30 results on '"Kyushu Univ"'
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2. Correlation between reduced p21(WAF1/CIP1) expression and abnormal p53 expression in esophageal carcinomas.
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Toh Y, Kuwano H, Sonoda K, Saeki H, Kawaguchi H, Kitamura K, Nakashima H, and Sugimachi K
- Abstract
p21(WAF1/CIP1) is a potent inhibitor of various cyclin-dependent kinases, the expression of which is transcriptionally regulated by tumor suppressor gene product p53. We immunohistochemically examined the expression of p53 and p21(WAF1/CIP1) in 61 esophageal squamous cell carcinomas. p53 protein was expressed in 37 (61%) of 61 carcinomas. p21(WAF1/CIP1) was consistently expressed in the normal stratified esophageal mucosa. In the carcinomas, the expression of p21(WAF1/CIP1) protein was markedly reduced or not expressed in 33 (54%) cases. Clinicopathologic analyses revealed that no significant correlation exists either between p53-positive and -negative cases or between p21(WAF1)/(CIP1)-positive and -negative cases. Twenty-four cases were p53-positive/p21(WAF1/CIP1) negative, 15 were p53-negative/p21(WAF1/CIP1)-positive, 13 were positive for both and 9 were negative for both, and these findings thus showed an inverse correlation of the positivity between p53 and p21(WAF1/CIP1) (p<0.05). Furthermore, of the 13 cases with positive staining for both, the distribution of the expression was mutually exclusive in 6 cases and coincidental in the remaining 7 cases. These findings showed the p53-dependent expression of p21(WAF1/CIP1) was observed in esophageal squamous cell carcinomas, while the lack of an absolute correlation between abnormal p53 expression and p21(WAF1/CIP1) expression suggested that the p53-independent expression of p21(WAF1/CIP1) might also occur in some portions of the esophageal squamous carcinomas, suggesting that the molecular mechanisms of esophageal carcinogenesis appear to be complicated.
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- 1997
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3. p53 mutations of lung cancer are not significantly affected by CYP1A1 or GSTM1 polymorphisms.
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Oyama T, Kawamoto T, Mizoue T, Nishida K, Osaki T, Sugio K, Yasumoto K, and Mitsudomi T
- Abstract
Cytochrome p4501A1 gene (CYP1A1) and glutathione S-transferase mu gene (GSTM1) are involved in the metabolic activation or detoxification of environmental carcinogens including benzo[a]pyrene in tobacco smoke. Individuals with both Val/Val and C type of CYP1A1 (CYP1A1; Val/Val and CYP1A1; C) or homozygous null (-/-) genotype of GSTM1 gene (GSTM1; -/-) show increased susceptibility to lung cancer. The incidence of p53 gene mutations are related to the smoking index of the lung cancer patients. Therefore we determined genotypes of these enzymes and screened p53 gene mutations in 123 non-small cell lung cancer (NSCLC) patients. p53 gene mutations were found in 35% (43/123) of the patients. The incidence of p53 gene mutation CYP1A1; Val/Val (60.0%), CYP1A1; C (50.0%) tended to be higher than those of CYPIAI; Ile/Ile and Ile/Val (40.4%) or CYP1A1; A and B (40.5%). We conclude that the incidence of the p53 mutations does not seem to be significantly affected by only CYP1A1 or GSTM1 polymorphisms in lung cancer patients.
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- 1997
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4. High frequency of the expression of the MAGE gene family in human esophageal carcinoma.
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Tanaka F, Mori M, Li J, Fujie T, Mimori K, Haraguchi M, Tanaka Y, Mafune K, and Akiyoshi T
- Abstract
The human gene MAGE encodes tumor specific peptide antigens and consists of at least 12 families. Some antigens coded by the MAGE genes may be potentially useful for cancer specific immunotherapy. There is, however, so far little information on the expression of these gene families in human esophageal carcinomas. We investigated the expression of MAGE-1, -2, -3, -4, -6, -8, -9, -10, -11, and -12 genes in 24 human esophageal carcinoma cell lines, and in 50 pairs of tumor and corresponding normal tissue specimens from the human esophagus by means of reverse transcription polymerase chain reaction. The expression rate varied from 13% of MAGE-6 and 8 to 79% of MAGE-4 in the esophageal carcinoma cell lines, and from 6% of MAGE-6 to 62% of MAGE-4 in clinical tumor samples. The most frequently and the least expressed gene were the MAGE-4 and MAGE-6 genes, respectively, in both the cell lines and the clinical samples. Forty-seven of the 50 clinical tumors expressed at least one MAGE gene. No significant clinicopathologic difference between the tumor cases was observed, regardless of the presence or absence of MAGE gene expression. The findings of this study thus demonstrated that the MAGE gene family is frequently expressed in clinical samples as well as in the cell lines of human esophageal carcinomas. Therefore, to identify the MAGE gene family may be useful, not only for esophageal tumor specific immunotherapy but for molecular diagnostic usage as well.
