Publications by authors named "Ku A"

Article Synopsis
  • - Phenotypic plasticity in cancer, particularly prostate cancer (PCa), leads to resistance against androgen receptor-targeted therapies, highlighting the need to understand its driving mechanisms to prevent resistance emergence.
  • - The study found that loss of the tristetraprolin (TTP) gene (ZFP36) increases NF-κB activation, correlating with more aggressive disease and recurrence, especially when PTEN, another key driver in PCa, is also lost.
  • - Targeting the NF-κB pathway with an inhibitor (DMAPT) showed promising therapeutic effects in tumors exhibiting co-loss of ZFP36 and PTEN, suggesting a potential new treatment strategy for castration-resistant PCa.
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The global transition to net-zero emissions necessitates the integration of clean hydrogen as a key solution. To facilitate the required expansion of clean hydrogen production, sustainable water sources are required to support the electrolysis process. Utilizing nontraditional water sources such as water resource recovery facility (WRRF) effluents could potentially alleviate the water constraints and create cobenefits, but the real-world feasibility has not been explored in depth.

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Background: Surgery, chemotherapy, and radiation often have limited utility for advanced metastatic disease in the liver, and despite its promising activity in select cancers, PD-1 blockade therapy similarly has minimal benefit in this setting. Curaxin, CBL0137, is an experimental anti-cancer drug that disrupts the binding of DNA to histones, destabilizes chromatin, and induces Z-DNA formation which may stimulate anti-tumor immune responses.

Methods: Murine cell lines of colon (CT26) and breast (4T1) cancer were interrogated for survival and CBL0137-associated DNA changes in vitro.

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Article Synopsis
  • Variations in access to drugs globally make it hard to assess the effectiveness of modern treatments for patients with relapsed and refractory mature T-cell and NK-cell lymphomas in a study of 925 patients.
  • * The study found that relapsed lymphoma patients had better overall survival rates compared to refractory patients after second-line treatment, with several factors identified as predictors of survival.
  • * A new prognostic index (PIRT) categorizes patients based on risk factors into low, intermediate, or high risk, impacting 3-year overall survival rates, and highlights the superior outcomes of novel therapies compared to traditional chemotherapy.
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Background: Approximately 15% of Lyme disease cases involve the nervous system and are termed "neuroborreliosis." A rare complication of neuroborreliosis is idiopathic intracranial hypertension with resulting neurological deterioration. There are very few reports of this in the literature, most of which consist of case reports and small case series.

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This case study demonstrates how knowledge of degradation products together with predictions can establish a lean stability strategy using the accelerated predictive stability (APS) principles. Applying all available data for AZD4831, (R)-1-(2-(1-aminoethyl)-4-chlorobenzyl)-2-thioxo-2,3-dihydro-1H-pyrrolo[3,2-d]pyrimidin-4(5H)-one, a reliable predictive model was developed despite minor differences in technical batch tablet compositions. Early forced degradation studies were performed to map potential degradation pathways.

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Autoantigen-specific immunotherapy using peptides offers a more targeted approach to treat autoimmune diseases, but clinical implementation has been challenging. We previously showed that multivalent delivery of peptides as soluble antigen arrays (SAgAs) efficiently protects against spontaneous autoimmune diabetes in the non-obese diabetic (NOD) mouse model. Here, we compared the efficacy, safety, and mechanisms of action of SAgAs versus free peptides.

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Men or mice with homozygous serine/threonine kinase 33 () mutations are sterile owing to defective sperm morphology and motility. To chemically evaluate STK33 for male contraception with STK33-specific inhibitors, we screened our multibillion-compound collection of DNA-encoded chemical libraries, uncovered potent STK33-specific inhibitors, determined the STK33 kinase domain structure bound with a truncated hit CDD-2211, and generated an optimized hit CDD-2807 that demonstrates nanomolar cellular potency (half-maximal inhibitory concentration = 9.2 nanomolar) and favorable metabolic stability.

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Background: Preclinical models recapitulating the metastatic phenotypes are essential for developing the next-generation therapies for metastatic prostate cancer (mPC). We aimed to establish a cohort of clinically relevant mPC models, particularly androgen receptor positive (AR) bone metastasis models, from LuCaP patient-derived xenografts (PDX) that reflect the heterogeneity and complexity of mPC.

Methods: PDX tumors were dissociated into single cells, modified to express luciferase, and were inoculated into NSG mice via intracardiac injection.

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To resist lineage-dependent therapies such as androgen receptor inhibition, prostate luminal epithelial adenocarcinoma cells often adopt a stem-like state resulting in lineage plasticity and phenotypic heterogeneity. Castrate-resistant prostate adenocarcinoma can transition to neuroendocrine (NE) and occasionally to amphicrine, co-expressed luminal and NE, phenotypes. We developed castrate-resistant prostate cancer (CRPC) patient-derived organoid models that preserve heterogeneity of the originating tumor, including an amphicrine model displaying a range of luminal and NE phenotypes.

