Challenges and applications of isotachophoresis coupled to mass spectrometry: A review.

Electrophoretic separations are of growing interest to tackle complex analytical challenges. Nevertheless, capillary electrophoresis, as the most common mode, still suffers from insufficient detection limits due to low capillary loadability. ITP is of growing interest as preconcentration method for capillary electrophoresis and is also interesting to be applied as an independent analytical method.

NSG mice as hosts for oncological precision medicine.

Patient-derived xenograft (PDX) models have been rediscovered as meaningful research tool. By using severely immunodeficient mice, high-engraftment rates can be theoretically achieved, permitting clinical stratification strategies. Apart from engraftment efficacy, tolerability towards certain cytostatic drugs varies among individual mouse strains thus impeding large-scale screenings.

Murine Endogenous Retroviruses Are Detectable in Patient-Derived Xenografts but Not in Patient-Individual Cell Lines of Human Colorectal Cancer.

Endogenous retroviruses are remnants of retroviral infections. In contrast to their human counterparts, murine endogenous retroviruses (mERV) still can synthesize infectious particles and retrotranspose. Xenotransplanted human cells have occasionally been described to be mERV infected.

Characterization of reconstructed human skin containing Langerhans cells to monitor molecular events in skin sensitization.

Human cell-based approaches to assess defined key events in allergic contact dermatitis (ACD) are well-established, but lack cutaneous penetration and biotransformation as well as cellular cross-talk. Herein, we integrated in vitro-generated immature MUTZ-3-derived Langerhans-like cells (MUTZ-LCs) or monocyte-derived LC-like cells (MoLCs) into reconstructed human skin (RHS), consistent of a stratified epidermis formed by primary keratinocytes on a dermal compartment with collagen-embedded primary fibroblasts. LC-like cells were mainly localized in the epidermal compartment and distributed homogenously in accordance with native human skin.

Generation of Xenotransplants from Human Cancer Biopsies to Assess Anti-cancer Activities of HDACi.

Human tumor in vivo cancer models raised in immunodeficient mice, the so-called patient-derived xenografts, are increasingly in use in preclinical development and evaluation of novel drug candidates including HDAC inhibitors. Here, we describe the techniques needed to generate novel patient-derived xenografts. The focus lies on vitally frozen tumor biopsies as starting material.

Sphingosine 1-phospate differentially modulates maturation and function of human Langerhans-like cells.

Background: As mediators between innate and adaptive immune responses, Langerhans cells (LCs) are in the focus of recent investigations to determine their role in allergic inflammatory diseases like allergic contact dermatitis and atopic dermatitis. Sphingosine 1-phosphate (S1P) is a crucial lipid mediator in the skin and potentially interferes with LC homeostasis but also functional properties, such as cytokine release, migration and antigen-uptake which are considered to be key events in the initiation and maintenance of pathological disorders.

Objective: Here, we used human Langerhans-like cells to study the influence of S1P-mediated signalling on LC maturation, cytokine release, migration and endocytosis.

Acute myeloid leukaemia-derived Langerhans-like cells enhance Th1 polarization upon TLR2 engagement.

Langerhans cells (LCs) represent a highly specialized subset of epidermal dendritic cells (DCs), yet not fully understood in their function of balancing skin immunity. Here, we investigated in vitro generated Langerhans-like cells obtained from the human acute myeloid leukaemia cell line MUTZ-3 (MUTZ-LCs) to study TLR- and cytokine-dependent activation of epidermal DCs. MUTZ-LCs revealed high TLR2 expression and responded robustly to TLR2 engagement, confirmed by increased CD83, CD86, PD-L1 and IDO expression, upregulated IL-6, IL-12p40 and IL-23p19 mRNA levels IL-8 release.

Chloroquine promotes IL-17 production by CD4+ T cells via p38-dependent IL-23 release by monocyte-derived Langerhans-like cells.

Recent studies suggest a role for autophagy in the secretion of IL-1 cytokines regulating the development of inflammatory diseases. The antimalarial drug and autophagy/lysosome inhibitor chloroquine (CHQ) is considered as potential trigger of drug-induced or drug-aggravated psoriasis, in which Th17 cells sustain a persistent inflammation. In this study, we investigated the effect of CHQ on human monocyte-derived Langerhans-like cells (MoLC) and dendritic cells (MoDC) in response to IL-1β.

Inflammatory conditions distinctively alter immunological functions of Langerhans-like cells and dendritic cells in vitro.

The specific function of human skin-resident dendritic cell (DC) subsets in the regulation of immunity or tolerance is still a matter of debate. Langerhans cells (LC) induce anti-viral immune responses but, conversely to dermal DC, maintain tolerance to bacteria. However, the definite function of epidermal LC and cutaneous DC appears even more complex under inflammatory conditions.

Biological evaluation of a novel doxorubicin-peptide conjugate for targeted delivery to EGF receptor-overexpressing tumor cells.

Epidermal growth factor receptor (EGFR) is overexpressed in a variety of epithelial malignancies and thus can be used for EGFR-targeted therapy to improve antitumor efficacy. Therefore we synthesized a novel conjugate of doxorubicin (DOX) with an EGFR-binding peptide (NH₂-CMYIEALDKYAC-COOH; EBP) via an ester bond at position 14 of DOX through a glutarate spacer. To confirm that the DOX-EBP conjugate is capable of targeting tumor cells overexpressing EGFR, we compared the cellular accumulation, intracellular distribution and in vitro cytotoxicity of DOX-EBP and free DOX.