Article
Pharmacology & Pharmacy
Xiaolan Yang, Yongqiang Xiao, Chenjian Zhong, Futing Shu, Shichu Xiao, Yongjun Zheng, Zhaofan Xia
Summary: ABT-263 exhibits therapeutic potential in treating hypertrophic scars by inducing apoptosis and inhibiting proliferation of myofibroblasts. Its mechanism involves releasing BIM from prosurvival proteins to selectively induce myofibroblast apoptosis, while also reducing the expression of fibrotic markers.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell Biology
Violetta Ritter, Franziska Krautter, Diana Klein, Verena Jendrossek, Justine Rudner
Summary: Hypoxia is a major obstacle to successful radiotherapy for solid tumors. Exposure to acute and adaptation to chronic cycling hypoxia alters Bcl-2 family proteins, leading to increased resistance to apoptosis and decreased radiotherapy success. Targeting the Bcl-2 rheostat with ABT-263 shows promise in overcoming radioresistance of cancer cells exposed to hypoxia.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Ibrahim Y. Abdelgawad, Kevin Agostinucci, Somia G. Ismail, Marianne K. O. Grant, Beshay N. Zordoky
Summary: The research found that DOX-induced senescence demonstrates similar phenotypes between EA.hy926 cells and HUVECs, but they respond differently to ABT-263.
Article
Oncology
Anbok Lee, Hyeon-Ok Jin, Md Masudul Haque, Hee Yeon Kim, Hana Jung, Jin Hee Park, Ilwhan Kim, Joo Yeon Song, Hye Kyoung Yoon, Hyoung Kyu Kim, Jin Han, In-Chul Park, Kwang Seok Kim, Sae Gwang Park
Summary: The present study identified acriflavine (ACF) as a novel MCL-1 inhibitor, demonstrating its anticancer effect in triple-negative breast cancer (TNBC) cells. ACF induced intrinsic apoptosis in TNBCs through downregulation of MCL-1 in a dose- and time-dependent manner. The study also explored the synergistic antitumor effect of ACF with the known MCL-1 inhibitor ABT-263. Additionally, the treatment potential of ACF in lung adenocarcinoma and glioblastoma multiforme (GBM) was investigated.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Wonseon Ryu, Chul-Woo Park, Junghoon Kim, Hyungwoo Lee, Hyewon Chung
Summary: Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly, and current treatments are invasive and carry the risk of infection. The pathogenic mechanism of AMD involves a combination of genetic predisposition and cellular senescence. Senolytic drugs, such as ABT-263, selectively eliminate senescent cells and have the potential to be a new treatment for AMD by targeting senescent retinal pigment epithelium (RPE) cells. Our study showed that ABT-263 can kill senescent ARPE-19 cells and alleviate retinal degeneration in a mouse model, suggesting it may be the first orally administered senolytic drug for AMD.
MOLECULES AND CELLS
(2023)
Article
Geriatrics & Gerontology
Kento Takaya, Tatsuyuki Ishii, Toru Asou, Kazuo Kishi
Summary: This study aimed to investigate the rejuvenating effects of ABT-263 on aging skin. The results showed that ABT-263 selectively eliminated senescent skin fibroblasts, reduced the expression of aging-related secretory phenotype molecules, and increased collagen density. This indicates that ABT-263 can improve the aging phenotype of human skin without side effects, making it a novel potential therapeutic agent for skin aging.
REJUVENATION RESEARCH
(2023)
Article
Oncology
Ying Wu, Patricia M. A. Zehnle, Jovana Rajak, Naile Koleci, Geoffroy Andrieux, Lorena Gallego-Villar, Konrad Aumann, Melanie Boerries, Charlotte M. Niemeyer, Christian Flotho, Sheila Bohler, Miriam Erlacher
Summary: JMML cells rely on both MCL-1 and BCL-XL for survival, and azacitidine and BH3 mimetic drugs can effectively target these proteins. Azacitidine acts in vivo through downregulation of MCL-1 and upregulation of BH3-only. Combination treatment of azacitidine with BCL-XL inhibition is more effective in eliminating JMML cells compared to BCL-2 inhibition. These findings highlight the need for clinically applicable MCL-1 or BCL-XL inhibitors in JMML refractory to standard therapy.
