Publications by authors named "Laryssa Manigat"

Article Synopsis
  • Metabolic dysfunction-associated steatohepatitis (MASH) is a serious liver condition with limited treatment options and relies on manual biopsies for assessment, which often shows high variability among readers.
  • A new artificial intelligence (AI) system, AIM-MASH, has been developed and validated across multiple sites to assist pathologists in scoring liver biopsies related to MASH, showing high reliability and consistency compared to traditional methods.
  • AIM-MASH significantly improved the accuracy of assessing key factors like inflammation and MASH resolution when used by expert pathologists, suggesting it can reduce variability and enhance the evaluation of new treatments in MASH clinical trials.
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Article Synopsis
  • - The standard method for assessing metabolic dysfunction-associated steatosis in clinical trials is by evaluating liver biopsies on glass slides; however, shipping these slides poses logistical challenges and risks of damage.
  • - This study found that using digital images on the AISight whole slide image management system for assessing steatohepatitis offers comparable accuracy to traditional glass slide evaluations, with both methods verified against a consensus score from expert pathologists.
  • - The results showed that the agreement between digital scoring and the established "ground truth" was not inferior to that of glass scoring, indicating that digital assessments can reliably replace traditional methods in clinical trial settings for liver disease.
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The diacylglycerol kinase (DGK) family of lipid enzymes catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA). Both DAG and PA are lipid signaling molecules that are of notable importance in regulating cell processes such as proliferation, apoptosis, and migration. There are ten mammalian DGK enzymes that appear to have distinct biological functions.

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The diacylglycerol kinases (DGKs) are a family of enzymes responsible for the conversion of diacylglycerol (DAG) to phosphatidic acid (PA). In addition to their primary function in lipid metabolism, DGKs have recently been identified as potential therapeutic targets in multiple cancers, including glioblastoma (GBM) and melanoma. Aside from its tumorigenic properties, DGKα is also a known promoter of T-cell anergy, supporting a role as a recently-recognized T cell checkpoint.

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Purpose: Due to the recent rise in immunotherapy research to treat glioblastoma (GBM), immunocompetent mouse models have become increasingly crucial. However, the character and kinetics of the immune response against the most prevalent immunocompetent GBM models, GL261 and CT2A, have not been well studied, nor has the impact of commonly-used marker proteins and foreign antigens.

Methods: In this study, we compared the immune response in these models using flow cytometry and immunohistochemistry as well as investigated several factors that influence the immune response, including kinetics, tumor size, and expression of commonly-used marker proteins and foreign antigens.

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Glioblastoma (GBM) is the most common primary brain malignancy and carries an extremely poor prognosis. Recent molecular studies revealed the CDK4/6-Rb-E2F axis and receptor tyrosine kinase (RTK) signaling to be deregulated in most GBM, creating an opportunity to develop more effective therapies by targeting both pathways. Using a phospho-RTK protein array, we found that both c-Met and TrkA-B pathways were significantly activated upon CDK4/6 inhibition in GBM cells.

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Background: The mesenchymal phenotype in glioblastoma (GBM) and other cancers drives aggressiveness and treatment resistance, leading to therapeutic failure and recurrence of disease. Currently, there is no successful treatment option available against the mesenchymal phenotype.

Methods: We classified patient-derived GBM stem cell lines into 3 subtypes: proneural, mesenchymal, and other/classical.

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Glioblastoma (GBM) is a deadly brain tumor marked by dysregulated signaling and aberrant cell-cycle control. Molecular analyses have identified that the CDK4/6-Rb-E2F axis is dysregulated in about 80% of GBMs. Single-agent CDK4/6 inhibitors have failed to provide durable responses in GBM, suggesting a need to combine them with other agents.

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