- Browse by Author
Browsing by Author "Sun, Yin"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
Item Hepatic Histopathology Among Excessive Drinkers Without Advanced Liver Disease(Oxford University Press, 2021) Chang, Binxia; Huang, Ang; Saxena, Romil; Sun, Yin; Liu, Shuhong; Zhou, Guangde; Li, Baosen; Teng, Guangju; Zhao, Jun; Zhang, Wei; Jiang, Yanchao; Han, Sen; Yang, Zhihong; Zhao, Jingmin; Zou, Zhengsheng; Liangpunsakul, Suthat; Pathology and Laboratory Medicine, School of MedicineAims: Alcohol-associated liver disease represents a spectrum of histopathological changes from steatosis to advanced fibrosis and cirrhosis. The major goals of this retrospective study were to characterize the histologic features in patients with excessive alcohol use who presented with an abnormal hepatic panel and/or abnormal radiographic imaging and did not meet the clinical diagnosis of alcoholic hepatitis or cirrhosis. Methods: We performed a retrospective study to describe hepatic histology of 62 and 83 excessive drinkers with normal and abnormal serum aspartate transaminase, respectively. The types of inflammatory cells in the liver were characterized by immunohistochemistry for CD4, CD8, CD20, CD68 and myeloperoxidase. Results: Among 62 patients with aspartate aminotransferase (AST) ≤ 50 U/L, 37% had histological evidence of steatosis. Of these, we found evidence of hepatocyte ballooning (21%), lobular inflammation (50%), portal inflammation (52%) and fibrosis (14%). For those with AST > 50 U/L, the presence of hepatic steatosis, lobular inflammation and portal inflammation was observed in 29, 60 and 69% of patients, respectively. Fibrosis was found in 33%, four with bridging fibrosis, and one with cirrhosis. We observed the aggregation of CD68+ macrophages, rather than normally distributed with minimal neutrophilic infiltration. Lobular and portal lymphocytic infiltrations are primarily CD8+ T cells. Conclusion: Abnormal hepatic histopathology occurs in excessive drinkers with normal transaminase activity. Future studies to determine the diagnostic modalities to detect such abnormalities and to better understand its clinical implications and long-term outcome are needed.Item LncRNA-p21 alters the antiandrogen enzalutamide-induced prostate cancer neuroendocrine differentiation via modulating the EZH2/STAT3 signaling(Springer Nature, 2019-06-12) Luo, Jie; Wang, Keliang; Yeh, Shuyuan; Sun, Yin; Liang, Liang; Xiao, Yao; Xu, Wanhai; Niu, Yuanjie; Cheng, Liang; Maity, Sankar N.; Jiang, Runze; Chang, Chawnshang; Pathology and Laboratory Medicine, School of MedicineWhile the antiandrogen enzalutamide (Enz) extends the castration resistant prostate cancer (CRPC) patients' survival an extra 4.8 months, it might also result in some adverse effects via inducing the neuroendocrine differentiation (NED). Here we found that lncRNA-p21 is highly expressed in the NEPC patients derived xenograft tissues (NEPC-PDX). Results from cell lines and human clinical sample surveys also revealed that lncRNA-p21 expression is up-regulated in NEPC and Enz treatment could increase the lncRNA-p21 to induce the NED. Mechanism dissection revealed that Enz could promote the lncRNA-p21 transcription via altering the androgen receptor (AR) binding to different androgen-response-elements, which switch the EZH2 function from histone-methyltransferase to non-histone methyltransferase, consequently methylating the STAT3 to promote the NED. Preclinical studies using the PDX mouse model proved that EZH2 inhibitor could block the Enz-induced NED. Together, these results suggest targeting the Enz/AR/lncRNA-p21/EZH2/STAT3 signaling may help urologists to develop a treatment for better suppression of the human CRPC progression.Item SPOP Promotes Ubiquitination and Degradation of the ERG Oncoprotein to Suppress Prostate Cancer Progression(Elsevier, 2015-09-17) Gan, Wenjian; Dai, Xiangpeng; Lunardi, Andrea; Li, Zhen; Inuzuka, Hiroyuki; Liu, Pengda; Varmeh, Shoreh; Zhang, Jinfang; Cheng, Liang; Sun, Yin; Asara, John M.; Beck, Andrew H.; Huang, Jiaoti; Pandolfi, Pier Paolo; Wei, Wenyi; Department of Pathology and Laboratory Medicine, IU School of MedicineThe ERG gene is fused to TMPRSS2 in approximately 50% of prostate cancers (PrCa), resulting in its overexpression. However, whether this is the sole mechanism underlying ERG elevation in PrCa is currently unclear. Here we report that ERG ubiquitination and degradation are governed by the Cullin 3-based ubiquitin ligase SPOP and that deficiency in this pathway leads to aberrant elevation of the ERG oncoprotein. Specifically, we find that truncated ERG (ΔERG), encoded by the ERG fusion gene, is stabilized by evading SPOP-mediated destruction, whereas prostate cancer-associated SPOP mutants are also deficient in promoting ERG ubiquitination. Furthermore, we show that the SPOP/ERG interaction is modulated by CKI-mediated phosphorylation. Importantly, we demonstrate that DNA damage drugs, topoisomerase inhibitors, can trigger CKI activation to restore the SPOP/ΔERG interaction and its consequent degradation. Therefore, SPOP functions as a tumor suppressor to negatively regulate the stability of the ERG oncoprotein in prostate cancer.