bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2842: Gene expression and genetic variation of the matrix metalloproteinase family: evidence for association with endometrial cancer risk and prognosis
Authors: O'Mara Tracy A. , Gregory Katie , Ferguson Kaltin , Morrison Jonathan , Clements Judith A. , Montgomery Grant , Webb Penelope M. ,   ANECS & SEARCH, Dunning Alison M. , Easton Douglas F. , Spurdle Amanda B. 
Published: February 2011

Abstract
Proteases such as the matrix metalloproteinase (MMP) family of proteases have emerged as being important to cancer aetiology and progression. Differences in gene and protein expression have been reported to be associated with many cancers and increased MMP expression is frequently reported to be associated with poor prognostic features. Although no MMP SNPs have been identified to be associated with cancer in all genome-wide association studies published to date, this is not be surprising given the extremely poor coverage of these gene families (1-38% for individual genes), and the knowledge that virtually all study designs to date have been underpowered to detect the small effect sizes expected for common SNPs. We have embarked on a study to assess the relevance of MMP expression and their SNPs in predisposition and prognosis of endometrial cancer, a largely hormonally driven cancer. An extensive literature review revealed that 62/69 studies reported overexpression of MMPs to be associated with poor prognostic features (grade, stage or survival) of hormone-related cancers, including endometrial cancer. Analysis of endometrial tumour MMP gene expression data from 18 different publications was undertaken to identify differentially expressed MMPs (&gt;2-fold) associated with tumour predisposition and/or prognosis, based preferably on raw expression data but otherwise on reported gene lists. Although coverage of the MMP gene family was incomplete for the different expression platforms, this exercise prioritized 14 MMPs for further study in relation to risk and/or prognosis of endometrial cancer. We then mined the stage 1 results for the genome-wide association study we are undertaking to identify novel genetic variants associated with endometrial cancer risk, which involves comparison of 1285 Australian and British endometrial cancer cases of endometrioid subtype reporting Caucasian ethnicity scanned with the Illumina 610K BeadChip, and existing genome-wide scan control data available from the Wellcome Trust Case Control Consortium. A SNP falling in a prioritized MMP with only 19% coverage was found to be significant at P=0.002 (trend test). This SNP has been selected for confirmation in replication sample sets from 9 studies for association with endometrial cancer predisposition, and will be analyzed with SNPs from other prioritized MMP genes for association with prognostic indicators such as grade.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2842.
Abstract 2845: Candidate genes related to CagA signal transduction pathway and risk of gastric cancer: A nested case-control study
Authors: Yang Jae Jeong , Cho Lisa Y. , Ko Kwang-Pil , Park Boyoung , Shin Aesun , Gwack Jin , Chang Soung-Hoon , Shin Hai-Rim , Kang Daehee , Yoo Keun-Young , Park Sue K. 
Published: February 2011

Abstract
Objectives: Cytotoxin-associated antigen (CagA) produced by Helicobacter pylori (H. pylori) plays a role in gastric carcinogenesis, but the role of genes coding proteins in the CagA pathway remains unclear. This genetic association study aimed to evaluate which genes involved in CagA signal transduction pathway are associated with gastric cancer development.
Methods: By literature reviews, we selected 34 candidate genes involved in CagA signal transduction pathway and screened a total of 580 SNPs within +/- 5kbp of target gene location. Within the Korean Multi-Center Cancer Cohort (KMCC), a 100 incident gastric cancer cases were matched to a cancer-free subject by age, sex, residential area and enrollment. Both raw and permutated p-values by 10,000 permutation tests were computed using the LRT with 1 degree of freedom in the trend model. Gastric cancer risk was estimated as odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age, smoking status, H. pylori infection, and CagA IgG antibody positivity in each genetic model.
Results: Twenty five SNPs in 8 genes, Erk, Dock180, C3G, Rap1, Src, CrkL, Mek and Crk, were significantly associated with gastric cancer risk in the single SNP analysis (p&lt;0.05). Specifically, Erk rs5999749 and Dock180 rs9418677 remained significant after correction of multiple comparisons. Except for Dock180 rs9418677 and Rap1 rs17028287, most SNPs downstream CagA/Crk signaling (Dock180, C3G, Rap1 and Mek) were significantly associated with a reduced risk for gastric cancer.
Conclusions: Our findings indicate that genes involved in the CagA signal transduction pathway can be major susceptible factors related to tyrosine kinase action, especially interaction with Crk. Further replication studies with wider genomic coverage and a greater number of subjects are still needed.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2845.
Abstract 2847: TagSNPs in the podocalyxin (PODXL) gene are associated with prostate cancer risk
Authors: Bock Cathryn H. , Schwartz Ann G. , Levin Albert M. , Ruterbusch Julie J. , Kittles Rick A. , Rybicki Benjamin A. 
Published: February 2011

