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Biomedical subjects

M Igawa

Publications and source records attributed to M Igawa.

At least 55 records · Page 3Linked to original sources
PubMed1997

[Androgen--biosynthesis, receptor and action].

Androgens play a key role in promoting normal sex differentiation and development, pubertal masculinization, initiation of spermatogenesis, and maintenance of male sexual function. In addition to these classical function, androgens are significantly associated with cell differentiation, proliferation as well as carcinogenesis. The function of androgens can be mediated by the androgen receptor (AR), which transduces the steroid signal within cells. AR belongs to the superfamily of nuclear receptors that employ complex genetic mechanisms to control the development and physiological functions of target tissues. AR activates or represses gene transcription through association with specific DNA elements and/or proteins. Moreover, molecular investigations of AR gene structure have provided new insights towards defining a genetic basis for the relationship between the diseased conditions and androgen action. Recent data on androgen biosynthesis, action of androgens and molecular genetic analysis of gene structure have led to a new understanding of the pathology in affected men. This review summarizes briefly our current view of androgen action with a special emphasis on the alterations of AR.

Androgen-Insensitivity Syndrome↗
PubMed1997

[Cryptorchidism].

Cryptorchidism represents the most common genital abnormalities in boys. Cryptorchidism means the abnormalities that lead to the empty scrotum and specifically refers to undescended testis. Testicular descent is multifactorial, and abnormalities of morphogenesis and hormonal aspects are considered to be the etiology of non-descent of the testis. Furthermore, hormonal abnormalities associated with cryptorchidism have the potential risks of infertility and malignancy that appear in later life. The modality of the management has undergone major refinements with the introduction of laparoscopy. Laparoscopy has become the most widely used and most useful diagnostic modality in the management of the impalpable undescended testes.

Child↗
PubMed1996

Immunohistochemical analysis of proliferating cell nuclear antigen, p53 protein and nm23 protein, and nuclear DNA content in transitional cell carcinoma of the bladder.

BACKGROUND: Transitional cell carcinoma (TCC) of the bladder displays an unpredictable biologic behavior and the morphologic methods of grading tumor malignancy are often insufficient to predict the clinical outcome of patients with TCC of the bladder. Thus, the new indicator should reliably reflect prognosis. In this study, the authors determined the prognostic significance of proliferating cell nuclear antigen (PCNA), p53 protein, and nm23 protein, as well as nuclear DNA content in specimens with TCC of the bladder. METHODS: Paraffin embedded materials taken from 77 patients with nonmetastatic untreated TCC of the bladder (classified as pTa-3b, NO, MO) treated with total cystectomy were employed in this study. PCNA expression, p53 protein and nm23 protein immunoreactivities, and the parameters for nuclear DNA content such as 2c deviation index (2cDI) and 5c exceeding rate (5cER) were evaluated using a computer-assisted image analyzer, and the results were compared with histologic findings and clinical outcome. RESULTS: PCNA expression positively correlated with p53 protein and nm23 protein immunoreactivities, 2cDI value, and 5cER. In addition, histologic grade positively correlated with all of these five parameters. Similarly, pT category and disease progression positively correlated with all of the five parameters, except for nm23 protein immunoreactivity. In tumors with high genetic instability as judged by 2cDI and 5cER, both PCNA expression and p53 protein immunoreactivity were elevated, whereas nm23 protein immunoreactivity was not. However, the percent coefficient of variation in PCNA expression was smaller than that observed in p53 protein immunoreactivity in each group of genetic instabilities. In univariate analysis, prognostic potential was found with histologic grade, pT category, PCNA expression, p53 protein immunoreactivity, 2cDI value, and 5cER, but was not noted in nm23 protein immunoreactivity. Multivariate analysis indicated that quantity and intensity of PCNA expression (chi 2 = 8; P = 0.0047 for quantity and chi 2 = 8.71; P = 0.0032 for intensity) and 2cDI value (chi 2 = 5.52; P = 0.0019) were independent variables of histologic grade and pT category when predicting survival. However, p53 protein and nm23 protein immunoreactivities and 5cER were not of independent significance. CONCLUSIONS: The tumor growth fraction as assessed by PCNA immunostaining is an independently significant predictor for survival of patients with TCC of the bladder.