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- 1997
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5. Clinical significance of pyrimidine nucleoside phosphorylase in colorectal carcinoma.
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Mimori K, Mori M, Shiraishi T, Haraguchi M, Ueo H, and Akiyoshi T
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The expression of pyrimidine nucleoside phosphorylase (PyNPase) mRNA in tumor (T) and normal (N) biopsy specimens obtained from 41 cases of colorectal carcinoma was examined by the reverse transcriptase/polymerase chain reaction (RT-PCR). The higher T/N ratio of the expression of PyNPase mRNA correlated significantly with the presence of lymph vessel invasion (p=0.039), the positive lymph node metastasis (p=0.014) and the advanced stage of the disease (p=0.014). There was a significant con-elation between the results determined by enzyme activity and those determined by RT-PCR (p=0.005). The findings suggested that the determination of PyNPase mRNA by RT-PCR may give useful information on tumor aggressiveness of colorectal carcinoma and this method can be used instead of enzyme activity.
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- 1997
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6. Expression of matrix metalloproteinases 1 and 2 genes in a possible association with metastatic abilities of human pancreatic cancer cells.
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Jimi S, Shono T, Ono M, Kuwano M, Tanaka M, Lopezotin C, and Kono A
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We determined if any extracellular matrix degradative proteases were possibly associated with metastatic potentials of human pancreatic cancer cells. Liver metastatic abilities of six human pancreatic cancer cell lines were examined in nude mice, and divided into two high (2 lines) and low (4 lines) metastatic cell lines. Of six cell lines, matrix metalloproteinases-1 (MMP-1) was overexpressed in two high metastatic cell lines: and MMP-2 was overexpressed in one high metastatic cell line. Of the four low metastatic lines, two cell lines had relatively higher mRNA levels of tissue inhibitors of metalloproteinases-3 (TIMP-3). MMP activities due to MMP-1 and MMP-2 might be positively associated with liver metastasis of pancreatic cancer cells. Moreover, expression of TIMP-3 might be partly involved in the low metastatic potentials of pancreatic cancer.
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- 1997
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7. Optimal duration of whole body hyperthermia when combined with cis-diamminedichloroplatinum(II).
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Makino M, Ohno S, Sakaguchi Y, Kaneko T, Strebel F, Jenkins G, and Bull J
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We examined the optimal duration of whole body hyperthermia (WBH, 41.5 degrees C) when administered simultaneously with cis-diamminedichloroplatinum(II) (CDDP) using F344 rat fibrosarcoma model. The antitumor efficacy was measured by tumor growth delay (TGD) and nephrotoxicity was evaluated by the day 5 blood urea nitrogen (BUN) associated with different duration of WBH (0.5, 1, 1.5, 2 or 3 h) with a constant dose of CDDP (2 mg/kg i.v. bolus). There was significant increase in TGD from 2.8 days to 5.4 days when the WBH duration was increased from 0.5 to 1 h (p<0.001). CDDP-induced nephrotoxicity was also enhanced by WBH. We estimated specific therapeutic efficacy (STE) for each treatment using the ratio of antitumor effect measured by TGD to nephrotoxicity calculated from the degree of increment of BUN. CDDP combined with 1 h WBH produced the best STE of 2.2. We conclude, that to maximize the therapeutic gain, a 1 h duration is optimal in the present setting of thermochemotherapy.
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- 1997
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8. The quinolinone derivative vesnarinone potentiates the cytotoxicity of doxorubicin in HL-60 leukemia cells.
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Yamamoto M, Maehara Y, Sakaguchi Y, Kusumoto T, Baba H, and Sugimachi K
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Vesnarinone, (3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1- piperazinyl]-2(1H)-quinolinone), a quinolinone derivative, is a positive inotropic agent. We examined the cytotoxicity either by vesnarinone alone or in combination with doxorubicin (DXR), in vitro. The cytotoxic effect of vesnarinone against HL-60 cells did not increase, even at concentrations as high as (50 mu g/ml). The cytotoxicity of DXR, however, was enhanced after being combined with 30 mu g/ml of vesnarinone. The intracellular level of DXR increased when DXR was administered after incubation with vesnarinone and the efflux of DXR was delayed when the cells were incubated in the presence of vesnarinone after DXR exposure. Flow cytometry showed that the combination of DXR and vesnarinone increased the cell population below the G(0)/G(1) region. Vesnarinone induced DNA ladder formation, but only when these cells were incubated for 72 h, while in addition, when DXR was combined with vesnarinone, the DNA ladder formation was enhanced. Based on the above findings, we thus conclude that the cytotoxicity of DXR was enhanced when combined with vesnarinone.
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- 1997
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9. Human telomeric binding proteins recognizing single and double stranded DNA.
