There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

Background Cabozantinib inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and 3, MET, and AXL, which are implicated in the progression of hepatocellul...

Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma

The structure

Induction of cell death and inhibition of cell survival are the main principles of cancer therapy. Resistance to chemotherapeutic agents is a major problem in oncology, which limits the effectiveness of anticancer drugs. A variety of factors contribute to drug resistance, including host factors, specific genetic or epigenetic alterations in the cancer cells and so on. Although various mechanisms by which cancer cells become resistant to anticancer drugs in the microenvironment have been well elucidated, how to circumvent this resistance to improve anticancer efficacy remains to be defined. Autophagy, an important homeostatic cellular recycling mechanism, is now emerging as a crucial player in response to metabolic and therapeutic stresses, which attempts to maintain/restore metabolic homeostasis through the catabolic lysis of excessive or unnecessary proteins and injured or aged organelles. Recently, several studies have shown that autophagy constitutes a potential target for cancer therapy and the induction of autophagy in response to therapeutics can be viewed as having a prodeath or a prosurvival role, which contributes to the anticancer efficacy of these drugs as well as drug resistance. Thus, understanding the novel function of autophagy may allow us to develop a promising therapeutic strategy to enhance the effects of chemotherapy and improve clinical outcomes in the treatment of cancer patients.

/pdf/autophagy-and-chemotherapy-resistance-a-promising-2pz6sno24p.pdf

Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment

Tumor hypoxia was first described in the 1950s by radiation oncologists as a frequent cause of failure to radiotherapy in solid tumors. Today, it is evident that tumor hypoxia is a common feature of many cancers and the master regulator of hypoxia, hypoxia-inducible factor-1 (HIF-1), regulates multiple aspects of tumorigenesis, including angiogenesis, proliferation, metabolism, metastasis, differentiation, and response to radiation therapy. Although the tumor hypoxia response mechanism leads to a multitude of downstream effects, it is angiogenesis that is most crucial and also most susceptible to molecular manipulation. The delineation of molecular mechanisms of angiogenesis has revealed a critical role for HIF-1 in the regulation of angiogenic growth factors. In this article, we review what has been described about HIF-1: its structure, its regulation, and its implication for cancer therapy and we focus on its role in angiogenesis and cancer.

HIFs, angiogenesis, and cancer.

Hepatocellular carcinoma (HCC) is one of the pestilent malignancies leading to cancer-related death. Discovering effective biomarkers for HCC diagnosis is an urgent demand. To identify potential metabolite biomarkers, we developed a urinary pseudotargeted method based on liquid chromatography-hybrid triple quadrupole linear ion trap mass spectrometry (LC-QTRAP MS). Compared with nontargeted method, the pseudotargeted method can achieve better data quality, which benefits differential metabolites discovery. The established method was applied to cirrhosis (CIR) and HCC investigation. It was found that urinary nucleosides, bile acids, citric acid, and several amino acids were significantly changed in liver disease groups compared with the controls, featuring the dysregulation of purine metabolism, energy metabolism, and amino metabolism in liver diseases. Furthermore, some metabolites such as cyclic adenosine monophosphate, glutamine, and short- and medium-chain acylcarnitines were the differential metabolites of HCC and CIR. On the basis of binary logistic regression, butyrylcarnitine (carnitine C4:0) and hydantoin-5-propionic acid were defined as combinational markers to distinguish HCC from CIR. The area under curve was 0.786 and 0.773 for discovery stage and validation stage samples, respectively. These data show that the established pseudotargeted method is a complementary one of targeted and nontargeted methods for metabolomics study.

Development of urinary pseudotargeted LC-MS-based metabolomics method and its application in hepatocellular carcinoma biomarker discovery.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/j.febslet.2011.02.031

Down‐regulation of miR‐23b may contribute to activation of the TGF‐β1/Smad3 signalling pathway during the termination stage of liver regeneration

Background:MicroRNAs are a class of small regulatory RNAs that modulate a variety of biological processes, includingcellular differentiation, apoptosis, metabolism and proliferation. This study aims to explore the effect of miR-34a inhepatocyte proliferation and its potential role in liver regeneration termination.Methodology/Principal Finding:MiR-34a was highly induced after partial hepatectomy. Overexpression of miR-34a in BRL-3A cells could significantly inhibit cell proliferation and down-regulate the expression of inhibin bB (INHBB) and Met. In BRL-3A cells, INHBB was identified as a direct target of miR-34a by luciferase reporter assay. More importantly, INHBB siRNAsignificantly repressed cell proliferation. A decrease of INHBB and Met was detected in regenerating liver.Conclusion/Significance: MiR-34a expression was upregulated during the late phase of liver regeneration. MiR-34a-mediated regulation of INHBB and Met may collectively contribute to the suppression of hepatocyte proliferation.

/pdf/mir-34a-is-upregulated-during-liver-regeneration-in-rats-and-4l2thdw38g.pdf

Mir-34a Is Upregulated during Liver Regeneration in Rats and Is Associated with the Suppression of Hepatocyte Proliferation

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/j.febslet.2012.05.054

Binghua Jiao

Papers

HIFs, angiogenesis, and cancer.

Development of urinary pseudotargeted LC-MS-based metabolomics method and its application in hepatocellular carcinoma biomarker discovery.

Down‐regulation of miR‐23b may contribute to activation of the TGF‐β1/Smad3 signalling pathway during the termination stage of liver regeneration

Mir-34a Is Upregulated during Liver Regeneration in Rats and Is Associated with the Suppression of Hepatocyte Proliferation

miR-376a suppresses proliferation and induces apoptosis in hepatocellular carcinoma.