IGF-1 is a potent mitogen of major importance in the mammary gland. IGF-1 binding to the cognate receptor, IGF-1R, triggers a signaling cascade leading to proliferative and anti-apoptotic events. Although many of the relevant molecular pathways and intracellular cascades remain to be elucidated, a growing body of evidence points to the important role of the IGF-1 system in breast cancer development, progression and metastasis. IGF-1 is a point of convergence for major signaling pathways implicated in breast cancer growth. In this review, we provide an overview and concise update on the function and regulation of IGF-1 as well as the role it plays in breast malignancies.

The Notch signaling pathway regulates developmental cell-fate decisions and has recently also been linked to inflammatory diseases. Although therapies targeting Notch signaling in inflammation in theory are attractive, their design and implementation have proven difficult, at least partly due to the broad involvement of Notch signaling in regenerative and homeostatic processes. In this review, we summarize the supporting role of Notch signaling in various inflammation-driven diseases, and highlight efforts to intervene with this pathway by targeting Notch ligands and/or receptors with distinct therapeutic strategies, including antibody designs. We discuss this in light of lessons learned from Notch targeting in cancer treatment. Finally, we elaborate on the impact of individual Notch members in inflammation, which may lay the foundation for development of therapeutic strategies in chronic inflammatory diseases.

Although androgen receptor (AR) signaling is the main molecular tool regulating growth and function of the prostate gland, estrogen receptor β (ERβ) is involved in the differentiation of prostatic epithelial cells and numerous antiproliferative actions on prostate cancer cells. However, ERβ splice variants have been associated with prostate cancer initiation and progression mechanisms. ERβ is promising as an anticancer therapy and in the prevention of prostate cancer. Herein, we review the recent experimental findings of ERβ signaling in the prostate.

Oral cancer is a common malignancy worldwide, with high disease-related death rates. Oral squamous cell carcinoma (OSCC) accounts for more than 90% of oral tumors, with surgical management remaining the treatment of choice. However, advanced and metastatic OSCC is still incurable. Thus, emphasis has been given lately in understanding the complex role of the oral tumor microenvironment (TME) in OSCC progression, in order to identify novel prognostic biomarkers and therapeutic targets. Tumor associated macrophages (TAMs) constitute a major population of the OSCC TME, with bipolar role in disease progression depending on their activation status (M1 vs. M2). Here, we provide an up to date review of the current literature on the role of macrophages during oral oncogenesis, as well as their prognostic significance in OSCC survival and response to standard treatment regimens. Finally, we discuss novel concepts regarding the potential use of macrophages as targets for OSCC immunotherapeutics and suggest future directions in the field.

Objective. To determine the expression of soluble TNF-like cytokine 1A (sTL1A), a new member of the TNF superfamily, in patients with AS. Methods. Seventy-five consecutive patients with AS [61 males, mean (s.d.) age: 47.2 (15.5) years, disease duration: 20.3 (13.9) years] were included in this study. Forty-four patients were anti-TNF treatment naïve, whereas the remaining patients were on infliximab (n = 21), adalimumab (n = 3) or etanercept (n = 7). The patients’ perceived disease activity was recorded by BASDAI and AS DAS using serum CRP levels (ASDAS-CRP), whereas functional status was assessed by BASFI and measurements of spinal mobility (AS Metrology). Serum concentrations of TL1A were measured by ELISA. Twenty-five age- and sex-matched healthy individuals served as controls. Results. Anti-TNF treatment-naïve patients demonstrated a 2.6-fold higher sTL1A average value [mean (s.e.m.) 581 (157.5) pg/ml] compared with healthy controls [226.7 (48.24) pg/ml, P = 0.042]. The sTL1A levels of anti-TNF-treated patients [178 (42)] were significantly lower than anti-TNF treatment-naïve patients (3.3-fold decrease, P = 0.0038) and comparable to those of healthy controls. No significant association was found between sTL1A level and functional status (BASFI score, AS Metrology parameters) or CRP measured in the same sera; however, a positive correlation was observed between individual levels of sTL1A and both BASDAI (P = 0.008) and ASDAS-CRP (P = 0.058) scores suggesting that sTL1A levels may reflect disease activity in patients with AS. Conclusion. TL1A is up-regulated in AS, associates with disease activity and is influenced by anti-TNF treatment, suggesting that TL1A may be of pathogenic and potentially of therapeutic importance in AS patients.