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Matsuo K, Yamada Y, Izumi H, Kuwano M, and Kohno K
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Telomeres of human chromosomes consist of a repeated TTAGGG sequence, and at the terminal of this repeat sequence, the 3' strand is longer than the 5' strand. In this study, we characterized single and double stranded telomere binding proteins (ssTBPs and dsTBPs) by gel mobility shift assay and South-Western blotting assay. At least two protein components with molecular weights of 29 and 33 kDa were bound to a single stranded telomeric sequence, and also two proteins with molecular weights of about 44 kDa and 70 kDa were bound to a double stranded telomeric sequence. A competition assay demonstrated that the binding properties of ssTBPs and dsTBPs were specific to the telomeric sequence. We further cloned a ssTBP cDNA (ssTBP-1) by screening a lambda-gt11 expression library and identified ssTBP-1 as a human heterogeneous nuclear ribonucleoprotein (hnRNP) Al on the basis of cDNA sequence. We also found that the expression of the hnRNP Al gene significantly decreased during in vitro passage of human microvascular endothelial cells.
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- 1996
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10. Significance of alpha-1-antitrypsin mRNA expression in esophageal carcinoma.
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Mimori K, Mori M, Mafune K, Tanaka Y, Li J, Fukumaki Y, Matsuda M, Sugimachi K, and Akiyoshi T
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Alpha-1-antitrypsin (alpha 1AT) is present not only in the normal gastrointestine, but in malignant gastrointestinal tissue as well. We studied the expression of alpha 1AT mRNA in 30 cases of esophageal carcinoma using a Northern blot analysis. In addition, we also examined the expression of matrix metalloproteinase 7 (MMP7) mRNA in the latest 15 cases by reverse transcriptase-polymerase chain reaction (RT-PCR) method to clarify the relationship between the alpha 1AT and MMP7. In 25 of the 30, the expression of alpha 1AT mRNA in esophageal carcinomatous tissue (T) was lower than that in the corresponding normal tissue (N) of the esophagus. The T/N ratio of alpha 1AT mRNA expression showed a significant inverse correlation with the depth of tumor invasion, lymph node metastasis and stage of disease (p=0.042, p=0.0001 and p=0.002, respectively). The T/N ratio of alpha 1AT bad a converse correlation with that of MMP7 (p=0.034). The current study thus suggested that i) the lower expression of T/N expression may be a marker for the biological aggressiveness of esophageal carcinoma, and ii) the reduction of alpha 1AT may be partially correlated with the overexpression of MMP7 in tumor tissue.
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- 1996
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11. Expression of prothymosin-alpha and c-myc mRNA in human gastric cancer.
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Shibuta K, Mori M, Mimori K, Inoue H, Nakashima H, Baba K, Haraguchi M, Karimine N, Ueo H, and Akiyoshi T
- Abstract
Prothymosin-alpha (PT-alpha) is a nuclear protein involved in cell proliferation. c-myc is implicated in the carcinogenesis of many human cancers. PT-alpha gene transcription is reported to be regulated by the c-myc gene in vitro. However, little has been reported on the PT-alpha and c-myc mRNA expressions in gastric cancer. We semi-quantitatively determined the PT-alpha and c-myc mRNA expressions in 60 pairs of gastric cancer tissue (T) and corresponding normal tissue (N) using the reverse transcriptase-polymerase chain reaction method. The average of T/N ratio was 1.20 for PT-alpha and 1.30 for c-myc. Cases demonstrating a T/N ratio of more than 1.0 were seen in 33 (55%) and 30 (50%) cases for PT-alpha and c-myc, respectively. No significant correlation was observed between either of these two mRNA expressions and any of the examined clinicopathologic factors for gastric cancer. However, a significant correlation was seen between the expressions of both genes (p<0.0001). The findings support the hypothesis that, regarding human gastric cancer, the transcription of PT-alpha is considered to be under the control of c-myc gene, however, the value of these gene expressions do not reflect biological behavior.
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- 1996
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12. Dependency of the efficiency of transformation by simian-virus-40 on the proliferative state of cultured fibroblasts at the time of virus inoculation.
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Tamura H, Okuda A, Ohtsu M, Kabemura M, and Kimura G
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We previously demonstrated that the efficiency of cell transformation by simian virus 40 (SV40) is reduced when proliferating rat 3Y1 cells are inoculated with SV40 as compared with when density-arrested cells are inoculated. In this study, we characterized in more detail the cellular state at the time of virus inoculation that affects the susceptibility to SV40 transformation. When density-arrested 3Y1 cells were stimulated to progress one round of cell cycle by refeeding with medium containing high serum, they began to reduce the susceptibility to SV40 transformation before entering S phase. After re-entry into the non-proliferative state, prolonged maintenance of cells in the non-proliferative state was necessary for restoration of the susceptibility to SV40 transformation. Such dependency of the transformation efficiency on the cellular state at the time of SV40 inoculation paralleled with that of the expression of T antigen in nuclei, while virus adsorption and degradation of the DNA of the adsorbed virus was not dependent on the cellular state. We conclude that after inoculation of proliferating cells with SV40, an unidentified event between the virus adsorption and the accumulation of T antigen protein in nuclei is blocked and that this blockage causes the inhibition of the initiation of transformation.
