Burkitt lymphoma – Nutritional support during induction treatment: Effect on anthropometric parameters and morbidity of treatment

Background: Malnutrition is common in children diagnosed with cancer in Africa, and it adds to the morbidity and mortality of treatment. Nutritional support is known to reduce morbidity and mortality of treatment. Aim: The aim of this study was to record changes in anthropometric parameters, morbidity and mortality in patients admitted with Burkitt lymphoma (BL) whose diet was supplemented with protein, vitamins and minerals during induction chemotherapy. Methods: Seventy consecutive newly diagnosed BL patients were enrolled. The diet was supplemented with a daily egg, 200 mL F-75 formula and vitamins. Guardians received 3 cups of dry rice and $1 daily to buy and prepare meals for the patient and themselves whilst in the hospital. Height, weight, triceps skinfold (TSF) and mid-upper arm circumference (MUAC) were recorded on days 1 and 28. Co-morbidities at diagnosis were treated, and neutropenia and febrile episodes managed with a standard protocol. Two patients who died within 24 h after admission were excluded from the anthropometric analyses. Results: The mean age was 8 (range 2–16) years and the male:female ratio was 42:28. The St Jude stage distribution was as follows: Stage I = 6%, II = 4%, III = 69%, IV = 21%. Weight for age was < 10th centile at diagnosis in 18% (but influenced by tumour mass). Weight was unchanged or increased by ≥ 5% in 66% of patients on Day 28. The TSF was < 3rd centile in 47% of patients and increased by ≥ 0.5 cm in 57%. The MUAC was < 3rd centile in 16% of patients at diagnosis and in 10% of patients on Day 28. Febrile episodes in 60% and neutropenia in 18% of patients were successfully treated. Two patients died from presumed renal failure. The overall death rate (including the two deaths within 24 h after admission before chemotherapy was started) was 5.5% (n = 4). Conclusion: The TSF improved in the majority and the MUAC improved in some patients. Febrile neutropenia and febrile episodes could be successfully managed. The death rate during induction was lower than in our previously published results with the same chemotherapy protocol. Dietary supplementation should be a standard component of treatment in paediatric patients with cancer

ING1 is involved in TSA-induced apoptosis and in the FADD/caspase 3 signaling pathway in human glioblastoma cells

Titelblatt und Inhaltsverzeichnis Einleitung Arbeitshypothese und Zielsetzung Material und Methoden Ergebnisse Diskussion LiteraturverzeichnisHintergrund: Die Prognose für Patienten mit einem Glioblastoma multiforme (GBM) ist nach wie vor schlecht. Inhibitoren der Histondeacetylasen (HDACi) wie Trichostatin A (TSA) stellen hoffungserweckende Alternativen zur konventionellen Therapie dar. Die fehlenden Funktionen von Tumorsuppressoren beispielsweise durch Mutationen von TP53 oder Deletionen von CDKN2A sind charakteristisch für GBM und können zu Resistenzen führen. Wir haben kürzlich berichtet, dass die Expression des Typ II Tumorsuppressor ING1 in Gliomen vermindert ist. Fragestellung: Um der Frage nachzugehen, ob die ING1-Proteine in die durch TSA induzierte Apoptose in GBM involviert sind, wurde die Wirkung von TSA in LN229-Glioblastomzellen, die eine TP53-Mutation und einen inaktivierten p14ARF/p16INK4a-Signalweg besitzen, mit verminderter ING1-Expression erreicht durch siRNA oder mit ektoper Überexpression von ING1 untersucht. Material und Methoden: Die Expression von ING1, acetylierten Histonen H3 und H4 und den Apoptose induzierenden Proteinen Caspase 3 und FADD wurde mittels Western Blot Analyse, die HDAC-Aktivität mit Hilfe eines HDAC- Assays und die Apoptoseraten mittels FACS-Analyse bestimmt. Ergebnisse: TSA induzierte die Hauptisoform von ING1 p33ING1b und erhöhte sowohl die Spiegel der Histonacetylierung als auch die Apoptoserate in LN229-Zellen. Bei den LN229-Zellen mit verminderter ING1-Expression war eine deutliche Resistenz gegenüber der durch TSA induzierten Apoptose, eine Beeinflussung der Aktivierung von Caspase 3 und die Hemmung von FADD zu beobachten. Diskussion: ING1 ist möglicherweise in die Veränderung der proapoptotischen Wirkung von TSA involviert - eventuell über die Regulierung des FADD/Caspase-3-Signalweges. Die endogenen ING1-Spiegel könnten daher vielleicht die Sensitivität von GBM mit fehlender p53- und p14ARF/p16INK4a- Funktion gegenüber der durch TSA ausgelösten Apoptose vorhersagen.Purpose: Prognosis for patients with glioblastoma multiforme (GBM) still remains poor. Inhibitors of histone deacetylases (HDACi) like Trichostatin A (TSA) are promising alternatives to conventional treatment. Deficient tumor suppressor functions, such as TP53 mutations and CDKN2A deletions, are characteristic for GBM and can cause resistance. We have previously reported that the type II tumor suppressor ING1 is downregulated in GBM. Problem: To test whether ING1 proteins function in TSA-induced apoptosis in GBM, we analysed TSA effects in LN229 GBM cells, which harbour TP53 mutations and inactive p14ARF/p16INK4a-signaling, following ING1 knockdown by siRNA or ectopic ING1 overexpression. Material and Methods: Expression of ING1-, acetylated histone H3- and H4-, and apoptosis-inducing proteins caspase 3 and FADD was determined by western blotting, HDAC activity by HDAC assay and apoptosis by FACS analysis. Results: TSA induced the major ING1 isoform p33ING1b and increased levels of both histone acetylation and apoptosis in LN229 cells. ING1 knockdown cells revealed marked resistance to TSA-induced apoptosis, impairment of caspase 3-activation and suppression of FADD. Discussion: ING1 might be involved in mediating the proapoptotic effects of TSA in GBM - possibly by regulating FADD/caspase 3-signaling. Therefore, endogenous ING1 levels may predict sensitivity to TSA-induced apoptosis in GBM with deficient p53- and p14ARF/p16INK4a-functions

