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.

Tumor-associated macrophages may either promote or suppress tumor growth depending on their activation status. Interferon-γ (IFN-γ) has been identified as a key factor for inducing tumoricidal M1 phenotype in macrophages. However, it remains unclear whether IFN-γ is sufficient or if additional stimuli are required. Here, we tested IFN-γ and a panel of toll-like receptor (TLR) agonists for the ability to activate murine macrophages toward a tumoricidal M1 phenotype. The following TLR ligands were used: TLR1/TLR2 agonist Pam3CSK4, TLR2/TLR6 agonist lipotechoic acid, TLR3 agonist poly(I:C), TLR4 agonist lipopolysaccharide (LPS), TLR5 agonist flagellin, TLR7 agonist CL264, and TLR9 agonist CpG. We used an in vitro growth inhibition assay to measure both cytotoxic and cytostatic activity of mouse macrophages against Lewis lung carcinoma (LLC) and MOPC315 plasmacytoma tumor cells. Production of nitric oxide (NO) and cytokines by activated macrophages was quantified. We found that IFN-γ alone was not able to render macrophages tumoricidal. Similarly, macrophage activation with single TLR agonists was inefficient. In sharp contrast, IFN-γ was shown to synergize with TLR agonists for induction of macrophage tumoricidal activity and production of both NO and pro-inflammatory cytokines (TNF-α, IL-12p40, and IL-12p70). Furthermore, IFN-γ was shown to suppress macrophage IL-10 secretion induced by TLR agonists. NO production was necessary for macrophage tumoricidal activity. We conclude that two signals from the microenvironment are required for optimal induction of antitumor M1 macrophage phenotype. Combination treatment with IFN-γ and TLR agonists may offer new avenues for macrophage-based cancer immunotherapy.

A patient's frequent request is the simultaneous surgical removal of a previously diagnosed myoma during cesarean section. The aim of this study was to evaluate the safety and efficacy of myomectomy during cesarean section. From January 1995 until December 2004, 47 pregnant women with coexisting uterine myomas underwent cesarean section and simultaneous myomectomy. All cesarean sections were performed by residents while myomectomies were conducted by the senior staff. Intraoperative and postoperative complications such as blood loss were estimated and compared with 94 women with uterine myomas who underwent surgical delivery without removal of the fibroids. Furthermore, the length of hospitalization was compared between the two groups. Myomectomy added a mean time of 15 min to the operative time of cesarean section. No hysterectomy was performed at the time of the cesarean section. No complications were developed during the puerperium. The difference between the preoperative and postoperative hemoglobin mean value was statistically significant (P=0.001) but did not differ between isolated cesarean and myomectomy-combined cesarean groups. None of the patients received blood transfusion. The length of hospitalization was comparable between the two groups. Despite controversial literature data, we suggest that myomectomy during cesarean section could be generally recommended. Depending on size and location of myomas, the associated risks are similar to those of isolated cesarean section.