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- 1995
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13. Multiple tumor-suppressor-1 gene and esophageal-carcinoma.
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Li J, Mori M, Yang Y, Inoue H, Mimori K, Shibuta K, Nakashima H, Mafune K, Shimada Y, Barnard G, Sugimachi K, and Akiyoshi T
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The multiple tumor suppressor 1 (MTS1) gene is homozygously deleted frequently in cell lines derived from a wide variety of tumors. We investigated the deletion of the MTS1 gene in esophageal cancer cell lines and primary esophageal squamous carcinomas using the polymerase chain reaction. Sixteen and 15 of 23 esophageal cancer cell lines showed homozygous deletion of MTS1 exon 1 and exon 2, respectively, while none of 21 primary esophageal carcinomas showed the deletion. An analysis of MTS1 gene mutations was carried out by direct DNA sequencing in 8 cell lines and 21 primary carcinomas showing no homozygous deletion. In contrast to previous reports of esophageal carcinoma, there were no mutations recognized in the region sequenced. Our study suggests that the inactivation of the MTS 1 gene may play an important role in esophageal carcinoma cell lines but may be less important in primary carcinomas of the human esophagus.
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- 1995
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14. Establishment of a new human uterine cervical adenocarcinoma cell-line, siso, and its reactivity to anticancer reagents.
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Sonoda K, Nakashima M, Saito T, Amada S, Kamura T, Nakano H, and Watanabe T
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A human cell line, SiSo, was established from a patient afflicted with uterine cervical adenocarcinoma. The SiSo cell expresses MHC class I antigen, various kinds of adhesion molecules and tumor-associated antigens such as CA125, CEA and GA733. The secretion of CA125 antigen was markedly suppressed by anti-cancer reagents. However, their growth was not affected by any of the anti-cancer reagents tested, suggesting a discrepancy between inhibition of tumor growth and suppression of secretion of tumor-associated antigens after treatment with anti-cancer reagents. The SiSo cell line will provide a tool for investigation of uterine adenocarcinoma.
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- 1995
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15. E1a-3y1 cell-specific toxicity of tea polyphenols and their killing mechanism.
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Mitsui T, Yamada K, Yamashita K, Matsuo N, Okuda A, Kimura G, and Sugano M
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To screen carcinostatic components in foodstuffs, the toxicity of tea polyphenols was compared between rat 3Y1 diploid fibroblasts and a variety of their virally transformed cells. Among tea polyphenols tested, epigallocatechin gallate killed 3Y1 cells transformed by E1A gene of human adenovirus type 12 (E1A-3Y1 cells) at a 100 times lower concentration than the parental 3Y1 cells. Epigallocatechin gallate also exerted a strong E1A-3Y1 cell-specific toxicity, while epicatechin and epicatechin gallate did not. When the activity of three antioxidant enzymes was compared between 3Y1 and its transformants, catalase activity was markedly low in the latter, especially in E1A-3Y1 cells, and the substrate of the enzyme, hydrogen peroxide, exerted a toxicity specific to this cell line. Then the inhibitory activities of various chemicals on E1A-3Y1 cell-specific toxicity of phospholipids or catechol were examined. Among lipoxygenase inhibitors, all of the polyphenolic compounds inhibited the toxicity of phospholipids, but not a nonpolyphenolic inhibitor (clofibrate). Two phospholipase A,inhibitors (dexamethasone and quinacrine) did not inhibit the toxicity. These results indicate that the triphenol structure of the B ring is essential for the E1A-3Y1 cell-specific toxicity of tea polyphenols, and that the decrease in catalase activity is partially responsible for the higher sensitivity of E1A-3Y1 cells against the polyphenols. The inhibitory effect of polyphenolic lipoxygenase inhibitors is ascribed at least in part to their antioxidant activities.
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- 1995
16. Reversible proliferation arrest of rat 3y1 fibroblasts and selective killing of simian-virus transformed derivation of 3y1 by short-chain Fatty-acids.
