Cell surface actions of adriamycin

Tritton, Thomas R.

doi:10.1016/0163-7258(91)90060-y

Cited by 98 publications

(47 citation statements)

References 96 publications

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“…According to these results, it is likely that the dysfunction of the pituitary cells in LH release resulted from an injury to the cell membrane-mediated signaling mechanisms involved in LH release rather than from an intracellular impairment of the second messenger mechanisms. This conclusion is supported by the findings that DOX, the parent compound of AN-201, can interact with biomembranes and alter normal biochemical functions of the membranes, without entering the cells (25,26). Based on our results, a temporary damage to gonadotroph cells might be the only side-effect on the pituitary expected in the case of clinical application of the cytotoxic analog AN-207.…”

Section: Discussionsupporting

confidence: 73%

See 1 more Smart Citation

Recovery of pituitary function after treatment with a targeted cytotoxic analog of luteinizing hormone-releasing hormone

Kovács

Schally

Nagy

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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Section: Discussionsupporting

confidence: 73%

“…intercalating agent that inhibits DNA synthesis (23,24), and its effect on cell membranes as the first target of action was also reported (25,26). Because the cycle of the pituitary cells is rather long, the damaging effect of DOX and its derivatives may be detectable by an impairment of cell functions other than mitotic division.…”

Section: Discussionmentioning

confidence: 99%

Recovery of pituitary function after treatment with a targeted cytotoxic analog of luteinizing hormone-releasing hormone

Kovács

Schally

Nagy

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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“…However, doxorubicin-induced toxicity may be mediated via several other mechanisms, including generation of free radicals, lipid peroxidation and interactions with iron (Bachur et al, 1979;Tritton, 1991). These non-topoisomerase II-dependent mechanisms may be important for toxicity in the drug concentration range used in this study.…”

mentioning

confidence: 99%

“…In human cells there are two closely related, but differentially expressed, topoisomerase II isoforms, designated topoisomerase Ila and P. Here, we report the production of a new polyclonal antibody raised against a fragment of the C-terminal domain of the 180 kDa form of topoisomerase II (the P isoform), which does not cross-react with the 170 kDa form (the a isoform). Using this antibody, together with a polyclonal antibody specific for the 170 al., 1991;Capranico and Zunino, 1992;Pommier, 1993). DNA topoisomerase II is a nuclear enzyme which alters DNA tertiary structure through transient double-stranded breakage of the DNA backbone and subsequent passage of a second intact DNA duplex through the break (reviewed in Osheroff et al, 1991;Wang, 1985;Austin and Fisher, 1990;Watt and Hickson, 1994).…”

mentioning

confidence: 99%

Relationship between expression of topoisomerase II isoforms and intrinsic sensitivity to topoisomerase II inhibitors in breast cancer cell lines

