Ground Breaking Development of World’s First CurativeTreatment of Intractable Hepatocellular Carcinoma Path to Establishment of Standard Treatment of Hepatocellular Carcinoma - Kindai University

Press releases   •   Aug 05, 2019 02:00 UTC

In a world first, the treatment has been proven to be nearly twice as effective at prolonging life as the current standard treatment, TACE (which was created in the 1970s). Further, it is an extremely effective treatment method for the disease, with the study showing just under 20% of patients experienced complete elimination of the cancer and are still living to date without any treatment. This clinical study was collaborative -research carried out between 2008 and 2018 cross-institutionally, with a total of eight -institutions (see below for details); seven domestic and one in Hong Kong. As per this announcement, these results change the face of the medical care world, with the development and establishment of a treatment for a previously incurable disease with no standard treatment.

1.Highlights of Study

- Establishment of a radical cure for multiple and/or large liver cancers - previously for which there was no standard treatment

- Pre-administration of lenvatinib followed by TACE treatment elucidated to prolong life in late phase intermediate stage liver cancer patients

- Positioned to be the new standard treatment for liver cancer which reaches the intractable stage.


Comparison of overall survival rates between LEN-TACE patients and those who only received TACE

2.Content of the Research

Hepatocellular carcinoma is the 5th leading cause of cancer deaths in Japanese people, an intractable disease which annually kills approximately 28,000 people. Hepatocellular carcinoma is divided into 5 stages: 1. Early stage liver cancer (3 nodules or less and/or 3cm or less), 2. Medium size and multiple nodules(intermediate-stage, early) 3. Large or multiple nodules throughout whole liver (intermediate-stage, advanced), 4. Advanced liver cancer (vascularinvasion, extrahepatic metastasis), 5. Terminal stage.

Surgical resection and use of radiofrequency ablation are the established treatment methods for early stage 1 liver cancer; for stage 2, TACE is the standard treatment. In stage 4 with advanced liver cancer - vascular invasion and extrahepatic metastasis - molecular targeted drugs are the standard treatment method, with clinical trials of immune checkpoint inhibitors also being extensively conducted. However, for most patients, who are in stage 3 with multiple and/or large HCCs, the effectiveness of the standard treatment, TACE, invented in the 1970’s, is limited, and many experience reoccurrences and move to advanced stage or terminal stage liver cancer. Although it is an important stage of liver cancer, until now there has been no established standard treatment. Therefore, the development of a treatment for this stage of liver cancer is an urgent task for liver cancer researchers around the world and has long been the largest theme, but it has remained an unresolved challenge until now.

In this study, the molecular targeted drug, lenvatinib, which is usually used only for advanced liver cancer, was first used as the initial therapy for this stage of liver cancer. By using this treatment, the following hypothesis was proven to be true:

1) Induces tumor shrinkage and necrosis

2) The irregular thickness (both thick and thin) of the blood vessels of the tumors are restored to the blood vessel diameter of normal blood vessels

3) Acts to uniformly distribute anti-cancer agents and embolic substances in the tumor interior added later

4) By using TACE at the time which the molecular targeted drug exerts its maximum effect, recurrence and metastasis is prevented by suppression of angiogenic factors (factors that cause tumor growth / invasive metastasis) induced by the TACE.

Further, by administering the molecular targeted drug, lenvatinib, to patients of this stage of liver cancer, and following it up by adding TACE (combined LEN-TACE sequential treatment), compared to just using TACE, life was prolonged by approximately double. In addition, it was found that the risk of death was reduced by approximately 52% (HR*4 0.48, p<0.01).

As it has been proven to prolong life, it is foreseen that this new treatment will significantly change the treatment strategy of liver cancer globally, and become the standard of care.