Abstract
Previous gene mapping efforts, including a recent admixture mapping study, concluded that there is likely at least one prostate cancer susceptibility locus on 7q32. Podocalyxin (PODXL) is the strongest candidate gene in this region, particularly for risk of aggressive disease (Casey et al. Human Molecular Genetics, 5: 735-741, 2006). Therefore, we examined 34 tagSNPs in the PODXL gene in relation to prostate cancer risk and aggressiveness in a sample of unrelated cases (n=626) and controls (n=239) from metropolitan Detroit, MI. Men were recruited from Henry Ford Health System; cases were diagnosed with prostate cancer between 2001 and 2004, and controls were frequency matched to cases on 5 year age groups and race. Logistic regression models were adjusted for family history of prostate cancer, race, age, and ancestry where appropriate. Carrying at least one copy of the variant A allele in SNP rs3212299 was associated with a decrease in prostate cancer risk (OR=0.60, 95% CI: 0.41, 0.90). Having at least on copy of the C allele in SNP rs11773254 was associated with a 70% increased risk of prostate cancer (OR = 1.70, 95% CI: 1.13, 2.58). The G allele of rs1733874 was marginally protective in the entire sample (OR=0.74, 95% CI: 0.49, 1.02). These risk estimates did not appreciably vary after stratifying by race [African American (AA), European American (EA)], age (&lt; age 62, &gt; age 62), or prostate cancer aggressiveness (Gleason sum 3+4 or lower, Gleason sum 4+3 or higher). In addition, a protective effect of the C allele in SNP rs3800684 was observed in AA men (OR=0.56, 95% CI: 0.35, 0.90) but not in EA men (OR=1.38, 95% CI: 0.92, 2.09), and there was a statistically significant interaction between race and genotype at this marker (p=0.005). After stratifying by median age, the A allele of SNP rs10224884 was marginally associated with increased prostate cancer risk in the older age group (OR=1.44, 95% CI : 0.92, 2.27), but not the younger age group (OR=0.69, 95% CI: 0.42, 1.13), and the interaction between age group and genotype was statistically significant (0.03). Overall, we conclude that SNPs in the PODXL gene are associated with prostate cancer risk, but not prostate cancer aggressiveness, and that some of these variants may have race- and age-specific effects.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2847.
Abstract 2862: Therapeutic intervention of preclinical symptoms in a NF1 mouse model
Authors: Zheng Huarui , Chang Lou , Zhu Yuan 
Published: February 2011

