Biomedical subjects

J Fujimoto

Publications and source records attributed to J Fujimoto.

At least 145 records · Page 8Linked to original sources

PubMed1998

Estrogen dependency in uterine endometrial cancers.

Estrogen dependency in uterine endometrial cancers involves complicated tumor biology. A transformed phenotype of uterine endometrial cancers is supported by estrogen-dependent oncogene (c-Ha-ras, c-fos and c-jun) expressions. The relative overexpression of estrogen receptor exon 5 splicing variant and the damaged expression of progesterone receptor A, which belong to a lack of estrogen dependency, are related to metastatic potential. The estrogen-related metastatic processes, detachment, invasion and angiogenesis in some uterine endometrial cancers can be inhibited by progestins.

Endometrial Neoplasms↗

PubMed1998

Effects of sex steroid hormones on corticosteroid-binding globulin gene expression in human endometrial cancer cell line Ishikawa.

The effect of progestins on intracellular corticosteroid-binding globulin (CBG) mRNA expression in an endometrial cancer cell line (Ishikawa) was examined in an attempt to understand the biological effects of high-dose progestins in the treatment of well-differentiated uterine endometrial cancers. Oestradiol-17 beta (E2) significantly increased CBG mRNA expression in a dose-dependent manner, while a high dose of progesterone with or without E2 suppressed it significantly. Furthermore, a high dose of progesterone or medroxyprogesterone acetate (MPA) suppressed CBG mRNA expression to a greater degree than did chlormadinone acetate or 17 alpha-hydroxyprogesterone caproate with or without E2. These findings suggest that the effects of high-dose progestins on cancer cells may be mediated via suppression of intracellular CBG.

Endometrial Neoplasms↗

PubMed1998

Expression of the extracellular levansucrase and invertase genes from Zymomonas mobilis in Escherichia coli cells.

We investigated the expression and localization in Escherichia coli of sucZE2 and sucZE3, encoding Zymomonas mobilis extracellular levansucrase and invertase, respectively, and lacking a typical N-terminal secretion signal. Levansucrase and invertase were expressed efficiently under the lac and tac promoters in E. coli cells, and some of the levansucrase produced was localized in the periplasmic space. The sucZE2 expression was not lethal to E. coli in the presence of 5% sucrose, and led to the accumulation of levan from sucrose.

Amino Acid Sequence↗

PubMed1998

Effect of medroxyprogesterone acetate on sex hormone-binding globulin mRNA expression in the human endometrial cancer cell line Ishikawa.

To understand the rationale of high-dose medroxyprogesterone acetate (MPA) in the treatment of well-differentiated uterine endometrial cancers, the effect of MPA on intracellular sex hormone-binding globulin (SHBG) mRNA expression in well-differentiated uterine endometrial cancer cell line Ishikawa was determined by competitive reverse transcription-polymerase chain reaction-Southern blot analysis. Estradiol-17beta (E2, 10(-8) mol/l) did not alter SHBG mRNA expression, but the addition of 10(-10) mol/l MPA increased it, while a high concentration of MPA (10(-6) to 10(-5) mol/l) with or without E2 suppressed it. Furthermore. a high dose (10(-6) mol/l) of chlormadinone acetate or danazol with or without E2 significantly suppressed its expression, while MPA was the most effective among the hormones tested. The effect of MPA and the other steroid hormone analogs on SHBG expression was not mediated via the progesterone receptor. These findings suggest that intracellular SHBG suppression might partly contribute to the abolition of the intracellular estrogen-dominant milieu, and may be involved as one of the mechanisms of the antitumoral effects of high-dose MPA on the development and growth of some well-differentiated endometrial cancer cells.

Antineoplastic Agents, Hormonal↗

PubMed1998

Expression of CD44 containing variant exon 9 (CD44v9) in gastric adenomas and adenocarcinomas: relation to the proliferation and progression.

