bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A8: Vasodilator-stimulated phosphoprotein Ser239 regulates matrix metalloproteinase-9 in colon cancer
Authors: Zuzga David S. , Hoffman Leah , Pelta-Heller Josh , Pitari Giovanni M. 
Published: January 2011

Abstract
Cancer invasion and spreading is promoted by membrane protrusion formation driven by actin polymerization and filament (F)-actin elongation, a process controlled by the actin-binding protein vasodilator-stimulated phosphoprotein (VASP). Tumor epithelial cell matrix metalloproteinase-9 (MMP-9) is a key promoter of carcinogenesis and invasion in colon cancer. Interestingly, both VASP and MMP-9 activities are regulated by intracellular cGMP signaling in colon cancer cells. However, direct functional relationships between VASP and MMP-9 are unrecognized. Here, human colon carcinoma cells were examined by immunoblotting, sucrose-gradient fractionation, confocal microscopy and imaging analysis. MMP-9 localizes at membrane protrusions and lipid rafts, cell surface microdomains specialized in signal transduction, in a cGMP-dependent manner. Activation of cGMP signaling disrupted membrane protrusion dynamics and induced intracellular MMP-9 redistribution. Strikingly, cancer cells expressing the serine-to-alanine VASP phosphomutant at Ser239, resistant to cGMP-dependent VASP phosphorylation, were insensitive to cGMP effects on membrane protrusions and MMP-9. Importantly, cGMP signaling through VASP Ser239, but not Ser157, critically regulates the ability of cancer cells to release MMP-9 in the extracellular environment. Together, these observations indicate tumor epithelial cell MMP-9, a key promoter of cancer invasion, is regulated by VASP Ser239 phosphorylation, a previously unappreciated paradigm in colon cancer biology.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A8.
Abstract B10: Side effects associated with aromatase inhibitor treatment among breast cancer patients
Authors: Gallicchio Lisa M. , MacDonald Ryan , Wood Bethany , Rushovich Errol , Helzlsouer Kathy 
Published: January 2011

Abstract
Introduction: Aromatase inhibitors (AIs), a first-line hormonal treatment for estrogen-receptor positive breast cancer, have clear benefit in reducing recurrence risk and increasing survival. Musculoskeletal symptoms are a well-known side effect of treatment, but the spectrum of other side effects is less well characterized. Side effects of AIs may impact quality of life and potentially medical adherence. The purpose of this study was to examine whether AI treatment was associated with side effects other than musculoskeletal symptoms.
Methods: A cohort study of 100 breast cancer patients initiating AI treatment (“cases”) and 200 women without a history of cancer (“controls”) was conducted. Questionnaire data on symptoms were collected prior to AI treatment for the cases and at the start of the study for the controls (baseline). All participants were followed for six months, with questionnaires being administered at three months and at the end of follow-up. Data on the frequency at which a number of symptoms were experienced was collected. The prevalence of each symptom at baseline among all cases and in the subgroup of cases who had not received chemotherapy was compared to controls. In addition, new onset of each specific symptom during the six month follow-up among cases compared to controls was examined. Analyses were conducted using logistic regression, and results are reported as age-adjusted odds ratios (OR) comparing cases to controls.
Results: At baseline, cases were more likely than the controls to have experienced hot flashes, decreased appetite, fatigue, fever, breast sensitivity, swelling of hands and feet, difficulty concentrating, and tendency to take naps. These differences remained when limiting the sample of cases to those who had not received chemotherapy. The initiation of AI treatment was significantly associated the new onset of the following symptoms during the follow-up period: hot flashes (OR 5.13; p&lt;0.01), night sweats (OR 4.15; p&lt;0.01), cold sweats (OR 4.73; p&lt;0.01), hair loss (OR 4.74; p&lt;0.01), leg cramps (OR 3.17; p&lt;0.01), weight gain (OR 3.19; p&lt;0.01), forgetfulness (OR 2.72; p=0.02), chest pain (OR 5.00; p=0.02), intestinal gas (OR 2.07; p = 0.04), cough (OR 2.58; p=0.01), depression (OR 2.67; p=0.01), breast sensitivity (OR 5.71; p&lt;0.01), sleep disturbance (OR 2.70; p=0.01), interrupted sleep (OR 2.22; p=0.03), irritability (OR 2.39; p=0.04), and a tendency to take naps (OR 2.76; p=0.02).
Conclusions: AI treatment results in an extreme estrogen-deficient state and is associated with the onset of a number of symptoms that occur much more frequently compared to postmenopausal women of similar age without a history of cancer. These symptoms may impact adherence. This study was funded by Susan G. Komen for the Cure, AstraZeneca, and the National Cancer Institute (CA132147).
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B10.
Abstract B23: Comparison of epithelial proliferation and lobular involution in normal and benign breast tissues
Authors: Degnim Amy C. , Frost Marlene H. , Hartmann Lynn C. , Maloney Shaun D. , Hoskin Tanya L. , Benetti Lorelle L. , Vierkant Robert A. , Allers Teresa M. , Pankratz V. Shane , Radisky Derek C. , Visscher Daniel W. 
Published: January 2011

