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Biomedical subjects

S Kagawa

Publications and source records attributed to S Kagawa.

At least 91 records · Page 5Linked to original sources
PubMed1998

[Pretreatment with chlormadinone acetate in prostate cancer patients treated with a luteinizing hormone-releasing hormone analogue].

We evaluated the efficacy of pretreatment with chlormadinone acetate (CMA) in preventing the initial testosterone surge induced by luteinizing hormone-releasing hormone (LH-RH) analogue. A total of 44 patients with previously untreated prostate cancer was included in this study. Patients were randomly assigned to 2 treatment groups: Group I-CMA therapy was begun 4 weeks before the initial LH-RH analogue injection. Group II-CMA therapy was begun 2 weeks before the initial LH-RH analogue injection. After the initial LH-RH analogue injection, CMA was administered for 12 weeks or more. After LH-RH analogue application mean values of serum luteinizing hormone (LH) and testosterone increased in both groups on day 3. However, LH and testosterone levels remained below pretreatment values in both groups. CMA pretreatment reduced the mean serum PSA. The mean relative PSA level slightly increased after administration of the LH-RH analogue in group I on day 7. In group II, the mean relative PSA level decreased after LH-RH analogue administration. Objective response rates at 12 weeks were 83.3% and 93.8% in group I and group II. Our results indicate that pretreatment with CMA for 2 weeks appeared to be sufficient to prevent the initial testosterone surge induced by LH-RH analogue.

Aged↗
PubMed1997

Novel combination therapy for human colon cancer with adenovirus-mediated wild-type p53 gene transfer and DNA-damaging chemotherapeutic agent.

Alteration of the wild-type (wt) p53 gene by mutation, deletion or re-arrangement is a major factor in the development of human colon cancer. Recent studies have demonstrated that p53 might be an essential component of the apoptotic pathway triggered by DNA-damaging stimuli such as chemotherapeutic agents and ionizing radiation. We examined the anti-tumor effects of adenovirus-mediated wt-p53 gene transfer in combination with a chemotherapeutic drug on the human colon cancer cell line WiDr, which is homozygous for a mutation in the p53 gene. Treatment with the chemotherapeutic drug cisplatin following infection with a replication-deficient, recombinant adenoviral vector expressing wt-p53 (termed AdCMVp53) significantly suppressed the growth of WiDr cells compared to single treatments alone. To evaluate the in vivo efficacy of AdCMVp53 and cisplatin given sequentially, WiDr cells were inoculated s.c. in nu/nu mice. After 3 days, AdCMVp53 was injected s.c. into the area where tumor cells were implanted, followed by i.p. administration of cisplatin. Analysis of initial growth inhibition at 21 days demonstrated a profound therapeutic cooperativity, though administration of either AdCMVp53 or cisplatin alone was followed only by a slowing of growth. Our results suggest that gene therapy using wt-p53-expressing adenovirus in combination with a chemotherapeutic DNA-damaging drug could be a useful strategy for treating human colon cancer.

Adenoviridae↗
PubMed1997

p53 expression overcomes p21WAF1/CIP1-mediated G1 arrest and induces apoptosis in human cancer cells.

