15 results on '"Dan, Yock Young"'
Search Results
2. Global Prevalence and Clinical Characteristics of Metabolic-associated Fatty Liver Disease: A Meta-Analysis and Systematic Review of 10 739 607 Individuals
- Author
-
Chan, Kai En, Koh, Tiffany Jia Ling, Tang, Ansel Shao Pin, Quek, Jingxuan, Yong, Jie Ning, Tay, Phoebe, Tan, Darren Jun Hao, Lim, Wen Hui, Lin, Snow Yunni, Huang, Daniel, Chan, Mark, Khoo, Chin Meng, Chew, Nicholas W S, Kaewdech, Apichat, Chamroonkul, Naichaya, Dan, Yock Young, Noureddin, Mazen, Muthiah, Mark, Eslam, Mohammed, and Ng, Cheng Han
- Published
- 2022
- Full Text
- View/download PDF
3. Pan-cancer pervasive upregulation of 3′ UTR splicing drives tumourigenesis
- Author
-
Chan, Jia Jia, Zhang, Bin, Chew, Xiao Hong, Salhi, Adil, Kwok, Zhi Hao, Lim, Chun You, Desi, Ng, Subramaniam, Nagavidya, Siemens, Angela, Kinanti, Tyas, Ong, Shane, Sanchez-Mejias, Avencia, Ly, Phuong Thao, An, Omer, Sundar, Raghav, Fan, Xiaonan, Wang, Shi, Siew, Bei En, Lee, Kuok Chung, Chong, Choon Seng, Lieske, Bettina, Cheong, Wai-Kit, Goh, Yufen, Fam, Wee Nih, Ooi, Melissa G., Koh, Bryan T. H., Iyer, Shridhar Ganpathi, Ling, Wen Huan, Chen, Jianbin, Yoong, Boon-Koon, Chanwat, Rawisak, Bonney, Glenn Kunnath, Goh, Brian K. P., Zhai, Weiwei, Fullwood, Melissa J., Wang, Wilson, Tan, Ker-Kan, Chng, Wee Joo, Dan, Yock Young, Pitt, Jason J., Roca, Xavier, Guccione, Ernesto, Vardy, Leah A., Chen, Leilei, Gao, Xin, Chow, Pierce K. H., Yang, Henry, and Tay, Yvonne
- Abstract
Most mammalian genes generate messenger RNAs with variable untranslated regions (UTRs) that are important post-transcriptional regulators. In cancer, shortening at 3′ UTR ends via alternative polyadenylation can activate oncogenes. However, internal 3′ UTR splicing remains poorly understood as splicing studies have traditionally focused on protein-coding alterations. Here we systematically map the pan-cancer landscape of 3′ UTR splicing and present this in SpUR (http://www.cbrc.kaust.edu.sa/spur/home/). 3′ UTR splicing is widespread, upregulated in cancers, correlated with poor prognosis and more prevalent in oncogenes. We show that antisense oligonucleotide-mediated inhibition of 3′ UTR splicing efficiently reduces oncogene expression and impedes tumour progression. Notably, CTNNB13′ UTR splicing is the most consistently dysregulated event across cancers. We validate its upregulation in hepatocellular carcinoma and colon adenocarcinoma, and show that the spliced 3′ UTR variant is the predominant contributor to its oncogenic functions. Overall, our study highlights the importance of 3′ UTR splicing in cancer and may launch new avenues for RNA-based anti-cancer therapeutics.
