bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract LB-440: Global DNA hypomethylation is independently associated with clinical diagnosis of gastric cancer, inflammation severity, and metaplasia
Authors: Guerrero-Preston Rafael E. , Jahuira-Arias Martha , Gilman Robert , Soudry Ethan , Perez Jimena , Mancinelli Andrea , Unger Helen , Ili-Gangas Carmen , Brebi-Mieville Priscilla , Sidransky David
Published: July 2012

Background: DNA hypomethylation of repetitive elements has been shown to play a significant role in gastric carcinogenesis. However, Biomarker Development Trials on gastric mucosa that quantify global 5-methyl cytosine (5mC) content across repetitive and non-repetitive regions of the genome are lacking.

Methods: We utilized an ELISA-based approach to quantify the global DNA Methylation Index (GMI) in a gastric cancer case-control study. Quantification of global DNA methylation was obtained by differential methylation calculation of 5mC relative to global cytidine (5mC +C) in samples compared to a hypermethylated human genomic DNA control.

Results: A cohort of 209 patients, a slight majority of which were women (52%) with a mean age of 63 years, were diagnosed by endoscopy at three outpatient clinics in Perú. Utilizing the updated Sydney, 50 adenocarcinoma cases and 159 non-tumor controls were subsequently confirmed by pathologists. The GMI mean was significantly lower (p-value < 0.0001) for clinically defined cases, mean = 3.6 (95% CI, 3.03, 4.07) compared to controls, mean = 6.2 (95% CI, 5.37,7.03). The GMI mean was also significantly lower (p-value = 0.0001) for cases defined by pathologists, mean = 3.7 (95% CI, 2.99, 4.39) compared to controls, mean = 5.6 (95% CI, 4.94, 6.34). In stratified analyses, we found the GMI mean to decrease as the severity of inflammation increased. The GMI mean was significantly lower (p-value =0.02) for moderate inflammation, mean = 4.7 (95% CI, 3.66, 5.72) compared to mild inflammation, mean = 6.4 (95% CI, 5.34,7.5). The GMI was also non-significantly reduced in patients with intestinal metaplasia, mean =4.81 (95% CI, 3.5,6.10) when compared to patients without metaplasia, mean = 5.96 (95% CI 5.09, 6.83).

Discussion: We have shown significant differential global DNA hypomethylation in the progression of gastric lesions through the multistep carcinogenesis stages leading to gastric cancer in a case-control study. In patients diagnosed as controls, global hypomethylation was shown to decrease as the levels of inflammation increased. Patients with intestinal metaplasia also had a lower GMI than those without metaplasia. GMI may be a potentially useful biomarker for clinical detection, inflammation severity, and disease progression in gastric cancer. These results should be replicated in a larger study.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-440. doi:10.1158/1538-7445.AM2011-LB-440
Abstract LB-444: Transforming growth factor beta polymorphisms and breast cancer survival among Chinese women
Authors: Beeghly-Fadiel Alicia C. , Zheng Wei , Lu Wei , Cai Hui , Long Jirong , Gao Yu-Tang , Delahanty Ryan J. , Cai Qiuyin , Shu Xiao-Ou
Published: July 2012

Aberrant transforming growth factor-beta (TGFB) signaling contributes to tumor progression. To clarify the role of TGFB pathway variants and breast cancer survival, we conducted a two stage study among 4,535 breast cancer patients recruited in two studies conducted in Shanghai, China. In Stage I, 111 variants in TGFB, TGFBR1, and TGFBR2 were evaluated for associations with disease-free (DFS) and overall survival (OS) among 2,923 participants with a median of 5.5 years of follow-up time after their cancer diagnosis. Nominally significant associations with either DFS or OS were found for 31 variants, which after considering linkage disequilibrium, were found to represent 13 independent loci. Stage II genotyping was conducted among 1,612 additional participants with a median follow-up time of 5.1 years; data was available for 11 loci. Genetic variants in 6 loci were not associated with breast cancer outcomes in Stage II. Variants in 4 loci showed associations in Stage II that were generally consistent, but did not reach statistical significance. One variant was significantly associated with overall breast cancer survival in both study stages, and overall and disease free survival in analyses of the two study stage samples combined. Specifically, women with two copies of the rare variant of TGFBR1 rs3773651 (GG) had increased hazards of recurrence or breast cancer specific mortality (HR: 2.05, 95% CI: 1.28–3.27) and overall mortality (HR: 2.44, 95% CI: 1.50–3.95) compared to women with one or more common alleles (AG, AA) in age adjusted analyses. Additional adjustment for disease stage, ER, PR, or treatment including surgery, chemotherapy, radiotherapy, and tamoxifen did not attenuate these effects. Further, the statistical significance of these associations was retained after consideration was made for multiple comparisons (DFS p-value 0.0027; OS p-value 0.0003). rs3773651 is located in intron six of TGFBR2, a TGFB ligand specific receptor critical for transduction of TGFB signaling. Our data support a role for individual variation in TGFBR2 in breast cancer survival outcomes; additional investigation is warranted.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-444. doi:10.1158/1538-7445.AM2011-LB-444
Abstract LB-445: Reappraisal of breast cancer incidence in the United States
Authors: Anderson William F. , Katki Hormuzd , Rosenberg Philip S.
Published: July 2012

