Trastuzumab inhibits pituitary tumor cell growth modulating the TGFB/SMAD2/3 pathway.

In pituitary adenomas, early recurrences and resistance to conventional pharmacotherapies are common, but the mechanisms involved are still not understood. The high expression of epidermal growth factor receptor 2 (HER2)/extracellular signal-regulated kinase (ERK1/2) signal observed in human pituitary adenomas, together with the low levels of the antimitogenic transforming growth factor beta receptor 2 (TBR2), encouraged us to evaluate the effect of the specific HER2 inhibition with trastuzumab on experimental pituitary tumor cell growth and its effect on the antiproliferative response to TGFB1. Trastuzumab decreased the pituitary tumor growth as well as the expression of ERK1/2 and the cell cycle regulators CCND1 and CDK4.

Cervicothoracic cutaneomeningospinal angiomatosis in adults (Cobb's syndrome): A case report of acute quadriparesis.

Background: Cutaneomeningospinal angiomatosis or Cobb syndrome is a rare, not well understood phacomatosis that features metameric cutaneous and spinal arteriovenous malformations (AVMs). The first case was described in Boston in 1915, and since then, few more cases have been reported in the English literature. No case was found to be from Argentina.

[Arteriovenous Malformations - checking and descriptive analysis of 52 AVMs treated for the 2000-2010 period].

Background: To describe our experience in treating AVMs based on age, sex, reasons for consultation and symptoms, localization and clinical diagnosis, size, types, relation with aneurysms, endovascular procedures used, postoperative results and complications.

Methods: We present 52 patients with AVMs, analysing Neurological Exam, Ct, Irm and Brain Arteriography.

Results: Average age: 37.

Myeloid cell diversification and complexity: an old concept with new turns in oncology.

Tumour development is accompanied by an enhanced haematopoiesis. This is not a widespread activation since only cells belonging to the myelo-monocytic compartment are expanded and mobilized from primary sites of haematopoiesis to other organs, reaching also the tumour stroma. This process occurs early during tumour formation but becomes more evident in advanced disease.

Therapeutic targeting of myeloid-derived suppressor cells.

Myeloid-derived suppressor cells (MDSCs) represent a subset of myeloid cells that expand under pathological conditions, such as cancer development, acute and chronic infections, trauma, bone marrow transplantations, and some autoimmune diseases. MDSCs mediate a negative regulation of the immune response by affecting different T lymphocyte subsets. Potential mechanisms, which underlie this inhibitory activity range from those requiring direct cell-to-cell contact with others, more indirect, and mediated by the modification of the microenvironment.

Decitabine, differently from DNMT1 silencing, exerts its antiproliferative activity through p21 upregulation in malignant pleural mesothelioma (MPM) cells.

Malignant pleural mesothelioma (MPM) is a locally aggressive neoplasm, principally linked to asbestos fibres exposure. Strong evidences associate this pollutant with induction of DNA breaks, aberrant chromosomes segregation and important chromosomal rearrangements, considered crucial events in malignant transformation. A considerable contribution to cellular transformation in MPM is also given by the presence of high genomic instability, as well as by the increased DNA methylation, and consequent decreased expression, of tumor-suppressor genes.

HER2/neu DNA vaccination for breast tumors.

Several studies of DNA vaccination against HER2/neu showed the effectiveness of immunization protocols in models of transplantable or spontaneous tumors. The DNA delivery system plays a crucial role in the success of DNA vaccination. In particular, our studies of DNA vaccination against HER2/neu tumor antigen showed that intramuscular injection of the vaccine followed by electroporation elicits an optimal protection against the development of spontaneous HER2/neu- tumors occurring in transgenic mice.

Effect of the silybin-phosphatidylcholine complex (IdB 1016) on the development of mammary tumors in HER-2/neu transgenic mice.

Silybin, a main component of the milk thistle of Silybum marianum, has been reported to possess anticancer activity. We investigated the effects of IdB 1016, a complex of silybin with phosphatidylcholine, on the development of mammary tumors appearing spontaneously in HER-2/neu transgenic mice. The mechanisms involved in the antitumor effect of IdB 1016 were evaluated by studying the apoptosis, senescent-like growth arrest, intratumoral leukocyte infiltrate, and the expression of HER-2/neu and p53 in tumoral mammary glands from transgenic mice and in human breast SKBR3 tumor cells.

Evaluation of different plasmid DNA delivery systems for immunization against HER2/neu in a transgenic murine model of mammary carcinoma.

Studies of DNA vaccination against HER2/neu showed the effectiveness of immunization protocols in models of transplantable or spontaneous tumors; scarce information, however, has been provided to identify the procedure of DNA administration that more effectively contributes to the activation of immune system against spontaneously arising HER2/neu-positive tumors. We compared the effectiveness of different procedures of DNA vaccine delivery (intradermic injection (ID), gene gun (GG) delivery and intramuscular injection (IM) alone or with electroporation) in a murine transgenic model of mammary carcinoma overexpressing HER2/neu. We highlighted the role of DNA delivery system in the success of DNA vaccination showing that, among the analysed methods, intramuscular injection of the vaccine, particularly when associated to electroporation, elicits a better protection against HER2/neu spontaneous tumor development inducing antibody and cell-mediated immune responsiveness against HER2/neu and a Th1 polarization of the immune response.

Imiquimod and S-27609 as adjuvants of DNA vaccination in a transgenic murine model of HER2/neu-positive mammary carcinoma.

DNA vaccination against HER-2/neu is an effective way to induce an immune response able to oppose the spontaneous development of mammary tumours occurring in HER-2/neu transgenic mice. In this study, we have evaluated the potential of Imiquimod and the analogue S-27609 as adjuvants of DNA vaccination against HER-2/neu in transgenic mice. The association of a DNA vaccine encoding a portion of rat HER2/neu with either Imiquimod or S-27609 was found to delay the development of spontaneous mammary tumours and to reduce their incidence, in comparison with DNA vaccination alone.