The p21WAF1/CIP1 gene, which encodes a cyclin-dependent kinase inhibitor, may be critical for tumor suppressor gene p53-induced cell cycle arrest. The p53 gene is known to regulate G1 checkpoint, which can either induce G1 arrest or initiate apoptosis. To directly examine the role of p21WAF1/CIP1 in the control of p53 function, we have introduced human p21WAF1/CIP1 gene into a p53-deficient human non-small cell lung cancer cell line H1299 using a p21WAF1/CIP1-expressing adenoviral vector (AdCMVp21). Infection with AdCMVp21 resulted in high levels of p21WAF1/CIP1 expression and significantly suppressed the growth of H1299 cells through the G1 arrest of the cell cycle. In contrast, transient expression of the wild-type p53 gene by a recombinant adenoviral vector (AdCMVp53) in H1299 cells induced apoptotic cell death and resulted in a rapid loss of cell viability. We then examined the effects of combined infection with AdCMVp21 and AdCMVp53 on H1299 cells to explore the dominant function of these molecules. Interestingly, introduction of exogenous p53 overcame p21WAF1/CIP1-mediated cell cycle arrest at G1 and induced apoptosis, although viral-transduced p21WAF1/CIP1 expression level was unaffected. These observations suggest that p53 expression converts a p21WAF1/CIP1-mediated growth arrest into apoptosis. The result was repeated with two additional human colon adenocarcinoma cell lines with the different p53 status, mutant p53-expressing DLD-1 and wild-type p53-expressing LoVo, suggesting that this phemonenon is a general event among human cancer cells. Thus, p53-mediated apoptotic pathway is dominant over the growth arrest pathway, indicating that p53 may be an essential upstream mediator of p21WAF1/CIP1 in the regulation of a cell process leading either to growth arrest or to apoptotic suicide.

Apoptosis↗
PubMed1997

Prognostic value of Ki-67 antigen and p53 protein in urinary bladder cancer: immunohistochemical analysis of radical cystectomy specimens.

OBJECTIVE: To investigate the role of tumour proliferation and p53 expression as a marker of survival in patients with urinary bladder cancer who undergo radical cystectomy. PATIENTS AND METHODS: Samples were obtained from 31 patients (29 men and two women, mean age 66.0 years, range 46-80) with transitional cell carcinoma of the bladder who underwent radical cystectomy. The 31 formalin-fixed radical cystectomy specimens were stained immunohistochemically for Ki-67 antigen and p53 protein using MIB1 and p53 antibodies, respectively, and the results correlated with tumour grade, stages and prognosis. RESULTS: The Ki-67 index was significantly greater in high-grade tumours and in those overexpressing p53 (> 20% positive nuclei). Patients whose tumour samples had a high Ki-67 index (> 32%) had a significantly worse prognosis than those with a lower index (P < 0.01). There was a similar correlation between Ki-67 index and prognosis in high-risk patients (grade 3 and pT3-4; P < 0.05). Although the associations between tumour grade, stage and p53 expression were not statistically significant, patients whose tumour samples overexpressed p53 had a lower survival rate (P < 0.05). No patients with tumours having a low Ki-67 and low p53 index (n = 14) died of urinary bladder cancer during the follow-up. CONCLUSION: These results suggest that immunohistochemical analyses for Ki-67 and p53 are useful prognostic indicators in patients with urinary bladder cancer who undergo radical cystectomy; the prognostic role of these markers was particularly important in high-risk (grade 3 and pT3-4) patients.

Aged↗
PubMed1997

[Long-term follow-up of the Le Duc-Camey antireflux technique].

BACKGROUND: An effective ureteroileal reimplantation without reflux and obstruction is indispensable for lower urinary reconstruction or diversion using an ileal segment. Based on our earlier experience of afferent nipple valve malfunction of the Kock pouch, we performed Le Duc-Camey antireflux ureteroileal implantation. In the present study, we evaluated the long-term outcome of the Le Duc-Camey technique on the upper urinary tract in patients with a postoperative observation period of 2 years or more. PATIENTS AND METHODS: From 1989 to 1994, 39 patients (73 ureters) underwent Le Duc-Camey technique for prevention of reflux of a Kock pouch. In 28 patients the ileal reservoir was connected to the skin for cutaneous urinary diversion, and in 11 it was connected to the urethra for lower urinary reconstruction. The ureters were implanted into the reservoir through the anterior wall window of the reservoir. In most patients, excretory urography (DIP) was performed once a year after the first year. Retrograde cystography or voiding cystourethrography was performed within 12 months postoperatively. After the first year, retrograde study was performed once during the follow-up period in the majority of the patients. The mean follow-up period was 44.8 months (range 24-71 months). RESULTS: There was no urinary tract dilatation in 68 renal units (93.1%), while slight dilatation was noted in 3 (4.1%), moderate dilatation in 1 (1.4%), and marked dilatation due to stenosis of ureteroileal anastomosis in 1 (1.4%). Retrograde studies revealed absence of reflux in all patients. Another complication that related to this procedure was not observed in any patients. CONCLUSION: We conclude that Le Duc-Camey technique is effective in reflux prevention and protection of the upper urinary tract, and recommend it for use with detubularized ileal reservoir.

