bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2383: A new approach to isolate label-free and viable circulating tumor cells for monitoring cancer patient treatment response
Authors: Lin Sanger Hung-Chih , Wu Min-Hsien , Hsu Hung-Chih , Hsieh Chia-Hsun , Cheng Ju-Chien , Tseng Ching-Ping 
Published: August 2012

Abstract
The number of circulating tumor cells (CTCs) has been demonstrated as a good indicator for cancer progression and for monitoring treatment response of cancer patients. Most of the current methods for detecting CTCs were based on positive selection using the antibody specific to epithelial cell surface marker. In this study, we established a novel PowerMag system for negative selection and enrichment of CTCs by depletion of CD45+ cells. The efficacy of PowerMag system in CTCs isolation was first analyzed by spiking prostatic PC3 cancer cells into the peripheral blood from healthy volunteers. Our data revealed that, when compared with the methods that have been reported, the PowerMag system had high sensitivity (6-7 log10 enrichment), comparable recovery rate (50-60%), broad detection range (more than 3 log10), and stable and reproducible experimental results (r2=0.999). Notably, the cancer cells obtained from PowerMag system were label-free and viable with the capability for proliferation. To validate the feasibility of PowerMag system in clinical application, the numbers and characteristics of CTCs from 38 metastatic cancer patients with a total of 175 blood samples were determined. At least two populations of CTCs with the surface markers of EpCAM+CD45−CD146− and EpCAM−CD45−CD146− were identified. The detection rate reached 100% for the patients in the baseline level before treatment. The change in CTCs numbers for both cell populations appears to correlate with patient clinical outcomes after chemotherapy. As a whole, the PowerMag system is proven to be capable of isolating CTCs from whole blood effectively and economically, by which time- consuming sample pretreatment and costly equipments are not required. PowerMag has paved an alternation rout to monitor the progression and treatment response of cancer patients.
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 2383. doi:1538-7445.AM2012-2383
Abstract 2384: Assessment of PITX2, BMP4, FGF4, ERalpha, ERbeta promoter methylation in the circulating tumor cells (CTCs) can predict metastasis and survival in primary invasive duct carcinoma (PIDC) patients
Authors: Bahnassy Abeer A. , zekri Abdel-Rahman N. , Salem Salem E. , Aziz Hala , Moustafa Abeer E. , Gaafar Rabab M. 
Published: August 2012

Abstract
Recent studies have focused on hematogenous tumor cell dissemination as predictive factors of breast cancer metastasis and several methods for detecting circulating tumor cells (CTCs) in peripheral blood were described. However, in early-stage breast cancer, molecular characterization of CTCs and their prognostic value is not well established. We previously found a significant correlation between DNA promotor methylation (PM) of PITX2, BMP4, FGF4, ERalpha, ERbeta and breast cancer recurrence and metastasis (unpublished data). Therefore, we sought to compare the frequency of PM of these genes in the CTC and the primary breast tumors (PBT) in relation to recurrence, progression free and overall survival rates (DFS& OS) CTCs were collected from the 10 cm peripheral blood of 80 primary invasive duct carcinoma (PIDC) patients by immunomagnetic beads separation. The number of CTCs was determined by flow cytometry (FCM) and RT-PCR (using CK-19, mammaglobin and CD44) for confirmation and comparison. Patients were first tested for CTC counts immediately before surgery, prior to therapy, at first follow-up (4-6 weeks later) and after 6 months. PM of PITX2, BMP4, FGF4, ERalpha, ERbeta was assessed by methylation specific PCR (MSP) in PBTs and CTCs and correlated with metastasis and survival. The number of CTCs ranged from 0-500/10 ml blood. The concordance between FCM and RT-PCR was 98% (p=0.01). At first assessment, 56 patients have β10 CTCs/10 ml blood and exhibited a significantly shorter progression-free survival (PFS) (12.7 months versus 20.6 months) and overall survival (OS) (28.1 months versus 49.5 months) than women with 10 CTCs was 16.1 months, compared to greater than 36 months in the cohort with &lt;10 CTCs. PM of PITX2, BMP4, FGF4, ERalpha and ERbeta, was reported in 42.90%, 50.00%, 51.20%, 63.10% and 46.40% compared to 63.15%, 73.75%, 62.5%, 81.2% and 78.75% in CTCs. PM of BMP4, and ERbeta was associated with reduced OS and PFS. Conclusions: 1) The presence of CTCs in the blood of PIDC patients can impact standard treatment and future research, 2) FCM provides a simple and accurate technique for enumerating CTCs in peripheral blood, 3) the significant increase in PM frequency of all studied genes except FGF4, suggests that aberrant PM may contribute to increased aggression and more liability to metastasis. More studies are still needed to assess the impact of CTCs in PIDC patients and how they might contribute to improving individualized cancer therapies.
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 2384. doi:1538-7445.AM2012-2384
Abstract 2385: A highly sensitive detection system of genetic alterations in circulating tumor cells using a telomerase-specific replication-competent adenovirus
Authors: Shigeyasu Kunitoshi , Hashimoto Yuuri , Morikawa Tatsuya , Mori Yoshiko , Sun Dong-Sheng , Kagawa Shunsuke , Uno Futoshi , Tazawa Hiroshi , Nagasaka Takeshi , Kyo Satoru , Mizuguchi Hiroyuki , Urata Yasuo , Fujiwara Toshiyoshi 
Published: August 2012

