Biomedical subjects
Publications and source records attributed to T Kamura.
Two cases of androgen-producing tumors, including a Sertoli-Leydig cell tumor in a woman of reproductive age and a Leydig cell tumor in a postmenopausal woman, are reported herein. In both cases, only selective venous sampling was able to detect the presence of the androgen-producing ovarian tumors.
OBJECTIVE: To compare retrospectively the efficacy of the anterior colporrhaphy procedure (AC) and the Marshall-Marchetti-Krantz operation (MMK) in the treatment of stress urinary incontinence (SUI). METHODS: A retrospective analysis through a review of the medical records of Japanese women with stress urinary incontinence who were surgically treated at Kyushu University Hospital from 1980 through 1996. A questionnaire regarding the current status of urinary incontinence was sent to all patients. RESULTS: A total of 103 patients could be evaluated, 77 of whom had undergone an AC, and 26 of whom had undergone an MMK. Postoperative complications were more common in the AC group (p < 0.05). There were no significant differences between the 2 groups in terms of the duration of hospital stay or postoperative catheterization. The long-term subjective cure rates of the ACs and the MMKs were 55% and 58%, respectively. CONCLUSIONS: The AC and the MMK were equally effective in treating stress urinary incontinence, and both showed decreased long-term subjective cure rates. The recurrence rate did not differ between the AC and the MMK. The AC had more postoperative complications and shorter recurrence intervals.
BACKGROUND: Lymph node metastasis has been one of the strongest prognostic factors in patients with cervical cancer. In order to select patients with high risk for recurrence, a relationship between status of lymph node and other histopathological parameters was investigated in the patients treated with radical hysterectomy with pelvic lymph adnectomy. METHODS: Of 483 patients undergoing radical hysterectomy with pelvic lymph adnectomy, 309 had stage Ib disease, 62 stage IIa, and 112 stage IIb. RESULTS: Pelvic lymph node metastasis(PLNM) was positive in 98 patients (20%). Of those positive patients, 51(56%) had metastasis in one site, 25 (26%) in two sites, and 22 (22%) in three or more sites. There was a significant difference in survival between patients with metastasis in one or no sites and those in two or more sites (p<0.0001). There was a relationship between PLNM in more than two sites and histological parameters such as histologic subtype, longitudinal diameter of cervical lesion, degree of stromal invasion, depth of stromal invasion, lymph-vascular space invasion, parametrial invasion, and corpus invasion. All of these parameters except for histologic subtype were significantly correlated with the number of positive lymph node sites. Multivariate analysis revealed that among these parameters, longitudinal diameter of the cervical lesion, parametrial invasion, and lymph-vascular space invasion were independently significantly correlated with PLNM in two or more sites. CONCLUSIONS: From these results, patients having these three histopathological parameters could be considered as those with extensive disease distribution.
We previously established (K. Sonoda et al., Int. J. Oncol., 6: 1099-1104, 1995) a novel monoclonal antibody, 22-1-1, generated from adenocarcinoma of the uterine cervix, and 22-1-1 antigen (Ag) was expressed in cancer cells derived mainly from the uterus and ovary. In this report, a relationship between 22-1-1 Ag expression and clinicopathological variables and the prognostic significance of 22-1-1 Ag were immunohistochemically investigated in adenocarcinoma of the cervix. Of 56 cases, the 22-1-1 Ag was negative in 7, 1+ in 14, 2+ in 26 and 3+ in 9 instances. The 22-1-1 Ag existed both in the cytoplasm and on the membrane of cancer cells. There was no correlation between 22-1-1 Ag expression and age, stage, grade, myometrial invasion, lymph-vascular space invasion, lymph node metastasis, and parametrial invasion. The estimated 5-year overall survival (OS) of patients with low 22-1-1 Ag expression (-/+) and high 22-1-1 Ag expression (++/ ) were 90.5 and 71.4%, respectively. Patients with high 22-1-1 Ag expression had significantly worse OS than those with low 22-1-1 Ag expression (log-rank test, P = 0.0193). In addition, lymph-node metastasis, age, and clinical stage were significantly related to OS in univariate analysis. Multivariate analysis for OS revealed a prognostic significance in 22-1-1 Ag expression, stage, age, and grade. These data suggest that 22-1-1 Ag expression may be related to prognosis in adenocarcinoma of the cervix.