- Published
- 2022
- Full Text
- View/download PDF
4. Clinical Service Incorporating Mobile Technology on Weight Loss in Patients With Metabolic Dysfunction–Associated Steatotic Liver Disease: A Translation From Research Trial
- Author
-
Ang, Siew Min, Lim, Su Lin, Dan, Yock Young, Chan, Yiong Huak, Yap, Qai Ven, and Chen, Juliana
- Abstract
The prevalence and healthcare cost of metabolic dysfunction–associated steatotic liver disease (MASLD) has increased alongside the epidemic surge in obesity and Type 2 diabetes. Weight loss through lifestyle modification remains the primary effective therapy for MASLD. Incorporation of mobile technology in lifestyle interventions has been previously found to be efficacious and cost‐effective in facilitating weight loss. However, there is a paucity of studies that have successfully translated lifestyle research into clinical service for weight loss to alleviate disease burden. Our study aimed to describe the process of translating a mobile technology–enabled trial into a tertiary hospital outpatient dietetics service for patients with MASLD. The Iowa Model of Evidence‐Based Practice to Improve Quality Care was used as a framework for this paper to guide implementation at the organizational level. Regular engagement of key operational staff and the hospital management team facilitated open discussions of the challenges faced and enabled rapid implementation of strategies that contributed to the smooth piloting of the service. A service adoption rate of 81% was achieved. Preliminary outcome evaluation found that the percentage of patients achieving ≥ 5% weight loss from baseline at 6 months was comparable at 54% and 52% for the service and trial groups, respectively. Evaluation of the implementation process found that a hybrid model of care (in‐person consultation supplemented with app coaching) preserved interpersonal connections while maximizing the convenience and scalability of mobile app–enabled service. Although high digital acceptance and adoption rates propelled by COVID‐19‐supported telehealth, it is prudent to assess patient's access to technology and digital literacy and offer resources to help them benefit from telehealth services. Adapted version of the Iowa Model of Evidence‐Based Practice to Improve Quality Care framework, illustrating the process of successfully translating a mobile technology–enabled research trial into a clinical dietetic service for patients with metabolic dysfunction–associated steatotic liver disease.
- Published
- 2024
- Full Text
- View/download PDF
5. Trial watch: immunotherapeutic strategies on the horizon for hepatocellular carcinoma
- Author
-
Koh, Benjamin, Tan, Darren Jun Hao, Lim, Wen Hui, Wong, Jeffrey S L, Ng, Cheng Han, Chan, Kai En, Wang, Meng, Yong, Wei Peng, Dan, Yock Young, Wang, Louis Z, Tan, Nigel, Muthiah, Mark, Kow, Alfred, Syn, Nicholas L., Huang, Daniel Q., and Yau, Thomas
- Abstract
ABSTRACTThe use of immune checkpoint inhibitors (ICIs) targeting PD-L1/PD-1 and CTLA-4 has transformed the oncology practice of hepatocellular carcinoma. However, only 25–30% of the patients with advanced HCC treated with atezolizumab-bevacizumab or tremelimumab-durvalumab (STRIDE) respond initially, and mechanistic biomarkers and novel treatment strategies are urgently needed for patients who present with or acquire resistance to first-line ICI-based therapies. The recent approval of the STRIDE regimen has also engendered new questions, such as patient selection factors (e.g. portal hypertension and history of variceal bleed) and biomarkers, and the optimal combination and sequencing of ICI-based regimens. Triumphs in the setting of advanced HCC have also galvanized considerable interest in the broader application of ICIs to early- and intermediate-stage diseases, including clinical combination of ICIs with locoregional therapies. Among these clinical contexts, the role of ICIs in liver transplantation – which is a potentially curative strategy unique to HCC management – as a bridge to liver transplant in potential candidates or in the setting of post-transplant recurrence, warrants investigation in view of the notable theoretical risk of allograft rejection. In this review, we summarize and chart the landscape of seminal immuno-oncology trials in HCC and envision future clinical developments.