Breast cancer incidence in the United States rose until 1999 then fell. This decline was most apparent among older women with easier-to-treat estrogen receptor (ER) positive tumors; reported incidence of more aggressive ER negative cancers was stable. However, these analyses did not account for missing ER data, which can reduce statistical power and more importantly bias the observed trends. We, therefore, developed an imputation method to correct for missing ER using a national sample of 379,323 breast cancers diagnosed from 1992 through 2007. After correction, current incidence of ER positive tumors was surprisingly similar to pre-1999 incidence, whereas ER negative cancers fell steadily by 1.8% per year. We show for the first time that the recent national decline in breast cancer overall reflects an unexpected drop in ER negative rates more than any changes in ER positive rates. These refined results challenge past interpretations and have the potential to better gauge breast cancer trends.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-445. doi:10.1158/1538-7445.AM2011-LB-445
Abstract LB-447: Non-steroidal anti-inflammatory drugs and brain cancer
Authors: Daugherty Sarah E. , Moore Steve , Pfeiffer Ruth , Park Yikyung , Rajaraman Preetha
Published: July 2012

Several case-control studies have suggested that non-steroidal anti-inflammatory drugs reduce risk for glioblastoma multiforme, a very aggressive form of brain cancer. Limited prospective investigations, on the other hand, have not observed an association between regular use of aspirin and brain cancer; however, these studies generally had small numbers of brain cancer, and did not investigate the association with NSAIDs by histologic subtype. We investigated the association between use of NSAIDs and glioma, and more specifically glioblastoma multiforme, in a large prospective study, the NIH-AARP Diet and Health Study. The frequency of aspirin and non-aspirin NSAID use one year prior to baseline was ascertained using a self-administered questionnaire. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models with age as the underlying time metric adjusted for sex, race, and history of heart disease. The analysis included 302,767 individuals, with 341 incident glioma and 257 glioblastoma multiforme cases. Preliminary results indicated no association between regular use (more than 2 times per week) of aspirin and risk of glioma (HR=1.16; 95% CI:0.87–1.56) or glioblastoma multiforme (HR=1.17; 95% CI:0.83–1.65) compared to never users. Null associations were also observed among regular non-aspirin NSAIDs users and risk of glioma (HR=0.90; 95% CI:0.65–1.25) and glioblastoma multiforme (HR=0.83; 95% CI:0.56–1.22) compared to never users. Our findings from this large prospective study do not support an inverse association between NSAIDs and risk of glioma or glioblastoma multiforme.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-447. doi:10.1158/1538-7445.AM2011-LB-447
Abstract LB-450: Gene expression of colonic submucosa differs between the inflammatory colitides. A possible reason for differences in IBD-associated CRC incidences
Authors: Schäffer Michael W. , Roy Tanusri Ghosh , Smith Joan C. , Wise Paul E. , El-Rifai Wael M. , Washington Mary K. , Schwartz David A. , Muldoon Roberta L. , Herline Alan J. , Moses Harold L. , Adunyah Samuel E. , M'Koma Amosy E.
Published: July 2012

Purpose: Differentiating ulcerative colitis (UC) and Crohn's colitis (CC) may be inaccurate in up to 30% of inflammatory bowel disease (IBD) cases due to overlapping features of these colitides. IBD-associated colorectal cancer (CRC) is frequently diagnosed in an advanced stage. Mass-spectrometric (MS) proteomic patterns found in colonic submucosa have been shown to discriminate UC and CC. To verify this, we aimed to conduct pilot gene expression analyses via microarray assessment of colonic submucosa. The significances of these genes to CRC initiation is as yet not been elucidated.

Methods: Laser capture microdissection of colonic submucosa from UC (n=8), CC (n=8), and normal (NL, n=8) samples was performed. The submucosal mRNA was extracted using the PicoPure(TM) RNA Isolation Kit. Comprehensive gene expression analysis of the pooled mRNA from each group was then performed using the Affymetrix GeneChip® Gene 1.0 ST Array System. To detect changes for UC, we compared UC to CC and UC to NL; and for CC, we compared CC to UC and CC to NL.

Results: 28,869 genes were represented on the array by 26 probes spread across the full length of each gene. When comparing UC to CC, 138 genes showed at least a 5-fold significant overexpression (p<0.01) with 5 of these genes showing a greater than 30-fold overexpression (Table, all p<0.0001). When comparing CC to UC, 5 different genes were overexpressed at greater than 30-fold change (Table, all p<0.0001). The results of the comparisons of these highly overexpressed genes in UC and CC vs. NL is noted in Table.

