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Biomedical subjects

N Miyao

Publications and source records attributed to N Miyao.

At least 37 records · Page 2Linked to original sources

Lymph node metastasis in patients with carcinomas of the renal pelvis and ureter.

OBJECTIVES: We evaluated the clinical significance of lymph node metastasis in patients with carcinomas of the renal pelvis and ureter. METHODS: 68 patients without distant metastasis were included in this study. Multivariate analysis by Cox's proportional hazards model was applied to detect the prognostic factor(s). RESULTS: 12 patients (17.6%) had nodal involvement. More than 10% of the patients with pT1-2 showed nodal metastasis. Preoperatively determined clinical factors were not a predictive factor for nodal involvement. Nodal metastasis was the only significant negative prognostic factor for patient survival by multivariate analysis. CONCLUSIONS: Lymph node dissection is valuable to predict the clinical outcome of the patients with carcinoma of the renal pelvis and ureter. Attention should be paid to nodal status to select patients for conservative surgery.

Adolescent↗

Preselected biopsy for normal-appearing mucosa of superficial bladder carcinoma.

OBJECTIVES: We examined the incidence of positive findings (concomitant carcinoma in situ (CIS), frank carcinoma and dysplasia) for normal-appearing mucosal biopsies in superficial bladder carcinoma and the clinical outcome of patients with positive biopsy results. METHODS: Eighty-four cases of newly diagnosed superficial bladder carcinoma, from whom biopsies of preselected cystoscopically normal-appearing mucosal tissue were taken at the time of initial treatment, were studied. Multivariate analysis by Cox's proportional hazards model was applied. RESULTS: Twenty-seven percent of the patients with superficial bladder carcinoma showed positive biopsy results. Positive biopsy results independently influenced intravesical recurrence by Cox's proportional hazards model. CONCLUSIONS: Positive mucosal biopsy results are a significant indicator of intravesical recurrence in patients with superficial bladder carcinoma.

Adult↗

Development of a testicular haemangioma after interferon therapy for hepatic haemangiomas: a case report.

UNLABELLED: We report a 2-month-old Japanese boy presenting with large multiple haemangiomas invading his liver. He was treated with daily subcutaneous injection of interferon alfa (IFN-alpha)-2a with progressive reduction of the hepatic haemangioma. He developed a scrotal mass 2 months after discontinuation of IFN, and this mass eventually required surgical management. Resected tumour was a juvenile haemangioma. The escape of this haemangioma from IFN therapy may be correlated to the quite low level of injected IFN in testis. CONCLUSION: IFN therapy may not be curative for testicular haemangioma although it is effective in shrinking haemangiomas of the liver and skin.

Hemangioma↗

Juvenile hemangioma of the testis: analysis of expression of angiogenic factors.

We present a case of juvenile hemangioma of the testis associated with hemangiomas of the liver and skin. The testicular hemangioma appeared to progress after therapy with interferon alpha-2a (IFN alpha-2a), whereas the liver and skin hemangiomas regressed. Analysis of growth factors responsible for proliferation of hemangioma revealed that the tumor expressed vascular endothelial growth factor but not basic fibroblast growth factor (bFGF), which is reported to be inhibited by IFN alpha-2a. This finding suggests that a possible explanation for the inadequate efficacy of IFN alpha-2a for testicular hemangioma is a lack of bFGF expression.

Angiogenesis Inducing Agents↗

Pre-operatively determined prognostic factors in metastatic renal cell carcinoma.

OBJECTIVES: The aim of this study was to clarify the pre-operatively determined factors affecting the prognosis in patients with metastatic renal cell carcinoma (RCC). METHODS: We analyzed 69 patients with metastatic RCC who received nephrectomy. Multivariate analysis by Cox's proportional hazards model and survival studies were applied. RESULTS: Tumor thrombus in a renal vein or vena cava was the most significant poor-prognostic factor, followed by multiple-organ metastases and three or more abnormal findings of factors related to acute-phase proteins, in this order. Seven patients having these three risk factors died of cancer within 7 months after nephrectomy. On the other hand, half of the patients without risk factors survived for more than 2 years. CONCLUSIONS: Risk status should be used for selection of metastatic-RCC patients for treatment of the primary site.

Acute-Phase Proteins↗

Disialosyl galactosylgloboside as an adhesion molecule expressed on renal cell carcinoma and its relationship to metastatic potential.

