Targeting tumor cells

Houshmand, Pantea; Zlotnik, Albert

doi:10.1016/s0955-0674(03)00106-6

Cited by 36 publications

(25 citation statements)

References 22 publications

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“…4 The sequence homology-searching program BLASTN 5 was run sequentially for each nucleotide sequence against all of the human nucleotide sequences to prevent redundancies. As a second filter, electronic Northern was done for all clones obtained by keyword search by doing a BLAST search of each DNA sequences of interest against EST database at National Center for Biotechnology Information (NCBI).…”

Section: Methodsmentioning

confidence: 99%

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A Placenta-Specific Gene Ectopically Activated in Many Human Cancers Is Essentially Involved in Malignant Cell Processes

Şahin²,

et al. 2007

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The identification and functional characterization of tumorspecific genes is a prerequisite for the development of targeted cancer therapies. Using an integrated data mining and experimental validation approach for the discovery of new targets for antibody therapy of cancer, we identified PLAC1. PLAC1 is a placenta-specific gene with no detectable expression in any other normal human tissue. However, it is frequently aberrantly activated and highly expressed in a variety of tumor types, in particular breast cancer. RNAimediated silencing of PLAC1 in MCF-7 and BT-549 breast cancer cells profoundly impairs motility, migration, and invasion and induces a G 1 -S cell cycle block with nearly complete abrogation of proliferation. Knockdown of PLAC1 is associated with decreased expression of cyclin D1 and reduced phosphorylation of AKT kinase. Moreover, PLAC1 is localized on the surface of cancer cells and is accessible for antibodies which antagonize biological functions of this molecule. These features, in summary, make PLAC1 an attractive candidate for targeted immunotherapeutic approaches. [Cancer Res 2007;67(19):9528-34]

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Section: Methodsmentioning

confidence: 99%

“…In addition to lack of expression in toxicity relevant normal tissues, robust and high expression on the surface of tumor cells and exhibition of a tumor-promoting function are desirable characteristics for an ideal antibody target (4).…”

Section: Introductionmentioning

confidence: 99%

A Placenta-Specific Gene Ectopically Activated in Many Human Cancers Is Essentially Involved in Malignant Cell Processes

Şahin²,

et al. 2007

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“…Theoretically, the observed selectivity of an anticancer agent can be further enhanced using a variety of drug delivery strategies. Broadly speaking, these approaches have been centered around Ehrlich's proposed "magic bullet" concept (Houshmand and Zlotnik, 2003;Imai and Takaoka, 2006). Accordingly, these strategies share a common requirement in that the active cytotoxic agent is expected to accumulate to a greater extent in or around transformed cells relative to normal cells.…”

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confidence: 99%

The Role of Lysosomes in Limiting Drug Toxicity in Mice

Ndolo

Forrest

Krise

2010

J Pharmacol Exp Ther

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The distribution behavior of a drug within a cell is an important, yet often overlooked, variable in both activity and differential selectivity. In normal cells, drugs with weakly basic properties are known to be extensively compartmentalized in acidic organelles such as lysosomes via ion trapping. Several cancer cell lines have been shown to have defective acidification of endocytic organelles and therefore have a diminished capacity to sequester such lysosomotropic agents. In this study, we tested the hypothesis that the low lysosomal pH of normal cells plays an important role in protecting normal tissues from the toxic effects of lysosomotropic anticancer drugs. The influence of lysosomal pH status on the toxicity of inhibitors of the molecular chaperone Hsp90 that did or did not possess lysosomotropic properties was evaluated in mice. Toxicity of Hsp90 inhibitors was evaluated in normal mice and in mice treated with chloroquine to elevate lysosomal pH by assessing morbidity and utilizing biochemical assays to diagnose hepatic and renal toxicity. Toxicity of the lysosomotropic inhibitor 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17-DMAG) was significantly enhanced in mice with elevated lysosomal pH relative to mice with normal lysosomal pH. In contrast, elevation of lysosomal pH had no significant impact on toxicity of the nonlysosomotropic inhibitor geldanamycin. These results support the notion that the low lysosomal pH of normal cells plays an important role in protecting these cells from the toxic effects of anticancer agents with lysosomotropic properties and has implications for the design/selection of anticancer drugs with improved safety and differential selectivity.

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“…The therapeutic use of monoclonal antibodies (mAb) has emerged as a very potent clinical strategy in the treatment of cancer (Houshmand and Zlotnik, 2003;Hudis, 2007). In multiple myeloma (MM), we previously demonstrated that an antagonistic anti-IGF-1R mAb (EM164, also named mAVE1642) can selectively inhibit the growth of CD45 neg human myeloma cell lines (HMCLs) (Descamps et al, 2006).…”

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confidence: 99%