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Taro Shuin

Publications and source records attributed to Taro Shuin.

At least 37 records · Page 2Linked to original sources
PubMed2005

Combined small cell carcinoma and sarcomatoid squamous cell carcinoma in the renal pelvis.

We report here a case of combined small cell carcinoma and sarcomatoid squamous cell carcinoma in the renal pelvis. A 61-year-old female presented with right flank discomfort, microhematuria and progressive renal dysfunction. Following diagnosis of right renal pelvic carcinoma, radical nephroureterectomy with lymph node dissection was performed through a midline incision. The tumor was pathologically diagnosed to be combined small cell carcinoma and sarcomatoid squamous cell carcinoma in the renal pelvis. The patient had no evidence of recurrence or metastasis, 16 months postoperatively. Small cell carcinoma or sarcomatoid squamous cell carcinoma of the renal pelvis is very rare. We believe this is the first such case to be reported in the world.

Carcinoma, Small Cell↗
PubMed2005

Renal matrix stones in an emphysematous pyelonephritis.

A 74-year-old-woman was referred to our hospital for further examination. Her chief complaint had been a high-grade fever, but she was seen at our hospital without fever. Plain fi lm of kidney, ureter and bladder drip infusion pyelography and abdominal computed tomography (CT) showed a gas shadow surrounding calcifications in the right renal pelvis. We diagnosed right emphysematous pyelonephritis. Since changes in the CT findings were not remarkable for 2 weeks, we performed laparoscopic right nephrectomy, even though her condition had not worsened. The renal pelvis contained brownish and clayish matter. We report here this rare case of renal matrix stones.

Aged↗
PubMed2005

New genetic causes of pheochromocytoma: current concepts and the clinical relevance.

Pheochromocytoma and paraganglioma are tumors of the autonomous nervous system mainly occurring in the adrenal medulla, but also in the extraadrenal paraganglias of the abdomen, thorax, neck and skull basis. The etiology comprises germline mutations of now 6 genes. About 10 years known are the RET gene susceptible for multiple endocrine neoplasia type 2, the VHL gene for von Hippel-Lindau Disease, and the NF 1 gene for neurofibromatosis Recklinghausen (neuro- fibromatosis type 1). Since 2000 the genes for succinatedehydrogenase subunits SDHB, SDHC, and SDHD have been identified for paraganglioma syndromes type 4, type 3, and type 1 respectively. Investigations of series of pheochromocytoma patients identified germline mutations in one of the genes SDHB, SDHD, VHL and RET in 24% to 50% of the patients. Multifocal tumors, young age and positive family history, known features associated with inheritence, have not been present in all patients. Therefore, analyses of blood DNA for mutations in these genes are recommended. Positive tests provide the patients and their relatives with essential platforms for clinical care. Experiences in this field of medicine have shown that optimal management of patients with pheochromocytoma-associated syndromes is a high challenge. National registries may be instrumental in order to provide with adequate facilities.

Adrenal Gland Neoplasms↗
PubMed2005

Renal cell carcinoma- and pheochromocytoma-specific altered gene expression profiles in VHL mutant clones.

Von Hippel-Lindau (VHL) disease is associated with various missense germline mutations in the VHL tumor suppressor gene. Some are associated with type 1 VHL disease, renal cell carcinoma (RCC) without pheochromocytoma, while others are associated with type 2A or 2B VHL disease, pheochromocytoma without and with RCC, respectively. These mutations may cause substitutions of specific amino acid residue and functional change of VHL protein (pVHL), which leads to the oncogenesis of the particular tumor types that characterize the different VHL disease types. To investigate, we transfected a pVHL-null RCC cell line with plasmids expressing wild-type pVHL (WT) or pVHL bearing 1 of 3 point mutations. These occur in the pVHL regions that bind hypoxia-inducible factor alpha (HIF-alpha ) or Elongin C. Microarray analysis showed that the clones bearing a mutation in the elongin-binding region (mutant 167) were unique, as many more genes were suppressed than up-regulated. The other two mutant groups, which bear a mutation in the HIF-alpha -binding region (mutants 98 and 111), showed the opposite pattern. The 167 mutation is associated with type 2B VHL disease. Real-time PCR analysis confirmed the altered expression of selected genes in the clones. Relative to WT, stratifin (14-3-3 sigma) and lysyl oxidase-like 1 were down-regulated in the 167 mutants, while the transforming growth factor beta-induced protein (beta ig-h3) was up-regulated in the 111 mutants. Thus, the location of pVHL mutations results in distinct gene expression patterns. Moreover, a mutation in the elongin-binding domain may induce type 2B tumors through different molecular pathways compared to those induced by type 1- or 2A-associated mutations in the HIF-alpha -binding region.