Abstract
We previously generated a mouse model by using Schwann cell lineage-specific ablation of Nf1, which recapitulates human plexiform neurofibroma with high penetrance throughout the peripheral nerves including the sciatic nerves. Although it takes more than 12 months for these mutant mice to develop frank neurofibromas, we have identified pre-neoplastic phenotypes in mutant sciatic nerves at as early as 3 months of age. In sciatic nerves of mutant mice at post natal day 90 (P90), we identified a subset of non-myelinating Schwann cells (nmSCs) as early stage neurofibroma cells, which exhibit a spectrum of abnormalities. These abnormal nmSCs are either dissociated or dissociating from axons, often accompanied by axonal degeneration and mast cell infiltration. Proliferation of these abnormal nmSCs leads to significantly increased cellularity in mutant nerves. Altered mTOR (mammalian target of rapamycin) activity was also observed at this stage.
Based upon these observations, we propose that deregulated mTOR activity may be underlying molecular mechanism of neurofibroma initiation. To test this hypothesis, we are using rapamycin, a mTOR inhibitor, to treat mice starting from P30 until P90, at which time point they are analyzed. The extent of pre-neoplastic phenotypes at P90 can serve as assays for the efficacy of this treatment.
Our preliminary data show that rapamycin treatment may have effect in alleviating pre-neoplastic phenotypes in some mutant mice, evidenced by the absence of dissociated SCs and unassociated SCs, as well as decreased cellularity in the sciatic nerves of those mice. However, further experiments need to be done to confirm these results.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2862.
Abstract 2863: Long term COX-2 inhibition in the small intestine of C57BL/6J Apc+/+ mice altered TGFβ signaling
Authors: Carothers Adelaide M. , Davids Jennifer S. , Damas Beatrice C. , Bertagnolli Monica M. 
Published: February 2011

Abstract
Previously, we showed that short term (3 weeks) treatment of ApcMin/+ mice with the COX-2 inhibitor, celecoxib, reduced intestinal tumorigenesis, but long term drug treatment (5 months) increased intestinal tumors, stromal myofibroblasts, fibrosis, and expression of COX-2, PGE2, and TGFβ1, 2, 3 (TGFβ). Because COX-2 inhibitors are often used in patients with chronic inflammation, we examined the effects of celecoxib in Apc+/+ mice by immunoblotting and immunohistochemistry. Short term treatment induced canonical TGFβ signaling with increased expression of TGFβ and its receptor, effector, and targeted product (TβRII, Smad4, and PAI-1). In parallel, integrin signaling was suppressed with reduced expression of β1 integrin, active Focal Adhesion Kinase (FAK-p-Y397), Integrin-Linked Kinase, and the RhoA inhibitor, p190RhoGAP. Enterocyte differentiation but not proliferation was reduced relative to controls. Although COX-2 and TGFβ expression remained higher than basal levels, long term treatment reversed the effects on canonical TGFβ and integrin signaling, resulting in increased proliferation and differentiation. These results suggest that in the normal intestine PGE2 plays a role in modulating mechanical changes in cell-matrix adhesion via crosstalk between TGFβ and integrins. The mechanism for this could depend on the ability of PGE2 to increase [cAMPi] and Protein Kinase A activity. Chronic exposure to celecoxib may promote tumorigenesis by enhancing enterocyte positive growth regulation via integrins, while suppressing its negative regulation via TGFβ.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2863.
Abstract 2864: Effect of resveratrol (RVT) on prior-, concurrent-, and post- benzo(a)pyrene (BaP) exposure in colon tumor development of ApcMin mice
Authors: Huderson Ashley C. , Niaz Mohammad S. , Washington Mary K. , Ramesh Aramandla 
Published: February 2011

Abstract
Colon cancer is one of the important cancers in terms of morbidity and mortality. In U.S. alone, around 60,000 lives/year are lost to colon cancer. Diet and environment are implicated in the development of sporadic colon cancers. Our laboratory has already reported the development of colon tumors in ApcMin mice orally exposed to BaP. In this study we investigated the timing of RVT administration on BaP-induced colon carcinogenesis in ApcMin mice. The mice were grouped under 5 treatment categories. For Group I, only BaP was administered (in peanut oil) at a dose of 100 μg/kg via oral gavage over a 60 day period. For Group II, RVT (in 10% ethanol + 90% deionized water) was co-administered with BaP at a dose of 45 μg/kg. For Group III, RVT was administered for 1 week prior to BaP dosing. For Group IV, RVT was administered for 1 week post BaP dosing. The Vth group received RVT only. Jejunum, colon and liver samples were collected at the end of exposure; adenomas in the jejunum and colon were counted and subjected to histopathology. RVT significantly inhibited the development of adenomas in the jejunum and colon by 45 and 40 % (P &lt; 0.001) respectively in Group II, compared to Group III (0 and 5%) and Group IV (0 and 2%). Though no significant difference was noted in the size of adenomas in jejunum of BaP + RVT-treated mice, compared to that of BaP-treated mice; the colon samples showed a different trend. RVT significantly reduced the size of colon adenomas in mice that received BaP & RVT simultaneously compared to mice that received BaP alone, RVT before BaP, and RVT post BaP. Though dysplasia of colon was observed in BaP-treated mice, it was of limited occurrence in RVT-treated mice. Our findings thus far reveal that the prevention colon tumorigenesis by RVT is effective only when given together with BaP, compared to prior and post BaP-exposure. Studies are in progress to see the underlying mechanisms for the differential preventive effects of RVT (funded by NIH grants 5T32 HL007735-14, RO3CA130112-01 and S11ES01415).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2864.
Abstract 2865: Protection from chemotherapy-induced alopecia by cytotech lbs API 31543 in a multichemotherapy course model of chloroleukemia
Authors: Narain Niven R. , Mauro Lucia M. , Yunis Adel , McCook John P. , Jimenez Joaquin J. 
Published: February 2011

