Shunsuke Imai

Osaka Prefectural Institute of Public Health, Ōsaka, Ōsaka, Japan

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Publications (98)182.12 Total impact

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    Full-text · Dataset · Nov 2013
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    ABSTRACT: Aberrant carbohydrate expression frequently occurs in breast cancer and may endow cells with metastatic potential. Here we first studied the relationship between expression of Vicia villosa agglutinin (lectin) (VVA)-binding carbohydrates and aggressive breast cancer. We then investigated the molecular characteristics of these glycoproteins and compared them with those of glycoproteins recognized by the mouse anti-Tn monoclonal antibody (MAb) HB-Tn1. Histochemical studies of samples from 322 cases of invasive ductal carcinoma demonstrated that VVA-binding carbohydrate expression correlated with tumor stage, lymphatic invasion, and lymph node metastasis (p=0.0385, p=0.0019, and p=0.0430. respectively). Western blotting analysis of frozen materials from 39 cases, under denaturing and reducing conditions, revealed that the major cancer cell-specific VVA-binding proteins were molecules of about 30, 33, and >200 kDa. Cases expressing the approximately 33 kDa molecule had significant lymphatic invasion more frequently than did cases not expressing this molecule (p=0.0076). Binding of VVA to the approximately 30 and approximately 33 kDa molecules was completely lost by preincubation of VVA with 1 mM Tn antigen (N-acetylgalactosamine alpha1-O-serine). The VVA-binding molecules appeared to react with VU-3C6 anti-MUC1 MAb. Expression of HB-Tn1 in breast cancer cells showed significant correlation with expression of VVA-binding carbohydrate(s) (p<0.0001) but HB-Tn1 reactivity was not clearly related to breast cancer aggressiveness. Because anti-Tn MAbs bound to Tn antigen clusters, we concluded that atypical MUC1 bearing the noncluster form of Tn antigen is implicated in aggressive growth of primary breast cancer cells, particularly in lymphatic metastasis.
    No preview · Article · Jul 2006 · Breast Cancer Research and Treatment
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    ABSTRACT: MUC1 is a transmembrane molecule characterized by a repeated sequence of 20 amino acid (TAP PAHGVTSAPDTRPAPGS). Abnormal overexpression of MUC1 in cancer cells is thought to contribute to their aggressive growth, but molecular mechanisms associated with this effect are still unclear. Our current study aimed to clarify whether MUC1 expression as recognized by VU-3C6 anti-MUC1 mouse IgG monoclonal antibody (MAb) with a dominant epitope of 12 amino acids: GVTSAPDTRPAP, correlated with aggressive properties of human breast cancer. Immunohistochemical studies of 309 samples of formalin-fixed and paraffin-embedded materials showed no statistical correlation between MUC1 expression and clinicopathological parameters, as well as several breast cancer aggressiveness-related markers. Expression or nonexpression of MUC1 in 50 frozen samples, as determined by Western blotting, demonstrated no correlation with aggressive properties of breast cancer. However, samples with one MUC1-positive band more often had lymphatic vessel invasion and lymph node metastasis than those with more than two or three MUC1-positive bands (p<0.014 and p<0.043, respectively). Because VU-3C6 MAb recognizes MUC1 with short branches of O-glycosylated core carbohydrates, we used immunohistological methods to examine Tn antigen (precursor antigen: GalNAcalpha-O-Ser/Thr), Thomsen-Friedenreich (T) antigen, and sialyl-Tn antigen (STn) antigen. We found a strong correlation between expression of MUC1 and Tn antigen (p<0.0006), and samples with Tn antigen expression had more lymphatic metastasis than those with no such expression (p<0.08). We concluded that the lack of polymorphic MUC1 expression with Tn antigen is one characteristic related to aggressive breast cancer.
    No preview · Article · Sep 2005 · Breast Cancer Research and Treatment