Adrenal Gland Neoplasms↗
PubMed2005

[A case of spindle cell carcinoma of the penis].

Spindle cell carcinoma of the penis is extremely rare. The present case report is the nineth case in the world literature. A 71-year-old man was referred to our institution for examination of a penile tumor that showed non-specific granuloma histopathologically. We performed biopsy and total tumor resection. The histopathological finding showed squamous cell carcinoma with spindle type cells constituting the majority of the tumor, and the switching over from squamous cell carcinoma to spindle cell carcinoma was clearly visible in the histopathological examination. Therefore, we diagnosed this as spindle cell carcinoma of penis and performed partial penectomy with inguinal lymph node dissection. Spindle cell carcinoma is an uncommon variant of squamous cell carcinoma. We report the histopathological findings including the data of p53 immunohistochemical study, and reviewed the eight previous reports of spindle cell carcinoma of the penis.

Aged↗
PubMed2004

Molecular features of the transition from prostatic intraepithelial neoplasia (PIN) to prostate cancer: genome-wide gene-expression profiles of prostate cancers and PINs.

To characterize the molecular feature in prostate carcinogenesis and the putative transition from prostatic intraepithelial neoplasia (PIN) to invasive prostate cancer (PC), we analyzed gene-expression profiles of 20 PCs and 10 high-grade PINs with a cDNA microarray representing 23,040 genes. Considering the histological heterogeneity of PCs and the minimal nature of PIN lesions, we applied laser microbeam microdissection to purify populations of PC and PIN cells, and then compared their expression profiles with those of corresponding normal prostatic epithelium also purified by laser microbeam microdissection. A hierarchical clustering analysis separated the PC group from the PIN group, except for three tumors that were morphologically defined as one very-high-grade PIN and two low-grade PCs, suggesting that PINs and PCs share some molecular features and supporting the hypothesis of PIN-to-PC transition. On the basis of this hypothesis, we identified 21 up-regulated genes and 63 down-regulated genes commonly in PINs and PCs compared with normal epithelium, which were considered to be involved in the presumably early stage of prostatic carcinogenesis. They included AMACR, OR51E2, RODH, and SMS. Furthermore, we identified 41 up-regulated genes and 98 down-regulated genes in the transition from PINs to PCs; those altered genes, such as POV1, CDKN2C, EPHA4, APOD, FASN, ITGB2, LAMB2, PLAU, and TIMP1, included elements that are likely to be involved in cell adhesion or the motility of invasive PC cells. The down-regulation of EPHA4 by small interfering RNA in PC cells lead to attenuation of PC cell viability. These data provide clues to the molecular mechanisms underlying prostatic carcinogenesis, and suggest candidate genes the products of which might serve as molecular targets for the prevention and treatment of PC.

Cell Division↗
PubMed2004

Recent advances in ideas on the molecular pathology and clinical aspects of Von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that is associated with various tumors and cysts in the central nervous system (CNS) and visceral organs. Inactivation of the VHL tumor-suppressor protein and subsequent loss of function in the VHL, and Elongin BC (VBC) complex result in dysfunction in the ubiquitination of hypoxia-inducible factor (HIF), which is an important step in the development of angiogenic tumors. The most frequent disorders in VHL disease are hemangioblastoma in the CNS and retina, pheochromocytoma in the adrenal gland, renal cell carcinoma, and pancreatic neuroendocrine tumor. Here, we review recent ideas on the pathogenesis and clinical diagnosis and treatment of VHL disease. Progress in molecular diagnosis and molecular targeting therapy is expected for improvement in the diagnosis and treatment of this disease. The family's support for patients with VHL disease is important, being mutually helpful to overcome various social and psychological problems in the patients.

Angiogenesis Inhibitors↗
PubMed2004

Oncogenic role of NALP7 in testicular seminomas.