Houlbrook

Addison²,

Davies³

et al. 1995

Br J Cancer

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Summary Topoisomerase II is a key target for many anti-cancer drugs used to treat breast cancer. In human cells there are two closely related, but differentially expressed, topoisomerase II isoforms, designated topoisomerase Ila and P. Here, we report the production of a new polyclonal antibody raised against a fragment of the C-terminal domain of the 180 kDa form of topoisomerase II (the P isoform), which does not cross-react with the 170 kDa form (the a isoform). Using this antibody, together with a polyclonal antibody specific for the 170 al., 1991;Capranico and Zunino, 1992;Pommier, 1993). DNA topoisomerase II is a nuclear enzyme which alters DNA tertiary structure through transient double-stranded breakage of the DNA backbone and subsequent passage of a second intact DNA duplex through the break (reviewed in Osheroff et al., 1991;Wang, 1985;Austin and Fisher, 1990;Watt and Hickson, 1994). The aforementioned drugs, as well as several other intercalating agents, including amsacrine (Nelson et al., 1984), trap the enzyme in a covalently bound reversible complex with DNA, termed the cleavable complex. The stabilisation of this complex prevents religation of the broken DNA and produces lesions which are thought to be cytotoxic by virtue of their ability to inhibit the passage of the replication fork. There is evidence that the cellular level of topoisomerase II determines the extent of cleavable complex formation after drug treatment and, therefore, the degree of drug toxicity. Low levels of topoisomerase II are associated with the induction of a reduced number of DNA lesions and hence increased drug resistance (Beck et al., 1993;Pommier, 1993). The converse relationship has been shown in mutant cell lines hypersensitive to topoisomerase II inhibitors (Davies et al., 1988) and also in testicular teratoma cell lines compared with bladder cell lines (Fry et al., 1991).There are two isoforms of topoisomerase II in mammalian cells that are products of different genes (Drake et al., 1989;Jenkins et al., 1992;Tan et al., 1992;Austin et al., 1993).These isoforms are termed a (170 kDa form) and , ((180 kDa form) and have different patterns of expression, suggesting that they might perform different functions. The a isoform is produced primarily in late S-phase and during the G2/M phase of the cell cycle (Woessner et al., 1991), and is apparently more sensitive to teniposide and merbarone than is the (Drake, et al., 1989). The gene encoding the a isoform has been mapped to chromosome 17q21-22 in humans (Tsai-Pflugfelder et al., 1988). The P isoform is expressed throughout the cell cycle, with higher levels seen in non-proliferating cells (Woessner et al., 1991) and is encoded on chromosome 3p24 in humans (Jenkins et al., 1992;Tan et al., 1992).Drug resistance is a major clinical problem in the treatment of solid tumours. Tumours often become resistant to multiple, structurally unrelated drugs as a result of expression of the membrane efflux pump, P-glycoprotein (reviewed in Bradley and Ling, 1994). This is the classi...

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“…13 DXR is known to both damage ionic pumps on the plasma membrane and to interfere with mitochondrial activity. [44][45][46] Moreover, DXR has been also reported to induce oncosis in different cells types, such as human endothelial cells, 15 melanoma 47 and myocytes. 48 Depletion of the glycogen content in ORS cells, which was clearly evident in our samples from T7 (data not shown) and T10, has been reported as one of the side effects of DXR.…”

Section: Epithelial Compartmentmentioning

confidence: 99%

Epithelium–mesenchyme compartment interaction and oncosis on chemotherapy-induced hair damage

Selleri

Arnaboldi

Vizzotto

et al. 2004

Laboratory Investigation

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It is known that chemotherapy induces alopecia in humans, with important psychological and social implications in spite of its reversibility. Among chemotherapeutic drugs, anthracyclines are widely used, yet cause severe alopecia. One of the causes for the elevated sensibility of hair follicles to anthracyclines, and to drugs in general, is the high proliferation rate of follicular epithelium and the long duration of the growth phase (up to 7 years in humans). To clarify the mechanism of anthracycline toxicity, we used a rat model and focused our attention on the morphological alterations in hair follicles induced by doxorubicin. We observed the progression of hair follicle degeneration in the epithelial and mesenchymal compartments until alopecia arose, by both light and electron microscopy. As a first sign of damage, significant apoptosis was detected in the proximal perifollicular connective tissue sheath and sporadically in the matrix, near the interface between matrix and follicular papilla. We propose the apoptotic remodeling of the mesenchymal compartment as a process that is fundamental to the progression of events leading to alopecia. Regarding the epithelial compartment, it is important to note that oncosis was observed in a large number of follicular cells in the outer root sheath during the last stages of hair follicle regression. This indicates that oncosis is involved in a major way in the damage of epithelial cells.

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Cell surface actions of adriamycin

Cited by 98 publications

References 96 publications

Recovery of pituitary function after treatment with a targeted cytotoxic analog of luteinizing hormone-releasing hormone

Recovery of pituitary function after treatment with a targeted cytotoxic analog of luteinizing hormone-releasing hormone

Relationship between expression of topoisomerase II isoforms and intrinsic sensitivity to topoisomerase II inhibitors in breast cancer cell lines

Epithelium–mesenchyme compartment interaction and oncosis on chemotherapy-induced hair damage

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