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Y Nakanishi

Publications and source records attributed to Y Nakanishi.

At least 19 recordsLinked to original sources
PubMed2007

Clinicopathological significance of microscopic abscess formation at the invasive margin of advanced low rectal cancer.

BACKGROUND: The aim of this study was to evaluate the clinicopathological significance of microscopic abscess formation (MAF) at the invasive front of advanced low rectal cancer. METHODS: The clinicopathological features of 226 consecutive patients with low rectal cancer, who underwent curative resection between May 1997 and December 2002, were analysed. RESULTS: Fifty-seven (25.2 per cent) of the 226 tumours had MAF and 169 (74.8 per cent) did not. Patients with tumours showing MAF were more likely to have extended surgery than those without MAF: 47 versus 31.4 per cent respectively underwent non-sphincter-preserving surgery (P=0.029) and 82 versus 60.9 per cent underwent lateral lymph node dissection (P=0.003). The incidence of lymph node metastases was lower in patients with MAF (30 versus 53.3 per cent; P=0.002). Univariable analysis of disease-free survival revealed that depth of invasion (P<0.001), lymph node status (P<0.001), histological type (P=0.035), lymphatic invasion (P<0.001), venous invasion (P<0.001), perineural invasion (P<0.001), focal dedifferentiation (P<0.001) and MAF (P<0.001) were significant prognostic factors. Multivariable analysis showed that lymph node status (P<0.001), perineural invasion (P=0.002), venous invasion (P=0.033) and MAF (P=0.012) remained independent prognostic factors. CONCLUSION: MAF may reflect indolent tumour behaviour and a more favourable outcome in patients with advanced low rectal cancer.

Abscess↗
PubMed2006

Vascular endothelial growth factor promoter-based conditionally replicative adenoviruses for pan-carcinoma application.

Treatment of advanced lung cancer is one of the major challenges in current medicine because of the high morbidity and mortality of the disease. Advanced stage lung cancer is refractory to conventional therapies and has an extremely poor prognosis. Thus, new therapeutic approaches are needed. Lung tumor formation depends on angiogenesis in which the vascular endothelial growth factor (VEGF) produced by cancer cells plays a pivotal role. Neutralizing VEGF with a soluble VEGF receptor suppresses tumor growth; however, the anticancer effect with this therapy is weakened after the intratumoral vascular network is completed. In this study, we turned the expression of VEGF by tumors to therapeutic advantage using a conditionally replication-competent adenovirus (CRAd) in which the expression of E1 is controlled by the human VEGF promoter. This virus achieved good levels of viral replication in lung cancer cells and induced a substantial anticancer effect in vitro and in vivo. As a further enhancement, the cancer cell killing effect was improved with tropism modification of the virus to express the knob domain of Ad3, which improved infectivity for cancer cells. These VEGF promoter-based CRAds also showed a significant cell killing effect for various types of cancer lines other than lung cancer. Conversely, the VEGF promoter has low activity in normal tissues, and the CRAd caused no damage to normal bronchial epithelial cells. Since tumor-associated angiogenesis via VEGF signalling is common in many types of cancers, these CRAds may be applicable to a wide range of tumors. We concluded that VEGF promoter-based CRAds have the potential to be an effective strategy for cancer treatment.

Adenoviridae↗
PubMed2006

Different transitions of multifocal electroretinogram recordings between patients with age-related macular degeneration and polypoidal choroidal vasculopathy after photodynamic therapy.

AIM: To compare and evaluate the transitions in retinal function after photodynamic therapy (PDT) between age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) using multifocal electroretinograms (mfERGs). METHODS: 10 eyes with choroidal neovascularisation (CNV) secondary to AMD and 11 eyes with CNV secondary to PCV were included in the study. mfERGs were recorded before PDT, and 1 week and 3 months after PDT. mfERG recordings were acquired by a Veris system (V.3.1.3) using a 103 hexagon stimulus. The first-order kernel was used to calculate amplitudes and latencies. Mean amplitudes and latencies from two central rings rated 0-4 degrees of visual angle were analysed and compared with each disease. RESULTS: In AMD, the mean first negative peak (N1) amplitudes tended to decrease, and the mean first positive peak (N1P1) amplitudes reduced to significant levels (p = 0.047) 1 week after PDT. 3 months after PDT, there were no significant differences in the mean N1 and N1P1 amplitudes compared with pre-PDT values. In PCV, there were no significant changes in the mean N1 and N1P1 amplitudes 1 week after treatment. However, 3 months after PDT, mean amplitudes showed significant increases in N1 (p = 0.008) and N1P1 (p = 0.006) amplitudes compared with pre-PDT values. CONCLUSIONS: mfERG recording transitions are different between patients with AMD and those with PCV. In patients with AMD, these results may show transient impairments in retinal function 1 week after PDT, but in those with PCV, the efficacy of PDT is superior to the impairment after PDT.

