bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B59: Magnetic resonance imaging monitoring of tumor promotion and tumor progression in mouse model of inflammation-promoted colon cancer
Authors: Young Matthew , Ileva Lilia , Riffle Lisa , Bernardo Marcelino , Jones Yava , Kim Young , Choyke Peter , Colburn Nancy 
Published: May 2012

Abstract
B59

Purpose
Early detection of pre-cancerous tissue has significantly increased survival for most cancers including colorectal cancer. Animal models that follow early stages of cancer are valuable for identifying molecular events and response indicators that correlate with the early stages of tumor development. The goal of this work was to generate new methods to monitor over time the early stages of colorectal cancer in mice using magnetic resonance imaging (MRI).

Experimental Design
Mice treated with azoxymethane and dextran sulafate sodium (DSS) were imaged by MRI throughout the tumor development. Early inflammation was imaged in T2-weighted MRI. Dark-lumen images were obtained in both T1 and T2-weighted images using a poly-fluorinated liquid enema. Individual tumor volumes were calculated and validated ex vivo.

Results
Using T2-weighted MRI, inflammation was detected 3 days after DSS exposure and subsided over the next week. The poly-fluorinated liquid enema distended the colon and provided a clear differentiation of the lumen of the colon from the mucosal lining. Tumors were detected as early as 29 days after initiation and as small as 1.2 mm3. Individual tumor growths were followed over time and tumor volumes measured by MRI correlated with volumes measured ex vivo.

Conclusions
Early detection of tumorigenesis is important for understanding tumor development. The use of MRI for detection of the initial stages of colon cancer allows real time evaluation of preclinical trials for prevention and intervention. The use of the poly-fluorinated liquid enema for Dark-lumen MRI in both T1 and T2-weighted imaging could simplify clinical MRI detection of colon cancer.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B59.
Abstract B60: Ultrasound microcalcification does not indicate psammoma bodies in thyroid nodules
Authors: Gamboa-Dominguez Armando , Tinoco-Ventura Erendi , Bezaury Paulina , Rivera-Moscoso Raul 
Published: May 2012

Abstract
B60

Background
The increasing incidence of thyroid nodules is associated with high resolution ultrasound (US) use. Thyroid nodules with irregular margins, vascular spots and microcalcifications in the US analysis have been described as malignant, and no fine needle aspiration (FNA) biopsy is suggested in some centers. It is thought that psammoma bodies, -a very specific finding of papillary thyroid carcinoma- within a nodule, produce the US microcalcifications.The aim of the present study is to identify if psammoma bodies are the source of the ultrasonographic microcalcifications.

Methods
Consecutive US performed in patients with thyroid nodules seen at the thyroid clinic between May 2007 and May 2008 were assessed to identify microcalcifications, margins and vasculature. Cases submitted to thyroidectomy were grossly sampled in suspected zones. Specimens were fixed in buffered formalin, embedded in paraffin and stained with haematoxylin and eosin for histological study. A systematic search for psammoma bodies, dystrophic/non dystrophic small and large calcifications was performed and a histological diagnosis was rendered. Correlation of US microcalcifications and the type of calcification in the different morphological categories was performed. Evaluators were blind and sampling was standardized according to nodule size.

Results
Fifty four patients were included (papillary carcinoma 35, goiter 16, adenoma, Hashimitos thyroiditis and anaplastic carcinoma 1 each). Morphologic analysis depicted psammoma bodies only in papillary carcinoma but also macro calcifications (29%), dystrophic micro calcifications (34%) and Monckeberg vascular calcifications (26%). Macro calcifications were evenly distributed between papillary carcinoma and goiter. No calcifications were identified in 30% of US interpreted as having microcalcifications.

