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T Kamoto

Publications and source records attributed to T Kamoto.

At least 19 recordsLinked to original sources

Failure of ureteric bud invasion: a new model of renal agenesis in mice.

FUBI (failure of ureteric bud invasion) is a highly inbred strain of mouse with a high spontaneous incidence of uni- or bilateral renal agenesis (60%). Bilateral renal agenesis is lethal within 2 days after birth. The primary defect of FUBI is failure of the ureteric bud to penetrate into the metanephric mesenchyme at around embryonic day 11, resulting in apoptosis of metanephric cells and leading to renal agenesis on the affected side. The metanephros seemed to be normal because co-culturing of the FUBI metanephros with homologous spinal cord induced differentiation of the rudiment, but co-culturing with the homologous ureteric bud frequently did not. Genetic analysis revealed that more than two genes were involved in this malformation and we mapped one of the modifier loci, fubi1, on chromosome 2, at approximately 65 cM from the centromere. In this region, there are two possible candidate genes, Wilms' tumor 1 and formin, that play important roles in kidney development. Some of formin mutants shared a similar phenotype with FUBI; however, there was no difference in the expression of formin in embryonic kidneys between FUBI and control NFS/N mice. Studies of fubi1 congenic mice indicated that interaction of two or more loci is essential for the FUBI phenotype.

Animals↗

[The sensitivity and clinical implications of periodical bladder biopsy following transurethral resection of superficial bladder transitional cell carcinoma].

The role of the periodical bladder biopsy after transurethral resection (TUR-Bt) of superficial bladder cancer (sBT) was evaluated. Sixty-four patients (85 TURs) with sBT who underwent TUR-Bt between 1993 and 1998 were divided into 14 (22 TURs) who had carcinoma in situ (CIS) at the first TUR (group A), and 50 (64 TURs) who had papillary tumors without concomitant CIS (group B). Post-TUR intravesical instillation was performed with bacillus Calmette-Guerin for the majority of group A, and mitomycin C for the majority of group B. The first biopsy was performed at 3 months postoperatively, and the second biopsy was done at 8 to 12 months postoperatively. The mean observation time was 4 years and 6 months. Residual cancer was detected in 7 out of 34 biopsies (20.6%) in group A, and 19 out of 94 (20.2%) in group B. Every residual lesion in group A was CIS with negative cytology. In group B, with exclusion of 11 recurrent papillary tumors, the detection rate was only 8/83 (9.6%). In both groups, even in the cases with no sign of disease in biopsies, the recurrence immediately after the termination of the biopsy protocol was common. The progression of the cancer was more frequent in group A (4 patients), than in group B (2 patients) (p < 0.01, log-rank test), and no case in group B showed local progression. The periodical biopsy may have a certain, but limited advantage over conventional examinations. A less invasive and more sensitive method in awaited.

Biopsy↗

[A case of malignant fibrous histiocytoma arising from the renal capsule].

A 62-year-old man was admitted with a chief complaint of general malaise. Computed tomography showed a large mass adjacent to the parenchyma of the left kidney. The mass was 17 x 13 x 12 cm in size. Preoperative diagnosis was left renal cell carcinoma and left radical nephrectomy was performed. Histopathologically, the tumor was diagnosed as malignant fibrous histiocytoma (MFH), and the tumor was considered to have arisen from the renal capsule. There has been no recurrence for 7 months postoperatively. We review 40 cases of MFH arising from the kidney or the renal capsule in the literature.

Diagnosis, Differential↗

[Progression from adenocarcinoma to small cell carcinoma of the prostate during endocrinotherapy: a case report].

A 72-year-old man had undergone surgical castration for metastatic prostate cancer (stage D2, the PSA value was 4,300 ng/ml) in September, 1997. He was well clinically for 16 months with undetected level of PSA. However, he presented with general malaise and gross hematuria in May, 1999. After admission to our hospital his condition rapidly deteriorated and he died one week later with respiratory failure. Autopsy revealed extensive involvement of the prostate and bladder by solid tumor with multiple metastases in lungs, liver, spleen, kidneys and bone. Histological examination revealed pure small cell carcinoma of the prostate.

