Kazunori Hattori

Antineoplastic activity of honey in an experimental bladder cancer implantation model: In vivo and in vitro studies

Objectives: The antitumor effect of bee honey against bladder cancer was examined in vitro and in vivo. Methods:u2003Three human bladder cancer cell lines (T24, 253J and RT4) and one murine bladder cancer cell line (MBT‐2) were used in these experiments. In an in vitro study, the antitumor activity was assessed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay, TdT‐mediated dUTP‐biotin nick end labeling (TUNEL) assay, 5‐Bromodeoxyuridine (BrdU) labeling index and flowcytometry (FCM). In the in vivo study, cancer cells were implanted subcutaneously in the abdomens of mice, and the effects were assessed by the tumor growth.

Immunocytochemical Demonstration of S Phase Cells by Antlbromobeoxyuribine Monoclonal Antibody in Human Prostate Adenocarcinoma

Using a monoclonal antibody to bromodeoxyuridine and immunohistochemistry, we measured the incorporation of this thymidine analogue into the deoxyribonucleic acid of human prostate adenocarcinoma cells exposed in situ. Fifteen patients with prostate cancer were given an intravenous infusion of 500 mg. bromodeoxyuridine at needle biopsy to label tumor cells in the deoxyribonucleic acid synthesis phase (S phase). The tumor specimens were fixed with 70 per cent ethanol, embedded in paraffin, sectioned and stained by an indirect immunoperoxidase method using anti-bromodeoxyuridine monoclonal antibody as the first antibody. The results showed that this method demonstrated bromodeoxyuridine-labeled nuclei satisfactorily in tissue section. The bromodeoxyuridine labeling index, S phase fraction, was determined by counting the number of bromodeoxyuridine-labeled cells in the tissue sections. Grade 3 tumors averaged 4.37 +/- 0.48 per cent labeling versus 2.41 +/- 0.49 per cent in grade 2 tumors, and grade 1 tumor in the series had an S phase fraction of 1.36 +/- 0.39 per cent. The average S phase fractions for single gland, cribriform, fused and medullary were 1.16, 2.30, 3.74 and 4.95 per cent, respectively. The results obtained with S phase fraction measured with bromodeoxyuridine labeling proved to be comparable to the results of histological grade and growth pattern. Thus, the higher S phase fraction may indicate biological malignancy. Moreover, the degree of heterogeneity concerning S phase fraction distribution within prostate cancer tissue could be compared to the morphological appearance. Our preliminary results suggest that the measurement of bromodeoxyuridine labeling index in prostate cancer may prove to be a new objective and quantitative assay of biological potential of individual tumor.

S Phase Fraction of Human Bladder Tumor Measured in Situ with Bromodeoxyuridine Labeling

A total of 18 patients with transitional cell bladder cancer was given a 0.5-hour intravenous infusion of bromodeoxyuridine at the time of endoscopic biopsy or transurethral resection to label tumor cells in the deoxyribonucleic acid synthesis phase (S phase). The tumor specimens were fixed with 70 per cent ethanol, embedded in paraffin, sectioned and stained by an indirect immunoperoxidase method with anti-bromodeoxyuridine monoclonal antibody as the first antibody. The bromodeoxyuridine labeling index, S phase fraction, was determined by counting the number of bromodeoxyuridine-labeled cells in the tissue sections. All grade 1 tumors had an S phase fraction of lower than 10 per cent. The average S phase fractions for noninvasive (11 cases) and invasive (7) tumors were 9.8 and 20.0 per cent, respectively. Two distant metastatic bladder tumors showed an average S phase fraction of 25.3 and 30.0 per cent. Thus, transitional cell bladder cancers with an S phase fraction of greater than 10 per cent appears to grow faster and be more invasive more often than those with an S phase fraction of less than 10 per cent. The higher S phase fraction may indicate greater biological malignancy. Our preliminary results suggest that measurement of the bromodeoxyuridine labeling index in bladder tumors may be a new objective and quantitative assay of biological potential of individual tumors.

Immunohistochemical Detection of Proliferating Cell Nuclear Antigen (Pcna)/Cyclin in Human Prostate Adenocarcinoma

Tissue specimens from 12 patients with adenocarcinoma of the prostate and 7 patients with benign prostate hypertrophy were stained by an indirect immunoperoxidase method using antiproliferating cell nuclear antigen (PCNA) monoclonal antibody. The PCNA labeling index was determined by counting the number of PCNA-labeled cells in the tissue sections. Average PCNA labeling index of the benign prostate hypertrophy was 1.2 +/- 0.5%. Poorly differentiated tumors averaged 7.6 +/- 3.9% labeling versus 4.6 +/- 1.3% in moderately differentiated tumors, and well differentiated tumor in the series had a PCNA labeling index of 2.5 +/- 0.9%. The PCNA labeling indices for atypical hyperplasia were 1.9, and 4.1%, respectively. Our preliminary results suggest that the measurement of PCNA labeling index in prostate cancer may prove to be a new objective and quantitative assay of biological potential of individual tumor.