Aberrant glycosylation expressed in specific types of human cancer may define stage, direction, and fate of tumor progression. Well-studied examples are expression of sialosyl-Lewis(x) or sialosyl-Lewis(a) in colorectal carcinoma and histo-blood group A and H/Le(y) in lung cancer. In renal cell carcinoma (RCC), expression of sialosyl-Lewis(x) has no correlation with metastatic potential. Clinicopathological studies have revealed that the degree of expression of disialosyl galactosylgloboside (DSGG) and monosialosyl galactosylgloboside is correlated with metastatic potential (to lung and lymph nodes) of RCC and inversely correlated with patient survival. In the present study, we compared the adhesion of RCC lines to sections of various tissues measured by Stamper-Woodruff assay and other similar assays under dynamic flow conditions. Of the eight RCC lines tested, only TOS-1 (which expresses DSGG) bound strongly to lung tissue sections. TOS-1 did not bind to sections of liver, kidney, or lymph nodes. In the same eight RCC lines, we also compared expression of DSGG and monosialosyl galactosylgloboside (reflected by reactivity with RM1 and RM2), overall ganglioside patterns, and correlation with lung tissue-binding ability. Under both static and dynamic flow conditions, the binding of TOS-1 cells to lung alveolar tissue was correlated with their DSGG expression, i.e., the binding was inhibited by RM2 but not by RM1. This binding was also inhibited by sialidase but not by EDTA (i.e., it was CA 2+ independent). The other seven cell lines (TOS-2, TOS-M, SMKT-R1, -R2, -R3, and -R4, and ACHN), which do not express DSGG, showed much weaker adhesion to lung tissue. None of the eight cell lines showed E- or P-selectin-dependent adhesion. These results suggest the existence of a yet-uncharacterized sialoadhesive receptor++ that specifically recognizes DSGG. This receptor could be the binding target in RCC metastasis to lung.

Carbohydrate Conformation↗

BCX-34: a novel T-cell selective immunosuppressant: purine nucleoside phosphorylase (PNP) inhibitor.

We evaluated the efficacy of a new purine nucleoside phosphorylase inhibitor, BCX-34, as an immunosuppressive agent. BCX-34 showed a complete inhibitory effect on the proliferation of T-cells in an in vitro system, whereas no influence was observed in B-cell lines. In addition, it was revealed that this inhibitory effect was not due to the suppression of interleukin-2 production. Therefore, BCX-34 might be a potentially useful drug that can be used in combination, not competition, with cyclosporine A and FK506.

Animals↗

[A clinical study of radial prostatectomy].

BACKGROUND: The objective of this study is to evaluate the efficacy of radical prostatectomy for patients with organ-confined prostate cancer. METHODS: From 1990 to 1994, a total of 50 patients with prostate cancer underwent radical retropubic prostatectomy. RESULTS: Eleven patients were in state A2, 34 in stage B and 5 in stage C according to clinical stage. Extended disease was observed pathologically in 45%, and 59% of patients in clinical stages A2 and B, respectively. Preoperative serum PSA levels were closely correlated with pathological extension of the disease. The disease-free rates for organ-confined disease, extended disease without lymph node metastasis and stage D1 disease were 75% (3 years), 82% (2 years) and 80% (3 years), respectively. Four patients had rectal injuries, and three of these underwent temporary colostomy diversion. Two patients had bladder neck contracture and received internal urethrotomy. Urinary incontinence improved in 60% of patients during the first 6 post-operative and in 90% of patients within 12 post-operative months. Urinary incontinence tended to improve earlier in patients with nerve-sparing than those without it. The erectile capacity in nerve sparing patients recovered good. CONCLUSION: Our results indicate that radical prostatectomy is a safe and temporarily satisfactory treatment for the patient with organ-confined prostate cancer.

Adenocarcinoma↗

Two molecular pathways to transitional cell carcinoma of the bladder.

