Abstract-Toward cancer treatment using terahertz radiation: demethylation of cancer cells

Joo-Hiuk Son; Hwayeong Cheon,

https://www.spiedigitallibrary.org/conference-proceedings-of-spie/11390/1139002/Toward-cancer-treatment-using-terahertz-radiation--demethylation-of-cancer/10.1117/12.2557655.short

Carcinogenesis involves DNA methylation, a primary alteration in DNA, in the development of cancer before genetic mutation. Because abnormal DNA methylation is found in most cancer cells, the assessment and manipulation of DNA methylation using terahertz radiation can be a novel optical method to detect and control cancer. By directly observing the methylation via terahertz spectroscopy at approximately 1.65 THz, this epigenetic chemical change can be manipulated to the state of demethylation using high-power terahertz radiation. Demethylation of cancer DNA is a key issue in epigenetic cancer therapy, and our results may lead to the treatment of cancer using electromagnetic waves.

Abstract-Effective demethylation of melanoma cells using terahertz radiation

Hwayeong Cheon, Hee-Jin Yang, Moran Choi, and Joo-Hiuk Son

 Schematic showing THz demethylation using resonant THz radiation system. High-power THz radiation was generated using a regenerative amplifier and LiNbO3 crystal. The THz filter limited the THz bandwidth to around the resonance frequency of the methyl-DNA bonds.

https://www.osapublishing.org/boe/abstract.cfm?uri=boe-10-10-4931

Terahertz (THz) demethylation is a photomedical technique applied to dissociate methyl-DNA bonds and reduce global DNA methylation using resonant THz radiation. We evaluated the performance of THz demethylation and investigated the DNA damage caused by THz irradiation. The demethylation rate in M-293T DNA increased linearly with the irradiation power up to 48%. The degree of demethylation increased with exposure to THz radiation, saturating after 10 min. Although THz demethylation occurred globally, most of the demethylation occurred within the partial genes in the CpG islands. Subsequently, we performed THz demethylation of melanoma cells. The degree of methylation in the melanoma cell pellets decreased by approximately 10–15%, inducing ∼5–8 abasic sites per 105 bp; this was considerably less than the damaged DNA irradiated by the high-power infrared laser beam used for generating THz pulses. These results provide initial data for THz demethylation and demonstrate the applicability of this technique in advanced cancer cell research. THz demethylation has the potential to develop into a therapeutic procedure for cancer, similar to that involving chemical demethylating agents.

© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Abstract-Near-Infrared Laser-Driven in Situ Self-Assembly as a General Strategy for Deep Tumor Therapy

Fu-Hua Liu, Yong Cong, Guo-Bin Qi, Lei Ji, Zeng-Ying Qiao,  Hao Wang

https://pubs.acs.org/doi/10.1021/acs.nanolett.8b03174#

Nanotherapeutics have encountered some bottleneck problems in cancer therapy, such as poor penetration and inefficient accumulation in tumor site. We herein developed a novel strategy for deep tissue penetration in molecular level and near-infrared (NIR) laser guided in situ self-assembly to solve these challenges. For the proof-of-concept study, we synthesized the polymer–peptide conjugates (PPCs) composed of (i) poly(β-thioester) as thermoresponsive backbone, (ii) functional peptides (cytotoxic peptide and cell-penetrating peptide), and (iii) the NIR molecule with photothermal property. The PPCs in the molecular level with small size (<10 nm) can penetrate deeply into the interior of the tumor at body temperature. Under the irradiation of NIR laser, the temperature rise induced by photothermal molecules led to the intratumoral self-assembly of thermoresponsive PPCs. The resultant spherical nanoparticles can accumulate in tumor and enter cells effectively, inducing cell apoptosis by destroying mitochondria membrane. Through the site-specific size control, a variety of merits of PPCs are realized including deep tumor penetration, enhanced accumulation, and cellular internalization in vivo. Taking advantage of the NIR guided in situ assembly strategy, numerous polymeric or nanoscaled therapeutics with high anticancer activity can be exploited.

Towards Cancer Treatment using Terahertz Radiation- Abstract and Presentation notice

https://physics.kaist.ac.kr/index.php?mid=p_news_event3&document_srl=9207

Verisante Technology, Inc. Announces Brain Tumour Study in the UK

http://finance.yahoo.com/news/verisante-technology-inc-announces-brain-143000588.html
VANCOUVER, BRITISH COLUMBIA--(Marketwired - Jan. 13, 2015) - Verisante Technology, Inc. (TSX VENTURE:VRS)(VRSEF) (the "Company" or "Verisante"), a leader in cancer detection technology, announced today it has entered into a collaboration with the BC Cancer Agency and Imperial College Healthcare NHS Trust to develop a new application for the Company's exclusively licensed platform technology. 

