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Toshikazu Bando - One of the best experts on this subject based on the ideXlab platform.

  • dna alkylation of the RUNX binding sequence by cbi pi polyamide conjugates
    Chemistry: A European Journal, 2020
    Co-Authors: Rina Maeda, Kaori Hashiya, Shinji Ito, Toshikazu Bando
    Abstract:

    Many types of molecular targeted drugs that inhibit cancer growth by acting on specific molecules have been developed. The runt-related Transcription Factor (RUNX) family, which induces cancer development by binding to a specific DNA sequence, has attracted attention as a new target for cancer treatment. We have developed Chb-M ¢ , which targets the RUNX-binding sequence. Chb-M ¢ was developed by conjugating pyrrole-imidazole (PI) polyamides and chlorambucil as an anticancer agent. It was recently reported that Chb-M ¢ had a remarkable anticancer effect in vivo. In this study, to explore the possibility of an alternative structure, we designed a new series of CBI-PI polyamides, in which seco-CBI was applied as a DNA-alkylating agent. We examined the characteristics of the CBI-PI polyamides targeting the RUNX-binding sequence and found that these conjugates have great potential for cancer treatment.

  • molecular characteristics of dna alkylating pi polyamides targeting RUNX Transcription Factors
    Journal of the American Chemical Society, 2019
    Co-Authors: Rina Maeda, Kaori Hashiya, Toshikazu Bando, Shinsuke Sato, Shunsuke Obata, Tomo Ohno, Hiroshi Sugiyama
    Abstract:

    The runt-related Transcription Factor (RUNX) family has been associated with cancer development. The binding of RUNX family members to specific DNA sequences is hypothesized to promote the expressi...

  • Molecular Characteristics of DNA-Alkylating PI Polyamides Targeting RUNX Transcription Factors
    2019
    Co-Authors: Rina Maeda, Kaori Hashiya, Toshikazu Bando, Shinsuke Sato, Shunsuke Obata, Tomo Ohno, Hiroshi Sugiyama
    Abstract:

    The runt-related Transcription Factor (RUNX) family has been associated with cancer development. The binding of RUNX family members to specific DNA sequences is hypothesized to promote the expression of downstream genes and cause cancer proliferation. On the basis of this proposed mechanism of cancer growth, we developed conjugate 1, which inhibits the binding of RUNX to its target DNA. Conjugate 1 is a DNA-alkylating pyrrole–imidazole (PI) polyamide conjugate containing chlorambucil as an anticancer agent. Conjugate 1 was reported to have a marked anticancer effect in mouse models of acute myeloid leukemia. Although the effectiveness of 1 has been demonstrated in vivo, the detailed mechanism by which it alkylates DNA is unknown. Here, we chemically elucidated the molecular characteristics of conjugate 1 to confirm its potential as a RUNX-inhibiting drug. We also generated an alternative conjugate 2, which targets the same DNA sequence, by replacing one pyrrole with β-alanine. Comparison of the characteristics of conjugates 1 and 2 suggested that reaction selectivity and binding affinity to the RUNX-binding sequence were improved by the introduction of β-alanine. These findings indicate the possibility of DNA-alkylating PI polyamides as candidates for cancer chemotherapeutics

Rina Maeda - One of the best experts on this subject based on the ideXlab platform.

  • dna alkylation of the RUNX binding sequence by cbi pi polyamide conjugates
    Chemistry: A European Journal, 2020
    Co-Authors: Rina Maeda, Kaori Hashiya, Shinji Ito, Toshikazu Bando
    Abstract:

    Many types of molecular targeted drugs that inhibit cancer growth by acting on specific molecules have been developed. The runt-related Transcription Factor (RUNX) family, which induces cancer development by binding to a specific DNA sequence, has attracted attention as a new target for cancer treatment. We have developed Chb-M ¢ , which targets the RUNX-binding sequence. Chb-M ¢ was developed by conjugating pyrrole-imidazole (PI) polyamides and chlorambucil as an anticancer agent. It was recently reported that Chb-M ¢ had a remarkable anticancer effect in vivo. In this study, to explore the possibility of an alternative structure, we designed a new series of CBI-PI polyamides, in which seco-CBI was applied as a DNA-alkylating agent. We examined the characteristics of the CBI-PI polyamides targeting the RUNX-binding sequence and found that these conjugates have great potential for cancer treatment.

