bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3413: A population of metastatic colorectal cancer (mCRC) patients with radiologically proven liver metastasis and EpCAM expressing primary tumors show low circulating tumor cell counts by Veridex Cellsearch
Authors: Das Avisnata , Joudeh Jamal , Peters Kristi L. , Allen Joshua E. , Zheng Siyang , Dicker David T. , Yang Zhaohai , El-Deiry Wafik S. 
Published: August 2012

Abstract
Circulating tumor cells (CTCs) have prognostic significance for metastatic cancers including colorectal, breast and prostate cancer. We have been evaluating CTC numbers as well as molecular markers as prognostic, treatment and disease-monitoring tools. The FDA recommends a cutoff value of &gt; 3 CTCs/7.5 ml of blood, using Johnson & Johnson Veridex Cellsearch technology as indicator of poor prognosis for metastatic colorectal cancer (mCRC). We report identifying a population of patients who have advanced disease and liver metastases (shown by CT/MRI/PET scan) but the CTC count using our CLIA-certified Veridex Cellsearch laboratory was &lt;3/7.5 ml of blood. As Cellsearch technology relies on Epithelial Cell Adhesion Molecule (EpCAM) expression for isolation of CTCs, we analysed the primary tumors for EpCAM positivity using immunostaining. All 5 patients we have identified so far showed moderate to strong EpCAM expression in their primary tumor. The low CTC count in these patients with reference to the FDA standard raises a question regarding use of CTC counts as an independent tool for measuring advanced disease as liver metastasis signifies progressive disease and is generally associated with poorer outcome. The epithelial-to-mesenchymal transition (EMT) in tumor cells in blood may provide a possible mechanism for loss of EpCAM expression in some CTCs although we have certainly detected similar patients with liver metastases from CRC with elevated levels of CTCs including about 10-15% of such CRC patients with very high levels at ∼10-20 times the cut-off of 3 CTCs/7.5 ml of blood. Technologies that involve detection of cancer cell proteins and do not rely on EpCAM-based isolation (eg. multiplex PCR) are not currently approved by the FDA for clinical application but may provide insights into this problem. Alternatively we are using microfluidic devices, that rely on size-based capture of CTCs in attempts to determine if such patients with liver metastases and no detectable CTCs by Veridex may have tumor cells that may be captured. We are particularly interested in determining whether the biology of the tumors varies among patients with liver metastases from CRC with no measurable CTCs versus those patients with high levels of CTCs. In this regard we are pursuing molecular characterization of primary tumors looking for possible molecular insights among these cohorts.
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 3413. doi:1538-7445.AM2012-3413
Abstract 3416: Ubiquitous Brms1 expression is critical for mammary carcinoma metastasis suppression via promotion of apoptosis
Authors: Cook Leah M. , Cao Xuemei , Dowell Alexander E. , Frost Andra A. , Desmond Renee A. , Edmonds Mick D. , Kesterson Robert A. , Hurst Douglas R. , Welch Danny R. 
Published: August 2012

Abstract
Morbidity and mortality in breast cancer patients are drastically increased when primary tumor cells are able to spread to distant sites and proliferate to become secondary lesions. Effective treatment of metastatic disease has been limited; therefore, increased molecular understanding to identify biomarkers and targets is needed. We have previously shown that breast cancer metastasis suppressor 1 (Brms1) can suppress development of pulmonary metastases when expressed in a variety of cancer types, including metastatic mammary carcinoma. Our lab has developed two transgenic Brms1 mouse models, one which expresses murine Brms1 cDNA specifically in mammary tissue (expression by the mouse mammary tumor virus (MMTV) promoter) and a ubiquitous Brms1 expression model (expression by the chicken beta actin promoter). The goal of this study was to investigate mechanisms of Brms1-mediated metastasis suppression in transgenic mice that express Brms1 using a polyoma middle T (PyMT) oncogene-induced model. Brms1 expression, either ubiquitously or predominantly in the mammary gland, did not significantly alter growth of the primary tumor, confirming earlier studies. When expressed ubiquitously, Brms1 suppressed pulmonary metastasis and promoted tumor cell apoptosis in the lung but not in the mammary gland. However, selective expression of Brms1 in the mammary gland using the MMTV promoter did not significantly block metastasis nor did it promote apoptosis in mammary glands or lungs despite increased expression within primary tumors and the lungs. These results suggest tissue- or cell-type specific expression of Brms1 is a critical determinant for Brms1-mediated metastasis suppression.
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 3416. doi:1538-7445.AM2012-3416
Abstract 3417: An in vivo functional screen to identify metastasis suppressor genes
Authors: Murugaesu Nirupa , Iravani Marjan , Johnson Damian , Antonopoulos Aristotelis , Sims David , Fenwick Kerry , Mitsopoulos Costas , Gao Qiong , Orr Nick , Zvelebil Marketa , Haslam Stuart , Dell Anne , Lord Christopher , Ashworth Alan , Isacke Clare 
Published: August 2012

