Liver metastasis is a leading cause of death in patients with colorectal cancer. We previously found that colorectal cancer tumor-initiating cells (TICs) expressing CD110, the thrombopoietin (TPO)-binding receptor, mediate liver metastasis. Here, we show that TPO promotes metastasis of CD110+ TICs to the liver by activating lysine degradation. Lysine catabolism generates acetyl-CoA, which is used in p300-dependent LRP6 acetylation. This triggers tyrosine phosphorylation of LRP6, ultimately activating Wnt signaling to promote self-renewal of CD110+ TICs. Lysine catabolism also generates glutamate, which modulates the redox status of CD110+ TICs to promote liver colonization and drug resistance. Mechanistically, TPO-mediated induction of c-myc orchestrates recruitment of chromatin modifiers to regulate metabolic gene expression. Our findings, therefore, establish TPO as a component of the physiological environment critical for metastasis of colorectal cancer to the liver.

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Hepatic ischemia/reperfusion (I/R) injury is an unavoidable consequence of major liver surgery, especially in liver transplantation with bowel congestion, during which endotoxemia is often evident. The inflammatory response aggravated by endotoxin after I/R contributes to liver dysfunction and failure. The purpose of the present study was to investigate the protective effect of butyrate, a naturally occurring four-carbon fatty acid in the body and a dietary component of foods such as cheese and butter, on hepatic injury complicated by enterogenous endotoxin, as well as to examine the underlying mechanisms involved. SD rats were subjected to a total hepatic ischemia for 30 min after pretreatment with either vehicle or butyrate, followed by 6 h and 24 h of reperfusion. Butyrate preconditioning markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathological changes. The inflammatory factors levels, macrophages activation, TLR4 expression, and neutrophil infiltration in live were attenuated by butyrate. Butyrate also maintained the intestinal barrier structures, reversed the aberrant expression of ZO-1, and decreased the endotoxin translocation. We conclude that butyrate inhibition of endotoxin translocation, macrophages activation, inflammatory factors production, and neutrophil infiltration is involved in the alleviation of total hepatic I/R liver injury in rats. This suggests that butyrate should potentially be utilized in liver transplantation.

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The cellular prion protein (PrPc) is a glycoprotein anchored by glycosylphosphatidylinositol to the cell surface and is abundantly expressed in various tissues. The putative roles of PrPc are thought to be related to cell signaling, survival, and differentiation and cancer progression. In this study, we demonstrated that the expression of PrPc correlates with a more aggressive and histologically unfavorable disease in colorectal carcinomas. Moreover, we found that PrPc mediates the process of epithelial-mesenchymal transition and, thereby, promotes CRC metastasis. Transcriptome profiling of PrPc-depleted cells revealed downregulation of the special AT-rich sequence-binding protein-1 (SATB1). PrPc is demonstrated to be involved in regulating SATB1 expression via the Fyn-SP1 pathway. Since SATB1 has been previously proposed as a key protein that controls tumor development and progression, knockdown of PrPc resulted in a reduced metastatic capacity in CRC cells, as well as a reduction in distant metastases in vivo. In conclusion, our data characterize a novel molecular mechanism that links PrPc expression to the regulation of CRC metastasis. Targeting PrPc will, therefore, be a promising strategy to overcome the metastatic advantage in colorectal tumors.

After reviewing the literature, we concluded that RDD should be considered as a differential diagnosis for lesions mimicking multiple meningiomas, especially in children. Resection of the intracranial lesion is the most effective treatment, and a definitive diagnosis should be based on histopathologic and immunocytochemical examinations.

Objective: To understand the pathological changes in pediatric craniopharyngiomas in order to determine the diagnosis and operative strategy and to prevent damage to the hypothalamus. Methods: A total of 189 cases of pediatric craniopharyngiomas from 1990 to 1998 were reviewed and analyzed based on computerized tomography scans, magnetic resonance imaging and operations. Results: Of the 189 cases, 187 (98.9%) were cystic tumors and calcification could be seen in 176 cases (93.1%). Two cases were solid tumors (1.1%), and calcification occurred in only 1 of these. There was a gliosis layer between the wall of the tumor and the hypothalamus. Conclusion: Cystic changes and calcification are the pathological features of pediatric craniopharyngiomas. There are some special relationships between the tumors and stalk. This is the basis for the total removal of pediatric craniopharyngiomas.

Germinoma in BG and thalamus predominate in a boy. The neuroimaging features are very informative for diagnosis. Surgical resection should not be the first choice although it is has lesser complications. The long-term outcome is favorable.