Abstract
Background: Malignant tumor cells often develop metastatic nodules at distant organs through circulation in blood flow and result in poor prognosis. Detection of circulating tumor cells (CTCs) is clinically an important issue to evaluate the metastatic potential of primary tumors in cancer patients. Furthermore, confirmation of genetic alterations in CTCs provides us the critical information to clarify the molecular mechanism in the acquisition of metastatic capability of tumor cells and to treat tumor metastasis by molecular targeted therapy. We recently developed a telomerase-specific replication-selective adenovirus (OBP-401; TelomeScan) expressing the green fluorescence protein (GFP). OBP-401-mediated GFP induction method was a simple and highly sensitive imaging system to detect a small population of viable CTCs in the peripheral blood. In this study, we assessed the potential of OBP-401-mediated CTC detection system to analyze the genetic alterations in CTCs. Methods: We used two types of human colon cancer cell lines SW480 and HCT116 that have the mutations in codon 12 and 13, respectively, of the K-ras gene. The detection method involved a 4-step procedure, including the lysis of red blood cells, the subsequent addition of OBP-401 to the cell pellets, the isolation of GFP-positive tumor cells using a fluorescence-activated cell sorting (FACS), and a confirmation of genetic mutations by direct sequencing. DNA was extracted from the captured cells using FACS and we investigated the mutation status in the K-ras gene by direct sequencing. Results: When only 10 cells of SW480 or HCT116 cells were added in a 5 ml of blood obtained from healthy volunteer, a total of 2-12 GFP-positive cells were captured from OBP-401-infected blood samples using FACS Aria. We confirmed the mutations in codon 12 and 13 of the K-ras gene in the FACS-captured cells from blood samples containing SW480 and HCT116 cells, respectively, by direct sequencing. Conclusion: These results suggest that OBP-401-mediated GFP induction and FACS-based capture system are useful methods to isolate small population of CTCs from peripheral blood samples and to evaluate the genetic alterations in CTCs. The combination method using OBP-401 and FACS would be a reliable strategy for the surveillance of genetic alterations in CTCs.
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 2385. doi:1538-7445.AM2012-2385
Abstract 2389: A microfluidic system for the selection of circulating tumor cells that utilizes both affinity and size capture technologies
Authors: Smirnov Denis , Merdek Keith , Sprott Kam , Skelley Alison , Huang Richard , Tenney Don , Jiang Chunsheng , Milutinovic Aladin , Tims David , Dong Yi , Cain Jason , Wolfe Michele , Pierceall Bill , Carney Walter 
Published: August 2012