Abstract
Background When breast carcinomas remain confined to breast tissue, cure rates exceed 90% (http://seer.cancer.gov/csr/1975_2006/). However, if the cancer disseminates through the body, long-term survival decreases depending upon the extent of, and the sites of, colonisation Genes that control the different stages of the metastatic process need to be identified to better delineate the process, and to aid in the development of metastatic biomarkers and provide potential targets for the treatment of metastatic disease. Genetic screens, such as those that exploit RNA interference (RNAi), provide an unbiased approach to the identification of genes associated with a phenotype of interest. Although cell-based screens have been highly informative in identifying genes involved in tumour cell survival, migration and invasion, these in vitro approaches are largely unsuitable for interrogating the later stages of the metastatic process, in particular the processes of cell dissemination, tumour cell extravasation from the circulation and colonisation of secondary sites. Method Using the 4T1 mouse model an in vivo functional metastasis screen that integrates RNAi technology and massively parallel sequencing was implemented to rapidly discover and validate metastasis genes. Results Using this approach, 12 ‘hits’ that suppress tumour cell colonisation of the lungs were identified. 3 of the top 5 hits have been validated as novel metastasis suppressor genes in both mouse and human cell lines and further studies have been undertaken to elucidate the mechanism of action of the top hit. Critically, these findings are clinically relevant in primary breast cancers where there is a significant correlation between elevated expression levels of these suppressor genes and reduced frequency of metastatic events. Conclusion This study demonstrates the value of adopting an unbiased methodology to discover novel metastatic genes and establishes, for the first time, that an in vivo metastasis screen can be combined with next generation sequencing to identify novel components of the metastatic process.
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 3417. doi:1538-7445.AM2012-3417
Abstract 342: Silencing of IGF1R induces mesenchymal-to-epithelial transition and inhibits the metastatic properties of triple negative breast cancer cells
Authors: Taliaferro-Smith LaTonia D. , Oberlick Elaine M. , Liu Tongriu , Adams Amy , Eggers Carrie , Kline Erik , Nagaraju Ganji P. , Cohen Cynthia , Marcus Adam , O'Regan Ruth 
Published: August 2012