3. About Publication

Research paper title: Lenvatinib as an Initial Treatment in Patients with Intermediate-

stage Hepatocellular Carcinoma Beyond up-to-seven Criteria and Child-Pugh A Liver Function: A Proof-of-Concept Study

Journal name: Cancers (IF:6.162)

Co-authors: Masatoshi Kudo1, Kazuomi Ueshima1, Stephan Chan2, Tomohiro Minami 1, Hirokazu Chishina1, Tomoko Aoki1, Masahiro Takita1, Satoru Hagiwara1, Yasunori Minami1, Hiroshi Ida1, Mamoru Takenaka1, Toshiharu Sakurai1, Tomohiro Watanabe1, Masahiro Morita3, Chikara Ogawa3, Yoshiyuki Wada4, Masafumi Ikeda5, Hiroshi Ishii6, 7, Namiki Izumi8, Naoshi Nishida1

1Kindai University, Faculty of Medicine(Department of – Gastroenterology and Hepatology), 2The Chinese University of Hong Kong - Translational Oncology, 3Takamatsu Red Cross Hospital - Department of Digestive Organs, 4National Hospital Organization Kyushu Medical Center – Department of Hepatobiliary and Pancreatic Surgery, 5National Cancer Center Hospital East – Department of Hepatobiliary and Pancreatic Oncology (Internal Medicine), 6Cancer Institute Hospital – Department of Gastroenterology, 7Chiba Cancer Center – Clinical Research Center, 8Musashino Red Cross Hospital – Department of Gastroenterology

4. Details of Research

The molecular targeted drug lenvatinib has, in the 10 years to 2017, been shown to be the first drug to be non-inferior to the only standard drug, sorafenib for advanced HCC until now, in prolonging life. The details of the results of the clinical trial were published in ‘Lancet’ in 2018 (Kudo M, et al. Lancet 2018). Currently this drug is approved worldwide as the first choice of drug for advanced liver cancer, of course in Asia, but also in the Americas and Europe etc., and therefore its use is widespread. Further, lenvatinib not only showed greater effectiveness in prolonging life in advanced liver cancer patients, but also excelled for tumor reduction and necrosis; objective response rate (ORR*5) was 40.6%, indicating excellent effectiveness as an anti-tumor agent. Conversely, TACE, the standard treatment for intermediate-stage liver cancer just before the advanced stage (multiple nodules/large-sized cancers without vascular invasion/extrahepatic metastasis) has poor effectiveness, with reoccurrence of cancers leading to liver function worsening and accelerating death; many cases of patients becoming terminally ill or progressing to more advanced stages of liver cancer even after treatment with TACE have been seen. This stage of the disease can be said to be an illness that causes suffering worldwide, with no standard treatment, it is an incurable cancer.

Prof. Kudo and his team focused on the superior tumor reduction and necrosis effectiveness of lenvatinib. Lenvatinib was purposely pre-administered before TACE treatment at the stage of multiple nodules/large-sized cancers, without the presence of vascular invasion/extrahepatic metastasis, and then TACE was performed. The hypothesis that pre-administration of lenvatinib, followed by TACE, (LEN-TACE sequential treatment), would enhance the effectiveness of the TACE was stated. At the time there were few researchers around the world with such a hypothesis. To verify this hypothesis, between 2008 and 2018, the research team analyzed 37 patients at this stage of liver cancer, administering lenvatinib as an initial treatment. The methodology used was a comparison of the treatment effectiveness with 139 patients who had TACE carried out during the same period. Further, the results of propensity score matching*6, a statistical method to unify the backgrounds of patients was used; 30 cases of lenvatinib pre-administration followed by TACE and 60 cases of only TACE therapy were extracted, with comparisons made between objective response rate (ORR), progression of liver function deterioration (ALBI score*7), progression-free survival (PFS*8), and overall survival (OS*9).

The results showed the group who were pre-administered lenvatinib had a much higher ORR of 73.3%, compared to 33.3% for the group who had only TACE (Odds ratio 5.29, <0.001), deterioration of liver function was also significantly lower (p<0.01), further, PFS was dramatically better in the lenvatinib pre-administered group (16mths vs 3mths, hazard ratio 0.19, p<0.001). In addition, there were four patients in the lenvatinib pre-administration group that experienced complete disappearance of all cancers and were completely cured, with follow up observations showing they were healthy with no treatment. Therefore, this treatment is considered to be a groundbreaking new cure, even for some advanced liver cancers (multiple nodules/large sized cancers). These results mark the announcement of the development of a ground-breaking world first, and will change medical treatment strategy globally by providing a treatment where no prior standard existed.

