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Biomedical subjects

E Tahara

Publications and source records attributed to E Tahara.

At least 55 records · Page 3Linked to original sources
PubMed2000

Regulation of disease-progression genes in human gastric carcinoma cells by interleukin 8.

The expression of interleukin 8 (IL-8) by human gastric carcinomas directly correlates with tumor vascularity and disease progression. To determine whether IL-8 can act in an autocrine manner to regulate the expression of other disease-progression genes, we examined the expression of IL-8 receptors IL-8RA (CXCR1) and IL-8RB (CXCR2) in six different human gastric carcinoma cell lines and 38 surgical specimens of human gastric carcinomas. All of the gastric carcinoma cell lines expressed mRNA and protein for IL-8RA and IL-8RB protein. In all surgical specimens, the majority of the tumor cells and small vessel endothelial cells stained positive for IL-8RA and IL-8RB protein. In vitro treatment of human gastric cancer MKN-1 cells with exogenous IL-8 enhanced the expression of epidermal growth factor receptor, type IV collagenase (metalloproteinase-9), vascular endothelial growth factor, and IL-8 mRNA. In contrast, treatment with exogenous IL-8 decreased expression of E-cadherin mRNA. IL-8 treatment increased invasive capacity of MKN-1 cells, which was associated with activity of metalloproteinase-9. Collectively, these results demonstrate that human gastric carcinoma cells express receptors for IL-8 and that IL-8 may play a role in the progressive growth of human gastric carcinoma by autocrine/paracrine mechanisms.

Cell Membrane↗
PubMed2000

Molecular aspects of invasion and metastasis of stomach cancer.

The scenario of multiple genetic and epigenetic alterations found in gastric carcinoma differs depending upon the two histological types, indicating that well differentiated or intestinal type and poorly differentiated or diffuse type gastric carcinomas have different genetic pathways. Cancer-stromal interaction through growth factor/cytokine receptor system which plays a central role in invasion and metastasis, is also different between the two types of stomach cancer. The majority of gastric carcinoma exhibit co-expression of IL-8 and its two receptors that evidently confer tumor angiogenesis. IL-8 increases the expression of EGF receptor, VEGF and IL-8 itself by tumor cells themselves, whereas IL-8 decreases expression of E-Cadherin, associated with increase in expression and activity of MMP-9 by tumor cells. These findings overall suggest that IL-8 produced by gastric cancer cells is used for sustained angiogenesis and tissue invasion and metastasis via autocrine/paracrine manners. On the other hand, co-expression of osteopontin (OPN) and CD44v9 in tumor cells correlates well with the degree of lyiphatic vessel invasion or long distant lymph node metastasis in diffuse type gastric carcinoma, indicating that mutual interaction between OPN and CD44v9 on the tumor cells is implicated in lymphogenous metastasis. In addition to these factors, tumor invasion and metastasis requires telomere maintenance regulated by telomerase activity. The human telomerase catalytic subunit, hTERT, is strongly expressed in almost all primary tumors and nodal metastasis.

Gene Expression Regulation, Neoplastic↗
PubMed1999

Effect of Shimotsu-to (a Kampo medicine, Si-Wu-Tang) and its constituents on triphasic skin reaction in passively sensitized mice.

Previous studies have reported that mice passively sensitized with anti-DNP (dinitrophenol) IgE antibody exhibited IgE-mediated skin reaction with an immediate phase response (IPR) at 1 h and a late phase response (LPR) at 24 h after the challenge of DNFB (dinitrofluorobenzene). We recently found that a third phase inflammatory reaction with intense and persisting infiltration of eosinophils, named very late phase response (vLPR), was induced by DNFB challenge peaking at 8 days. In this study, we examined the effects of a Kampo medicine, Shimotsu-to (Si-Wu-Tang), and its constituent crude drugs on triphasic skin reaction in passively sensitized mice. Shimotsu-to inhibited ear swelling in LPR and vLPR after DNFB challenge in a dose-dependent manner, and slightly diminished the scratching behavior considered to be associated with pruritus in IPR. The inhibitory effect on LPR and vLPR was partly due to Cnidii Rhizoma (Senkyu) in Shimotsu-to formulation, especially its fraction 5 containing cnidilide. On the other hand, Angelicae Radix (Toki) rather than Cnidii Rhizoma (Senkyu) in Shimotsu-to, inhibited the scratching behavior, although it did not inhibit the ear swelling in IPR. These findings indicate that the Shimotsu-to formulation is useful for the inhibition of cutaneous inflammatory diseases.

