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Biomedical subjects

Ana Aparicio

Publications and source records attributed to Ana Aparicio.

4 recordsLinked to original sources

The potential of histone deacetylase inhibitors in lung cancer.

In the nucleus, DNA is wrapped around octamers of histone proteins. Histones, like other proteins, are posttranslationally modified by the addition of an array of chemical groups that affect their interactions with surrounding structures. Histone acetyltransferases and histone deacetylases (HDACs) are the enzymes involved in the addition and removal, respectively, of acetyl groups from the aminoterminal tails of histones. A number of structurally diverse compounds are capable of inhibiting HDACs and exert a variety of biologic effects on cancer cells in preclinical models. Early clinical trials with the first generation of HDAC inhibitors (HDACIs) have demonstrated promising therapeutic activity, and HDACs have become one of the hottest targets in drug development today.

Animals↗

Epigenetics in human disease and prospects for epigenetic therapy.

Epigenetic mechanisms, which involve DNA and histone modifications, result in the heritable silencing of genes without a change in their coding sequence. The study of human disease has focused on genetic mechanisms, but disruption of the balance of epigenetic networks can cause several major pathologies, including cancer, syndromes involving chromosomal instabilities, and mental retardation. The development of new diagnostic tools might reveal other diseases that are caused by epigenetic alterations. Great potential lies in the development of 'epigenetic therapies'--several inhibitors of enzymes controlling epigenetic modifications, specifically DNA methyltransferases and histone deacetylases, have shown promising anti-tumorigenic effects for some malignancies.

DNA Methylation↗

Neoplastic meningitis.

Neoplastic meningitis (NM) is a common problem in neuro-oncology, occurring in approximately 5% of all patients with cancer. Notwithstanding frequent focal signs and symptoms, NM is a disease that affects the entire neuraxis; therefore, staging and treatment need to encompass all cerebrospinal fluid (CSF) compartments. Central nervous system (CNS) staging of NM includes contrast-enhanced cranial computerized tomography or magnetic resonance imaging, contrast-enhanced spine magnetic resonance imaging or computerized tomographic myelography, and radionuclide CSF flow study. Treatment of NM involves involved-field radiotherapy of bulky or symptomatic disease sites and intra-CSF drug therapy. The inclusion of concomitant systemic therapy may benefit patients with NM and may obviate the need for intra-CSF chemotherapy. At present, intra-CSF drug therapy is confined to three chemotherapeutic agents (ie, methotrexate, cytosine arabinoside, and thio-triethylene thiophosphoramide) administered by a variety of schedules either by intralumbar or intraventricular drug delivery. Although treatment of NM is palliative with an expected median patient survival of 2 to 6 months, it often affords stabilization and protection from further neurologic deterioration in patients with NM.

Central Nervous System Neoplasms↗

Review of the clinical experience with 5-azacytidine and 5-aza-2'-deoxycytidine in solid tumors.

In recent years the importance of epigenetic changes in carcinogenesis has been unfolding. It is now clear that the fifth base of the genome, methylcytosine, plays a critical role in the control of gene expression during normal development and carcinogenesis. Efforts to decrease methylation in neoplasias as a therapeutic strategy have been productive in hematologic malignancies but disappointing in solid tumors. The following is a review of the clinical experience with the agents 5-azacytidine and 5-aza-2'-deoxycytidine in solid malignancies and a discussion of the difficulties encountered.

Antimetabolites, Antineoplastic↗