Biomedical subjects

Toru Kameya

Publications and source records attributed to Toru Kameya.

27 records · Page 2Linked to original sources

PubMed2003

Microtubule-associated protein-2 and class III beta-tubulin are expressed in extraskeletal myxoid chondrosarcoma.

Extraskeletal myxoid chondrosarcoma is a rare soft tissue sarcoma of uncertain histogenetic origin. Because recent reports have indicated neural-neuroendocrine differentiation in some extraskeletal myxoid chondrosarcomas, we investigated 25 tumors for expressions of microtubule-associated protein-2 and Class III beta-tubulin, which are major components of microtubules and specifically localized in neurons and their derivatives. Immunohistochemical expression of microtubule-associated protein-2 and Class III beta-tubulin was studied in extraskeletal myxoid chondrosarcomas using formalin-fixed, paraffin-embedded tissues. Cytoplasmic expressions of microtubule-associated protein-2 and Class III beta-tubulin were detected in 21 (84%) and 13 (52%) of the 25 extraskeletal myxoid chondrosarcomas, respectively, although the number of positively stained tumor cells varied. Expression of the Class III beta-tubulin gene was also assessed in two immunohistochemically positive cases by in situ hybridization using an oligonucleotide probe specific for its transcript, and both cases showed expression of Class III beta-tubulin transcript. Another case was examined with immunoelectron microscopy, and immunogold particles for Class III beta-tubulin were localized to microtubular aggregates. Our data indicate that microtubules in extraskeletal myxoid chondrosarcoma are similar to those found in neurons, further supporting the concept that neural-neuroendocrine differentiation occurs in a significant number of extraskeletal myxoid chondrosarcoma.

Chondrosarcoma↗

PubMed2002

Clinical significance of p53, mdm2, and bcl-2 proteins in renal cell carcinoma.

OBJECTIVES: To improve our understanding of the clinical relevance of p53, mdm2, and bcl-2 protein overexpression in renal cell carcinoma, we retrospectively investigated the immunohistochemical expression of p53, murine double minute 2 (mdm2), and bcl-2 and the relationship of this expression to clinicopathologic characteristics. p53 regulates the transcription of downstream effectors such as the oncoprotein mdm2, and bcl-2 has been shown to inhibit apoptosis triggered by wild-type p53. METHODS: The expression of p53, mdm2, and bcl-2 protein was studied by immunohistochemical methods in paraffin-embedded nephrectomy specimens from 112 patients whose clinicopathologic data confirmed renal cell carcinoma. RESULTS: The expression of the p53 and bcl-2 protein was recognized in 15 (13.4%) and 52 (42.0%) cases, respectively; the expression of the mdm2 protein, however, was seen in only 2 cases (1.8%). No correlation was noted between these three proteins and any clinicopathologic parameters, except p53 expression and Stage T1-2/T3-4 (P = 0.0208). However, in multivariate analysis, stage (hazard ratio 3.586; P = 0.0002), expression of p53 (hazard ratio 6.090; P = 0.0126) and of mdm2 (hazard ratio 22.016; P = 0.0156), and coexpression of p53/mdm2 (hazard ratio 6.146; P = 0.0005) demonstrated a statistically significant effect on prognosis by proportional hazards regression tests. CONCLUSIONS: Our results indicate that stage, p53 expression, mdm2 expression, and coexpression of p53/mdm2 are useful to predict the clinical outcome in patients with renal cell carcinoma.

Adult↗

PubMed2002

Detection of epstein-barr virus in nasal T-cell lymphoma.

The close relationship between Epstein-Barr virus (EBV) and nasal T-cell lymphoma (NTL) has frequently been reported. However, the status of the infection, either lytic or latent, is obscure. This study involved 16 patients with NTL. Phenotypes of lymphoma cells were examined by immunohistochemical staining using CD3, CD4, CD8, CD20 and CD45RO monoclonal antibodies. EBV-encoded small nuclear RNA (EBER)-1 and EBV NotI tandem repeat region were detected by reverse transcription, using a rapid (< or = 60 min) in situ hybridization technique. Tumor cells expressed at least one T-cell marker, such as CD3, CD4, CD8 and CD45RO. CD20 was not detected in any of the cases. EBER-1 was identified in all cases; no Notl tandem DNA repeat was demonstrated. All cases demonstrated a T-cell phenotype. These data suggest that NTL is associated with EBV infection in the latent phase.

