bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A123: Serum levels of hormones and breast tissue composition in young women
Authors: Martin Lisa , Chavez Sofia , Gunasekara Anoma , Salleh Ayesha , Melnichouk Olga , Yaffe Martin , Minkin Salomon , Bronskill Michael , Boyd Norman 
Published: May 2012

Abstract
A123

Background
Percent mammographic density (PMD) is a strong and heritable risk factor for breast cancer with characteristics that suggest it may be a marker of susceptibility to the disease. We have examined serum hormone levels and other factors associated with breast tissue composition in young women, when susceptibility to breast carcinogens is greatest.

Methods
In 400 young women aged 15-30 years we obtained quantitative measures of breast water, which reflects fibro-glandular tissue, and breast fat using magnetic resonance (MR), and collected anthropometric and other data. All examinations were performed in the follicular phase of the menstrual cycle and fasting blood samples for hormone assays were obtained on the morning of the MR examination.

Results
Serum levels of growth hormone (GH) and sex hormone binding globulin (SHBG) were positively associated with percent breast water content in all young women aged 15-30, and the associations remained statistically significant after adjustment for height, weight and other covariates. IGF-I was not associated with any MR breast measures. Serum levels of estradiol, progesterone, and testosterone, were not associated with MR breast measures in all young women, or in those aged 20-30, but did show evidence of positive associations with percent water in those aged 15-19 years.
After adjustment for other covariates, interactions of age and serum levels of testosterone (p=0.02) and progesterone (p=0.03) were associated with percent water, and estradiol with total water (p=0.07).

Conclusions
Serum levels of sex hormones were associated with breast tissue composition in young women aged less than 20, while GH and SHBG were associated with breast tissue composition in all young women.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A123.
Abstract A126: Characteristics of menstruation and pregnancy and the risk of lung cancer in women
Authors: Koushik Anita , Parent Marie-Elise , Siemiatycki Jack 
Published: May 2012

Abstract
A126
Differences between men and women in the descriptive epidemiology of lung cancer suggest that hormonal factors may influence lung carcinogenesis in women. Few epidemiological studies have been conducted on hormone-related variables and lung cancer risk and the findings have not been consistent. We investigated the association between characteristics of menstruation and pregnancy in relation to lung cancer risk in a population-based case-control study carried out in Montreal, Canada. Between January 1996 and December 1997, newly diagnosed lung cancer cases were identified and recruited from 18 Montreal-area hospitals that together diagnose 98% of cases that occur among Montreal residents. Population controls from Montreal were identified from the provincial electoral lists and were randomly selected, stratified to the expected age and sex distribution of cases. The participation rate was 81.7% among cases and 69.4% among controls. Among cases, interviews were conducted an average of 12.1 months after diagnosis. For each variable, odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression modeling. Each hormone-related variable was modeled separately. Associations were also examined according to age at diagnosis and level of smoking and by lung cancer histology. All statistical tests were two-sided. Among 422 women with lung cancer and 577 controls, we observed that most characteristics of menstruation and pregnancy were not associated with the risk of lung cancer. However, an increased lung cancer risk was observed for women who had had surgical menopause with bilateral oophorectomy compared to women who had had a natural menopause (OR=1.95, 95% CI: 1.29-3.17). These results did not vary by age at diagnosis or level of smoking, and they were similar for different histological types. Our results suggest that hormonal factors, related to surgical menopause and/or ovary removal, may play a role in the risk of lung cancer. Further studies are needed to confirm these findings, and to assess the possible contribution of hormone replacement therapy.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A126.
Abstract A129: Alpha-fetoprotein-derived peptide (AFPep): A novel drug in translational studies for the treatment and prevention of breast cancer.
Authors: Jacobson Herbert , Bennett James , Andersen Thomas 
Published: May 2012

