bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1494: The role of microenvironment in mammary epithelial cell plasticity
Authors: Correia Ana Luisa , Mori Hidetoshi , Schmitt Fernando C. , Bissell Mina J. 
Published: June 2012

Abstract
Understanding breast cancer heterogeneity is crucial for the development of targeted therapeutic interventions. One source of this intratumoral diversity comes from changes induced in epithelial cells by signals they receive from the stromal microenvironment. These changes include the epithelial-to-mesenchymal transition (EMT), a process of cellular plasticity by which epithelial cells disengage cell-cell and cell-extracellular matrix interactions, alter cytoskeletal structure, and implement a transcriptional program that facilitates the acquisition of aggressive traits, such as increased motility, invasiveness and resistance to apoptosis.
Bissell lab has demonstrated that an extracellular protease, matrix metalloproteinase-3 (MMP3), is able to initiate the formation of mammary tumors in mice, as well as trigger EMT in mammary epithelial cells when activated. Furthermore, the observed EMT in MMP3-overexpressing cells was found to be dependent upon reactive oxygen species (ROS) production. However, it is not clear how this extracellular secreted protein functions with an epithelial cell to affect its intracellular events.
To understand the mechanism by which MMP3 drives transformation of mammary cells, we asked which domain of MMP3 is required for ROS production or EMT in mammary epithelial cells, and we are investigating cell surface proteins that may be target of degradation or binding partner of MMP3 during tumorigenesis. This work will unravel new candidates for specific inhibition, providing attractive options for treatment of this and other diseases in which MMP3 plays a pathological role.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1494. doi:10.1158/1538-7445.AM2011-1494
Abstract 153: Reduction of microRNAs miR-15a and miR-16-1 in odontogenic keratocyst
Authors: Gomez Ricardo S. , Diniz Marina G. , Gomes Carolina C. , Castro Wagner H. , Guimarães Andre Luiz S. , de Paula Alfredo Maurício B. 
Published: June 2012

Abstract
Odontogenic keratocyst (OKC) is a benign destructive recurrent odontogenic cystic neoplasm. MicroRNAs (miRNAs) miR-15a and miR-16-1 are small non-protein coding RNAs that function as negative regulators of the anti-apoptotic gene BCL-2 at the post-transcriptional level. Increased immunoexpression of BCL-2 protein is reported in OKC. The purpose of the present study was to investigate whether miR-15a and miR-16-1 transcription is altered in OKC and if it is associated with BCL-2 expression in such lesions. Compared to dental follicles, we found higher BCL-2 mRNA expression and immunoreactivity in OKC. Our findings also showed that miR-15a and/or miR-16-1 are downregulated in the majority of OKC samples (24/28). Furthermore, in all five OKC paired samples (primary and marsupialized lesions) investigated there was an increase in the expression of miR-15a after marsupialization. Our results suggest that OKC neoplastic cells present an anti-apoptotic profile to which lower miR-16-15a expression might contribute. Additionally, our findings strongly suggest that marsupialization reduces BCL-2 expression in the OKC and this downregulation may result from microRNA post-transcriptional activity, even though this cause-effect relationship remains to be proved.
This study was supported by FAPEMIG and CAPES, Brazil.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 153. doi:10.1158/1538-7445.AM2011-153
Abstract 1534: Laminin binding integrin functions in human bone metastatic cancer
Authors: Sroka Isis C. , Gard Jaime M.C. , Pond Erika , Pawar Sangita C. , Nagle Raymond B. , Cress Anne E. 
Published: June 2012

