Article
Immunology
Ofir Fursht, Mirit Liran, Yuval Nash, Vijay Krishna Medala, Dor Ini, Tabitha Grace Royal, Guy Goldsmith, Limor Nahary, Itai Benhar, Dan Frenkel
Summary: Inhibiting insulin-degrading enzyme (IDE) with an IDE-specific antibody shows promise in improving insulin activity in diabetes. Researchers have isolated an IDE-specific antibody that can specifically inhibit insulin degradation by IDE and demonstrated its efficacy in improving insulin activity in a diabetes mouse model.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yun Hee Sim, Yun Jung Um, Jeong-Yang Park, Min-Duk Seo, Sang Gyu Park
Summary: This study developed a novel anti-Nectin-2 antibody and an antibody-drug conjugate (c12G1-DM1) that exhibited potent cytotoxic effects against Nectin-2-positive ovarian cancer cells, suggesting its potential as a therapeutic agent.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Guanjie Li, Tomokazu Ohishi, Mika K. Kaneko, Junko Takei, Takuya Mizuno, Manabu Kawada, Masaki Saito, Hiroyuki Suzuki, Yukinari Kato
Summary: A novel defucosylated mouse-dog chimeric anti-EGFR monoclonal antibody, E134Bf, showed high efficacy in vitro and in vivo against canine cancer cells expressing dEGFR, suggesting its potential as a valuable component of antibody treatment regimens for dogs with cancer.
Article
Oncology
Hiroyuki Suzuki, Tomokazu Ohishi, Teizo Asano, Tomohiro Tanaka, Masaki Saito, Takeo Yoshikawa, Takuya Mizuno, Manabu Kawada, Mika K. K. Kaneko, Yukinari Kato
Summary: The study demonstrates that the anti-HER2 monoclonal antibody H77Bf possesses high binding affinity and exerts antitumor activities against dHER2-positive canine cancers, suggesting it could be a valuable treatment regimen for canine cancers.
Article
Oncology
Rosa Nguyen, Anand G. Patel, Lyra M. Griffiths, Jason Dapper, Elizabeth A. Stewart, Jim Houston, Melissa Johnson, Walter J. Akers, Wayne L. Furman, Michael A. Dyer
Summary: Faithful tumor mouse models are essential research tools for advancing the field of immuno-oncology, especially in diseases with low incidence like pediatric malignancies. Current conventional mouse models fail to replicate the tumor heterogeneity and microenvironment complexity of human pathology.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Pharmacology & Pharmacy
Nami Tateyama, Hiroyuki Suzuki, Tomokazu Ohishi, Teizo Asano, Tomohiro Tanaka, Takuya Mizuno, Takeo Yoshikawa, Manabu Kawada, Mika K. Kaneko, Yukinari Kato
Summary: The bispecific antibody E134Bf-H77scFv exhibited antitumor activities against dEGFR/dHER2-positive canine tumors, suggesting its potential as a valuable treatment regimen.
Article
Oncology
Daniel Eberli, Benedikt Kranzbuhler, Lukas Prause, Valentin Baumgartner, Sheryl Preda, Rosa Sousa, Fabienne Lehner, Souzan Salemi
Summary: The combination treatment of APA and Chloroquine led to reduced autophagy levels and better tumor suppression compared to APA monotherapy. The antitumor effect of APA can be enhanced by combining with autophagy inhibitors, offering a potential new therapeutic approach for patients.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2022)
Article
Endocrinology & Metabolism
Maria Fernanda Garces, Haiver Antonio Rodriguez-Navarro, Julieth Daniela Buell-Acosta, Alvaro Javier Burgos-Cardenas, Roberto Franco-Vega, Luis Miguel Maldonado-Acosta, Javier Eslava-Schmalbach, Arturo Jose Parada-Banos, Andres Castro-Pinzon, Elizabeth Sanchez, Edith Angel-Muller, Ezequiel Lacunza, Justo P. Castano, Carlos Dieguez, Ruben Nogueiras, Ariel Ivan Ruiz-Parra, Jorge Eduardo Caminos