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    ABSTRACT: p53, a tumor suppressor gene, is a target of genetic alternations in many human and animal cancers. Compared to normal tissues, cancer tissues overexpress mutant p53 protein thus allowing their detection by a number of immunochemical procedures. To what extent the expression of mutant p53 correlates with dog mammary tumorigenesis has not been fully studied. In the present study, 20 spontaneously arising canine mammary tumors were examined for overexpression of mutant p53. Two different monoclonal antibodies, BP53-12 and PAb122, which recognize different epitopes of the p53 product, were used. The canine tumors in the present study exhibited five different histological types: i) osteosarcoma (n=7); ii) carcinosarcoma (n=4); iii) solid carcinoma (n=5); iv) complex carcinoma (n=3); and v) tubulopapillar carcinoma (n=1). The positive ratios against BP53-12 and PAb122 antibodies were 50% (10/20) and 60% (12/20) respectively. Among these positive samples, 35% (7/20) reacted to both antibodies. Finally, 15 out of 20 tumors showed positivity against one of the monoclonal antibodies. Mostly, as in human mammary tumor cells, BP53-12 staining was observed in the nuclei of tumor cells. PAb122 staining, however, was confined to cytoplasm of osteosarcoma or carcinosarcoma cells. To confirm the location of the staining, immunoelectron microscopy was done. The results showed that the cytoplasm of cartilage cells in the sarcomas had positive staining. These results indicate that anti-p53 antibodies BP53-12 and PAb122, generated against human p53 are cross reacting with the same molecule in canine cells and that the role of p53 in tumorigenesis is not only confined to tumors in human. Our finding suggests that a combination of p53 monoclonal antibodies should be used to screen, not only canine mammary tumors but also human mammary tumors, to obtain a better tumor prognosis.
    No preview · Article · Nov 2001 · Oncology Reports
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    ABSTRACT: Marginisporum crassissimum (Yendo) Ganesan, a marine red alga found in the ordinal coastal sea around Japan, revealed antitumor (antimetastatic) effects in vitro and in vivo. In in vitro experiments, extracts of this alga inhibited not only the growth of several tumor cell lines, such as B16-BL6 (a mouse melanoma cell line), JYG-B (a mouse mammary carcinoma cell line) and KPL-1 (a human mammary carcinoma cell line), but also invasion of B16-BL6 cells in a culture system. In in vivo experiments, the lung metastasis of B16-BL6 cells inoculated to the tail vein of B57BL/6J mice was inhibited by intraperitoneal administration of an extract from the alga. In addition, life prolongation of B57BL/6J mice inoculated with B16-BL6 cells was also observed by the intraperitoneal administration of the extract. An effective substance showing B16-BL6 growth inhibition in vitro was partially purified by filtration and hydrophobic column chromatography, and was revealed to be sensitive to trypsin-digestion and heat-treatment. The molecular weight of the substance was greater than 100 kDa. This is the first study demonstrating antitumor (antimetastatic) effects of M. crassissimum.
    No preview · Article · Jul 2001 · Cancer Letters
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    ABSTRACT: Sixteen research groups participated in the ISOBM TD-4 Workshop in which the reactivity and specificity of 56 monoclonal antibodies against the MUC1 mucin was investigated using a diverse panel of target antigens and MUC1 mucin-related synthetic peptides and glycopeptides. The majority of antibodies (34/56) defined epitopes located within the 20-amino acid tandem repeat sequence of the MUC1 mucin protein core. Of the remaining 22 antibodies, there was evidence for the involvement of carbohydrate residues in the epitopes for 16 antibodies. There was no obvious relationship between the type of immunogen and the specificity of each antibody. Synthetic peptides and glycopeptides were analyzed for their reactivity with each antibody either by assay of direct binding (e.g. by ELISA or BiaCore) or by determining the capacity of synthetic ligands to inhibit antibody binding interactions. There was good concordance between the research groups in identifying antibodies reactive with peptide epitopes within the MUC1 protein core. Epitope mapping tests were performed using the Pepscan analysis for antibody reactivity against overlapping synthetic peptides, and results were largely consistent between research groups. The dominant feature of epitopes within the MUC1 protein core was the presence, in full or part, of the hydrophilic sequence of PDTRAPAP. Carbohydrate epitopes were less easily characterized and the most useful reagents in this respect were defined oligosaccharides, rather than purified mucin preparations enriched in particular carbohydrate moieties. It was evident that carbohydrate residues were involved in many epitopes, by regulating epitope accessibility or masking determinants, or by stabilizing preferred conformations of peptide epitopes within the MUC1 protein core. Overall, the studies, highlight concordance between groups rather than exposing inconsistencies which gives added confidence to the results of analyses of the specificity of antimucin monoclonal antibodies.
