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Biomedical subjects

J Fujimoto

Publications and source records attributed to J Fujimoto.

At least 109 records · Page 6Linked to original sources
PubMed1999

Expression of platelet-derived endothelial cell growth factor (PD-ECGF) related to angiogenesis in ovarian endometriosis.

Platelet-derived endothelial cell growth factor (PD-ECGF) is expressed in the lining epithelial cells of ovarian endometriomas, and in interstitial cells of the subepithelial area with angiogenesis. The expression of PD-ECGF persists in endometriotic endometrium during the menstrual cycle. This might suggest that PD-ECGF contributes to the growth of ovarian endometriomas via subepithelial angiogenesis independently of the sex steroidal milieu.

Adult↗
PubMed1999

Levels of sex hormone-binding globulin and corticosteroid-binding globulin mRNAs in corpus luteum of human subjects: correlation with serum steroid hormone levels.

To understand regulation of the function of human ovarian corpus luteum by sex steroid-binding proteins, the levels of luteal intracellular sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) mRNAs and serum steroid hormones were simultaneously determined. The expression of SHBG and CBG mRNAs was detected in all samples analyzed. SHBG mRNA level was positively correlated with serum estradiol-17 beta level (p < 0.05), but not with serum progesterone level. There was a positive correlation between SHBG mRNA level and serum estradiol-17 beta/progesterone ratio (p < 0.01). On the other hand, CBG mRNA level was positively correlated with serum estradiol-17 beta and progesterone level (p < 0.01 and p < 0.01, respectively). There was no correlation between CBG mRNA level and serum estradiol-17 beta/progesterone ratio. SHBG and CBG mRNA levels were not correlated with the levels of serum testosterone, free testosterone or cortisol. These findings suggest that the synthesis of luteal SHBG and CBG is complexly regulated by estrogen and progesterone, and that SHBG and CBG interact with estrogen and progesterone, respectively, for luteal steroidal activity.

Adult↗
PubMed1999

[Second primary malignancy after surgical adjuvant therapy for gastric cancer].

Immunopotentiators are expected to intensify the effects of chemotherapy, but anticancer agents are in greater or lesser degree carcinogenic in humans. The carcinogenic risk after adjuvant chemo-immunotherapy was examined in 786 gastric cancer patients who underwent curative gastrectomy between 1963 and 1981. They consisted of 420 patients without any chemo- or immunotherapy (cont group), 302 with chemotherapy (chem group) with mitomycin C and/or fluorinated pyrimidines, and 64 with chemo-immunotherapy (chem-immu group) with both chemotherapy and immuno-potentiator (s), levamisole or PSK and/or OK-432. The incidence of cancers other than gastric cancer 5 or more years after gastrectomy was 9 out of 64 in the chem-immu group (14.1%), which was higher than the 25 out of 302 in the chem group (8.3%) and significantly higher than the 27 out of 420 in the cont group (6.4%) (p < 0.05). The 5/10-year survival rate after gastrectomy was 76.0%/72.5% in the chem-immu group, which was significantly higher than the 66.1% /59.4% in the chem group and the 64.7%/59.3% in the cont group (p < 0.05). Among 215 patients under 50 years of age, the survival rate was 72.7%/65.6% in the chem group, which was significantly lower than the 75.0%/71.7% in the cont group (p < 0.01) and lower than the 81.9%/81.9% in the chem-immu group. However, the incidence of a second malignancy showed a tendency to increase in the order of the cont, chem and chem-immu groups.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Biologic implications of the expression of vascular endothelial growth factor subtypes in ovarian carcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) has been identified as an important factor for tumor angiogenesis, which is essential for the growth, invasion, and metastasis of solid tumors. This study examines the clinical significance of VEGF subtypes in ovarian carcinoma. METHODS: Tumor specimens from 128 patients with ovarian carcinoma were evaluated for VEGF and its mRNA expression. The expression of VEGF, especially its subtypes, was determined by Western blot analysis with a sandwich enzyme immunoassay in ovarian carcinomas and reverse transcription-polymerase chain reaction and Southern blot analysis in normal ovaries that served as controls, and the relation between VEGF expression and the histologic types and clinical stages of ovarian carcinomas was analyzed. RESULTS: Among the four subtypes of VEGF, the populations of VEGF165 and VEGF121 were dominant in normal ovaries and ovarian carcinomas. The levels of VEGF and VEGF165 mRNA in ovarian carcinomas were significantly higher than in normal ovaries (P < 0.05). On the other hand, there was no significant difference in the levels of VEGF and VEGF165 mRNA among ovarian carcinomas classified according to histopathologic type or clinical stage. CONCLUSIONS: This analysis suggests that VEGF165 may be elevated in all stages of ovarian carcinoma via angiogenic activity, regardless of histopathologic type.