Abstract
Cancer is a disease of uncontrolled cell growth and dissemination. As tumors increase in size and vascularity, populations of cells break off from the primary tumor, enter into the circulation, and are transported to distant parts of the host. These circulating tumor cells (CTCs) may constitute a seed population that is responsible for subsequent growth of additional tumors (metastasis) in different tissues. Therefore capture, and subsequent characterization of CTCs from patient's blood, offers an opportunity to both study and monitor progression of the disease. One of the most common methodologies used for CTC capture is affinity based, where specific antibodies bind to cell surface antigens and allow cell capture. A second technique employs size filtration. CTCs are generally larger than normal leukocytes and this size differential can be exploited to enrich CTCs. Here we describe a CTC dual capture platform developed at On-Q-ity Inc. that combines both of these isolation techniques to offer more efficient CTC capture than either technology alone. Performance of On-Q-ity platform will be compared to Veridex's CellSearch. Utility of On-Q-ity platform for sophisticated molecular and cellular characterization of captured cells will also be described.
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 2389. doi:1538-7445.AM2012-2389
Abstract 2392: A novel approach for detecting viable and tissue-specific circulating tumor cells
Authors: Wu Ping , Oh Daniel , Chowdhury Wasim H. , Kudrolli Tarana A. , Liu Minzhi M. , Sokoll Lori , Rodriguez Ronald , Lupold Shawn E. 
Published: August 2012

Abstract
Circulating tumor cells (CTCs) offer a new strategy to access cancer tissue through a simple blood sample. CTCs levels can be predictive of overall survival in patients with metastatic cancers and changes in CTC levels following therapy can be indicative of therapeutic response. Moreover, CTCs may provide a means to select patients for specific therapeutic approaches by identifying active or susceptible pathways. However, most of the current methods for detecting CTCs have limitations including the need for specialized equipment, the reliance on cell capture through cell surface markers such as EpCAM, limited sensitivity, the inability to distinguish cancer from normal, tissue type, active pathways, or cell viability. Here we present a novel CTC detection approach which applies tissue-selective replicating adenoviruses and highly sensitive secreted reporters. These Circulating Tumor Cell Reporter Viruses (CTC-RVs) were generated by replacing the early viral E1A gene promoter with the prostate specific probasin promoter and prostate specific antigen enhancer (PSE-PBN). The secreted reporter gene, humanized metridia luciferase (hMLuc), was incorporated into the viral major late transcriptional unit, at the fiber gene locus, to limit reporter expression to only those cells in which the virus has replicated. Cells from total blood, including mononuclear cells and CTCs, are placed in tissue culture media and infected with the CTC-RV. After three days, viral replication dramatically amplifies reporter levels within infected prostate cancer cells with active Androgen Receptor pathways leading to the secretion of the bioluminescent reporter. Non-prostatic cells will not amplify the virus or express the reporter gene. LNCaP cellular dilution study results show that as few as five CTCs per million lymphocytes cells could be readily detected without any cell isolation. LNCaP cells diluted in healthy volunteer blood samples identified the optimal time and dosing conditions. Initial studies in clinical samples support the detection of viable CTCs with this assay. This new approach offers a means to quantify live CTC levels in a tissue-specific manner, without the need for cell capture, through the use of a secreted signal which can be detected separate from the large blood cell population.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2392. doi:1538-7445.AM2012-2392
Abstract 2399: Syntenin-1 promotes cell invasion though regulating Slug-dependent epithelial-mensenchymal transition in non-small cell lung cancer
Authors: Wang Lu-Kai , Chen Yuh-Ling , Hong Tse-Ming , Yang Pan-Chyr 
Published: August 2012