Adult↗
PubMed1996

Clinical study on estramustine binding protein (EMBP) in human prostate.

To elucidate the characteristics of estramustine binding protein (EMBP) in human prostate, tissue EMBP concentration was examined in 42 benign prostatic hypertrophy (BPH), 34 untreated prostatic carcinoma (PC), 8 hormone refractory PC (hr-PC), as well as 13 control prostate human tissue samples by RIA using rat-EMBP antibody, and the concentration thus obtained was compared with dihydrotestosterone (DHT), prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), and zinc, indices exhibiting androgen dependency in the prostate. EMBP concentration correlated significantly with DHT and PSA levels in the control prostate and BPH, but not in untreated PC. In BPH, EMBP concentration increased significantly after administration of fluoxymesterone (4 mg/day for 2 weeks), whereas it decreased significantly after estramustine phosphate (280 mg/day for 2 weeks). The EMBP/DHT ratio in moderately and poorly differentiated, and the hr-PC was significantly higher than in controls, BPH, and well-differentiated PC. In addition, untreated PC with an EMBP/DHT ratio of more than 40 showed significantly lower progression-free probability as compared with PC with an EMBP/DHT of less than 40. These results suggest that (1) EMBP in BPH and well-differentiated PC preserves androgen dependency, but not in moderately and poorly differentiated, nor in hr-PCs, indicating that EMBP is a protein different from PAP and PSA, and (2) that the tissue EMBP/DHT ratio might be useful as a marker for predicting disease progression.

Acid Phosphatase↗
PubMed1996

Preliminary results of concurrent methotrexate, cisplatin and radiation treatment for locally advanced urothelial cancers.

Ten patients with invasive bladder cancer and one with locally advanced renal pelvic cancer were treated with concurrent methotrexate, cisplatin and radiotherapy. Methotrexate 30 mg/m2 was administered intravenously on the day of the initiation of radiotherapy and cisplatin 70 mg/m2 on the second day. The number of chemotherapy cycles delivered was 1 in 7 patients and 2 in 4. The median dose of radiation was 50 Gy. Of 11 patients, 7 (64%) achieved a partial response and 4 had no change in disease. The median duration of response was 16 months for patients with a partial response. Six patients with a partial response (55%) are alive for a median of 22.5 months and 2 of 4 with no change are alive for 4 and 15 months, respectively. Leukopenia less than 3000 cell/mm3 was observed in 4 (36%) and thrombocytopenia less than 100,000 cells/mm3 in 3 (27%). Local control could be achieved safely with concurrent methotrexate, cisplatin and radiation therapy in patients with locally advanced urothelial cancer who were unsuitable for surgery.

Aged↗
PubMed1996

Secondary plasmacytoma of the testis: report of a case.

We report a case of secondary plasmacytoma of the testis. The patient previously had had plasmacytoma of the nasal cavity, and then recurrences occurred in the right ethmoid sinus, sphenoid sinus, nasopharynx and clavicle before testicular plasmacytoma has developed. This is the 49th case of testicular plasmacytoma reported in the world literature.

Humans↗
PubMed1996

Genomic heterogeneity in bladder cancer as detected by fluorescence in situ hybridization.