Abstract
Laminin binding integrins are major determinants of cancer cell migration, invasion and metastasis. In human prostate cancer, both A6B1 and A3B1 laminin-binding integrins are expressed on tumor cell surfaces as observed in either prostatectomy or needle biopsy specimens. In human breast cancer, the A6 integrin is expressed in both primary tumors and in metastatic lesions. Integrin A6B1 is post-translationally modified on the tumor cell surface by urokinase-type plasminogen activator (uPA), producing a structural variant, A6pB1. While the A6pB1 form is devoid of the ligand binding domain, A3B1 is fully functional and not subject to cleavage. In this study, we observed the continued expression of the A6B1 integrin on tumor cell surfaces within human bone metastatic lesions as well as in human tumor xenografts growing within bone. The cleavage function of the A6 integrin was found to be constitutively expressed on nine different cancer cell lines derived from breast, prostate, lung, pancreatic tumors. Interestingly, five different normal cell types expressing the adhesion active A6B1 integrin did not have the constitutive cleavage function. However, the cleavage function in normal cells was inducible by the exogenous addition of uPA. Selection of successive bone resident cancer cells selects for constitutive cleavage of A6 integrin and increasing expression of A3B1 integrin. Taken together, these data suggest that the cleavage function is constitutively activated in cancer specimens and opens the possibility cleavage mediated release from laminin binding may be coordinated with A3 dependent adhesion. (Supported in part by CA23752 and the TACMASS core service of the Arizona Cancer Center).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1534. doi:10.1158/1538-7445.AM2011-1534
Abstract 1540: Targeting PI3K/mTOR inhibitor induced survival programs abrogates resistance to cell death in ECM-attached cancer cells
Authors: Muranen Taru E. , Morales Fabiana , Selfors Laura , Worster Devin , Albeck John , Gao Sizhen , Iwanicki Marcin , Mills Gordon , Brugge Joan S. 
Published: June 2012

Abstract
Alterations in the PI3-kinase pathway are common in breast, endometrial, and ovarian cancer and are thought to serve as major drivers of proliferation and survival. Multiple compounds targeting PI3-kinase pathway are currently in clinical trials.
We have examined the sensitivity of ovarian and breast tumor cell lines to dual PI3K/mTOR inhibitors in 3D tumor spheroid assays. Interestingly, tumor cells in the center of the spheroids that are not attached to matrix are generally highly sensitive to NVP-BEZ235 and undergo apoptosis, whereas those in contact with matrix are highly resistant. In order to understand the basis for the differential sensitivity to NVP-BEZ235 and to identify candidate targets to abrogate this resistance, we performed reverse phase protein array of tumor spheroids treated with NVP-BEZ235. While NVP-BEZ235 inhibited known downstream targets of PI3K/mTOR, there was significant up-regulation of multiple proteins known to regulate cell survival including IGF1R, p-EGFR and several Bcl-2 family members. This response raised the question whether combined inhibition of PI3K/mTOR and any of the induced proteins would sensitize the matrix-attached cells. Interestingly, inhibition of Bcl-2 by ABT737 caused widespread apoptosis in the 3D structures, but only in combination with NVP-BEZ235. In addition, matrix-resistance was abrogated by combined treatment with NVP-BEZ235 and inhibition of EGFR or knockdown IGF1R.
These results indicate that inhibition of PI3K/mTOR leads to induction of several protective pathways and that suppression of these pathways can significantly enhance sensitivity to PI3K/mTOR targeted therapies. In addition, these studies suggest a rational approach to the development of combination therapies – that is, through identification of drug-induced survival pathways and targeting these pathways in combination. Our current efforts center on investigating the mechanisms of PI3K/mTOR inhibition resistance and addressing the efficacy of the dual treatment in preclinical models.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1540. doi:10.1158/1538-7445.AM2011-1540
Abstract 1556: Adipose tissue upregulates MMP9 expression in oesophageal cancer promoting invasion and migration in vitro and correlates with obesity status and poor differentiation in vivo
Authors: Pidgeon Graham Philip , Allott Emma , Donohoe Claire , Cathcart MaryClare , McGarrigle Sarah , Cummins Robert , Kay Elaine , Reynolds John 
Published: June 2012

