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Biomedical subjects

Yukiko Mori

Publications and source records attributed to Yukiko Mori.

14 recordsLinked to original sources

Gli-1 expression is associated with lymph node metastasis and tumor progression in esophageal squamous cell carcinoma.

OBJECTIVE: We investigated the expression and function of the hedgehog (Hh) pathway in human esophageal squamous cell carcinoma (ESCC). METHODS: The expression of Hh pathway molecules were detected in 34 human ESCC cell lines by RT-PCR. Subsequently, we investigated the effects of cyclopamine, a specific inhibitor of the Hh pathway, on cell proliferation, migration and invasion. Next, the effects of siRNA targeting Gli-1 were examined. Immunohistochemically, the expression of Gli-1 was studied in 104 ESCC specimens and compared with the clinicopathological characteristics of the patients. RESULTS: Gli-1 were expressed in 31 of 34 cell lines (91%), while Sonic hedgehog (SHh), Patched (Ptch), and Smoothened (Smo) expression was noted in all 34 cell lines. Cyclopamine significantly inhibited cell proliferation and migration in ESCC cells that expressed Gli-1. siRNA targeting Gli-1 inhibited cell growth in ESCC cells. Gli-1 was expressed in 52 of 104 cancer specimens (50%). Gli-1 expression was associated with tumor depth (p < 0.001), positive lymph node metastasis (p = 0.004) and a poor prognosis (p = 0.0047). CONCLUSION: Our results raise the possibility that the inhibition of the Hh pathway could be a novel target for esophageal cancer therapy.

Antineoplastic Agents↗

The biological role of the low-affinity p75 neurotrophin receptor in esophageal squamous cell carcinoma.

UNLABELLED: In this study, we investigated the clinicopathologic significance of the low-affinity p75 neurotrophin receptor (p75NTR; which is expressed in the stem/progenitor cell fraction of normal esophageal epithelial cells) in 187 resected esophageal squamous cell carcinoma (ESCC) specimens and found that approximately 50% of ESCC expressed p75NTR. Our investigation using ESCC cell lines showed that p75NTR was intensely expressed in the cells with high colony-forming capacity but they were sensitive to cell death on inhibition of p75NTR expression with transient transfection of small interfering RNA (siRNA). These findings suggest that p75NTR is necessary for survival and maintenance of ESCC tumors, providing us with a potential target for novel therapies. PURPOSE: p75NTR is expressed in a stem/progenitor cell fraction of human normal esophageal epithelial cells. In this study, we investigated the expression and biological role of p75NTR in ESCC. EXPERIMENTAL DESIGN: The expression of p75NTR in 187 resected ESCC specimens was immunohistochemically investigated. The expression of p75NTR in 30 ESCC cell lines (KYSEs) was assessed by reverse transcription-PCR, immunocytochemistry, and flow cytometry. The p75NTR-bright and p75NTR-dim/negative cells were isolated from KYSE150 by magnetic beads and colony formation was investigated. The role of p75NTR in KYSEs was assessed by transient transfection of siRNA. RESULTS: p75NTR was expressed in 92 of 187 (49.2%) tumors. In well-differentiated tumors, positive staining was apparent in the first one to two layers from infiltrative margin of the tumors where most of the cells were actively proliferating. In moderately differentiated tumors, p75NTR was expressed in wider range from the margin of the tumors whereas p75NTR was diffusely distributed in poorly differentiated tumors. p75NTR was expressed in all examined KYSEs and the mean proportion of the p75NTR-bright fraction was 30.1%. The size of p75NTR-positive colonies was larger than that of p75NTR-negative colonies derived from KYSE150 (P<0.0001). The purified p75NTR-bright cells formed p75NTR-positive large colonies more frequently than the p75NTR-dim/negative cells (P<0.0001). Down-regulation of p75NTR expression by siRNA resulted in marked growth inhibition with induction of apoptosis. CONCLUSIONS: Our findings suggest that p75NTR is necessary for survival and maintenance of ESCC tumors, providing us with a potential target for novel therapies.

Adult↗

Red light causes a reduction in IAA levels at the apical tip by inhibiting de novo biosynthesis from tryptophan in maize coleoptiles.

