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Toshio Nishikawa

Publications and source records attributed to Toshio Nishikawa.

33 records · Page 2Linked to original sources
PubMed2003

Expression of matrix metalloproteinase, tissue inhibitors of metalloproteinase and adhesion molecules in silicotic mice with lung tumor metastasis.

The number of metastatic foci in silicotic mice is approximately 1.5-fold that in normal mice and in mice treated with TiO2 as inert particles. Expression of matrix metalloproteinases (MMPs) tissue inhibitors of metalloproteinases (TIMPs) and selectins was investigated in silicotic mice with lung tumor metastasis. Expression of MMP-9 and P-selectin mRNA, but not MMP-2 and E-selectin, increased significantly, showing decreases of the ratio of expression in TIMPs/MMP-9 in tumor-bearing silicotic mice compared with the tumor-bearing normal mice and mice treated with TiO2. Pretreatment with anti-P-selectin antibody inhibited number of metastatic foci significantly in silicotic mice, while pretreatment of animals with anti MMP-9 antibody showed slight decrease of metastatic foci. This evidence indicated that up-regulation of P-selectin expression contributed to enhanced rate of tumor metastasis in lung with silicosis.

Animals↗
PubMed2003

Outcome of breast-conserving therapy in the Tokyo Women's Medical University Breast Cancer Society experience.

BACKGROUND: The results of BCT in Japanese women have not been fully evaluated. The Tokyo Women's Medical University Breast Cancer Society initiated BCT protocols in 1987. Here, we present a retrospective analysis of BCT outcomes and identify prognostic factors. METHODS: The study population comprised 348 patients (353 breasts) with UICC clinical stage 0,I or II breast cancer, for whom wide excision (n= 294), quadrantectomy (n= 56) and tumorectomy (n= 3) were performed. The final pathological margin states were positive in 102 breasts (cancer cells remained within 5 mm of the surgical margin). The whole breast was irradiated to a total dose with 44 Gy/20 fractions or 46 Gy/23 fractions in the patients with negative surgical margins. The patients with positive or close margins received 48.4 Gy/22 fractions or 50 Gy/25 fractions irradiation to the whole breast. All but 2 patients received a radiation boost to the tumor bed and all tumor beds were irradiated to more than 53 Gy. Adjuvant therapy was administered in 240 cases. The median follow-up time was 4.3 years. RESULTS: The 5-year overall, cause-specific and disease-free survival rates were 95.8%, 97.3% and 92.5%, respectively. Recurrence was observed in 29 patients including 11 patients with loco-regional recurrence. Local recurrence was observed in 6 patients, 5 of whom were premenopausal. The 5-year local control and loco-regional control rates were 98.9% and 96.6%, respectively. T status (T1 to T2) was the only significant prognostic factor for disease-free survival. No severe morbidity has been observed. Cosmetic results were excellent or good in 73% of patients. CONCLUSION: Our BCT protocols provide a high rate of local control and good cosmetic outcome. Pathologic margin status was not a major prognostic factor for local recurrence. Long term follow-up is required to reach a definite conclusion on optimal BCT protocols.

Adult↗
PubMed2003

Stage IVB uterine endometrial cancer successfully salvaged by chemoradiotherapy and surgery.

A case of stage IVB adenoacanthoma of the uterine corpus is described. The patient was admitted with a large amount of atypical genital bleeding. Computed tomography and magnetic resonance imaging revealed a large tumor accompanied by lymph node involvement in the left inguinal, multiple pelvic, and paraaortic regions. She was diagnosed as having stage IVB endometrial adenoacanthoma. Neoadjuvant chemotherapy with carboplatin (CBDCA) and 5-fluorouracil (5-FU) was performed, followed by radiotherapy. The tumor responded very well, but still remained in Douglas' pouch after treatment. The patient therefore underwent a simple hysterectomy, pelvic and paraaortic lymphadenectomy, and partial rectal resection. Histopathologically, viable cancer cells were observed only in the fundus of the uterus. The patient is alive with no evidence of recurrence 4 years after the initiation of chemoradiotherapy.

Adenocarcinoma↗
PubMed2003

Biological activity of 8,11-dideoxytetrodotoxin: lethality to mice and the inhibitory activity to cytotoxicity of ouabain and veratridine in mouse neuroblastoma cells, Neuro-2a.

