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Pediatric Blood & Cancer Oct 2023
Topics: Child; Humans; Cardiotoxicity; Dexrazoxane; Anthracyclines; Neoplasms; Antibiotics, Antineoplastic; Polyketides; Razoxane; Cardiotonic Agents
PubMed: 37505793
DOI: 10.1002/pbc.30604 -
Heliyon Jun 2023An improved optimal drug scheduling model with considering two control drugs is proposed and the Gauss pseudospectral-based optimization method is studied to decrease...
An improved optimal drug scheduling model with considering two control drugs is proposed and the Gauss pseudospectral-based optimization method is studied to decrease the tumor size and drug toxicity in this work. Firstly, the Dexrazoxane drug, which has significant clinical effect to reduce the toxicity of the anticancer drug, is introduced. By analyzing the growth kinetics model of cancer chemotherapy, the toxicity reduction drug is regarded as the second input in the cancer dynamic equations. Correspondingly, the drug scheduling optimization problem with particular optimization goal and necessary constraints is established. Next, a model transformation technique is proposed to reduce the complexity of dynamic equations. With deriving the Gaussian time grid discretization detailly, the Gauss pseudospectral method (GPM)-based cancer chemotherapy drug scheduling algorithm is presented to test the performance of the proposed model within different rates. Finally, the implementation structure of drug scheduling optimization is given in detail. To test and validate the performance of proposed chemotherapy model, extensive simulation results and comparative evaluation are carried out on a specific mathematical model. Simulation results show that the improved optimization model is superior to other literature studies, resulting in the average improvement of performance index by 66.54% and revealing the significant guiding property for cancer chemotherapy.
PubMed: 37484317
DOI: 10.1016/j.heliyon.2023.e17297 -
Pediatric Hematology and Oncology 2023Children with acute lymphoblastic leukemia (ALL) are at high risk of developing long-term cardiometabolic complications during their survivorship. Maximal fat oxidation...
Children with acute lymphoblastic leukemia (ALL) are at high risk of developing long-term cardiometabolic complications during their survivorship. Maximal fat oxidation (MFO) is a marker during exercise of cardiometabolic health, and is associated with metabolic risk factors. Our aim was to characterize the carbohydrate and fat oxidation during exercise in childhood ALL survivors. Indirect calorimetry was measured in 250 childhood ALL survivors to quantify substrate oxidation rates during a cardiopulmonary exercise test. A best-fit third-order polynomial curve was computed for fat oxidation rate (mg/min) against exercise intensity (%Opeak) and was used to determine the MFO and the peak fat oxidation (Fat). The crossover point was also identified. Differences between prognostic risk groups were assessed (ie, standard risk [SR], high risk with and without cardio-protective agent dexrazoxane [HR + DEX and HR]). MFO, Fat and crossover point were not different between the groups ( = .078; = .765; = .726). Fat and crossover point were achieved at low exercise intensities. A higher MFO was achieved by men in the SR group (287.8 ± 111.2 mg/min) compared to those in HR + DEX (239.8 ± 97.0 mg/min) and HR groups (229.3 ± 98.9 mg/min) ( = .04). Childhood ALL survivors have low fat oxidation during exercise and oxidize carbohydrates at low exercise intensities, independently of the cumulative doses of doxorubicin they received. These findings alert clinicians on the long-term impact of cancer treatments on childhood ALL survivors' substrate oxidation.
Topics: Male; Child; Humans; Adipose Tissue; Oxygen Consumption; Oxidation-Reduction; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Survivors; Cardiovascular Diseases
PubMed: 37440691
DOI: 10.1080/08880018.2023.2232399 -
International Journal of Molecular... Jun 2023The anticancer efficacy of doxorubicin (DOX) is dose-limited because of cardiomyopathy, the most significant adverse effect. Initially, cardiotoxicity develops...
The anticancer efficacy of doxorubicin (DOX) is dose-limited because of cardiomyopathy, the most significant adverse effect. Initially, cardiotoxicity develops clinically silently, but it eventually appears as dilated cardiomyopathy with a very poor prognosis. Dexrazoxane (DEX) is the only FDA-approved drug to prevent the development of anthracycline cardiomyopathy, but its efficacy is insufficient. Carvedilol (CVD) is another product being tested in clinical trials for the same indication. This study's objective was to evaluate anthracycline cardiotoxicity in rats treated with CVD in combination with DEX. The studies were conducted using male Wistar rats receiving DOX (1.6 mg/kg b.w. , cumulative dose: 16 mg/kg b.w.), DOX and DEX (25 mg/kg b.w. ), DOX and CVD (1 mg/kg b.w. ), or a combination (DOX + DEX + CVD) for 10 weeks. Afterward, in the 11th and 21st weeks of the study, echocardiography (ECHO) was performed, and the tissues were collected. The addition of CVD to DEX as a cardioprotective factor against DOX had no favorable advantages in terms of functional (ECHO), morphological (microscopic evaluation), and biochemical alterations (cardiac troponin I and brain natriuretic peptide levels), as well as systemic toxicity (mortality and presence of ascites). Moreover, alterations caused by DOX were abolished at the tissue level by DEX; however, when CVD was added, the persistence of DOX-induced unfavorable alterations was observed. The addition of CVD normalized the aberrant expression of the vast majority of indicated genes in the DOX + DEX group. Overall, the results indicate that there is no justification to use a simultaneous treatment of DEX and CVD in DOX-induced cardiotoxicity.
