Toshiki Tanikawa

Pinpoint targeted immunosuppression: anti‐CD20/MMF desensitization with anti‐CD25 in successful ABO‐incompatible kidney transplantation without splenectomy

Abstract: Background: In Japan, ABO‐incompatible (ABO‐I) kidney transplantation began in 1989; these transplantations have flourished because of the lack of cadaveric donors, and more than 600 cases were performed up to 2004. Splenectomy has been considered to be necessary for successful ABO‐I kidney transplantation, and the majority of pre‐conditioning protocols include splenectomy in Japan. However, we have lost some grafts due to antibody‐mediated rejection (AMR) accompanying explosive elevation of anti‐A/B antibody (Ab) titer even though the patients had a low pre‐operative Ab titer.

Immunohistochemical Detection of Intercellular Adhesion Molecule-1 (ICAM-1) and Major Histocompatibility Complex Class I Antigens in Seminoma

Expression of intercellular adhesion molecule-1 (ICAM-1) and major histocompatibility complex (MHC) antigens, and characterization of tumor-infiltrating mononuclear cells (TIM) were examined immunohistologically in 10 specimens of seminoma. ICAM-1 and MHC antigens were not detected on normal spermatogenic cells. ICAM-1 and MHC class I antigens were variably expressed in 7 and 9 seminomas, respectively, whereas class II antigens were not detected. Although the degree of expression of ICAM-1 and MHC antigens was not correlated with any clinical or histopathological factors, neither of the antigens was detected on an anaplastic seminoma. Various numbers of TIM were detected in all of the seminoma, and comprised mainly T cells bearing the lymphocyte function-associated antigen (LFA)-1. No significant correlation was noticed between the degree of lymphocyte infiltration and ICAM-1 or MHC antigen expression. Although ICAM-1 and MHC class I antigens were expressed in seminoma, possibly facilitating an anti-tumor reaction of host, their expression remained low in several cases, despite marked lymphocyte infiltration within the tumor.

Correlation of p53 protein expression in human urothelial transitional cell cancers with malignant potential and patient survival.

The p53 gene product has been detected frequently in various human malignancies. We have studied the expression of p53 protein in urothelial transitional cell cancers (TCCs) and examined its correlation with pathologic grade, stage(pT) and patient survival. Specimens from 69 surgically‐resected TCCs (38 cases of urinary bladder cancer, 17 cases of ureteral cancer and 14 cases of renal pelvic cancer) were examined by immunohistochemical staining, using two anti‐p53 monoclonal antibodies, PAb1801 and PAb240, and a polyclonal antibody, CM‐1. Twenty‐six TCCs (37.6%) were positively stained by at least one of the three antibodies. Statistical analysis showed a significant correlation between p53 expression and high pathologic grade (p less than 0.05, p less than 0.001) or progressive pathologic stage (p less than 0.01). In addition, in 51 of the patients who were available for follow‐up (23 cases of urinary bladder cancer, 13 cases of ureteral cancer, and 15 cases of renal pelvic cancer), the correlation between p53 protein expression and prognosis was examined. The survival of patients exhibiting positive p53 protein expression was significantly worse than those with p53‐negative tumors (p less than 0.05). These results suggest that an immunohistochemical test for p53 protein may be a useful method of evaluating the malignant potential of TCCs. Additionally, expression of p53 protein in TCCs is an indicator of a poor prognosis which should be considered in drawing up treatment strategies.

mRNA and protein expression of p53 mutations in human bladder cancer cell lines

We investigated mRNA and protein expression in p53 gene mutations in four human bladder cancer cell lines using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and Northern blot and Western blot analyses. The following mutations were identified in three of the four cell lines: a missense transversion at codon 110, a missense transition at codon 250 and a non-sense transversion at codon 126. These mutations were located outside previously identified hot spot codons and have rarely been reported in bladder cancer tissues or other neoplasms. Positive intranuclear p53 immunostaining in neoplastic cells in the two missense mutations and the premature stop codon in the non-sense mutation suggested the presence of structural and functional alterations in the p53 protein. Northern and Western blot analyses revealed either an intense or a weak p53 mRNA band together with an intense p53 protein band in the missense mutations, but no p53 mRNA or protein band in the non-sense mutation. A weak p53 mRNA band, but no distinct p53 protein band was observed in the cell line without a mutation and in normal control bladder cells. Our findings suggest that regulation of p53 expression in these cell lines differs at the post-transcriptional and/or post-translational level between the wildtype and the mutant p53 genes and also among different mutant p53 genes. The three cell lines with mutations were derived from high-grade carcinomas; the cell line without mutation was derived from a low-grade carcinoma.

Adoptive Immunotherapy of Patients with Metastatic Renal Cell Cancer Using Lymphokine-Activated Killer Cells, lnterleukin-2 and Cyclophosphamide: Long-Term Results

Background Initial results of adoptive immunotherapy using lymphokine‐activated killer (LAK) cells and interleukin‐2 (IL‐2) appeared to offer promise for treating renal cell cancer (RCC). However, lower response rates were seen in subsequent trials, and the long‐term results of this treatment method have not been fully reported. In this study, we examine long‐term results of adoptive immunotherapy using LAK cells, IL‐2, and cyclophosphamide (LAK/IL‐2/CPM therapy).