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Matsuo N, Yamada K, Noda S, Yamashita K, Okuda A, Kimura G, and Sugano M
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We examined the effect of saturated fatty acids with carbon number from 2 to 10 on proliferation and survival of rat untransformed fibroblast 3Y1 cells and its transformed derivation induced by Simian virus 40 (SV-3Y1). Acetic acid (C2) had no effect on proliferation of these cells. Among medium-chain fatty acids (C6-C10), caproic acid (C6) showed the lowest proliferation inhibitory effect. Caprylic (C8), pelargonic (C9), and capric acid (C10) exerted killing activity to both 3Y1 cells and SV-3Y1 cells, and the toxicity increased with the elongation of their alkyl chains. The toxicity was a little greater to 3Y1 cells than to SV-3Y1 cells. In contrast, short-chain fatty acids caused reversible proliferation arrest in 3Y1 cells at 25 mM in propionic (C3), 5 mM in butyric (C4) and 10 mM in valeric (C5) acids. These short-chain fatty acids arrested 3Y1 cells not only in the GI phase but also in the G2 phase of the cell cycle. To SV-3Y1 cells, however, these short-chain fatty acids were cytotoxic. The cytotoxicity to SV-3Y1 cells was the greatest in butyric acid among short-chain fatty acid tested. These results suggest that short-chain fatty acids exert ploliferation-arresting activity against normal cells while exerting killing activity to the transformed cells.
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- 1994
17. Nm23 expression in human gastric cancers - possible correlation of nm23 with lymph-node metastasis.
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Muta H, Iguchi H, Kono A, Seo Y, Tomoda H, and Nawata H
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In order to elucidate the relationship between nm23 and metastasis in human gastric cancers, we analyzed gene and protein expression of nm23-H1 using Northern blot and immunohistochemical techniques. nm23-H1 gene expression was identified in 17 out of 19 gastric cancer tissues. The signals in the tumor tissues presenting regional lymph node metastasis seem to be lower than those in the tumor tissues without regional lymph node metastasis, suggesting a role of nm23-H1 in the regional lymph node metastasis in the gastric cancers. However, the protein expression detected immunohistochemically was not correlated to the gene expression, partly because of difficulty in quantifying the amount of protein. Expression of the nm23-H1 gene as well as the nm23-H1 protein in the tumor tissues was higher than those in the corresponding normal mucosae. This suggests a linkage of nm23-H1 in the process of the gastric cancer progression. We also analyzed the sequence abnormalities of the nm23-H1 gene in the gastric cancer tissues using a direct sequencing technique, no mutations were observed.
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- 1994
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18. Drug-induced endothelial injury potentiates lung colonization in a murine fibrosarcoma model.
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Fujita Y, Iwamoto Y, Okuyama K, Tanaka K, Maeda T, and Sugioka Y
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Lung colonization induced by the intravenous injection of fibrosarcoma cells into syngeneic mice was enhanced by the pretreatment of mice with cyclophosphamide (CPA), adriamycin (ADM), cis-diammine-dichloroplatinum II (DDP) and methotrexate (MTX). At equitoxic levels, CPA showed greater enhancement of the lung colonization than the other drugs treated. After a two-hour pretreatment of an endothelial monolayer culture, the adhesion of fibrosarcoma cells to endothelial cells was enhanced by all drugs, and the greatest enhancement was obtained with CPA. Data from these experiments supports the hypothesis that endothelial cell damag by anticancer drugs may facilitate metastasis of circulating tumor cells.
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- 1994
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19. The effects of Cisplatin on the epiphyseal growth-plate.
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Miyoshi K, Iwamoto Y, and Sugioka Y
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In rabbit models, the inhibition of proteoglycan (PG) biosynthesis in the epiphyseal growth plate of the ribs was observed in the group given cisplatin both in vitro and in vitro. Serum alkaline phosphatase (ALP) and the bone-derived ALP isoenzyme were observed to decrease in the young rabbits given cisplatin. In rat models, the length of the tibias in both the groups given cisplatin was significantly shorter than that of those in the control rats. The results described may thus suggest that the injury of the epiphyseal growth plate and growth retardation possibly occur due to the use of cisplatin.
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- 1994
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20. Synergism of cytotoxicity between cis-diaminedichloro-platinum-(ii) and cis-diamine(1,1-cyclobutanedicarboxylate)-platinum-(ii).
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Baba H, Maehara Y, Takeuchi H, Inutsuka S, Yamamoto M, Endo K, and Sugimachi K
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In an attempts to increase the antitumor effect and to reduce normal tissue toxicity, the combined cytotoxic effect of cis-Diamminedichloroplatinum (II) (CDDP) and cis-diammine(1,1-cyclobutane dicarboxylate) platinum (II) (CBDCA) was investigated using HeLa and colon 26 cell lines and the combination index (CI). Cytotoxicity of the combination of CDDP and CBDCA on 27 surgically resected specimens of human gastric and colorectal adenocarcinomas was also evaluated using the in vitro succinate dehydrogenase inhibition (SDI) test. The CI values varied with the dose ratio examined (1:1-1:6) of CDDP and CBDCA, with findings that CI<1, synergy, was obtained at fraction affected (Fa)>0.75 for HeLa cells and at Fa<0.9 for colon 26 cells in cases of a dose ratio of 1:1 to 1:2. Of all 27 clinical human adenocarcinomas, the succinate dehydrogenase (SD) activity was significantly lower in cancer cells concomitantly exposed to both CDDP and CBDCA than in those exposed to either drug alone. These positive effects of a combination of two platinum analogues on human malignant tissues have heretofore not been reported, which would warrant the clinical application of this combination for human malignant tumors.
