C MYC EXPRESSION DURING ALV LYMPHOMAGENESIS
C MYC EXPRESSION DURING ALV LYMPHOMAGENESIS
批准号:
6946179
负责人:
M ALANNA RUDDELL
金额:
$6.5万
依托单位国家:
美国
项目类别:
财政年份:
1996
资助国家:
美国
项目状态:
已结题
起止时间:
1996-05-15 至 2005-05-31
关键词:
中文摘要
描述:(改编自研究者的摘要)禽白血病病毒
(ALV) 快速诱导淋巴瘤易感者发生转移性法氏囊淋巴瘤
携带原病毒 c-myc 的 B 细胞克隆扩增后的鸡品系
转化卵泡内的基因整合。脉冲追踪标记
增殖和法氏囊移出的测量将检查 c-myc 如何
过度表达会诱导这些转化的卵泡快速扩张。一样的
分析将确定为什么转化的滤泡具有淋巴瘤抗性
鸡品系无法扩大并形成肿瘤。法氏囊移植
来自逆转录病毒载体的过表达外源 myc 的祖细胞将进行测试
这种耐药性是否是由于 ALF LTR 驱动的 myc 表达减少所致,或者
改变靶细胞对 myc 表达的反应。免疫组织化学研究
myc 对淋巴瘤易感鸟类的影响揭示了早期血管生成
c-myc 或 v-myc 转化的滤泡和肿瘤内的阶段。血管生成
B 细胞中 myc 过度表达诱导的活性将使用
内皮增殖、迁移和血管的体外和体内测定
成长。在法氏囊淋巴瘤发生过程中,血管生成将被操纵
表达myc和/或血管生成的法氏囊祖细胞移植
来自逆转录病毒载体的抑制剂,以确定是否抑制
血管生成阻止 myc 转化的卵泡或其早期生长
形成转移性淋巴瘤的能力。法氏囊淋巴细胞过表达 myc
显示血管内皮生长因子(VEGF)的产生增加。的
这种内皮生长因子对 myc 诱导的血管生成的贡献将
通过 B 细胞中 VEGF 的过度表达或表达不足来评估。效果
低 myc B 细胞系中 VEGF 过表达的特征是
内皮增殖、迁移和血管生成测定以及法氏囊
将评估过度表达 VEGF 的祖细胞诱导
体内血管生成。 VEGF 基因将从 myc 过表达 B 中删除
通过同源重组对细胞系进行分析,以确定这是否会减少
体外血管生成活性和体内血管生成肿瘤的形成。这些
研究将深入了解 myc 和 VEGF 诱导的血管生成的作用
在淋巴瘤的产生过程中。实验模型的结果将
可应用于人类淋巴瘤和其他癌症的血管生成研究
涉及 c-myc 表达失调,以确定 myc 是否诱导
血管生成有助于 myc 过度表达与
人类癌症。
英文摘要
DESCRIPTION: (Adapted from the investigator's abstract) Avian leukosis virus
(ALV) rapidly induces metastatic bursal lymphomas in lymphoma-susceptible
chicken strains, after clonal expansion of B cells harboring a proviral c-myc
gene integration within transformed follicles. Pulse-chase labelling
measurements of proliferation and bursal emigration will examine how c-myc
overexpression induces rapid expansion of these transformed follicles. The same
analysis will determine why transformed follicles from lymphoma-resistant
chicken strains fail to expand and form tumors. Transplantation of bursal
progenitors overexpressing exogenous myc from retroviral vectors will test
whether this resistance results from reduced ALF LTR-driven myc expression, or
altered target cell response to myc expression. Immunohistochemical studies of
the effects of myc in lymphoma-susceptible birds revealed angiogenesis at early
stages within c-myc or v-myc-transformed follicles and tumors. The angiogenic
activity induced by myc overexpression in B cells will be characterized using
in vitro and in vivo assays of endothelial proliferation, migration, and vessel
growth. Angiogenesis will be manipulated during bursal lymphomagenesis by
transplantation of bursal progenitors expressing myc and/or angiogenic
inhibitors from retroviral vectors, to determine whether inhibition of
angiogenesis prevents early growth of myc-transformed follicles or their
ability to form metastatic lymphomas. Bursal lymphocytes overexpressing myc
show increased vascular endothelial growth factor (VEGF) production. The
contribution of this endothelial growth factor to myc-induced angiogenesis will
be assessed by overexpressing or underexpressing VEGF in B cells. The effects
of VEGF overexpression in low myc B cell lines will be characterized by
endothelial proliferation, migration, and angiogenesis assays, and bursal
progenitors overexpressing VEGF will be assessed for their ability to induce
angiogenesis in vivo. The VEGF gene will be deleted from myc-overexpressing B
cell lines by homologous recombination, to determine whether this reduces
angiogenic activity in vitro, and formation of angiogenic tumors in vivo. These
studies will give insight to the role of myc- and VEGF-induced angiogenesis
during the generation of lymphomas. Findings from the experimental model will
be applied to studies of angiogenesis in human lymphomas and other cancers
involving de-regulated c-myc expression, to determine whether myc-induced
angiogenesis contributes to the common association of myc overexpression with
human cancers.
