bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A141: Chemopreventive properties of omeprazole against azoxymethane-induced colonic aberrant crypt foci formation in fats
Authors: Patlolla Jagan Mohan R. , Zhang Yuting , Qian Li , Steele Vernon E. , Rao Chinthalapally V. 
Published: May 2012

Abstract
Omeprazole is a proton-pump inhibitor which is widely used to treat ulcers and gastroesophageal reflux diseases (GERD). Previous studies show that omeprazole exhibits possible anti-tumorigenic properties in preclinical models of colon cancer. However, no systematic studies were carried to establish the potential anti-carcinogenic potential of omeprazole using established animal models of colon cancer. In the present study, omeprazole was evaluated for its colon cancer chemopreventive properties using azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) as a efficacy endpoint in F344 rats. In addition, we analyzed the growth inhibitory effects and induction of apoptosis in human colon cancer HCA-7 cells. We also studied its possible anti-inflammatory properties in Raw 264.7 macrophage cell line. Prior to efficacy studies we evaluated the maximum tolerated dose (MTD) of omeprazole. For MTD assay, seven week-old rats were fed either control AIN-76 diet, diets containing 5 different dose levels of omeprazole (100, 200, 400, 600 and 800 ppm) for six weeks. Based on body weight gain and toxicity symptoms, the MTD of Omeprazole is found to be ∼600 ppm. To evaluate the inhibitory properties of omeprazole on colonic ACF, seven-week-old male F344 rats were fed experimental diets containing 0, 200, and 400 ppm of omeprazole. One week later, rats received s.c. injections of azoxymethane (AOM) (15 mg/kg body wt., once weekly for two weeks) or equal volume of normal saline (vehicle). Rats were continued on experimental diets for seven weeks before being sacrificed. Colons were evaluated histopathologically for ACF and immunohistochemistry for PCNA marker to assess the crypt cell proliferation. Administration of omeprazole at 400 ppm significantly suppressed total colonic ACF formation (∼30%, p&lt;0.001) when compared to the control diet group. Rats fed with 200 ppm and 400 ppm of Omeprazole showed significantly lower numbers (∼30–50%, p&lt;0.05–0.001) of multi-crypt foci (≥4 or more). Overall, omeprazole produced significant dose-response effect in preventing colonic ACF formation. In in vitro assays, Omeprazole inhibited phorbol-12-myristate 13-acetate -induced iNOS expression in macrophages in a dose dependent manner. Furthermore, omeprazole induced apoptosis by suppressing survivin in HCA-7 colon cancer cells. The results from this study provides evidence for the first time that omeprazole, a proton-pump inhibitor may be used as a chemopreventive agent against colon carcinogenesis. (Supported by NOI-N01-CN-53300).
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A141.
Abstract A142: Radiation-induced acute toxicity in head and neck cancers: Nutritional status as a special parameter
Authors: Dastidar Aloke Ghosh , Dastidar Anjana Basu Ghosh , Chakroborty Indranil 
Published: May 2012

Abstract
Introduction: Acute radiation toxicity is a limiting factor of radiotherapy for head and neck cancers. This acute toxicity depends on number of factors like dose of radiation, dose per fraction, total dose, treatment portals, machines used etc. Nutritional status (NS) of the patient is also an important factor of head and neck cancer so far, development of acute toxicity and tolerance is concerned. Keeping other variables unchanged, how NS affects radiation induced toxicity was the main object of the study.
Patients and Methods: Total 280 patients of squamous cell carcinoma of upper aero-digestive tract were selected for the study. NS of all patients were calculated. The degree of acute toxicity during the course of radiation and 3 weeks after completion of external radiation were noted. The acute toxicity was recorded as per RTOG acute toxicity criteria.
NS is assessed by 1. clinical examination, 2. anthropometric measurement, 3. biochemical investigations, 4. hematological examinations, 5. dietetic assessment.
Anthropometric measurement done by: 1. weight (kg), 2. height (cm), 3. wrist circumference, 4. waist circumference, 5. waist: hip ratio, 6. body mass index = weight (kg) height2 (m2), 7. triceps skin fold thickness. Biochemical Estimation is done by: 1. serum albumin, 2. serum transferrin, 3. serum ceruloplasmin.