Article
Biochemistry & Molecular Biology
Simona Pergolizzi, Alessio Alesci, Antonio Centofanti, Marialuisa Aragona, Socrate Pallio, Ludovico Magaudda, Giuseppina Cutroneo, Eugenia Rita Lauriano
Summary: Crohn's disease is a chronic intestinal inflammation that is associated with inflammatory bowel disease. Intestinal 5-HT signaling is linked to patients with inflammatory bowel disease. Our study reveals the correlation between different types of intestinal cells in maintaining the inflammatory state in Crohn's disease.
Article
Biochemistry & Molecular Biology
Hao Li, Shuheng Dong, Lili Duan
Summary: The study compared the binding modes of Bcl-xL and Bcl-2 with ligands ABT-263/43b, finding that the Bcl-2 and ABT-263 system had stronger binding ability. The predicted hot spot residues and their energy distributions can guide the design of peptide and small-molecule drugs targeting Bcl-xL and Bcl-2.
JOURNAL OF MOLECULAR MODELING
(2021)
Review
Gastroenterology & Hepatology
Ayseguel Aksan, Karima Farrag, Irina Blumenstein, Oliver Schroeder, Axel U. Dignass, Juergen Stein
Summary: Chronic intestinal failure, a rare complication of Crohn's disease, can greatly impact quality of life and treatment options include home-based parenteral nutrition and intravenous infusion. However, 60% of patients may need lifelong reliance on parenteral nutrition, and promising new drugs have brought new dimensions to therapy.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Gastroenterology & Hepatology
Aito Ueno, Humberto B. Jijon, Richard Peng, Steven Sparksman, Barbara Mainoli, Alexis Filyk, Yan Li, Stephanie Wilson, Kerri Novak, Remo Panaccione, Simon Hirota, Antoine Dufour, Cathy Lu, Paul L. Beck
Summary: This study provides evidence supporting a potential role of fibrocytes in collagen deposition in Crohn's disease strictures and suggests that fibrocyte numbers may predict the need for therapy escalation.
INFLAMMATORY BOWEL DISEASES
(2022)
Article
Gastroenterology & Hepatology
Robert H. Hollis, Nicholas Smith, Ipek Sapci, Benjamin Click, Miguel Regueiro, Tracy L. Hull, Amy L. Lightner
Summary: This retrospective cohort study found that over one third of patients who underwent total proctocolectomy for Crohn's disease were estimated to have small bowel Crohn's recurrence at 5 years after surgery. Patients with a history of small bowel surgery for Crohn's and diagnosis at any early age may have a higher risk of recurrence.
DISEASES OF THE COLON & RECTUM
(2022)
Review
Oncology
Naveen Pemmaraju, Jacqueline S. Garcia, Andrew Perkins, Jason G. Harb, Andrew J. Souers, Michael E. Werner, Christopher M. Brown, Francesco Passamonti
Summary: Myelofibrosis is a myeloproliferative neoplasm characterized by chronic inflammation, bone marrow failure, and extramedullary hematopoiesis. Current treatments provide symptom relief but lack durable disease modification. This review highlights the potential role of navitoclax, a BCL-X-L/BCL-2 inhibitor, in modifying the disease course.
Article
Engineering, Biomedical
Jingbo Zhao, Donghua Liao, Rune Wilkens, Klaus Krogh, Henning Glerup, Hans Gregersen
Summary: This study aimed to quantify the mechanical properties of intestinal stenosis in CD patients and found that the changes in mechanical properties were mainly associated with chronic inflammation, fibrosis, and collagen fraction.
ACTA BIOMATERIALIA
(2021)
Review
Surgery
Pramodh Chandrasinghe
Summary: Differentiating the type and extent of Crohn's disease in the small bowel is crucial for effective management. Currently, a combination of medical and surgical therapies is commonly used, but there is ongoing debate about which therapy is better. Imaging plays a pivotal role in identifying the disease process, as inflammatory strictures respond to anti-TNF and biological agents, while fibrotic strictures require endoscopic or surgical intervention.