Conclusion
Micro calcifications observed in US are not specific of psammoma bodies or malignancy. A careful interpretation of US micro calcifications is mandatory in thyroid nodule screenings.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B60.
Abstract B61: Modulation of antioxidant gene expression by a fruit juice rich in polyphenols: an intervention study with hemodialysis patients
Authors: Janzowski Christine , Soyalan Bulent , Albert Franz , Rath Thomas , Dietrich Helmut , Will Frank , Eisenbrand Gerhard 
Published: May 2012

Abstract
B61
Patients with chronic renal failure undergoing hemodialysis (HD) face an elevated risk for cancer, artheriosclerosis and other diseases. Factors considered to contribute to such increased health risks include oxidative stress exerted in several ways by the extracorporal blood circuit, but also malnutrition and iron supplementation. A red fruit juice with especially high flavonoid/ polyphenol content previously has been found by us to diminish oxidative cell damage in healthy probands (Weisel et al. Biotechnol. J., 1, 388, 2006). In HD-patients this juice was highly effective as well: In a ten week intervention study with 21 subjects (three week run-in phase (R), four week 200 ml/d juice-uptake (J), three week wash-out phase (W), weekly blood samplings) markedly reduced DNA oxidation damage, protein oxidation, lipid peroxidation and NFκB-DNA binding activity were observed concomitant with significantly elevated glutathione level/status in blood (Spormann et al., Arch. Pharmacol.; 375, 1, 95, 2007).
To evaluate effects on antioxidant genes in a subset of the HD-patients, RNA was isolated from lymphocytes obtained from the blood samplings and gene expression measured by Real-Time TaqMan PCR. Target genes studied where γ-glutamate-cysteine ligase (γ-GCl, catalytic, GCLC and modulatory, GCLM subunits); encoding the enzyme which catalyzes the rate limiting step of glutathione synthesis, glutathione peroxidase 1 (GPX1), glutathione reductase (GSR) and the transcription factor Nrf2 (NF-E2-related factor 2). NFκB regulated cycloxygenase 2 (Cox-2), which plays a pivotal role in inflammatory processes, was also included. Results obtained from 11 patients show a significant induction of both γ-GCL subunits during juice uptake. In the subsequent wash-out phase, GCLC transcription decreased, whereas transcription of GCLM remained elevated. Distinct juice dependent induction of GPX1 and Nrf2 gene expression was also observed, whereas GSR transcription was at best slightly elevated. For Cox-2, the results show a depletion of mRNA transcripts during juice uptake.
In conclusion, the juice intervention clearly lead to elevated transcription of antioxidant genes, reduction of oxidative damage and an increase of antioxidant defense in HD-patients. This provides promising perspectives into prevention of cancer and other diseases in population subgroups exposed to enhanced oxidative stress.
(Supported by Karin Nolte Foundation)
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B61.
Abstract B63: VKORC1 haplotypes influence serum PIVKAII and transaminases levels in hepatocellular carcinoma patients
Authors: Luo Fang , Wang Yibo , Zheng Yi , Fan Xiaohan , Chen Jinxing , Zhang Yu , Hui Rutai 
Published: May 2012

Abstract
B63

Background
VKORC1 haplotypes influence VKORC1 expression and vitamin K-dependent proteins. PIVKAII, named des-γ-carboxy prothrombin, can be used for detecting hepatocellular carcinoma (HCC), and vitamin K deficiency would be associated with low values of serum aspartate transaminase. Whether VKORC1 haplotypes may influence PIVKAII in detecting HCC and serum transaminase?

Methods
A number of measures were compared between patients with different VKORC1 haplotype in 228 HCC patients. VKORC1 haplotypes impact on PIVKAII in detecting HCC was detected in 76 HCC patients and 86 controls. Spearman correlation was used to assess the correlation. Youden's index and positive likelihood ratio were used to weigh the proper concentration of PIVKAII for HCC’s prognosis.

Results
In 228 HCC patients, the genotype-frequencies were similar with Chinese common frequencies, while serum PIVKAII and transaminases levels were significantly higher in CC/CT carriers than those in TT carriers. Both in cases and controls, serum PIVKAII levels were significantly higher in SNP2255-CC/CT carriers than those in TT carriers. The estimated optimal cut-off value of PIVKAII for detecting HCC was 2.0ng/ml and 3.0ng/ml in CC/CT carriers and in TT carriers, respectively.

