Prospective assessment of risk biomarkers of sinusoidal obstruction syndrome after hematopoietic cell transplantation.

BACKGROUNDCurrently, no laboratory tests exist to stratify for the risk of developing sinusoidal obstruction syndrome (SOS), an early endothelial complication after hematopoietic cell transplantation (HCT). Risk biomarkers of SOS have not been verified in a prospective cohort accounting for differences between practices across institutions. Herein, we aimed to define risk groups for SOS occurrence using 3 proteins: L-ficolin, hyaluronic acid (HA), and stimulation 2 (ST2).

Identify potential driver genes for PAX-FOXO1 fusion-negative rhabdomyosarcoma through frequent gene co-expression network mining.

Background: Rhabdomyosarcoma (RMS) is a soft tissue sarcoma usually originated from skeletal muscle. Currently, RMS classification based on PAX-FOXO1 fusion is widely adopted. However, compared to relatively clear understanding of the tumorigenesis in the fusion-positive RMS, little is known for that in fusion-negative RMS (FN-RMS).

Integrative Multi-OMICs Identifies Therapeutic Response Biomarkers and Confirms Fidelity of Clinically Annotated, Serially Passaged Patient-Derived Xenografts Established from Primary and Metastatic Pediatric and AYA Solid Tumors.

Establishment of clinically annotated, molecularly characterized, patient-derived xenografts (PDXs) from treatment-naïve and pretreated patients provides a platform to test precision genomics-guided therapies. An integrated multi-OMICS pipeline was developed to identify cancer-associated pathways and evaluate stability of molecular signatures in a panel of pediatric and AYA PDXs following serial passaging in mice. Original solid tumor samples and their corresponding PDXs were evaluated by whole-genome sequencing, RNA-seq, immunoblotting, pathway enrichment analyses, and the drug−gene interaction database to identify as well as cross-validate actionable targets in patients with sarcomas or Wilms tumors.

A biomarker panel for risk of early respiratory failure following hematopoietic cell transplantation.

Plasma biomarkers associated with respiratory failure (RF) following hematopoietic cell transplantation (HCT) have not been identified. Therefore, we aimed to validate early (7 and 14 days post-HCT) risk biomarkers for RF. Using tandem mass spectrometry, we compared plasma obtained at day 14 post-HCT from 15 patients with RF and 15 patients without RF.

An adolescent rat model of vincristine-induced peripheral neuropathy.

Childhood acute lymphoblastic leukemia (ALL) is a significant clinical problem that can be effectively treated with vincristine, a vinca alkaloid-based chemotherapeutic agent. However, nearly all children receiving vincristine treatment develop vincristine-induced peripheral neuropathy (VIPN). The impact of adolescent vincristine treatment across the lifespan remains poorly understood.

Simultaneous quantification of vincristine and its major M1 metabolite from dried blood spot samples of Kenyan pediatric cancer patients by UPLC-MS/MS.

Vincristine (VCR) is an integral part of chemotherapy regimens in the US and in developing countries. There is a paucity of information about its disposition and optimal therapeutic dosing. VCR is preferentially metabolized to its major M1 metabolite by the polymorphic CYP3A5 enzyme, which may be clinically significant as CYP3A5 expression varies across populations.

Assessment of Pediatric Chemotherapy-Induced Peripheral Neuropathy Using a New Patient-Reported Outcome Measure: The P-CIN.

Chemotherapy-induced peripheral neuropathy (CIPN) is commonly experienced by children receiving neurotoxic chemotherapy. No validated pediatric CIPN patient-reported outcome (PRO) measures exist. To test sensitivity, internal consistency reliability, content and convergent validity, and feasibility of the Pediatric Chemotherapy-Induced Neuropathy (P-CIN), an electronic PRO measure for assessing CIPN in children who received neurotoxic chemotherapy.

Systems Biology Approach Identifies Prognostic Signatures of Poor Overall Survival and Guides the Prioritization of Novel BET-CHK1 Combination Therapy for Osteosarcoma.