Summary: The study found that serum ANGPTL3 levels significantly decreased in healthy pregnant women during pregnancy, with no significant differences in levels between different trimesters and healthy states. Additionally, a significant positive correlation was observed between serum ANGPTL3 levels and triglyceride, very low-density lipoprotein cholesterol, and total cholesterol levels in healthy non-pregnant women.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Endocrinology & Metabolism
Kuan-Yu Chen, Shin-Yu Lin, Chien-Nan Lee, Hung-Tsung Wu, Ching-Hua Kuo, Han-Chun Kuo, Chia-Chi Chuang, Chun-Heng Kuo, Szu-Chi Chen, Kang-Chih Fan, Ming-Wei Lin, Chi-Tai Fang, Hung-Yuan Li
Summary: This study investigated the relationship between maternal lipids during pregnancy and placental growth factors on excess fetal growth, finding that certain free fatty acids can induce placental IGF-1 secretion, potentially linking maternal plasma lipids and large-for-gestational-age (LGA) neonates.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Endocrinology & Metabolism
Kuan-Yu Chen, Shin-Yu Lin, Chien-Nan Lee, Hung-Tsung Wu, Ching-Hua Kuo, Han-Chun Kuo, Chia-Chi Chuang, Chun-Heng Kuo, Szu-Chi Chen, Kang-Chih Fan, Ming-Wei Lin, Chi-Tai Fang, Hung-Yuan Li
Summary: It was found in the study that maternal lipids during pregnancy and placental growth factors are closely associated with excess fetal growth, suggesting a potential link between certain free fatty acids and induction of placental IGF-1 secretion.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Oncology
Tracy R. Daniels-Wells, Pierre V. Candelaria, Emiko Kranz, Jing Wen, Lan Wang, Masakazu Kamata, Juan C. Almagro, Otoniel Martinez-Maza, Manuel L. Penichet
Summary: Individuals infected with HIV have an increased risk of developing certain cancers, including non-Hodgkin lymphoma. This study demonstrates that antibodies targeting the transferrin receptor 1 (TfR1) can prolong survival in mouse models of AIDS-NHL. Targeting TfR1 with these antibodies may be a potential therapy for AIDS-NHL.
Article
Nutrition & Dietetics
Jun S. Lai, Keith M. Godfrey, Choon Nam Ong, Kok Hian Tan, Fabian Yap, Yap Seng Chong, Jerry K. Y. Chan, Shiao-Yng Chan, Mary F. -F. Chong
Summary: This study examined the associations between perinatal plasma carotenoids and E vitamers concentrations and glycemia, insulin resistance, and gestational and type 2 diabetes mellitus in GUSTO women. The findings suggest that higher concentrations of alpha- and beta-carotene and lutein may be beneficial for gestational fasting glycemia, while higher concentrations of vitamin E may increase gestational and post-pregnancy glycemia.
Article
Oncology
Sofia Xanthoulea, Gonda F. J. Konings, Niina Saarinen, Bert Delvoux, Loes F. S. Kooreman, Pasi Koskimies, Merja R. Hakkinen, Seppo Auriola, Elisabetta D'Avanzo, Youssef Walid, Frank Verhaegen, Natasja G. Lieuwes, Florian Caiment, Roy Kruitwagen, Andrea Romano
Summary: The study demonstrates that pharmacological inhibition of 17β-HSD-1 can inhibit the development of endometrial cancer. Through experiments on mice, it was found that treatment with the inhibitor significantly reduces tumor growth and metastatic spread.
