Impact of sex hormones on pheochromocytomas, paragangliomas, and gastroenteropancreatic neuroendocrine tumors.

Objective: The effects of sex hormones remain largely unexplored in pheochromocytomas and paragangliomas (PPGLs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Methods: We evaluated the effects of estradiol, progesterone, Dehydroepiandrosterone sulfate (DHEAS), and testosterone on human patient-derived PPGL/GEP-NET primary culture cell viability (n = 38/n = 12), performed next-generation sequencing and immunohistochemical hormone receptor analysis in patient-derived PPGL tumor tissues (n = 36).

Results: In PPGLs, estradiol and progesterone (1 µm) demonstrated overall significant antitumor effects with the strongest efficacy in PPGLs with NF1 (cluster 2) pathogenic variants.

Symptom burden and relief in palliative care units of German Comprehensive Cancer Center and other hospitals.

Purpose: The National Hospice and Palliative Registry contains patient data from German hospice and palliative care facilities about symptoms. The aim of the study at hand is to differentiate symptom burden of patients in palliative care units between Comprehensive Cancer Center (CCC) and other hospitals regarding symptom burden and relief of patients in palliative care units.

Methods: The registry analysis provided data of patients in palliative care units (2014-2018).

Viral host range factors antagonize pathogenic SAMD9 and SAMD9L variants.

SAMD9 and SAMD9L encode homologous interferon-induced genes that can inhibit cellular translation as well as proliferation and can restrict viral replication. Gain-of-function (GoF) variants in these ancient, yet rapidly evolving genes are associated with life-threatening disease in humans. Potentially driving population sequence diversity, several viruses have evolved host range factors that antagonize cell-intrinsic SAMD9/SAMD9L function.

[Health- and disease-related data of inpatients in palliative care units of the Comprehensive Cancer Centers and other hospitals in comparison-Data from the Hospice and Palliative Care Register].

Background: The National Hospice and Palliative Registry is a database for palliative care facilities documenting a core data set for quality assurance and scientific evaluations.

Objectives: The study aims identifying differences between patients in palliative care units treated in Comprehensive Cancer Centers (CCC) or other hospitals (OH) focussing on sociodemographic and health/disease-related characteristics.

Methods: Descriptive data analysis using IBM SPSS Statistics 21 included patients treated from 2014 to 2018.

[Cooperation between intensive care and palliative care : The status quo in German Comprehensive Cancer Centers].

Background: For intensive care patients with limited life expectancy the integration of palliative care in intensive care may be beneficial. However, little is known about the extent of this interdisciplinary collaboration.

Objectives: The support given by palliative medicine in German oncological centers and used by the intensive care units should be recorded.

Standard Operating Procedures (SOPs) for Palliative Care in German Comprehensive Cancer Centers - an evaluation of the implementation status.

Background: The working group for palliative medicine within the Comprehensive Cancer Center (CCC) network funded by the German Cancer Aid in Germany has developed and published 14 Standard Operating Procedures (SOPs) for palliative care in CCCs. This study analyzed to what extent these SOPs have been implemented in the clinical routine in the CCC network one year after their publication.

Methods: An online-based survey on the implementation status, limitations in daily practice and further themes was conducted between April and July 2018.

Implementation of Best Practice Recommendations for Palliative Care in German Comprehensive Cancer Centers.

Background: From 2014 to 2017, the Palliative Medicine Working Group developed and published best practice recommendations for the integration of palliative care in Comprehensive Cancer Centers (CCCs) in Germany. To evaluate the implementation level of these recommendations in the CCCs an online survey was performed. Based on the results of this study, strategic tandem partnerships between CCCs should be built in order to foster further local development.

[Palliative Care Teams in the German Comprehensive Cancer Centers].

Background: A palliative care team is recognized as a quality indicator in the consultation and care of patients with a tumor disease and is used nationally (92 %) in the National Cancer Institutes, model of the German Comprehensive Cancer Center (CCC). This begs the question of how palliative care teams are presently integrated into the CCCs.

Method: From July to August 2017, a paper-based quantitative survey of 16 locations of the CCCs, supported to that date, gathered information on the existence, personnel situation, use and prospects of a specialized inpatient palliative care service.

In vivo monitoring of the anti-angiogenic therapeutic effect of the pan-deacetylase inhibitor panobinostat by small animal PET in a mouse model of gastrointestinal cancers.