5. Glossary

*1 Molecular target drug

Different from previous anticancer drugs that also cause harm to normal functioning cells, molecular targeted drugs are drugs that only target the specific molecules that are involved in proliferation of cancer cells and suppress their activity. In the case of liver cancer, approved medicines include the following four: lenvatinib (Lenvima), sorafenib (Nexavar), regorafenib (Stivarga) and ramucirumab (Cyramza).

*2 Transcatheter arterial embolization therapy (TACE)

The liver gains nourishment through two blood vessels; the hepatic artery and the portal vein. As liver cancer cells gain nutrition and 100% of their oxygen from the hepatic artery, TACE is a method of using a catheter to completely block the hepatic artery, thus killing the cancer cells. If the size or number of cancers is small, this method is effective, but if the cancer size is large or numerous, the disadvantages of this method are, as well as it being difficult to have the catheter close to the tumor, it also to an extent kills the surrounding normally-functioning cells, decreasing liver function.

*3 Immune checkpoint inhibitor

When cancer forms in a living organism, lymphocytes should be activated to attack the cancer cells to try to kill them. However, when this reaction occurs, cancer cells release a molecule called PD-L1, and by binding this molecule to the PD-1 on the surface of lymphocytes, they are able to evade immune cell attack, successively proliferate and spread to and invade other locations. When antibodies that bind to PD-1 or PD-L1 are administered, the cancer cells’ avoidance mechanism (against the immune response) is blocked, and lymphocytes can again attack the cancer cells. This mechanism was discovered by Prof. Honjo of Kyoto University in 2018 and he was awarded a Nobel Prize in the field of Physiology or Medicine.

*4 Hazard Ratio

“Hazard Ratio” is a term used in statistics, it is used to describe a method used to objectively compare the relative degree of risk in clinical trials. It can be abbreviated to HR.

When investigating a new treatment, HR is used to compare it to the standard treatment. A hazard ratio of 1 shows that the two treatment methods are not different. Less than 1 shows that the new treatment is more effective than the standard treatment, with the lower the number showing greater effectiveness. For example, if a clinical study comparing the effectiveness of medicine A to medicine B results in 0.94, medicine A is deemed to have reduced the risk by 6% compared to medicine B. The HR of OS in this clinical study was 0.48, therefore it can be stated that the new treatment method reduces the risk by 52% of death.

*5 Objective Response Rate (ORR)

A commonly used standard indicator to evaluate the results of treatment using anticancer drugs, by comparing the size of the tumor before and after treatment. Tumor reduction (or necrosis of tumor) of 30% or more is deemed to be ‘partial response’ (PR), and 100% complete disappearance or complete necrosis of the tumor is called ‘complete response’ (CR). The efficacy is measured by adding the CR and PR of the whole mass, with a higher number corresponding to greater efficacy.

*6 Propensity score matching

A method of statistically proving clinical usefulness. In order to prove that hypothesis (e.g. A treatment method is better than the standard one) is of the highest importance, a prospective randomized control trial (RCT) is the method with the highest level of evidence. However, the method with the next highest level of evidence is this one, created in 1983. That is, it is a statistical analysis method recommended in recent years as a so-called “method for eliminating selection bias” by making uniform the extraneous factors related to the survival to both groups.

*7 ALBI score (Albumin-Bilirubin score)

Conventionally, Child-Pugh Classification and Child-Pugh Score have been used as indicators of hepatic functional reserve. ALBI Score is a more accurate and objective indicator than Child-Pugh Classification as it is calculated using only albumin and bilirubin. In recentyears, ALBI Score has become more commonly used than Child-Pugh Score. It has also been adopted into the protocols of the Liver Cancer Study Group of Japan. Although the calculations are complex, most hospitals have adopted systems that automatically calculate the value and display them to electronic medical records, making the process extremely simple.

