Corticosteroid co-treatment induces resistance to chemotherapy in surgical resections, xenografts and established cell lines of pancreatic cancer

Zhang, Chengwen; Kolb, Armin; Büchler, Peter; Cato, Andrew C. B.; Mattern, J; Rittgen, Werner; Edler, Lutz; Debatin, Klaus‐Michael; Büchler, Markus W.; Frieß, Helmut; Herr, Ingrid

doi:10.1186/1471-2407-6-61

Cited by 42 publications

(30 citation statements)

References 32 publications

(33 reference statements)

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“…The results of Wang et al 87 however, can not be explained on the basis of cell kinetics. Thus, the results from our 6,90,91,95 and other studies in murine and human tumor xenografts indicate that, in GC-sensitive tumors, concurrent treatment with steroids and anticancer drugs may be contraindicated and that the effectiveness of cycle stage-specific agents may be considerably reduced due to unfavorable cell cycle distributions. On the other hand, GCs may add significantly to the effectiveness of a sequential chemotherapy program when used appropriately by altering the temporal relationship of the recovery events in the tumor and the normal tissues.…”

Section: © 2 0 0 8 L a N D E S B I O S C I E N C E D O N O T D I S mentioning

confidence: 70%

Cell Cycle Arrest by Glucocorticoids May Protect Normal Tissue and Solid Tumors from Cancer Therapy

Mattern¹,

Büchler²,

Herr³

2007

Cancer Biology & Therapy

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ABBrevIAtIons DEX ABstrActGlucocorticoids have been widely used as cotreatment for patients with cancer due to potent pro-apoptotic properties in lymphoid cells, reduction of nausea and diminishing acute toxicity on normal tissue. There are now data from preclinical and, to some extent, clinical studies, demonstrating that these medicaments are highly suspicious to induce therapy resistance in the majority of malignant solid tumors-irrespective of tumor origin and the nature of specific anticancer drugs or irradiation used for treatment. Despite these huge amounts of data, the underlying mechanisms of cell type-specific signaling by these steroid hormones are just beginning to be described. This review summarizes our present understanding of a relationship between glucocorticoid-induced reversible cell cycle arrest and therapy resistance in solid tumors. We give a summary of our current knowledge of decreased proliferation rates in response to glucocorticoid pre and combination treatment which are suspicious to be involved not only in protection of normal tissues, but also in protection of solid tumors from cytotoxic effects of anticancer agents. The inhibition of cell cycle progression by pretreatment with GCs may be crucially involved in switching the balance of several interacting pathways to survival upon treatment with GCs.

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Section: © 2 0 0 8 L a N D E S B I O S C I E N C E D O N O T D I S mentioning

confidence: 70%

Cell Cycle Arrest by Glucocorticoids May Protect Normal Tissue and Solid Tumors from Cancer Therapy

Mattern¹,

Büchler²,

Herr³

2007

Cancer Biology & Therapy

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“…Prolonged elevation of glucocorticoids could have a direct impact upon tumorigenesis. It has been reported that glucocorticoids promote survival and proliferation of tumor cells and the chemotherapeutic resistance of tumor cells (13). However, the underlying mechanisms are largely unknown.…”

Section: Glucocorticoids Decrease P53 Protein Levels and Function In mentioning

confidence: 99%

Chronic restraint stress attenuates p53 function and promotes tumorigenesis

Feng

Liu²,

Zhang³

et al. 2012

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

169

138

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Epidemiological studies strongly suggest that chronic psychological stress promotes tumorigenesis. However, its direct link in vivo and the underlying mechanisms that cause this remain unclear. This study provides direct evidence that chronic stress promotes tumorigenesis in vivo; chronic restraint, a well-established mouse model to induce chronic stress, greatly promotes ionizing radiation (IR)-induced tumorigenesis in p53 +/− mice. The tumor suppressor protein p53 plays a central role in tumor prevention. Loss or attenuation of p53 function contriubutes greatly to tumorigenesis. We found that chronic restraint decreases the levels and function of p53 in mice, and furthermore, promotes the growth of human xenograft tumors in a largely p53-dependent manner. Our results show that glucocorticoids elevated during chronic restraint mediate the effect of chronic restraint on p53 through the induction of serum-and glucocorticoid-induced protein kinase (SGK1), which in turn increases MDM2 activity and decreases p53 function. Taken together, this study demonstrates that chronic stress promotes tumorigenesis in mice, and the attenuation of p53 function is an important part of the underlying mechanism, which can be mediated by glucocortcoids elevated during chronic restraint.

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“…Correspondingly, a huge amount of data suggests that GCs acutely induce resistance in normal and transformed cells of epithelial origin, including the majority of human solid malignant tumor cells. Tumors involved have been found to be derived from bladder, brain, breast, cervix, colon, liver, lung, kidney, ovary, pancreas, prostate, rectum and testis, and also neuroblastomas, melanomas and osteosarcomas are rendered therapy resistant by GCs [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. These GC-induced prosurvival effects may become clinically relevant when they interfere with the effect of chemotherapeutics [28].…”

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confidence: 99%

Regulation of differential pro- and anti-apoptotic signaling by glucocorticoids

et al. 2006

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More than a quarter of a century ago, the phenomenon of glucocorticoid-induced apoptosis in the majority of hematological cells was first recognized. More recently, glucocorticoid-induced antiapoptotic signaling associated with apoptosis resistance has been identified in cells of epithelial origin, most of malignant solid tumors and some other tissues. Despite these huge amount of data demonstrating differential pro- and anti-apoptotic effects of glucocorticoids, the underlying mechanisms of cell type specific glucocorticoid signaling are just beginning to be described. This review summarizes our present understanding of cell type-specific pro- and anti-apoptotic signaling induced by glucocorticoids. In the first section we give a summary and update of known glucocorticoid-induced pathways mediating apoptosis in hematological cells. We shortly introduce mechanisms of glucocorticoid resistance of hematological cells. We highlight and discuss the emerging molecular evidence of a general induction of survival signaling in epithelial cells and carcinoma cells by glucocorticoids. We provide a model for glucocorticoid-induced resistance in cells growing in a tissue formation. Thus, attachment to the extracellular matrix and cell-cell contacts typical for e.g. epithelial and tumor cells may be crucially involved in switching the balance of several interacting pathways to survival upon treatment with glucocorticoids.

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Corticosteroid co-treatment induces resistance to chemotherapy in surgical resections, xenografts and established cell lines of pancreatic cancer

Abstract: These data show that DEX induces therapy resistance in pancreatic carcinoma cells and raise the question whether GC-mediated protection of tumour cells from cancer therapy may be dangerous for patients.

Cited by 42 publications

References 32 publications

Cell Cycle Arrest by Glucocorticoids May Protect Normal Tissue and Solid Tumors from Cancer Therapy

Cell Cycle Arrest by Glucocorticoids May Protect Normal Tissue and Solid Tumors from Cancer Therapy

Chronic restraint stress attenuates p53 function and promotes tumorigenesis

Regulation of differential pro- and anti-apoptotic signaling by glucocorticoids

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