bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3260: Allele-specific tumor spectrum in Pten knockin mice
Authors: Wang Hui , Karikomi Matt , Naidu Shan , Rajmohan Ravi , Caserta Enrico , Chen Hui-Zi , Rawahneh Maysoon , Moffitt Julie , Stephens Julie A. , Fernandez Soledad A. , Weinstein Michael , Perle Krista La , Stromberg Paul , Rosol Thomas J. , Eng Charis , Ostrowski Michael C. , Leone Gustavo 
Published: February 2011

Abstract
Germline mutations in the PTEN tumor suppressor cause Cowden and Bannayan-Riley-Ruvalcaba syndromes, two dominantly inherited disorders characterized by mental retardation, multiple hamartomas and variable cancer risk. Here we modeled three sentinel mutant alleles of PTEN identified in Cowden patients and show that the nonsense PtenΔ4–5 and missense PtenC124R and PtenG129E alleles lacking lipid phosphatase activity cause similar developmental abnormalities but distinct tumor spectra with varying severity and age-of-onset. Allele-specific differences may be accounted by loss-of-function for Pten Δ4-5, hypomorphic function for PtenC124R and gain-of-function for PtenG129E. These data demonstrate that the variable tumor phenotypes observed in Cowden and Bannayan-Riley-Ruvalcaba syndrome patients can be attributed to specific mutations in PTEN that alter protein function through distinct mechanisms.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3260.
Abstract 3265: Immortalization and comprehensive characterization of a human ovarian adenocarcinoma cell line derived from an Ashkenazi Jewish patient
Authors: Rozenblum Ester , Sotelo Jose , Kim Gina Y. , Korolevich Susana , Liao Hongling , Cherry James , Munroe David J. , Roschke Anna 
Published: February 2011

Abstract
We have established and characterized a new ovarian cancer cell line derived from stage IV serous ovarian adenocarcinoma metastatic tissue from a 47 year old Ashkenazi Jewish patient. The patient developed ovarian cancer at age 44 and died of the disease at age 48. The tissue was obtained after an extensive secondary cytoreductive intraperitoneal surgery. Prior to the surgery the patient underwent primary cytoreduction followed by several systemic therapies with recurrences. A culture of the metastatic tissue was transfected with Simian Virus 40 Large T-Antigen and telomerase. The cell line has been in culture on and off during 3 years.
The identity of the cell line was confirmed by Short Tandem Repeat genotyping on genomic DNA extracted from early and late passages as well as from frozen metastatic tissue. The cell line was further characterized by array-Comparative Genomic Hybridization and gene expression microarray; and by Spectral Karyotyping and Fluorescent In Situ Hybridization. The results of these analyses were compared, when appropriate, with those of frozen metastatic tissue. A low level of genetic instability was detected in the cell line, but the karyotypes seem to be near diploid and relatively stable, after several years of cultivation.
We believe that this novel ovarian cancer cell line could contribute to the understanding of the molecular genetic basis of the disease in this advanced stage, and be representative of the tumors of a great number of patients that become resistant to the majority if not all known cancer therapies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3265.
Abstract 3267: Human population based engineered breast tumor model for in vivo biomarker discovery
Authors: Wu Min , Clark Kimberly , Deng Nanhua , Cai Zuhua , Serpa Megan E. , Zi Tong , Sun Xiaojian , Nicoletti Richard , Sun Kathryn , Feng Bing , Lin Jie , Heyer Joerg , Chiu M Isabel , Robinson Murray O. 
Published: February 2011

Abstract
Human breast cancer development is a complex pathobiological process driven by genetic changes in normal epithelial cells which lead to uncontrollable growth in a permissive microenvironment. Therefore, it is not surprising that tumors from different patients exhibit variable responses to standard of care therapy with unfortunately only a small percentage of patients benefitting from therapy. It has therefore become a priority in oncology and personalized medicine to match patients to drugs that will result in a favorable treatment outcome. In this report, we describe a population based approach for response prediction featuring naturally occurring variation in tumors derived from genetically defined human-in-mouse models of cancer.
De novo human breast tumors were generated by genetically engineering normal primary human breast epithelial cells with HER2 and SV40 early region (HER2/SV40er) or KRAS and SV40 early region (KRAS/SV40er) in an in vivo Human_In_Mouse (HIM) tissue transgenic model. The HER2/SV40er and the KRAS/SV40er HIM tumors develop as human breast adenocarcinoma that are histologically similar to those observed in patients. Also similar to that observed in human tumors, microarray profiling demonstrated significant inter-tumor variation among the established tumors. Moreover, the KRAS/SV40er tumors could be clustered with basal type breast cancers from patients, a poor prognosis human breast cancer subtype. Both HER2/SV40er and KRAS/SV40er tumors exhibited variable responses to treatments with the potent selective triple VEGFR inhibitor, tivozanib. Further characterization of those tumors, both pre- and post- treatment, identified potential biomarkers for tumor response to tivozanib. This population-based approach enables us to identify and validate biomarkers of therapeutic response in an in vivo human tumor model.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3267.
Abstract 3268: Alcohol, obesity and estrogen modulate mammary tumor growth through adiposity and angiogenensis
Authors: Hong Jina , Holcomb Valerie B. , Nunez Nomeli P. 
Published: February 2011

