In this multicenter, single‐arm, phase II study, the efficacy and safety of ibrutinib were examined in Japanese patients with relapsed or refractory mantle cell lymphoma (MCL). Patients (age ≥20 years) with relapsed or refractory MCL who had progressed after receiving at least one prior treatment regimen, were enrolled. Patients were treated with oral ibrutinib (560 mg once daily; 28‐day cycle) until disease progression (or relapse), unacceptable toxicity, or study end. The primary end‐point was overall response rate. Secondary end‐points included duration of response (DOR), time to response, progression‐free survival (PFS), overall survival, and safety. Of the 16 patients who received treatment, 5 patients discontinued the study (progressive disease, 4; sepsis, 1). Median duration of ibrutinib exposure was 6.5 months (range, 2.8–8.3 months). The overall response rate was 87.5% (90% confidence interval, 65.6–97.7; complete response = 2 [12.5%]; partial response = 12 [75.0%]). Median time to response for all responders (n = 14) was 1.8 months (range, 0.7–5.3 months). The median DOR and PFS were not estimable due to censoring (range: DOR, 1.1–6.4+ months; PFS, 2.8–8.0+ months). Overall survival data were immature due to the limited observation period. A total of 8/16 patients (50%) had at least one grade 3 adverse event (AE), and 5 (31.3%) patients reported serious AEs. The most commonly reported AEs were diarrhea and stomatitis (37.5% each), platelet count decrease (31.3%), and anemia (25%). Overall, orally administered single agent ibrutinib was efficacious with an acceptable safety profile in Japanese patients with relapsed or refractory MCL. Clinical trial registration NCT02169180 (ClinicalTrials.gov).

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The injection of B16F10 melanoma cells with recombinant human tumor necrosis factor alpha (TNF-alpha) into the tail vein of C57BL/6 mice resulted in 2- to 25-fold more metastatic foci in the lungs than the injection of tumor cells alone. Clearly, TNF-alpha significantly enhanced experimental tumor metastasis. Furthermore, it enhanced the metastasis of Lewis lung carcinoma cells. In contrast, a mutein of TNF-alpha, designated as F4236, having the cell-adhesive sequence (Tyr-Ile-Gly-Ser-Arg) at the N-terminus of the TNF molecule did not enhance metastasis, but rather exhibited similar antitumor activity to wild-type TNF-alpha in fibrosarcoma-bearing mice.

As part of a basic study on the prevention of cerebral injury, ajoene (0.5 mg/d) and oil-macerated garlic extract (OMGE, containing 0.5 mg ajoene/d) were administrated to stroke-prone spontaneously hypertensive rats (SHRSP) among 8 weeks from 9 weeks of age. In the control group, 3 of 10 rats died (30%), whereas all SHRSP treated by ajoene or OMGE survived. Our results suggested that ajoene and OMGE-treatment reduced the mortality and cerebral injury in SHRSP. The levels of thiobarbituric acid reactive substance (TBARS) and the enzymatic activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) in the serum of stroke stage of SHRSP were measured. The results obtained were as follows; the TBARS level of the ajoene and OMGE-treated groups were lower than those of control groups. On the other hand, the GSH-Px and SOD activities of the ajoene and OMGE-treated groups were higher. Our results suggested that ajoene and OMGE were capable of having prophylactic effects on cerebral injury in SHRSP.

Acute pulmonary embolism is a serious perioperative complication. Current guidelines focus on hemodynamic stabilization and rapid restoration of pulmonary artery blood flow. However, various complications, most notably bleeding, are associated with treatment of the embolism. We report a case of acute pulmonary embolism with cardiopulmonary arrest during orthopedic surgery. Prompt thrombolysis and gaining control of both thrombolytic therapy-induced bleeding from the wound and a hepatic cyst enabled the patient to recover without neurological deficits.