Adenocarcinoma↗

[Molecular epidemiology and cancer prevention].

Environmental factors act in concert with individual susceptibility to cause most human cancers. The modulation of these environmental factors by host susceptibility has rarely been evaluated. Recently, the molecular epidemiology of human cancer has been extended to a study clarifying individual variation and gene-environmental interactions by integrating molecular biology, in vitro and in vivo laboratory models, biochemistry and epidemiology to infer individual cancer risk. This article briefly reviews genetic polymorphisms frequently used in molecular epidemiological studies and shows, as an example, a possible association between the genetic polymorphisms of CYP17 genes and prostate cancer risk.

Androgens↗

Rapid detection of candidate metastatic foci in the orthotopic inoculation model of androgen-sensitive prostate cancer cells introduced with green fluorescent protein.

BACKGROUND: An in vivo spontaneous metastatic model using androgen-sensitive prostate cancer cells is needed to the better understanding of prostate cancer progression. Orthotopically inoculated LNCaP cells to SCID mice manifests metastases, but it takes no less than 12 weeks to detect them by conventional methods. METHODS: The green fluorescent protein (GFP) gene was introduced into LNCaP cells by conventional lipofection technique. Biological characteristics of a subline (LNCaP-GFP) that expressed GFP at high level were compared to those of the parental cells. LNCaP-GFP cells were orthotopically inoculated to the SCID mouse, and metastases to distant organs were chronologically examined under fluorescence microscopy. RESULTS: There was no difference in growth rates and androgen-responsiveness in vitro between LNCaP-GFP and LNCaP cells. LNCaP-GFP cells inoculated to SCID mice produced prostate specific antigen. Histopathological examination at 12 weeks after inoculation of LNCaP-GFP revealed that metastases were identified as the inoculation of LNCaP cells. Colonies consisting of a few LNCaP-GFP cells, however, were detected in the lung under fluorescence microscopy as early as 4 weeks after inoculation. CONCLUSIONS: Orthotopic inoculation of LNCaP-GFP to SCID mice may provide a useful tool to investigate the molecular mechanism of progression, in particular the early stage of metastasis, of androgen-sensitive prostate cancer cells.

Androgens↗

Increased risk of prostate cancer and benign prostatic hyperplasia associated with a CYP17 gene polymorphism with a gene dosage effect.

The CYP17 gene (CYP17) codes for the cytochrome P450c17alpha enzyme, which mediates two key steps in the sex steroid synthesis. There is a polymorphism (a T-to-C substitution) in the 5'-untranslated region, which may influence the transcription level of CYP17 mRNA. There is a continuing controversy as to whether the variant allele is associated with a subset of breast cancer or polycystic ovary syndrome. In prostate cancer research, there are contradictory data concerning the CYP17 risk allele. We explored the association between CYP17 polymorphism and a risk of prostate cancer or benign prostatic hyperplasia (BPH) in a Japanese population. This study included 252 prostate cancer patients, 202 BPH patients, and 131 male controls. A 451-bp fragment encompassing the polymorphic site was amplified by PCR, treated with restriction enzyme MspA1, and electrophoresed on an agarose gel. The MspA1-undigested allele with the published sequence and the MspA1-digested variant allele were designated as A1 and A2, respectively. There was a significant difference (P < 0.05) in the genotypes between prostate cancer patients and male controls, and between BPH patients and male controls. Men with the A1/A1 CYP17 genotype had an increased risk of prostate cancer [odds ratio (OR), 2.57; 95% confidence interval (CI) = 1.39-4.78] and BPH (OR, 2.44; 95% CI = 1.26-4.72) compared with those with the A2/A2 genotype. Men with the A1/A2 genotype had an intermediate increased risk of prostate cancer (OR, 1.45; 95% CI = 0.84-2.54) and BPH (OR, 1.60; 95% CI = 0.89-2.87) compared with those with the A2/A2 genotype. The trend of an increasing risk of prostate cancer and BPH with an increasing number of the A1 allele was statistically significant (prostate cancer versus male control, P = 0.003; OR, 1.57; 95% CI = 1.16-2.12; BPH versus male control, P = 0.008; OR, 1.55; 95% CI = 1.12-2.13). There was no significant association between the CYP17 genotype and the tumor status (grade and stage) of prostate cancer. Our results suggest that the A1 allele of the CYP17 polymorphism is associated with an increased risk of prostate cancer and BPH, with a gene dosage effect. However, the CYP17 genotype does not seem to influence the disease status in prostate cancer.