- Published
- 2023
- Full Text
- View/download PDF
6. Development of a new patient-derived xenograft humanised mouse model to study human-specific tumour microenvironment and immunotherapy
- Author
-
Zhao, Yue, Shuen, Timothy Wai Ho, Toh, Tan Boon, Chan, Xue Ying, Liu, Min, Tan, Sue Yee, Fan, Yong, Yang, Hechuan, Lyer, Shridhar Ganpathi, Bonney, Glenn Kunnath, Loh, Eva, Chang, Kenneth Tou En, Tan, Thiam Chye, Zhai, Weiwei, Chan, Jerry Kok Yen, Chow, Edward Kai-Hua, Chee, Cheng Ean, Lee, Guan Huei, Dan, Yock Young, Chow, Pierce Kah-Hoe, Toh, Han Chong, Lim, Seng Gee, and Chen, Qingfeng
- Abstract
ObjectiveAs the current therapeutic strategies for human hepatocellular carcinoma (HCC) have been proven to have limited effectiveness, immunotherapy becomes a compelling way to tackle the disease. We aim to provide humanised mouse (humice) models for the understanding of the interaction between human cancer and immune system, particularly for human-specific drug testing.DesignPatient-derived xenograft tumours are established with type I human leucocyte antigen matched human immune system in NOD-scid Il2rg−/−(NSG) mice. The longitudinal changes of the tumour and immune responses as well as the efficacy of immune checkpoint inhibitors are investigated.ResultsSimilar to the clinical outcomes, the human immune system in our model is educated by the tumour and exhibits exhaustion phenotypes such as a significant declination of leucocyte numbers, upregulation of exhaustion markers and decreased the production of human proinflammatory cytokines. Notably, cytotoxic immune cells decreased more rapidly compared with other cell types. Tumour infiltrated T cells have much higher expression of exhaustion markers and lower cytokine production compared with peripheral T cells. In addition, tumour-associated macrophages and myeloid-derived suppressor cells are found to be highly enriched in the tumour microenvironment. Interestingly, the tumour also changes gene expression profiles in response to immune responses by upregulating immune checkpoint ligands. Most importantly, in contrast to the NSG model, our model demonstrates both therapeutic and side effects of immune checkpoint inhibitors pembrolizumab and ipilimumab.ConclusionsOur work provides a model for immune-oncology study and a useful parallel-to-human platform for anti-HCC drug testing, especially immunotherapy.
- Published
- 2018
- Full Text
- View/download PDF
7. Long‐Term Fate of Human Fetal Liver Progenitor Cells Transplanted in Injured Mouse Livers
- Author
-
Irudayaswamy, Antony, Muthiah, Mark, Zhou, Lei, Hung, Hau, Jumat, Nur Halisah Bte, Haque, Jamil, Teoh, Narcissus, Farrell, Geoffrey, Riehle, Kimberly J., Lin, Jaymie Siqi, Su, Lin Lin, Chan, Jerry Ky, Choolani, Mahesh, Wong, Peng Cheang, Wee, Aileen, Lim, Seng Gee, Campbell, Jean, Fausto, Nelson, and Dan, Yock Young
- Abstract
Liver progenitor cells have the potential to repair and regenerate a diseased liver. The success of any translational efforts, however, hinges on thorough understanding of the fate of these cells after transplant, especially in terms of long‐term safety and efficacy. Here, we report transplantation of a liver progenitor population isolated from human fetal livers into immune‐permissive mice with follow‐up up to 36 weeks after transplant. We found that human progenitor cells engraft and differentiate into functional human hepatocytes in the mouse, producing albumin, alpha‐1‐antitrypsin, and glycogen. They create tight junctions with mouse hepatocytes, with no evidence of cell fusion. Interestingly, they also differentiate into functional endothelial cell and bile duct cells. Transplantation of progenitor cells abrogated carbon tetrachloride‐induced fibrosis in recipient mice, with downregulation of procollagen and anti‐smooth muscle actin. Paradoxically, the degree of engraftment of human hepatocytes correlated negatively with the anti‐fibrotic effect. Progenitor cell expansion was most prominent in cirrhotic animals, and correlated with transcript levels of pro‐fibrotic genes. Animals that had resolution of fibrosis had quiescent native progenitor cells in their livers. No evidence of neoplasia was observed, even up to 9 months after transplantation. Human fetal liver progenitor cells successfully attenuate liver fibrosis in mice. They are activated in the setting of liver injury, but become quiescent when injury resolves, mimicking the behavior of de novo progenitor cells. Our data suggest that liver progenitor cells transplanted into injured livers maintain a functional role in the repair and regeneration of the liver. StemCells2018;36:103–113 Human hepatocytes engrafting in mouse liver 4 weeks after transplantation illustrated with immunofluorescence of human‐ and mouse‐specific Zona occludens‐1 (ZO‐1) antibodies. Human‐specific ZO‐1 (green) colocalize with mouse ZO‐1 (red) showing yellow canaliculi junctions where human and neighboring mouse cells have integrated within the liver cords. ×80 magnification.
