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Hiroyuki Nakamura

Publications and source records attributed to Hiroyuki Nakamura.

At least 127 records · Page 7Linked to original sources
PubMed2002

Intravenous anesthetic, propofol inhibits invasion of cancer cells.

Intravenous anesthetic, propofol (2,6-diisopropylphenol), is extensively used for general anesthesia without knowing the effects on cancer. We found here that clinically relevant concentrations of propofol (1-5 microg/ml) decreased the invasion ability of human cancer cells (HeLa, HT1080, HOS and RPMI-7951). In the HeLa cells treated with propofol, formation of actin stress fibers as well as focal adhesion were inhibited, and propofol had little effect on the invasion ability of the HeLa cells with active Rho A (Val(14)-Rho A). In addition, continuous infusion of propofol inhibited pulmonary metastasis of murine osteosarcoma (LM 8) cells in mice. These results suggest that propofol inhibits the invasion ability of cancer cells by modulating Rho A and this agent might be an ideal anesthetic for cancer surgery.

Actins↗
PubMed2002

Palladium-catalyzed aminoallylation of activated olefins with allylic halides and phthalimide.

The three-component aminoallylation reaction of the activated olefins 2 with the phthalimide 1a and allyl chloride proceeded very smoothly in the presence of Pd(2)dba(3).CHCl(3) (5 mol %)/P(4-FC(6)H(4))(3) (40 mol %) and Cs(2)CO(3) (3 equiv against 2) in dichloromethane at room temperature to give the corresponding aminoallylated products, N-pent-4-enylphthalimides 3, in 58-99% yields. The reaction of oxazolidinone 1b also proceeded very smoothly to give N-(2,2-dicyano-1-phenylpent-4-enyl)oxazolidinone in a quantitative yield; however, the Tsuji-Trost-type allylation products 4 were obtained in the case of dibenzylamine, N-tosylaniline, and pyrrolidin-2-one. Further, 2 underwent cycloaddition with N-tosylvinylaziridine 9a in the presence of Pd(2)dba(3).CHCl(3) (5 mol %)/P(4-FC(6)H(4))(3) (40 mol %) in THF at room temperature, giving the corresponding pyrrolidines 11 in 69-99% yields.

Journal Article↗
PubMed2002

Ipriflavone inhibits osteolytic bone metastasis of human breast cancer cells in a nude mouse model.

Osteolytic bone metastasis is a frequent problem in the treatment of cancer. Ipriflavone, a synthetic isoflavone that inhibits osteoclastic bone resorption, has been used for the treatment of osteoporosis in some countries. Some other isoflavones also exhibit an antitumor effect in vitro and in vivo. Here, we studied the effects of ipriflavone on osteolytic bone metastasis of MDA-231 human breast cancer cells injected intracardially into athymic nude mice (ICR-nu/nu). Daily oral administration of ipriflavone at 12 mg/mouse significantly inhibited the development of new osteolytic bone metastases (p < 0.05) and the progression of established osteolytic lesions (p = 0.01), prolonging the life of tumor-bearing mice (p = 0.01 vs. control). In addition, ipriflavone reduced the number of osteoclasts at the bone-cancer interface with no severe adverse effects on the host. In vitro, ipriflavone inhibited the proliferation and DNA synthesis of MDA-231 cells and blocked the ligand-induced phosphorylation of Tyr(845) of the EGFR. Ipriflavone did not promote apoptosis of MDA-231 cells. Our results show that ipriflavone not only directly inhibits the growth of cancer cells but also reduces osteoclasts to prevent the soft tissue tumor burden and osteolytic bone metastases. These findings raise the possibility that ipriflavone may be of use as a therapeutic agent against osteolytic bone metastasis.

Analgesics↗
PubMed2002

Hydrogen activation on Mo-based sulfide catalysts, a periodic DFT study.