Abstract
Alcohol, obesity and estrogen modulate mammary tumor growth through adiposity and angiogenensis
Jina Hong, Valerie B. Holcomb, and Nomelí P Núñez
Background: Alcohol consumption increases breast cancer risk in women. Postmenopausal women who consume alcohol come in all shapes and sizes, including overweight and obese; some of these women may also take estrogen to prevent the side effects of menopause. It is unclear whether the effects of alcohol on breast cancer development are modified by body weight or exogenous estrogen. In this study, we will determine if the effects alcohol on breast cancer are modified by body weight and exogenous estrogen.
Methods: To determine whether the effects of alcohol on mammary cancer are modified by body weight, we injected subcutaneously Met-1 mouse mammary cancer cells to lean, overweight, and obese female mice consuming water or alcohol. Likewise, to determine if the effects of alcohol on mammary tumorigenesis are modified by exogenous estrogen, we implanted estrogen pellets (0.18mg/day or 0.72mg/day) into ovariectomized female mice; subsequently, we injected Met-1 cancer cells into these mice and then measured tumor growth.
Results: Results show that alcohol-consuming mice were more insulin sensitive than water-consuming mice; also, alcohol-consuming mice developed earlier and larger tumors than water-consuming mice (p&lt;0.05). Our data show that obese mice developed larger tumors than lean mice. Obese mice had higher levels of insulin, IGF-1, and leptin. The only mammary tumor growth factor that was increased by alcohol consumption was leptin (p&lt;0.05). Additionally, alcohol intake increased the pro-angiogenesis factor VEGF (p&lt;0.05).
Conclusion: Results suggest that alcohol consumption, obesity, and estrogen treatment modulate mammary tumorigenesis through adipose tissue and angiogenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3268.
Abstract 3270: Environmental stress results in an earlier onset of tumors in a HER2/Neu breast cancer model
Authors: Bovbjerg Dana H. , Henning Jill D. , Gutkin Dmitriy W. , Potter Douglas M. , McCarty Kenneth S. , Jenkins Frank J. 
Published: February 2011

Abstract
Introduction
Possible environmental effects on the development of HER2+ breast cancer have received relatively little research attention. Here we used the well-established MMTV-neu mouse model, which overexpresses mammary ErbB2 (HER2-neu) and stochastically develops primary tumors over 6-12 months, to test the hypothesis that chronic exposure to environmental stressors may result in an earlier onset of tumors.
Experimental Procedures
Female mice (FVB/N-Tg(MMTVneu)202Mul/J) were purchased from Jackson Labs at age 4-5 weeks, housed in standard cages in an isolation chamber in a controlled-access animal room, and randomly assigned to one of four experimental exposure conditions in a factorial design that was maintained for the course of the study: 1) Restraint stress (RS) 90 min - 1x/wk (n=24); 2) Social disruption stress (SD) (via cage mate switching across home cages) 2x/wk (n=23); 3) RS&SD (n=22); 4) home cage control (HC)(n=20). Mice were visually inspected and palpated for tumor development 1x/wk (blinded as to treatment group). All mammary glands from each mouse were processed for histologic evaluation one week following positive tumor palpation. All palpated tumors were histologically confirmed by a pathologist's evaluation of H&E sections (blinded as to treatment group).
Results
Consistent with the study hypothesis, the results indicated that mice chronically exposed to the two environmental stressors (RS&SD) developed primary tumors at a significantly (p&lt;0.002, Cox regression) younger age (mean +/− se: 29.8 +/− 0.7 wk) than the controls (HC) (34.4 +/− 0.8 wk). The mice chronically exposed to just one of the stressors developed tumors at an intermediate age (RS = 32.0 +/− 0.8; SD = 32.3 +/− 0.8 wk), suggesting a possible additive pattern of stress responses. Consistent with stress effects early in the process of tumorigenesis, evidence of mammary hyperplasia in the H&E sections was also significantly (p&lt;0.04) more frequent in mice exposed to both stressors (RS&SD) compared with the control group (HC). Body weights increased significantly over the entire course of the study and did not differ across groups, suggesting that the group differences in tumor development were not due to a failure to thrive.
Conclusions
Exposure to environmental stressors may speed the development of tumors in this transgenic model of HER2+ breast cancer. These novel findings suggest the importance of further investigation to determine the mechanisms responsible for these effects of exposure to environmental stressors.
(Support: CA120795)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3270.
Abstract 3272: Chromosome engineered mouse model for human 8q24 amplicon observed in breast cancer patients
Authors: Tseng Yuen-Yi , Schwertfeger Kathryn L. , Bagchi Anindya 
Published: February 2011

