Mammalian Target of Rapamycin Inhibitors Permit Regulatory T Cell Reconstitution and Inhibit Experimental Chronic Graft-versus-Host Disease

Chronic graft-versus-host disease (GVHD) remains a major late complication of allogeneic bone marrow transplantation (BMT). In a previous study, impaired thymic negative selection of the recipients permitted the emergence of pathogenic T cells that cause chronic GVHD using MHC class II-deficient (H2-Ab1 KO) B6 into OH model and CD4(+) T cells isolated from chronic GVHD mice caused chronic GVHD when administered into the secondary recipients. In this study, we evaluated the kinetics of regulatory T cell (Treg) reconstitution in wild type B6 into C3H model. After myeloablative conditioning, host Tregs disappeared rapidly, followed by expansion of Tregs derived from the donor splenic T cell inoculum. However, the donor splenic T cell derived Treg pool contracted gradually and was almost completely replaced by newly generated donor bone marrow (BM)-derived Tregs in the late post-transplantation period. Next, we compared the effects of cyclosporine (CSA) and mammalian target of rapamycin (mTOR) inhibitors on Treg reconstitution. Administration of CSA significantly impaired Treg reconstitution in the spleen and thymus. In contrast, BM-derived Treg reconstitution was not impaired in mTOR inhibitor-treated mice. Histopathological examination indicated that mice treated with GSA, but not mTOR inhibitors, showed pathogenic features of chronic GVHD on day 120. Mice treated with CSA until day 60, but not mTOR inhibitors, developed severe chronic GVHD followed by adoptive transfer of the pathogenic CD4(+) T cells isolated from H2-Ab1 KO into C3H model. These findings indicated that long-term use of CSA impairs reconstitution of BM-derived Tregs and increases the liability to chronic GVHD. The choice of immunosuppression, such as calcineurin inhibitor-free GVHD prophylaxis with mTOR inhibitor, may have important implications for the control of chronic GVHD after BMT

TWO CASES OF PRIMITIVE TRIGEMINAL ARTERY Two cases of persistent carotid basilar anastomosis are reported

The first case is 28 years old femal who admitted with porphyrin-uria and left sided visual disturbance which was occured suddenly with vomitting. The carotid cerebral angiograpby demonstrated the occulsion of left side int. carotid artery at the point of C(2) and the primitive trigeminal artery the same side. The anastomosis to the anterior cerebral artery and the middle cerebral artery are made through this anomalous artery and Willis circle. The second case is 20 years old female who admitted with Jacksonian type seizures and no neurological signs. The cerebral carotid angiography demonstrated the primitive trigeminal artery in right side

Phase II Study of Irinotecan plus S-1 Combination for Previously Untreated Advanced Non-Small Cell Lung Cancer: Hokkaido Lung Cancer Clinical Study Group Trial (HOT) 0601

Objective: Platinum-free regimens can represent an alternative for advanced non-small cell lung cancer (NSCLC) if similar efficacy is provided with better tolerability. This study evaluated the efficacy and safety of combined irinotecan and S-1 for chemotherapy-naïve advanced NSCLC. Methods: Chemotherapy consisted of 4-week cycles of intravenous irinotecan (100 mg/m2, days 1 and 15) and oral S-1 (80 mg/m2, days 1-14). The primary endpoint was response rate, while secondary endpoints were overall survival (OS), progression-free survival (PFS), and safety. Results: A total of 112 cycles was administered to 40 patients (median, 3 cycles; range 1-6 cycles). Twelve patients showed partial response (PR) and 17 patients exhibited stable disease (SD), representing a response rate of 30% and a disease control rate of 72.5%. Median survival time and median PFS were 16.1 months and 4.8 months, respectively. Hematological toxicities of grade 3 or 4 were neutropenia (32.5%) and anemia (5.0%). The most common non-hematological toxicities of grade 3 or 4 included diarrhea (15.0%) and anorexia (17.5%). Patients homo- or heterozygous for UGTA1A*6 tended to show a higher incidence of grade 3 diarrhea (p = 0.055). Conclusion: The combination of irinotecan and S-1 offers good efficacy and tolerability for previously untreated advanced NSCLC

Hepatic Hodgkin lymphoma with delayed enhancement on CT and MRI

Hepatic Hodgkin lymphoma is a rare disease, characterized by the presence of abundant granulofibrous stroma, and its radiological features have rarely been described. We report a 67-year-old man, who presented with liver masses that showed apparent delayed enhancement, along with systemic lymphadenopathy and musculoskeletal lesions. Repeated percutaneous needle biopsy, however, failed to confirm the diagnosis, and surgical biopsy finally revealed small amount of Hodgkin cells and Reed-Sternberg cells. In this report, the radiological features of hepatic Hodgkin lymphoma will be presented and discussed, in correlation with its histological findings