Roles of Lipids in Cancer

The term ‘lipids’ refers to a class of biological molecules primarily composed of hydrocarbons such as fatty acids, glycerolipids, sphingolipids and sterol lipids. Lipids take part in a variety of physiological functions and have specific roles depending on their chemical structure and localisation within or outside cells. For example, glycerolipids (e.g. triglycerides) are often used as energy stores, sterol lipids (e.g. cholesterol) and glycerophospholipids as structural components of cell membranes (e.g. the lipid bilayer), and sphingolipids as part of a signalling cascade. Since lipids are a source of energy and basic building block of all living cells, it is not surprising that development of cancer (i.e. uncontrolled proliferation of cells) is closely tied to the metabolism of lipids. This notion is supported by studies into the reprogrammed metabolic machinery in cancer cells, and also cell and animal model experiments showing that cancer growth and metastasis can be induced or inhibited by the exogenous addition of lipids. Here, we review how cancer cells can alter their lipid metabolism to meet their metabolic requirements, and the potential tumorigenic and tumour-suppressive mechanisms in which lipids are involved

Emerging Targeted Therapies for Treatment of Hepatocellular Carcinoma (HCC)

Hepatocellular carcinoma (HCC) has dismal diagnosis due to the presence of underlying cirrhosis, late diagnosis, and limited treatment options. Surgery or liver transplantation is restricted to those with small tumours or well-compensated liver diseases. Despite advances in early screening and diagnosis of HCC, survival of patients has not improved greatly. Furthermore, treatment options for advanced HCC are restricted to best supportive care. Currently, sorafenib is the only drug approved for the treatment of advanced HCC patients as well as for those not suitable for transarterial chemoembolization (TACE). Therefore, there is an urgent need to develop new agents for treatment. Hepatocarcinogenesis is a complex multistep process that involves deregulation of various signalling pathways. Thus, there is no dominant molecular mechanism in HCC and understanding of these pathways provides an opportunity for development of potential therapeutic agents in an effort to reverse, prevent or delay tumourigenesis. This review will summarise the significance of these pathways in HCC and discuss the therapeutic benefits or drawbacks of the potential target agents against these pathways especially those that have been part of clinical trials

The central policy unit in the governance of Hong Kong : a study of institutional dynamics

published_or_final_versionPolitics and Public AdministrationMasterMaster of Public Administratio

Clarifying the origin of Houzao

Abstract Background Houzao (bezoar) is a valuable imported Chinese medicine that is commonly used as a pediatric medicine to transform phlegm. There are mainly two types of Houzao, “Southeast Asian Houzao” and “Indian Houzao”. “Indian Houzao” is the dominant commercial product accounts for over 95% of the actual utilization in the market. However, its origin, formation, composition, efficacy and pharmacology remain unclear. Therefore, we have conducted on-site investigation to clarify the origin of Indian Houzao. We have dissected one male and one female domestic Indian goats in the pastoral areas of Telangana province in south-central India. Our results show: 1.Indian Houzao originates from Indian goats rather than from macaques; it comes from goats and not sheep, and is not limited to female goats.2.The exact location of the bezoar is in the caecum and not stomach or intestines.3.Acacia seeds serve as the primer to induce the formation of bezoar in the caecum.4.The formation and development of the bezoar are closely related to the special local ecosystem and food chain. These goats eat the shoots of Acacia nilotica, and also other local plants in the families of Euphorbiaceae, Rutaceae, Combretaceae, etc.5.It takes around 120 days for the bezoar to be fully developed inside the goat. Many goats are slaughtered in the Indian festival Dusserah from October to December.Indian Houzao is the bezoar from the caecum of Indian goats, formed in response to pathological stimulation, and is the dominant commercial form of “Houzao” on the market. It has been used historically. It has natural supply source. Producers can guarantee a sustainable supply of the bezoars for the market. The usage of bezoar as medicine is also acceptable from the perspective of animal protection. Many patients and people in the Chinese medicine field do not know Indian Houzao comes from Indian goats but from other unsustainable animal sources, which has a negative influence on its actual use and scientific research potential. Conclusion Our study has clarified the origin of Indian Houzao, which can help to further develop Indian Houzao for the treatment of diseases

Brevilin A exerts anti-colorectal cancer effects and potently inhibits STAT3 signaling in vitro

Colorectal cancer (CRC) is the third most common cause of cancer-related morbidity worldwide, with an estimated of 1.85 million new cases and 850,000 deaths every year. Nevertheless, the current treatment regimens for CRC have many disadvantages, including toxicities and off-targeted side effects. STAT3 (signal transducer and activator of transcription 3) has been considered as a promising molecular target for CRC therapy. Brevilin A, a sesquiterpene lactone compound rich in Centipedae Herba has potent anticancer effects in nasopharyngeal, prostate and breast cancer cells by inhibiting the STAT3 signaling. However, the anti-CRC effect of brevilin A and the underlying mechanism of action have not been fully elucidated. In this study, we aimed to investigate the involvement of STAT3 signaling in the anti-CRC action of brevilin A. Here, HCT-116 and CT26 cell models were used to investigate the anti-CRC effects of brevilin A in vitro. HCT-116 cells overespressing with STAT3 were used to evaluate the involvement of STAT3 signaling in the anti-CRC effect of brevilin A. Screening of 49 phosphorylated tyrosine kinases in the HCT-116 cells after brevilin A treatment was performed by using the human phospho-receptor tyrosine kinase (phospho-RTK) array. Results showed that brevilin A inhibited cell proliferation and cell viability, induced apoptosis, reduced cell migration and invasion, inhibited angiogenesis, lowered the protein expression levels of phospho-Src (Tyr416), phospho-JAK2 (Y1007/1008) and phospho-STAT3 (Tyr705), and inhibited STAT3 activation and nuclear localization. Brevilin A also significantly reduced the protein expression levels of STAT3 target genes, such as MMP-2, VEGF and Bcl-xL. More importantly, over-activation of STAT3 diminished brevilin A's effects on cell viability. All these results suggest that brevilin A exerts potent anti-CRC effects, at least in part, by inhibiting STAT3 signaling. Our findings provide a strong pharmacological basis for the future exploration and development of brevilin A as a novel STAT3-targeting phytotherapeutic agent for CRC treatment

