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KAIST debuts “DreamWaQer” - a quadrupedal robot that can walk in the dark
- The team led by Professor Hyun Myung of the School of Electrical Engineering developed “DreamWaQ”, a deep reinforcement learning-based walking robot control technology that can walk in an atypical environment without visual and/or tactile information
- Utilization of “DreamWaQ” technology can enable mass production of various types of “DreamWaQers”
- Expected to be used in exploration of atypical environment involving unique circumstances such as disasters by fire.
A team of Korean engineering researchers has developed a quadrupedal robot technology that can climb up and down the steps and moves without falling over in uneven environments such as tree roots without the help of visual or tactile sensors even in disastrous situations in which visual confirmation is impeded due to darkness or thick smoke from the flames.
KAIST (President Kwang Hyung Lee) announced on the 29th of March that Professor Hyun Myung's research team at the Urban Robotics Lab in the School of Electrical Engineering developed a walking robot control technology that enables robust 'blind locomotion' in various atypical environments.
< (From left) Prof. Hyun Myung, Doctoral Candidates I Made Aswin Nahrendra, Byeongho Yu, and Minho Oh. In the foreground is the DreamWaQer, a quadrupedal robot equipped with DreamWaQ technology. >
The KAIST research team developed "DreamWaQ" technology, which was named so as it enables walking robots to move about even in the dark, just as a person can walk without visual help fresh out of bed and going to the bathroom in the dark. With this technology installed atop any legged robots, it will be possible to create various types of "DreamWaQers".
Existing walking robot controllers are based on kinematics and/or dynamics models. This is expressed as a model-based control method. In particular, on atypical environments like the open, uneven fields, it is necessary to obtain the feature information of the terrain more quickly in order to maintain stability as it walks. However, it has been shown to depend heavily on the cognitive ability to survey the surrounding environment.
In contrast, the controller developed by Professor Hyun Myung's research team based on deep reinforcement learning (RL) methods can quickly calculate appropriate control commands for each motor of the walking robot through data of various environments obtained from the simulator. Whereas the existing controllers that learned from simulations required a separate re-orchestration to make it work with an actual robot, this controller developed by the research team is expected to be easily applied to various walking robots because it does not require an additional tuning process.
DreamWaQ, the controller developed by the research team, is largely composed of a context estimation network that estimates the ground and robot information and a policy network that computes control commands. The context-aided estimator network estimates the ground information implicitly and the robot’s status explicitly through inertial information and joint information. This information is fed into the policy network to be used to generate optimal control commands. Both networks are learned together in the simulation.
While the context-aided estimator network is learned through supervised learning, the policy network is learned through an actor-critic architecture, a deep RL methodology. The actor network can only implicitly infer surrounding terrain information. In the simulation, the surrounding terrain information is known, and the critic, or the value network, that has the exact terrain information evaluates the policy of the actor network.
This whole learning process takes only about an hour in a GPU-enabled PC, and the actual robot is equipped with only the network of learned actors. Without looking at the surrounding terrain, it goes through the process of imagining which environment is similar to one of the various environments learned in the simulation using only the inertial sensor (IMU) inside the robot and the measurement of joint angles. If it suddenly encounters an offset, such as a staircase, it will not know until its foot touches the step, but it will quickly draw up terrain information the moment its foot touches the surface. Then the control command suitable for the estimated terrain information is transmitted to each motor, enabling rapidly adapted walking.
The DreamWaQer robot walked not only in the laboratory environment, but also in an outdoor environment around the campus with many curbs and speed bumps, and over a field with many tree roots and gravel, demonstrating its abilities by overcoming a staircase with a difference of a height that is two-thirds of its body. In addition, regardless of the environment, the research team confirmed that it was capable of stable walking ranging from a slow speed of 0.3 m/s to a rather fast speed of 1.0 m/s.
The results of this study were produced by a student in doctorate course, I Made Aswin Nahrendra, as the first author, and his colleague Byeongho Yu as a co-author. It has been accepted to be presented at the upcoming IEEE International Conference on Robotics and Automation (ICRA) scheduled to be held in London at the end of May. (Paper title: DreamWaQ: Learning Robust Quadrupedal Locomotion With Implicit Terrain Imagination via Deep Reinforcement Learning)
The videos of the walking robot DreamWaQer equipped with the developed DreamWaQ can be found at the address below.
Main Introduction: https://youtu.be/JC1_bnTxPiQ Experiment Sketches: https://youtu.be/mhUUZVbeDA0
Meanwhile, this research was carried out with the support from the Robot Industry Core Technology Development Program of the Ministry of Trade, Industry and Energy (MOTIE). (Task title: Development of Mobile Intelligence SW for Autonomous Navigation of Legged Robots in Dynamic and Atypical Environments for Real Application)
< Figure 1. Overview of DreamWaQ, a controller developed by this research team. This network consists of an estimator network that learns implicit and explicit estimates together, a policy network that acts as a controller, and a value network that provides guides to the policies during training. When implemented in a real robot, only the estimator and policy network are used. Both networks run in less than 1 ms on the robot's on-board computer. >
< Figure 2. Since the estimator can implicitly estimate the ground information as the foot touches the surface, it is possible to adapt quickly to rapidly changing ground conditions. >
< Figure 3. Results showing that even a small walking robot was able to overcome steps with height differences of about 20cm. >
2023.05.18 View 9203 -
KAIST gearing up to train physician-scientists and BT Professionals joining hands with Boston-based organizations
KAIST (President Kwang Hyung Lee) announced on the 29th that it has signed MOUs with Massachusetts General Hospital, a founding member of the Mass General Brigham health care system and a world-class research-oriented hospital, and Moderna, a biotechnology company that developed a COVID-19 vaccine at the Langham Hotel in Boston, MA, USA on the morning of April 28th (local time). The signing ceremony was attended by officials from each institution joined by others headed by Minister LEE Young of the Korean Ministry of SMEs and Startups (MSS), and Commissioner LEE Insil of the Korean Intellectual Property Office.
< Photo 1. Photo from the Signing of MOU between KAIST-Harvard University Massachusetts General Hospital and KAIST-Moderna >
Mass General is the first and largest teaching hospital of Harvard Medical School in Boston, USA, and it is one of the most innovative hospitals in the world being the alma mater of more than 13 Nobel Prize winners and the home of the Mass General Research Institute, the world’s largest hospital-based research program that utilizes an annual research budget of more than $1.3 billion.
KAIST signed a general agreement to explore research and academic exchange with Mass General in September of last year and this MOU is a part of its follow-ups.
Mass General works with Harvard and the Massachusetts Institute of Technology (MIT), as well as local hospitals, to support students learn the theories of medicine and engineering, and gain rich clinical research experience.