The expression of CD44 splice variant containing exon 14 (variant exon 9: CD44v9) was examined immunohistochemically in non-neoplastic mucosa, adenoma and adenocarcinoma of the stomach and analyzed the relation with the expression of Ki-67 antigen and p53 protein. In non-neoplastic gastric mucosa, basolateral membrane of the epithelial cells in the pyloric glands showed the expression of CD44v9. The epithelial cells in the intestinal metaplastic mucosa of the stomach sometimes expressed CD44v9. In the neoplastic lesions, the expression of CD44v9 was detected in 20% (34/170) of the adenomas and 28% (132/478) of the adenocarcinomas, respectively. The incidence of CD44v9 expression did not differ among histological type of gastric carcinoma. Twelve per cent of the adenocarcinomas showed strong expression of CD44v9, whereas non of the adenomas did. The incidence of CD44v9 expression was significantly higher in carcinomas invading into muscularis propria or the cases of stages 3 and 4 in comparison with that in carcinomas limited to submucosa or the stages 1 and 2 cases (p<0.05). The incidence of positive cases was higher in carcinomas with lymph node metastasis than those without metastasis (p<0.05). The expression of CD44v9 was significantly correlated with the expression of Ki-67 (p<0.05). It was also correlated with the expression of p53 protein in the tumor cells (p<0.01). These findings overall suggest that the expression of CD44v9 may be associated with the development as well as progression of the gastric carcinomas.

Adenocarcinoma↗

PubMed1998

Estrogen and progestin inhibit invasiveness of gynecologic metastatic cancer cells to blood vessel endothelium.

The Boyden chamber method showed that the invasiveness to reconstituted blood vessel endothelium of metastatic gynecologic cancer cell lines of the uterine cervix (MS751 and ME-180), endometrium (AN3 CA), and ovary (SK-OV-3 and PA-1) was significantly higher than of primary cancer cell lines of the cervix (HeLa and C-33 A), endometrium (Ishikawa, HEC-1-A and HHUA), and ovary (MCAS and Caov-3), and that the invasiveness was inhibited by estradiol or progestin in the metastatic cells but not in the primary cells. These results suggest that metastatic cancer cells by themselves increase the potential of blood vessel invasion, which can be inhibited by estrogen and progestin administration.

Adenocarcinoma↗

PubMed1998

Expressions of E-cadherin and alpha- and beta-catenin mRNAs in uterine endometrial cancers.

To know the biological function of the adherens junction associated with histological dedifferentiation, intramuscular invasion, and clinical staging, we studied the expressions of E-cadherin and alpha- and beta-catenin mRNAs in endometrial cancers in comparison with those in normal uterine counterparts. As dedifferentiation, myometrial invasion and staging advanced, the expressions of E-cadherin and beta-catenin mRNAs decreased. This suggests that the function of adhesive molecules in the adherens junction might be disturbed, leading to invasiveness and metastatic potential.

Adult↗

PubMed1998

[TAL1 gene analysis in T-cell malignancies].

Site-specific recombination of the TAL1 gene was analyzed by Southern blotting and polymerase chain reaction (PCR) in 44 cases of childhood T-cell acute lymphoblastic leukemia (T-ALL), 20 cases of childhood T-cell non-Hodgkin's lymphoma (T-NHL) and 35 cases of adult T-cell malignancies. This recombination was found in 10 (22.7%) of 44 childhood T-ALL patients, but in none of the T-NHL or adult T-cell malignancies. Recombination of the TAL1 gene was therefore suggested to be specific for childhood T-ALL. The immunophenotypic features of the 10 T-ALL patients with this recombination were CD1-, CD2+, CD4-, CD7+, CD10-, and they had a significantly better outcome than other T-ALL cases without the recombination. The PCR technique revealed minimal residual disease (MRD) in 2 patients. One showed persistent MRD, while in the other MRD was recognized only at initial diagnosis. Further investigation is needed whether T-ALL with this recombination constitutes a distinct clinical subgroup among childhood T-ALL patients.

Adolescent↗

PubMed1998

[Acute angle-closure glaucoma following surgery for oral cancer].

A 60-year-old woman who had undergone surgery of oral cancer under general anesthesia developed an attack of acute angle-closure glaucoma the next morning. Her intraocular pressure decreased immediately by adequate treatments including surgical procedures (laser iridotomy and trabeculectomy), and her symptom improved. It is considered that this event was induced by several factors such as atropine given before and during general anesthesia, perioperative hypertension and anatomical abnormalities. However the definite cause of this event is unclear. We conclude that it is difficult to predict a glaucoma attack following surgery under general anesthesia, but this complication is an important ophthalmologic emergency. Immediate diagnosis and appropriate treatment should be done to prevent the grave prognosis.

Acute Disease↗

PubMed1997

Expression of sex hormone-binding globulin exon VII splicing variant messenger RNA in human uterine endometrial cancers.

