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ABSTRACT: BACKGROUND: We evaluated the safety, efficacy, and compliance of 1-year treatment with S-1 in patients with stage II/III resectable colorectal cancer. METHODS: S-1 was administered orally in two divided doses daily. The dose was assigned according to body surface area (BSA) as follows: BSA <1.25 m(2), 80 mg/day; BSA ≥1.25 to <1.5 m(2), 100 mg/day; and BSA ≥1.5 m(2), 120 mg/day. S-1 was given for 28 consecutive days, followed by a 14-day rest. The study objects were the rate of completion of treatment as planned at 1 year, the ratio of the actually administered dose to the planned dose at 1 year, and the total number of days of treatment. RESULTS: At 1 year, the rate of completion of treatment as planned was 77.7 % (42/54 patients), and the ratio of the actually administered dose to the planned dose was 82.9 %. The mean and median total numbers of days of treatment were 209 and 252, respectively. Grade 3 or higher toxicity (watery eyes) occurred in only 1 patient. CONCLUSION: S-1 adjuvant chemotherapy had acceptable compliance, safety, and efficacy in patients with colorectal cancer. S-1 adjuvant chemotherapy is considered a possible standard treatment regimen for colorectal cancer.
International Journal of Clinical Oncology 05/2012; · 1.41 Impact Factor
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ABSTRACT: A girl presented with a right adrenal mass, and multiple hepatic lesions and subcutaneous nodules 3 months after complete resection of left adrenal neuroblastoma in the neonatal period. She was treated with six cycles of chemotherapy and is well after 13 months' follow-up. This is the first case report of heterochronous bilateral adrenal stage 4S NB.
Pediatric Surgery International 01/2012; 28(1):59-62. · 1.25 Impact Factor
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Akira Morimoto,
Yoko Shioda,
Toshihiko Imamura,
Hirokazu Kanegane,
Takashi Sato,
Kazuko Kudo,
Shinichiro Nakagawa,
Hisaya Nakadate,
Hisamichi Tauchi,
Asahito Hama,
Masahiro Yasui,
Yoshihisa Nagatoshi,
Akitoshi Kinoshita,
Ryosuke Miyaji, Tadashi Anan,
Miharu Yabe,
Junji Kamizono
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ABSTRACT: Several studies have suggested that Langerhans cell histiocytosis (LCH) is responsive to treatment with bisphosphonates (BPs). However the efficacy and safety of BPs therapy for childhood LCH is unknown.
Data on children with LCH who had received BPs therapy were collected retrospectively from hospitals participating in the Japanese Pediatric Leukemia/Lymphoma Study Group.
Twenty-one children with histologically proven LCH were identified. Of these, the case histories of 16 children who had been treated with pamidronate (PAM) for disease reactivation were analyzed in detail. The median post-PAM therapy follow-up period was 2.8 years (range: 0.9-9.3 years). The median age at commencement of PAM therapy was 9.4 years (range: 2.3-15.0 years). All children had one or more bone lesions but none had risk organ (RO) involvement. In the majority of the children, six courses of PAM were administered at a dose of 1.0 mg/kg/course at 4-week intervals. In 12 of the 16 children, all active lesions including lesions of the skin (n = 3) and soft tissues (n = 3) resolved. Of these children, eight children had no active disease for a median of 3.3 years post-PAM therapy (range: 1.8-9.3 years). Progression-free survival (PFS) was 56.3 ± 12.4% at 3 years. PFS was significantly higher in children with a first reactivation compared with children experiencing a second or subsequent reactivation.
PAM may be an effective treatment for reactivated LCH with bone lesions. A prospective trial of the efficacy of PAM in recurrent pediatric LCH is warranted.
