Korea University

Treatment with direct-acting antivirals improve liver-related clinical outcomes and reduce liver fibrosis in patients with Hepatitis C virus infection SEOUL, South Korea, Aug. 21, 2024 /PRNewswire/ -- HCV infection is the underlying cause for chronic Hepatitis C (CHC), liver cirrhosis, and liver cancer or hepatocellular carcinoma (HCC). In 2019, over 2,90,000 people died of HCV-related diseases. Recent medical advancement made a new breakthrough treatment available for patients with hepatitis C. DAAs that block replication of HCV has dramatically transformed the treatment approach with around 90% effective anti-viral response rates. However, it is unclear whether DAAs impact the severity of disease burden caused by liver fibrosis. Continue Reading Researchers from multiple institutions across South Korea collected individual participant data from the medical records of patients with hepatitis C virus infection, treated with direct-acting antivirals. They compared liver fibrosis, a key feature of disease severity, and liver-related clinical outcomes of untreated group with the DAA group. To answer this critical question, Associate Professor Seungbong Han from the Department of Biostatistics, Korea University College of Medicine, South Korea collaborated with his colleagues across multiple centers in South Korea to evaluate the impact of DAAs on the fibrotic disease burden in patients with chronic HCV infection. Their study was made available online on May 30, 2024 and was published in Volume 73 of the journal eClinicalMedicine on July 1, 2024. Sharing his vision, Associate Prof. Han says, "For individuals, early detection and effective treatment would mean fewer complications, better health outcomes, and enhanced quality of life. Successful strategies could serve as models for other countries with high Hepatitis C prevalence, leading to global improvement in Hepatitis C management." The team collected medical records of 11,725 patients with HCV infection from 29 institutions in South Korea. They compared individual participant data from 3,261 untreated to 8,464 patients treated with DAAs, for a follow-up period of 27.5 months. To evaluate liver disease severity and outcomes, they analyzed non-invasive reporters of liver fibrosis and stiffness, and evaluated their risk of developing liver cancer, damaged liver function, and death. They observed that DAA treatment reduced fibrotic disease burden and lowered the risk of disease progression to cancer or cirrhosis, increasing life expectancy. The differences were most prominent in age groups 40–60 years. One of the limitations of this study is the reliance on non-invasive tests for measuring liver fibrosis. "Noninvasive scores and liver stiffness, are not accurate for detecting reduced fibrosis after sustained viral response in patients with HCV infection because improvements in noninvasive tests typically reflect the expected reduction of necro-inflammation but not that of fibrosis," explains Associate Prof. Han. How important are liver biopsies for accurate assessment? Biopsy of the liver is the gold standard method to accurately measure and stage liver fibrosis. However, the risks and expertise needed to perform this challenging procedure limits repeatability. Despite the limitation, this study provides scientific evidence that use of DAA is a crucial strategy for reducing liver fibrosis-based disease burden and improving clinical outcomes. Sustainability in healthcare requires evidence-based allocation of healthcare resources. The findings from this study merits public health campaigns raising awareness about Hepatitis C and its risks that will promote nationwide screening for HCV positivity. Early intervention with advanced antiviral approaches is likely to decrease healthcare costs associated with treating advanced liver diseases like cancer or cirrhosis, freeing up resources for other critical healthcare needs. "Our study can help improve public health, healthcare systems, and individual lives by encouraging the development of early intervention and effective treatment strategies for HCV infection," concludes Associate Prof. Han. Reference Title of original paper: Effect of direct-acting antivirals on disease burden of hepatitis C virus infection in South Korea in 2007–2021: A nationwide, multicentre, retrospective cohort study Journal: eClinicalMedicine DOI: About Korea University College of Medicine Website: Media Contact: Soo-Jin Jeon +82 2 3407 4040 [email protected] SOURCE Korea University College of Medicine