Osteosarcoma (OS) patients exhibit poor overall survival, partly due to copy number variations (CNVs) resulting in dysregulated gene expression and therapeutic resistance. To identify actionable prognostic signatures of poor overall survival, we employed a systems biology approach using public databases to integrate CNVs, gene expression, and survival outcomes in pediatric, adolescent, and young adult OS patients. Chromosome 8 was a hotspot for poor prognostic signatures.

A Metabolomics Approach for Early Prediction of Vincristine-Induced Peripheral Neuropathy.

Vincristine is a core chemotherapeutic drug administered to pediatric acute lymphoblastic leukemia patients. Despite its efficacy in treating leukemia, it can lead to severe peripheral neuropathy in a subgroup of the patients. Peripheral neuropathy is a debilitating and painful side-effect that can severely impact an individual's quality of life.

Assessment of ST2 for risk of death following graft-versus-host disease in pediatric and adult age groups.

Assessment of prognostic biomarkers of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (HCT) in the pediatric age group is lacking. To address this need, we conducted a prospective cohort study with 415 patients at 6 centers: 170 were children age 10 years or younger and 245 were patients older than age 10 years (both children and adults were accrued from 2013 to 2018). The following 4 plasma biomarkers were assessed pre-HCT and at days +7, +14, and +21 post-HCT: stimulation-2 (ST2), tumor necrosis factor receptor 1 (TNFR1), regenerating islet-derived protein 3α (REG3α), and interleukin-6 (IL-6).

Obesity as a Potential Risk Factor for Vincristine-induced Peripheral Neuropathy.

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Vincristine is a core chemotherapeutic agent for patients with ALL; unfortunately, ∼78% will develop vincristine-induced peripheral neuropathy (VIPN). VIPN can result in vincristine dose reductions that decrease therapeutic efficacy: making it important to understand which children are at highest risk for VIPN.

Gene Co-Expression Networks Restructured Gene Fusion in Rhabdomyosarcoma Cancers.

Rhabdomyosarcoma is subclassified by the presence or absence of a recurrent chromosome translocation that fuses the and or genes. The fusion protein (FOXO1-PAX3/7) retains both binding domains and becomes a novel and potent transcriptional regulator in rhabdomyosarcoma subtypes. Many studies have characterized and integrated genomic, transcriptomic, and epigenomic differences among rhabdomyosarcoma subtypes that contain the gene fusion and those that do not; however, few investigations have investigated how gene co-expression networks are altered by .

Integration of genomic copy number variations and chemotherapy-response biomarkers in pediatric sarcoma.

Background: While most pediatric sarcomas respond to front-line therapy, some bone sarcomas do not show radiographic response like soft-tissue sarcomas (rhabdomyosarccomas) but do show 90% necrosis. Though, new therapies are urgently needed to improve survival and quality of life in pediatric patients with sarcomas. Complex chromosomal aberrations such as amplifications and deletions of DNA sequences are frequently observed in pediatric sarcomas.

Genetic Variants Associated With Vincristine-Induced Peripheral Neuropathy in Two Populations of Children With Acute Lymphoblastic Leukemia.

Vincristine is one of the core chemotherapy agents used in the treatment of pediatric acute lymphoblastic leukemia (ALL). However, one of the major toxicities resulting from vincristine exposure is vincristine-induced peripheral neuropathy (VIPN). When VIPN results in significant morbidity, the vincristine dose may need to be reduced, thus potentially decreasing the effectiveness of treatment.

CYP3A5 genotype and its impact on vincristine pharmacokinetics and development of neuropathy in Kenyan children with cancer.

Background: Vincristine (VCR) is a critical part of treatment in pediatric malignancies and is associated with dose-dependent peripheral neuropathy (vincristine-induced peripheral neuropathy [VIPN]). Our previous findings show VCR metabolism is regulated by the CYP3A5 gene. Individuals who are low CYP3A5 expressers metabolize VCR slower and experience more severe VIPN as compared to high expressers.

Low serum albumin levels prior to pediatric allogeneic HCT are associated with increased need for critical care interventions and increased 6-month mortality.

