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Hironobu Kimura

Publications and source records attributed to Hironobu Kimura.

14 recordsLinked to original sources
PubMed2006

[A case of nonresected gastric cancer with peritoneal dissemination maintained on TS-1, cisplatin (CDDP) and docetaxel combination chemotherapy with good QOL].

A 64-year-old woman was admitted to the hospital for abdominal fullness and constipation. In the pelvic cavity, an abdominal CT scan revealed massive ascites showing malignancy on histological examination. Upper GI endoscopy revealed type 3 gastric cancer from the anglus to the cardia. A barium-enema showed a stenotic lesion at the sigmoid colon due to peritoneal dissemination. An abnormally high CA125(1,400 mg/ml) level was detected in serum. We performed systemic chemotherapy of TS-1, CDDP and peritoneal infusion of docetaxel on the nonresected gastric cancer with peritoneal dissemination. After 2 cycles, cytology of ascites revealed no malignancy, and the serum CA125 value regained its normal level. After 3 cycles, the killer cell effect was recognized by laparoscopic examination and the stenotic change of sigmoid colon had almost disappeared. The patient clinically achieved good QOL by this method, which was very effective for nonresected gastric cancer with peritoneal dissemination.

Adenocarcinoma, Mucinous↗
PubMed2005

Nanog expression in mouse germ cell development.

Nanog is a newly identified transcriptional factor bearing a homeodomain and expressed in pluripotential cells of preimplantation and early postimplantation embryos, and embryonic stem (ES) and embryonic germ (EG) cells. Knockout experiments indicate that Nanog functions as a key player in maintaining the pluripotency of stem cells. Importantly, Nanog expression is highly expressed in primordial germ cells (PGCs) of E11.5 and E12.5 mouse embryos. However, its temporal and spatial expression pattern and function in germ cells are largely unknown. To address these issues, whole embryos and cryosections of embryos were immunostained with anti-NANOG and anti-STELLA/PGC7 antibodies. NANOG expression, repressed in colonized PGCs of E7.25-E7.5 embryos, became detectable in migrating PGCs of E7.75-E8.0 embryos. Both male and female PGCs migrating in E9.5 and E10.5 embryos and colonizing the genital ridges of E11.5 and E12.5 embryos were positive for NANOG immunostaining, while the NANOG expression pattern differed between the sexes in the later developmental stage. In female gonadal PGCs of E13.5 and E14.5 embryos, NANOG became undetectable in germ cells positive for the synaptonemal complex-specific protein SCP3, while in male PGCs of E14.5-E16.5 embryos, the number of NANOG-positive germ cells drastically decreased during the mitotic arrest. No germ cells positive for NANOG were detectable in testes and ovaries of adult mice. Thus, in germ cell development, NANOG is expressed in proliferating germ cells, in which nuclear reprogramming is progressing.

Animals↗
PubMed2005

Pluripotential competence of cells associated with Nanog activity.

Nanog is a novel pluripotential cell-specific gene that plays a crucial role in maintaining the undifferentiated state of early postimplantation embryos and embryonic stem (ES) cells. We have explored the expression pattern and function of Nanog and a Nanog-homologue, Nanog-ps1.Nanog-ps1 was mapped on Chromosome 7 and shown to be a pseudogene. Immunocytochemical analysis in vivo showed that the NANOG protein was absent in unfertilized oocytes, and was detected in cells of morula-stage embryos, the inner cell mass of blastocysts and the epiblast of E6.5 and E7.5 embryos, but not in primordial germ cells of early postimplantation embryos. In monkey and human ES cells, NANOG expression was restricted to undifferentiated cells. Furthermore, reactivation of the somatic cell-derived Nanog was tightly linked with nuclear reprogramming induced by cell hybridization with ES cells and by nuclear transplantation into enucleated oocytes. Notably, mouse Nanog (+/-) ES cells, which produced approximately half the amount of NANOG produced by wild-type ES cells, readily differentiated to multi-lineage cells in culture medium including LIF. The labile undifferentiated state was fully rescued by constitutive expression of exogenous Nanog. Thus, the activity of Nanog is tightly correlated with an undifferentiated state of cells even in nuclear reprogrammed somatic cells. Nanog may function as a key regulator for sustaining pluripotency in a dose-dependent manner.

Amino Acid Sequence↗
PubMed2005

Octamer and Sox elements are required for transcriptional cis regulation of Nanog gene expression.

