Inhibition of Tumor Microenvironment Cytokine Signaling Sensitizes Ovarian Cancer Cells to Antiestrogen Therapy

Antiestrogen therapy (AET) is an alternative to cytotoxic chemotherapy for recurrent ovarian cancer, yet the often short duration of response suggests mechanisms of resistance. We previously demonstrated that tumor microenvironment interleukin-6/leukemia inhibitory factor (IL6/LIF) cytokines induce tumor cell JAK-STAT signaling to promote cancer growth. Crosstalk between estrogen signaling and cytokine signaling has been reported. Therefore, we sought to characterize the impact of IL6/LIF signaling on estrogen signaling in epithelial ovarian cancer and investigate the efficacy of combination therapy. We first assessed patient tumors for cytokine expression and compared it with response to AET to determine clinical relevance. In vitro, we determined the effect of IL6/LIF on estrogen receptor expression and signaling. Cell viability assays were used to determine the efficacy and potential synergy of cytokine blockade and AET. We then extended studies to animal models, incorporating patient-derived stromal cells. Our results demonstrated shorter progression-free interval on AET in patients with stromal IL6/LIF expression. In vitro, IL6/LIF increased tumor cell estrogen receptor expression and signaling, and combination cytokine blockade and AET resulted in synergistic inhibition of tumor cell growth. The anticancer effect was verified in a mouse model. In conclusion, due to crosstalk between IL6/LIF cytokine signaling and estrogen signaling, dual blockade is a potential new treatment approach for ovarian cancer

Information asymmetries in banking and financial contracts: possible solutions from legal design.

In banking the strength of the Credit Institution is manifested in relation to the customer, who therefore assumes the role of a weak contractor, deserving of particular protection. Awareness of the characteristics of the products offered by banks, the comparison between the different services offered on the market and the opportunity to make an informed choice are all consequences linked to the information that is made available. Such information is above all unclear, so much so as to make it difficult to effectively evaluate the convenience of the operations and services offered. Specific rules are envisaged that intervene in the various phases in which the bank-customer relationship is divided. But it almost always happens that the documentation prepared by intermediaries is difficult to read and understand due to their technicality or to the use of a language that is not always easily understood. Everything described falls within the general discipline of banking and financial contracts which is today extremely complex, requires a particular study analysis of the various sectors governed by practices and regulatory interventions that are not always clear to customers and which should, instead, be made accessible through new solutions proposed by the world of legal design