FRONTIERS IN SURGERY
(2022)
Review
Gastroenterology & Hepatology
Calen A. Steiner, Jeffrey A. Berinstein, Jeremy Louissaint, Peter D. R. Higgins, Jason R. Spence, Carol Shannon, Cathy Lu, Ryan W. Stidham, Joel G. Fletcher, David H. Bruining, Brian G. Feagan, Vipul Jairath, Mark E. Baker, Dominik Bettenworth, Florian Rieder
Summary: This comprehensive systematic review examines biomarkers for predicting and diagnosing Crohn's disease-associated strictures. Thirty-five potential biomarkers were identified across three groups, including promising markers such as cartilage oligomeric matrix protein and hepatocyte growth factor activator. However, limitations exist, including the lack of standardized definition for stricturing disease and incomplete knowledge of their operating properties.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Michael D. Kappelman, Kimberly N. Weaver, Xian Zhang, Xiangfeng Dai, Runa Watkins, Jeremy Adler, Marla C. Dubinsky, Arthur Kastl, Athos Bousvaros, Jenifer A. Strople, Raymond K. Cross, Peter D. R. Higgins, Ryan C. Ungaro, Meenakshi Bewtra, Emanuelle A. Bellaguarda, Francis A. Farraye, Margie E. Boccieri, A. Firestine, Kelly Y. Chun, Manory Fernando, Monique Bastidas, Michael Zikry, Millie D. Long
Summary: Although most patients with IBD show an initial response to SARS-CoV-2 vaccination, older patients and those treated with anti-TNF and immunomodulator have blunted responses and may benefit from an additional vaccine dose. Patients treated with other classes of immunosuppressive medications have more robust initial immune responses to vaccination.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Gastroenterology & Hepatology
Benjamin L. Cohen, Phillip Fleshner, Sunanda Kane, Hans H. Herfarth, Nicole Palekar, Francis A. Farraye, Jonathan A. Leighton, Jeffry A. Katz, Russell D. Cohen, Mark E. Gerich, Raymond K. Cross, Peter D. R. Higgins, Andrew Tinsley, Sarah Glover, Corey A. Siegel, Jaime L. Bohl, Heba Iskandar, Jiayi Ji, Liangyuan Hu, Bruce E. Sands
Summary: The aim of this study was to determine whether preoperative treatment of inflammatory bowel disease (IBD) with tumor necrosis factor inhibitors (TNFis) increases the risk of postoperative infectious complications. The results showed that preoperative TNFi exposure was not associated with postoperative infectious complications.
Review
Gastroenterology & Hepatology
Jessica L. Sheehan, Janson Jacob, Elliot M. Berinstein, LaVana Greene-Higgs, Calen A. Steiner, Sameer K. Berry, Carol Shannon, Shirley A. Cohen-Mekelburg, Peter D. R. Higgins, Jeffrey A. Berinstein
Summary: Pain management in patients with inflammatory bowel disease is challenging due to the potential adverse effects of opioids. This study systematically reviewed the impact of opioid use on healthcare utilization in inflammatory bowel disease patients.
INFLAMMATORY BOWEL DISEASES
(2022)
Article
Biochemical Research Methods
Yunhao Zhu, Linyu Ni, Guorong Hu, Laura A. Johnson, Kathryn A. Eaton, Xueding Wang, Peter D. R. Higgins, Guan Xu
Summary: The feasibility of using endoscopic photoacoustic imaging to characterize intestinal inflammation and fibrosis has been demonstrated in previous studies. A photoacoustic/ultrasound imaging probe integrating a miniaturized ultrasound array and an optical fiber has been developed for clinical translation of the imaging technology.
BIOMEDICAL OPTICS EXPRESS
(2022)
Article
Pediatrics
Nadeen Abu-Ata, Jonathan R. Dillman, Jonathan M. Rubin, Margaret H. Collins, Laura A. Johnson, Rebecca S. Imbus, Erin L. Bonkowski, Lee A. Denson, Peter D. R. Higgins
Summary: Ultrasound shear wave elastography can evaluate the relationship between bowel wall stiffness and intestinal fibrosis and smooth muscle hypertrophy in surgically resected ileal strictures from pediatric Crohn disease patients.
