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Background:Due to the frequent use of medical imaging including ultrasonography, the incidence of benign liver tumors has increased. There is a large variety of different solid benign liver tumors, of which hemangioma, focal nodular hyperplasia (FNH), and hepatocellular adenoma (HCA) are the most frequent. Advanced imaging techniques allow precise diagnosis in most of the patients, which reduces the need for biopsies only to limited cases. Patients with benign liver tumors are mostly asymptomatic and do not need any kind of treatment. Symptoms can be abdominal pain and pressure effects on adjacent structures. The 2 most serious complications are bleeding and malignant transformation. Summary:This review focuses on hepatic hemangioma (HH), FNH, and HCA, and provides an overview on clinical presentations, surgical and interventional treatment, as well as conservative management. Treatment options for HHs, if indicated, include liver resection, radiofrequency ablation, and transarterial catheter embolization, and should be carefully weighed against possible complications. FNH is the most frequent benign liver tumor without any risk of malignant transformation, and treatment should only be restricted to symptomatic patients. HCA is associated with the use of oral contraceptives or other steroid medications. Unlike other benign liver tumors, HCA may be complicated by malignant transformation. HCAs have been divided into 6 subtypes based on molecular and pathological features with different risk of complication. Key Message:The vast majority of benign liver tumors remain asymptomatic, do not increase in size, and rarely need treatment. Biopsies are usually not needed as accurate diagnosis can be obtained using modern imaging techniques.

Acute myeloid leukemia (AML) is characterized by a high relapse rate and dismal long-term overall survival which is related to persistence of leukemia-initiating cells in their niche. Different animal models of myeloid malignancies reveal how neoplastic cells alter the structural and functional characteristics of the hematopoietic stem cell niche to reinforce malignancy. Understanding and disruption of the microenvironmental interactions with AML cells are a vital need. Malignant niches frequently go along with inflammatory responses, but their impact on cancerogenesis often remains unexplored. Here, we uncovered an aberrant production of inflammatory cytokines in untreated AML bone marrow that was proved to promote the proliferation of leukemia cells. This inflammatory response induced an activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in AML blasts as well as bone marrow stromal cells that also fostered leukemia proliferation. Inhibition of JAK/STAT signaling using the selective JAK1/2 inhibitor ruxolitinib resulted in significant antileukemic activity in AML in vitro which is mediated through both cell-autonomous and microenvironment-mediated mechanisms. However, in a xenograft transplantation model, monotherapy with ruxolitinib did not achieve substantial antileukemic activity, possibly suggesting a complementary function of JAK1/2 inhibition in AML.

Acute myeloid leukemia (AML) is characterized by a high relapse rate and dismal long-term overall survival which is related to persistence of leukemia-initiating cells in their niche. Different animal models of myeloid malignancies reveal how neoplastic cells alter the structural and functional characteristics of the hematopoietic stem cell niche to reinforce malignancy. Understanding and disruption of the microenvironmental interactions with AML cells are a vital need. Malignant niches frequently go along with inflammatory responses, but their impact on cancerogenesis often remains unexplored. Here, we uncovered an aberrant production of inflammatory cytokines in untreated AML bone marrow that was proved to promote the proliferation of leukemia cells. This inflammatory response induced an activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in AML blasts as well as bone marrow stromal cells that also fostered leukemia proliferation. Inhibition of JAK/STAT signaling using the selective JAK1/2 inhibitor ruxolitinib resulted in significant antileukemic activity in AML in vitro which is mediated through both cell-autonomous and microenvironment-mediated mechanisms. However, in a xenograft transplantation model, monotherapy with ruxolitinib did not achieve substantial antileukemic activity, possibly suggesting a complementary function of JAK1/2 inhibition in AML.

To increase the reliability of translating preclinical findings to humans, large animal models, such as the transgenic (tg) Libechov minipig, were established. As minipigs possess high genetic homology with humans and have similarities in anatomy, physiology and metabolism to humans, they are considered for studying neurodegenerative diseases longitudinally. Recently, sleep abnormalities and changes in circadian rhythm in Huntington’s disease (HD) patients were acknowledged to present one of the early symptoms in HD. The aim of the present study was to explore the activity behaviour of Libechov minipigs and to investigate whether tgHD and wildtype (wt) minipigs exhibit differences in activity behaviour. Furthermore, it was investigated whether activity assessments may serve as reliable endpoints for phenotyping minipigs transgenic for the Huntington gene. Activity behaviour of minipigs was studied by video recording the stables twice a week over a total study period of five weeks for a cohort of five tgHD minipigs and five wt minipigs. Statistical analysis was performed using the linear mixed model. Once a week, the distances covered by two minipigs in focus (tgHD, wt) were measured using the VideoMotionTracker®software. Libechov minipigs showed a biphasic pattern of activity, spending most of the time inactive or grubbing in litter. Differences in activity behaviour (rooting, resting and standing) were detected between wt and tgHD minipigs. The influence of the genotype on behavioural patterns was observed during circadian monitoring. TgHD minipigs covered longer distances on average and during every 24 h observation period than wt minipigs. Activity behaviour may be a viable marker for phenotyping minipigs transgenic for the Huntington gene. Video recordings of behavioural patterns provide a non-invasive opportunity to capture potential disease signs. Phenotypic progression including the age of disease manifestation may be explored by documentation of circadian characteristics.

