bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3552: Cancer immunoediting: Profile of cytokines in a mammary adenocarcinoma tumor model
Authors: Pagura Lucas , Caceres Juan M. , Cardinale Albertina , Scharovsky Olga G. , Di Masso Ricardo J. , Rico María J. , Rozados Viviana R.
Published: August 2012

Cancer immunoediting is a dynamic process composed of three phases: elimination (EL), equilibrium (EQ), and escape (ES), that encompasses the potential host-protective and tumor-sculpting functions of the immune system throughout tumor development. Inbred mice models provide an interesting tool for identifying genes that control susceptibility to breast cancer. Inbred CBi/L FS mice were artificially selected by body conformation from CBi mice. The M-406 mammary adenocarcinoma appeared spontaneously in CBi female mouse and it is maintained in vivo in mice of the same line. When CBi/L FS mice are s.c. challenged with M-406 they show the three phases: 51.6% in ES, 18.5% in EQ en 29.8% in EL. The aim of this study was to evaluate in CBi/L FS mice in the three phases of M-406 tumor growth: 1) the profile of cytokines Th1(IL-2; INF-γ); Th2(IL-4; IL-10) in serum and 2) the effect of conditioned media (CM) from CBi/L FS mononuclear cells on tumor cells proliferation. The serum and CM cytokines were evaluated by ELISA. CMs were obtained after 24h incubation of mononuclear cells from CBi/L FS seeded at 4x105 cells/well, in RPMI + 10% BFS. Tumor cells (5x104 cells/well) were incubated 24h with different CMs and proliferation evaluated (WST-1). In serum we observed the presence of high levels of INF-γ in the ES condition, compared with EQ and EL (p<0.0001). Also, we found that IL-10 was increased in EL (p<0.049), and IL-4 presented high levels in ES followed by EQ and then EL (p<0.001). On the other hand, IL-2 did not show significant variations between conditions. The percentage of proliferation of M-406 cells was significantly higher with CM prepared from naive mice than with RPMI control medium (p=0.0048). No significant differences were found in proliferation between control medium and CM prepared from EL or ES mononuclear cells. Detectable levels of IL-4 and IL-10 were found in CMs. Interestingly, CM IL-10 level correlated negatively (p=0.0016, r=−0.8252) with M-406 proliferation. In conclusion we observed that while IL-4 concentration varied as expected in the three tumor phases, IL-10 and IFN-γ did the opposite. Furthermore, both in vivo and in vitro experiments would indicate that IL-10 might act as an inhibitor of tumor growth.These results are supported by new findings that endow immune inhibitory and stimulatory functions to IFN- γ and IL-10, respectively.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3552. doi:1538-7445.AM2012-3552
Abstract 3554: The histone deacetylase inhibitor LBH589 augments anti-tumor immunity through direct effects on tumor and immune cells leading to impaired tumor progression in vivo
Authors: Woods David M. , Woan Karrune V. , Wang Hongwei , Cheng Fengdong , Wang Zi , Vazquez Lianet , Perez Patricio , Lienlaf Maritza , Rock-Klotz Jennifer , Sahakian Eva , Powers John , Deng Susan , Oscar Merino , Atadja Peter , Seto Ed , Pinilla-Ibarz Javier , Weber Jeffrey S. , Sotomayor Eduardo M. , Villagra Alejandro
Published: August 2012

Overcoming immune tolerance is critical for the development of effective immunotherapy against cancer. Tumor cells induce tolerance through a variety of modalities including the secretion of IL-10 and TGF-β, the expression of inhibitory ligands, and the generation of cells with regulatory properties. Epigenetic modifiers have gained special attention due to their ability to modify immune regulatory pathways. In this context, a group of chemical compound collectively named histone deacetylase inhibitors (HDACi) have recently been shown to modulate tumor cell immunogenicity, adding a new property to their already well-documented cytotoxic effect against transformed cells. LBH589 is a potent, pan-HDACi that has been used in clinical trials for the treatment of several hematological malignancies. Here, we provide evidence of the anti-melanoma effect of LBH589 through its direct effects upon tumor cells as well as its modulatory effects upon immune cells. Indeed, treatment of human and murine melanoma cells in vitro with LBH589 resulted in inhibition of melanoma proliferation, characterized by cell cycle arrest in G1. Moreover, we found that LBH589 enhances the expression of MHC class I and II molecules on melanoma cells, which is critical for immune recognition. In addition, LBH589 treatment inhibits the production of IL-10, while enhancing the secretion of pro-inflammatory cytokines such as IL-12 and the expression of the costimulatory molecule B7.2 on antigen-presenting cells (APCs). LBH-treated APCs also displayed an enhanced capability to activate naïve antigen-specific T-cells as evidenced by their increased production of IL-2 and IFN-γ. More importantly, LBH589-treated APCs also restored the function of anergic T-cells isolated from tumor bearing mice. Finally, in vivo treatment of B16 melanoma bearing mice with LBH589 resulted in a substantial decrease in tumor growth when compared to vehicle-control treated mice (mean 602mm3 vs. 1316mm3, respectively). In conclusion, the dual ability of the pan-HDACi LBH589 to target both melanoma cells and to enhance anti-tumor immune responses provides the rationale for evaluating this compound either alone or in combination with immune enhancing therapeutic approaches (eg, CTLA4 blockade) for melanoma treatment.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3554. doi:1538-7445.AM2012-3554
Abstract 3557: Reduced ovarian hormones & reduced mammographic & MRI determined breast density in BRCA carriers following a hormonal chemo-prevention regimen of gonadotropin releasing hormone agonist (GnRHA) & low-dose add-back estrogen & testosterone
Authors: Sand Sharon R. , Klifa Catherine , Press Michael F. , Pike Malcolm , Ursin Giske , Spicer Darcy , Vora Lalit , Daniels AnnaMarie , Blazer Kathleen R. , Herzog Josef , Villalobos Ivonne , Weitzel Jeffrey N.
Published: August 2012

