Copper drives remodeling of metabolic state and progression of clear cell renal cell carcinoma.

Copper (Cu) is a cofactor of cytochrome c oxidase (CuCOX), indispensable for aerobic mitochondrial respiration. This study reveals that advanced clear cell renal cell carcinomas (ccRCCs) accumulate Cu, allocating it to CuCOX. Using a range of orthogonal approaches, including metabolomics, lipidomics, isotope-labeled glucose and glutamine flux analysis, and transcriptomics across tumor samples, cell lines, xenografts, and PDX models, combined with genetic and pharmacological interventions, we explored Cu's role in ccRCC.

Coordinated Targeting of S6K1/2 and AXL Disrupts Pyrimidine Biosynthesis in PTEN-Deficient Glioblastoma.

Unlabelled: Intrinsic resistance to targeted therapeutics in PTEN-deficient glioblastoma (GBM) is mediated by redundant signaling networks that sustain critical metabolic functions. Here, we demonstrate that coordinated inhibition of the ribosomal protein S6 kinase 1 (S6K1) and the receptor tyrosine kinase AXL using LY-2584702 and BMS-777607 can overcome network redundancy to reduce GBM tumor growth. This combination of S6K1 and AXL inhibition suppressed glucose flux to pyrimidine biosynthesis.

HDAC1 and HDAC6 are essential for driving growth in IDH1 mutant glioma.

Low-grade and secondary high-grade gliomas frequently contain mutations in the IDH1 or IDH2 metabolic enzymes that are hypothesized to drive tumorigenesis by inhibiting many of the chromatin-regulating enzymes that regulate DNA structure. Histone deacetylase inhibitors are promising anti-cancer agents and have already been used in clinical trials. However, a clear understanding of their mechanism or gene targets is lacking.

miR-221 Augments TRAIL-Mediated Apoptosis in Prostate Cancer Cells by Inducing Endogenous TRAIL Expression and Targeting the Functional Repressors SOCS3 and PIK3R1.

miR-221 is regarded as an oncogene in many malignancies, and miR-221-mediated resistance towards TRAIL was one of the first oncogenic roles shown for this small noncoding RNA. In contrast, miR-221 is downregulated in prostate cancer (PCa), thereby implying a tumour suppressive function. By using proliferation and apoptosis assays, we show a novel feature of miR-221 in PCa cells: instead of inducing TRAIL resistance, miR-221 sensitized cells towards TRAIL-induced proliferation inhibition and apoptosis induction.

Long tail balloon as a new approach for fetoscopic tracheal occlusion for a treatment of severe congenital diaphragmatic hernia.

Severe congenital diaphragmatic hernia (CDH) remains a significant challenge for neonatal specialists. In order to reduce complications during extraction of the surgical balloon after fetoscopic tracheal occlusion (FETO) CDH, we have developed a FETO with a 'long tail balloon' of 2.5 mL volume.

ERRα regulates the growth of triple-negative breast cancer cells via S6K1-dependent mechanism.

Estrogen-related receptor alpha (ERRα) is an orphan nuclear factor that is a master regulator of cellular energy metabolism. ERRα is overexpressed in a variety of tumors, including ovarian, prostate, colorectal, cervical and breast, and is associated with a more aggressive tumor and a worse outcome. In breast cancer, specifically, high ERRα expression is associated with an increased rate of recurrence and a poor prognosis.

Correlations between intravoxel incoherent motion (IVIM) parameters and histological findings in rectal cancer: preliminary results.

Our purpose was to correlate different intravoxel incoherent motion (IVIM), histopathological and clinical parameters in rectal cancer. 17 patients with histologically proven rectal cancer investigated on a 3.T device were included into the study.

Pharmacologic Targeting of S6K1 in PTEN-Deficient Neoplasia.

Genetic S6K1 inactivation can induce apoptosis in PTEN-deficient cells. We analyzed the therapeutic potential of S6K1 inhibitors in PTEN-deficient T cell leukemia and glioblastoma. Results revealed that the S6K1 inhibitor LY-2779964 was relatively ineffective as a single agent, while S6K1-targeting AD80 induced cytotoxicity selectively in PTEN-deficient cells.

Diffusion-Weighted Imaging Using a Readout-Segmented, Multishot EPI Sequence at 3 T Distinguishes between Morphologically Differentiated and Undifferentiated Subtypes of Thyroid Carcinoma-A Preliminary Study.

Background: Thyroid carcinomas represent the most frequent endocrine malignancies. Recent studies were able to distinguish malignant from benign nodules of the thyroid gland with diffusion-weighted imaging (DWI). Although this differentiation is undoubtedly helpful, presurgical discrimination between well-differentiated and undifferentiated carcinomas would be crucial to define the optimal treatment algorithm.

Thymic pathologies in myasthenia gravis: a preoperative assessment of CAT scan and nuclear based imaging.

Precise diagnostic work up of a suspected thymic pathology in patients with myasthenia gravis (MG) is very important for potential surgical implications and further disease course. In this study the diagnostic value of combined preoperative radiological (CAT scan) and nuclear based imaging (octreotide and thallium scintigraphy) in patients with MG was evaluated. Twenty four patients were included.