Immunologicalparameters are: 1. total circulating lymphocyte count (more than 2000 cells / cu mm normal value, 1200 – 2000 cells / cu mm mild malnutrition, 800 – 1200 cells / cu mm moderate malnutrition, less than 800 cells / cu mm severe malnutrition), 2. delayed cutaneous hypersensitivity (DCH) test, 3. DNCB challenge test, 4. Mantoux test
Acute radiation morbidity scoring was done as per criteria (RTOG).
Result Analysis: There was significantly increased toxicity in patients who were poorly nutritious (n=135) as compared to those who were normally nourished (n=88). Those patients who were under nutritious also showed poor standard of oral hygiene. Rest 57 patients NS were undetermined and were excluded from evaluation. In under nutritious group, acute radiation toxicity grading was: Gr.1 (0%), Gr.2 (42.96%), Gr.3 (55.55%), & Gr.4 (1.48%) respectively. On the contrary, the normal nutritious group acute toxicity developed Gr.1 (11.36%), Gr.2 (81.81%), Gr.3 (6.81%) & Gr.4 (0%) respectively. Oral hygiene of poor standard was 12.5% in under nutritious patients and 4.5% in normal nutritious patients.
Conclusion: Aim of this paper lies in its attempt to explore the acceptability of “Nutritional Status” as a variable in development of radiation induced toxicity, as far as acute morbidity is concerned. In that sense it is a successful phase I trial. One can conclude that there exists some correlation between radiation morbidity and NS of the patients. Therefore correction of NS before onset of radiation provides better tolerance to radiotherapy.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A142.
Abstract A145: Atorvastatin (Lipitor) delays progression of PanINs to pancreatic carcinoma through AKT pathway in a conditional LSL-K-rasG12D transgenic mice
Authors: Mohammed Altaf , Qian Li , Lightfoot Stan , Vernon Steele E. , Rao Chinthalapally V. 
Published: May 2012

Abstract
Pancreatic ductal adenocarcinoma (PDAC) a devastating disease with a dismal prognosis is the most common pancreatic malignancy and is the fourth leading cause of deaths in the U.S. with a 5-year survival rate of less than 5%. Thus, developing novel strategies to prevent or delay the progression of pancreatic cancer is of intense interest. In the present study, we studied chemopreventive efficacy of atorvastatin on pancreatic intraepithelial neoplasms (PanINs) and adenocarcinoma in conditional LSL-K-RasG12D transgenic mice. LSL-K-RasG12D and P48Cre mice were bred and offspring of activated K-rasG12D were generated. Six-week old male KrasG12D (20/group) and wild-type (12/group) mice were fed (AIN-76A) diets containing 0, 200, and 400 ppm Atorvastatin for 35 weeks. At the end of experimental feeding, pancreas were collected, weighed, and evaluated histopathologically for PanINs and adenocarcinomas. To understand the mechanisms, expression levels of PCNA, p21, Akt-1, cdK2, Cav1, cyclin E, survivin, Rho A and p2X7 were determined by IHC, Western blotting or RT-PCR. Results suggest that control diet fed mice showed 100% incidence of pancreatic ductal adenocarcinomas; whereas, mice fed with 200 and 400 ppm atorvastatin had significantly reduced (p&lt;0.0001) ductal adenocarcinomas. Importantly, significant reduction of pancreatic ducts with carcinoma (56–94%, p&lt; 0.0001) was observed in mice fed 200 and 400 ppm Atorvastatin. Similarly, significant suppression of PanIN 3 (22.63%) was observed in mice fed 400 ppm Atorvastatin. However, we did not find any statistically significant inhibition of PanIN 2 lesions between control and atorvastatin fed groups. Whereas, mice fed high dose Atorvastatin showed a significant increase in PanIN 1 lesions compared to mice fed with control diet. Also, mice fed Atorvastatin showed reduced pancreatic tumor weights (∼50%) compared to control diet fed mice. Furthermore, treated mice showed ∼75% of pancreas free from carcinoma. The pancreas of mice fed Atorvastatin diets showed significantly reduced expressions of PCNA, survivin, Akt-1, cyclin E, cdK2 and Cav1 with a significant increase in p21 (p&lt;0.005) levels compared to pancreas of control diet fed mice. In summary, our results suggest that Atorvastatin delays the progression of pancreatic cancer precursor lesions in PanIN 1 and 2 stages from further progressing to adenocarcinoma in a preclinical model. These data highlight the promise of chemoprevention in pancreatic cancer and administration of statins represents an important strategy to prevent pancreatic cancer in high-risk patients. {Supported by NCI-NO1-CN53300}
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A145.