The Elongin BC complex was identified initially as a positive regulator of RNA polymerase II (Pol II) elongation factor Elongin A and subsequently as a component of the multiprotein von Hippel-Lindau (VHL) tumor suppressor complex, in which it participates in both tumor suppression and negative regulation of hypoxia-inducible genes. Elongin B is a ubiquitin-like protein, and Elongin C is a Skp1-like protein that binds to a BC-box motif that is present in both Elongin A and VHL and is distinct from the conserved F-box motif recognized by Skp1. In this report, we demonstrate that the Elongin BC complex also binds to a functional BC box present in the SOCS box, a sequence motif identified recently in the suppressor of cytokine signaling-1 (SOCS-1) protein, as well as in a collection of additional proteins belonging to the SOCS, ras, WD-40 repeat, SPRY domain, and ankyrin repeat families. In addition, we present evidence (1) that the Elongin BC complex is a component of a multiprotein SOCS-1 complex that attenuates Jak/STAT signaling by binding to Jak2 and inhibiting Jak2 kinase, and (2) that by interacting with the SOCS box, the Elongin BC complex can increase expression of the SOCS-1 protein by inhibiting its degradation. These results suggest that Elongin BC is a multifunctional regulatory complex capable of controlling multiple pathways in the cell through interaction with a short degenerate sequence motif found in many different proteins.
BACKGROUND: Angiogenesis is essential for tumor growth, progression, and metastases. Microvessel density (MVD), a measure of tumor angiogenesis, has been found to have prognostic significance in many tumor types for predicting metastasis and survival. METHODS: Between 1979-1989, 56 cases of FIGO Clinical Stage I and II adenocarcinoma of the uterine cervix treated by hysterectomy were reviewed histologically. All hysterectomy specimens were stained immunohistologically for factor VIII-related antigen. MVD was counted in a x200 field (0.785 mm2 per field) in the most active area of neovascularization. Results were expressed as the highest number of microvessels identified within any single x200 field. MVD and several other prognostic parameters were examined for correlation with progression free survival (PFS) and overall survival (OS) by a multivariate analysis according to the Cox proportional hazards model. RESULTS: In early adenocarcinoma of the uterine cervix, MVD was increased significantly in invasive areas compared with adjacent nonneoplastic areas (median: 62.5 [range, 30-105] vs. median: 36.5 [range, 23-47]; P=0.0003). MVD also was significantly correlated with ascites cytology (P=0.0377). There was no correlation between microvessel count and lymph node status, depth of invasion, disease stage, lymph-vascular space invasion, grade, or parametrial involvement. Patients with high MVD (> or=75) had significantly worse PFS and OS than those with low MVD (< 75) (log rank test, P=0.0180 and 0.0199, respectively). Multivariate analysis showed that MVD correlated significantly and independently with PFS and OS. CONCLUSIONS: In adenocarcinoma of the cervix, MVD is an independent prognostic factor for PFS and OS.