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- 1994
21. Enhancing effect of ethanol on aflatoxin b1-induced DNA-damage in glutathione-depleted rat hepatocytes.
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Tsutsumi N and Miyazaki K
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The effect of reduced glutathione (GSH) and ethanol on aflatoxin B1 (AFB1)-induced DNA single strand breaks was studied in primary cultured hepatocytes. Buthionine sulfoximine (BSO) which decreased intracellular GSH to 13% of those of the control levels increased DNA fragmentation of AFB1-treated hepatocytes by over 17% of those without BSO. Thus, a decrease in hepatocyte GSH levels increased AFB1-induced DNA damage. Although ethanol in itself did not induce DNA damage, a combination of BSO and ethanol increased the percentage by over 23% of that with BSO only. Ethanol did not affect the amount of GSH, total cytochrome P-450 (P450), glutathione S-transferase (GST) and epoxide hydrolase (EHase) in cultured hepatocytes. However, GSH-depleted rat hepatocytes exposed to ethanol significantly increased the level of P450IIIA, which activates AFB1. The enhancing effects of ethanol in the presence of BSO are probably due to the induction of this isozyme in rat hepatocytes. The GSH-depleted hepatocytes are more susceptible to chemical carcinogens in the presence of ethanol.
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- 1994
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22. Expression of hepatocyte growth factor(hgf) and C-met gene in human gastric-cancer cell-lines.
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Fushida S, Yonemura Y, Urano T, Yamaguchi A, Miyazaki I, Nakamura T, and Shiku H
- Abstract
It has become evident that the hepatocyte growth factor (HGF) could be involved in the growth of various epithelial cells. In addition, it has recently been elucidated that the c-met gene, a proto-oncogene, encodes the HGF receptor. We examined the expression of HGF and c-met gene in human gastric cancer, using seven gastric cancer cell lines. The Northern blotting method revealed that, among seven cell lines used, only MKN45 expressed the c-met gene at a high efficiency, while the Southern blotting method demonstrated the amplification of the c-met gene. When the expression of HGF gene was studied by the Northern blot method, the expression of this gene was also observed only in MKN45, which was confirmed by immunostaining with polyclonal antibodies to HGF. The above results suggest the possibility that in MKN45, a gastric cancer cell line, the autocrine mechanism by HGF-met might be involved in its growth.
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- 1993
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23. Prognosis for gastric-cancer invading the serosa evaluated by argyrophilic nucleolar organizer region staining.
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Qi L, Maehara Y, Oshiro T, Okuyama T, Takeuchi H, Baba H, Adachi Y, and Sugimachi K
- Abstract
Eighty-five patients with gastric cancer invading the serosa following curative resection were analyzed with respect to clinicopathological features and prognosis by staining the argyrophilic nucleolar organizer region (AgNOR). The AgNOR was counted in 200 cancer cells per tissue and the mean number per cell was identified as the AgNOR score. The AgNOR count varied from 1.79 to 5.71, while the mean value was 2.92 +/- 0.74 and the median score was 2.95. The patients were divided into two groups: the AgNOR high group (AgNOR count greater-than-or-equal-to 2.95, n=44) and the AgNOR low group (AgNOR count < 2.95, n=41). There were no differences between the two groups with respect to sex, age, tumor size, location of the tumor, macroscopic appearance, histological differentiation, growth pattern and vascular involvement. The lymphatic advancement of tumor cells was prominent and the rate of lymph node metastasis was higher (p<0.01) in patients in the AgNOR high group. The AgNOR high group had a higher rate of recurrence and also had a variety of recurrence styles. The prognosis of the AgNOR high group was poorer, with statistical significance (p<0.01), while the 10-year survival rate was 35.3% for the AgNOR high group and 77.2% for the AgNOR low group. Therefore, the AgNOR count was found to be closely related to tumor advancement and thus is considered to have a predictive value for the prognosis of patients with gastric cancer invading the serosa after curative resection.
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- 1993
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24. L-histidinol potentiates hyperthermic cell-killing in-vitro.