Antigens, CD↗

PubMed2002

Expression of Epstein-Barr virus-encoded small nuclear RNA 1 in Japanese nasopharyngeal carcinomas.

An examination was made of the incidence of the Epstein-Barr virus (EBV) genome and its exact localization in 39 cases of nasopharyngeal carcinoma (NPC) in Japanese patients by means of in situ hybridization (ISH) with a digoxigenin-labeled Epstein-Barr virus-encoded small nuclear RNA 1 (EBER1) oligonucleotide probe. Hybridization signals were observed in the nucleus of tumor cells in all 39 NPCs, including keratinizing carcinomas. The signals varied greatly in intensity from case to case and even from cell to cell in the same tumor, but were recognized in most tumor cells in each case. Signals could occasionally be seen in limiting number of infiltrating small lymphocytes but were absent in all tumors of the tongue, midpharynx and hypopharynx. Combined immunohistochemistry-ISH studies indicated that EBER1 signals were restricted to tumor cells positive for cytokeratin. As a result of this study, it is now possible to perform large-scale retrospective analyses using routine formalin-fixed, paraffin-embedded tissue sections and to combine ISH for the EBV genome with immunohistochemistry for cytokeratin to determine the epithelial features of EBV genome-possessing cells. All NPCs were clearly shown to be EBV-infected, thus indicating that EBV is essential for the oncogenesis of NPCs.

Carcinoma↗

PubMed2002

Expression of Pit-1 and growth hormone-releasing hormone receptor mRNA in human pituitary adenomas: difference among functioning, silent, and other nonfunctioning adenomas.

We analyzed the expression of Pit-1 and growth hormone-releasing hormone receptor (GHRH-R) mRNA in various types of functioning and nonfunctioning adenomas using a quantitative reverse transcriptase polymerase chain reaction (RT-PCR) method. Among clinically nonfunctioning adenomas, tumors considered as silent adenomas were reclassified on a pathologic basis. Competitive RT-PCR showed that the levels of Pit-1 and GHRH-R mRNA expression in silent somatotroph adenomas and silent prolactinomas were similar to those in the corresponding functioning adenomas. In silent thyrotroph adenomas, both mRNAs showed high levels of expression that were similar to those in functioning and silent somatotroph adenomas. The results suggest that the cause of the silence in these tumors seems to be in the downstream to transcription of Pit-1 gene in the signaling pathway leading to hormone secretion. Competitive RT-PCR assay could distinguish silent adenomas of the Pit-1 group from the other nonfunctioning adenomas in the expression levels of Pit-1 and GHRH-R mRNAs. In the future, precise diagnosis of various adenomas may become possible by assaying transcription factors such as steroidogenic factor-1 and thyrotroph embryonic factor, which are thought to be related to adenohypophyseal cytodifferentiation.

Adenoma↗

PubMed2000

Proprotein-Processing Endoprotease Furin and its Substrate Parathyroid Hormone-Related Protein Are Coexpressed in Insulinoma Cells.

Parathyroid hormone-related protein (PTHrP) is frequently produced in pancreatic endocrine tumors. PTHrP is synthesized as the precursor pro-PTHrP and undergoes a series of posttranslational processing reactions, among which cleavage of a 12 amino acid sequence from its precursor is crucial for the biological activation of PTHrP. This cleavage is catalyzed by furin, a proprotein-processing endoprotease that cleaves the consensus sequence -Arg-X-(Lys/Arg)-Arg-X-. We previously reported that furin is highly expressed in rat pancreatic islets during the perinatal stage and that the expression of furin in pancreatic-cells induces faster cell growth. From this, we postulated that furin may be co-expressed with PTHrP in insulinomas. We immunostained insulin, PTHrP, and furin in 21 human pancreatic endocrine tumors: 10 insulinomas, 5 VIPomas, 4 gastrinomas, and 2 somatostatinomas. Of these 21 endocrine tumors, furin was positively stained in all 10 insulinomas. Likewise, PTHrP was detected in the same insulinomas. We found one VIPoma and one gastrinoma contained a few insulin-positive cells scatteringly, which were also positive for furin and PTHrP. But other non-insulinoma endocrine tumors did not display furin and PTHrP positivity. We conclude that furin and its substrate pro-PTHrP are co-expressed specifically in insulinomas.

