Assuntos
Mutação em Linhagem Germinativa , Síndrome de Li-Fraumeni , Neoplasias Peritoneais , Proteína Supressora de Tumor p53 , Humanos , Síndrome de Li-Fraumeni/genética , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Proteína Supressora de Tumor p53/genética , Mesotelioma/genética , Mesotelioma/patologia , Feminino , Masculino , CriançaRESUMO
OBJECTIVES: In the etiology of childhood cancers, many genetic and environmental factors play a role. One of these factors could be cigarette smoking, and the main source of tobacco smoke exposure of children is parental smoking. However, establishing a causal relationship between parental smoking and childhood cancers has proven challenging due to difficulties in accurately detecting tobacco smoke exposure METHODS: To address this issue, we used hair cotinine analysis and a questionnaire to get information about tobacco smoke exposures of pediatric cancer patients and healthy children. A total of 104 pediatric cancer patients and 99 healthy children participated in our study. Parental smoking behaviors (pre-conceptional, during pregnancy, and current smoking) and environmental tobacco smoke (ETS) exposures of children are compared. RESULTS: We have found no differences between two groups by means of maternal smoking behaviors. However, the rates of paternal pre-conceptional smoking and smoking during pregnancy were significantly low in cancer patients (p < .05). These data suggest that social desirability bias among fathers of cancer patients may have contributed to this discrepancy. According to questionnaire, cancer patients had significantly lower ETS exposures than healthy children (p < .05). However, ETS exposure assessment through cotinine analysis demonstrated that cancer patients had higher exposure to ETS compared to healthy children (p < .001). CONCLUSION: Our findings provide evidence supporting the potential role of smoking as a risk factor for childhood cancers. This study also revealed that questionnaires could cause biases. We suggest that cotinine analysis along with validated questionnaires can be used to prevent biases in studies of tobacco smoke in the etiology of childhood cancers.
Assuntos
Cotinina , Cabelo , Neoplasias , Poluição por Fumaça de Tabaco , Humanos , Feminino , Poluição por Fumaça de Tabaco/efeitos adversos , Poluição por Fumaça de Tabaco/análise , Masculino , Cotinina/análise , Criança , Inquéritos e Questionários , Neoplasias/etiologia , Neoplasias/epidemiologia , Cabelo/química , Pré-Escolar , Pais , Gravidez , Adulto , Estudos de Casos e Controles , Adolescente , Fumar/efeitos adversos , SeguimentosRESUMO
BACKGROUND: Oxidative stress has a potential role in carcinogenesis. Anti-oxidant enzymes have a neutralizing effect on both cancer initiation and progression. We aimed to assess the oxidant and anti-oxidant levels of pediatric cancer patients and to compare the levels in healthy controls. MATERIALS AND METHODS: The study involved 105 pediatric cancer patients (40 undergoing chemotherapy, 65 survivors) and 40 healthy children. The serum total oxidant status (TOS) and total anti-oxidant status (TAS) were measured. RESULTS: The oxidative stress index was significantly lower in pediatric cancer patients compared to the levels in the controls (0.20 ± 0.07 vs. 0.26 ± 0.10; P = 0.001). The mean serum TAS level was significantly higher in patient groups compared to the level in the control (1.87 ± 0.48 vs. 1.63 ± 0.32 mmol/L, P = 0.001). The TAS level of children with cancer in survivors was also found to be significantly higher compared to the levels in the control group (1.85 ± 0.45 vs. 1.63 ± 0.32 mmol/L, P = 0.005). Radiotherapy, surgery, relapsed disease, presence of metastases, and receiving enteral nutritional support caused no change in the TAS/TOS level. CONCLUSION: It has been revealed for the first time that the serum total anti-oxidant level was high in children undergoing chemotherapy and the survivor group as well. Moreover, the oxidative stress index was low in children with cancer. Longitudinal prospective studies are needed to reveal the alterations in oxidant status among children with cancer.
Assuntos
Antioxidantes , Neoplasias , Criança , Humanos , Antioxidantes/metabolismo , Oxidantes , Estresse Oxidativo , Neoplasias/terapia , Estudos de Casos e ControlesRESUMO
Preserving cells in a functional, non-senescent state is a major goal for extending human healthspans. Model organisms reveal that longevity and senescence are genetically controlled, but how genes control longevity in different mammalian tissues is unknown. Here, we report a new human genetic disease that causes cell senescence, liver and immune dysfunction, and early mortality that results from deficiency of GIMAP5, an evolutionarily conserved GTPase selectively expressed in lymphocytes and endothelial cells. We show that GIMAP5 restricts the pathological accumulation of long-chain ceramides (CERs), thereby regulating longevity. GIMAP5 controls CER abundance by interacting with protein kinase CK2 (CK2), attenuating its ability to activate CER synthases. Inhibition of CK2 and CER synthase rescues GIMAP5-deficient T cells by preventing CER overaccumulation and cell deterioration. Thus, GIMAP5 controls longevity assurance pathways crucial for immune function and healthspan in mammals.
Assuntos
Ceramidas , Proteínas de Ligação ao GTP , Animais , Humanos , Longevidade/genética , Células Endoteliais/metabolismo , Mamíferos/metabolismoRESUMO
BACKGROUND: Long-term survivors of Hodgkin lymphoma (HL) are at risk of developing a range of late effects, with a second malignant neoplasm and cardiovascular diseases being the leading causes of death in these patients. The present study aims to evaluate the late side effects in children with HL. MATERIALS AND METHODS: Out of 53 HL patients, we assessed the long-term effects of childhood HL survivors (HLSs; n = 50) diagnosed between 1998 and 2019. Patient data related to chronic health conditions, and sociodemographic characteristics were compared with their siblings (n = 56). RESULTS: The cumulative overall survival (OS) at 1, 5, and 10 years from diagnosis was 98.1 ± 1.9%, 93.3 ± 3.8%, and 93.3 ± 3.8%, respectively. Groups of HLSs and their siblings were matched according to age and gender. Compared with siblings, survivors had will be changed as 'a higher frequency of nephrotoxicity (P = 0.02)', cardiotoxicity (P = 0.12), thyroid dysfunction (P = 0.001), health care service usage (P < 0.01), limitation of physical function (P = 0.01), and pulmonary disease (P = 0.01). The control group of siblings had a higher incidence of marital status (P < 0.01), parenthood (P = 0.01), and smoking habit (P = 0.03). Thyroid dysfunction was associated with neck radiotherapy (P < 0.01). No secondaryneoplasm was detected. In relapsed, refractory setting (n = 10), autologous transplantation (n = 9) is performed after a complete remission. Brentuximab vedotin with or without bendamustine and rituximab is also used in selected patients. CONCLUSIONS: Increased number of chronic health conditions and social problems point to the significance of long-term follow-up of HLSs. We are currently preparing a survivorship guideline appropriate for Turkey's conditions. IMPLICATIONS FOR CANCER SURVIVORS: Renal, heart, pulmonary impairment, thyroid dysfunction, limitation in physical functioning, and deterioration in social status (marriage, having children, education).