Aged↗

Use of pretreatment prostate-specific antigen doubling time to predict outcome after radical prostatectomy.

The objective of this study was to better understand the implications of the rate of prostate-specific antigen (PSA) changes in prostate carcinoma. We retrospectively calculated PSA doubling times prior to surgery in 62 patients with prostate carcinoma. The calculated values were compared with final pathologic findings and with rates of PSA failure after surgery. PSA values increased during the period of observation in 82.3% of the patients, whereas 17.7% had levels that remained stable. The median calculated PSA doubling time in those with increasing levels was 25.8 months, with doubling times </=24 months observed in 37.1% of the patients. Stage pT3 disease was more common in patients with PSA doubling times of </=36 months than in those with doubling times >36 months (P=0.02). Biochemical failure was more common in patients with rapid PSA doubling times (P<0.01). The calculated PSA doubling time prior to radical surgery is significantly associated with the final pathologic findings. Early PSA failure is more common in patients with rapid PSA doubling times prior to radical surgery. Prostate Cancer and Prostatic Diseases (2000) 3, 269-274

Journal Article↗

Per-operative frozen section examination of pelvic nodes is unnecessary for the majority of clinically localized prostate cancers in the prostate-specific antigen era.

BACKGROUND: The incidence of unsuspected lymph node metastasis seems to be decreasing in the prostate-specific antigen (PSA) era. It remains controversial as to whether routine pelvic lymph node dissection and per-operative frozen section examination should be performed. In addition, it is still unclear whether an aggressive approach to local disease by surgery or irradiation confers survival benefits on stage D1 patients. METHODS: Eighty-eight consecutive patients with clinically localized prostate cancer who underwent pelvic lymph node dissection prior to radical prostatectomy during the period between 1985 and 1998 were analyzed. The incidence of lymph node metastases after 1992 was compared with that before 1992. Sensitivity and specificity of frozen section examination was assessed. Progression-free survival and cause-specific survival curves of node-positive patients who underwent radical prostatectomy were estimated by the Kaplan-Meier method. RESULTS: Six of 17 patients (35.3%) treated before 1992 and five of 71 patients (7.0%) treated after 1992 showed unsuspected lymph node metastasis (P = 0.0059). Eight of 11 node-positive patients underwent radical prostatectomy and two have so far demonstrated clinical progression and cancer death with a median follow-up period of 63 months. The 5 year progression-free rate and the cause-specific survival rate for these patients were 71.4 and 85.7%, respectively. Sensitivity of frozen section examination for micrometastasis and gross-metastasis cases, respectively, was 3/6 (50%) and 4/4 (100%), while specificity was 85/85 (100%). CONCLUSIONS: The incidence of unsuspected lymph node metastases has been significantly decreased in the PSA era. Frozen section examination of pelvic nodes can be omitted and radical prostatectomy is an acceptable choice of treatment in patients without macroscopically apparent nodal metastases.

Aged↗

Allelic imbalances on chromosome 20 in human transitional cell carcinoma.

