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Masahiro Seike

Publications and source records attributed to Masahiro Seike.

At least 19 recordsLinked to original sources
PubMed2006

Neuronal conditions of spinal cord in dermatitis are improved by olopatadine.

Intense pruritus and cutaneous reactivity represent cardinal features of eczema. The resulting scratching behaviors alter neuronal conditions of the spinal dorsal horn where the primary sensory afferent fibers transmit cutaneous stimulation and deteriorate eczematous skin lesions. We investigated the effects of olopatadine hydrochloride (olopatadine) on alteration of neuronal conditions of the spinal dorsal horn and eczematous skin lesions induced by contact dermatitis. Eczematous lesions were induced by repeated application of diphenylcyclopropenone (DCP) in BALB/c mice. Olopatadine suppressed scratching behavior caused by repeated application of DCP in mice. Increased expressions of c-Fos and substance P in the spinal dorsal horn following DCP application were improved by olopatadine. Furthermore, olopatadine diminished the number of infiltrating cells and levels of cytokines in eczematous skin lesions resulting from DCP application. Olopatadine improves neurological conditions in the spinal cord and eczematous skin lesions in a murine contact dermatitis model.

Animals↗
PubMed2006

Anticancer drug clustering in lung cancer based on gene expression profiles and sensitivity database.

BACKGROUND: The effect of current therapies in improving the survival of lung cancer patients remains far from satisfactory. It is consequently desirable to find more appropriate therapeutic opportunities based on informed insights. A molecular pharmacological analysis was undertaken to design an improved chemotherapeutic strategy for advanced lung cancer. METHODS: We related the cytotoxic activity of each of commonly used anti-cancer agents (docetaxel, paclitaxel, gemcitabine, vinorelbine, 5-FU, SN38, cisplatin (CDDP), and carboplatin (CBDCA)) to corresponding expression pattern in each of the cell lines using a modified NCI program. RESULTS: We performed gene expression analysis in lung cancer cell lines using cDNA filter and high-density oligonucleotide arrays. We also examined the sensitivity of these cell lines to these drugs via MTT assay. To obtain our reproducible gene-drug sensitivity correlation data, we separately analyzed two sets of lung cancer cell lines, namely 10 and 19. In our gene-drug correlation analyses, gemcitabine consistently belonged to an isolated cluster in a reproducible fashion. On the other hand, docetaxel, paclitaxel, 5-FU, SN-38, CBDCA and CDDP were gathered together into one large cluster. CONCLUSION: These results suggest that chemotherapy regimens including gemcitabine should be evaluated in second-line chemotherapy in cases where the first-line chemotherapy did not include this drug. Gene expression-drug sensitivity correlations, as provided by the NCI program, may yield improved therapeutic options for treatment of specific tumor types.

Antimetabolites, Antineoplastic↗
PubMed2006

Unique microRNA molecular profiles in lung cancer diagnosis and prognosis.

MicroRNA (miRNA) expression profiles for lung cancers were examined to investigate miRNA's involvement in lung carcinogenesis. miRNA microarray analysis identified statistical unique profiles, which could discriminate lung cancers from noncancerous lung tissues as well as molecular signatures that differ in tumor histology. miRNA expression profiles correlated with survival of lung adenocarcinomas, including those classified as disease stage I. High hsa-mir-155 and low hsa-let-7a-2 expression correlated with poor survival by univariate analysis as well as multivariate analysis for hsa-mir-155. The miRNA expression signature on outcome was confirmed by real-time RT-PCR analysis of precursor miRNAs and cross-validated with an independent set of adenocarcinomas. These results indicate that miRNA expression profiles are diagnostic and prognostic markers of lung cancer.

Adenocarcinoma↗
PubMed2005

Hyaluronan forms complexes with low density lipoprotein while also inducing foam cell infiltration in the dermis.

BACKGROUND: Xanthoma is a foam cell infiltrating lesion similar to atherosclerosis. Glycosaminoglycans and proteoglycans have long been considered to play a role in atherogenesis. OBJECTIVE: The purpose of this study is to investigate the role of hyaluronan, the main dermal glycosaminoglycan, in xanthoma formation. METHODS: The complex formation of low density lipoprotein (LDL) with hyaluronan was investigated by assaying the cholesterol level of precipitates that were formed by incubating LDL, hyaluronan and cetylpyridinium chloride in the presence of Ca2+. The uptake of LDL by mouse peritoneal macrophages was studied by assaying the cellular cholesterol esterification activity. The responsible receptor for the LDL internalization was examined by saturating hyaluronan receptor and blocking class A macrophage scavenger receptor (CD204). Hyaluronan was injected into the dorsal skin of diet-induced hypercholesterolemic rabbits to reveal the xanthoma inducing activity of hyaluronan. RESULTS: Cetylpyridinium chloride precipitated hyaluronan, which had formed complexes with LDL. The macrophages incorporated hyaluronan-LDL complexes and oxidized LDL via CD204. Foam cell infiltration and cholesterol accumulation were induced by intradermal injections of hyaluronan in diet-induced hypercholesterolemic rabbits. CONCLUSION: Hyaluronan, like other sulfated glycosaminoglycans, retains LDL by forming a complex. Via macrophage scavenger receptors, macrophages incorporate not only LDL-hyaluronan complexes, but also oxidized LDL, which has been oxidized during the retention time.

