided development of purine amide, hydroxamate, and amidoxime for the inhibition of non-small cell lung cancer.

An 8-oxopurine-6-carboxamide compound (1a) was previously identified as an inhibitor of non-small cell lung cancer (NSCLC). In this study, more than 30 purine-6-carboxamide derivatives with variations at the C2, N7, C8, and N9 positions were synthesized to investigate the structure-activity relationship as a basis for the construction of an advanced pharmacophore model. This model suggests that purine-6-hydroxamate and purine-6-amidoxime analogs could form more hydrogen bonds with a target protein to enhance the inhibitory activities against H1975 cells. Among the series of analogs, hydroxamate 17 and amidoxime 19a exhibited excellent potency against H1975 cells (IC50 < 1.5 µM) and other lung cancer cells with either wild-type or mutated epidermal growth factor receptor (EGFR). Mouse experiments indicated that compounds 17 and 19a were efficient anticancer agents with no appreciable toxicity. The mechanisms of action for the induction of cell apoptosis were determined to involve microtubule fragmentation and p53-mediated signaling pathways.