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1.
Polymers (Basel) ; 9(7)2017 Jun 24.
Article in English | MEDLINE | ID: mdl-30970923

ABSTRACT

N-alkoxybenzyl aromatic polyamides were synthesized by polycondensation of N-alkoxybenzyl aromatic diamine with equimolar dicarboxylic acid chloride in the presence of 2.2 equiv. of pyridine at room temperature for 2 days. The obtained polyamides were mainly cyclic polymers, as determined by means of matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, and showed higher solubility in organic solvents than unprotected aromatic polyamides. Photodeprotection of N-alkoxybenzyl aromatic polyamide film containing photo acid generator (PAG) proceeded well under UV irradiation (5 J/cm²), followed by heating at 130 °C for 15 min. The nature of the polymer end groups of N-alkoxybenzyl aromatic polyamides was found to be crucial for photodeprotection reactivity. These polymers are promising candidates for photosensitive heat-resistant materials for fine Cu wiring formation by electroless Cu plating of high-density semiconductor packaging substrates.

2.
Cancer Sci ; 101(4): 920-6, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20175781

ABSTRACT

Vaults are evolutionarily highly conserved ribonucleoprotein (RNP) particles with a hollow barrel-like structure. Although roles in multidrug resistance and innate immunity have been suggested, the physiological function of vaults remains unclear. Major vault protein (MVP), the main component of the vault particle, has been reported to be induced by hypoxia. However, there are no reports about the effect of vaults on cellular responses to hypoxia. We thus examined whether vaults are implicated in cellular responses to hypoxia. In this study, we focused on hypoxia-inducible factor-1alpha (HIF-1alpha), which is a master regulator of hypoxic responses, and found that: (i) MVP knockdown by RNA interference increases HIF-1alpha protein levels induced by hypoxia and hypoxia mimetics; (ii) MVP knockdown does not affect HIF-1alpha mRNA levels, but decreases the ubiquitination and degradation of HIF-1alpha protein; and (iii) vaults form complexes with HIF-1alpha, PHD2, and pVHL. Taken together, these results suggest that vaults function as scaffolds in HIF-1alpha degradation pathway and promote the ubiquitination and degradation of HIF-1alpha.


Subject(s)
Adenocarcinoma/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Kidney Neoplasms/metabolism , Vault Ribonucleoprotein Particles/metabolism , Cell Hypoxia , Cell Line, Tumor , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , RNA Interference , RNA, Messenger/metabolism , Ubiquitination , Vault Ribonucleoprotein Particles/genetics
3.
Biochem Biophys Res Commun ; 378(3): 650-5, 2009 Jan 16.
Article in English | MEDLINE | ID: mdl-19059207

ABSTRACT

The extracellular signal-regulated kinase (ERK) signaling pathway is constitutively activated in many human tumor cell types. Given the cytoprotective role of this pathway, we examined whether its specific blockade might sensitize human tumor cells to the induction of apoptosis by various anticancer drugs. Although blockade of ERK signaling alone did not induce substantial cell death, it resulted in marked and selective enhancement of the induction of apoptosis by microtubule-destabilizing agents in tumor cells in which the ERK pathway is constitutively activated. The synergistic activation of c-Jun NH(2)-terminal kinase by the combination of an ERK pathway inhibitor and a microtubule-destabilizing agent appeared to be responsible, at least in part, for this effect. These results suggest that administration of the combination of an ERK pathway inhibitor and a microtubule-destabilizing agent is a potential chemotherapeutic strategy for the treatment of tumor cells with constitutive activation of the ERK pathway.


Subject(s)
Apoptosis , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Microtubules/drug effects , Neoplasms/enzymology , Protein Kinase Inhibitors/pharmacology , Tubulin Modulators/pharmacology , Cell Line, Tumor , Flavonoids/pharmacology , Humans , Vincristine/pharmacology
4.
Exp Cell Res ; 314(16): 3017-26, 2008 Oct 01.
Article in English | MEDLINE | ID: mdl-18671966