Animals↗
PubMed2005

Histamine helps development of eczematous lesions in experimental contact dermatitis in mice.

Histamine is released from mast cells in the skin, causing urticaria and itching. However, little is known about the roles of histamine in development of eczematous lesions in contact dermatitis. Effects of histamine on development of eczematous lesions in contact dermatitis were assessed using histamine-deficient mice in which contact dermatitis was developed by repeated application of diphenylcyclopropenone. Development of eczematous lesions in contact dermatitis was suppressed in histamine-deficient mice compared to wild-type mice. H(1) agonist ((6-12-(4-imidazol)ethylamino)-N-(4-trifluoro- methylphenyl)hepatanecarboxamide) promoted development of eczematous lesions in histamine-deficient mice. H(1) receptor antagonist (loratadine) suppressed development of eczematous lesions in wild-type mice, whereas H(2) agonist (dimaprit) and receptor antagonist (cimetidine) were ineffective. These results suggest that histamine facilitates the development of eczematous lesions in a murine model of contact dermatitis via H(1) receptors.

Animals↗
PubMed2005

Proteomic signatures for histological types of lung cancer.

We performed proteomic studies on lung cancer cells to elucidate the mechanisms that determine histological phenotype. Thirty lung cancer cell lines with three different histological backgrounds (squamous cell carcinoma, small cell lung carcinoma and adenocarcinoma) were subjected to two-dimensional difference gel electrophoresis (2-D DIGE) and grouped by multivariate analyses on the basis of their protein expression profiles. 2-D DIGE achieves more accurate quantification of protein expression by using highly sensitive fluorescence dyes to label the cysteine residues of proteins prior to two-dimensional polyacrylamide gel electrophoresis. We found that hierarchical clustering analysis and principal component analysis divided the cell lines according to their original histology. Spot ranking analysis using a support vector machine algorithm and unsupervised classification methods identified 32 protein spots essential for the classification. The proteins corresponding to the spots were identified by mass spectrometry. Next, lung cancer cells isolated from tumor tissue by laser microdissection were classified on the basis of the expression pattern of these 32 protein spots. Based on the expression profile of the 32 spots, the isolated cancer cells were categorized into three histological groups: the squamous cell carcinoma group, the adenocarcinoma group, and a group of carcinomas with other histological types. In conclusion, our results demonstrate the utility of quantitative proteomic analysis for molecular diagnosis and classification of lung cancer cells.

Adenocarcinoma↗
PubMed2005

Efficacy of an overtube for reducing the risk of peristomal infection after PEG placement: a prospective, randomized comparison study.

BACKGROUND: With the conventional pull method of PEG placement, there is a significant risk of wound infection from contamination of the gastrostomy catheter as it passes through the oral cavity. This study compared the occurrence of peristomal wound infection associated with PEG placement with and without use of an overtube. METHODS: Consecutive patients with dysphagia were randomized to undergo PEG placement with (Group I) or without (Group II) an overtube. For each patient, the peristomal area was evaluated daily for 1 week after PEG placement. The presence of erythema and of exudate were scored on a scale of 0 to 4; induration was scored on a scale of 0 to 3. Criteria for infection were a maximum combined score of 8 or higher, or the presence of microscopic and microbiologic evidence of suppurating exudate. In each group, cefazolin was administered prophylactically (2 g/d intravenously) for 3 days. For patients who had received an antibiotic(s) before PEG placement, the same antibiotic(s) was used. All procedures in both groups were performed by one of two investigators who used the pull method. RESULTS: A total of 76 patients were randomized; 3 were excluded from analysis, because death occurred within 1 week after the procedure. Two of 3 deaths were procedure-related (aspiration pneumonia in Group I, peritonitis in Group II). Data for 37 patients in Group I and 36 in Group II were analyzed. There was no significant difference between the groups with respect to baseline characteristics. The occurrence of peristomal infection within 1 week of PEG was significantly lower in Group I compared with Group II (2 vs. 12; p = 0.0029). The mean daily combined scores in Group I also were significantly lower than those in Group II ( p < 0.0001), and the median maximum parameter scores in Group I were significantly lower than those in Group II (erythema, p = 0.0062; induration, p = 0.0390; exudate, p < 0.0001), although the nominal significance for induration was removed by correction for the multiple testing of data. One patient excluded from Group II died from sepsis because of procedure-induced peritonitis. Among the 73 enrolled patients, there was no procedure-related mortality or clinically important wound infections that required surgical intervention in either group. CONCLUSIONS: Use of an overtube during PEG placement reduces the risk of peristomal wound infection.

