The Histone Deacetylase Inhibitor Trichostatin A Sensitizes Human Renal Carcinoma Cells to TRAIL-Induced Apoptosis through Down-Regulation of c-FLIP(L)

Histone acetylation plays a critical role in the regulation of transcription by altering the structure of chromatin, and it may influence the resistance of some tumor cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) by regulating the gene expression of components of the TRAIL signaling pathway. In this study, we investigated the effects and molecular mechanisms of trichostatin A (TSA), a histone deacetylase inhibitor, in sensitizing TRAIL-induced apoptosis in Caki human renal carcinoma cells. Our results indicate that nontoxic concentrations of TSA substantially enhance TRAIL-induced apoptosis compared with treatment with either agent alone. Cotreatment with TSA and TRAIL effectively induced cleavage of Bid and loss of mitochondrial membrane potential (MMP), which was associated with the activation of caspases (-3, -8, and -9) and degradation of poly (ADP-ribose) polymerase (PARP), contributing toward the sensitization to TRAIL. Combined treatment with TSA and TRAIL significantly reduced the levels of the cellular Fas-associated death domain (FADD)-like interleukin-1beta-converting enzyme (FLICE) inhibitory protein (c-FLIP), whereas those of death receptor (DR) 4, DR5, and FADD remained unchanged. The synergistic effect of TAS and TRAIL was perfectly attenuated in c-FLIP(L)-overexpressing Caki cells. Taken together, the present study demonstrates that down-regulation of c-FLIP contributes to TSA-facilitated TRAIL-induced apoptosis, amplifying the death receptor, as well as mitochondria-mediated apoptotic signaling pathways.

Hemichorea Associated with Hyperglycemia: A Case Showing Increased Blood Flow in the Contralateral Striatum

We report a diabetic woman who developed paroxysmal hemichorea during an episode of non-ketotic hyper-glycemia. A MRI showed a high signal intensity on T1-weighted images and a low signal intensity on T2-weighted images in the contralateral putamen. SPECT on the 30th day after the onset revealed an increased blood flow in the contralateral striatum. Although these abnormalities in the left putamen are considered to be the cause of her involuntary movement, the exact pathophysiological mechanisms of these abnormalities are not yet clear and further investigations are needed.

Clinical Study of Mucocutaneous Lymph Node Syndrome

We observed clinically 27 cases of MCLS at this pediatric department from Jan. 1980 to Jun. 1984 and following result were obtained. 1) The peak incidence of these cases was from 1 year to 4 year of age(74%) and male children were affected more frequently than female children at a ratio of 2.4:1. 2) Clinical manifestation of MCLS were high fever, conjunctioval injection, changes of oral cavity and lips, erythematous rash, cervical lymphadenopathy, changes of the extremities. 3) The abnormal laboratory findings include leukocytosis, slight anemia, raised ESR, positive CRP, mild proteinuria or pyeuria, and slight increase of serum transaminase and LDH. 4) The abnormal cardiovascular findings were as follow : heart murmur in 15% cardiomegaly in 19% by chest roentgenogram, electrocardiographic abnormalities in 59%, suspicious aneurysmal dilatation and coronary aneurysm by 2-D echocardiogram in 11%. 5) Aspirin was given in acute febrile stage as antiinflammatory dose(100mg/kg/day), in non-febrile convalescent stage to maintain low dose of aspirin(20-30mg/kg/day) as antiplatelet effect, and completely recovered in all cases without andy complication.