The current understanding on the impact of KRAS on colorectal cancer

KRAS (kirsten rat sarcoma viral oncogene) is a member of the RAS family. KRAS mutations are one of most dominant mutations in colorectal cancer (CRC). The impact of KRAS mutations on the prognosis and survival of CRC patients drives many research studies to explore potential therapeutics or target therapy for the KRAS mutant CRC. This review summarizes the current understanding of the pathological consequences of the KRAS mutations in the development of CRC; and the impact of the mutations on the response and the sensitivity to the current front-line chemotherapy. The current therapeutic strategies for treating KRAS mutant CRC, the difficulties and challenges will also be discussed

Gut-Microbial Metabolites, Probiotics and Their Roles in Type 2 Diabetes

Type 2 diabetes (T2D) is a worldwide prevalent metabolic disorder defined by high blood glucose levels due to insulin resistance (IR) and impaired insulin secretion. Understanding the mechanism of insulin action is of great importance to the continuing development of novel therapeutic strategies for the treatment of T2D. Disturbances of gut microbiota have been widely found in T2D patients and contribute to the development of IR. In the present article, we reviewed the pathological role of gut microbial metabolites including gaseous products, branched-chain amino acids (BCAAs) products, aromatic amino acids (AAAs) products, bile acids (BA) products, choline products and bacterial toxins in regulating insulin sensitivity in T2D. Following that, we summarized probiotics-based therapeutic strategy for the treatment of T2D with a focus on modulating gut microbiota in both animal and human studies. These results indicate that gut-microbial metabolites are involved in the pathogenesis of T2D and supplementation of probiotics could be beneficial to alleviate IR in T2D via modulation of gut microbiota

The anticancer effect of oridonin is mediated by fatty acid synthase suppression in human colorectal cancer cells

Background: Fatty acid synthase (FAS) inhibitors could be a therapeutic target in cancer treatment. However, only a few FAS inhibitors showing clinical potential have been reported. Oridonin is a diterpenoid isolated from Rabdosia rubescens. Although it has antiproliferative activity in cancers, little was known about its anticancer effect on colorectal cancer. In this regard, we aimed to investigate if oridonin could be a novel FAS inhibitor and its anticancer mechanism in human colorectal cancer cells. Methods: Two human colorectal cancer cell lines SW480 and SW620 were used as models for this study. Results: We demonstrated that oridonin reduced viability and induced apoptosis in colorectal cancer cells. Knockdown of the expression of FAS in colorectal cancer cells by siRNA induced apoptosis. This led us to examine whether oridonin-induced apoptosis was mediated by FAS suppression in these cells. We found that oridonin effectively inhibited FAS and SREBP1 mRNA and protein expression in human colorectal cancer cells. In a transient reporter assay, oridonin also reduced transcriptional activity of the FAS promoter region containing the SREBP1 binding site. The FAS inhibition was paralleled by reduction in cellular palmitate and stearic acid. Upregulation of SREBP1 and FAS expression by insulin rescued these cells from oridonin-induced apoptosis. Conclusion: These results not only provide a novel molecular mechanism for the anticancer effect of oridonin in colorectal cancer, but also suggest oridonin could be a novel FAS inhibitor in cancer treatment. These results strengthen the scientific basis for the therapeutic use of oridonin in colorectal cancer

Elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditions

Abstract The cargo content in small extracellular vesicles (sEVs) changes under pathological conditions. Our data shows that in obesity, extracellular matrix protein 1 (ECM1) protein levels are significantly increased in circulating sEVs, which is dependent on integrin-β2. Knockdown of integrin-β2 does not affect cellular ECM1 protein levels but significantly reduces ECM1 protein levels in the sEVs released by these cells. In breast cancer (BC), overexpressing ECM1 increases matrix metalloproteinase 3 (MMP3) and S100A/B protein levels. Interestingly, sEVs purified from high-fat diet-induced obesity mice (D-sEVs) deliver more ECM1 protein to BC cells compared to sEVs from control diet-fed mice. Consequently, BC cells secrete more ECM1 protein, which promotes cancer cell invasion and migration. D-sEVs treatment also significantly enhances ECM1-mediated BC metastasis and growth in mouse models, as evidenced by the elevated tumor levels of MMP3 and S100A/B. Our study reveals a mechanism and suggests sEV-based strategies for treating obesity-associated BC