Usefulness of hexamethylenetetramine in combination with chemotherapy using free and pegylated liposomal doxorubicin in vivo, referring to the effect on quiescent cells

  • Authors:
    • Shin-Ichiro Masunaga
    • Kenji Kono
    • Jun Nakamura
    • Keizo Tano
    • Hiroyuki Yoshida
    • Masami Watanabe
    • Genro Kashino
    • Minoru Suzuki
    • Yuko Kinashi
    • Yong Liu
    • Koji Ono
  • View Affiliations

  • Published online on: May 1, 2009     https://doi.org/10.3892/or_00000355
  • Pages: 1307-1312
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Abstract

SCC VII tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all intratumor proliferating (P) cells. They received hexamethylenetetramine (HMTA) either once intraperitoneally or continuously subcutaneously together with chemotherapy using intraperitoneally administered free doxorubicin (DXR) or intravenously injected pegylated liposomal doxorubicin (PLD). One hour after the free DXR loading or 24 h after the PLD loading, the response of intratumor quiescent (Q) cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. The response of the total (P + Q) tumor cell population was determined from the tumors not treated with BrdU. Encapsulation of DXR into pegylated liposomes significantly enhanced cytotoxicity, especially in Q cells. HMTA, especially when administered continuously, efficiently increased the sensitivity to DXR, particularly in Q cells. The increase in sensitivity on the continuous rather than single administration of HMTA was a little clearer in the total cell population than in Q cells. DXR's encapsulation into pegylated liposomes and combination with HMTA, particularly when administered continuously, apparently reduced the difference in sensitivity to free DXR between the total and Q cell populations. In terms of the tumor cell-killing effect as a whole, including Q cells, the encapsulation of DXR into pegylated liposomes and combination with HMTA, particularly through continuous administration, are very promising, taking into account that HMTA has been used clinically.

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May 2009
Volume 21 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Masunaga S, Kono K, Nakamura J, Tano K, Yoshida H, Watanabe M, Kashino G, Suzuki M, Kinashi Y, Liu Y, Liu Y, et al: Usefulness of hexamethylenetetramine in combination with chemotherapy using free and pegylated liposomal doxorubicin in vivo, referring to the effect on quiescent cells. Oncol Rep 21: 1307-1312, 2009
APA
Masunaga, S., Kono, K., Nakamura, J., Tano, K., Yoshida, H., Watanabe, M. ... Ono, K. (2009). Usefulness of hexamethylenetetramine in combination with chemotherapy using free and pegylated liposomal doxorubicin in vivo, referring to the effect on quiescent cells. Oncology Reports, 21, 1307-1312. https://doi.org/10.3892/or_00000355
MLA
Masunaga, S., Kono, K., Nakamura, J., Tano, K., Yoshida, H., Watanabe, M., Kashino, G., Suzuki, M., Kinashi, Y., Liu, Y., Ono, K."Usefulness of hexamethylenetetramine in combination with chemotherapy using free and pegylated liposomal doxorubicin in vivo, referring to the effect on quiescent cells". Oncology Reports 21.5 (2009): 1307-1312.
Chicago
Masunaga, S., Kono, K., Nakamura, J., Tano, K., Yoshida, H., Watanabe, M., Kashino, G., Suzuki, M., Kinashi, Y., Liu, Y., Ono, K."Usefulness of hexamethylenetetramine in combination with chemotherapy using free and pegylated liposomal doxorubicin in vivo, referring to the effect on quiescent cells". Oncology Reports 21, no. 5 (2009): 1307-1312. https://doi.org/10.3892/or_00000355