    No preview · Article · Feb 1998 · Tumor Biology
  • Shunsuke Imai · Satomi Haga · Yashuhiko Kiyozuka
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    ABSTRACT: The 56 MAbs submitted to the ISOBM TD-4 Workshop were analysed by ELISA assay for reactivity against synthetic MUC1 mucin protein core-related peptides. With peptides comprising 5, 7 and 20 amino acids, 4/56 (7.1%), 33/56 (58.9%) and 51/56 (91.1%) of antibodies showed positive reactivity, respectively. Peptides with 60, 80, 100 and 120 amino acids showed 50/56 (98.2%), 54/56 (96.4%), 53/56 (94.6%) and 47/56 (83.9%) antibodies with positive reactivity, respectively. The reactivity of each MAb with synthetic peptides was classified into 3 groups. In group A (15 MAbs), the reactivity increased depending on the peptides in length and was maximal with 20-, 60-, 80-, 100- and 120-mer peptides. In group B (24 MAbs), most antibodies showed very weak binding affinity to peptides with a small increase in reactivity with the 100- and 120-mer peptides. In group C (17 MAbs), the reactivity showed strong binding affinity with the 20-mer peptide followed by a reduced uneven pattern of reactivity with the 60-, 80-, 100- and 120-mer peptides. These results show that the binding affinity of MAbs against synthetic peptides does not depend on the recognition of antibodies to the epitopes of core protein.
    No preview · Article · Feb 1998 · Tumor Biology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sixteen research groups participated in the ISOBM TD-4 Workshop in which the reactivity and specificity of 56 monoclonal antibodies against the MUC1 mucin was investigated using a diverse panel of target antigens and MUC1 mucin- related synthetic peptides and glycopeptides. The majority of antibodies (34/56) defined epitopes located within the 20-amino acid tandem repeat sequence of the MUC1 mucin protein core. Of the remaining 22 antibodies, there was evidence for the involvement of carbohydrate residues in the epitopes for 16 antibodies. There was no obvious relationship between the type of immunogen and the specificity of each antibody. Synthetic peptides and glycopeptides were analyzed for their reactivity with each antibody either by assay of direct binding (e.g. by ELISA or BiaCore) or by determining the capacity of synthetic ligands to inhibit antibody binding interactions. There was good concordance between the research groups in identifying antibodies reactive with peptide epitopes within the MUC1 protein core. Epitope mapping tests were performed using the Pepscan analysis for antibody reactivity against overlapping synthetic peptides, and results were largely consistent between research groups. The dominant feature of epitopes within the MUC1 protein core was the presence, in full or part, of the hydrophilic sequence of PDTRPAP. Carbohydrate epitopes were less easily characterized and the most useful reagents in this respect were defined oligosaccharides, rather than purified mucin preparations enriched in particular carbohydrate moieties. It was evident that carbohydrate residues were involved in many epitopes, by regulating epitope accessibility or masking determinants, or by stabilizing preferred conformations of peptide epitopes within the MUC1 protein core. Overall, the studies highlight concordance between groups rather than exposing inconsistencies which gives added confidence to the results of analyses of the specificity of anti-mucin monoclonal antibodies.