Abstract
Slug, a transcriptional repressor, is involved in the regulation of epithelial-mesenchymal transition (EMT) during development and can promote cancer cell invasion and metastasis. Through Yeast-two hybrid screening, we found that syntenin-1, a tandem PDZ protein, can associate with Slug. Syntenin-1 is known to involve in many biological functions such as protein traffics and cytoskeleton remodeling. Recently, it has been found that overexpression of syntenin-1 may promote cancer cell invasion by altering defined biochemical and signaling pathways, including c-Src/ focal adhesion kinase (FAK) and NF-kappaB. Conversely, knock-down the expression of syntenin-1 can also increase cell aggregation. All these findings indicate that syntenin-1 may play an important role in cell adhesion and movement. Whether syntenin-1 is involved in the process of EMT should be further clarified. In this study, we showed that syntenin-1 could enhance Slug-dependent cell invasion and regulate the EMT in lung cancer cells. Syntenin-1 can interact with Slug through its PDZ-1 domain and increase their nuclear localization in cells. Overexpression of syntenin-1 increases Slug-induced cell migration and invasion though regulating the repression activity of Slug. Knock down the expression of syntenin-1 may also inhibit the repression activity of Slug on promoter of E-cadherin in highly invasive lung cancer cell lines. In Sum, Syntenin-1 may promote cell Invasion though regulating Slug-dependent EMT process in Non-small cell lung cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2399. doi:1538-7445.AM2012-2399
Abstract 24: Role of S100A14 in proliferation and invasion of oral cancer-derived cells
Authors: Sapkota Dipak , Costea Daniela , Bruland Ove , Vasstrand Endre N. , Ibrahim Salah 
Published: August 2012

Abstract
Members of multifunctional S100 protein family have been reported to be differentially expressed in a variety of human cancers and are functionally linked with various aspects of carcinogenesis. S100A14 is a recently identified member of the S100 protein family. Despite reports of altered expression in different cancer types, functional significance of S100A14 in carcinogenesis is largely unknown. In this study, we aimed to investigate the functional role of S100A14 proliferation and invasion of oral squamous cell carcinoma (OSCC)-derived cell. S100A14 mRNA and protein levels were found to be down-regulated in OSCCs and OSCC-derived cells compared to the corresponding normal controls. In addition, membranous S100A14 immunoexpression was found to be gradually lost in the invasive fronts/islands compared to the central/superficial part of OSCCs. Over-expression of S100A14, by using retroviral expression construct, was found to be associated with the inhibition of cell proliferation, induction of G1-arrest and up-regulation of p21 in OSCC-derived cell lines (CaLH3 and OSCC1) with wild type p53. Similarly, over-expression of S100A14 was associated with inhibition of invasive potential of OSCC-derived cells in the in vitro Matrigel invasion assay. S100A14 mediated inhibition of cellular invasion was found to be associated with modulation of mRNA signature of genes involved in tumor invasion and metastasis, in particular MMP1, MMP9. Taken together, these data suggest that similar to other multifunctional S100 protein members, S100A14 might be involved in OSCC progression by regulating cell proliferation and invasion. Hence, further characterization of the molecular pathways/targets of S100A14 might lead to the better understanding of proliferation and invasion of OSCC and this process, in future, might be useful as a diagnostic or therapeutic approach in cancers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 24. doi:1538-7445.AM2012-24
Abstract 2406: The effect of anoxia/reoxygenation on epithelial-mesenchymal transition in human colon cancer cell lines
Authors: Okajima Manabu , Kokura Satoshi , Ishikawa Takeshi , Matsuyama Tatsuzo , Tsutiya Reiko , Adachi Satoko , Sakamoto Naoyuki , Naito Yuji , Yamane Tetsuro 
Published: August 2012