- Published
- 2018
- Full Text
- View/download PDF
8. Management of hepatitis C virus infection in the Asia-Pacific region: an update
- Author
-
Lim, Seng Gee, Aghemo, Alessio, Chen, Pei-Jer, Dan, Yock Young, Gane, Edward, Gani, Rino, Gish, Robert G, Guan, Richard, Jia, Ji Dong, Lim, Kieron, Piratvisuth, Teerha, Shah, Samir, Shiffman, Mitchell L, Tacke, Frank, Tan, Soek Siam, Tanwandee, Tawesak, Win, Khin Maung, and Yurdaydin, Cihan
- Abstract
The Asia-Pacific region has disparate hepatitis C virus (HCV) epidemiology, with prevalence ranging from 0·1% to 4·7%, and a unique genotype distribution. Genotype 1b dominates in east Asia, whereas in south Asia and southeast Asia genotype 3 dominates, and in Indochina (Vietnam, Cambodia, and Laos), genotype 6 is most common. Often, availability of all-oral direct-acting antivirals (DAAs) is delayed because of differing regulatory requirements. Ideally, for genotype 1 infections, sofosbuvir plus ledipasvir, sofosbuvir plus daclatasvir, or ombitasvir, paritaprevir, and ritonavir plus dasabuvir are suitable. Asunaprevir plus daclatasvir is appropriate for compensated genotype 1b HCV if baseline NS5A mutations are absent. For genotype 3 infections, sofosbuvir plus daclatasvir for 24 weeks or sofosbuvir, daclatasvir, and ribavirin for 12 weeks are the optimal oral therapies, particularly for patients with cirrhosis and those who are treatment experienced, whereas sofosbuvir, pegylated interferon, and ribavirin for 12 weeks is an alternative regimen. For genotype 6, sofosbuvir plus pegylated interferon and ribavirin, sofosbuvir plus ledipasvir, or sofosbuvir plus ribavirin for 12 weeks are all suitable. Pegylated interferon plus ribavirin has been replaced by sofosbuvir plus pegylated interferon and ribavirin, and all-oral therapies where available, but cost and affordability remain a major issue because of the absence of universal health coverage. Few patients have been treated because of multiple barriers to accessing care. HCV in the Asia-Pacific region is challenging because of the disparate epidemiology, poor access to all-oral therapy because of availability, cost, or regulatory licensing. Until these problems are addressed, the burden of disease is likely to remain high.
- Published
- 2017
- Full Text
- View/download PDF
9. Type 2 diabetes mellitus in metabolic-associated fatty liver disease vs. type 2 diabetes mellitus non-alcoholic fatty liver disease: a longitudinal cohort analysis
- Author
-
Muthiah, Mark, Ng, Cheng Han, Chan, Kai En, Fu, Clarissa Elysia, Lim, Wen Hui, Tan, Darren Jun Hao, Nah, Benjamin, Kong, Gwyneth, Xiao, Jieling, Yong, Jie Ning, Tan, Bryan, Syn, Nicholas, Wang, Jiong-Wei, Sayed, Nilofer, Tan, Eunice, Chew, Nicholas WS, Dan, Yock Young, Siddiqui, Mohammad Shadab, Sanyal, Arun J., and Noureddin, Mazen
- Abstract
Type 2 Diabetes Mellitus (T2DM) is comorbidity commonly presenting with fatty liver. A recently proposed definition of "metabolic associated fatty liver disease" (MAFLD) is thought to replace non-alcoholic fatty liver disease (NAFLD). Yet, despite the significant prevalence of T2DM among fatty liver, there remains limited evidence on the impact of the change in the definition of T2DM.
- Published
- 2023
- Full Text
- View/download PDF
10. Hepatitis C: An Eastern Perspective
- Author
-
Dan, Yock Young and Lim, Seng Gee
- Abstract
HCV in the East is a complex scenario with prevalence rates of 0.5% to as high as 4.7%, and variable distributions of genotypes, with a dominance of genotype 1b in East Asia, genotype 3 in South Asia and South East Asia, and genotype 6 in Indochina. Approvals for the new oral directing antiviral agents (DAAs), in the East have been very slow, but ultimately will be achieved by 2019, consequently, pegylated interferon and ribavirin are still widely used. Nonetheless the main issues are the problems of screening and linkage to management, and the considerable barriers to access HCV care.