Abstract
Next to skin cancer, breast cancer is the second most common cancer diagnosed among American women and affects nearly 1.3 million women worldwide each year. Aggressive, metastatic disease is directly responsible for the majority of breast cancer-related deaths. Breast tumors lacking expression of three receptors, estrogen receptor (ER), progesterone receptor (PR), and HER2, are commonly referred to as triple negative breast cancers (TNBCs) and make up 15-20% of all diagnosed breast cancers cases. Disparities exist in terms of survival following diagnosis of TNBC, and a devastating reality is that this diagnosis is highly correlated with incurable, metastatic disease. Despite tremendous advantages in treatments for hormone-sensitive breast tumors, a significant number of women with TNBC experience disease progression due to the unavailability of targeted therapies. Insulin-like growth factor-1 receptor (IGF1R) plays a role in breast cancer proliferation, adhesion, invasion, and migration. Overexpression of IGF1R has been noted in 50% of primary breast tumors and in nearly 65% of TNBCs. Consequently, high IGF1R expression in breast cancers correlates well with, high tumor grade, shorter disease-free survival, and poor prognosis. We report the in vitro effects of IGF1R inhibition on the metastatic properties of mesenchymal TNBC cells lines using two methods: (1) shRNA lentiviral system and (2) picropodophyllin (PPP), an IGF1R tyrosine kinase inhibitor. Stably transfected mesenchymal TNBC cells showed down-regulation of IGF1R protein levels, which resulted in mesenchymal-epithelial-transition (MET), as confirmed by up-regulation of epithelial marker, E-cadherin, and down-regulation of mesenchymal marker, vimentin. Importantly, this MET was accompanied by reduced colony formation, cell motility, and invasion. Cell survival assays and fluorescence-activated cell sorting (FACS) analysis revealed that PPP also effectively decreased cell viability and induced cell death, respectively, in TNBC cells. Furthermore, PPP dramatically inhibited cell invasion and migration. Our findings indicate that inhibitors of IGF1R exhibit promising anti-cancer activity in TNBC cells of mesenchymal origin by triggering MET, inducing cell death, and reducing invasive and metastatic properties. Given the very poor outcomes for patients with metastatic TNBCs, we believe the use of IGF1R inhibitors warrant further investigation as prospective anti-cancer options for treating a subset of mesenchymal TN breast carcinomas.
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 342. doi:1538-7445.AM2012-342
Abstract 3422: N-α-acetyltransferase 10 protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity
Authors: Hua Kuo-Tai , Tan Ching-Ting , Chen Chi-Kuan , Chen Min-Wei , Hsiao Michael , Kuo Min-Liang 
Published: August 2012

Abstract
80%-90% of eukaryotic proteins are N-α-terminally acetylated. They are mediated by specific N-α-acetyltransferases. However, the biological importance of these N-α-acetyltransferases remains largely unknown. Recently, these N-α-acetyltransferases have been recognized as important characters in many biological processes, including embryonic development, neuron disease and cancer. N-α-acetyltransferase A (Nat A) was first characterized in yeast, it composed of Naa10p, also known as hARD1 (human Arrest defective 1), and Naa15p, also known as NATH (N-acetyl transferase human), are responsible for the N-α-acetylation of majority proteins in mammalian cells. Naa10p is known to be involved in cell cycle control and apoptosis. However, the role of Naa10p in human cancers is elusive. In this study, we found that elevated Naa10p levels are associated with less metastasis to lymph nodes and better prognosis of cancer patients. Naa10p significantly suppressed migration, tumor growth, and metastasis independent of its enzymatic activity. Instead, Naa10p binds to the GIT-binding domain of PIX, thereby preventing the formation of the GIT-PIX-Paxillin complex, resulting in reduced intrinsic Cdc42/Rac1 activity and decreased cell migration. Forced expression of PIX in Naa10-transfected tumor cells restored the migration and metastasis ability. We suggest that Naa10p functions as a tumor metastasis suppressor by disrupting the migratory complex, PIX-GIT- Paxillin, in cancer cells. Our study not only highlights the potential of Naa10p as a therapeutic target for tumor metastasis, but also identifies Naa10p as a regulatory component of the migration complex PIX-GIT-Paxillin.
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 3422. doi:1538-7445.AM2012-3422
Abstract 3441: Silencing glucosylceramide synthase using MBO-asGCS eliminates tumor metastasis
Authors: Bhinge Kaustubh N. , Gupta Vineet , Liu Yong Yu 
Published: August 2012