Abstract
Background and Aim: Epithelial-mesenchymal transition (EMT) is considered as crucial events in cancer metastasis. Anoxia/reoxygenation (A/R) is known to occur in cancer tissues, due to the process of angiogenesis and the change of the pressure in tissue growth. In this study, we investigated whether A/R induces EMT in the human colon cancer cells. Materials and Methods: Colon cancer cells, HT29 cells, were exposed to anoxia (2 h) followed by reoxygenation (4-22 h). To evaluate EMT, morphological changes were assessed by light microscopy, immunofluorescence and Western blot analyses. Moreover, RT-PCR for the EMT-related transcription factors (Snail and ZEB1) was performed and the activation of nuclear factor kappa B (NF-κB) was analyzed in the nuclear extracts using an ELISA method. To determine whether NF-kB was involved in A/R-induced EMT, HT-29 cells were treated with proteasome inhibitors. Results: Colon cancer cells exposed to A/R showed phenotypic changes consistent with EMT: spindle-shape and intercellular separation. The expression of E-cadherin on the cell surface and the total amount of E-cadherin protein were reduced after A/R. The EMT-related transcriptional factors such as Snail and ZEB1 were induced after exposure to A/R. Furthermore, exposure to A/R caused an activation of NF-κB and pretreatment with proteasome inhibitors significantly attenuated the effects of exposure to A/R. Conclusions: These results indicate that A/R induces EMT in human colon cancer cells through partially NF-κB dependent transcriptional pathway.
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 2406. doi:1538-7445.AM2012-2406
Abstract 2408: CD44s is required for a tumor-initiating stem-like mesenchymal phenotype in hepatocellular carcinoma via ligand-independent c-Met activation
Authors: Dang Hien T. , Ding Wei , Rountree Carl Bart 
Published: August 2012

Abstract
c-Met, a high affinity receptor for hepatocyte growth factor (HGF), plays a critical role in cancer growth, invasion and metastasis. Hepatocellular carcinoma (HCC) patients with active HGF/c-Met signaling have a significantly worse prognosis. CD44, the receptor for hyaluronic acid, is utilized as a surface marker to identify mesenchymal tumor-initiating stem-like cells (TISC) in several cancers. CD44v6 (spice variant 6) has been shown to promote HGF activation of c-Met. In this work, we examine the role of CD44s as a deregulator and activator of c-Met signaling in HCC. In a transcriptome profile analysis of 149 human HCC cases, we identified a significant positive correlation (R2=0.8993) between up-regulated CD44 and c-Met expression. The human HCC cell lines MHCC97-H and Huh7 were further utilized to investigate the direct relationship between c-Met and CD44s. Metastatic MHCC97-H cells are 95% CD44+ and demonstrate ligand-independent c-Met activation. CD44+/c-Met+ MHCC97-H cells demonstrate a mesenchymal phenotype with low expression of E-cadherin, high level of tumorsphere formation, increased expression of fibronectin and Zeb2 compared to Huh7 cells, which have are CD44neg/c-Metneg. In MHCC97-H cells, a direct interaction between CD44s and c-Met was demonstrated by immunoprecipitation/immuno-blot analysis. Transient and stable inhibition of c-Met in MHCC97-H cells results in increased E-cadherin, decreased CD44s, and reduced tumor-initiating characteristics and loss of tumorsphere formation. Likewise, inhibition of CD44s demonstrates similar phenotype with increased E-cadherin, decreased tumorsphere formation, and decreased c-Met activation and loss of downstream Akt and Erk phosphorylation. CD44s knockdown recovered c-Met to a regulated HGF-dependent state. Selective inhibition of either PI3K (Ly294002) or MAPK (PD98059) pathways in MHCC97-H cells demonstrate that PI3K/Akt activation signals drive CD44s expression in a feed forward fashion. Conversely, the over-expression of CD44s in Huh7 cells demonstrates a mesenchymal phenotype with fibroblastic-like cell morphology, decreased E-cadherin, increased Zeb1, increased PI3K/Akt signaling, and increased tumorsphere formation compared to control Huh7 cells. Selective inhibition of PI3K/Akt signaling in CD44+ Huh7 cells resulted in reduced CD44s expression and decreased tumorsphere formation. In conclusion, CD44s induces a mesenchymal phenotype and tumor initiating characteristics in HCC through the deregulation of c-Met and activation of a positive feedback loop through PI3K/Akt signaling.
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 2408. doi:1538-7445.AM2012-2408