Tag: Chinese herbal medicine

Pancreatic Cancer Drug is Promising Against Most Aggressive Medulloblastoma Subtype

Pancreatic cancer. Credit: Scientific Animations CC BY-SA 4.0

A drug that was developed to treat pancreatic cancer has now been shown to increase symptom-free survival in preclinical medulloblastoma models – all without showing signs of toxicity. Survival rates for medulloblastoma vary according to which one of the four subtypes a patient has, but the worst survival rates of about 40%, are for Group 3. The research, published in the Journal of Clinical Investigation, focused on this most aggressive subtype.

Jezabel Rodriguez Blanco, PhD, an assistant professor at Medical University of South Carolina, led the research. Her work focused on the drug triptolide, which is extracted from a vine used in traditional Chinese medicine, and its water-soluble prodrug version, Minnelide. A prodrug is an inactive medication that the body converts into an active drug through enzymatic or chemical reactions.

MYC is an oncogene, or gene that has the potential to cause cancer. MYC is dysregulated, or out of control, in about 70% of human cancers, and it shows up in much higher levels in Group 3 medulloblastoma than in the other medulloblastoma subgroups. Despite its well-known role in cancer, this oncogene historically has been considered impossible to target with drugs.

Despite its poor druggability, previous research in other cancers had shown that triptolide and its derivatives had the ability to target MYC. When Blanco was still a postdoctoral fellow at the University of Miami, her mentor, David Robbins, PhD, attended a presentation by the research team that showed that the more copies of MYC that a tumour has, the better that triptolide works.

“He came to me, and he told me, ‘You know, as Group 3 medulloblastoma has many MYC copies, you should get some research models and try the drug,” Blanco recalled. She started the project from scratch. “I started talking to people, getting cell lines and animal models, learning how to propagate them, getting the drug, using it.” 

Blanco received initially received grants to on the Group 3 research, and continued it as a side project. She knew how well triptolide was working in these hard-to-treat tumours, and she did not want her initial results to fall through the cracks.

Determining the mechanism of action has been the most challenging part of the project, she noted, due to the drug’s multiple effects, and there could still be additional mechanisms beyond those that Blanco identified.

“It was affecting MYC gene expression by affecting the RNA pol II activity, and then it was affecting how long the protein lasts. So, the fact that it’s working through two different mechanisms on this oncogene may explain why it’s so effective in tumours that have extra copies of MYC,” she said, explaining that RNA polymerase II is a protein that helps to make copies of DNA instructions, which are used to produce proteins in the cell.

Despite the challenges of narrowing down the mechanism of action specific to the cancer, it was quite clear that however it worked, it did work, she said.

The efficacy was 100 times higher in the Group 3 tumours with extra MYC copies than in the Sonic Hedgehog tumours with normal levels of MYC, she said. She found that Minnelide reduced tumour growth and the spread of cancer cells to the thin tissues that cover the brain and spinal cord, called leptomeninges. It also increased the efficacy of the chemotherapy drug cyclophosphamide, which is currently used in treatment.

Blanco decided to move forward with publication rather than waiting to write a manuscript that answered all possible questions. Knowing that most parents whose children receive a Group 3 medulloblastoma diagnosis will lose their child in less than two years was the incentive she needed to push this work out.

“There was a point at which I could not hold these data anymore because it was working so well that it needed to go out,” she said. “The preclinical models were showing such a nice efficacy that it was like, ‘OK, I cannot keep on holding this work, digging deeper into the mechanism of action because the kids that have Group 3 medulloblastoma are dying while we are doing those experiments.”

Minnelide has been tested or is currently in testing in phase I and phase II clinical trials of adults with different types of cancer, including pancreatic cancer, where it showed some efficacy.

Blanco is hopeful that, with this new research on Group 3 medulloblastoma, a clinical trial for children with this disease can be launched.

Her paper is dedicated to the memory of Insley Horn, a 9-year-old Charleston girl who succumbed to one of these aggressive brain tumours. Research, Blanco said, is the only tool we have to prevent the loss of lives like Insley’s.

Source: Medical University of South Carolina

Assessing the Effectiveness of Chinese Traditional Medicine for Rheumatoid Arthritis

Hand osteoarthritis
Source: Pixabay CC0

Chinese traditional medicine based on combinations of typically 5 to ten plants, usually boiled and administered as a decoction or tea, has long been used to treat rheumatoid arthritis (RA), but few clinical trials have tested its potential. A review in the Journal of Internal Medicine outlines a strategy to analyse the ability of different mixtures of plants used in Chinese medicine to combat RA.

One fundamental of traditional medicine is to prevent disease. RA is an autoimmune, inflammatory and chronic disease that primarily affects the joints of 0.5%–1% of the population. In two out of three of the cases, the patients are characterised by the presence of autoantibodies such as the rheumatoid factor and the more disease-specific autoantibody against citrullinated proteins, so-called ‘ACPA’ (anticitrullinated protein/peptide antibodies). ACPA positivity is also strongly associated with specific variations in the HLA-DRB1 gene, the shared epitope alleles. Together with smoking, these factors account for the major risks of developing RA. 

The researchers’ strategy involves isolating the active components of individual plants and testing them alone or in combinations against key pathways of disease pathology, followed by experiments conducted in animal models of RA.

“A substantial number of our current drugs are natural products or derivatives thereof, and without doubt nature will continue to be a source of future discoveries,” the authors wrote. “Therefore continuous research based on the traditional use of plants is highly motivated. In our opinion, the strategy of starting from knowledge in traditional medicine, followed by the combination of in vivo evidence of efficacy and bioassay-guided isolation to understand the chemistry and pathways involved, is one effective way forward.”

Source: Wiley

Compound in Chinese Herbal Medicine May Prevent Colon Cancer

Colon cancer cells
Colon cancer cells. Source: National Cancer Institute on Unsplash

Emodin, an active compound found in Chinese herbal medicine, can prevent colon cancer in mice, according to researchers, and may be applicable in humans as well, a study has found. The mechanism behind this is likely emodin’s ability to reduce the number of pro-tumour macrophages.

The study is published in the American Journal of Physiology-Gastrointestinal and Liver Physiology.

Emodin, a major bioactive anthraquinone derivative extracted from rhubarb, represents multiple health benefits in the treatment of a host of diseases, such as immune-inflammatory abnormality, tumor progression, bacterial or viral infections, and metabolic syndrome. Emerging evidence has made great strides in clarifying the multi-targeting therapeutic mechanisms underlying the therapeutic efficacy of emodin, including anti-inflammatory, immunomodulatory, anti-fibrosis, anti-tumor, anti-viral, anti-bacterial, and anti-diabetic properties.

Besides investigating if emodin could prevent colon cancer, the study’s researchers especially wanted to know whether its anti-cancer properties “could be attributed to its actions on immune cells and particularly macrophages,” said Angela Murphy, PhD, co-author of the study. In this murine model, emodin was shown to reduce both polyp count and size. Also, mice treated with emodin “exhibited lower protumorigenic M2-like macrophages in the colon,” researchers wrote in the study.

Roughly 70% of colon cancer cases can be attributed to diet or other lifestyle factors, said Dr Murphy. Because emodin is also found in some fresh fruits and vegetables, it is hoped that consuming these emodin-containing foods could prevent colon cancer in humans.

Source: American Physiological Society