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2015 ; 8
(4
): 308-17
Nephropedia Template TP
gab.com Text
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English Wikipedia
Preparation, In Vivo Administration, Dose-Limiting Toxicities, and Antineoplastic
Activity of Cytochalasin B
#MMPMID26310377
Trendowski M
; Zoino JN
; Christen TD
; Acquafondata C
; Fondy TP
Transl Oncol
2015[Aug]; 8
(4
): 308-17
PMID26310377
show ga
An effective and inexpensive protocol for producing cytochalasins A and B is
being disclosed to propose a viable method by which to examine the in vivo
antineoplastic activity of these congeners in preclinical tumor-bearing mammalian
models. In addition, we determine the maximum tolerated doses of cytochalasin B
using multiple routes and formulations, characterize the tissue distribution of
intravenous bolus cytochalasin B, and assess the in vivo antineoplastic activity
of cytochalasin B in comparison in doxorubicin in Balb/c mice challenged
intradermally with M109 murine lung carcinoma. We also examine the effects of
cytochalasin B against several other murine neoplastic cell lines (Lewis lung,
LA4, B16F10, and M5076). Finally, we examine a potential mechanism of the
antimetastatic activity of cytochalasin B by observing the effects of the agent
on the secretion of N-acetylglucosaminidase (GlcNACase) by B16BL6 and B16F10
murine melanomas in vitro. The results of the study can be summarized as follows:
1) Cytochalasin B can be safely administered intravenously, intraperitoneally,
and subcutaneously in murine models, with the maximum tolerated dose of all
routes of administration being increased by liposome encapsulation. 2)
Cytochalasin B can significantly inhibit the growth of tumors in mice challenged
with M109, Lewis lung, LA4, B16F10, or M5076, producing long-term survival
against lung carcinomas and adenocarcinomas (M109, Lewis lung, and LA4) and
B16F10 melanoma, but not M5076 sarcoma. These effects were comparable to
intraperitoneally administered doxorubicin. 4) Low concentrations of cytochalasin
B inhibit the secretion of GlcNACase, indicating that cytochalasin B may inhibit
metastatic progression by mechanisms not directly associated with its influence
on cell adhesion and motility.