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C-MYC EXPRESSION DURING ALV LYMPHOMAGENESIS
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批准号:2112259
-
项目类别:
-
资助金额:$16.4万
-
财政年份:1996
-
负责人:M ALANNA RUDDELL
-
依托单位:
C-MYC EXPRESSION DURING ALV LYMPHOMAGENESIS
-
批准号:2668021
-
项目类别:
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资助金额:$17.72万
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财政年份:1996
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负责人:M ALANNA RUDDELL
-
依托单位:
c-Myc Expression during Lymphomagenesis
-
批准号:6927769
-
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资助金额:$35.33万
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负责人:M ALANNA RUDDELL
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依托单位:
Lymph Node Alterations in Cancer
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批准号:8587127
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资助金额:$16.64万
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负责人:M ALANNA RUDDELL
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依托单位:
Lymph Node Alterations in Cancer
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批准号:8225378
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资助金额:$18.56万
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c-Myc Expression during Lymphomagenesis
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批准号:7406119
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资助金额:$33.72万
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C MYC EXPRESSION DURING ALV LYMPHOMAGENESIS
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批准号:6512767
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项目类别:
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资助金额:$34.89万
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依托单位:
Lymph Node Alterations in Cancer
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批准号:7988050
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资助金额:$37.66万
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Lymph Node Alterations in Cancer
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项目类别:
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资助金额:$29.67万
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c-Myc Expression during Lymphomagenesis
-
批准号:7918483
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资助金额:$5.03万
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C MYC EXPRESSION DURING ALV LYMPHOMAGENESIS
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批准号:6195686
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资助金额:$26.94万
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批准号:2591017
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项目类别:
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资助金额:$8.76万
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依托单位:
C-MYC EXPRESSION DURING ALV LYMPHOMAGENESIS
-
批准号:2376980
-
项目类别:
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资助金额:$7.83万
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财政年份:1996
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负责人:M ALANNA RUDDELL
-
依托单位:
c-Myc Expression during Lymphomagenesis
-
批准号:7050532
-
项目类别:
-
资助金额:$32.93万
-
财政年份:1996
-
负责人:M ALANNA RUDDELL
-
依托单位:
c-Myc Expression during Lymphomagenesis
-
批准号:7231005
-
项目类别:
-
资助金额:$33.76万
-
财政年份:1996
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负责人:M ALANNA RUDDELL
-
依托单位:
Lymph Node Alterations in Cancer
-
批准号:8063168
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项目类别:
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资助金额:$35.73万
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依托单位:
C MYC EXPRESSION DURING ALV LYMPHOMAGENESIS
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项目类别:
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资助金额:$34.83万
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财政年份:1996
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负责人:M ALANNA RUDDELL
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依托单位:
C MYC EXPRESSION DURING ALV LYMPHOMAGENESIS
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批准号:6633080
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项目类别:
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资助金额:$35.03万
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财政年份:1996
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负责人:M ALANNA RUDDELL
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依托单位:
REGULATION OF ALV EXPRESSION AND PATHOGENESIS
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批准号:2096139
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项目类别:
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资助金额:$16.36万
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财政年份:1992
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负责人:M ALANNA RUDDELL
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依托单位:
REGULATION OF ALV EXPRESSION AND PATHOGENESIS
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批准号:3199303
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项目类别:
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资助金额:$14.79万
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财政年份:1992
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依托单位:
海外基金