Conclusions: Microarray assessments show significantly different gene overexpression in UC and CC colonic submucosa, with a few select genes showing dramatic overexpression. Preliminary results indicate that we have the tools in hand to successfully validate the results from the microarray analysis using TR-qPCR and immunohistochemistry (IHC). These genes may assist in delineation of the previously identified differentiating MS submucosal proteomic peaks, potentially facilitating protein biomarker identification to discriminate the inflammatory colitides. These genes may relate to CRC initiation.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-450. doi:10.1158/1538-7445.AM2011-LB-450
Abstract LB-451: Detection of urinary HE4 as a biomarker for epithelial ovarian cancer
Authors: Li Zhong-Qian , Radwan Rachel , Polkowski Julie , Raju Savitha , Falcone Katherine , Simamora Rebecca , Kettlety Timothy , Moore Richard G. , Barnes Grady
Published: July 2012

Human epididymis protein 4 (HE4) has been shown to be a promising serum biomarker for epithelial ovarian cancer (EOC). Recently, Hellstrom et al. reported the detection of HE4 in urine as a biomarker for ovarian neoplasms (Cancer Lett.2010;296:43–8). We investigated the feasibility of urinary HE4 in detection of EOC in a pilot study. METHODS: This retrospective study measured the HE4 levels in urine samples obtained from an institutional review board-approved sample bank. HE4 was measured with HE4 EIA (Fujirebio Diagnostics, Inc.). Creatinine was measured via colorimetric determination by the Jaffe Reaction and used to normalize the HE4 levels. Clinical diagnosis of the subjects was based on the pathological diagnosis. Single-point urine samples were analyzed from 232 subjects; 72 with EOC or low malignant potential tumors and 160 with benign disease. RESULTS: The medians of HE4 levels in subjects with EOC and with benign disease were 29833 pmol/L (95% Confidence Interval (CI): 21185–54728) and 8515 pmol/L (95% CI: 7077–9314) respectively. The medians of HE4/Creatinine ratios in subjects with EOC and with benign disease were 420 (95% CI: 269–491) and 75 (95% CI: 68–83), respectively. Both the medians of HE4 levels and HE4/Creatinine ratios in EOC subjects were significantly higher than that in subjects with benign disease (P<0.0001 in Median test). Receiver operator characteristic (ROC) analysis showed that areas under the curve (AUC) were 0.87 for HE4/Creatinine ratio (95% CI = 0.81–0.92) and 0.83 for HE4 level (95% CI = 0.76–0.89). There was no significant difference between the AUC for HE4 level and HE4/Creatinine ratio (P>0.05). Using the shoulder point of each ROC curve as the cut-off, the cut-off values were 152.5 for HE4/Creatinine ratio and 19161 pmol/L for HE4 level respectively. The sensitivity, specificity, positive predictive value and negative predictive value at the set cut-off values were 70.8% (95% CI = 58.9% – 81.0%), 93.1% (95% CI = 88.0% – 96.5%), 82.3% and 87.6% for HE4/Creatinine ratio, and 65.3% (95% CI = 53.1% – 76.1%), 89.4% (95% CI = 83.5% – 93.7%), 73.4% and 85.1% for HE4 level, respectively. Concordance rates versus clinical diagnosis were 86.2% for HE4/creatinine ratio and 81.9% for HE4 level. CONCLUSIONS: This pilot study demonstrated the utility of urinary HE4 level alone or HE4/Creatinine ratio as potential biomarkers for the detection of EOC. The HE4/Creatinine ratio appeared to be better than the HE4 level in correlating with the clinical pathological diagnosis of EOC.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-451. doi:10.1158/1538-7445.AM2011-LB-451
Abstract LB-457: Effect of naproxen and NO-naproxen on intestinal neoplasia in the Apc +/Min-FCCC mouse model
Authors: Chang Wen-Chi L. , Ferrara Christina M. , Cooper Harry S. , Mosier Stacy L. , Kaunga Esther , Grubbs Clinton J. , Lubet Ronald A. , Clapper Margie Lee
Published: July 2012

