Modulation of Stemness and Differentiation Regulators by Valproic Acid in Medulloblastoma Neurospheres.

Changes in epigenetic processes such as histone acetylation are proposed as key events influencing cancer cell function and the initiation and progression of pediatric brain tumors. Valproic acid (VPA) is an antiepileptic drug that acts partially by inhibiting histone deacetylases (HDACs) and could be repurposed as an epigenetic anticancer therapy. Here, we show that VPA reduced medulloblastoma (MB) cell viability and led to cell cycle arrest.

Results of the Latin American Pediatric Oncology Group (GALOP-2011) Trial for Patients With Localized Ewing Sarcoma: A Multicentric Study of Interval-Compressed Multiagent Chemotherapy.

Background: GALOP investigators developed a prospective cooperative protocol for localized Ewing sarcoma (ES) incorporating interval-compressed chemotherapy (VDC/IE, vincristine, doxorubicin, cyclophosphamide/ifosfamide and etoposide). After completing conventional treatment, patients were randomized to 1 year of metronomic chemotherapy (vinblastine and cyclophosphamide).

Methods: Phase III randomized prospective trial.

Genetic Variants Influence the Severity of Oral Mucositis in Pediatric Osteosarcoma Patients.

Background: The variability in patients' risk of oral mucositis (OM) has been, in part, attributed to differences in host genomics. The aim better define the role of genomics as an OM risk by investigating the association between genetic variants and the presence and severity of OM in pediatric patients with osteosarcoma (OS) undergoing chemotherapy (CT).

Methods: A longitudinal observational retrospective study was conducted.

Anticipating Leucovorin Rescue Therapy in Patients with Osteosarcoma through Methotrexate Population Pharmacokinetic Model.

Methotrexate (MTX), which presents high inter-individual variability, is part of the Brazilian Osteosarcoma Treatment Group (BOTG) protocol. This work aimed to develop a MTX population pharmacokinetic model (POPPK) for Brazilian children with osteosarcoma (OS) following the BOTG protocol to guide rescue therapy and avoid toxicity. The model was developed in NONMEM 7.

Stemness and Cell Cycle Regulators and Their Modulation by Retinoic Acid in Ewing Sarcoma.

Retinoic acid (RA) regulates stemness and differentiation in human embryonic stem cells (ESCs). Ewing sarcoma (ES) is a pediatric tumor that may arise from the abnormal development of ESCs. Here we show that RA impairs the viability of SK-ES-1 ES cells and affects the cell cycle.

Histone Methyltransferases G9a/ and GLP/ Are Associated with Cell Viability and Poorer Prognosis in Neuroblastoma and Ewing Sarcoma.

Changes in epigenetic programming have been proposed as being key events in the initiation and progression of childhood cancers. HMT euchromatic histone lysine methyltransferase 2 (G9a, EHMT2), which is encoded by the () gene, as well as its related protein GLP, which is encoded by the / gene, participate in epigenetic regulation by contributing to a transcriptionally repressed chromatin state. G9a/GLP activation has been reported in several cancer types.

Population Pharmacokinetic Model of Methotrexate in Brazilian Pediatric Patients with Acute Lymphoblastic Leukemia.

Objectives: Methotrexate (MTX) is subject to therapeutic drug monitoring because of its high pharmacokinetic variability and safety risk outside the therapeutic window. This study aimed to develop a population pharmacokinetic model (popPK) of MTX for Brazilian pediatric acute lymphoblastic leukemia (ALL) patients who attended the Hospital de Clínicas de Porto Alegre, Brazil.

Methods: The model was developed using NONMEM 7.

Targeting the epigenome of cancer stem cells in pediatric nervous system tumors.

Medulloblastoma, neuroblastoma, and pediatric glioma account for almost 30% of all cases of pediatric cancers. Recent evidence indicates that pediatric nervous system tumors originate from stem or progenitor cells and present a subpopulation of cells with highly tumorigenic and stem cell-like features. These cancer stem cells play a role in initiation, progression, and resistance to treatment of pediatric nervous system tumors.

Cancer Stem Cells and Chemoresistance in Ewing Sarcoma.

Resistance to chemotherapy poses a major challenge for cancer treatment. Reactivating a stem cell program resembling that seen in embryonic development can lead cancer cells to acquire a stem-cell phenotype characterized by expression of stemness genes, pluripotency, high self-renewal ability, and tumor-initiating capability. These cancer stem cells (CSCs) are usually resistant to anticancer drugs and are likely involved in treatment failure in many cancer types.

Illness perceptions in childhood cancer survivor and caregivers' dyads.

Unlabelled: Surviving childhood cancer is a difficult experience for children and their caregivers, it can produce long-term emotional distress. Illness perceptions refer to the way people understand the different aspects related to illness from their individual and collective experiences.

Objective: to compare the illness perceptions of adolescent childhood cancer survivors and their caregivers and examine the relationship between illness perception of childhood cancer survivors, their caregivers, and sociodemographic, illness, and treatment variables.

Investigation of oral and general health status and IL-1β gene polymorphism as risk factors for oral mucositis in hematopoietic stem cell transplantation patients.

The aim of the present study was to analyze the relationship of OM with possible risk factors such as oral health condition, immunological status and IL-1β profile in patients submitted to hematopoietic stem cell transplantation (HSCT). Fifty-four individuals submitted to HSCT were included. All patients received previous dental treatment and photobiomodulation (PBM) as the institutional OM preventive protocol.

Incidence and risk factors for oral mucositis in pediatric patients receiving chemotherapy.

