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BACKGROUND: Practical cancer biomarkers for oral cavity cancer are currently in limited use. OBJECTIVE: We aimed to investigate the differences in soluble E-cadherin between patients with oral cavity cancer and matched healthy participants via Proximity Ligation Assay (PLA). METHODS: Samples were taken from both patients diagnosed with oral cavity cancer, as well as non-cancerous participants. PLA was used to detect soluble E-cadherin and Cycle threshold (Ct) values derived from qPCR in order to calculate the number of starting amplicons. RESULTS: In total, 74 patients with oral cavity cancer and 55 matched non-cancerous participants were included for final analysis. The Ct value of E-cadherin was found to be lower in oral cavity cancer patients when compared with that of the matched non-cancerous participants (20.72 ± 0.39 versus 21.27 ± 0.45, P < 0.001). Using a Ct value of 20.9 as a cut-off point, the sensitivity and specificity of discriminating patients with oral cavity cancer from the healthy controls was 63.5% and 87.3%, respectively. CONCLUSION: Plasma soluble E-cadherin levels were significantly higher in patients with oral cavity cancer when compared with those from the matched non-cancerous participants. [ABSTRACT FROM AUTHOR]

To characterize the somatic alterations of papillary thyroid carcinomas (PTC) in Chinese patients, we performed the next-generation-sequencing (NGS) study of the tumor-normal pairs of DNA and RNA samples extracted from 16 Chinese PTC patients. The whole genome sequencing (WGS) and transcriptome sequencing (RNA-seq) were conducted for 6 patients who were either current or former smokers and the whole exome sequencing (WES) and RNA-seq were conducted for another 10 patients who were never smokers. The NGS data were analyzed to identify somatic alteration events that may underlie PTC in Chinese patients. We identified a number of PTC driver genes harboring somatic driver mutations with significant functional impact such as COL11A1, TP53, PLXNA4, UBA1, AHNAK, CSMD2 and TTLL5 etc. Significant driver pathways underlying PTC were found, namely, the metabolic pathway, the pathway in cancer, the olfactory transduction pathway and the calcium signaling pathway. In addition, this study revealed genes with significant somatic copy number aberrations and corresponding somatic gene expression changes in PTC tumors, the most promising ones being BRD9, TRIP13, FZD3, and TFDP1 etc. We also identified several structural variants of PTCs, especially the novel in-frame fusion proteins such as TRNAU1AP-RCC1, RAB3GAP1-R3HDM1, and ENAH-ZSWIM5. Our study provided a list of novel PTC candidate genes with somatic alterations that may function as biomarkers for PTC in Chinese patients. The follow-up mechanism studies may be conducted based on the findings from this study. [ABSTRACT FROM AUTHOR]

Background: Lung cancer remains the most common cause of cancer-related death, with a 5-year survival rate of only 18%. In recent years, the development of targeted pharmacological agents and immunotherapies has substantially increased the survival of a subset of patients. However, most patients lack such efficacious therapy and are, thus, treated with classical chemotherapy with poor clinical outcomes. Therefore, novel therapeutic strategies are urgently needed. In recent years, the development of epigenetic assays and their application to cancer research have highlighted the relevance of epigenetic regulation in the initiation, development, progression and treatment of lung cancer. Conclusions: A variety of epigenetic modifications do occur at different steps of lung cancer development, some of which are key to tumor progression. The rise of cutting-edge technologies such as single cell epigenomics is, and will continue to be, crucial for uncovering epigenetic events at a single cell resolution, leading to a better understanding of the biology underlying lung cancer development and to the design of novel therapeutic options. This approach has already led to the development of strategies involving single agents or combined agents targeting epigenetic modifiers, currently in clinical trials. Here, we will discuss the epigenetics of every step of lung cancer development, as well as the translation of these findings into clinical applications. [ABSTRACT FROM AUTHOR]

BACKGROUND: Discoidin domain receptors (DDRs), a collagen receptor tyrosine kinase, play a major role in cancer progression. DDR2 has been suggested as a prognostic marker in several cancer types; however, the correlation between DDR2 expression and clinical outcome of oral cancer patients in Taiwan population has not been investigated. MATERIALS AND METHODS: In the present study we sought to determine the clinical significance of Discoidin Domain Receptor Tyrosine Kinase 2 (DDR2) expression in oral squamous cell carcinoma (OSCC) patients. We examined DDR2 expression in OSCC specimens by immunohistochemistry and then we analyzed the association of DDR2 expression with clinicopathological factors in OSCC. RESULTS: We divided 254 OSCC cases into two groups based on DDR2 expression levels and compared with several clinicopathological factors and their overall survival. The group with high DDR2 expression had significantly higher frequencies of lymph node metastasis ( P = 0.0094) and AJCC stage ( P = 0.0058) compared to the group with low DDR2 expression. Furthermore, the lymph node metastasis oral cancer patients with high DDR2 expression had low survival rate than low DDR2 group ( P = 0.0458). CONCLUSIONS: Our data indicate that DDR2 is a potent biomarker that can be used as an effective therapeutic target for treating OSCC patients with lymph node metastasis. [ABSTRACT FROM AUTHOR]