Recent efforts to improve the vascular and gastrointestinal safety of nonsteroidal anti-inflammatory drugs (NSAIDs) have included the addition of a nitric oxide-donating moiety. The ability of the common NSAID naproxen and nitric oxide (NO)-naproxen to inhibit azoxymethane-induced aberrant crypt foci in the rat colon has been demonstrated. However, the chemopreventive activity of these agents against spontaneous colorectal tumors has not been reported. The goal of the present study was to compare the ability of naproxen and NO-naproxen (low- and high-dose molar equivalents) to inhibit colorectal adenomas in a unique strain of mice (Apc+/Min-FCCC) that spontaneously develops multiple colorectal tumors. Male Apc+/Min-FCCC mice (50 days of age) were randomized (n = 17 per group) to receive control diet or diet supplemented with naproxen (132 or 400 ppm) or NO-naproxen (182 or 550 ppm) for 45 days. Body weights were recorded weekly and did not differ significantly among treatment groups. At sacrifice, small intestinal and colonic tissues were examined grossly and the entire colon was submitted for histopathologic analysis. Low-dose naproxen and low-dose NO-naproxen decreased the multiplicity of gross small intestinal adenomas by 70.3% (mean ± SEM – 9.9 ± 1.45, P = 0.04) and 64.0% (12.0 ± 1.9), respectively, as compared to that of control mice (33.3 ± 14.0). No additional benefit was obtained by administering a higher dose of either agent. Histopathologic analyses revealed that the incidence of colorectal adenomas in mice treated with naproxen (low dose – 70.6%; high dose – 64.7%) was significantly less than that of both control mice (100%) (P = 0.019 and 0.0076, respectively) and mice treated with NO-naproxen (low dose – 88.2% and high dose – 100%). Low-dose naproxen reduced the multiplicity of colorectal adenomas by 41.5% as compared to control (mean ± SEM, 1.8 ± 0.5, 3.1 ± 0.7, respectively), while the efficacy of all other treatments was less. Interestingly, treatment with high-dose naproxen caused a dramatic (89.3%) reduction in the multiplicity of microadenomas as compared to unsupplemented control diet. This study represents the first demonstration that naproxen can inhibit spontaneous colorectal adenomas in a controlled model system. The ability of naproxen to disrupt the formation of colorectal lesions early in the carcinogenesis process (microadenomas) provides strong support for its further development as a regimen for the chemoprevention of colorectal cancer in high-risk individuals. (Supported by NIH N01 CN-43309.)

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-457. doi:10.1158/1538-7445.AM2011-LB-457
Abstract LB-54: Gap Junction Enhancer Increases Efficacy of Cisplatin to Attenuate Mammary Tumor Growth
Authors: Shishido Stephanie N. , Nguyen Thu A.
Published: July 2012

INTRODUCTION: Cisplatin treatment has an overall 19% response rate in animal models with malignant tumors (Knapp et al. 1988). Increasing gap junction activity or enhancing GJIC in tumor cells provides the targets to enhance antineoplastic therapies. A new class of substituted quinolines (PQs) possesses inhibitory activities against breast cancer cells through the enhancement of gap junctional intercellular communication. We examined the effect of combinational treatment of PQ and antineoplastic drugs in an animal model to show an increase in efficacy of antineoplastic drugs via the enhancement of gap junctions.

MATERIALS AND METHODS: Mice were implanted with estradiol-17ß (1.7 mg/pellet) before the injection of 1 × 107 T47D breast cancer cells subcutaneously into the inguinal region of mammary fat pad. Animals were treated intraperitoneally with DMSO (control), Cisplatin (3.5mg/kg), PQ (25mg/kg), or a combining treatment of Cisplatin and PQ.

RESULTS: Cisplatin alone decreased mammary tumor growth by 29% while combinational treatment of Cisplatin and PQ showed a 36% reduction after 7 treatments at every 2 days. Histological results showed a significant increase of gap junction proteins, Cx43 and Cx26, in PQ-treated tissues compared to control or Cisplatin. Furthermore, evidence of highly stained caspase 3 in tumors of combinational treatment (PQ and Cisplatin) was seen compared to Cisplatin alone.

CONCLUSIONS: We have showed for the first time an increase in the efficacy of antineoplastic drugs via the enhancement of gap junctions with PQs, a specific class of gap junction enhancers.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-54. doi:10.1158/1538-7445.AM2011-LB-54
Abstract LB-56: LGR5 is differentially expressed in hepato-gastrointestinal tumors
Authors: Simon Eva , Petke Diana , Böger Christine , Warneke Viktoria , Behrens Michael , Rocken Christoph
Published: July 2012

Background: The orphan G-protein-coupled receptor (GPCR) and Wnt-target protein LGR5 was recently identified as a stem cell marker for cells with intestinal differentiation. In this study we generated a polyclonal anti-LGR5 antibody to investigate protein expression in various hepato-gastrointestinal carcinomas and its correlation with clinico-pathological patient characteristics.

Materials and Methods: Differential expression of LGR5 was studied on transcriptional (real time-polymerase chain reaction) and translational level (immunohistochemistry) in carcinomas and corresponding normal mucosal specimens comprising seven different primary tumor sites, i.e. oesophagus, pancreas, stomach, liver, colon and rectum. The putative clinico-pathological relevance of LGR5-expression in terms of patient survival was studied in tissue micro arrays obtained from a cohort of 488 gastric carcinomas.

Results: We succeeded to establish and characterize a highly specific antibody that recognizes the C-terminal tail of LGR5. LGR5 was differentially expressed on transcriptional and translational level in adenocarcinomas of the oesophagus, pancreas, stomach, colon, rectum, hepatocellular and cholangiocellular carcinoma of the liver compared with the adjacent non-neoplastic tissue. However, in gastric cancer tissue microarrays the expression of LGR5 had no impact on patient survival. Nevertheless, expression of LGR5 by endothelial cells of tumor vessels correlated significantly with the tumor type and tumor grade.