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Among the 191 patients with complete hydatidiform moles who were diagnosed and treated at Kyushu University Hospital from 1982 until 1996, 167 patients were diagnosed with uneventful moles retrospectively. The serial beta human chorionic gonadotropin (hCG) values in the 167 patients with uneventful moles were analyzed by a stepwise piecewise linear regression analysis in order to establish a normal regression curve of a human chorionic gonadotropin after a molar pregnancy. This normal regression curve is considered to be excellent regarding sensitivity (24/24-100%) and to be equivalent to the identification based on a plateau or a rise regarding specificity (156/167-93.4%). To distinguish patients with persistent trophoblastic disease (PTD) from uneventful moles, this normal curve is thus considered to be accurate since the accuracy was 180/191 (94. 2%). The weeks exceeding the normal regression curve in 24 PTD patients were 5.04 +/- 3.85 weeks and were also earlier than the weeks based on a plateau or a rise (P = 0.01). Within 7 weeks after evacuation, in 21/24 (87.5%) of the PTD cases, the beta-hCG values exceeded the normal range, while in only 14/24 (58.3%) the beta-hCG showed a change in the shape of a plateau or a rise. In addition, in 19/24 (79.2%) of the PTD patients, the time exceeding the normal range was shorter than the time exhibiting a plateau or a rise in the beta-hCG change. The above findings thus led us to conclude that this normal regression curve was useful for discriminating PTD from uneventful moles more precisely and more quickly than by identification based on a plateau or a rise.
We experienced a case of multiple bilateral giant bullae of the lungs and treated by thoracoscopic bilateral resection. A 46-year-old male was admitted to our hospital on the diagnosis of bilateral giant bullae of the lungs. Chest CT scan and lung perfusion scintigraphy showed giant bullae at the apex of both lungs and at the left lower lobe. The border of the bullae was relatively clear, and the other lung was almost normal although it was compressed by the bullae. We evaluated this case and found that it was a good indication for a thoracoscopic bilateral resection. The patient was positioned on his back, and a successful thoracoscopic bilateral resection was performed. The patient was discharged from the hospital on the 10th day postoperatively. Chest CT scan, lung perfusion scintigraphy and respiratory function test performed 2 months postoperatively, showed remarkable improvement. We would recommend this surgical technique in patients with similar diagnosis.
To establish a more suitable model for reflecting biological aggressiveness in clinically recurrent cancers after chemotherapy, we made the in-vitro-established cisplatin-resistant cell lines, by exposing the parental tumor cell lines to cisplatin in a culture system, and also the in-vivo-established cisplatin-resistant cell lines by repeated cisplatin administration to parental tumor-bearing mice. Although both cell lines similarly demonstrated a clinically relevant low level of drug resistance (from 1.5 to 2.9 times more resistance to cisplatin than their parental cell lines), only the in-vivo-established cisplatin-resistant cell lines showed significantly enhanced metastatic properties with a 2.1- to 3.4-fold increase in the number of lung metastatic nodules. These enhanced metastatic properties were caused by tumor invasiveness in combination with various levels of enhancement of cell attachment, proteolytic enzyme activity and cell motility. We concluded that anticancer drugs such as cisplatin could promote tumor progression only in the drug-resistant cell lines established in vivo. As a result, these cell lines are considered to be a more faithful and useful model for expressing biological aggressiveness in clinically recurrent cancers after chemotherapy than the conventional drug-resistant cell lines established in vitro.
OBJECTIVE: To compare the efficacy of adjuvant chemotherapy after radical hysterectomy with that of adjuvant radiotherapy. METHODS: One hundred one women with invasive cervical carcinoma (stage IB through early stage IIB) underwent radical hysterectomy at Saga Medical School Hospital. Of these patients, 53 with squamous or adenosquamous carcinoma were classified as high risk, based on the presence of one or more of the following high-risk factors for recurrence: 1) lymph node metastasis, 2) deep cervical stromal invasion (greater than 3/4 thickness), and 3) parametrial invasion. Adjuvant chemotherapy with a combination of cis-diamminedichloroplatinum (CDDP), vincristine, mitomycin C, and peplomycin (POMP), was prescribed. The outcome was compared with that for 127 patients who were classified as high risk under the same criteria and who received adjuvant radiotherapy at Kyushu University Hospital. RESULTS: The 5-year survival rates were much the same: 83.0% for adjuvant chemotherapy and 81.7% for adjuvant radiotherapy. In the chemotherapy group, intra- and extrapelvic recurrences accounted for 85 and 23% of all recurrences, respectively, whereas recurrences were noted for 38 and 71% in the radiotherapy group, respectively (P < .01). CONCLUSION: The use of adjuvant chemotherapy reduces extrapelvic recurrences. The combination of both adjuvant therapies may improve the prognosis for high-risk patients.
