Limited Margins Using Modern Radiotherapy Techniques Does Not Increase Marginal Failure Rate of Glioblastoma

PURPOSE: We investigate the patterns of failure in the treatment of glioblastoma(GBM) based on clinical target volume(CTV) margin size,dose delivered to the site of initial failure,and the use of temozolomide and intensity-modulated radiotherapy(IMRT).METHODS: Between August 2000 and May 2010,161 patients with GBM were treated with radiotherapy with or without concurrent temozolomide.Patients were treated with CTV expansions that ranged from 5 to 20 mm using a shrinking field technique.Patterns of failure and time to progression and overall survival were compared based on CTV margin,use of temozolomide,and use of IMRT.Kaplan Meier analysis was used to estimate survival times,and χ test was used for comparison of cohorts.RESULTS: For patients treated with 5-,10-,and 15-to 20-mm CTV,79%,77%,and 86% experienced failures in the 60 Gy volume,respectively.Forty-eight percent,55%,and 66% of patients with 5-,10-,and 15-to 20-mm CTV experienced failures in the 46 Gy volume,respectively.There was no statistical difference between patients treated with 5-,10-,15-to 20-mm margins with regard to 60 Gy failure(P=0.76),46 Gy failure(P=0.51),or marginal failure(P=0.73).Eighty percent of patients receiving temozolomide experienced failures in the 60 Gy volume.There was no increased likelihood of marginal failures in patients receiving IMRT(P =0.97).CONCLUSIONS: Modern treatment techniques including use of concurrent temozolmide,limited CTV margin size,and IMRT have not greatly changed the patterns of failure of GBM.     

临床医护

细菌的耐药笥民为一个全球性问题,并从医院扩展到了家庭及社区。同时,抗生素的滥用对微生物的生态环境造成了极大的破坏。我们可以通过改变抗生素的使用频度和改变耐药性基因来逆转药性问题,同时需要有一个全球性的监测系统来追踪耐药菌的、去向及新菌种的出现。     

Human burst-forming units-erythroid need direct interaction with stem cell factor for further development

To understand the factors that regulate the early growth and development of immature erythroid progenitor cells, the burst-forming units-erythroid (BFU-E), it is necessary to have both highly purified target cells and a medium free of serum. When highly purified human blood BFU-E were cultured in a serum-free medium adequate for the growth of later erythroid progenitors, BFU-E would not grow even with the addition of recombinant human interleukin-3 (rIL-3), known to be essential for these cells. However, the addition of recombinant human stem cell factor (rSCF), which supports germ cell and pluripotential stem cell growth, stimulated BFU-E to grow equally well in serum-free as in serum-containing medium. Limiting dilution studies showed that rSCF acts directly on the BFU-E that do not require accessory cells for growth. Furthermore, rSCF was necessary for BFU-E development during the initial 7 days of culture, until these cells reached the stage of the late progenitors, the colony-forming units-erythroid (CFU-E). These studies indicate that early erythropoiesis is dependent on the direct action of SCF that not only affects early stem cells but is continually necessary for the further development of committed erythroid progenitor cells until the CFU-E stage of maturation.     

Serum interleukin 2 receptor levels in childhood acute lymphoblastic leukemia

The clinical significance of interleukin 2 receptor (IL2R) concentrations in serum was determined for 344 children with newly diagnosed acute lymphoblastic leukemia (ALL). Serum levels of IL2R in patients (267 to 80,000 U/mL, median 2,007 U/mL) were significantly higher than normal control values (170 to 738 U/mL, median 347 U/mL) (P less than .0001). Measurements in cases of T cell ALL were lower than in the non-T, non-B cases (P = .02). Among the 264 patients with non-T, non-B ALL, but not in those with T cell disease, higher serum IL2R levels (greater than 2,000 U/mL) were associated with a poorer treatment outcome (P = .04). In a multivariate analysis, serum IL2R level contributed independent prognostic information beyond that conveyed by leukocyte count, race, and age (P = .04). One explanation for these results is that soluble IL2R competes with normal lymphocyte- integrated IL2R for the ligand and thus could suppress host antitumor immunity.     

Is growth hormone a radioprotective agent?