Article
Neurosciences
Aditya N. Bade, JoEllyn M. McMillan, Yutong Liu, Benson J. Edagwa, Howard E. Gendelman
Summary: Research indicates that Dolutegravir inhibits matrix metalloproteinases activities that could affect fetal neurodevelopment, with studies in pregnant mice showing that DTG reaches the fetal central nervous system and leads to neuroinflammation and neuronal impairment.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Immunology
Yu-Chen Enya Chen, Melinda Burgess, Sally Mapp, Peter Mollee, Devinder Gill, Antje Blumenthal, Nicholas A. Saunders
Summary: The study reveals that the SIRP alpha axis suppresses ADP responses to the anti-CD20 antibody by NLCs derived from CLL patients, and further demonstrates that this innate immune checkpoint contributes to resistance through the regulation of the Shp1-mediated pathway.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Cecilie L. Matthiesen, Lili Hu, Astrid S. Torslev, Ebbe T. Poulsen, Ulrike G. Larsen, Kasper Kjaer-Sorensen, Jesper S. Thomsen, Annemarie Bruel, Jan J. Enghild, Claus Oxvig, Steen V. Petersen
Summary: The study revealed that SOD3 plays an unappreciated role in bone development and homeostasis, with Sod3b showing specific expression in skeletal tissue in zebrafish.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Cell Biology
Laurie K. Bale, Marissa J. Schafer, Elizabeth J. Atkinson, Nathan K. Le Brasseur, Andrew J. Haak, Claus Oxvig, Cheryl A. Conover
Summary: This study found that PAPP-A plays an important role in idiopathic pulmonary fibrosis (IPF) and is closely correlated with disease severity. TGF-beta and cell senescence regulate PAPP-A and IGF signaling, which may contribute to the resistance to apoptosis and the progression of fibrosis in IPF. Furthermore, PAPP-A-associated extracellular vesicles (EVs) may serve as a means of communication, promoting fibrosis and senescence with other cells in the lung.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Oncology
Laura Gomez-Cuadrado, Esme Bullock, Zeanap Mabruk, Hong Zhao, Margarita Souleimanova, Pernille Rimmer Noer, Arran K. Turnbull, Claus Oxvig, Nicholas Bertos, Adam Byron, J. Michael Dixon, Morag Park, Syed Haider, Rachael Natrajan, Andrew H. Sims, Valerie G. Brunton
Summary: This study demonstrates the molecular differences in the tumor microenvironment (TME) between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC), identifying differences in matrix organization and growth factor signaling pathways. These differences are associated with the long-term survival outcomes in ILC.
Article
Endocrinology & Metabolism
Alvaro Martin-Rivada, Santiago Guerra-Cantera, Ana Campillo-Calatayud, Eva Maria Andres-Esteban, Maria Sanchez Holgado, Gabriel A. Martos-Moreno, Jesus Pozo, Maria Guemes, Leandro Soriano-Guillen, Adelina Pellicer, Claus Oxvig, Jan Frystyk, Julie A. Chowen, Vicente Barrios, Jesus Argente
Summary: This study provides reference values for pappalysins and stanniocalcins, which modulate the activity of IGF-I by changing the concentrations of cleaved and uncleaved IGFBPs.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Endocrinology & Metabolism
Malene R. Jepsen, Jakob A. Ostergaard, Cheryl A. Conover, Lise Wogensen, Henrik Birn, Soren P. Krag, Robert A. Fenton, Claus Oxvig
Summary: This study found a significant increase in the activity of PAPP-A in diabetic kidneys, which correlated with glomerular filtration rate. Furthermore, it was discovered that STC1 and STC2 may balance IGF signaling in renal tissue by regulating PAPP-A activity, and imbalances in this system could potentially contribute to the development of DN.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2022)
Article
Multidisciplinary Sciences
Sara Dam Kobbero, Michael Gajhede, Osman Asghar Mirza, Soren Kloverpris, Troels Ronn Kjaer, Jakob Hauge Mikkelsen, Thomas Boesen, Claus Oxvig
Summary: PAPP-A plays a key role in IGF signaling by cleaving IGFBPs. The structure of PAPP-A in complex with its inhibitor STC2 was reported, revealing a mechanism of proteolytic inhibition that could support the development of specific pharmaceutical agents for modulating IGF signaling.
NATURE COMMUNICATIONS
(2022)
Review
Endocrinology & Metabolism
Claus Oxvig, Cheryl A. Conover
Summary: PAPP-A and PAPP-A2 are specific proteolytic enzymes involved in IGF signaling regulation by cleaving IGFBPs and increasing IGF bioactivity. This molecular network plays a significant role in the IGF system, but its precise operation needs further investigation.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Review
Endocrinology & Metabolism
Cheryl A. Conover, Claus Oxvig
Summary: PAPP-A is a placental protein that was initially discovered in pregnant women and later found to be a metalloproteinase expressed by nonplacental cells. It regulates local insulin-like growth factor (IGF) activity by cleaving high-affinity IGF binding proteins (IGFBPs). This proteolytic regulation is important for cell proliferation, differentiation, migration, and survival in normal and cancer cells.
Article
Cardiac & Cardiovascular Systems
Morten Krogh Christiansen, Kasper Kjaer-Sorensen, Natacha C. Clavsen, Sven Dittmann, Maja Fuhlendorff Jensen, Halvor Osterby Guldbrandsen, Lisbeth Norum Pedersen, Rikke Hasle Sorensen, Dorte Launholt Lildballe, Klara Mueller, Patrick Mueller, Kira Vogel, Boris Rudic, Martin Borggrefe, Claus Oxvig, Christian Aalkjaer, Eric Schulze-Bahr, Vladimir Matchkov, Henning Bundgaard, Henrik Kjaerulf Jensen
Summary: This study investigated the prevalence of potential disease-causing variants in SQTS patients, with a focus on the SLC4A3 gene. Results showed that nonsynonymous variants in SLC4A3 were the most common cause of SQTS, highlighting the importance of including SLC4A3 in the genetic screening of SQTS or sudden cardiac death patients.