*8 Progression-free survival (PFS)

A commonly used indicator used for the evaluation of the results of treatments of anticancer drugs. It is defined as the period from beginning a study or treatment start date to confirmation of disease progression or death. Often the median is used as the representative figure.

*9 Overall Survival (OS)

A commonly used indicator used for the evaluation of the results of treatments of anticancer drugs. It is defined as the time from the registration date of the study or treatment start date of the target patient, to confirmation of death. Often the median is used as the representative figure.

Senior Administrator Masatoshi Kudo of Kindai University Faculty of Medicine, Department of Gastroenterology and Hepatology, with his research group has invented a new method (LEN-TACE) of treating patients with intractable multinodular or large liver cancers, particularly those with near advanced liver cancer.

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Mechanism Behind Onset of Autoimmune Pancreatitis Caused by Changes in Intestinal Flora Elucidated Development of New Treatment Methods Expected - Kindai University

Press releases   •   Jul 10, 2019 01:00 UTC

Kindai University have discovered, for the first time in the world, a deep link between changes in the maintained balance of accumulated co-existing intestinal flora (bacteria) and immune responses in patients with chronic disease of the pancreas caused by autoimmune pancreatitis. This paper will be published online at midnight Japan time, July 10th, 2019, in “International Immunology”.

Successful Construction of Artificial Cell Nuclei Inside of Fertilized Egg; A World First One Part of the Cell Nuclei Structure Formation Mechanism Elucidated - Kindai University

Press releases   •   Jun 13, 2019 05:50 UTC

A Research group comprised of Kindai University’s Faculty of Biology-oriented Science and Technology , the National Institute of Information and Communications Technology and Osaka University have focused their attention on the building blocks of life, DNA, and in a world first, the group has artificially created cell nuclei structures in living mouse fertilized eggs.

Cell nuclei of 28,000-years-old mammoth reacted in living embryos by cloning technology

Press releases   •   Mar 12, 2019 02:03 UTC

-We have succeeded in observing the reconstruction of cell nuclei collected from mammoth fossils inside living mouse oocytes. -Mammoth’s cell nuclei were found to have retained biological activity for 28,000 years in permafrost. -This study paves a way for decoding old biological information using cell nuclei of ancient creatures and future leaps of evolutionary biology are expected.

Prospects and Possibilities for Japan’s 2019 G20 Osaka Summit - Soka University

Press releases   •   Dec 03, 2018 00:30 UTC

This international conference will contribute to the start of Japan's Presidency of the Group of Twenty (G20). It will bring together G20 government officials, scholars, and key stakeholders to discuss and contribute to the agenda for Japan's host presidency. This will include a focus on the plans and prospects for Japan's Osaka G20 Summit on June 28-29, 2019. The panels and speakers will debate important G20 issues, on themes such as the global economy, gender, sustainable development, and climate change, at a time of rising protectionism, populism, and geopolitical risks. There are growing concerns about the effectiveness and legitimacy of the G20 and global governance, linked to power shifts, intensifying vulnerabilities, and insecurities. The Soka University Peace Research Institute and partner institutions from Australia, Canada, and Russia have convened this one-day conference to address these issues, constructively engaging and contributing to Japan's G20 Presidency agenda.

[Research theme of the speakers]
1) G20 Governance
2) Japan's Plans for the Osaka Summit
3) G20 and Global Economic Governance
4) G20 and Global Gender Governance
5) G20 Climate, Energy and Sustainability Governance
6) Possibilities and Prescriptions for Osaka 2019: A Panel

[Event Details]
- Date and Time
Monday December 10th 8:45~18:05
*Sign in will be located at Soka University Global Square 1F

- Venue
Soka University Global Square (1-236 Tangi-machi, Hachioji City, Tokyo; 15 minutes by bus from JR Hachioji station)