Noninvasive transitional cell carcinomas of the bladder can have two distinct morphologies suggesting they contain different genetic alterations. Papillary transitional cell carcinomas (T(a) tumors) are often multifocal and only occasionally progress, whereas flat tumors (carcinomas in situ, CIS), frequently progress to invasive disease. We examined 216 bladder tumors of various stages and histopathologies for two genetic alterations previously described to be of importance in bladder tumorigenesis. Loss of heterozygosity of chromosome 9 was observed in 24 of 70 (34%) T(a) tumors but was present in only 3 of 24 (12%) CIS and dysplasia lesions (P = 0.04). In contrast, only 1 of 36 (3%) T(a) tumors contained a p53 gene mutation compared to 15 of 23 (65%) CIS and dysplasias (P < 0.001), a frequency comparable to that observed in muscle invasive tumors (25 of 49; 51%). The presence of p53 mutations in CIS and dysplasia could explain their propensities to progress since these mutations are known to destabilize the genome. Analysis of several tumor pairs involving a CIS and an invasive cancer provided evidence that the chromosome 9 alteration may in some cases be involved in the progression of CIS to more invasive tumors, in addition to its role in the initiation of T(a) tumors. However, the CIS and secondary tumor were found to contain different genetic alterations in some patients suggesting divergent progression pathways. Bladder carcinogenesis may therefore proceed through two distinct genetic alteration pathways responsible for generating superficial tumors with differing morphologies and pathologies.

Alleles↗

Inhibitory effect of minocycline on in vitro invasion and experimental metastasis of mouse renal adenocarcinoma.

Degradation of the extracellular matrix by metalloproteinases is a critical phenomenon in cancer invasion and metastasis. Recent studies have revealed that minocycline (minocycline hydrochloride, a tetracycline) suppresses in vivo and in vitro mammalian collagenolytic activity. We investigated whether minocycline inhibited in vitro invasion and experimental pulmonary metastasis in subline-2 of streptozotocin-induced mouse renal adenocarcinoma (MRAC-PM2) cells. In vitro invasion assay demonstrated that treatment with 0.5 microgram/ml or 5.0 micrograms/ml minocycline significantly inhibited the invasion of MRAC-PM2 cells. In addition, intraperitoneal administration of 0.5 mg per mouse minocycline reduced the number of metastatic nodules in the lung when MRAC-PM2 cells were injected intravenously. Minocycline also suppressed type IV collagenolytic activity of the cells. However, the drug did not affect [3H]-thymidine uptake, growth of subcutaneously inoculated cells, attachment to the extracellular matrices, or haptotactic migration of the cells. These results indicated that the inhibitory action of type IV collagen degradation by minocycline can contribute, in part, to suppression of the in vitro invasion and metastatic potential of MRAC-PM2 cells.

Adenocarcinoma↗

Cellular polarity correlates with vimentin distribution, but not to keratin, in human renal cell carcinoma cells in vitro.

To investigate the relationships among vimentin, keratin and cellular polarity, reorganized glands composed of renal cell carcinoma cells were investigated in vitro. We employed two different three-dimensional collagen gel culture methods, the "floating sandwich method (FSM)" and the "dispersed embedding method (DEM)." The cells composed of reorganized glands formed by FSM culture showed distinct polarity. In contrast, the cellular polarity of the cells formed by DEM culture was less distinct. Keratin was evenly distributed throughout the cytoplasm regardless of the culture method. In contrast, in reorganized glands obtained by FSM culture, vimentin was distinctly polarized at the basal pole while glands obtained by DEM culture showed random distribution of vimentin. These results suggest that there is a close relationship between cell polarity and intracellular localization of vimentin, and that there may be different mechanisms controlling the organization of the two intermediate filament (IF) networks.

Carcinoma, Renal Cell↗

Microsatellite instability in bladder cancer.

Somatic instability at microsatellite repeats was detected in 6 of 200 transitional cell carcinomas of the bladder. Instabilities were apparent as changes in (GT)n repeat lengths on human chromosome 9 for four tumors and as alterations in a (CAG)n repeat in the androgen receptor gene on the X chromosome for three tumors. Single locus alterations were detected in three tumors, while three other tumors revealed changes in two or more loci. In one tumor we found microsatellite instability in all five loci analyzed on chromosome 9. The alterations detected were either minor 2-base pair changes or larger (> 2 base pairs) alterations in repeat length. All six tumors were low stage (Ta-T1), suggesting that these alterations can occur early in bladder tumorigenesis.

Base Sequence↗

Role of chromosome 9 in human bladder cancer.