Animals↗
PubMed1999

Alterations of p73 preferentially occur in gastric adenocarcinomas with foveolar epithelial phenotype.

To establish the possible involvement of p73, a newly discovered p53-related candidate as a tumor-suppressor gene in human stomach carcinogenesis, the allelic status, allele-specific expression and mutations of the gene were investigated using PCR-restriction fragment length polymorphism (PCR-RFLP) analysis, RT-PCR SSCP analysis and direct DNA sequencing in 95 gastric adenocarcinomas. Of these, 32 exhibited the heterozygous p73 allele for the StyI restriction site in exon 2. Among these, the cancer DNA of 12 revealed loss of heterozygosity (LOH) of p73. All of the cancers with p73 LOH exhibited phenotypes of foveolar epithelium of the stomach. RT-PCR SSCP analysis of p73 heterozygous cases demonstrated not only bi-allelic expression of the gene but also relatively reduced expression of the affected allele in 6 of 8 tumors with p73 LOH. No gene mutation was detected in the remaining allele of LOH-positive cancers. Our results suggest that alterations of p73, including LOH and abnormal expression, may play roles in the genesis of foveolar-type gastric adenocarcinomas, though this is not in line with a classical Knudson's "2-hit" model.

Adenocarcinoma↗
PubMed1999

Telomerase activity in central nervous system malignant lymphoma.

BACKGROUND: Primary central nervous system malignant lymphoma (PCNSL) has been regarded as a rare neoplasm. Recently, however, its incidence has been rapidly increasing. Despite active clinical trials, its clinical and biologic features remain unknown and there has been no effective treatment or prognostic factor. The current study attempted to elucidate telomerase activity and expression of the telomere-related RNA of PCNSL as novel prognostic factors. METHODS: The subjects were 12 patients with histologically diagnosed PCNSL. All patients were treated with chemoradiotherapy consisting of whole-brain radiation, vincristine, etoposide, and prednisolone. Telomerase activity in the resected tumor was analyzed both qualitatively and quantitatively using the TRAP (telomeric amplification assay protocol)/TRAP-HPA (hybridization protection assay) method. The expression of telomere-related RNA (hTERT, hTERC, and TEP1) was analyzed by reverse transcriptase-polymerase chain reaction. RESULTS: Telomerase activity was detected in 10 of 12 patients with PCNSL, with an average activity of 148.9 relative light units. The average telomere length was 5.55 kb. The expression of hTERT correlated with telomerase activity, and there was a statistically significant correlation between telomerase activity and both the duration of survival and the interval to tumor progression. CONCLUSIONS: Telomerase activity and the expression of hTERT may be novel prognostic factors in patients with PCNSL.

Adult↗
PubMed1999

Effect of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)- quinolinone (vesnarinone) on the growth of gastric cancer cell lines.

Vesnarinone (OPC-8212; 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone ) is a synthetic oral cardiotonic agent that has been used for the treatment of patients with congestive heart failure. Six days of treatment with 30 microg/ml of vesnarinone induced 20-80% growth inhibitions in five out of six gastric carcinoma cell lines examined. Cell cycle analysis revealed that the vesnarinone-sensitive TMK-1 gastric cancer cell line exhibited a significant G0-G1 arrest without evidence of apoptotic cell death induction after 48 h of treatment. Interestingly, this phenomenon was preceded by a marked reduction in the expression of cyclin A, D1 and E as well as cyclin-dependent kinase 2 (CDK2). On the other hand, no significant change was observed in the expression of p21(Waf1/Cip1), p27Kip1 nor various growth factors and their receptor genes. Overall these results indicate that vesnarinone inhibits the growth of gastric cancer cells by down-regulating G1 cyclins and CDK2 to induce G0-G1 arrest through a pathway different from that of cyclin inactivation by p21(Waf1/Cip1) or p27Kip1.

Antineoplastic Agents↗
PubMed1999

Expression of the E2F family in human gastrointestinal carcinomas.

