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991.
The p53 tumor suppressor continues to hold distinction as the most frequently mutated gene in human cancer. The ability of p53 to induce programmed cell death, or apoptosis, of cells exposed to environmental or oncogenic stress constitutes a major pathway whereby p53 exerts its tumor suppressor function. In the past decade, we have discovered that p53 is not alone in its mission to destroy damaged or aberrantly proliferating cells: it has two homologs, p63 and p73, that in various cellular contexts and stresses contribute to this process. In this review, the mechanisms whereby p53, and in some cases p63 and p73, induce apoptosis are discussed. Other reviews have focused more extensively on the contribution of individual p53-regulated genes to apoptosis induction by this protein, whereas in this review, we focus more on those factors that mediate the decision between growth arrest and apoptosis by p53, p63 and p73, and on the post-translational modifications and protein-protein interactions that influence this decision. 相似文献
992.
Gerber NU von Hoff K von Bueren AO Treulieb W Deinlein F Benesch M Zwiener I Soerensen N Warmuth-Metz M Pietsch T Mittler U Kuehl J Kortmann RD Grotzer MA Rutkowski S 《European journal of cancer (Oxford, England : 1990)》2012,48(13):2028-2036
BackgroundDue to the lacking specificity of symptoms making a correct diagnosis can be a challenge in children with medulloblastoma. This can lead to prediagnostic symptomatic intervals (PSIs) of several weeks to months. It is unknown whether the length of the PSI is associated with an inferior survival outcome in this population.MethodsTo study the association of PSI with disease stage at diagnosis, tumour control and survival in children with medulloblastoma, prospectively collected data on PSI, clinical, and biological features were analysed in 224 patients diagnosed at the age of 3–18 years and treated within the prospective randomised multicentre trial HIT’91.ResultsPatients with lower-stage disease tended towards a longer median PSI than those with higher-stage disease (M0 stage, 2.0 months; M1 stage, 2.0 months; M2/M3 stage, 1 month; p = 0.094. M0/1 stage versus M2/3 stage; p = 0.025). The patient group with the longest PSI had the best survival outcome (PSI ⩾4.0 months: 10-year overall survival rate (OS), 71%; PSI <4.0 months, 10-year OS, 61%; p = 0.056). Age at diagnosis was positively correlated with PSI (p = 0.027). No associations were found between PSI and sex histological subtype, presence of postoperative residual tumour, or c-myc and TrkC mRNA expression.ConclusionContrary to a common belief that a longer PSI may adversely affect prognosis, a longer PSI was associated with a trend towards lower metastatic stage and better survival probabilities. Nevertheless these findings do not obviate the importance of a timely diagnosis in paediatric patients with medulloblastoma. 相似文献
993.
BACKGROUND: To evaluate the feasibility and efficacy of intensive chemotherapy given prior to irradiation in pediatric patients with malignant glioma, the Society of Pediatric Oncology in Germany started a randomized trial in 1991. The high-grade glioma strata had to be closed because of insufficient patient accrual. The follow-up data from these patients are reported. METHODS: Fifty-two patients with World Health Organization (WHO) Grade 4 malignant glioma (n = 27 patients) or with WHO Grade 3 anaplastic astrocytoma (n = 25 patients) between the ages of 3 years and 17 years were available for analysis. The tumor locations were supratentorial in 42 patients, the cerebellum in 8 patients, and the spinal cord in 2 patients (the brainstem was excluded). Tumor surgeries were biopsy in 10 patients, partial resection in 5 patients, subtotal resection in 10 patients, and macroscopic total resection in 21 patients. Patients received either 54 grays of irradiation (n = 22 patients) followed by chemotherapy with lomustine, vincristine, and cisplatin (maintenance chemotherapy) or sandwich chemotherapy (n = 30 patients), which consisted of ifosfamide, etoposide, methotrexate, cisplatin, and cytosine arabinoside followed by irradiation. RESULTS: The extent of resection was the most important prognostic factor. The median survival was 5.2 years for patients who underwent tumor resection of > or = 90% compared with 1.3 years for patients who underwent less than complete resection (P < 0.0005). After undergoing macroscopic total resection, sandwich chemotherapy (n = 15 patients) resulted in better overall survival (median, 5.2 years) compared with the maintenance protocol (n = 16 patients; median survival, 1.9 years; P = 0.015). A Cox multivariate regression analysis showed better survival for female patients (P = 0.025), WHO Grade 3 disease (P = 0.016), tumor resection of > or = 90% (P = 0.003), irradiation with > or = 54 grays (P = 0.003), and sandwich chemotherapy (P = 0.006). CONCLUSIONS: These data suggest that early, intensive chemotherapy increases survival rates in patients with malignant glioma who undergo complete resection. 相似文献
994.
995.