Prostate cancer (PCa), the most common cancer and second leading cause of cancer death in American men, presents the clinical challenge of distinguishing between indolent and aggressive tumors for proper treatment. PCa presents significant alterations in metabolic pathways that can potentially be measured using techniques like mass spectrometry (MS) or MS imaging (MSI) and used to characterize PCa aggressiveness. MS quantifies metabolomic, proteomic, and lipidomic profiles of biological systems that can be further visualized for their spatial distributions through MSI. PubMed was queried for all publications relating to MS and MSI in human PCa from April 2007 to April 2017. With the goal of reviewing the utility of MSI in diagnosis and prognostication of human PCa, MSI articles that reported investigations of PCa-specific metabolites or metabolites indicating PCa aggressiveness were selected for inclusion. Articles were included that covered MS and MSI principles, limitations, and applications in PCa. We identified nine key studies on MSI in intact human prostate tissue specimens that determined metabolites which could either differentiate between benign and malignant prostate tissue or indicate PCa aggressiveness. These MSI-detected biomarkers show promise in reliably identifying PCa and determining disease aggressiveness. MSI represents an innovative technique with the ability to interrogate cancer biomarkers in relation to tissue pathologies and investigate tumor aggressiveness. We propose MSI as a powerful adjuvant histopathology imaging tool for prostate tissue evaluations, where clinical translation of this ex vivo technique could make possible the use of MSI for personalized medicine in diagnosis and prognosis of PCa. Moreover, the knowledge provided from this technique can majorly contribute to the understanding of molecular pathogenesis of PCa and other malignant diseases.

Supplemental digital content is available in the text.

Supplemental digital content is available in the text.

A constitutive and dynamic interaction between tumor cells and their surrounding stroma is a prerequisite for tumor invasion and metastasis. Fibroblasts and myofibroblasts (collectively called cancer associated fibroblasts, CAFs) often represent the major cellular components of tumor stroma. Tumor cells secret different growth factors which induce CAFs proliferation and differentiation, and, consequently, CAFs secrete different chemokines, cytokines or growth factors which induce tumor cell invasion and metastasis. In this study we showed here that CAFs from breast cancer surgical specimens significantly induced the invasion of breast cancer cells in vitro. Most interestingly, the novel multiple tyrosine kinase inhibitor Dovitinib significantly blocked the CAFs-induced invasion of breast cancer cells by, at least in part, inhibition of the expression and secretion of CCL2, CCL5 and VEGF in CAFs. Inhibition of PI3K/Akt/mTOR signaling could be responsible for the effects of Dovitinib, since Dovitinib antagonized the promoted phosphorylated Akt after treatment with PDGF, FGF or breast cancer cell-conditioned media. Treatment with Dovitinib in combination with PI3K/Akt/mTOR signaling inhibitors Ly294002 or RAD001 resulted in additive inhibition of cell invasion. This is the first in vitrostudy to show that the multiple tyrosine kinase inhibitor has therapeutic activities against breast cancer metastasis by targeting both tumor cells and CAFs.

One mechanism underlying the link between multiple sclerosis (MS) and Epstein-Barr virus (EBV) might be a direct CNS infection. Viral CNS infections cause elevated antibody indices (AIs). Elevated EBV AIs were found in MS; however, patients with MS frequently show a polyspecific intrathecal immune response with elevated antiviral AIs. To discriminate whether elevated EBV AIs indicate a virus-driven or a polyspecific intrathecal immune response, we determined the intrathecal fraction of anti-EBV antibodies.

Statistical data from prostate cancer (PCa) clinics indicates that a large patient population discovered by annual prostate specific antigen (PSA) screening may have a latent form of the disease. However, current medical tests cannot differentiate slow from fast growing PCa, resulting in many unnecessary radical treatments and morbidities. It is thus necessary to find new screening tests that enable us to differentiate between fast- and slow-growing tumors. Inspired by the reported functions of spermine in carcinogenesis, we analyzed spermine and mRNA expression levels of rate-limiting enzymes in the spermine metabolic pathway for nine cases of PCa with accurately defined PSA velocity (Vpsa). Using MR spectroscopy, histopathology, laser-capture microdissection and real-time PCR techniques, we analyzed relationships between changes in spermine levels, mRNA expression levels of spermine anabolic and catabolic enzymes and human prostate cancer growth rates represented by serum Vpsa. The expression levels of spermine anabolic enzymes: ornithine decarboxylase (ODC1) and S-adenosylmethionine decarboxylase (AMD1) in benign epithelia surrounding cancer glands was logarithmically reduced with the increase of Vpsa (ODC1, p

Angiotensin (Ang) II enhances renal sympathetic neurotransmission and stimulates nitric oxide (NO) release. The present study investigates whether Ang II-mediated modulation of sympathetic neurotransmission is dependent on NO production in the kidney. AT2−/y receptor-deficient mice are used to identify the Ang II receptor subtype involved.

Sinn: LEO: Research Funding; Bayer Healthcare AG: Research Funding; Servier: Honoraria, Research Funding; Astra Zeneca: Honoraria, Research Funding; Amgen: Honoraria; Sanofi: Honoraria. Scholz:Celgene: Consultancy; GILEAD: Consultancy, Speakers Bureau; Roche: Consultancy; Janssen-Cilag: Consultancy; Hexal: Consultancy; Novartis: Consultancy; Pfizer: Speakers Bureau; Takeda: Consultancy; Daiichi Sankio: Consultancy. Klamroth:Bayer, Biomarin, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, SOBI, Takeda: Consultancy; Bayer, Novo Nordisk, SOBI: Research Funding.

Background: National and international guidelines for the diagnosis and treatment of cancer associated venous thromboembolism (CAT) recommend anticoagulation treatment for 3 to 6 months and a re-evaluation for resumption depending on the individual risk of every patient. In CAT low molecular weight heparin (LMWH) was estimated to be the most effective and safest treatment option in 2015. However, it remains unclear how cancer patients with VTE were (treated in clinical daily care in Germany. In former register trials, the specific characteristics of individual cancer patients were insufficiently characterized and inadequately discussed. Special aspects of daily care are lacking in most publications.