Abstract
Chromosomal abnormalities like deletion, amplification and translocation are hallmarks of almost all the cancers. Amplification of human 8q24, a locus that contains the proto-oncogene C-MYC has been implicated in many human cancers, particularly in solid tumors. Importantly, this amplification is often associated with poor progonosis of breast cancer. Mouse models for studying the effects of c-Myc overexpression have been helpful in elucidating its in neoplastic transformation. However, the mammary tumors arising in these transgenic animals are focal and form with variable latency, strongly suggesting the need for additional genetic lesion to mirror the highly penetrant and aggressive tumors associated with C-MYC amplification. Moreover, in many cancers, C-MYC is co-amplified with the neighboring genetic elements which have also been implicated in tumorigenesis in multiple studies. We argue that overexpression of C-MYC alone is not sufficient to result in the poor prognosis seen in the breast cancer patients with 8q24 amplification and hypothesize that additional genes in the 8q24 amplicon contribute substantially to the mammary tumor initiation and/or aggressive progression of neoplasia. To test this hypothesis, we are modeling this genetic lesion in mice by using chromosome engineering to generate an altered allele containing a 4.5 Mb amplification in mouse chromosome 15 syntenic to Hu 8q24. The tumor susceptibility of these mice are compared with the ones that harbor an amplification of c-myc gene alone. Also, human breast tumors arising from BRCA1 mutations have been reported to have higher incidence of 8q24 amplifications (53%) than are usually found in sporadic breast cancers (10-15%). We hypothesize that a 4.5 Mb amplification of 8q24 has deleterious effects on BRCA1 linked breast cancer, resulting in poor outcome in these patients. To test this hypothesis, we will cross the mice carrying amplification of the 4.5 Mb c-myc locus with brca1 mutant mice. The effects of these amplifications on mammary tumorigenesis will be assessed by scoring the latency of mammary tumors arising in these mice.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3272.
Abstract 3273: Prolactin promotes breast lesion progression and alters tumor histotype
Authors: O'Leary Kathleen A. , Moser Amy R. , Schuler Linda A. 
Published: February 2011

Abstract
Prolactin (PRL) is critical for mammary development and lactation. Epidemiological studies also support a role for PRL in breast cancer (1). In order to study the contributions of PRL to tumor development and progression, we developed a transgenic mouse model that expresses PRL in the mammary epithelial cells (NRL-PRL), mimicking the mammary PRL production in women (2). To explore the interactions of PRL and Wnts in mammary tumorigenesis, NRL-PRL mice were crossed with APCmin/+ mice, which have elevated canonical Wnt signals secondary to reduced β-catenin degradation. Females were administered a single ip dose of ENU (50 mg/kg body weight) at 35-40 days of age. This paradigm in the F1 (FVB/N x C57BL/6J) strain background resulted in few mammary tumors (14%) in NRL-PRL nonparous females. APCmin/+ animals developed tumors at a slightly higher incidence (27%), as previously reported (3). However, penetrance rose to 66% in NRL-PRL/APCmin/+ females, indicating that PRL potentiates APCmin/+-induced tumorigenesis (P=0.008). The presence of PRL also strongly impacted the tumor histotype (P&lt;0.0001). The majority of tumors in APCmin/+ animals were composed of squamous nodules with pilar lesions (63%), while tumors in PRL/ APCmin/+ animals were most often adenocarcinomas of varying histotype (75%). Glands from younger age-matched nonparous females (120 d), prior to palpable lesions, were examined to begin to determine the mechanism of PRL actions. Analyses of “whole mounted” glands showed that both APCmin/+ and PRL/ APCmin/+ animals exhibited multiple epithelial hyperplasias. However, although the numbers of hyperplasias were similar between the two genotypes, the lesions were significantly larger in the PRL/ APCmin/+ glands (P&lt;0.05). This correlated with an increase in the proliferation rate (P&lt;0.01), but no change in apoptosis. Thus, PRL appears to promote tumor progression and affect factors influencing tumor histotype in the APCmin/+ model. The NRL-PRL mouse provides a means of studying how PRL promotes breast cancer alone and in conjunction with other oncogenes.
1Tworoger SS, Hankinson SE. (2008) J Mammary Gland Biol Neoplasia. 13:41-53.
2Arendt LM, Schuler LA. (2008) J Mammary Gland Biol Neoplasia. 13:29-40.
3Moser AR, Hegge LF, Cardiff RD. (2001) Cancer Res. 61: 3480-3485.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3273.
Abstract 3274: Loss of interleukin 10 (IL-10) decreases mouse mammary gland development and lactogenic differentiation
Authors: Masso-Welch Patricia , Merhige Patricia M. , Veeranki Omkara Lakshmi M. , Kuo Shiu-Ming 
Published: February 2011