- Published
- 2015
- Full Text
- View/download PDF
11. Cost-Effectiveness of Boceprevir Co-Administration versus Pegylated Interferon-a2b and Ribavirin Only for Patients with Hepatitis C Genotype 1 in Singapore
- Author
-
Dan, Yock Young, Ferrante, Shannon A, Elbasha, Elamin H, and Hsu, Tun-Ying
- Abstract
Background Patients infected with chronic HCV genotype 1 experience liver complications as the disease progresses. This study aims to project the long-term reduction of liver complications and cost-effectiveness of treatment strategies, including co-administrating boceprevir (BOC) with pegylated interferon-a2b (PEG-IFN) and ribavirin compared with standard of care (SOC) of PEG-IFN and ribavirin only.Methods A Markov model was created to estimate the expected costs and quality-adjusted life-years (QALYs) associated with treatment strategies outlined in the BOC package insert in Singapore. Patient characteristics were from pivotal trials, the transition probabilities and QALYs were estimated from publications, and the pharmaceutical and health status costs were obtained from a public hospital in Singapore. The threshold of cost-effectiveness was chosen as 65,000 SGD for this study.Results For treatment-naive patients, BOC is highly cost-effective compared with SOC (179 SGD/QALY) and cost-saving for patients who have failed prior treatment, due to higher QALYs from better sustained virological response (SVR) and lower costs from avoidance of complications. Sub-group analyses show that BOC is cost-effective for non-cirrhotic treatment-experienced patients and null responders. It out-performs SOC for treatment-naive non-cirrhotic and cirrhotic patients who have failed prior treatment. Even after adjusting for higher prevalence of favourable IL28B genotype in Asians, BOC is cost-effective compared with SOC. Only untreated cirrhotic patients showed inconclusive cost-effectiveness for BOC.Conclusions Compared with SOC, BOC prevents more HCV liver complications from HCV genotype 1, particularly in patients who have failed previous SOC. Improved SVR and shortened duration of treatment result in BOC being potentially cost-saving or cost-effective in an Asian population.
- Published
- 2015
- Full Text
- View/download PDF
12. Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in hepatocellular carcinoma: the PLANET study
- Author
-
Zhai, Weiwei, Lai, Hannah, Kaya, Neslihan Arife, Chen, Jianbin, Yang, Hechuan, Lu, Bingxin, Lim, Jia Qi, Ma, Siming, Chew, Sin Chi, Chua, Khi Pin, Alvarez, Jacob Josiah Santiago, Chen, Pauline Jieqi, Chang, Mei Mei, Wu, Lingyan, Goh, Brian K P, Chung, Alexander Yaw-Fui, Chan, Chung Yip, Cheow, Peng Chung, Lee, Ser Yee, Kam, Juinn Huar, Kow, Alfred Wei-Chieh, Ganpathi, Iyer Shridhar, Chanwat, Rawisak, Thammasiri, Jidapa, Yoong, Boon Koon, Ong, Diana Bee-Lan, de Villa, Vanessa H, Dela Cruz, Rouchelle D, Loh, Tracy Jiezhen, Wan, Wei Keat, Zeng, Zeng, Skanderup, Anders Jacobsen, Pang, Yin Huei, Madhavan, Krishnakumar, Lim, Tony Kiat-Hon, Bonney, Glenn, Leow, Wei Qiang, Chew, Valerie, Dan, Yock Young, Tam, Wai Leong, Toh, Han Chong, Foo, Roger Sik-Yin, and Chow, Pierce Kah-Hoe
- Abstract
Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of the largest prospective surgical cohorts for hepatocellular carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% of patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types.Using a prospective cohort for Hepatocellular Carcinoma (the PLANET study), this work revealed a dynamic landscape of phenotypic intra-tumor heterogeneity, providing several novel approaches for patient treatment and prognosis prediction.
- Published
- 2022
- Full Text
- View/download PDF
13. Clinical Outcomes of Lamivudine-Adefovir Therapy in Chronic Hepatitis B Cirrhosis
- Author
-
Lim, Seng Gee, Aung, Myat Oo, Mak, Belinda, Sutedja, Dede, Lee, Yin Mei, Lee, Guan Huei, Fernandes, Mark, Low, How Cheng, Lai, Vincent, and Dan, Yock Young
- Abstract
To determine the clinical outcome of chronic hepatitis B cirrhotics on antiviral therapy.
