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Biomedical subjects

Y Makiguchi

Publications and source records attributed to Y Makiguchi.

34 records · Page 2Linked to original sources
PubMed1996

Effect of MUC1 mucin, an anti-adhesion molecule, on tumor cell growth.

MUC1 mucin is expressed in a wide variety of tumors and is considered to function as an anti-adhesion molecule which inhibits cell-to-cell interactions. To reveal the biological significance of this activity in tumor cells, MUC1 cDNA was transfected into EJNIH3T3 cells and human colon cancer cell lines, CHCY1 and DLD1. The in vivo growth rate of MUC1+ (MUC1-transfected) EJNIH3T3, CHCY1 and DLD1 cells in SCID mice was clearly lower than that of MUC1- (mock transfectant) cells. Several in vitro experiments using MUC1+ EJNIH3T3 cells were performed to analyze the mechanisms for the decreased in vivo tumor growth. It was found that (i) the in vitro growth rate of MUC1+ EJNIH3T3 cells was also decreased compared to that of MUC1- cells, (ii)the DNA synthesis of MUC1+ EJNIH3T3 cells after stimulation with either growth factor (fetal calf serum or bombesin) or extracellular matrix (collagen or fibronectin) was lower than that of MUC1- cells, and (iii) MUC1+ EJNIH3T3 cells grew more slowly than MUC1- cells on both collagen- and fibronectin-coated dishes. These data suggest that MUC1 mucin may regulate tumor cell growth through inhibition of cell-to-cell, growth factor-to-receptor and cell-to-matrix interactions.

Acetylgalactosamine↗
PubMed1996

[Functions of mucin molecules in gastrointestinal cancer].

Studies about the function of mucin molecules as surface molecule of adenocarcinoma of gastrointestinal tract had just started, and several important function of mucins had been revealed. In the process of the malignant transformation, class of the expressed mucin core protein and content of glycochain of mucin molecule was changed. Changes of glycoprotein of mucin molecule during transformation affect immunogenesity, tumorigenesity, metastatic ability and sensitivity for anti-cancer drugs. Glycosylated mucin acts important roles during metastatic sequence and prognosis of the gastrointestinal cancer was collerated with expression of immatured mucin of cancer cells. A type of mucin with immature type of glycochain, MUC1, had a protective function for cytotoxicity, e.g. natural killer cell and cytotoxic T-cell, and deglycosilation of MUC1 sensitize cancer cells for cytotoxicity. And MUC1 reduce sensitivity for anti-cancer drugs and MUC1 was glycosilated during process to get resistance for anti-cancer drug. The functions of mucin molecules is not fully revealed, but further studies will indicate importance of mucin molecules in tumor progression.

Adenocarcinoma↗
PubMed1994

Expression of MUC1 on myeloma cells and induction of HLA-unrestricted CTL against MUC1 from a multiple myeloma patient.

Polymorphic epithelial mucin (MUC1) was detected in myeloma cells and in sera of multiple myeloma patients. HLA-unrestricted CTL that recognize tumor-associated epitopes on MUC1 has been shown to be induced from breast and pancreas cancer patients. To investigate whether such CTL can also be induced from multiple myeloma patients, an allogeneic mixed leukocyte tumor cell culture was performed. PBMCs of a multiple myeloma patient were stimulated by different allogeneic breast carcinoma and myeloma cell lines. The cultured PBMCs were proliferated and a CTL line TN was established. TN exclusively expressed TCR-alpha/beta, CD3, and CD8. TN lysed breast carcinoma and myeloma cell lines but did not lyse K562, which is sensitive to NK cells. The cytotoxicity of TN was inhibited by anti-CD3 Abs but not by anti-HLA Abs. Thus, the TCR-alpha/beta was considered to be involved in the recognition of the target cells but HLA was not. Furthermore, TN lysed transformed mouse fibroblast cells transfected with MUC1 cDNA, suggesting that this CTL line recognizes MUC1 directly. Thus, it is concluded that precursors of HLA-unrestricted and anti-MUC1 reactive CTL could exist in the peripheral blood of multiple myeloma patients and that myeloma cells can express epitopes on MUC1, which can be recognized by the CTL.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1994

Expression of cytoskeletal-associated protein tyrosine phosphatase PTPH1 mRNA in human hepatocellular carcinoma.