ABSTRACT

The major vault protein (MVP) is the major constituent of the vault particle, the largest ribonuclear protein complex described to date and is identical to lung resistance-related protein (LRP). Although MVP is also expressed in several normal tissues, little is known about its physiological role. MVP played a protective role against some xenobiotics and other stresses. We thus investigated the effect of osmotic stress on MVP expression by treating human colon cancer SW620 cells with sucrose or NaCl. The expression level of both MVP protein and MVP mRNA was increased by the osmostress. Sucrose or sodium chloride could also enhance MVP promoter activity. Inhibition of p38 MAPK in SW620 cells by SB203580 inhibited the expression of MVP under hyperosmotic stress. These findings suggested that osmotic stress up-regulated the MVP expression through p38 MAPK pathway. Down-regulation of MVP expression by MVP interfering RNA (RNAi) in SW620 cells increased the sensitivity of the cells to hyperosmotic stress and enhanced apoptosis. Furthermore, MVP RNAi prevented the osmotic stress-induced, time-dependent increase in phosphorylated Akt. These findings suggest that the PI3K/Akt pathway might be implicated in the cytoprotective effect of MVP. Our data demonstrate that exposure of cells to hyperosmotic stress induces MVP that might play an important role in the protection of the cells from the adverse effects of osmotic stress.


Subject(s)
Cell Line, Tumor , Colonic Neoplasms/metabolism , Gene Expression Regulation , Vault Ribonucleoprotein Particles/metabolism , Animals , Cell Survival , Chromones/metabolism , Enzyme Inhibitors/metabolism , Genes, Reporter , Humans , Morpholines/metabolism , Osmotic Pressure , Promoter Regions, Genetic , RNA Interference , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Sodium Chloride/metabolism , Sucrose/metabolism , Vault Ribonucleoprotein Particles/genetics , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , p38 Mitogen-Activated Protein Kinases/metabolism
5.
Cancer Lett ; 270(1): 156-63, 2008 Oct 18.
Article in English | MEDLINE | ID: mdl-18583030

ABSTRACT

5-FU is commonly used for treatment of various solid tumors including colon carcinoma. We have previously demonstrated that Egr-1 induced by 5-FU enhanced TSP-1 expression in human colon cancer KM12C cells. In this study, a Genechip analysis of KM12C cells treated with 5-FU revealed down-regulation of 924 genes and up-regulation of 460 genes. The decreased expression of c-Myc mRNA and phosphorylated c-Myc were detected and confirmed by RT-PCR and immunoblotting. Since 5-FU induced the expression of TSP-1, we examined the effect of c-Myc on the TSP-1 promoter. Deletion of the TSP-1 promoter region in which binding sites for c-Myc reside had no effect on the TSP-1 promoter activity induced by 5-FU. Meanwhile, 5-FU dose-dependently decreased the expression of miR-17-92 cluster. These findings suggest that 5-FU decreased the expression of c-Myc and consequently miR-17-92 cluster and increased the expression of TSP-1 mRNA.


Subject(s)
Angiogenesis Inhibitors/genetics , Antimetabolites, Antineoplastic/pharmacology , Colonic Neoplasms/drug therapy , Fluorouracil/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Genes, myc , Promoter Regions, Genetic , Thrombospondin 1/genetics , Cell Line, Tumor , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Down-Regulation , Humans , MicroRNAs/genetics , Multigene Family , Oligonucleotide Array Sequence Analysis
6.
Biochem Biophys Res Commun ; 370(2): 220-4, 2008 May 30.
Article in English | MEDLINE | ID: mdl-18359286

ABSTRACT

An angiogenic factor, thymidine phosphorylase (TP), confers resistance to apoptosis induced by hypoxia. We investigated the molecular basis for the suppressive effect of TP on hypoxia-induced apoptosis using Jurkat cells transfected with TP cDNA, Jurkat/TP, and a mock transfectant, Jurkat/CV. TP and 2-deoxy-d-ribose, a degradation product of thymidine generated by TP enzymatic activity, suppressed hypoxia-induced apoptosis. They also inhibited the upregulation of hypoxia-inducible factor (HIF) 1alpha and the proapoptotic factor, BNIP3, and caspase 3 activation induced by hypoxia. Introduction of siRNA against BNIP3 in Jurkat cells decreased the proportion of apoptotic cells under hypoxic condition. These findings suggest that the suppression of BNIP3 expression by TP prevents, at least in part, hypoxia-induced apoptosis. Expression levels of TP are elevated in many malignant solid tumors and thus 2-deoxy-d-ribose generated by TP in these tumors might play an important role in tumor progression by preventing hypoxia-induced apoptosis.