Imperial College Healthcare NHS Trust will be using Verisante's laser Raman system in a study to determine if the system is able to assist in ascertaining the margins between tumour and normal brain tissue. Verisante is providing Imperial College Healthcare NHS Trust with a Raman system. Dr. Haishan Zeng, a distinguished scientist in the Integrative Oncology Department at BC Cancer Agency is leading the development of the endoscopic Raman probe that will be used in the study. 

"Using Verisante Core™ for delineation of brain tumour margins could be a significant new use for the device," said Dr. Zeng, who is also a professor of dermatology and skin science at the University of British Columbia in addition to his work at the BC Cancer Agency. "Our collaboration with Imperial College Healthcare NHS Trust enables us to keep testing the technology on real patients in a clinical setting using new applications."

Brain tumours are rare but have a disproportionate effect on society as they often strike the young. For this reason brain tumours result in more years of life lost than any other tumour. The first step in the patient pathway is often brain surgery which is understandably delicate and highly precise. One of the major obstacles to removing brain tumours is the fact that the boundary between the tumour and normal brain is very hard to see using the naked eye, even with an operating microscope. The group will focus on collecting data during brain tumour surgery done at Charing Cross Hospital in London, England. 

"With this new international partnership between Verisante and Imperial College Healthcare NHS Trust, London, we are hopeful we will be able see beyond the naked eye to diagnose and map brain tumours during surgery using Verisant's Raman laser spectroscopy system," said Mr. Babar Vaqas, a Neurosurgeon and Principle Investigator of the study at Imperial College Healthcare NHS Trust. "This study will be unique in that it will be the first ever application of Raman spectroscopy during human brain surgery."

About the BC Cancer Agency

The BC Cancer Agency is part of the Provincial Health Services Authority (PHSA), providing province-wide specialty healthcare in British Columbia (BC), Canada. The BC Cancer Agency provides a comprehensive cancer control program for the people of BC by working with community partners to deliver a range of oncology services, including prevention, early detection, diagnosis and treatment, research, education, supportive care, rehabilitation and palliative care. For more information, visit www.bccancer.bc.ca.

About Imperial College Healthcare NHS Trust

Imperial College Healthcare NHS Trust comprises Charing Cross, Hammersmith, Queen Charlotte's & Chelsea, St Mary's and Western Eye hospitals. With more than one million patient contacts each year, it is one of the largest acute Trusts in the country and, in partnership with Imperial College London, is the UK's first Academic Health Science Centre (AHSC). It has an annual turnover of around £970 million. The Trust was created on 1 October 2007, by merging Hammersmith Hospitals NHS Trust and St Mary's NHS Trust.

Imperial College Healthcare is one of eleven NIHR Biomedical Research Centres. This designation is given to the most outstanding NHS and university research partnerships in the country; leaders in scientific translation and early adopters of new insights in technologies, techniques and treatments for improving health. Imperial College Healthcare has some of the lowest mortality rates in the country according to the Dr. Foster Guide - an annual, independent report published 2012.

For more information about the Trust visit http://www.imperial.nhs.uk

About Verisante Technology, Inc.

Verisante is a medical device company committed to commercializing innovative systems for the early detection of cancer. The Verisante Aura™ for skin cancer detection and the Verisante Core™ series for lung, colon and cervical cancer detection utilize a proprietary cancer detection platform while the operating software and probe technology are unique to each device. The cancer detection platform was developed by the BC Cancer Agency and tested and refined at the Skin Care Centre at Vancouver General Hospital. This exclusive platform technology allows Verisante to develop and offer a range of compact, non-invasive cancer detection devices that offer physicians immediate results for many of the most common cancers. Aura™ has been approved for sale in Canada, Europe and Australia. The Core™ has not yet been approved for sale. 

Verisante Aura™ was awarded the 2014 North American Technology Innovation of the Year Award for In Vivo Cancer Detection by Frost & Sullivan, Popular Science Magazine's "Best of What's New Award" for 2011, awarded a 2013 Prism Award for Innovation in Photonics and an Edison Award for Excellence in Innovation in 2013. Verisante Core™ was named one of the top 10 cancer breakthroughs of 2011 by the Canadian Cancer Society. 

The TSX Venture Exchange has neither approved nor disapproved of the contents of this press release. Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this press release. 

Forward-Looking Statements 

This release contains forward-looking statements, including, but not limited to, statements regarding the future commercialization of medical devices, the market demand for these products and the proprietary protections the Company will obtain with regard to the technology, all of which statements are subject to market risks, and the possibility that the Company will not be able to obtain patent protection or obtain sufficient customer demand. These statements are made based upon current expectations and actual results may differ from those projected due to a number of risks and uncertainties.

