Effectiveness of Trastuzumab for Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in a Real-Life Setting: One Decade of Experience Under National Treatment Coverage Regulations.

Purpose: Trastuzumab has shown an overall survival (OS) benefit in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), in both the adjuvant and the metastatic setting. We assessed the effectiveness of trastuzumab in patients treated in daily practice according to national treatment coverage protocols and compared our results with those reported by randomized clinical trials. These coverage protocols included patient selection criteria similar to those of those clinical trials and were developed by the Uruguayan National Resource Fund (FNR), the agency that has funded these prescriptions for more than a decade.

Two Opposing Faces of Retinoic Acid: Induction of Stemness or Induction of Differentiation Depending on Cell-Type.

Stem cells have the capacity of self-renewal and, through proliferation and differentiation, are responsible for the embryonic development, postnatal development, and the regeneration of tissues in the adult organism. Cancer stem cells, analogous to the physiological stem cells, have the capacity of self-renewal and may account for growth and recurrence of tumors. Development and regeneration of healthy tissues and tumors depend on the balance of different genomic and nongenomic signaling pathways that regulate stem cell quiescence, proliferation, and differentiation.

All-trans-retinoic acid activates the pro-invasive Src-YAP-Interleukin 6 axis in triple-negative MDA-MB-231 breast cancer cells while cerivastatin reverses this action.

All-trans-retinoic acid (RA), the active metabolite of vitamin A, can reduce the malignant phenotype in some types of cancer and paradoxically also can promote cancer growth and invasion in others. For instance, it has been reported that RA induces tumor suppression in tumor xenografts of MDA-MB-468 breast cancer cells while increasing tumor growth and metastases in xenografts of MDA-MB-231 breast cancer cells. The signaling pathways involved in the pro-invasive action of retinoic acid remain mostly unknown.

Inhibition of the canonical IKK/NF kappa B pathway sensitizes human cancer cells to doxorubicin.

The NF kappa B family is composed by five subunits (p65/RelA, c-Rel, RelB, p105-p50/NF kappa B(1), p100-p52/NF kappa B(2)) and controls the expression of many genes that participate in cell cycle, apoptosis, and other key cellular processes. In a canonical pathway, NF kappa B activation depends on the IKK complex activity, which is formed by three subunits (IKKalpha and IKKbeta and IKKgamma/NEMO). There is an alternative NF kappa B activation pathway that does not require IKKbeta or IKKgamma/NEMO, in which RelB is a major player.

Antiangiogenic effects of anti-tumor necrosis factor alpha therapy with infliximab in psoriatic arthritis.

Objective: Neovascularization, with an increased number of synovial vessels with a characteristic morphology, seems to contribute to the progression of psoriatic arthritis (PsA). Accordingly, angiogenesis may be an important therapeutic target in PsA. The aim of this study was to analyze the effects of infliximab on angiogenesis in the synovial membrane of patients with PsA who responded to this therapy.

Down-regulation of Flt-1 gene expression by the proteasome inhibitor MG262.

The mechanisms involved in the anti-angiogenic actions of the proteasome inhibitors are poorly understood. Here, we report that the gene expression of the VEGF receptor Flt-1 (vascular endothelial growth factor receptor 1) was down-regulated by the reversible proteasome inhibitor MG262 in explant cultures of the developing chicken pecten oculi, a vascular organ consisting of endothelial cells, pericytes, and macrophages. In addition, the inhibitor prevented the induction of Flt-1 by lipopolysaccharide (LPS) in macrophages and down-regulated the expression of Flt-1 after LPS induction.

Constitutive and heat-shock induced expression of Hsp70 mRNA during chicken testicular development and regression.

The constitutive and heat shock induced expression of Hsp70 mRNA was investigated in normal adult chicken testis and in adult testis after testicular regression induced by diethylstilbestrol (DES) treatment. In addition to the canonical form of Hsp70 mRNA, we have detected transcripts with an extended 5'UTR and transcripts containing, in the 5'UTR, sequences of the 18S ribosomal RNA. Hsp70 was expressed in unstressed male gonads in adult and regressed testis, being the expression much lower in regressed testis.

Genomic structure and alternative splicing of chicken angiopoietin-2.

Angiopoietin-1 (Ang-1) prevents endothelial cell apoptosis and promotes blood vessel stability, while angiopoietin-2 (Ang-2), a natural antagonist of Ang-1, disrupts blood vessel structure and induces apoptosis. We have sequenced the chicken angiopoietin-2 gene that spans about 46 kb of DNA and is split in 9 exons by 8 introns. Alternative splicing of the gene gives rise to three different species of Ang-2 mRNAs: Ang-2A, Ang-2B, and Ang-2C.

Expression of lactate dehydrogenases A and B during chicken spermatogenesis: characterization of testis specific transcripts.

The substrates required for glycolysis change markedly at successive stages of spermatogenesis suggesting a considerable plasticity in the expression of glycolytic enzymes. Lactate dehydrogenase (LDH) isoenzymes, LDH-A and LDH-B, are expressed in premeiotic, meiotic cells, and early spermatids, both in avian and mammalian spermatogenesis. Highly polyadenylated forms, particularly of LDH-A, were detected in chicken testis.

Characterization of a novel form of angiopoietin-2 (Ang-2B) and expression of VEGF and angiopoietin-2 during chicken testicular development and regression.

