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排序方式: 共有1237条查询结果,搜索用时 656 毫秒
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Qin Shu Barbara Antalffy Jack Meng Feng Su Adekunle Adesina Ching-Nan Ou Torsten Pietsch Susan M Blaney Ching C Lau Xiao-Nan Li 《Clinical cancer research》2006,12(15):4687-4694
PURPOSE: To develop novel orthotopic xenograft models of medulloblastoma in severe combined immunodeficient mice and to evaluate the in vivo antitumor efficacy of valproic acid. EXPERIMENTAL DESIGN: Orthotopic xenografts were developed by injecting 10(3) to 10(5) tumor cells from four medulloblastoma cell lines (D283-MED, DAOY, MHH-MED-1, and MEB-MED-8A) into the right cerebellum of severe combined immunodeficient mice. Animals were then examined for reproducibility of tumorigenicity, cell number-survival time relationship, and histopathologic features. Tumor growth was monitored in vivo by serially sectioning the xenograft brains at 2, 4, 6, and 8 weeks postinjection. Valproic acid treatment, administered at 600 microg/h for 2 weeks via s.c. osmotic minipumps, was initiated 2 weeks after injection of 10(5) medulloblastoma cells, and treated and untreated animals were monitored for differences in survival. Changes in histone acetylation, proliferation, apoptosis, differentiation, and angiogenesis in xenografts were also evaluated. RESULTS: Tumorigenicity was maintained at 100% in D283-MED, DAOY, and MHH-MED-1 cell lines. These cerebellar xenografts displayed histologic features and immunohistochemical profiles (microtubule-associated protein 2, glial fibrillary acidic protein, and vimentin) similar to human medulloblastomas. Animal survival time was inversely correlated with injected tumor cell number. Treatment with valproic acid prolonged survival time in two (D283-MED and MHH-MED-1) of the three models and was associated with induction of histone hyperacetylation, inhibition of proliferation and angiogenesis, and enhancement of apoptosis and differentiation. CONCLUSION: We have developed intracerebellar orthotopic models that closely recapitulated the biological features of human medulloblastomas and characterized their in vivo growth characteristics. Valproic acid treatment of these xenografts showed potent in vivo anti-medulloblastoma activity. These xenograft models should facilitate the understanding of medulloblastoma pathogenesis and future preclinical evaluation of new therapies against medulloblastoma. 相似文献
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Specific c-K-ras Gene Mutations as a Tumor-Response Marker in Locally Advanced Rectal Cancer Treated With Preoperative Chemoradiotherapy 总被引:3,自引:0,他引:3
Luna-Pérez P Segura J Alvarado I Labastida S Santiago-Payán H Quintero A 《Annals of surgical oncology》2000,7(10):727-731
Background: Forty percent of patients with colorectal cancer develop mutations in the K-ras gene.Objective: Our objective was to evaluate whether the presence of c-K-ras gene mutations is a useful tumor-response marker in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy.Material and Methods: Thirty seven patients with locally advanced rectal cancer were treated with preoperative chemoradiotherapy. Four to six weeks later, surgery was performed. Specimens were classified according to the UICC-AJC classification. A segment of the tumor was obtained to analyze specific c-K-ras gene mutations. Restriction fragment length polymorphism (RFLP) and single strand confirmation polymorphism (SSCP) techniques were used with a set of probes to detect specific c-K-ras mutations in codons 12, 13, and 61. The 37 patients were divided into Group A (with mutations) and Group B (without mutations).Results: All 37 patients completed the scheduled treatment. Group A consisted of 12 patients, whose tumors were classified and specific c-K-ras mutations were located as follows: eight in codon 12, two in codon 13, and one in codon 61. Group B consisted of 25 patients. The tumors were classified and there were more early-stage tumors in Group A, whereas in Group B there were more advanced-stage tumors (P 5 .05, respectively). The mean follow-up was 36.2 6 18.3 months. All Group A patients survived, whereas 8 of the 25 patients in Group B died due to progressive metastatic disease. Survival in Group A was 100%, whereas in Group B it was 59% (P 5 .03).Conclusions: The presence of specific c-K-ras mutations is an indicator of tumor response in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy and surgery. Therefore, responding patients may be more amenable to less radical surgical procedures based on c-K-ras mutations. 相似文献
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Leaf AN Wolf BC Kirkwood JM Haselow RE 《Medical oncology (Northwood, London, England)》2000,17(1):47-51
This study of etoposide in thyroid cancer was designed to determine the activity and toxicity of etoposide in a variety of
inoperable, thyroid hormone insensitive, and radio-iodine resistant primary cancers of the thyroid. The patients were required
to have an ECOG performance status of at least 3 and no previous exposure to chemotherapy. The etoposide was given at a dose
of 140 mg/m2 daily for 3 days and every 3 weeks until progression. The study was closed after 18 months because of poor accrual. There
were no responses seen among the 10 patients accrued. The toxicity was primarily hematologic. There was no evidence of activity
of etoposide in thyroid carcinoma, although this study lacked significant power because of the poor accrual. 相似文献
79.
STANTON School Of Rehabilitation Sciences University Of British Columbia Vancouver BC Canada S 《Occupational therapy international》2001,8(2):96-106
Despite a high demand for continuing professional education, it is becoming more challenging to provide education in a resource-limited environment that meets the varied needs of learners. The advent of user-friendly, interactive communication technology led the University of British Columbia in Canada to explore the feasibility of developing a web-based distance learning programme shared by undergraduate and practising therapists to address this problem. Potential benefits and challenges of distance learning, undergraduate web-learning, pilot-test results and an assessment of therapists’ interests and needs are profiled. 相似文献
80.
Calorie restriction in nonhuman primates: mechanisms of reduced morbidity and mortality 总被引:1,自引:0,他引:1
Long term chronic calorie restriction (CR) of adult nonhuman primates
significantly reduces morbidity and increases median age of death. The
present review is focused upon an ongoing study of sustained adult- onset
calorie restriction, which has been underway for 15 years. Monkeys,
initially calorie restricted at about 10 years of age, are now
approximately 25 years old. The median life span of these restricted
monkeys is increasing, now exceeding that of ad libitum (AL)-fed monkeys.
In our laboratory, maximum life span for AL-fed monkeys appears to be about
40 years. Thus, whether CR can also increase maximal life span, as it does
in rodents, cannot be determined for at least another 15 years. The
earliest detectable positive benefit on morbidity in these monkeys was
previously reported as the prevention of obesity. Current evidence, as
reviewed here, suggests that much obesity- associated morbidity is also
mitigated by sustained calorie restraint in nonhuman primates. Furthermore,
probably because of the prevention of obesity, diabetes has also been
prevented. Recent findings include the identification of extraordinary
changes in the glycogen synthesis pathway, and on the phosphorylation of
glycogen synthase in response to insulin. This calorie restriction-induced
prevention of morbidity does not require excessive leanness, but is clearly
present when body fat is within the normal range of 10 to 22%, and this is
likely to be true in humans as well.
相似文献