Through this MOU, KAIST will explore cooperation with an innovative ecosystem created through the convergence of medicine and engineering. In particular, KAIST’s goal is to develop a Korean-style training program and implement a differentiated educational program when establishing the science and technology-oriented medical school in the future by further strengthening the science and engineering part of the training including a curriculum on artificial intelligence (AI) and the likes there of.
Also, in order to foster innovative physician-scientists, KAIST plans to pursue cooperation to develop programs for exchange of academic and human resources including programs for student and research exchanges and a program for students of the science and technology-oriented medical school at KAIST to have a chance to take part in practical training at Mass General.
David F.M. Brown, MD, Mass General President, said, “The collaboration with KAIST has a wide range of potentials, including advice on training of physician-scientists, academic and human resource exchanges, and vitalization of joint research by faculty from both institutions. Through this agreement, we will be able to actively contribute to global cooperation and achieve mutual goals.”
Meanwhile, an MOU between KAIST and Moderna was also held on the same day. Its main focus is to foster medical experts in cooperation with KAIST Graduate School of Medical Science and Engineering (GSMSE), and plans to cooperate in various ways in the future, including collaborating for development of vaccine and new drugs, virus research, joint mRNA research, and facilitation of technology commercialization.
In over 10 years since its inception, Moderna has transformed from a research-stage company advancing programs in the field of messenger RNA (mRNA) to an enterprise with a diverse clinical portfolio of vaccines and therapeutics across seven modalities. The Company has 48 programs in development across 45 development candidates, of which 38 are currently in active clinical trials.
“We are grateful to have laid a foundation for collaboration to foster industry experts with the Korea Advanced Institute of Science and Technology, a leader of science and technology innovation in Korea,” said Arpa Garay, Chief Commercial Officer, Moderna. “Based on our leadership and expertise in developing innovative mRNA vaccines and therapeutics, we hope to contribute to educating and collaborating with professionals in the bio-health field of Korea.“
President Kwang Hyung Lee of KAIST, said, “We deem this occasion to be of grave significance to be able to work closely with Massachusetts General Hospital, one of the world's best research-oriented hospitals, and Moderna, one of the most influential biomedical companies.”
President Lee continued, "On the basis of the collaboration with the two institutions, we will be able to bring up qualified physician-scientists and global leaders of the biomedical business who will solve problems of human health and their progress will in turn, accelerate the national R&D efforts in general and diversify the industry."
2023.04.29 View 13071 -
Seanie Lee of KAIST Kim Jaechul Graduate School of AI, named the 2023 Apple Scholars in AI Machine Learning
Seanie Lee, a Ph.D. candidate at the Kim Jaechul Graduate School of AI, has been selected as one of the Apple Scholars in AI/ML PhD fellowship program recipients for 2023. Lee, advised by Sung Ju Hwang and Juho Lee, is a rising star in AI.
< Seanie Lee of KAIST Kim Jaechul Graduate School of AI >
The Apple Scholars in AI/ML PhD fellowship program, launched in 2020, aims to discover and support young researchers with a promising future in computer science. Each year, a handful of graduate students in related fields worldwide are selected for the program. For the following two years, the selected students are provided with financial support for research, international conference attendance, internship opportunities, and mentorship by an Apple engineer.
This year, 22 PhD students were selected from leading universities worldwide, including Johns Hopkins University, MIT, Stanford University, Imperial College London, Edinburgh University, Tsinghua University, HKUST, and Technion. Seanie Lee is the first Korean student to be selected for the program.
Lee’s research focuses on transfer learning, a subfield of AI that reuses pre-trained AI models on large datasets such as images or text corpora to train them for new purposes.
(*text corpus: a collection of text resources in computer-readable forms)
His work aims to improve the performance of transfer learning by developing new data augmentation methods that allow for more effective training using few training data samples and new regularization techniques that prevent the overfitting of large AI models to training data. He has published 11 papers, all of which were accepted to top-tier conferences such as the Annual Meeting of the Association for Computational Linguistics (ACL), International Conference on Learning Representations (ICLR), and Annual Conference on Neural Information Processing Systems (NeurIPS).
“Being selected as one of the Apple Scholars in AI/ML PhD fellowship program is a great motivation for me,” said Lee. “So far, AI research has been largely focused on computer vision and natural language processing, but I want to push the boundaries now and use modern tools of AI to solve problems in natural science, like physics.”
2023.04.20 View 6331 -
KAIST Team Develops Highly-Sensitive Wearable Piezoelectric Blood Pressure Sensor for Continuous Health Monitoring
- A collaborative research team led by KAIST Professor Keon Jae Lee verifies the accuracy of the highly-sensitive sensor through clinical trials
- Commercialization of the watch and patch-type sensor is in progress
A KAIST research team led by Professor Keon Jae Lee from the Department of Materials Science and Engineering and the College of Medicine of the Catholic University of Korea has developed a highly sensitive, wearable piezoelectric blood pressure sensor.
Blood pressure is a critical indicator for assessing general health and predicting stroke or heart failure. In particular, cardiovascular disease is the leading cause of global death, therefore, periodic measurement of blood pressure is crucial for personal healthcare.
Recently, there has been a growing interest in healthcare devices for continuous blood pressure monitoring. Although smart watches using LED-based photoplethysmography (PPG) technology have been on market, these devices have been limited by the accuracy constraints of optical sensors, making it hard to meet the international standards of automatic sphygmomanometers.
Professor Lee’s team has developed the wearable piezoelectric blood pressure sensor by transferring a highly sensitive, inorganic piezoelectric membrane from bulk sapphire substrates to flexible substrates. Ultrathin piezoelectric sensors with a thickness of several micrometers (one hundredth of the human hair) exhibit conformal contact with the skin to successfully collect accurate blood pressure from the subtle pulsation of the blood vessels.
Clinical trial at the St. Mary’s Hospital of the Catholic University validated the accuracy of blood pressure sensor at par with international standard with errors within ±5 mmHg and a standard deviation under 8 mmHg for both systolic and diastolic blood pressure. In addition, the research team successfully embedded the sensor on a watch-type product to enable continuous monitoring of blood pressure.
Prof. Keon Jae Lee said, “Major target of our healthcare devices is hypertensive patients for their daily medical check-up. We plan to develop a comfortable patch-type sensor to monitor blood pressure during sleep and have a start-up company commercialize these watch and patch-type products soon.”
This result titled “Clinical validation of wearable piezoelectric blood pressure sensor for health monitoring” was published in the online issue of Advanced Materials on March 24th, 2023. (DOI: 10.1002/adma.202301627)
Figure 1. Schematic illustration of the overall concept for a wearable piezoelectric blood pressure sensor (WPBPS).