Hydrogen adsorption on Mo[bond]S, Co[bond]Mo[bond]S, and Ni[bond]Mo[bond]S (10 1 macro 0) surfaces has been modeled by means of periodic DFT calculations taking into account the gaseous surrounding of these catalysts in working conditions. On the stable Mo[bond]S surface, only six-fold coordinated Mo cations are present, whereas substitution by Co or Ni leads to the creation of stable coordinatively unsaturated sites. On the stable MoS(2) surface, hydrogen dissociation is always endothermic and presents a high activation barrier. On Co[bond]Mo[bond]S surfaces, the ability to dissociate H(2) depends on the nature of the metal atom and the sulfur coordination environment. As an adsorption center, Co strongly favors molecular hydrogen activation as compared to the Mo atoms. Co also increases the ability of its sulfur atom ligands to bind hydrogen. Investigation of surface acidity using ammonia as a probe molecule confirms the crucial role of sulfur basicity on hydrogen activation on these surfaces. As a result, Co[bond]Mo[bond]S surfaces present Co[bond]S sites for which the dissociation of hydrogen is exothermic and weakly activated. On Ni[bond]Mo[bond]S surfaces, Ni[bond]S pairs are not stable and do not provide for an efficient way for hydrogen activation. These theoretical results are in good agreement with recent experimental studies of H(2)[bond]D(2) exchange reactions.

Journal Article↗
PubMed2002

Novel carboranes with a DNA binding unit for the treatment of cancer by boron neutron capture therapy.

The synthesis and biological evaluation of two ortho-carborane derivatives which contain a 5,6,7-trimethoxyindole (TMI) unit for use in boron neutron capture therapy is described. The TMI moiety is known to be the DNA-binding part of the highly potent anticancer agent duocarmycin A. The ortho-carborane derivatives were prepared from amino alkynes which were bound to a protected TMI carboxylic acid. Addition of decaborane(14) to the alkyne triple bond with subsequent removal of the tert-butoxycarbonyl (Boc) and benzyl protecting groups gave the desired product. Boron uptake from the ortho-carborane derivatives into B-16 melanoma cells was higher and faster than that observed with L-p-boronophenylalanine (BPA), which is in use in the clinic.

Animals↗
PubMed2002

Epinephrine inhibits invasion of oral squamous carcinoma cells by modulating intracellular cAMP.

In oral and maxillofacial surgery, epinephrine is routinely used for cancer resection and it is important to clarify the effects of this agent on cancer. We found here that the clinically relevant concentrations of epinephrine (10, 50 and 100 microg/ml) decreased the invasion ability of oral squamous carcinoma (Sa3) cells. In the Sa3 cells treated with epinephrine (10, 50 and 100 microg/ml), migration, morphological changes and formation of actin stress fibers were inhibited and intracellular cyclic adenosine monophosphate (cAMP) increased significantly. These findings suggest that epinephrine inhibits the invasion of cancer cells by modulating intracellular cAMP and that clinicians could use epinephrine effectively for the surgical resection of the cancer.

Actins↗
PubMed2002

Infiltration anesthetic lidocaine inhibits cancer cell invasion by modulating ectodomain shedding of heparin-binding epidermal growth factor-like growth factor (HB-EGF).

Although the mechanism is unknown, infiltration anesthetics are believed to have membrane-stabilizing action. We report here that such a most commonly used anesthetic, lidocaine, effectively inhibited the invasive ability of human cancer (HT1080, HOS, and RPMI-7951) cells at concentrations used in surgical operations (5-20 mM). Ectodomain shedding of heparin-binding epidermal growth factor-like growth factor (HB-EGF) from the cell surface plays an important role in invasion by HT1080 cells. Lidocaine reduced the invasion ability of these cells by partly inhibiting the shedding of HB-EGF from the cell surface and modulation of intracellular Ca2+ concentration contributed to this action. The anesthetic action of lidocaine (sodium channel blocking ability) did not contribute to this anti-invasive action. In addition, lidocaine (5-30 mM), infiltrated around the inoculation site, inhibited pulmonary metastases of murine osteosarcoma (LM 8) cells in vivo. These data point to previously unrecognized beneficial actions of lidocaine and suggest that lidocaine might be an ideal infiltration anesthetic for surgical cancer operations.

Anesthetics, Local↗
PubMed2002

Tumor debulking by radiofrequency ablation in hypertrophic pulmonary osteoarthropathy associated with pulmonary carcinoma.

A 73-year-old male with stage IV lung adenocarcinoma presented with leg swelling and clubbing of the fingers on both hands upon physical examination, and bone scintigrams demonstrated marked accumulation of 99mTc-MDP in the long bones adjacent to the patellae. A diagnosis of hypertrophic pulmonary osteoarthropathy associated with primary lung cancer was made. Radiofrequency ablation (RFA) was utilized for cytoreduction, because the patient refused chemotherapy. One-month follow-up CT scans revealed low density of the ablated area associated with ablation necrosis. Cytoreduction by RFA rapidly alleviated the arthralgia and swelling, but not the clubbing of fingers. Follow-up bone scintigrams demonstrated a reduction in patellar uptake after RFA.