Adult↗
PubMed1997

[The role of serum soluble interleukin 2 receptor (sIL-2R) levels in patients with renal cell carcinoma].

PURPOSE: The correlation between the serum soluble interleukin-2 receptor (SIL-2R) levels and clinical stage is demonstrable in a variety of non-Hodgkin lymphomas. The prognostic significance of sIL-2R levels in the serum of patients with renal cell carcinoma (RCC) was investigated. METHOD: sIL-2R were measured in patients with RCC (n=39) and normal control (n=6) by the enzyme immunoassay technique. Cases of RCC were classified according to the clinical stage, pathological grade and growth type. The IL-2R expression of RCC was evaluated by RT-PCR. RESULT: The serum sIL-2R levels of patients with RCC showed significantly higher values than those of controls (p < 0.05). The serum sIL-2R levels in RCC were closely associated with the stage, grade and growth type of disease. The patients with high serum sIL-2R level (> = 1,000 U/L) exhibited a significantly poorer prognosis than those with low serum sIL-2R level (<1,000 U/L). The band of IL-R was detected only by using the template from the mRNA extracted from a resected tumor tissue of the RCC but not from the RCC cell lines. CONCLUSION: It was suggested that the measurement of serum sIL-2R levels is useful for predicting the prognosis.

Adult↗
PubMed1997

[Bropirimine (U-54461S) late phase II clinical study for carcinoma in situ of the bladder. Japan Bropirimine Study Group].

Late Phase II clinical study with bropirimine (U-54461S), a novel oral antitumor agent that has interferon inducing and anti-proliferative activities, was conducted in patients with bladder CIS at 38 institutions nationwide. To investigate the efficacy and safety of the treatment, bropirimine was administered to the patients at the dose of 750 mg every two hours, three times a day, for three consecutive days with four-day drug withdrawal, based on the results of the preceding clinical studies up to early phase II. Among the 48 patients registered, 41 patients were evaluable for antitumor efficacy. Complete response (CR) was observed in 17 of them, no change (NC) in 18 patients, and progressive disease (PD) in 6 patients; so the efficacy rate was 41.5%. Classified by patient background, the efficacy rates were 58.3% (7/12) in patients with primary bladder CIS, 34.5% (10/29) in those with secondary bladder CIS, 45.5% (10/22) in those with Grade 3, and 23.8% (5/21) in those previously given chemotherapeutic agents or BCG by intravesical or other routes. Adverse drug reactions frequently observed were influenza-like symptoms such as fever and generalized malaise and gastrointestinal symptoms like anorexia and nausea/vomiting; these symptoms were all Grade 2 or milder. Abnormalities in laboratory tests, such as an elevation in GOT/GPT, neutropenia, and leukopenia were observed. These adverse effects were all tolerated by the patients. From the above results, bropirimine was considered to be a useful oral agent for the treatment of bladder CIS.

Administration, Oral↗
PubMed1997

Localization of NADPH diaphorase and vasoactive intestinal polypeptide-containing neurons in the efferent pathway to the rat corpus cavernosum.