Young women at high risk of breast and/or ovarian cancer due to a BRCA mutation need risk-reducing options that preserve childbearing capacity. Purpose: Correlate changes in breast tissue determined by magnetic resonance imaging (MRI) & mammography with ovarian hormone levels following GnRHA treatment. Methods: In this prospective phase 2 biomarker chemoprevention trial, 10 premenopausal high-risk women, mean age 29.4 (21-43), were treated with intranasal GnRHA (deslorelin), low-dose add-back estradiol & testosterone once daily for 10 months. MPA was given for 10 days starting Day 140. Serum hormone levels were measured pre-administration of study drugs on Day 1, 29, 169 & 300. All participants underwent mammography, breast MRI & breast biopsy before & after 300 days of treatment. Mammographic density was measured & compared to volumetric breast density from MRI at both time points for all participants & fibroglandular tissue volume was also determined. Results: Significant decreases (p < .05) were shown in estradiol (-61%) and testosterone (-41%) over time. Nine out of 10 participants showed a mean reduction in MRI volumetric breast density of 17.3% (p=0.045), a mean reduction in MRI fibroglandular volume of 15.1% (p=0.041) and a mean reduction in mammographic density of 31.9% (p=0.0033). Conclusion: Changes in breast tissue composition were significant after 10 months of hormonal chemoprevention, validating the proof of principle that density as a risk biomarker can be manipulated in BRCA carriers. We documented reduction in breast density by both mammographic and MRI assessment. While greater quantitative change in density was detected by mammography, MRI yields additional qualitative structural observations. Our findings confirm that MRI can be used to measure hormonal chemoprevention effects in women at high-risk of breast cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3557. doi:1538-7445.AM2012-3557
Abstract 3558: A pilot clinical study of limonene in women with early stage breast cancer: Effects of short-term treatment on tissue limonene disposition and serum markers
Authors: Miller Jessica A. , Lang Julie E. , Hsu Chiu-Hsieh , Ley Michele , Waer Amy L. , Cordova Catherine , Chow H-H. Sherry
Published: August 2012

Background: Limonene is a highly lipophilic monoterpene found in citrus peel oil that has demonstrated anticancer properties in preclinical studies. The purpose of this study was to evaluate whether limonene and its primary metabolite perillic acid (PA) would distribute extensively to the breast tissue and reach an effective drug concentration. Secondary endpoints included evaluation of changes in cancer-related biomarkers in plasma and tissue. Methods: Participants (N = 40) with newly diagnosed stage 0 - 2 breast cancer took 2 grams daily of oral limonene for 2 - 6 weeks (21.5 ± 8.8 days) prior to planned surgical tumor resection. Blood was drawn pre/post intervention for measurement of serum concentration of limonene, PA, and protein biomarkers, as well as to assess toxicity profiles. A small piece of breast tissue adjacent to the tumor mass was also collected for analysis of limonene and PA levels. Limonene and PA levels in tissue and serum were analyzed using specific chromatography-based assays. Results: Limonene was found to preferentially concentrate in breast tissue (332.3 + 336.1 uM) versus plasma (0.49 + 0.67 uM) with tissue-to-plasma concentration ratio (TPCR) of 1,667 + 312.5 (P<0.001). PA did not concentrate in breast tissue (5.73 + 10.28 uM) versus plasma (3.89 + 6.81 uM) with TPCR of 1.4 + 0.56. Post-intervention serum levels of leptin, adiponectin, TGF-beta1, IGFBP-3 and IL-6 were unchanged from baseline. There was a small but statistically significant post-intervention increase in IGF-1, however the change was no longer significant after adjustment for number of days on agent. Possibly or probably related adverse events were primarily GI-related and were not dose-limiting. No clinically significant changes in complete blood count, renal, hepatic or other blood chemistry studies were noted. Analysis of the intervention effects on tissue biomarkers of proliferation, apoptosis, and cell cycle regulation is ongoing. Discussion: Oral limonene preferentially concentrates in the breast tissue and has a favorable side effect profile. PA does not readily concentrate in breast tissue when administered as oral limonene. Short-term limonene intervention resulted in minimal changes in systemic biomarkers. Further clinical trials with a longer intervention are necessary to establish limonene's potential role as a chemopreventive agent in breast cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3558. doi:1538-7445.AM2012-3558
Abstract 356: Photoacoustic imaging of pancreatic cancer proliferation via sigma-2 receptor/PGRMC1-eYFP
Authors: Xu Jinbin , Cai Xin , Yao Junjie , Dirk Spitzer , Zeng Chengbo , Hawkins William G. , Wang Lihong V. , Mach Robert H.
Published: August 2012

