Articles: oligonucleotides.
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We hypothesized that adenosine, acting via the A1 receptor, is a key factor in the homeostatic control of sleep. The increase in extracellular levels of adenosine during prolonged wakefulness is thought to facilitate the transition to sleep by reducing the discharge activity of wakefulness-promoting neurons in the basal forebrain. Adenosine A1 receptor control of the homeostatic regulation of sleep was tested by microdialysis perfusion of antisense oligonucleotides against the mRNA of the A1 receptor in the magnocellular cholinergic region of the basal forebrain of freely behaving rats. ⋯ Control experiments with microdialysis perfusion of nonsense (randomized antisense) oligonucleotides and with artificial CSF showed no effect during postdeprivation recovery sleep or spontaneously occurring behavioral states. Antisense to the A1 receptor suppressed A1 receptor immunoreactivity but did not show any neurotoxicity as visualized by Fluoro-Jade staining. These data support our hypothesis that adenosine, acting via the A1 receptor, in the basal forebrain is a key component in the homeostatic regulation of sleep.
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Zhonghua Zhong Liu Za Zhi · May 2003
[Antisense oligodeoxynucleotides of human telomerase reverse transcriptase inhibit endometrial carcinoma cell HEC-1A proliferation].
To evaluate antisense technology for human telomerase inhibition in the treatment of endometrial cancer. ⋯ Antisense oligodeoxynucleotides of human telomerase transcriptase definitely inhibits the proliferation of endometrial cancer cell line. Telomerase inhibitor may thus become a new gene therapeutic agent for endometrial carcinoma.
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Seminars in oncology · Apr 2003
ReviewAntisense therapy directed to protein kinase C-alpha (Affinitak, LY900003/ISIS 3521): potential role in breast cancer.
As our understanding of the biology of cancer increases, the attempts to target specific molecules associated with the promotion of cancer are accelerating. One of the targets currently being studied as an important tumor-promoting factor is protein kinase C-alpha (PKC-alpha). ⋯ Although its single-agent activity in breast cancer is modest, its potential role may be in concert with traditional chemotherapy. This is a review of the pharmacology and current status of the clinical development of LY900003 and its potential role in treating patients with breast cancer.
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Epidermal growth factor receptor (EGFR) and protein kinase A type I(PKAI) play an important role in the control of cancer cell growth and angiogenesis. Inhibitors of EGFR and PKAI have antitumor activity in vitro and in vivo in a variety of tumor types, and some of these agents are active after oral administration. Increasing evidence shows that cyclooxygenase (COX)-2 also plays a role in promoting cancer cell proliferation and angiogenesis. COX-2 expression can be induced by EGFR activation and is regulated by cAMP and PKA. Combination of an EGFR inhibitor with a nonselective COX-1/COX-2 inhibitor prevents the development of intestinal cancer in nude mice. Therefore, we investigated whether any cooperative antitumor effect can be obtained by the combined blockade of COX-2, EGFR, and PKAI. ⋯ This is the first demonstration that three novel agents blocking multiple signaling pathways, in absence of cytotoxic drugs, may have a potent antitumor and antiangiogenic activity after oral administration. Because all agents are under clinical evaluation, our results provide a rationale to translate this feasible therapeutic strategy into a clinical setting.
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MDM2 oncogene is overexpressed in many human cancers including prostate cancer and MDM2 levels are associated with poor prognosis. This study was undertaken to investigate the functions of MDM2 oncogene in prostate cancer growth and the value of MDM2 as a drug target for prostate cancer therapy by inhibiting MDM2 expression. ⋯ These results indicate that MDM2 has a role in prostate tumor growth through both p53-dependent and p53-independent mechanisms, indicating that MDM2 inhibitors have a broad spectrum of anti-tumor activities in human prostate cancers regardless of p53 status.