Adenocarcinoma↗
PubMed2002

Nestin immunoreactivity in local neurons of the adult rat striatum after remote cortical injury.

Nestin is a marker for the neuronal and glial precursor cells and is expressed in reactive astrocytes after brain injury. Following restricted neocortical injury, we found that cells with neuronal morphology in the adult rat striatum became immunoreactive for both nestin and the neuronal marker, microtubule-associated protein 2 (MAP-2), but not for the astroglial marker, glial fibrillary acidic protein (GFAP). The number of nestin-positive cells transiently increased in the striatum. Continuous administration of 5-bromo-2'-deoxyuridine (BrdU) after cortical injury did not reveal any newly generated neurons in the striatum. Double-labeling fluorescent immunocytochemistry revealed that the nestin-positive striatal cells were also substance-P-positive. These findings suggest that some factors released from the injured cortex may induce nestin immunoreactivity in striatal neurons.

Animals↗
PubMed2002

Gamma-knife radiosurgery for brain metastasis of renal cell carcinoma: results in 42 patients.

BACKGROUND: The present study provides data from clinical experience with gamma-knife radiosurgery (GK) in patients with brain metastasis from renal cell carcinoma (RCC) and shows the value of this less invasive treatment modality. METHODS: Forty-two patients received GK. Twenty of the 42 cases had multiple brain metastases. Extracranial metastases were observed in the lung (38 cases), bone (12 cases), liver (9 cases), lymph node (5 cases) and skin (6 cases). RESULTS: Neurological symptoms seen in 40 patients were rapidly improved after GK in 32 patients (80%). Magnetic resonance imaging (MRI) evaluation after GK in 32 patients showed the disappearance of brain tumor in 9 patients (28%). Complete response was obtained by GK in tumors up to 30 mm in diameter. Repeated GK for newly developed lesions was conducted in 11 patients. Extracranial tumor resection was conducted in 7 cases (lung: 3, skin: 2, liver: 1, adrenal: 1). Chemo-radiotherapy or immunotherapy was effective in 8 cases (lung: 5, liver: 2, bone: 1). The actual one-, two- and three-year survival rates were 44.9%, 16.8%, and 11.2%, respectively. The median survival time was 12.5 months. In univariate analysis, the patients with successfully treated extracranial metastases had significantly better prognosis. In multivariate analysis, the patients with Karnofsky performance scale (KPS) > or = 80%, who were treated by GK more than once and obtained complete response (CR) or partial response (PR) by GK, had significantly better prognosis. CONCLUSION: Gamma-knife radiosurgery for RCC is an effective non-invasive modality of treatment. It offers a high local control rate and an improved quality of life and survival rate.

Adult↗
PubMed2002

3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors reduce human pancreatic cancer cell invasion and metastasis.

BACKGROUND & AIMS: Inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase blocks the mevalonate metabolic pathway, which is necessary for the isoprenylation of a number of small guanosine triphosphatases. We examined the effects of HMG-CoA reductase inhibitors, fluvastatin and lovastatin, on human pancreatic cancer cell invasion in vitro and experimental liver metastasis in vivo. METHODS: Cell invasion was studied in a modified Boyden chamber assay. The translocation of RhoA was assessed by immunoblotting. Experimental liver metastases were induced in nude mice by intrasplenic inoculation of ASPC-1 human pancreatic cancer cells. RESULTS: Fluvastatin and lovastatin inhibited the in vitro cancer cell invasion induced by epidermal growth factor (EGF) in a manner sensitive to C3 transferase, a specific inhibitor of Rho. Treatment of ASPC-1 cells with fluvastatin markedly attenuated the EGF-induced translocation of RhoA from the cytosol to the membrane fraction and caused cell rounding. The effects of fluvastatin could be reversed by the addition of all-trans-geranylgeraniol. Administration of fluvastatin to nude mice reduced both metastatic tumor formation in the liver and the growth of established liver metastases at doses recommended for the treatment of hypercholesterolemia in humans. CONCLUSIONS: HMG-CoA reductase inhibitors can be antimetastatic agents with the potential for useful clinical applications.

Adenocarcinoma↗
PubMed2002

Immunohistochemical artifact for nitrotyrosine in eosinophils or eosinophil containing tissue.