Purpose: To investigate the incidence and risk factors for oral mucositis (OM) in patients with childhood cancer undergoing chemotherapy.

Methods: Eight hundred and twenty-nine cycles of chemotherapy were evaluated in 112 patients with childhood cancer undergoing chemotherapy. Chemotherapy protocol, hematological, hepatic, and renal function parameters were collected and compared to presence and severity of OM, as graded by the World Health Organization (WHO) scale.

Risk factors associated with the development of oral mucositis in pediatric oncology patients: Systematic review and meta-analysis.

Objectives: Oral mucositis (OM) is an acute toxicity related to cancer treatment. This systematic review aimed to identify potential risk factors associated with the development of OM in pediatric cancer patients.

Methods: A search was performed in four electronic databases to identify studies that analyzed risk factors for OM in pediatric cancer patients.

The effect of hospital care volume on overall survival of children with cancer in Southern Brazil.

Purpose: The purpose of this study was to analyze the effect of hospital care volume on the overall survival of children with cancer in Southern Brazil.

Patients And Methods: We performed a retrospective cohort study of 1378 cancer patients aged 0-19 years, diagnosed with cancer between August 1, 2009 and December 31, 2015 in Rio Grande do Sul, who received hospital treatment in institutions affiliated with the Universal Health Care System (Sistema Único de Saúde [SUS]).

Results: Most children and adolescents were male (56.

Assessing the Relationship between PTSS in Childhood Cancer Survivors and Their Caregivers and Their Quality of Life.

Childhood cancer is a traumatic experience for survivors and their families. The experience of this disease affects survivors' and families' quality of life, even years after it occurs. The purpose of the present study was to assess if the caregivers' posttraumatic stress symptoms mediated the associations between survivors' posttraumatic stress symptoms and caregivers' quality of life, in a sample of 46 dyads of caregivers and childhood cancer survivors.

Neurotrophin Signaling in Medulloblastoma.

Neurotrophins are a family of secreted proteins that act by binding to tropomyosin receptor kinase (Trk) or p75NTR receptors to regulate nervous system development and plasticity. Increasing evidence indicates that neurotrophins and their receptors in cancer cells play a role in tumor growth and resistance to treatment. In this review, we summarize evidence indicating that neurotrophin signaling influences medulloblastoma (MB), the most common type of malignant brain cancer afflicting children.

Oral mucositis in childhood cancer patients receiving high-dose methotrexate: Prevalence, relationship with other toxicities and methotrexate elimination.

Background: Oral mucositis (OM) is one of the main adverse effects of the chemotherapeutic agent methotrexate (MTX).

Aim: To evaluate the relationship of OM with MTX metabolism time and other toxicities in childhood, cancer patients receiving high-dose of methotrexate (HD-MTX).

Design: Seventy-seven childhood patients receiving HD-MTX for treatment of leukaemia, osteosarcoma or lymphoma were evaluated.

A consensus document for the clinical management of invasive fungal diseases in pediatric patients with hematologic cancer and/or undergoing hematopoietic stem cell transplantation in Brazilian medical centers.

In the present paper we summarize the suggestions of a multidisciplinary group including experts in pediatric oncology and infectious diseases who reviewed the medical literature to elaborate a consensus document (CD) for the diagnosis and clinical management of invasive fungal diseases (IFDs) in children with hematologic cancer and those who underwent hematopoietic stem-cell transplantation. All major multicenter studies designed to characterize the epidemiology of IFDs in children with cancer, as well as all randomized clinical trials addressing empirical and targeted antifungal therapy were reviewed. In the absence of randomized clinical trials, the best evidence available to support the recommendations were selected.

Activation of BDNF/TrkB/Akt pathway is associated with aggressiveness and unfavorable survival in oral squamous cell carcinoma.

Objectives: To evaluate the expression of brain-derived neurotrophic factor (BDNF), its tyrosine kinase receptor B (TrkB), and two downstream targets of this pathway, Akt and ribosomal protein S6 (RPS6), in normal oral mucosa (NOM), oral leukoplakia (OL), and oral squamous cell carcinoma (OSCC) and correlate this expression with OSCC patients' outcomes, cell senescence, and "stemness" profile.

Materials And Methods: Ten cases of NOM, 32 OL, and 72 primary OSCC were included. Immunohistochemical analysis for BDNF, TrkB, p-TrkB, p-Akt, and p-RPS6 was performed.

Antitumor Activities and Cellular Changes Induced by TrkB Inhibition in Medulloblastoma.

Neurotrophins are critically involved in regulating normal neural development and plasticity. Brain-derived neurotrophic factor (BDNF), a neurotrophin that acts by binding to the tropomyosin receptor kinase B (TrkB) receptor, has also been implicated in the progression of several types of cancer. However, its role in medulloblastoma (MB), the most common type of malignant brain tumor afflicting children, remains unclear.

Expression of neurotrophins and their receptors in primary osteosarcoma.

Objective: to determine the expression of neurotrophins and their tyrosine-kinase receptors in patients with osteosarcoma (OS) and their correlation with clinical outcomes.

Methods: we applied immunohistochemistry to biopsy specimens of patients consecutively treated for primary OS at a single institution between 2002 and 2015, analyzing them for expression receptors of tyrosine kinase A and B (TrKA and TrKB), neural growth factor (NGF) and brain derived neurotrophic factor (BDNF). Independently, two pathologists classified the immunohistochemical markers as negative (negative or weak focal) or positive (moderate focal/diffuse or strong focal/diffuse).