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Kohnoe S, Maehara Y, Takahashi I, Yoshida M, Emi Y, Baba H, and Sugimachi K
- Abstract
To clarify the effect of L-histidinol on hyperthermic killing of cells, HeLa and mouse sarcoma-180 (S-180) cells were exposed to heat in vitro in the presence of L-histidinol and the clonogenic surviving fraction of the cells was examined. After pretreating the cells with L-histidinol for 4 h, exposure of the cells to the combination of heat at 43-degrees-C and L-histidinol for various times (30 min to 4 h) reduced the surviving fraction more prominently than heat alone. Optimal concentrations to confer effective enhancement of heat on HeLa and S-180 cells were 9 mM and 3 mM, respectively. Those concentrations showed little toxicity of L-histidinol alone. Enhancement of the effect of heat by L-histidinol was observed only at 43-degrees-C, but not at 41 and 42-degrees-C. Flow cytometric DNA analysis was used to examine the cell cycle transit effect of L-histidinol. L-histidinol alone arrested the HeLa cells in G1-phase. Heat treatment at 43-degrees-C led to an accumulation of the cells in G2/M-phase and a decrease in the G1-phase fraction. The effect of combined treatment with heat and L-histidinol was complementary, in which L-histidinol attenuated the accumulation of the cells in G2/M-phase and prevented a decrease in the G1-phase fraction. Thus, L-histidinol has the capacity to potentiate hyperthermic cell killing in vitro by a mechanism that may be related to the cell cycle transit effect.
- Published
- 1993
25. Small-cell carcinoma of the gallbladder - a clinicopathological, immunohistochemical and flow cytometric study of 15 cases.
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Nishihara K and Tsuneyoshi M
- Abstract
Small cell carcinoma (SC) of the gallbladder is an uncommon tumor, and not enough information of this tumor has been previously reported. The SCs in this series occured in nine women and six men (mean age; 64.5 years). Histologically, they consisted of small atypical cells with scanty cytoplasm, hyperchromatic nuclei and inconspicuous nucleoli growing in sheets and cords. Two tumors contained neoplastic glands similar to those of well-differentiated adenocarcinoma and a histological transition between SC and adenocarcinoma was seen in one of the two tumors. Argyrophil granules were present in 10 tumors. The tumor cells were immunoreactive to epithelial markers (epithelial membrane antigen: 12/14; AE1/AE3: 12/14; CAM 5.2: 9/14; carcinoembryonic antigen: 7/14) and neuroendocrine markers (neuron specific enolase: 11/14; chromagranin A: 4/14; Leu 7: 10/14; adrenocorticotrophic hormone: 6/14). Abnormalities in tumor suppressor gene p53 expression were found in 9 of 14 SCs by using monoclonal antibody PAb 1801. Flow cytometry revealed aneuploidy in 7 (78%) of 9 in the SC and 26 (40%) of 65 in the adenocarcinoma. The survival curve of the SCs was less favorable than that of papillary adenocarcinoma and well differentiated adenocarcinoma in pTNM stage 2-4 (P=0.0027, P=0.0017, respectively). These results suggested that the SCs of the gallbladder arose from common primitive cells capable of endocrine and epithelial differentiation, while most SCs (78%) showed DNA aneuploid by flow cytometry and their prognosis was worse than that of differentiated adenocarcinoma of the gallbladder.
- Published
- 1993
- Full Text
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26. Gastric-carcinoma developing in the reconstructed gastric tube following esophagectomy - analysis of 58 cases.
- Author
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Kitamura K and Sugimachi K
- Abstract
Fifty-eight Japanese patients with secondary adenocarcinoma, which developed in the reconstructed gastric tube after esophagectomy for carcinoma of the esophagus, were reviewed from 20 case reports published over a period of twenty years. Following esophagectomy the gastric tube was replaced through the antesternal route in 32 patients (55.2%), through the retrosternal route in 19 (32.7%) and through the intrathoracic route in 7 (12.1%). Regarding the initial diagnosis of the secondary carcinoma, 28 patients (48.3%) had a self-palpable tumor in the anterior chest, 10 patients (17.2%) had a feeling of dysphagia, and two (3.4%) experienced epigastralgia. In eighteen patients (31.1%), the secondary carcinoma was detected incidentally at follow-up examinations, including two autopsied cases. The interval between esophagectomy and the detection of the secondary carcinoma in the gastric tube ranged from 7 to 255 months (mean 72.4 +/- 54.2 months). In 31 patients (53.4%) the secondary carcinoma was detected more than 5 years after esophagectomy. The mean survival period was 81.2 +/- 54.3 months with a range from 21 to 227 months after esophagectomy. These results thus emphasise the significance of lifetime check-ups for the reconstructed gastric tube, especially when the stomach is used as substitution for the esophagus.
- Published
- 1993
- Full Text
- View/download PDF
27. Growth-inhibition and change in morphology and motility of sclc cell-lines by hepatocyte growth-factor scatter factor.
