Study expands understanding of the production of ET-743 compound

In continuation of my update on Trabectedin

For decades, scientists have known that ET-743, a compound extracted from a marine invertebrate called a mangrove tunicate, can kill cancer cells. The drug has been approved for use in patients in Europe and is in clinical trials in the U.S.

Scientists suspected the mangrove tunicate, which is a type of a sea squirt, doesn't actually make ET-743. But the precise origins of the drug, which is also known as trabectedin, were a mystery.

By analyzing the genome of the tunicate along with the microbes that live inside it using advanced sequencing techniques, researchers at the University of Michigan were able to isolate the genetic blueprint of the ET-743's producer--which turns out to be a type of bacteria called Candidatus Endoecteinascidia frumentensis.

The findings greatly expand understanding of the microbe and of how ET-743 is produced, the researchers reported online May 27 in the journal Environmental Microbiology. They're optimistic that the insights will help make it possible to culture the bacteria in the laboratory without its host.

"These symbiotic microbes have long been thought to be the true sources of many of the natural products that have been isolated from invertebrates in the ocean and on the land. But very little is known about them because we're not able to get most of them to grow in a laboratory setting," said study senior author David Sherman, the Hans W. Vahlteich Professor of Medicinal Chemistry in the College of Pharmacy and a faculty member of the U-M Life Sciences Institute, where his lab is located.

"Currently, many of these compounds can only be harvested in small amounts from host animals, which is unsustainable from an economic and environmental perspective," said Michael Schofield, one of two first authors on the study and a member of the Sherman lab before she graduated from U-M this spring. "Our hope is that understanding the genomes of these micro-organisms and the chemical reactions that occur inside of them will provide new avenues to economical and sustainable production of the medicinal molecules they make."

ET-743 is currently made using a complicated, partially synthetic process.

"A major challenge of sequencing genomes from samples containing a mixture of different organisms is figuring out which DNA sequences go with which organisms. We used bioinformatic approaches that allowed us to tease that apart," said Sunit Jain, a bioinformatics specialist in the U-M Department of Earth and Environmental Sciences, and the study's other first author.

Study expands understanding of the production of ET-743 compound

This Little Known Chinese Herb Kills 12,000 Cancer Cells For Every Healthy Cell | Collective-Evolution

A little known Chinese herb might be eligible for the growing list of cancer killers via alternative methods of treatment. According to  studies published  in Life Sciences, Cancer Letters and Anticancer Drugs, artemesinin, a derivative of the wormwood plant commonly used in Chinese medicine, can kill off  cancer cells, and do it at a rate of 12,000 cancer cells for every healthy cell.

Henry Lai and his team of researchers from the University of Washington synthesized the compound, which uses a cancer cells appetite for iron to make them the target. The great thing about artemisinin is that alone it can selectively kill cancer cells while leaving normal cells unharmed.

“By itself, artemisinin is about 100 times more selective in killing cancer cells as opposed to normal cells. Artemisinin is 34,000 times more potent in killing the cancer cells as opposed to their normal cousins. So the tagging process appears to have greatly increased the potency of artemisinin’s cancer-killing properties.” – Henry Lai

Despite the compound being licensed to Holley Pharmaceuticals, it has yet to be used for cancer treatment in humans.

“We call it a Trojan horse because the cancer cell recognizes transferrin as a natural, harmless protein. So the cell picks up the compound without knowing that a bomb (artemisinin) is hidden inside.”  – Henry Lai

The wormwood extract was used many centuries ago in China for healing purposes. The treatment became lost over time and has now been rediscovered thanks to an ancient manuscript containing medical remedies. It kills 12,000 cancer cells for every healthy cell, which means it could be turned into a drug with minimal side effects.

“The compound is currently being licensed by the University of Washington to Artemisia Biomedical Inc., a company that Lai, Sasaki and Narendra Singh, UW associate professor of bioengineering, founded in Newcastle, Washington for development and commercialization. Human trials are at least several years away. Artemisinin is readily available, Sasaki said, and he hopes their compound can eventually be cheaply manufactured to help cancer patients in developing countries.”

This Little Known Chinese Herb Kills 12,000 Cancer Cells For Every Healthy Cell | Collective-Evolution

Cimetidine drug could be one of many common over-the-counter medicines to treat cancer...

   

We know that, Cimetidine is a histamine H₂-receptor antagonist that inhibits stomach acid production. It is largely used in the treatment of heartburn and peptic ulcers. It has been marketed by GlaxoSmithKline (which is selling the brand to Prestige Brands) under the trade name Tagamet (sometimes Tagamet HB or Tagamet HB200). Cimetidine was approved in the UK in 1976 and was approved in the US by the Food and Drug Administration for prescriptions starting January 1, 1979.