Pediatric Blood & Cancer 01/2011; 56(1):110-5. · 1.89 Impact Factor
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Hideaki Okajima,
Yuki Ohya,
Kwang-Jong Lee,
Hidekazu Yamamoto,
Katsuhiro Asonuma,
Yuko Nagaoki,
Kazunori Ohama,
Masahiko Korogi, Tadashi Anan,
Motohiro Hashiyama,
Fumio Endo,
Kenichi Iyama,
Yukihiro Inomata
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ABSTRACT: We present the cases of 3 children with huge undifferentiated sarcoma of the liver who were treated with surgical excision including liver transplantation as an option and adjuvant chemotherapy. All 3 patients were males aged 10, 13, and 15 years old. The size of the tumor was 10, 15, and 20 cm in diameter, respectively. The youngest patient is disease free and doing well 43 months after resection. The 13-year-old patient presented with tumor rupture and underwent operation. The primary tumor and the ruptured tissue fragments were removed and he was given postoperative chemotherapy. The patient is disease free and doing well 52 months after surgery. The oldest patient had an unresectable tumor in the hilar region. Preoperative chemotherapy was given but later discontinued owing to severe side effects. He underwent living donor liver transplantation followed by postoperative chemotherapy. The patient had recurrent tumor 24 months after transplantation that was excised at reoperation. He is doing well and is disease free 18 months after the second procedure. Complete removal of the tumor including total hepatectomy and transplantation when indicated and suitable pre- and/or postoperative chemotherapy is an effective treatment for children with undifferentiated sarcoma of the liver.
Journal of Pediatric Surgery 03/2009; 44(2):e33-8. · 1.45 Impact Factor
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ABSTRACT: We investigated the necessity of preparation for blood transfusion in gastric cancer surgery to save costs for blood typing, antibody screening, cross-matching, and disposal of the blood product. The subjects of the study were 52 patients who underwent gastric cancer surgery at our department between 2000 and 2004. The requirement for blood transfusion during surgery was investigated in terms of patient characteristics, hemoglobin before surgery, and performance status as well as treatment regimen. Furthermore, economic effects were investigated when typing and screening (T&S) were performed instead of typing and cross-matching (T&X). Of 9 patients who received blood transfusion, 8 had gastric cancer of stage IIIB or higher, or underwent combined resection. Blood transfusion was not used in surgery for patients with early gastric cancer. The volumes of blood prepared, lost, and disposed of in 28 patients who underwent T&X were 831.3+/-249.4, 219.3+/-228.5 and 600+/-333.1 ml, respectively, whereas the blood loss in 24 patients who underwent T&S was 161.1+/-95.6 ml; this difference had a major economic effect. The practice of T&S for patients undergoing gastric surgery in the absence of combined resection for early gastric cancer seems to be a safe and cost-effective practice that abrogates disposal of blood in hospital management.
International journal of surgery (London, England) 06/2008; 6(3):234-7.
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ABSTRACT: Small ubiquitin-related modifier (SUMO) processing and deconjugation are mediated by sentrin-specific proteases/ubiquitin-like proteases (SENP/Ulps). We show that SUMO-specific protease 1 (SUSP1), a mammalian SENP/Ulp, localizes within the nucleoplasm. SUSP1 depletion within cell lines expressing enhanced green fluorescent protein (EGFP) fusions to individual SUMO paralogues caused redistribution of EGFP-SUMO2 and -SUMO3, particularly into promyelocytic leukemia (PML) bodies. Further analysis suggested that this change resulted primarily from a deficit of SUMO2/3-deconjugation activity. Under these circumstances, PML bodies became enlarged and increased in number. We did not observe a comparable redistribution of EGFP-SUMO1. We have investigated the specificity of SUSP1 using vinyl sulfone inhibitors and model substrates. We found that SUSP1 has a strong paralogue bias toward SUMO2/3 and that it acts preferentially on substrates containing three or more SUMO2/3 moieties. Together, our findings argue that SUSP1 may play a specialized role in dismantling highly conjugated SUMO2 and -3 species that is critical for PML body maintenance.
The Journal of Cell Biology 10/2006; 174(7):939-49. · 10.26 Impact Factor
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ABSTRACT: Here we show that the PIASy protein is specifically required for mitotic modification of Topoisomerase-II by SUMO-2 conjugation in Xenopus egg extracts. PIASy was unique among the PIAS family members in its capacity to bind mitotic chromosomes and recruit Ubc9 onto chromatin. These properties were essential, since PIASy mutants that did not bind chromatin or failed to recruit Ubc9 were functionally inactive. We observed that PIASy depletion eliminated essentially all chromosomal accumulation of EGFP-SUMO-2-conjugated species, suggesting that it is the primary E3-like factor for mitotic chromosomal substrates of SUMO-2. PIASy-dependent SUMO-2-conjugated species were highly concentrated on the inner centromere, and inhibition of PIASy blocked anaphase sister chromatid segregation in egg extracts. Taken together, our observations suggest that PIASy is a critical regulator of mitotic SUMO-2 conjugation for Topoisomerase-II and other chromosomal substrates, and that its activity may have particular relevance for centromeric functions required for proper chromosome segregation.