When maize coleoptiles were unilaterally exposed to red light (7.9 micromol m(-2)s(-1) for 5 min), 3 h after treatment IAA levels in coleoptiles decreased in all regions, from top to basal, with levels about 60% of dark controls. Localized irradiation in the 5 mm top zone was sufficient to cause the same extent of IAA reduction in the tips to that in the tips of whole irradiated shoots. When coleoptiles were treated with N-1-naphthylphthalamic acid (NPA), an accumulation of IAA in the tip and a decrease of diffusible IAA from tips were simultaneously detected. IAA accumulation in red-light treated coleoptiles by NPA was much lower than that of dark controls. NPA treatment did not affect the content of conjugated IAA in either dark or light treated coleoptile tips. When (13)C(11) (15)N(2)-tryptophan (Trp) was applied to the top of coleoptiles, substantial amounts of stable isotope were incorporated into free IAA in dark and red-light treated coleoptile tips. The ratio of incorporation was slightly lower in red-light treated coleoptile tips than that in dark controls. The label could not be detected in conjugated IAA. The rate of basipetal transport of IAA was about 10 mm h(-1) and the velocity was not affected by red light. These results strongly suggest that red light does not affect the rates of conversion of free IAA to the conjugate form or of the basipetal transport, but just reduces the IAA level in the tips, probably inhibited by IAA biosynthesis from Trp in this region.

Indoleacetic Acids↗

Urinary creatinine excretion and protein/creatinine ratios vary by body size and gender in children.

Urinary protein/creatinine ratio (Up/cr) is a simple measurement for evaluation of proteinuria. However, exact effects of body size and gender on urinary excretion of creatinine and Up/cr remain unknown. We aimed to clarify their effects. Early morning urine samples were collected from 124 children with urinary tract disorders. Urinary hourly excretion of creatinine, Ucr (in milligrams per hour), urinary hourly excretion of protein per body surface area, Up (milligrams per square meter per hour), and Up/cr (milligrams per milligram) were calculated. Effects of gender, age, body height, body weight and body surface area on Ucr and Up/cr were analyzed, respectively, in a multiple linear regression model. Body surface area and gender affected Ucr (r2=0.842, P<0.0001). Ucr adjusted by body surface area increased as body surface area grew with moderate variation. Up/cr showed a close correlation with Up and was affected by body height and gender as well. The regression equation showed that Up/cr values corresponding to the normal upper limit of Up, i.e., 4 mg/m2/h, in boys and girls 170 cm tall were approximately one third of those in children 80 cm tall (0.121 vs 0.043 for boys, 0.132 vs 0.047 for girls). The present study indicates that estimation of Up/cr needs to include consideration of children's body height and gender.

Adolescent↗

Clinical significance of osteopontin in esophageal squamous cell carcinoma: comparison with common tumor markers.

OBJECTIVE: Osteopontin (OPN) is a secreted integrin-binding glycophosphoprotein that may have a role in head and neck squamous cell carcinoma (SCC). To evaluate the clinical significance of OPN in esophageal squamous cell carcinoma (ESCC), we compared plasma OPN levels with those of common tumor markers. METHODS: Preoperative plasma OPN levels were measured by enzyme immunoassay in 103 ESCC patients. Serum SCC antigen, Cyfra 21-1, and carcinoembryonic antigen (CEA) levels were also measured routinely at admission by radioimmunoassay. RESULTS: Plasma OPN levels ranged from 82.8 to 1,980 ng/ml. High OPN level was associated with lymph node metastasis (p = 0.05), but not with tumor histology or depth of invasion. The overall survival of the patients with high OPN levels was worse than that of those with low OPN levels (p = 0.02). SCC antigen and Cyfra 21-1 levels were associated with the depth of tumor invasion, the tumor diameter, lymph node metastasis, and the overall survival, but CEA was not associated with these clinicopathological factors. Combined evaluation of OPN plus Cyfra 21-1 or OPN plus SCC antigen was useful as an independent prognostic indicator. CONCLUSION: Measurement of the plasma OPN level, as well as serum SCC antigen and Cyfra 21-1, may help to predict the progression of ESCC.

Aged↗

Quantification of L-type fatty acid binding protein in the urine of preterm neonates.

We measured urinary excretion of L-type fatty acid binding protein (L-FABP) in preterm neonates on days 1, 5-10, and 25-30 of life. Urinary L-FABP levels (expressed as the ratio to creatinine) in preterm neonates were considerably higher than those of healthy adults. They did not change significantly during the study period. Urinary L-FABP levels showed significant positive correlation with those of urinary N-acetyl-beta-D-glucosaminidase activity on day 1, and with those of 8-hydroxy-2'-deoxyguanosine on days 25-30. These results suggest that L-FABP is expressed in the neonatal kidney. Our results may also point to potential effects of proximal tubular damage and oxidative stress on urinary excretion of L-FABP.

8-Hydroxy-2'-Deoxyguanosine↗

Formation of embryogenic cell clumps from carrot epidermal cells is suppressed by 5-azacytidine, a DNA methylation inhibitor.

