Background and Aims Vascular invasion (VI) is a critical risk factor for HCC recurrence and poor survival. The molecular drivers of vascular invasion in HCC are open for investigation. Deciphering the molecular landscape of invasive HCC will help identify therapeutic targets and noninvasive biomarkers. Approach and Results To this end, we undertook this study to evaluate the genomic, transcriptomic, and proteomic profile of tumors with VI using the multiplatform cancer genome atlas (The Cancer Genome Atlas; TCGA) data (n = 373). In the TCGA Liver Hepatocellular Carcinoma cohort, macrovascular invasion was present in 5% (n = 17) of tumors and microvascular invasion in 25% (n = 94) of tumors. Functional pathway analysis revealed that the MYC oncogene was a common upstream regulator of the mRNA, miRNA, and proteomic changes in VI. We performed comparative proteomic analyses of invasive human HCC and MYC‐driven murine HCC and identified fibronectin to be a proteomic biomarker of invasive HCC (mouse fibronectin 1 [Fn1], P = 1.7 × 10−11; human FN1, P = 1.5 × 10−4) conserved across the two species. Mechanistically, we show that FN1 promotes the migratory and invasive phenotype of HCC cancer cells. We demonstrate tissue overexpression of fibronectin in human HCC using a large independent cohort of human HCC tissue microarray (n = 153; P < 0.001). Lastly, we showed that plasma fibronectin levels were significantly elevated in patients with HCC (n = 35; mean = 307.7 μg/mL; SEM = 35.9) when compared to cirrhosis (n = 10; mean = 41.8 μg/mL; SEM = 13.3; P < 0.0001). Conclusions Our study evaluates the molecular landscape of tumors with VI, identifying distinct transcriptional, epigenetic, and proteomic changes driven by the MYC oncogene. We show that MYC up‐regulates fibronectin expression, which promotes HCC invasiveness. In addition, we identify fibronectin to be a promising noninvasive proteomic biomarker of VI in HCC.

Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) share similar clinical features and mechanisms. In very rare circumstances, the two diseases coexist in the same patient. Here we report such a patient, who was first diagnosed with Hand-Schüller-Christian disease (HSC), a type of LCH. Several years later, the patient presented with severe exophthalmos and osteosclerosis on radiograph. New biopsy revealed ECD. We also analyze 54 cases of LCH and 6 cases of ECD diagnosed in our hospital, as well as their progression during a follow-up period of 8 years. In five cases of HSC (9.3% of LCH), a triad of central diabetes insipidus, hyperprolactinemia, and pituitary stalk thickening on magnetic resonance imaging (MRI) preceded the typical bone lesions by 4 -9 years. In addition, LCH was featured as elevated plasma alkaline phosphatase (ALP), which was normal in ECD. Combined with a literature review, several features are summarized to differentiate ECD from HSC. In patients with diabetes insipidus, concomitant hyperprolactinemia and pituitary stalk thickening on MRI indicate a possible HSC. Additionally, if osteosclerosis is observed in a patient with LCH, the coexistence of ECD should be considered. The Oncologist 2013;18:19 -24 Implications for Practice: Central diabetes insipitus (CDI) is usually the first or one of the first symptoms of Hand-Schüller-Christian disease (HSC). It is difficult to determine whether CDI is part of HSC at its onset. We propose a new triad of symptoms including central diabetes insipitus, hyperprolactinemia, and pituitary stalk thickening on MRI. If a patient is present with the triad, HSC should be considered. Bone scans are very useful to reveal HSC in the absence of bone pain. Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) are featured with osteolytic lesions and osteosclerosis, respectively. If osteosclerosis is observed in a patient with LCH, coexistence of ECD should be considered. A new biopsy is helpful for the diagnosis.

The intravenously transplanted EPCs diminish the brain injury through restoring cerebral blood perfusion and increasing the cerebral microvasculature in the injured region in rat model with TBI.

Orosomucoid 1 (ORM1) has been shown to be upregulated in the serum of breast cancer patients; however, the expression and function of ORM1 in breast cancer remains unknown. We measured the expression of ORM1 in breast cancer tissues and cell lines using qRT-PCR. A colony formation assay was done to assess cell proliferation and Transwell and wound healing assays were performed to determine the migration and invasion capacity of the cells, respectively. In addition, a CCK-8 assay was used to measure epirubicin cytotoxicity and western blot assays were done to analyze the putative mechanisms of epirubicin sensitivity. We found that the expression of ORM1 was upregulated in breast cancer tissues and cell lines. The expression of ORM1 enhanced the proliferation and migration of the cell lines. In contrast, down-regulation of ORM1 inhibited the expression of MMP-2 and MMP-9 and activation of the AKT/ERK signaling pathway. Therefore, ORM1 may represent a potential therapeutic target for breast cancer and promote epirubicin resistance by regulating the expression of MMP-2 and MMP-9, as well as activating the AKT/ERK signaling pathway.