Abstract A146: Meloxicam inhibits prostate tumor growth and progression in prostate specific-PTEN conditional gene targeting knockout mice
Authors: De Velasco Marco A. , Tanaka Motoyoshi , Shimada Keiji , Nishio Kazuto , Uemura Hirotsugu 
Published: May 2012

Abstract
A high incidence of prostate cancer in older men suggests that agents that inhibit or delay the disease process could be beneficial in reducing cancer mortality and morbidity. Increased expression of COX-2 has been found in most of the cancers and compelling evidence from genetic and clinical studies indicates that COX-2 upregulation is one of the key steps in carcinogenesis. There is a strong body of evidence pointing out the role of COX-2 early in the prostate carcinogenesis process, particularly in the progression of prostatic intraepithelial neoplasia (PIN) lesions to prostate carcinoma. Epidemiological data suggests that treatments with non-steroidal anti-inflammatory drugs (NSAIDs) were associated with reduced risk in a number of malignancies. We evaluated the chemopreventive efficacy of meloxicam, a selective COX-2 inhibitor, against prostate cancer in prostate-specific PTEN knockout mice. In our mouse model, homozygous inactivation of PTEN leads to PIN at 8 weeks of age with 50% of the mice progressing to prostate cancer by the age of 10 weeks and 100% by 20 weeks of age. Mice were fed meloxicam (3.0 mg/l ad libitum) in drinking water beginning at 4 or 11 weeks of age for 5 to 28 weeks in stage-specific manners. There were no bodyweight differences were seen between treatment groups. Our data showed a significant reduction (19–23%, p&lt;0.05) of genitourinary tract weights in meloxicam-fed mice. There was a strong reduction in the incidence and extent of adenocarcinoma and increases in PIN in meloxicam-fed mice. Significant differences in tumor differentiation scores were also noted in the treatment groups (p&lt;0.05). Immunohistochemical analysis revealed that meloxicam treatment did in fact reduce COX-2 expression without inhibiting COX-1. Furthermore, meloxicam-fed mice also showed reduced proliferation rates as well as increases in apoptotic rates. Moreover, a reduction of VEGF expression in tumors and tumor stroma was also observed in mice treated with meloxicam. These results suggest that meloxicam safely inhibited tumor growth and progression in the PTEN knockout mouse model by antiproliferative, pro-apoptotic and anti-angiogenic effects and may thus be a suitable candidate for use in human chemoprevention trials.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A146.
Abstract A16: DNA microarray analysis of the UPII-SV40Tag model for invasive bladder TCC: Identification of markers for bladder premalignancy
Authors: Stone Randolph , Sabichi Anita L. , Gill Jennifer , Lee I-ling , Cvek Urska , Trutschl Marjan , Loganantharaj Rasiah , Clifford John L. 
Published: May 2012

Abstract
Transitional cell carcinoma of the bladder (TCC) ranks 4th in incidence of all cancers in the developed world, yet the mechanisms of its origin and progression remain poorly understood. There are a few commercially available urine-based tests for screening and surveillance for bladder cancer, but none of these can detect premalignancy. We have combined a transgenic mouse model for invasive bladder cancer (UPII-SV40Tag mice) with DNA microarray technology, in order to determine molecular mechanisms involved in early TCC development and to identify new biomarkers for detection, diagnosis and prognosis of TCC. We have identified genes that are differentially expressed between the bladders of UPII-SV40Tag mice and their age-matched wild type (WT) littermates at 3, 6, 20 and 30 weeks of age. These are ages which correspond to premalignant, carcinoma in-situ, and early and later stage papillary TCC, respectively. There were approximately 1,900 unique genes differentially expressed (&gt;= 3-fold difference at one or more time points) between WT and UPII-SV40Tag urothelium during the time course of tumor development. Among these, there were a high proportion of cell cycle regulatory genes and proliferation signaling genes that are more strongly expressed in the UPII-SV40Tag bladder urothelium. We have tested several of the genes upregulated in UPII-SV40Tag urothelium, including autocrine motility factor (AMFR), hyaluronan-mediated motility receptor (Hmmr), proliferating cell nuclear antigen (PCNA), Rac GTPase activating protein 1 (RacGAP 1) and others as biomarkers for premalignancy, in urine samples from a recently completed Phase II, randomized, placebo controlled chemoprevention trial (N01 CN85186, PI: A. Sabichi) that was designed to test whether celecoxib can prevent recurrence in patients successfully treated by TUR for non-muscle invasive bladder cancer.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A16.
