Prolonged In-use Stability of Reconstituted Herceptin in Commercial Intravenous Bags.

Herceptin is a humanized monoclonal antibody that selectively binds to the extracellular domain of human epidermal growth factor receptor 2 (HER2). Herceptin has an important role in the treatment of HER2-positive breast cancer when used in the neoadjuvant, adjuvant, and metastatic settings, and in the treatment of HER2-positive metastatic gastric cancer, and gastroesophageal junction adenocarcinoma. Prior to intravenous infusion, Herceptin must be reconstituted with sterile water for injection and then diluted in intravenous bags with normal saline.

Antibody arrays--an emerging tool in cancer proteomics.

Cancer is a result of complex changes that occur in normal cells as they transform to become malignant and further when they become metastatic. These changes are not a consequence of a single protein but rather involve multiple proteins that function in pathways and networks. Thus, profiling cancer-associated changes requires simultaneous measurement of many proteins in a single sample.

Melanoma cells exhibit strong intracellular TASK-3-specific immunopositivity in both tissue sections and cell culture.

Amplification of the kcnk9 gene and overexpression of the encoded channel protein (TASK-3) seems to be involved in carcinogenesis. In the present work, TASK-3 expression of melanoma cells has been studied. For the investigation of TASK-3-specific immunolabelling, a monoclonal antibody has been developed and applied along with two, commercially available polyclonal antibodies targeting different epitopes of the channel protein.

A RUNX/AML-binding motif residing in a novel 13-bp DNA palindrome may determine the expression of the proximal promoter of the human uPA gene.

Urokinase-type plasminogen activator (uPA) is a multifunctional extracellular serine protease implicated in different events including fibrinolysis, tissue remodeling, and hematopoiesis. The human uPA gene contains a major promoter region at around 2000 bp upstream from the transcription start site (+1), and a second regulatory region spanning nucleotides -90/+32 within the proximal promoter. Here, an inspection of this region revealed a novel 13-bp palindrome residing at position +8/+20.

Panorama Ab Microarray Cell Signaling kit: a unique tool for protein expression analysis.

Antibody arrays are a promising new tool for mass analysis of protein level changes in cells responding to different stimuli. Here we describe a novel antibody array system called Panorama Ab Microarray Cell Signaling, that contains 224 antibodies spotted on FAST nitrocellulose-coated slides that can detect protein levels as low as a few nanograms per mL. The antibodies spotted are specific for proteins important in various areas of cell signaling such as phosphorylation, cell cycle, apoptosis, nuclear signaling and cytoskeleton proteins.

Down-regulation of the phosphatidylinositol 3-kinase/Akt pathway is involved in retinoic acid-induced phosphorylation, degradation, and transcriptional activity of retinoic acid receptor gamma 2.

Nuclear retinoic acid (RA) receptors (RARs) are phosphorylated at conserved serine residues located in their N-terminal domain. Phosphorylation of RARgamma2 at these residues is increased in response to RA subsequently to the activation of p38MAPK. We show here that this RA-induced phosphorylation of RARgamma2 resulted from the down-regulation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway.

Coordinate regulation of RARgamma2, TBP, and TAFII135 by targeted proteolysis during retinoic acid-induced differentiation of F9 embryonal carcinoma cells.

Background: Treatment of mouse F9 embryonal carcinoma cells with all-trans retinoic acid (T-RA) induces differentiation into primitive endodermal type cells. Differentiation requires the action of the receptors for all trans, and 9cis-retinoic acid (RAR and RXR, respectively) and is accompanied by growth inhibition, changes in cell morphology, increased apoptosis, proteolytic degradation of the RARgamma2 receptor, and induction of target genes.

Results: We show that the RNA polymerase II transcription factor TFIID subunits TBP and TAFII135 are selectively depleted in extracts from differentiated F9 cells.

Dimerization with retinoid X receptors and phosphorylation modulate the retinoic acid-induced degradation of retinoic acid receptors alpha and gamma through the ubiquitin-proteasome pathway.