Sigma-2 receptor binding sites, recently identified as progesterone receptor membrane component 1 (PGRMC1) (Nature Communications, 2011; 2:380), are highly expressed in tumor cells. We have previously reported that measuring the sigma-2 receptor expression is a novel strategy for evaluating the proliferative status of tumors in vivo using the non-invasive imaging technique, positron emission tomography (PET). Our group has developed a series of sigma-2 receptor radioligands as PET imaging probes, one sigma-2 receptor radiotracer [18F]ISO-1 is under clinical evaluation for imaging the proliferation status in the patients with different types of cancers. PGRMC1 depleted human ovarian SKOV-3 cancer cells have been reported to lack tumor formation in mice and PGRMC1 depleted tumors displayed poor microvasculature system (Endocrinology, 2009; 150:4846-4854). To further understand the regulation of PGRMC1 in cell cycle and cancer proliferation, we have stably transfected PGRMC1-eYFP, enhanced yellow fluorescent protein conjugated PGRMC1, into human pancreatic BxPC3 cancer cells and those cells were transplanted into immunodeficient nude mice to grow into solid tumors; subsequently, a traditional fluorescence imaging system and an optical-resolution photoacoustic microscopy (OR-PAM) were utilized for in vivo monitoring of BxPC3 cancer cells growth and observing the surrounding microvasculature development for those tumors under conditions of sigma-2 receptor/PGRMC1 overexpression. Tumor tissue sections were prepared and in vitro fluorescence microscopy analysis of PGRMC1-eYFP cells revealed that PGRMC1-eYFP overexpressed cells form cluster patterns which may represent the proliferation priority created by PGRMC1 overexpression. The subcellular localization of PGRMC1-eYFP appeared to be similar to that of sigma-2 receptors reported previously by our group using the sigma-2 receptor fluorescent probes (Cancer Res 2007; 67, 6708-6716). PGRMC1-eYFP BxPC3 cells were surrounded by fully developed microvasculature system. Further application of this in vivo imaging platform for evaluating the sigma-2 receptor pharmacology and imaging proliferation is ongoing in our group. (Supported by CA 102869 and CA136398).

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 356. doi:1538-7445.AM2012-356
Abstract 3560: Application of metabolomics to assess serum profiles in limonene-treated breast cancer patients
Authors: Miller Jessica A. , Want Elizabeth J. , Thompson Patricia A. , Lang Julie E. , Lance Peter , Chow H-H. Sherry
Published: August 2012

Background. Limonene is a highly lipophilic monoterpene found in citrus peel that has demonstrated anticancer effects in preclinical models. Limonene likely affects multiple targets with varying potency. Advanced techniques to obtain metabolomic profiles from biofluids have the potential to provide a non-invasive means to assess these multiple effects. This strategy was applied to a clinical trial with women with early stage breast cancer receiving limonene treatment. Methods. Forty women with stage 0 - 2 breast cancer received 2 g QD limonene daily for 2 - 6 weeks (21.5 + 8.8 days) before scheduled surgical resection of their tumor. Pre/post intervention blood draws were taken for metabolomics analysis. Metabolomics profiling was conducted using ultra performance liquid chromatography tandem time-of-flight mass spectrometry (UPLC-QToF). Chromatographic separation was achieved using a gradient of two mobile phases; A: 0.1% formic acid in water, and B: 0.1% formic acid in methanol with a flow rate of 0.4 mL/min. A Waters Aquity UltraPerformance LC HSS T3 column was used. Metabolomics data was preprocessed with XCMS. Preliminary metabolite identification was conducted by mining the Human Metabolome Database (HMDB). Results. Over 1,000 metabolite features were identified by metabolomic profiling. In negative ion mode, three metabolites exhibited a 48-fold change or higher from pre to post-intervention; 183.1 m/z at 9.4 min, 177.0 m/z at 10.0 min, and 345.1 m/z 8.9 min (P's<0.001). Two distinct peaks with m/z of 103.0 elute at 1.9 and 2.25 minutes respectively and changed >20% (P's<0.05). Twenty potential metabolites were identified in positive ion mode with >20% change by the intervention (P's< 0.05), of these, two exhibited 10-fold change or higher; 312.2 m/z at 8.7 min, and 369.2 m/z at 9.0 min (P's<0.001). Discussion. This study demonstrates that 2 g QD daily oral limonene results in significant changes in approximately 20 metabolites in serum. Candidate compounds include limonene metabolites, carnitines and end products of arachindonic acid metabolism. Efforts are ongoing to identify these metabolites for analyte specific verification and quantitation. Further clinical trials with limonene are necessary to establish its potential role as a chemopreventive agent in breast cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3560. doi:1538-7445.AM2012-3560
Abstract 3565: Colorectal cancer screening among US adults with and without doctor's specific recommendation regarding choice of screening modality
Authors: Laiyemo Adeyinka O. , Doubeni Chyke , Adebogun Akeem O. , McDonald-Pinkett Shelly , Han Paul , Meissner Helen I. , Klabunde Carrie
Published: August 2012

