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中文摘要
翻译
描述:(改编自申请人摘要)促性腺激素释放
英文摘要
DESCRIPTION: (adapted from the applicants abstract) Gonadotropin releasing hormone (GnRH), through its G-protein -coupled, high-affinity receptor located on gonadotropes of the anterior pituitary, stimulates the secretion of gonadotropins (LH and FSH). It is now known that GnRH receptors (GnRHR) are also present in extra pituitary tissues, hormone-responsive tumors and tumors derived cell lines, suggesting that GnRH may serve additional functions. GnRHR expression is highly regulated in exhibiting both up and down regulation by its cognate ligand, by gonadal steroids and peptides. However, the mechanisms involved in altering the rate of expression of the GnRHR at molecular levels is unknown. In order to understand the regulation of GnRHR gene expression in the pituitary, extra-pituitary tissues and hormone responsive tumors, the PI isolated the human GnRHR gene and defined its genomic organization. The human GnRHR gene is composed of two introns and three exons, and spans over 20 kb. It contains multiple transcriptional initiation sites and a large number of putative regulatory sequences for various hormones and other regulatory factors raising the possibility of tightly-regulated, differential expression of the receptor gene, which may be tissue specific. Thus the GnRHR may play a key role in the regulation of hormone-responsive tumors growth and its responsiveness to various stimuli and/or it's expression may be regulated by such stimuli. The long termed goals are to understand at the molecular level the DNA components and transcriptional factors that are responsible for the tissue specific expression and hormonal regulation of the human GnRHR gene, and to define the molecular mechanism of inhibition of tumor cell growth by GnRH. The specific aims are: 1) To characterize the promoter sequence for GnRH-receptor gene in pituitary, extra-pituitary tissue and in hormone responsive tumors, 2) To study GnRHR, transcriptional regulation by estrogen, progesterone, glucocorticoid, testosterone, GnRH, inhibin, TPA and cAMP, 3) To identify the cells in tumors expressing GnRH receptor using a monoclonal antibody, and 4) To determine the expression of GnRH and GnRHR in normal and tumor tissues. These studies will likely provide a greater understanding of the regulation of the GnRH-receptor gene and allow us to better understand the complex mechanism of its transcriptional regulation. These studies have the potential to provide the basis for the development of a new class of drugs for treatments of hormone-responsive tumors.
期刊论文(15)
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Identification of gene networks modulated by activin in LbetaT2 cells using DNA microarray analysis.
使用 DNA 微阵列分析鉴定 LbetaT2 细胞中激活素调节的基因网络。
DOI: 10.14670/hh-21.167
发表时间: 2006
期刊: Histology and histopathology
影响因子: 2
作者: [Mazhawidza,W, Winters,SJ, Kaiser,UB, Kakar,SS]
通讯作者: Kakar,SS
Chronic administration of the luteinizing hormone-releasing hormone (LHRH) antagonist cetrorelix decreases gonadotrope responsiveness and pituitary LHRH receptor messenger ribonucleic acid levels in rats.
长期服用黄体生成素释放激素 (LHRH) 拮抗剂西曲瑞克会降低大鼠的促性腺激素反应性和垂体 LHRH 受体信使核糖核酸水平。
DOI: 10.1210/endo.137.8.8754771
发表时间: 1996
期刊: Endocrinology.
影响因子: --
作者: [Pinski,J, Lamharzi,N, Halmos,G, Groot,K, Jungwirth,A, Vadillo-Buenfil,M, Kakar,SS, Schally,AV]
通讯作者: Schally,AV
Inhibition of growth and proliferation of EcRG293 cell line expressing high-affinity gonadotropin-releasing hormone (GnRH) receptor under the control of an inducible promoter by GnRH agonist (D-Lys6)GnRH and antagonist (Antide).
在 GnRH 激动剂 (D-Lys6)GnRH 和拮抗剂 (Antide) 的诱导型启动子控制下,抑制表达高亲和力促性腺激素释放激素 (GnRH) 受体的 EcRG293 细胞系的生长和增殖。
DOI: --
发表时间: 1998
期刊: Cancer research.
影响因子: --
作者: [Kakar,SS]
通讯作者: Kakar,SS
DOI: 10.1016/0304-3835(95)90203-1
发表时间: 1995-11-27
期刊: CANCER LETTERS
影响因子: 9.7
作者: [Kakar, SS, Jennes, L]
通讯作者: Jennes, L
8
    Current Trends in Stem Cell Therapies
    • 批准号:
      10158506
    • 项目类别:
    • 资助金额:
      $22.69万
    • 财政年份:
      2017
    • 负责人:
      Sham S. Kakar
    • 依托单位:
    Current Trends in Stem Cell Therapies
    • 批准号:
      9359106
    • 项目类别:
    • 资助金额:
      $12.88万
    • 财政年份:
      2017
    • 负责人:
      Sham S. Kakar
    • 依托单位:
    PTTG Role in Ovarian Tumorigenesis and Matastasis
    • 批准号:
      7538374
    • 项目类别:
    • 资助金额:
      $25.31万
    • 财政年份:
      2007
    • 负责人:
      Sham S. Kakar
    • 依托单位:
    PTTG Role in Ovarian Tumorigenesis and Matastasis
    • 批准号:
      7754388
    • 项目类别:
    • 资助金额:
      $25.31万
    • 财政年份:
      2007
    • 负责人:
      Sham S. Kakar
    • 依托单位:
    海外基金