DNA repair pathways and cisplatin resistance: an intimate relationship.

The main goal of chemotherapeutic drugs is to induce massive cell death in tumors. Cisplatin is an antitumor drug widely used to treat several types of cancer. Despite its remarkable efficiency, most tumors show intrinsic or acquired drug resistance.

Aptamer delivery of siRNA, radiopharmaceutics and chemotherapy agents in cancer.

Aptamers are oligonucleotide reagents with high affinity and specificity, which among other therapeutic and diagnostic applications have the capability of acting as delivery agents. Thus, aptamers are capable of carrying small molecules, nanoparticles, radiopharmaceuticals or fluorescent agents as well as nucleic acid therapeutics specifically to their target cells. In most cases, the molecules may possess interesting therapeutic properties, but their lack of specificity for a particular cell type, or ability to internalise in such a cell, hinders their clinical development, or cause unwanted side effects.

Caspase-3 activation and increased procollagen type I in irradiated hearts.

The caspase-3-cleaved presence was evaluated in this study in the heart of irradiated rats, during the decline of ventricular function. Female Wistar rats were irradiated with a single dose of radiation (15 Gy) delivered directly to the heart and the molecular, histological and physiological evaluations were performed at thirteen months post-irradiation. The expressions of procollagen type I, TGF-ß1 and caspase-3-cleaved were analyzed using Western blotting.

Novel XPG (ERCC5) mutations affect DNA repair and cell survival after ultraviolet but not oxidative stress.

Nucleotide excision repair (NER) is the most flexible of all known DNA-repair mechanisms, and XPG is a 3'-endonuclease that participates in NER. Mutations in this gene (ERCC5) may result in the human syndrome xeroderma pigmentosum (XP) and, in some cases, in the complex phenotype of Cockayne syndrome (CS). Two Brazilian XP siblings, who were mildly affected, were investigated and classified into the XP-G group.

Up-regulation of angiotensin-converting enzyme and angiotensin II type 1 receptor in irradiated rats.

Purpose: To investigate changes in cardiac functional parameters and the cardiac expression of angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AT1), procollagen type I (proc-I) and transforming growth factor-ß1 (TGF-ß1) in rats irradiated at heart.

Material And Methods: Male Wistar rats were irradiated with a single dose of radiation (0, 5, 10 and 15 Gray [Gy]) delivered directly to the heart and the molecular evaluations were performed at various times post-irradiation (two days, 15 days and four months). The expression of ACE, AT1, proc-I and TGF-ß1 were analysed using Real Time-Polymerase Chain Reaction (RT-PCR) and/or Western blotting.

Analysis of GSTM1 and GSTT1 polymorphisms in circulating plasma DNA of lung cancer patients.

The concentration of free circulating plasma DNA and the genetic profile of patients suffering from various types of tumors were studied in an effort to increase the understanding of the biomarkers and genetic factors involved in predisposing an individual to lung cancer (LC). The polymorphic inheritance of glutathione S-transferases (GST), which modulate the effects of various genotoxic agents, especially those derived from benzo[a]pyrene, one of the main tobacco carcinogens, has been implicated in both cancer risk and prognostics. We investigated gene polymorphisms in the blood serum of patients previously diagnosed at the Pneumology Division of the Clementino Fraga Filho University Hospital of the Federal University of Rio de Janeiro and in buccal swab samples of exfoliated oral cells obtained from a population of healthy controls.

Effects of lanthanum on human lymphocytes viability and DNA strand break.

Lanthanum (La) is a rare-earth metal with applications in agriculture, industry, and medicine. Since lanthanides show a broad spectrum of applications there is an increased risk of contamination for humans. We examined the effects of lanthanum in Jurkat cells and human peripheral lymphocytes (HPL), and we found that it was cytotoxic and genotoxic on both cell lines.

Changes in protein expression due to deleterious mutations in the FA/BRCA pathway.

Inherited deleterious mutations in one of the Fanconi anemia genes lead to a disease, characterized by bone marrow failure, myeloid leukemia, and hypersensitivity to DNA damage. We identified proteins likely associated to the molecular signaling pathways involved in DNA repair of interstrand cross-link lesions and in mechanisms of genomic stability mediated by FA/BRCA pathways. We compared protein maps resolved by bidimensional electrophoresis and analyzed differentially expressed proteins, by mass spectrometry, between FA complementation group C (FANCC)-deficient cells, and their ectopically corrected counterpart in physiological conditions or after treatment with MMC.