Adult↗
PubMed1998

Expressions of vascular endothelial growth factor (VEGF) and its mRNA in uterine endometrial cancers.

To know the potential of growth, invasion and metastasis of uterine endometrial cancer associated with neovascularization, the expressions of VEGF and its mRNA, especially their subtypes, in uterine endometrial cancers and normal uterine endometria as controls were determined by Western blot analyses with a sandwich enzyme immunoassay and RT-PCR-Southern blot analysis, respectively, and the relation between their expressions and histological grades, grades of myometrial invasion and clinical stages of uterine endometrial cancers was analyzed. The levels of VEGF (VEGF165 and VEGF121) protein and mRNA were in a wide range and higher in normal uterine endometria than in the malignant counterparts. The levels of VEGF protein were higher in order of histopathological differentiation (normal uterine endometrium > well-differentiated (G1) > moderately differentiated (G2) and poorly differentiated (G3)) and those of VEGF protein and VEGF121 mRNA were lower in order of the advance of clinical stages (normal uterine endometrium > stage I > stage II > stages III and IV). There was, however, no significant difference in their levels among uterine endometrial cancers classified according to grades of myometrial invasion. This suggests that VEGF is downregulated during uterine endometrial cancer progression with dedifferentiation. Namely, VEGF in some endometrial cancers might contribute to the early process of advancing of malignancy via angiogenic activity.

Adult↗
PubMed1998

Flow cytometric diagnosis of the cell lineage and developmental stage of acute lymphoblastic leukemia by novel monoclonal antibodies specific to human pre-B-cell receptor.

Three novel monoclonal antibodies (MoAbs) have been established that recognize distinct epitopes of a human pre-B-cell receptor (pre-BCR) composed of a mu heavy (muH) chain and a lambda5/VpreB surrogate light (SL) chain. HSL11 reacts with lambda5 whereas HSL96 reacts with VpreB. Intriguingly, HSL2 does not bind to each component of the pre-BCR but does bind to the completely assembled pre-BCR complex. Flow cytometric analyses with cytoplasmic staining of a panel of human cell lines showed that HSL11 and HSL96 specifically stained cell lines derived from the pro-B and pre-B-cell stages of B-cell development. In contrast, HSL2 stained exclusively cell lines derived from the pre-B-cell stage. These results prompted us to explore the possibility of clinical application of these MoAbs for the determination of the cell lineage and developmental stage of acute lymphoblastic leukemia (ALL). Whereas none of mature B-lineage ALLs (B-ALLs), T-lineage ALLs (T-ALLs), and acute myeloid leukemias analyzed were stained in the cytoplasm with these three MoAbs, the vast majority of non-B- and non-T-ALLs (53 out of 56 cases) were found positive for either lambda5, Vpre-B, or both in their cytoplasm. Among these 53 cytoplasmic SL chain-positive ALLs, 19 cases were also positive for cytoplasmic muH chain, indicative of pre-B-cell origin. Interestingly, 6 out of these 19 pre-B-ALL cases were found negative for cytoplasmic staining with HSL2. From these results, we propose a novel classification of B-ALL in which five subtypes are defined on the basis of the differential expression of SL chain, muH chain, pre-BCR, and light chain along the B-cell development.

Antibodies, Monoclonal↗
PubMed1998

Identification of various exon-deleted progesterone receptor mRNAs in human endometrium and ovarian endometriosis.