OBJECTIVE: To investigate the relationship between genomic heterogeneity and tumour grade, stage and DNA content in 30 transitional cell carcinomas (TCCs) of the urinary bladder. MATERIALS AND METHODS: Tissue specimens from 30 patients (25 men and five women) with newly diagnosed TCC of the urinary bladder were examined for genomic heterogeneity using fluorescence in situ hybridization (FISH) with chromosome-specific DNA probes; the copy number of pericentromeric sequences on chromosomes 7, 9 and 17 was detected within interphase nuclei in contact preparations from the tumour specimens. RESULTS: The aneusomy of chromosomes 7, 9 and 17 was significantly higher in aneuploid than in diploid tumours (P < 0.001). Tumour grade and stage were strongly associated with aneusomy for chromosome 17 (P < 0.01, P < 0.001, respectively). The aneusomy of chromosomes 7 and 9 were significantly correlated with increasing tumour stage (P < 0.001), but not with tumour grade. CONCLUSION: These results suggest that the measurement of aneusomy using FISH, especially for chromosome 17, in bladder cancer may offer a new objective and quantitative assay of the biological potential of individual tumours.

Aged↗
PubMed1996

Biological characteristics of inverted papilloma of the urinary bladder.

OBJECTIVES: To elucidate the biological characteristics of inverted papilloma (IP) of the bladder. MATERIALS AND METHODS: The immunoreactivity of p53, nuclear DNA content (assessed by ploidy and 2c deviation index [2cDI]) and the expression of proliferating cell nuclear antigen (PCNA) in 17 IPs were evaluated using a computer-assisted image analyser and compared with those in 12 superficial transitional cell carcinomas (TCCs), 29 invasive TCCs and one inverted papillary TCC of the bladder. RESULTS: Positive staining for p53 and PCNA and intense staining with Feulgen were observed predominantly in the basal layer of the bladder mucosa. All IPs and most superficial TCCs were diploid, while most invasive TCCs were aneuploid. Although the 2cDI and the immunoreactivities for PCNA and p53 were significantly lower in IPs than in invasive TCCs, there was no significant difference in these three variables between IPs and superficial TCCs. However, some IPs were more immunoreactive for p53 than were the superficial TCCs. CONCLUSIONS: The distribution of cells with p53 and PCNA immunoreactivity, and with intense Feulgen staining, indicated that IP of the bladder might have high proliferative activity and that those IPs with a high immunoreactivity for p53 may be susceptible to malignant transformation.

Carcinoma, Transitional Cell↗
PubMed1996

Intravesical instillation of epirubicin: effect on tumour recurrence in patients with dysplastic epithelium after transurethral resection of superficial bladder tumour.

OBJECTIVE: To evaluate whether the intravesical instillation of epirubicin is effective in preventing the recurrence of tumour in the bladder where dysplastic mucosa remains after transurethral resection of tumour. PATIENTS AND METHODS: Biopsy specimens were taken from apparently normal areas of the bladder mucosa in patients undergoing transurethral resection of the primary tumours. Of the 75 evaluable patients, 18 (24%) had abnormalities in at least one or more specimens. The patients were divided into two groups, 57 with normal and 18 with abnormal biopsy results. Intravesical chemotherapy with epirubicin (20 mg/40 mL saline) was randomized to patients in each group. Tumour recurrence rates were estimated and compared amongst the groups. Factors related to tumour recurrence were evaluated using univariate and multivariate analyses. RESULTS: The risks of tumour recurrence and progression were evaluated in 18 patients with concomitant mucosal abnormalities. All 10 patients with abnormal biopsy results who were treated with epirubicin had recurrence of tumour within a mean interval of 9 months, whereas six of eight controls had recurrence within a mean of 10.9 months. While there was progression in grade in four of 10 patients with abnormal biopsy results and treated with epirubicin, none of the recurrent tumours in six control patients with mucosal abnormalities progressed in grade. The overall recurrence-free rate of the patients with mucosal abnormalities was higher in controls than in those receiving epirubicin, but the difference was not statistically significant. There were no significant differences in recurrence rate for those treated with epirubicin and controls in the 57 patients with normal biopsy results. Univariate analysis showed that the recurrence-free rates were significantly influenced by tumour multiplicity and the mucosal biopsy results (P < 0.001 and P = 0.02, respectively). In a Cox proportional-hazards model, tumour multiplicity alone had prognostic significance for tumour recurrence (P = 0.002). CONCLUSIONS: The prophylactic intravesical instillation of epirubicin had no effect in preventing tumour recurrence and, conversely, it may promote tumour progression in bladders with dysplastic mucosal changes.