K. Müller M.D. A. Gnekow F. Falkenstein J. Scheiderbauer I. Zwiener T. Pietsch M. Warmuth-Metz J. Voges G. Nikkhah M. Flentje S.E. Combs D. Vordermark M. Kocher R.-D. Kortmann 《Strahlentherapie und Onkologie》2013,189(8):647-655
Purpose
We evaluated clinical outcomes in the subset of patients who underwent radiotherapy (RT) due to progressive pilocytic astrocytoma within the Multicenter Treatment Study for Children and Adolescents with a Low Grade Glioma HIT-LGG 1996.Patients and methods
Eligibility criteria were fulfilled by 117 patients. Most tumors (65?%) were located in the supratentorial midline, followed by the posterior fossa (26.5?%) and the cerebral hemispheres (8.5?%). Median age at the start of RT was 9.2 years (range 0.7–17.4 years). In 75 cases, external fractionated radiotherapy (EFRT) was administered either as first-line nonsurgical treatment (n?=?58) or after progression following primary chemotherapy (n?=?17). The median normalized total dose was 54 Gy. Stereotactic brachytherapy (SBT) was used in 42 selected cases.Results
During a median follow-up period of 8.4 years, 4 patients (3.4?%) died and 33 (27.4?%) experienced disease progression. The 10-year overall (OS) and progression-free survival (PFS) rates were 97 and 70?%, respectively. No impact of the RT technique applied (EFRT versus SBT) on progression was observed. The 5-year PFS was 76?±?5?% after EFRT and 65?±?8?% after SBT. Disease progression after EFRT was not influenced by gender, neurofibromatosis type 1 (NF1) status, tumor location (hemispheres versus supratentorial midline versus posterior fossa), age or prior chemotherapy. Normalized total EFRT doses of more than 50.4 Gy did not improve PFS rates.Conclusion
EFRT plays an integral role in the treatment of pediatric pilocytic astrocytoma and is characterized by excellent tumor control. A reduction of the normalized total dose from 54 to 50.4 Gy appears to be feasible without jeopardizing tumor control. SBT is an effective treatment alternative. 相似文献996.
Marco Gessi David Capper Felix Sahm Kristin Huang Andreas von Deimling Stephan Tippelt Gudrun Fleischhack Daniel Scherbaum Joachim Alfer Björn-Ole Juhnke Katja von Hoff Stefan Rutkowski Monika Warmuth-Metz Lukas Chavez Stefan M. Pfister Torsten Pietsch David T. W. Jones Dominik Sturm 《Acta neuropathologica》2016,132(4):635-637
997.
998.
Zusammenfassung. Im Krankheitsverlauf von Patienten mit schweren Gallengangverletzungen im Rahmen einer laparoskopischen Cholecystektomie
werden oft sekund?re Komplikationen beobachtet. Berichtet wird über eine Patientin mit langem Krankheitsverlauf nach intraoperativer
Gallengangverletzung und anschlie?ender Rekonstruktion durch End-zu-End-Anastomose über einer T-Drainage. Mehr als 5 Jahre
nach wiederholten endoskopischen Gallenwegdilatationen und mehrfachen Einlagen von Stents wurde zuletzt ein selbstexpandierender
Metallgitterstent eingesetzt. Die Symptomatik mit rezidivierenden Cholestasen und Cholangitiden wurde nicht beherrscht. Bei
der erneuten Operation wurde jetzt der stenttragende D. choledochus reseziert, die Gallenwegrekonstruktion erfolgte durch
ein isoperistaltisches Jejunuminterponat. Mehr als 24 Monate sp?ter ist die Patientin beschwerdefrei und arbeitet wieder.
相似文献
999.
RM Hardie LH Newton JC Bruce JF Glasgow AP Mowat JB Stephenson SM Hall 《Archives of disease in childhood》1996,74(5):400-405
OBJECTIVE: To describe trends in the clinical pattern of Reye's syndrome in the British Isles between 1982 and 1990; and to determine the relation between any changes and the June 1986 warnings against the use of aspirin in children. DESIGN: Development, and application to reported cases, of a scoring system designed such that patients showing the typical clinical and pathological features of 'classical' Reye's syndrome scored highly. The relations between 'Reye scores' and a number of explanatory variables were explored using multivariable analysis. SETTING: British Isles. SUBJECTS: 445 cases fulfilling the Reye's syndrome case definition reported to the surveillance scheme between January 1982 and December 1990. MAIN OUTCOME MEASURE: Individual 'Reye score'. RESULTS: Cases with high scores were more likely to have occurred in the 4 1/2 year period before June 1986 compared with the subsequent period (p < 0.006). Numbers of cases in the low and intermediate score categories declined by about 50% after June 1986, whereas those in the high category fell by 79%. High scorers were more likely to have received aspirin (p < 0.0001) and were older than intermediate and low scorers (p < 0.008). No relation was identified between score and season of onset. CONCLUSIONS: The decline in Reye's syndrome after the aspirin warnings cannot be explained entirely, as has been proposed, by improved diagnosis of 'Reye-like' inherited metabolic and other disorders: this would not account for the greater decline of the high scoring subgroup which also contained those cases most likely to resemble 'classical' Reye's syndrome and to have received aspirin. This study provides further evidence for the role of aspirin in a subset of cases meeting the standard diagnostic criteria for Reye's syndrome and supports the need to consider this disorder as a heterogeneous group of conditions including Reye-like inherited metabolic disorders. 相似文献
1000.
W Cao HP Shah AV Glushakov AP Mecca P Shi C Sumners CN Seubert AE Martynyuk 《British journal of pharmacology》2009,158(8):2005-2013