Background: Osteopontin (OPN) is a secreted glycophosphoprotein that has been implicated in the regulation of cancer development. The function of OPN is primarily regulated through post-translational modification such as glycosylation. As yet, however, the relationship between OPN glycosylation and lung cancer development has not been investigated. In this study, we addressed this issue by studying the effect of a triple mutant (TM) of OPN, which is mutated at three O-glycosylation sites, on lung cancer development in K- ras mice, a murine model for human non-small cell lung cancer. Methods: Aerosolized lentivirus-based OPN TM was delivered into the lungs of K- ras mice using a nose-only-inhalation chamber 3 times/wk for 4 wks. Subsequently, the effects of repeated delivery of OPN TM on lung tumorigenesis and its concomitant OPN-mediated signaling pathways were investigated. Results: Aerosol-delivered OPN TM inhibited lung tumorigenesis. In addition, the OPN-mediated Akt signaling pathway was inhibited. OPN TM also decreased NF-κB activity and the phosphorylation of 4E-BP1, while facilitating apoptosis in the lungs of K- ras mice. Conclusions: Our results show that aerosol delivery of OPN TM successfully suppresses lung cancer development in the K- ras mouse model and, therefore, warrant its further investigation as a possible therapeutic strategy for non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL), especially T-acute lymphoblastic leukemia (T-ALL), is a common childhood malignant neoplastic disorder. Chemotherapy agents, particularly those that can induce apoptosis, are the major intervening strategy in the treatment of ALL. In this study, we investigated in T-ALL cell line, CCRF-CEM, the in vitro cytotoxic effect and the mechanism of action of baicalin, a compound extracted from Scutellaria baicalensis Georgi and S. rivularis Benth (Labiateae). Results demonstrated that baicalin displayed a remarkable cytotoxic effect in CCRF-CEM, with an IC(50) value of 10.6 microg/ml. It triggered apoptotic effect by fragmentizing cellular DNA and arrested the cell cycle at G(0)/G(1) phase. Baicalin (37.5 microg/ml) had not effected the expression of p53 and Fas protein. It was shown to decline the expression of Bcl-2 (22.0 pg/ml), which consequently caused the loss (52.7%) of transmembrane potential (Delta Psi m) in the mitochondria after 72 hours of treatment. Baicalin (37.5 microg/ml) also elevated the amount of cytosolic cytochrome c (19.2 microg/ml), which finally triggered the activation of caspase-3 (50.1 pmol/min). In conclusion, baicalin was found to induce apoptosis in T-ALL cell lines through multiple pathways. This finding encourages further investigation of baicalin in its role as a potential candidate for chemotherapeutic agents in T-ALL. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL), especially T-acute lymphoblastic leukemia (T-ALL), is a common childhood malignant neoplastic disorder. Chemotherapy agents, particularly those that can induce apoptosis, are the major intervening strategy in the treatment of ALL. In this study, we investigated in T-ALL cell line, CCRF-CEM, the in vitro cytotoxic effect and the mechanism of action of baicalin, a compound extracted from Scutellaria baicalensis Georgi and S. rivularis Benth (Labiateae). Results demonstrated that baicalin displayed a remarkable cytotoxic effect in CCRF-CEM, with an IC50 value of 10.6 μg/ml. It triggered apoptotic effect by fragmentizing cellular DNA and arrested the cell cycle at G0/G1 phase. Baicalin (37.5 μg/ml)had not effected the expression of p53 and Fas protein. It was shown to decline the expression of Bcl-2 (22.0 pg/ml), which consequently caused the loss (52.7%)of transmembrane potential (ΔΨm) in the mitochondria after 72 hours of treatment. Baicalin (37.5 μg/ml) also elevated the amount of cytosolic cytochrome c (19.2 μg/ml), which finally triggered the activation of caspase-3 (50.1 pmol/min). In conclusion, baicalin was found to induce apoptosis in T-ALL cell lines through multiple pathways. This finding encourages further investigation of baicalin in its role as a potential candidate for chemotherapeutic agents in T-ALL. [ABSTRACT FROM AUTHOR]