Aged↗
PubMed2006

Genomic loss and epigenetic silencing of very-low-density lipoprotein receptor involved in gastric carcinogenesis.

Homozygous loss in the genomic sequence, a mechanism for inactivating tumor-suppressor genes (TSGs) in cancer, has been used as a tag for the identification of novel TSGs, and array-based comparative genomic hybridization (array-CGH) has a great potential for high-throughput identification of this change. We identified a homozygous loss of the very-low-density lipoprotein receptor (VLDLR) gene (9p24.2) from genome-wide screening for copy-number alterations in 32 gastric cancer (GC) cell lines using array-CGH. Although previous reports demonstrated mRNA or protein expression of VLDLR in various cancers including GC, the association between genomic losses or epigenetic silencing of this gene and carcinogenesis has never been reported before. Homozygous deletion of VLDLR was also seen in primary GCs, albeit infrequently, and about half of GC cell lines showed lost or reduced VLDLR expression. The VLDLR expression was restored in gene-silenced GC cells after treatment with 5-aza 2'-deoxycytidine. According to methylation analyses, hypermethylation of the VLDLR promoter region, which all of GC lines without its expression showed, occurred in some primary GCs. Restoration of VLDLR type I expression in GC cells reduced colony formation. These results suggest that not only the expression of VLDLR but also genetic or epigenetic silencing of this gene may contribute to tumor formation and be involved in gastric carcinogenesis.

Biopsy↗
PubMed2006

Prevention of radiation-induced pneumonitis by recombinant adenovirus-mediated transferring of soluble TGF-beta type II receptor gene.

To investigate whether radiation-induced pneumonitis in the mouse-irradiated lung could be prevented by recombinant adenovirus-mediated soluble transforming growth factor-beta (TGF-beta) type II receptor gene therapy. Radiation fibrosis-prone mice (C57BL/6J) were randomly divided into four groups consisting of a (1) control group (sham-irradiated); (2) radiation (RT)-alone group; (3) RT+AdCMVsTbetaR group and (4) RT+AdCMVluc group. The RT-alone and sham-irradiated mice were killed at several time points after thoracic irradiation with a single dose of 9 Gy, and then the TGF-beta1 concentrations in serum and broncho-alveolar lavage fluid (BALF) were quantified by enzyme-linked immunosorbent assay (ELISA). We used an adenoviral vector expressing a soluble TGF-beta type II receptor (AdCMVsTbetaR), which can bind to TGF-beta and then block the TGF-beta receptor-mediated signal transduction. The C57BL/6J mice were intraperitoneally (i.p.) injected with either 5 x 10(8) plaque-forming units of AdCMVsTbetaR or AdCMVluc, a control adenovirus-expressing luciferase, a week preceding and a week following the X-ray thoracic irradiation. Four weeks after irradiation, the mice were killed and the concentration of TGF-beta1 in the serum and BALF were then measured using ELISA and the lung tissue specimens were examined histopathologically. Following thoracic irradiation with a single dose of 9 Gy, radiation-induced TGF-beta1 release in the serum reached the first peak concentration at 12 h and then declined. It reached a maximal value at 2 weeks after irradiation. In the BALF, the TGF-beta1 concentration was appreciable within the first hour and thereafter declined. It reached a maximal value at 3 days after irradiation. A one-time i.p. injection of AdCMVsTbetaR 1 week before irradiation could not completely suppress the two peaks of the radiation-induced TGF-beta1 increase, whereas an injection a week preceding and a week following thoracic irradiation was able to suppress those two peaks thoroughly. The TGF-beta1 was completely suppressed in the AdCMVsTbetaR-treated mouse serum and BALF; however, no statistical difference was observed in the serum and BALF between the AdCMVluc-infected mice and the control mice at 4 weeks after irradiation (P < 0.05). A histopathological examination showed only mild radiation pneumonitis in the irradiated lungs of AdCMVsTbetaR-treated mice in comparison to the AdCMVluc-infected and RT-alone mice. Our results demonstrated that TGF-beta1 plays an important role in radiation pneumonitis, thus suggesting that the adenovirus-mediated overexpression in soluble TGF-beta type II receptor gene therapy may be a potentially feasible and effective strategy for the prevention of radiation pneumonitis.