Abstract
Disseminated metastasis is often observed in cancer patients fail in chemotherapy. Tumor metastasis is known to rely on the interaction of cancer cells and the extracellular matrix components but the molecular mechanism by which drug resistance promotes tumor metastasis is still not clear. Glucosylceramide synthase (GCS) that is a limiting enzyme for ceramide glycosylation and regulates glycosphingolipid (GSL) synthesis can cause drug resistance. Hence we report that GCS is a determinant of metastatic properties of drug-resistant cancer cells, and silencing GCS eliminates tumor metastasis. Our recent study found that the metastatic potency of drug-resistant cancer cells depended on the overexpression of GCS. Compared with drug-sensitive MCF-7 cells, the wound healing, matrigel attachment and MMP-9 activity significantly was 1.5 fold faster, 3 fold more and 2 folds higher respectively in the drug resistant MCF-7/Dox that also had 39-fold higher GCS protein level and 2-fold higher GCS enzyme activity. Introduction of GCS gene enhanced the metastatic potency of MCF-7 cells, because its matrigel attachment and invasion potential significantly increased by 2-fold and 1.5-fold after transfection. In contrast, silencing GCS by using mixed-backbone oligonucleotide against GCS (MBO-asGCS, 100 nM) substantially diminished the metastatic potency of MCF-7/Dox cells, as the wound healing, matrigel attachment and invasion reduced by 2-fold, 1.5-fold and 3-fold respectively. MBO-asGCS treatments eliminated lung metastasis of MCF-7/Dox tumors. Further mechanistic studies disclosed that silencing GCS by MBO-asGCS decreased its expression and enzyme activity and also decreased the levels of globo-series glycosphingolipids (GSLs) in GSL-enriched microdomain located on the plasma membrane. Sequentially, silencing GCS decreased the expression levels of uPA, MMP-9, VEGF and FGF-2 that actively mediated the migration and invasion of cancer cells. This study thus indicates that GCS is determinant for the metastatic potency of drug-resistant cancer cells and silencing GCS by using MBO-asGCS is an effective approach to target the metastasis of tumor with drug resistance.
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 3441. doi:1538-7445.AM2012-3441
Abstract 345: Circulating tumor cells from perfusable tumor nodules grown on decellularized rat lung scaffold has mesenchymal characteristics
Authors: Mishra Dhruva K. , Baird Brandi N. , Ott Harald C. , Gibbons Don L. , Kurie Jonathan M. , Kim Min P. 
Published: August 2012

Abstract
Circulating tumor cells are thought to be responsible for metastasis. These cells leave the primary site of cancer and enter the circulation after undergoing epithelial to mesenchymal transition. The tumor cells lose the epithelial features, such as expression of E-cadherin, and acquire mesenchymal characteristics, such as expression of Twist1, Zeb and N-cadherin. In this study, we developed a novel ex vivo model that utilizes a decellularized rat lung scaffold to grow tumor nodules and study circulating tumor cells. We hypothesized that circulating tumor cells in our ex vivo model will have mesenchymal characteristics. We created the decellularized rat lung scaffold using SDS and Triton-X. We then placed 344SQ or 393P mice lung cancer cell lines in the decellularized rat lung scaffold and perfused them in a customized bioreactor. We measured tumor growth on the scaffold and the number of circulating tumor cells for 14 days. We then analyzed the functional characteristics of the circulating tumor cells using the Boyden chamber and determined gene expression of E-cadherin, N-cadherin, Zeb1 and Twist. Both the 344SQ and 393P lung cancer cell lines formed tumor nodules that gradually increased in size with an increase in the number of circulating tumor cells over the 14-day period in our model. The circulating tumor cells had greater ability to migrate than the monolayer cell cultures in the Boyden chamber assay, with 100% of the circulating tumor cells migrating in contrast to 69% and 71% of the monolayer cell cultures of 344SQ and 393P, respectively. The circulating 393P tumor cells had a significant increase in Twist (58-fold), Zeb (20-fold) and N-cadherin (14-fold) and decrease in E-cadherin compared to the 393P cells from the monolayer cell culture. This difference was even more dramatic for the circulating 344SQ tumor cells with an increase in Twist (&gt;6000-fold), Zeb (14-fold) and N-cadherin (88-fold) compared to the 344SQ cells from the monolayer. There was small 4-fold increase in E-cadherin expression in the circulating 344SQ tumor cells compare to the 344SQ cells from the monolayer. The circulating tumor cells in our model have both phenotypic and genotypic characteristics of mesenchymal cells. The cancer cells that are more mesenchymal at the baseline have a greater difference in these characteristics. The circulating tumor cells in our model may be the sub-population of cells responsible for metastasis.
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 345. doi:1538-7445.AM2012-345
Abstract 3458: Wnt activation is implicated in glioblastoma radioresistance
Authors: Kim Yonghyun , Kim Kang Ho , Lee Hyewon , Yang Heekyoung , Kim Donggeon , Kang Wonyoung , Jin Juyoun , Joo Kyeung Min , Lee Jeongwu , Nam Do-Hyun 
Published: August 2012