Topics: Male; Rats; Animals; Dexrazoxane; Anthracyclines; Carvedilol; Cardiotoxicity; Rats, Wistar; Antibiotics, Antineoplastic; Cardiomyopathies; Doxorubicin; Topoisomerase II Inhibitors
PubMed: 37373350
DOI: 10.3390/ijms241210202 -
Pediatric Blood & Cancer Jun 2023Cardiovascular disease is the leading cause of non-malignant morbidity and mortality in childhood cancer survivors (CCSs). Anthracyclines are included in many treatment...
Cardiovascular disease is the leading cause of non-malignant morbidity and mortality in childhood cancer survivors (CCSs). Anthracyclines are included in many treatment regimens for paediatric cancer, but unfortunately, these compounds are cardiotoxic. One in 10 CCSs who has received an anthracycline will develop a symptomatic cardiac event over time. Given the crucial need to mitigate anthracycline-related cardiotoxicity (ARC), the authors critically examined published data to identify effective cardioprotective strategies. Based on their expert analysis of contemporary literature data, it was concluded that consideration should be given for routine use of dexrazoxane in children with cancer who are at risk of ARC.
PubMed: 37355856
DOI: 10.1002/pbc.30515 -
Journal of Medicine and Life Apr 2023Cancer is a major public health problem, and chemotherapy plays a significant role in the management of neoplastic diseases. However, chemotherapy-induced cardiotoxicity... (Review)
Review
Cancer is a major public health problem, and chemotherapy plays a significant role in the management of neoplastic diseases. However, chemotherapy-induced cardiotoxicity is a serious side effect secondary to cardiac damage caused by antineoplastic's direct and indirect toxicity. Currently, there are no reliable and approved methods for preventing or treating chemotherapy-induced cardiotoxicity. Understanding the mechanisms of chemotherapy-induced cardiotoxicity may be vital to improving survival. The independent risk factors for developing cardiotoxicity must be considered to prevent myocardial damage without decreasing the therapeutic efficacy of cancer treatment. This systematic review aimed to identify and analyze the evidence on chemotherapy-induced cardiotoxicity, associated risk factors, and methods to decrease or prevent it. We conducted a comprehensive search on PubMed, Google Scholar, and Directory of Open Access Journals (DOAJ) using the following keywords: "doxorubicin cardiotoxicity", "anthracycline cardiotoxicity", "chemotherapy", "digoxin decrease cardiotoxicity", "ATG7 activators", retrieving 59 articles fulfilling the inclusion criteria. Therapeutic schemes can be changed by choosing prolonged infusion application over boluses. In addition, some agents like Dexrazoxane can reduce chemotherapy-induced cardiotoxicity in high-risk groups. Recent research found that Digoxin, ATG7 activators, Resveratrol, and other medical substances or herbal compounds have a comparable effect on Dexrazoxane in anthracycline-induced cardiotoxicity.
Topics: Humans; Resveratrol; Cardiotoxicity; Dexrazoxane; Anthracyclines; Digoxin; Polyketides; Antineoplastic Agents
PubMed: 37305823
DOI: 10.25122/jml-2022-0322 -
Translational Pediatrics May 2023Adamantinoma craniopharyngioma (ACP) is a non-malignant tumour of unknown pathogenesis that frequently occurs in children and has malignant potential. The main treatment...
BACKGROUND
Adamantinoma craniopharyngioma (ACP) is a non-malignant tumour of unknown pathogenesis that frequently occurs in children and has malignant potential. The main treatment options are currently surgical resection and radiotherapy. These treatments can lead to serious complications that greatly affect the overall survival and quality of life of patients. It is therefore important to use bioinformatics to explore the mechanisms of ACP development and progression and to identify new molecules.