Adenoviridae↗
PubMed2006

Muir-torre syndrome with intriguing squamous lesions: a case report and review of the literature.

Muir-Torre syndrome (MTS) is an autosomal, dominantly inherited disorder characterized by sebaceous neoplasms and visceral malignancies. We report a 56-year-old woman who underwent resections of extraocular sebaceous carcinoma, sebaceous epithelioma, actinic keratosis, and keratoacanthoma (KA)-like squamous cell carcinoma (SCC) with venous invasion metachronously over a 9-year period. Because of the mixed, unusual features of the skin lesions, and her history of endometrial and colorectal cancers that had been resected 12 years and 1 year, respectively, before the present event, a possible diagnosis of Muir-Torre syndrome was suggested. Immunohistochemical studies revealed loss of hMSH2 expression in all the cutaneous lesions including the actinic keratosis, and also in the endometrial and colorectal cancers. This patient presented with intriguing squamous lesions including keratoacanthoma-like squamous cell carcinoma that showed venous invasion and actinic keratosis, and associated loss of hMSH2 expression, in addition to the sebaceous neoplasms typical of Muir-Torre syndrome.

Adenocarcinoma, Sebaceous↗
PubMed2006

Coexpression of an unusual form of the EWS-WT1 fusion transcript and interleukin 2/15 receptor betamRNA in a desmoplastic small round cell tumour.

BACKGROUND: The beta chain of the interleukin 2/15 receptor (IL-2/15Rbeta) is induced by the expression of the EWS-WT1. A case of desmoplastic small round cell tumour (DSRCT) expressing only an unusual EWS-WT1 treated by us is reported here. AIM: To characterise an unusual form of EWS-WT1. METHODS: Frozen tissue sections of the axillary tumour were examined using a laser-assisted microdissection technique and reverse transcriptase polymerase chain reaction. RESULTS: The novel fusion of exon 8 of EWS and the defective exon 10 of WT1 (-KTS) was detected. Although it was an unusual form, the coexpression of the present EWS-WT1, IL-2/15Rbeta and Janus kinase (JAK1) mRNA was detected in the tumour cells. IL-2 and signal transducers and activators of transcription (STAT5) mRNA were detected in both tumour and stromal cells. CONCLUSION: The induction of the IL-2/15 receptor signalling pathway may contribute to tumorigenesis in DSRCT through a paracrine or an autocrine system, even though the EWS-WT1 was an unusual form.

Adult↗
PubMed2006

Time course of blood pressure changes immediately after maximal exercise.

AIM: The aim of this study was to investigate the effect of exhaustive exercise on the time course of arterial blood pressure (BP) and heart rate (HR) during upright resting (inactive) and loadless pedaling (active) recovery from a bicycle exercise to exhaustion. METHODS: The subjects were 11 healthy normotensive males. Systolic, diastolic and mean BP, and HR were recorded every 20 s for the initial 6 min of the recovery period. RESULTS: The time course of all BP measures during inactive and active recovery was characterized by a marked and sudden drop during the initial 20-s period, followed by a quick rise. This was followed by a gradual decline till the end of the recovery period. The time course of HR recovery, on the other hand, exhibited a smooth decline without the initial drop. With active recovery, the initial drop of diastolic and mean BP was less than the inactive recovery. After the 20 s period, the diastolic BP and HR were kept slightly higher with the active recovery than the inactive recovery. CONCLUSIONS: A sudden drop of the BP occurred at the initial recovery period of postcycle exercise to exhaustion though HR did not show such a change. The initial BP drop could be attenuated by the actively pedaling the cycle without load.