  • molecular characteristics of dna alkylating pi polyamides targeting RUNX Transcription Factors
    Journal of the American Chemical Society, 2019
    Co-Authors: Rina Maeda, Kaori Hashiya, Toshikazu Bando, Shinsuke Sato, Shunsuke Obata, Tomo Ohno, Hiroshi Sugiyama
    Abstract:

    The runt-related Transcription Factor (RUNX) family has been associated with cancer development. The binding of RUNX family members to specific DNA sequences is hypothesized to promote the expressi...

  • Molecular Characteristics of DNA-Alkylating PI Polyamides Targeting RUNX Transcription Factors
    2019
    Co-Authors: Rina Maeda, Kaori Hashiya, Toshikazu Bando, Shinsuke Sato, Shunsuke Obata, Tomo Ohno, Hiroshi Sugiyama
    Abstract:

    The runt-related Transcription Factor (RUNX) family has been associated with cancer development. The binding of RUNX family members to specific DNA sequences is hypothesized to promote the expression of downstream genes and cause cancer proliferation. On the basis of this proposed mechanism of cancer growth, we developed conjugate 1, which inhibits the binding of RUNX to its target DNA. Conjugate 1 is a DNA-alkylating pyrrole–imidazole (PI) polyamide conjugate containing chlorambucil as an anticancer agent. Conjugate 1 was reported to have a marked anticancer effect in mouse models of acute myeloid leukemia. Although the effectiveness of 1 has been demonstrated in vivo, the detailed mechanism by which it alkylates DNA is unknown. Here, we chemically elucidated the molecular characteristics of conjugate 1 to confirm its potential as a RUNX-inhibiting drug. We also generated an alternative conjugate 2, which targets the same DNA sequence, by replacing one pyrrole with β-alanine. Comparison of the characteristics of conjugates 1 and 2 suggested that reaction selectivity and binding affinity to the RUNX-binding sequence were improved by the introduction of β-alanine. These findings indicate the possibility of DNA-alkylating PI polyamides as candidates for cancer chemotherapeutics

Hiroshi Sugiyama - One of the best experts on this subject based on the ideXlab platform.

  • molecular characteristics of dna alkylating pi polyamides targeting RUNX Transcription Factors
    Journal of the American Chemical Society, 2019
    Co-Authors: Rina Maeda, Kaori Hashiya, Toshikazu Bando, Shinsuke Sato, Shunsuke Obata, Tomo Ohno, Hiroshi Sugiyama
    Abstract:

    The runt-related Transcription Factor (RUNX) family has been associated with cancer development. The binding of RUNX family members to specific DNA sequences is hypothesized to promote the expressi...

  • Molecular Characteristics of DNA-Alkylating PI Polyamides Targeting RUNX Transcription Factors
    2019
    Co-Authors: Rina Maeda, Kaori Hashiya, Toshikazu Bando, Shinsuke Sato, Shunsuke Obata, Tomo Ohno, Hiroshi Sugiyama
    Abstract:

    The runt-related Transcription Factor (RUNX) family has been associated with cancer development. The binding of RUNX family members to specific DNA sequences is hypothesized to promote the expression of downstream genes and cause cancer proliferation. On the basis of this proposed mechanism of cancer growth, we developed conjugate 1, which inhibits the binding of RUNX to its target DNA. Conjugate 1 is a DNA-alkylating pyrrole–imidazole (PI) polyamide conjugate containing chlorambucil as an anticancer agent. Conjugate 1 was reported to have a marked anticancer effect in mouse models of acute myeloid leukemia. Although the effectiveness of 1 has been demonstrated in vivo, the detailed mechanism by which it alkylates DNA is unknown. Here, we chemically elucidated the molecular characteristics of conjugate 1 to confirm its potential as a RUNX-inhibiting drug. We also generated an alternative conjugate 2, which targets the same DNA sequence, by replacing one pyrrole with β-alanine. Comparison of the characteristics of conjugates 1 and 2 suggested that reaction selectivity and binding affinity to the RUNX-binding sequence were improved by the introduction of β-alanine. These findings indicate the possibility of DNA-alkylating PI polyamides as candidates for cancer chemotherapeutics

Kaori Hashiya - One of the best experts on this subject based on the ideXlab platform.

