Alternative lengthening of telomere-based immortalization renders H3G34R -mutant diffuse hemispheric glioma hypersensitive to PARP inhibitor combination regimens.

Background: Diffuse hemispheric glioma, H3G34R/V-mutant (DHG-H3G34) is characterized by poor prognosis and lack of effective treatment options. DHG-H3G34R further harbor deactivation of Alpha-Thalassemia/Mental Retardation Syndrome X-linked protein (ATRX; DHG-H3G34R_ATRX) suggesting a unique interaction of these two oncogenic alterations. In this study, we dissect their cell biological interplay, investigate the impact on telomere stabilization and, consequently, validate a targeted therapy approach.

Inducible overexpression of a FAM3C/ILEI transgene has pleiotropic effects with shortened life span, liver fibrosis and anemia in mice.

FAM3C/ILEI is an important factor in epithelial-to-mesenchymal transition (EMT) induction, tumor progression and metastasis. Overexpressed in many cancers, elevated ILEI levels and secretion correlate with poor patient survival. Although ILEI's causative role in invasive tumor growth and metastasis has been demonstrated in several cellular tumor models, there are no available transgenic mice to study these effects in the context of a complex organism.

Distinct structural and dynamic components of portal hypertension in different animal models and human liver disease etiologies.

Background And Aims: Liver fibrosis is the static and main (70%-80%) component of portal hypertension (PH). We investigated dynamic components of PH by a three-dimensional analysis based on correlation of hepatic collagen proportionate area (CPA) with portal pressure (PP) in animals or HVPG in patients.

Approach And Results: Different animal models (bile duct ligation: n = 31, carbon tetrachloride: n = 12, thioacetamide: n = 12, choline-deficient high-fat diet: n = 12) and patients with a confirmed single etiology of cholestatic (primary biliary cholangitis/primary sclerosing cholangitis: n = 16), alcohol-associated (n = 22), and metabolic (NASH: n = 19) liver disease underwent CPA quantification on liver specimens/biopsies.

The effect of phosphate binder therapy with sucroferric oxyhydroxide on calcification propensity in chronic haemodialysis patients: a randomized, controlled, crossover trial.

Background: Calcification propensity is associated with the risk for cardiovascular events and death in end-stage renal disease patients. Here we investigated the effect of lowering serum phosphate with oral phosphate binder therapy on calcification propensity.

Methods: We performed an open-label, randomized, controlled, crossover study in chronic haemodialysis patients with hyperphosphataemia.

Evaluation of F8-TNF-α in Models of Early and Progressive Metastatic Osteosarcoma.

The targeted delivery of tumor necrosis factor-α (TNF-α) with antibodies specific to splice isoforms of fibronectin [e.g., F8-TNF, specific to the extra-domain A (EDA) domain of fibronectin] has already shown efficacy against experimental sarcomas but has not yet been investigated in orthotopic sarcomas.

Foscan and foslip based photodynamic therapy in osteosarcoma in vitro and in intratibial mouse models.

Current osteosarcoma therapies cause severe treatment-related side effects and chemoresistance, and have low success rates. Consequently, alternative treatment options are urgently needed. Photodynamic therapy (PDT) is a minimally invasive, local therapy with proven clinical efficacy for a variety of tumor types.

Evaluation of intraarterial and intravenous cisplatin chemotherapy in the treatment of metastatic osteosarcoma using an orthotopic xenograft mouse model.

Background: Osteosarcoma is the most common primary malignancy of bone. Its treatment relies on the administration of neoadjuvant and adjuvant chemotherapy combined with surgery. Alternative to common intravenous (i.

Altered CXCL12 expression reveals a dual role of CXCR4 in osteosarcoma primary tumor growth and metastasis.

Purpose: Better understanding of the molecular mechanisms of metastasis-the major cause of death in osteosarcoma (OS)-is a key for the development of more effective metastasis-suppressive therapy. Here, we investigated the biological relevance of the CXCL12/CXCR4 axis in OS.

Methods: We interfered with CXCL12/CXCR4 signaling in CXCR4-expressing human 143-B OS cells through stable expression of CXCL12, of its competitive antagonist P2G, or of CXCL12-KDEL, designed to retain CXCR4 within the cell.

Prognostic value and in vitro biological relevance of Neuropilin 1 and Neuropilin 2 in osteosarcoma.