The E2F family of transcription factors plays a key role in the control of cell-cycle progression. Some family members may act as oncogenes, others as tumor-suppressor genes. The genetic changes and the expression of E2F-1 and -3 were examined in human gastric and colorectal carcinomas by Southern, Northern and Western blots. Gene amplification of E2F-1 was detected in 4% (1/23) of gastric carcinomas and 25% (3/12) of the colorectal carcinomas. Increased expression of E2F-1 mRNA was observed in 40% (12/30) of the gastric carcinomas and in 60% (3/5) of the colorectal carcinomas in comparison with the corresponding non-neoplastic mucosa. Over-expression of E2F-1 protein was confirmed in many of the gastric carcinomas. In contrast, expression levels of E2F-3 mRNA were lower in 70% (21/30) of the gastric carcinomas and in 20% (1/5) of the colorectal carcinomas than in their corresponding normal counterparts, while gross alteration of the E2F-3 gene was not detected. These results suggest that gene amplification and anomalous expression of the E2F gene may permit development of gastrointestinal carcinomas.

Adult↗
PubMed1999

Expression and up-regulation of retinoic acid receptor-beta is associated with retinoid sensitivity and colony formation in esophageal cancer cell lines.

Retinoids exhibit chemotherapeutic and chemopreventive activities, possibly due to their ability to modulate cell growth, differentiation, and apoptosis. These effects are thought to be mediated by nuclear retinoic acid (RA) receptors (RARs) and retinoid X receptors, each of which includes three subtypes (alpha, beta, and gamma) that act as transcription factors. To determine whether RARs play a role in mediating the effects of RA on human esophageal cancer (HEC) cells, we analyzed the effects of RA on: (a) the growth, differentiation, and apoptosis in seven HEC cell lines; (b) receptor expression; (c) receptor modulation by RA; and (d) expression of receptors in 20 surgical HEC specimens. RA inhibited the growth of five of seven cell lines and also the constitutive expression of the squamous differentiation markers cytokeratin 1 and transglutaminase I in all cell lines. The growth inhibition by RA was due to the induction of apoptosis in the five cell lines. All seven cell lines expressed RAR-alpha and RAR-gamma, and four cell lines showed some changes by RA, but not associated with apoptosis. In contrast, RAR-beta was expressed in five of seven cell lines and up-regulated by RA in these five cell lines, which were associated with apoptosis. Two cell lines that failed to express RAR-beta showed no growth inhibition or apoptosis and no RAR-beta inducibility. Interestingly, only these two cell lines were able to form colonies in soft agar. RAR-alpha, RAR-beta, and RAR-gamma mRNAs were expressed in all 20 adjacent normal esophageal tissues. The expression of RAR-alpha and RAR-gamma remains positive in HEC specimens, but RAR-beta expression was detected in only 6 of 20 HEC specimens. These data suggest that the expression of RAR-beta is associated with response of HEC cells to RA and that the loss of RAR-beta expression may be associated with HEC development.

Apoptosis↗
PubMed1999

Immuno-histochemical detection of human telomerase catalytic component, hTERT, in human colorectal tumor and non-tumor tissue sections.

Human telomerase is expressed in germ tissues and in the majority of primary tumors. Cell renewal tissues and some pre-cancerous tissues also have weak telomerase activity. Yet, neither the exact location and frequency of telomerase-positive cells nor the changes in telomerase expression during differentiation or carcinogenesis of individual cells are known. This paper reports on the expression of hTERT (telomerase reverse transcriptase) protein in tumor and non-tumor colorectal tissues by Western blotting and tissue sections by immunohistochemistry using antibodies raised against partial peptides of hTERT. Though telomerase activity and hTERT expression at both mRNA and protein levels were generally higher in tumor part than in non-tumor part, these two were not always correlated: expression of hTERT did not always give rise to high telomerase activity. Colonic carcinoma cell nuclei were stained with anti-hTERT antibodies but not with antigen-preabsorbed antibodies. In normal mucosa, hTERT protein was expressed, though weaker than in carcinoma, in all colonic crypt epithelial cells except those at the tip; the expressing-cell distribution was much wider than that of Ki-67 positive cells which were located at the bottom of the crypt. Isolated crypt contained a significant level of hTERT protein revealed by Western blotting, while having very weak telomerase activity. Telomerase activity was detected in epithelial cells only at the bottom half of the crypt. Specific hTERT-staining was positive in tissue lymphocytes but negative in almost all other stromal cells. It is of interest to see whether a significant level of hTERT expression with low telomerase activity is characteristic of physiologically regenerating tissues containing stem cells. In situ detection of the hTERT protein will permit further analysis of cancer diagnosis and stem cell differentiation.

