Fibroblast activation protein-α, a stromal cell surface protease, shapes key features of cancer associated fibroblasts through proteome and degradome alterations.

Cancer associated fibroblasts (CAFs) constitute an abundant stromal component of most solid tumors. Fibroblast activation protein (FAP) α is a cell surface protease that is expressed by CAFs. We corroborate this expression profile by immunohistochemical analysis of colorectal cancer specimens. To better understand the tumor-contextual role of FAPα, we investigate how FAPα shapes functional and proteomic features of CAFs using loss- and gain-of function cellular model systems. FAPα activity has a strong impact on the secreted CAF proteome ("secretome"), including reduced levels of anti-angiogenic factors, elevated levels of transforming growth factor (TGF) ß, and an impact on matrix processing enzymes. Functionally, FAPα mildly induces sprout formation by human umbilical vein endothelial cells. Moreover, loss of FAPα leads to a more epithelial cellular phenotype and this effect was rescued by exogenous application of TGFß. In collagen contraction assays, FAPα induced a more contractile cellular phenotype. To characterize the proteolytic profile of FAPα, we investigated its specificity with proteome-derived peptide libraries and corroborated its preference for cleavage carboxy-terminal to proline residues. By "terminal amine labeling of substrates" (TAILS) we explored FAPα-dependent cleavage events. Although FAPα acts predominantly as an amino-dipeptidase, putative FAPα cleavage sites in collagens are present throughout the entire protein length. In contrast, putative FAPα cleavage sites in non-collagenous proteins cluster at the amino-terminus. The degradomic study highlights cell-contextual proteolysis by FAPα with distinct positional profiles. Generally, our findings link FAPα to key aspects of CAF biology and attribute an important role in tumor-stroma interaction to FAPα.

[Contact allergies to recently introduced preservatives]. / Kontaktallergien gegen neuere Konservierungsmittel.

Preservatives have come under fire due to their possible detrimental properties and the high rate of contact allergies some of them cause. Therefore, the pharmaceutical industry is searching for alternatives that will be effective, safe and economical. The present paper introduces a selection of new or revived biocides (Kathon CG, benzisothiazolinone, Euxyl K 400, Biobans, Grotans, Bronopol, Germall II), and the range of application and the sensitization potency of each are discussed. Test concentrations for patch tests are recommended. Kathon CG is the most commonly used preservative among these biocides, although it has a high sensitization potency and is a frequently encountered contact allergen. To make discovery of a new allergen easier and to reduce the risk of side effects, manufacturers should be required to specify the ingredients of their products on the labels.

Allergic contact dermatitis to naftifine. Report of two cases.

We report on two cases of allergic contact dermatitis due to naftifine, an antimycotic substance. Epicutaneous tests were positive with the reagent itself but not with other compounds of the ointment. Additionally, one of the patients reacted to an ointment containing clotrimazole. Until now, only few cases of contact allergy to naftifine have been described, but an increasing number is expected.

[Changes in the oral mucosa in psoriasis pustulosa generalisata]. / Mundschleimhautveränderungen bei Psoriasis pustulosa generalisata.

A case of 7-year-old female patient with generalized pustular psoriasis associated with geographical tongu is described. Antipsoriatic therapy with etretinate caused a remarkable regression in the tongue lesions. In accordance with previous case reports, observations suggest that geographic tongue can after be a typical symptom of psoriasis pustulosa generalisata.

[Sex hormones in lupus erythematosus]. / Sexualhormone beim Lupus erythematodes.

In 23 male and female patients suffering from systemic lupus erythematosus (LEV) and discoid (LEI), estradiol and androgen serum levels were determined. 11 female patients showed normal levels of estrogen. 4 out of 6 patients with LEV and 1 patient with LEI showed reduced levels of testosterone. 4 out of 5 men with LEV and 4 out of 7 men with LEI showed elevated levels of estradiol. 10 out of 12 patients showed reduced levels of testosterone. These results suggest that sexual hormones may play a part in the origination and course of LEV and LEI.

[Drug-induced pemphigus]. / Arzneimittelbedingter Pemphigus.

A review of the literature on previous cases of drug-induced pemphigus as well as two case reports of pyritinole-induced pemphigus show a few characteristics: D-penicillamine was responsible in 42 cases, pyritinole in 4 cases, the two case reports included. Superficial pemphigus was seen in about 75% of the cases, most times associated with preexistent autoimmunological disorders. Immunological findings were identical with normal, non-drug-induced pemphigus, while the prognosis was better under mostly necessary immunosuppressive therapy at relatively low doses.