Biomedical subjects

Hiroyuki Konishi

Publications and source records attributed to Hiroyuki Konishi.

7 recordsLinked to original sources

PubMed2003

Detailed characterization of a homozygously deleted region corresponding to a candidate tumor suppressor locus at distal 17p13.3 in human lung cancer.

17p13.3 is one of the chromosomal regions most frequently affected by allelic loss in a variety of human neoplasms including lung cancer. A number of loss of heterozygosity (LOH) analyses have suggested the existence of a tumor suppressor gene at 17p13.3, distal to the p53 locus at 17p13.1. In the present study, we characterized a homozygous deletion at 17p13.3 in a small cell lung cancer cell line by constructing a bacterial artificial chromosome (BAC) contig and a restriction map surrounding the region, as well as by utilizing publicly available draft sequences. We defined the breakpoint, assigned and analysed two known genes, 14-3-3 epsilon and CRK, and a novel gene LOST1 within or at the end of the homozygous deletion of about 170 kb in size. Marked reduction of LOST1 expression was detected in 69% (11/16) of lung cancer specimens by quantitative real-time RT-PCR, while significant DNA hypermethylation was observed at the 5' end of the LOST1 gene in four of six lung cancer cell lines with negligible LOST1 expression. We also show here that a polymorphic marker D17S1174, which resides within the homozygous deletion, was apparently located in the middle of the minimum LOH region, providing further supportive evidence for the presence of a tumor suppressor gene(s) in this region.

Amino Acid Sequence↗

PubMed2003

Gamma loop dysfunction in quadriceps on the contralateral side in patients with ruptured ACL.

PURPOSE: The aim of our study was to test for any neurophysiological abnormality in the gamma loop in the quadriceps femoris muscle on the uninjured side of patients with unilateral rupture of the anterior cruciate ligament (ACL). METHODS: Maximal voluntary contraction of knee extension and integrated electromyography (I-EMG) of the vastus medialis, vastus lateralis, and rectus femoris were measured in the uninjured limb of 13 patients with unilateral ACL rupture and 10 normal subjects, before and after 20-min vibration stimulation applied to the infrapatellar tendon. RESULTS: The mean percentage changes of maximal voluntary contraction and I-EMG in quadriceps femoris of the uninjured side of patients with ACL rupture were significantly different from those of the control group. Maximal voluntary contraction and I-EMG after prolonged vibration stimulation did not decrease as much as those of the control group even though the same protocol of vibration stimulation was applied. CONCLUSION: The abnormal response to prolonged vibration stimulation could represent abnormal gamma loop in the quadriceps femoris muscle of the uninjured side in patients with ACL rupture since the normal response of maximal voluntary contraction and I-EMG to prolonged vibration stimulation could not be evoked without normal function of the gamma loop.

Adolescent↗

PubMed2003

[The lambda in the rorschach comprehensive system].

The purpose of the present study was to investigate the relationships between Lambda (L) and other variables in the Rorschach comprehensive system. Individual Rorschach tests based on the comprehensive system was administrated to 102 female normal adults (over 20 years old). High L group and Low L group were defined on the basis of median value. The two groups were compared on major variables. The high L group had significantly higher values on variables such as DQo, D, Dd, S, Hd than the low L group. In contrast, the low L group had significantly higher values on variables such as DQ+, Blends, M, FM + m, Sum C', "active", H, COP than the high L group. Clinician who use the Rorschach test should consider these variables in relation to L, when interpreting the structural summary of the comprehensive system.

Adult↗

PubMed2002

Significant up-regulation of a novel gene, CLCP1, in a highly metastatic lung cancer subline as well as in lung cancers in vivo.

Most lung cancer patients are unfortunately uncurable and die because of widespread metastases, thus indicating the importance of identification of molecules with a crucial role in this process. Our previous expression profiling analysis of a highly metastatic lung cancer cell line, NCI-H460-LNM35, and its parental low metastatic line, NCI-H460-N15, revealed significant up-regulation of both known and unknown genes in LNM35. In this study, we describe the isolation and detailed characterizations of a novel gene, named CLCP1, which corresponds to one of such expression sequence tags with up-regulated expression in LNM35. The CLCP1 gene was found to encode a protein with 775 amino acids with structural similarities to, but distinct from neuropilins, cell surface receptors for VEGF165 and semaphorins. Notably, CLCP1 was shown to be up-regulated not only in LNM35 in association with its acquisition of metastatic phenotype during in vivo selection, but also in a significant fraction of lung cancers in vivo with high frequency in metastatic lesions, warranting future studies for a better understanding of the molecular mechanisms of lung cancer metastasis.

