Atypical cellular responses mediated by intracellular constitutive active TrkB (NTRK2) kinase domains and a solely intracellular NTRK2-fusion oncogene.

Trk (NTRK) receptor and NTRK gene fusions are oncogenic drivers of a wide variety of tumors. Although Trk receptors are typically activated at the cell surface, signaling of constitutive active Trk and diverse intracellular NTRK fusion oncogenes is barely investigated. Here, we show that a high intracellular abundance is sufficient for neurotrophin-independent, constitutive activation of TrkB kinase domains.

Differences in stem cell marker and osteopontin expression in primary and recurrent glioblastoma.

Background: Despite of a multimodal approach, recurrences can hardly be prevented in glioblastoma. This may be in part due to so called glioma stem cells. However, there is no established marker to identify these stem cells.

The Radiosensitizing Effect of Zinc Oxide Nanoparticles in Sub-Cytotoxic Dosing Is Associated with Oxidative Stress In Vitro.

Radioresistance is an important cause of head and neck cancer therapy failure. Zinc oxide nanoparticles (ZnO-NP) mediate tumor-selective toxic effects. The aim of this study was to evaluate the potential for radiosensitization of ZnO-NP.

MAGE-A9 in head and neck cancer: Prognostic value and preclinical findings in the context of irradiation.

Radiotherapy alone, or as an addition to surgery is important for the treatment of head and neck squamous cell carcinoma (HNSCC). In addition to their expression in germ cells, melanoma associated antigens-A (MAGE-A) are only expressed in malignant tissue. Notably, there is a known correlation between MAGE-A9 expression and poor prognosis in HNSCC patients.

Combination of salinomycin and radiation effectively eliminates head and neck squamous cell carcinoma cells in vitro.

The antibiotic drug salinomycin has been reported to mediate cancer cell-specific cytotoxicity, especially regarding cancer stem cells. Since salinomycin has also been reported to arrest cancer cells in the G2 phase, it may have possible radiosensitizing effects. Radiotherapy is a common therapeutic strategy for head and neck squamous cell carcinoma (HNSCC).

Hypoxia induces differential expression patterns of osteopontin and CD44 in colorectal carcinoma.

The plasma protein osteopontin (OPN) is considered to be a tumor biomarker, where elevated plasma levels are associated with poor prognosis. Additionally, OPN is expressed in the presence of tumor hypoxia, which is an adverse prognostic factor in radiation oncology. One of its receptors, the proposed tumor stem cell marker CD44, is also associated with aggressive tumors, shown for example in colon cancer.

Perioperative changes in osteopontin and TGFβ1 plasma levels and their prognostic impact for radiotherapy in head and neck cancer.

Background: In head and neck cancer little is known about the kinetics of osteopontin (OPN) expression after tumor resection. In this study we evaluated the time course of OPN plasma levels before and after surgery.

Methods: Between 2011 and 2013 41 consecutive head and neck cancer patients were enrolled in a prospective study (group A).

Influence of hypoxia and irradiation on osteopontin expression in head and neck cancer and glioblastoma cell lines.

Background: Tumor hypoxia is a known risk factor for reduced response to radiotherapy. The evaluation of noninvasive methods for the detection of hypoxia is therefore of interest. Osteopontin (OPN) has been discussed as an endogenous hypoxia biomarker.

Influence of osteopontin silencing on survival and migration of lung cancer cells.

Background And Purpose: Osteopontin (OPN) is a multifunctional protein overexpressed in many cancers and is involved in tumor progression and metastasis. In lung cancer, elevated OPN expression is associated with an unfavorable prognosis. Therefore, inhibition of OPN is an attractive approach for improving survival.

Probiotic Escherichia coli Nissle 1917 suppresses allergen-induced Th2 responses in the airways.

Background: Recent clinical trials, epidemiological studies and animal experiments have suggested that probiotics may help suppress the development of allergic responses.

Objective: To investigate whether the application of the probiotic Escherichia coli strain Nissle 1917 (EcN) protects mice from developing ovalbumin (OVA)-specific T helper-2 responses in the airways.

Methods: OVA-specific Th2 responses were induced by 2 intraperitoneal (i.

Helminth-derived products inhibit the development of allergic responses in mice.

Rationale: Epidemiological studies suggest that infections with helminths protect from the development of asthma. Supporting this view is our published finding that infection with Nippostrongylus brasiliensis decreased ovalbumin-induced Th2 responses in the lung of mice.

Objectives: To evaluate if N.

Immune stimulatory strategies for the prevention and treatment of asthma.

The severity and incidence of asthma has dramatically increased in the developed nations over the last decades. Although the reason for this development is unknown, epidemiological studies and experimental data have lead to the suggestion that this phenomenon is associated with the decline of infectious diseases, which induce T helper 1 and/or T regulatory responses. Supporting this view are recent publications showing that animals can be protected from developing asthma by using different immune stimulatory strategies.

Murine polyomavirus-like particles induce maturation of bone marrow-derived dendritic cells and proliferation of T cells.

We analysed the effects of murine polyomavirus-like particles (PLPs) on bone marrow-derived dendritic cells (BMDCs) and T cells in vitro. BMDCs activated with PLPs up-regulated CD40, CD80, CD86 and major histocompatibility complex (MHC) class II surface markers and produced proinflammatory cytokines. Chimeric PLPs [expressing the ovalbumin (OVA)-peptides OVA(257-264) or OVA(323-339)], but not wildtype PLPs, activated OVA-specific CD8 T cells and OVA-specific CD4 T cells, respectively, indicating both MHC class I and II presentation of the peptides by antigen-presenting cells.

The stability and anti-apoptotic function of A1 are controlled by its C terminus.