OBJECTIVE: We examined the coexistence of nitric oxide synthase (NOS) and vasoactive intestinal peptide (VIP) in the efferent pathway to the rat corpus cavernosum. METHODS: We used NADPH diaphorase (ND) histochemical staining, a specific marker of neuronal NOS, in combination with retrograde axonal transport of True Blue (TB) and VIP immunohistochemistry. RESULTS: Many neurons were labeled by TB in the cavernous nerve and the body of the major pelvic ganglion (MPG), and fewer neurons in the pelvic nerve. In the cavernous nerve, about 90% of TB-labeled efferent neurons were ND positive, and about 80% in the body of the MPG and pelvic nerve. Besides, 60-80% of TB-labeled efferent neurons projecting to the corpus cavernosum showed VIP immunoreactivity. VIP was colocalized with NOS in 70-80% of neurons. CONCLUSIONS: These findings suggest that most of the ND-positive nerves and terminals in the corpus cavernosum come from the MPG via the cavernous nerve and that NO plays an important role; it may act in combination with NO because most NOS-containing neurons simultaneously showed VIP immunoreactivity.

Animals↗
PubMed1996

The proliferation index of MIB-1 as a prognostic factor for patients with transitional cell carcinoma of the upper urinary tract.

BACKGROUND: Recently, several reports have shown that immunohistochemical analysis using MIB-1 antibody, which recognizes Ki-67 (a human nuclear antigen expressed of proliferating cells), is a useful method for determining the proliferative activity of various cancers. In this study, the authors evaluated the prognostic usefulness of the proliferation index using MIB-1 antibody in transitional cell carcinoma of the upper urinary tract. METHODS: Proliferation activity was investigated immunohistochemically using monoclonal antibody MIB-1 in formalin fixed, paraffin embedded tissues obtained from 67 specimens of renal pelvic and ureteral cancer. The MIB-1 proliferation index values were calculated from each sample as the percentage of positive nuclei expressed in tumor cells and the clinicopathologic correlation evaluated. RESULTS: The MIB-1 proliferation index values were correlated with prognostic parameters such as pathologic stage ( < or = pT1 vs. > or = pT2, P < 0.0005), histologic grade (G1 vs. G2, P < 0.01; G1 vs. G3, P < 0.0001; G2 vs. G3, P < 0.001), and prognosis (P < 0.0001). When patients were subgrouped using index values, patients with higher indices ( > or = 24%) had significantly poorer survival (P < 0.0001). This was especially observed in the G2 group, in which 9 of 10 patients in the higher indices subgroup had a high incidence of recurrence and died. In contrast, only 2 of 29 patients in the lower indices subgroup died. The higher indices subgroup had significantly worse cause specific survival (P < 0.0001). Furthermore, with regard to the muscle invasive tumors ( > or = pT2), the higher indices subgroup also had significantly worse cause specific survival (P < 0.0001). CONCLUSIONS: The results of the evaluation of prognostic parameters indicate that the MIB-1 proliferation index is a useful prognostic factor and may enhance the accuracy of conventional morphologic grading and pathologic staging systems.

Adult↗
PubMed1996

Immunocytochemical localization of 5 alpha-reductase type 1 in the prostate of normal and castrated rats.

We immunohistochemically studied the localization of 5 alpha-reductase type 1 in combination with androgen receptor (AR) expression in individual lobes of the prostates of intact and castrated rats. In the normal rat prostate, 5 alpha-reductase was localized in the cytoplasm of most epithelial cells in the ventral, dorsal, and lateral type 1 (L1) lobes. Epithelial cells of lateral type 2 (L2) lobes were negative for 5 alpha-reductase. AR was present in the nuclei of all epithelial and stromal cells throughout the prostate. The number of 5 alpha-reductase-immunoreactive cells rapidly decreased in the ventral and L1 lobes after castration, whereas many positive cells remained in the dorsal lobe even at 4 weeks after castration. AR immunostaining was lost in the ventral, dorsal, and L1 lobes at 1 week after castration, but remained in the L2 lobe of 4-week-castrated rats. Electron microscopic immunocytochemistry showed that 5 alpha-reductase was exclusively localized in the rough endoplasmic reticulum membranes and that there were no distinct structural differences between the positively and negatively stained epithelial cells. These findings suggested that the expression of 5 alpha-reductase type 1 in the epithelial cell is heterogeneous within and among the individual lobes of the rat prostate, and does not correspond to AR expression.

