Biomedical subjects

Keisuke Kikuchi

Publications and source records attributed to Keisuke Kikuchi.

4 recordsLinked to original sources

PubMed2004

Unique cellular features of peripheral primitive neuroectodermal tumor: ultrastructural evidence of its unique cytodifferentiation.

We present a case of primitive neuroectodermal tumor (PNET) showing a unique differentiation phenotype based on ultrastructural observation. Rapidly growing tumor involving the retroperitoneum of a 68-year-old woman was characterized by histological findings including proliferation of diffuse poorly differentiated small round cells with scattered rosette formation similar to Homer-Wright type and by the ultrastructure demonstrating cytoplasmic neurosecretary granules and short cytoplasmic cilial structures. These cells revealed immunoreactivity only with neuron-specific enolase (NSE). We also observed a chromosomal translocation, t (11; 22) (q24; q12), which is an identical recurrent alteration found in the neoplastic cells in the spectrum of PNETs. These findings may support the explanation that tumor cells observed in our case shared phenotypes of both neuronal and ependymal cell lineages and give a unique insight suggesting the possible histogenesis of PNETs.

Aged↗

PubMed2003

Hepatocyte nuclear factor (HNF)-4alpha triggers formation of functional tight junctions and establishment of polarized epithelial morphology in F9 embryonal carcinoma cells.

F9 murine embryonal carcinoma cells provide an attractive system for facilitating molecular mechanisms for epithelial morphogenesis, since they have the capability of differentiating into polarized epithelial cells bearing an apical junctional complexes. We previously showed that a specific retinoid X receptor-retinoic acid receptor heterodimer transduced retinoid signals for biogenesis of functional tight junctions in F9 cells (Exp. Cell Res. 263, (2001) 163). In the present study we generated F9 cells expressing doxycycline-inducible hepatocyte nuclear factor (HNF)-4alpha, a nuclear receptor. We herein show that induction of HNF-4alpha initiates differentiation of F9 cells to polarized epithelial cells, in which tight-junction proteins occludin, claudin-6, claudin-7, and ZO-1 are concentrated at the apical-most regions of lateral membranes. Expression of occludin, claudin-6, and claudin-7 was induced in the cells by doxycycline treatment in a dose- and time-dependent manner, in terms of the amount of HNF-4alpha. In contrast, expression levels of ZO-1, ZO-2, E-cadherin, and beta-catenin were not altered by HNF-4alpha. We also demonstrate, by analysis of diffusion of labeled sphingomyelin, that the fence function of tight junctions is achieved by induction of HNF-4alpha. These findings indicate that HNF-4alpha triggers de novo formation of functional tight junctions and establishment of epithelial cell polarity.

Animals↗

PubMed2003

Tight junctions and human diseases.

Tight junctions are intercellular junctions adjacent to the apical end of the lateral membrane surface. They have two functions, the barrier (or gate) function and the fence function. The barrier function of tight junctions regulates the passage of ions, water, and various macromolecules, even of cancer cells, through paracellular spaces. The barrier function is thus relevant to edema, jaundice, diarrhea, and blood-borne metastasis. On the other hand, the fence function maintains cell polarity. In other words, tight junctions work as a fence to prevent intermixing of molecules in the apical membrane with those in the lateral membrane. This function is deeply involved in cancer cell biology, in terms of loss of cell polarity. Of the proteins comprising tight junctions, integral membrane proteins occludin, claudins, and JAMs have been recently discovered. Of these molecules, claudins are exclusively responsible for the formation of tight-junction strands and are connected with the actin cytoskeleton mediated by ZO-1. Thus, both functions of tight junctions are dependent on the integrity of the actin cytoskeleton as well as ATP. Mutations in the claudin14 and the claudin16 genes result in hereditary deafness and hereditary hypomagnesemia, respectively. Some pathogenic bacteria and viruses target and affect the tight-junction function, leading to diseases. In this review, the relationship between tight junctions and human diseases is summarized.

Claudins↗

PubMed2002

Rhabdomyosarcoma arising from a dormant dumbbell ganglioneuroma of the lumbar spine: a case report.

STUDY DESIGN: A case report of a lumbar dumbbell tumor that showed a sequential change in histology from ganglioneuroma into rhabdomyosarcoma after long-term dormancy. OBJECTIVE: To present a case of non-neurogenic malignancy arising from ganglioneuroma. SUMMARY OF BACKGROUND DATA: Ganglioneuromas rarely form the dumbbell variety. Whereas conversion of ganglioneuroma into neurogenic malignancies occurs occasionally, between ganglioneuroma and mesenchymal malignancies it has so far been limited to a case in which ganglioneuroma developed after chemo- and radiotherapy for orbital rhabdomyosarcoma. METHODS: A 61-year-old man was referred with a recurrent retroperitoneal tumor that had been excised as ganglioneuroma. Using imaging, histologic, and immunohistochemical studies, a comparative analysis of the primary and recurrent tumors was performed. RESULTS: A total of 44 histologic sections were examined for the primary and the recurrent tumors that had been excised surgically, with an 8-month interval between resections. Histologic and immunohistochemical findings in the primary tumor were consistent with ganglioneuroma, whereas those in the recurrent tumor indicated rhabdomyosarcoma. CONCLUSIONS: It is assumed that the rhabdomyosarcoma arose from a dumbbell ganglioneuroma as a component of malignant ectomesenchymoma.

Disease Progression↗