Abstract
Alopecia remains the one side-effect of chemotherapy for which there is no therapeutic intervention. We have recently developed a multi-course chemotherapy rat model of transplantable chloroleukemia (MIAC51) in which to study Chemotherapy-[[Unsupported Character - Codename &shy;]]Induced Alopecia (CIA). This model provides the opportunity to study CIA and the cancer cells throughout multiple courses of chemotherapy. In the present study, we investigated the effect of calcitriol in a proprietary delivery system, Cytotech Labs API 31543 to protect from CIA using the following chemotherapy regimens: cyclophosphamide; cyclophosphamide and doxorubicin; cyclophosphamide, doxorubicin and cytarabine; cyclophosphamide, paclitaxel and etoposide; doxorubicin, paclitaxel and etoposide. Animals were injected intraperitoneally with 1×105 MIAC51 on day 5. Thereafter, 0.2µg of API 31543 or vehicle control was applied topically over the head area daily starting on day 6 for 6 consecutive days for the first course. Rats were isolated for 6 hours. Subsequently, the treated area was cleaned with soap and water and rats were returned to their litters. For the first cycle, chemotherapy regimens were administered on day 13, intraperitoneally in a total volume of 0.1 mL. Animals positive for leukemic cells in smears were euthanized on day 23. On day 31, a second anagen cycle was induced by clipping the hair in the neck area on leukemia survivors. Animals were then treated with 0.2 µg API 31543 on day 40 for 6 days in the shaven area. Chemotherapy regimens were then administered on day 46. In both cycles, alopecia was recorded 10 days after the last dose of chemotherapy. Neonatal rats treated with 0.2µg of API 31543 in the head area exhibited localized protection. Similarly, in the adult rats 0.2µg of API 31543 exerted a localized protective effect at the site of application. In both groups, rats that received chemotherapy alone became totally alopecic. Pretreatment with API 31543 protected the hair follicles against chemotherapy without having an effect on the efficacy of chemotherapy treatment of leukemia. In summary, the results herein set a solid foundation for clinical investigation of API 31543.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2865.
Abstract 2866: Western-type diet accelerates intestinal tumorigenesis in APCmin mice
Authors: Niku Mikael , Sarantaus Laura , Päivärinta Essi , Heiman-Lindh Anu , Nyström Minna , Mutanen Marja 
Published: February 2011