Contribution of the C-8 hydroxyl group of tetrodotoxin to its sodium channel blocking activity has never been clearly evaluated. Isobe et al. recently synthesized 8,11-dideoxytetrodotoxin, the first 8-deoxy analog of tetrodotoxin. In this study, the biological activity of this compound was investigated to compare with that of 11-deoxytetrodotoxin. Intraperitoneal injection of 8,11-dideoxytetrodotoxin at the level of 700 microg/kg did not kill a mouse (n=2), indicating that the lethal dose of this compound was more than 70 and 10 folds larger than LD(50) of tetrodotoxin and 11-deoxytetrodotoxin, respectively. The inhibitory activity of 8,11-dideoxytetrodotoxin to cytotoxicity of ouabain and veratridine in mouse neuroblastoma cells (Neuro-2a) was also examined. The ED(50) for 8,11-dideoxytetrodotoxin was estimated to be 9.3+/-3.3 microM (n=3), approximately 2000 and 34 folds larger than those of tetrodotoxin (4.6+/-0.70 nM, n=3) and 11-deoxytetrodotoxin (270+/-74 nM, n=4), respectively. These data suggest that the C-8 hydroxyl group of tetrodotoxin is also important for its activity, as well as all the other hydroxyl groups.

Animals↗
PubMed2002

Expression of peroxisome proliferator-activated receptor-gamma in vascular smooth muscle cells is upregulated in cystic medial degeneration of annuloaortic ectasia in Marfan syndrome.

BACKGROUND: Cystic medial degeneration (CMD) is a histological abnormality that is common in annuloaortic ectasia (AAE) and aortic dissection with Marfan syndrome. Apoptosis and loss of vascular smooth muscle cells (VSMCs) is one of the features of CMD, but little is known about its pathogenesis. Peroxisome proliferator-activated receptor-gamma (PPARgamma), a transcription factor of the nuclear receptor superfamily, has been reported to show antiproliferative effects on VSMCs as well as anti-inflammatory effects on macrophages. PPARgamma agonist has been recently reported to induce apoptosis of cultured VSMCs. METHODS: We examined the histopathology of ascending aortas in AAE of Marfan patients (n=21) and control patients (n=6) at surgery. RT-PCR was performed to demonstrate expression of PPARgamma in CMD. Localization of PPARgamma was determined by double immunostaining using antibodies against PPARgamma and cell-specific markers (ie, SMCs, macrophages, and T lymphocytes). RESULTS: PPARgamma expression was upregulated in AAE samples but minimal in control samples by RT-PCR (P=0.07). Immunoreactivity against PPARgamma in numerous nuclei of VSMCs was observed in CMD lesions. Severity of CMD correlated with positive immunoreactivity of PPARgamma in medial VSMCs (P=0.03). No inflammatory cells (ie, macrophages or T lymphocytes) were detected in CMD lesions. CONCLUSION: PPARgamma expression is upregulated in SMCs of CMD without any inflammatory response. Activated PPARgamma in VSMCs might be involved in the pathogenesis of CMD in Marfan's aortas. Regulation of PPARgamma might lead to clinical implication in protection against progression of AAE.

Adult↗
PubMed2002

Stereocontrolled synthesis of 8,11-dideoxytetrodotoxin, unnatural analogue of puffer fish toxin.

[structure: see text] 8,11-Dideoxytetrodotoxin, an unnatural tetrodotoxin analogue, was synthesized in a highly stereoselective manner from a common intermediate in our synthetic studies on tetrodotoxin. The synthesis features neighboring group participation of trichloroacetamide for stereoselective hydroxylation, protection of ortho ester, and guanidine installation with Boc-protected isothiourea.

Stereoisomerism↗
PubMed2002

Asymmetric total synthesis of 11-deoxytetrodotoxin, a naturally occurring congener.

Tetrodotoxin, a toxic principle of puffer fish poisoning, is a specific blocker of sodium channel. Despite many synthetic efforts since the structure elucidation in 1964, the only total synthesis of the racemic tetrodotoxin has been reported by Kishi and co-workers. In the course of our studies directed toward the total synthesis to analyze biologically interesting issues associated with tetrodotoxin, we accomplished a highly stereocontrolled synthesis of (-)-5,11-dideoxytetrodotoxin in 1999. Based on the synthesis, we describe herein the first total synthesis of 11-deoxytetrodotoxin, a naturally occurring analogue. The synthesis started from an allylic alcohol, the same intermediate for the synthesis of 5,11-dideoxytetrodotoxin. Epoxidation of the allylic alcohol was followed by isomerization with Ti(i-PrO)(4) to give an alpha-hydroxy allylic alcohol, in which the configurations of the two hydroxyl groups were inverted by oxidation and then a 2-step reduction. Further epoxidation of the allylic alcohol and ozonolysis of the remaining vinyl group gave an aldehyde, which reacted with magnesium acetylide to give a propargyl alcohol in a stereoselective manner. Oxidative cleavage of the acetylenic moiety with RuO(4) afforded a fully functionalized lactone for 11-deoxytetrodotoxin. Crucial guanidinylation was achieved from trichloroacetamide according to our own method to give acetyldibenzylguanidine. Finally, deprotection of benzyl groups, acetates, and acetal furnished 11-deoxytetrodotoxin.