Figure 2. Wearable piezoelectric blood pressure sensor (WPBPS) mounted on a watch (a) Schematic design of the WPBPS-embedded wristwatch. (b) Block diagram of the wireless communication circuit, which filters, amplifies, and transmits wireless data to portable devices. (c) Pulse waveforms transmitted from the wristwatch to the portable device by the wireless communication circuit. The inset shows a photograph of monitoring a user’s beat-to-beat pulses and their corresponding BP values in real time using the developed WPBPS-mounted wristwatch.
2023.04.17 View 7331 -
Using light to throw and catch atoms to open up a new chapter for quantum computing
The technology to move and arrange atoms, the most basic component of a quantum computer, is very important to Rydberg quantum computing research. However, to place the atoms at the desired location, the atoms must be captured and transported one by one using a highly focused laser beam, commonly referred to as an optical tweezer. and, the quantum information of the atoms is likely to change midway.
KAIST (President Kwang Hyung Lee) announced on the 27th that a research team led by Professor Jaewook Ahn of the Department of Physics developed a technology to throw and receive rubidium atoms one by one using a laser beam.
The research team developed a method to throw and receive atoms which would minimize the time the optical tweezers are in contact with the atoms in which the quantum information the atoms carry may change. The research team used the characteristic that the rubidium atoms, which are kept at a very low temperature of 40μK below absolute zero, move very sensitively to the electromagnetic force applied by light along the focal point of the light tweezers.
The research team accelerated the laser of an optical tweezer to give an optical kick to an atom to send it to a target, then caught the flying atom with another optical tweezer to stop it. The atom flew at a speed of 65 cm/s, and traveled up to 4.2 μm. Compared to the existing technique of guiding the atoms with the optical tweezers, the technique of throwing and receiving atoms eliminates the need to calculate the transporting path for the tweezers, and makes it easier to fix the defects in the atomic arrangement. As a result, it is effective in generating and maintaining a large number of atomic arrangements, and when the technology is used to throw and receive flying atom qubits, it will be used in studying new and more powerful quantum computing methods that presupposes the structural changes in quantum arrangements.
"This technology will be used to develop larger and more powerful Rydberg quantum computers," says Professor Jaewook Ahn. “In a Rydberg quantum computer,” he continues, “atoms are arranged to store quantum information and interact with neighboring atoms through electromagnetic forces to perform quantum computing. The method of throwing an atom away for quick reconstruction the quantum array can be an effective way to fix an error in a quantum computer that requires a removal or replacement of an atom.”
The research, which was conducted by doctoral students Hansub Hwang and Andrew Byun of the Department of Physics at KAIST and Sylvain de Léséleuc, a researcher at the National Institute of Natural Sciences in Japan, was published in the international journal, Optica, 0n March 9th. (Paper title: Optical tweezers throw and catch single atoms).
This research was carried out with the support of the Samsung Science & Technology Foundation.
<Figure 1> A schematic diagram of the atom catching and throwing technique. The optical tweezer on the left kicks the atom to throw it into a trajectory to have the tweezer on the right catch it to stop it.
2023.03.28 View 5978 -
The cause of disability in aged brain meningeal membranes identified
Due to the increase in average age, studies on changes in the brain following general aging process without serious brain diseases have also become an issue that requires in-depth studies. Regarding aging research, as aging progresses, ‘sugar’ accumulates in the body, and the accumulated sugar becomes a causative agent for various diseases such as aging-related inflammation and vascular disease. In the end, “surplus” sugar molecules attach to various proteins in the body and interfere with their functions.
KAIST (President Kwang Hyung Lee), a joint research team of Professor Pilnam Kim and Professor Yong Jeong of the Department of Bio and Brain Engineering, revealed on the 15th that it was confirmed that the function of being the “front line of defense” for the cerebrocortex of the brain meninges, the layers of membranes that surrounds the brain, is hindered when 'sugar' begins to build up on them as aging progresses.
Professor Kim's research team confirmed excessive accumulation of sugar molecules in the meninges of the elderly and also confirmed that sugar accumulation occurs mouse models in accordance with certain age levels. The meninges are thin membranes that surround the brain and exist at the boundary between the cerebrospinal fluid and the cortex and play an important role in protecting the brain. In this study, it was revealed that the dysfunction of these brain membranes caused by aging is induced by 'excess' sugar in the brain. In particular, as the meningeal membrane becomes thinner and stickier due to aging, a new paradigm has been provided for the discovery of the principle of the decrease in material exchange between the cerebrospinal fluid and the cerebral cortex.
This research was conducted by the Ph.D. candidate Hyo Min Kim and Dr. Shinheun Kim as the co-first authors to be published online on February 28th in the international journal, Aging Cell. (Paper Title: Glycation-mediated tissue-level remodeling of brain meningeal membrane by aging)
The meninges, which are in direct contact with the cerebrospinal fluid, are mainly composed of collagen, an extracellular matrix (ECM) protein, and are composed of fibroblasts, which are cells that produce this protein. The cells that come in contact with collagen proteins that are attached with sugar have a low collagen production function, while the meningeal membrane continuously thins and collapses as the expression of collagen degrading enzymes increases.
Studies on the relationship between excess sugar molecules accumulation in the brain due to continued sugar intake and the degeneration of neurons and brain diseases have been continuously conducted. However, this study was the first to identify meningeal degeneration and dysfunction caused by glucose accumulation with the focus on the meninges itself, and the results are expected to present new ideas for research into approach towards discoveries of new treatments for brain disease.
Researcher Hyomin Kim, the first author, introduced the research results as “an interesting study that identified changes in the barriers of the brain due to aging through a convergent approach, starting from the human brain and utilizing an animal model with a biomimetic meningeal model”.
Professor Pilnam Kim's research team is conducting research and development to remove sugar that accumulated throughout the human body, including the meninges. Advanced glycation end products, which are waste products formed when proteins and sugars meet in the human body, are partially removed by macrophages. However, glycated products bound to extracellular matrix proteins such as collagen are difficult to remove naturally. Through the KAIST-Ceragem Research Center, this research team is developing a healthcare medical device to remove 'sugar residue' in the body.
This study was carried out with the National Research Foundation of Korea's collective research support.
Figure 1. Schematic diagram of proposed mechanism showing aging‐related ECM remodeling through meningeal fibroblasts on the brain leptomeninges. Meningeal fibroblasts in the young brain showed dynamic COL1A1 synthetic and COL1‐interactive function on the collagen membrane. They showed ITGB1‐mediated adhesion on the COL1‐composed leptomeningeal membrane and induction of COL1A1 synthesis for maintaining the collagen membrane. With aging, meningeal fibroblasts showed depletion of COL1A1 synthetic function and altered cell–matrix interaction.
Figure 2. Representative rat meningeal images observed in the study. Compared to young rats, it was confirmed that type 1 collagen (COL1) decreased along with the accumulation of glycated end products (AGE) in the brain membrane of aged rats, and the activity of integrin beta 1 (ITGB1), a representative receptor corresponding to cell-collagen interaction. Instead, it was observed that the activity of discoidin domain receptor 2 (DDR2), one of the tyrosine kinases, increased.
