Home About us Contact
|
Home About us Contact | ||
|
|
||
Target Candidate (target + candidate)
Selected AbstractsIdentifying Early Cardiovascular Disease to Target Candidates for TreatmentJOURNAL OF CLINICAL HYPERTENSION, Issue 3 2008Daniel A. Duprez MD Most attempts to identify individuals at risk for cardiovascular morbid events have involved screening for risk factors. These traditional risk factors do not identify the underlying atherosclerotic disease nor assess the severity of disease in individual patients. The goal for identifying a marker or markers for early cardiovascular disease that could serve as a surrogate for disease progression and ultimate morbid events is to improve the precision for early detection and treatment. The authors utilize a variety of techniques, which consist of 7 vascular tests (large and small artery elasticity, resting blood pressure and exercise blood pressure response, optic fundus photography, carotid intimal-media thickness, and microalbuminuria) and 3 cardiac tests (electrocardiography, [N-terminal pro-] B-type natriuretic peptide, and left ventricular ultrasonography). Each test is individually scored, and the total disease score is the sum of all the test scores. A study is ongoing to compare the new disease score vs the classical Framingham risk estimate in the prediction of cardiovascular events. [source] Identification of SPARC as a candidate target antigen for immunotherapy of various cancersINTERNATIONAL JOURNAL OF CANCER, Issue 6 2010Mitsuhiro Inoue Abstract To establish efficient anticancer immunotherary, it is important to identify tumor-associated antigens (TAAs) directing the immune system to attack cancer. A genome-wide cDNA microarray analysis identified that secreted protein acidic and rich in cysteine (SPARC) gene is overexpressed in the gastric, pancreatic and colorectal cancer tissues but not in their noncancerous counterparts. This study attempted to identify HLA-A24 (A*2402)-restricted and SPARC-derived CTL epitopes. We previously identified H-2Kd -restricted and SPARC-derived CTL epitope peptides in BALB/c mice, of which H-2Kd -binding peptide motif is comparable with that of HLA-A24 binding peptides. By using these peptides, we tried to induce HLA-A24 (A*2402)-restricted and SPARC-reactive human CTLs and demonstrated an antitumor immune response. The SPARC-A24-1143,151 (DYIGPCKYI) and SPARC-A24-4225,234 (MYIFPVHWQF) peptides-reactive CTLs were successfully induced from peripheral blood mononuclear cells by in vitro stimulation with these two peptides in HLA-A24 (A*2402) positive healthy donors and cancer patients, and these CTLs exhibited cytotoxicity specific to cancer cells expressing both SPARC and HLA-A24 (A*2402). Furthermore, the adoptive transfer of the SPARC-specific CTLs could inhibit the tumor growth in nonobese diabetic/severe combined immunodeficient mice bearing human cancer cells expressing both HLA-A24 (A*2402) and SPARC. These findings suggest that SPARC is a potentially useful target candidate for cancer immunotherapy. [source] Structure of human protein kinase CK2,2 with a potent indazole-derivative inhibitorACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 2 2009Tetsuko Nakaniwa Casein kinase 2 (CK2) is a serine/threonine kinase that functions as a heterotetramer composed of two catalytic subunits (CK2,1 or CK2,2) and two regulatory subunits (CK2,). The two isozymes CK2,1 and CK2,2 play distinguishable roles in healthy subjects and in patients with diseases such as cancer, respectively. In order to develop novel CK2,1-selective inhibitors, the crystal structure of human CK2,2 (hCK2,2) complexed with a potent CK2, inhibitor which binds to the active site of hCK2,2 was determined and compared with that of human CK2,1. While the two isozymes exhibited a high similarity with regard to the active site, the largest structural difference between the isoforms occurred in the ,4,,5 loop responsible for the CK2,,CK2, interface. The top of the N-terminal segment interacted with the ,4,,5 loop via a hydrogen bond in hCK2,2 but not in hCK2,1. Thus, the CK2,,CK2, interface is a likely target candidate for the production of selective CK2,1 inhibitors. [source] Differential phosphoproteome profiling reveals a functional role for VASP in Helicobacter pylori -induced cytoskeleton turnover in gastric epithelial cellsCELLULAR MICROBIOLOGY, Issue 11 2008Olivia Knauer Summary Infection with Helicobacter pylori induces various gastric diseases, including ulceration, gastritis and neoplasia. As H. pylori -induced cellular mechanisms leading to these disease states are widely unclear, we analysed the phosphoproteome of H. pylori -infected gastric epithelial cells. Phosphoproteins from infected cells were enriched using affinity columns and analysed by two-dimensional gel electrophoresis and mass spectrometry. Eleven novel phosphoproteins that showed differentially regulated phosphorylation levels during H. pylori infection were identified. Interestingly, the identified proteins were actin-binding, transport and folding, RNA/DNA-binding or cancer-associated proteins. We analysed functions of one identified H. pylori -regulated candidate, the vasodilator-stimulated phosphoprotein (VASP). H. pylori induced VASP phosphorylation at residues Ser157, Ser239 and Thr278, which was enhanced by the bacterial oncogene cytotoxin-associated gene A. Overexpression of a phosphorylation-resistant VASP mutant efficiently blocked host cell elongation. We identified cGMP-dependent protein kinase G-mediated Ser239 and Thr278 phosphorylation of VASP as a crucial event in H. pylori -dependent host cell elongation. These results suggest that phosphorylated VASP could be a novel target candidate for therapeutic intervention in H. pylori -related gastric diseases. [source] High throughput functional genomics: Identification of novel genes with tumor suppressor phenotypesINTERNATIONAL JOURNAL OF CANCER, Issue 3 2005Kerstin Koenig-Hoffmann Abstract We have used a combination of high throughput functional genomics, computerized database mining and expression analyses to discover novel human tumor suppressor genes (TSGs). A genome-wide high throughput cDNA phenotype screen was established to identify genes that induce apoptosis or reduce cell viability. TSGs are expressed in normal tissue and frequently act by reduction of growth of transformed cells or induce apoptosis. In agreement with that and thus serving as platform validation, our pro-apoptotic hits included genes for which tumor suppressing activities were known, such as kangai1 and CD81 antigen. Additional genes that so far have been claimed as putative TSGs or associated with tumor inhibitory activities (prostate differentiation factor, hRAS-like suppressor 3, DPH2L1-like and the metastasis inhibitor Kiss1) were confirmed in their proposed TSG-like phenotype by functionally defining their growth inhibitory or pro-apoptotic function towards cancer cells. Finally, novel genes were identified for which neither association with cell growth nor with apoptosis were previously described. A subset of these genes show characteristics of TSGs because they (i) reduce the growth or induce apoptosis in tumor cells; (ii) show reduced expression in tumor vs. normal tissue; and (iii) are located on chromosomal (LOH-) loci for which cancer-associated deletions are described. The pro-apoptotic phenotype and differential expression of these genes in normal and malignant tissue make them promising target candidates for the diagnosis and therapy of various tumors. [source] | ||||||||||