Biomedical subjects

H Namba

Publications and source records attributed to H Namba.

238 records · Page 14Linked to original sources

PubMedDate not supplied

The p73 gene is not mutated in oligodendrogliomas which frequently have a deleted region at chromosome 1p36.3.

An allelic loss of the chromosome 1p36 region is frequently found in oligodendrogliomas, which suggests the presence of putative tumor suppressor gene(s) in the region. Since the p73 gene, which encodes a protein with significant homology with p53, is mapped to the 1p36.33 region, we examined genetic alterations of the p73 gene in oligodendrogliomas. We screened 10 specimens for mutation throughout the p73 coding regions by polymerase chain reaction (PCR)-single strand conformation polymorphism analysis and by sequencing aberrantly migrated PCR products. We found several polymorphic nucleotide changes, but no somatic mutations that caused an amino acid change. The p73 gene is thus unlikely to be a tumor suppressor gene for oligodendrogliomas.

Chromosome Deletion↗

PubMedDate not supplied

Inhibition of angiogenesis and tumorigenesis, and induction of dormancy by p53 in a p53-null thyroid carcinoma cell line in vivo.

Our recent in vitro findings for suppression of thrombospondin-1 (TSP1; an antiangiogenic factor) expression by wild-type (wt) p53 in a p53-null thyroid carcinoma cell line, FRO, prompted us to investigate the in vivo effect of exogenous wt-p53 and TSP1 expression on tumor growth and angiogenesis of FRO xenografts in nude mice. Overexpression of TSP1, which did not affect the in vitro cell growth, significantly inhibited the in vivo tumor growth and neovascularization but not tumorigenesis; all the mice inoculated with FRO cells expressing TSP1 developed tumors, which were smaller and less vascularized than those derived from FRO cells. In contrast, restoration of wt-p53 expression, which reduced the in vitro cell growth rate, inhibited tumorigenesis and induced a state of "dormancy". Thus, approximately 40% of mice inoculated with FRO cells expressing wt-p53 (FRO-p53) were tumor free and the remaining mice developed hypovascular tumors which remained small (< or = 5 mm in size) for up to 60 days. Of interest, the phenotype of FRO-p53 tumors reverted to a well vascularized, progressively expanding tumor by exogenous expression of vascular endothelial growth factor (a proangiogenic factor). Our data demonstrated wt-p53 inhibition of tumorigenesis and induction of dormancy by suppression of neovascularization in FRO cells. The results suggest that p53 gene therapy for thyroid carcinoma harboring p53 mutation may be more efficacious than we had expected from previous in vitro data.

Animals↗

PubMedDate not supplied

Involvement of wild-type p53 in radiation-induced c-Jun N-terminal kinase activation in human thyroid cells.

c-jun-N-terminal kinases (JNKs) play an important role in defense against external stresses including ionizing radiation (IR). We have previously shown that sensitivity to IR is influenced by p53 status in human thyroid cells. In this study, we investigated the effect of p53 status on IR-induced JNK activation in human thyroid cells. Our results showed high basal JNK activity in the p53-null thyroid cancer cell line, FRO. In contrast, primary cultured thyroid cells (PT), which harbor wild-type p53, had low basal JNK activity. IR increased JNK activity in PT, however, no such increase was noted in FRO cells. Introduction of the wild-type p53 into FRO cells reduced JNK activity to a low basal level and rendered it responsive to IR. There was no difference in IR-induced ceramide production between PT and FRO cells. Our results provide clear evidence that p53 status influences, directly or indirectly, radiation-induced JNK activation in human thyroid cells, suggesting that a feedback or interaction pathway between p53 and JNK regulates radiation-induced cell fate.

Cells, Cultured↗

PubMedDate not supplied

Treatment of thyroid carcinoma cells with four different suicide gene/prodrug combinations in vitro.

To develop a suitable suicide gene/prodrug therapy for the treatment of thyroid carcinomas, the relative therapeutic efficacy of four different suicide gene/prodrug combinations was compared in thyroid carcinomas in vitro. Herpes simplex virus thymidine kinase and ganciclovir (HSV-TK/GCV), Escherichia coli cytosine deaminase and 5-fluorocytosine (CD/5FC), E coli nitroreductase and CB1954 (NTR/CB1954), and human deoxycytidine kinase and cytosine arabinoside (dCK/AraC) were employed. The suicide genes were transduced into two thyroid carcinoma cell lines with retroviral vectors in which all the suicide genes were under the control of the same promoter. When the relative efficacy of four suicide gene/prodrugs was compared with therapeutic index and degree of bystander effect, we found a clear dissociation between these two parameters. Thus, HSV-TKIGCV demonstrated the widest therapeutic index, while CD/5FC and NTR/CB1954 showed the stronger bystander effect than HSV-TK/GCV. dCK/AraC had little efficacy. Advantages and limitations of each suicide gene/prodrug combinations are discussed.

Antineoplastic Agents↗