Abstract
A129
It has been well established that parity is associated with reduced lifetime risk for breast cancer. Recent U.S. Census data note that the proportion of American women who remain nulliparous has doubled over the last 30 years. These data suggest that the incidence of breast cancer will increase in the coming years. Is there a molecule in pregnancy that can be isolated, shown to inhibit breast cancer, and be converted into a drug that can be used to treat and prevent breast cancer?
The studies reported here demonstrate that a-fetoprotein (AFP) is such a molecule, that the anti-breast cancer site within that molecule is an 8-amino acid sequence in the third domain of the protein, and that this site has been synthesized in a form that can be used as a novel, non-toxic drug for the treatment and chemoprevention of breast cancer. We refer to this agent as AFPep.
AFPep is active after oral administration. It stops the growth of human breast cancers growing as xenografts in immune deficient mice, and it prevents the development of carcinogen-induced mammary cancers in rats. Its anti-breast cancer activity is additive in combination with tamoxifen, and it prevents the uterine hyperplasia induced by tamoxifen. Moreover, AFPep is active against breast cancers which have become resistant to tamoxifen. Its anti-oncotic mechanism is different from that of tamoxifen, aromatase inhibitors, anti-gonadotropins, and cytotoxic chemotherapy. There has been no evidence of toxicity in mice and rats receiving AFPep even when its dose was escalated 100-fold above its effective dose. Grant proposals are currently in review to support further development of AFPep including completion of its preclinical toxicology and initiation of Phase I clinical trials.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A129.
Abstract A131: Molecular events associated with the anti-tumor effects of black raspberries in N-nitrosomethylbenzylamine-induced rat esophageal carcinogenesis
Authors: Wang Li-Shu , Dombkowski Alan , Larue Bethany , Cukovic Daniela , Mukundan Anju , Henry Cassandra , Rocha Claudio , Lechner John , Stoner Gary 
Published: May 2012

Abstract
A131
We reported that the feeding of a diet containing 5 or 10% freeze-dried black raspberries (BRB) to N-nitrosomethylbenzylamine (NMBA)-treated rats results in a 39-64% reduction in the number of esophageal papillomas when using either anti-initiation or anti-promotion/progression protocols. The molecular events associated with the effects of BRB on NMBA-induced preneoplastic and papillomatous esophageal lesions however, have not been fully elucidated. In the present study, 4-5 week-old male F344 rats were injected s.c. with NMBA (0.3 mg/kg b.w., 3x/wk for 5 wks) after which they were fed either control diet or diet containing 5% BRB until the end of the study (35 wks). Control rats were injected s.c. with a solution of DMSO/water (20:80), the vehicle for NMBA. Esophagi from vehicle control, NMBA- and NMBA + BRB-treated rats were collected at 35 weeks for histologic grading, and for microarray and Real-Time PCR analyses. Treatment with 5% BRB reduced the number of preneoplastic lesions (dysplasias) and the number and size of papillomas in the esophagus of NMBA-treated rats. When compared to esophagi from vehicle control rats, NMBA treatment alone led to the differential expression of 4,807 genes in preneoplastic esophagus and 17,846 genes in esophageal papillomas. Treatment with 5% BRB resulted in a modulation towards control levels of expression of 626 genes in preneoplastic esophagus and 627 genes in papillomas. In both preneoplastic esophagus and in papillomas, the berry-modulated genes were associated with regulation of cell proliferation, inflammation and receptor-mediated pathways. Twenty-five genes were commonly modulated (down- or up-regulated) by BRB in both preneoplastic lesions and in papillomas. Interestingly, several of these genes are associated with matrix metalloproteinases involved in tissue invasion and metastasis, cell-cell adhesion and with calcium signaling. This is the first report suggesting that berries might influence genes involved in tissue invasion and metastasis in the rat esophagus. (Supported by NCI grant No. CA103180)
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A131.
Abstract A133: Time-dependent gene expression changes in a human colon polyp cell line induced by a clinically relevant concentration of atorvastatin
Authors: Elmore Eugene , Jain Aarti , Steele Vernon , Redpath J. Leslie 
Published: May 2012

