Nuclear receptors for vitamins A and D belong to the nuclear hormone receptor superfamily and act as ligand-inducible transcription factors. Therefore, most of the biological actions of vitamins A and D are now considered to be exerted through nuclear vitamin receptor-mediated gene expression. The vitamin A nuclear receptors compromise six members, three all-trans retinoic acid receptors (RARal...

Chemoprevention is the use of noncytotoxic therapeutic intervention at the early stages of carcinogenesis against the development and progression of mutant clones to invasive cancer. Retinoids are the most extensively studied and one of the most prominent groups of chemopreventive agents to reach clinical trials. Acute promyelocytic leukemia is the first human malignancy that is successfully tr...

Normal brain function requires that the overall synaptic activity in neural circuits be kept constant. Long-term alterations of neural activity lead to homeostatic regulation of synaptic strength by a process known as synaptic scaling. The molecular mechanisms underlying synaptic scaling are largely unknown. Here, we report that all-trans retinoic acid (RA), a well-known developmental morphogen...

Despite the success of the current therapy for patients with acute promyelocytic leukemia (APL), relapse occurs in up to 30% of patients. The characteristics of relapsed APL are not well described. We evaluated a group of APL cases at relapse and compared the clinicopathologic, immunophenotypic, molecular, and cytogenetic findings with those at initial diagnosis. From a group of 207 patients wi...

Retinoids play key roles in differentiation, growth arrest, and apoptosis and are increasingly being used in the clinic for the treatment of a variety of cancers, including neuroblastoma. Here, using a large-scale RNA interference-based genetic screen, we identify ZNF423 (also known as Ebfaz, OAZ, or Zfp423) as a component critically required for retinoic acid (RA)-induced differentiation. ZNF4...

In the prechemotherapy era arsenic derivatives were used for treatment of chronic myelogenous leukemia, a myeloproliferative disorder characterized by the t(9;22) translocation, the Philadelphia chromosome (Ph+). In acute promyelocytic leukemia response to arsenic trioxide (As2O3) has been shown to be genetically determined by the acute promyelocytic leukemia-specific t(15;17) translocation pro...

Nuclear receptors for retinoic acid are important modulators of epidermal cell proliferation and terminal differentiation. Aberrant expression of retinoic acid receptors (RARs) and retinoid X receptors in the epidermis has been associated with altered differentiation capacity and tumor progression. In this study, we describe a human squamous cell carcinoma line, SCC 12F, which displays reduced ...

Cancer is often associated with venous thrombosis, a phenomenon that was first described by Trousseau in 1865 (Trousseau syndrome). Recent studies have begun to explain how oncogenic events may deregulate the hemostatic system. For instance, activated oncogenes (K-ras, EGFR, PML-RARalpha, and MET) or inactivated tumor suppressors (e.g., 53 or PTEN) may increase the risk of thrombosis by inducin...

The gastrointestinal tract is replete with commensal microbes and dietary nutrients that provide homeostatic signals. Antigen presenting dendritic cells (DC) residing in the underlying lamina propria (Lp) respond to these signals; however, how they contribute to intestinal T cell homeostasis is unclear. In Chapter 2, LpDC are revealed to uniquely induce naïve T cell differentiation into the Fox...

Three heteroarotinoids containing a nitrogen atom in the first ring and a C-O linking group between the two aryl rings were synthesized and evaluated for RAR and RXR retinoid receptor transactivation, tumor cell growth inhibition, and transglutaminase (TGase) induction. Ethyl 4-(N,4,4-trimethyl-1,2,3,4-tetrahydroquinolinyl)benzoate (1) contained an N-CH(3) group and activated all retinoid recep...