Adenocarcinoma↗

PubMed2002

Frequent and histological type-specific inactivation of 14-3-3sigma in human lung cancers.

One isoform of the 14-3-3 family, 14-3-3sigma, plays a crucial role in the G2 checkpoint by sequestering Cdc2-cyclinB1 in the cytoplasm, and the expression of 14-3-3sigma is frequently lost in breast cancers. This loss of expression is thought to cause a G2 checkpoint defect, resulting in chromosomal aberrations. Since lung cancers frequently carry numerous chromosomal aberrations, we examined the DNA methylation status and expression level of the 14-3-3sigma gene in 37 lung cancer cell lines and 30 primary lung tumor specimens. We found that small cell lung cancer (SCLC) cell lines frequently showed DNA hypermethylation (9 of 13 lines, 69%), and subsequent silencing of the 14-3-3sigma gene. Among non-small cell lung cancers (NSCLC), large cell lung cancer cell lines showed frequent hypermethylation and silencing of 14-3-3sigma (4 or 7 lines, 57%). In contrast, in other NSCLC cell lines, hypermethylation occurred very rarely (1 of 17 lines, 6%). All eight primary SCLC specimens examined also showed a loss or significant reduction in 14-3-3sigma expression in vivo, while a loss or reduction of 14-3-3sigma expression was very rare in primary NSCLC specimens (1 of 22 tissues, 5%). This is the first description that indicates lung cancers frequently show significant inactivation of the 14-3-3sigma gene mainly due to DNA hypermethylation in SCLC, but rarely in NSCLC, suggesting involvement of the 14-3-3sigma gene in lung tumorigenesis in a histological type-specific manner.

14-3-3 Proteins↗

PubMed2002

Aberrant hypermethylation of the CHFR prophase checkpoint gene in human lung cancers.

The CHFR gene, which was recently cloned by Scolnick and Halazonetis in search for a novel mitotic checkpoint gene with fork-head association motifs, has been suggested to play a key role in the mitotic prophase checkpoint. In this study, we demonstrated tumor-specific aberrant hypermethylation of the promoter region of the CHFR gene in a significant fraction of lung cancers in association with loss of detectable levels of CHFR transcripts. Aberrant hypermethylation was observed in seven of 37 primary lung cancer cases. Treatment with the demethylating agent 5-aza-2'-deoxycytidine restored expression of the CHFR gene in lung cancer cell lines exhibiting aberrant hypermethylation and loss of its expression. In contrast, genetic alterations were found to be infrequent in lung cancers. This is the first description of aberrant hypermethylation of the CHFR gene in any type of human cancer, and provides further evidence of the involvement of multiple checkpoint alterations in lung cancer.

Base Sequence↗

PubMed2002

Identification of frequent G(2) checkpoint impairment and a homozygous deletion of 14-3-3epsilon at 17p13.3 in small cell lung cancers.

Accumulating evidence suggests that a coordinately controlled G(2) checkpoint prevents cells with damaged DNA from entering mitosis, thus playing an important role in the maintenance of chromosomal integrity. In the study presented here, we identified a homozygous deletion of the 14-3-3epsilon gene, which resides within a previously identified, commonly deleted region at 17p13.3 in lung cancers, in two small cell lung cancer cell lines that originate from distinct metastatic sites of the same patients. The introduction of 14-3-3epsilon induced significantly restored G(2) checkpoint responses, which resulted in the reduction of mitotic cells as well as of aberrant mitotic figures in the X-ray-irradiated 14-3-3epsilon-null small cell lung cancer cell line. Interestingly, we also found that the G(2) checkpoint response is frequently impaired to various degrees in a large fraction of small cell lung cancer cell lines. These findings suggest the possible involvement of the perturbed G(2) checkpoint in the pathogenesis of this aggressive form of human lung cancers.

14-3-3 Proteins↗