Abstract
A133
The identification of biomarkers for chemopreventive agent efficacy in cell cultures from relative target tissues is of great importance. We have utilized a cell line from a human precancerous colon polyp cell line, VACO-235, to evaluate the changes in gene expression following continuous exposure to a clinically relevant concentration of atorvastatin (0.3 nM). The changes were monitored relative to the time matched controls at 48 and 96 hours of continuous exposure. The total RNA was isolated from three replicate cultures for each time point and from four replicate cultures of the time matched controls. The RNA was analyzed using Affymetrix human genome U133 plus 2 arrays. The data were analyzed using Genespring GX (Agilent Technologies) software to determine agent induced changes and to determine significant changes (P&lt; 0.05) that occurred at either 48 or 46 hours (2613 genes) or at both 48 and 96 hours (334 genes). The data were further analyzed using Ariadne Pathway Studio. A number of pathways showed responses that suggest possible changes in the regulation of proliferation and apoptosis. The tumor necrosis factor receptor superfamily, member 1a pathway also showed important changes. Caspase 3 was induced by 5.4 fold at 48 hours and 2.4 fold at 96 hours. Pak1(P21 activated kinease 1), caspase 8, caspase 2, and caspase 4 were also induced. The p38 MAP kinase pathway showed inhibition with MAP3K4 (MAP/ERK kinase kinase 4), which showed a 5 fold inhibition at 48 hours and 2 fold at 96 hours. Changes in the p38 MAP kinase pathway suggested inhibition of multiple kinase genes. As could be predicted, the most significantly modified pathway was LRP5 (low density lipoprotein receptor-related protein 5) which regulates low density lipoprotein. This finding suggests that atorvastatin was evaluated at a concentration that was similar to in vivo. Longer term exposure studies are currently underway to determine the effect of continuous atorvastatin exposure on the culture morphology and growth of VACO 235 cells. These data suggest that the use of a clinically-relevant concentration of atorvastatin can modify the expression of several key potential biomarkers for colon cancer prevention.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A133.
Abstract A136: A systems approach to the preclinical evaluation of targeted chemoprevention for lung cancer
Authors: Hazra Saswati , Krysan Kostyantyn , Walser Tonya , Gardner Brian , Lee Gina , Shay Jerry , Minna John , Horvath Steve , Dubinett Stven 
Published: May 2012

Abstract
A136
The possibility of an “individualized medicine” approach to chemoprevention targeted to the specific molecular abnormalities in the individual at risk has been suggested as a means to tailor prevention strategies (Markowitz, N Engl J Med. 2007;356:2195-8). In order to initiate targeted chemoprevention for lung cancer, we have developed a pre-clinical system to assess potential chemoprevention agents against mutated human bronchial epithelial cell lines (HBEC). HBECs are exposed to drugs such as rosiglitazone, erlotinib and celecoxib and selected proliferative responses, gene expression, micro-RNA profiles and protein panels are assessed. This data is then assessed by systems analysis to determine the optimal chemopreventive agents against specific mutations. These data will ultimately be utilized both for agent selectivity and agent specific biomarker identification. In preliminary studies, we evaluated rosiglitazone, erlotinib and celecoxib against three genetically altered HBEC cell lines harboring mutations relevant in the pathogenesis of human lung cancer (p53 knockdown, K-rasV12 and EGFR L858R mutations). As a model of long-term tobacco exposure, NNK- treated HBEC cells are also being utilized. In addition to selected proliferation assays, we assessed each agent against HBEC cell lines and evaluated a 50 protein luminex profile as well as a panel of more than 700 micro RNAs. These potential chemopreventive agents reveal specific patterns of alterations in proliferation, gene expression, protein secretion and microRNA profiles. Based on these findings, assessment of combinations of preventive agents are in progress. We anticipate that these methods will assist in the development of agent specific biomarkers and a personalized approach to chemoprevention for lung cancer.
This work is supported by the UCLA SPORE in Lung Cancer P50 90388, UT Southwestern SPORE in Lung Cancer P50CA75907 and The Flight Attendant Medical Research Institute (FAMRI) Young Clinical Scientist Awards.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A136.
Abstract A137: NO initiates progression of human melanoma via a feedback loop mediated by APE/Ref-1, new opportunities for chemoprevention.
Authors: Yang Zhen , Yang Sun , Misner Bobbye , Chiu Rita , Meyskens Frank 
Published: May 2012