Sclerosing stromal tumor (SST) is a rare ovarian neoplasm occurring predominantly in young women and is histologically characterized by cellular heterogeneity, prominent vasculature, and a pseudolobular appearance composed of cellular and hypocellular areas. In the current study, three cases of SST were ultrastructurally examined and the tumors were found to be composed of several kinds of cells, i.e., luteinized thecalike cells, spindle-shaped fibroblastic cells, and primitive mesenchymal cells. These findings thus supported the ovarian stromal origin of SST. Twelve cases of SST also were analyzed immunohistochemically and demonstrated an expression of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) in the luteinized thecalike cells and its receptor, fms-like tyrosine kinase 1 (flt-1), in capillary to medium-sized blood vessels. Reverse transcription-polymerase chain reaction (RT-PCR) also showed an expression of VPF/VEGF messenger RNA in SSTs. Accordingly, the characteristic vasculature and edema of SSTs were considered to be associated with the expression of VPF/VEGF. In addition, a fluorescence in situ hybridization (FISH) analysis also showed cells with three copy number of chromosome 12 in 13-21% of all examined SST cells, which suggested the presence of chromosome 12 trisomy in SSTs as well as in other ovarian stromal tumors.
The von Hippel-Lindau tumor suppressor protein (pVHL) binds to elongins B and C and posttranscriptionally regulates the accumulation of hypoxia-inducible mRNAs under normoxic (21% O2) conditions. Here we report that pVHL binds, via elongin C, to the human homolog of the Caenorhabditis elegans Cul2 protein. Coimmunoprecipitation and chromatographic copurification data suggest that pVHL-Cul2 complexes exist in native cells. pVHL mutants that were unable to bind to complexes containing elongin C and Cul2 were likewise unable to inhibit the accumulation of hypoxia-inducible mRNAs. A model for the regulation of hypoxia-inducible mRNAs by pVHL is presented based on the apparent similarity of elongin C and Cul2 to Skp1 and Cdc53, respectively. These latter proteins form complexes that target specific proteins for ubiquitin-dependent proteolysis.
We have reported that a novel tumor-associated antigen (Ag), 22-1-1, was expressed in cancer cells derived mainly from the uterus and ovary [K. Sonoda et al., Cancer (Phila.), 77: 1501-1509, 1996]. The 22-1-1 Ag existed not only in adenocarcinomas but also in squamous cell carcinomas in the uterine cervix. Here, a relationship between tumor progression and invasion and 22-1-1 Ag expression was investigated in squamous cell neoplasms of the uterine cervix using immunohistochemical staining. The 22-1-1 Ag was not detected in normal uterine cervix (0 of 10 total cases) and dysplasias (0 of 47 total cases). However, 20% of carcinoma in situ (4 of 20 total cases) and 16.7% of microinvasive carcinomas (2 of 12 total cases) stained positively for 22-1-1 Ag. Moreover, areas depicting microinvasion on histology in uterine cancers (stage Ia) were more strongly stained than carcinoma in situ lesions. 22-1-1 Ag expression was found to be more frequent in invasive squamous cell carcinomas (82.6%; 57 of 69 total cases). The 22-1-1 Ag existed both in the cytoplasm and on the membrane of cancer cells. These findings suggest that 22-1-1 Ag expression might be related to tumor cell progression and invasion in the uterine cervical squamous cell epithelium.