In eukaryotic cells, the ubiquitin-proteasome pathway is the major mechanism for targeted degradation of proteins. We show that, in F9 cells and in transfected COS-1 cells, the nuclear retinoid receptors, retinoic acid receptor gamma2 (RARgamma2), RARalpha1, and retinoid X receptor alpha1 (RXRalpha1) are degraded in a retinoic acid-dependent manner through the ubiquitin-proteasome pathway. The degradation of RARgamma2 is entirely dependent on its phosphorylation and on its heterodimerization with liganded RXRalpha1.

Retinoic acid induces proteasome-dependent degradation of retinoic acid receptor alpha (RARalpha) and oncogenic RARalpha fusion proteins.

Analyzing the pathways by which retinoic acid (RA) induces promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha) catabolism in acute promyelocytic leukemia (APL), we found that, in addition to caspase-mediated PML/RARalpha cleavage, RA triggers degradation of both PML/RARalpha and RARalpha. Similarly, in non-APL cells, RA directly targeted RARalpha and RARalpha fusions to the proteasome degradation pathway. Activation of either RARalpha or RXRalpha by specific agonists induced degradation of both proteins.

The expression of the H19 gene and its function in human bladder carcinoma cell lines.

The human H19 gene is a paternally imprinted oncofetal gene, highly expressed in several fetal tissues, down-regulated in nearly all adult tissues but re-expressed in carcinomas of tissues which express the gene in fetal life. It has no known protein product and till today, no function could be designated to H19 RNA. Cells derived from bladder carcinomas and hepatocellular carcinomas were transfected with plasmids carrying a luciferase reporter gene under the control of a 800 nucleotides long promoter region of the H19 gene either alone or together with different parts of a 5 kb downstream region, previously shown to possess enhancer activity.

The effect of retinoic acid on the activation of the human H19 promoter by a 3' downstream region.

The human H19 is paternally imprinted (maternally expressed). It is transcribed by RNA pol II, but has no protein product. Its function is unknown.

The 3'-untranslated region of the urokinase gene enhances the expression of chimeric genes in cultured cells and correlates with specific brain expression in transgenic mice.

Transgenic mice were previously described, carrying the cDNA of the human or murine protease urokinase-type plasminogen activator (uPA) while linked to the cell-specific promoter of the alphaA-crystallin gene. Surprisingly, these mice produced transgenic uPA in an ectopic manner specifically in the brain. Here we tested the possibility that this ectopic expression could have been contributed primarily by the uPA transgenic moiety.

The expression of the imprinted H19 and IGF-2 genes in human bladder carcinoma.

The imprinted H19 gene is highly expressed in human embryos, fetal tissues and is nearly completely shut off in adults. However, it is reexpressed in a number of tumors including bladder carcinoma, demonstrating that H19 RNA is an oncofetal RNA. Tumors induced by injection of bladder carcinoma cell lines express H19 in contrast to the cells before injection.

Ipsilateral cortical connections from the second and fourth somatic sensory areas in the cat.

The ipsilateral corticocortical connections of the second and fourth somatic sensory areas (SII and SIV) were traced with the aid of anterograde or retrograde axonal transport techniques involving horseradish peroxidase conjugated to wheat germ agglutinin (HRP-WGA) or tritiated amino acids. The injections were placed into physiological defined components of the body representation in SII or SIV. The results from cases with localized injections into SII showed precise topographically organized, reciprocal connections with SI and motor cortex area 4.

Connections between the thalamus and the somatosensory areas of the anterior ectosylvian gyrus in the cat.

The thalamocortical and corticothalamic connections of the second somatic sensory area (SII) and adjacent cortical areas in the cat were studied with anterograde and retrograde tracers. Injections consisted of horseradish peroxidase conjugated to wheat germ agglutinin (HRP-WGA) or a mixture of equal parts of tritiated leucine and proline. The cortical regions to be injected were electrophysiologically studied with microelectrodes to determine the localization of the selected components of the body representation in SII.

Glomus tumor treated by prostaglandin inhibition. Report of a case.

Glomus tumor is a very painful pericytal lesion of the arteriovenous anastomotic complex that controls circulation in a limb. Glomus tumor usually involves a digit. Prostaglandin inhibition may control the glomus tumor pain, but surgical removal is the cure.