To isolate novel molecular targets for treatment of testicular germ cell tumor (TGCT), we performed genome-wide expression profile analysis of testicular seminomas using a cDNA microarray. We here report identification of NACHT, leucine-rich repeat and PYD containing 7 (NALP7 ), that was significantly transactivated in testicular seminomas. Subsequent semi-quantitative RT-PCR and northern blot analyses confirmed an approximately 3.3-kb transcript that was expressed exclusively in testis, although the expression level of this gene in normal testis was much lower than in tumor cells, suggesting an important role of this gene in germ-cell proliferation. Immunohistochemical analysis using anti-NALP7 polyclonal antibody detected the endogenous NALP7 protein in the cytoplasm of embryonal carcinoma cells and testicular seminoma tissues. Transfection of small interfering RNA (siRNA) for NALP7 significantly reduced the NALP7 expression and resulted in growth suppression of testicular germ-cell tumors. These findings imply that NALP7 may play a crucial role in cell proliferation, as well as testicular tumorigenesis, and it appears to be a promising candidate for development of targeted therapy for TGCTs.

Animals↗
PubMed2004

Low-grade tubular-mucinous renal neoplasm with neuroendocrine differentiation: a histological, immunohistochemical and ultrastructural study.

Low-grade tubular-mucinous renal neoplasm (LGTMRN) was recently established as a distinct carcinoma classification. A 70-year-old, female traffic accident victim underwent a detailed examination that disclosed a huge mass in the lower pole of the left kidney. The patient underwent a nephrectomy based on a diagnosis of renal tumor. Macroscopically, the tumor was well demarcated and a whitish color with focal hemorrhage. Histological examination showed that tumor cells proliferated through tubular, trabecular, and solid growth patterns in the mucinous background. Focally, foci of clear cells or the proliferation of spindle cells was also observed. Nuclei were generally round and uniform in size. No abnormal mitotic figures were identified. Immunohistochemically, tumor cells were diffusely positive for AE1/AE3, vimentin and chromogranin A, and focally positive for cytokeratin (CK) 18, CK19, Ulex europaeus agglutinin-1, epithelial membrane antigen, neuron-specific enolase (NSE), CD9 and CD57. Ultrastructurally, tumor cells contained a moderate number of mitochondria, rough endoplasmic reticulum and dense-core granules. No renin granules or glycogen were observed. Microvilli were focally seen. Our results render further evidence that LGTMRN is a distinct entity from the hitherto established renal neoplasms. Foci of clear cells and neuroendocrine differentiation should be added to the histological spectrum of LGTMRN.

Adenocarcinoma, Mucinous↗
PubMed2004

Infrequent alteration in the p53R2 gene in human transitional cell carcinoma of the urinary tract.

OBJECTIVE: Functional defects in DNA repair have been shown to be associated with genomic instability followed by cancer. Recently, p53R2 [p53-inducible ribonucleotide reductase (RR) small subunit 2 homologous] was identified as a novel RR gene which is directly regulated by p53 protein in the G1 and G2 phases of the cell cycle supplying nucleotides to repair damaged DNA. METHODS: We performed genetic analyses of p53R2 to determine whether p53R2 alterations play significant roles in urothelial tumorigenesis. Genomic DNA from 108 primary transitional cell carcinomas (TCCs; 81 of the urinary bladder and 27 of the renal pelvis or ureter) was analyzed for mutation in the p53R2 gene by direct sequencing. We focused on three domains of the p53R2 gene: one RR small subunit signature involving codons 120-146 (region 1) and two putative nuclear localization signal sequences, involving codons 149-155 (region 2) and codons 163-169 (region 3). In addition, a p53-binding site of 20 nucleotides in intron 1 of p53R2 was also analyzed. RESULTS: One renal pelvic TCC (0.9%: 1/108) had a single-base substitution in p53R2 with a G to T transversion resulting in the amino acid substitution Glu136 --> Asp. This base substitution was localized within the domain of exon 4 encoding the RR small subunit signature, and causes an amino acid substitution in one of the most highly conserved regions of p53R2, in which human R2 and yeast RNR2 and RNR4 proteins are highly homologous. CONCLUSION: This finding provides the in vivo evidence for the infrequent involvement of alterations in p53R2 inhuman urothelial TCCs.

Aged↗
PubMed2004

Multicystic malignant mesothelioma of the tunica vaginalis with an unusually indolent clinical course.