Animals↗
PubMed1996

CDNA cloning of p112, the largest regulatory subunit of the human 26s proteasome, and functional analysis of its yeast homologue, sen3p.

The 26S proteasome is a large multisubunit protease complex, the largest regulatory subunit of which is a component named p112. Molecular cloning of cDNA encoding human p112 revealed a polypeptide predicted to have 953 amino acid residues and a molecular mass of 105,865. The human p112 gene was mapped to the q37.1-q37.2 region of chromosome 2. Computer analysis showed that p112 has strong similarity to the Saccharomyces cerevisiae Sen3p, which has been listed in a gene bank as a factor affecting tRNA splicing endonuclease. The SEN3 also was identified in a synthetic lethal screen with the nin1-1 mutant, a temperature-sensitive mutant of NIN1. NIN1 encodes p31, another regulatory subunit of the 26S proteasome, which is necessary for activation of Cdc28p kinase. Disruption of the SEN3 did not affect cell viability, but led to temperature-sensitive growth. The human p112 cDNA suppressed the growth defect at high temperature in a SEN3 disruptant, indicating that p112 is a functional homologue of the yeast Sen3p. Maintenance of SEN3 disruptant cells at the restrictive temperature resulted in a variety of cellular dysfunctions, including defects in proteolysis mediated by the ubiquitin pathway, in the N-end rule system, in the stress response upon cadmium exposure, and in nuclear protein transportation. The functional abnormality induced by SEN3 disruption differs considerably from various phenotypes shown by the nin1-1 mutation, suggesting that these two regulatory subunits of the 26S proteasome play distinct roles in the various processes mediated by the 26S proteasome.

Amino Acid Sequence↗
PubMed1996

Serological evaluation of soluble CD44 in renal cancer.

In this study, we examined the feasibility of using elevated serum CD44 concentration as an indicator in renal cancer. We performed enzyme-linked immunosorbent assays using 63 sera obtained from 47 patients with renal cancer and 16 healthy controls and evaluated the clinico-pathological parameters. The concentration of soluble CD44 standard (sCD44std), indicating the concentration of all circulating CD44 isoforms, was significantly higher in renal cancer patients than in normal individuals (745+/-170 ng/ml vs. 563+/-159 ng/ml, P=0.001). The concentration of soluble CD44 splice isoforms sharing exon v6 (sCD44v6) was also higher in the same patients (287+/-121 vs. 220+/-59, P=0.056). However, there were no correlations between the concentrations of sCD44std or sCD44v6 and clinico-pathological parameters such as grade, stage, histological type, tumor size and growth type. The ratio of sCD44std/sCD44v6 was higher in the rapid growth-type cancers than in the slow growth-type cancers (3.95+/-2.12 vs. 2.63+/-0.82, P = 0.014). These findings suggested that the serum concentration of unknown soluble CD44 isoforms not sharing exon v6, which are present in sCD44std, increases in patients with rapid growth-type cancers. These findings indicated that sCD44std and sCD44v6 are not useful indicators of tumor burden and metastasis in patients with renal cancer, but that an unknown sCD44 isoform(s) plays a role in the biological behavior of the rapid growth-type cancers.

Adolescent↗
PubMed1996

Papillary cystadenocarcinoma of the prostate.

We report a papillary adenocarcinoma with cystic formation in the prostate of a 64-year-old man, who presented with gross hematuria and pollakisuria. Immunohistochemically, the origin of this tumor was considered to be the prostate gland. Interestingly, this tumor grew into the muscle layer of the bladder with large glandular formation but no stromal changes.