Abstract
Glioblastoma (GBM) patients have dismal median survival even with the most rigorous treatments currently available. Radiotherapy is the most effective non-surgical therapy for GBM patients; however, patients succumb due to tumor recurrence within a year. To develop a curative therapeutic approach, we need to better understand the underlying molecular mechanism of radiation resistance in GBM. Towards this goal, we developed an in vivo orthotopic GBM model system that mimics the radiation response of human GBM, using both established-GBM cell line and patient-derived freshly dissociated GBM specimen. In-vivo ionizing radiation (IR) treatment prolonged the survival of mice with intracranical tumor derived from U373MG, but failed to prevent tumor recurrence. U373MG and GBM578 cells isolated after in-vivo IR (U373-IR and 578-IR) were more clonogenic and enriched with stem cell-like characteristics, compared with mock-treated control tumor cells. Transcriptomic analyses and quantitative real-time reverse-transcription PCR analyses using these matched GBM cells before and after radiation treatment revealed that Wnt pathways were preferentially activated in post-IR GBM cells. U373-IR cells and 578-IR were enriched with cells positive for both active b-catenin (ABC) and Sox2 population, and this subpopulation was further increased after additional in-vitro radiation treatment, suggesting that radiation resistance of GBM is mediated due, in part, to the activation of stem cell-associated pathways including Wnt. Finally, pharmacological and siRNA inhibition of Wnt pathway significantly decreased the survival and clonogenicity of GBM cells and reduced their ABCþ/Sox2þ population. Together, these data suggest that Wnt activation is a molecular mechanism to confer GBM radioresistance and an important therapeutic target.
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 3458. doi:1538-7445.AM2012-3458
Abstract 3459: Radioresistence mechanism of prostate cancer stem cells
Authors: jung Kang Mun , Kim Young Seok , Cho Yong Mee 
Published: August 2012

Abstract
BACKGOUND. Radiotherapy induces tumor cell killing mainly by DNA damage and is widely used as one of the main therapeutic modalities for prostate cancer. However, a significant proportion of prostate cancer patients experiences tumor recurrence after radiotherapy and eventually dies of the disease. We previously observed that ionizing radiation (IR) initially damaged prostate cancer stem cells (pCSCs) but levels of CSCs were increased in the recurrent tumors of prostate cancer cell lines and human prostate cancer tissues. METHODS. To define the radioresistance mechanism of pCSCs, we examined expressions of DNA-repair proteins [Ku70, Ku80 and Ataxia telangiectasia and Rad3-related protein kinase (ATR)], cell cycle distribution, and levels of intracellular reactive oxygen species (ROS) in prostaspheres, which is one of pCSC models, and compared to those of total population of a prostate cancer cell line LNCaP. Expressions of DNA-repair proteins were also examined in human prostate cancer tissues harvested before and after radiotherapy. RESTULTS. In non-irradiated cells, the expressions of Ku70 and Ku80 were higher in prostaspheres compared to those of total population. ATR expression was inconspicuous in both cells. After IR with 10 Gy, the expressions of Ku 70, Ku 80, and ATR proteins were increased in both cells with higher levels in prostaspheres than those of total population. Although there was a tendency that prostaspheres belonged to more in G1 phase and less in S phase of cell cycle, it was not statistically significant. Apoptotic cell population and expressions of total and cleaved forms of caspase 3 were not different between prostaspheres and total population. Prostaspheres contained one group of cells that had low levels of ROS. In recurrent human prostate cancer tissue after radiotherapy, expressions of Ku70 and Ku80 were tended to increase. CONCLUSIONS. These results demonstrate that pCSCs contain more DNA-repair proteins and less amount of RCO compared to total population. They suggest that pCSCs have better DNA-repair mechanism and less vulnerability to oxidative damage compared to differentiated cells.
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 3459. doi:1538-7445.AM2012-3459