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Patients diagnosed with localized high-risk prostate cancer have higher rates of recurrence, and the introduction of neoadjuvant intensive hormonal therapies seeks to treat occult micrometastatic disease by their addition to definitive treatment. Sufficient profiling of baseline disease has remained a challenge in enabling the in-depth assessment of phenotypes associated with exceptional vs. poor pathologic responses after treatment.

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ZNRF3 and RNF43 are closely related transmembrane E3 ubiquitin ligases with significant roles in development and cancer. Conventionally, their biological functions have been associated with regulating WNT signaling receptor ubiquitination and degradation. However, our proteogenomic studies have revealed EGFR as the protein most negatively correlated with mRNA levels in multiple human cancers.

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: Multimodal imaging provides important pharmacokinetic and dosimetry information during nanomedicine development and optimization. However, accurate quantitation is time-consuming, resource intensive, and requires anatomical expertise. : We present NanoMASK: a 3D U-Net adapted deep learning tool capable of rapid, automatic organ segmentation of multimodal imaging data that can output key clinical dosimetry metrics without manual intervention.

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Introduction: Fatty infiltration (FI) of the rotator cuff has important clinical implications. Quantitatively estimating FI using ultrasound (US) has considerable benefits for assessing FI in a non-invasive, accessible manner. This research investigated whether FI of the supraspinatus (SS) and infraspinatus (IS), estimated using US was related to intramuscular fat fractions measured from magnetic resonance images (MRI).

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Article Synopsis
  • Sjögren's Disease (SjD) is an autoimmune disorder affecting salivary glands, but the cause and effective treatments are still unclear.
  • Researchers used advanced techniques like single-cell and spatial transcriptomics to analyze both healthy and diseased salivary glands, revealing key differences in cellular composition.
  • The study found that specific immune cells, particularly +CD8 T cells, are involved in damaging secretory cell types in SjD, highlighting the complex immune interactions that contribute to the disease's progression.
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Triple-negative breast cancer (TNBC) has a high risk for recurrence and metastasis. We studied the effectiveness of Auger electron (AE) radioimmunotherapy (RIT) with antiepidermal growth factor receptor (EGFR) panitumumab conjugated with DOTA complexed to In ([In]In-DOTA-panitumumab) for preventing metastatic progression after local treatment of 231/LM2-4 Luc+ human TNBC tumors in the mammary fat pad of NRG mice. Prior to RIT, the primary tumor was resected, and tumor margins were treated with X-irradiation (XRT; 5 days × 6 Gy/d).

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Background: The COVID-19 pandemic has caused an international healthcare crisis and produced a large healthcare burden. Diabetes mellitus (DM) is a common disease that can be controlled via pharmacologic agents; however, many patients have poor glycemic control, leading to disease-related complications. DM has been reported in the literature to be associated with increasing morbidity and mortality in COVID-19 patients.

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Background: Early reports have indicated a relationship between ABO and rhesus blood group types and infection with SARS-CoV-2. We aim to examine blood group type associations with COVID-19 mortality and disease severity.

Methods: This is a retrospective chart review of patients ages 18 years or older admitted to the hospital with COVID-19 between January 2020 and December 2021.

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Antibody-drug conjugates (ADCs) are a promising targeted cancer therapy; however, patient selection based solely on target antigen expression without consideration for cytotoxic payload vulnerabilities has plateaued clinical benefits. Biomarkers to capture patients who might benefit from specific ADCs have not been systematically determined for any cancer. We present a comprehensive therapeutic and biomarker analysis of a B7H3-ADC with pyrrolobenzodiazepine(PBD) payload in 26 treatment-resistant, metastatic prostate cancer (mPC) models.

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Objective: This study aims to examine the impact of the COVID-19 pandemic on breast cancer screening in an underserved population, identify patient barriers, and discuss strategies to promote the importance of screening. Methods/operations: The Rutgers New Jersey Medical School Screening Access of Value for Essex (SAVE) program delivers cancer prevention services to the most vulnerable population in Essex County, New Jersey. The SAVE program was shut down from March 2020 to June 2020 due to COVID-19.

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Objective: This study aimed to determine if a disproportionate number of radiologists practice in high-income versus low-income counties in New Jersey (NJ), identify which vulnerable populations are most in need of more radiologists, and discuss how these relative differences can ultimately influence health outcomes.

Methods: The NJ Health Care Profile, a database overseen and maintained by the Division of Consumer Affairs, was queried for all actively practicing radiologists within the state of NJ. These results were grouped into diagnostic and interventional radiologists followed by further stratification of physicians based on the counties where they currently practice.

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Distant metastasis is the major cause of cancer-related deaths in men with prostate cancer (PCa). An in vivo functional screen was used to identify microRNAs (miRNAs) regulating metastatic dissemination of PCa cells. PC3 cells transduced with pooled miRZiP™ lentivirus library (anti-miRNAs) were injected intraprostatic to 13 NSG mice followed by targeted barcode/anti-miR sequencing.

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We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity.

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