METHODS
Sequencing data of ACP was downloaded from the comprehensive gene expression database for differentially expressed gene identification and visualized by Gene Ontology, Kyoto Gene, and gene set enrichment analyses (GSEAs). Weighted correlation network analysis was used to identify the genes most strongly associated with ACP. GSE94349 was used as the training set and five diagnostic markers were screened using machine learning algorithms to assess diagnostic accuracy using receiver operating characteristic (ROC) curves, while GSE68015 was used as the validation set for verification.
RESULTS
Type I cytoskeletal 15 (KRT15), Follicular dendritic cell secreted peptide (FDCSP), Rho-related GTP-binding protein RhoC (RHOC), Modulates negatively TGFB1 signaling in keratinocytes (CD109), and type II cytoskeletal 6A (KRT6A) (area under their receiver operating characteristic curves is 1 for both the training and validation sets), Nomograms constructed using these five markers can predict progression of ACP patients. Whereas ACP tissues with activated T-cell surface glycoprotein CD4, Gamma delta T cells, eosinophils and regulatory T cells were expressed at higher levels than in normal tissues, which may contribute to the pathogenesis of ACP. According to the analysis of the CellMiner database (Tumor cell and drug related database tools), high CD109 levels showed significant drug sensitivity to Dexrazoxane, which has the potential to be a therapeutic agent for ACP.
CONCLUSIONS
Our findings extend understandings of the molecular immune mechanisms of ACP and suggest possible biomarkers for the targeted and precise treatment of ACP.
PubMed: 37305719
DOI: 10.21037/tp-23-152 -
Current Treatment Options in Oncology Aug 2023As chemotherapy continues to improve the lives of patients with cancer, understanding the effects of these drugs on other organ systems, and the cardiovascular system in... (Review)
Review
As chemotherapy continues to improve the lives of patients with cancer, understanding the effects of these drugs on other organ systems, and the cardiovascular system in particular, has become increasingly important. The effects of chemotherapy on the cardiovascular system are a major determinant of morbidity and mortality in these survivors. Although echocardiography continues to be the most widely used modality for assessing cardiotoxicity, newer imaging modalities and biomarker concentrations may detect subclinical cardiotoxicity earlier. Dexrazoxane continues to be the most effective therapy for preventing anthracycline-induced cardiomyopathy. Neurohormonal modulating drugs have not prevented cardiotoxicity, so their widespread, long-term use for all patients is currently not recommended. Advanced cardiac therapies, including heart transplant, have been successful in cancer survivors with end-stage HF and should be considered for these patients. Research on new targets, especially genetic associations, may produce treatments that help reduce cardiovascular morbidity and mortality.
Topics: Humans; Adolescent; Young Adult; Child; Antineoplastic Agents; Cardiotoxicity; Neoplasms; Heart; Cardiomyopathies; Anthracyclines
PubMed: 37296365
DOI: 10.1007/s11864-023-01100-4 -
Journal of Pediatric Hematology/oncology Jul 2023There is a shortage of relevant studies interested in cardiac mechanical performance. Thus, it is clinically relevant to study the impact of cancer treatments on...
BACKGROUND
There is a shortage of relevant studies interested in cardiac mechanical performance. Thus, it is clinically relevant to study the impact of cancer treatments on survivors' cardiac mechanical performance to improve our knowledge. The first objective of this study is to assess survivors' cardiac mechanical performance during a cardiopulmonary exercise test (CPET) using both ventricular-arterial coupling (VAC) and cardiac work efficiency (CWE) from cardiac magnetic resonance (CMR) acquisitions. The second objective is to assess the impact of doxorubicin and dexrazoxane (DEX) treatments.
METHODS
A total of 63 childhood acute lymphoblastic leukemia survivors underwent a CMR at rest on a 3T magnetic resonance imaging system, followed by a CPET on ergocycle. The CircAdapt model was used to study cardiac mechanical performance. At different levels of exercise, arterial elastance, end-systolic elastance, VAC, and CWE were estimated.
RESULTS
We observed significant differences between the different levels of exercise for both VAC ( P <0.0001) and CWE parameters ( P =0.001). No significant differences were reported between prognostic risk groups at rest and during the CPET. Nevertheless, we observed that survivors in the SR group had a VAC value slightly lower than heart rate (HR)+DEX and HR groups throughout the CPET. Moreover, survivors in the SR group had a CWE parameter slightly higher than HR+DEX and HR groups throughout the CPET.
CONCLUSIONS
This study reveals that the combination of CPET, CMR acquisitions and CircAdapt model was sensitive enough to observe slight changes in the assessment of VAC and CWE parameters. Our study contributes to improving survivors' follow-up and detection of cardiac problems induced by doxorubicin-related cardiotoxicity.
Topics: Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Doxorubicin; Survivors; Prognosis; Exercise; Exercise Test
PubMed: 37278566
DOI: 10.1097/MPH.0000000000002682