Journal Article↗

PubMed1999

GH and PRL-Producing Pituitary Adenoma with Neuron-Like Differentiation.

A pituitary adenoma with neuron-like differentiation in the sella turcica is reported. Sections of the tumor showed a mixture of adenoma cells, ganglionic cells, and neuropil-like structures by light microscopy. Both pituitary adenoma cells and large cells recognized as ganglionic cells by H&E were strongly immunoreactive for both growth hormone (GH) and prolactin (PRL), which indicated that these large cells had properties similar to those of pituitary adenoma cells. Furthermore, electron microscopy (EM) revealed characteristic low electron-dense secretory granules as well as GH-type large electron-dense secretory granules in adenoma cells, neuropils, and swollen bulbs of neuronal endings, which indicated that these three populations may be of the same origin. Furthermore, we could not find typical cell bodies of ganglionic cells by EM. These results are consistent with a hypothesis that attempts to explain the origin of the neuronal components by the neuronal differentiation of adenoma cells. Thus, the best designation of our tumor may be "pituitary adenoma with neuron-like differentiation."

Journal Article↗

PubMed1995

An Atypical Acidophil Cell Line Tumor Showing Focal Differentiation Toward Both Growth Hormone and Prolactin Cells.

We report a case of giant pituitary adenoma in a child. Computerized tomography (CT) scan revealed a suprasellar extension tumor mass with hydrocephalus. There was no clinical evidence of acromegaly, gigantism, and other hormonal symptoms. Endocrinologic studies showed within normal value of serum growth hormone (GH: 4.2 ng/mL) and slightly increased levels of prolactin (PRL: 78 ng/mL) and other pituitary hormone values were within normal range. On suppression test by bromocryptin, both GH and PRL levels were reduced. Histopathological findings revealed that the tumor consisted of predominantly chromophobic and partly eosinophilic adenoma cells. Immunohistochemical staining detected GH and PRL in a small number of distinctly different adenoma cells, respectively. Nonradioactive in situ hybridization (ISH) also showed GH and PRL mRNA expression in identical immunopositive cells. Electron microscopy (EM) demonstrated adenoma cells with moderate or small numbers of two types of dense granules and without fibrous body which are characteristic of sparsely granulated GH-cell adenomas. The adenoma does not fit into any classification but may be an atypical acidophil cell line tumor showing focal differentiation toward both GH and PRL cells.

Journal Article↗

PubMedDate not supplied

Cdk4/cyclin D1 kinase, a universal and critical regulator of apoptosis.

BACKGROUND: We have previously described that overexpression of cdk4/cyclin D1 is the primary and critical mediator of apoptosis in PC12 cells even under otherwise physiological conditions. However, it is unclear whether this phenomenon is specific to neuronal cells or is more universally true. MATERIALS AND METHODS: Cyclins and cdks were transiently overexpressed in a variety of cultured cells, and examined for apoptosis. RESULTS: By flow cytometry, apoptosis was observed in all cell lines overexpressing cdk4 or cyclin D1. Immunofluorescence revealed that cells overexpressing cdk4 or cyclin D1 exhibited nuclear features characteristic of apoptosis. Furthermore, in cells defective for retinoblastoma protein (Rb), apoptosis could be induced by overexpression of any cdks or cyclins. CONCLUSION: Up-regulation of cdk4 kinase activity is the primary and critical mediator of apoptosis regardless of the cell types. In addition, inactivation of Rb renders cells further susceptible to apoptosis by abnormal expression of any of the cell cycle regulators.

Apoptosis↗