Adolescent↗
PubMed2005

Involvement of dysadherin and E-cadherin in the development of testicular tumours.

Testicular neoplasms are comprised of a variety of histologically different forms, and their pathogenesis has not been elucidated. Dysadherin is a recently described cell membrane glycoprotein, which has an anticell-cell adhesion function and downregulates E-cadherin. In this study, we examined immunohistochemically the expression of E-cadherin and dysadherin in 120 testicular neoplasms (37 seminomas-26 classic, five spermatocytic and six anaplastic-, 45 embryonal carcinomas, 10 mixed germ cell tumours, two yolk sac tumours, 10 mature and eight immature teratomas and eight non-Hodgkin B-cell lymphomas), clinical stage I. The intensity, the expression pattern and the percentage of neoplastic cell staining was recorded and correlated with the histologic type and vascular/lymphatic invasion. Dysadherin was not expressed in non-neoplastic germ cells, neither in CIS/ITGCNU, but it was highly expressed in all types of germ cell tumours, that demonstrated either embryonic phenotype or somatic differentiation, in most terminally differentiated neoplasms, and in all lymphomas. Dysadherin expression did not correlate with vascular invasion. Increased dysadherin expression was correlated with aberrant E-cadherin expression in most tumours. In 17% of embryonal carcinomas colocalisation of dysadherin and membranous E-cadherin staining was noted. This is the first report on dysadherin expression and its association with E-cadherin in testicular tumours. Since dysadherin is not normally expressed in non-neoplastic testis, it is conceivable that it plays a role in the neoplastic transformation of germ cells. In testicular tumours, as in other neoplasms, dysadherin downregulates E-cadherin expression, at least in part.

Adolescent↗
PubMed2005

Macular thickness reduction in eyes with unilateral optic atrophy detected with optical coherence tomography.

AIMS: To assess the changes in macular and peripapillary retinal nerve fibre layer (RNFL) thickness in eyes with unilateral optic atrophy and to evaluate the relationship between retinal thickness and visual function. METHODS: Enrolled were 22 patients with unilateral optic atrophy. Macular thickness at the divided nine areas and peripapillary RNFL thickness in quadrantic sections were measured by optical coherence tomography. Thickness values in the affected eyes were compared with those in the contralateral unaffected eyes. The correlation of foveal thickness with best-corrected visual acuity (BCVA) was evaluated. The correlation between retinal thickness and the remaining visual field area circumscribed with I-4-e isopter in superior and inferior hemifield was assessed. RESULTS: Macular thinning was observed in all areas (P < 0.001 in each area) other than the fovea (P = 0.068). Peripapillary RNFL thickness decreased in all quadrantic sections (P < 0.001 in each section). The affected to unaffected eye ratio of retinal thickness was more than 0.6 in each area. BCVA did not correlate with foveal thickness (correlation coefficient = 0.094, P = 0.668). Although not statistically significant (P = 0.281, superior hemifield; P = 0.053, inferior hemifield), there was a tendency that eyes with severe visual field loss show more marked retinal thinning. CONCLUSIONS: Macular thinning with the preserved foveal thickness is a hallmark of eyes with optic atrophy. Together with no correlation between foveal thickness and BCVA, this finding would help in differential diagnosis of macular and optic nerve diseases.

Adult↗
PubMed2005

Surgery for clinical T3 carcinomas of the upper thoracic oesophagus and the need for new strategies.

BACKGROUND: Patients with T3 carcinomas have a dismal prognosis, even after complete resection of the primary tumour and metastatic nodes. This study focused on the clinicopathological characteristics and outcomes after surgical resection of clinical T3 carcinomas of the upper thoracic oesophagus. METHODS: Between January 1988 and February 2000, 888 consecutive patients underwent surgical removal of carcinomas of the thoracic oesophagus or oesophagogastric junction at the National Cancer Centre Hospital, Japan. The case records of 51 consecutive patients with clinical T3 tumours of the upper thoracic oesophagus were analysed retrospectively. RESULTS: No patient received preoperative therapy. Complications occurred in 41 (80 per cent). In-hospital and 30-day postoperative mortality rates were 10 and 4 per cent respectively. Gross residual primary tumour or metastasis in regional nodes invading adjacent structures was noted in 14 patients (27 per cent) and incomplete resection including microscopic residual tumour in 23 (45 per cent). Overall 3- and 5-year survival rates were 20 and 12 per cent; median survival was 13.1 months. CONCLUSION: Surgical resection of clinical T3 carcinomas of the upper thoracic oesophagus is associated with a high postoperative complication rate, incomplete resection and unsatisfactory outcome. Reconsideration of the surgical treatment strategy for these tumours is needed.