Conclusion: Our results substantiate the significance of LGR5 on the biology of hepato-gastrointestinal carcinomas and provide evidence for its function as potential stem cell marker and candidate therapeutic target in the stomach. With our anti-LGR5 antibody we now have a useful tool for detection and further analyzes of LGR5 biological function.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-56. doi:10.1158/1538-7445.AM2011-LB-56
Abstract LB-57: Multiplexed detection of phospho-ERK as a marker of H-Ras signaling, EGFR and cancer stem cell marker expression in breast cancer cells recovered from human blood
Authors: Navaraj Arunasalam , Dicker David T. , Dolloff Nathan , El-Deiry Wafik S.
Published: July 2012

Breast cancer is the most frequent malignancy among women, causing 373,000 deaths per year worldwide. Recent studies indicate that breast cancer is initiated by breast cancer stem cells (BCSCs) which express CD44+/high CD24−/low surface markers. Mammospheres are non-adherent spherical cell clusters grown in selective culture conditions. Our experimental results using mammosphere cultures of different metastatic, human breast cancer cells such as MDA-MB-231 and MDA-MB-468, showed drastic enrichment of breast cancer stem-like cells with the phenotype of CD44+/high CD24−/low in flow cytometry analysis, with specific antibody conjugates. Using the FDA-approved Veridex CellSearch System, we successfully recovered Epcam+/cytokeratin+/CD45− breast cancer cells from 7.5 ml of human blood to which a known number of MDA-MB-468 or H-Ras transformed MCF10A cells had been added. When these recovered breast cancer cells were subjected to Q-Dot conjugated p-ERK antibody staining and quantification, signal intensity clearly demonstrated higher levels of nuclear p-ERK in MCF10A-Ras cells whereas immunostaining for surface EGFR expression was much stronger in MDA-MB-468 cells. We are modeling mammosphere-derived breast cancer cells enriched for stem cell markers by orthotopic implantation into mammary fat pads of nude mice, sampling blood from tumor-bearing animals to detect the presence of Circulating Tumor Cells (CTCs) using the Veridex CellSearch System and further for breast cancer specific multiplexed marker analysis. These stem cell marker enriched xenografted human breast tumors are facilitating our understanding of cellular signaling pathways active in CTCs, and also in understanding of the role of cancer stem cells in human breast cancer metastasis.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-57. doi:10.1158/1538-7445.AM2011-LB-57
Abstract LB-60: A Local Consumer Research Panel's Role in the work of the National Institute for Health Research (NIHR) in the U.K
Authors: Ardron David
Published: July 2012

The poster explains how patient advocacy fits into the world of health research, the relationship between research networks, and how research is planned at both the national and local levels in the United Kingdom. It describes the role of a local consumer research panel in helping to enhance research for maximum patient benefit. David Ardon has been a member and chair of a local panel for eight years and of the national consumer research group for seven years. The poster explains where in the research cycle patients and caregivers have been active, demonstrating the logos of local and national research organizations, and in diagrammatic form, showing the kind of activities that a consumer researcher tackles.

The North Trent Cancer Research Network Consumer Research Panel was established in 2001 by the Academic Unit of Supportive Care at the University of Sheffield. North Trent is an area in the North East Midlands of England. The panel works alongside and is a constituent of the National Cancer Research Institute Consumer Liaison Group. The panel, composed of 40 past and current cancer patients and caregivers, is funded by the North Trent Cancer Network and the South Yorkshire CLRN to provide a consumer perspective at strategic meetings within North Trent and for individual research studies within the network. The panel has hosted and led ten conferences aimed at raising awareness of clinical research. The objective of the panel is to improve the quality of communication and information exchange between health care professionals, patients, and caregivers by providing a consumer perspective at all stages of cancer research and clinical trials. The governing body of health research in the U.K. is the National Institute for Health Research, which monitors eight research areas, one of which is cancer. Cancer research is governed and managed by the National Cancer Research Institute (NCRI), and the National Cancer Research Network (NCRN). Health research locally is delivered by a Comprehensive Local Research Network (CLRN). Mr. Ardon's local CLRN is the South Yorkshire CLRN, and this group includes the North Trent Cancer Research Network.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-60. doi:10.1158/1538-7445.AM2011-LB-60
Abstract LB-62: Breast Cancer Research Advocacy
Authors: Blath Lorry , Blath Lorry
Published: July 2012

Lorry Blath works with fellow research advocates who are breast cancer survivors with a passion for learning the science of breast cancer and applying it to a variety of local and national opportunities. Advocates support research by understanding and conveying the patient's point of view to the medical and research community. The St. Louis Research Advocacy Committee is the only such group associated with a Susan G. Komen Affiliate in the country.

At the advocacy monthly meetings members review articles, mentor each other, introduce activities that match their advocacy interests and talents, and invite speakers several times a year to the “Ask the Expert” series. In the last two years the speakers have included: Dr. Graham Colditz, Dr. Ron Bose, Dr. Shiela Stewart, Dr. Will Gillanders, Dr. Craig Allred, and representatives from the Breast Navigation Program.