Figure 3. Substance flux through the brain membrane decreases with aging. It was confirmed that the degree of adsorption of fluorescent substances contained in cerebrospinal fluid (CSF) to the brain membrane increased and the degree of entry into the periphery of the cerebral blood vessels decreased in the aged rats. In this study, only the influx into the brain was confirmed during the entry and exit of substances, but the degree of outflow will also be confirmed through future studies.
2023.03.15 View 7177 -
KAIST develops 'MetaVRain' that realizes vivid 3D real-life images
KAIST (President Kwang Hyung Lee) is a high-speed, low-power artificial intelligence (AI: Artificial Intelligent) semiconductor* MetaVRain, which implements artificial intelligence-based 3D rendering that can render images close to real life on mobile devices.
* AI semiconductor: Semiconductor equipped with artificial intelligence processing functions such as recognition, reasoning, learning, and judgment, and implemented with optimized technology based on super intelligence, ultra-low power, and ultra-reliability
The artificial intelligence semiconductor developed by the research team makes the existing ray-tracing*-based 3D rendering driven by GPU into artificial intelligence-based 3D rendering on a newly manufactured AI semiconductor, making it a 3D video capture studio that requires enormous costs. is not needed, so the cost of 3D model production can be greatly reduced and the memory used can be reduced by more than 180 times. In particular, the existing 3D graphic editing and design, which used complex software such as Blender, is replaced with simple artificial intelligence learning, so the general public can easily apply and edit the desired style.
* Ray-tracing: Technology that obtains images close to real life by tracing the trajectory of all light rays that change according to the light source, shape and texture of the object
This research, in which doctoral student Donghyun Han participated as the first author, was presented at the International Solid-State Circuit Design Conference (ISSCC) held in San Francisco, USA from February 18th to 22nd by semiconductor researchers from all over the world.
(Paper Number 2.7, Paper Title: MetaVRain: A 133mW Real-time Hyper-realistic 3D NeRF Processor with 1D-2D Hybrid Neural Engines for Metaverse on Mobile Devices (Authors: Donghyeon Han, Junha Ryu, Sangyeob Kim, Sangjin Kim, and Hoi-Jun Yoo))
Professor Yoo's team discovered inefficient operations that occur when implementing 3D rendering through artificial intelligence, and developed a new concept semiconductor that combines human visual recognition methods to reduce them. When a person remembers an object, he has the cognitive ability to immediately guess what the current object looks like based on the process of starting with a rough outline and gradually specifying its shape, and if it is an object he saw right before. In imitation of such a human cognitive process, the newly developed semiconductor adopts an operation method that grasps the rough shape of an object in advance through low-resolution voxels and minimizes the amount of computation required for current rendering based on the result of rendering in the past.
MetaVRain, developed by Professor Yu's team, achieved the world's best performance by developing a state-of-the-art CMOS chip as well as a hardware architecture that mimics the human visual recognition process. MetaVRain is optimized for artificial intelligence-based 3D rendering technology and achieves a rendering speed of up to 100 FPS or more, which is 911 times faster than conventional GPUs. In addition, as a result of the study, the energy efficiency, which represents the energy consumed per video screen processing, is 26,400 times higher than that of GPU, opening the possibility of artificial intelligence-based real-time rendering in VR/AR headsets and mobile devices.
To show an example of using MetaVRain, the research team developed a smart 3D rendering application system together, and showed an example of changing the style of a 3D model according to the user's preferred style. Since you only need to give artificial intelligence an image of the desired style and perform re-learning, you can easily change the style of the 3D model without the help of complicated software. In addition to the example of the application system implemented by Professor Yu's team, it is expected that various application examples will be possible, such as creating a realistic 3D avatar modeled after a user's face, creating 3D models of various structures, and changing the weather according to the film production environment. do.
Starting with MetaVRain, the research team expects that the field of 3D graphics will also begin to be replaced by artificial intelligence, and revealed that the combination of artificial intelligence and 3D graphics is a great technological innovation for the realization of the metaverse.
Professor Hoi-Jun Yoo of the Department of Electrical and Electronic Engineering at KAIST, who led the research, said, “Currently, 3D graphics are focused on depicting what an object looks like, not how people see it.” The significance of this study was revealed as a study that enabled efficient 3D graphics by borrowing the way people recognize and express objects by imitating them.” He also foresaw the future, saying, “The realization of the metaverse will be achieved through innovation in artificial intelligence technology and innovation in artificial intelligence semiconductors, as shown in this study.”
Figure 1. Description of the MetaVRain demo screen
Photo of Presentation at the International Solid-State Circuits Conference (ISSCC)
2023.03.13 View 6460 -
KAIST team develops smart immune system that can pin down on malignant tumors
A joint research team led by Professor Jung Kyoon Choi of the KAIST Department of Bio and Brain Engineering and Professor Jong-Eun Park of the KAIST Graduate School of Medical Science and Engineering (GSMSE) announced the development of the key technologies to treat cancers using smart immune cells designed based on AI and big data analysis. This technology is expected to be a next-generation immunotherapy that allows precision targeting of tumor cells by having the chimeric antigen receptors (CARs) operate through a logical circuit. Professor Hee Jung An of CHA Bundang Medical Center and Professor Hae-Ock Lee of the Catholic University of Korea also participated in this research to contribute joint effort.
Professor Jung Kyoon Choi’s team built a gene expression database from millions of cells, and used this to successfully develop and verify a deep-learning algorithm that could detect the differences in gene expression patterns between tumor cells and normal cells through a logical circuit. CAR immune cells that were fitted with the logic circuits discovered through this methodology could distinguish between tumorous and normal cells as a computer would, and therefore showed potentials to strike only on tumor cells accurately without causing unwanted side effects.
This research, conducted by co-first authors Dr. Joonha Kwon of the KAIST Department of Bio and Brain Engineering and Ph.D. candidate Junho Kang of KAIST GSMSE, was published by Nature Biotechnology on February 16, under the title Single-cell mapping of combinatorial target antigens for CAR switches using logic gates.
An area in cancer research where the most attempts and advances have been made in recent years is immunotherapy. This field of treatment, which utilizes the patient’s own immune system in order to overcome cancer, has several methods including immune checkpoint inhibitors, cancer vaccines and cellular treatments. Immune cells like CAR-T or CAR-NK equipped with chimera antigen receptors, in particular, can recognize cancer antigens and directly destroy cancer cells.
Starting with its success in blood cancer treatment, scientists have been trying to expand the application of CAR cell therapy to treat solid cancer. But there have been difficulties to develop CAR cells with effective killing abilities against solid cancer cells with minimized side effects. Accordingly, in recent years, the development of smarter CAR engineering technologies, i.e., computational logic gates such as AND, OR, and NOT, to effectively target cancer cells has been underway.