We have demonstrated the intracellular expression of sex hormone-binding globulin (SHBG) exon VII splicing variant mRNA in human uterine endometrial cancer using the reverse transcription-PCR-Southern blot and DNA sequencing analyses. Analysis of the missing base pairs proved that they corresponded to the entire exon VII, which is considered to encode a portion of the steroid-binding site, suggesting that the steroid-binding affinity of this variant might be different from that of the SHBG wild type. In uterine endometrial cancers, the wild-type mRNA levels significantly (P < 0.01) decreased, and the ratio of the SHBG variant to wild-type mRNA levels (P < 0.01) increased with the advance of histological dedifferentiation. These results suggest that dedifferentiation of endometrial cancers might induce a reduction in their estrogen-dependent properties via intracellular SHBG.

Adult↗

PubMed1997

Expression of E-cadherin and alpha- and beta-catenin mRNAs in ovarian cancers.

To know the biological role of the adherens junction, mainly consisting of E-cadherin and alpha- and beta-catenins, associated with invasion and metastasis of ovarian cancers, we studied the expressions of E-cadherin and alpha- and beta-catenin mRNAs in the cancers in comparison with those in normal counterparts. The integral expression of E-cadherin and alpha- and, beta-catenin mRNAs was suppressed in the metastatic lesions of advanced ovarian cancers, while it was not in the primary tumors. Therefore, the suppressed expression of main adhesion molecules in the adherens junction might contribute to adherens junctional dysfunction, which might lead to the acquirement of invasiveness and metastatic potential by advanced ovarian cancers as one of the rate-limiting steps.

Adult↗

PubMed1997

Plausible novel therapeutic strategy of uterine endometrial cancer with reduction of basic fibroblast growth factor secretion by progestin and O-(chloroacetyl-carbamoyl) fumagillol (TNP-470; AGM-1470).

To know the potential of growth, invasion and metastasis of endometrial cancer associated with neovascularization, the effects of sex steroids and O-(chloroacetyl-carbamoyl) fumagillol (TNP-470; AGM-1470) on basic fibroblast growth factor (FGF) expression and secretion and its mRNA expression were investigated in well-differentiated endometrial cancer cell line Ishikawa and in undifferentiated endometrial cancer cell line AN3 CA. Basic FGF expression and secretion and its mRNA expression in Ishikawa cells, but not in AN3 CA cells, were increased by estrogen, while progesterone diminished the estrogen-induced increases. TNP-470 reduced the levels regardless of estrogen treatment in AN3 CA cells. Therefore, basic FGF secretion may be inhibited by progestin in differentiated cells, and by TNP-470 in undifferentiated cells. Since endometrial cancer consists of differentiated and undifferentiated cells as heterogeneity, a combination therapy for endometrial cancer with progestin and TNP470 might be effective.

Antibiotics, Antineoplastic↗

PubMed1997

Chromosomal mapping of the mouse and rat brt genes.

brt encodes a receptor-type protein-tyrosine kinase and was isolated from fetal mouse brain by using a PCR-mediated cloning procedure; this gene is expressed preferentially in the brain of both embryo and adult. Chromosomal locations of the mouse and rat brt genes were determined by fluorescence in situ hybridization using a mouse cDNA fragment as a probe. The brt gene was localized to mouse Chromosome 2F1 and rat Chromosome 3q36.1, where a conserved linkage homology has been identified between the two species. Interspecific backcross analysis genetically demonstrated no recombination between the mouse BRT locus and D2Mit63.

Agammaglobulinaemia Tyrosine Kinase↗

PubMed1997

Host F1 mice pretreated with granulocyte colony-stimulating factor accept parental bone marrow grafts in hybrid resistance system.

In the setting of hybrid resistance, parental C57BL/6 bone marrow (BM) grafts are vigorously rejected by lethally irradiated (C57BL/6xDBA/2) F1 mice. However, F1 mice pretreated by continuous administration of granulocyte colony-stimulating factor (G-CSF) with a miniosmotic pump before BM grafting developed day-8 splenic colonies of donor origin. This inhibitory effect on rejection was reversible because F1 mice regained the capacity to reject parental BM when the pump ceased functioning. The appearance of only a small number of colonies with the administration of G-CSF soon after BM grafting suggested the importance in producing this inhibitory effect of pre-exposure of host mice to G-CSF. Because G-CSF administration with a syngeneic combination did not influence the number of colonies, an altered distribution of grafted precursors was unlikely. The absence of a reduction in the number of NK1.1-positive cells in G-CSF-treated mice suggested functional impairment of natural killer cells, major effectors in hybrid resistance, but further study is necessary to elucidate the mechanism underlying this phenomenon. However, our results indicate the importance of G-CSF as a regulator in a certain type of immune response and raise the possibility of clinical application in transplantation medicine.