Abstract
A137
It is well recognized that nitric oxide (NO) is involved in tumor progression, including melanoma. Measurement of proliferative and metastatic capacity by MTS and Matrigel-invasion assays respectively were done. NO-treated melanoma cells(especially metastatic Lu1205) exhibited a higher capacity compared with control, especially metastatic Lu 1205 cells. Apurinic/apyrimidinic endonuclease-1/redox effector factor-1 (APE/Ref-1) is a multifunctional protein, and its role in tumor biology has attracted considerable attention. To determine whether APE/Ref-1 plays a role in mediating NO-stimulation of melanoma progression, we investigated the effect of DETA/NO on levels of APE/Ref-1 and related downstream targets (Activator Protein-1 (AP-1)/Jun D, Matrix Metalloproteinase-1 (MMP-1), Bcl-2, and inducible nitric oxide synthase (iNOS)) by Western Blot and RT-PCR analysis. Following DETA/NO treatment, APE/Ref-1 and other downstream molecules were induced. Knockdown of APE/Ref-1 or AP-1/Jun D by specific siRNA markedly reversed the induction by NO stress of target proteins. These results present evidence for the existence of a functional feedback loop contributing to progression and metastatic capacity of melanoma cells. Resveratrol has been demonstrated to be an APE/Ref-1 inhibitor, and significant decreases in AP-1/JunD, MMP-1, Bcl-2, and iNOS protein levels occurred after exposure to resveratrol. This phenolic antioxidant as well as other inhibitors of Ref-1 may be an appropriate choice for combining with other compounds against melanoma cells that develop resistance by up-regulations of these molecules.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A137.
Abstract A138: Vaccination with HPV 16 L2E6E7 with GPI-0100 adjuvant elicits protective humoral as well as cell-mediated immune responses
Authors: Karanam Balasubramanyam , Roden Richard , Gambhira Ratish , Jagu Subhashini 
Published: May 2012

Abstract
A138
L1 virus-like particle (VLP) vaccines provide effective protection against Human papillomavirus (HPV) type from which the L1 was derived via the induction of neutralizing antibodies. While partial protection can occur against very closely related types, it is generally type-restricted and necessitates highly multivalent L1 VLP vaccines to obtain broad coverage. The minor capsid protein, L2, is emerging as an attractive alternative cross-protective antigen. Unfortunately, neither L1 VLP nor L2-based vaccines are effective against pre-existing disease, suggesting the need to develop therapeutic vaccines. Unlike the capsid proteins, the E6 and E7 oncoproteins are both required to maintain and expressed throughout cervical intraepithelial neoplasia (CIN) and cancer. TA-CIN, a vaccine comprising the HPV16 L2, E6 and E7 in a single tandem fusion protein, attempts to combine the advantages of broad cross-protection against HPV transmission with therapeutic responses targeting HPV16 early proteins. Here we test TA-CIN formulated along with GPI-0100, a semi-synthetic quillaja saponin analog, that was developed to promote both humoral and cellular immune responses. TA-CIN administered subcutaneously to mice three times at monthly intervals (125μg of clinical-grade protein) with 50μg GMP-grade GPI-0100 was found to elicit high titer antibodies that effectively neutralized not only HPV16 but also other oncogenic HPV types including HPV18, HPV31, HPV45, HPV58. Similarly, vaccination of pigtail macaques (Macaca nemestrina) with TA-CIN (three doses of 125μg of TA-CIN with 1000μg GMP-grade GPI-0100 at monthly intervals) was well tolerated and induced serum antibodies that neutralized HPV16, HPV18, and HPV31 in vitro. Notably, vaccination of mice with TA-CIN protected them from cutaneous HPV16 challenge as effectively as HPV16 L1 VLP. Combination of TA-CIN along with adjuvant GPI-0100 enhanced production of E7-specific, interferon gamma producing CD8+ T cell precursors by 20-fold. Vaccination with TA-CIN in adjuvant GPI-0100 completely prevented tumor growth after challenge with 5 x 104 HPV16-transformed TC-1 tumor cells. Protection of the mice immunized with TA-CIN plus GPI-0100 against TC-1 in a prophylactic setting was significantly more effective than TA-CIN alone or GPI-0100 alone. Patients vaccinated with TA-CIN alone develop weak HPV neutralizing antibody and E6/E7-specific T cell responses. GPI-0100 has been used safely as an adjuvant in several human trials suggesting that the combination of TA-CIN and GPI-0100 warrants further study.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A138.
Abstract A28: Loss of inhibitory IRS-1 phosphorylation is an early event in mTOR-dependent endometrial hyperplasia and carcinoma
Authors: McCampbell Adrienne , Harris Heather , Crabtree Judy , Winneker Richard , Walker Cheryl , Broaddus Russell 
Published: May 2012

