Publications by authors named "Jason K Sa"

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  • - Polyhexamethylene guanidine phosphate (PHMG-p) is commonly found in personal hygiene products but its long-term health effects, specifically regarding lung damage and cancer from respiratory exposure, are not well understood.
  • - The study investigated the kinds of lung lesions and cancer risk from PHMG-p through CT scans and pathology over 54 weeks, revealing that PHMG-p is linked to mutations in key cancer-related genes and disruptions in DNA repair pathways.
  • - Molecular analyses showed PHMG-p promotes necroptosis and activates certain signaling pathways while inhibiting others related to immune responses, suggesting a mechanism for how PHMG-p exposure leads to lung-related health issues and potential cancer development.
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  • * Researchers developed a deep learning model using a ResNet architecture to predict HKA angles from lower limb radiographs, eliminating the need for manual annotations of anatomical landmarks.
  • * The model’s performance was validated using a cohort of 300 knee OA patients, assessing both its accuracy in predicting HKA angles and its effectiveness in classifying the severity of varus deformity, with additional testing on a separate group of 50 patients.
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  • Breast cancer (BC) exhibits complex genomic changes, but the impact of age and ethnicity on its molecular variations is still not well understood.
  • This study analyzed 843 BC patients in the K-MASTER program, focusing on differences between age groups and comparing findings with larger genomic databases to uncover ethnic disparities.
  • Key results included a higher frequency of specific mutations in older patients and significant differences in cancer subtypes across ethnic groups, leading to the development of a model to predict responses to platinum-based chemotherapy based on unique molecular signatures.
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  • The study highlights the importance of accurately diagnosing acute loss of consciousness (LOC) as different causes require distinct treatments, despite having similar symptoms.
  • Researchers developed AI models that analyze brain connectivity patterns in electroencephalography (EEG) data to differentiate between conditions like nonconvulsive status epilepticus and benzodiazepine intoxication.
  • The convolutional neural network (CNN) model achieved high accuracy in classifying LOC causes, particularly using 20-second EEG data, indicating that these AI tools could significantly improve diagnostic procedures and treatment decisions in clinical settings.
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Patients with IDH-wild-type glioblastomas have a poor five-year survival rate along with limited treatment efficacy due to immune cell (glioma-associated microglia and macrophages) infiltration promoting tumour growth and resistance. To enhance therapeutic options, our study investigated the unique RNA-RNA-binding protein complex LOC-DHX15. This complex plays a crucial role in driving immune cell infiltration and tumour growth by establishing a feedback loop between cancer and immune cells, intensifying cancer aggressiveness.

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Background: Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults, with limited treatment modalities and poor prognosis. Recent studies have highlighted the importance of considering sex differences in cancer incidence, prognosis, molecular disparities, and treatment outcomes across various tumor types, including colorectal adenocarcinoma, lung adenocarcinoma, and GBM.

Methods: We performed comprehensive analyses of large-scale multi-omics data (genomic, transcriptomic, and proteomic data) from TCGA, GLASS, and CPTAC to investigate the genetic and molecular determinants that contribute to the unique clinical properties of male and female GBM patients.

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Background: Immune-modulating antibodies targeting programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) have demonstrated promising antitumor efficacy in various types of cancers, especially highly mutated ones. Genetic alterations in DNA damage response and repair (DDR) genes can lead to genetic instability, often accompanied by a high tumor mutation burden (TMB). However, few studies have validated the aberration of DDR genes as a predictive biomarker for response to immune-modulating antibodies.

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  • MSI (microsatellite instability) and TMB (tumor mutational burden) are important biomarkers for predicting responses to immunotherapy in various cancers, but their relationship, especially in lung cancer, is not fully understood.
  • Analysis of over 46,000 cancer patients revealed that many with MSI-H (high) also had TMB-low across different cancer types, with colorectal and stomach cancers showing the strongest links between the two.
  • In lung cancer patients receiving immunotherapy, TMB-H significantly improved overall and progression-free survival compared to TMB-low, while the MSI-H group did not show notable benefits, highlighting the need for tailored biomarker use in immunotherapy.
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Background: The FGF/FGFR signaling pathway plays a critical role in human cancers. We analyzed the anti-tumor effect of AZD4547, an inhibitor targeting the FGF/FGFR pathway, in epithelial ovarian cancer (EOC) and strategies on overcoming AZD4547 resistance.

Methods: The effect of AZD4547 on cell viability/migration was evaluated and in vivo experiments in intraperitoneal xenografts using EOC cells and a patient-derived xenograft (PDX) model were performed.

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The evolutionary trajectory of glioblastoma (GBM) is a multifaceted biological process that extends beyond genetic alterations alone. Here, we perform an integrative proteogenomic analysis of 123 longitudinal glioblastoma pairs and identify a highly proliferative cellular state at diagnosis and replacement by activation of neuronal transition and synaptogenic pathways in recurrent tumors. Proteomic and phosphoproteomic analyses reveal that the molecular transition to neuronal state at recurrence is marked by post-translational activation of the wingless-related integration site (WNT)/ planar cell polarity (PCP) signaling pathway and BRAF protein kinase.