Conclusions
VKORC1 haplotypes could be a complementary to PIVKAII in detecting HCC, and are associated with serum transaminases levels in HCC patients.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B63.
Abstract B65: Atypia in ductal lavage: A reproducible marker of risk?
Authors: Casano Ashley , Tondre Julianne , Mills Dixie , Love Susan 
Published: May 2012

Abstract
B65

Background
The majority of breast cancers originate in the ductal epithelium of the breast. Ductal lavage provides a minimally invasive tool for assessing epithelial cells and their microenvironment. Previous studies of pathological atypical hyperplasia on biopsy, and cytological aypia in nipple aspirate fluid (NAF) and random fine needle aspiration (FNA) have suggested that these cells are precancerous because of the subsequent increased risk of cancer. It has therefore been hypothesized that serial ductal lavage could be used to identify atypia and monitor the effects of chemoprevention over time. This report is part of a larger study examining the differences in hormone levels and cytology between ducts and their reproducibility. This report presents a cohort of women unselected for risk who voluntarily underwent ductal lavage of the same ducts on two occasions six months apart. Samples were analyzed for epithelial cells and macrophages.

Methods
A total of 107 women were recruited in this IRB-approved prospective study to undergo ductal lavage of three fluid or non-fluid-yielding ducts within a breast. Women were unselected for risk: the average Gail score was 1.67 and ten women had a history of contralateral breast cancer. The average age was 51 years. Fifty-four women were premenopausal, 4 were perimenopausal and 49 were postmenopausal. Samples were submitted in a blinded fashion to a central laboratory and were analyzed by duct for both macrophage and epithelial cell number on Papanicolaou-stained slides. If adequate epithelial cells were present (&gt;10), a diagnosis of each duct (benign, mild atypia, or marked aytpia) was made by an experienced cytopathologist.

Results
Of the 107 women, 317 (99%) ducts were successfully cannulated without regard to nipple aspirate fluid (NAF) production. Thirty ducts in 23 women were diagnosed with mild or marked atypia on either of the two visits. Of these ducts, 16 were diagnosed at the initial visit and 13 at the second visit. Only one duct was diagnosed with mild atypia on both visits, in a woman with a Gail score of 1.4. Cellular atypia in ductal lavage was not reproducible at a six month interval (p=0.45). This absence of reproducibility was seen in women at all risk levels. Macrophage and epithelial cell numbers also showed a lack of reproducibility at the six month interval (p=0.31 and p=0.22, respectively).

Conclusion
Atypia on cytology in ductal lavage in women unselected for risk was not reproducible at a six month interval, suggesting that a single diagnosis of atypia on lavage should not be used as a marker for the identification of women at risk. Further studies are necessary to indicate whether persistent atypia over an extended interval could represent an elevated risk for breast cancer. In addition, ongoing studies are being performed to identify better cellular markers of premalignancy and subsequent risk.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B65.
Abstract B71: Decreased expression of Tgfβ family members appears to be an acquired phenotype of progression to malignancy in the context of loss of Brca1 in mammary epithelial cells.
Authors: Assefnia Shahin , Mitchell Shermaine , Furth Priscilla 
Published: May 2012

Abstract
B71

Rational
Loss of full length Brca1 in mammary epithelial cells of conditional knockout mice is associated with an aberrant proliferative response to estrogen treatment promoting cancer progression. We had previously found that loss of full-length Brca1 in mammary epithelial cells was associated with decreased expression of Tgfβ family members at early stage of malignancy. Initial time course study was conducted to find if decreased expression of growth inhibitory Tgfβ family members is directly related to loss of Brca1 in mammary epithelial cells.

Methods
Mammary gland tissue of Brca1f/f;MMTV-Cre and control wild-type mice from different time points: prior to puberty (age 2½ weeks), mid-puberty (age 6 weeks), end of puberty (age 10 weeks) and maturity (4 and 6 months) was isolated at the time of necropsy(N=3 per cohort). RNA expression levels of TGF-β 1,2,3 and TGF-βRI, II were measured by real time RT-PCR.

Results
No significant differences in the expression levels of Tgfβ family members between Brca1f/f;MMTV-Cre and wild-type mice were found at these time-points using current number of samples.

