Implementation of a formalized evaluation and planning tool to improve pediatric oncology outcomes in Kenya.

Background: Survival from pediatric cancers in low middle-income countries is often very low compared to that of high-income countries due to multifactorial etiologies, including late presentation, delayed diagnosis, difficulty with accessing healthcare, drug unavailability, and treatment abandonment. The St. Jude Pediatric Oncology Facility Integrated Local Evaluation Tool (PrOFILE) was developed to map and evaluate childhood cancer healthcare delivery in individual institutions and entire countries, identifying the strengths and weaknesses, as well as opportunities for advancement of care.

Pediatric renal tumor epidemiology: Global perspectives, progress, and challenges.

Pediatric renal tumors account for 3%-11% of childhood cancers, the most common of which is Wilms tumor or nephroblastoma. Epidemiology plays a key role in cancer prevention and control by describing the distribution of cancer and discovering risk factors for cancer. Large pediatric research consortium trials have led to a clearer understanding of pediatric renal tumors, identification of risk factors, and development of more risk-adapted therapies.

Development and pilot testing of PROACTIVE: A pediatric onco-critical care capacity and quality assessment tool for resource-limited settings.

Background: Nearly 90% children with cancer reside in low- and middle-income countries, which face multiple challenges delivering high-quality pediatric onco-critical care (POCC). We recently identified POCC quality and capacity indicators for PROACTIVE (PediatRic Oncology cApaCity assessment Tool for IntensiVe carE), a tool that evaluates strengths and limitations in POCC services. This study describes pilot testing of PROACTIVE, development of center-specific reports, and identification of common POCC challenges.

"Money was the problem": Caregivers' self-reported reasons for abandoning their children's cancer treatment in southwest Uganda.

Introduction: Treatment abandonment contributes significantly to poor survival of children with cancer in low- and middle-income countries (LMIC). In order to inform an approach to this problem, we investigated why caregivers withdraw their children from treatment.

Methods: In a qualitative study, carried out in October and November 2020, in-depth interviews were conducted with caregivers of children who had abandoned cancer treatment at the Pediatric Cancer Unit of Mbarara Regional Referral Hospital in south-western Uganda.

Pediatric Solid Tumors in Resource-Constrained Settings: A Review of Available Evidence on Management, Outcomes, and Barriers to Care.

International disparities in outcomes from pediatric solid tumors remain striking. Herein, we review the current literature regarding management, outcomes, and barriers to care for pediatric solid tumors in low- and middle-income countries (LMICs). In sub-Saharan Africa, Wilms Tumor represents the most commonly encountered solid tumor of childhood and has been the primary target of recent efforts to improve outcomes in low-resource settings.

Chronic radiation exposure of neuroblastoma cells reduces nMYC copy number.

Neuroblastoma accounts for >15% of cancer-associated mortalities of children in the USA. Despite aggressive treatment regimens, the long-term survival for these children remains <40%. The identification of v-Myc avian myelocytomatosis viral oncogene neuroblastoma-derived homolog (nMYC) gene amplification during diagnosis is associated with poor prognosis in neuroblastoma.

SPARC overexpression suppresses radiation-induced HSP27 and induces the collapse of mitochondrial Δψ in neuroblastoma cells.

Neuroblastoma is the cause of >15% of cancer-associated mortality in children in the USA. Despite aggressive treatment regimens, the long-term survival rate for these children remains at <40%. The current study demonstrates that secreted protein acidic and rich in cysteine (SPARC) suppresses radiation-induced expression of heat shock protein 27 (HSP27) and suppresses mitochondrial membrane potential (Δψ) in neuroblastoma cells.

Genetic and chromosomal alterations in Kenyan Wilms Tumor.

Wilms tumor (WT) is the most common childhood kidney cancer worldwide and poses a cancer health disparity to black children of sub-Saharan African ancestry. Although overall survival from WT at 5 years exceeds 90% in developed countries, this pediatric cancer is alarmingly lethal in sub-Saharan Africa and specifically in Kenya (36% survival at 2 years). Although multiple barriers to adequate WT therapy contribute to this dismal outcome, we hypothesized that a uniquely aggressive and treatment-resistant biology compromises survival further.

Risk factors for abandonment of Wilms tumor therapy in Kenya.

Background: Survival from Wilms tumor (WT) in sub-Saharan Africa remains dismal as a result of on-therapy mortality and treatment abandonment. Review of patients diagnosed from 2008 to 2011 in our Kenyan Wilms Tumor Registry showed a loss to follow up (LTFU) rate approaching 50%. The purpose of this study was to trace those LTFU, estimate the survival rate, and identify risk factors for treatment abandonment.

Race disparities in peptide profiles of North American and Kenyan Wilms tumor specimens.

Background: Wilms tumor (WT) is the most common childhood kidney cancer worldwide and arises in children of black African ancestry with greater frequency and severity than other race groups. A biologic basis for this pediatric cancer disparity has not been previously determined. We hypothesized that unique molecular fingerprints might underlie the variable incidence and distinct disease characteristics of WT observed between race groups.

Aberrant activation, nuclear localization, and phosphorylation of Yes-associated protein-1 in the embryonic kidney and Wilms tumor.

Background: The Yes-associated-protein-1 (YAP1) is a novel, direct regulator of stem cell genes both in development and cancer. FAT4 is an upstream regulator that induces YAP1 cytosolic sequestering by phosphorylation (p-Ser 127) and therefore inhibits YAP1-dependent cellular proliferation. We hypothesized that loss of FAT4 signaling would result in expansion of the nephron progenitor population in kidney development and that YAP1 subcellular localization would be dysregulated in Wilms tumor (WT), an embryonal malignancy that retains gene expression profiles and histologic features reminiscent of the embryonic kidney.

CITED1 expression in liver development and hepatoblastoma.

Hepatoblastoma, the most common pediatric liver cancer, consists of epithelial mixed embryonal/fetal (EMEF) and pure fetal histologic subtypes, with the latter exhibiting a more favorable prognosis. Few embryonal histology markers that yield insight into the biologic basis for this prognostic discrepancy exist. CBP/P-300 interacting transactivator 1 (CITED1), a transcriptional co-activator, is expressed in the self-renewing nephron progenitor population of the developing kidney and broadly in its malignant analog, Wilms tumor (WT).