المؤلفون: Guan, Meijian, Muthuswamy, Anantharaman, Sun, Susan, Drew, Clifton, Kaufmann, Jenny, Belete, Merzu, Sridhar, Sriram, Higgs, Brandon, Si, Han

المصدر: Regular and Young Investigator Award Abstracts

الإتاحة: https://doi.org/10.1136/jitc-2023-sitc2023.1288Test

المؤلفون: Fan, Li, Harris, Angelo, Franken, Patrick, Loya, Matthew, Suppa, Gabrielle, Pencheva, Nora, Sun, Susan, Muthuswamy, Anantharaman, Adams, Homer, Fereshteh, Mark, Jabado, Omar

المصدر: Regular and Young Investigator Award Abstracts

الإتاحة: https://doi.org/10.1136/jitc-2023-sitc2023.0080Test

المؤلفون: Soong, David, Muthuswamy, Anantharaman, Drew, Clifton, Pencheva, Nora, Jure-Kunkel, Maria, Sasser, Kate, Hamadeh, Hisham, Couto, Suzana, Higgs, Brandon

المصدر: Regular and Young Investigator Award Abstracts

الإتاحة: https://doi.org/10.1136/jitc-2021-sitc2021.833Test

المؤلفون: Devalaraja-Narashimha, Kishor, Meagher, Karoline, Luo, Yifan, Huang, Cong, Kaplan, Theodore, Muthuswamy, Anantharaman, Halasz, Gabor, Casanova, Sarah, O’Brien, John, Peyser Boiarsky, Rebecca, McWhirter, John, Gartner, Hans, Bai, Yu, MacDonnell, Scott, Liu, Chien, Hu, Ying, Latuszek, Adrianna, Wei, Yi, Prasad, Srinivasa, Huang, Tammy, Yancopoulos, George, Murphy, Andrew, Olson, William, Zambrowicz, Brian, Macdonald, Lynn, Morton, Lori G.

المساهمون: Regeneron Pharmaceuticals

المصدر: Journal of the American Society of Nephrology ; volume 32, issue 1, page 99-114 ; ISSN 1046-6673 1533-3450

الوصف: Significance Statement C3 glomerulopathy (C3G) is a rare, progressive kidney disease, characterized by alternative pathway hyperactivation and glomerular complement deposition. Animal models are valuable to explore modulators of C3G progression. A severe C3G mouse model was developed by replacing the mouse C3 gene with the human equivalent. The humanized C3 mice mimic pathologic features of patients with C3G, potentially due to dysregulated interaction of human C3 protein with mouse complement regulators. A C5-blocking antibody showed that C5 dominates pathogenesis of humanized C3 mice. C3b- and complement factor B–blocking antibodies provide benefit, indicating that alternative-pathway hyperactivation drives pathology in these mice. The humanized model exhibits rapid, severe renal disease, offering the opportunity to genetically and pharmacologically dissect critical contributors to complement-driven renal pathology. Background C3 glomerulopathy (C3G) is characterized by the alternative-pathway (AP) hyperactivation induced by nephritic factors or complement gene mutations. Mice deficient in complement factor H (CFH) are a classic C3G model, with kidney disease that requires several months to progress to renal failure. Novel C3G models can further contribute to understanding the mechanism behind this disease and developing therapeutic approaches. Methods A novel, rapidly progressing, severe, murine model of C3G was developed by replacing the mouse C3 gene with the human C3 homolog using VelociGene technology. Functional, histologic, molecular, and pharmacologic assays characterize the presentation of renal disease and enable useful pharmacologic interventions in the humanized C3 (C3 hu/hu ) mice. Results The C3 hu/hu mice exhibit increased morbidity early in life and die by about 5–6 months of age. The C3 hu/hu mice display elevated biomarkers of kidney dysfunction, glomerulosclerosis, C3/C5b-9 deposition, and reduced circulating C3 compared with wild-type mice. Administration of a C5-blocking mAb improved ...

