A phase I study of binimetinib (MEK162) in Japanese patients with advanced solid tumors.

PURPOSE: Binimetinib is a potent, selective MEK1/2 inhibitor with demonstrated efficacy against BRAF- and RAS-mutant tumors. Retinal adverse events associated with MEK inhibitors have been reported in some cases. The aim of this study was to assess single-agent binimetinib, with detailed ophthalmologic monitoring, in Japanese patients with advanced solid tumors. METHODS: This was an open-label phase I dose-escalation and dose-expansion study (NCT01469130). Adult patients with histologically confirmed, evaluable, advanced solid tumors were enrolled and treated with binimetinib 30 or 45 mg twice daily (BID). The primary objective was to determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of single-agent binimetinib in Japanese patients. RESULTS: Twenty-one patients were enrolled; 3 and 8 patients had documented BRAF and KRAS mutations, respectively. Two of 6 patients (33 %) receiving binimetinib 45 mg BID in dose-escalation experienced recurrent grade 2 retinal adverse events (AEs) which were reversible, and this dose was declared the MTD and RP2D. All patients experienced ≥1 AE suspected to be treatment related; the most common (>50 %) were blood creatine phosphokinase increase (76 %), retinal detachment and aspartate aminotransferase increase (62 % each), and diarrhea (52 %). There were no complete or partial responses; 14 patients (67 %) had stable disease, which lasted >180 days in 5 patients. Expression of phospho-ERK decreased in the skin following binimetinib treatment at both dose levels, indicating target inhibition. CONCLUSIONS: Binimetinib demonstrated efficacy and acceptable safety in Japanese patients with solid tumors, supporting the 45 mg BID dose of binimetinib as the RP2D.

Band structure of the heavily-electron-doped FeAs-based Ba(Fe,Co)2As2 superconductor suppresses antiferromagnetic correlations.

In the heavily-electron-doped regime of the Ba(Fe,Co)2As2 superconductor, three hole bands at the zone center are observed and two of them reach the Fermi level. The larger hole pocket at the zone center is apparently nested with the smaller electron pocket around the zone corner. However, the (pi,0) Fermi surface reconstruction reported for the hole-doped case is absent in the heavily-electron-doped case. This observation shows that the apparent Fermi surface nesting alone is not enough to enhance the antiferromagnetic correlation as well as the superconducting transition temperature.

[The event-related potential characteristics of reading disabilities in children under condition of continuous performance test].

OBJECTIVE: To investigate the characteristics of event-related potential (ERP) of reading disabilities (RD) in children under the condition of continuous performance test (CPT) and their possible neurological basis. METHODS: Using ERP technique with CPT conditions, such as semantics, direction and pitch identification, 16 RD boys and their matched normal boys were tested. A comparative study was conducted to analyze these indicators of accuracy, reaction time, false alarm, wave amplitude and latency between the two groups. RESULTS: Among the three kinds of identification tests, RD children had lower accuracy in pitch identification (65.4 +/- 15.9) to (78.5 +/- 12.6) and lower reaction speed (557.0 +/- 97.8) ms to (493.0 +/- 47.8) ms, as compared to the control group (P < 0.05). The false alarm rate was much higher in RD children than that in the control group with unattended-high simulation (1.1 +/- 0.7)% to (0.6 +/- 0.3)%, P < 0.05. Moreover, the P300 amplitude decreased with direction of (20.8 +/- 7.3) to (27.7 +/- 8.3) microV and pitch of (9.1 +/- 4.3) to (14.6 +/- 8.3) microV, P < 0.05. And, the latency delayed in pith of (571 +/- 78) ms to (512 +/- 62) ms, semantic cognition processing negativity Nd of (398 +/- 76) ms to (342 +/- 67) ms, pitch Nd of (373 +/- 56) ms to (327 +/- 53) ms, P < 0.05. CONCLUSIONS: There was defect in selective attention of RD children, which suggested relationship between dysfunction of frontal-basal ganglia circle and RD. The ERP combined with CPT was much better than that with single target stimulation to indicate children's cognitive characteristics.

[A case of primary pleural leiomyosarcoma].

A 70-year-old man was admitted to our hospital with complaints of chest pain and exertional dyspnea. Chest radiography and computed tomography (CT) revealed right pleural effusion and pleural thickening on admission. The pleural fluid was bloody. Microbiological and cytologic examinations of the fluid were negative. The chest CT revealed progress of pleural thickening after hospitalization. A thoracoscopic pleural biopsy was performed, and the histological finding of the excised specimen was leiomyosarcoma. Because no organ of origin of the leiomyosarcoma, other than the pleura, was detected, this case was diagnosed as a primary pleural leiomyosarcoma. It is thought that leiomyosarcoma originating from the pleura is rare.

[A case of tuberculous peritonitis diagnosed by ultrasonography-guide peritoneal biopsy].

The diagnosis of tuberculous peritonitis is quite difficult because the symptoms are not specific for the disease and the incidence of occurrence are relatively rare. We report a case of tuberculous peritonitis diagnosed by ultrasonography-guided peritoneal biopsy. A 64-year-old male was admitted to our hospital because of fever, dyspnea and abdominal pain. Laboratory findings revealed an elevated ESR (53 mm/1 hr.) and positive CRP. The tuberculin skin test was negative. The chest radiograph revealed bilateral pleural effusion. Abdominal ultrasonographic examination and computed tomography showed ascitic fluid, thickening of the mesentery and peritoneum, and inflammatory pseudotumor of the omentum. Ascitic fluid was exudate with a high lymphocyte count and elevated ADA (184 IU/l). Microbiological studies with the fluid were negative. Peritoneal biopsy guided by ultrasonography was performed, and the specimens showed central caseous necrosis surrounded by epitheloid cells and acid-fast bacilli were demonstrated. The size of the pseudotumor, pleural effusion and ascites decreased after antituberculous chemotherapy with corticosteroid was given. Diagnosis of tuberculous peritonitis has often been made by laparotomy or laparoscopy. In a case of this kind, percutaneous peritoneal biopsy guided by ultrasonography is safe and useful.

A case report of a presumptive +i(18p) associated with serum IgA deficiency.

The case of a 4-month-old male infant with retarded psychomotor development and multiple anomalies is presented. Cytogenetic studies on peripheral blood and skin cultures revealed a normal male complement with a supernumerary small metacentric chromosome. According to its size and its banding patterns, the metacentric chromosome was postulated to be an isochromosome for the short arm of number 18. A deficiency of serum IgA was observed in this patient.