Multi-biomarker pattern for tumor identification and prognosis

In last decades, the basic, clinical, and translational research efforts have been directed to the identification of standard biomarkers associated with the degree of malignancy. There is an increasingly public health concern for earlier detection of cancer development at stages in which successful treatments can be achieved. To meet this urgent clinical demand, early stage cancer biomarkers supported by reliable and robust experimental data that can be readily applicable in the clinical practice, are required. In the current standard protocols, when one or two of the canonical proliferating index biomarkers are analyzed, contradictory results are frequently reached leading to incorrect cancer diagnostic and unsuccessful therapies. Therefore, the identification of other cellular characteristics or signatures present in the tumor cells either alone or in combination with the well-established proliferation markers emerge as an alternative strategy in the improvement of cancer diagnosis and treatment. Because it is well known that several pathways and processes are altered in tumor cells, the concept of "single marker" in cancer results incorrect. Therefore, this review aims to analyze and discuss the proposal that the molecular profile of different genes or proteins in different altered tumor pathways must be established to provide a better global clinical pattern for cancer detection and prognosis.     

The potential impact of P53 and APO-1 genetic polymorphisms on hepatitis C genotype 4a susceptibility

The hepatitis C virus (HCV), the main cause of morbidity and mortality, is endemic worldwide. HCV causes cirrhosis and other complications that often lead to death. HCV is most common in underdeveloped nations, with the highest prevalence rates in Egypt. Tumor suppressor gene (P53) induces the expression of apoptotic antigen-1 gene (APO-1) by binding to its promoter for mediating apoptosis; an important mechanism for limiting viral replication. This study aims at investigating the impact of P53 72 Arg/Pro and APO-1 − 670 A/G polymorphisms on HCV genotype 4a susceptibility. Two hundred and forty volunteers were enrolled in this study and divided into two major groups; 160 HCV infected patient group and 80 healthy control group. HCV patients were classified according to Metavir scoring system into two subgroups; 72 patients in F0/1-HCV subgroup (patients with no or mild fibrotic stages) and 38 patients in F3/4-HCV subgroup (patients with advanced fibrotic stages). Quantification of HCV-RNA by qRT-PCR and fibrotic scores as well as genotyping of HCV-RNA, P53 at 72 Arg/Pro, and APO-1 at − 670 A/G were performed for all subjects. It was resulted that F0/1-HCV patients have significant differences of P53 at 72 (Pro/Pro and Arg/Arg) genotypes and dominant/recessive genetic models as well as APO-1 − 670 A/A genotype and dominant genetic model as compared to F3/4-HCV patients. Moreover, HCV patients have significant differences of P53 at 72 (Pro/Pro) genotype and recessive genetic model as well as APO-1 − 670 A/A genotype and dominant genetic model as compared to those of healthy individuals. Finally, it was concluded that P53 rs 1042522 (Pro/Pro and Arg/Arg) genotypes and APO-1 rs 1800682 A/A genotype may be potentially used as sensitive genetic markers for HCV genotype 4a susceptibility.     

Biochemical Differences Between Products of the ADH Locus in Olive Fruit Fly (Bactrocera oleae)

Purified alcohol dehydrogenases from olive fruitflies of genotypes SS, II, and SI were biochemicallycompared. The enzymes were found to differ in thespecific activity, in the influence of pH andtemperature on activity, and in the affinity with differentsubstrate-alcohols. The probable relationships of thesefindings with the dramatic changes in allele frequenciesobserved when natural populations are introduced in the laboratory are discussed.     

The inhibitory effect of alacepril,an angiotensin-converting enzyme inhibitor,on endothelial inflammatory response induced by oxysterol and TNF-α

Abstract

The objectives were to determine the effects of alacepril, an angiotensin-converting enzyme inhibitor, on the expression of adhesion molecules and monocyte adherence to endothelial cells induced by 7-ketocholesterol (7-KC) and tumor necrosis factor (TNF)-α. We used human aortic endothelial cells (HAECs) and U937 monocytic cells. Surface expression and mRNA levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) were determined by EIA and RT-PCR. Adherence of U937 to HAECs was assessed by adhesion assay. Incubation of HAEC with 7-KC increased the surface expression of protein and mRNA levels of ICAM-1 and VCAM-1 on HAECs and the production of reactive oxygen species (ROS) in HAECs. Pretreatment with alacepril reduced the enhanced expression of these molecules in a dose-dependent manner. The inhibitory effect of alacepril against 7-KC or TNF-α-induced CAMs expression was stronger than that of captopril or enalapril. Alacepril inhibited the production of ROS in HAECs stimulated by 7-KC or TNF-α. These results suggest that alacepril works as anti-atherogenic agent through inhibiting endothelial-dependent adhesive interactions with monocytes induced by 7-KC and TNF-α.     

Predicting enzyme family class in a hybridization space

Given the sequence of a protein, how can we predict whether it is an enzyme or a non‐enzyme? If it is, what enzyme family class it belongs to? Because these questions are closely relevant to the biological function of a protein and its acting object, their importance is self‐evident. Particularly with the explosion of protein sequences entering into data banks and the relatively much slower progress in using biochemical experiments to determine their functions, it is highly desired to develop an automated method that can be used to give fast answers to these questions. By hybridizing the gene ontology and pseudo‐amino‐acid composition, we have introduced a new method that is called GO‐PseAA predictor and operate it in a hybridization space. To avoid redundancy and bias, demonstrations were performed on a data set in which none of the proteins in an individual class has ≥40% sequence identity to any other. The overall success rate thus obtained by the jackknife cross‐validation test in identifying enzyme and non‐enzyme was 93%, and that in identifying the enzyme family was 94% for the following six main Enzyme Commission (EC) classes: (1) oxidoreductase, (2) transferase, (3) hydrolase, (4) lyase, (5) isomerase, and (6) ligase. The corresponding rates by the independent data set test were 98% and 97%, respectively.     

Aldolase sequesters WASP and affects WASP/Arp2/3‐stimulated actin dynamics

In addition to its roles in sugar metabolism, fructose‐1,6‐bisphosphate aldolase (aldolase) has been implicated in cellular functions independent from these roles, termed “moonlighting functions.” These moonlighting functions likely involve the known aldolase–actin interaction, as many proteins with which aldolase interacts are involved in actin‐dependent processes. Specifically, aldolase interacts both in vitro and in cells with Wiskott–Aldrich Syndrome Protein (WASP), a protein involved in controlling actin dynamics, yet the function of this interaction remains unknown. Here, the effect of aldolase on WASP‐dependent processes in vitro and in cells is investigated. Aldolase inhibits WASP/Arp2/3‐dependent actin polymerization in vitro. In cells, knockdown of aldolase results in a decreased rate of cell motility and cell spreading, two WASP‐dependent processes. Expression of exogenous aldolase rescues these defects. Whether these effects of aldolase on WASP‐dependent processes were due to aldolase catalysis or moonlighting functions is tested using aldolase variants defective in either catalytic or actin‐binding activity. While the actin‐binding deficient aldolase variant is unable to inhibit actin polymerization in vitro and is unable to rescue cell motility defects in cells, the catalytically inactive aldolase is able to perform these functions, providing evidence that aldolase moonlighting plays a role in WASP‐mediated processes. J. Cell. Biochem. 114: 1928–1939, 2013. © 2013 Wiley Periodicals, Inc.