Abstract:The mechanisms underlying the recurrence and metastasis of hepatocellular carcinoma (HCC) are poorly understood. In 2015, Zhuang and her colleagues identified a unique histopathological structure in HCC tissues, which they dubbed VETC, standing for vessels that encapsulate tumor clusters. 1 In the VETC structure, sinusoid-like vessels form a cobweb-like network that encapsulates individual tumor cell clusters. These endotheliumwrapped tumor cell clusters were released into the blood stream and formed metastati… Show more
“…In the patient samples, a lower AR correlated with higher metastatic risk and poorer survival in liver cancers. The authors also paid attention to the specific type of peritumoral vascularization and the expression of Rac (plasma membrane-associated small GTPase) and angiopoietin [ 92 ].…”
Section: Androgens Endoplasmic Reticulum Stress and Liver Disordersmentioning
Finasteride (Fin) causes androgen imbalance by inhibiting the conversion of testosterone (T) to its more active metabolite, dihydrotestosterone (DHT). Androgen receptors (AR) are present (e.g., in hepatocytes), which have well-developed endoplasmic reticulum (ERet). Cellular protein quality control is carried out by ERet in two paths: (i) unfolded protein response (UPR) and/or (ii) endoplasmic reticulum associated degradation (ERAD). ERet under continuous stress can generate changes in the UPR and can direct the cell on the pathway of life or death. It has been demonstrated that genes involved in ERet stress are among the genes controlled by androgens in some tissues. Oxidative stress is also one of the factors affecting the functions of ERet and androgens are one of the regulators of antioxidant enzyme activity. In this paper, we discuss/analyze a possible relationship between androgen imbalance in paternal generation with ERet stress and liver disorders in both paternal and filial generation. In our rat model, hyperglycemia and subsequent higher accumulation of hepatic glycogen were observed in all filial generation obtained from females fertilized by Fin-treated males (F1:Fin). Importantly, genes encoding enzymes involved in glucose and glycogen metabolism have been previously recognized among UPR targets.
“…In the patient samples, a lower AR correlated with higher metastatic risk and poorer survival in liver cancers. The authors also paid attention to the specific type of peritumoral vascularization and the expression of Rac (plasma membrane-associated small GTPase) and angiopoietin [ 92 ].…”
Section: Androgens Endoplasmic Reticulum Stress and Liver Disordersmentioning
Finasteride (Fin) causes androgen imbalance by inhibiting the conversion of testosterone (T) to its more active metabolite, dihydrotestosterone (DHT). Androgen receptors (AR) are present (e.g., in hepatocytes), which have well-developed endoplasmic reticulum (ERet). Cellular protein quality control is carried out by ERet in two paths: (i) unfolded protein response (UPR) and/or (ii) endoplasmic reticulum associated degradation (ERAD). ERet under continuous stress can generate changes in the UPR and can direct the cell on the pathway of life or death. It has been demonstrated that genes involved in ERet stress are among the genes controlled by androgens in some tissues. Oxidative stress is also one of the factors affecting the functions of ERet and androgens are one of the regulators of antioxidant enzyme activity. In this paper, we discuss/analyze a possible relationship between androgen imbalance in paternal generation with ERet stress and liver disorders in both paternal and filial generation. In our rat model, hyperglycemia and subsequent higher accumulation of hepatic glycogen were observed in all filial generation obtained from females fertilized by Fin-treated males (F1:Fin). Importantly, genes encoding enzymes involved in glucose and glycogen metabolism have been previously recognized among UPR targets.
“…AR is the androgen receptor, and AR signalling pathway is related to many hormone‐dependent diseases such as prostate cancer, 49 breast cancer 50 , 51 , 52 and ovarian cancer, 53 as well as malignant tumours, for example gastric cancer, 54 , 55 lung cancer, 56 , 57 bladder cancer, 58 , 59 pancreatic cancer, 60 , 61 liver cancer 62 and kidney cancer. 63 The distribution of AR in cells is closely related to the survival of tumours.…”
Section: Discussionmentioning
confidence: 99%
“…pancreatic cancer, 60,61 liver cancer 62 and kidney cancer. 63 The distribution of AR in cells is closely related to the survival of tumours.…”
Section: Effects Of Oridonin On the Tgfβ Signalling Pathway In Sgc-79...mentioning
Statistics provided by GLOBOCAN list gastric cancer as the sixth most common, with a mortality ranking of third highest for the year 2020. In China, a herb called Rabdosia rubescens (Hemsl.) H.Hara, has been used by local residents for the treatment of digestive tract cancer for hundreds of years. Oridonin, the main ingredient of the herb, has a curative effect for gastric cancer, but the mechanism has not been previously clarified. This study mainly aimed to investigate the role of TNF‐alpha/Androgen receptor/TGF‐beta signalling pathway axis in mediating the proliferation inhibition of oridonin on gastric cancer SGC‐7901 cells. MTT assay, cell morphology observation assay and fluorescence assay were adopted to study the efficacy of oridonin on cell proliferation. The network pharmacology was used to predict the pathway axis regulated by oridonin. Western blot assay was adopted to verify the TNF‐α/Androgen receptor/TGF‐β signalling pathway axis regulation on gastric cancer by oridonin. The results showed Oridonin could inhibit the proliferation of gastric cancer cells, change cell morphology and cause cell nuclear fragmentation. A total of 11signaling pathways were annotated by the network pharmacology, among them, Tumour necrosis factor alpha (TNF‐α) signalling pathway, androgen receptor (AR) signalling pathway and transforming growth factor (TGF‐β) signalling pathway account for the largest proportion. Oridonin can regulate the protein expression of the three signalling pathways, which is consistent with the results predicted by network pharmacology. These findings indicated that oridonin can inhibit the proliferation of gastric cancer SGC‐7901 cells by regulating the TNF‐α /AR /TGF‐β signalling pathway axis.
“…Since the incidence of obesity-related HCC is much higher in men than in women, androgen receptors may produce ontogenetic efficacy through alternative mechanisms, such as interaction with signal transducer and activator of transcription 3 (STAT3) [ 129 ]. AR plays a role in developing of neovascularization and liver cancer metastasis, which may participate in the progression from NASH to HCC [ 130 ].…”
Section: Transcriptional Regulation Of Lipid Metabolism By Nrs In Nafldmentioning
The overproduction of reactive oxygen species (ROS) and consequent oxidative stress contribute to the pathogenesis of acute and chronic liver diseases. It is now acknowledged that nonalcoholic fatty liver disease (NAFLD) is characterized as a redox-centered disease due to the role of ROS in hepatic metabolism. However, the underlying mechanisms accounting for these alternations are not completely understood. Several nuclear receptors (NRs) are dysregulated in NAFLD, and have a direct influence on the expression of a set of genes relating to the progress of hepatic lipid homeostasis and ROS generation. Meanwhile, the NRs act as redox sensors in response to metabolic stress. Therefore, targeting NRs may represent a promising strategy for improving oxidation damage and treating NAFLD. This review summarizes the link between impaired lipid metabolism and oxidative stress and highlights some NRs involved in regulating oxidant/antioxidant turnover in the context of NAFLD, shedding light on potential therapies based on NR-mediated modulation of ROS generation and lipid accumulation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.