    Full-text · Article · Jan 1998 · Tumor Biology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sixteen research groups participated in the ISOBM TD-4 Workshop in which the reactivity and specificity of 56 monoclonal antibodies against the MUC1 mucin was investigated using a diverse panel of target antigens and MUC1 mucin- related synthetic peptides and glycopeptides. The majority of antibodies (34/56) defined epitopes located within the 20-amino acid tandem repeat sequence of the MUC1 mucin protein core. Of the remaining 22 antibodies, there was evidence for the involvement of carbohydrate residues in the epitopes for 16 antibodies. There was no obvious relationship between the type of immunogen and the specificity of each antibody. Synthetic peptides and glycopeptides were analyzed for their reactivity with each antibody either by assay of direct binding (e.g. by ELISA or BiaCore) or by determining the capacity of synthetic ligands to inhibit antibody binding interactions. There was good concordance between the research groups in identifying antibodies reactive with peptide epitopes within the MUC1 protein core. Epitope mapping tests were performed using the Pepscan analysis for antibody reactivity against overlapping synthetic peptides, and results were largely consistent between research groups. The dominant feature of epitopes within the MUC1 protein core was the presence, in full or part, of the hydrophilic sequence of PDTRPAP. Carbohydrate epitopes were less easily characterized and the most useful reagents in this respect were defined oligosaccharides, rather than purified mucin preparations enriched in particular carbohydrate moieties. It was evident that carbohydrate residues were involved in many epitopes, by regulating epitope accessibility or masking determinants, or by stabilizing preferred conformations of peptide epitopes within the MUC1 protein core. Overall, the studies highlight concordance between groups rather than exposing inconsistencies which gives added confidence to the results of analyses of the specificity of anti-mucin monoclonal antibodies.
    No preview · Article · Jan 1998
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sixteen research groups participated in the ISOBM TD-4 Workshop in which the reactivity and specificity of 56 monoclonal antibodies against the MUC1 mucin was investigated using a diverse panel of target antigens and MUC1 mucin-related synthetic peptides and glycopeptides. The majority of antibodies (34/56) defined epitopes located within the 20-amino acid tandem repeat sequence of the MUC1 mucin protein core. Of the remaining 22 antibodies, there was evidence for the involvement of carbohydrate residues in the epitopes for 16 antibodies. There was no obvious relationship between the type of immunogen and the specificity of each antibody. Synthetic peptides and glycopeptides were analyzed for their reactivity with each antibody either by assay of direct binding (e.g. by ELISA or BiaCore) or by determining the capacity of synthetic ligands to inhibit antibody binding interactions. There was good concordance between the research groups in identifying antibodies reactive with peptide epitopes within the MUC1 protein core. Epitope mapping tests were performed using the Pepscan analysis for antibody reactivity against overlapping synthetic peptides, and results were largely consistent between research groups. The dominant feature of epitopes within the MUC1 protein core was the presence, in full or part, of the hydrophilic sequence of PDTRPAP. Carbohydrate epitopes were less easily characterized and the most useful reagents in this respect were defined oligosaccharides, rather than purified mucin preparations enriched in particular carbohydrate moieties. It was evident that carbohydrate residues were involved in many epitopes, by regulating epitope accessibility or masking determinants, or by stabilizing preferred conformations of peptide epitopes within the MUC1 protein core. Overall, the studies highlight concordance between groups rather than exposing inconsistencies which gives added confidence to the results of analyses of the specificity of antimucin monoclonal antibodies.
    No preview · Article · Dec 1997 · Tumor Biology
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    ABSTRACT: We report a case of colonic type adenocarcinoma of the appendix with perforating peritonitis in a 92-year-old man. The preoperative diagnosis was localized peritonitis due to acute appendicitis and emergency laparotomy was performed. A gray, hard tumor was palpated at the base of the appendix. Appendiceal cancer was suspected, and right hemicolectomy was performed. The histopathological diagnosis was moderately differentiated adenocarcinoma of the appendix. The tumor obstructed the orifice of the appendix, and this may have caused the perforation of the appendix. The patient had an uneventful postoperative course and there have been no signs of recurrence in the 2 years since the operation.
    No preview · Article · Nov 1997 · Journal of Gastroenterology