Abstract A18: Spatial dynamics of cellular proliferation in preneoplastic lesions: Comparison between bronchial, oral, and cervical epithelium
Authors: Guillaud Martial D. , van Niekerk Dirk , Khojasteh Mehrnoush , Carraro Anita , Korbelik Jagoda , Frung Priscilla , Kamalov Rassim , Rosin Miriam P. , Follen Michele , Lam Stephen , MacAulay Calum 
Published: May 2012

Abstract
Introduction: Uncontrolled proliferation is a hallmark of cancer and a biologically plausible risk biomarker for preneoplastic epithelium. The expression Ki-67 has been widely used as a marker of cellular proliferation even though it does not specifically elucidate the complexity of clonal growth that eventually drives a normal homeostatic epithelium towards carcinoma in situ. Our objective is to quantify the spatial dynamics of cellular proliferation in pre-neoplastic lesions of three different tissue types; bronchial, oral and cervical epithelium.
Materials and Methods: Five hundred sixty-two bronchial lesions, seventy nine oral mucosa lesions, and two hundred sixty five cervical lesions were reviewed by at least two pathologists. Expression of Ki-67 was studied by Mib-1 immunohistochemistry. Using an in-house imaging system, a mapping of the regions of interest were performed; nuclei positions were registered; Mib-1 positive cells were manually marked, the basal membrane and the external surface delineated. Using graph-theory tools, the spatial arrangements of all nuclei, in addition to the spatial distribution of Mib-1 positive nuclei were measured. The percentage of Mib-1 positive nuclei within each layer - from the basal layer to the superficial layer - was a study focus.
Results: On average, proliferation increased with pathology grade. Nevertheless, the amplitude and the patterns of cellular proliferation within the different layers differ among the different tissue types. The propotions of Mib-1 positive cells in the bronchial, oral, and cervical normal epithelium were respectively: 19.8%, 6.3%, and 6.1% in the basal layer; 18.7%, 28.5% and 33.2 in the layer 1; 8.0%, 18.7% and 31.1% in the layer 2. For specimens classified as mild dysplasia, the proportion of Mib-1 positive cells in bronchial, oral and cervical dysplastic epithelium were respectively: 42.0%, 19.3%, and 21.5% in the basal layer; 63,2%, 19.3%, and 43.5% in layer 1; 61.8%, 9.9% and 50.0% in layer 2. Furthermore, we observed a high variability of the proliferation patterns (along the different layers) in each tissue within each pathology grade. The significance of these findings and their correlation with other biomarkers (quantitative nuclear phenotype, p16 staining, LOH, etc.) and with clinical parameters (age, sex, HPV status, cancer progression, etc..) will be shown.
Conclusions: Quantitative analysis of spatial patterns and arrangement of proliferating cells squamous dysplastic lesions provide additional insights in the dynamic nature of these early neoplastic changes.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A18.
Abstract A19: S100A7, a prognosticator and early predictive marker for head and neck/oral squamous cell carcinoma
Authors: Tripathi Satyendra C. , Matta Ajay , Kaur Jatinder , Chauhan Shyam S. , Shukla Nootan K. , Duggal Ritu , Gupta Siddhartha D. , Ralhan Ranju , Siu K.W. Michael 
Published: May 2012

Abstract
Recently using multidimensional LC-MS/MS with iTRAQ-tagging, we identified a panel of potential Head and Neck/Oral Squamous cell carcinoma (HNOSCC) biomarkers. S100A7 was one of the promising candidate biomarkers in this panel. S100A7 is 11.4 kDa calcium-binding protein of S100 protein family, found to be highly expressed in pre-invasive ductal carcinoma in situ of the breast. Here, we firstly report its potential as a prognostic biomarker for HNOSCC. The present study also further explores the clinical significance of S100A7 in identification of oral leukoplakic lesions in early stages.
