Christopher Loffredo - Academia.edu (original) (raw)

Papers by Christopher Loffredo

Cancer Epidemiology Biomarkers Prevention, Dec 6, 2011

Background-We investigated associations between tobacco exposure, history of schistosomiasis and ... more Background-We investigated associations between tobacco exposure, history of schistosomiasis and bladder cancer risk in Egypt.

Food Additives and Contaminants Part a Chemistry Analysis Control Exposure and Risk Assessment, May 12, 2008

Cell cycle checkpoints play critical roles in the maintenance of genomic integrity. The inactivat... more Cell cycle checkpoints play critical roles in the maintenance of genomic integrity. The inactivation of checkpoint genes by genetic and epigenetic mechanisms is frequent in all cancer types, as a less-efficient cell cycle control can lead to genetic instability and tumorigenesis. In an on-going case-control study consisting of 216 patients with non-small cell lung cancer, 226 population-based controls, and 114

Carcinogenesis, Jan 5, 2015

Although it is widely recognized that telomere dysfunction plays an important role in cancer, the... more Although it is widely recognized that telomere dysfunction plays an important role in cancer, the relationship between telomere function and bladder cancer risk is not well defined. In a case-control study of bladder cancer in Egypt, we examined relationships between two telomere features and bladder cancer risk. Telomere fluorescent in situ hybridization was used to measure telomere features using short-term cultured blood lymphocytes. Logistic regression was used to estimate the strength of association between telomere features and the risk of urothelial carcinoma of the bladder. High telomere length variation (TLV) across all chromosomal ends was significantly associated with an increased risk of bladder cancer [adjusted odds ratios (OR) = 2.22, 95% confidence interval (CI) = 1.48-3.35], as was long average telomere length (OR = 3.19, 95% CI = 2.07, 4.91). Further, TLV and average telomere length jointly affected bladder cancer risk: when comparing individuals with long telomere ...

Molecular carcinogenesis, Jan 21, 2015

The number of validated biomarkers of tobacco smoke exposure is limited, and none exist for tobac... more The number of validated biomarkers of tobacco smoke exposure is limited, and none exist for tobacco-related cancer. Additional biomarkers for smoke, effects on cellular systems in vivo are needed to improve early detection of lung cancer, and to assist the Food and Drug Administration in regulating exposures to tobacco products. We assessed the effects of smoking on the gene expression using human cell cultures and blood from a cross-sectional study. We profiled global transcriptional changes in cultured smokers' peripheral blood mononuclear cells (PBMCs) treated with cigarette smoke condensate (CSC) in vitro (n = 7) and from well-characterized smokers' blood (n = 36). ANOVA with adjustment for covariates and Pearson correlation were used for statistical analysis in this study. CSC in vitro altered the expression of 1 178 genes (177 genes with > 1.5-fold-change) at P < 0.05. In vivo, PBMCs of heavy and light smokers differed for 614 genes (29 with > 1.5-fold-change)...

Pacific Symposium on Biocomputing, 2008

We present a computational framework for analysis of MALDI-TOF mass spectrometry data to enable q... more We present a computational framework for analysis of MALDI-TOF mass spectrometry data to enable quantitative comparison of glycans in serum. The proposed framework enables a systematic selection of glycan structures that have good generalization capability in distinguishing subjects from two pre-labeled groups. We applied the proposed method for a biomarker discovery study that involves 203 participants from Cairo, Egypt; 73 hepatocellular carcinoma (HCC) cases, 52 patients with chronic liver disease (CLD), and 78 healthy individuals. Glycans were enzymatically released from proteins in serum and permethylated prior to mass spectrometric quantification. A subset of the participants (35 HCC and 35 CLD cases) was used as a training set to select global and subgroup-specific peaks. The peak selection step is preceded by peak screening, where we eliminate peaks that seem to have association with covariates such as age, gender, and viral infection based on the 78 spectra from healthy individuals. To ensure that the global peaks have good generalization capability, we subjected the entire spectral preprocessing and peak selection step to a cross-validation; a randomly selected subset of the training set was used for spectral preprocessing and peak selection in multiple runs with resubstitution. In addition to global peak identification method, we describe a new approach that allows the selection of subgroup-specific glycans by searching for glycans that display differential abundance in a subgroup of patients only. The performance of the global and subgroup-specific peaks is evaluated via a blinded independent set that comprises of 38 HCC and 17 CLD cases. Further evaluation of the potential clinical utility of the selected global and subgroup-specific candidate markers is needed. † Corresponding author