Using a direct somatic embryogenesis system in carrot, we examined the role of DNA methylation in the change of cellular differentiation state, from somatic to embryogenic. 5-Azacytidine (aza-C), an inhibitor of DNA methylation suppressed the formation of embryogenic cell clumps from epidermal carrot cells. Aza-C also downregulated the expression of DcLEC1c, a LEC1-like embryonic gene in carrot, during morphogenesis of embryos. A carrot DNA methyltransferase gene, Met1-5 was expressed transiently after the induction of somatic embryogenesis by 2,4-dichlorophenoxyacetic acid (2,4-D), before the formation of embryogenic cell clumps. These findings suggested the significance of DNA methylation in acquiring the embryogenic competence in somatic cells in carrot.

2,4-Dichlorophenoxyacetic Acid↗

Marked renal damage in a child with hydronephrosis infected by Trichosporon asahii.

We describe a case of urinary infection caused by Trichosporon asahii, which drastically aggravated renal function in a left hydronephrotic kidney. Previous implantation of a nephrostomy tube and a ureteral J-stent and administration of broad-spectrum antibiotics seemed to have predisposed the non-granulocytopenic child to the urinary fungal infection.

Child↗

Overexpression of HER-2/neu is not a risk factor in ovarian clear cell adenocarcinoma.

OBJECTIVE: To evaluate the significance of the expression of HER-2/neu as a prognostic factor, we retrospectively examined its overexpression rates chiefly in ovarian clear cell adenocarcinoma (CCA) and their relationships with FIGO stage, lymph node metastasis, and prognosis. METHODS: In addition to 90 specimens of CCA (stage I, 52; stage II, 7; stage III, 28; stage IV, 3) obtained between 1987 and 2002, 19 specimens of serous adenocarcinoma (S), 19 specimens of mucinous adenocarcinoma (M), and 19 specimens of endometrioid adenocarcinoma (E) collected at initial surgery were studied. The expression of HER-2/neu was immunohistologically scored on a scale of 0 to 3+ according to the HercepTest scoring system, and 2+ and 3+ were regarded as overexpression. The relationship between HER-2/neu overexpression and outcome was evaluated by the Kaplan-Meier method and the log-rank test. The relationship with advanced-stage cancer was analyzed by Fisher's exact test. The relationships with lymph node metastasis and histologic types were compared by the t test. RESULTS: The rate of HER-2/neu overexpression in CCA was 45.6% (0, 1+, 2+, and 3+ in 14, 35, 36, and 5 cases, respectively), and no differences in the overexpression rate were noted among histologic types: 52.7% in S, 42.1% in M, and 26.4% in E. In CCA, no association was observed between HER-2/neu overexpression and cumulative survival rate (P = 0.5708), FIGO stage (P = 0.5147), or lymph node metastasis (P = 0.3624). CONCLUSION: The absence in CCA of an association between HER-2/neu overexpression and outcome, stage, or lymph node metastasis indicates that HER-2/neu overexpression is not a prognostic risk factor.

Adenocarcinoma, Clear Cell↗

Infiltration of neutrophils is required for acquisition of metastatic phenotype of benign murine fibrosarcoma cells: implication of inflammation-associated carcinogenesis and tumor progression.

QR-32 tumor cells, a clone derived from a murine fibrosarcoma, are poorly tumorigenic and nonmetastatic when injected into syngeneic C57BL/6 mice. However, they are converted to highly malignant ones once they have grown in vivo after being co-implanted in a subcutaneous site with a foreign body, a gelatin sponge. Early phase of inflammation induced by the gelatin sponge participates in the conversion and histological analysis shows predominant infiltration of neutrophils. The objective of this study was to determine whether the depletion of the infiltrating neutrophils has any effect on the tumor progression. Intraperitoneal administration of a monoclonal anti-granulocyte antibody, RB6-8C5 (RB6), depleted neutrophils from both the peripheral blood circulation and the local inflamed site in mice with co-implantation of QR-32 tumor cells and gelatin sponge. The RB6 administration did not inhibit either tumor development or growth of QR-32 tumor cells. In contrast, tumor cell lines established from RB6-administered mice showed a significant decrease in metastatic incidence as compared with the tumor cell lines obtained from the mice with administration of control rat IgG or saline. Metastatic ability was significantly suppressed when RB6 had been administered in the early phase (from day -2 to day 6 after implantation); however, the administration in the middle (from day 6 to day 14) or late (from day 14 to day 22) phase did not affect the metastatic ability. We confirmed the phenomena by using integrin beta(2) knockout mice that had impaired neutrophil infiltration into inflamed sites. In the knockout mice, neutrophils hardly infiltrated into the gelatin sponge and the tumors showed dramatically suppressed metastatic phenotype as compared with those in wild-type mice or nude mice. Immunohistochemical analysis demonstrated that expressions of 8-hydroxy-2'-deoxyguanosine and nitrotyrosine were parallel to those in the presence of neutrophils. These results suggested that inflammation, especially when neutrophils infiltrate into tumor tissue, is primarily important for benign tumor cells to acquire metastatic phenotype.

