Ueda Y

Apoptosis of bladder cancer by sodium butyrate and cisplatin

The effects of sodium butyrate (SB), a histone deacetylase inhibitor, in combination with cisplatin (CDDP), for inhibition of cell growth and induction of apoptosis were investigated in bladder cancer cell lines in vitro. Bladder cancer cell lines T24, 253J, and UMUC3 were treated with different concentrations of CDDP or SB. Cell proliferation was studied by XTT assay. Cell-cycle analysis and induction of apoptosis were analyzed by laser scanning cytometry (LSC). Western blot analysis was used to determine expression of p21, p27, TRADD, FADD, caspase-2, and caspase-7. We observed that SB in combination with CDDP induced significant inhibition of cell growth in a dose-dependent manner through G1 arrest and apoptosis, as determined by LSC. When bladder cancer cell lines were treated with SB plus CDDP, Western blotting showed increased expression of p21 but not p27 in T24 cells, whereas both p21 and p27 increased in 253J and UMUC3 cells. All cell lines exhibited a moderate increase in TRADD and decrease in procaspase-2 but no significant change in FADD and procaspase-7. The results showed the synergistic anticancer effect of SB in combination with CDDP, their potential for treatment of bladder cancer, and their mechanism of action in terms of cell signal transduction and induction of apoptosis.

Primary carcinoid tumor of the urinary bladder with prominent subnuclear eosinophilic granules.

Primary carcinoid tumor of the urinary bladder is a very rare neoplasm. We report here a case of primary carcinoid tumor of the urinary bladder with an unusual cytological feature in a 72-year-old Japanese man. A bladder polypoid mass was incidentally found by ultrasonography during the follow-up of a benign prostate hyperplasia. Histological examination of the transurethrally resected tissue revealed that the upper part of the mass was a tumor showing tubuloglandular anastomosing structures. Most of the tumor cells had peculiar subnuclear eosinophilic granules. The features of the granules were reminiscent of those observed in neuroendocrine cells of the intestine. The tumor cells were immunohistochemically positive for chromogranin A and synaptophysin. The tumor was diagnosed as carcinoid tumor of pure form of the urinary bladder. The lower part of the mass showed the findings of glandular cystitis, as its coexistence with carcinoid tumors of the bladder has often been described in previous reports.

Successful ABO-incompatible kidney transplantation in patient with congenital afibrinogenemia.

Dear Editors, Congenital afibrinogenemia is a rare coagulation disorder with an estimated prevalence of 1 in 1 million. Fibrinogen plays an important role in clot formation through its conversion to fibrin by the action of thrombin and is also involved in normal wound repair. Fibrinogen replacement therapy is the only treatment for bleeding episodes in affected patients. However, that therapy elevates the risk of thrombosis. Herein, we report successful ABO-incompatible kidney transplantation in a patient with congenital afibrinogenemia. A 33-year-old male was diagnosed with congenital afibrinogenemia shortly after birth and treated with fibrinogen replacement therapy when bleeding episodes occurred. End-stage renal disease caused by unidentified chronic glomerulonephritis was a comorbid condition, and continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) were required from the age of 32. He had been given fibrinogen during each HD session for hemostasis. The patient, blood type A, underwent ABOincompatible living related kidney transplantation in January 2009 from his father, who was blood type AB. Pretransplant anti-B agglutinin titers were 1:4 for IgG and 1:4 for IgM. Human leukocyte antigen (HLA)-A, -B, and -DR typing showed one identical haplotype. Pretransplant Tand B-cell cross matching using complement-dependent-cytotoxicity and flow cytometry cross-match were negative. The pretransplant desensitization regimen consisted of mycophenolate mofetil, and methylprednisolone started at 14 days before transplantation, cyclosporine for 3 days, two doses (each 100 mg/m) of rituximab (RIT) was given 14 and 7 days, respectively, before transplantation, and two sessions of double filtration plasmapheresis. The fibrinogen replacement therapy started at 1 day before transplantation in addition to each HD session. On the day of transplantation, anti-B agglutinin titers were decreased to 1:<1 for IgG and 1:1 for IgM, thus it was considered to be safe to perform. The CAPD catheter was removed before the procedure. The total operation time was 11 h 25 min, and total and warm ischemic times were 135 and 7 min, respectively. Estimated blood loss was 570 ml. One week after transplantation, the level of serum fibrinogen was controlled above 100 mg/dl by fibrinogen replacement therapy (Fibrinogen HT i.v. Benesis , Benesis Corporation, Osaka, Japan) and anti-coagulation therapy was started concurrently on day 1. Although a ureteral stent was inserted because of urinary leakage, no other wound repair problems, abnormal bleeding, or thrombosis was observed during the posttransplant course with fibrinogen replacement and anticoagulation therapy. The clinical course of the patient is detailed in the Figure. The ureteral stent was removed on postoperative day 34 following disappearance of urinary leakage. Protocol graft biopsies were performed safely on the day of and 8 months after transplantation with fibrinogen replacement. The biopsy specimen had normal findings. At 15 months after transplantation, graft function was stable, with a Cr level of 1.7 mg/dl and fibrinogen replacement therapy being administered once or twice a month. Anti-B agglutinin titers were stable to 1:4 for IgG and 1:4 for IgM. Congenital afibrinogenemia, first described by Rabe in 1920 [1], is a rare bleeding disorder with an estimated prevalence of 1 in 1 million. The disease is characterized by the complete absence of fibrinogen production by a mutation in genes that encode the polypeptide chains of fibrinogen. The condition is considered to be inherited as an autosomal recessive trait, and is characterized by bleeding events that often start at birth with uncontrolled umbilical cord hemorrhaging. Bleeding may also occur after a scarcely noticed trauma or small intervention into the skin, mucosa, muscle, or brain, with the latter often fatal. This is the first report of kidney transplantation in a patient with congenital afibrinogenemia, who was diagnosed at birth from umbilical cord hemorrhaging. Fibrinogen plays an important role in clot formation through its conversion to fibrin by the action of thrombin as well as in normal wound healing, with reports of wound healing following surgery [2]. Fibrinogen replacement therapy is effective for treating bleeding episodes in congenital afibrinogenemia, in which the patient receives fresh frozen plasma (FFP), cryoprecipitate, or fibrinogen concentrate. Fibrinogen concentrate is the treatment of