Lung cancer (Amsterdam, Netherlands), Jan 20, 2015

In this report the associations between telomere length variation (TLV), mean telomere length in ... more In this report the associations between telomere length variation (TLV), mean telomere length in blood lymphocytes and lung cancer risk were examined. The study design is case-control. Cases (N=191) were patients newly diagnosed with histologically confirmed non-small cell lung cancer. Controls (N=207) were healthy individuals recruited from the same counties as cases and matched to cases on age and gender. Telomere fluorescent in situ hybridization was used to measure telomere features using short-term cultured blood lymphocytes. Logistic regression was used to estimate the strength of association between telomere features and lung cancer risk. Telomere length variation across all chromosomal ends was significantly associated with lung cancer risk; adjusted odds ratios 4.67 [95% confidence interval (CI): 1.46-14.9] and 0.46 (95% CI: 0.25-0.84) for younger (age≤60) and older (age>60) individuals, respectively. TLV and mean telomere length jointly affected lung cancer risk: when c...

Carcinogenesis, 2014

Aberrant expression of subgroup k human endogenous retroviruses (HERV-K) has been observed in pro... more Aberrant expression of subgroup k human endogenous retroviruses (HERV-K) has been observed in prostate cancer. This subgroup is unique because it encodes sequences in the human genome containing open reading frames for near intact retroviruses. We hypothesized that HERV-K reactivation could serve as a non-invasive early disease detection marker for prostate cancer. We evaluated HERV-K gag messenger RNA (mRNA) expression in blood samples of African-American and European-American men using a case-control design via quantitative real-time PCR. Additionally, we examined HERV-K envelope protein expression in prostate tumors by immunohistochemistry. HERV-K envelope protein was commonly upregulated in prostate tumors, but more so in tumors of African-American than European-American patients (61% versus 40%, P < 0.01). Examining HERV-K gag expression in peripheral blood mononuclear cells (PBMC) from 294 cases and 135 healthy men, we found that the abundance of HERV-K gag message was sign...

Journal of the Egyptian Public Health Association, 2014

Smoking addiction is influenced by cultural and environmental factors and personality traits. We ... more Smoking addiction is influenced by cultural and environmental factors and personality traits. We assessed the associations between neuroticism and depression and smoking behavior and motives among Egyptian adult men in rural Qalyubia Governorate. Using a cross-sectional design, we administered questionnaires to randomly selected 201, 278, and 120 adult men aged 18 years or above who were never, current, and former smokers, respectively. We used Center for Epidemiologic Studies Short Depression (CES-D) scale, Eysenck Personality Inventory (EPI), Fagerström Test for Nicotine Dependence (FTND), and Wisconsin Inventory of Smoking Dependence Motives scales to assess the associations between neuroticism, depression, and smoking risk. The mean CES-D and EPI scores were significantly higher among current smokers as compared with never smokers (P=0.02 and 0.006, respectively). The greatest risk for ever smoking was observed among those with both neuroticism and depression [adjusted odds ratio (95% confidence interval) were 1.98 (1.23-3.19); 2.56 (1.34-4.88); and 1.82 (1.10-3.03) for ever, former, and current smokers, respectively]. Both CES-D and EPI scores were associated with a variety of smoking motives and with the level of severity or intensity of nicotine dependence on FTND. Neuroticism and depression were associated with smoking behavior and motives among Egyptians, and thus attention should be given to individual needs in designing and implementing smoking cessation interventions.

2005 IEEE Symposium on Computational Intelligence in Bioinformatics and Computational Biology, 2005

... Fig. 4c shows the binned, normalized, and baseline corrected spectrum. For peak detection, ab... more ... Fig. 4c shows the binned, normalized, and baseline corrected spectrum. For peak detection, abin is identified as a peak if the sign of the intensity's slope changes from positive to negative. ... 10, pp. 860-8, 2004. [19] H. Ressom, RS Varghese, D. Saha, E. Orvisky, L. Goldman, EF ...

2006 IEEE Symposium on Computational Intelligence and Bioinformatics and Computational Biology, 2006

... The dimension of the spectra was reduced to 23,846 m/z bins. A bin size of 100 ppm was found ... more ... The dimension of the spectra was reduced to 23,846 m/z bins. A bin size of 100 ppm was found adequate. ... REFERENCES [1] Orvisky, E., Drake, SK, Martin, BM, Ressom, H., Varghese, RS, Saha, D., Hortin, GL, Loffredo, CA, and Goldman, R., "Enrichment of low molecular ...

2008 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2008

Quantitative comparison of peptides and glycans in serum is conducted using matrix-assisted laser... more Quantitative comparison of peptides and glycans in serum is conducted using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to identify biomarkers. A peak selection algorithm is developed to identify a panel of integrated peptide and glycan peaks to distinguish hepatocellular carcinoma (HCC) cases from high-risk population of patients with chronic liver disease (CLD). Candidate peptide and glycan markers selected frequently in multiple runs of the algorithm are presented. The performance of these markers is evaluated in terms of their ability to distinguish HCC cases from patients with CLD in a blinded validation set.