PEDIATRIC RADIOLOGY
(2023)
Article
Gastroenterology & Hepatology
Arthur J. Kastl, Kimberly N. Weaver, Xian Zhang, Jennifer A. Strople, Jeremy Adler, Marla C. Dubinsky, Athos Bousvaros, Runa Watkins, Xiangfeng Dai, Wenli Chen, Raymond K. Cross, Peter D. R. Higgins, Ryan C. Ungaro, Meenakshi Bewtra, Emanuelle A. Bellaguarda, Francis A. Farraye, Kelly Y. Chun, Michael Zikry, Manory Fernando, Monique Bastidas, Cristian G. Hernandez, Riley G. Craig, Margie E. Boccieri, Anne Firestine, Millie D. Long, Michael D. Kappelman
Summary: Children with IBD show a robust immune response to COVID-19 vaccination with low adverse events, providing a high level of reassurance to the medical community and patients.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2023)
Letter
Gastroenterology & Hepatology
Kira L. Newman, Kara Jencks, Victor Chedid, Sonali Paul, Peter D. R. Higgins, Sunanda Kane, Millie Long
Article
Gastroenterology & Hepatology
Julian Panes, Edward Loftus, Peter D. R. Higgins, James O. Lindsay, Wen Zhou, Xuan Yao, Dapo Ilo, Charles Phillips, Jacinda Tran, Yuri Sanchez Gonzalez, Severine Vermeire
Summary: The study evaluated the benefits of UPA on the HRQoL of patients with ulcerative colitis, and found that UPA treatment significantly improved patients' quality of life.
INFLAMMATORY BOWEL DISEASES
(2023)
Article
Immunology
Jeffrey A. Berinstein, Calen A. Steiner, Samara Rifkin, D. Alexander Perry, Dejan Micic, Daniel Shirley, Peter D. R. Higgins, Vincent B. Young, Allen Lee, Krishna Rao
Summary: By developing and validating a model to predict the risk of complications from CDI, this study demonstrates that it is possible to accurately estimate the risk of CDI complications. The model performed well in a large and diverse population, but showed poorer performance in non-White patients.
OPEN FORUM INFECTIOUS DISEASES
(2023)
Review
Gastroenterology & Hepatology
Elliot M. Berinstein, Jessica L. Sheehan, Janson Jacob, Calen A. Steiner, Ryan W. Stidham, Carol Shannon, Shrinivas Bishu, Jacob Levine, Shirley A. Cohen-Mekelburg, Akbar K. Waljee, Peter D. R. Higgins, Jeffrey A. Berinstein
Summary: Dual targeted therapy is a promising approach for improving the treatment of inflammatory bowel disease in patients who do not respond well to targeted monotherapy. However, more research is needed to confirm its effectiveness and identify the patients who would benefit the most from this treatment.
DIGESTIVE DISEASES AND SCIENCES
(2023)
Article
Biology
Antony B. Kim, Emma M. Beaver, Stephen G. Collins, Lance J. Kriegsfeld, Steven W. Lockley, Kwoon Y. Wong, Lily Yan
Summary: Through multielectrode array recordings, this study found that non-image-forming effects mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs) are able to stably encode irradiance. These effects include entrainment of daily rhythms and light-induced arousal, and stimulating S-cones is found to be important in these processes.
JOURNAL OF BIOLOGICAL RHYTHMS
(2023)
Article
Gastroenterology & Hepatology
Remo Panaccione, Eric B. Collins, Gil Y. Melmed, Severine Vermeire, Silvio Danese, Peter D. R. Higgins, Christina S. Kwon, Wen Zhou, Dapo Ilo, Dolly Sharma, Yuri Sanchez Gonzalez, Si-Tien Wang
Summary: Indirect evidence suggests that Upadacitinib may be more effective than other advanced therapies in achieving clinical response, clinical remission, and endoscopic response in patients with moderately to severely active ulcerative colitis over a one-year period, with similar safety profiles across different therapies.
CROHNS & COLITIS 360
(2023)
Meeting Abstract
Gastroenterology & Hepatology
Kira L. Newman, Peter D. Higgins
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2022)