At this point in time, the research team built a large-scale database for cancer and normal cells to discover the exact genes that are expressed only from cancer cells at a single-cell level. The team followed this up by developing an AI algorithm that could search for a combination of genes that best distinguishes cancer cells from normal cells. This algorithm, in particular, has been used to find a logic circuit that can specifically target cancer cells through cell-level simulations of all gene combinations. CAR-T cells equipped with logic circuits discovered through this methodology are expected to distinguish cancerous cells from normal cells like computers, thereby minimizing side effects and maximizing the effects of chemotherapy.
Dr. Joonha Kwon, who is the first author of this paper, said, “this research suggests a new method that hasn’t been tried before. What’s particularly noteworthy is the process in which we found the optimal CAR cell circuit through simulations of millions of individual tumors and normal cells.” He added, “This is an innovative technology that can apply AI and computer logic circuits to immune cell engineering. It would contribute greatly to expanding CAR therapy, which is being successfully used for blood cancer, to solid cancers as well.”
This research was funded by the Original Technology Development Project and Research Program for Next Generation Applied Omic of the Korea Research Foundation.
Figure 1. A schematic diagram of manufacturing and administration process of CAR therapy and of cancer cell-specific dual targeting using CAR.
Figure 2. Deep learning (convolutional neural networks, CNNs) algorithm for selection of dual targets based on gene combination (left) and algorithm for calculating expressing cell fractions by gene combination according to logical circuit (right).
2023.03.09 View 8666 -
KAIST Holds 2023 Commencement Ceremony
< Photo 1. On the 17th, KAIST held the 2023 Commencement Ceremony for a total of 2,870 students, including 691 doctors. >
KAIST held its 2023 commencement ceremony at the Sports Complex of its main campus in Daejeon at 2 p.m. on February 27. It was the first commencement ceremony to invite all its graduates since the start of COVID-19 quarantine measures.
KAIST awarded a total of 2,870 degrees including 691 PhD degrees, 1,464 master’s degrees, and 715 bachelor’s degrees, which adds to the total of 74,999 degrees KAIST has conferred since its foundation in 1971, which includes 15,772 PhD, 38,360 master’s and 20,867 bachelor’s degrees.
This year’s Cum Laude, Gabin Ryu, from the Department of Mechanical Engineering received the Minister of Science and ICT Award. Seung-ju Lee from the School of Computing received the Chairman of the KAIST Board of Trustees Award, while Jantakan Nedsaengtip, an international student from Thailand received the KAIST Presidential Award, and Jaeyong Hwang from the Department of Physics and Junmo Lee from the Department of Industrial and Systems Engineering each received the President of the Alumni Association Award and the Chairman of the KAIST Development Foundation Award, respectively.
Minister Jong-ho Lee of the Ministry of Science and ICT awarded the recipients of the academic awards and delivered a congratulatory speech.
Yujin Cha from the Department of Bio and Brain Engineering, who received a PhD degree after 19 years since his entrance to KAIST as an undergraduate student in 2004 gave a speech on behalf of the graduates to move and inspire the graduates and the guests.
After Cha received a bachelor’s degree from the Department of Nuclear and Quantum Engineering, he entered a medical graduate school and became a radiation oncology specialist. But after experiencing the death of a young patient who suffered from osteosarcoma, he returned to his alma mater to become a scientist. As he believes that science and technology is the ultimate solution to the limitations of modern medicine, he started as a PhD student at the Department of Bio and Brain Engineering in 2018, hoping to find such solutions.
During his course, he identified the characteristics of the decision-making process of doctors during diagnosis, and developed a brain-inspired AI algorithm. It is an original and challenging study that attempted to develop a fundamental machine learning theory from the data he collected from 200 doctors of different specialties.
Cha said, “Humans and AI can cooperate by humans utilizing the unique learning abilities of AI to develop our expertise, while AIs can mimic us humans’ learning abilities to improve.” He added, “My ultimate goal is to develop technology to a level at which humans and machines influence each other and ‘coevolve’, and applying it not only to medicine, but in all areas.”
Cha, who is currently an assistant professor at the KAIST Biomedical Research Center, has also written Artificial Intelligence for Doctors in 2017 to help medical personnel use AI in clinical fields, and the book was selected as one of the 2018 Sejong Books in the academic category.
During his speech at this year’s commencement ceremony, he shared that “there are so many things in the world that are difficult to solve and many things to solve them with, but I believe the things that can really broaden the horizons of the world and find fundamental solutions to the problems at hand are science and technology.”
Meanwhile, singer-songwriter Sae Byul Park who studied at the KAIST Graduate School of Culture Technology will also receive her PhD degree.
Natural language processing (NLP) is a field in AI that teaches a computer to understand and analyze human language that is actively being studied. An example of NLP is ChatGTP, which recently received a lot of attention. For her research, Park analyzed music rather than language using NLP technology.
To analyze music, which is in the form of sound, using the methods for NLP, it is necessary to rebuild notes and beats into a form of words or sentences as in a language. For this, Park designed an algorithm called Mel2Word and applied it to her research.
She also suggested that by converting melodies into texts for analysis, one would be able to quantitatively express music as sentences or words with meaning and context rather than as simple sounds representing a certain note.
Park said, “music has always been considered as a product of subjective emotion, but this research provides a framework that can calculate and analyze music.”
Park’s study can later be developed into a tool to measure the similarities between musical work, as well as a piece’s originality, artistry and popularity, and it can be used as a clue to explore the fundamental principles of how humans respond to music from a cognitive science perspective.
Park began her Ph.D. program in 2014, while carrying on with her musical activities as well as public and university lectures alongside, and dealing with personally major events including marriage and childbirth during the course of years. She already met the requirements to receive her degree in 2019, but delayed her graduation in order to improve the level of completion of her research, and finally graduated with her current achievements after nine years.
Professor Juhan Nam, who supervised Park’s research, said, “Park, who has a bachelor’s degree in psychology, later learned to code for graduate school, and has complete high-quality research in the field of artificial intelligence.” He added, “Though it took a long time, her attitude of not giving up until the end as a researcher is also excellent.”
Sae Byul Park is currently lecturing courses entitled Culture Technology and Music Information Retrieval at the Underwood International College of Yonsei University.
Park said, “the 10 or so years I’ve spent at KAIST as a graduate student was a time I could learn and prosper not only academically but from all angles of life.” She added, “having received a doctorate degree is not the end, but a ‘commencement’. Therefore, I will start to root deeper from the seeds I sowed and work harder as a both a scholar and an artist.”
