Keio University Research: Ancient antiviral response could help treat cancer

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Keio University publishes its October 2017 issue of Keio University Research Highlights. This issue includes updates of recent research by Keio University scientists on ‘ancient antiviral response could help treat cancer’ and ‘digital 3D-fabrication technology for nursing and healthcare’.

Three-dimensional organoids derived from human cholangiosarcoma tumor cells. © 2017 Yoshimasa Saito, Keio University.

Organoids are budding, cyst-like structures that closely recapitulate the properties of the original tumors

Keio University publishes its October 2017 issue of Keio University Research Highlights. This issue includes updates of recent research by Keio University scientists on ‘ancient antiviral response could help treat cancer’ and ‘digital 3D-fabrication technology for nursing and healthcare’.

Keio Research Highlights website

Ancient antiviral response could help treat cancer
A class of drugs can harness the power of the body’s immune system to fight diverse tumors

By stimulating a patient’s immune system, a drug already in use to treat a blood disorder can thwart the growth of a variety of solid tumors, finds a team at Keio University[1].

The drug 5-aza-CdR is currently approved for treating a blood disorder that can lead to leukemia. It inhibits the methylation of DNA, preventing enzymes from chemically modifying genomic DNA. Such modifications can greatly alter the expression of genes that control a variety of critical cellular functions, including cell growth and survival.

Some studies have shown that methylation inhibitors such as 5-aza-CdR could be used to treat other cancers. These effects have generally been attributed to the drugs reactivating tumor-suppressor genes, but the actual mechanism remains poorly understood.

Yoshimasa Saito and his co-workers at Keio University set about figuring out how the drugs work. They began by assessing the effects of 5-aza-CdR on a mouse model of intestinal cancer. The team found that the drug cut the number of tumors that formed by roughly a third and that animals that received the drug tended to have smaller tumors than those that did not.

Having demonstrated that 5-aza-CdR can act on such cancers, the researchers then cultured cells derived from mouse intestinal tumors under conditions that promote the formation of three-dimensional ‘organoids’.

“Organoids are budding, cyst-like structures that closely recapitulate the properties of the original tumors,” explains Saito, “This makes them a powerful tool for studying how cancers respond to treatment.”

The researchers found that 5-aza-CdR strongly inhibited the growth of tumor-derived organoids and were minimally toxic to healthy intestinal cells.

Delving deeper, Saito’s team looked at which genes were turned off and on by this treatment and noticed a striking pattern. “Our findings indicated that DNA demethylation suppresses the proliferation of intestinal tumor organoids by inducing an anti-viral response,” says Saito. He and his colleagues suggest that the methylation inhibitors are somehow reactivating endogenous retroviruses — ancient viral DNA sequences that have accumulated over evolutionary history and now lie dormant throughout the genome. This initial antiviral response leads to immune activation and the shutting down of tumor proliferation.

“These findings represent a major shift in our understanding of the anti-tumor mechanisms of DNA demethylating agents,” says Saito.

The team believes the strategy could be effective for treating other cancers, and it has already obtained promising results with organoids derived from challenging tumors such as cholangiosarcoma and pancreatic cancer. “We are trying to develop a personalized therapy for refractory cancers,” says Saito.

Digital 3D-fabrication technology for nursing and healthcare
Innovative 3D-printed ‘caring-tools’ to enhance the quality of life of elderly people

3D printing technology has important medical applications, such as manufacturing prosthetic parts, implants, and models of human organs. Here, researchers at Keio University in Tokyo describe the potentially important role of 3D printing in nursing and long-term care for the elderly. Given Japan’s rapidly ageing society, demand for terminal care in hospitals or care facilities will exceed capacity in the near future. Furthermore, there are insufficient visiting nurses to provide in-house care. Therefore, strengthening in-house care is an urgent task for healthcare of the elderly. The introduction of information technology (IT) is an essential strategy from both aspects of work efficiency and providing high quality care.

Specifically, Shoko Miyagawa and colleagues at Keio University noticed the increased availability of 3D printers in self-help community centers throughout Japan. Based on interactions with nurses, medical practitioners, engineers and material designers, Miyagawa and her collaborators established a benchmark for specific digitally fabricated objects needed by patients and classified them into three types.

Firstly, are self-help devices enabling individuals to carry out specific tasks. For example, someone with paralyzed fingers who is unable to pinch, is assisted by a customized 3D-printed penholder for signing important documents.

Second, ‘caring tools’ facilitate interaction between care-givers and care-receivers. For instance, cutting out plasters in fun shapes — such as animals — with a laser cutter helps patients overcome negative perception of surgical tape.

Third, Miyagawa and colleagues identified educational objects as tools to learn how to perform therapy actions. For example, a 3D-printed semi-transparent cranial model can be used for practicing the insertion of a tube for vacuuming phlegm from a patient’s throat with light-emitting diodes acting as guides to follow its position inside the model. The researchers also addressed the question of safety, as the proposed 3D-printed objects must be washable and not produce skin irritation. Another important aspect of the research project of the Keio scientists is an assessment of the usage level of the objects. To this end, the researchers are currently developing an ‘internet-of-things’ sensing system: a data logger that can collect information about an object’s use for one month.

Having established the relevance of 3D printing techniques for improving the quality of life and the independence of elderly people, Miyagawa and colleagues conclude that, “in order to make digital fabrication more useful it is necessary to further reduce the cost of introduction and operation and to develop technologies to do so.”

Keio University

Keio Research Highlights

About Keio University
Keio University is a private, comprehensive university with six major campuses in the Greater Tokyo area along with a number of affiliated academic institutions. Keio prides itself on educational and research excellence in a wide range of fields and its state-of-the-art university hospital.

Keio is Japan’s first modern institution of higher learning, founded in 1858. Over the last century and a half, it has evolved into and continues to maintain its status as a leading university in Japan through its ongoing commitment to producing leaders of the future. Founder Yukichi Fukuzawa, a highly respected educator and one of the most important intellectuals of modern Japan, aspired for Keio to be a pioneer of new discoveries and contribute to society through learning.

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