The committee organizes a workshop to introduce advocacy to potential candidates. This seminar presents volunteer and educational opportunities, basic breast cancer science, and encourages the attendees to set personal goals. Two breast cancer researchers give lectures in their particular area of interest, followed by demonstrations in their labs. After the workshop, the attendees choose their level of involvement: they may serve in official capacities as community representatives on hospital IRBs, DoD grant reviewers, Komen national and community grant reviewers, and asked to collaborate with scientists on their grant submissions. A few aspire to more advanced instruction by representing Susan G. Komen at national research and/or educational conferences and sharing their gained knowledge with the group. In April, 2011, the research advocacy committee will hold its first RA201 workshop. This seminar, to be held at the Washington University Genome Center, will host breast cancer scientists explaining their original research.

The committee's first community-wide event will take place in March at the Missouri History Museum. Based on The Immortal Life of Henrietta Lacks, this book discussion will reach constituencies from a variety of St. Louis neighborhoods. A panel, consisting of a History professor of African American Studies, a clinical trial analyst, and a physician/medical ethicist, will lead the discussion.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-62. doi:10.1158/1538-7445.AM2011-LB-62
Abstract LB-66: Benefits and Barriers to Clinical Engagement with Cancer Consumer Representatives in New Zealand
Authors: Fletcher Stephanie
Published: July 2012

The Central Cancer Network (CCN), established in 2007, is one of four regional cancer networks in New Zealand. These networks were developed to facilitate initiatives contained in the Cancer Control Strategy Action Plan 2005–2010. The Network serves an urban and rural mixed population of approximately one million people.

The purpose of the Network is to take a proactive leadership, facilitation, collaborative and coordinated approach across organizational and service boundaries to ensure all providers of cancer prevention and care in the network area work together with the community to: manage the implementation of the Strategy and Action Plan in order to reduce the incidence and impact of cancer and the inequalities with respect to cancer, as well as to improve the journey of cancer patients and their family/wh ānau through the complex pathway of care, ensuring equitable, high quality, patient centered, evidence-based and multidisciplinary care.

There is an immense amount of research looking at the involvement of consumers in decision-making advisory and working groups. In New Zealand, there are consumer groups successfully working with clinicians in mental health and diabetes service improvement. However, there is limited research into the clinician's role and their influence of the functioning of such groups. Sitzia, Cotterell and Richardson (2006) spoke of the challenge of managing change when both professionals and lay people are involved in determining service change. Their work found that if professionals did not hold a belief that patient involvement would lead to positive service engagement, then the motivation to engage would be lost.

CCN proposes a two phased approach to improving clinical involvement with consumer representatives in cancer service improvement working groups:

1. Training workshops to disseminate the Health Service Co-Design Guide and Toolkit in 2011: The introduction of the Health Service Co-design Toolkit and Guide introduces the tools available to service providers to ensure that they fully utilize consumer experiences to enact service improvement.

2. Research proposal to conduct a qualitative research study in 2012, examining the barriers and benefits clinicians preserve enhance or hinder consumer participation in cancer service improvement groups. The research study will identify perceived barriers and benefits to clinicians engaging with consumer representatives and therefore work towards addressing the issues involved.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-66. doi:10.1158/1538-7445.AM2011-LB-66
Abstract LB-79: The Impact of Biospecimen Quality on Cancer Research and Patient Care
Authors: Newman-McCown Kimberly
Published: July 2012

The National Disease Research Interchange (NDRI) is a non-profit organization funded by The National Institute of Health. The organization was founded in 1980 at the request of researchers studying diabetes who found that obtaining the human pancreas they needed for their studies presented a major challenge to scientific development. NDRI was awarded a $3.6 million grant to participate in a two-year pilot study for the Genotype Tissue Expression (GTEx) initiative, which will afford all researchers an opportunity to have collaborative access to quality human tissue in order to advance cancer research and other disease discoveries.

The availability of high-quality biospecimens is essential to ongoing cancer research. These resources allow researchers to ask questions that can be answered only by testing hundreds or thousands of patient samples. Such an analysis would provide greater insight into how the cancer progresses and uncover potential new targets for interventions to disrupt the malignancy process. High-quality biospecimens are also essential for research aimed at the development of personalized medicine in which treatments and other interventions will be tailored to patients based on their genetic profile and the unique molecular features of their disease. However, the research that will lead to personalized cancer medicine is hampered at present by an inadequate supply of biospecimens that have been collected and stored according to standard protocols.

If an ample supply of high quality biospecimens were made available the following advances may be possible: the identification of specific proteins or other biomarkers associated with various stages or different types of individual cancers which could lead to new screening or diagnostic tests; the grouping of patients, based on biomarkers of the disease and other genetic characteristics to receive the best, most effective and least toxic treatment; and the identification of drug delivery or other agents to cancer cells and to measure responses to treatment. The necessary supply of biospecimens will be available for research only if patients agree to donate tissue when they undergo biopsy, surgery or other medical procedures. There are several ways in which patients, their families and the general public can help support cancer research that uses biospecimens: stay informed, consider donating a biospecimen, and spread the word.