- Program
* Welcome: 9:15-9:30
* G20 Governance: 9:30-10:30
* Japan's Plans for the Osaka Summit: 10:45-11:30
* G20 and Global Economic Governance: 11:30-12:45
* G20 and Global Gender Governance: 2:00-3:15
* G20 Climate, Energy and Sustainability Governance: 3:15-4:30
* Possibilities and Prescriptions for Osaka 2019: A Panel: 4:45-5:55
* Closing Remarks: 5:55-6:05

- Participants
Researchers from universities and research institutes, senior diplomats and government officials, representatives of official G20 Engagement Groups(Application in advance)

- Language
English

- Sponsored by
Soka University Peace Research Institute; G20 Research Group, University of Toronto; Griffith Asia Institute, Griffith University; and Russian Presidential Academy of National Economy and Public Administration

If you wish to cover the conference, please contact Soka University Public Relations Department by Wednesday December 5th through email (publicrelation@soka.ac.jp)

There are growing concerns about the effectiveness and legitimacy of the G20 and global governance. The Soka University Peace Research Institute and partner institutions from Australia, Canada, and Russia have convened this one-day conference to address these issues, constructively engaging and contributing to Japan’s G20 Presidency agenda.

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Immuno-pathogenesis of Chronic Pancreatic Diseases Uncovered Applications expected for the treatment of pancreatic diseases and preventive measures for pancreatic cancer - Kindai University

Press releases   •   Oct 25, 2018 16:00 UTC

Associate Professor Tomohiro Watanabe's research group of Clinical Internal Medicine (Gastroenterology) at the Faculty of Medicine of Kindai University (Osakasayama City, Osaka Prefecture) unraveled a part of the pathogenic immune response that is common to two different chronic pancreatic diseases, namely autoimmune pancreatitis and chronic pancreatitis. The results of this study are expected to be applied to the development of new treatments of pancreatic diseases and for the prevention of pancreatic cancer.

A paper relating to this study will be featured by the online edition of "Trends in Immunology", a United States-based scientific journal issued by Cell Press - the publisher of "Cell", a journal primarily focused on life sciences. The feature will begin 1:00 AM (JST) on October 26th, 2018 (Fri).

[Key aspects of this study]
- Until now, the barely understood immuno-pathogenesis for chronic inflammation of the pancreas has been uncovered.
- The pathogenic immune response that is common for both autoimmune pancreatitis and chronic pancreatitis was elucidated for the first time in the world.
- Applications are expected for new treatments of chronic pancreatic inflammation and new preventive measures for pancreatic cancer.

[Overview of the study]
Chronic inflammatory diseases of the pancreas can be largely categorized into two groups; autoimmune pancreatitis and chronic pancreatitis.

Autoimmune pancreatitis is thought to be triggered by the erroneous attack of pancreatic tissues in one's own body by the immune system. Many such instances are considered to be pancreatic manifestation of systemic IgG4-related diseases (*1), which are recognized as intractable diseases and are associated with concurrence of pancreatic, and various other types of cancer.

Chronic pancreatitis is a disease that arises from prolonged inflammation of the pancreas due to excessive intake of alcohol, which leads to loss of pancreatic functions as the condition progresses and involves a variety of symptoms, such as diarrhea, abdominal pain, malabsorption, and diabetes. The presence of chronic pancreatitis increases the incidence of pancreatic cancer. As immuno-pathogenesis has not been fully understood, definitive treatments for these two diseases have not existed.

The research group led by Watanabe discovered that the immuno-pathogenesis of these two different diseases involved two types of cytokines (*2), which are secreted by cells. One of these is type I Interferon (IFN) (*3) and the other is the Interleukin 33 (IL-33) (*4).

Unraveling the immuno-pathogenesis of autoimmune pancreatitis and chronic pancreatitis not only leads to the establishment of new treatments for patients suffering from chronic inflammation of the pancreas, but it can also potentially pave the way for the development of preventive measures of pancreatic cancer.

[Details of this study]
Name of journal: "Trends in Immunology", a scientific journal in the United States published by Cell Press, the publisher of "Cell", which is a journal primarily for the field of life science (impact factor: 14.188).

