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Gürsel DB Beyene RT Hofstetter C Greenfield JP Souweidane MM Kaplitt M Arango-Lievano M Howard B Boockvar JA 《Journal of neuro-oncology》2011,104(2):509-522
It has been postulated that brain tumor stem cells (TSCs) may be the population of cells responsible for the maintenance and
recurrence of glioblastoma multiforme (GBM). The purpose of this study was to optimize a reproducible protocol for generating
TSCs for their subsequent transfection or transduction. Patient GBMs were enzymatically and mechanically dissociated and tumor
spheres were resuspended in appropriate media and analyzed to ensure they met stem cell criteria. These cells were then transfected
with a plasmid or transduced with a viral vector to introduce a previously absent gene and then allowed to form tumor spheres.
Tumor spheres were generated from patient GBMs without contamination. These cells met stringent criteria as stem cells, including
multipotentiality and self-renewal. High efficiency transfection and transduction of tumor spheres was possible, even at the
core of the sphere. This allowed for the introduction of new genes to the TSCs, as evidenced by fluorescent microscopy and
Western blot analysis. This study is a guide to optimize the generation of patient derived GBM tumor spheres without RBC and
dead cell contamination. GBM TSCs within tumor spheres can easily be transfected with plasmids or transduced with a virus.
This is important from a therapeutic perspective if gene replacement is to be successful in replacing genes lost in GBM progression
or to knock down or silence genes that are over-expressed in malignant brain tumors. 相似文献
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C Killowe NC Mkandawire 《Malawi medical journal : the journal of Medical Association of Malawi》2005,17(1):9-11
A study was conducted among football players and team doctors in the football super league in Malawi to determine the level of knowledge, skills and attitude in sports medicine. One hundred football players and thirteen team doctors were involved in the study. Standardised questionnaires were used to collect data in an interview format. Among the players 37% had completed tertiary education and 60% had finished secondary school education. Most players had poor knowledge on prevention of injuries; had poor advice on diet; used illicit drugs or knew of fellow players using illicit drugs and believed in the role of magic in sports. All 13 team ‘doctors’ worked full-time in paramedical fields: 3 were orthopaedic clinical officers, 2 were physiotherapists and the rest were in various fields, such as dental technician, pharmacy assistant, medical assistant and dermatology technician, where trauma is not part of their basic training. Most team “doctors” were aware of the impact of HIV/AIDS on sports but few had good knowledge of the role of nutrition in sports and the effect of performance enhancing drugs in sports. Most believed in the role of magic in sports. Recommendations are made on the basis of these findings. 相似文献
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Atak R Turhan H Senen K Yalta K Ayaz S Alyan O Basar N Demirkan D 《The Journal of heart valve disease》2004,13(2):159-164
BACKGROUND AND AIM OF THE STUDY: Systemic thromboembolism is a major complication in patients with mitral stenosis (MS), especially in those who have atrial fibrillation (AF). It has been suggested that systemic coagulation activity may be increased in these patients. The study aim was to investigate the relationship between control of ventricular rate and systemic coagulation factors in patients with MS and AF by measuring plasma levels of prothrombin fragment (PF) 1+2, thrombin-antithrombin III complex (TAT) and plasminogen activator inhibitor-1. METHODS: Fifty-four consecutive patients with moderate to severe MS and AF were included in the study. Patients with resting heart rates < 100 beats per min were considered as having a controlled ventricular response rate (group A; n = 28) and those with > 100 beats per min as an uncontrolled ventricular response rate (group B; n = 26). RESULTS: Group A patients had a lower mean mitral gradient and pulmonary artery pressure than group B patients (11 +/- 6 versus 15 +/- 5 and 35 +/- 7 versus 39 +/- 8; p < 0.05, respectively). Plasma concentrations of PF 1+2 (4.17 +/- 2.1 versus 2.95 +/- 1.21; p < 0.01) and TAT III (4.61 +/- 1.75 versus 3.12 +/- 1.01; p < 0.01) were elevated in group B compared with group A. Similarly, group B patients had higher plasminogen activator inhibitor-1 levels than group A patients (7.87 +/- 3.8 versus 5.8 +/- 2.9; p < 0.05). A significant correlation was found between heart rate and plasma PF 1+2 and TAT levels. Multiple logistic regression analysis revealed that heart rate and mean mitral gradient were independent predictors of systemic coagulation activation. CONCLUSION: Besides contributing towards hemodynamic and symptomatic relief, the control of AF rate in MS patients induces a drastic decline in coagulation activation, and may also reduce the incidence of thromboembolism. 相似文献
150.
Gorin NC; Douay L; Laporte JP; Lopez M; Mary JY; Najman A; Salmon C; Aegerter P; Stachowiak J; David R 《Blood》1986,67(5):1367-1376
The sensitivity of human myeloblastic leukemic (CFU-L) and normal hemopoietic stem cells (CFU-GM and BFU-e) to Asta Z 7557 (INN Mafosfamide) was studied with regard to autologous bone marrow transplantation (ABMT) with cleansed marrow for consolidation therapy in adult patients with acute leukemia (AL) in remission. Establishment of the dose-response curves for CFU-GM (n = 37), BFUe (n = 11), and myeloblastic CFU-L (n = 9) demonstrated a wide range of sensitivity from patient to patient for all three progenitors. Whereas CFU-L, CFU- GM, and BFU-e grown in semisolid cultures disclosed similar sensitivities to Asta Z 7557, long-term culture (LTC) studies (n = 41) indicated a higher resistance of early progenitors. In an effort to achieve a maximum tumor cell kill and yet spare a sufficient amount of normal stem cells to ensure consistent engraftment, we defined the optimal dose for marrow cleansing as the dose sparing 5% CFU-GM (LD95). This dose was established from a preincubation test (PIT) realized on a 10-mL marrow aspirate taken 15 days before marrow collection in each individual patient. Twenty-four adult patients while in remission of AL (20 in complete remission, four in partial remission) were consolidated by cyclophosphamide 60 mg/kg X 2 and total body irradiation at 10 Gy followed by ABMT with marrow cleansed by Asta Z 7557 according to the specification described above. Patients were divided in two groups: group 1, unfavorable prognosis (11 patients); group 2, standard prognosis [13 patients in first complete remission (CR)]. All patients engrafted on leukocytes (median day for recovery to 10(9)/L: day 30), patients with ALL recovered faster than patients with ANL (median day 19 v 34). Similarly, recovery of platelets to 50.10(9)/L occurred sooner in patients with ALL (median day 67, range day 23 through 90) whereas three patients with acute nonlymphoblastic leukemia (ANLL) in group 2 had to be supported with platelet transfusions for more than one year. In group 1, six patients had recurrent tumor within six months; three patients died from toxicity with no evidence of tumor. Two patients are still disease-free with a short follow-up (nine and ten months). In group 2, two patients died from toxicity with no evidence of leukemia three and 16 months post-ABMT. One patient with a M5 ANLL and one patient with ALL relapsed at six and 15 months, respectively. Nine patients have remained in CR or are disease-free with a median follow-up of 22 months.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献