Subject(s)
Apoptosis , Membrane Proteins/antagonists & inhibitors , Proto-Oncogene Proteins/antagonists & inhibitors , Thymidine Phosphorylase/metabolism , Apoptosis/drug effects , Apoptosis/genetics , Caspase 3/metabolism , Caspase 8/metabolism , Cell Hypoxia/genetics , Deoxyribose/metabolism , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Jurkat Cells , Membrane Proteins/genetics , Proto-Oncogene Proteins/genetics , RNA, Small Interfering/genetics , RNA, Small Interfering/pharmacology , Thymidine Phosphorylase/genetics , Transfection
8.
Tokai J Exp Clin Med ; 32(1): 42-7, 2007 Mar 20.
Article in English | MEDLINE | ID: mdl-21319056

ABSTRACT

Autoimmune bullous diseases are classified into pemphigus and pemphigoid. Pemphigus is designated as incurable disease by the Ministry of Health, Labor and Welfare, and it is said that pemphigus is difficult to care and can be fatal. The clinical course of bullous pemphigoid (BP) is better than that of pemphigus. However, as to the incidence of internal malignancies, it is well known that there is a significant difference between the two diseases. As the incidence of internal malignancies is high in BP, it is described in textbooks that patients with BP should be followed by a detailed screening for internal malignancies. We investigated the incidence of internal malignancies in 204 Japanese patients with autoimmune bullous disease who visited Tokai University Hospital in Kanagawa, Japan. We found that the incidence of internal malignancies was 11.2% in patients with pemphigus and 10.4% in patients with BP. Among pemphigus variants, the incidence was as high as 20% for pemphigus erythematosus. No relationship was found between malignancies and the severity of the autoimmune bullous diseases. Therefore it is clinically important to carry out a detailed screening for internal malignancies in patients with pemphigus as well as in patients with BP.


Subject(s)
Autoimmune Diseases , Neoplasms/epidemiology , Neoplasms/etiology , Pemphigoid, Bullous , Pemphigus , Adolescent , Adult , Aged , Aged, 80 and over , Autoimmune Diseases/complications , Autoimmune Diseases/epidemiology , Autoimmune Diseases/pathology , Female , Humans , Japan/epidemiology , Male , Middle Aged , Pemphigoid, Bullous/complications , Pemphigoid, Bullous/epidemiology , Pemphigoid, Bullous/pathology , Pemphigus/complications , Pemphigus/epidemiology , Pemphigus/pathology , Young Adult
9.
Biol Pharm Bull ; 29(9): 1815-9, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16946491

ABSTRACT

Myoblasts respond to growth factor deprivation either by diffentiation into multinucleated myotubes or by undergoing apoptosis. The induction of apoptosis and differentiation in myogenic lineage may use overlapping cellular mechanisms. Here we demonstrate that the expression of the small heat shock protein alphaB-crystallin as well as MyoD and myogenin is induced during myogenic differentiation in C2C12 cells, and these inductions occur at an early stage in the differentiation in vitro. To investigate the effect of alphaB-crystallin on myogenic differentiation and apoptosis, C2C12 cells were infected with adenovirus vector bearing full-length alphaB-crystallin cDNA. Overexpression of alphaB-crystallin in C2C12 cells suppressed differentiation-induced apoptosis and activation of caspase 3, and also decreased the expression of MyoD and myogenin during myogenic differentiation of C2C12 cells induced by the differentiation medium. Our findings suggest that stress such as growth factor deprivation plays an important role in triggering apoptosis associated with myogenic differentiation and alphaB-crystallin suppressed the differentiation, apoptosis and caspase 3 activity.


Subject(s)
Caspases/physiology , Muscle Development , alpha-Crystallin B Chain/physiology , Animals , Apoptosis , Caspase 3 , Cell Differentiation , Cells, Cultured , Enzyme Activation , Mice , Muscle, Skeletal/cytology
10.
J Dermatol ; 33(2): 122-7, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16556281

ABSTRACT

A 51-year-old man visited our hospital complaining of a tumor located above his lip. He had been hit on his upper left lip by a chopstick holder 2 months previously. The lesion turned into a tumor and gradually enlarged. The tumor was well circumscribed, smooth and covered with reddish, partially milk-white skin. During surgery to remove the tumor, a piece of a chopstick was found in the subcutaneous tissue, and a diagnosis of implantation dermatosis (ID) was made. On histology, the tumor appeared as an abscess that had increased fibroblasts, small vessels and a large number of neutrophils. In the Japanese published work, we found 86 cases of ID; three were similar to our case and had been clinically diagnosed as adnexal tumors. There were also six cases that showed abscess formation similar to our case on histology. In a survey of the published work from other countries, there were 44 ID cases. There were no common features found among the cases reported in the published work.