Burkitt lymphoma – nutritional support during induction treatment : effect on anthropometric parameters and morbidity of treatment

CITATION: Hesseling, P. B. et al. 2018. Burkitt lymphoma – nutritional support during induction treatment : effect on anthropometric parameters and morbidity of treatment. South African Journal of Oncology, 2:a53, doi:10.4102/sajo.v2i0.53.The original publication is available at https://sajo.org.zaBackground: Malnutrition is common in children diagnosed with cancer in Africa, and it adds to the morbidity and mortality of treatment. Nutritional support is known to reduce morbidity and mortality of treatment. Aim: The aim of this study was to record changes in anthropometric parameters, morbidity and mortality in patients admitted with Burkitt lymphoma (BL) whose diet was supplemented with protein, vitamins and minerals during induction chemotherapy. Methods: Seventy consecutive newly diagnosed BL patients were enrolled. The diet was supplemented with a daily egg, 200 mL F-75 formula and vitamins. Guardians received 3 cups of dry rice and $1 daily to buy and prepare meals for the patient and themselves whilst in the hospital. Height, weight, triceps skinfold (TSF) and mid-upper arm circumference (MUAC) were recorded on days 1 and 28. Co-morbidities at diagnosis were treated, and neutropenia and febrile episodes managed with a standard protocol. Two patients who died within 24 h after admission were excluded from the anthropometric analyses. Results: The mean age was 8 (range 2–16) years and the male:female ratio was 42:28. The St Jude stage distribution was as follows: Stage I = 6%, II = 4%, III = 69%, IV = 21%. Weight for age was < 10th centile at diagnosis in 18% (but influenced by tumour mass). Weight was unchanged or increased by ≥ 5% in 66% of patients on Day 28. The TSF was < 3rd centile in 47% of patients and increased by ≥ 0.5 cm in 57%. The MUAC was < 3rd centile in 16% of patients at diagnosis and in 10% of patients on Day 28. Febrile episodes in 60% and neutropenia in 18% of patients were successfully treated. Two patients died from presumed renal failure. The overall death rate (including the two deaths within 24 h after admission before chemotherapy was started) was 5.5% (n = 4). Conclusion: The TSF improved in the majority and the MUAC improved in some patients. Febrile neutropenia and febrile episodes could be successfully managed. The death rate during induction was lower than in our previously published results with the same chemotherapy protocol. Dietary supplementation should be a standard component of treatment in paediatric patients with cancer.https://sajo.org.za/index.php/sajo/article/view/53Publisher's versio