Aged↗
PubMed2005

Alteration of sensorineural circuits in spinal cord by chronic contact dermatitis.

In the present study, eczema-induced alteration of sensorineural circuits of the spinal dorsal horn was investigated. Eczematous lesions resembling atopic dermatitis were induced by repeated application of diphenylcyclopropenone (DCP) onto murine right hind paws. Immunohistochemical labeling of calcitonin gene-related peptide and substance P was increased in the dorsal horn on the DCP-treated side. Expression of calcium binding proteins, calretinin and calbindin-D28K, normally widely seen in dorsal horn interneurons, was up-regulated on the DCP-treated side. E-Cadherin and alpha-N-catenin, synapse-related molecules, were intensely expressed in the spinal dorsal horn of the DCP-treated side. Interestingly, c-Fos positive cells were also significantly increased in laminae I and III of the DCP-treated side. These results suggest an enhanced release of neuropeptides from peripheral afferents and alterations in the sensorineural circuitry of the dorsal horn. These changes may account for the enhanced sensory sensitivity recognized in patients with chronic eczema and atopic dermatitis.

Animals↗
PubMed2005

Spindle cell squamous cell carcinoma showing continuous mesenchymal dedifferentiation in a single tumor.

We report the case of an 85-year-old man who presented with an enlarging tumor on the right temple. Histologically, spindle-shaped cells were proliferating continuously within well-differentiated squamous cell carcinoma that was immunohistochemically negative for vimentin and alpha-smooth muscle actin (ASMA) but positive for cytokeratin (AE1/3). These spindle-shaped cells expressed vimentin and ASMA but not cytokeratin (AE1/3). Intermediate cells with round nuclei and small amounts of cytoplasm displayed slight expression of vimentin, ASMA, and cytokeratin. This case illustrated spindle cell squamous cell carcinoma with mesenchymal metaplasia of malignant epithelial cells.

Actins↗
PubMed2005

Discrete papular mucinosis on the back.

A rare case of papular mucinosis on the back of a 78-year old man is described. The patient developed approximately 20 discrete papules on the upper back. His serum glucose concentration was borderline elevated, but no other systemic symptoms or signs were apparent. A biopsy revealed mucin deposits only in the upper reticular dermis. The papules were distinctly different from lichen myxedematosus in clinical and histochemical appearance. The present case may represent very early-stage lichen myxedematosus complicated by borderline diabetes mellitus.

Aged↗
PubMed2004

Alternative splice variant of actinin-4 in small cell lung cancer.

Tumor-associated alternative RNA splicing has gained considerable attention. We identified a novel alternative splice variant RNA of actinin-4 in human small cell lung cancer (SCLC). Expression of the splice variant was highly specific to SCLC cell lines (10/10), biopsies (3/3), and testis. The variant encoded a peptide with a three amino-acid change in exon 8, where the germline missense mutation takes place in familial focal segmental glomerulosclerosis (FSGS). The variant protein showed high affinity to filamentous actin polymers and was not localized with cortical actin. Alternatively spliced actinin-4 may be a new diagnostic marker of SCLC and a candidate target for selective therapy.

Actinin↗
PubMed2004

Proteomic signature of human cancer cells.

We assessed proteomic profiles as biomarkers for monitoring cell phenotypes. Protein expression profiles were obtained by fluorescence two-dimensional difference gel electrophoresis (2-D-DIGE), in which quantitative ability is improved by labeling proteins with fluorescent dyes prior to electrophoresis. Integrated protein spot intensities were analyzed by a statistical approach. The proteomic data of two groups of cell lines: (1) adenocarcinoma (AC) cell lines derived from lung, pancreas and colon tissues and (2) lung cancer cell lines with different histological backgrounds, including AC, squamous cell carcinoma and small cell carcinoma, were assessed on the basis of prior biological information. Hierarchical clustering analysis and principal component analysis were used to divide the cell lines into subgroups on the basis of similarities between their protein expression profiles. The majority of cell lines were grouped according to their organ of origin or histological background. A machine-learning algorithm selected 32 protein spots that were responsible for the classification. The results indicate that proteomic data generated by 2-D-DIGE can provide a signature of essential cell phenotypes, suggesting that it might be possible to apply this technique to developing tumor markers that could identify the organ of origin of metastatic tumors and contribute to the differential diagnosis of lung cancer.

Cell Line, Tumor↗
PubMed2004

Weekly administration of irinotecan (CPT-11) plus cisplatin for refractory or relapsed small cell lung cancer.

