Disease Markers - Volume 19, issue 1

Authors: Mehta, Arpita I. | Ross, Sally | Lowenthal, Mark S. | Fusaro, Vincent | Fishman, David A. | Petricoin III, Emanuel F. | Liotta, Lance A.

Article Type: Research Article

Abstract: Mass spectroscopic analysis of the low molecular mass (LMM) range of the serum/plasma proteome is a rapidly emerging frontier for biomarker discovery. This study examined the proportion of LMM biomarkers, which are bound to circulating carrier proteins. Mass spectroscopic analysis of human serum following molecular mass fractionation, demonstrated that the majority of LMM biomarkers exist bound to carrier proteins. Moreover, the pattern of LMM biomarkers bound specifically to albumin is distinct from those bound to …non-albumin carriers. Prominent SELDI-TOF ionic species (m/z 6631.7043) identified to correlate with the presence of ovarian cancer were amplified by albumin capture. Several insights emerged: a) Accumulation of LMM biomarkers on circulating carrier proteins greatly amplifies the total serum/plasma concentration of the measurable biomarker, b) The total serum/plasma biomarker concentration is largely determined by the carrier protein clearance rate, not the unbound biomarker clearance rate itself, and c) Examination of the LMM species bound to a specific carrier protein may contain important diagnostic information. These findings shift the focus of biomarker detection to the carrier protein and its biomarker content. Show more

Citation: Disease Markers, vol. 19, no. 1, pp. 1-10, 2004

Authors: Rodríguez-Burford, Cristina | Chhieng, David C. | Stockard, Cecil R. | Kleinberg, Marc J. | Barnes, Mack N. | Partridge, Edward E. | Weiss, Heidi L. | Grizzle, William E.

Article Type: Research Article

Abstract: Ovarian cancer has a high mortality rate largely due to the limited number of ovarian carcinomas detected at an early stage. Understanding the molecular changes occurring during the progression of ovarian carcinoma would aid in the development of therapies that may inhibit or target metastasis. Primary and metastatic lesions from 54 and 40 patients with advanced ovarian carcinoma, respectively (including matched primary and metastatic lesions from 30 patients) were evaluated for nuclear accumulation of p53 (clone …BP53-12-1) and cytoplasmic and membranous immunostaining of p185 erbB-2 (clone 3B5) by immunohistochemistry. No differences in the immunostaining of p53 and p185erbB-2 (cytoplasm or membrane) were observed between primary and metastatic lesions of the matched cases. Similarly, no differences in the proportion of positive cases of p53 between primary and metastatic lesions of the matched cases was observed. Thus, novel therapies that target p53 or p185erbB-2 can utilize specimens from either primary or metastatic lesions to characterize these targets prior to therapy. Spearman correlations between p53 and p185erbB-2 (cytoplasm or membrane) immunohistochemistry scores were insignificant for the matched cases, all primary lesions, and all metastatic lesions. Also, no significant associations occurred between nuclear accumulation of p53 (positive versus negative) and phenotypic expression of p185erbB-2 (cytoplasm or membrane) immunostaining scores for the matched cases, all primary lesions, and all metastatic lesions. Thus, the nuclear accumulation of p53 and immunostaining of p185erbB-2 in the cytoplasm or on the cellular membranes are independent. Show more

Keywords: ovarian carcinoma, molecular markers, p53, and p185 erbB-2

Citation: Disease Markers, vol. 19, no. 1, pp. 11-17, 2004

Authors: Abdellatif, Awad | Al-tonsy, Ahmad H. | Awad, Mahmoud E. | Roberfroid, M. | Khan, M. Nezam Ullah

Article Type: Research Article

Abstract: Although peroxisome proliferators are considered non-genotoxic agents, most of them, nevertheless, were found to promote and/or induce, hepatocellular carcinoma (HCC) in rodents. The aim of the present study is, first, to investigate whether the peroxisome proliferator perfluorooctanoic acid (PFOA) possesses inherent liver cancer promoting activity, and second, to study the possible mechanisms involved. To acheive these aims two protocols have been applied, a biphasic protocol (initiation by diethyl-nitrozamine (DEN) 200 mg/kg i.p. …followed by treatment with 0.005% or 0.02% perflourooctanoic acid (PFOA) for 14 and 25 weeks) and a triphasic initiation, selection-promotion (IS) protocol (initiation by giving 200 mg/kg DEN i.p. followed by a selection procedure for 2 weeks consisting of giving 0.03% 2-acetylaminofluorene (2-AAF) in diet). In the middle of this treatment a single oral dose of carbon tetrachloride (2.0 ml/kg) was given, followed by giving diet containg 0.015% of PFOA for 25 weeks. After applying both protocols, our results showed slight increase in the catalase activity while acyl CoA oxidase activity was markedly increased. Both experiments indicated that PFOA has a liver cancer promoting activity. Other groups of rats were given either basal diet or diet containing 0.02% PFOA. Five or nine weeks later they were sacrificed and the levels of 8-hydroxydeoxyguanosine in the isolated DNA were estimated. The data showed a slight nonetheless insignificant increase in 8-hydroxydeoxyguanosine. From the present data, it is concluded that PFOA is a true liver cancer promoter that may not require extensive initial DNA damage for its promoting activity. Show more

Keywords: perfluorooctanoic acid (PFOA), diethylnitrosamine, (DEN), hepatocellular carcinoma (HCC), 2-acetylaminofluorene (2-AAF)

Citation: Disease Markers, vol. 19, no. 1, pp. 19-25, 2004

Authors: Moselhy, S.S. | Demerdash, S.H.