The EMBO Journal 07/2005; 24(12):2172-82. · 9.20 Impact Factor
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ABSTRACT: Ubiquitin ligases define the substrate specificity of protein ubiquitination and subsequent proteosomal degradation. The catalytic sequence was first characterized in the C terminus of E6-associated protein (E6AP) and referred to as the HECT (homologous to E6AP C terminus) domain. The human homologue of the regulator of cell proliferation hyperplastic discs in Drosophila, designated hHYD, is a HECT-domain ubiquitin ligase. Here we show that hHYD provides a ubiquitin system for a cellular response to DNA damage. A yeast two-hybrid screen showed that DNA topoisomerase IIbeta-binding protein 1 (TopBP1) interacted with hHYD. Endogenous hHYD bound the BRCA1 C-terminus domains of TopBP1 that are highlighted in DNA damage checkpoint proteins and cell cycle regulators. Using an in vitro reconstitution, specific E2 (ubiquitin-conjugating) enzymes (human UbcH4, UbcH5B, and UbcH5C) transferred ubiquitin molecules to hHYD, leading to the ubiquitination of TopBP1. TopBP1 was usually ubiquitinated and degraded by the proteosome, whereas X-irradiation diminished the ubiquitination of TopBP1 probably via the phosphorylation, resulting in the stable colocalization of up-regulated TopBP1 with gamma-H2AX nuclear foci in DNA breaks. These results demonstrated that hHYD coordinated TopBP1 in the DNA damage response.
Journal of Biological Chemistry 03/2002; 277(5):3599-605. · 4.77 Impact Factor
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Tadashi Anan,
Yoichi Nagata,
Hisashi Koga,
Yoshiomi Honda,
Nami Yabuki,
Chikara Miyamoto,
Akira Kuwano,
Ichiro Matsuda,
Fumio Endo,
Hideyuki Saya,
Mitsuyoshi Nakao
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ABSTRACT: Background
Nedd4 is a ubiquitin-protein ligase containing a calcium/lipid-binding domain, multiple WW domains and a C-terminal Hect domain, which is required for both the ubiquitin transfer and the association with E2 ubiquitin-conjugating enzymes. Nedd4 has been reported to be involved in the selective ubiquitination of some regulatory proteins in transcription and membrane transport.ResultsThree mRNA species for human Nedd4 were found to be 6.4-, 7.8- and 9.5-kb in size, and their expression patterns varied among normal tissues and cancer cell lines, indicating the tissue- and cell-specificities of Nedd4 expression. The Nedd4 protein, ≈120 kDa in weight, was found in the cytoplasm, mainly in the perinuclear region and cytoplasmic periphery, of human cultured cells. Neural differentiation induced not only the down-regulation of Nedd4 but also the localization of the protein to both the cytoplasm and neurites. To identify the ubiquitination pathway that is linked to Nedd4, we demonstrated that specific E2 enzymes, including human Ubc4, UbcH5B, UbcH5C, UbcH6 and UbcH7, could transfer ubiquitin molecules to Nedd4 at the active cysteine residue, whereas E6AP accepted ubiquitins from Ubc4, UbcH5B, UbcH5C and UbcH7. Furthermore, nuclear localization of N-terminal deletion mutant Nedd4 enabled us to investigate the interaction between Nedd4 and E2 enzyme (Ubc4 or UbcH7) in the cell. The simultaneous expression of the full-length Nedd4 and E2 enzyme revealed that both proteins mostly colocalized in the cytoplasmic periphery, while the N-terminal deleted Nedd4 induced the nuclear and perinuclear colocalization with E2 enzyme.Conclusion
Our findings suggested that Nedd4 plays an important role in the cell regulation, including neural differentiation through cooperation with specific E2 ubiquitination pathways.
Genes to Cells 10/1998; 3(11):751 - 763. · 2.68 Impact Factor