Research paper title: Mechanistic Insights into Autoimmune Pancreatitis and IgG4-Related Disease

Authors: Tomohiro Watanabe, Kosuke Minaga, Ken Kamata, Masatoshi Kudo and Warren Strober.

[Details of this study]
The research group led by Watanabe, in their search for the immuno-pathogenesis of autoimmune pancreatitis and chronic pancreatitis, discovered that two types of cytokines, type I IFN and IL-33, are involved in the development of two different types of diseases. Cells producing both type I IFN and IL-33 are different from each other, in that type I IFN and IL-33 are produced by the plasmacytoid dendritic cells (*5) in case of autoimmune pancreatitis, while type I IFN and IL-33 are produced by the pancreatic acinar cells (*6) in the case of chronic pancreatitis.

[Expectations for the future]
Animal experiments as well as observations of human patients revealed that autoimmune pancreatitis and chronic pancreatitis share the abnormal immune responses, excessive production of type I IFN and IL-33. The cells that produce type I IFN and IL-33 for these two diseases, on the other hand, are fundamentally different. In cases of the autoimmune pancreatitis, plasmacytoid dendritic cells produce type I IFN and IL-33, while the pancreatic acinar cells produce type I IFN and IL-33 to trigger chronic pancreatitis. It is hoped in the future that the mechanisms accounting for the findings that different cells producing the two cytokines (type I IFN and IL-33) lead to the development of different diseases can be elucidated. From the perspective of applications for patients, there are expectations for the effectiveness of a drug that can inhibit the actions of type I IFN and IL-33 for both autoimmune pancreatitis and chronic pancreatitis.

[Notes on research paper]
The research group led by Watanabe has been trying for last ten years to uncover the immuno-pathogenesis of autoimmune pancreatitis and chronic pancreatitis. The results of their study at various stages were presented in a number of scientific journals. The research paper presented this time will be featured in "Trends in Immunology" as a review article for the results of the study. This research paper is the fruit of a joint study conducted with Dr. Warren Strober, a Senior Investigator of Mucosal Immunity at the National Institute of Health in the United States.
Results of the study so far are introduced on the next page.

First of all, this research group demonstrated that type I IFN and IL-33 produced by the plasmacytoid dendritic cells are essential for the onset of the autoimmune pancreatitis, based on their study that used model animals (Figure A). The development of the autoimmune pancreatitis can be prevented by administering antibodies that reduce the number of plasmacytoid dendritic cells, as well as those that suppress signals from type I IFN and IL-33. Furthermore, pancreatic localization of the plasmacytoid dendritic cells producing both the type I IFN and the IL-33 has been confirmed in patients suffering from autoimmune pancreatitis. These series of findings were published in "Journal of Immunology 2015: 195:3033-44" and "Journal of Immunology 2017: 198:3886-96".

The research group also demonstrated that the type I IFN and IL-33 produced by pancreatic acinar cells were essential for the development of chronic pancreatitis, by using model animals for pancreatitis they have established (Figure B). This was demonstrated by an experiment that involved mice deficient in type I IFN-mediated signaling pathways and an experiment that involved the use of antibodies inhibiting IL-33-mediated signaling pathways. Furthermore, pancreatic localization of the acinar cells producing the IL-33 was confirmed in the patients suffering from chronic pancreatitis. These series of findings were published in "Immunity 2012;37:326-38", "Mucosal Immunology 2016;9:1234-49" and "Mucosal Immunology 2017;10:283-298".

These studies directed the research group led by Watanabe to the discovery that the production of the type I IFN and the IL-33 by the plasmacytoid dendritic cells leads to the development of the autoimmune pancreatitis, while the production of the type I IFN and the IL-33 by the pancreatic acinar cells leads to the development of the chronic pancreatitis.

[Glossary of terms]
*1: IgG4 related diseases: An autoimmune disease that is chracterized by increase of IgG4, which is one of antibodies. Such diseases trigger multiple organ injury including pancreas, salivary glands, lungs, kidneys and a variety of other organs. This is a new disease entity proposed by researchers in Japan and is currently attracting much attention.