Immunohistochemical artifacts for nitrotyrosine were investigated in eosinophils with regard to fixatives. Immunoreactivity for nitrotyrosine was revealed in separated eosinophils and in gastric mucosa fixed with periodate, lysine-paraformaldehyde (PLP). The increase in immunoreactivity by PLP was due to periodate itself, a component of PLP. Nitrotyrosine formed by peroxidase using NO2- and H2O2 or by peroxynitrite was not completely inhibited by 100 mM dithionite but the immunoreactivity for nitrotyrosine antibodies by PLP was completely inhibited by 5.7 mM dithionite. Although untreated eosinophils or ovalbumin (OVA) did not show protein tyrosine nitration in a standard Western blot, the treatment of the blotted membrane with PLP increased the reactivities of proteins from eosinophils with anti-nitrotyrosine antibodies. The increase in immunoreactivity of OVA with anti-nitrotyrosine antibodies by PLP did not change with pre-treatment with dithionite but was abolished by treatment with dithionite after PLP fixation. In HPLC assays, periodate did not generate nitrotyrosine from L-tyrosine and aminotyrosine. These results suggest that the treatment of eosinophils or eosinophil-containing tissues with PLP fixative augments the immunoreactivity of nitrotyrosine antibodies with eosinophils due to the formation of epitopes similar to nitrotyrosine by an oxidation reaction of periodate, which evokes an artifact in nitrotyrosine immunohistochemistry.

Artifacts↗
PubMed2002

Expression of S100A6 and S100A4 in matched samples of human colorectal mucosa, primary colorectal adenocarcinomas and liver metastases.

OBJECTIVE: S100A6 and S100A4, two of S100 protein family, have been suggested to be associated with cancer tumorigenesis and metastasis. The aim of this study was to evaluate the expression levels of S100A6 and S100A4 in matched samples of primary human colorectal adenocarcinomas (T), adjacent normal colorectal mucosa (N) and liver metastases (M). This gave us the advantage of directly comparing levels of S100A6 and S100A4 expression within the same genetic background. METHODS: In matched samples of N, T and M from 10 colorectal adenocarcinoma patients, expressions of S100A6 and S100A4 were studied by Western blot and immunohistochemical analyses using specific antibodies against each protein. RESULTS: The expression levels of S100A6 were significantly higher in T than in N (p < 0.05), while those of S100A4 showed no difference between T and N. There were no significant differences in the expression levels of S100A6 or S100A4 between M and T. Similar results were obtained by immunohistochemical analysis. Moreover, S100A6 was stained more intensely in invading fronts than in central portions of both T and M. CONCLUSIONS: The observed differential expression of S100A6 and S100A4 suggests that S100A6, rather than S100A4, is associated with human colorectal adenocarcinoma tumorigenesis and invasion/metastasis.

Adenocarcinoma↗
PubMed2002

Intralobar pulmonary sequestration presenting increased serum CA19-9 and CA125.

A 39-year-old man was admitted to our hospital for further evaluation of a consolidated shadow and clarification of the cause of serum tumor marker elevation (CA19-9 496.2 U/ml, CA125 160.6 U/ml). Chest computed tomography revealed a well-defined homogeneous nodule in the left S(10). Angiography showed one aberrant artery, branching from the ascending aorta. Intralobar pulmonary sequestration was diagnosed and the sequestrated lung was resected. Microscopic findings of the sequestrated lung showed a mucus-containing cystically dilated bronchus, which was covered with ciliated cylindrical epithelium. Immunohistochemical staining showed positive staining for CA19-9 and CA125 in both the ciliated cylindrical epithelium and mucus. Serum values of tumor markers returned to their normal range after surgery.

Adult↗
PubMed2002

[Improvement of extrapulmonary lesions of eosinophilic granuloma after cessation of smoking].

We encountered a case of pulmonary eosinophilic granuloma complicated with pneumothorax. A 24-year-old man was admitted to our department because of respiratory difficulty. Chest radiography on admission showed a right pneumothorax. A thoracic catheter was therefore inserted, and the pneumothorax was improved. A chest radiograph obtained after treatment showed diffuse linear reticular shadows; and a chest CT scan showed starlike nodular lesions and multiple cysts in the lungs, and a large nodule in the left rib. Because an ulcer had been diagnosed in the oral cavity 1 year previously, a mandible biopsy was performed, and a granulomatous lesion consisting of eosinophils was recognized. Taken together with the pulmonary findings, an eosinophilic granuloma was diagnosed. The patient was instructed not to smoke and the clinical course was observed. The pulmonary, mandibular, and costal lesions improved.

Adult↗