الإتاحة: https://doi.org/10.1681/asn.2020050698Test

المؤلفون: Bakema, Jantine E, van Walsum, Marijke Stigter, Harris, Jeffrey R, Ganzevles, Sonja H, Muthuswamy, Anantharaman, Houtkamp, Mischa, Plantinga, Theo S, Bloemena, Elisabeth, Brakenhoff, Ruud H, Breij, Esther C W, van de Ven, Rieneke

المصدر: Bakema , J E , van Walsum , M S , Harris , J R , Ganzevles , S H , Muthuswamy , A , Houtkamp , M , Plantinga , T S , Bloemena , E , Brakenhoff , R H , Breij , E C W & van de Ven , R 2023 , ' An antibody-drug conjugate directed to tissue factor shows preclinical anti-tumor activity in head and neck cancer as a single agent and in combination with chemoradiotherapy ' , Molecular Cancer Therapeutics . https://doi.org/10.1158/1535-7163.MCT-23-0298Test

الوصف: Head and neck squamous cell carcinoma (HNSCC) is a solid tumor type that arises in the squamous epithelial cells lining of the mucosal surfaces of the upper aerodigestive tract¬. Long term survival of patients with advanced disease stage remains disappointing with current treatment options. We show that tissue factor is abundantly expressed on patient-derived HNSCC cell lines, xenograft tumor material, and tumor biopsies from patients with HNSCC. Tisotumab vedotin (TV) is an antibody-drug conjugate (ADC) directed to tissue factor, a protein expressed in many solid tumors. HNSCC cells and xenograft tumors were efficiently eliminated in vitro and in vivo with TV-monotherapy compared to treatment with a control antibody conjugated to monomethyl auristatin E (MMAE). Anti-tumor activity of TV was also tested in vivo in combination with chemoradiotherapy, standard of care for patients with advanced stage HNSCC tumors outside the oral cavity. Preclinical studies showed that by adding TV to chemoradiotherapy, survival was markedly improved, and TV, not radiotherapy or chemotherapy, was the main driver of anti-tumor activity. Interestingly, TV-induced cell death in xenograft tumors showed an influx of macrophages indicative of a potential immune-mediated mode-of-action. In conclusion, based on these preclinical data, TV may be a novel treatment modality for patients suffering from head and neck cancer and is hypothesized to improve efficacy of chemoradiotherapy.

العلاقة: https://research.vumc.nl/en/publications/48e400d0-12df-42b6-a3dd-e9a1453c2f32Test

الإتاحة: https://doi.org/10.1158/1535-7163.MCT-23-0298Test
https://research.vumc.nl/en/publications/48e400d0-12df-42b6-a3dd-e9a1453c2f32Test

المؤلفون: Turner, Oliver C., Aeffner, Famke, Bangari, Dinesh S., High, Wanda, Knight, Brian, Forest, Tom, Cossic, Brieuc, Himmel, Lauren E., Rudmann, Daniel G., Bawa, Bhupinder, Muthuswamy, Anantharaman, Aina, Olulanu H., Edmondson, Elijah F., Saravanan, Chandrassegar, Brown, Danielle L., Sing, Tobias, Sebastian, Manu M.

المصدر: Toxicologic Pathology ; volume 48, issue 2, page 277-294 ; ISSN 0192-6233 1533-1601

مصطلحات موضوعية: Cell Biology, Toxicology, Molecular Biology, Pathology and Forensic Medicine

الوصف: Toxicologic pathology is transitioning from analog to digital methods. This transition seems inevitable due to a host of ongoing social and medical technological forces. Of these, artificial intelligence (AI) and in particular machine learning (ML) are globally disruptive, rapidly growing sectors of technology whose impact on the long-established field of histopathology is quickly being realized. The development of increasing numbers of algorithms, peering ever deeper into the histopathological space, has demonstrated to the scientific community that AI pathology platforms are now poised to truly impact the future of precision and personalized medicine. However, as with all great technological advances, there are implementation and adoption challenges. This review aims to define common and relevant AI and ML terminology, describe data generation and interpretation, outline current and potential future business cases, discuss validation and regulatory hurdles, and most importantly, propose how overcoming the challenges of this burgeoning technology may shape toxicologic pathology for years to come, enabling pathologists to contribute even more effectively to answering scientific questions and solving global health issues. [Box: see text]

الإتاحة: https://doi.org/10.1177/0192623319881401Test

المؤلفون: Keller, Krista A., Guzman, David Sanchez-Migallon, Muthuswamy, Anantharaman, Forrest, Lisa J., Steinberg, Howard, Sladky, Kurt, Petersen, Sophie

المصدر: Journal of Avian Medicine and Surgery, 2011 Sep 01. 25(3), 216-224.