We demonstrated the expression of various exon-deleted progesterone receptor (PR) variant mRNAs in human uterine endometrium and ovarian endometriosis using the reverse transcription-polymerase chain reaction-DNA sequencing analyses. In addition to PR wild-type mRNA, various exon-deleted PR variant mRNAs were identified in all samples analyzed. The sequence of these variants showed a perfect junction between exons surrouding the deletion area. PR wild-type, exon 6-deleted, exon 4-deleted, exon 5, 6-deleted and exon 4, 5, 6-deleted PR variant mRNAs were observed in all samples analyzed. Exon 4, 6-deleted PR mRNA was observed only in ovarian endometriosis. This is the first study to demonstrate the coexpression of various PR exon-deleted variant mRNAs with the wild-type in uterine endometrium and ovarian endometriosis. All resulting variant proteins might indicate functional diversity and modify the progestational action of wild-type PR, and thus be involved in the pathophysiology of ovarian endometriosis.

Adult↗
PubMed1998

Human microvascular endothelial cells are strongly sensitive to Shiga toxins.

We show here that the susceptibility of endothelial cells to Shiga toxin (Stx)s differs remarkably depending on their cellular origins. The concentration of Stx-1 required to reduce cell viability by 50% as measured by MTT assay was 30 and 300 fM for neonatal and adult human microvascular endothelial cells (HMVEC), respectively, and 30 pM for human coronary artery endothelial cells (HCAEC). Human umbilical venous endothelial cells (HUVEC) and bovine aortic endothelial cells (BAEC) showed no sensitivities to Stx-1. Surprisingly, Stx-2 was approximately 10-100 times more toxic to HMVEC than Stx-1. Moreover sodium butyrate sensitized HMVEC by 100-fold to the cytotoxic activity of Stxs. These results were found to reflect the amount of Gb3/CD77 on the cell surface on a per cell basis using flow cytometrical analysis. The high sensitivity of HMVEC to Stxs suggests their involvement in the pathogenesis of organ failure induced by Stx-producing Escherichia coli.

Adult↗
PubMed1998

Dominant expression of sex-hormone-binding-globulin exon-7 splicing variant over wild-type mRNA in human ovarian cancers.

The intracellular expression of sex-hormone-binding-globulin(SHBG) exon-7-splicing-variant mRNA in human ovarian cancers was demonstrated by reverse-transcription/polymerase-chain-reaction, Southern-blot and DNA-sequencing analyses. Analysis of the missing base pairs proved that they corresponded to the entire exon 7, 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. SHBG wild-type and variant mRNA was detected in all normal ovaries and in benign and malignant ovarian tumors analyzed. There were no significant differences in mean SHBG wild-type and variant mRNA levels among the 3 types of tissue, but the ratio of SHBG exon-7-splicing-variant to wild-type mRNA level in ovarian cancers was significantly higher (p < 0.05) than that in normal ovaries, with over-expression in some benign tumors. SHBG mRNA levels and the ratio of SHBG variant to wild-type mRNA was not associated with histological classification or clinical stages of ovarian cancers. These results suggest that over-expression of SHBG-exon 7-splicing-variant mRNA to the wild type might indicate the potential for neoplastic transformation.

Blotting, Southern↗
PubMed1998

Expression of platelet-derived endothelial cell growth factor (PD-ECGF) and its mRNA in uterine endometrial cancers.

To determine the potential of growth, invasion and metastasis of uterine endometrial cancer cells associated with neovascularization, the expressions of platelet-derived endothelial cell growth factor (PD-ECGF) and its mRNA in uterine endometrial cancers and in normal uterine endometria as controls were determined and the relationship between their expressions and histological grades, grades of myometrial invasion and clinical stages of uterine endometrial cancers was analyzed. The levels of PD-ECGF were significantly higher in uterine endometrial cancers of well-differentiated grade (G1) with invasion to < or =1/2 myometrium (B) and of stage 1 than in those of moderately and poorly differentiated grades (G2 and G3, respectively) limited to endometrium (A) and with invasion to >1/2 myometrium (C) and of stages II and III/IV and in normal uterine endometria. There was no significant difference in the levels between uterine endometrial cancers of G2 and G3, A and C, or stages II and III/IV and normal uterine endometria. Therefore, the active availability of PD-ECGF might contribute to the acceleration of angiogenic activity in the early process of invasion of well-differentiated uterine endometrial cancers.

Adult↗
PubMed1998

Suppression of growth of hepatocellular carcinoma by sodium butyrate in vitro and in vivo.