Abstract
Background: Epithelial proliferation in benign breast disease (BBD) is a well-established biomarker of breast cancer risk, and BBD tissues can be used as a platform to assess other biomarkers for breast cancer risk. Lobular involution (the degree of age-related atrophy in lobules) is a new biomarker, with greater degrees of involution associated with lower breast cancer risk. Successful application of tissue biomarkers of risk to breast tissues from normal women would be valuable for risk prediction in the general population. We hypothesized that normal breast tissue samples would differ from BBD tissues in these histologic features of breast cancer risk, with less epithelial proliferation but a similar degree of involution compared to BBD tissues.
Methods: Core biopsy samples from the Mayo Benign Breast Disease Cohort Study were compared to core biopsy samples of normal breast tissue obtained from the Susan G. Komen for the Cure Tissue Bank at IU Simon Cancer Center (KTB), a unique resource of breast tissue from donor women without any known breast abnormalities. All core biopsies were assessed histologically by a single breast pathologist for degree of epithelial proliferation (classified as non-proliferative, proliferative without atypia, or atypical hyperplasia) and extent of lobular involution (classified as none, 1-24%, 25-74%, or &gt;75% of lobules). Data were analyzed using chi-square tests and logistic regression.
Results: Overall, 318 Mayo BBD and 303 normal (KTB) core breast biopsy samples were evaluated. As anticipated, significantly less epithelial proliferation was present in normal samples compared to BBD samples. Proliferative disease occurred in 9/303 (3%) of normals versus 79/318 (25%) of BBD, and atypical hyperplasia was seen in 2/303 (0.7%) of normal samples versus 24/318 (8%) of BBD core biopsies, p &lt; 0.0001. This difference remained significant after adjusting for age (which was greater overall in the BBD samples). Complete involution was more frequent in normal compared to BBD tissues, although the difference did not reach statistical significance. The age-adjusted odds ratio of complete involution in normal versus BBD tissues was 1.46 (95% CI 0.98-2.17, p = 0.06), suggesting a possible delay or failure of involution in women with BBD.
Conclusions: Histologic features of normal breast tissues are different from those of BBD tissues, with less epithelial proliferation and more lobular involution, consistent with a lower risk of breast cancer expected for women with normal breast tissue compared to those with benign breast disease. Normal breast tissues are a valuable and distinct resource that should be considered for biomarker validation studies.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B23.
Abstract B27: DNA polymorphisms in sex hormone pathway genes and risk of esophageal squamous cell carcinoma
Authors: Hyland Paula L. , Hu Nan , Wheeler Bill , Yu Kai , Cook Michael B. , Dawsey Sanford M. , Abnet Christian C. , Goldstein Alisa M. , Freedman Neal D. , Taylor Philip R. 
Published: January 2011