Article
Medicine, Research & Experimental
Marie Louise Naestholt Dahl, Jakob Hauge Mikkelsen, Malene Hvid, Trine-Line Korsholm, Kirstine Overgaard Nielsen, Christian Brix Folsted Andersen, Stinne Greisen, Bent Deleuran
Summary: We established an indirect ELISA method to detect autoantibodies against full-length TRIM21 protein and its four domains, and validated the efficacy using plasma from anti-SSA positive patients and healthy controls. Our results showed significantly higher levels of autoantibodies against full-length TRIM21, PRY/SPRY, Coiled-Coil, and RING domains in patients compared to healthy controls. There was no significant difference in autoantibody levels against the B-box domain. Our protocols allow for further study of different autoantibodies in anti-SSA positive patients, enabling stratification of patients based on autoantibody profile and specific phenotypes or endotypes.
SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION
(2023)
Article
Biochemical Research Methods
Rasmus Hejlesen, Kasper Kjaer-Sorensen, Angela Fago, Claus Oxvig
Summary: By using the CRISPR/Cas system, three distinct zebrafish mb knockout lines were generated, all of which did not exhibit significant phenotypic changes during development. The validated knockout line, mb(Auzf13.2), showed no signs of genetic compensation or off-target effects in adult zebrafish, suggesting promise for investigating the biological role of Mb.
TRANSGENIC RESEARCH
(2023)
Article
Multidisciplinary Sciences
Anne Skakkebaek, Kasper Kjaer-Sorensen, Vladimir V. Matchkov, Lise-Lotte Christensen, Jesper Just, Cagla Comert, Niels Holmark Andersen, Claus Oxvig, Claus Hojbjerg Gravholt
Summary: The genetic basis of the QT interval, which represents the time for heartbeat repolarization, is not fully understood. This study explores the contribution of the pseudoautosomal gene SLC25A6 to QT interval variation using human participants and zebrafish models. The results show that higher expression of SLC25A6 is associated with shorter QTc intervals, and pharmacological modulation of K-ATP channels can restore the interval duration. This indicates that SLC25A6 plays a role in QT interval variation.
SCIENTIFIC REPORTS
(2023)
Article
Cell Biology
Pernille Bogetofte Thomasen, Alena Salasova, Kasper Kjaer-Sorensen, Lucie Woloszczukova, Josef Lavicky, Hande Login, Jeppe Tranberg-Jensen, Sergio Almeida, Sander Beel, Michaela Kavkova, Per Qvist, Mads Kjolby, Peter Lund Ovesen, Stella Nolte, Benedicte Vestergaard, Andreea-Cornelia Udrea, Lene Niemann Nejsum, Moses Chao, Philip Van Damme, Jan Krivanek, Jeremy Dasen, Claus Oxvig, Anders Nykjaer
Summary: SorCS2 is a receptor for PGRN that plays an important role in MN diversification and axon outgrowth, as well as affecting neuromuscular junction morphology and fish motility. Deficiency of SorCS2 disrupts cell-fate decisions of brachial MNs and leads to innervation deficits of posterior nerves. In addition, SorCS2 knockout mice exhibit slower motor nerve regeneration. The interaction between primitive macrophages expressing high levels of PGRN and SorCS2-positive motor axons is crucial for axon pathfinding.
Article
Physiology
Arimantas Lionikas, Ana I. Hernandez Cordero, Audrius Kilikevicius, Andrew M. Carroll, Guy S. Bewick, Lutz Bunger, Aivaras Ratkevicius, Lora K. Heisler, Mette Harboe, Claus Oxvig
Summary: This study suggests that STC2 inhibits muscle growth by inhibiting the activity of PAPP-A, a protease that promotes muscle growth through the IGF axis. Mice lacking STC2 showed increased muscle mass and larger muscle fibers. Functional overload increased muscle mass and the levels of IGF axis components, including IGF1, IGF2, IGFBP-4, PAPP-A, and STC2.
PHYSIOLOGICAL REPORTS
(2023)