Most Bcl-2 family members can localize to intracellular membranes via hydrophobic sequences within their C-terminal portion. We found that the C terminus of the anti-apoptotic family member A1 did not function as a membrane anchor. Instead, this stretch of the protein rendered A1 highly unstable by mediating its polyubiquitination and rapid proteasomal degradation.

Vaccinations with T-helper type 1 directing adjuvants have different suppressive effects on the development of allergen-induced T-helper type 2 responses.

Background: Allergen-induced T-helper type 2 (Th2) responses can be inhibited with Th1 directing vaccines. However, studies comparing the efficacy of the different adjuvants have not been performed in detail.

Objective: For this reason we compare the effects of live Bacillus-Calmette-Guerin(BCG), heat-killed (hk)-BCG, CpG-ODN (oligodeoxynucleotide) or PPD on the development of allergen-induced Th2 responses in mice.

The absence of IFN-gamma leads to increased Th2 responses after influenza A virus infection characterized by an increase in CD4+ but not CD8+ T cells producing IL-4 or IL-5 in the lung.

The cytokine IL-4 has been shown to be responsible for the switch of both CD4+ and CD8+ T cells to a Th2 or TC2 functional phenotype in vitro which both secrete IL-4 after stimulation. In contrast the presence of IFN-gamma interferes with the generation of Th2 and TC2 cells in vitro. Furthermore, it is well established that in the absence of IFN-gamma and the presence of IL-4 Th2 cells also develop in vivo.

CYP2D6 genotype: impact on adverse effects and nonresponse during treatment with antidepressants-a pilot study.

Objective: Treatment with antidepressants is frequently associated with adverse effects or insufficient clinical response. Several antidepressants are metabolized by cytochrome P450 (CYP) 2D6. The activity of this enzyme markedly varies among individuals from poor to ultrarapid metabolism on the basis of the polymorphism of the CYP2D6 gene.

Helminth infection modulates the development of allergen-induced airway inflammation.

It has been proposed that infections with helminths can protect from the development of allergic diseases. However, epidemiological and experimental studies have yielded conflicting results. Therefore we investigated if an infection with Nippostrongylus brasiliensis influenced the development of allergen-induced Th2 cell responses in mice.

Mice deficient in nuclear factor of activated T-cell transcription factor c2 mount increased Th2 responses after infection with Nippostrongylus brasiliensis and decreased Th1 responses after mycobacterial infection.

Infection of nuclear factor of activated T-cell transcription factor c2 (NFATc2)-deficient mice with the helminth Nippostrongylus brasiliensis led to a distinct increase in interleukin-4 (IL-4) and IL-5 protein synthesis by lymph node and spleen cells and to elevated serum immunoglobulin E (IgE) levels in comparison to those seen with infected control mice. While IL-4, IL-5, and IL-13 mRNA expression was also enhanced in lymph node cells from the lungs of infected NFATc2(-/-) mice, the number of T cells secreting Th2-type lymphokines remained the same in mice infected with N. brasiliensis.

Inhibition of the IL-4/IL-13 receptor system prevents allergic sensitization without affecting established allergy in a mouse model for allergic asthma.

Background: IL-4 and IL-13 are considered as key regulators for the development of atopic disease.

Objective: This study addresses the therapeutic potential of an IL-4/IL-13 inhibitor on the basis of a mutated IL-4 variant (Q116D, Y119D) during allergic sensitization and in established disease in a murine asthma model with persistent airway pathologic condition.

Methods: BALB/c mice were sensitized with ovalbumin intranasally.

Inflammation versus immunoregulation: what is the key to the development of an effective antiallergy vaccine?

The incidence and severity of allergic disorders is currently increasing worldwide. The reason for this development is unclear. However, epidemiological studies and experimental data suggest that this increase may be due to a decline in infectious diseases which induce T helper type 1 (Th1) and/or T regulatory (Tr) responses.

Influenza A virus infection inhibits the efficient recruitment of Th2 cells into the airways and the development of airway eosinophilia.

Most infections with respiratory viruses induce Th1 responses characterized by the generation of Th1 and CD8(+) T cells secreting IFN-gamma, which in turn have been shown to inhibit the development of Th2 cells. Therefore, it could be expected that respiratory viral infections mediate protection against asthma. However, the opposite seems to be true, because viral infections are often associated with the exacerbation of asthma.

Novel vaccines protecting against the development of allergic disorders: a double-edged sword?

The severity and incidence of allergic disorders is steadily increasing despite the widespread use of steroids and other drugs. Recent results obtained in animals suggest that it may be possible to develop novel anti-allergy vaccines for human use, thereby stopping this alarming worldwide increase in allergic diseases. The most promising approaches are the induction of allergen-specific T helper 1 or allergen-specific T regulatory responses.

[Heat-killed Mycobacterium bovis-Bacillus Calmette-Guerin prevents experimental respiratory tract eosinophilia in mice].

Introduction: The increased prevalence of asthma has become a major public health issue worldwide. It has been proposed that this increase is due to the steady decline of infectious diseases such as tuberculosis.

Aim Of The Study: Supporting this view was, the suppressive effect of live Bacillus Calmette-Guerin (BCG) infection on allergen (ovalbumin) induced airway eosinophilia was published previously.

Analysis of maturation states of rat bone marrow-derived dendritic cells using an improved culture technique.

In this study, we examined in more detail the development of rat bone marrow-derived dendritic cells (BMDC). A two-stage culture system was used to propagate BMDC from rat bone marrow precursors. BMDC developed within clusters of proliferating cells after repetitive addition of rat granulocyte/macrophage colony-stimulating factor and rat interleukin (IL)-4 at a concentration of 5 ng/ml to the cultures.