Placement makes a difference: accuracy of an accelerometer in measuring step number and stair climbing.

Unlabelled: Accurate and easy-to-use measurement tools are required to evaluate the effect of treatments on patient activity. Comfortable device placement and fixation are important for patient compliance. The aim of this study was the evaluation of the accuracy of an accelerometer at different placements and slow velocities.

Mouse models for melanoma: a personal perspective.

Complex biological processes often require in vivo analysis, and many important research advances have been made using mice as a model for the study of various biological systems. Cutaneous melanomas are tumors originating from skin melanocytes, which are present in hair follicles, and interfollicular epidermal and dermal layers. Until recently, mouse melanoma models were largely based on transplantation models, i.

Identification and characterization of survivin-derived H-2Kb-restricted CTL epitopes.

Survivin is overexpressed in several malignancies and in tumor-associated endothelium making it an attractive target for therapeutic cytotoxic T-cell responses. Thus, it would be important to test this notion in preclinical models. Consequently, we screened the murine survivin sequence for potential binding K(b)-restricted octamer peptide epitopes.

MAPK-independent impairment of T-cell responses by the multikinase inhibitor sorafenib.

Sorafenib, originally developed as CRAF inhibitor but soon recognized as a multikinase inhibitor, is currently widely tested for the treatment of different cancers either alone or in combination therapy. However, the clinical success, particularly in immunogenic tumors such as melanoma, was less than anticipated. Because T-cell activation is tightly regulated by a multitude of kinases, we scrutinized effects of sorafenib on immune responses.

CD147 impacts angiogenesis and metastasis formation.

CD147 is highly expressed on many tumor cells; its role for tumor invasiveness and metastasis has been deduced from its capacity to induce MMPs, i.e., MMP-1, -2, -3, and -9.

The immunodominant HLA-A2-restricted MART-1 epitope is not presented on the surface of many melanoma cell lines.

Among the relatively large number of known tumor-associated antigens (TAA) which are recognized by human CD8 T-cells, Melan-A/MART-1 is one of the most-if not the most-frequently used target for anti-cancer vaccines in HLA-A2 + melanoma patients. In this study, we analyzed the killing of a large panel of melanoma cells by a high avidity, MART-1-specific T-cell clone or a MART-1-specific, polyclonal T-cell culture. Strikingly, we observed that the MART-1-specific T-cells only killed around half of the analyzed melanoma cell lines.

Macrophage migration inhibitory factor contributes to the immune escape of ovarian cancer by down-regulating NKG2D.

The proinflammatory cytokine macrophage migration inhibitory factor (MIF) stimulates tumor cell proliferation, migration, and metastasis; promotes tumor angiogenesis; suppresses p53-mediated apoptosis; and inhibits antitumor immunity by largely unknown mechanisms. We here describe an overexpression of MIF in ovarian cancer that correlates with malignancy and the presence of ascites. Functionally, we find that MIF may contribute to the immune escape of ovarian carcinoma by transcriptionally down-regulating NKG2D in vitro and in vivo which impairs NK cell cytotoxicity toward tumor cells.

Leishmania major-specific B cells are necessary for Th2 cell development and susceptibility to L. major LV39 in BALB/c mice.

B lymphocytes are considered to play a minimal role in host defense against Leishmania major. In this study, the contribution of B cells to susceptibility to infection with different strains of L. major was investigated in BALB/c mice lacking mature B cells due to the disruption of the IgM transmembrane domain (microMT).

Microphthalmia-associated transcription factor gene amplification in metastatic melanoma is a prognostic marker for patient survival, but not a predictive marker for chemosensitivity and chemotherapy response.

Purpose: The microphthalmia-associated transcription factor (MITF) is regarded as a key oncogene of the melanocytic lineage since it was detected by a genome-wide analysis to be strongly amplified in 15% to 20% of metastatic melanomas. MITF gene amplification was shown to be associated with a reduced survival in metastatic melanoma patients, and reduction of MITF activity was shown to sensitize melanoma cell lines to chemotherapeutics, suggesting the intratumoral MITF gene copy number as a predictive biomarker of response and survival after chemotherapy.