8-Hydroxy-2'-Deoxyguanosine↗

Preoperative diagnosis of malignant transformation arising from mature cystic teratoma of the ovary.

OBJECTIVE: Mature cystic teratoma of the ovary (MCT) is the most common ovarian cystic disease in young women. Although it is a rare occurrence, some cases develop malignant transformation (MT), which results in serious consequences. However, MT is currently diagnosed only by postoperative pathology in most cases. We have conducted a retrospective study in an attempt to seek the factor to diagnose MT from MCT prior to surgery. STUDY DESIGN: Eighty-one patients with MCT and 39 patients with MT were entered in this study. Patient's age, tumor size, serum CEA levels, and serum SCC levels were tested by the Mann-Whiteney U test. Sensitivity and specificity were calculated, and the most suitable point was searched from the receiver operating characteristic (ROC) curve. RESULTS: A significant difference was recognized in both patient's age and serum SCC level (P < 0.0001). For a patient less than 40 years old, the sensitivity to MT was 95%, and then the specificity to MT was 63%. When the standard value of the SCC level of the serum was established as 2.5 ng/ml, the sensitivity to MT was 80% and the specificity to MT was 94%. We apply two criteria at the same time (serum SCC levels less than 2.5 ng/ml and patient's age less than 40 years old). The sensitivity for MT was 77% and specificity was 96%. CONCLUSION: The combination of the two criteria which are patient's age (under 40 years old) and serum SCC level (under 2.5 ng/ml) was considered a suitable marker for differential diagnosis between MCT and MT. Further the possibility for MT is quite low when the patient is 39 years old or younger and the serum SCC level is under 2.5 ng/ml. When any patient satisfies this condition, laparoscopic surgery will be able to be planned safely.

Adult↗

Procedural memory in schizophrenia assessed using a mirror reading task.

The preservation of procedural memory in individuals with schizophrenia has been confirmed by methods such as the Tower of Hanoi, pursuit rotor and mirror reading tests. However, the cognitive procedural memory of Japanese subjects with schizophrenia has never been assessed using mirror reading. To better determine the characteristics of cognitive procedural memory in schizophrenia, a Japanese version of the mirror reading task, consisting of cards with words written in Japanese katakana characters in mirror image, was administered to 18 Japanese patients with schizophrenia and 21 normal controls. The results indicated that the patients indeed learned the skill despite exhibiting lower overall performances in reading time than the controls, their scores displaying correlation with the severity of schizophrenic negative symptoms. This suggests that procedural memory for this task is retained in individuals with schizophrenia. It is important for them to use their preserved procedural memory for efficient rehabilitative efforts.

Adult↗

Variation of the amino acid content of Arabidopsis seeds by expressing soybean aspartate aminotransferase gene.

We have increased the contents of several amino acids in the seeds of Arabidopsis thaliana by introduction of aspartate aminotransferase (AAT), an enzyme of the aspartate biosynthetic pathway. mRNA was prepared from one-week-old seedlings of Glycine max cv. enrei and the cDNA encoding AAT5 was isolated and linked to the CaMV35S promoter in the plant vector pBI121. The AAT5 gene encodes a protein of 462 amino acid residues that shows 51% amino acid sequence similarity to A. thaliana chloroplast Asp3. The soybean AAT5 also contains a chloroplast transit peptide and is able to functionally complement a Saccharomyces cerevisiae mutant lacking the Asp5 gene. A. thaliana was transformed with the AAT5 gene from Agrobacterium tumefaciens by the vacuum infiltration method. The AAT5 gene was detected in the transcript and genomic DNA from the transgenic T2 plants. The T3 progeny showed a 3:1 segregation ratio indicating the presence of a single integration. Expression of G. max AAT5 in A. thaliana transformants caused 3-, 4-, 23-, and 50-fold increases in the contents of free glycine, alanine, asparagine, and glutamine, respectively, in the T3 seeds. A decrease in the contents of valine, tyrosine, isoleucine, leucine, and phenylalanine by several folds was also observed. Thus, it is of interest that a key gene expression resulted in marked changes of metabolites in plant seeds.

Journal Article↗