Targeting Non-Oncogene Addiction for Cancer Therapy.

While Next-Generation Sequencing (NGS) and technological advances have been useful in identifying genetic profiles of tumorigenesis, novel target proteins and various clinical biomarkers, cancer continues to be a major global health threat. DNA replication, DNA damage response (DDR) and repair, and cell cycle regulation continue to be essential systems in targeted cancer therapies. Although many genes involved in DDR are known to be tumor suppressor genes, cancer cells are often dependent and addicted to these genes, making them excellent therapeutic targets. In this review, genes implicated in DNA replication, DDR, DNA repair, cell cycle regulation are discussed with reference to peptide or small molecule inhibitors which may prove therapeutic in cancer patients. Additionally, the potential of utilizing novel synthetic lethal genes in these pathways is examined, providing possible new targets for future therapeutics. Specifically, we evaluate the potential of TONSL as a novel gene for targeted therapy. Although it is a scaffold protein with no known enzymatic activity, the strategy used for developing PCNA inhibitors can also be utilized to target TONSL. This review summarizes current knowledge on non-oncogene addiction, and the utilization of synthetic lethality for developing novel inhibitors targeting non-oncogenic addiction for cancer therapy.

Electrochemical degradation of ibuprofen using an activated-carbon-based continuous-flow three-dimensional electrode reactor (3DER).

We developed a continuous-flow three-dimensional electrode reactor (3DER) to remove ibuprofen (IBP) from water. The effects of the operating parameters on the 3DER performance were investigated. The 3DER was constructed by filling a conventional two-dimensional electrode reactor with granular activated carbon, which acted as particle electrodes. The IBP removal efficiency of the 3DER was 98% in 4 h, which was 2.5 times higher than the removal efficiency for the two-dimensional electrode reactor. IBP removal kinetics tests indicated that the current density (1-20 mA/cm2) correlated better than the other operating parameters with the first-order rate constant (k). The flow rate affected the IBP removal kinetics to a small degree. Chloride and sulfate supporting electrolyte concentrations between 17 and 100 mM affected the IBP removal kinetics in opposite ways. Increasing the chloride concentration increased k, but increasing the sulfate concentration decreased k. Radical quenching experiments indicated that much more IBP degradation occurred through both indirect and direct oxidation mechanisms in the 3DER than in the two-dimensional electrode reactor. The particle electrodes caused hydroxyl radicals to form when the 3DER treatment was started, but the particle electrodes later acted as third electrodes and favored direct oxidation of IBP.

Different treatment protocols for different pulpal and periapical diagnoses of 72 cracked teeth.

INTRODUCTION: The treatment plan for cracked teeth depends on the extent of the crack. A tooth with an extensive crack of long duration may be more likely to require root canal treatment. The purpose of this study was to analyze the characteristics of cracked teeth and to assess the outcome of different treatment protocols depending on the pulpal and periapical diagnoses. METHODS: Seventy-two of 476 crown-restored teeth were diagnosed as cracked teeth. The location of the cracked teeth, age and sex of the patients, restoration materials, a diagnosis of pulp and apex, and the periodontal probing depth were analyzed. Cracked teeth were treated by different treatment protocols depending on the pulpal and periapical diagnoses. RESULTS: Mandibular first molars (27.8%) were the most frequently involved teeth followed by maxillary first molars (25%), maxillary second molars (22.2%), and mandibular second molars (19.4%). The most frequently involved ages were 40-49 and 50-59 years. Cracks occurred mainly in nonbonded restorations such as gold (26.4%) and amalgam (12.5%), and 48.6% of cracks were found in intact teeth. In this study, 60 teeth (83.3%) were treated with root canal treatment before being restored with a permanent crown, and only 12 teeth (16.7%) remained vital and were restored with a permanent crown without root canal treatment. The proportion of teeth treated with root canal treatment increased along with a deep periodontal probing depth corresponding to the crack. The prognosis was less favorable in cracked teeth with a deep probing depth. CONCLUSIONS: In this study, the proportion of root canal treatment in the cracked teeth was higher than other studies. Many patients are referred to an endodontist in a university hospital after a long time has passed since the symptom started. Early recognition can help to avoid the propagation of a crack into the pulp chamber or subgingival level. Furthermore, it is important to investigate factors related to cracked teeth and develop different treatment protocols for different pulpal and periapical diagnoses.