2006 International Conference of the IEEE Engineering in Medicine and Biology Society, 2006

We present a novel method that combines ant colony optimization with support vector machines (ACO... more We present a novel method that combines ant colony optimization with support vector machines (ACO-SVM) to select candidate biomarkers from MALDI-TOF serum profiles of hepatocellular carcinoma (HCC) patients and matched controls. The method identified relevant mass points that achieve high sensitivity and specificity in distinguishing HCC patients from healthy individuals. The results indicate that the MALDI-TOF technology could provide the means to discover novel biomarkers for HCC.

2007 IEEE/NIH Life Science Systems and Applications Workshop, 2007

... A binning algorithm reduced the dimension of the peptide spectra from ~136,000 to 23,846 m/z ... more ... A binning algorithm reduced the dimension of the peptide spectra from ~136,000 to 23,846 m/z bins and the glycan spectra were reduced from ~121,000 to 13,030 m/z bins using a bin size of 100 ppm. ... 6, No. 9, pp. 2895-902, 2006. [4] HW Ressom, RS Varghese, M. Abdel ...

Urologic Oncology: Seminars and Original Investigations, 2012

To examine associations between urinary bladder cancer risk and polymorphisms of the gene encodin... more To examine associations between urinary bladder cancer risk and polymorphisms of the gene encoding the catechol estrogen-metabolizing enzyme, catechol-O-methyltransferase (COMT), among Egyptian women and men.

Toxicologic Pathology, 2004

Therapeutic Drug Monitoring, 2009

Organophosphates are pesticides ubiquitous in the environment and have been hypothesized as one o... more Organophosphates are pesticides ubiquitous in the environment and have been hypothesized as one of the risk factors for acute lymphoblastic leukemia (ALL). In this study, we evaluated the associations of pesticide exposure in a residential environment with the risk for pediatric ALL. This is a case-control study of children newly diagnosed with ALL, and their mothers (n = 41 child-mother pairs) recruited . Cases and controls were matched for age, sex, and county of residence. Environmental exposures were determined by questionnaire and by urinalysis of pesticide metabolites using isotope dilution gas chromatography-high-resolution mass spectrometry. We found that more case mothers (33%) than controls (14%) reported using insecticides in the home (P , 0.02). Other environmental exposures to toxic substances were not significantly associated with the risk of ALL. Pesticide levels were higher in cases than in controls (P , 0.05). Statistically significant differences were found between children with ALL and controls for the organophosphate metabolites diethylthiophosphate (P , 0.03) and diethyldithiophosphate (P , 0.05). The association of ALL risk with pesticide exposure merits further studies to confirm the association.

The American Naturalist, 1986

$Research paper thumbnail of Enrichment of low molecular weight fraction of serum for MS analysis of peptides associated with hepatocellular carcinoma$

PROTEOMICS, 2006

A challenging aspect of biomarker discovery in serum is the interference of abundant proteins wit... more A challenging aspect of biomarker discovery in serum is the interference of abundant proteins with identification of disease-related proteins and peptides. This study describes enrichment of serum by denaturing ultrafiltration, which enables an efficient profiling and identification of peptides up to 5 kDa. We consistently detect several hundred peptide-peaks in MALDI-TOF and SELDI-TOF spectra of enriched serum. The sample preparation is fast and reproducible with an average CV for all 276 peaks in the MALDI-TOF spectrum of 11%. Compared to unenriched serum, the number of peaks in enriched spectra is 4 times higher at an S/N ratio of 5 and 20 times higher at an S/N ratio of 10. To demonstrate utility of the methods, we compared 20 enriched sera of patients with hepatocellular carcinoma (HCC) and 20 age-matched controls using MALDI-TOF. The comparison of 332 peaks at p , 0.001 identified 45 differentially abundant peaks that classified HCC with 90% accuracy in this small pilot study. Direct TOF/TOF sequencing of the most abundant peptide matches with high probability des-Ala-fibrinopeptide A. This study shows that enrichment of the low molecular weight fraction of serum facilitates an efficient discovery of peptides that could serve as biomarkers for detection of HCC as well as other diseases.

PLoS Neglected Tropical Diseases, 2010

Background: Metronidazole is the most commonly used drug for the treatment of giardiasis in human... more Background: Metronidazole is the most commonly used drug for the treatment of giardiasis in humans. In spite of its therapeutic efficacy for giardiasis, low patient compliance, especially in children, side effects, and the emergence of metronidazole-resistant strains may restrict its use. Albendazole has been used to treat Giardia duodenalis infections in recent years. However, efficacy studies in vivo and in vitro have produced diverse results as to its effectiveness. A moderately benign side effect profile, combined with established efficacy against many helminths, renders it promising for treatment of giardiasis in humans.