Identification of Biochemical and Molecular Markers of Early Aging in Childhood Cancer Survivors

Survival rates of childhood cancer patients have improved over the past four decades, although cancer treatments increase the risk of developing chronic diseases typical of aging. Thus, we aimed to identify molecular/metabolic cellular alterations responsible for early aging in childhood cancer survivors (CCS). Biochemical, proteomic, and molecular biology analyses were conducted on mononuclear cells (MNCs) isolated from peripheral blood of 196 CCS, the results being compared with those obtained on MNCs of 154 healthy subjects. CCS-MNCs showed inefficient oxidative phosphorylation associated with low energy status, and increased lipid peroxidation and lactate fermentation compared with age-matched normal controls. According to a mathematical model based on biochemical parameters, CCS-MNCs showed significantly higher metabolic ages than their real ages. The dysfunctional metabolism of CCS-MNCs is associated with lower expression levels of genes and proteins involved in mitochondrial biogenesis and metabolism regulation, such as CLUH, PGC1-alpha, and SIRT6 in CCS, not observed in the age-matched healthy or elderly subjects. In conclusion, our study identified some biochemical and molecular alterations possibly contributing to the pathophysiology of aging and metabolic deficiencies in CCS. These results identify new targets for pharmacological interventions to restore mitochondrial function, slowing down the aging-associated pathologies in CCS.

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Identification of Biochemical and Molecular Markers of Early Aging in Childhood Cancer Survivors

10.1101/2021.04.01.438017 ◽

2021 ◽

Author(s):

Silvia Ravera ◽

Tiziana Vigliarolo ◽

Silvia Bruno ◽

Fabio Morandi ◽

Danilo Marimpietri ◽

...

Keyword(s):

Cancer Survivors ◽

Childhood Cancer ◽

Childhood Cancer Survivors ◽

Antioxidant Defenses ◽

Elderly Subjects ◽

Cancer Type ◽

Metabolism Regulation ◽

Increased Risk ◽

Early Aging ◽

The Impact

ABSTRACTPurposeSurvival rates of Childhood Cancer Patients have improved tremendously over the past four decades. However, cancer treatments are associated with an increased risk of developing an anticipated onset of chronic diseases typical of aging. Thus, we aimed to identify molecular/metabolic cellular alterations responsible for early aging in Childhood Cancer Survivors (CCS).Patients and MethodsBiochemical, proteomic and molecular biology analyses were conducted on mononuclear cells (MNCs) isolated from peripheral blood of 196 CCS, comparing the results with those obtained on MNCs of 154 healthy subjects.ResultsData demonstrate that CCS-MNCs show: i) inefficient oxidative phosphorylation associated with low energy status and a metabolic switch to lactate fermentation compared with age-matched normal controls; ii) increment of lipid peroxidation due to an unbalance among the oxidative stress production and the activation of the antioxidant defenses; (iii) significantly lower expression of genes and proteins involved in mitochondrial biogenesis and metabolism regulation, such as CLUH, PGC1-α, and SIRT6 in CCS, not observed in the age-matched healthy or elderly subjects. The application of a mathematical model based on biochemical parameters predicts that CCS have a biological age significantly increased by decades compared to the chronological age. Overall, the results show that the impact of chemo/chemoradiotherapy on mitochondria efficiency in 196 CCS was rather homogeneous, irrespective of cancer type, treatment protocols, and time elapsed from the end of the curative period.ConclusionsOur study identifies some biochemical and molecular alterations possibly contributing to the pathophysiology of anticipated aging and metabolic deficiency described in CCS. These results may be useful in identifying approaches to restore the mitochondrial function, slowing down the aging and the associated pathological conditions in CCS.

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Exploring food preparation practices in families with and without school-aged childhood cancer survivors

Public Health Nutrition ◽

10.1017/s1368980019002672 ◽

2019 ◽

Vol 23 (3) ◽

pp. 410-415

Author(s):

Margaret Raber ◽

Karla Crawford ◽

Tom Baranowski ◽

Shreela V Sharma ◽

Vanessa Schick ◽

...