Abstract
Increased expression of IL-10 has been associated with a decreased breast cancer risk but the mechanism is not clear. The purpose of this study was to examine the effects of IL-10 loss on mouse mammary gland development. Female wild-type and IL-10 knockout mouse littermates born to and raised by IL-10 +/− mothers were maintained under specific pathogen-free (SPF) condition with NIH31 diet. They were sacrificed at days 21, 50-55, 80, and 150 of postnatal age, and at day 2 of lactation. IL-10 loss had no effect on body weight at any age. Whole mounts and paraffin sections of mammary glands from wild type and IL-10 knockout mice were compared for changes in development, differentiation, and the presence of any preneoplastic histologic changes. Interactions between genotype and estrus stage were also examined. Despite its role as an anti-inflammatory immune regulator, IL-10 loss did not result in the enlargement of the intramammary lymph node or frank leukocyte infiltration under SPF condition. No significant differences in mammary gland development were observed in prepubertal glands (day 21). In the pubertal gland at day 50-55 of age, loss of IL-10 was associated with significantly decreased epithelial area, decreased terminal end buds, and decreased adipose tissue. This decrease in peripheral structures and terminal end buds was maintained at day 80 and day 150 of age. Pregnancy and lactogenesis was unable to rescue this phenotype: at day 2 of lactation, the IL-10 knockout mouse maintained a decreased lobular complexity and glandular area, accompanied by abnormal retention of large adipocytes, compared to wild-type mice, consistent with published reports of decreased pup growth in pups born to and raised by IL-10 knock-out mother. Lactating IL-10 knockout mice had a significant increase in abundance of cysts, but no other signs of hyperplasia or neoplasia were present. In conclusion, IL-10 loss decreases epithelial branching in the resting gland, resulting in a compromised differentiation during lactogenesis with decreased glandular area. Although the loss of IL-10 alone was not sufficient to induce frank neoplastic changes in the resting mouse mammary gland, our observation suggests a epithelial differentiation-promoting role of IL-10 which is consistent with its association with a decreased breast cancer risk.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3274.
Abstract 328: Complex oligonucleotide libraries enable high-resolution cytogenetic analysis of human and mouse genomes with fluorescence in situ hybridization (FISH)
Authors: Ach Robert A. , Yamada N. Alice , Tsang Peter , Aleksic Kristina , Begus-Nahrmann Yvonne , Scheffer-Wong Alicia , Laderman Stephen , Lechel Andre , Rudolph K. Lenhard , Speicher Michael , Bruhn Laurakay 
Published: February 2011

Abstract
Cytogenetic analysis of chromosomes using Fluorescence in situ Hybridization (FISH) is a powerful method for the study of chromosome structure, organization, and stability. However, to date, the utility of FISH has largely depended upon access to cloned template DNA used to generate probes. Clones for specific regions are often unavailable, or the genomic template may contain repetitive and other non-informative sequences which can confound FISH analysis. We have leveraged our ability to chemically synthesize oligonucleotides in massively parallel reactions to produce DNA libraries that can be used to generate FISH probes. The sequences of the oligonucleotides in these libraries are selected in silico using empirically determined criteria so as to target only the most informative elements in the genomic region to be analyzed and avoiding any repetitive elements or regions homologous to other non-targeted loci. Our FISH protocol is similar to ones used for FISH with BAC probes. Using our methods, human chromosomal regions as small as 1.8 kb and as large as chromosome arms were successfully visualized in both metaphase and interphase cells. Using our probe design methods, we readily obtained specific and robust signals for chromosomal regions rich in repeats and/or GC content.
We also investigated the utility of these probes for studies of mouse chromosomes by generating probes for over ten loci in the mouse genome. All the probes hybridized well using cytologic and cryosectioned samples. In addition, FFPE samples showed promising preliminary results. We have also applied our FISH methods to develop chromosome-specific enumeration probes for the mouse genome at pericentromeric regions. These enumeration probes should be useful for detecting aneuploidies, polyploidies, and other genomic rearrangements that were previously difficult to study at single-cell resolution, particularly in tissue samples. Successful co-hybridization of chromosome enumeration probes and loci-specific probes in mouse intestinal crypt cells allowed for accurate copy number analyses in tissue samples. We are also continuing to explore other breakthrough applications that are enabled by our oligonucleotide-based FISH methodology.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 328.