Contact:

Verisante Technology, Inc.
Thomas Braun
President & CEO
(604) 605-0507
info@verisante.com

Terahertz Pulses Simultaneously Kills Skin Tissue, Increases Tumor-Suppressing Proteins

My Note: Yet one more interesting article on the recent paper from the University of Alberta, University of Edmonton, about the health effect of exposure to very high levels of THz photons
By BiotechDaily International staff writers
Posted on 01 Apr 2013
http://www.biotechdaily.com/lab_technologies/articles/294745472/terahertz_pulses_simultaneously_kills_skin_tissue_increases_tumorsuppressing_proteins.html

Terahertz (THz) radiation, a sliver of the electromagnetic spectrum that lies in the middle region between microwaves and infrared light, is providing significant benefits in medical diagnostics and scientific research.

As scientists and engineers find more real-world uses for this type of radiation, however, questions remain about its potential human health risks. New research performed on lab-grown human skin suggests that short but powerful bursts of THz radiation may both cause DNA damage and increase the production of proteins that help the body fight cancer. The findings, which are the result of a collaboration between physicists at the University of Alberta (Edmonton, Canada) and molecular biologists at the University of Lethbridge (Lethbridge, Canada) was published March 18, 2013, in the Optical Society’s (OSA) open-access journal Biomedical Optics Express.

“While these investigations of the biological effects of intense THz pulses are only just beginning,” said Dr. Lyubov Titova, with the University of Alberta and a member of the research team, “the fact that intense THz pulses can induce DNA damage but also DNA repair mechanisms in human skin tissue suggests that intense THz pulses need to be evaluated for possible therapeutic applications.”

THz photons, similar to their longer wavelength cousins in the microwave range, are not strong enough to disrupt the chemical ties that bind DNA together in the nucleus of cells. These waves, however, have just the right frequency to galvanize water molecules, causing them to vibrate and generate heat, which is why microwave ovens are so effective at cooking food. For this reason, it was believed that heat-related injuries were the primary risks posed by THz radiation exposure.

Recent theoretic studies, however, suggest that intense THz pulses of picosecond (one trillionth of a second) duration may directly affect DNA by amplifying natural vibrations (so-called “breathing” mode) of the hydrogen bonds that bind together the two strands of DNA. As a result, “bubbles” (openings in DNA strands) can form. According to the researchers, this brought up the question if intense THz pulses can destabilize DNA structure enough to cause DNA strand breaks.

As shown in earlier animal cell culture studies, THz exposure may indeed affect biologic function under specific conditions such as high power and extended exposure. There is, however, a huge gap between animal research and conclusions that can be drawn about human health.

In a first of its kind study, the Canadian researchers exposed laboratory-grown human skin tissue to intense pulses of THz electromagnetic radiation and have detected the telltale signs of DNA damage through a chemical marker known as phosphorylated H2AX. At the same time, they observed THz-pulse induced increases in the levels of multiple tumor-suppressor and cell-cycle regulatory proteins that facilitate DNA repair. This may suggest that DNA damage in human skin arising from intense picosecond THz pulse exposure could be quickly and effectively repaired, therefore lessening the risk of carcinogenesis.

The researchers used a skin tissue model made of healthy, human-derived epidermal and dermal cells. This tissue is able to undergo mitosis and is metabolically active, thus providing a suitable platform for assessing the effects of exposure to high intensity THz pulses on human skin. For their study, Dr. Titova and her colleagues exposed the skin tissue to picosecond bursts of THz radiation at levels far above what would typically be used in current real-world applications. They then examined the sample for the presence of phosphorylated H2AX, which “flags” the DNA double-strand break site and attracts cellular DNA repair machinery to it.

“The increase in the amount of phosphorylated H2AX in tissues exposed to intense THz pulses compared to unexposed controls indicated that DNA double strand breaks were indeed induced by intense THz pulses,” noted Dr. Titova. Once DNA breaks occur, they can ultimately lead to tumors if unrepaired. “This process,” she continued, “is very slow and cells have evolved many effective mechanisms to recognize damage, pause cell cycle to allow time for damage to be repaired, and—in case repair is unsuccessful—to prevent damage accumulation by inducing apoptosis, or programmed cell death of the affected cell.”

The researchers validated that these cellular repair mechanisms were taking place by detecting an elevated presence of multiple proteins that play vital roles in DNA repair, including protein p53 (frequently called “a guardian of the genome”); p21, which works to stop cell division to allow time for repair; protein Ku70, which helps reconnect the broken DNA strands; and several other important cell proteins with known tumor-suppressor roles. These observations indicate that exposure to intense THz pulses activates cellular processes that repair DNA damage. However, the researchers noted, it is too soon to make forecasts on the long-term implications of exposure.

“In our study we only looked at one moment in time—30 minutes after exposure,” Dr. Titova said. “In the future, we plan to study how all the observed effects change with time after exposure, which should allow us to establish how quickly any induced damage is repaired.”

The Canadian researchers hope to study the potential therapeutic effects of intense THz radiation exposure to see if directed treatment with intense THz pulses can become a new approach to combat cancer.
Related Links:
University of Alberta
University of Lethbridge