The complex process of angiogenesis is controlled by the vascular endothelial growth factor (VEGF) and its receptors and by the recently isolated angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) that signal through the transmembrane endothelial receptor tyrosine kinase Tie2. We report here the characterization of a novel form of Ang-2 (Ang-2B) with a truncated amino-terminal domain resulting from an alternative splicing of the gene. While previous reports have found the expression of Ang-2 limited to the embryo, female reproductive organs, and tumor tissues, we have observed striking changes in Ang-2 expression during chicken testicular development and regression.

Novel transcripts of carbonic anhydrase II in mouse and human testis.

Intracellular and extracellular sources of bicarbonate are essential for sperm motility, sperm binding to the zona pellucida and the acrosome reaction. Carbonic anhydrase II, catalysing the synthesis of bicarbonate within spermatozoa, must play a significant role in these mechanisms. We report here the expression of carbonic anhydrase II during mouse spermatogenesis and the primary structure of testicular transcripts coding for carbonic anhydrase II isolated from adult mouse and human testes.

Marked differences between avian and mammalian testicular cells in the heat shock induction and polyadenylation of Hsp70 and ubiquitin transcripts.

Mammalian male germ cells undergo apoptosis at the body's internal temperature of 37 degrees C. Birds, however, are unique among homeothermic animals in developing spermatogenesis at the elevated avian internal body temperature of 40-41 degrees C. To shed light on the mechanisms that maintain an efficient avian spermatogenesis at elevated temperatures we compared, in mouse and chicken testicular cells, the expression of genes that are essential for stress resistance: Hsp70 and ubiquitin.

Several novel transcripts of glyceraldehyde-3-phosphate dehydrogenase expressed in adult chicken testis.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in addition to being a classic glycolytic enzyme, is a multifunctional protein involved in relevant cell functions such as DNA replication, DNA repair, translational control of gene expression, and apoptosis. Although the multifunctional nature of GAPDH suggests versatility in the mechanisms regulating its expression, no major qualitative changes and few quantitative changes in the GAPDH transcripts have been reported. While studying the expression of GAPDH during spermatogenesis, we detected alternative initiations to TATA box and alternative splicings in the 5' region of the pre-mRNA, resulting in at least six different types of mRNAs.

Ascites fluid of nephrotic rats: sodium dodecyl sulphate-polyacrylamide gel electrophoresis protein pattern and the renin-angiotensin system.

1. The concentration of renin and angiotensinogen (Ao) and the activity of angiotensin I-converting enzyme (ACE) was measured in the ascites fluid of nephrotic rats obtained 8 days after puromycin aminonucleoside (PAN) injection. 2.

Four isoforms of the signal-transduction and RNA-binding protein QKI expressed during chicken spermatogenesis.

Genes expressed during spermatogenesis undergo alternative initiation and alternative splicing and may be under the control of a coordinated mechanism of RNA processing. A family of proteins that combine features of signal-transduction and RNA-binding molecules could be instrumental in this process. We have characterized a cDNA from adult chicken testis that codifies a highly conserved member of the STAR protein family, the orthologue of the mouse quaking gene qki.

Characterization and expression of two chicken cDNAs encoding ubiquitin fused to ribosomal proteins of 52 and 80 amino acids.

We have determined the complete nucleotide sequence of two chicken cDNAs, Ub-t52 and Ub-t80, encoding ubiquitin fused to ribosomal proteins of 52 and 80 amino acids. The deduced amino acid sequences of the ribosomal proteins are identical or very similar to the homologous human and rat proteins and to the corresponding proteins of other species. Unexpectedly, the ubiquitin moiety of the Ub-t52 protein showed two amino acid substitutions: serine-20 has been replaced by asparagine and serine-57 by alanine.

Differential expression of bcl-2 and bcl-x during chicken spermatogenesis.

We report the isolation and characterization of a chicken testis bcl-XL cDNA coding for a long bcl-x protein with a hydrophobic tail, and the expression of bcl-2 and bcl-x during chicken spermatogenesis. Bcl-2 is highly expressed in embryonic and immature testes enriched in spermatogonia and barely detectable in mature testes, where most of the cells are meiotic and postmeiotic. Bcl-x is expressed in both mature and immature testes, but in a lesser amount in mature testes.

Heat-shock inducible polyubiquitin gene UbI undergoes alternative initiation and alternative splicing in mature chicken testes.

Ubiquitin, a heat-shock protein highly expressed during spermatogenesis, plays an essential role in the differentiation of the germinal cells, particularly in the structural changes of chromatin taking place at the end of the process. To shed light on the mechanisms that modulate transcriptional activity of the heat-shock inducible polyubiquitin gene UbI during spermatogenesis and stabilize the message when transcription is not longer active, we have compared the characteristics of UbI transcripts in mature and immature testes and somatic cells. In mature chicken testes, transcription starts at a site placed closer to the heat-shock promoters than in somatic tissues.

Alternative transcriptional initiation and alternative use of polyadenylation signals in the alphaB-crystallin gene expressed in different chicken tissues.

Overexpression of alphaB-crystallin is associated with numerous neurodegenerative diseases and abnormal cell growth patterns. To study the mechanisms involved in the control of the transcriptional activity of the gene we have characterized its expression in different chicken tissues. The sequence of the alphaB-crystallin cDNA isolated from chicken testis and 6-day-old chick embryo is highly homologous to the duck alphaB-crystallin cDNA and differs from the previously reported chicken lens alphaB-crystallin cDNA in the 5' untranslated region (5'-UTR) and in one amino acid of the coding sequence.