Background: Absence of a physician's recommendation is among the most commonly reported barriers to undergoing colorectal cancer (CRC) screening. It is unknown whether a physician's specific recommendation of a particular screening modality, rather than a patient's choice from a menu of screening options, improves CRC screening uptake. Aim: To assess whether healthcare providers’ discussion of CRC screening options and recommending a specific screening modality improve uptake of screening. Methods: We used the 2007 Health Information National Trends Survey (HINTS) to evaluate how respondents who were 50 years and older (n = 4,342) were informed of CRC screening. We used logistic regression analyses to examine the association of recommendations and being current with CRC screening (Fecal occult blood testing (FOBT) within 1 year, sigmoidoscopy within 5 years, or colonoscopy within 10 years). Results: The mean age of responders was 64.9 years, 60.3% female, 81.5% white, 8.6% black, and 92.7% had health insurance. CRC screening discussions occurred with 3,320 (77.5%) respondents; 94.7% of which occurred with a doctor as opposed to a nurse or other health care professional. Colonoscopy was the most recommended test. Overall, 2,824 (65.0%) respondents were up to date with CRC screening regardless of the screening modality. After adjusting for age, sex, race, highest education, income, marital status and health insurance, having a discussion about screening and receiving a specific test recommendation were associated with being up to date with CRC screening (Table). Conclusion: Uptake of CRC screening is better when providers discuss CRC screening and make specific CRC screening test recommendations. Table: Association of the patterns of CRC screening recommendations with being up to date with CRC screening

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3565. doi:1538-7445.AM2012-3565
Abstract 357: Nonclinical tumor efficacy studies of [18F]AH113804, a novel PET imaging agent with high affinity for the human c-Met receptor
Authors: Evans Paul M. , Battle Mark , Getvoldsen Gareth , McRobbie Graeme , Bjerke Roger , Morrison Matthew , Johannesen Edvin , Dalsgaard Grethe T.
Published: August 2012

c-Met, the tyrosine-kinase receptor for hepatocyte growth factor (HGF)/scatter factor, is involved in tumour growth, invasion and metastasis in many human cancers of epithelial origin. Various tumour types are reported to overexpress c-Met, whilst expression in most normal tissues is relatively low. [18F]AH113804 is a peptide-based molecular imaging agent being developed by GE Healthcare for the in vivo evaluation of tumour and metastatic c-Met expression by PET imaging. In vitro affinity studies with fluorescently labelled analogues confirmed that whilst the AH113804 peptide had high affinity for human c-Met (hc-Met), there was limited or no affinity for dog or rodent c-Met, respectively. In mice, relatively high uptake of [18F]AH113804 was observed in human xenograft tumours known to express high levels of hc-Met, with rapid clearance from key background tissues such as muscle (tumour to muscle ratio of >5 achieved by 30 minutes post-injection). This biodistribution profile allowed the tumour to be clearly visualised by micro-PET imaging. Tumour uptake was significantly reduced by co-administration of excess non-radioactive peptide, confirming tumour uptake was specific. Tumour uptake of [18F]AH113804 was also shown to correlate with expression of hcMet, with a relative retention of 2.0±0.1, 1.2±0.2 and 0.7±0.2% retained dose per gram normalised for body weight (% rd/g/100g bw) 60 minutes post-injection in xenograft tumours with relatively high (HT-29 tumours), lower (U87 tumours) and no (LLC tumours) expression of hc-Met respectively (as assayed by ELISA). Finally, 111InCl3 was used in a dual tumour model as a non-specific marker of blood pool to confirm differences in tumour uptake were not related to differences in tumour blood pool or delivery. There was a significant difference in [18F]AH113804 uptake between HT-29 (2.2±0.8% rd/g/100 g bw) and LLC (0.9±0.2% rd/g/100 g bw) tumours (p<0.001) 30 minutes post-injection, whilst uptake of 111InCl3 was similar for the two tumour types (HT-29; 0.9±0.2% rd/g/100 g bw, LLC; 1.1±0.2% rd/g/100 g bw). Overall, these results confirmed that [18F]AH113804 has desirable properties for a c-Met targeted molecular imaging agent. Since there are a number of anti-c-Met therapies in clinical development, [18F]AH113804 has potential to be used as an aid in therapy selection and/or monitoring. Furthermore, [18F]AH113804 may be of use in patient stratification and prediction of patient outcome for specific cancers.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 357. doi:1538-7445.AM2012-357
Abstract 3571: UKLS - United Kingdom Lung Cancer Screening Trial
Authors: Field John K. , Baldwin David , Stephen Duffy W. , Devaraj Anand , Hansell David M.
Published: August 2012

