Treatment of endemic Burkitt lymphoma (BL) with cyclophosphamide (CPM) and intrathecal methotrexate (IT MTX) can cure 50% of patients. In this study, induction therapy with CPM and IT MTX was followed by consolidation chemotherapy adapted for stage, clinical response, and abdominal ultrasound findings. One hundred and twenty-nine consecutive patients with BL, 77 male and 52 female with a median age of 7.9 years, were treated in mission hospitals in Cameroon. The diagnosis rested on fine-needle aspirate (79%), biopsy, bone marrow, cerebrospinal fluid, abdominal ultrasound, and clinical examination. Six percent had St Jude stage I, 13% stage II, 72% stage III, and 12% stage IV disease. The abdomen (76%) and face (50%) were mainly involved. Induction chemotherapy was CPM 40 mg/kg and IT MTX 12.5 mg and IT hydrocortisone 12.5 mg on days 1, 8, and 15. Stage I and II patients received CPM 60 mg/kg on day 29, and stage III patients CPM 60 mg/kg on days 29 and 43 if in remission on day 28. Stage IV patients and patients not in remission received CPM 60 mg/kg on days 29, 43, and 57 and 1.0 g/m(2) MTX intravenous (IV) and vincristine 1.5 mg/m(2) IV on day 29. Event-free survival (EFS) at mean 365 days was 61% (n = 79) and 100% in stage I, 85% in stage II, 60% in stage III, and 27% in stage IV patients. Deaths (n = 24) were disease or treatment related and 26 patients relapsed (mean 135 days). Risk-adapted treatment achieved 61% 1-year EFS.

It is possible to provide an effective children's PC service that meets the most urgent needs of recipients in a rural setting in SSA. Recommendations include improved counselling, specialist education for staff, expansion of local support networks and more frequent home visits. More studies are needed to help define the need for PC in children with life-limiting diseases.

Prognosis for patients with glioblastoma multiforme (GBM) is 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 p14(ARF)/p16(INK4a) deletions, are characteristic for GBM and can cause resistance to DNA damaging agents such as cisplatin and to HDACi like TSA. The type II tumor suppressor Inhibitor of growth 1 (ING1) is involved in DNA damage response and histone modification. We have previously shown that ING1 is downregulated in GBM and involved in glioma-induced angiogenesis and in cisplatin-induced apoptosis in malignant glioma cells. Hence, the goal of our present study was to investigate whether TSA affects ING1 protein expression and also whether modulating ING1 levels affects TSA-induced apoptosis in malignant glioma cells that contain deficient p53 function and inactive pl4(ARF)/p16(INK4a) signaling. If so, we asked, which apoptotic pathway might be the major mediator beyond this interaction. To test whether ING1 proteins function in TSA-induced apoptosis in GBM, we analyzed TSA effects in LN229 GBM cells, which harbor TP53 mutations and INK4a deletion, following ING1 knockdown by siRNA. Expression of ING1, acetylated core histones H3 and H4, and the proapoptotic proteins caspase 3 and Fas-associated death domain (FADD) was determined by Western blotting. Percentages of apoptotic cells were obtained by flow cytometry. TSA induced the major ING1 isoform p33(ING1b) 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. The data suggest that ING1 contributes to TSA-induced apoptosis in GBM cells with deficient p53 and p14(ARF)/p16(INK4a) functions, possibly by regulating FADD/caspase 3 signaling.

The inhibitor of growth 1 (ING1) homologue ING4 has previously been implicated as a negative regulator of angiogenesis in a murine glioma and a multiple myeloma model. An association between ING1 and angiogenesis has not been reported yet. Our previous studies using tumor samples from patients have shown that ING1 levels are downregulated in glioblastoma multiforme (GBM), one of the most highly vascularized malignancies. Based on this background, the goal of this study was to test the effects of the major ING1 splicing isoforms, p47ING1a and p33ING1b, on pathological angiogenesis induced by human GBM cells. We used a chorioallantoic membrane (CAM) assay to examine whether LN229 human GBM cells can induce angiogenesis and whether alterations in ING1 expression, such as ING1 knockdown by siRNA or ectopic ING1 overexpression using ING1a and ING1b expression constructs, can affect this process. Increased ING1 protein expression significantly suppressed LN229 cell-induced angiogenesis in the CAM assay. While no effects on the proangiogenic factors VEGF or IL-8 were noted, the expression of angiopoietins (Ang) 1 and 4 were increased by the p47ING1a, but not by the p33ING1b isoform. Levels of Ang-2 were not sensitive to altered ING1 levels. Our data are the first to suggest that ING1 proteins suppress neoangiogenesis in GBM. Moreover, our results may support the idea that ING1 proteins regulate the expression of proteins that are critical for angiogenesis in GBM such as the angiopoietins.

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.