Expression of E-Cadherin and Catenins on Testis Tumor

E-cadherin (ECD) is a homophilic Ca2+-dependent adhesion molecule associated with cell-to-cell interactions and normal growth. Recent reports have suggested that decrease or loss of ECD facilitates tumor progression and/or metastasis. ECD functions in a complex called an adherens junction, which includes several other proteins including α- and β-catenin. In the present study, fresh-frozen sections from 32 testis cancers, 16 seminomas and 16 non-seminomatous germ cell tumors (NSGCT), were examined immunohistochemically. E-cadherin was not expressed on normal germ cells, but expressed on 3 (18.8%) of 16 seminomas and 10 (62.5%) of 16 NSGCTs, mainly on the epithelial component of teratoma cells. α-Catenin was detected on 0 (0%) of 13 seminomas and 4 (25%) of 16 NSGCTs. β-Catenin was detected on 10 (71.4%) of 14 seminomas and 13 (81.2%) of 16 NSGCTs. ECD was detected significantly more frequently on NSGCTs than on seminomas. Immunoblot analysis confirmed the expression of ECD and β-catenin in NSGCTs. Expression of ECD and catenins may reflect the degree of differentiation and provide some information on the character of the tumor.

Mixed epithelial and stromal tumor of the kidney in a 12-year-old girl.

Mixed epithelial and stromal tumor of the kidney (MESTK) is a rare kidney neoplasm that almost exclusively occurs in perimenopausal women, and long‐term estrogen replacement is relevant to its pathogenesis. Herein is described an atypical case of MESTK uncovered in a 12‐year‐old premenarcheal girl without a history of prior estrogen use. On surgical specimen it was found that the well‐circumscribed tumor measuring 14 cm arose from the lower pole of the right kidney, showing solid and fibrous‐cystic areas. Microscopically, it was composed both of epithelial structures similar to renal tubules and stroma comprising non‐specific spindle cells. Some intratumoral tubules showed affinities to distal‐nephron‐specific lectins, and those immunoreactive for proximal‐tubule‐specific CD15 were also present. In addition, primitive ductal structures were reactive both for CD15 and lectins, but immature epithelial elements typical of nephroblastoma were absent. Spindle cells were positive for actin, desmin and vimentin, and expressed progesterone and estrogen receptors. The tumor was comparable with MESTK, although some epithelia were associated with the immunophenotype of proximal tubules. The patient was free of disease postoperatively for 40 months. In the present case, remnants of the primitive periductal mesenchyme might be promoted to neoplastic cells by a sex‐steroid surge during puberty.

Effect of preoperative chemotherapy on survival of patients with upper urinary tract urothelial carcinoma clinically involving regional lymph nodes

To determine the effect of preoperative chemotherapy on survival in patients with upper urinary tract urothelial carcinoma clinically involving regional lymph nodes.

Changes in urinary excretion of endothelin-1-like immunoreactivity in patients with testicular cancer receiving high-dose cisplatin therapy.

To assess the value of endothelin-1 (ET-1) in estimating renal injury in patients receiving high doses of cisplatin, urinary excretion of ET-1-like immunoreactivity (U-ET-1), beta 2-microglobulin (U-beta 2-MG), and N-acetyl-beta-d-glucosaminidase (NAG) were measured before, 1 week after, and 2 weeks after the administration of cisplatin in eight patients with testicular cancer (mean age, 33.3 years). Levels of U-ET-1/creatinine (Cr) during and 1 week after cisplatin treatment were significantly higher than before cisplatin treatment. There were no differences in U-ET-1/Cr levels during, 1 week after, and 2 weeks after cisplatin treatment. The level of U-beta 2-MG/Cr during cisplatin treatment was significantly higher than levels before, 1 week after, and 2 weeks after treatment. However, there were no differences in U-beta 2-MG/Cr levels before, 1 week after, and 2 weeks after cisplatin treatment. The level of U-NAG/Cr during cisplatin treatment was higher than levels before, 1 week after, and 2 weeks after treatment; U-NAG/Cr during cisplatin treatment was higher than levels before, 1 week after, and 2 weeks after treatment; U-NAG/Cr gradually decreased after cisplatin treatment. Among the three parameters, only U-ET-1/Cr maintained a higher level after cisplatin treatment. The U-beta 2-MG/Cr level returned most rapidly to normal after cisplatin treatment. Although U-ET-1/Cr did not show any significant correlation with U-NAG/Cr (r = 0.282, P = NS), it showed a significant correlation with U-beta 2-MG/Cr (r = 0.454, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of upper urinary tract dynamics by diuresis renography in patients receiving urinary reservoir operation : comparison of full and empty reservoir

Upper urinary tract dynamics was evaluated using diuresis renography during full and empty reservoir in 14 patients (11 men, 3 women, 13-70 years old) with intestinal urinary reservoir or intestinal bladder augmentation. Types of operation were Mainz pouch urinary diversion 5, Mainz neobladder to urethra, 5, Kock pouch urinary diversion 2, and Mainz bladder augmentation 2. Diuresis renography was performed using 99mTc-DTPA and furosemide during full and empty reservoir, and several parameters (Tmax, T75, T50, GFR) in addition to the patterns of renogram were evaluated. In the normal control, none of the parameters of the diuresis renogram with full bladder differed from those with empty bladder. In 5 of 14 patients, abnormal waves on cystometry (CMG) were found, and in 4 of these 5 patients, the patterns of diuresis renogram of full reservoir were worse than those of empty reservoir. However, the patterns of diuresis renogram of full reservoir were not different from those of empty reservoir in 9 patients without abnormal waves on CMG. In conclusion, renal injury may easily occur in patients with intestinal reservoir and abnormal waves on CMG.