Posts Tagged ‘hcc’

Thunder God Vine, with assists by nanotechnology, could shake up future cancer treatment

Now a team of scientists, led by Prof. Taeghwan Hyeon at the Institute for Basic Science (IBS)/Seoul National University and Prof. Kam Man Hui at the National Cancer Center Singapore, has screened a library containing hundreds of natural products against a panel of HCC cells to search a better drug candidate. The screen uncovered a compound named triptolide, a traditional Chinese medicine isolated from the thunder god vine (Tripterygium wilfordii (Latin) or lei gong teng (Chinese)) which was found to be far more potent than current therapies. Studies from other researchers corroborate our findings as triptolide has also found to be very effective against several other malignant cancers including; pancreatic, neuroblastoma and cholangiocarcinoma. However this excitement was tempered when the drug was administered to mice as the increased potency was coupled with increased toxicity as well.

Maximizing potency, mitigating toxicity

Prof. Hyeon et al. endeavoured to alleviate the toxic burden by increasing the specific delivery of the drug to the tumor using a nanoformulation. The designed formulation was a pH-sensitive nanogel coated with the nucleotide precursor, folate. The researchers began by esterfying the polymer pluronic F127 with folate to make the coating material. They then polymerized β-benzyl-L-aspartate N-carboxy anhydride to make the core material pH-sensitive due to repulsive forces upon protonation under acidic conditions. “The combination of the two polymers forms a core/shell structured nanoparticle in water,” explains Prof. Hyeon. “We loaded triptolide into the hydrophobic core to produce a kind of drug-nanogel.”

A tumor model of folate-overexpressing HCC was then used to examine the effect of the nanogel formulation versus the free drug. As expected, the nanogel triptolide showed increased tumor accumulation and uptake into the tumor cells where the decreasing pH efficiently triggered release of the entrapped triptolide. The result was as hypothesized: In experiments on mice with HCC, the team found that its coated triptolide accumulated in the inflamed tumour tissues. Once there, the folate-targeted ligand enhances the HCC cells to take up the anticancer drug. Since the fluid inside tumour cells is more acidic (with a pH of around 6.8) compared to normal tissue (which has a pH of about 7.4), the drop in pH causes the coating to fall apart, and release the pure form of the triptolide, which then destroys the tumor cells, showing greater efficacy against the tumor and decrease the overall toxicity.

The mechanism of action of Nf-Trip-FR+ represents an auspicious therapeutic approach

While these initial proof-of-concept studies have been promising, many drugs fail to become an IND (Investigational New Drug); fewer still effectively replicate their results in human trials. However, a felicitous discovery occurred while the researchers were examining the mechanism of triptolide’s activity. Researchers at the National Cancer Center Singapore ran a profile on the effects triptolide had on protein expression in a variety of HCC cells. From this they learned triptolide primarily reduced the levels of two proteins, AURKA and CKS2, although the mechanism is still not known. The researchers then cross-checked these proteins against a clinical database of HCC patients and found an increased expression of these proteins correlates with the aggressiveness of the cancer. Thus it is hoped the negative effect triptolide has on these proteins could prove beneficial in terms of clinical outcomes when this drug finally becomes accepted for clinical studies in cancer patients.

The present work is detailed in ACS Nano.

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Coffee consumption reduces risk of liver cancer

"Our research confirms past claims that coffee is good for your health, and particularly the liver," said Carlo La Vecchia, MD, study author from the department of epidemiology, Istituto di Ricerche Farmacologiche "Mario Negri," and department of clinical sciences and community health, Università degli Studi di Milan, Italy. "The favorable effect of coffee on liver cancer might be mediated by coffee’s proven prevention of diabetes, a known risk factor for the disease, or for its beneficial effects on cirrhosis and liver enzymes."

Researchers performed a meta-analysis of articles published from 1996 through September 2012, ultimately studying 16 high-quality studies and a total of 3,153 cases. This research fills an important gap as the last meta-analysis was published in 2007, and since then there has been data published on more than 900 cases of HCC.

Despite the consistency of results across studies, time periods and populations, it is difficult to establish whether the association between coffee drinking and HCC is causal, or if this relationship may be partially attributable to the fact that patients with liver and digestive diseases often voluntarily reduce their coffee intake.

"It remains unclear whether coffee drinking has an additional role in liver cancer prevention," added Dr. La Vecchia. "But, in any case, such a role would be limited as compared to what is achievable through the current measures."

Primary liver cancers are largely avoidable through hepatitis B virus vaccination, control of hepatitis C virus transmission and reduction of alcohol drinking. These three measures can, in principle, avoid more than 90 percent of primary liver cancer worldwide.

Liver cancer is the sixth most common cancer in the world, and the third most common cause of cancer death. HCC is the main type of liver cancer, accounting for more than 90 percent of cases worldwide. Chronic infections with hepatitis B and C viruses are the main causes of liver cancer; other relevant risk factors include alcohol, tobacco, obesity and diabetes.

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