- Author
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Rygaard K, Klausen B, Nakamura T, and Spangthomsen M
- Abstract
Expression of the c-met proto-oncogene is common iii small cell lung cancer (SCLC) cell lines. The product of this proto-oncogene is the receptor for hepatocyte growth factor (HGF), also known as scatter factor (SF) and hepatopoietin A. We examined the effect of HGF/SF on 8 SCLC cell lines of which six expressed c-Met and 2 control cell lines did not. The effect was monitored by growth curves, in vitro migration in Boyden chambers. and by examination of morphology. Three cell lines responded in one or more of the following ways: Growth inhibition, morphological alterations. and increased migration in Boyden chambers. We conclude that functional c-Met receptors are frequently expressed in SCLC and may contribute to the behaviour of this tumour type.
- Published
- 1993
- Full Text
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28. Cytotoxic and cytostatic effects of polyphenols against rat 3y1 fibroblasts transformed by e1a gene of human adenovirus-type-12.
- Author
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Yamada K, Mitsui T, Okuda A, Kimura G, and Sugano M
- Abstract
Toxicity of polyphenols against rat 3Y1 fibroblasts and the cells transformed by human adenovirus (Ad12-3Y1), its EIA gene (EIA-3Y1), or simian virus 40 (SV-3Y1) was examined. Among the diphenol compounds examined, pyrocatechol (o-diphenol) and hydroquinone (p-diphenol) showed selective toxicity against Ad12-3Y1 and EIA-3Y1 cells, while resorcinol (m-diphenol) showed a much weaker non-specific toxicity against these cells. Another o-diphenol (dopamine) and triphenols (gallic acid and pyrogallol) were less toxic but showed selective toxicity. At lower concentrations where they were not toxic, all polyphenols attenuated toxicity of phosphatidylcholine against EIA-3Y1 cells. Among antioxidants examined, ascorbic acid reduced the toxicity of pyrocatechol, but alpha-tocopherol and butyrated hydroxytoluene did not. Oxidation of pyrocatechol was not enhanced in the presence of 3Y1 or EIA-3Y1 cells and their homogenates. These results suggest that the selective toxicity of polyphenols against Ad12-3Y1 and E1A-3Y1 cells is not related to their oxidation velocity but other factors such as the activity of active oxygen-scavenging enzymes.
- Published
- 1993
- Full Text
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29. Liver adenosquamous carcinoma invading the esophagogastric junction - a case-report and a review of the literature.
- Author
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Baba H, Yasunaga C, Tsujitani S, Korenaga D, Maehara Y, Sugimachi K, and Sueishi K
- Abstract
A case of adenosquamous carcinoma of the liver involving the esophago-gastric junction is reported. The preoperative diagnosis of a submucosal tumor of the cardia of the stomach was made following a barium meal study, gastrofiberscopy, ultrasonography, and computed tomography. At surgery, a tumor was found measuring 6x5 cm in diameter and involving the left lobe of the liver, lower esophagus and cardia of the stomach, and the origin of the tumor was unclear. Post-operative histopathology revealed that the tumor contained two different malignant components of glandular and squamous cells. An adenosquamous carcinoma originating in the liver was suspected, since the cancer cells did not involve the esophago-gastric mucosa and were mainly located in the S2 of the liver. Despite aggressive adjuvant chemotherapy, the patient died of a recurrence in the liver seven months later. This seems to be the first documentation of adenosquamous carcinoma of the liver invading the esophago-gastric junction.
- Published
- 1992
30. Simple and efficient chemosensitivity assay for human primary tumor-cells using contact-sensitive microtiter plates.
- Author
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Mitsugi K, Nakano S, Nakayama M, Ichinose I, Anzai K, Kuroki M, Nakamura M, Nagafuchi S, and Niho Y
- Abstract
A simple and efficient chemosensitivity assay for human primary tumors has been developed using 96-well microtiter plates covered totally with lethally irradiated 3T3 monolayers termed cell mats, on which the proliferation of normal human fibroblasts is preferentially inhibited. Two days after the inoculation of tumor cells into the microtiter cell mat plates, the cells were treated with various anticancer drugs, and the cell numbers were assessed by radioactivity using a 96-well automatic scintillation counter after subsequent radiolabeling with H-3-deoxyuridine for 24h. In this manner, complete dose response curves of many anticancer drugs were available from one plate within 5 days. Drugs tested in triplicate were adriamycin, mitomycin C, cisplatin, etoposide, and 5-fluorouracil at 0.01, 0.1, and Ix the peak tolerated drug concentrations in serum. Clinically, of the 39 primary tumor specimens of different types received, 4 were contaminated. The remaining 35 samples were successfully cultured, with 5 cultures being abandoned due to an insufficient cpm. As a result, cell survival curves were obtained from 30 (77%) specimens. This high evaluable rate might be due to the feeder effect brought by cell mats. Although optimization of the assay system has yet to be determined, the ability to have multiple drug sensitivity per plate with short-term duration would make this system an efficient assay for chemosensitivity test of human primary tumor cells.
- Published
- 1992
- Full Text
- View/download PDF
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