Neoadjuvant chemotherapy in osteosarcoma increased the long-term survival of patients with localized disease considerably but metastasizing osteosarcoma remained largely treatment resistant. Neuropilins, transmembrane glycoproteins, are important receptors for VEGF dependent hyper-vascularization in tumor angiogenesis and their aberrant expression promotes tumorigenesis and metastasis in many solid tumors. Our analysis of Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2) immunostaining in a tissue microarray of 66 osteosarcoma patients identified NRP2 as an indicator of poor overall, metastasis-free and progression free survival while NRP1 had no predictive value.

Prognostic value of tumor suppressors in osteosarcoma before and after neoadjuvant chemotherapy.

Background: Primary bone cancers are among the deadliest cancer types in adolescents, with osteosarcomas being the most prevalent form. Osteosarcomas are commonly treated with multi-drug neoadjuvant chemotherapy and therapy success as well as patient survival is affected by the presence of tumor suppressors. In order to assess the prognostic value of tumor-suppressive biomarkers, primary osteosarcoma tissues were analyzed prior to and after neoadjuvant chemotherapy.

Expression of MSH2 and MSH6 on a tissue microarray in patients with osteosarcoma.

Background/aim: Reliable prognostic factors for the outcome of patients with osteosarcoma (OS) remain elusive. We analyzed the relationship between immunohistochemical expression of deoxyribonucleic acid (DNA) mismatch repair (MMR) proteins, MutS protein homolog 2 (MSH2) and MSH6 using a tissue microarray (TMA) with respect to OS patient demographics and survival time.

Materials And Methods: We retrieved tumor tissue specimens from bone tissue originating from surgical primary tumor specimens of OS patients to generate a TMA and stained sections with antibodies against MSH2 and MSH6.

ΔNp63α enhances the oncogenic phenotype of osteosarcoma cells by inducing the expression of GLI2.

Background: ΔNp63, a splice variant of p63, is overexpressed and exhibits oncogenic activity in many cancers including pancreatic and breast cancer and promotes cell survival by inhibiting apoptosis. Despite its role in tumorigenesis, mechanistic activity of ΔNp63 mediated oncogenic function in osteosarcoma is poorly understood.

Methods: The expression levels of p63 isoforms in osteosarcoma cell lines were identified using quantitative techniques.

Worse prognosis of osteosarcoma patients expressing IGF-1 on a tissue microarray.

Background: It is hardly possible to define osteosarcoma (OS) patients at greatest risk for non-response to chemotherapy, metastasis and short survival times. Our goal was the investigation of local expression of insulin-like growth factor (IGF-1) with regard to survival time of OS patients using a tissue microarray (TMA).

Materials And Methods: Tumor tissue specimens from surgical primary tumor resections were collected from patients with OS.

Reconstitution of the central and peripheral nervous system during salamander tail regeneration.

We show that after tail amputation in Ambystoma mexicanum (Axolotl) the correct number and spacing of dorsal root ganglia are regenerated. By transplantation of spinal cord tissue and nonclonal neurospheres, we show that the central spinal cord represents a source of peripheral nervous system cells. Interestingly, melanophores migrate from preexisting precursors in the skin.

A case of healthcare-associated, multidrug-resistant tuberculosis in Austria: reconsidering the value of cohorting of patients with culture-positive tuberculosis.

Cohorting of patients with culture-positive tuberculosis is still widely practiced in Austria, a country where approximately 1% of Mycobacterium tuberculosis isolates are multidrug resistant. Cohorting of patients with tuberculosis prior to determination of drug susceptibility is unacceptable because M. tuberculosis superinfection can occur.

Immunoadsorption in severe C4d-positive acute kidney allograft rejection: a randomized controlled trial.

Antibody-mediated rejection (AMR) frequently causes refractory graft dysfunction. This randomized controlled trial was designed to evaluate whether immunoadsorption (IA) is effective in the treatment of severe C4d-positive AMR. Ten out of 756 kidney allograft recipients were included.

A community outbreak of tuberculosis in Southern Austria: lessons learned for a targeted use of molecular epidemiological methods and tuberculin skin testing.

A cluster of 10 cases of tuberculosis disease (one of them extrapulmonary) occurred from July 2001 until November 2003 in a health district in Southern Austria. Eight patients were culture confirmed and shared an identical strain. One of these eight cases was identified as outbreak-related by molecular strain typing only.

Polarization-sensitive optical coherence tomography of dental structures.

Optical coherence tomography (OCT) has been developed during the last 10 years as a new noninvasive imaging tool and has been applied to diagnose different ocular and skin diseases. This technique has been modified for cross-sectional imaging of dental structures. In this first preliminary study the technique was applied to obtain tomographic images of extracted sound and decayed human teeth in order to evaluate its possible diagnostic potential for dental applications.