Administration, Intravesical↗
PubMed1996

Bacillus Calmette-Guérin perfusion therapy for carcinoma in situ of the upper urinary tract.

OBJECTIVE: To analyse the clinical and therapeutic consequences of bacillus Calmette-Guérin (BCG) perfusion therapy for carcinoma in situ (CIS) of the upper urinary tract. PATIENTS AND METHODS: Eight pyelo-ureteric systems in five patients with cytologically confirmed CIS of the upper urinary tract were treated using perfusion of BCG through a percutaneous nephrostomy tube in five and a retrograde ureteric catheter in three. Follow-up cystoscopy, retrograde pyelography and selective urinary cytology were obtained 4 weeks after the last treatment and every 3 months thereafter. RESULTS: In three patients (five pyelo-ureteric systems) the cytology remained negative for 10-46 months after the treatment was completed. The remaining two patients (three pyelo-ureteric systems) had persistently positive cytology. Of two patients who received BCG therapy through a ureteric catheter, one developed a ureteric stricture and the other developed renal tuberculosis. CONCLUSIONS: Although long-term adaptation to a nephrostomy tube disturbs the quality of life of the patient, percutaneous perfusion therapy through a nephrostomy tube seems to be safer than retrograde perfusion through a ureteric catheter.

Aged↗
PubMed1996

Estramustine-binding protein to dihydrotestosterone ratio in human prostatic carcinoma: a new marker for predicting disease progression.

OBJECTIVE: To elucidate the clinical significance of estramustine-binding protein (EMBP) in human prostatic carcinoma (PC) as an indicator for predicting disease progression. PATIENTS AND METHODS: EMBP concentrations in prostate tissue samples taken from 35 patients with benign prostatic hyperplasia (BPH), 33 patients with prostatic carcinoma (PC) taken before treatment, and from nine patients with hormone-refractory PC (hr-PC) were measured by radioimmunoassay using an antibody raised against rat EMBP. The dihydrotestosterone (DHT), prostatic acid phosphatase (PAP), prostate-specific antigen (PSA) and zinc levels in the tissue were also measured. RESULTS: The EMBP concentration in well differentiated PC (W-PC) samples was no higher than in samples of BPH tissue, whereas concentrations in moderately differentiated PC (M-PC) and poorly differentiated PC (P-PC) were significantly higher (P < 0.01 and P < 0.005, respectively); the highest levels were those in tissue from hr-PC (P < 0.001). Levels of PAP, PSA and zinc were significantly lower in tissue from PC than from BPH, while the differences in levels between W-PC, M-PC and P-PC were not significant. The EMBP to DHT ratio in the tissue increased significantly from W-PC through M-PC to P-PC and was greatest in hr-PC tissue. Conversely, the PAP:DHT, PSA:DHT and zinc:DHT ratios did not correlate with the progress of histological grade. In addition, the pre-treatment EMBP:DHT and zinc:DHT ratios in 14 patients who developed hr-PC within 3 years after the administration of estramustine phosphate were significantly higher when compared with the remaining 19 patients (P < 0.001 and P = 0.0184, respectively), whereas the PAP:DHT and PSA:DHT ratios showed no significant difference between the groups. Moreover, patients with a high EMBP:DHT ratio (> or = 82) had a low progression-free probability compared to those with a lower ratio. CONCLUSION: The androgen-dependent property of EMBP tends to decline with the transformation of prostatic tissue into biologically more malignant disease. The tissue EMBP:DHT ratio before treatment may be a good indicator of the individual malignant potential of PCs.

Aged↗
PubMed1996

Immunohistochemical evaluation of proliferating cell nuclear antigen, prostate-specific antigen and alpha 1-antichymotrypsin in human prostate cancer.