Adjuvants, Immunologic↗

PubMed1997

Solid phase synthesis and restriction endonuclease cleavage of oligodeoxynucleotides containing 5-(hydroxymethyl)-cytosine.

Emerging data suggest an important role for cytosine methylation in tumorigenesis. Simultaneously, recent studies indicate a significant contribution of endogenous oxidative DNA damage to the development of human disease. Oxidation of the 5-methyl group of 5-methylcytosine (5mC) residues in DNA results in the formation of 5-(hydroxymethyl)cytosine (hmC). The biological consequences ofhmC residues in vertebrate DNA are as yet unknown; however, conversion of the hydrophobic methyl group to the hydrophilic hydroxymethyl group may substantially alter the interaction of sequence-specific binding proteins with DNA. Central to both biophysical and biochemical studies on the potential consequences of specific DNA damage products such as hmC are efficient methods for the synthesis of oligodeoxynucleotides containing such modified bases at selected positions. In this paper, we describe a method for the placement of hmC residues in oligodeoxynucleotides using established phosphoramidite chemistry. In addition, we have examined the influence of specific hmC residues on enzymatic cleavage of oligodeoxynucleotides by the methylation-sensitive restriction endonucleases MspI and HpaII.

5-Methylcytosine↗

PubMed1997

Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system.

The 2;5 chromosomal translocation is frequently associated with anaplastic large cell lymphomas (ALCLs). The translocation creates a fusion gene consisting of the alk (anaplastic lymphoma kinase) gene and the nucelophosmin (npm) gene: the 3' half of alk derived from chromosome 2 is fused to the 5' portion of npm from chromosome 5. A recent study shows that the product of the npm-alk fusion gene is oncogenic. To help understand how the npm-alk oncogene transform cells, it is important to investigate the normal biological function of the alk gene product, ALK. Here, we show molecular cloning of cDNAs for both the human and mouse ALK proteins. The deduced amino acid sequences reveal that ALK is a novel receptor protein-tyrosine kinase having a putative transmembrane domain and an extracellular domain. These sequences are absent in the product of the transforming npm-alk gene. ALK shows the greatest sequence similarity to LTK (leukocyte tyrosine kinase) whose biological function is presently unknown. RNA blot hybridization analysis of various tissues reveals that the alk mRNA is dominantly detected in the brain and spinal cord. Immunoblotting with anti-ALK antibody shows that ALK is highly expressed in the neonatal brain. Furthermore, RNA in situ hybridization analysis shows that the alk mRNA is dominantly expressed in neurons in specific regions of the nervous system such as the thalamus, mid-brain, olfactory bulb, and ganglia of embryonic and neonatal mice. These data suggest that ALK plays an important role(s) in the development of the brain and exerts its effects on specific neurons in the nervous system.

Amino Acid Sequence↗

PubMed1997

Determination of delta-opioid in NG108-15 cells.

The delta-opioid receptors in mouse neuroblastoma x rat glioma NG108-15 cells were characterized by receptor binding and cAMP assays. Saturation binding assays using [3H][D-Pen5]enkephalin (DPDPE) or [3H][D-Ser2, Leu5, Thr6]enkephalin (DSLET) gave similar binding capacities (Bmax). Competition binding assays showed that DPDPE and DSLET have similar affinity for the [3H]DPDPE or 3[H]DSLET binding sites. The rank order of potency of competition with [3H]DPDPE and [3H]DSLET was similar: naltriben approximately DSLET > or = DPDPE > 7-benzylidenenaltrexone (BNTX). Both DPDPE and DSLET were found to decrease cAMP formation. The action of DSLET was antagonized by naltriben but not BNTX, while the action of DPDPE was reversed by both antagonists. Therefore, the delta-opioid receptor in NG108-15 cells has similar affinity for the agonists DPDPE and DSLET, and a higher affinity for the antagonist naltriben than BNTX.

Animals↗

PubMed1997

Expression of basic fibroblast growth factor and its mRNA in advanced uterine cervical cancers.

To know the potential of growth, invasion and metastasis of uterine cervical cancer cells associated with neovascularization, the expression of basic fibroblast growth factor (FGF) and its mRNA in uterine cervical cancers and normal uterine cervices as controls were determined by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction-Southern blot (RT-PCR-SB), respectively. Then, the relations between the expression and the histological grading and clinical staging in cervical cancers were analyzed. The levels of basic FGF and its mRNA were significantly higher in advanced primary uterine cervical cancers, regardless of histological type. Therefore, this status might contribute to the acceleration of growth, invasion, and metastasis with neovascularization in advanced uterine cervical cancers.

Adult↗