Diagnostics and treatment of hepatocellular carcinoma
ONKOLOGE
Authors: van Boemmel, Florian; Denecke, Timm; Seehofer, Daniel; Schindler, Aaron; Veelken, Rhea; Berg, Thomas
Abstract
The incidence of hepatocellular carcinoma (HCC) has been increasing worldwide in recent years. The basis for the development of HCC is usually liver cirrhosis from various causes. Ultrasound examinations for early detection should be performed at 6-month intervals in all patients with an increased risk of HCC. Hepatic lesions >1 cm in size should be further clarified using contrast-enhanced tomography. A characteristic contrast agent behavior of the lesion can be evidence for the presence of HCC. Histological examination can be helpful in the diagnosis of HCC in unclear situations. HCCs necessitate an interdisciplinary approach. All patients with HCC should be referred to a specialized center to consider possible curative approaches. Palliative treatment includes locoregional treatment in the intermediate stage and systemic treatment in the advanced stage (since very recently in combination with immune checkpoint inhibitors).
From population to neuron: exploring common mediators for metabolic problems and mental illnesses
MOLECULAR PSYCHIATRY
Authors: Takayanagi, Yoichiro; Ishizuka, Koko; Laursen, Thomas M.; Yukitake, Hiroshi; Yang, Kun; Cascella, Nicola G.; Ueda, Shuhei; Sumitomo, Akiko; Narita, Zui; Horiuchi, Yasue; Niwa, Minae; Taguchi, Akiko; White, Morris F.; Eaton, William W.; Mortensen, Preben B.; Sakurai, Takeshi; Sawa, Akira
Abstract
Major mental illnesses such as schizophrenia (SZ) and bipolar disorder (BP) frequently accompany metabolic conditions, but their relationship is still unclear, in particular at the mechanistic level. We implemented an approach of "from population to neuron", combining population-based epidemiological analysis with neurobiological experiments using cell and animal models based on a hypothesis built from the epidemiological study. We characterized high-quality population data, olfactory neuronal cells biopsied from patients with SZ or BP, and healthy subjects, as well as mice genetically modified for insulin signaling. We accessed the Danish Registry and observed (1) a higher incidence of diabetes in people with SZ or BP and (2) higher incidence of major mental illnesses in people with diabetes in the same large cohort. These epidemiological data suggest the existence of common pathophysiological mediators in both diabetes and major mental illnesses. We hypothesized that molecules associated with insulin resistance might be such common mediators, and then validated the hypothesis by using two independent sets of olfactory neuronal cells biopsied from patients and healthy controls. In the first set, we confirmed an enrichment of insulin signaling-associated molecules among the genes that were significantly different between SZ patients and controls in unbiased expression profiling data. In the second set, olfactory neuronal cells from SZ and BP patients who were not pre-diabetic or diabetic showed reduced IRS2 tyrosine phosphorylation upon insulin stimulation, indicative of insulin resistance. These cells also displayed an upregulation of IRS1 protein phosphorylation at serine-312 at baseline (without insulin stimulation), further supporting the concept of insulin resistance in olfactory neuronal cells from SZ patients. Finally, Irs2 knockout mice showed an aberrant response to amphetamine, which is also observed in some patients with major mental illnesses. The bi-directional relationships between major mental illnesses and diabetes suggest that there may be common pathophysiological mediators associated with insulin resistance underlying these mental and physical conditions.