*2: Cytokines: Proteins secreted by cells. It is one of factors that determine immune responses.
Excessive secretion of cytokines can trigger autoimmune diseases.

*3: type I IFN: One of cytokines. It is produced upon exposure to microbial infections, particularly virus infections and plays an important role in host defense against microbial infections. Production in large amounts without presence of infection, on the other hand, triggers autoimmune diseases, represented by systemic lupus erythematosus.

*4: IL-33: A cytokine . It plays an important role for inflammations, allergies and fibrosis of tissues.

*5: Plasmacytoid dendritic cell: A type of immune cells; a dendritic cell with the ability to produce a large amount of type I interferons (IFN).

*6: Pancreatic acinar cell: A type of cell in the pancreas that secrets digestive enzymes necessary for digestion and absorption in gastrointestinal tracts.

Until now, the barely understood immuno-pathogenesis for chronic inflammation of the pancreas has been uncovered. The pathogenic immune response that is common for both autoimmune pancreatitis and chronic pancreatitis was elucidated for the first time in the world. Applications are expected for new treatments of chronic pancreatic inflammation and new preventive measures for pancreatic cancer.

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Permeation Mechanism of Water through Polymeric Membrane; Clarified for the First Time in the World Expectations for Development of Membranes with Functions, Such As Seawater Desalination - Kindai University

Press releases   •   Oct 14, 2018 23:00 UTC

Associate Professor Noriyoshi Arai and his research group at the Mechanical Engineering Department at the Faculty of Science and Engineering of Kindai University have elucidated the mechanism of permeation through polymeric membranes. The findings of this research will be featured in the Journal of Membrane Science , on October 15, 2018 at 8:00 AM (JST).

Successful Use of AI Technology for Efficient Prediction of Physical Properties of Substances with Complex Molecular Structures

Press releases   •   Sep 14, 2018 23:00 UTC

- The study demonstrated that machine learning can be applied to predict physical properties of functional materials that have complex structures. - For the first time in the world, machine learning methodology has been applied to the analysis of complex molecular structures of surfactants that are used in our immediate surroundings, such as detergents and cosmetic products.

Luminol reaction for fecal occult blood -New application of a forensic blood detection method-

Press releases   •   Aug 24, 2018 14:00 UTC

  Bleeding in the digestive system occurs when patients have ulcers, inflammation and cancers. Therefore, an early sign of such diseases may be microscopic blood in stool, which doctors refer to as “fecal occult blood” (FOB). The luminol reaction, which has been used in forensics to detect trace amounts of concealed blood, can also be applied for detection of FOB, according to Kindai University researchers, led by Ah-Mee Park, Ph.D, Associate Professor in the Department of Microbiology, Faculty of Medicine.

Key Points
1.Experiments have shown that the luminol reaction can be used to detect FOB in animals.
2.This is the first standard method to detect FOB in animal models for ulcers and cancers in the digestive system - which is simple, quick, economical and quantitative - making it applicable to use for any research laboratories.
3.It is hoped these findings will contribute to the furthering of research on gastric ulcers and colon cancer.

Overview
  FOB, or microscopic blood in the stool, is a sign of gastrointestinal diseases, such as intestinal ulcers and colon cancers. To discover the precise cause and new treatments for such diseases requires animal models, in which the levels of FOB are measured to assess the severity of gastrointestinal bleeding. Unlike in clinical human stool samples, however, there is no standard method to detect FOB in experimental animals.
Kindai University researchers present a simple method to detect FOB in mice, using the luminol reaction, which has been used to detect bloodstains at crime scenes, like those often seen in detective stories and TV shows. By mixing feces with a luminol solution, hemoglobin-containing fecal samples produce visible blue light (chemiluminescence). The levels of FOB are measured by the hemoglobin content; a higher content corresponding to a higher brightness level of the chemiluminescence - as measured by a luminometer. This method is simple, quick, economical, and quantitative, allowing researchers to detect FOB in experimental animals. The application of the luminol reaction in clinical medicine is expected to contribute to furthering disease research.