Adult↗
PubMed2005

Overexpression of anti-apoptotic Mcl-1 in testicular germ cell tumours.

AIMS: To determine the expression of Mcl-1 in testicular germ cell tumours in order to clarify the role of this anti-apoptotic factor in these tumours. Various members of the Bcl-2 family have been implicated in the apoptotic mechanisms regulating germ cell apoptosis. Mcl-1 is an anti-apoptotic Bcl-2 family member and has recently been reported to be related to the progression of malignancy; however, the involvement of Mcl-1 in the development of germ cell tumours is still unknown. METHODS AND RESULTS: Mcl-1 expression in testicular germ cell tumours was investigated by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). By immunohistochemistry, overexpression of Mcl-1 was present in all germ cell tumours that were studied, including embryonal carcinoma and yolk sac tumour, as well as choriocarcinoma and teratoma. In teratomas, Mcl-1 was widely distributed in the epithelial, myogenic, neural and mesenchymal components. RT-PCR analysis after microdissection revealed high levels of Mcl-1 mRNA in all tumour variants compared with non-neoplastic germ cells. CONCLUSION: Overexpression of anti-apoptotic Mcl-1 may function to enhance the viability of testicular germ cells, thereby leading to tumorigenesis.

Adolescent↗
PubMed2005

The p53-Mdm2 association in epithelial cells in idiopathic pulmonary fibrosis and non-specific interstitial pneumonia.

BACKGROUND: Wild-type p53 is increased during cellular responses to various stresses. Mdm2, which is induced by p53, regulates p53 protein concentrations through the ubiquitin-proteasome pathway. AIM: To investigate whether the Mdm2 mediated ubiquitination of p53 is associated with epithelial cell apoptosis in idiopathic pulmonary fibrosis (IPF). METHODS: Immunohistochemistry and western blot analysis were carried out on lung samples obtained by lung biopsy from patients with IPF and non-specific interstitial pneumonia (NSIP). RESULTS: The expression of p53, phosphorylated p53, Mdm2, p21, and Bax was upregulated in epithelial cells from patients with IPF and NSIP compared with normal lung parenchyma. Except for p21, there was a significant increase in the expression of these factors in IPF compared with NSIP. In addition, the number of apoptotic cells and the number of p53 and Bax positive cells was increased compared with controls. p53 conjugated with Mdm2 was decreased in IPF compared with NSIP and controls. Ubiquitinated p53 was increased in both IPF and NSIP compared with controls. CONCLUSIONS: Signalling molecules associated with p53 mediated apoptosis may participate in epithelial cell apoptosis, and the attenuation of p53-Mdm2 conjugation and of p53 degradation may be involved in the epithelial cell apoptosis seen in IPF. Augmented epithelial apoptosis in IPF may lead to the poor prognosis compared with NSIP.

Adult↗
PubMed2005

Apoptosis signaling pathways in lung diseases.

Evidence that apoptosis plays an important role in the pathophysiology of lung diseases has been accumulated. Apoptosis signaling is classically composed of two principle pathways. One is a direct pathway from death receptor ligation to caspase cascade activation and cell death. Death receptor ligation triggers recruitment of the precursor form of caspase-8 to a death-inducing complex, through the adaptor protein FADD, which leads to caspase-8 activation. The other pathway triggered by stimuli such as drugs, radiation, infectious agents and reactive oxygen species is initiated in mitochondria. After cytochrome c is released into the cytosol from the mitochondria, it binds to Apaf1 and ATP, which then activate caspase-9. Recently, endoplasmic reticulum has also been shown to be the organelle to execute apoptosis. Further understanding of molecular mechanisms of apoptosis and its regulation by novel drugs may lead to the development of effective strategies against lung diseases. We overview the signaling pathways of apoptosis and discuss the involvement of apoptosis in the pathophysiology of various lung diseases.