OBJECTIVE: To determine the relationship between growth fractions defined by proliferating cell nuclear antigen (PCNA), prostate-specific antigen (PSA) and alpha 1-antichymotrypsin (ACT) staining in prostate cancer. MATERIALS AND METHODS: A total of 96 lesions, including 71 from prostate cancers and 25 from benign prostatic hyperplasia (BPH) were evaluated in microscopic sections of the prostatic tissues from 34 patients with prostate cancer. Immunohistochemical staining was performed with an avidin-biotin system using monoclonal anti-PCNA antibodies, polyclonal anti-PSA and anti-ACT antibodies. RESULTS: There was a significant difference in the mean PCNA labelling index between tissue from prostate cancer (4.2 +/- 7.1) and BPH (0.5 +/- 1.1) (P = 0.002). The mean labelling index of PCNA tended to increase with increasing Gleason score. The proportion of cells positive for PSA was significantly higher in tissue from BPH than from prostate cancer (P = 0.005). While the proportion of cells immunostaining for ACT was significantly higher in tissue from BPH compared to that from prostate cancer (P = 0.02), there was no significant difference in the proportion of ACT-positive cells among prostate cancers of differing Gleason score. The mean labelling index of PCNA decreased significantly with the increase in the proportion of PSA-positive cells (P = 0.013). There was a significant relationship between the proportion of ACT- and PSA-positive cells (P = 0.001). CONCLUSION: These results indicate a reciprocal relationship between cell growth and tumour differentiation in prostate cancer. Although the significance of ACT deserves further study, there was evidence for the complexing of PSA with ACT from the immunohistochemical studies.

Humans↗
PubMed1996

Immunohistochemical analysis of bcl-2 expression in transitional cell carcinoma of the bladder.

AIMS: To evaluate the expression of bcl-2 in transitional cell carcinoma (TCC) of the bladder; to compare bcl-2 expression with clinicopathological findings, p53 immunoreactivity, proliferating cell nuclear antigen (PCNA) expression, 2c deviation index (2cDI), 5c exceeding rate (5cER), and the mean nuclear area (MNA). METHODS: Cystectomy specimens from 77 patients with untreated, non-metastatic TCC of the bladder were studied. Expression of bcl-2, p53 and PCNA was detected immunohistochemically using the following monoclonal antibodies: bcl-2/124, DO-7 and PC10, respectively. Nuclear DNA content was analysed using static cytometry. RESULTS: Bcl-2 was expressed in 19 (24.7%) of 77 TCCs and in 74 (96.1%) of 77 normal samples of transitional epithelium (taken from normal tissue adjacent to the tumour in each case). In all cases, bcl-2 immunoreactivity was more intense in normal transitional epithelium than in TCC. In normal transitional epitehlium and superficial TCC bcl-2 immunoreactivity was observed at the basal layer, and not at the invasive front. Bcl-2 immunoreactivity was invesely correlated with histological grade and p53 immunoreactivity, and was not correlated with the pT category, disease progression, PCNA expression, 2cDI, 5cER, and the MNA. No significant correlation was found between bcl-2 expression and overall survival. CONCLUSIONS: Bcl-2 expression in TCC of the bladder seems to be associated with a less aggressive phenotype and does not play an important role in tumour progression.

Adult↗
PubMed1996

Limitations of ureteroscopy in diagnosis of invasive upper tract urothelial cancer.

The efficacy of ureteroscopic evaluation of upper tract abnormalities was evaluated in 40 patients. Twenty-eight patients presented with a radiologic filling defect, 9 with a filling defect and hematuria and 3 individuals exhibited hematuria alone. Cold cup biopsies revealed transitional cell carcinoma in 7 of 9 patients with papillary tumors and in 2 of 3 with nonpapillary tumors. Four patients without ureteroscopic diagnosis of urothelial cancer were found to have invasive tumors on subsequent nephroureterectomy. Of 15 patients with upper tract urothelial cancer, 12 were treated with total nephroureterectomy. Three individuals with grade 1 neoplasms received conservative ureteroscopic ablative therapy. Ureteroscopy is effective when combined with biopsy in the diagnosis and treatment of papillary lesions, but exhibits a low sensitivity in patients with invasive lesions.