Abstract
Introduction: Obesity is an independent risk-factor for oesophageal adenocarcinoma. Adipose tissue is an endocrine organ secreting numerous factors with different biological activities. We aimed to investigate the molecular mechanisms linking obesity and cancer in oesophageal cancer.
Methods: Adipose conditioned media (ACM) was prepared from omental adipose tissue of oesophageal adenocarcinoma patients. Proliferation of oesophageal adenocarcinoma cells(OE33, OE19) in response to ACM was examined by BrdU. OE33 cell line was co-culture with visceral adipose tissue and gene expression pathways assessed by Cancer-Pathway-Finder and Affymetrix arrays. Identified genes were assessed in 50 resected oesophageal tumours and related to clinic-pathological data. Migration and invasion following culture with ACM was assessed in oesophageal cell lines.
Results: Culture of both the OE33 and OE19 cell lines with ACM from omental adipose tissue increased proliferation by 142% and 145% respectively. Co-culture of OE33 with adipose tissue increased the expression of genes regulating invasion and metastasis between 10-5000 fold, with MMP9 the most upregulated gene and TP53 down-regulated 2-fold. Altered genes were validated in an independent cohort. Functionally, co-culture of adipose tissue with tumour cells increased both mingration and invasion of tumour cells. Notably, adipose tissue from viscerally obese patients had a significantly higher effect. Markers of focal adhesions(SPP1, integrins), endothelial mesenchymal transition(SNAI2, Laminins) and thrombosis (pai-1) were also significantly upregulated. Expression of pai-1 and MMP9 was significantly (p&lt;0.05) higher in tumours from centrally obese patients.
Conclusion: Omental adipose tissue promoted oesophageal cancer aggressiveness by increasing proliferative, migratory and invasive capacity via upregulation of MMP2, MMP9, SERPINE1, PAI-1, SPP1 and SNAI2. Upregulation of genes in tumours from obese patients suggest a molecular progression of cancer associated with excess adipose tissue.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1556. doi:10.1158/1538-7445.AM2011-1556
Abstract 1572: Characterising the tumor vasculature in vivo in mouse models of colorectal cancer using contrast enhanced high-frequency ultrasound
Authors: Marston Gemma , Jones Pam F. , Evans John A. , Hull Mark A. , Markham Alex F. , Coletta Patricia L. 
Published: June 2012

Abstract
Angiogenesis is essential for tumours to grow beyond a few millimetres in size and to metastasise, making it an attractive target for both cancer imaging and therapeutic intervention. Although microvessel density (MVD) is routinely used to assess tumour vascularity in fixed tissue, few techniques are currently available for imaging and quantitating tumour vasculature parameters in vivo.
High-frequency ultrasound (HFUS) allows high resolution, non-invasive longitudinal imaging of tumours in vivo. Incorporation of microbubble contrast agent into imaging protocols allows visualisation of the vasculature, determination of relative blood flow and perfusion, and the ability to directly target and quantify molecular biomarkers of disease in vivo.
We have been investigating in vivo tumour blood flow and vascularity in the growth of human colorectal cancer (CRC) cell xenografts. CD1 Nu/Nu mice implanted with SW480 cell xenografts were used to investigate the relationship between tumour growth and different vascular parameters obtained by contrast enhanced (CE) HFUS. Mice were imaged at day 21 and day 27 of tumour growth using the VisualSonics Vevo 770 system. A single bolus of microbubbles was injected via a syringe driver into the tail vein during 2D CE HFUS imaging, with the wash-in data loops captured prior to 3D CE HFUS imaging, and tissue samples collected for histology and immunohistochemistry. Time intensity curves were generated post-acquisition and used to determine perfusion kinetics and vascular data. A number of strongly significant correlations were observed relating in vivo and histological tumour characteristics with relative blood flow and total vascularity. These included the size of the tumour, tumour growth and the total vascular space.
This study shows that CE HFUS is a powerful qualitative and quantitative tool for the analysis of tumour angiogenesis in vivo. It provides a relatively non-invasive method to monitor tumour blood flow and vascularity in longitudinal studies thus allowing effects on angiogenesis due to therapeutic intervention to be monitored. We are currently developing this technique for use with autochthonous colorectal cancer models.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1572. doi:10.1158/1538-7445.AM2011-1572
Abstract 1611: Hepatocellular carcinoma xenograft models and biomarkers are powerful tools for the evaluation of the new drugs targeting HCC
Authors: Sun Yanmei , Zhang Juan , Li Nan , Song Xiaoming , Cai Jie , Chen Taiping , Wery Jean-Pierre , Chen Yiyou 
Published: June 2012

