University of Crete

About: University of Crete is a education organization based out in Rethymno, Greece. It is known for research contribution in the topics: Population & Galaxy. The organization has 8681 authors who have published 21684 publications receiving 709078 citations. The organization is also known as: Panepistimio Kritis.

Cytokeratin-19 mRNA-Positive Circulating Tumor Cells After Adjuvant Chemotherapy in Patients With Early Breast Cancer

Abstract: Purpose To evaluate the prognostic significance of cytokeratin-19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in peripheral blood of women with early-stage breast cancer after the completion of adjuvant chemotherapy. Patients and Methods Blood was obtained from 437 patients with early breast cancer before the start and after the completion of adjuvant chemotherapy, and the presence of CK-19 mRNA-positive CTCs was assessed by real-time reverse transcriptase polymerase chain reaction. Interaction with known prognostic factors and association of CTCs with clinical outcome were investigated. Results CK-19 mRNA-positive CTCs were detected before chemotherapy in 179 patients (41.0%). After adjuvant chemotherapy, a significant change in CK-19 status was observed, as status for 51% of patients with initially CK-19 mRNA-positive disease turned negative, and status for 22% of patients with initially CK-19 mRNA-negative disease became positive (McNemar test P .004). The detection of CK-19 mRNA-positive CTCs postchemotherapy was associated with involvement of more than three axillary lymph nodes (P .026). Clinical relapses and disease-related deaths were significantly increased in patients with detectable postchemotherapy CK-19 mRNA-positive CTCs (both P .001, respectively). Disease-free and overall survival were significantly reduced in patients with detectable CK-19 mRNA-positive CTCs postchemotherapy (P .001 and P .001, respectively). In multivariate analysis, the detection of CK-19 mRNA-positive CTCs before and after adjuvant chemotherapy was an independent factor associated with reduced disease-free survival (P .001) and overall survival (P .003). Conclusion The detection of CK-19 mRNA-positive CTCs in the blood after adjuvant chemotherapy is an independent risk factor indicating the presence of chemotherapy-resistant residual disease.

Non-critical holography and four-dimensional CFT's with fundamentals

Abstract: We find non-critical string backgrounds in five and eight dimensions, holographically related to four-dimensional conformal field theories with = 0 and = 1 supersymmetries. In the five-dimensional case we find an AdS5 background metric for a string model related to non-supersymmetric, conformal QCD with large number of colors and flavors and discuss the conjectured existence of a conformal window from the point of view of our solution. In the eight-dimensional string theory, we build a family of solutions of the form AdS5 ? 3 with 3 a squashed three-sphere. For a special value of the ratio Nf/Nc, the background can be interpreted as the supersymmetric near-horizon limit of a system of color and flavor branes on 1,3 times a known four-dimensional generalization of the cigar. The = 1 dual theory with fundamental matter should have an IR fixed point only for a fixed ratio Nf/Nc. General features of the string/gauge theory correspondence for theories with fundamental flavors are also addressed.

VectorBase: a data resource for invertebrate vector genomics

Abstract: VectorBase (http://www.vectorbase.org) is an NIAID-funded Bioinformatic Resource Center focused on invertebrate vectors of human pathogens. VectorBase annotates and curates vector genomes providing a web accessible integrated resource for the research community. Currently, VectorBase contains genome information for three mosquito species: Aedes aegypti, Anopheles gambiae and Culex quinquefasciatus, a body louse Pediculus humanus and a tick species Ixodes scapularis. Since our last report VectorBase has initiated a community annotation system, a microarray and gene expression repository and controlled vocabularies for anatomy and insecticide resistance. We have continued to develop both the software infrastructure and tools for interrogating the stored data.

Structural basis for protein antiaggregation activity of the trigger factor chaperone.

