Ataxia-Telangiectasia Mutated and the Mre11-Rad50-NBS1 Complex:Promising Targets for Radiosensitization

Radiotherapy plays a central part in cancer treatment, and use of radiosensitizing agents can greatly enhance this modality. Although studies have shown that several chemotherapeutic agents have the potential to increase the radiosensitivity of tumor cells, investigators have also studied a number of molecularly targeted agents as radiosensitizers in clinical trials based on reasonably promising preclinical data. Recent intense research into the DNA damage-signaling pathway revealed that ataxia-telangiectasia mutated (ATM) and the Mre11-Rad50-NBS1 (MRN) complex play central roles in DNA repair and cell cycle checkpoints and that these molecules are promising targets for radiosensitization. Researchers recently developed three ATM inhibitors (KU-55933, CGK733, and CP466722) and an MRN complex inhibitor (mirin) and showed that they have great potential as radiosensitizers of tumors in preclinical studies. Additionally, we showed that a telomerase-dependent oncolytic adenovirus that we developed (OBP-301 [telomelysin]) produces profound radiosensitizing effects by inhibiting the MRN complex via the adenoviral E1B55kDa protein. A recent Phase I trial in the United States determined that telomelysin was safe and well tolerated in humans, and this agent is about to be tested in combination with radiotherapy in a clinical trial based on intriguing preclinical data demonstrating that telomelysin and ionizing radiation can potentiate each other. In this review, we highlight the great potential of ATM and MRN complex inhibitors, including telomelysin, as radiosensitizing agents

Laparoscopic and Endoscopic Cooperative Surgery for Gastric Submucosal Tumor Near Esophagogastric Junction With Sliding Hiatal Hernia

The usefulness of laparoscopic and endoscopic cooperative surgery (LECS) for gastric submucosal tumors in the cardiac region has been reported in recent years. However, LECS for submucosal tumors at the esophagogastric junction with hiatal sliding esophageal hernia has not been reported, and its validity as a treatment method is unknown. The patient was a 51-year-old man with a growing submucosal tumor in the cardiac region. Surgical resection was indicated because a definitive diagnosis of the tumor was not determined. The lesion was a luminal protrusion tumor, located on the posterior wall of the stomach 20 mm from the esophagogastric junction, and had a maximum diameter of 16.3 mm on endoscopic ultrasound examination. Because of the hiatal hernia, the lesion could not be detected from the gastric side by endoscopy. Local resection was considered to be feasible because the resection line did not extend into the esophageal mucosa and the resection site could be less than half the circumference of the lumen. The submucosal tumor was resected completely and safely by LECS. The tumor was diagnosed as a gastric smooth muscle tumor finally. Nine months after surgery, a follow-up endoscopy showed reflux esophagitis. LECS was a useful technique for submucosal tumors of the cardiac region with hiatal hernia, but fundoplication might be considered for preventing backflow of gastric acid

Significant enhancement of ferromagnetism in Zn1−x_{1-x}Crx_{x}Te doped with iodine as an n-type dopant

The effect of additional doping of charge impurities was investigated in a ferromagnetic semiconductor Zn$_{1-x}$Cr$_{x}$Te. It was found that the doping of iodine, which is expected to act as an n-type dopant in ZnTe, brought about a drastic enhancement of the ferromagnetism in Zn$_{1-x}$Cr$_{x}$Te while the grown films remained electrically insulating. In particular, at a fixed Cr composition of x = 0.05, the ferromagnetic transition temperature Tc increased up to 300K at maximum due to the iodine doping from Tc = 30K of the undoped counterpart, while the ferromagnetism disappeared due to the doping of nitrogen as a p-type dopant. The observed systematic correlation of ferromagnetism with the doping of charge impurities of both p- and n-type, suggesting a key role of the position of Fermi level within the impurity d-state, is discussed on the basis of the double exchange interaction as a mechanism of ferromagnetism in this material.Comment: 5 figures, to be published in Phys. Rev. Let

Direct Measurement of Thermal Fluctuation of High-Q Pendulum

We achieved for the first time a direct measurement of the thermal fluctuation of a pendulum in an off-resonant region using a laser interferometric gravitational wave detector. These measurements have been well identified for over one decade by an agreement with a theoretical prediction, which was derived by a fluctuation-dissipation theorem. Thermal fluctuation is dominated by the contribution of resistances in coil-magnet actuator circuits. When we tuned these resistances, the noise spectrum also changed according to a theoretical prediction. The measured thermal noise level corresponds to a high quality factor on the order of 10^5 of the pendulum.Comment: 10 pages, 4 figure