Blotting, Western↗
PubMed1999

Effect of antisense human telomerase RNA transfection on the growth of human gastric cancer cell lines.

The majority of gastric cancers express high levels of human telomerase template RNA (hTR) that is essential for cellular survival. In this study, we examined whether antisense hTR (ahTR) had a growth inhibitory effect on three gastric cancer cell lines, MKN-1, MKN-28, and TMK-1, through transfection via an ahTR expression vector. Both the ahTR transfected MKN-1 and TMK-1 cells changed morphologically into multinucleate giant cells, and subsequently underwent cell death. Conversely, the ahTR transfected MKN-28 cells survived over 50 PDs in spite of telomere shortening. Surprisingly, high levels of telomerase activity were observed in the telomere-reduced cells. Furthermore, the expression of mRNAs for p21/Waf1/Cip1/Sdi1, IRF-1 and IFN inducible 6-16 was higher in the telomere-reduced cells than in the parental cells. These results suggest overall that the ahTR expression may bring about telomere shorting, leading to cell death or cellular senescence in gastric cancer cells.

Cell Cycle↗
PubMed1999

Overexpression of human telomerase RNA is an early event in oesophageal carcinogenesis.

Telomerase, the ribonucleoprotein enzyme that elongates telomeres, is repressed in normal human somatic cells but is reactivated during tumour progression. The purpose of this study was to investigate the localization of human telomerase RNA (hTR) expression in human oesophageal dysplasia and cancer by using in situ mRNA hybridization (ISH) with avidin-biotin staining. Ki-67 immunoreactivity was also examined. We analysed 51 squamous cell carcinomas, 9 dysplasias and 60 normal mucosae. The integrity of the mRNA in each sample was verified by using a poly d(T)20 probe. Seventy-six samples (63%) showed no mRNA degradation; these included 30 carcinomas, 7 dysplasias and 39 normal mucosae. At the single-cell level, high levels of hTR expression were found in the cytoplasm and especially in the nucleus. Most (>90%) cancer cells demonstrated high levels of hTR expression in 29 (97%) of the 30 tumours. Most dysplastic cells also showed high levels of hTR in all 7 dysplastic cases. In all 39 normal mucosae, most basal cells indicated high levels of hTR expression, which were also seen in infiltrating lymphocytes. The distribution of hTR-expressing cells was similar to that of Ki-67-positive cells. These data suggest that overexpression of hTR may be correlated with the proliferative activity that defined by Ki-67 immunoreactivity and is an early event in carcinogenesis of the oesophagus.

Esophageal Neoplasms↗
PubMed1999

Transfection of interleukin-8 increases angiogenesis and tumorigenesis of human gastric carcinoma cells in nude mice.

The growth and spread of tumour cells depends on adequate vasculature. We have previously reported that the expression of interleukin-8 (IL-8) directly correlates with the vascularity of human gastric carcinomas. To provide evidence for a causal role of IL-8 in angiogenesis and tumorigenicity of human gastric cancer, we used the lipofectin method to stably transfect the human TMK-1 gastric carcinoma cells (low endogenous IL-8) with an IL-8 expression vector or control vector. Transfection with IL-8 did not affect the proliferation of cultured cells, yet the culture supernatants of the transfected (but not control) cells stimulated proliferation of human umbilical vein endothelial cells. The IL-8-transfected and control cells were injected into the gastric wall of nude mice. IL-8-transfected cells produced rapidly growing, highly vascular neoplasms as compared to control cells. These results provide direct evidence for the role of IL-8 in the angiogenesis and tumorigenicity of human gastric carcinomas.

Animals↗
PubMed1999

Cutaneous ciliated cyst of the right lower leg.

A 23-year-old Japanese woman with a cutaneous ciliated cyst on her right lower leg is reported. A subcutaneous cyst, measuring 2.5 cm in diameter with papillary projections into the lumen, was lined with ciliated cuboidal to columnar epithelia with partial stratification, histologically. These lining cells did not produce mucin. Immunohistochemically, the ciliated lining cells of the cyst were diffusely positive to epithelial membrane antigen and cytokeratin. In addition, positive immunoreaction with anti-desmin monoclonal antibody was observed in the body of the cilia. Less than 10% of the epithelial cells revealed positive immunoreaction to S-100 protein and estrogen receptor.

Adult↗
PubMed1999

Molecular-pathological diagnosis of gastrointestinal tissues and its contribution to cancer histopathology.