Abstract: Introduction Molecular chaperones prevent aggregation and misfolding of proteins in the cellular environment and are thus central to maintaining protein homeostasis. Molecular chaperones are thought to recognize and bind to exposed hydrophobic regions of the unfolded proteins, thereby shielding these regions from the solvent. If unprotected, the proteins would likely aggregate or misfold to bury the hydrophobic residues. Despite the central importance of the binding of chaperones to unfolded proteins, the structural basis of their interaction remains poorly understood. The scarcity of structural data on complexes between chaperones and unfolded proteins is primarily due to technical challenges originating in the size and dynamic nature of these complexes. Structural basis of PhoA binding by TF. PhoA (blue/gray) is captured in an unfolded state by three TF chaperone molecules (orange). Complex formation is mediated by multivalent binding of hydrophobic surfaces, which are shielded from water, thereby preventing folding and, at the same time, aggregation of the substrate protein.Structural basis of PhoA binding by TF. PhoA (blue/gray) is captured in an unfolded state by three TF chaperone molecules (orange). Complex formation is mediated by multivalent binding of hydrophobic surfaces, which are shielded from water, thereby preventing folding and, at the same time, aggregation of the substrate protein. Rationale Recent advances in nuclear magnetic resonance (NMR) and isotope labeling approaches make it possible to study large, dynamic complexes. We used NMR spectroscopy to characterize the binding of the 48-kD unfolded alkaline phosphatase (PhoA) to the 50-kD trigger factor (TF) chaperone. We obtained atomic insight into the dynamic binding and determined the solution structure of PhoA captured in an extended, unfolded state by three TF molecules. Based on our NMR studies, we gained insight into how TF rescues an aggregation-prone protein and how it exerts its unfoldase activity. Results We show that TF uses multiple sites, which are located in two different domains and extend over a distance of ~90 A, to bind to several regions of the unfolded PhoA that are dispersed throughout its entire length. Three TF molecules are required to interact with the entire length of PhoA, giving rise to a ~200-kD complex in solution. The TF-PhoA interactions are mediated primarily by hydrophobic contacts. TF interacts with PhoA in a highly dynamic fashion, giving rise to a rugged landscape for the free energy of interaction. As the number and length of the PhoA regions engaged by TF increases, a more stable complex gradually emerges. The multivalent binding keeps PhoA in an extended, unfolded conformation. Crucially, even the lowest-energy TF-PhoA complex remains rather dynamic with a lifetime of ~20 ms. The structural data of the three TF molecules in complex with different regions of PhoA reveal how the same binding sites within a molecular chaperone can recognize and interact with a large number of substrates with unrelated primary sequences. This promiscuous recognition is further enabled by the notable plasticity of the substrate-binding sites in TF. We finally show that TF in the cytosol prevents aggregation by interacting transiently with the low-populated, aggregation-prone unfolded state of the substrate but acts as a powerful unfoldase when it is bound at the ribosome and thus is colocalized with translating substrate. Conclusion The structural data reveal a multivalent binding mechanism between the chaperone and its protein substrate. This mechanism of binding presents several advantages as it enables chaperones to function as holdases and unfoldases by exerting forces to retain proteins in the unfolded state and at the same time protect them from aggregation by shielding their exposed hydrophobic regions. Given the existence of multiple binding sites in other molecular chaperones, this may present a general mechanism for the action of molecular chaperones. The fast kinetics of substrate binding enables chaperones to interact with transiently exposed, aggregation-prone regions of unstable proteins in the cytosol, thereby preventing their aggregation and increasing their solubility.

Recent experience with Pseudomonas aeruginosa bacteremia in patients with cancer: Retrospective analysis of 245 episodes.

Abstract: BACKGROUND Pseudomonas aeruginosa bacteremia is a serious and possibly fatal condition in patients with cancer. OBJECTIVES To ascertain the frequency, demographics, and predisposing factors for P. aeruginosa bacteremia in patients with cancer and to determine the efficacy of various therapeutic regimens. SUBJECTS AND METHODS Patient records of the Clinical Microbiology Laboratory, The University of Texas, M. D. Anderson Cancer Center, Houston, were reviewed. From January 1, 1991, through December 31, 1995, 245 eligible cases of P. aeruginosa bacteremia were identified. We examined the patient records for the underlying malignant neoplasm and its management, symptoms and signs of infection, culture results of appropriate specimens, antibiotic therapy, and outcome. We also compared our present experience with a previous analysis from this institution covering the period from January 1, 1972, to December 31, 1981. RESULTS The incidence of P. aeruginosa bacteremia has decreased compared with the previous study (2.8 vs 4.7 cases per 1000 admissions). It was most common in patients with acute leukemia (55 of 1000 registrations), and the frequency in this disease has not changed. Half of the patients were not in the hospital when they developed their infection. The overall cure rate was 80%, which was a significant (P<.001) increase compared with the 62% cure rate in the previous study. In this study, no significant difference in the cure rates was observed between monotherapy with a beta-lactam and combination therapy overall (P = .72), and in patients with shock (P = 1.0) and those with pneumonia (P = .60). The patients' initial neutrophil counts were not of prognostic value; however, the cure rate depended on subsequent changes in neutrophil count during therapy. CONCLUSIONS The frequency rate of P. aeruginosa bacteremia has decreased in patients with solid tumors but has remained unchanged in patients with acute leukemia. Antibiotic regimens for empirical therapy of neutropenic patients and especially patients with acute leukemia should still provide coverage against P. aeruginosa.