We report an extremely rare case of a multicystic malignant mesothelioma in the tunica vaginalis with an unusually indolent clinical course. A 48-year-old man presented with a one-month history of painless swelling of right scrotal contents. Ultrasonography and computed tomography (CT) revealed a multicystic mass in the right scrotal sac with evidence of neither distant nor lymph node metastases. The testicular tumor markers were within the normal limits. Inguinal orchiectomy was performed under the suspicion of a malignant tumor. The cystic tumor consisted of fibrocellular, microcystic and adenomatoid elements microscopically was diagnosed biphasic malignant mesothelioma of tunica vaginalis but no invasion into the testis, epididymis and also scrotum. The patient has been disease-free for 72 months and is being followed on an outpatient basis with no further adjuvant therapy.

Humans↗
PubMed2004

Hypermethylation of the RASSF1A tumor suppressor gene in Japanese clear cell renal cell carcinoma.

Hypermethylation associated inactivation of RASSF1A tumor suppressor gene at chromosome 3p21.3 has been observed in several human malignancies. Relatively high (91%) or low (23%) frequencies were reported in the methylation status of promoter region of the RASSF1A gene in clear cell renal carcinoma (RCC) depending on the country the report was from. To clarify exact contribution of the hypermethylation of RASSF1A gene in the development of RCC in Japan, we analyzed the methylation status of the RASSF1A promoter region in 50 Japanese clear cell RCC and RCC cell lines. Although relatively high frequency of hypermethylation in RASSF1A promoter (39 of 50 tumors, 78%) was observed, most of matched proximal normal tissue DNA also showed weak methylation. By comparison with methylation level of adapted normal kidney tissue DNA, tumor preferential hypermethylation in RASSF1A promoter was recognized as 40% (20/50 matched sets) of primary clear cell RCCs. Hypermethylation in RASSF1A promoter was observed in 36% (15/42) and 64% (5/8) of stage I-II or III-IV tumors, and also observed in 42% (11/26) and 38% (9/24) of our tumor samples with pathological grade I or II, respectively. In addition, 16 of 19 RCC cell lines (84%) showed complete or partial methylation of RASSF1A promoter region. There was no association between the frequency of RASSF1A methylation and inactivation of VHL tumor suppressor gene in either primary RCCs or RCC cell lines. Our results showed tumor specific RASSF1A promoter hypermethylation in up to 40% of low grade or low stage clear cell RCCs. It is essential to compare the methylation status of RASSF1A promoter in tumor with normal tissue to understand tumor specific hypermethylation. Since considerable cases of normal kidney are hypermethylated, contribution of the RASSF1A for the development and progression of kidney cancer may be more complex than expected.

Adenocarcinoma, Clear Cell↗
PubMed2004

[Partial nephrectomy using microwave tissue coagulator--application for laparoscopic operation].

We report our clinical findings on 12 tumors (11 patients) successfully resected by partial nephrectomy with a microwave tissue coagulator (MTC) without renal pedicle clamping, including laparoscopic operation in 4 patients. All patients presented with a renal tumor detected incidentally by ultrasonography or computed tomography. The mean size of renal tumor was 1.9 (range 0.8-3.4) cm. Pathological diagnosis was renal cell carcinoma in 9 tumors and hemorrhagic cyst in 3 tumors. Mean operative time was 249 minutes. Mean blood loss was 183 ml in cases with a laparoscopic operation, that was statistically less than 486 ml in cases with an open operation (p<0.05), and 376 ml in all cases. There was no significant change in the creatinine clearance of cases with laparoscopic operation, compared with that of cases with an open operation. There were no other serious complications postoperatively. These findings suggested that partial nephrectomy with the MTC can be safely and successfully carried out while sparing renal function. Moreover, partial nephrectomy with the MTC for a laparoscopic operation may provide these patients with more benefits.

Adult↗
PubMed2003

Identification of EloA-BP1, a novel Elongin A binding protein with an exonuclease homology domain.

The Elongin complex stimulates the rate of transcription elongation by RNA polymerase II by suppressing the transient pausing of the polymerase at many sites along the DNA template. Elongin is composed of a transcriptionally active A subunit, and two positive regulatory B and C subunits. Although the NH(2)-terminal approximately 120 amino acid region of Elongin A is dispensable for its transcriptional activity in vitro, it shares significant sequence similarity with the NH(2)-terminus of other class of transcription factors SII and CRSP70, suggesting that the NH(2)-terminus mediates interactions important for the regulation of transcription in vivo. To identify proteins that can bind to these conserved sequences, a human B cell cDNA library was screened using the NH(2)-terminus of Elongin A as bait in a yeast two-hybrid system. Here, we report on the cloning and characterization of a novel human exonuclease domain-containing protein, Elongin A-binding protein 1 (EloA-BP1). EloA-BP1 is composed of 1221 amino acids and its mRNA is ubiquitously expressed. Double immunofluorescence labeling in COS7 cells suggested that EloA-BP1 and Elongin A are colocalized to the cell nucleus. By using an in vitro binding assay, we show that EloA-BP1 is capable of binding not only the NH(2)-terminal approximately 120 amino acid region of Elongin A, but also that of SII. Although the purified EloA-BP1 had no detectable effect on the rate of transcription elongation in vitro, it may play some role in the regulation of elongation in vivo.

