Publications by authors named "Irene Pak"

Background: Telehealth was an important strategy for maintaining continuity of cancer care during the coronavirus pandemic and has continued to play a role in outpatient care; however, it is unknown whether services are equally available across cancer hospitals.

Objective: This study aimed to assess telehealth availability at cancer hospitals for new and established patients with common cancers to contextualize the impact of access barriers to technology on overall access to health care.

Methods: We conducted a national cross-sectional secret shopper study from June to November 2020 to assess telehealth availability at cancer hospitals for new and established patients with colorectal, breast, and skin (melanoma) cancer.

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CD44 is an extracellular matrix receptor implicated in cancer progression. CD44 increases the invasibility of skin (SF) and endometrial stromal fibroblasts (ESF) by cancer and trophoblast cells. We reasoned that the evolution of CD44 expression can affect both, the fetal-maternal interaction through CD44 in ESF as well as vulnerability to malignant cancer through expression in SF.

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Evolutionary profiling has been largely limited to the nucleotide level. Using consistent proteomic methods, we quantified proteomic and phosphoproteomic layers in fibroblasts from 11 common mammalian species, with transcriptomes as reference. Covariation analysis indicates that transcript and protein expression levels and variabilities across mammals remarkably follow functional role, with extracellular matrix-associated expression being the most variable, demonstrating strong transcriptome-proteome coevolution.

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Importance: Although there have been significant increases in the number of US residents insured through Medicaid, the ability of patients with Medicaid to access cancer care services is less well known.

Objective: To assess facility-level acceptance of Medicaid insurance among patients diagnosed with common cancers.

Design, Setting, And Participants: This national cross-sectional secret shopper study was conducted in 2020 in a random sample of Commission on Cancer-accredited facilities in the United States using a simulated cohort of Medicaid-insured adult patients with colorectal, breast, kidney, and melanoma skin cancer.

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Lower clearance of immune checkpoint inhibitors is a predictor of improved overall survival (OS) in patients with advanced cancer. We investigated a novel approach using machine learning to identify a baseline composite cytokine signature via clearance, which, in turn, could be associated with OS in advanced melanoma. Peripheral nivolumab clearance and cytokine data from patients treated with nivolumab in two phase III studies (n = 468 (pooled)) and another phase III study (n = 158) were used for machine-learning model development and validation, respectively.

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Purpose: The success of checkpoint blockade has led to a significant increase in the development of a broad range of immunomodulatory molecules for the treatment of cancer, including agonists against T-cell costimulatory receptors, such as OX40. Unlike checkpoint blockade, where complete and sustained receptor saturation may be required for maximal activity, the optimal dosing regimen and receptor occupancy for agonist agents is less well understood and requires further study.

Experimental Design: We integrated both preclinical and clinical biomarker data sets centered on dose, exposure, receptor occupancy, receptor engagement, and downstream pharmacodynamic changes to model the optimal dose and schedule for the OX40 agonist antibody BMS-986178 alone and in combination with checkpoint blockade.

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Purpose: A detailed analysis of hepatitis C virus (HCV) resistance-associated substitutions (RASs) is required to understand why people fail direct-acting antiviral therapies. This study was conducted to assess RASs in an analysis of 2 trials evaluating the second-generation NS3/4A protease inhibitor grazoprevir (GZR) in combination with peginterferon/ribavirin.

Patients And Methods: From a total of 113 participants with HCV genotype 1 infection, RASs were evaluated in 25 patients who relapsed and 6 patients with on-treatment virologic breakthrough using consensus Sanger and clonal sequence analysis of NS3/NS4a genes, with in vitro testing of replicon mutants.

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Dengue is one of the most important mosquito-borne infections accounting for severe morbidity and mortality worldwide. Recently, the tetravalent chimeric live attenuated Dengue vaccine Dengvaxia® was approved for use in several dengue endemic countries. In general, live attenuated vaccines (LAV) are very efficacious and offer long-lasting immunity against virus-induced disease.

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Elbasvir is an investigational NS5A inhibitor with in vitro activity against multiple HCV genotypes. Antiviral activity of elbasvir was measured in replicons derived from wild-type or resistant variants of genotypes 1a, 1b, and 3. The barrier to resistance was assessed by the number of resistant colonies selected by exposure to various elbasvir concentrations.

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Functional T-cell epitope discovery is a key process for the development of novel immunotherapies, particularly for cancer immunology. In silico epitope prediction is a common strategy to try to achieve this objective. However, this approach suffers from a significant rate of false-negative results and epitope ranking lists that often are not validated by practical experience.

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The aim of this study was to evaluate the efficacy of genetic vaccination with rat ErbB2 antigen in a therapeutic setting for the BALB-neuT mouse model of mammary carcinoma and to establish immunological correlates with vaccine efficacy. To define an early therapeutic setting we performed imaging studies of mouse mammary glands with a high-frequency ultrasound system that allowed the diagnosis of tumor lesions before they become palpable, starting from week 13 after mouse births. An intensive immunization protocol of vaccination was implemented at this stage, consisting of four weekly DNA injections with electroporation followed by two injections of adenovirus carrying the codon usage-optimized cDNA encoding the extracellular-transmembrane domain of rat ErbB2.

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