Treatment of HuH-7 human hepatocellular carcinoma (HCC) cells with 1-10 mM sodium butyrate (SB) resulted in growth inhibition in a dose-dependent manner. At 3 mM and higher concentrations, SB caused nuclear fragmentation and DNA ladder formation characteristic of apoptosis. In the treated cells, the expression of p21 (WAFI/CIPI) increased and that of alpha-fetoprotein (AFP) decreased. These characteristic changes were also observed with 5 other human HCC cell lines with or without mutation of the p53 gene. The ability of these cells to form colonies in soft agar was suppressed by either pretreating the cells with SB prior to soft agar plating or incubating untreated cells in SB-containing soft agar. Direct injection of SB into tumors developed from HuH-7 cells in nude mice resulted in an increase in the p21 level, a decrease in the tumor size and an increase in the survival time of mice. When the inoculation of HuH-7 cells into nude mice was immediately followed by subcutaneous injection of SB, development of tumors was either significantly delayed or completely suppressed. These results suggest that SB induces cellular differentiation and suppresses growth and tumorigenicity of HCC cells in vitro and in viva by a mechanism independent of p53 but possibly dependent on p21.

Animals↗
PubMed1998

Expression of platelet-derived endothelial cell growth factor (PD-ECGF) and its mRNA in ovarian cancers.

The potential of growth, invasion and metastasis of ovarian cancer cells associated with neovascularization, and the expression of platelet-derived endothelial growth factor (PD-ECGF) and its mRNA in ovarian cancers were determined. The relationship between their expression and histopathological types and clinical stages of ovarian cancers was also analyzed. The levels of PD-ECGF and its mRNA were higher in ovarian cancers than in normal ovaries. Furthermore, some endometrioid carcinomas and serous cystadenocarcinomas of the ovary and some ovarian cancers in stages III and IV expressed remarkably high levels of PD-ECGF and its mRNA. Therefore, in some ovarian cancers, PD-ECGF might be related to advanced stages of ovarian cancers associated with neovascularization.

Adult↗
PubMed1998

Genomic aberrations in early stage human hepatocellular carcinomas.

BACKGROUND: Primary liver cancer, which most often takes the form of hepatocellular carcinoma (HCC), is among the 10 most common cancers in humans worldwide. In hepatocarcinogenesis, evidence of a multistep process is supported by the marked increase of HCC incidence with age; most HCCs are diagnosed in the second half of life, generally after a long period of chronic liver disease and in frequent association with cirrhosis. This long process may be correlated with the development of multiple genetic lesions, the origin of which currently remain largely unknown. In a previous study, the authors collected data on genomic DNA aberrations in primary HCC by restriction landmark genomic scanning (RLGS), a powerful screening method for the human genome. METHODS: The authors examined the genomic aberrations that occurred in early stage HCCs by means of RLGS of NotI-cleaved and 32P-end-labeled genomic DNA resolved by electrophoresis in a two-dimensional gel. More than 2000 radioactive spots originating from NotI cleavage sites were compared among six small HCC nodules and their normal counterparts. RESULTS: The intensities of five spots were consistently higher in the small HCCs, and the same effect was observed in large HCCs. In addition, the intensities of 22 spots were consistently half those of normal tissue, suggesting the loss of one allele. CONCLUSIONS: The occurrence of certain genomic alterations in early stage HCCs, as reflected by an increase or decrease in spot intensity, seems to reflect early events that occur during HCC development.

Adult↗
PubMed1998

Telomerase activity in hepatocellular carcinoma and adjacent liver tissues.

BACKGROUND AND OBJECTIVES: Activation of telomerase and stabilization of telomeres are considered necessary for immortalization of tumor cells. Telomerase activity was analyzed in 69 hepatocellular carcinomas and adjacent chronic liver disease tissues. The telomerase activity level was examined in relation to clinicopathologic features. METHODS: Telomerase activity was determined by a telomeric repeat amplification protocol. Immature and mature leukocytes were removed from homogenized tissue of adjacent livers using anti-CD45 and anti-CD15 monoclonal antibody-coated magnetic beads. RESULTS: Telomerase activity was detected in hepatocellular carcinomas and leukocytes, but not in liver cells from adjacent chronic liver disease tissues after the separation of leukocytes. All hepatocellular carcinomas displayed telomerase activity, and the activity level correlated with the degree of differentiation (P=0.021) and patient survival (P=0.039). CONCLUSIONS: These results indicate that activation of telomerase may be required as a critical step in hepatocarcinogenesis and tumor development, and detection of telomerase activity with removal of contaminating leukocytes may be useful in the characterization or prognostication of hepatocellular carcinoma.