We investigated the mRNA expression of cytosolic protein tyrosine phosphatase (PTPH1), which has a homologous domain to cytoskeletal-associated proteins, in human hepatocellular carcinomas (HCCs) by using reverse transcriptase-polymerase chain reaction (RT-PCR). PTPH1 mRNA was detected in all HCC cell lines (n = 6), and HCC and adjacent noncancerous tissues (n = 8) examined, indicating that PTPH1 was expressed in HCCs and hepatocytes. There was no remarkable difference in the level expression of PTPH1 mRNA between HCC and adjacent noncancerous tissues. We also performed RT-PCR single-strand conformation polymorphism (SSCP) analysis in HCC cell lines and tissues in the C-terminal region of the catalytic domain of PTPH1. In the cHc4 cell line and a HCC tissue specimen, a shifted band was detected, although it was not found in the non-cancerous tissue of the HCC specimen. Nucleotide sequence analysis showed a common mutation from T to C at the third letter of codon 919 which did not lead to amino acid substitution. These results suggest that another mutation leading to the development of HCC could occur in some region of PTPH1 other than that investigated in this study.

Base Sequence↗
PubMed1993

Detection of a circulating antibody against a peptide epitope on a mucin core protein, MUC1, in ulcerative colitis.

This study aims at clarifying whether the humoral immune response to the tandem repeat domain of MUC1 can be induced or not in vivo. The expression of MUC1 mRNA in the colon was revealed by Northern blot analysis, and cDNA cloning of an extracellular tandemly repeated domain of MUC1 was then performed to prepare the recombinant MUC1 protein. A cDNA clone coding for ten repeat domains was ligated into an expression vector in prokaryotes, resulting in a recombinant protein which could react with the MAb MUSE11 against an adenocarcinoma-associated antigen whose epitope has been shown to be localized in the tandem repeat domain on MUC1. The reactivity of sera from patients with ulcerative colitis with the recombinant protein was evaluated by SDS-PAGE and Western blot analysis to detect the antibodies against this tandem repeat domain. Five out of 19 serum samples tested positive, and these reactions were totally inhibited by MAb MUSE11, suggesting that the epitope recognized by these antibodies in sera is almost identical to that recognized by MAb MUSE11. The data represent the first demonstration of antibody production against a peptide epitope of the tandem repeat domain of MUC1.

Adolescent↗
PubMed1993

Expression of c-kit and kit ligand in human colon carcinoma cells.

To determine whether c-kit and kit ligand (KL) mRNAs could be expressed in human epithelial tumors, reverse transcriptase-polymerase chain reaction and Northern blot analysis were performed. KL mRNA was shown to be expressed in a variety of epithelial tissues and cell lines. The expression of c-kit mRNA was then examined in hepatocellular and colon carcinoma cell lines. While hepatocellular carcinoma cell lines did not express c-kit mRNA as far as we could ascertain, 2 of 5 colon carcinoma cell lines showed the expression of both c-kit and KL mRNAs. Furthermore, the expression of c-kit in these cells was demonstrated at the protein level by flow cytometry. These data suggest that c-kit and KL may play an important role as an autocrine loop in the proliferation of some colon carcinoma cells.

Base Sequence↗
PubMed1992

A novel chromosomal translocation t(3;17)(q29;q11) in a case with polycythemia vera.

We report a novel chromosomal translocation t(3;17)(q29;q11) in a case with polycythemia vera (PV). The present case (38-year-old male) developed the spent phase of PV after a 10 years' clinical course and showed excessive proliferation of myeloid cells in the bone marrow. The karyotype analysis of the bone marrow cells showed chromosomal translocation t(3;17)(q29;q11), and the same aberration was detected in the granulocyte-colony-stimulating-factor-stimulated peripheral blood cells, suggesting the cells with the t(3;17)(q29;q11) showed myeloid differentiation. It is known as well that the retinoic acid receptor gene, which is related with a myeloid disorder, is located in 17q11. Thus, the novel chromosomal translocation could be associated with the pathogenesis of the disorder in this patient.

Adult↗