Ninety-nine HNOSCCs, 100 leukoplakias and 50 non-malignant archived tissues were retrieved from the research tissue bank to determine the expression of psoriasin using immunohistochemistry. The immunohistochemical data were subjected to statistical analyses using the SPSS 13.0 software (Chicago). Sensitivity and specificity were calculated and quantified using receiver operating characteristic (ROC) analysis. The expression of S100A7 in oral lesions was further validated by immunoblotting and RT-PCR analyses in the same tissue samples as used for immunohistochemical analysis.
S100A7 expression was found to be significantly increased from normal mucosa to leukoplakia with or without dysplasia to HNOSCC (ptrend&lt;0.001). Receiver Operating Characteristic (ROC) analysis was used to determine the potential of S100A7 as a biomarker for diagnosis of leukoplakia and OSCC. The area-under-the-curve (AUC) value was 0.732 and 0.843 for leukoplakia and OSCC respectively. S100A7 overexpression was significantly associated with dedifferentiation of tumors also. Cytoplasmic S100A7 was significantly associated with tumor size (p=0.015) and stage (p=0.023) of HNOSCC patients. In univariate analysis, nuclear localization of S100A7 was found to be associated poor survival (p &lt; 0.014), while multivariate analysis revealed nuclear S100A7 as independent indicator of disease free survival (hazard ratio, 2.7; 95% confidence interval, 1.4–5.3; p &lt; 0.004).
This is the first large-scale study that suggests overexpression of S100A7 to be an early event and a poor prognostic factor in HNOSCC progression. On the basis of our current findings, S100A7 may serve as a potential biomarker in diagnosis and prognosis of HNOSCCs.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A19.
Abstract A2: Genetic variation in estrogen receptor genes and mammographic breast density
Authors: Lloyd Stacy M. , Diergaarde Brenda 
Published: May 2012

Abstract
Mammographic density is one of the strongest, independent risk factors in the development of breast cancer. Women with mammographically dense breasts, those with greater than or equal to 75% dense tissue, are at a four to six-fold greater risk of developing breast cancer when compared to those with “no measurable dense tissue,” in which the breasts are composed entirely of fat. Many of the established risk factors for breast cancer have been shown to be associated with variations in breast density (i.e., age, menopausal status, parity, BMI, and postmenopausal hormone use). Additionally, twin studies have also shown that heritability accounts for approximately 60% of the variance in mammographic density. Given the established role of estrogens in the development and progression of breast cancer, we have evaluated the role of 17 single-nucleotide polymorphisms (SNPs) in the estrogen receptor 1 and 2 genes (ESR1 and ESR2), and the recently identified G-Protein Coupled Estrogen Receptor 1 (GPER) gene, which has been demonstrated to regulate physiologic responses to estrogens independent of the traditional estrogen receptors.
This study population consisted of 370 cancer-free (excluding cancers of the skin) Caucasian, postmenopausal women enrolled in the Mammograms and Masses Study (MAMS). Three different measures of mammographic density were computed: dense breast area, total breast area, and percent breast density, using the classification system developed by Wolfe in 1976, and a compensating polar planimeter, wax pencil, and transparent overlay. Breast density was calculated as the proportion of visibly dense breast to total breast area, expressed as a percentage. DNA was extracted from buffy coat samples, and genotyping was done using the Sequenom iPLEX Gold Assay. Heterozygote and homozygous variant genotypes were collapsed and compared to the common allele genotype for all statistical analyses. General linear models and χ2 analyses were conducted. We arranged our percent density variable into tertiles for further analysis.
We observed that three SNPs in ESR2 (rs12435857, rs1256044, and rs1256031) were significantly associated with percent mammographic density. For ESR2 rs1256044 and rs1256031, mean percent mammographic density was significantly higher among women with at least one rare allele compared to women homozygous for the common allele (respectively, P=0.02 and P=0.03). Conversely, mean percent mammographic density was significantly higher among women with ESR2 rs12435857 GG genotype compared to those with GA/AA genotypes, 29.0 and 23.7, respectively (P=0.03).
Our results suggest that common genetic variation in ESR2 is associated with percent mammographic density. Since estrogen receptor genes are highly expressed in breast tissue, functional SNPs in these genes may alter breast cancer risk, by altering mammographic density.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A2.