  • dna alkylation of the RUNX binding sequence by cbi pi polyamide conjugates
    Chemistry: A European Journal, 2020
    Co-Authors: Rina Maeda, Kaori Hashiya, Shinji Ito, Toshikazu Bando
    Abstract:

    Many types of molecular targeted drugs that inhibit cancer growth by acting on specific molecules have been developed. The runt-related Transcription Factor (RUNX) family, which induces cancer development by binding to a specific DNA sequence, has attracted attention as a new target for cancer treatment. We have developed Chb-M ¢ , which targets the RUNX-binding sequence. Chb-M ¢ was developed by conjugating pyrrole-imidazole (PI) polyamides and chlorambucil as an anticancer agent. It was recently reported that Chb-M ¢ had a remarkable anticancer effect in vivo. In this study, to explore the possibility of an alternative structure, we designed a new series of CBI-PI polyamides, in which seco-CBI was applied as a DNA-alkylating agent. We examined the characteristics of the CBI-PI polyamides targeting the RUNX-binding sequence and found that these conjugates have great potential for cancer treatment.

  • molecular characteristics of dna alkylating pi polyamides targeting RUNX Transcription Factors
    Journal of the American Chemical Society, 2019
    Co-Authors: Rina Maeda, Kaori Hashiya, Toshikazu Bando, Shinsuke Sato, Shunsuke Obata, Tomo Ohno, Hiroshi Sugiyama
    Abstract:

    The runt-related Transcription Factor (RUNX) family has been associated with cancer development. The binding of RUNX family members to specific DNA sequences is hypothesized to promote the expressi...

  • Molecular Characteristics of DNA-Alkylating PI Polyamides Targeting RUNX Transcription Factors
    2019
    Co-Authors: Rina Maeda, Kaori Hashiya, Toshikazu Bando, Shinsuke Sato, Shunsuke Obata, Tomo Ohno, Hiroshi Sugiyama
    Abstract:

    The runt-related Transcription Factor (RUNX) family has been associated with cancer development. The binding of RUNX family members to specific DNA sequences is hypothesized to promote the expression of downstream genes and cause cancer proliferation. On the basis of this proposed mechanism of cancer growth, we developed conjugate 1, which inhibits the binding of RUNX to its target DNA. Conjugate 1 is a DNA-alkylating pyrrole–imidazole (PI) polyamide conjugate containing chlorambucil as an anticancer agent. Conjugate 1 was reported to have a marked anticancer effect in mouse models of acute myeloid leukemia. Although the effectiveness of 1 has been demonstrated in vivo, the detailed mechanism by which it alkylates DNA is unknown. Here, we chemically elucidated the molecular characteristics of conjugate 1 to confirm its potential as a RUNX-inhibiting drug. We also generated an alternative conjugate 2, which targets the same DNA sequence, by replacing one pyrrole with β-alanine. Comparison of the characteristics of conjugates 1 and 2 suggested that reaction selectivity and binding affinity to the RUNX-binding sequence were improved by the introduction of β-alanine. These findings indicate the possibility of DNA-alkylating PI polyamides as candidates for cancer chemotherapeutics

Toshiaki Tanaka - One of the best experts on this subject based on the ideXlab platform.

  • loss of RUNX3 immunoreactivity in non neoplastic rectal mucosa may predict the occurrence of ulcerative colitis associated colorectal cancer
    Digestion, 2020
    Co-Authors: Takahide Shinagawa, Keisuke Hata, Teppei Morikawa, Keigo Matsunaga, Shigenobu Emoto, Koji Murono, Manabu Kaneko, Kazuhito Sasaki, Takeshi Nishikawa, Toshiaki Tanaka
    Abstract:

    Background/aims Runt-related Transcription Factor (RUNX) 3 is a tumor suppressor whose expression is reduced in non-neoplastic rectal mucosa of patients with ulcerative colitis (UC) with coexisting colitis-associated cancer (CAC). We aimed to evaluate RUNX3 utility as a predictive marker for CAC using immunohistochemistry (IHC) for non-neoplastic UC mucosa. Methods We retrospectively compared the RUNX3 expression detected by IHC between non-neoplastic rectal biopsy specimens from 20 cases with invasive cancer (CAC group) and 20 cases selected from 138 patients without CAC (non-CAC group) that were treated during the same period (2006-2017) and were matched for sex, duration, extension, and age. We validated the results using tissue microarrays (TMA) of 44 operated cases with CAC. The RUNX3 expression level was determined by calculating the percentage of RUNX3-positive-cells. Results The RUNX3 expression was lower in the CAC than that in the non-CAC group (35.6 vs. 70.7%, p = 0.03). For a cutoff value of 58%, the sensitivity and specificity for predicting CAC were 75.0 and 70.0% respectively. The immunostaining results for the TMA showed the same trend; 74% of cases with CAC were negative for the RUNX3 expression. Conclusion RUNX3 immunostaining of non-neoplastic mucosa is useful for identifying UC patients at a high risk of developing CAC.