Now, it has been concluded that, a popular indigestion medication can increase survival in colorectal cancer, according to research published in ecancermedicalscience. But in fact, scientists have studied this for years - and a group of cancer advocates want to know why this research isn't more widely used.

University of Leeds researchers make new synthetic anti-cancer molecule

Researchers at the University of Leeds have made a new synthetic anti-cancer molecule that targets two key mechanisms in the spread of malignant tumours through the body. A study published in the journal PLOS ONE today reports that the synthetic molecule JK-31 blocks the signalling of a "growth factor" chemical that promotes the creation of networks of blood vessels to feed tumours.

But the researchers also found that the new molecule intervened directly in the growth of the cancer itself, inhibiting a protein that controls the division and proliferation of malignant cells.

Dr Vas Ponnambalam, Reader in Human Disease Biology in the University of Leeds' Faculty of Biological Sciences, said: "The ability to mount this two-pronged attack on cancerous growths is exciting. There is a great need for better drugs against cancer than what we currently have and JK31 may represent an important addition to the toolkit for drug makers developing the next generation of drugs."

The researchers observed the effect of the synthetically produced molecule, JK-31, on the growth and proliferation of a model human breast cancer cell line and found that it effectively blocked the protein cyclin-dependent kinase 1 (CDK1), which plays a key part in the process of the division of cancer cells, and therefore inhibited the proliferation of the cells.

In a separate laboratory experiment, they found the same JK-31 molecule also blocked a specific growth factor (VEGF-A) produced by the cancer to attract the growth of blood vessels.

Other molecules exhibiting similar dual effects are known but JK-31 is the only compound so far shown to successfully target CDK1 and block VEGF-A.

University of Leeds researchers make new synthetic anti-cancer molecule

Bowel cancer breakthrough may benefit thousands of patients

Researchers at Queen's University have made a significant breakthrough that may benefit
patients with bowel cancer. 

Dr Sandra van Schaeybroeck and her team have discovered how two genes cause bowel cancer cells to become resistant to treatments used against the disease. The research, which was funded by Cancer Research UK, was published this month in the international journal CellReports.

The activity of the two genes, called MEK and MET, was uncovered when the researchers looked at all the different pathways and interactions taking place in bowel cancer cells.

Dr van Schaeybroeck and her group found that these bowel cancers switch on a survival mechanism when they are treated with drugs that target faulty MEK genes. But when the researchers added drugs that also block the MET gene, the bowel cancer cells died.

The team are now testing a new approach to target these two genes in the most aggressive forms of bowel cancer in a European Commission funded clinical trial that is being led by Dr van Schaeybroeck.

Bowel cancer breakthrough may benefit thousands of patients

Liver Cancer Drug Fails to Live Up to Early Promise...

In continuation of my update on everolimus

Although it looked promising in early studies, the drug everolimus didn't improve survival for people with advanced liver cancer in its latest trial, a new study found.

The findings from the phase 3 clinical trial are disappointing because earlier research suggested that everolimus (Afinitor) prevented tumor progression and improved survival for in advanced liver cancer. Normally, these patients can expect a median overall survival of less than one year.

The only drug currently shown to significantly improve survival of advanced liver cancer patients is sorafenib (Nexavar). But that drug's benefits are temporary and the cancer eventually progresses, according to background information in the new study.

The current study included 546 adults with advanced liver cancer whose disease progressed during or after treatment with sorafenib, or who could not take sorafenib. The patients were divided into two groups, with 362 given everolimus and 184 given a placebo.

Liver Cancer Drug Fails to Live Up to Early Promise 

Breast Cancer Drug May Help Women Fight a Leading Cause of Infertility: Study

Women with polycystic ovary syndrome have a better chance of getting pregnant if they take a breast cancer drug instead of the currently preferred medication, a new study suggests.

Polycystic ovary syndrome -- the most common cause of female infertility in the United States -- causes higher than normal levels of the male hormone androgen, infrequent periods and small cysts on the ovaries. It affects 5 to 10 percent of reproductive-age women, according to background information in the study.

Currently, doctors typically prescribe clomiphine (Clomid) to boost fertility for women with polycystic ovary syndrome. However, this new study suggests the drug letrozole (Femara) results in better ovulation, conception and birth rates.

"We found a simple and comparatively safe and vastly more effective treatment for [polycystic ovary syndrome]," said lead researcher Dr. Richard Legro, a professor of obstetrics and gynecology at Penn State University's College of Medicine in Hershey, Penn.

Clomiphine, which works by stimulating ovulation, has been the standard treatment for years, but has a high rate of multiple births, Legro said.

Letrozole, a treatment for breast cancer in postmenopausal women, works by blocking estrogen production, tricking the ovaries into producing more of the hormone, he explained.

The new study, funded by the U.S. National Institutes of Health, was published July 10 in the New England Journal of Medicine.

Breast Cancer Drug May Help Women Fight a Leading Cause of Infertility: Study - Drugs.com MedNews