The pluripotential cell-specific gene Nanog encodes a homeodomain-bearing transcription factor required for maintaining the undifferentiated state of stem cells. However, the molecular mechanisms that regulate Nanog gene expression are largely unknown. To address this important issue, we used luciferase assays to monitor the relative activities of deletion fragments from the 5'-flanking region of the gene. An adjacent pair of highly conserved Octamer- and Sox-binding sites was found to be essential for activating pluripotential state-specific gene expression. Furthermore, the 5'-end fragment encompassing the Octamer/Sox element was sufficient for inducing the proper expression of a green fluorescent protein reporter gene even in human embryonic stem (ES) cells. The potential of OCT4 and SOX2 to bind to this element was verified by electrophoretic mobility shift assays with extracts from F9 embryonal carcinoma cells and embryonic germ cells derived from embryonic day 12.5 embryos. However, in ES cell extracts, a complex of OCT4 with an undefined factor preferentially bound to the Octamer/Sox element. Thus, Nanog transcription may be regulated through an interaction between Oct4 and Sox2 or a novel pluripotential cell-specific Sox element-binding factor which is prominent in ES cells.

5' Flanking Region↗
PubMed2004

Pedunculated giant gastrointestinal stromal tumor of the stomach showing extragastric growth: report of a case.

We report an unusual case of a pedunculated gastrointestinal stromal tumor (GIST) of the stomach with extragastric growth. An 84-year-old woman was referred to our hospital for investigation of anemia. Barium meal examination showed a defect occupying the lesser curvature of the stomach from the middle of the corpus to the fornix and an abdominal computed tomography scan, showed a lesion, 20 cm in diameter, touching the surface of the spleen. Laparotomy revealed a tumor located between the liver and spleen. As the tumor appeared to be connected with the posterior wall of the gastric corpus by a pedicle, it was resected with a pedunculated lesion of the stomach. Based on the pathological findings, the tumor was diagnosed as a GIST of uncommitted type, with low-grade malignancy.

Aged↗
PubMed2004

Feasibility study of adjuvant chemotherapy with S-1 (TS-1; tegafur, gimeracil, oteracil potassium) for gastric cancer.

BACKGROUND: We conducted a feasibility study using S-1, a novel oral derivative of 5-fluorouracil, as postoperative adjuvant chemotherapy for curatively resected gastric cancer patients. METHODS: Adjuvant chemotherapy consisted of eight courses (4-week administration and 2-week withdrawal) of S-1, at 80-120 mg/body per day. Forty-one patients from 11 institutions were enrolled in this pilot study, from November 1999 to October 2000. RESULTS: Thirty-five patients were eligible. In 7 patients, S-1 administration was discontinued due to recurrence. Among the 28 patients without recurrence, the planned eight courses of S-1 were administered to 17 patients (60.7%). In 4 patients, S-1 administration was discontinued due to subjective symptoms, such as anorexia, in the first course. Adverse reactions such as neutropenia, leukopenia, elevated total bilirubin, anorexia, general fatigue, diarrhea, nausea, and stomatitis were seen in more than half of the patients. Although grade 3 neutropenia (29.3%), leukopenia (9.8%), and diarrhea (9.8%) were observed, no grade 4 adverse effects appeared. Compared with the treatment of unresectable or recurrent gastric cancer with S-1, the incidence of adverse reactions in the adjuvant setting was slightly higher, probably due to the influence of gastrectomy. CONCLUSION: Except for the early development of anorexia, most likely due to adverse effects of surgery, postoperative administration of S-1 for 1 year seems feasible as adjuvant chemotherapy for gastric cancer.

Adenocarcinoma↗
PubMed2004

Histone code modifications on pluripotential nuclei of reprogrammed somatic cells.

Following hybridization with embryonic stem (ES) cells, somatic genomes are epigenetically reprogrammed and acquire pluripotency. This results in the transcription of somatic genome-derived tissue-specific genes upon differentiation. During nuclear reprogramming, it is expected that DNA and chromatin modifications, believed to function in cell-type-specific epigenotype memory, should be significantly modified. Indeed, current evidence indicates that acetylation and methylation of histone H3 and H4 amino termini play a major role in the regulation of gene activity through the modulation of chromatin conformation. Here, we show that the reprogrammed somatic genome of ES hybrid cells becomes hyperacetylated at H3 and H4, while lysine 4 (K4) of H3 becomes globally hyper-di- and -tri-methylated. In the Oct4 promoter region, histones H3 and H4 are acetylated and H3-K4 is highly tri-methylated on both the ES and reprogrammed somatic genomes, which correlates with gene activation and DNA demethylation. However, H3-K4 is also di- and tri-methylated in the promoter regions of Neurofilament-M (Nfm), Nfl, and Thy-1, which are all silent in both ES and hybrid cells. Thus, H3-K4 di- and tri-methylation of reprogrammed somatic genomes is independent of gene activity and represents one of the major events that occurs during somatic genome reprogramming towards a transcriptional activation-permissive state.

Acetylation↗
PubMed2003

Pluripotency of reprogrammed somatic genomes in embryonic stem hybrid cells.

