Role of Akt inhibition on Notch1 expression in hepatocellular carcinoma: potential role for dual targeted therapy.

Background: We have shown that an Akt inhibitor, MK2206, reduces hepatocellular carcinoma (HCC) proliferation. To further delineate MK2206, we sought to investigate the Notch1 pathway and hypothesize that MK2206 treatment will result in Notch1 inhibition with either subsequent or parallel Akt suppression.

Methods: HCC cell lines were treated with various concentrations of MK2206.

Potential Molecular Targeted Therapeutics: Role of PI3-K/Akt/mTOR Inhibition in Cancer.

Primary liver cancer is one of the most commonly occurring cancers worldwide. Hepatocellular carcinoma (HCC) represents the majority of primary liver cancer and is the 3rd most common cause of cancer-related deaths globally. Survival rates of patients with HCC are dependent upon early detection as concomitant liver dysfunction and advanced disease limits traditional therapeutic options such as resection or ablation.

Xanthohumol inhibits Notch signaling and induces apoptosis in hepatocellular carcinoma.

Despite improvement in therapeutic strategies, median survival in advanced hepatocellular carcinoma (HCC) remains less than one year. Therefore, molecularly targeted compounds with less toxic profiles are needed. Xanthohumol (XN), a prenylated chalcone has been shown to have anti-proliferative effects in various cancers types in vitro.

Dilong: food for thought and medicine.

dì lóng, Japanese: Mimizu, Korean: Jireongi, Spanish: Lombriz de tierra, French: Ver de terre, German: Regenwurm, Italian: Lombrico, Swedish: Daggmask, Portuguese: Minhoca). They have long been used as a food source as well as treatments of various ailments. Many alternative and traditional disciplines of medicine, such as those in China, Japan, and Korea, developed medicinal uses of dilong from an initial utilization as nutrition.

Earthworms dilong: ancient, inexpensive, noncontroversial models may help clarify approaches to integrated medicine emphasizing neuroimmune systems.

Earthworms have provided ancient cultures with food and sources of medicinal cures. Ayurveda, traditional Chinese medicine (TCM), and practices in Japan, Vietnam, and Korea have focused first on earthworms as sources of food. Gradually fostering an approach to potential beneficial healing properties, there are renewed efforts through bioprospecting and evidence-based research to understand by means of rigorous investigations the mechanisms of action whether earthworms are used as food and/or as sources of potential medicinal products.

Hypothetical mode of action of earthworm extract with hepatoprotective and antioxidant properties.

The hepatoprotective potential of earthworm extract (EE) (Lampito mauritii, Kinberg) was evaluated against paracetamol-induced liver injury in Wistar albino rat, in comparison with silymarin, the standard hepatoprotective drug. We observed a reduction in liver antioxidants, such as glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) and in serum total protein, and an increase in serum alkaline phosphatase (ALP), serum aspertate aminotranferase (AST), serum alanine aminotranferase (ALT), bilirubin and liver thiobarbituric acid reactive substances (TBARS) due to liver injury in the paracetamol-administered rats (2 g/kg). On the contrary, increased activities of liver GSH, SOD, GPx, CAT and serum total protein level, and decrease in the contents of serum ALP, AST, ALT, bilirubin and liver TBARS were observed in rats administered with different doses of EE (100, 200 and 300 mg/kg), which are similar to the activities of hepatoprotective drug silymarin (150 mg/kg).