Amino Acid Sequence↗
PubMed2003

Downregulation of Cap43 gene by von Hippel-Lindau tumor suppressor protein in human renal cancer cells.

We previously identified 9 genes (i.e., thymosin beta4, secreted protein acidic and rich in cysteine, Cap43, ceruloplasmin, serum amyloid A, heat shock protein 90, LOT1, osteopontin and casein kinase Igamma) that are more highly expressed in cancerous regions than in noncancerous regions in human renal cancers. In our study, we considered the possibility that the von Hippel-Lindau (VHL) tumor suppressor gene might be able to affect the expression of these 9 genes in renal cancer cells. We first established 2 VHL-positive cell lines, 786/VHL-1 and 786/VHL-2, after the introduction of wild-type VHL into VHL-negative renal cancer 786-O cells. Of these 9 genes, expression of the Cap43 gene was specifically downregulated by VHL. Expression of Cap43 was also much lower in 4 other VHL-positive renal cancer cell lines than in VHL-negative 786-O cells. Cap43 promoter assays with several deletion or mutation constructs demonstrated that the Sp1 site in the element from -286 base pairs (bp) to -62 bp was partly responsible for VHL-induced suppression of the Cap43 gene. Immunostaining analysis with human specimens of renal cancers demonstrated that the Cap43 protein was expressed in most cancer cells and macrophages. We also observed a marked and specific increase of Cap43 mRNA levels in response to hypoxia or nickel in all VHL-positive cell lines. Cellular expression of Cap43 mRNA in response to hypoxia or nickel thus is closely associated with VHL gene expression in renal cancer cells. Although the function of the Cap43 protein remains unclear, the expression of Cap43 protein could be a molecular marker closely associated with VHL in renal cancer.

Carcinoma, Renal Cell↗
PubMed2003

Overexpression of hepatocyte growth factor receptor in renal carcinoma cells indirectly stimulates tumor growth in vivo.

We examined the role of increased expression of HGFR kinase in in vivo growth of renal carcinoma. Human renal carcinoma cell line, ACHN cells, was transfected with plasmid encoding wild-type HGFR gene to generate cell lines with increased HGFR protein. ACHN cells with elevated HGFR expression, denoted clones 8 and 10, respectively, showed higher basal kinase activities of HGFR and PI3-kinase than those of empty-vector (mock)-transfected cells. Clone 8 and 10 cells grew similar to mock cells in culture. In mice, tumors of these clones grew more rapidly than those of mock cells. Microvessel density of clone 8 or 10 tumors was higher than that of mock tumors. Clone 8 and 10 cells secreted vascular endothelial growth factor-A (VEGF-A) more than mock cells and the secretion was PI3-kinase inhibitor, LY294002-sensitive. Anti-VEGF-A neutralizing antibody significantly inhibited tumor growth of clones 8 and 10 in mice. These results indicate for the first time that overexpression of HGFR tyrosine kinase in renal carcinoma cells participates in rapid tumor growth in vivo.

Animals↗
PubMed2003

Mammalian elongin A is not essential for cell viability but is required for proper cell cycle progression with limited alteration of gene expression.

Elongin A is a transcription elongation factor that increases the overall rate of mRNA chain elongation by RNA polymerase II. To investigate the function of Elongin A in vivo, the two alleles of the Elongin A gene have been disrupted by homologous recombination in murine embryonic stem (ES) cells. The Elongin A-deficient ES cells are viable, but show a slow growth phenotype because they undergo a delayed mitosis. The cDNA microarray and RNase protection assay using the wild-type and Elongin A-deficient ES cells indicate that the expression of only a small subset of genes is affected in the mutant cells. Taken together, our results suggest that Elongin A regulates transcription of a subset but not all of genes and reveal a linkage between Elongin A function and cell cycle progression.

Animals↗