Introduction: Deacetylase inhibitors have recently been established as a novel therapeutic approach to solid and hematologic cancers and have also been demonstrated to possess anti-angiogenic properties. Although these compounds show a good efficacy in vitro and in vivo, no data on monitoring and predicting treatment response are currently available. We therefore investigated the effect of the pan-deacetylase inhibitor panobinostat (LBH589) on gastrointestinal cancer models and the suitability of 2-[(18)F]FGlc-RGD as a specific agent for imaging integrin αvβ3 expression during tumor angiogenesis using small animal positron emission tomography (PET).

The pan-deacetylase inhibitor panobinostat affects angiogenesis in hepatocellular carcinoma models via modulation of CTGF expression.

Post-translational modifications of chromatin components are significantly involved in the regulation of tumor suppressor gene and oncogene expression. Connective tissue growth factor (CTGF) is an epigenetically regulated growth factor with functions in angiogenesis and cell-matrix interactions and plays a pivotal role in hepatocellular carcinoma (HCC). The pharmacologic inhibition of histone and protein deacetylases represents a new approach to interfere with pathways of apoptosis and angiogenesis.

Mapping and Expression of Candidate Genes for Development Rate in Rainbow Trout (Oncorhynchus mykiss).

Development rate has important implications for individual fitness and physiology. In salmonid fishes, development rate correlates with many traits later in life, including life-history diversity, growth, and age and size at sexual maturation. In rainbow trout (Oncorhynchus mykiss), a quantitative trait locus for embryonic development rate has been detected on chromosome 5 across populations.

EGFR mutational status in a large series of Caucasian European NSCLC patients: data from daily practice.

Background: The prognosis of metastatic non-small cell lung cancer (NSCLC) is still poor. Activating epithelial growth factor receptor (EGFR) mutations are important genetic alterations with dramatic therapeutical implications. Up to now, in contrast to Asian populations only limited data on the prevalence of those mutations are available from patients with Caucasian and especially European ethnicity.

Inhibition of DNA methyltransferase activity and expression by treatment with the pan-deacetylase inhibitor panobinostat in hepatocellular carcinoma cell lines.

Background: Hepatocellular carcinoma (HCC) still represents an unmet medical need. Epigenetic inactivation of tumor suppressor genes like RASSF1A or APC by overexpression of DNA methyltransferases (DNMTs) has been shown to be common in HCC and to be linked to the overall prognosis of patients. Inhibitors of protein and histone deacetylases (DACi) have been demonstrated to possess strong anti-tumor effects in HCC models.

Combination of the deacetylase inhibitor panobinostat and the multi-kinase inhibitor sorafenib for the treatment of metastatic hepatocellular carcinoma - review of the underlying molecular mechanisms and first case report.

Advanced hepatocellular carcinoma still represents an unmet medical need that has only a limited overall survival despite the introduction of the multi-kinase inhibitor sorafenib. Recently, inhibitors of histone and other protein deacetylases have been established as novel therapeutic approaches to cancer diseases. We here review the molecular rationale for combining these two novel targeted therapies and report a patient with metastasized hepatocellular carcinoma who showed a partial remission of primary and metastatic lesions for five months after a combination therapy with sorafenib and the orally available pan-deacetylase inhibitor panobinostat.

Identification and expression of Smads associated with TGF-β/activin/nodal signaling pathways in the rainbow trout (Oncorhynchus mykiss).

The Smad proteins are essential components of the TGF-β/activin/nodal family signaling pathway. We report the identification and expression of transcripts representing three receptor Smads (Smad2a, Smad2b, and Smad3), two common Smads (Smad4a and Smad4b), and one inhibitory Smad (Smad7). Phylogenetic analysis suggests this gene family evolved through the combination of ancient and more recent salmonid genome duplication events.

Pseudohypocalcemia caused by perchlorate (Irenat).

Background: Blood gas analysis (BGA), including measurement of ionized calcium, is performed routinely in patients with end stage renal disease on renal replacement therapy, especially when using citrate for regional anticoagulation. After installation of a new blood gas analyzer (RAPIDpoint 405; BGA), we observed lower ionized calcium concentrations in a few patients without signs of hypocalcemia, whereas calcium concentrations were normal using a standard laboratory method. Pseudohypocalcemia was of limited duration and correlated with the short-term intake of sodium perchlorate monohydrate (Irenat).

The pan-deacetylase inhibitor panobinostat inhibits growth of hepatocellular carcinoma models by alternative pathways of apoptosis.