  • No preview · Article · Jan 1997 · Microbes and Environments

  • No preview · Article · Mar 1996 · Acta cytologica

  • No preview · Article · Oct 1995 · In Vitro Cellular & Developmental Biology - Animal
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    ABSTRACT: We present our data on the cytotoxicity of microtubule inhibitors (paclitaxel and taxotere) and their mode of action against cisplatin-sensitive or -resistant ovarian cancer cell lines in vitro. To try to establish an optimal administration schedule in clinical use, the cytotoxicity of microtubule inhibitors alone and in sequential combination with cisplatin was investigated. With microtubules alone, a marked dose- and schedule-dependent growth inhibition was demonstrated in lower concentrations and only schedule-dependency in higher concentrations. The cytotoxicity of taxotere was approximately 0.8- to 132-fold that of paclitaxel. No cross resistance to cisplatin was observed. In the relation between assay AUC (area under the concentration curve) and growth inhibition, increasing AUC by dose escalation seemed not to be advantageous. In a combination with cisplatin, the treatment of microtubules over 48 h followed by cisplatin administration demonstrated the most effective cytotoxicity in cisplatin-resistant cell line.
    No preview · Article · Jul 1995 · Oncology Reports
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    ABSTRACT: We report a rare case of leiomyomatosis peritonealis disseminata (LPD) which we attempted to treat by administering the Gn-RH superagonist, buserelin. A 48-year-old woman presented with a 6-month history of hypermenorrhea. Hysterectomy revealed a benign leiomyoma. Light and electron microscopic studies revealed that the tumors were composed of well- or poorly-differentiated smooth muscle cells. Their clinical appearance together with the mitotic figures found in tumor sections suggested an uncertain malignant potential. In the immunohistochemical study of intermediate filaments, antidesmin and anti-actin antibody reacted with tumor cells. Tumor re-growth in the pelvic cavity led to a second operation. The administration of the Gn-RH analogue, 900 mu g daily for two months, decreased the tumor size. The average final volume was 68.7% of the original. However, the tumors recurred during the next four weeks. The combined administration of the Gn-RH analogue and etoposide (25 mg x 2/day) did not prevent recurrence after a third operation. The serum level of immune-suppressive acid protein (IAP) was useful in monitoring the clinical course of this patient, finally diagnosed as having LPD.
    No preview · Article · May 1995 · Oncology Reports