الوصول الحر: https://www.jstor.org/stable/41318143Test

المؤلفون: Muthuswamy, Anantharaman, Hu, Ying, Chen, Henry, Turner, Oliver, Aina, Olulanu

الوصف: Normal retina and its cell layers are essential for processing visual stimuli, and loss of its integrity has been documented in many disease processes. The numbers and the axonal processes of retinal ganglion cells are reduced substantially in glaucoma, leading to vision loss and blindness. Similarly, selective loss of photoreceptors in age-related macular degeneration and hereditary retinal dystrophies also results in the compromise of visual acuity. Development of genetically modified mice has led to increased understanding of the pathogenesis of many retinal diseases. Similarly, in this digital era, usage of modalities to quantify the retinal cell loss has grown exponentially leading to a better understanding of the suitability of animal models to study human retinal diseases. These quantification modalities provide valuable quantifiable data in studying pathogenesis and disease progression. This review will discuss the immunohistochemical markers for various retinal cells, available automated tools to quantify retinal cells, and present an example of retinal ganglion cell quantification using HALO image analysis platform. Additionally, we briefly review retinal cell types and subtypes, salient features of retina in various laboratory animal species, and a few of the main disease processes that affect retinal cell numbers in humans.

العلاقة: Muthuswamy, Anantharaman, Hu, Ying , Chen, Henry, Turner, Oliver and Aina, Olulanu (2020) Mammalian Retinal Cell Quantification. Toxicologic Pathology. ISSN 15331601

الإتاحة: https://doi.org/10.1177/0192623320976375Test
https://oak.novartis.com/43109Test/

المؤلفون: Muthuswamy, Anantharaman, Pardo, Ingrid D., Rao, Deepa B., Switzer, Robert C., Sharma, Alok K., Bolon, Brad

المصدر: Toxicologic Pathology ; volume 49, issue 3, page 455-471 ; ISSN 0192-6233 1533-1601

مصطلحات موضوعية: Cell Biology, Toxicology, Molecular Biology, Pathology and Forensic Medicine

الوصف: Visual system toxicity may manifest anywhere in the visual system, from the eye proper to the visual brain. Therefore, effective screening for visual system toxicity must evaluate not only ocular structures (ie, eye and optic nerve) but also multiple key brain regions involved in vision (eg, optic tract, subcortical relay nuclei, and primary and secondary visual cortices). Despite a generally comparable pattern across species, the neuroanatomic organization and function of the visual brain in rodents and rabbits exhibit appreciable differences relative to nonrodents. Currently recognized sampling practices for general toxicity studies in animals, which are based on easily discerned external neuroanatomic landmarks and guided by extant stereotaxic brain atlases, typically will permit histopathologic evaluation of many brain centers involved in visual sensation (eg, optic chiasm, optic tract, dorsal lateral geniculate nucleus, primary and secondary visual cortices) and often some subcortical brain nuclei involved in light-modulated nonvisual activities needed for visual attention and orientation (eg, rostral colliculus in quadrupeds, termed the superior colliculus in bipeds; several cranial nerve nuclei). Pathologic findings induced by toxicants in the visual brain centers are similar to those that are produced in other brain regions.

الإتاحة: https://doi.org/10.1177/0192623320967279Test

المؤلفون: Piskun, Caroline M., Muthuswamy, Anantharaman, Huelsmeyer, Michael K., Thompson, Victoria, Stein, Timothy J.

المساهمون: Agoulnik, Irina

المصدر: PLoS ONE ; volume 6, issue 10, page e26106 ; ISSN 1932-6203

الإتاحة: https://doi.org/10.1371/journal.pone.0026106Test