Animals↗
PubMed2002

Expression and mutation of p53 gene in the lung of mice intratracheal injected with crystalline silica.

The genotoxic effect of crystalline silica (Qt) in the lung was studied to clarify that silicosis conferred a significant increase in risk subsequent lung cancer. C57BL/6N mice received a single tracheal injection of Qt at dose of 2 mg/mouse. Lung p53mRNA was suppressed significantly, but no change of p21mRNA 15 months after treatment. Mutation of p53 gene was not identified at 15 months in the Qt group. Silicotic lesions were observed in the lungs of Qt group, but silicosis with pulmonary neoplasia was no detected. These results indicated that genetic changes in the silicotic lung might lead to facilitation of carcinogenesis.

Animals↗
PubMed2002

Tenascin-C is a useful marker for disease activity in myocarditis.

Tenascin-C (TNC) is an extracellular matrix protein which appears at active sites of tissue remodelling during embryogenesis or cancer invasion. In normal heart, TNC is only present during the early stages of development but reappears in pathological states. This study examined the diagnostic value of TNC for assessing disease activity of myocarditis. Expression of TNC was examined in myosin-induced autoimmune myocarditis mouse models. Sequential changes in amount, localization and the producing cells were analysed by reverse transcriptase-polymerase chain reaction, western blotting, immunohistochemistry and in situ hybridization and compared with the histological picture. The expression of TNC was upregulated at a very early stage of myocarditis. Immunostaining was detectable before cell infiltration and myocytolysis became histologically apparent, remained during the active stage while cell infiltration and necrosis continued, and disappeared in scar tissue with healing. TNC immunostaining was always observed at the periphery of necrotic or degenerating cardiomyocytes in foci of inflammation, the expression level correlating with histological evidence of inflammatory activity. Interstitial fibroblasts were the major source of TNC, expressing the large isoform containing alternative splicing sites. These data demonstrate that TNC is a useful marker for evaluation of disease activity in myocarditis.

Acute Disease↗
PubMed2002

Subepicardial aneurysm after anticoagulant therapy for a mural thrombus following anterior myocardial infarction.

A subepicardial aneurysm became evident in a male patient after anticoagulant therapy. On admission, it appeared to be an old anterior infarction accompanied by a mural thrombus. After warfarin administration, the thrombus disappeared and an echo-free space emerged outside the apical myocardial wall. The echo-free space communicated with the left ventricular cavity through the apical myocardial wall. Emergency surgery was undertaken and the patient survived. The aneurysm was covered with epicardium and there was an endomyocardial rupture of the muscle in the apical wall, which was the entrance of the aneurysm. This case suggests that cautious follow-up with echocardiography is necessary when anticoagulant therapy is selected for thrombi following myocardial infarction.

Anticoagulants↗
PubMed2002

Blood vessel invasion as a predictor of long-term survival for Japanese patients with breast cancer.

A wide range of frequencies has been reported for blood vessel invasion (BVI) among patients with breast cancer, however, the prognostic significance of BVI remains controversial. Three hundred ninety-eight Japanese patients with breast cancer, operated on during the period between 1971 and 1987, were studied. We investigated five factors, including BVI, lymph-node status (n), clinical tumor size (T), histological grade (HG), and tumor necrosis (TN), followed for a median of 10 years. BVI was detected by hematoxylin and eosin (HE) staining and both factor VIII-related antigen and elastica van Gieson staining. BVI detected by HE staining alone was defined as BVIh. The subtypes of BVI were classified as follows: BVI e, BVI detected only by elastica van Gieson staining; BVI f, BVI detected only by factor VIII-related antigen staining; and BVI e/f, BVI detected by both factor VIII-related antigen and elastica van Gieson staining. BVI-positive tumors were defined as lesions showing BVI e, BVI f, or BVI e/f. BVI and BVIh were presented in 27.4%, 6.5% of all cases, respectively. The mean diameters of the calibers of BVI e, BVI f, and BVI e/f were 141.9+/-80.5 microm, 61.0+/-37.4 microm, 136.0+/-102.0 microm, respectively (P<0.0001). Seventy-three patients (18.3%) had recurrence and 60 patients (15.1%) died of breast cancer. Univariate analysis showed that BVIh (P <0.0001), BVI (P<0.0001), n, T, and HG were significantly predictive of 20-year RFS and OS. Multivariate analysis showed that BVI (P<0.0001, P = 0.0088, respectively), n, T, and HG were all significant and independent prognostic factors for RFS and OS. On the other hand, BVIh was an independent factor for RFS (P = 0.0475), but of borderline significance for OS (P = 0.0506). When stratified by BVI, BVI e, and BVI e/f were significantly predictive of 20-year RFS or OS (P < 0.0001). We can confirm BVI, especially BVI e and BVI e/f, are significant independent prognostic factors associated with long-term survival in Japanese breast cancer patients.

