Publications by authors named "Victoria Koch"
Background: Venous thromboembolism (VTE) is a frequent complication of childhood acute lymphoblastic leukemia (ALL).
Objectives: We aimed to identify molecular markers and signatures of leukemia microenvironment associated with VTE in childhood ALL, by dual-omics approach of gene expression (GEP) and DNA-methylation profiling.
Patients/methods: Eligible children were aged 1-21 years old with newly diagnosed ALL enrolled on the Dana Farber Cancer Institute 16-001 trial with available RNA sequencing data from bone marrow at diagnosis.
In 2015, the oncolytic herpes simplex virus 1 (HSV-1) T-VEC (talimogene laherparepvec) was approved for intratumoral injection in non-resectable malignant melanoma. To determine whether viral replication is required for oncolytic activity, we compared replication-deficient HSV-1 d106S with replication-competent T-VEC. High infectious doses of HSV-1 d106S killed melanoma (n = 10), head-and-neck squamous cell carcinoma (n = 11), and chondrosarcoma cell lines (n = 2) significantly faster than T-VEC as measured by MTT metabolic activity, while low doses of T-VEC were more effective over time.
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- The study explores how household material hardship (HMH), which refers to issues like food and housing insecurity, impacts parental psychological distress during their child's cancer treatment.
- Data from 375 parents of children with acute lymphoblastic leukemia showed that those experiencing HMH had more than twice the odds of severe psychological distress at the beginning of treatment, and over five times the odds six months in.
- The findings highlight the need for targeted interventions to support parents facing HMH, as their psychological well-being is significantly affected during their child's treatment.
Oral chemotherapy nonadherence is a challenge in clinical oncology. During therapy for acute lymphoblastic leukemia (ALL), poor adherence to 6-mercaptopurine (6MP) increases relapse risk. Clinically significant nonadherence is reported in 30% of children treated for ALL on Children's Oncology Group (COG) trials.
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- Social determinants of health (SDoH) significantly impact cancer outcomes, yet data collection on SDoH is largely absent from oncology clinical trials.
- A study involving a pediatric oncology trial found that a high percentage (87.5%) of participants agreed to take part in an SDoH investigation, with most completing baseline surveys and maintaining strong response rates over two years.
- The results demonstrate that incorporating SDoH data collection into oncology trials is both feasible and essential for improving health equity and understanding health disparities.
T cell-directed cancer immunotherapy often fails to generate lasting tumor control. Harnessing additional effectors of the immune response against tumors may strengthen the clinical benefit of immunotherapies. Here, we demonstrate that therapeutic targeting of the interferon-γ (IFN-γ)-interleukin-12 (IL-12) pathway relies on the ability of a population of natural killer (NK) cells with tissue-resident traits to orchestrate an antitumor microenvironment.
View Article and Find Full Text PDFThe relevance of extracellular magnesium in cellular immunity remains largely unknown. Here, we show that the co-stimulatory cell-surface molecule LFA-1 requires magnesium to adopt its active conformation on CD8 T cells, thereby augmenting calcium flux, signal transduction, metabolic reprogramming, immune synapse formation, and, as a consequence, specific cytotoxicity. Accordingly, magnesium-sufficiency sensed via LFA-1 translated to the superior performance of pathogen- and tumor-specific T cells, enhanced effectiveness of bi-specific T cell engaging antibodies, and improved CAR T cell function.
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- RNA sequencing (RNA-seq) is being tested in a phase 3 clinical trial for children with newly diagnosed acute lymphoblastic leukemia (ALL) to identify hidden genetic alterations and improve diagnosis.
- In a study with 173 patients, RNA-seq successfully detected at least one genetic alteration in 91% of cases, verifying its accuracy against traditional methods and uncovering additional significant gene fusions.
- The results from RNA-seq enabled better classification of B-cell ALL subgroups and identified numerous mutations, highlighting its potential to enhance treatment strategies and patient outcomes compared to conventional analyses.
Purpose: Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia (ALL) Consortium Protocol 11-001 assessed efficacy and toxicity of calaspargase pegol (calaspargase), a novel pegylated asparaginase formulation with longer half-life, compared with the standard formulation pegaspargase.
Methods: Patients age 1 to ≤ 21 years with newly diagnosed ALL or lymphoblastic lymphoma were randomly assigned to intravenous pegaspargase or calaspargase, 2,500 IU/m/dose. Patients received one induction dose.
The 18 kDa translocator protein (TSPO) is an evolutionary conserved cholesterol binding protein localized in the outer mitochondrial membrane. It has been implicated in the regulation of various cellular processes including oxidative stress, proliferation, apoptosis, and steroid hormone biosynthesis. Since the expression of TSPO in activated microglia is upregulated in various neuroinflammatory and neurodegenerative disorders, we set out to examine the role of TSPO in an immortalized human microglia C20 cell line.
View Article and Find Full Text PDFBackground And Purpose: Rehabilitation care after stroke is highly variable and increasingly shorter in duration. The effect of therapeutic exercise on impairments and functional limitations after stroke is not clear. The objective of this study was to determine whether a structured, progressive, physiologically based exercise program for subacute stroke produces gains greater than those attributable to spontaneous recovery and usual care.
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