Abstract
Hepatocellular Carcinoma (HCC) is a major health problem, as the fifth most common cancer and the third most common cause of cancer death worldwide. Many pharmaceutical companies lead the effort to design new medicines on this cancer type. The overwhelming need to improve preclinical models of HCC requires robust models that closely mimic the disease population and therefore have the potential to better predict clinical outcome with novel therapies. Here we successfully validated subcutaneous and orthotopic xenograft models derived from HepG2, SK-HEP-1, Hep3B, PLC/PRF/5, HUH-1, HUH-7 and MHCC97H cell lines and also directly from HCC patient tumors (HuPrime®). Four HCC serum markers (AFP, α-fetoprotein; AFP-L3; DCP, Des-gamma-Carboxyprothrombin; GP73, Golgi Protein-73) have been used or will be potentially used clinically in detection of this disease. AFP is the most widely used biomarker in HCC, somehow it is not always correlated well with the liver cancer progress, even it gives false result, and some liver lesion or liver cirrhosis can also produce high level of AFP; while GP73 is reported a promising alternative as HCC serum marker. AFP and GP73 were tested at both mRNA level and protein level. They were also compared in the sensitivity and correlation with the tumor burden using the blood samples from the orthotopic xenograft models. Our results demonstrated that biomarkers released by the tumor models could well monitor the tumor take rate, growth and response to treatments. Furthermore, Sorafenib, one popular anti- HCC medicine, was tested, and the serum biomarkers could be utilized for confidence in evaluating the efficacy of Sorafenib. In conclusion, the use of HCC xenograft models combined with the biomarker strategies is helpful in maximizing the value of in vivo research and designing clinical trials
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1611. doi:10.1158/1538-7445.AM2011-1611
Abstract 1625: Role of EphB4 in esophageal cancer: Expression, amplification, and therapeutic inhibition
Authors: Hasina Rifat , Kanade Geetanjali , Yala Soheil , Mollberg Nathan , Muller Jeffery , Surati Mosmi , Kanteti Rajani , Husain Aliya , Posner Mitchell , Waxman Irvine , Vigneswaran Wickii , Ferguson Mark , Villaflor Victoria , Vokes Everette E. , Gill Parkash , Salgia Ravi 
Published: June 2012

Abstract
EphB4 is a member of the largest family of receptor tyrosine kinases (RTKs), classically associated with neural development and vascular patterning in embryonic life. The cellular responses to Eph receptor stimulation by their ephrin ligands are important in mediating a wide range of biological activities, including angiogenesis, cell segregation, cell attachment, shape, and motility. EphB4 has been showed to play an oncogenic role in a number of tumors, and we report the first investigation into its role in esophageal cancer, a disease whose survival has not improved and would benefit from the identification of new targets in its treatment. We have addressed this need by exploring the Eph/ephrin receptor tyrosine kinase pathway. We utilized tissues archived at the University of Chicago as well as commercially purchased TMAs to evaluate the expression of EphB4 by IHC. Approximately 93 squamous cell carcinoma, 100 adenocarcinoma and 25 adjacent normal control samples were utilized. In addition, four adenocarcinoma and nine squamous cell carcinma cell lines were used for in vitro studies. Statistical analysis of IHC data showed a consistently higher expression of EphB4 in both squamous and adenocarcinoma compared to adjacent normal tissue. A statistically significant correlation was established between EphB4 expression and higher grades of squamous cell carcinoma, suggesting that overexpression of EphB4 in squamous cell carcinoma is directly linked to clinically aggressive tumors. The EphB4 gene was found amplified in 8/16 squamous cell carcinoma (30% with a gene copy number ≥ 3, 30% with &gt;8 copies and 10% with a copy number of 20. Of the adenocarcinomas, 3/7 samples were amplified (43% with a gene copy number of ≥4, and 14% &gt;8 copies). Three of 9 squamous cell carcinoma cell lines had a gene copy number ≥4 and rest of them had no significant variation. Only one of four adenocarcinoma cell lines had an increased gene copy number. In vitro experiments with EphB4 specific siRNA inhibited the motility and proliferation of cultured cells and the inhibition of EphB4 specifically abrogated the phosphorylation of functional proteins associated with cell motility and proliferation, especially that of phospho-FAK and phospo-AKT, the expression of which were abrogated completely by the inhibition of EphB4. Our data imply that EphB4 plays a crucial role in esophageal cancer and should be further evaluated as a therapeutic target in this disease.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1625. doi:10.1158/1538-7445.AM2011-1625
Abstract 1713: Mechanisms of resistance to platinum based drugs uncovered by protection caused by substituted coumarins
Authors: Nolan Karen A. , Scott Katherine A. , Griffiths Gareth , Stratford Ian J. 
Published: June 2012