Article Type: Research Article

Abstract: Hyperhomocysteinemia (Hhcy) has been associated with pathological and stressfull conditions and is a risk factor for cardiovascular disease (CVD). The aim of this study was to evaluate the correlation between plasma homocysteine (hcy) and lipid peroxidation in patient with CVD. This study was carried out on 40 patients with CVD as well as 15 healthy volunteers of comparable age and gender as control group. The patients were divided into 2 groups as follows: group I, included …20 patients with acute myocardial infarction and group II, included 20 patients with atherosclerotic coronary artery disease with no evidence of previous myocardial infarction . Plasma hcy, nitric oxide (NO) and malondialdhyde (MDA) [as index of lipid peroxidation] were measured in all groups. In addition serum total-cholesterol, HDL, LDL and triglycerides were evaluated. Results obtained showed that, there was a significant elevation in the levels of plasma hcy, NO and MDA in groups I and II as compared to control group. There was a strong positive correlation between plasma hcy and MDA (r = 0.59, p < 0.001). Also NO was positively correlated with both hcy (r = 0.49, p < 0.001) and MDA (r = 0.51, p < 0.001) . Serum total cholesterol, LDL, and triglycerids were also significantly elevated while serum HDL was significantly decreased in groups I and II as compared to control group. It can be concluded that, hyperhomocysteinemia is a possible factor in free radical generation and therefore cardiovascular diseases. Show more

Citation: Disease Markers, vol. 19, no. 1, pp. 27-31, 2004

Authors: Xiao, Xueyuan | Liu, Danhui | Tang, Ying | Guo, Fuzheng | Xia, Liang | Liu, Jin | He, Dacheng

Article Type: Research Article

Abstract: Lung cancer is at present the number one cause of cancer death and no biomarker is available to detect early lung cancer in serum samples so far. The objective of this study is to find specific biomarkers for detection of lung cancer using Surface Enhanced Laser Desorption/Ionization (SELDI) technology. In this study, serum samples from 30 lung cancer patients and 51 age-and sex-matched healthy were analyzed by SELDI based ProteinChip reader, PBSII-C. The spectra were generated …on WCX2 chips and protein peaks clustering and classification analyses were performed utilizing Biomarker Wizard and Biomarker Patterns software packages, respectively. Three protein peaks were automatically chosen for the system training and the development of a decision classification tree. The constructed model was then used to test an independent set of masked serum samples from 15 lung cancer patients and 31 healthy individuals. The analysis yielded a sensitivity of 93.3%, and a specificity of 96.7%. These results suggest that the serum is a capable resource for detection of specific lung cancer biomarkers. SELDI technique combined with an artificial intelligence classification algorithm can both facilitate the discovery of better biomarkers for lung cancer and provide a useful tool for molecular diagnosis in future. Show more

Citation: Disease Markers, vol. 19, no. 1, pp. 33-39, 2004

Authors: Tjensvoll, Kjersti | Bruland, Ove | Floderus, Ylva | Skadberg, Øyvind | Sandberg, Sverre | Apold, Jaran

Article Type: Research Article

Abstract: Acute intermittent porphyria (AIP), the most common of the acute porphyrias, is caused by mutations in the gene encoding hydroxymethylbilane synthase (HMBS) also called porphobilinogen deaminase (PBGD). The mutation spectrum in the HMBS gene is characterized by a majority of family specific mutations. Among the exceptions are R116W and W198X, with high prevalence in both the Dutch and Swedish populations. These two mutations were also detected in unrelated Norwegian patients. Thus, Norwegian and Swedish patients were …haplotyped using closely linked flanking microsatellites and intragenic single nucleotide polymorphisms (SNPs) to see if the high frequency of these two mutations is due to a founder effect. Twelve intragenic SNPs were determined by a method based on fluorescent restriction enzyme fingerprinting single-strand conformation polymorphism (F-REF-SSCP). W198X occurred exclusively on one haplotype in both Norwegian and Swedish patients, showing that it has originated from a common gene source. In contrast, R116W was found on three different haplotypes in three Norwegian families, and in five Swedish families on four or five haplotypes. This extreme haplotype heterogeneity indicates that R116W is a recurrent mutation, maybe explained by the high mutability of CpG dinucleotides. This can also explain why it is the only AIP mutation reported to occur in seven different populations (Norway, Sweden, Finland, Netherlands, France, Spain and South Africa). Show more

Keywords: acute intermittent porphyria, AIP, porphyria, SNP, microsatellites, haplotyping, genetic markers, HMBS, PBGD, V215E, L238P

Citation: Disease Markers, vol. 19, no. 1, pp. 41-46, 2004