Patients And Methods: To validate this hypothesis, we investigated MITF gene amplification in tumor tissues obtained from 116 metastatic melanoma patients before an individualized sensitivity-directed chemotherapy using quantitative real-time PCR.

Matrix metalloproteinase induction in the tumor stroma does not depend on CD147 expression in murine B16 melanoma.

Background: It was conclusively demonstrated that the cell surface glycoprotein CD147 on tumor cells mediates induction of matrix metalloproteinases (MMPs) by stromal cells in humans. However, for murine models such evidence remains elusive.

Methods And Results: To address the impact of CD147 on MMP expression in the murine B16 melanoma model, we consequently stably knocked down CD147 expression in two B16 sublines.

Immunological tumor destruction in a murine melanoma model by targeted LTalpha independent of secondary lymphoid tissue.

Background: We previously demonstrated that targeting lymphotoxin alpha (LTalpha) to the tumor evokes its immunological destruction in a syngeneic B16 melanoma model. Since treatment was associated with the induction of peritumoral tertiary lymphoid tissue, we speculated that the induced immune response was initiated at the tumor site.

Methods And Results: In order to directly test this notion, we analyzed the efficacy of tumor targeted LTalpha in LTalpha knock-out (LTalpha(-/-)) mice which lack peripheral lymph nodes.

Dendritic cell based antitumor vaccination: impact of functional indoleamine 2,3-dioxygenase expression.

Background: Recent reports have demonstrated that the enzyme indoleamine 2,3-dioxygenase (IDO) is upregulated in human dendritic cells (DCs) upon in vitro maturation. IDO is supposed to convey immunosuppressive effects by degrading the essential amino acid tryptophan, thereby downregulating T-cell functions. Hence, we evaluated IDO expression in DC preparations used for therapeutic DC vaccination and its in vivo effects.

Therapeutic efficacy of tumor-targeted IL2 in LTalpha(-/-) mice depends on conditioned T cells.

An effective immunological eradication of tumors by the adaptive immune system depends on T cell priming, expansion of specific T cells and their effector function. It has been shown that either step may be impaired in the tumor-bearing host, and several strategies have been used to improve antitumor immune responses. In this regard, tumor-targeted IL2 therapy leads to the destruction of established melanoma metastases in fully immune competent mice as previously demonstrated.

Characterization of mouse MAGE-derived H-2Kb-restricted CTL epitopes.

Immunogenic peptide epitopes from tumor-associated antigens serve as targets for cellular immune responses in numerous clinical trials for therapeutic vaccinations. From these it became evident that prevailing questions can only be addressed in animal models. Hence, problems arise from the fact that while for human melanoma many different immunogenic peptide epitopes are known, for mouse melanoma the available selection is very restricted.

Overexpression of myosin IB in living Entamoeba histolytica enhances cytoplasm viscosity and reduces phagocytosis.

The human parasite Entamoeba histolytica is an ancient protozoan that expresses only one unconventional myosin, which has homology with myosin IB from other amoebae. Myosin IB is involved in phagocytosis of human cells by E. histolytica.

Experimental cutaneous Leishmaniasis: a powerful model to study in vivo the mechanisms underlying genetic differences in Th subset differentiation.

The murine model of infection with Leishmania major has allowed the demonstration in vivo of the importance CD4+ T cell subsets, distinguishable by the pattern of cytokines they produce, on the outcome of infectious diseases. Genetically determined resistance and susceptibility to infection with this parasite are the result of the development of Th1 and Th2 response, respectively. In this short paper, we present some results obtained in our group pertaining to the analysis of the mechanisms, operational during the early phase of this infection, responsible for the maturation of these functionally distinct CD4+ responses.