< Photo 2. From left) Yujin Cha (Valedictorian, Medical-Scientist Program Ph.D. graduate), Saebyeol Park (a singer-songwriter, Ph.D. graduate from the Graduate School of Culture and Technology), Junseok Moon and Inah Seo (the two highlighted CEO graduates from the Department of Management Engineering's master’s program) >
Young entrepreneurs who dream of solving social problems will also be wearing their graduation caps. Two such graduates are Jun-seok Moon and Inah Seo, receiving their master’s degrees in social entrepreneurship MBA from the KAIST College of Business.
Before entrance, Moon ran a café helping African refugees stand on their own feet. Then, he entered KAIST to later expand his business and learn social entrepreneurship in order to sustainably help refugees in the blind spots of human rights and welfare.
During his master’s course, Moon realized that he could achieve active carbon reduction by changing the coffee alone, and switched his business field and founded Equal Table. The amount of carbon an individual can reduce by refraining from using a single paper cup is 10g, while changing the coffee itself can reduce it by 300g.
1kg of coffee emits 15kg of carbon over the course of its production, distribution, processing, and consumption, but Moon produces nearly carbon-neutral coffee beans by having innovated the entire process. In particular, the company-to-company ESG business solution is Moon’s new start-up area. It provides companies with carbon-reduced coffee made by roasting raw beans from carbon-neutral certified farms with 100% renewable energy, and shows how much carbon has been reduced in its making. Equal Table will launch the service this month in collaboration with SK Telecom, its first partner.
Inah Seo, who also graduated with Moon, founded Conscious Wear to start a fashion business reducing environmental pollution. In order to realize her mission, she felt the need to gain the appropriate expertise in management, and enrolled for the social entrepreneurship MBA.
Out of the various fashion industries, Seo focused on the leather market, which is worth 80 trillion won. Due to thickness or contamination issues, only about 60% of animal skin fabric is used, and the rest is discarded. Heavy metals are used during such processes, which also directly affects the environment.
During the social entrepreneurship MBA course, Seo collaborated with SK Chemicals, which had links through the program, and launched eco-friendly leather bags. The bags used discarded leather that was recycled by grinding and reprocessing into a biomaterial called PO3G. It was the first case in which PO3G that is over 90% biodegradable was applied to regenerated leather. In other words, it can reduce environmental pollution in the processing and disposal stages, while also reducing carbon emissions and water usage by one-tenth compared to existing cowhide products.
The social entrepreneurship MBA course, from which Moon and Seo graduated, will run in integration with the Graduate School of Green Growth as an Impact MBA program starting this year. KAIST plans to steadily foster entrepreneurs who will lead meaningful changes in the environment and society as well as economic values through innovative technologies and ideas.
< Photo 3. NYU President Emeritus John Sexton (left), who received this year's honorary doctorate of science, poses with President Kwang Hyung Lee >
Meanwhile, during this day’s commencement ceremony, KAIST also presented President Emeritus John Sexton of New York University with an honorary doctorate in science. He was recognized for laying the foundation for the cooperation between KAIST and New York University, such as promoting joint campuses.
< Photo 4. At the commencement ceremony of KAIST held on the 17th, President Kwang Hyung Lee is encouraging the graduates with his commencement address. >
President Kwang Hyung Lee emphasized in his commencement speech that, “if you can draw up the future and work hard toward your goal, the future can become a work of art that you create with your own hands,” and added, “Never stop on the journey toward your dreams, and do not give up even when you are met with failure. Failure happens to everyone, all the time. The important thing is to know 'why you failed', and to use those elements of failure as the driving force for the next try.”
2023.02.20 View 17327 -
KAIST confers Honorary Doctorate of Science on NYU President Emeritus John Edward Sexton
< Photo 1. NYU President Emeritus John Edward Sexton posing with KAIST President Kwang Hyung Lee holding the Honorary Doctorate at the KAIST Commencement Ceremony >
KAIST (President Kwang Hyung Lee) announced that it conferred an honorary doctorate of science degree on NYU President Emeritus John Edward Sexton at the Commencement Ceremony held on the 17th.
An official from KAIST explained, "KAIST is conferring an honorary doctorate for President Sexton's longstanding leadership in higher education, and for his contributions to the process of establishing the groundwork for collaboration with NYU through which KAIST is to become a leading global value-creating university."
President Emeritus Sexton served as the president of NYU from 2002 to 2015, establishing two degree-granting campuses and several global academic sites of NYU around the world. Because of its steady rise in university rankings, such as its medical school earning the number two position in the United States, not only has NYU joined the ranks of first-class universities, but it has also achieved remarkable growth, with the number of students increasing dramatically from 29,000 to 60,000.
In addition, during his tenure as president at NYU, President Emeritus Sexton successfully expanded fundraising to support the University’s academic goals. During his 14-year tenure as president, he organized initiatives such as 'Raise $1 Million Every Day' and 'Call to Action' to raise $4.9 billion in donations, the largest in NYU history to date.
President Emeritus Sexton is famous for teaching full time even during his presidential tenure and for the anecdotes about his special care for students, addressing the school members as “family”. In particular, he is famous for giving hugs to all graduates at the commencement ceremony. Minister Park Jin of the Ministry of Foreign Affairs of Korea, who graduated from NYU School of Law in 1999 with a Master of Studies in Law, is one of the graduates who received President Sexton's hug.
President Emeritus Sexton, born in 1942, visited KAIST on the 17th to receive the honorary doctorate and to encourage the expedited development of the KAIST-NYU Joint Campus, for which he helped lay the foundation.
President Emeritus Sexton said, "I like the slogan, 'Onward and upward together,'" and added, "I look forward to having the two universities achieve their shared vision of becoming the world-class universities together through cooperation to establish the KAIST-NYU Joint Campus."
< Photo 2. NYU President Emeritus John Edward Sexton giving the acceptance speech at the KAIST Commencement Ceremony >
The US Ambassador to Korea, the Honorable Philip Goldberg, also attended the commencement ceremony at KAIST to congratulate President Emeritus Sexton on the conferment of the honorary doctorate. Ambassador Goldberg has been serving as the US Ambassador to Korea since July of last year.
President Kwang Hyung Lee said, “President Emeritus Sexton was a president best described as an innovator who promoted diversity in education and pursued academic excellence throughout his life.” He went on to say, “The KAIST-NYU Joint Campus, which will be completed on the foundation laid by President Emeritus Sexton, will serve as the focal point that will attract global talents flooding into New York by the driving force created from the synergy of the two universities as well as serving as a starting point for KAIST's outstanding talents to pursue their dreams toward the world.”
KAIST signed a cooperation agreement with NYU in June of 2022 to build a joint campus, and held a presentation of signage for the KAIST-NYU Joint Campus in September. Currently, about 60 faculty members are planning to begin joint research initiatives in seven fields, including robotics, AI, brain sciences, and climate change. In addition, cooperation in the field of education, including student exchange, minors, double majors, and joint degrees, is under discussion.
