Sequential Local Injection of Low-Dose Interferon-Beta for Maintenance Therapy in Stage II and III Melanoma: A Single-Institution Matched Case-Control Study
ABSTRACT To determine the beneficial effect of maintenance therapy in stage II and III melanoma by sequential local injection of low-dose interferon-β.
We reviewed 46 patients with stage II and III primary melanoma at our institution from 2004 through 2009. Twenty-one patients were treated with interferon-β maintenance therapy consisting of subcutaneous injection of natural interferon-β at a dose of 3 × 10(6) IU/day for 10 consecutive days, and 25 patients underwent observation alone.
Compared with all patients, overall survival and relapse-free survival were significantly worse in the observation group than in the interferon-β group (p = 0.024 and 0.029, respectively). In stage II, a significant difference in overall survival, but not in relapse-free survival, was seen between the two groups (p = 0.041). When the interferon-β group was stratified by subgroup, there was a statistical difference only between dosage and duration (p = 0.027 and p < 0.001, respectively).
This study demonstrates that maintenance therapy by interferon-β is beneficial in the outcome of the disease without substantial toxic effects, especially in patients with stage II melanoma. Extension of the duration of treatment beyond 2 years could further improve the therapeutic efficacy of interferon-β.
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ABSTRACT: Interferons (IFNs) are a family of naturally existing glycoproteins known for their antiviral activity and their ability to influence the behavior of normal and transformed cell types. Type I Interferons include IFN- α and IFN- β . Currently, IFN- α has numerous approved antitumor applications, including malignant melanoma, in which IFN- α has been shown to increase relapse free survival. Moreover, IFN- α has been successfully used in the intralesional treatment of cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In spite of these promising clinical results; however, there exists a paucity of knowledge on the precise anti-tumor action of IFN- α / β at the cellular and molecular levels in cutaneous malignancies such as SCC, BCC, and melanoma. This review summarizes current knowledge on the extent to which Type I IFN influences proliferation, apoptosis, angiogenesis, and immune function in normal skin, cutaneous SCC, BCC, and melanoma.Dermatology Research and Practice 01/2014; 2014:847545. DOI:10.1155/2014/847545
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ABSTRACT: High basal or induced expression of the tripartite motif protein, TRIM16, leads to reduce cell growth and migration of neuroblastoma and skin squamous cell carcinoma cells. However, the role of TRIM16 in melanoma is currently unknown. TRIM16 protein levels were markedly reduced in human melanoma cell lines, compared with normal human epidermal melanocytes due to both DNA methylation and reduced protein stability. TRIM16 knockdown strongly increased cell migration in normal human epidermal melanocytes, while TRIM16 overexpression reduced cell migration and proliferation of melanoma cells in an interferon beta 1 (IFNβ1)-dependent manner. Chromatin immunoprecipitation assays revealed TRIM16 directly bound the IFNβ1 gene promoter. Low level TRIM16 expression in 91 melanoma patient samples, strongly correlated with lymph node metastasis, and, predicted poor patient prognosis in a separate cohort of 170 melanoma patients with lymph node metastasis. The BRAF inhibitor, vemurafenib, increased TRIM16 protein levels in melanoma cells in vitro, and induced growth arrest in BRAF-mutant melanoma cells in a TRIM16-dependent manner. High levels of TRIM16 in melanoma tissues from patients treated with Vemurafenib correlated with clinical response. Our data, for the first time, demonstrates TRIM16 is a marker of cell migration and metastasis, and a novel treatment target in melanoma.Oncotarget 09/2014; · 6.63 Impact Factor
- The Journal of Dermatology 04/2014; 41(4):364-5. DOI:10.1111/1346-8138.12435 · 2.35 Impact Factor