Biopsy↗
PubMed1996

[Detection of hepatitis B virus by using polymerase chain reaction and nonradioactive DNA probes. II. Identification of mutations in the core gene by PCR-direct sequencing and ASO probe method].

Mutants of hepatitis B virus (HBV) in the pre-core/core gene exist in patients chronically infected with HBV. The core gene of HBV DNA is preceded by the pre-core region which takes a role of synthesis and secretion of HBe antigen (HBeAg). Previous studies have suggested that products of the core gene could be immunological targets of cytotoxic T lymphocytes as well as those of variant pre-core genes and subsequently, that the clinical courses of HBV carriers might be influenced due to infected HBV variants. In this study, we therefore examined mutations in the core gene of HBV DNA on strains with or without a translational stop codon at the 28th codon of the pre-core region, using allele-specific oligonucleotide (ASO) probes and PCR-direct sequencing. The analysis of nucleotide sequences (codon 27-100) of HBV DNA in anti-HBe positive sera showed that there were two hypervariable segments of codon 31-49 and codon 87-97, where amino acid substitutions of L31I, S49T, S87G/N, K96N and I87F/1 frequently occurred regardless of the presence or absence of the mutation in the pre-core region. Meanwhile, less mutations were detected in the core gene of HBV DNA in HBeAg positive sera. Furthermore, we could identify the mutations at codon 87, 96 and 97 by using nonradioactive probes in a good coincidence with results by PCR-direct sequencing. The ASO probe method is useful for detection of mutations in the core gene in many specimens.

Amino Acid Sequence↗
PubMed1996

[Clinical studies for venogenic impotence with color Doppler ultrasonography--evaluation of resistance index of the cavernous artery].

BACKGROUND: Pharmaco-dynamic infusion cavernosometry and cavernosography (pharmaco-DICC) is essential for diagnosis of venogenic impotence, however it is so invasive. On the other hand, color Doppler ultrasonography is non-invasive and has become one of the useful diagnostic methods for arteriogenic impotence. And there are some reports evaluating whether venogenic impotence can be diagnosed using color Doppler ultrasonography. In this study, we investigated whether the resistance index (RI) could be useful for screening for venogenic impotence. METHODS: We performed color Doppler ultrasonography in 49 patients who had shown negative responses to an intracavernous injection of 20 mcg of prostaglandin E1 (PGE1). They previously underwent pharmaco-DICC and were diagnosed venogenic impotent when the maintenance flow rate was equal to or more than 20 ml/min. In 49 patients, 17 patients had DICC normality, while 32 patients had corporal leakages. After an intracavernous injection of 20 mcg of PGE1, we performed color Doppler ultrasonography, and measured peak systolic velocity (PSV) and end diastolic velocity (EDV) in the cavernous artery. RI was calculated as follows. RI = (PSV-EDV)/PSV We adopted the RI value near to 1 as the case's RI from two RI values of bilateral cavernous arteries, and compared RI values with the results of pharmaco-DICC. RESULTS: RI range in patients with normal DICC results was 0.895 +/- 0.092 (0.70-1.00), while RI range in patients with corporal leakages was 0.742 +/- 0.095 (0.55-0.97). RI values in patients with corporal leakages were significantly lower than those in patients with normal DICC results although there was some overlap in each group. From receiver-operating-characteristic curve (ROC curve) of the correlation between sensitivity and specificity at various RI values compared with DICC results, the RI cut off values were set up at 0.75 and 0.90, and classified the patients into 3 group according to their RI cut off values. In 10 patients with 0.9 < RI, 9 patients (90%) had DICC normality. In 17 patients with 0.75 < RI < or = 0.9, 7 patients had DICC normality while 10 patients had corporal leakages. In 22 patients with RI < or = 0.75, 21 patients (95.5%) had corporal leakages. CONCLUSION: We consider without carrying out pharmaco-DICC that patients with 0.9 < RI were not venogenic impotent, while patients with RI < or = 0.75 had corporal leakages. Pharmaco-DICC will remain essential only in patients with 0.75 < RI < or = 0.9.

