CTGF and integrin αvβ6 are potential Selleck Rapamycin therapeutic targets to control DRs and fibrosis in related liver disease. (Hepatology 2014) “
“The ubiquitously expressed transcriptional regulator Serum Response Factor (SRF) is controlled by both Ras/MAPK and Rho/actin signaling pathways, which are frequently activated in hepatocellular carcinoma (HCC). We generated SRF-VP16iHep mice, which conditionally express constitutively active SRF-VP16
in hepatocytes, thereby controlling subsets of both Ras/MAPK- and Rho/actin-stimulated target genes. All SRF-VP16iHep mice develop hyper-proliferative liver nodules that progresses to lethal HCC. Some mHCCs acquire Ctnnb1 mutations equivalent to those in hHCC. Resulting transcript signatures mirror those of a distinct Copanlisib in vitro subgroup of hHCCs, with shared activation of oncofetal genes including Igf2, correlating with CpG hypo-methylation at the imprinted Igf2/H19 locus. Conclusion: SRF-VP16iHep mHCC reveal convergent Ras/MAPK and Rho/actin
signaling as highly oncogenic driver mechanism for hepato-carcinogenesis. This suggests simultaneous inhibition of Ras/MAPK and Rho/actin signaling as treatment strategy in human HCC therapy. (Hepatology 2014;) “
“A 35 year-old Chinese female patient with Hereditary Hemorrhagic Telengiectasia (HHT) and a prior history of 2 uneventful pregnancies, had undergone an emergent caesarian section at 36 weeks gestation, due to the development of high-output cardiac failure. Post-partum she developed drowsiness and required intensive care support. Radiological imaging of the brain (CT and MCE MRI) excluded meningoencephalitis, intracranial haemorrhage and arteriovenous
malformations (AVMs). The patient subsequently developed active pulmonary haemorrhage and gastrointestinal (GI) bleeding. CT imaging of the thorax and abdomen demonstrated multiple AVMs in the lung bases and the liver (Figure 1). Bronchoscopy showed bleeding AVMs in the left lingular branch and an emergent embolisation of the feeding vessel was performed successfully. A duodenal ulcer with a clean base was diagnosed as well (via endoscopy) but further GI bleeding prompted a CT mesenteric angiogram which demonstrated air-fluid levels in the posterior aspect of the large bowel loops indicative of ruptured AVMs (White arrow, Figure 2). Embolisation was not performed due to concerns about bowel infarction. Despite maximal supportive therapy, she deteriorated into disseminated intravascular coagulation. Prior to her demise, she developed a sudden, tense abdominal distension with subsequent hypovolaemic shock and cardio-respiratory arrest. A post-mortem revealed massive haemorrhage in the intra-peritoneal cavity with multiple AVMs in the gastrointestinal tract. Massive intraperitoneal haemorrhage associated with HHT is seen in 25–30% of patients. During pregnancy, the plasma volume expands 30–50% and thus the cardiac output increases and peripheral vascular resistance reduces.