Conclusions
Decreased expression of Tgfβ family members in these mice does not seem to be directly associated with loss of Brca1 in mammary epithelial cells and appears to be an acquired phenotype as part of the malignancy progression, which would suggest that it is due to modulation of other signaling pathways.
Funding: This study was supported by U.S. Army Medical Research and Material Command WX81XWH-07-1-0588(S. A. and P. A. F.) and Bridges to the Doctorate NIGMS 1R25GM075360-01(S. K. M.).
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B71.
Abstract B77: Translational effects of alternative NAT1 mRNA isoforms
Authors: Millner Lori , Barker David , Howarth Ashley , Doll Mark , States J. Christopher , Hein David 
Published: May 2012

Abstract
B77
N-acetyltransferase 1 (NAT1) catalyzes the N-acetylation of many aromatic amine carcinogens such as 2-aminofluorene and 4-aminobiphenyl. Following N-oxidation by cytochrome P450’s, NAT1 catalyzes the O-acetylation of the N-hydroxy metabolites of many aromatic and heterocyclic amine carcinogens. NAT1 genetic polymorphisms have been associated with differential risks to various cancers related to aromatic and heterocyclic amine carcinogens, but the findings have been inconsistent. Individual susceptibility to these carcinogenic compounds could be modified by genetic polymorphism or by other factors causing differences in NAT1 expression. Our laboratory and others have reported that NAT1 is transcribed from a major promoter, NATb, and an alternative promoter, NATa, resulting in mRNAs with distinct 5’-UTR regions. The 117 nucleotide NATb 5’-UTR contains two noncoding exons, while the 371 nucleotide NATa 5’UTR contains four noncoding exons. The two 5’UTRs share a 79 nucleotide exon immediately upstream of the open reading frame (ORF). We hypothesized that mRNAs including either the NATa or NATb 5’-UTR may be associated with differences in protein expression and that SNPs included in variant NAT1 alleles may modify this effect. We therefore investigated effects on protein expression due to interaction of the different 5’-UTRs with the ORF and region 3’ to the ORF of the reference NAT1*4 allele, and two variant alleles: NAT1*10 and NAT1*11 that are associated with modified risk to arylamine-induced cancers. pcDNA5/FRT plasmid constructs were prepared for transient transfection of full length human mRNAs including either the NATa or NATb 5’-UTR, the ORF, and 885 nucleotides of the region 3’ to the ORF. For each allele of interest, two constructs were made, one including the NATa 5’-UTR and one including the NATb 5’-UTR. Following transient transfection into Chinese hamster ovary cells, NAT1-catalyzed N-acetylation of p-aminobenzoic was measured by HPLC and NAT1 protein expression was measured by Western blot. A difference of approximately 10 fold (p&lt;0.05) in both NAT1 catalytic activity and protein was observed between the NATa and NATb mRNA forms but there was no evidence for allele specific 5’-UTR interactions. These results suggest that differences in NAT1 expression are modified by factors other than polymorphisms in the ORF. Further experiments to examine the possible roles of mRNA production, mRNA stability or differences in mRNA translation efficiency on NAT1 expression are needed. Partially supported by USPHS grants CA034627, ES014559, ES011564, and ES014443.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B77.
Abstract B82: First report of genotype F and novel mutations in the core promoter region of HBV isolates from a northern Indian population
Authors: Singh Jasbir , Pahal Vikas , Kumar Rajesh 
Published: May 2012

Abstract
B82
Hepatitis B virus (HBV) isolates (35) from North India having different stages of hepatitis were studied for genotypes distribution, core promoter mutations and phylogenetic origin. Assays of SGOT, SGPT and HBeAg were performed in all samples using commercial available kits. Genotypes were determined in all the studied subjects by restriction fragment length polymorphism and core promoter mutations by direct sequencing of PCR products. HBV genotype D was found in 57% of the isolates while 40 % isolates have genotype A and 3% have genotype F. This is the first report of genotype F in Indian population. Earlier it was reported from population from Japan, USA, Argenita and Venezuela. Subgenotype D 1 was predominant among genotype D isolates followed by genotype D2 and D6. Subgenotype A1 was predominant among genotype A followed by A3. Genotype F has subgenotype F2. 1762A -T and 1764G-A mutations were observed in 50% isolates having active viral replication of HBV virus. These are also present in the sera of HCC patients. Wild types were observed in many asymptomatic patients. Novel mutations like 1697G 1698C1727A 1740T were observed in the 50% isolates having nearly normal or slightly high ALT/AST level and all the samples were positive for HBeAg. 1811C 1812C1813T mutations were observed in 15% isolates with slightly high ALT/AST level. 1858T was observed in genotype D with HBeAg positive. 1898A stop codon mutations responsible for HBeAg negativity as observed in Japanese, South African and other world populations could not be observed in the isolates under study. Phylogenetic tree of HBV isolates based on the precore/core gene sequences was drawn with HBV sequences from other parts of the world and previously reported Indian strains from eastern part. Majority of strains shows a high degree of closeness with Chinese and eastern Indian strains. Two rare sequences having nearly 46% and 26% difference in the nucleotide sequence with the available wild type with respect to the CP region were also observed. Efforts are going on to amplify the genotype F to full length. The studies regarding mutations, their role in disease progression and potential as biomarkers of hepatitis B is actively underway.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B82.
Abstract B85: Comparison of three oxidative stress biomarkers in a sample of healthy adults
Authors: Watters Joanne , Satia Jessie , da Costa Kerry-Ann , Boysen Gunnar , Collins Leonard , Morrow Jason , Milne Ginger , Swenberg James 
Published: May 2012