The tumors of 20 patients with multifocal primary transitional cell carcinoma of the bladder or lymph node metastases were examined for molecular genetic defects which we have previously found to be present in > 50% of invasive tumors. These included loss of heterozygosity (LOH) of chromosome 9, which occurs in superficial as well as invasive bladder tumors, and LOH of chromosome 17p and p53 mutations, which are commonly found only in invasive tumors. Analysis of multiple or recurrent primary tumors in 7 patients for these markers was generally consistent with recently published data that the tumors are monoclonal in origin and that p53 mutations occur as a late event in the generation of invasive bladder cancers. Comparison of the primary tumors and metastases to regional lymph nodes in 14 patients demonstrated a complete concordance between the molecular genetic defects present, showing that LOH of chromosomes 9 and 17p and p53 mutations occurred in the primary tumors before metastasis. Because of the importance of chromosome 9 in bladder cancer, we mapped the location of a putative tumor suppressor gene by restriction fragment length polymorphism analysis of 123 cases obtained in this and earlier studies. Most of the tumors showed LOH for more than one marker on chromosome 9. Results of mapping of 4 tumors with partial deletion of chromosome 9 suggests that the tumor suppressor gene is located between 9p12 and 9q34.1.

Carcinoma, Transitional Cell↗

Sulfolipids and glycolipid sulfotransferase activities in human renal cell carcinoma cells.

A cell line (SMKT-R3) established from human renal cell carcinoma was characterized for the presence of sulfolipids and glycolipid sulfotransferases. Sulfolipids were found to constitute a large part of the acidic glycolipid fraction in SMKT-R3 cells. These findings were confirmed by metabolic labelling with 35S-sulfate. These sulfolipids were expressed at the surface of SMKT-R3 cells as ascertained by cytofluorometry using a monoclonal antibody directed to sulfolipids. Furthermore, markedly high activity levels of glycolipid sulfotransferases were observed in SMKT-R3 cells compared with other cell lines. These results suggest that the increased synthesis of sulfolipids in renal cell carcinoma tissue (Sakakibara et al., 1989. Cancer Res., 49, 335-339) is due to the elevation of the sulfotransferase activities of renal carcinoma cells themselves.

Carcinoma, Renal Cell↗

Leydig cell tumor: a case report with reference to its endocrinological features.

We reported an adult case of Leydig cell tumor, which demonstrated an increase of serum estradiol (E2) and suppression of serum testosterone (T) before orchiectomy. The direct inhibitory action of the elevated E2 on the enzymes involved in steroidogenesis and the negative feedback action on luteinizing hormone (LH) secretion of the E2 possibly caused the suppression of serum T. A human chorionic gonadotropin test before the operation revealed the elevation of T and E2, although the response was poor compared with that in normal subjects. However, the postoperative test showed no elevation of these hormones. This result may indicate that the Leydig cell tumor preserves a response to LH stimulation.

Chorionic Gonadotropin↗

Squamous cell carcinoma-associated antigen in uroepithelial carcinoma.

We investigated the clinical significance of squamous cell carcinoma (SCC) antigen determined by radioimmunoassay on patients with uroepithelial carcinoma. Serum SCC antigen levels and the positive rates were significantly higher in uroepithelial carcinoma having an SCC component than in normal controls, benign urologic diseases, other urogenital carcinomas, or in pure transitional cell carcinoma (TCC) of uroepithelial carcinomas. A substantial number of patients with pure TCC showed a positive serum level of SCC antigen. Immunohistochemical staining of SCC antigen on the uroepithelial carcinomas confirmed that some, not all, pure TCC, mostly grade 3, expressed SCC antigen in their cells. These results suggested a biologic characteristic of grade 3 TCC which is closely related to that of SCC. The serum levels of SCC antigen correlated well with the disease extensions in uroepithelial carcinoma containing SCC component. Changes in serum levels of SCC antigen following treatment reflected the clinical courses of patients, particularly in those with elevated pretreatment levels. The results of our study indicated that the determination of SCC antigen would be clinically useful for monitoring clinical courses of patients with uroepithelial carcinomas containing SCC component and of those with pure TCC whose pretreatment level was elevated.

Antigens, Neoplasm↗

Interleukin-6 in renal cell carcinoma.

We studied interleukin-6 production in 4 human renal cell carcinoma cell lines and measured the serum level in 71 patients with renal cell carcinoma, thus, clarifying a relationship between interleukin-6 secretion and an occurrence of the paraneoplastic syndrome in the carcinoma. Interleukin-6 was produced by 3 cell lines and detected in 25% of the patients. The level of interleukin-6 did not directly correlate with tumor volume and the differentiation grade of the carcinoma. However, the positive rate increased with progression of the stage. The serum level affected the 5-year survival of patients without distant metastasis. When serum interleukin-6 was elevated patients had a significantly higher frequency of unexplained fever and an elevation of acute phase proteins. These results suggest that some renal cell carcinomas can produce interleukin-6 and this cytokine is responsible for several paraneoplastic syndromes in the carcinoma.

Carcinoma, Renal Cell↗