Keyword(s):

Cancer Survivors ◽

Childhood Cancer ◽

Survival Rates ◽

Childhood Cancer Survivors ◽

Nutrition Intervention ◽

Food Preparation ◽

Nutrition Interventions ◽

Meal Preparation ◽

Increased Risk ◽

Healthy Family

AbstractObjective:Survival rates for paediatric cancers have increased dramatically since the 1970s, but childhood cancer survivors (CCS) are at increased risk for several chronic diseases throughout life. Nutrition interventions promoting healthy family meals may support wellness for survivors, but little research has explored CCS family food preparation habits. The goal of the present study was to describe and compare food preparation practices of CCS and non-CCS families.Design:Observational.Setting:Typical evening meal preparation events were observed and recorded in participant homes. Recordings and notes were analysed using the Healthy Cooking Index (HCI), a measure of nutrition-optimizing food preparation practices relevant to survivor wellness. Demographics, BMI and nutrient composition of prepared meals were also collected.Participants:Forty parents with a CCS or non-CCS child aged 5–17 years were recruited.Results:There were no major differences between the CCS and non-CCS families with regard to summative HCI score or specific food preparation behaviours. Meals prepared by CCS and non-CCS families had similar nutrient compositions.Conclusions:The study revealed areas for practical nutrition intervention in CCS and non-CCS families. Future studies should consider adopting and tailoring nutrition intervention methods that have been successful in non-CCS communities.

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Possible Mechanisms of Subsequent Neoplasia Development in Childhood Cancer Survivors: A Review

Cancers ◽

10.3390/cancers13205064 ◽

2021 ◽

Vol 13 (20) ◽

pp. 5064

Author(s):

Jarmila Kruseova ◽

Ales Vicha ◽

Barbara Feriancikova ◽

Tomas Eckschlager

Keyword(s):

Cancer Survivors ◽

Childhood Cancer ◽

Survival Rates ◽

Childhood Cancer Survivors ◽

Good Prognosis ◽

Malignant Neoplasms ◽

Term Survival ◽

Improved Outcomes ◽

Prediction And Prevention ◽

Life Threatening

Advances in medicine have improved outcomes in children diagnosed with cancer, with overall 5-year survival rates for these children now exceeding 80%. Two-thirds of childhood cancer survivors have at least one late effect of cancer therapy, with one-third having serious or even life-threatening effects. One of the most serious late effects is a development of subsequent malignant neoplasms (histologically different cancers, which appear after the treatment for primary cancer), which occur in about 3–10% of survivors and are associated with high mortality. In cancers with a very good prognosis, subsequent malignant neoplasms significantly affect long-term survival. Therefore, there is an effort to reduce particularly hazardous treatments. This review discusses the importance of individual factors (gender, genetic factors, cytostatic drugs, radiotherapy) in the development of subsequent malignant neoplasms and the possibilities of their prediction and prevention in the future.

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Cardiac complications in childhood cancer survivors treated with anthracyclines

Cardiology in the Young ◽

10.1017/s1047951115000906 ◽

2015 ◽

Vol 25 (S2) ◽

pp. 107-116 ◽

Cited By ~ 22

Author(s):

Vivian I. Franco ◽

Steven E. Lipshultz

Keyword(s):

Cancer Survivors ◽

Cancer Treatment ◽

Childhood Cancer ◽

Management Strategies ◽

Survival Rates ◽

Childhood Cancer Survivors ◽

Cardiac Complications ◽

Cardiac Abnormalities ◽

Survivors Of Childhood Cancer

AbstractCardiovascular complications are among the leading causes of morbidity and mortality among survivors of childhood cancer, after cancer relapse and secondary malignancies. Although advances in cancer treatment have improved the 5-year survival rates, the same treatments, such as anthracyclines, that cure cancer also increase the risk for adverse cardiovascular effects. Anthracycline-related cardiotoxicity in survivors of childhood cancer is progressive and can take years to develop, initially presenting as sub-clinical cardiac abnormalities that, if left undetected or untreated, can lead to heart failure, myocardial infarction, or other clinical cardiac dysfunction. A higher cumulative dose of anthracycline is associated with cardiotoxicity in children; however, sub-clinical cardiac abnormalities are evident at lower doses with longer follow-up, suggesting that there is no “safe” dose of anthracycline. Other risk factors include female sex, younger age at diagnosis, black race, trisomy 21, longer time since treatment, and the presence of pre-existing cardiovascular disease and co-morbidities. Cardioprotective strategies during treatment are limited in children. Enalapril provides only temporary cardioprotection, whereas continuous anthracycline infusion extends none. On the other hand, dexrazoxane successfully prevents or reduces anthracycline-related cardiotoxicity in children with cancer, without increased risks for recurrence of primary or second malignancies or reductions in anti-tumour efficacy. With more childhood cancer survivors now reaching adulthood, it is vital to understand the adverse effects of cancer treatment on the cardiovascular system and their long-term consequences to identify and establish optimal prevention and management strategies that balance oncologic efficacy with long-term safety.

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