Contact the National Disease Research Interchange (NDRI) 1–800–222–6374 or at http://www.ndriresource.org or visit our booth in the Exhibit Hall[[Unsupported Character –  ]]

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-79. doi:10.1158/1538-7445.AM2011-LB-79
Abstract LB-8: A novel function of Vps34 in regulation of cell proliferation
Authors: Su Hang , Henry Kevin Mc , Xu Teng , Yuan Zhi-Min
Published: July 2012

Many new insights into the biology of class III PI3Kinase have recently been reported. Most of these studies, however, used mainly transformed cells. It is unclear whether class III PI3Kinase works similarly in non-transformed mammalian cells. We explored this by depleting two non-transformed human epithelial cell lines of Vps34, the catalytic subunit of the lipid kinase using shRNA. Interestingly, in a stark contrast to transformed cells where depletion of Vps34 was associated with decreased growth, Vps34 deficiency in non-transformed cells resulted in a marked increase in cell proliferation. The deregulated autophagy function and E-cadherin-dependent cell-cell contacts found in Vps34-depleted cells appeared to be not involved in cell growth regulation as neither silence of Atg7 expression nor inactivation of E-cadherin had any effect on cell proliferation. Reporter luciferase-based ten-pathway screens suggested an altered activity of the MAPK pathway. Indeed, biochemical analysis indicated a sustained ERK activation resulting from the impediment of endosome-mediated EGFR turnover in Vps34 deficient cells. A contribution of the endosomal pathway to Vps34-mediated regulation of cell proliferation was further confirmed by using Rab5 and Rab11 mutants that perturbed early and recycling endosomes, respectively. Importantly, inactivation of Vps34 compromised the cellular barrier against oncogene-mediated transformation, as demonstrated by the increased susceptibility of Vps34 depleted cells to Ras-induced colony formation in vitro and tumor development in mice. Our data collectively uncover a novel role for the class III PI3Kinase-endosomal pathway in regulation of cell proliferation.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-8. doi:10.1158/1538-7445.AM2011-LB-8
Abstract LB-81: SHARE'S Achievements
Authors: Polinsky Deborah
Published: July 2012

SHARE's mission is to create and sustain a supportive community of women affected by breast or ovarian cancer in which survivors provide their experiences to newly-diagnosed women, their families and their friends. SHARE enables participants with the opportunity to receive and exchange information, support, strength, and hope. The organization's work focuses on patient empowerment, personal and community education, and public policy advocacy to bring about an improved quality of life, better heath care, and a cure for these diseases. For nearly thirty-five years SHARE has been providing peer support services and the latest research findings. SHARE is now an international organization which annually helps over 20,000 women and men affected by breast or ovarian cancer. It has helped establish similar affiliate programs around the United States and in Russia, the Ukraine, Bosnia, Poland and Israel.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-81. doi:10.1158/1538-7445.AM2011-LB-81
Abstract LB-92: Isoflurane increases the metastatic potential of renal cell carcinoma cells via the hypoxia inducible factor pathway- an in vitro study
Authors: Benzonana Laura L. , Perry Nicholas J. , Watts Helena R. , Ma Daqing
Published: July 2012

Background: Patients with solid tumours are likely to have to undergo surgery during the course of their disease. Surgery and anaesthesia may influence the tumour's metastatic potential. Isoflurane is known to up-regulate hypoxia inducible factors (HIFs). HIFs are heavily implicated in tumorigenesis and may play an important role in tumour cell proliferation, migration, invasion and angiogenesis (VEGF signaling). Our aim was to investigate the potential impact of isoflurane on tumour cell progression in vitro.

Methods: Human Renal Cell Carcinoma (RCC4) cells were exposed to 2% isoflurane for 2 hours at 37°C. HIF-1α, HIF-2α, p-Akt, and VEGFA protein levels were measured by Western Blotting at different time points (0, 2, 4, 8 and 24 hours) following isoflurane exposure. HIF-1α was also measured by fluorescent immunocytochemistry after cell fixation. Cell proliferation was measured by MTT and trypan blue exclusion assays. Cell migration was measured using an Oris cell migration assay.

Results: Isoflurane up-regulated HIF-1α in a time-dependent manner, with the highest levels being detected at 8 hours post gas exposure (p<0.001). These results were confirmed by immunofluorescence, showing a significant accumulation of HIF-1 α in the nucleus at 8 hours. Isoflurane also up-regulated HIF-2α, maximal levels were detected at 24 hours (p<0.01). Isoflurane activated the PI3K pathway, as indicated by significantly raised levels of p-Akt from 4 to 24 hours, with highest levels at 8 hours (p<0.001). An increase in VEGFA accumulation was seen at 24 hours (p<0.01). MTT assays performed 8 hours following gas exposure demonstrated that isoflurane increased the rate of cell proliferation (p<0.01), as confirmed by immunofluorescence findings at this time point. Cell migration assays showed an increased migration of Isoflurane treated cells 8 hours post exposure (p<0.01), as confirmed by immunofluorescence, where an increased number of cells showing filipodia (cells migrating) was observed.