Adenocarcinoma↗
PubMed2002

Synthesis of novel alpha-C-glycosylamino acids and reverse regioselectivity in Larock's heteroannulation for the synthesis of the indole nucleus.

An alpha-C-iodoethynylglucose derivative was coupled with an L-serine-derived zinc-copper reagent to give alpha-C-glucosylpropargyl glycine, which underwent palladium catalyzed-heteroannulation with o-iodoaniline to give not alpha-C-glucosyl-tryptophan but alpha-C-glucosyl-iso-tryptophan. This is the first observation of complete reverse regioselectivity to Larock's proposal.

Amino Acids↗
PubMedDate not supplied

C-erbB-2 and PCNA as prognostic indicators of long-term survival in breast cancer.

This study was designed to evaluate the prognostic importance of c-erbB-2 and proliferating cell nuclear antigen (PCNA) with long-term follow-up in Japanese patients with breast cancer. Four hundred and eight patients with breast cancer were studied. We investigated 6 factors, including c-erbB-2, PCNA, lymph-node status (n), clinical tumor size (T), histological grade (HG) and lymphatic vessel invasion, followed for a median of 10 years. c-erbB-2 overexpression was found in 35.0% and PCNA in 43.1% of the carcinomas. c-erbB-2 positivity was correlated with PCNA (p < 0.0001), n (p<0.0001), T (p = 0.0016), and HG (p = 0.0110). Univariate analysis showed that c-erbB-2 was significantly predictive of 20-year overall survival (OS) (p = 0.0247), but not of 20-year relapse-free survival (RFS). PCNA was significantly associated with 20-year RFS and OS (p <0.0001, p < 0.0001, respectively). Multivariate analysis showed that PCNA was an independent prognostic factor in node-negative patients, but c-erbB-2 and PCNA were not independent prognostic indicators in all patients. Although c-erbB-2 expression and PCNA were obviously important from a biological standpoint, they were not recognized as independent molecular markers.

Adolescent↗
PubMedDate not supplied

p53, mitosis, apoptosis and necrosis as prognostic indicators of long-term survival in breast cancer.

This study was designed to evaluate the prognostic importance of p53, mitosis, apoptosis and necrosis with long-term follow-up in Japanese patients with breast cancer. Four hundred and twenty-two patients with breast cancer were studied. We investigated 7 factors, including p53, mitotic index (MI), apoptotic index (AI), necrosis, lymph-node status (n), clinical tumor size (T) and lymphatic vessel invasion, followed for a median of 10 years. p53 accumulation was found in 30.1%, MI in 35.2%, AI in 36.3% and necrosis in 38.5%. p53 accumulation was correlated with MI (p = 0.0324), AI (p = 0.0010), necrosis (p = 0.0003), T (p = 0.0320), n (p < 0.0001), estrogen receptor (p = 0.0005) and progesterone receptor (p = 0.0287). Univariate analysis showed that p53, MI and necrosis were significantly predictive of 20-year overall survival (OS) or of 20-year relapse-free survival (RFS) (p < 0.0001 or p = 0.0003, p< 0.0001 or p < 0.0001 and p = 0.0131 or p = 0.0068, respectively), but AI was not. Multivariate analysis showed that p53 was an independent prognostic factor with RFS in all the patients, especially, with relapse-free survival (RFS) in the patients with T1 and with RFS and overall survival (OS) in the patients with a node-negative tumor. MI was an independent prognostic factor with OS in all the patients and with RFS and OS in the patients with a node-negative tumor. However, AI and necrosis were not independent predictors.

Adolescent↗