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Background: Oncogenic KRAS mutation, the most frequent mutation in non-small cell lung cancer (NSCLC), is an aggressiveness risk factor and leads to the metabolic reprogramming of cancer cells by promoting glucose, glutamine, and fatty acid absorption and glycolysis. Lately, sotorasib was approved by the FDA as a first-in-class KRAS-G12C inhibitor. However, sotorasib still has a derivative barrier, which is not effective for other KRAS mutation types, except for G12C.

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Non-alcoholic steatohepatitis (NASH) is a complex disease resulting from chronic liver injury associated with obesity, type 2 diabetes, and inflammation. Recently, the importance of developing multi-target drugs as a strategy to address complex diseases such as NASH has been growing; however, their manufacturing processes remain time- and cost-intensive and inefficient. To overcome these limitations, we developed UniStac, a novel enzyme-mediated conjugation platform for multi-specific drug development.

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Ulipristal acetate (UPA) is a selective progesterone receptor modulator and is used for the treatment of uterine leiomyoma (a benign tumor). Uterine sarcoma which is highly malignant cancer with a poor prognosis is clinically resembled with uterine leiomyoma. There has been no experimental research on the effect of UPA on uterine sarcoma.

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  • Scientists are studying how gliomas, a type of brain tumor, change and can become resistant to treatments after they start with the tumor cells that are present when diagnosed.
  • They found that certain genetic features at diagnosis can predict how the tumor will behave later after treatment, like when it might become more aggressive or mutate.
  • They created a new tool called CELLO2 to help doctors understand these changes better and figure out which patients might need extra help based on their tumor's characteristics.
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Glioblastoma (GBM) is the most lethal brain cancer with a dismal prognosis. Stem-like GBM cells (GSCs) are a major driver of GBM propagation and recurrence; thus, understanding the molecular mechanisms that promote GSCs may lead to effective therapeutic approaches. Through in vitro clonogenic growth-based assays, we determined mitogenic activities of the ligand molecules that are implicated in neural development.

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  • Temozolomide (TMZ) is commonly used to treat glioblastoma, but its effectiveness is challenged in IDH-wt cases due to drug resistance, necessitating a deeper understanding of the underlying molecular mechanisms.
  • A study involved analyzing 69 primary IDH-wt GBM patients, categorizing them into TMZ-resistant and sensitive groups, and utilizing genomic and transcriptomic data to uncover key molecular differences and develop a machine learning model for predicting TMZ response.
  • Results indicated that specific gene expressions and genetic alterations are related to either resistance or sensitivity to TMZ, ultimately helping to improve treatment strategies and patient outcomes through personalized medicine.
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We have recently reported on how transplantation of human mesenchymal stem cells (MSCs) into the mouse parenchyma generated immune responses. To facilitate the clinical translation of MSC-based AD therapy, the safety and efficacy of human derived MSCs (hMSCs) must be confirmed in the pre-clinical stage. Thus, it is imperative to investigate measures to reduce immune responses exerted via xenotransplantation.

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To overcome the hurdles of immunotherapy, we investigated whether calcipotriol, a synthetic vitamin D analog, could overcome the immune evasion of glioblastoma multiforme (GBM) by modulating immune responses and the immunosuppressive tumor microenvironment. Administration of calcipotriol considerably reduced tumor growth. Both in vivo and in vitro studies revealed that CD8+T and natural killer (NK) cell gene signatures were enriched and activated, producing high levels of IFN-γ and granzyme B.

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Through the wide adaptation of next-generation sequencing (NGS) technology within clinical practice, molecular profiling of the tumor has been the principal component of personalized treatment. In our study, we have generated a large collection of cancer genomes on East Asian epithelial ovarian carcinoma (EOC) patients and demonstrate the feasibility and utility of NGS platforms to explore the dynamic interrelations of major cancer driver alterations and their impacts on clinical prognosis and management. A total of 652 EOC patients have undergone clinical NGS panels to determine the prevalence of germline and somatic mutations.

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Non-small cell lung carcinoma (NSCLC), which affects the brain, is fatal and resistant to anti-cancer therapies. Despite innate, distinct characteristics of the brain from other organs, the underlying delicate crosstalk between brain metastatic NSCLC (BM-NSCLC) cells and brain tumor microenvironment (bTME) associated with tumor evolution remains elusive. Here, a novel 3D microfluidic tri-culture platform is proposed for recapitulating positive feedback from BM-NSCLC and astrocytes and brain-specific endothelial cells, two major players in bTME.

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Objective: Poly (ADP)-ribose polymerase inhibitors (PARPi) are effective clinical agents for treatment of epithelial ovarian cancer (EOC) harboring BRCA mutations as well as those without BRCA mutations. In this study, we evaluate the efficacy of combined PARPi and DNA methyltransferase inhibitor (DNMTi) in EOCs.

Methods: Expression levels of DNMT1 and PARP1 proteins in EOC cells were assessed using western blot analysis and immunohistochemistry.

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Background: A limited number of studies have characterized genomic properties of hepatocellular carcinoma (HCC) patients in response to anti-PD-1 immunotherapy.

Methods: Herein, we performed comprehensive molecular characterization of immediate (D-42 to D-1) pre-treatment tumor biopsy specimens from 60 patients with sorafenib-failed HCC in a single-arm prospective phase II trial of pembrolizumab. Objective response rate was the primary efficacy endpoint.

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