Poor nutritional status in HCT patients is a negative prognostic factor. There are no pediatric studies evaluating albumin levels prior to HCT and need for critical care interventions. We hypothesized that pediatric patients with low albumin levels, routinely measured 30 days (±10 days) prior to allogeneic HCT, have a higher risk of critical care interventions in the post-transplant period.

Weight gain and supplemental O : Risk factors during the hematopoietic cell transplant admission in pediatric patients.

Background: Respiratory failure in the pediatric hematopoietic cell transplant (HCT) recipient is the leading cause for admission to the intensive care unit and carries a high mortality rate. The objective of this study is to investigate the association of clinical risk factors with the development of respiratory failure in the pediatric allogeneic HCT recipient.

Procedures: This is a single-center, retrospective review of allogeneic pediatric HCT from 2008 to 2014.

Glutathione-S-transferase P1 may predispose children to a decline in pulmonary function after stem cell transplant.

Rationale: Pulmonary complications after hematopoietic stem cell transplant (SCT) are associated with increased mortality. Genetic markers for those at risk for pulmonary impairment post-SCT have not been widely investigated.

Methods: Forty-nine patients were retrospectively selected from a single institution's biorepository with linked clinical data.

The Immune System in Cancer Pathogenesis: Potential Therapeutic Approaches.

Interplay among immune activation and cancer pathogenesis provides the framework for a novel subspecialty known as immunooncology. In the rapidly evolving field of immunooncology, understanding the tumor-specific immune response enhances understanding of cancer resistance. This review highlights the fundamentals of incorporating precision medicine to discover new immune biomarkers and predictive signatures.

Differential effects of hydrocortisone, prednisone, and dexamethasone on hormonal and pharmacokinetic profiles: a pilot study in children with congenital adrenal hyperplasia.

Background: Little is known about the comparative effects of different glucocorticoids on the adrenal and growth hormone (GH) axes in children with congenital adrenal hyperplasia (CAH). We sought to compare the effects of hydrocortisone (HC), prednisone (PDN), and dexamethasone (DEX) in children with classic CAH and to investigate a potential role of pharmacogenetics.

Methods: Subjects were randomly assigned to three sequential 6-week courses of HC, PDN, and DEX, each followed by evaluation of adrenal hormones, IGF-1, GH, and body mass index (BMI).

Identifying Genetic Variants in Adolescents With Oppositional Defiant Disorders and/or Conduct Disorders: A Brief Report.

Problem: To add to diversity in our state biobank, we explored the feasibility of collecting genetic material from adolescents with oppositional defiant disorder (ODD) and/or conduct disorder (CD) and their family members. We also preliminarily explored genetic factors associated with ODD and/or CD by comparing participant data to 1000 Genome Project data on minor allele frequencies.

Methods: Adolescents with ODD and/or CD and family members provided saliva samples for genetic testing.

Hypoxia-Inducible Factor-1α Regulates CD55 in Airway Epithelium.

Airway epithelial CD55 down-regulation occurs in several hypoxia-associated pulmonary diseases, but the mechanism is unknown. Using in vivo and in vitro assays of pharmacologic inhibition and gene silencing, the current study investigated the role of hypoxia-inducible factor (HIF)-1α in regulating airway epithelial CD55 expression. Hypoxia down-regulated CD55 expression on small-airway epithelial cells in vitro, and in murine lungs in vivo; the latter was associated with local complement activation.

Raising the Level of Nursing Involvement in the National Precision Medicine Initiative: An Example.

Purpose: The Precision Medicine Initiative (PMI) goal of ushering in a new and more effective era of health care that benefits all Americans requires two critical and interdependent components: a cohort assembly of 1 million or more Americans who reflect the diversity of the United States of America and an interdisciplinary workforce that includes nursing. The purpose of this article is to provide an example of nursing involvement in PM, specifically as related to gathering biospecimens (saliva) from vulnerable, understudied adolescents with disruptive behavior disorders and their family members.

Source(s): First, we provide a brief description of important concepts related to PM as well as current roles of nurses in PM.