In the UK 33,500 individuals die from lung cancer each year. The effectiveness of screening pre-symptomatic individuals urgently requires evaluation. The aim of UK Lung cancer Screening trial (UKLS) is to provide data required for an informed decision about the desirability of introducing population screening for lung cancer in the UK. The aim of the UKLS is to demonstrate a 25-30% mortality advantage and cost effectiveness of the screening. The UKLS pilot has started to recruit in 2011. The pilot sites are based at the Liverpool Heath & Chest Hospital, Liverpool and the Papworth Hospital, Cambridgeshire with a second reading site at the Royal Brompton Hospital, London. It will randomise 4,000 high risk patients identified by the Liverpool Lung Project (LLP) Risk Prediction Model. If the pilot trial is successful and funding is available, we plan to randomise a further 28,000 subjects from seven centres in the UK. Individuals are invited to participate if they have at least 5% risk of developing lung cancer over 5 years as predicted by the LLP risk model. The “Wald Single Screen” Design has been chosen for the UKLS pilot trial. Individuals meeting the inclusion/exclusion criteria will be sent invitations to participate and selected on the basis of the LLP risk questionnaire and selected to attend one of the pilot recruitment sites. After consent has been obtained, the participant will undertake spirometry and be asked to provide specimens (of blood, oral and nasal brushings and sputum) and to complete baseline lifestyle, psychosocial, and health economic questionnaire. Participants will be randomised to the study arm and will have a single low dose computed tomography scan (CT); those in the control arm will have usual care (no CT). CT scans will be read both locally and centrally and volumetric analysis will be performed on detected nodules. Both arms will be followed up for lung cancer incidence and mortality. Mortality will be documented after 10 years of follow-up. Modelling has resulted in the development of the UKLS care pathway to manage identified nodules. The aim of the main UKLS trial is to assess whether screening by low dose CT will confer a mortality advantage of 30% and also be cost effective for the UK population.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3571. doi:1538-7445.AM2012-3571
Abstract 3574: Detection of serum CYFRA 21-1 as a biomarker for stratification of ovarian cancer risk in women with a pelvic mass
Authors: Li Zhong-Qian , Smalley Robert J. , Glover Curtis L. , Radwan Rachel R. , Raju Savitha , Falcone Katherine L. , Fegely Maryellen , He Kuanglin , Kettlety Timothy R.
Published: August 2012

CYFRA 21-1 is a known lung cancer biomarker. In subjects with ovarian cancer (N = 159) and those with benign gynecological diseases (N = 53), serum CYFRA 21-1 reported a sensitivity (SN) of 44% and a specificity (SP) of 95% for ovarian cancer detection at a cut-off value of 2.4 ng/mL using an ELISA assay (Hasholzner U, et al, 1994). Another report showed a SN of 41% and a SP of 95% for ovarian cancer (N = 37) versus benign ovarian cysts, endometriosis, pelvic inflammatory disease, bowel disease and liver cirrhosis (N = 168) using an ELISA assay (Tempfer C, et al, 1998). We carried out a pilot study to evaluate the serum CYFRA 21-1 as a biomarker for stratification of ovarian cancer risk in women with a pelvic mass. Methods: ARCHITECT CYFRA 21-1 was used to measure the levels of serum CYFRA 21-1. Single point frozen serum samples from 171 female subjects with a pelvic mass were randomly selected from the archive clinical trial described by Moore R et al (2009). Of the 171 subjects, 42 had epithelial ovarian cancer (EOC), 5 with low malignant potential tumor (LMP) and 124 with benign pelvic masses. Results: To stratify EOC from benign pelvic masses and LMP, the following performance was obtained for serum CYFRA 21-1: Notes: The cutpoints were set at 1.2 and 1.8 ng/mL to reach a 75% and 95% SP, respectively. Conclusion: Serum CYFRA 21-1 appears to be a useful biomarker for stratification of EOC from benign pelvic mass and LMP.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3574. doi:1538-7445.AM2012-3574
Abstract 3580: Pre-diagnostic alcohol consumption and breast cancer recurrence and survival in postmenopausal women
Authors: Chang-Claude Jenny C.
Published: August 2012