Animals↗
PubMed2004

Exercise blood pressure in young adults as a predictor of future blood pressure: a 12-year follow-up of medical school graduates.

It has not been fully clarified whether exercise blood pressure (BP) in young adult men and women is useful to predict future BP, especially in Asian people. A long-term prospective study was conducted in graduates of a medical school in Japan; 138 men and 76 women whose mean age was 19.8 and 19.2, respectively, at baseline. A 5-min exercise tolerance test was performed at baseline, and BP immediately after exercise was measured. BP at 50% intensity exercise was also calculated. Multiple regression analysis was carried out to clarify the relationship of exercise BP at baseline to follow-up BP after an average of 12 years. In multivariate-adjusted models, the relationship of systolic blood pressure (SBP) at follow-up was stronger to SBP immediately after exercise (F=7.7, P=0.006) than to resting SBP (F=3.7, P=0.055) in men. The models in men showed that SBP immediately after exercise was a stronger predictor of follow-up SBP than SBP at 50% intensity exercise, and the results were similar for diastolic blood pressure (DBP) in men. For SBP in women, resting SBP was the strongest predictor of follow-up SBP (F=14.3, P<0.001), and exercise SBP was not significant predictor. For DBP in women, any DBP at rest or after exercise was not significantly related to DBP at follow-up. In young adult men, SBP and DBP immediately after exercise would be a stronger predictor of future SBP and DBP rather than BP at rest. However, in young adult women, resting SBP rather than exercise SBP would be better to predict future SBP.

Adult↗
PubMed2004

The perforin mediated apoptotic pathway in lung injury and fibrosis.

AIMS: The perforin mediated pathway is the major pathway of cytotoxicity induced by activated T cells and natural killer cells, and may be involved in the development of pulmonary fibrosis. METHODS: Perforin and granzyme B expression were examined in idiopathic pulmonary fibrosis by means of immunohistochemistry, and perforin knockout mice were used to examine whether or not perforin mediated cytotoxicity participates in the pathophysiology of bleomycin induced pneumopathy. RESULTS: Perforin and granzyme B expression were upregulated in infiltrating lymphocytes in lung tissue from patients with idiopathic pulmonary fibrosis compared with normal lung parenchyma. Perforin and granzyme B expression were upregulated predominantly in infiltrating mononuclear cells after bleomycin instillation in wild-type mice. Although the development of bleomycin induced pneumopathy was not completely prevented, the pathological grade of inflammation and fibrosis, and the number of apoptotic cells in lung tissue, were significantly decreased in perforin knockout mice compared with wild-type mice. CONCLUSIONS: These results suggest that perforin mediated apoptosis may be associated with the pathophysiology of lung injury and fibrosis.

Animals↗
PubMed2004

Retinoic acid fails to reverse emphysema in adult mouse models.

BACKGROUND: Previous work has shown that all-trans-retinoic acid reverses elastase induced emphysema in rats. Since there is currently no effective treatment for pulmonary emphysema, the effect of retinoic acid should be further investigated in other adult species. A study was undertaken using two murine models of emphysema to evaluate the effect of retinoic acid. METHODS: The models used were an elastase induced emphysema model for acute alveolar destruction and a tumour necrosis factor (TNF)-alpha transgenic mouse which exhibits chronic air space enlargement, loss of elastic recoil, increased lung volume, and pulmonary hypertension comparable to human pulmonary emphysema. All-trans-retinoic acid (2 mg/kg) was injected for 12 successive days after the establishment of emphysema. The effects of treatment were evaluated using physiological and morphometric analyses. RESULTS: In contrast to the rat, administration of all-trans-retinoic acid in these murine models did not improve the emphysema. Moreover, worsening of emphysema was observed in TNF-alpha transgenic mice treated with all-trans-retinoic acid. The level of keratinocyte chemoattractant (KC), a CXC chemokine, in bronchoalveolar lavage fluid was increased in TNF-alpha transgenic mice following retinoic acid treatment. These data raise the possibility that retinoic acid causes deterioration of emphysema by promoting inflammation in this model. CONCLUSIONS: In these models, retinoic acid did not show positive effects on emphysema. The effect of retinoic acid in the treatment of pulmonary emphysema remains controversial, and further studies are required to determine its physiological effects under a variety of experimental conditions.

Animals↗