- Published
- 2011
- Full Text
- View/download PDF
14. A Randomized, Placebo-Controlled Trial of Thymosin-a1 and Lymphoblastoid Interferon for Hbeag-Positive Chronic Hepatitis B
- Author
-
Lim, Seng Gee, Wai, Chun-Tao, Lee, Yin Mei, Dan, Yock Young, Sutedja, Dede Selamat, Wee, Aileen, Suresh, Shirley, Wu, Ying Juan, Machin, David, Lim, Chee Chian, Fock, Kwong Ming, Koay, Evelyn, Bowden, Scott, Locarnini, Steven, and Ishaque, Shamsuddin Mohammed
- Abstract
Combination therapy between two immunomodulators used for treatment of chronic hepatitis B was explored based on reported therapeutic efficacy of interferon-a, and thymosin-a1 as monotherapeutic agents to determine if combination therapy was superior to interferon alone. This double-blinded, randomized, placebo-controlled trial compares the addition of thymosin-a1, 1.6 µg taken three times per week (combination therapy) or thymosin placebo (monotherapy) to lymphoblastoid interferon (Wellferon®), 5 million international units (MIU) taken three times per week, for 24 weeks. Entry criteria included positive hepatitis B e antigen (HBeAg); alanine aminotransferease (ALT) =1.5x upper normal limit, but =10xupper normal limit; positive HBV DNA; absence of cirrhosis; treatment naivety and no co-morbid factors. A total of 98 HBeAg-positive patients were recruited, of which 48 were randomized to combination therapy and 50 to monotherapy. The primary endpoint was the loss of HBeAg at 72 weeks. The secondary endpoints were HBeAg seroconversion, normalization of ALT, loss of HBV DNA and improvement in histology. The HBeAg loss was 45.8% and 28.0% for combination therapy and monotherapy, respectively (difference, 17.8%; 95% CI -1.2%-35.3%, P=0.067). There was a trend towards HBeAg loss when using combination therapy. There were also no statistically significant differences between the different therapies with respect to the secondary endpoints of HBeAg seroconversion, changes in histology, normalization of ALT or loss of HBV DNA. In conclusion, this trial showed a 17.8% improvement in HBeAg loss rates using combination therapy over interferon monotherapy. This could clinically indicate a potential important difference that would need confirmation in subsequent trials.
- Published
- 2006
- Full Text
- View/download PDF
15. Targeting RNA Editing of Antizyme Inhibitor1: a Potential Oligonucleotide-Based Antisense Therapy for Cancer
- Author
-
Tai Tay, Daryl Jin, Song, Yangyang, Peng, Boya, Toh, Tan Boon, Hooi, Lissa, Kaixin Toh, Desiree-Faye, Hong, HuiQi, Tang, Sze Jing, Han, Jian, Gan, Wei Liang, Man Chan, Tim Hon, Krishna, Manchugondanahalli S., Patil, Kiran M., Maraswami, Manikantha, Loh, Teck Peng, Dan, Yock Young, Zhou, Lei, Bonney, Glenn Kunnath, Kah-Hoe Chow, Pierce, Chen, Gang, Kai-Hua Chow, Edward, Le, Minh TN., and Chen, Leilei
- Abstract
Dysregulated adenosine-to-inosine (A-to-I) RNA editing is implicated in various cancers. However, no available RNA editing inhibitors have so far been developed to inhibit cancer-associated RNA editing events. Here we decipher the RNA secondary structure of antizyme inhibitor 1(AZIN1), one of the best-studied A-to-I editing targets in cancer, by locating its editing site complementary sequence (ECS) at the 3’end of exon 12. Chemically modified antisense oligonucleotides (ASOs) which target the editing region of AZIN1caused a substantial exon 11 skipping; while ECS-targeting ASOs effectively abolish AZIN1editing without affecting splicing and translation. We demonstrate that complete 2′-O-methyl (2’-O-Me) sugar ring modification in combination with partial phosphorothioate (PS) backbone modification may be an optimal chemistry for editing inhibition. ASO3.2, which targets the ECS, specifically inhibits cancer cell viability in vitroand tumor incidence and growth in xenograft models. Our results demonstrate that this AZIN1-targeting, ASO-based therapeutics may be applicable to a wide range of tumor types.
- Published
- 2021
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.