Introduction: Alcohol consumption has been consistently associated with breast cancer risk. However, studies on its association with breast cancer survival produced inconsistent results. Methods: We assessed the association of alcohol consumption (in four categories <0.5 g/d, 0.5 to <6.0 g/d, 6.0 to <12.0 g/d, α12.0 g/d, and continuous) with survival and recurrence in a prospective cohort study in Germany of 2,706 postmenopausal breast cancer patients aged 50-74 years after excluding those with previous cancer and/or missing information on alcohol intake. Patients were diagnosed between 2001 and 2005 and vital status, causes of death, and recurrences were verified through the end of 2009. Delayed-entry Cox proportional hazards models were stratified by age at diagnosis and study centre and adjusted for other prognostic factors. Fractional polynomials were used to assess the true dose-response relation for alcohol consumption. Results: Women were enrolled in the study a median time of 105 days after diagnosis. Median follow-up times from recruitment until death/censoring or recurrence/censoring were 5.5 years and 5.6 years, respectively. Overall, 326 deaths occurred, 239 (73.3%) due to breast cancer. Further causes of death were other cancers (n=41, 12.6%), cardiovascular disease (n=22, 6.7%), and other causes (n=24, 7.4%). Of the 2,199 patients with stage I to IIIa disease and available data on recurrence status, 250 had a breast cancer recurrence. Alcohol consumption ≤ 12 g/day compared to < 0.5 g/day was linearly associated with a statistically significantly higher breast cancer mortality (HR, 1.71; 95% CI, 1.12 to 2.62; P for trend = 0.03). Results were no longer statistically significant when restricted to Stage I-IIIa patients (HR, 1.28; 95% CI, 0.75 to 2.20). There was no effect modification by body mass index, hormone replacement therapy use, and estrogen receptor status. Alcohol consumption ≤ 12 g/day was not associated with overall mortality (HR, 1.27; 95% CI, 0.90 to 1.80) and mortality due to other causes (HR, 0.73; 95% CI, 0.38 to 1.42). Also, no association with breast cancer recurrence was found (HR, 1.05; 95% CI, 0.71 to 1.56). Conclusion: Consumption of more than 12 g alcohol (equivalent to one alcoholic drink) per day is associated with increased breast cancer mortality but not with breast cancer recurrence.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3580. doi:1538-7445.AM2012-3580
Abstract 3587: Effect of race on outcome in women with uterine cancers
Authors: Nevadunsky Nicole S. , Smotkin David , Einstein Mark , Harris Kimala , Kim Ryung , Goldberg Gary
Published: August 2012

Background: Incidence rates for malignant tumors of the uterine corpus have been reported to be lower among women of color than among whites, whereas mortality rates have been reported to be higher among African-American women and women of Latina origin. Reasons for the higher level of mortality among women of color are currently unknown. Methods: After Institutional Review Board approval, we accessed the prospective clinical databases in the Division of Gynecologic Oncology at our institution. We abstracted socio-demographic and survival data from all women who were diagnosed with endometrial cancer from January 1990-January 2010. Pathology records were reviewed and the final pathology confirmed. Results: Nine hundred and ninety patients were identified. Racial distribution was 381 (38%) white, 310 (31%) black, 231 (23%) Hispanic, 21 (2%) other, and 72 (3%) unknown or unclassified. Five hundred and ninety-six (60%) patients had Type I endometriod histological subtype. At time of censor, 269 (27%) were confirmed deceased. The hazard ratio for black verses white women was 1.91 (p<0.001) when all histological subtypes were included. However, when patients were divided into Type I and Type II histological subtypes there was no significant difference in survival by race. Conclusion: Our data show no difference in survival among women of Asian, African-American/Caribbean, and Caucasian races with uterine cancer after control for histological subtype.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3587. doi:1538-7445.AM2012-3587
Abstract 3588: Treatment differences are associated with black-white disparities in advanced epithelial ovarian cancer
Authors: Howell Elizabeth A. , Egorova Natalia , Hayes Monica P. , Wisnivesky Juan , Franco Rebeca , Bickell Nina A.
Published: August 2012

Background: Racial differences in survival for ovarian cancer are well documented. Previous research suggests that black-white mortality disparities are partially explained by more advanced disease among black women. Whether differences in receipt of guideline recommended care (including both surgery and chemotherapy) also explain mortality differences between black and white women with advanced epithelial ovarian cancer is not known. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) linked to Medicare claims for 1997-2007, we identified a cohort of 4363 women age 65 and older with histologically confirmed stage III or IV epithelial ovarian cancer. We evaluated long-term survival for black and white women in the entire fee-for-service Medicare population, and then in patients matched by propensity score to create two similar cohorts for comparison with Kaplan-Meier analysis. We investigated the association between race, stage, and survival among women who received guideline recommended care and those who received incomplete care. Adjusted analyses were conducted using Cox modeling. Results: Overall, black women with advanced epithelial ovarian cancer were more likely to die than white women; unadjusted hazard ratio (HR):1.29 (95% confidence interval [CI]: 1.12-1.48). Black women were more likely than white women to present with stage 4 disease (40% vs. 32%, p=0.02) and comorbid conditions (55% vs. 36%, p<0.0001). Black women were less likely than white women to receive guideline recommended care (61% vs. 73%, p=0.0001) and women who received incomplete care had lower survival than women who received recommended care, unadjusted HR of 0.27 (95% CI: 0.25-0.29). In multivariable models including demographic factors, stage of disease, comorbidity, and extent of surgery, there was no racial difference in mortality among women who received guideline recommended care, HR for mortality for black women at 1.09 (95% CI: 0.90-1.13) or among women who received incomplete care, HR for black women at 1.15 (0.89-1.39). The survival analysis of patients matched by propensity score showed no difference between white and black women with recommended care (p=0.68) and no racial difference with incomplete care (p=0.87). Conclusions: Differences in receipt of guideline recommended care partially explain black-white mortality disparities among women with advanced epithelial ovarian cancer. Patients who receive incomplete treatment have worse prognosis. Our findings suggest a need to identify and rectify the cause for disparate treatment rates.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3588. doi:1538-7445.AM2012-3588
Abstract 3591: Triple negative (c-KIT, BRAF, NRAS) acral lentiginous melanoma in Hawaii: Molecular profiling in a multi-ethnic population
Authors: Morita Shane Y. , Lum Christopher A. , Davis James W.
Published: August 2012

