A clinical phase I/II trial of rhIL-4 applied topically in patients with oral squamous cell carcinomas to assess safety and therapeutic activity

Werkmeister, R.; Fillies, Thomas; Gaertner, Christoph; Joos, Ulrich; Berdel, Wolfgang E.

doi:10.3892/or.13.3.449

Cited by 2 publications

(2 citation statements)

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“…Administration by the intra-tumoral route has been tested in patients with recurrent head and neck cancer. In one of the treated patients, rapidly advancing disease was observed after cytokine administration, although it remains uncertain whether this was related to IL-4 therapy [26]. …”

Section: Introductionmentioning

confidence: 99%

Clinical Investigation of the Role of Interleukin-4 and Interleukin-13 in the Evolution of Prostate Cancer

Goldstein

Hanley

Morris

et al. 2011

Cancers

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Prostate cancer is the most common cancer in men, both in the USA and Europe. Although incurable, metastatic disease can often be controlled for years with anti-androgen therapy. Once the disease becomes castrate resistant, the median survival is 18 months. There is growing evidence that the immune system, and in particular cytokines, play an important role in prostate cancer immunosurveillance and progression. Here, we have undertaken a clinical investigation of the role of two closely related cytokines, IL-4 and IL-13 in prostate cancer. In the largest series studied to date, we show that serum IL-4, but not IL-13 is significantly elevated in castrate resistant, compared to androgen sensitive disease. Notably however, serum IL-4 levels are also raised in patients with benign prostatic disease. Analysis of benign and malignant prostate tissue demonstrates that the source of IL-4 is epithelial cells rather than infiltrating leukocytes. Together, our data are consistent with a dual role for IL-4 in prostate cancer development. In benign disease, our data add to the evidence that IL-4 serves a protective role. By contrast, the data support a direct role for IL-4 in the progression of prostate cancer from androgen responsive, to advanced castrate-resistant disease.

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Section: Introductionmentioning

confidence: 99%

Clinical Investigation of the Role of Interleukin-4 and Interleukin-13 in the Evolution of Prostate Cancer

Goldstein

Hanley

Morris

et al. 2011

Cancers

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“…In fact, adenoviral transfer of IL-4 has been shown to be protective against cartilage degradation induced by injection of rheumatoid arthritis synovial tissue into joints of SCID mice [12] and against collagen-induced arthritis [13]. However, a phase I/II clinical trial testing topical application of IL-4 in patients with oral squamous cell carcinoma was terminated early due to limiting toxicity [14]. It would therefore be beneficial to understand the molecular basis of the beneficial effects of IL-4 in order to facilitate the design of therapeutics that mimic those effects, but with fewer side-effects.…”

Section: Introductionmentioning

confidence: 99%

IL-4 inhibition of IL-1 induced Matrix Metalloproteinase-3 (MMP-3) expression in human fibroblasts involves decreased AP-1 activation via negative crosstalk involving of Jun N-terminal Kinase (JNK)

Chambers

Kirkpatrick

Evans

et al. 2013

Experimental Cell Research

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Matrix metalloproteinase-3 (MMP-3) over-expression is associated with tissue destruction in the context of chronic inflammation. Previous studies showed that IL-4 inhibits induction of MMP-3 by IL-1β, and suggested that AP-1 might be involved. Here we show that IL-1 induced binding of transcription factor AP-1 to the MMP-3 promoter consists primarily of c-Jun, JunB, and c-Fos and that binding of c-Jun and c-Fos is inhibited by the combination of cytokines while binding of Jun B is not. Mutation of the AP-1 site in the MMP-3 promoter decreased the ability of IL-4 to inhibit its transcription in transfected MG-63 cells. Western blotting showed that both cytokines activate Jun N-terminal kinase (JNK), but with somewhat different kinetics, and that activation of JNK by both cytokines individually is inhibited by the combination. These results indicate that IL-4 inhibition of MMP-3 expression is associated with reduction of IL-1 induced binding of active forms of the AP-1 dimer, while less active JunB-containing dimers remain, and suggest that these changes are associated with decreased activation of JNK.

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A clinical phase I/II trial of rhIL-4 applied topically in patients with oral squamous cell carcinomas to assess safety and therapeutic activity

Cited by 2 publications

References 0 publications

Clinical Investigation of the Role of Interleukin-4 and Interleukin-13 in the Evolution of Prostate Cancer

Clinical Investigation of the Role of Interleukin-4 and Interleukin-13 in the Evolution of Prostate Cancer

IL-4 inhibition of IL-1 induced Matrix Metalloproteinase-3 (MMP-3) expression in human fibroblasts involves decreased AP-1 activation via negative crosstalk involving of Jun N-terminal Kinase (JNK)

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