Inhibition of deacetylases represents a new treatment option for human cancer diseases. We applied the novel and potent pan-deacetylase inhibitor panobinostat (LBH589) to human hepatocellular carcinoma models and investigated by which pathways tumor cell survival is influenced. HepG2 (p53wt) and Hep3B (p53null) responded to panobinostat treatment with a reduction of cell proliferation and a significant increase in apoptotic cell death at low micromolar concentrations.

Identification, characterization and genetic mapping of TLR1 loci in rainbow trout (Oncorhynchus mykiss).

Induction of innate immune pathways is critical for early anti-microbial defense but there is limited understanding of how teleosts recognize microbial molecules and activate these pathways. In mammals, Toll-like receptors (TLR) 1 and 2 form a heterodimer involved in recognizing peptidoglycans and lipoproteins of microbial origin. Herein, we identify and describe the rainbow trout (Oncorhynchus mykiss) TLR1 gene ortholog and its mRNA expression.

Identification, characterization and genetic mapping of TLR7, TLR8a1 and TLR8a2 genes in rainbow trout (Oncorhynchus mykiss).

Induction of the innate immune pathways is critical for early anti-viral defense but there is limited understanding of how teleost fish recognize viral molecules and activate these pathways. In mammals, Toll-like receptors (TLR) 7 and 8 bind single-stranded RNA of viral origin and are activated by synthetic anti-viral imidazoquinoline compounds. Herein, we identify and describe the rainbow trout (Oncorhynchus mykiss) TLR7 and TLR8 gene orthologs and their mRNA expression.

Liver function under interferon/ribavirin therapy of chronic hepatitis C.

Background: Quantitative testing of liver function (QTLF) is one way to show the efficacy of antiviral treatment of Hepatitis C. Data on liver function in patients with chronic Hepatitis C during antiviral therapy are lacking. We therefore investigated if and to what extent antiviral therapy influenced quantitative testing of liver function (QTLF).

Cellular plasticity of trans- and dedifferentiation markers in human hepatoma cells in vitro and in vivo.

Tumor cells have the capability to trans- and to dedifferentiate, for example by reactivating embryonic development genes and stem cell characteristics. The aim of our study was to show the differential expression of stem- and progenitor cell markers in human hepatocellular carcinoma cell lines (HCC). Different human HCC cell lines (HUH7, HUH7 5-15, HUH7 pcDNA3.

[Three-dimensional visualization for preoperative planning and evaluation in head and neck surgery].

There are a lot of diagnostic possibilities for the preoperative planning in head and neck surgery. So far, no study was performed to evaluate if there is an advantage of three-dimensional visualization compared to conventional computed tomography yet. Additionally, there are no specifications for such a visualization prior surgery in head and neck surgery.

The expression pattern of PDX-1, SHH, Patched and Gli-1 is associated with pathological and clinical features in human pancreatic cancer.

Background And Aims: Pancreatic cancer cells have been shown to possess stem-cell-like properties, especially by reactivating embryonic transcription factors involved in tissue differentiation. We therefore investigated if and to what extent developmental genes of the human pancreas are expressed in pancreatic ductal adenocarcinomas and precursor lesions, pancreatic intraepithelial neoplasia (PanIN), and if this correlates or predicts response to treatment and overall survival.

Material And Methods: Invasive ductal adenocarcinomas of the pancreas [UICC pT3pN0 (n = 13) vs.

A second generation genetic map for rainbow trout (Oncorhynchus mykiss).

Background: Genetic maps characterizing the inheritance patterns of traits and markers have been developed for a wide range of species and used to study questions in biomedicine, agriculture, ecology and evolutionary biology. The status of rainbow trout genetic maps has progressed significantly over the last decade due to interest in this species in aquaculture and sport fisheries, and as a model research organism for studies related to carcinogenesis, toxicology, comparative immunology, disease ecology, physiology and nutrition. We constructed a second generation genetic map for rainbow trout using microsatellite markers to facilitate the identification of quantitative trait loci for traits affecting aquaculture production efficiency and the extraction of comparative information from the genome sequences of model fish species.

The histone-deacetylase inhibitor MS-275 and the CDK-inhibitor CYC-202 promote anti-tumor effects in hepatoma cell lines.

Effective therapies for advanced stages of hepatocellular carcinoma (HCC) have yet to be developed. We investigated how far a combination of the HDAC inhibitor MS-275 and the CDK inhibitor CYC-202 synergizes to inhibit proliferation and promotes apoptosis of hepatoma cells in vitro. Human hepatoma cell lines Hep3B and HepG2 as well as primary human foreskin fibroblasts as non-malignant controls were cultured under standardized conditions and incubated with increasing concentrations of CYC-202 and MS-275 as single agents and in combination.