One determinant of the survival time of cancer-bearing patients may be genetic factors. In chemically induced bladder cancers of mice, differences in survival time have been observed among several inbred strains. Genetic analyses of such differences in crosses between C57BL / 6 and NON mice revealed that the survival period is determined by two quantitative trait loci on mouse chromosomes 6 and 2, respectively. We explored the possibility that genetic alterations may be observed in the syntenic conserved chromosomal regions of human transitional cell carcinoma corresponding to mouse chromosomes 6 and 2. Human chromosome 7, containing a region syntenic to mouse chromosome 6, is reported to harbor frequent genetic alterations in bladder cancers. In this study, we investigated 70 human urothelial cancers for possible genetic alterations on human chromosome 20p and 20q containing regions syntenic to mouse chromosome 2. Allelic imbalances were observed in 22 cases (31.4%) on 20p and 18 cases (25.7%) on 20q. Those allelic imbalances, however, did not show a direct correlation with the prognosis of the patients. Higher grade tumors tended to show more frequent imbalances on chromosome 20; however, this tendency was not significant.

Alleles↗

Clinical significance of nonpalpable prostate cancer with favorable biopsy features in Japanese men.

OBJECTIVE: To assess the clinical significance of nonpalpable localized prostate cancers with relatively favorable six sextant biopsy features in Japanese men. PATIENTS AND METHODS: 136 nonpalpable prostate cancers of which biopsy features confined to (1) a Gleason score of 6 or less, (2) one or two positive cores per six sextant cores, and (3) 50% or less involvement of any positive core were collected. The Gleason score, tumor extension, and cancer volume were compared with preoperative serum PSA and PSA density for the patients who underwent radical prostatectomy. PSA doubling time was measured for the patients who were treated expectantly. RESULTS: Treatments chosen for 136 patients with favorable biopsy features were radical prostatectomy alone for 48 and with preoperative androgen deprivation for 30, radiation to the prostate for 12, androgen deprivation therapy for 21, and watchful waiting for 25. Of 48 patients who underwent radical prostatectomy without androgen deprivation therapy, 25% had nonorgan-confined cancers. Seven cancers (14.6%) were Gleason score of 7, but no cancers were 8 or greater. Among 42 prostatectomy specimens for which cancer volume was measured, 22 (52.4%) had cancer volume >0.5 cm(3). Pretreatment serum PSA levels were correlated neither with the Gleason score, tumor extension nor cancer volume. There was only one nonorgan-confined cancer in the 23 cancers for which PSA density was <0.2 ng/ml/g. The ability of PSA density to predict cancer volume <0. 5 cm(3) was 0.61 using a cut-off of 0.2 ng/ml/g. Of the 25 patients treated expectantly, the PSA doubling time was less than 2 years for 3 patients, while it was stable or fluctuated for 13. CONCLUSIONS: Tumor extension can be predicted based on PSA density in nonpalpable prostate cancer with favorable biopsy features, but predictability of cancer volume based on PSA or PSA density is not satisfactorily high. New parameters or biomarkers that complement needle biopsy findings are needed to predict clinical significance of T1c prostate cancer with favorable biopsy features.

Aged↗

Use of a Technovit 7200 VLC to facilitate integrated determination of aluminum by light and electron microscopy.

Technovit 7200 VLC is an excellent embedding medium for both inorganic histochemistry by light microscopy and X-ray microanalysis by scanning and transmission electron microscopy. Liver samples from rats after intraperitoneal treatment with aluminum chloride were fixed in glutaraldehyde and embedded in the resin. Thick sections were easily cut on an ultramicrotome and stained with aluminon for aluminum (Al). An intense positive reaction with aluminon was observed in the Kupffer cells by light microscopy. The surface structures of the same resin block cut for light microscopy were observed under a scanning electron microscope fitted with an energy dispersive X-ray spectrometer. The Kupffer cells appeared white in the backscattered mode. Localization of Al in the Kupffer cells was confirmed by an X-ray distribution map in the scanning electron microscope. Subcellular localization of Al in the Kupffer cells was performed on the same semithin sections using a transmission electron microscope equipped with an energy dispersive X-ray spectrometer. Most Al was found in lysosomes of the Kupffer cells. The resin was stable in the electron beam and chlorine-free.