2023.02.17 View 8506 -
KAIST presents a fundamental technology to remove metastatic traits from lung cancer cells
KAIST (President Kwang Hyung Lee) announced on January 30th that a research team led by Professor Kwang-Hyun Cho from the Department of Bio and Brain Engineering succeeded in using systems biology research to change the properties of carcinogenic cells in the lungs and eliminate both drug resistance and their ability to proliferate out to other areas of the body.
As the incidences of cancer increase within aging populations, cancer has become the most lethal disease threatening healthy life. Fatality rates are especially high when early detection does not happen in time and metastasis has occurred in various organs. In order to resolve this problem, a series of attempts were made to remove or lower the ability of cancer cells to spread, but they resulted in cancer cells in the intermediate state becoming more unstable and even more malignant, which created serious treatment challenges.
Professor Kwang-Hyun Cho's research team simulated various cancer cell states in the Epithelial-to-Mesenchymal Transition (EMT) of lung cancer cells, between epithelial cells without metastatic ability and mesenchymal cells with metastatic ability. A mathematical model of molecular network was established, and key regulators that could reverse the state of invasive and drug resistant mesenchymal cells back to the epithelial state were discovered through computer simulation analysis and molecular cell experiments. In particular, this process succeeded in properly reverting the mesenchymal lung cancer cells to a state where they were sensitive to chemotherapy treatment while avoiding the unstable EMT hybrid cell state in the middle process, which had remained a difficult problem.
The results of this research, in which KAIST Ph.D. student Namhee Kim, Dr. Chae Young Hwang, Researcher Taeyoung Kim, and Ph.D. student Hyunjin Kim participated, were published as an online paper in the international journal “Cancer Research” published by the American Association for Cancer Research (AACR) on January 30th. (Paper title: A cell fate reprogramming strategy reverses epithelial-to-mesenchymal transition of lung cancer cells while avoiding hybrid states)
Cells in an EMT hybrid state, which are caused by incomplete transitions during the EMT process in cancer cells, have the characteristics of both epithelial cells and mesenchymal cells, and are known to have high drug resistance and metastatic potential by acquiring high stem cell capacity. In particular, EMT is further enhanced through factors such as transforming growth factor-beta (TGF-β) secreted from the tumor microenvironment (TME) and, as a result, various cell states with high plasticity appear. Due to the complexity of EMT, it has been very difficult to completely reverse the transitional process of the mesenchymal cancer cells to an epithelial cell state in which metastatic ability and drug resistance are eliminated while avoiding the EMT hybrid cell state with high metastatic ability and drug resistance.
Professor Kwang-Hyun Cho's research team established a mathematical model of the gene regulation network that governs the complex process of EMT, and then applied large-scale computer simulation analysis and complex system network control technology to identify and verify 'p53', 'SMAD4', and 'ERK1' and 'ERK 2' (collectively ERKs) through molecular cell experiments as the three key molecular targets that can transform lung cancer cells in the mesenchymal cell state, reversed back to an epithelial cell state that no longer demonstrates the ability to metastasize, while avoiding the EMT hybrid cell state.
In particular, by analyzing the molecular regulatory mechanism of the complex EMT process at the system level, the key pathways were identified that were linked to the positive feedback that plays an important role in completely returning cancer cells to an epithelial cell state in which metastatic ability and drug resistance are removed.
This discovery is significant in that it proved that mesenchymal cells can be reverted to the state of epithelial cells under conditions where TGF-β stimulation are present, like they are in the actual environment where cancer tissue forms in the human body.
Abnormal EMT in cancer cells leads to various malignant traits such as the migration and invasion of cancer cells, changes in responsiveness to chemotherapy treatment, enhanced stem cell function, and the dissemination of cancer. In particular, the acquisition of the metastatic ability of cancer cells is a key determinant factor for the prognosis of cancer patients. The EMT reversal technology in lung cancer cells developed in this research is a new anti-cancer treatment strategy that reprograms cancer cells to eliminate their high plasticity and metastatic potential and increase their responsiveness to chemotherapy.
Professor Kwang-Hyun Cho said, "By succeeding in reversing the state of lung cancer cells that acquired high metastatic traits and resistance to drugs and reverting them to a treatable epithelial cell state with renewed sensitivity to chemotherapy, the research findings propose a new strategy for treatments that can improve the prognosis of cancer patients.”
Professor Kwang-Hyun Cho's research team was the first to present the principle of reversal treatment to revert cancer cells to normal cells, following through with the announcement of the results of their study that reverted colon cancer cells to normal colon cells in January of 2020, and also presenting successful re-programming research where the most malignant basal type breast cancer cells turned into less-malignant luminal type breast cancer cells that were treatable with hormonal therapies in January of 2022. This latest research result is the third in the development of reversal technology where lung cancer cells that had acquired metastatic traits returned to a state in which their metastatic ability was removed and drug sensitivity was enhanced.
This research was carried out with support from the Ministry of Science and ICT and the National Research Foundation of Korea's Basic Research in Science & Engineering Program for Mid-Career Researchers.
< Figure 1. Construction of the mathematical model of the regulatory network to represent the EMT phenotype based on the interaction between various molecules related to EMT.
(A) Professor Kwang-Hyun Cho's research team investigated numerous literatures and databases related to complex EMT, and based on comparative analysis of cell line data showing epithelial and mesenchymal cell conditions, they extracted key signaling pathways related to EMT and built a mathematical model of regulatory network (B) By comparing the results of computer simulation analysis and the molecular cell experiments, it was verified how well the constructed mathematical model simulated the actual cellular phenomena. >
< Figure 2. Understanding of various EMT phenotypes through large-scale computer simulation analysis and complex system network control technology.
(A) Through computer simulation analysis and experiments, Professor Kwang-Hyun Cho's research team found that complete control of EMT is impossible with single-molecule control alone. In particular, through comparison of the relative stability of attractors, it was revealed that the cell state exhibiting EMT hybrid characteristics has unstable properties. (B), (C) Based on these results, Prof. Cho’s team identified two feedbacks (positive feedback consisting of Snail-miR-34 and ZEB1-miR-200) that play an important role in avoiding the EMT hybrid state that appeared in the TGF-β-ON state. It was found through computer simulation analysis that the two feedbacks restore relatively high stability when the excavated p53 and SMAD4 are regulated. In addition, molecular cell experiments demonstrated that the expression levels of E-cad and ZEB1, which are representative phenotypic markers of EMT, changed similarly to the expression profile in the epithelial cell state, despite the TGF-β-ON state. >
< Figure 3. Complex molecular network analysis and discovery of reprogramming molecular targets for intact elimination of EMT hybrid features.