Subject(s)
Foreign Bodies/complications , Foreign-Body Reaction/etiology , Foreign-Body Reaction/pathology , Skin Diseases/etiology , Skin , Biopsy, Needle , Face , Follow-Up Studies , Foreign-Body Reaction/surgery , Humans , Immunohistochemistry , Male , Middle Aged , Risk Assessment , Severity of Illness Index , Skin Diseases/pathology , Skin Diseases/surgery , Treatment Outcome
11.
Tokai J Exp Clin Med ; 31(2): 53-5, 2006 Jul 20.
Article in English | MEDLINE | ID: mdl-21302222

ABSTRACT

We report a case of a 19-year-old man who showed a brownish, elastic-soft, multilocular, pedunculated, solid tumor (10 × 6 × 6 cm), with scale crust and erosion, on the medial side of the right thigh. The histopathology of a specimen removed completely revealed a tumor that was located between the middle layer of the dermis and the subcutaneous fatty tissue, was filled with a mucoid material, and was surrounded by a fibrous tissue. The tumor consisted of small thin-walled blood vessels and spindle-shaped or stellate tumor cells without cytological atypia in addition to the mucoid material. Immunohistochemistory revealed that the tumor cells express the vimentin stain. Based on these clinical and histologic findings, we diagnosed the skin condition as superficial angiomyxoma.


Subject(s)
Myxoma/diagnosis , Skin Neoplasms/diagnosis , Biomarkers, Tumor/metabolism , Humans , Male , Myxoma/pathology , Myxoma/surgery , Skin Neoplasms/pathology , Skin Neoplasms/surgery , Vimentin/metabolism , Young Adult
12.
Tokai J Exp Clin Med ; 30(2): 97-102, 2005 Jul.
Article in English | MEDLINE | ID: mdl-16146199

ABSTRACT

BACKGROUND: The efficacy of herbal medicines is thought to be ambiguous. The quality of life (QOL) of patients has been well-recognized as an useful measurement and we thought it to be a measurement of the efficacy of herbal medicine. OBJECTIVE: The aim of this study was to examine the feasibility of modified DLQI-based questionnaires in evaluating the efficacy of herbal drugs in chronic skin diseases. METHODS: 19 in-patients with chronic skin diseases were selected and treated by the herbal medicines just added on the previous drugs. By using the QOL-sheet, the patients' QOL before and after herbal treatments were converted to scores and we examined the scores to be a useful measurement. The QOL-sheet was made referring to the dermatology life quality index (DLQI) with our original questions and visual analogue scale (VAS) in Japanese. RESULTS: The herbal drugs were effective as the treatment with significant difference (P < 0.05) at clinical impression, DLQI and VAS. No significant differences of correlation between clinical impression, DLQI/DLQI with AQ and VAS/VAS with AQ was proved (P > 0.05). CONCLUSIONS: The QOL-sheet scored both by DLQI and by VAS may be useful to evaluate the efficacy of herbal medicines. However it may be necessary to reconsider the contents of our original questions.


Subject(s)
Medicine, East Asian Traditional , Outcome Assessment, Health Care/methods , Plant Preparations/therapeutic use , Quality of Life , Skin Diseases/drug therapy , Surveys and Questionnaires/standards , Adolescent , Adult , Aged , Aged, 80 and over , Chronic Disease , Feasibility Studies , Female , Humans , Japan , Male , Middle Aged
13.
Tokai J Exp Clin Med ; 29(3): 127-30, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15595471

ABSTRACT

A 20-year-old Japanese woman with an epidermal cyst on the back is described. Physical examination revealed a deep blue and round shaped cystic lesion measuring 10 min in diameter. A comedo-like keratotic plug also could be seen at the center. Histologically, the inner surface of the cyst was clearly separated of two types of the cells. The one was layers of epidermal keratinocytes and the other looked like a basal layer of epidermis, which immunohistochemically stained by S-100, HMB-45, cytokeratin (CK19) and Fontana-Masson staining. We diagnosed this case as epidermal cyst with pilomatrical differentiation.


Subject(s)
Epidermal Cyst/diagnosis , Epidermal Cyst/pathology , Hair Follicle/metabolism , Skin Diseases/diagnosis , Skin Diseases/pathology , Adult , Cell Differentiation , Epidermal Cyst/metabolism , Epidermal Cyst/surgery , Epidermis/metabolism , Epidermis/pathology , Female , Hair Follicle/pathology , Humans , Immunohistochemistry , Keratinocytes/cytology , Keratins/metabolism , S100 Proteins/metabolism , Silver Nitrate , Skin Diseases/metabolism , Skin Diseases/surgery , Staining and Labeling , Treatment Outcome
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