Acrylic Resins↗

[A study on parameters to predict tumor volume for stage T1c prostate cancers of Gleason score 6 or less].

The number of cases of stage T1c prostate cancer has dramatically been increasing since the introduction of PSA as a screening test. The patients with T1c prostate cancer are usually treated by radical prostatectomy. In this group, however, some cancers are of small tumor volume and with a Gleason score of less than 7. These cancers are considered to be good candidates for watchful waiting management. We have investigated 40 patients with T1c prostate cancer treated by radical prostatectomy between 1996 and 1998. All 9 patients harboring tumors of Gleason score 7 or greater had tumors larger than 0.5 cm3. We have investigated PSA-related parameters including total PSA (PSA), PSA density (PSAD), free PSA, and % free PSA in 31 patients with T1c cancers of Gleason score 6 or less in order to clarify good preoperative predictors of tumor volume. We compared the distribution of PSA, PSAD, free PSA, and % PSA between the larger and smaller tumor groups. There was no significant difference in PSA, PSAD, or free PSA value. The small tumor group had a greater mean % free PSA than the larger tumor group (23.27 versus 11.88, p = 0.007). Areas under receiver operating characteristic curves were 0.715, 0.794, 0.636, and 0.842 for PSA, PSAD, free PSA and % free PSA. In stage T1c prostate cancer of Gleason score 6 or less, % free PSA may be the most useful preoperative predictor for tumor volume of 0.5 cm3 or greater.

Aged↗

[Long-term clinical results of 5 cases of urachal carcinoma].

Five cases of urachal carcinoma experienced in our hospital during the past 20 years are reported. Surgical resection is considered as the first treatment option of this disease, and other therapies to be less beneficial. Complete surgical extirpation and detection of recurrence in the early stage are considered to be important since local recurrence occurs frequently. We enforced the bladder preserving operation for 4 patients with urachal carcinoma except for 1 case with peritonitis carcinomatosa in the initial diagnosis, and multiple surgical treatment was performed again for 2 patients with recurrence. The bladder was preserved with no evidence of malignancy in three patients for 24, 19 and 5 years, respectively. In the initial management of urachal carcinoma, we believe that bladder-preserving surgery should be considered in selected cases though close follow-up is demanded. Herein, we also report the immunohistochemical study of paraffin-embedded specimens using anti-CEA, CA19-9, CA125 and p53 monoclonal antibodies. The positive reaction was observed in 100% (5/5) for CEA, 80% (4/5) for CA19-9, and 20% (1/5) for CA125. These results suggest that CEA may be a useful marker in the diagnosis of this neoplasm and early detection of its recurrence. Nuclear accumulation of p53 was observed in 80% (4/5), but it did not correlate with the disease progression.

Adult↗

Vasculitis-susceptible genes in mice with a deficit in Fas-mediated apoptosis.

Autoimmune diseases show complex pathological manifestations, which frequently involve systemic vasculitis. This complication is understood to be a manifestation of advanced disease, or to represent distinct entities, restricted by genetic and/or environmental factors. An MRL/Mp strain of mice bearing the Fas deletion mutant gene, lpr (MRL/lpr), spontaneously develop systemic vasculitis coincidentally with glomerulonephritis, arthritis and sialoadenitis, but a C3H/HeJ-lpr/lpr (C3H/lpr) strain does not. Thus, this is a suitable model for analyzing the genetic basis of vasculitis in autoimmune diseases. To genetically dissect these complex pathological manifestations, a linkage analysis of each lesion with polymorphic microsatellite markers was performed by using MRL/lpr x (MRL/lpr x C3H/lpr)F1 backcross mice. Vasculitis-susceptible gene loci were mapped on chromosomes 3 and 4, which were not associated with glomerulonephritis, arthritis and sialoadenitis. These results indicate that systemic vasculitis in MRL/lpr mice may be under the control of host genes which are different from those for other autoimmune diseases.

Animals↗