Multiple genetic and epigenetic alterations of cancer-related genes and molecules are involved in the course of the development and progression of gastrointestinal cancers. These include telomerase activation, genetic instability, and abnormalities of oncogenes, tumor suppressor genes, cell cycle regulators, cell adhesion molecules and DNA repair genes. By analyzing these alterations in pathology specimens, we can improve differential diagnosis of cancer, obtain information of grade of malignancy, and identify patients at high risk for developing multiple primary cancers. Since 1993, a system of molecular-pathological diagnosis was established, and has been performed as a routine service in collaboration with Hiroshima City Medical Association Clinical Laboratory. More than 10 000 cases of gastrointestinal biopsy and surgery have been analyzed, and additional information of differential diagnosis, biological malignancy and tumor multiplicity could be obtained. Molecular-pathological diagnosis may provide a new approach to cancer diagnosis and novel therapeutics for the 21st century. Furthermore, the analysis of the genetic and epigenetic abnormalities in clinical materials may clarify the molecular mechanism of carcinogenesis and comparative morphological changes. From the analyses of p27KIP1 and telomerase in gastrointestinal adenomas, we have learned that morphological abnormality of the nucleus is an indicator for cells with immortality and malignant potential that must participate in super-early diagnosis (detection of true precancerous lesions) of gastrointestinal cancer. Molecular-pathological diagnosis thus contributes to detailed understanding of cancer histopathology and improves the histopathological diagnosis.

Adenocarcinoma↗
PubMed1999

No mutations of the Smad2 gene in human sporadic gastric carcinomas.

BACKGROUND: The majority of cancer cells escape from TGF-beta-mediated growth control. However, the mechanism of resistance to the growth inhibitory effects by TGF-beta is not clear. TGF-beta signaling is initiated when the type I receptor phosphorylates the SMAD proteins, Smad2 and Smad3. Recently, mutations of Smad2 have been detected in human colon and lung cancers. Mutation of coding sequences of Smad2 in gastric carcinomas has not yet been elucidated adequately. METHODS: PCR-SSCP analysis of the entire coding region of Smad2 in 35 human sporadic gastric cancers and eight gastric cancer cell lines was performed using 11 sets of intron-based primers. RESULTS: No mutations of Smad2 were detected in any tumor or cell line. CONCLUSIONS: The results suggest that mutation of Smad2 does not play a key role in human stomach carcinogenesis.

DNA-Binding Proteins↗
PubMed1999

Silencing of the CD44 gene by CpG methylation in a human gastric carcinoma cell line.

We analyzed 8 human gastric carcinoma cell lines for the expression of CD44 by northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR), and identified 1 cell line MKN-28 that did not express CD44. In an attempt to clarify the mechanism responsible for the inactivation of CD44 gene expression in this cell line, we investigated the methylation status around the promoter region of CD44 gene by digestion of the DNA with the methylation-sensitive restriction enzyme HpaII. The promoter region of CD44 in MKN-28 revealed hypermethylation, whereas other CD44-positive cell lines did not. Furthermore, treatment of MKN-28 with the demethylating agent 5-azacytidine restored the expression of the gene. These results suggest that CD44 expression is controlled by a DNA hypermethylation mechanism in MKN-28.

DNA Methylation↗
PubMed1999

Immunohistochemical detection of human telomerase reverse transcriptase in normal mucosa and precancerous lesions of the stomach.

Telomerase activity confers cell immortality through stabilization of the chromosome, participating in the development of a majority of human cancers. Human telomerase reverse transcriptase (TERT) has been identified as a catalytic subunit of telomerase, and is overexpressed in most gastric carcinomas. We immunohistochemically examined the expression of TERT in normal gastric mucosa and candidate precancerous lesions such as intestinal metaplasia and adenoma. In non-neoplastic gastric mucosa including intestinal metaplasia and normal fundic mucosa, weak but significant expression of TERT was detected in nuclei of epithelial cells located in the lower two-thirds of the glands (wider than the proliferative zone). The telomerase activity was found in a half of gastric adenomas, whose levels of the activity were about 10% of those in gastric carcinomas. TERT protein was expressed in the nuclei of the adenoma cells at moderate levels, that were not necessarily comparable with the telomerase activities. These findings overall suggest that TERT expression may be one of the prerequisites for telomerase activation in an early stage of stomach carcinogenesis.

Adenoma↗