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BACKGROUND: Tumor angiogenesis is essential for tumor growth and metastases. Recently, microvessel density (MVD), a measure of tumor angiogenesis, has been found to have prognostic significance for predicting metastasis and survival in many tumor types. This study was conducted to determine how MVD was related to several clinicopathologic parameters and correlated with metastasis and survival in patients with endometrial carcinoma. METHODS: From 1979 through 1989, 85 cases of clinical Stage I and II endometrial carcinomas treated initially by hysterectomy with pelvic lymph node dissection were reviewed histologically. All hysterectomy specimens were stained immunohistologically for factor VIII-related antigen. MVD was counted in a x200 field (x20 objective lens and x10 ocular lens, 0.785 mm2 per field) in the most active area of neovascularization. Results were expressed as the highest number of microvessels identified within any single x200 field. Statistical analysis included the Mann-Whitney U test, Kruskal-Wallis test of variance, and the Spearman rank correlation test. Survival was calculated using the Kaplan-Meier method and differences in survival were analyzed using the log rank test. MVD and several other prognostic parameters were examined for their correlation with progression free survival (PFS) and overall survival (OS) by a multivariate analysis according to the Cox proportional hazards model. RESULTS: MVD was significantly correlated with tumor grade (P = 0.0281), myometrial invasion (P = 0.0282), and lymph-vascular space invasion (P = 0.0073). There was no correlation between microvessel count and lymph node status and stage. Patients with a high MVD (> or =60) had significantly worse PFS and OS than those with a low MVD (<60) (log rank test, P = 0.0116 and P = 0.0096, respectively). Multivariate analysis showed that MVD correlated significantly and independently with PFS and OS. CONCLUSIONS: In this study, MVD was found to be an independent prognostic factor for PFS and OS in patients with endometrial carcinoma.
Thrombopoietin (TPO), the ligand for c-Mpl, is a cytokine that regulates megakaryocyte growth and development. We have cloned the 5'-flanking region of the human TPO gene and analyzed its promoter activity. The human TPO gene promoter lacks a TATA box and directs transcription initiation at multiple sites over a 50-nucleotide region. Transient expression in a human liver cell line (PLC) of promoter fragment-luciferase reporter gene constructs containing a series of 5'-truncated sequences or site-directed mutations identified a sequence 5'-ACTTCCG-3' from -69 to -63 as a positive cis-acting element for high level expression of TPO gene. This sequence contains a core motif (C/A)GGA(A/T) for Ets family proteins in the noncoding strand. Gel mobility shift assays performed with nuclear protein from PLC cells identified a DNA binding protein(s) specific for the element. Anti-E4TF1-60(GABPalpha) or anti-E4TF1-53/47(GABPbeta) antibodies supershifted the complex in gel shift assay. Furthermore, co-expression of E4TF1-60 and E4TF1-53/47 squelched TPO gene expression in PLC and HepG2 cells. It is concluded that Ets family transcription factor E4TF1(GABPalpha/beta), an ubiquitously expressed protein, is required for high level expression of the TPO gene in liver.
We reviewed the clinical and pathological features of seven cases of adenocarcinoma of the uterine cervix with predominantly villogladular papillary growth pattern. The patients, who ranged in age from 33 to 54 (mean, 45) years, underwent radical hysterectomy. In all seven cases, the tumors were papillary exophytic architecture lined by stratified epithelial cells with mild to moderate nuclear atypicality. In one of seven cases, the majority of the tumor showed villogladular papillary component, but the small foci of small cell carcinoma was present in the endocervical end of the tumor. The lymph vascular invasion was demonstrated in two of seven cases, and these two had pelvic lymph node metastases. One of these two patients had recurrence 30 months after the initial treatment and died of disease after 46 months. The follow-up ranged from 9 to 169 (median, 46) months. The presence or absence of lymph vascular invasion and minor components of this tumor such as small cell carcinoma, serous cell carcinoma, and clear cell carcinoma with a poor prognosis may be important histological findings before deciding to manage this tumor by the conservative treatment.