Abstract
A28
Activation of IGF-I receptor signaling contributes to the development of endometrioid-type endometrial carcinoma in humans and in rodent models. This signaling pathway is under both positive and negative regulation, including S6K phosphorylation of IRS-1 at S636/639, which occurs downstream of mTOR activation to inhibit this adapter protein. We observed activation of mTOR signaling with a high frequency in human endometrial hyperplasia and carcinoma, but an absence of IRS1 phosphorylation at S636/639, despite the high levels of activated S6K in these tumors. To explore when during disease progression mTOR activation and loss of inhibitory IRS-1 phosphorylation occurred, we utilized the Eker rat (Tsc2Ek/+) model for this disease, where endometrial hyperplasia develops as a result of loss of Tsc2, the “gatekeeper” for mTOR signaling. We observed mTOR activation early in progression in hyperplasias and in some histologically normal appearing epithelial cells, suggesting that event(s) in addition to loss of Tsc2 were required for progression to hyperplasia. In contrast, IRS-1 phosphorylation at S636/639 was observed in normal appearing epithelium, but was absent from all hyperplasias, indicating loss of IRS-1 inhibition by S6K occurred during progression to hyperplasia. Furthermore, treatment of Eker rats with an mTOR inhibitor resulted in a decreased incidence of endometrial hyperplasia [54/79 hyperplasias/uterine cross section in vehicle controls to 6/90 in treated rats (p&lt;0.001)] and decreased the proliferative index of hyperplastic endometrial epithelial cells by &gt;95% (p &lt; 0.05). Since progression from normal epithelium to endometrial carcinoma proceeds via the intermediate step of endometrial hyperplasia, these data suggest a progression sequence where activation of mTOR is followed by loss of negative feedback to IRS-1 during the initial stages of development of this disease.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A28.
Abstract A3: Bcl-w-induced invasive pathways in gastric cancer cells
Authors: Um Hong Duck , Bae In Hwa , Yoon Sung Hwan 
Published: May 2012

Abstract
A3
We have reported previously that Bcl-w, a pro-survival member ofthe Bcl-2 family, is expressed in gastric cancer cells, particularly in those with an infiltrative morphology. Functional studies utilizing Bcl-w-overexpressing cells have consistently demonstrated that Bcl-w enhances not only the survivability of the cancer cells, but also their migratory and invasive potentials. The Bcl-w-induced invasive pathway was determined to involve a sequential activation of phosphoinositide 3-kinase (PI3K), Akt, and Sp1, which subsequently results in the expression of metalloproteinase-2 (MMP-2). In this study, we have demonstrated that Bcl-w also induces the urokinase-type plasminogen activator(uPA), which was prevented by treatment with pharmacological inhibitors of PI3K, Akt, or Sp1. These inhibitors also attenuated the ability of Bcl-w to promote cell migration. Similar results were obtained when the actions of MMP-2 and uPA were blocked using their inhibitors or small interfering RNAs (siRNAs), thereby suggesting that these enzymes stimulate migratory signals in this system. Bcl-w overexpression was shown to activate focal adhesion kinase (FAK) in a manner dependent on PI3K, Akt, Sp1, MMP-2, and uPA, and the prevention of FAK action using its siRNAs or dominant negative mutants abolished Bcl-w-induced migration. Overall, it appears that Bcl-w induces both MMP-2 and uPA via the PI3K-Akt-Sp1 pathway, which then promotes cell invasion not only via the degradation of the extracellular matrix, but also via the stimulation of the FAK-dependent migratory pathway.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A3.
Abstract A30: MicroRNA-27a functions as an oncogene in gastric adenocarcinoma by targeting prohibitin
Authors: Tang Hua , Liu Tao , Lang Yuanyuan , Liu Min , Li Yixuan , Li Xin 
Published: May 2012

Abstract
A30
MicroRNAs (miRNAs) may function as oncogenes or tumor suppressors. Here, we show that miR-27a is up-regulated in human gastric adenocarcinoma. Suppression of miR-27a inhibits gastric cancer cell growth. Subsequently, prohibitin is identified as a potential miR-27a target, combining bioinformatics and microarray analysis. EGFP report experiment also confirms that the 3’ untranslated region (3’ UTR) of prohibitin carries the directly binding site of miR-27a. After knockdown of miR-27a in gastric cancer cells, mRNA level and protein level of prohibitin are both elevated. Down-regulation of prohibitin by miR-27a may explain why suppression ofmiR-27a can inhibit gastric cancer cell growth, further supporting that miR-27a functions as an oncogene.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A30.