  • No preview · Article · Feb 1995 · In Vitro Cellular & Developmental Biology - Animal
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    ABSTRACT: We report herein the case of a 71-year-old-Japanese woman who was admitted to hospital for surgical treatment of a lower abdominal tumor. At laparotomy the tumor was found to be pedunculated and growing extramurally from the greater curvature of the stomach. Thus, a wedge resection of the stomach, including the mass, was performed. The tumor measured about 9 x 8 x 7 cm and histological examination of the resected specimen showed that the main elements consisted of wavy, long-spindled cells, which crossed irregularly, indicating that it was palisading negative. Immunohistochemically, the specimen was positive for both S-100 protein and Alcian blue. From these findings, the tumor was histologically diagnosed as a neurofibroma. The patient had an uneventful postoperative course and no signs of recurrence have been recognized in the 3 years since her operation.
    No preview · Article · Feb 1995 · Surgery Today
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    ABSTRACT: M.MOL-MSM (MSM) mice derived from Mus musculus molossinus progenitors showed extreme resistance to the induction of lymphomas following whole-body X-irradiation with four doses of 1.7 Gy. (BALB/cHeA x MSM) F1 mice between a high lymphoma strain, BALB/cHeA and the MSM showed a high incidence of radiation-induced lymphomas which was quite similar to that in BALB/cHeA mice, but the latent period was prolonged in the hybrids. Susceptibility in incidence was dominant over resistance in these crosses. Incidences of (BALB/cHeA x MSM)F1 hybrids irradiated with four doses of 2.5 Gy X-rays were 77% in females and 88% in males. F1 hybrids between BALB/cHeA and another resistant strain STS/A, (BALB/cHeA x STS/A) F1, also showed a high level of susceptibility, that is, lymphoma incidence was 64% in females and 63% in males. The mean latent period in the (BALB/cHeA x STS/A) F1 hybrids was similar to that in (BALB/cHeA x MSM) F1 hybrids. As all cases of tumors developed in F1 hybrids are informative concerning the detection of the loss of heterozygosity in the loci depending on the combination of two parental strains, the radiation-induced lymphomas obtained from (BALB/cHeA x MSM) F1 and (BALB/cHeA x STS/A) F1 hybrids could be useful for fine analysis of the genetic alterations involved in lymphomagenesis.
    No preview · Article · Feb 1995 · Experimental Animals
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    ABSTRACT: Mammary tumors of a newly isolated strain of Chinese wild mouse (JYG mouse) harbor exogenous mouse mammary tumor virus (MMTV). The complete nucleotide sequence of exogenous JYG-MMTV was determined on the proviral 5' long terminal repeat (LTR)(partial)-gag-pol-env-3' LTR (partial) fragment cloned into a plasmid vector and the cDNA sequence from JYG-MMTV producing cells. Similarly to the other MMTV species the LTR of JYG-MMTV contains an open reading frame (ORF). The amino acid sequence of the JYG-MMTV ORF resembles that of SW-MMTV (92% identity) and endogenous Mtv-7 (93% identity) especially at the C-terminal region. Thus, a functional similarity in T-cell receptor V beta recognition as a superantigen is implicated among these MMTV species. Analysis of the viral gag nucleotide sequence revealed that this gene is not disrupted by the bacterial insertion sequence IS1 or IS2, which have been reported to be present in the majority of the plasmids containing the gag region. Comparison of amino acid sequences of JYG-MMTV with those of BR6-MMTV showed that over 96% of the amino acids of gag, pol, protease and env products are identical. These results suggest the intact nature of the nucleotide sequence of the near full-length MMTV genome cloned in the plasmid.
    No preview · Article · Jan 1995 · Breast Cancer

Publication Stats

920 Citations
182.12 Total Impact Points

Institutions

  • 2001-2006
    • Osaka Prefectural Institute of Public Health
      Ōsaka, Ōsaka, Japan
  • 1998
    • Aichi Prefectural Institute of Public Health
      Nagoya, Aichi, Japan
  • 1995
    • Nippon Zenyaku Kogyo Co., Ltd.
      Hukusima, Fukushima, Japan
  • 1991-1995
    • Osaka Prefecture University
      • Department of Applied Bioscience
      Sakai, Osaka-fu, Japan
  • 1981-1995
    • Nara Medical University
      • Department of Pathology
      Kashihara, Nara, Japan
  • 1994
    • Kurume University
      • Department of Obstetrics and Gynecology
      Куруме, Fukuoka, Japan
    • Georgia Health Sciences University
      Augusta, Georgia, United States
  • 1992
    • Kyoto University
      • Institute for Virus Research
      Kioto, Kyōto, Japan
    • Meiji University
      Edo, Tōkyō, Japan
  • 1979-1992
    • Nara Hospital
      Ikuma, Nara, Japan
  • 1982
    • Netherlands Cancer Institute
      Amsterdamo, North Holland, Netherlands