Abstract
B85
Oxidative stress is a potentially important etiologic factor for many chronic diseases, including cardiovascular disease, neurodegenerative disease, and cancer, yet studies often find inconsistent results. Three of the most widely-used biomarkers of oxidative stress are F2-isoprostanes for lipid peroxidation and 8-hydroxy-2-deoxyguanosine (8-oxo-dG) and the comet assay with FPG for oxidative DNA damage. The aim of this study was to examine associations among three biomarkers of oxidative stress, F2-isoprostanes, 8-oxo-dG, and the comet assay with FPG, in a sample of 135 healthy African American and White adults. The strongest associations were observed between F2-isoprostanes and the Comet tail moment (r=0.22, p=0.01). There were non-statistically significant weak correlations between 8-oxo-dG and the comet assay (r= -0.09), as well as F2-IsoP (r= -0.04). There were also significant differences between the oxidative stress assessment methods by several participant characteristics, including sex, race, physical activity, and passive cigarette smoke exposure. The results of our study are informative, particularly for researchers seeking to compare results pertaining to oxidative stress across studies and/or assessment methods. The development and use of oxidative stress biomarkers is an exciting and promising field, however additional validation studies are necessary to establish accuracy and comparability across studies and oxidative stress assessment markers.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B85.
Abstract B86: Antioxidant enzymes status in carcinoma cervix patients before and after radiotherapy.
Authors: Sharma Nidhi , Kumar Ashok , Chougle Arun 
Published: May 2012

Abstract
B86

Background and Objectives
Cancer is defined as a cellular growth due to uncontrolled cell division. This involves protein synthesis triggered by unusual acceleration of the process of translation, transcription and replication. The extent of free radical induced oxidative stress can be exacerbated by the decreased efficiency of antioxidant defense mechanisms. Low levels of essential antioxidants in the circulation have been found to be associated with an increased risk of cancer. Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) are the major antioxidant enzymes present in the human body that protect against the oxygen toxicity. Oxidative stress may be a consequence of reduced efficiency of these endogenous antioxidants that may render carcinoma cervix patients more vulnerable to oxidative stress. There are reports suggesting a decrease in SOD and other antioxidant enzymes activities and increase in various markers of lipid peroxidation in carcinoma cervix patients.

Methods
We have undertaken this study to ascertain the possibility of oxidative damage in carcinoma cervix patients by measuring the cytosolic antioxidant enzymes viz., superoxide dismutase (SOD), catalase (CAT), Glutathione (GSH) and lipid peroxidation as well as lactate dehydrogenase levels in circulation of women with cervical carcinoma prior to radiotherapy and at the end of therapy (60~70 Gy tumor dose) in II, IIIA and IIIB and to compare our findings with age matched controls.

Results
In the present study significant decrease (P&lt;0.05) was observed in SOD, CAT, GSH and significantly high plasma lipid peroxide levels and lactate dehydrogenase levels were observed in carcinoma cervix patients when compared to the normal subjects.

Interpretation and Conclusion
Antioxidants play a significant role in the aetiology of human cancer.Result of the present study showed involvement of oxidative stress as one of the risk factors, which can be co-related with the severity of the disease,furthermore these biochemical tests has got excellent prognostic significance
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B86.