The rapid development of microbial resistance to conventional antibiotics has accelerated efforts to find anti-infectives with a novel mode-of-action, which are less prone to bacterial resistance. Intense nonclinical and clinical research is today ongoing to evaluate antimicrobial peptides (AMPs) as potential next-generation antibiotics. Currently, multiple AMPs are assessed in latestage clinical trials, not only as novel anti-infective drugs, but also as innovative product candidates for immunomodulation, promotion of wound healing, and prevention of post-operative scars. The efforts to translate AMP-based research findings into pharmaceutical product candidates are expected to accelerate in coming years due to technological advancements in multiple areas, including an improved understanding of the mechanism-of-action of AMPs, smart formulation strategies, and advanced chemical synthesis protocols. At the same time, it is recognized that cytotoxicity, low metabolic stability due to sensitivity to proteolytic degradation, and limited oral bioavailability are some of the key weaknesses of AMPs. Furthermore, the pricing and reimbursement environment for new antimicrobial products remains as a major barrier to the commercialization of AMPs.

We identified previously a region on chromosome 19p13.2 spanning the genes encoding the intercellular adhesion molecules (ICAM), ICAM1, ICAM4 and ICAM5 as a breast cancer susceptibility locus. Genetic variants in this region were also associated with indicators of disease severity, including higher rates of metastases to other organs. Based on this association, we set out to explore the role of ICAM1 in proliferation and invasion of human breast cancer cells. We observed that ICAM1 downregulation at the mRNA and protein levels led to a strong suppression of human breast cell invasion through a matrigel matrix. Under the same conditions, no significant effect on cell proliferation in vitro was seen. Incubation of cells with an antibody against ICAM1 blocked invasion of the highly metastatic MDA-MB-435 cell line in a dose-dependent manner without affecting cell migration. We also demonstrated that the level of ICAM1 protein expression on the cell surface positively correlated with metastatic potential of five human breast cancer cell lines and that ICAM1 mRNA levels were elevated in breast tumor compared with adjacent normal tissue. These results corroborate our previous genetic finding that variations in the ICAM region are associated with the occurrence of metastases and establish a causal role of ICAM1 in invasion of metastatic human breast carcinoma cell lines.

Biological markers for acquisition and extinction of fear conditioning were studied in 40 individuals selected for displaying either good or poor acquisition of fear conditioning. as estimated by the skin conductance response. Participants with a short serotonin transporter (5-HTT) promoter allele or low monoamine oxidase activity in platelets (trbc-MAO) displayed better acquisition than those with only long alleles or high trbc-MAO, whereas participants with a long dopamine D4 receptor (D4DR) exon III allele showed delayed extinction compared with those with only short alleles. The findings, that D4DR exon III and 5-HTT promoter genotypes and trbc-MAO activity are related to human fear conditioning, a basic form of associative learning, are consistent with animal studies suggesting a genetic contribution to fear conditioning. The authors suggest that in humans these genetic mechanisms are partly dopaminergic and serotonergic in origin.

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