(A) Controlling the expression of p53 and SMAD4 in lung cancer cell lines was expected to overcome drug resistance, but contrary to expectations, chemotherapy responsiveness was not restored. (B) Professor Kwang-Hyun Cho's research team additionally analyzed computer simulations, genome data, and experimental results and found that high expression levels of TWIST1 and EPCAM were related to drug resistance. (C) Prof. Cho’s team identified three key molecular targets: p53, SMAD4 and ERK1 & ERK2. (D), (E) Furthermore, they identified a key pathway that plays an important role in completely reversing into epithelial cells while avoiding EMT hybrid characteristics, and confirmed through network analysis and attractor analysis that high stability of the key pathway was restored when the proposed molecular target was controlled. >
< Figure 4. Verification through experiments with lung cancer cell lines.
When p53 was activated and SMAD4 and ERK1/2 were inhibited in lung cancer cell lines, (A), (B) E-cad protein expression increased and ZEB1 protein expression decreased, and (C) mesenchymal cell status including TWIST1 and EPCAM and gene expression of markers related to stem cell potential characteristics were completely inhibited. In addition, (D) it was confirmed that resistance to chemotherapy treatment was also overcome as the cell state was reversed by the regulated target. >
< Figure 5. A schematic representation of the research results.
Prof. Cho’s research team identified key molecular regulatory pathways to avoid high plasticity formed by abnormal EMT of cancer cells and reverse it to an epithelial cell state through systems biology research. From this analysis, a reprogramming molecular target that can reverse the state of mesenchymal cells with acquired invasiveness and drug resistance to the state of epithelial cells with restored drug responsiveness was discovered.
For lung cancer cells, when a drug that enhances the expression of p53, one of the molecular targets discovered, and inhibits the expression of SMAD4 and ERK1 & ERK2 is administered, the molecular network of genes in the state of mesenchymal cells is modified, eventually eliminating metastatic ability and it is reprogrammed to turn into epithelial cells without the resistance to chemotherapy treatments. >
2023.01.30 View 16019 -
Afternoon chemotherapy proved to deliver more desirable results for female lymphoma patients
Chemotherapy is a commonly used regimen for cancer treatment, but it is also a double-edged sword. While the drugs are highly effective at killing cancer cells, they are also notorious for killing healthy cells in the body. As such, minimizing the drug’s damage to the patient’s body is necessary for improving the prognosis of chemotherapy.
Recently, “chrono-chemotherapy” have been gaining interest in the research community. As the name suggests, the aim is timing the delivery of the drugs when the body is least vulnerable to their harmful effects and while the cancer cells are at their most vulnerable.
< Figure 1. Chrono-chemotherapy considering circadian rhythm >
Chrono-chemotherapy exploits the fact that human physiological processes, including cell proliferation and differentiation, are regulated by an endogenous timer called the circadian clock. However, this has not been widely exploited in real-world clinical settings because, as of now, there is no systematic method for finding the optimal chemotherapy delivery time.
This problem was tackled by an interdisciplinary team of researchers from South Korea. They were led by principal investigators Jae Kyoung Kim (a mathematician from the Biomedical Mathematics Group, Institute for Basic Science) and Youngil Koh (an oncologist at Seoul National University Hospital). The researchers studied a group of patients suffering from diffuse large B-cell lymphoma (DLBCL).
Terminology
* Diffuse large B-cell lymphoma (DLBCL): Lymphoma is a type of blood cancer caused by the malignant transformation of lymphoid tissue cells. Lymphoma is divided into Hodgkin's lymphoma and non-Hodgkin's lymphoma (malignant lymphoma), and diffuse large B-cell lymphoma accounts for about 30 to 40% of non-Hodgkin's lymphoma.
The research team noticed that DLBCL patients at Seoul National University Hospital received chemotherapy on two different schedules, with some patients receiving morning treatment (8:30 a.m.) and others taking the drugs in the afternoon (2:30 p.m.). All patients received the same cancer treatment (R-CHOP), which is a combination of targeted therapy and chemotherapy, four to six times in the morning or afternoon at intervals of about three weeks.
They analyzed 210 patients to investigate whether there was any difference between morning and afternoon treatments. It was found that female patients who received the afternoon treatment had a 12.5 times reduced mortality rate (25% to 2%), while the cancer recurrence after 60 months decreased by 2.8 times (37% to 13%). In addition, chemotherapy side effects such as neutropenia were more common in female patients who received the morning treatment.
Surprisingly, there was no differences found in treatment efficiency depending on the treatment schedule in the cases of male patients.
To understand the cause of the gender differences, the research team analyzed upto 14,000 blood samples from the Seoul National University Hospital Health Examination Center. It was found that in females, white blood cell counts tended to decrease in the morning and increase in the afternoon. This indicates that the bone marrow proliferation rate was higher in the morning than in the afternoon because there is a upto 12 hour delay between bone marrow proliferation and blood cell production.
This means that if a female patient receives chemotherapy in the morning when bone marrow is actively producing blood cells, the possibility of adverse side effects becomes greater. These results are consistent with the findings from recent randomized clinical trials that showed female colorectal cancer patients treated with irinotecan in the morning suffered from higher drug toxicities.
One confounding variable was the drug dose. Since the morning female patients suffered from greater adverse side effects, oftentimes the dose had to be reduced for these patients. On average, the drug dose was reduced by upto 10% compared to the dose intensity given to female patients receiving the afternoon treatment.
Unlike the female patients, it was found that male patients did not show a significant difference in white blood cell count and bone marrow cell proliferation activity throughout the day, which explains why the timing of the treatment had no impact.
Professor Youngil Koh said, “We plan to verify the conclusions of this study again with a large-scale follow-up study that completely controls for the confounding variables, and to confirm whether chrono-chemotherapy has similar effects on other cancers.”
CI Jae Kyoung Kim said, “Because the time of the internal circadian clock can vary greatly depending on the individual's sleep-wake patterns, we are currently developing a technology to estimate a patient’s circadian clock from their sleep pattern. We hope that this can be used to develop an individualized anti-cancer chronotherapy schedule.”
< Figure 2. Chemotherapy in the afternoon can improve treatment outcomes. >
The daily fluctuation of proliferative activity of bone marrow is larger in females than in males, and it becomes higher in the morning (left). Thus, chemotherapy in the morning strongly inhibits proliferative activity in female lymphoma patients, resulting in a higher incidence of adverse events such as neutropenia and infections. This forced the clinicians to reduce the dose intensity (center). Consequently, female patients undergoing the morning treatment showed a lower survival probability than those undergoing the afternoon treatment (right). Specifically, only ~13% of female patients treated in the afternoon had a worse outcome and ~2% of them died while ~37% of female patients treated in the morning had a worse outcome and ~25% of them died. Male patients did not show any difference in treatment outcomes depending on the chemotherapy delivery time.
2023.01.27 View 6465