Adult↗
PubMed1996

Fibroepithelial polyp in the renal pelvis.

Benign tumors in the renal pelvis are unique and rarely reported. We report a case of a benign polyp in the renal pelvis. A 68-year-old woman presented with a mass in the right renal sinus and underwent right nephrectomy. Histological investigations of the tumor revealed a polypoid angiofibromatous lesion of the renal pelvis which was benign in nature. Final pathological diagnosis was a benign fibroepithelial polyp.

Aged↗
PubMed1996

Comparison of ureteropelvic transitional cell carcinoma with bladder transitional cell carcinoma using an image analyzer.

To elucidate whether a significant difference in malignant potential between ureteropelvic transitional cell carcinoma (TCC) and bladder TCC is present, the argyrophilic nucleolar organizer region (AgNOR), nuclear DNA content and mean nuclear area (MNA) were evaluated in 32 ureteropelvic TCCs and 60 bladder TCCs, and were also compared with histological grade and stage. The parameters used were the mean AgNOR count (C-AgNOR), the percentage of cells exhibiting more than 3 AgNOR dots within nuclei (P-AgNOR), 2c deviation index (2cDI), 5c exceeding rate (5cER) and MNA. No significant difference in these 5 parameters was found between ureteropelvic and bladder TCCs. In addition, within each histological grade of tumor, no significant difference in each parameter between ureteropelvic and bladder TCCs was noted. Similarly, within pTa or pT1 TCCs, there was no significant difference in the parameters between ureteropelvic and bladder TCCs. On the other hand, invasive TCCs (pT2 and higher), the C-AgNOR and P-AgNOR were significantly higher in ureteropelvic than in bladder TCC (p < 0.05), while no significant difference in 2cDI, 5cFR and MNA was noted. These findings suggest that: (i) as a whole, the difference in malignant potential between ureteropelvic and bladder TCCs appears to be less significant, and (ii) factors other than the malignant potential of a tumor might contribute to the unfavorable clinical outcome in patients with ureteropelvic TCC.

Aged↗
PubMed1996

Evaluation of the argyrophilic nucleolar organizer region, nuclear DNA content and mean nuclear area in transitional cell carcinoma of bladder using a quantitative image analyzer.

To search for reliable parameters that reflect the biological potential of bladder cancer, the argyrophilic nucleolar organizer region (AgNOR), nuclear DNA content and mean nuclear area (MNA) were studied in paraffin-embedded materials of 75 primary transitional cell carcinomas (TCCs) using a quantitative image analyzer, and were also compared with histological findings and prognosis. The AgNOR parameters studied were the mean AgNOR count (C-AgNOR) and the percentage of cells exhibiting more than 4 AgNOR dots within nuclei (P-AgNOR), whereas the DNA parameters were the 2c deviation index (2cDI) and 5c exceeding rate (5cER). These 5 parameters significantly correlated with the histological grade (p < 0.0001, respectively). Similarly, these 5 parameters correlated with the histological stage, but the correlation was higher in 2cDI and 5cER (p < 0.0001, respectively) in comparison with the AgNOR parameters and MNA. Using univariate analysis, the prognostic relevance was noted in all but P-AgNOR. The 5cER value could discriminate histological grade-II tumors in relation to prognosis, whereas the remaining parameters could not. In addition, the significant difference between noninvasive and invasive tumors was noted in 2cDI and 5cER (p < 0.05, respectively), but not in C-AgNOR, P-AgNOR and MNA. These results suggest that (i) 2cDI and 5cER exhibit superiority over the AgNOR parameters and MNA in predicting survival, and (ii) in histological grade-II tumors, evaluation of the 5cER value is most important when predicting survival as well as judging the necessity for further aggressive treatment in patients with TCCs of the bladder.

Adult↗