New C-terminal HSP90 Inhibitor Demonstrates Efficacy Against Drug-Resistant Breast Cancer Cells SEOUL, South Korea, June 26, 2024 /PRNewswire/ -- Korean scientists have investigated HVH-2930, an innovative HSP90 inhibitor in reshaping HER2-positive breast cancer treatment. Unlike previous HSP90 inhibitors, this compound circumvents limitations by bypassing heat shock response induction. It demonstrates promising efficacy in inducing cancer cell apoptosis and effectively overcomes treatment resistance. In preclinical studies, HVH-2930 showed substantial promise, offering hope for better treatment outcomes. Its potential for diverse HER2-overexpressing malignancies indicates a paradigm shift in cancer therapy, anticipating enhanced effectiveness and increased availability. HER2-positive breast cancer, known for its aggressive nature due to the overexpression of the HER2 protein, poses significant challenges in treatment. Current standard treatments for HER2-positive breast cancer typically involve a combination of HER2-targeted therapies like trastuzumab, chemotherapy, and hormone therapy. However, the emergence of resistance highlights the need for novel approaches for improved outcomes. In this relentless pursuit of treatment solutions, a team of researchers at Korea University led by Professor Jae Hong Seo have achieved a significant milestone with the development of HVH-2930, a promising inhibitor targeting heat shock protein 90 (HSP90), the findings of which were published in Theranostics on 31 March 2024. Prof. Seo shares, "We have highlighted the pivotal role of HSP90, an oncogenic protein, in fueling tumor growth by activating key receptor tyrosine kinases, including HER2. While previous N-terminal HSP90 inhibitors faced challenges like inducing the heat shock response (HSR) and toxicity, HVH-2930, a C-terminal HSP90 inhibitor, shows promise." The study utilized both in vivo and in vitro methods to investigate HER2-positive breast cancer and potential treatments. In laboratory settings, breast cancer cells were cultured alongside normal mammary cells, using advanced cytometry techniques to assess cell viability, apoptosis, and functionality. Additionally, protein interactions were studied to uncover underlying molecular processes. In mouse models, tumor cell implantation was used to study tumor growth dynamics and treatment responses. The findings revealed that HVH-2930 effectively induced apoptosis in breast cancer cells without triggering the heat shock response (HSR), a notable feature that distinguishes it from other treatments. By selectively targeting HSP90, HVH-2930 downregulated HER2 signaling, crucial in breast cancer progression. Impressively, in xenograft mouse models, HVH-2930 inhibited tumor growth, angiogenesis, and cancer stem cell-like properties without causing toxicity. Moreover, when combined with paclitaxel, HVH-2930 exhibited a synergistic antitumor effect, suggesting its potential as a promising therapeutic strategy for HER2-positive breast cancer. These results signify a significant advancement in targeting the HSP90 chaperone machinery for breast cancer treatment. Prof. Seo shares "HVH-2930 stands as a groundbreaking advancement in meeting the critical needs of HER2-positive breast cancer patients, notably those resistant to trastuzumab. With its potential application in other HER2-overexpressing cancers like gastric and esophageal cancers, it holds promise for treating a wider range of patients. Moreover, its anticipated affordability compared to current therapies could significantly enhance accessibility, particularly in resource-limited settings such as underdeveloped countries." Reference Title of original paper: The HSP90 inhibitor HVH-2930 exhibits potent efficacy against trastuzumab-resistant HER2-positive breast cancer Journal: Theranostics DOI: About Korea University College of Medicine Website:

A team achieves successful mass production of metalenses designed for application in the ultraviolet region. Ultraviolet rays find diverse applications in medical and healthcare, serving purposes such as disinfection, sterilization, and therapy. They are also used in the semiconductor industry for creating microcircuits and patterns. A metalens fabrication process, developed by a team of researchers at Pohang University of Science and Technology (POSTECH), enables control over the optical properties of these UV rays. This innovation has garnered significant attention across industries, sparking interest in potential advancements. A collaborative research team, comprising Professor Junsuk Rho from the Department of Mechanical Engineering and the Department of Chemical Engineering and PhD candidates Joohoon Kim and Yeseul Kim from the Department of Mechanical Engineering at POSTECH, and Professor Heon Lee and Wonjoong Kim from the Department of Materials Science and Engineering at Korea University, has devised a technique for the mass production of large-area metalenses tailored for use in the ultraviolet region. The findings of their research have been published in Materials Today, an international journal in the field of materials. Metalenses control light properties through nanometer-scale patterns or structures on lens surfaces. With the ability to reduce the thickness of conventional lenses by a factor of 10,000, they hold significant promise in medical devices that are inserted in the body and wearable devices. Ongoing active research aims to achieve mass production and commercialization of metalenses. However, ultraviolet light poses challenges as it is absorbed by most materials due to its high energy level. The shorter wavelength of ultraviolet light requires more structures for the same area. Furthermore, unlike visible and infrared light, the limited availability of materials transparent to ultraviolet light complicates the production of large-area metalenses. Additionally, nanoprocessing technology constraints have resulted in most reported metalenses for ultraviolet light being smaller than 500 μm (micrometers). In prior research endeavors, the team collaborated with Dr. Gyoseon Jeon's team at the Research Institute of Industrial Science and Technology (RIST) to achieve successful mass production of metalenses for visible light as published in Nature Materials, and for infrared light as recently reported in 'Laser and Photonics Reviews'. The researchers extended their process by incorporating a zirconium oxide (ZrO2) material, transparent in the ultraviolet region, enabling the mass production of a metalense measuring 1 centimeter (cm) on a wafer. Employing a nano-imprinting process that engraves the pattern like a stamp, the team achieved the rapid and inexpensive production of metalenses that are 20,000 times larger than conventional ones. Professor Junsuk Rho who led the research expressed the team's commitment by stating, "This marks the first instance of implementing a metalens with exceptional light-modulation capabilities over a large area in the ultraviolet region." He added, "We are committed to continually improving the technology for potential applications in industrial sectors such as semiconductor inspection equipment through further research efforts." The research was conducted with support from the N.EX.T Impact Project of POSCO Holdings, and the STEAM Research Program, the RLRC Program, the Nanomaterial Technology Development Program, and the Future Material Discovery Program of the Ministry of Science and ICT.