Abstract
Background: Esophageal cancer (EC) is the sixth most common cancer in the world and exhibits a dramatic geographic distribution in incidence and histological subtype. In China, EC is the fourth leading cause of cancer death, the predominant histologic type being squamous cell carcinoma (ESCC), as opposed to adenocarcinoma which is more common in developed counties of the western world. Recently it has been suggested that sex hormones may be associated with the risk of aero-digestive tract cancers including those of the colon, head and neck, and stomach. To evaluate the potential role of sex hormones in ESCC, we examined sex hormone metabolizing gene variants and ESCC risk in a high risk population from north central China.
Methods: A combined total of 1027 ESCC cases and 1452 controls from separate studies were genotyped for 752 tagged SNPs in 46 sex hormone-related genes. SNP-, gene-, and pathway-based associations with ESCC risk were evaluated using the adaptive rank-truncated product (ARTP) method and the additive model within unconditional logistic regression adjusted for age and sex. Statistical significance was determined through use of a permutation-based sampling procedure (20,000 permutations).
Results: No significant pathway-based association was observed when all 46 sex hormone genes were considered together (P=0.16). Gene-based associations with ESCC were observed for 6 genes: SULT2B1 (ARTP P=0.012), CYP1B1 (P=0.019), CYP3A7 (P=0.03), CYP3A5 (P=0.033), SHBG (P=0.037), and CYP11A1 (P=0.038). Of examined individual SNPs, sixty three SNPs in 21 genes were also statistically significant (P&lt;0.05). Among the strongest effects observed were rs4149455 in SULT2B1 (per allele OR 0.81, 95% CI 0.72-0.91, P=0.0007); rs9341266 in CYP1B1 (OR 1.45, 1.16-1.82, P=0.001); rs17161780 in CYP3A5 (OR 1.19, 1.04-1.35, P=0.009); rs2005548 in CYP3A7 (OR 1.15, 1.02-1.29, P=0.02), and rs727428 in SHBG (OR 0.85, 0.76-0.96, P=0.01).
Conclusion: Genetic variation in specific sex hormone-related genes may contribute to ESCC risk among Chinese individuals at high risk for ESCC.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B27.
Abstract B36: Circulating FGF-23 is associated with metachronous colorectal adenomas
Authors: Jacobs Elizabeth T. , Martinez Maria Elena , Buckmeier Julie A. , Lance Peter , May Melissa , Thompson Patricia A. , Jurutka Peter W. 
Published: January 2011

Abstract
Fibroblast growth factor-23 (FGF-23) is a phosphaturic peptide and a key component of an endocrine feedback loop with the hormonal vitamin D metabolite 1,25(OH)2D. It is both induced by and represses the synthesis of 1,25(OH)2D in a concerted effort to maintain both calcium and phosphate homeostasis. Vitamin D has been shown to be inversely related to colorectal neoplasia; therefore, we hypothesized that the effect of FGF-23 on 1,25(OH)2D concentrations could have implications for the risk of colorectal neoplasia. The purpose of this study was to prospectively evaluate the association between circulating concentrations of FGF-23 and odds of metachronous (recurrent) colorectal adenomas, the precursors to colorectal cancer. FGF-23 levels were assessed in 100 male and female participants from the Ursodeoxycholic Acid trial, 50 of whom had a metachronous colorectal adenoma and 50 who did not. Compared to the lowest tertile of FGF-23, the adjusted ORs (95% CIs) for the second and third tertiles were 2.80 (0.94-8.31) and 3.41 (1.09-10.67), respectively; a significant trend was shown for the relationship between FGF-23 concentration and odds for metachronous adenoma (p=0.03). In addition, there was a statistically significant inverse relationship between FGF-23 and 1,25(OH)2D, with those in the highest tertile of circulating 1,25(OH)2D having the lowest concentrations of FGF-23. Levels of FGF-23 were 81.4 + 36.6 RU/ml, 75.0 + 34.5 RU/ml, 55.7 + 15.8 RU/ml for low, medium, and high tertiles of 1,25(OH)2D, respectively (p-trend=0.001). In contrast, no statistically significant trend was observed between FGF-23 and 25(OH)D concentrations, with FGF-23 levels of 66.4 + 223.4 RU/ml, 69.1 + 38.6 RU/ml, and 76.1 + 40.7 RU/ml among participants who were vitamin D insufficient (&lt;20 ng/ml); sub-optimal (&gt;20 ng/ml and &lt;30 n/ml), and sufficient (&gt;30 ng/ml); p-trend=0.28. This work provides novel evidence of an association between FGF-23 and risk for colorectal neoplasia, and the results support an important role for FGF-23 as a potential risk biomarker of early colorectal carcinogenesis. The effects of FGF-23 may be mediated through biologic effects on individual 1,25(OH)2D levels. Further studies in larger populations are necessary for confirmation of these results.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B36.
Abstract B4: Impact of obesity on the effectiveness of aromatase inhibitors (AIs): Can breast cancer survivors on AIs lose weight compared to non-AI users?
Authors: Klemp Jennifer R. , Aversman Sonya , Befort Christie , Harvey Katherine , Khan Qamar J. , Sharma Priyanka , Kimler Bruce , Phillips Teresa , Fabian Carol J. 
Published: January 2011