Background: Acral lentiginous melanoma (ALM) is the least common subtype among patients with melanoma. There is a higher preponderance in the minority population. A different pathogenesis has been proposed for ALM. Previous studies have profiled the importance of c-KIT, BRAF and NRAS mutations in melanoma treatment and prognosis. However, characterization of these somatic mutations in a specific non-Caucasian ALM population has not been reported. The Pacific Basin provides a unique opportunity to study diseases in diverse ethnic groups, including Pacific Islanders and Filipinos. We sought to determine the frequency of a “triple negative” genotype in our multi-ethnic cohort. Methods: IRB approval was obtained for this molecular analysis. From 1999 to 2011, 12 non-Caucasian patients (8-Filipino, 3-Pacific Islander and 1-Vietnamese) histologically confirmed to have ALM were evaluated at a tertiary institution. Data including age, gender, tumor location, Breslow thickness, Clark level, ulceration, regression, and mitoses per mm squared were compiled. Direct sequencing (c-KIT [Exons 8,9,11,13,17,18], NRAS [Exons 2,3]) and real-time PCR (BRAF [Exon 15]) was performed on formalin-fixed/ paraffin-embedded archived biospecimens (primary lesions). Results: Our findings demonstrated that 7/12 (58%) patients exhibited the “triple negative” genotype. Mutually exclusive somatic mutations (4 c-KIT and 1 BRAF) were identified in the remaining 5/12 (42%) patients. Those in the “triple negative” group trended toward a deeper Breslow thickness, when compared to those with a mutation (depth 4.73 mm vs. 3.07 mm). Demographics of the entire non-Caucasian cohort included a mean age of 72.0 years old (range 52-87) and male gender 6/12 (50%). Tumor location principally involved the foot 10/12 (83%); mean Breslow thickness was 4.04 mm (range 2.20-7.75), Clark IV or higher 11/12 (92%), ulceration 8/12 (67%), regression 12/12 (100%), and mean mitoses per mm squared was 5.71 (range 0-30). Conclusions: Non-Caucasian patients with ALM were found to have a high prevalence of the “triple negative” genotype. Those within that group appeared to have thicker tumors. Nearly half of our cohort had thick primary lesions with a high propensity for ulceration. This is the first study to our knowledge that has profiled somatic mutations (c-KIT, BRAF, NRAS) in a multi-ethnic population of ALM patients and examined the histologic correlates of a “triple negative” genotype. This novel concept highlights the relevance of alternate pathways and molecular targets, such as PI3KCA in prognosis and therapy.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3591. doi:1538-7445.AM2012-3591
Abstract 3592: Risk factors of prostate cancer in African American men
Authors: Chornokur Ganna , Han Gang , Tanner Richard E. , Lin Hui-Yi , Gwede Clement , Kumar Nagi B. , Pow-Sang Julio , Phelan Catherine M.
Published: August 2012

Background. African American men have 1.6 times the incidence and 2.4 times the mortality rate of prostate cancer, compared to Caucasian men. Thus, prostate cancer constitutes one of the most striking racial health disparities, the causation of which is not well understood. Main hypothesis. We hypothesized that select clinical and/or bio-behavioral risk factors are associated with prostate cancer in African American men. Participants and Methods. 105 African American men aged 34-80 (35 cases and 70 controls) were recruited. Univariable and multivariable logistic regression models were built to test the marginal and joint effects of the variables when predicting the cancer status. Results. In the univariable regression models, PSA (ng/ml; p<.001), smoking (cigarettes/day; p=0.011), diagnosis of benign prostatic hyperplasia (BPH, yes/no; p<.001), diagnosis of prostatitis (yes/no; p<.001) and prostatic intraepithelial neoplasia (PIN, yes/no; p=<.001) were independently associated with the prostate cancer diagnosis. However, only PSA (4.340; (1.484, 12.689)) and diagnosis of BPH (14.248; (1.132, 179.310)) remained significant in the age-adjusted multivariable logistic regression model. Conclusions. Our results suggest that, as expected, PSA levels are associated with prostate cancer in African American men. Interestingly, a history of BPH is also associated with prostate cancer in African American men. Despite the limitation of a small sample size, our data is in agreement to a recent report (Pettaway et al, 2011) in which African Americans with BPH were observed to have a much greater risk of developing prostate cancer than similar Caucasian men, highlighting differences in the biology of prostate cancer between populations. References Curtis A. Pettaway, Lois E. Lamerato, Michael T. Eaddy et al. Benign prostatic hyperplasia: racial differences in treatment patterns and prostate cancer prevalence. BJU International (1 0 8) 1 3 0 2 - 8, 2011