There is currently substantial clinical interest in growth hormone (GH) as a protective agent against radiation-related normal tissue injury. To further assess the potential radiation injury-preventive effects of GH, these effects were studied in rats by using a radiation-induced skin injury model. Group 1 received neither GH nor irradiation (control group). Group 2 received 30 Gy of gamma irradiation as a single dose to the right hind legs of the rats (radiation group). Group 3 and 4 received the same irradiation plus either 0.01 U/kg/day GH (RT + 0.01 GH group) or 0.02 U/kg/day GH (RT + 0.02 GH group) subcutaneously. Clinically and histopathologically, acute skin reactions were assessed by two independent experts in radiation oncology and pathology, respectively. Irradiation increased dermatitis in rats when compared with the control group. The severity of radiodermatitis in the rats in the RT + 0.01 GH and RT + 0.02 GH groups was significantly lower than that in the RT group; radiodermatitis developed earlier in the RT group than in the other groups. GH was efficacious in preventing epidermal atrophy, dermal degeneration such as oedema and collagen fibre loss, and hair follicle atrophy, but not better than in the control group. These results are preliminary to studies that will be performed with higher doses of GH in radiation-treated cancer patients, with the aim of reducing radiation-induced toxicity.     

人白血病HL60细胞的分化状态对细胞凋亡的影响

用细胞培养和流式细胞术等方法,研究人白血病HL60细胞诱导分化后,对三尖杉酯碱(Har)和喜树碱(Cam)诱导细胞凋亡的影响。结果表明,12-豆蔻酰及13-乙酸佛波酯以16nmol·L^-1浓度处理HL60细胞24h,细胞向单核/巨噬细胞方向分化,阻断于G_{1期;分化细胞抗Har和Cam诱导的细胞凋亡,但其c-myc基因的表达无变化。1.4%二甲基亚砜处理HL60细胞48h,细胞向粒细胞方向分化,阻断于G1期;分化细胞抗Cam,而不抗Har诱导的细胞凋亡;分化细胞的c-myc基因表达明显下降。结果提示,人白血病HL60细胞的分化状态,明显影响三尖杉酯碱和喜树碱诱导的细胞凋亡,但可能与c-myc基因的表达变化无关。}     

Polynitroxylated-pegylated hemoglobin attenuates fluid requirements and brain edema in combined traumatic brain injury plus hemorrhagic shock in mice

Polynitroxylated-pegylated hemoglobin (PNPH), a bovine hemoglobin decorated with nitroxide and polyethylene glycol moieties, showed neuroprotection vs. lactated Ringer''s (LR) in experimental traumatic brain injury plus hemorrhagic shock (TBI+HS). Hypothesis: Resuscitation with PNPH will reduce intracranial pressure (ICP) and brain edema and improve cerebral perfusion pressure (CPP) vs. LR in experimental TBI+HS. C57/BL6 mice (n=20) underwent controlled cortical impact followed by severe HS to mean arterial pressure (MAP) of 25 to 27 mm Hg for 35 minutes. Mice (n=10/group) were then resuscitated with a 20 mL/kg bolus of 4% PNPH or LR followed by 10 mL/kg boluses targeting MAP>70 mm Hg for 90 minutes. Shed blood was then reinfused. Intracranial pressure was monitored. Mice were killed and %brain water (%BW) was measured (wet/dry weight). Mice resuscitated with PNPH vs. LR required less fluid (26.0±0.0 vs. 167.0±10.7 mL/kg, P<0.001) and had a higher MAP (79.4±0.40 vs. 59.7±0.83 mm Hg, P<0.001). The PNPH-treated mice required only 20 mL/kg while LR-resuscitated mice required multiple boluses. The PNPH-treated mice had a lower peak ICP (14.5±0.97 vs. 19.7±1.12 mm Hg, P=0.002), higher CPP during resuscitation (69.2±0.46 vs. 45.5±0.68 mm Hg, P<0.001), and lower %BW vs. LR (80.3±0.12 vs. 80.9±0.12%, P=0.003). After TBI+HS, resuscitation with PNPH lowers fluid requirements, improves ICP and CPP, and reduces brain edema vs. LR, supporting its development.