Metrics of Justice. A Sundial's Nomological Figuration.

This paper examines a polyhedral dial from the British Museum made by the instrument maker Ulrich Schniep, and discusses the status of multifunctional scientific instruments. It discerns a multifaceted iconic meaning considering different dimensions such as scientific functionality (astronomy), the complex allegorical figure of Justice (iconography), and the representation of the sovereign (politics), the court and the Kunstkammer of Albrecht v of Bavaria. As a numen mixtum the figure of "Justicia" touches different fields that go far beyond pure astronomical measurement and represents the power of the ruler as well as the rules of economic justice.

Muscle metastases: comparison of features in different primary tumours.

Background: Muscle metastases (MM) from solid tumours are rare. The aim of this study was to describe radiological features of MM, and to compare their patterns in different malignancies.

Methods: A retrospective search in the statistical database of our institution revealed 61 cases of MM.

Treatment of rare co-occurrence of Epstein-Barr virus-driven post-transplant lymphoproliferative disorder and hemophagocytic lymphohistiocytosis after allogeneic stem cell transplantation.

In both conditions, post-transplant lymphoproliferative disorder (PTLD) and hemophagocytic lymphohistiocytosis (HLH), infection with Epstein-Barr virus (EBV) is a key mechanism: almost all PTLD in allogeneic stem cell transplantation (alloSCT) is caused by EBV-related neoplastic lymphoproliferation, and secondary HLH is most frequently triggered by EBV infection. Therefore, concomitant EBV-driven PTLD and HLH early after alloSCT require an approach to eliminate EBV and balance immune activation simultaneously. We report on a patient who developed simultaneous PTLD and signs of HLH on day 64 after alloSCT.

Diffusion-weighted imaging of skeletal muscle lymphoma.

Objective: Muscle lymphoma (ML) is a relatively uncommon condition. On magnetic resonance imaging (MRI), ML can manifest with a broad spectrum of radiological features. The aim of this study was to demonstrate the features of DW images of muscle lymphoma (ML).

Pulmonary embolism in oncologic patients: frequency and embolus burden of symptomatic and unsuspected events.

Background: Pulmonary embolism (PE) is a common cause of morbidity and mortality in oncologic patients. Furthermore, PE is an unsuspected finding in many cases.

Purpose: To determine the frequency and embolus burden of PE in a consecutive oncologic patient group including symptomatic as well as incidental and initially unreported events.

Imaging of nonthrombotic pulmonary embolism: biological materials, nonbiological materials, and foreign bodies.

Nonthrombotic pulmonary embolism is defined as embolization to the pulmonary circulation caused by a wide range of substances of endogenous and exogenous biological and nonbiological origin and foreign bodies. It is an underestimated cause of acute and chronic embolism. Symptoms cover the entire spectrum from asymptomatic patients to sudden death.

Radio-opacity and incidental identified mechanical complications of totally implantable venous access devices placed in the chest.

Background: Totally implantable venous access devices (TIVAD) may be associated with different complications. Certain mechanical port disorders can easily be diagnosed on chest radiographs if the implanted systems are radiopaque and well visible. There are no reports regarding the visibility of TIVAD on chest X-rays.

Prevalence and imaging of hepatic involvement in malignant lymphoproliferative disease.

From January 2005 to January 2010, 668 consecutive patients with lymphoproliferative disease were retrospectively identified. Hepatic infiltration was present at initial staging in patients with non-Hodgkin's lymphoma [12 of 364=3.3%; age median=45; male:female (M:F)=10:2] but also Hodgkin's disease (5 of 41=12.

[Endocrine surgery for neck paraganglioma: operation, radiation therapy or wait and scan?].

Background: Head and neck paraganglioma (HNP) represent rare endocrine tumors. Therapy is decided on genetic findings, tumor characteristics (e.g.

C19orf12 mutations in neurodegeneration with brain iron accumulation mimicking juvenile amyotrophic lateral sclerosis.

Mutations in C19orf12 have been recently identified as the molecular genetic cause of a subtype of neurodegeneration with brain iron accumulation (NBIA). Given the mitochondrial localization of the gene product the new NBIA subtype was designated mitochondrial membrane protein-associated neurodegeneration. Frequent features in the patients described so far included extrapyramidal signs and pyramidal tract involvement.

Prevalence and patterns of renal involvement in imaging of malignant lymphoproliferative diseases.

Background: Renal involvement in patients with lymphoproliferative disease is an uncommon radiological finding.

Purpose: To determine its prevalence and radiological appearances in a patient population.

Material And Methods: All forms of lymphoproliferative disease (ICD: C81-C96) were considered.

Intramammary incidental findings on staging computer tomography.

Purpose: Incidental findings are a common feature in computer tomographic examinations of the chest. Breast incidentalomas, however, were described only sporadically. The purpose of this study was to evaluate retrospectively incidental breast findings and to compare radiological features of benign and malignant breast lesions.