Cytokines in breast cancer

Nicolini, Andrea; Carpi, Angelo; Rossi, Giuseppe

doi:10.1016/j.cytogfr.2006.07.002

Cited by 248 publications

(223 citation statements)

References 86 publications

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“…All these data confirm that recombinant IL-1 receptor antagonist is a potential drug in cancer treatment [14]. Current clinical trials in breast cancer include other cytokines alone or in combination with other drugs [35].…”

Section: Il-1 Family: Generalitiessupporting

confidence: 63%

IL‐1 family in breast cancer: Potential interplay with leptin and other adipocytokines

2008

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Edited by Masayuki MiyasakaKeywords: IL-1 Leptin Adipocytokine Breast cancer Obesity a b s t r a c t Obesity is associated with an increased risk of breast cancer. interleukin-1 (IL-1), a pro-inflammatory cytokine secreted by adipose tissue, is involved in breast cancer development. There is also convincing evidence that other adipocytokines including leptin not only have a role in haematopoiesis, reproduction and immunity but are also growth factors in cancer. Therefore, IL-1 family and leptin family are adipocytokines which could represent a major link between obesity and breast cancer progression. This minireview provides insight into recent findings on the prognostic significance of IL-1 and leptin in mammary tumours, and discusses the potential interplay between IL-1 family members and adipocyte-derived hormones in breast cancer.

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Section: Il-1 Family: Generalitiessupporting

confidence: 63%

IL‐1 family in breast cancer: Potential interplay with leptin and other adipocytokines

2008

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“…We have previously shown that pharmacologic inhibition of p38 MAPK activity in tumor-infiltrating macrophages in vivo is associated with an antitumor effect (13). Similarly, IL-6 and CXCL8 have proliferative and proangiogenic properties; importantly, elevated levels of these cytokines are correlated with poor prognosis in breast and ovarian cancers (14,15).…”

mentioning

confidence: 99%

Characterization of LY2228820 Dimesylate, a Potent and Selective Inhibitor of p38 MAPK with Antitumor Activity

Campbell

Anderson

Brooks

et al. 2014

Molecular Cancer Therapeutics

101

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p38a mitogen-activated protein kinase (MAPK) is activated in cancer cells in response to environmental factors, oncogenic stress, radiation, and chemotherapy. p38a MAPK phosphorylates a number of substrates, including MAPKAP-K2 (MK2), and regulates the production of cytokines in the tumor microenvironment, such as TNF-a, interleukin-1b (IL-1b), . p38a MAPK is highly expressed in human cancers and may play a role in tumor growth, invasion, metastasis, and drug resistance. LY2228820 dimesylate (hereafter LY2228820), a trisubstituted imidazole derivative, is a potent and selective, ATP-competitive inhibitor of the a-and b-isoforms of p38 MAPK in vitro (IC 50 ¼ 5.3 and 3.2 nmol/L, respectively). In cellbased assays, LY2228820 potently and selectively inhibited phosphorylation of MK2 (Thr334) in anisomycinstimulated HeLa cells (at 9.8 nmol/L by Western blot analysis) and anisomycin-induced mouse RAW264.7 macrophages (IC 50 ¼ 35.3 nmol/L) with no changes in phosphorylation of p38a MAPK, JNK, ERK1/2, c-Jun, ATF2, or c-Myc 10 mmol/L. LY2228820 also reduced TNF-a secretion by lipopolysaccharide/IFNg-stimulated macrophages (IC 50 ¼ 6.3 nmol/L). In mice transplanted with B16-F10 melanoma, tumor phospho-MK2 (p-MK2) was inhibited by LY2228820 in a dose-dependent manner [threshold effective dose (TED) 70 ¼ 11.2 mg/kg]. Significant target inhibition (>40% reduction in p-MK2) was maintained for 4 to 8 hours following a single 10 mg/kg oral dose. LY2228820 produced significant tumor growth delay in multiple in vivo cancer models (melanoma, non-small cell lung cancer, ovarian, glioma, myeloma, breast). In summary, LY2228820 is a p38 MAPK inhibitor, which has been optimized for potency, selectivity, drug-like properties (such as oral bioavailability), and efficacy in animal models of human cancer. Mol Cancer Ther; 13(2); 364-74. Ó2013 AACR.

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“…IFN-γ administration can increase survival outcomes in a variety of cancers [33] by stimulating cellular immunity [34]. Low IFN-γ serum level, elevated IL-6 levels, extensive disease, malnutrition, and acute phase response were all related to a shorter survival time [35].…”

Section: Discussionmentioning

confidence: 99%

Changes in cytokine production and morphology of murine lymphoma NK/Ly cells in course of tumor development

2007

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Abstract:The main goal of this study was to evaluate if specific cytokine expression in the NK/Ly lymphoma cells might be involved in development of intoxication in the tumor-bearing animals. RT-PCR analysis was used to study an expression of mRNA coding for IL-1α, IL-6, TNF-α, TNF-β and VEGF. ELISA was used to evaluate IL-6 and IFN-γ concentration in the ascitic fluid. Cytomorphological investigation of tumor cells was done after standard Romanovsky-Giemsa staining, and chromatin staining was performed with hematoxyline and neutral red. Lactate dehydrogenase and acid phosphatase release from tumor cells was estimated. It was revealed that the level of mRNA coding for VEGF and IL-6 was significant in the lymphoma cells. The level of VEGF mRNA was initially high and did not change during tumor progression, while the level of expression of IL6 mRNA was low at the initial stages of tumor growth and markedly increased (up to 5-fold) at the terminal stages. The obtained data on IL-6 mRNA expression were confirmed by ELISA, which showed more than 6-fold increase (from 90 to 570 pg/ml) in the IL-6 concentration in the ascitic fluid at late stages of NK/Ly tumor development. On the contrary to IL-6, concentration of IFN-γ in the ascitic fluid was very high at early stages of tumor development (1,000 pg/ml) and it markedly decreased (up to 30-fold, 30 pg/ml) at the terminal stages of tumor development. The high levels of IL-6 mRNA in tumor cells and IL-6 content in extracellular medium correlated with cell deterioration, as revealed by cytomorphologic study and the release of intracellular enzymes into extracellular medium. We suggest that an enhanced production and release of IL-6 by lymphoma cells can cause intoxication and exhaustion of the organism observed at terminal stages of tumor growth.

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Cytokines in breast cancer

Cited by 248 publications

References 86 publications

IL‐1 family in breast cancer: Potential interplay with leptin and other adipocytokines

IL‐1 family in breast cancer: Potential interplay with leptin and other adipocytokines

Characterization of LY2228820 Dimesylate, a Potent and Selective Inhibitor of p38 MAPK with Antitumor Activity

Changes in cytokine production and morphology of murine lymphoma NK/Ly cells in course of tumor development

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