PURPOSE: Weekly administrations of CPT-11 plus cisplatin together with an anti-diarrheal program, the Oral Alkalization and Control of Defecation [Int J Cancer 1999;83:491; Int J Cancer 2001;92:269; Cancer Res 2002;62:179], were evaluated in this phase II study for patients with refractory or relapsed small cell lung cancer. METHODS: Patients were treated by weekly administrations of 60 mg/m(2) CPT-11 plus 30 mg/m(2) cisplatin on Days 1, 8 and 15 over 4 weeks. Coinciding with the infusions and for 4 days thereafter, the anti-diarrheal program was practiced using orally administered sodium bicarbonate, magnesium oxide and basic water. RESULTS: Twenty-five patients who had prior treatments of etoposide and platinum containing regimens (16 refractory patients and nine relapsed patients) were entered. The mean dose-intensities of CPT-11 and cisplatin were 154.8 and 77.4 mg/m(2) per course, respectively. Therefore, 86% of the planned dose was delivered. There were 20 partial responses and an overall response rate of 80% (95% confidence interval, 62-96%) was obtained. The median time to progression and the median survival after starting this regimen were 3.6 and 7.9 months, respectively. The major toxicity was myelosuppression. Grades 3 and 4 neutropenia occurred in 24 and 12% of patients, respectively. One patient with febrile neutropenia was experienced, and Grade 3 diarrhea was observed in 8%. But there was no treatment death. CONCLUSION: Weekly administrations of CPT-11 plus cisplatin together with Oral Alkalization and Control of Defecation provide a practical and well tolerated regimen that was active for refractory or relapsed small cell lung cancer.

Aged↗
PubMed2004

Mutational analysis of the macrophage scavenger receptor 1 (MSR1) gene in primary lung cancer.

Allelic deletion at chromosome 8p21-25 is an early and frequent event in the carcinogenesis and development of various cancers. To facilitate investigation of alterations of the macrophage scavenger receptor 1 (MSR1), which is located on 8p22, and to determine the role of this gene in human carcinogenesis and tumor progression, we determined intronic primers designed to amplify the coding region. Since frequent deletion of 8p21-23 has been previously reported in lung cancer, we searched for mutations throughout the coding sequence of the MSR1 gene within a panel of genomic DNA samples obtained from 30 primary lung cancers. Our approach, which involved polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct DNA sequencing, revealed nucleotide variants of the MSR1 gene in only one of the 30 cases examined, with this sample displaying both a 6 bp deletion and a thymine-to-cytosine substitution, the latter occurring within intron 7. The 6 bp deletion was located at a DNA microsatellite region and the thymine-to-cytosine substitution seemed to be a polymorphism. These results suggest that the MSR1 gene is not commonly mutated in lung cancer and not important in susceptibility to lung cancer. Further studies may focus on alternative mechanisms through which the MSR1 gene might be inactivated, such as aberrant DNA methylation, and/or pursue analyses of other genes on 8p21-23 for mutational events. Nevertheless, the panel of intronic PCR primer pair sequences presented here will facilitate future studies to determine the full spectrum and frequency of genetic events that may affect expression/activity of the MSR1 gene in human tumors.

Chromosomes, Human, Pair 8↗
PubMed2003

Proteomic analysis of intestinal epithelial cells expressing stabilized beta-catenin.

Aberrant accumulation of beta-catenin protein because of mutation of either the beta-catenin or adenomatous polyposis coli gene plays an essential role in the development of colorectal carcinoma. We established previously a stable clone of the rat small intestinal epithelial cell line IEC6, which is capable of inducing stabilized beta-catenin protein lacking NH(2)-terminal glycogen synthase kinase-3beta phosphorylation site under a strict control of the tetracycline-regulatory system. This clone, IEC6-TetOFF-beta-catenin DeltaN89, shows in vitro polypoid growth on the removal of doxycycline and seems to be an appropriate model for analyzing the molecular mechanisms of early intestinal carcinogenesis. Of >2000 protein spots displayed by newly developed two-dimensional difference gel electrophoresis, 22 were found to be up- or down-regulated on the induction of stabilized beta-catenin. The majority of these proteins fell into two categories: (a) redox-status regulatory proteins and (b) cytoskeleton-associated proteins. Representatively, a key redox-status regulatory protein, manganese superoxide dismutase, up-regulated in IEC6 cells expressing stabilized beta-catenin protein, was overexpressed in adenoma and adenocarcinoma cells of familial adenomatous polyposis patients in parallel with the accumulation of beta-catenin. These results suggest that aberrant accumulation of beta-catenin might contribute to colorectal carcinogenesis by affecting redox status in the mitochondria of intestinal epithelial cells.

Adenocarcinoma↗