Abstract
Lifestyle factors contribute to incidence of colorectal cancer (CRC). Western-type diet (WD) containing considerable amounts of saturated fat, sugar and red meat but little dietary fibre, vitamins, minerals and plant-derived nutrients is associated with elevated CRC risk. We have recently started to investigate the mechanisms explaining these observations using APCmin mice, a model of human familial adenomatous polyposis.
METHODS: 12 APCmin mice were fed a WD (modified AIN-93G with high fat, low vitamin D and folate) for 10 weeks, starting at the age of 5 weeks. 14 control APCmin mice were fed the unmodified AIN-93G diet. The mice were sacrificed at the age of 15 weeks. The intestines were removed and opened. Number and size of adenomas were measured by blinded observers using a stereomicroscope. Tissue samples were collected from various locations of the small intestines, where the adenomas occur in this model. Epithelial renewal dynamics was analyzed in histologically normal areas of the mucosa. Paraffin tissue sections were immunostained using markers of cycling cells (Ki67 antigen), actually mitotic cells (phospho-histone H3) and apoptotic cells (cleaved caspase 3). The stained sections were analyzed using the ImageJ analysis software.
RESULTS: The average number of adenomas in the small intestine was significantly higher in the WD mice (p=0.002). The average size of adenomas was not statistically different between the two diet groups. The heights of the actively cycling cell compartment (measured from the crypt base to the last Ki67-antigen positive cells in the villi) and the numbers of mitotic cells (measured as phospho-histone H3 positive cell count per area of mucosal base cross-section) were similar in both diet groups. The number of apoptotic cells (measured as cleaved caspase 3 positive bodies per area of intestinal tissue section) was also similar between the groups.
CONCLUSIONS: In this model, Western-type diet accelerates tumor initiation but does not affect progression. The accelerated tumor initiation is not caused by changes in the general renewal dynamics of the epithelium, as the proliferation and apoptosis rates are not significantly affected. The results suggest that the epithelial stem or progenitor cells are more specifically targeted. To dissect the underlying mechanisms, we are currently analyzing the inflammatory and metabolic status of the intestinal mucosa.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2866.
Abstract 2867: Anthocyanin and carotenoid rich fresh vs. processed colored potatoes suppress human colon cancer cell proliferation and elevate apoptosis via suppression of inducible nitric oxide synthase (iNOS) pathway
Authors: Vanamala Jairam , Reddivari Lavanya 
Published: February 2011

Abstract
The potato (Solanum tuberosum L.) is the world's 3rd largest food crop and the leading vegetable crop in the United States, with per capita consumption of about 126 lbs annually. Specialty/colored potatoes rich in anti-proliferative, pro-apoptotic and anti-inflammatory anthocyanins and/or carotenoids can be an attractive “delivery system” for these bioactive compounds in humans. Unlike other carotenoid- or anthocyanin-rich sources such as blueberries or pears, potatoes are stored and processed before consumption (80 lbs industrially processed potatoes/capita/year in the US). We previously demonstrated that colored potato extracts suppress cancer cell proliferation and induce apoptosis via both caspase-dependent and independent pathways; however, the effect of processing methods on these functional compounds is unknown. We hypothesized that potato bioactive compounds retain their chemoprotective properties against human colon cancer cells even after processing (chipping and baking) compared to the DMSO solvent controls. To test this hypothesis the anti-proliferative (WST assay), pro-apoptotic (cell death detection ELISA) and anti-inflammatory (iNOS pathway; immunoblots) properties of Atlantic (white; phenolics), Yukon Gold (yellow; carotenoids) and Purple Majesty (purple; anthocyanins) potato extracts before and after processing were determined using HCT116 p53+/+ and p53−/− human colon cancer cells. Potato extracts from processed potatoes (5 −15μg/ml) suppressed both p53+/+ and p53−/− human colon cancer cell proliferation and elevated apoptosis compared to the DMSO control after 24 hr incubation period. Similar results were observed after 48 and 72 hr of incubation. However, processing suppressed (p &lt; 0.05) anti-proliferative and pro-apoptotic properties of potato bioactive compounds compared to the fresh potato extracts. Purple potato extracts were more potent in suppressing (p &lt; 0.05) colon cancer cell proliferation and elevating apoptosis compared to the white and yellow colored potatoes. Potato extracts suppressed inducible nitric oxide synthase (iNOS) levels, a critical pro-inflammatory enzyme. Our results suggest that it is important to consider the processing effects on bioactive compounds in foods while conducting nutritional and epidemiological studies. We plan to determine whether colored potatoes suppress chemically-induced colon carcinogenesis in rodent models via suppression of inflammation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2867.