Conclusion: Isoflurane at clinically relevant concentrations up-regulates HIF-1α and HIF-2α, which may be due to upstream PI3K pathway activation. Isoflurane up-regulates the major pro-angiogenic factor VEGFA and increases the rate of proliferation and migration in RCC4 cells in vitro. These findings may have major clinical implications for patients undergoing cancer surgery under general isoflurane anaesthesia.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-92. doi:10.1158/1538-7445.AM2011-LB-92
Abstract PL03-02: Microenvironment survival signals for disseminated cancer cells
Authors: Massagué Joan
Published: July 2012

To form metastases, circulating cancer cells that egress into a distant parenchyma must be able to survive in the newly invaded microenvironment. Identifying these survival mechanisms may provide therapeutic strategies for the eradication of disseminated disease and the prevention of metastasis. In breast cancer, where relapse develops in an organ-specific manner, we have identified metastasis progression genes that prime cancer cells for extravasation into specific organs, as well as genes that mediate overt metastatic colonization. However, the survival of newly extravasated cells depends on a distinct set of genes and pathways. SRC primes breast cancer cells for survival in the bone marrow by potentiating AKT activation by CXCL12 and IGF1, cytokines that are abundant in the marrow. Recent work revealed how bone metastatic seeds may be preselected in the primary tumor. In the lungs, VCAM1- and tenascin-C support the survival of micrometastatic cancer cells. The mechanisms involve interactions with tumor-infiltrating leukocytes and an extracellular matrix niche. Inhibition of SRC, VCAM1 and tenascin-C suppresses experimental micrometastases and the growth of aggressive lesions.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr PL03-02. doi:10.1158/1538-7445.AM2011-PL03-02
Abstract PL04-03: Targeting the hedgehog pathway in meduloblastoma and basal cell carcinoma
Authors: de Sauvage Frederic J.
Published: July 2012

The hedgehog (Hh) pathway is an ancient signaling cascade that directs patterning in most animals and is crucial for proper development. While Hh signaling is very active during embryogenesis, it remains relatively quiet in adult life. However, aberrant reactivation of the pathway in adult tissues can lead to the development of cancer. Hh pathway activation in tumors such as basal cell carcinoma (BCC) and medulloblastoma is the result of inactivating mutations in PATCHED (PTCH) or activating SMOOTHENED (SMO) mutations. Targeting the Hh pathway with small molecule antagonists therefore provides a new therapeutic opportunity for the treatment of these tumor types. GDC-0449, an oral Hedgehog (Hh) pathway inhibitor, was tested in a first-in-human, first-in-class, phase I study in BCC patients. Strong antitumor activity was observed in patients with locally advanced and metastatic BCC, thereby highlighting the potential benefit of inhibiting aberrant Hh signaling in tumors where the pathway is mutated. While most BCC tumors display Hh pathway activity, only a subset of medulloblastoma tumors are caused by mutations in the Hh pathway. Early evidence of clinical benefit of GDC-0449 in a medulloblastoma patient selected for Hh pathway activity was demonstrated. However, as is the case for most targeted therapies used in cancer, mechanisms of resistance to Hedgehog pathway inhibitors have started to emerge in man and mouse models, highlighting the importance of this pathway for these tumors. Characterization of various resistance mechanisms such as SMO mutations or amplification of downstream pathway components suggests potential for therapeutic strategies for the treatment of HPI resistant tumors.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr PL04-03. doi:10.1158/1538-7445.AM2011-PL04-03
Abstract SY01-04: Tackling breast cancer: from genetic screens to new therapeutic strategies
Authors: Westbrook Thomas F.
Published: July 2012

Breast cancer is a collection of diseases with distinct clinical behaviors and underlying genetic causes. Triple-negative breast cancer (TNBC) is a common subtype of breast cancer that confers a particularly poor prognosis and is refractory to current targeted therapies. Unfortunately, the molecular determinants driving this aggressive malignancy are poorly understood. Using an unbiased genetic screen, we have identified a novel tumor suppressor network that governs proliferation and transformation of TNBCs in vitro and in vivo. We define PTPN12 as a core component in this network and a commonly inactivated tumor suppressor in TNBC. PTPN12 is a potent suppressor of human mammary epithelial cell proliferation and transformation. PTPN12 function is frequently compromised in human TNBCs by inactivating mutations, deletion, or loss of protein expression. Mechanistically, PTPN12 is a tyrosine phosphatase that suppresses cellular transformation by interacting with and inhibiting several oncogenic receptor tyrosine kinases including HER2, EGFR, and PDGFR. Notably, the tumorigenic and metastatic potential of PTPN12-deficient TNBCs is severely impaired by restoring PTPN12 function or by inhibiting kinase targets of PTPN12, suggesting that TNBCs are dependent on the proto-oncogenic tyrosine kinases constrained by PTPN12. Collectively, these data identify PTPN12 as a commonly inactivated tumor suppressor and provide a rationale for combinatorially targeting tyrosine kinases in TNBC and other cancers based on their profile of tyrosine phosphatase activity.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY01-04. doi:10.1158/1538-7445.AM2011-SY01-04