Adult↗
PubMed1996

[A morphological study of renal adenoma and latent renal cell carcinoma in autopsy cases].

PURPOSE: We investigated histopathological features of renal adenoma and latent renal cell carcinoma in order to find relationship between these two entities. MATERIALS AND METHODS: Renal adenomas or latent renal cell carcinomas found macro- and microscopically in 2,201 autopsy materials were used. Histological examination was focused on the size, and the presence or absence of hemorrhage, necrosis and capsulation of tumors. Additionally, we analyzed morphologically the mean nuclear area (MNA), N/C ratio, mean nuclear volume (MNV) and nuclear roundness factor (NRF) using image analyzer system (CIA-10; Olympus). RESULTS: A total of 71 foci of renal cortical tumor was found and classified into renal adenoma (59 foci), latent renal cell carcinoma (8 foci), and intermediate type (4 foci). Intermediate type contained of small element of clear cell and were difficult to distinguish from renal cell carcinoma or ordinary adenoma. The mean diameter of renal adenomas was 1.9 mm. The capsulation was found in only 3 foci (5.1%) of them, and bleeding and necrosis were found in none of them. On the other hand, the mean diameter of latent renal cell carcinoma and intermediate type were 15.7 mm and 6.6 mm, respectively, and larger than that of renal adenomas (p < 0.005). In latent renal cell carcinoma, capsulation were found in all foci, bleeding in 6 (75.0%) and necrosis in 3 (37.5%), and their incidence were significantly higher than those of adenoma (p < 0.005). In intermediate type, capsule and bleeding were found in each two foci. Morphologically, there were significant difference in MNV and NRF but no difference in MNA and N/C ratio between renal adenomas and latent renal cell carcinomas. Intermediate type was larger in NRF compared to adenoma. CONCLUSION: Morphological characteristics of intermediate type resemble that of latent renal cell carcinoma in terms of tumor size, the presence of bleeding and capsule and NRF when compared to adenomas. These results suggest that, in some renal cell carcinoma, adenoma might be able to change to carcinoma.

Adenoma↗
PubMed1996

[Evaluation of Ki67 antigen using MIB1 antibody as a prognostic factor in renal pelvic and ureteral cancer].

(PURPOSE). Recently, several reports showed that immunohistochemistry using MIB-1 antibody, which recognizes Ki-67 antigen, is one of the useful methods to determine the proliferative activity in various cancer. To evaluate the prognostic usefulness of the MIB-1, antibody we assessed the cell proliferation immunohistochemically in urothelial cancer. (METHODS). The proliferative activity of thirty cases of renal pelvic and ureteral cancer has been investigated immunohistochemically using MIB-1 antibody, which recognizes Ki-67 antigen, a human nuclear antigen expressed in proliferating cells. (RESULTS). The Ki-67 index correlated with prognostic factors such as pathological stage and histological grade. The patients with early stage or low grade tumors had lower Ki-67 indices. And the Ki-67 index significantly correlated with recurrence and prognosis. The tumors of patients with recurrence or cancer death had higher Ki-67 indices. When the patients were suggrouped according to Ki-67 indices (more than 22%) had significantly worse prognosis even in the same grade. Especially in the grade 2 group, all the four patients in the higher Ki-67 index subgroup had recurred and died of cancer, whereas, in the subgrouped patients with tumors of lower Ki-67 indices, only three patients had bladder cancer recurrence, and no patients had died of cancer, except one case with advanced tumor (T4, N3, M0) resected incompletely. (CONCLUSIONS). These results indicate that the Ki-67 index is a useful prognostic factor and may enhance the prognostic accuracy determined by conventional morphological grading systems.

Aged↗