Abstract
Background and Objectives: Weight at diagnosis and weight gain after diagnosis are associated with increased risk of breast cancer (BrCa) recurrence and mortality. In addition, post-menopausal obese breast cancer survivors on anti-hormonal therapy were 40% more likely to develop a local recurrence and 46% more likely to develop a distant recurrence compared to their normal weight counterparts. This evaluation was conducted to examine if a diet/exercise/behavioral weight loss intervention for overweight breast cancer survivors: 1) would impact BrCa risk biomarkers and 2) would the response differ by aromatase inhibitor (AI) status.
Methods: 84 BrCa survivors with a BMI 25-45 kg/m,2 ≥3 months from chemotherapy were recruited, and 52 agreed to participate. 6 (11%) participants did not complete the intervention. The 6-month intervention included: 225 minutes/week of aerobic exercise, resistance training, 1200-1500 calorie/day diet, and weekly group behavioral meetings. Pre and postintervention assessments included: anthropometrics (weight, BMI), body composition (DEXA % body fat), and serum biomarkers (estradiol, testosterone, SHBG, IGF-1/IGFBP3, insulin, leptin, adiponectin, glucose, CRP, cholesterol). Results are shown for 52 women (median age 52 ± 8 years) who initiated the program and 45 (87%) who completed the 6-month intervention.
Results: Women were approximately 4.25 years from diagnosis, their median weight at diagnosis was 84.1 kg (±15.8), and BMI was 31.3 kg/m2 (±5.6). Median pre-intervention weight was 91.8 kg (±13.4) and participants lost an average of 10.6 kg (±6.0)* or 13.3% (±28.8)* of their starting weight after the 6-month intervention. BMI decreased from 32.6 kg/m2 (±4.7) to 28.2 kg/m2 (±4.7)* and total percent body fat decreased by 5.6% (±4.5)*. Favorable changes in serum biomarkers of BrCa risk were observed for insulin*, leptin*, adiponectin*, and estradiol*. When comparing AI users to nonusers the significant favorable change in estradiol was not seen for those on AI's. There was a significant difference in decrease in % body fat* between AI users and nonusers. No other differences were significant. (*p-values &lt;0.05)
Conclusions: Overall, results suggest a 6-month diet/exercise/behavioral weight loss intervention in overweight post-menopausal BrCa survivors results in a significant decrease in weight and change in serum biomarkers of BrCa risk in both current AI users and nonusers, however, due to the small sample size significant between group difference were not seen. Larger studies evaluating the effects of weight and weight loss based on exposure to antihormonal therapy are needed.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B4.
Abstract B53: Metformin treatment suppresses colorectal aberrant crypt foci in humans: Results from a short-term feasibility study
Authors: Hosono Kunihiro , Takahashi Hirokazu , Sakai Eiji , Uchiyama Takashi , Endo Hiroki , Nakajima Atsushi 
Published: January 2011

Abstract
Metformin is a biguanide derivative that has been widely used for diabetic treatment. Previously, we reported the chemopreventive effect of metformin in two rodent models of colorectal carcinogenesis. However, besides epidemiologic studies, little is known about the effects of metformin on human colorectal carcinogenesis. The objective of this pilot study was to evaluate the chemopreventive effects of metformin on rectal aberrant crypt foci (ACF), which are the endoscopic surrogate marker of colorectal cancer. We prospectively randomized 30 non-diabetic patients with ACF to treatment with metformin (250 mg/day; n = 15) or no treatment (control; n = 15); 27 patients were evaluable for endpoint analyses (12 metformin; 15 control); the two groups were similar in ACF number and other baseline clinical characteristics. Magnifying colonoscopy determined the number of rectal ACF in each patient at baseline and after 1 month in a blinded fashion (as were all laboratory-endpoint analyses). In addition, the proliferative activity of the colonic epithelium was examined by determining the proliferating cell nuclear antigen labeling index, and the apoptotic activity by terminal deoxynucleotidyl transferase dUTP nick end labeling. At 1 month, significant decrease in the mean number of ACF per person was observed in the metformin group (8.54 ± 6.37 before treatment versus 5.32 ± 4.87 at 1 month; P = 0.009), whereas in the control group the mean number of ACF did not change significantly. The proliferating cell nuclear antigen index was significantly decreased and the apoptotic cell index remained unaltered in normal rectal epithelium in metformin patients. The present study demonstrated that metformin has the potential to suppress colonic epithelial proliferation and rectal ACF formation in humans, suggesting that its promise for the chemoprevention of colorectal cancer.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B53.
Abstract B68: EGCG and theaflavin are direct inhibitors of the oncogenic lipid kinase, sphingosine kinase 1
Authors: Hengst Jeremy A. , Wang XuJun , Desai Dhimant , Amin Shantu , Yun Jong K. 
Published: January 2011