Somatic nuclei can be epigenetically reprogrammed by factors present in undifferentiated embryonic stem (ES) cells. The acquisition of pluripotency by somatic genomes could render such cells a viable source of personalized cell type(s) for therapeutic application, avoiding the need for controversial therapeutic cloning. To investigate this possibility, we first determined the origin of transcripts in teratomas generated from mouse (ES x somatic cell) hybrid clones. Transcription of markers from the somatic genome demonstrated efficient in vivo differentiation down independent lineages. The induction of dopaminergic neurons by coculture with stromal PA6 feeder cells also demonstrated efficient capacity to differentiate in vitro. Hybrid clone-derived neurons expressed appropriate markers, and transcription of Pitx3 from the somatic genome was confirmed. When transplanted into mouse brains, the dopaminergic neurons were successfully integrated and expressed tyrosine hydroxylase. Thus, it should be possible to produce personalized ES-like cells with the reprogrammed somatic genomes.

Animals↗
PubMed2002

Exogenous expression of mouse Dnmt3 induces apoptosis in Xenopus early embryos.

Mouse DNA (cytosine-5) methyltransferases Dnmt3a and Dnmt3b are expected to be de novo-type DNA methyltransferases. In the present study, we found that exogenously expressed mouse Dnmt3a or Dnmt3b induced abnormal cell clusters at the gastrulation stage in Xenopus embryos. The abnormal cells were judged to be apoptotic from the positive staining with the TdT dUTP nucleotide end-labeling method and the rescue by hBcl-x(L), a Bcl-2 homologue. On the other hand, neither bacterial DNA (cytosine-5) methyltransferase nor Dnmt3b3, one of the three isoforms of Dnmt3b that has no DNA methylation activity, induced apoptosis. In addition, mutant Dnmt3a and the other two Dnmt3b isoforms, Dnmt3b1 and Dnmt3b2, which have no DNA methylation activity due to a change of the cysteine residue in the catalytic center to an alanine residue, retained the ability to induce apoptosis. This indicates that the apoptosis was not induced by DNA methylation activity. The domain of Dnmt3b1 (3b2) responsible for the apoptosis is the catalytic domain in the carboxyl-terminal half.

Animals↗
PubMedDate not supplied

Correlation between expression levels of thymidine phosphorylase (dThdPase) and clinical features in human gastric carcinoma.

BACKGROUND/AIMS: dThdPase (thymidine phosphorylase) is an enzyme that is involved in pyrimidine nucleoside metabolism. It has been recently reported that dThdPase is identical to platelet-derived endothelial cell growth factor. Previous studies demonstrated that the immunohistochemical expression of dThdPase was related with disease progression. The purpose of this study was to examine the expression levels of dThdPase and their prognostic significance in gastric carcinoma, prospectively. METHODOLOGY: We obtained fresh samples (tumors and adjacent normal mucosa) from 263 patients with gastric cancer who underwent gastrectomy between April 1998 and March 2000. dThdPase was analyzed by the enzyme-linked immunosorbent assay method. RESULTS: The expression levels of dThdPase in tumors (98.4 +/- 62.5 U/mg protein) was significantly higher than that in normal mucosa (46.5 +/- 27.8 U/mg protein) (P < 0.0001). Intratumoral dThdPase levels were significantly higher in Borrmann types II and III macroscopically (P < 0.01), in poorly differentiated type histologically (P < 0.05), and in the tumor-invading serosa (P < 0.001). The expression levels of dThdPase were also significantly higher in tumor tissue from patients with lymph node metastasis (P < 0.01) and in that from patients with lymphatic invasion (P < 0.05). The survival rate of patients with tumor of high dThdPase (> or = 100 U/mg protein) was significantly poorer than that of patients with tumor of low dThdPase (< 100 U/mg protein) (P < 0.05). CONCLUSIONS: These findings indicate that the measurement of dThdPase may provide useful information for predicting prognosis in gastric carcinomas.

Adult↗
PubMedDate not supplied

Successful resection of locally advanced rectal carcinoma combined with preoperative chemoradiation.

Chemoradiation increases the local control and colostomy-free survival in patients with advanced anal canal carcinomas. We recently experienced a 50-year-old female patient with locally advanced carcinoma of the rectum invading to the sacrum, which could not be surgically resected. Therefore, we performed a colostomy and transarterial infusion of anti-tumor drugs including 50 mg cisplatin and 10 mg mitomycin C via the inferior mesentery artery in September 1999. She then underwent radiotherapy with a total dose of 64 Gy for the primary tumor. After the radiotherapy the patient received 125 mg/body of 1-leucovorin by 2-hour infusion and, one hour after starting the 1-leucovorin infusion, she received an intravenous bolus of 250 mg/body of 5-fluorouracil. This regimen was conducted biweekly for 13 courses followed by oral administration of 400 mg 5'-deoxyfluorouridine for one year. Since the chemoradiation resulted in a successful response, the patient underwent curative resection of the primary tumor in June 2001. The resected tumor (32 x 35 mm) had clean margins. Although the carcinoma cells had disappeared, fibrous lesions were observed over a broad area. Based on these pathologic findings, the treatment effect was judged as grade Ib.

Antineoplastic Combined Chemotherapy Protocols↗