Abstract
Disruption of p53 can have a profound effect on cellular sensitivity to Platinum-based drugs. Inhibition of NQO1 by dicoumarol and other substituted coumarins can target p53 for degradation. Thus, we tested the ability of NQO1 inhibitors to protect HCT116 cells (containing wild type p53) against the cytotoxic effects of cisplatin. All the NQO1 inhibitors protect cells against the damaging effects of cisplatin (see the table for representative data for one of the inhibitors, AS3). Protection was also seen in a second cell line with wild type p53 (RT112 bladder carcinoma cells). To confirm p53 dependence, experiments were carried out using cells with mutant (MDA231) or null (HCT116 -/-) p53. Surprisingly, the coumarin-based agents also protected these cells against cisplatin-induced damage. In addition, these observations were not dependent on NQO1, since MDA231 cells, with negligible NQO1, and cells overexpressing NQO1 (MDA321-DTD) were similarly protected. Protection is also observed for oxaliplatin but, interestingly, there is no protection against etoposide toxicity.
Cell cycle analysis of HCT116 cells treated with cisplatin show that, 24 hours after treatment, cells are blocked in G2. When cells are given the dicoumarol analogues at the same time as the cisplatin, no cell cycle delay is observed. Further, analysis of apoptosis mediators shows that treatment with AS3 inhibits oxaliplatin induction of Bak and reduces caspase-3 activity. Understanding the mechanism by which treatment with the dicoumarol analogues can cause resistance to cisplatin could reveal new methods for potentially overcoming resistance to platinum-based drugs in the clinic.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1713. doi:10.1158/1538-7445.AM2011-1713
Abstract 220: BRCA1 regulates p53 target expression via DNp73
Authors: Scata Kimberly A. , El-Deiry Wafik S. 
Published: June 2012

Abstract
In response to cellular stresses, the tumor suppressor gene p53 is stabilized and transactivates several categories of target genes, including cell cycle arrest genes and pro-apoptotic genes. These sets of genes are not activated simultaneously and how the differential expression of these targets occurs has been the subject of intense scrutiny. We have previously shown that overexpression of BRCA1 stabilizes p53 but fails to activate the expression of its proapoptotic targets. When BRCA1 is overexpressed, the posttranslational modifications of p53 are the same as those that occur in response to stress and p53 is still able to bind to the promoters of the proapoptotic targets. In order to determine how BRCA1 regulates p53 gene expression, we've explored the role of the p53 family members. We find that BRCA1 is able to induce DNp73, a dominant negative acting isoform of p73. Unexpectedly, we found that BRCA1 upregulates DNp73 expression, an isoform of the p53 family member p73 lacking the transactivation domain, which has been previously implicated in cell survival. This observation has important implications for understanding the selectivity of p53-dependent transcription as well as the tumor suppressive action of BRCA1 that favors DNA repair over cell death.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 220. doi:10.1158/1538-7445.AM2011-220