Adult↗
PubMed1998

Activation of mitogen-activated protein kinases/extracellular signal-regulated kinases in human hepatocellular carcinoma.

Mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) is a key molecule in intracellular signal transducing pathways that transport extracellular stimuli from cell surface to nuclei. MAPK/ERK has been revealed to be involved in the physiological proliferation of mammalian cells and also to potentiate them to transform. However, its role in the outgrowth of human hepatocellular carcinoma (HCC) has yet to be clarified. Therefore, in this study, we investigated the activation of MAPK/ERK and its associated gene expression in HCC. MAPK/ERK was activated in 15 of 26 cases of HCC we examined (58%), and its activity level was significantly higher in HCC than in the adjacent non-cancerous lesions. Besides, MAPK/ERK activation in HCC was positively correlated with protein expression of transcription factor c-Fos. Furthermore, in 25 of 26 cases of HCC which genomic DNA was available, 22 cases without genomic DNA amplification exhibited positive correlation, not only between protein expression of c-Fos and cyclin D1, but also between MAPK/ERK activation and cyclin D1 expression. Concerning the relationship between MAPK/ERK activation and the clinicohistopathological features of HCC, the tumor (HCC) versus non-tumor (non-cancerous counterpart) ratio (T/N) of MAPK/ERK activity was positively correlated with tumor size, but neither with the stage of HCC nor the degree of differentiation of HCC. In conclusion, these findings suggest that MAPK/ERK activation in human HCC may play an important role in multistep hepatocarcinogenesis, especially in the progression of HCC; at least in part, through cyclin D1 up-regulation primarily induced by MAPK/ERK via c-Fos.

Aged↗
PubMed1998

Expression of sex hormone-binding globulin exon VII splicing variant messenger ribonucleic acid in human ovarian endometriosis.

OBJECTIVE: To investigate the expression of sex hormone-binding globulin (SHBG) exon VII splicing variant messenger RNA (mRNA) in human ovarian endometriosis. DESIGN: The expression of SHBG variant mRNA in normal uterine endometrium and endometriotic tissue was determined. SETTING: Department of Obstetrics and Gynecology, Gifu University Hospital. PATIENT(S): Fourteen women with endometriosis and 18 women without endometriosis. INTERVENTION(S): Normal uterine endometrial and ovarian endometriotic tissues from patients who had undergone gynecological surgery were studied. MAIN OUTCOME MEASURE(S): Levels of SHBG wild-type and variant mRNAs were determined using the quantitative reverse transcription-polymerase chain reaction. RESULTS(S): Analysis of the missing base pairs proved that they corresponded to the entire exon VII. There was no significant difference between the levels of SHBG wild-type mRNA in normal endometria and in endometriotic endometria, although the levels of SHBG variant mRNA in endometriotic endometria were significantly higher than that in normal endometria. The ratio of SHBG variant to wild-type mRNA levels was significantly higher in endometriotic endometria than in normal endometria. CONCLUSION(S): This study demonstrates the coexpression of SHBG exon VII splicing variant mRNA with its wild-type and the dominant expression of the variant in ovarian endometriosis. These results might be involved in the cellular estrogenic interaction, plausibly assisting in the development and growth of ovarian endometriosis.

Adult↗
PubMed1998

DNA polymorphism in B-domain of the estrogen receptor-alpha among Japanese women.

A silent mutation in B-domain of the estrogen receptor-alpha (ER B) change codon 87 (from GCG to GCC) is clinically correlated with frequent spontaneous abortion and familial history of breast cancer among Caucasian patients. However, none of the 167 Japanese female patients and 46 Japanese female healthy volunteers showed ER B variant. Therefore, this DNA polymorphism might involve a genetic racial difference, and appears not to be correlated with frequent spontaneous abortion or familial history of breast cancer at least among Japanese women.

Abortion, Spontaneous↗