Uroepithelial cells can directly respond to Mycobacterium bovis bacillus Calmette-Guérin through Toll-like receptor signalling

To investigate, in a human urinary tract cell line, the interaction of Toll‐like receptor (TLR) signals with cytoplasmic adapter proteins MyD88 and bacillus Calmette‐Guérin (BCG), and evaluate the epithelial cytokine response to BCG infection. Intravesical BCG therapy is effective against carcinoma in situ and as prophylaxis for recurrence, but although immunological mechanisms have been assumed, the mechanisms of the antitumour effects of BCG have not been completely elucidated.

Splenogonadal fusion: Case report and review of published works

Abstractu2002 Splenogonadal fusion is a rare congenital anomaly. We report herein a case of splenogonadal fusion associated with contra lateral testicular aplasia, and review the etiology, pathogenesis and management of this rare disease. As far as we know, this is the first reported case of splenogonadal fusion associated with testicular aplasia.

Bladder reconstruction using a collagen patch prefabricated within the omentum

Objective:u2002 We present our experience with a novel bladder reconstruction model using a collagen sponge pre‐embedded within the omentum. The aim of the study is to evaluate tissue regeneration of the reconstructed bladder and the effect of prefabricating the collagen patch within the omentum.

Lectin-reactive alpha-fetoprotein as a marker for testicular tumor activity

Abstractu2002 Background:u2002 Lens culinaris agglutin (LCA)‐affinity electrophoresis resolves serum α‐fetoprotein (AFP) into three isoforms, AFP‐L1, ‐L2 and ‐L3. The ratio of AFP‐L3 to total AFP (AFP‐L3%) is frequently high in hepatocellular carcinoma (HCC) patients, and thus, it is widely used for early diagnosis of HCC. In the present study, we used the subfraction profile of LCA‐binding AFP to diagnose and monitor testicular tumor activity.

Prognostic Significance of Nucleolar Organizer Region (AgNOR) in Renal Cell Carcinoma

PURPOSEnEvaluation of prognostic significance of nucleolar organizer regions (NORs) in renal cell carcinoma (RCC).nnnMATERIALS AND METHODSnNuclear organizer regions were quantified in a series of 59 cases of RCC by the silver colloid method, and the NOR index was obtained from the ratio between mean NOR counts in each neoplastic nucleus and in normal nucleus. The patients were staged pathologically and divided into 2 groups by average NOR index of all cases, which was 0.76. Correlations between the NOR index and other parameters were statistically analyzed, and the prognostic value of the NOR index was also examined.nnnRESULTSnThe NOR indices from each group were correlated with the survival curve. In low stage tumors (pT1 or 2 N0M0), the low NOR index group had a survival rate of almost 100 per cent while in those patients with higher NOR indices, there was a significantly increased mortality (p < 0.01). In patients presenting with high stage tumors (excluding pT1 and 2 N0M0), the survival rate was significantly improved in those patients with a low NOR index (p < 0.01). On the other hand, the patients with a low NOR index have a better prognosis than those with a high NOR index within each tumor grade (p < 0.01). Statistical analysis by the log rank test indicated NORs to be a significant predictor of survival over the whole series within low and high pathological stages and within each tumor grade. Analysis of the data with Coxs proportional hazard model showed that NOR index had a stronger hazard ratio than grade or stage of tumor (p = 0.0005).nnnCONCLUSIONSnOur study has demonstrated that NOR index is a new prognostic indicator for patients with RCC (p = 0.0005).

The Importance of Dose Intensity in Chemotherapy of Advanced Testicular Cancer

PVB regimen, the combination of cisplatin (CDDP), vinblastine (VLB) and bleomycin (BLM), has improved the treatment results of testicular cancer patients. However, modification of doses and schedules were strongly related with the treatment results. We analyzed the relative dose intensity (RDI) of each patient undergoing PVB regimen, in relation to the chemotherapeutic effect. In addition, a role of granulocyte colony-stimulating factor (G-CSF) on dose intensity of PVB regimen was analyzed. During the period 1981-1992, 33 patients with testicular cancer were treated with PVB regimen. Among the 25 evaluable patients, 5 (20%) achieved a complete response (CR), 15 (60%) had a partial response (PR), and the overall response rate was 80%. The average 5-year survival rate of all cases was 78.4%. The RDI in CR and PR cases were significantly higher than nonresponders in BLM (0.89 for CR and 0.91 for PR against 0.32 for NC + PD) in the combination of the three drugs (1.05 for CR and 0.97 for PR against 0.69 for NC + PD). The standard-dose group (RDI > or = 0.9) had a higher survival rate than the modified-dose group (RDI < 0.9). The RDI of PVB regimen with administration of G-CSF was 0.98, whereas in the PVB-alone group it was 0.87 (p < 0.01). Our findings indicate that the RDI of BLM may be one of the most important factors in achieving a chemotherapeutic effect from the PVB regimen. G-CSF is useful for the completion of the schedule through the increase in dose intensification, and the prevention of leukocytopenia due to chemotherapy.