Abstract
Epigallocatechin-3-gallate (EGCG) and theaflavin are polyphenols from green and black tea, respectively, that have been shown to have anti-cancer/anti-inflammatory effects through their antioxidant properties. Recent studies indicate that these tea polyphenols may also target the sphingosine kinase (SphK)/sphingosine-1-phosphate (S1P) signaling pathway. Therefore we examined whether these tea polyphenols can directly inhibit SphK1 catalytic activity. To accomplish this, we performed in vitro SphK activity assays to determine the kinetics properties of EGCG and theaflavin toward SphK1. These analyses indicate that EGCG, and its related tea polyphenols theaflavin, GCG and catechin all directly inhibit SphK1 catalytic activity. Further kinetic analysis indicates that EGCG is a non-competitive inhibitor of SphK1 (Ki = 450-500 nM). These data are the first demonstration of a direct inhibitory effect of tea polyphenols on SphK1 catalytic activity. Importantly, given the oncogenic role of SphK1, they suggest that SphK1 is a target of the anti-cancer/anti-inflammatory actions of the tea polyphenols such as EGCG and theaflavin. They further suggest that inhibiting SphK1 activity, using tea polyphenols, can be an effective chemopreventative strategy and that the structures of these polyphenols could serve as novel molecular scaffolds for the development of SphK inhibitors.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B68.
Abstract B81: Racial differences in serum adiponectin and leptin before and after weight loss
Authors: Azrad Maria , Gower Barbara A. , Hunter Gary R. , Nagy Tim R. 
Published: January 2011

Abstract
Background: In vitro and in vivo data have shown that adiponectin is antiangiogenic and that leptin increases angiogenesis. The divergent roles that these two adipocytokines play in cancer biology may be underlying mechanisms for racial disparities in cancer severity and mortality. The purpose of this study was to determine whether there were differences in serum concentrations of adiponectin and leptin before and after weight loss in healthy premenopausal African-American (AA) and European-American (EA) women.
Methods: Sixty-three African-American (AA) and 58 European-American (EA) premenopausal women were weight-reduced from body mass index (BMI) 27-30 kg/m2 to BMI≤24 kg/m2. Body composition measurements and fasting blood samples were collected before and after weight loss. Repeated-measures mixed models were used to assess the change in adiponectin and leptin from baseline to the weight-reduced state and whether there were racial differences after adjusting for covariates.
Results: Following weight loss leptin significantly decreased and adiponectin significantly increased similarly in both racial groups. Mix-model analyses indicated that adiponectin differed with race after adjusting for age, time, intra-abdominal fat, interleukin-6, limb fat and trunk fat (p=0.039). Adjusted least squared means (mean 95% confidence interval) showed that AA women had lower adiponectin relative to EA women at baseline [7.64 (6.8, 8.59) µg/ml vs 9.59 (8.61, 10.7) µg/ml, p=0.011] and in the weight-reduced state [9.84 (8.77, 11.0) µg/ml vs 11.5 (10.3, 12.8) µg/ml, p=0.075]. Mixed-model analyses indicated that leptin differed with race after adjusting for age, time, total fat mass, estradiol, testosterone and insulin (p&lt;.0001). According to the adjusted least squared means, AA women had higher leptin relative to EA women at baseline [25.1 (22.8, 27.7) ng/dl vs 19.6 (18.0, 21.4) ng/dl, p=0.0003] and in the weight-reduced state [12.1 (10.6, 13.7) ng/dl vs 8.23 (7.32, 9.24), p&lt;.0001].
Conclusions: Weight reduction may reduce the risk for cancer severity and mortality through increased serum adiponectin and reduced leptin in both AA and EA women. However, AA women may have worse outcomes as a result of cancer compared to EA women due to differences in the serum concentrations of these adipocyte derived factors that influence tumor angiogenesis.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B81.