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3592. doi:1538-7445.AM2012-3592
Abstract 3601: Telomere length assessment in human archival tumor tissues by quantitative PCR method (qTL)
Authors: Wang Hui
Published: August 2012

Telomeres are essential for maintenance of genomic stability. Short telomeres have been associated with genomic instability, and initiation and progression of human cancers. To protect their telomeres, up to 90% of human cancers activate telomerase. Inhibition of telomerase by imetelstat, a specific and potent inhibitor, has resulted in telomere shortening, as well as tumor response in animal models. We propose that tumors with short telomeres may be more responsive to imetelstat than tumors with long telomeres. This hypothesis will be tested by measuring baseline telomere lengths in archival tumors of patients in imetelstat Phase II clinical trials, and correlating tumor telomere length with clinical outcome. In order to accomplish this, a fast, high-throughput qPCR-based method for telomere length measurement in genomic DNA extracted from FFPE tissue sections was developed. Using this assay, telomere repetitive DNA sequences and single-copy gene control were successfully amplified. The assay required very little genomic DNA (1-10ng per PCR reaction). Thus, small tissue sections (20 mm2) could be easily accommodated. Using this technique, we were able to perform the first comparison of relative telomere lengths in 22 human breast cancer samples and 8 human tumor cell lines in matched fresh-frozen and FFPE samples. Telomere lengths measured in FFPE samples by the qPCR method strongly correlated with the telomere lengths measured by TRF in matched fresh-frozen samples. Therefore, our method provides a useful tool for assessment of telomere length as a potential predictive biomarker of responsiveness to telomerase inhibition in clinical archival tumor tissue.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3601. doi:1538-7445.AM2012-3601
Abstract 3606: Dynamic expression of pepsinogen I in gastric diseases sequence and relationship with Helicobacter pylori infection
Authors: Li Ping , Sun Liping , Yuan Yuan
Published: August 2012

Serum PG I and PG I /PGII levels seemed to be related to the functional changes in the stomach, and their use as ‘serological biopsy’ in gastric cancer and precancerous diseases has been reported over 20 years. But the dynamic expression of pepsinogen I in situ of gastric mucosa and the value to detect gastric cancer and precancerous diseases, relative to the serum pepsinogen I is still unclear. Helicobacter pylori is a gram-negative bacterium that colonizes the stomach. More than 50% of the adult population are infected with H. pylori worldwide. Numerous studies have reported that healthy volunteers and gastric ulcer patients with H pylori infection have increased serum pepsinogen I levels which decrease after H pylori eradication. The evidence whether expression of pepesinogen I in situ affected by H pylori infection is not available. We thus conducted this study to investigate the dynamic expression of pepsinogen I in superficial gastritis, atrophic gastritis, gastric cancer and also H.pylori-associated gastric lesions and evaluate the application value of pepsinogen I in classifying gastric cancer and its precancerous diseases, and also the influence of H pylori on pepsinogen I expression. The expression of pepsinogen I was determined by immunohistochemistry method in 185 cases with mucosa taken from gastric corpus as well as from antrum. H.pylori infection was determined by histological examination and ELISA. Serum pepsinogen I and II were determined by ELISA. We found that Pepsinogen I was only expressed in the gastric corpus. There were 185 cases from gastric corpus and the positive rate of pepsinogen I expression in superficial gastritis, atrophic gastritis and gastric cancer decreased significantly in sequence (P<0.05;100% vs. 83.3%vs0.0%), and the over-expression rate also decreased along with the sequence: normal, superficial gastritis, atrophic gastritis and gastric cancer (p<0.05; 93.3%vs72.9% vs22.2vs0.0%). The over-expression rate of pepsinogen I in superficial gastritis with H pylori infection was higher than that without H pylori infection (P=0.035; β2 = 4.46).The serum expression of Pepsinogen I had no statistical difference (P>0.05) and the ratio of sPGA to sPGC decreased along with the above groups. (P<0.05). In conclusion, expression of PGI in situ has positive correlation with the degree of malignancy of gastric mucosa. and it is good biomarker for the diagnosis of gastric cancer and precancerous diseases. Also, The expression of PGI has positive correlation with H.pylori infection, and maybe is an important part in the H pylori- related damage or a good marker for screening H.pylori infection.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3606. doi:1538-7445.AM2012-3606