Journal
  Ah-Mee Park and Ikuo Tsunoda, “Forensic luminol reaction for detecting fecal occult blood in experimental mice” is published in the British scientific journal, BioTechniques, August 2018(Impact factor 2.030)

Details of the research
  Bloody stool samples were collected from mice with intestinal ulcers, which were induced by injection of indomethacin, a non-steroidal anti-inflammatory drug. Fecal samples were mixed with a luminol solution and observed in dark field. The blue chemiluminescence became detectable 4 hours after the injection, and the intensity of the chemiluminescence was measured by a luminometer. The levels of FOB were calculated by the ratios of the chemiluminescence intensities of fecal samples to the chemiluminescence intensity of a luminol solution alone.

Background
  To detect FOB in human stool, there are two standard methods; the stool guaiac test and the hemoglobin antibody immunochemical test. The guaiac test using the colorimetric method is easy to operate, but lacks quantification and can be affected by other factors. On the contrary, the immunochemical test is expensive, but allows quantification of the hemoglobin content, is specifically for hemoglobin and is not affected by other factors. On the other hand, for experimental animal studies, researchers often assess the FOB levels by stool color and appearance since there is no standard method to detect and quantify FOB in animals.

Outlook for the future
  Since this FOB detection method is simple, quick, economical, and quantitative, most researchers in the field of gastrointestinal diseases can use it easily in their laboratories as a gold standard method, allowing for more precise assessment of their experimental results, as well as comparison of reports between different laboratories and scientific articles. The limitations of the luminol reaction applying to human stool samples include several factors that affect the reaction, for example, food or bleach. Nevertheless, this discovery will help advance the field of research in gastrointestinal diseases.

Profiles of Researchers
Name: Ah-Mee Park, Ph.D.
Affiliation: Dept. Microbiology, Kindai University Faculty of Medicine
Specialty: Microbiology, Free radicals
Awards:
  Metropolitan DC Thoracic Society Annual Meeting: First Prize
  Annual Meeting of American Thoracic Society: Travel Award

1.Experiments have shown that the luminol reaction can be used to detect FOB in animals. 2.This is the first standard method to detect FOB in animal models for ulcers and cancers in the digestive system - which is simple, quick, economical and quantitative - making it applicable to use for any research laboratories.

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Japanese High School Students Set the World as the Stage Proposing a Project for Contributing to Society -Entrepreneurship World Competition-

Press releases   •   Aug 09, 2018 05:30 UTC

Summary
[Time and Date] August 8th - August 14th
[Location] Durban, South Africa
[Sponsored] SAGE Global
[Participated Countries] USA, Ukraine, Canada, Chile, China, India, Iran, Ireland, Nigeria, Korea, Russia, Pakistan, Australia, Japan, etc. Around 30 countries and regions

A domestic event held in March (sponsored by SAGE JAPAN CUP・Tokyo Metropolitan Government Board of Education etc.) the first place team H.O.P.E from Tokyo Metropolitan Kokusai High School will participate in the Sage World Cup held in South Africa.

SAGE was established in the United States of America in 2002, and this year will the 16th year of the World Cup and high school teams from around 30 countries and regions will participate this year. Japan will send a high school team for the third straight year. Two years ago at the Philippines World Cup, Tokyo Metropolitan Ryogoku High School represented Japan and last year at the Ukraine World Cup, Yokohama Science Frontier High School represented Japan. This year, Tokyo Metropolitan Kokusai High School will challenge themselves to make a presentation, aiming to claim the top prize.

During the World Cup, high schools from each country will participate in culture exchanges.

<Contact in regard to the event>
Professor Takeshi Miyazaki, Soka University: Iwaki
Phone: 042-691-4099
Email: sageglobal.japan@gmail.com
HP: http://sagejapan.jp
*For more information please visit the homepage

[Time and Date] August 8th - August 14th [Location] Durban, South Africa [Sponsored] SAGE Global [Participated Countries] USA, Ukraine, Canada, Chile, China, India, Iran, Ireland, Nigeria, Korea, Russia, Pakistan, Australia, Japan, etc. Around 30 countries and regions

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