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Genetic loci of Mycoplasma agalactiae involved in systemic spreading during experimental intramammary infection of sheep

Mycoplasmas are amongst the most successful pathogens of both humans and animals yet the molecular basis of mycoplasma pathogenesis is poorly understood. This is partly due to the lack of classical virulence factors and little similarity to common bacterial pathogenic determinants. Using Mycoplasma agalactiae as a model we initiated research in this direction by screening a ...

Dysfunctional Presynaptic M2 Receptors in the Presence of Chronically High Acetylcholine Levels: Data from the PRiMA Knockout Mouse

The muscarinic M2 receptor (M2R) acts as a negative feedback regulator in central cholinergic systems. Activation of the M2 receptor limits acetylcholine (ACh) release, especially when ACh levels are increased because acetylcholinesterase (AChE) activity is acutely inhibited. Chronically high ACh levels in the extracellular space, however, were reported to down-regulate M2R to ...

The German AugUR study: study protocol of a prospective study to investigate chronic diseases in the elderly

Background The majority of patients suffering from chronic health disabilities is beyond 70 years of age. Typical late-onset chronic diseases include those affecting the heart, the kidney, cancer, and conditions of the eye such as age-related macular degeneration. These diseases disable patients for many years and largely compromise autonomy in daily life. Due to challenges in ...

MVP and vaults: a role in the radiation response

Vaults are evolutionary highly conserved ribonucleoproteins particles with a hollow barrel-like structure. The main component of vaults represents the 110 kDa major vault protein (MVP), whereas two minor vaults proteins comprise the 193 kDa vault poly(ADP-ribose) polymerase (vPARP) and the 240 kDa telomerase-associated protein-1 (TEP-1). Additionally, at least one small and ...

Attenuated and Protease-Profile Modified Sendai Virus Vectors as a New Tool for Virotherapy of Solid Tumors

Multiple types of oncolytic viruses are currently under investigation in clinical trials. To optimize therapeutic outcomes it is believed that the plethora of different tumor types will require a diversity of different virus types. Sendai virus (SeV), a murine parainfluenza virus, displays a broad host range, enters cells within minutes and already has been applied safely as a gene ...

Dynamics of Tumor Hypoxia in Response to Patupilone and Ionizing Radiation

Tumor hypoxia is one of the most important parameters that determines treatment sensitivity and is mainly due to insufficient tumor angiogenesis. However, the local oxygen concentration in a tumor can also be shifted in response to different treatment modalities such as cytotoxic agents or ionizing radiation. Thus, combined treatment modalities including microtubule stabilizing ...

Upregulation of α7 Nicotinic Receptors by Acetylcholinesterase C-Terminal Peptides

Background The alpha-7 nicotinic acetylcholine receptor (α7-nAChR) is well known as a potent calcium ionophore that, in the brain, has been implicated in excitotoxicity and hence in the underlying mechanisms of neurodegenerative disorders such as Alzheimer's disease. Previous research implied that the activity of this receptor may be modified by exposure to a peptide fragment ...

Optical Detection and Virotherapy of Live Metastatic Tumor Cells in Body Fluids with Vaccinia Strains

Metastatic tumor cells in body fluids are important targets for treatment, and critical surrogate markers for evaluating cancer prognosis and therapeutic response. Here we report, for the first time, that live metastatic tumor cells in blood samples from mice bearing human tumor xenografts and in blood and cerebrospinal fluid samples from patients with cancer were successfully ...

Selective Protection of Human Liver Tissue in TNF-Targeting of Cancers of the Liver by Transient Depletion of Adenosine Triphosphate

Background Tumor necrosis factor alpha (TNF) is able to kill cancer cells via receptor-mediated cell death requiring adenosine triphosphate (ATP). Clinical usage of TNF so far is largely limited by its profound hepatotoxicity. Recently, it was found in the murine system that specific protection of hepatocytes against TNF's detrimental effects can be achieved by fructose-mediated ...

Efficient Colonization and Therapy of Human Hepatocellular Carcinoma (HCC) Using the Oncolytic Vaccinia Virus Strain GLV-1h68

Virotherapy using oncolytic vaccinia virus strains is one of the most promising new strategies for cancer therapy. In this study, we analyzed for the first time the therapeutic efficacy of the oncolytic vaccinia virus GLV-1h68 in two human hepatocellular carcinoma cell lines HuH7 and PLC/PRF/5 (PLC) in cell culture and in tumor xenograft models. By viral proliferation assays and ...

Artificial neural networks allow the use of simultaneous measurements of Alzheimer Disease markers for early detection of the disease

Background Previous studies have shown that in platelets of mild Alzheimer Disease (AD) patients there are alterations of specific APP forms, paralleled by alteration in expression level of both ADAM 10 and BACE when compared to control subjects. Due to the poor linear relation among each key-element of beta-amyloid cascade and the target diagnosis, the use of systems able to ...

CLINICAL TRIALS

INTRODUCTION: Bevacizumab, irinotecan, and temozolomide have promising activity in a variety of central nervous system tumors. For children with high-grade gliomas or recurrent brain tumors, new agents in new combinations are needed. METHODS: Cycles were 28 days. Patients were selected for study based on relapsed or progressive disease with no other standard therapy available. ...

MEDULLOBLASTOMA

Medulloblastoma (MB) is the most common children brain cancer. Recent advances in cancer biology strMBongly suggest that impaired microRNAs expression is one of the critical events driving cancer development. Previous studies of microRNA expression profiling suggested hsa-miR-383 as one of the down-regulated microRNAs in MB. However, the functions of this microRNA in MB remain ...

EPENDYMOMA

BACKGROUND: Children's brain is continuously developing. Radiation oncologists usually refrain from radiating brain in the first 3 years. PURPOSE: To identify the feasibility of irradiating infratentorial ependymoma postoperatively in children below 3 years and to report on its effect on survival and toxicity. PATIENTS AND METHODS: Thirty seven children were diagnosed as ependymoma ...