Apaf-1 expression in malignant melanoma

Soengas, Marı́a S.; Gerald, William L.; Cordon‐Cardo, Carlos; Lazebnik, Yuri; Lowe, Scott W.

doi:10.1038/sj.cdd.4401755

Cited by 19 publications

(16 citation statements)

References 26 publications

(38 reference statements)

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“…This does not mean that loss of components of the apoptotic pathway could not play a role in the MDR phenotype of some tumors of epithelial origin. Indeed, there is evidence that a decrease in Apaf-1 could contribute to therapy resistance of melanomas (35). That blocks in apoptosis/senescence can contribute to chemotherapy resistance of lymphomas/leukemias is not in dispute and is also supported by recent work on other mouse models (36,37).…”

Section: Discussionmentioning

confidence: 53%

Selective induction of chemotherapy resistance of mammary tumors in a conditional mouse model for hereditary breast cancer

Rottenberg¹,

Nygren

Pajic³

et al. 2007

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

273

256

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We have studied in vivo responses of ''spontaneous'' Brca1-and p53-deficient mammary tumors arising in conditional mouse mutants to treatment with doxorubicin, docetaxel, or cisplatin. Like human tumors, the response of individual mouse tumors varies, but eventually they all become resistant to the maximum tolerable dose of doxorubicin or docetaxel. The tumors also respond well to cisplatin but do not become resistant, even after multiple treatments in which tumors appear to regrow from a small fraction of surviving cells. Classical biochemical resistance mechanisms, such as up-regulated drug transporters, appear to be responsible for doxorubicin resistance, rather than alterations in drug-damage effector pathways. Our results underline the promise of these mouse tumors for the study of tumor-initiating cells and of drug therapy of human cancer.multidrug resistance ͉ P-glycoprotein ͉ cancer stem cells

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Section: Discussionmentioning

confidence: 53%

Selective induction of chemotherapy resistance of mammary tumors in a conditional mouse model for hereditary breast cancer

Rottenberg¹,

Nygren

Pajic³

et al. 2007

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

273

256

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“…Current knowledge of signaling may provide an explanation of why previous therapies have failed. Phosphoinositol-3 kinase activation has been shown to mediate against extrinsic pathways of apoptosis, which include apoptosis due to TRAIL, TNF alpha, and interferons (10). Monotherapies of these cytokines may be frustrated in the face of phosphoinositol-3 kinase activation.…”

Section: Discussionmentioning

confidence: 99%

“…Even melanomas that do not carry activated B-raf demonstrate activation of MAP kinase, and constitutive expression of activated MAP kinase kinase is sufficient to transform melanocytes to melanoma (3, 4, 5). Other pathways that are known to be activated in advanced melanoma include phosphoinositol-3 kinase/akt and nuclear factor kappa beta (NFκB) (6, 7, 8, 9, 10). All of these pathways confer survival and proliferative advantages to melanoma, such as induction of angiogenic factors, including vascular endothelial growth factor, interleukin-8, survivin, IAP, and mcl-1 (11, 12, 13).…”

Section: Introductionmentioning

confidence: 99%

Tris (Dibenzylideneacetone) Dipalladium, aN-Myristoyltransferase-1 Inhibitor, Is Effective against Melanoma GrowthIn vitroandIn vivo

Bhandarkar

Bromberg

Carrillo

et al. 2008

Clinical Cancer Research

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Purpose Melanoma is a solid tumor that is notoriously resistant to chemotherapy, and its incidence is rapidly increasing. Recently, several signaling pathways have been demonstrated to contribute to melanoma tumorigenesis, including constitutive activation of MAP kinase, Akt and Stat-3. The activation of multiple pathways may account in part for the difficulty in treatment of melanoma. In a recent screen of compounds, we found that an organopalladium compound, tris (dibenzylideneacetone) dipalladium (Tris DBA), demonstrated significant antiproliferative activity against melanoma cells. Studies were carried out to determine the mechanism of action of Tris DBA Experimental Design Tris DBA was tested on efficacy on proliferation of human and murine melanoma cells. In order to find the mechanism of action of Tris DBA, we performed Western Blot analysis and gene array analysis. The ability of Tris DBA to block tumor growth in vivo was assessed. Results (Tris DBA), has activity against B16 murine and A375 human melanoma in vivo. Tris DBA inhibits several signaling pathways including activation of MAP kinase, Akt, Stat-3 and S6 kinase activation, suggesting an upstream target. Tris DBA was found to be a potent inhibitor of N-myristoyltransferase 1 (NMT-1), which is required for optimal activity of membrane based signaling molecules. Tris DBA demonstrated potent antitumor activity in vivo against melanoma. Conclusion Tris DBA is thus a novel inhibitor of NMT-1 with significant antitumor activity and is well tolerated in vivo. Further preclinical evaluation of Tris DBA and related complexes is warranted.

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“…7 However, there is still controversy as to whether APAF1 silencing is really essential in vivo for tumor ontogenesis and/or progression. 26 It should be mentioned that recent works postulated that experimental conditions may invalidate the evaluation of APAF1 expression levels by western blotting. 24,25 In spite of this finding, although APAF1 expression level has been considered constant in PDAC cell lines, 32 we decided to investigate this aspect by several approaches.…”

Section: Discussionmentioning

confidence: 99%

Analysis of apoptosome dysregulation in pancreatic cancer and of its role in chemoresistance

Corvaro

Fuoco²,

Wagner³

et al. 2007

Cancer Biology & Therapy

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Apaf-1 expression in malignant melanoma

Cited by 19 publications

References 26 publications

Selective induction of chemotherapy resistance of mammary tumors in a conditional mouse model for hereditary breast cancer

Selective induction of chemotherapy resistance of mammary tumors in a conditional mouse model for hereditary breast cancer

Tris (Dibenzylideneacetone) Dipalladium, aN-Myristoyltransferase-1 Inhibitor, Is Effective against Melanoma GrowthIn vitroandIn vivo

Analysis of apoptosome dysregulation in pancreatic cancer and of its role in chemoresistance

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