bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3064: Importance of circulating tumor cells in newly diagnosed colorectal cancer
Authors: Dalum Guus van , Groot Marco R. de , Stam Gerrit-Jan , Scholten Loes F.A. , Mastboom Walter J.B. , Vermes Istvan , Tibbe Arjan G.J. , Terstappen Leon W.M.M. 
Published: May 2015

Abstract
Background: The presence of circulating tumor cells (CTC) is associated with poor prognosis in patients with metastatic colorectal cancer (CRC). This study was conducted to determine if the presence of CTC prior to surgery and during follow-up in patients with newly diagnosed non-metastatic CRC identifies patients who are at risk for disease recurrence.
Methods: In a prospective single center study 183 patients with newly diagnosed non-disseminated CRC scheduled for surgery were enrolled from 2003 till 2008 and followed up for a median of 5.1 years. CTC were enumerated with the CellSearch System in 4 aliquots of 7.5 ml of peripheral blood before and after surgery (1-26 weeks), after adjuvant therapy and 1, 2, 3 and 4 years after surgery.
Findings: ≥1 CTC/ 30ml of blood were detected in 44 (24%) patients before surgery. CTC frequency did not change significantly at the time points after surgery. Patients with CTC before surgery had a significant decrease in Recurrence Free Survival (RFS, logrank test p=0.014) and Colon Cancer Related Survival (CCRS, p=0.002). Five year RFS dropped from 75% to 61% and five year CCRS from 83% to 69% for patients with CTC before surgery. In a multivariate analysis of CTC, T-Stage and N-stage, the presence of CTC and N-stage remained as significant factors for RFS and CCRS. Surprisingly the presence of CTC after surgery was not significantly associated with RFS and CCRS whereas CTC 2-3 years after surgery was again significantly associated with RFS and CCRS.
Interpretation: The presence of CTC in patients with stage I-III CRC before surgery is associated with a significant reduction RFS and CCRS. Although similar amounts of CTC were detected within 3 months after surgery they were not associated with RFS or CCRS. In contrast CTC were again highly significant for RFS and CCRS 2-3 years after surgery. These findings suggest a role of CTC detection, to assess which patients need adjuvant treatment. To implement CTC detection in the non-metastatic setting a validated CTC detection technology is needed with increased sensitivity and specificity.
Citation Format: Guus van Dalum, Marco R. de Groot, Gerrit-Jan Stam, Loes F.A. Scholten, Walter J.B. Mastboom, Istvan Vermes, Arjan G.J. Tibbe, Leon W.M.M. Terstappen. Importance of circulating tumor cells in newly diagnosed colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3064. doi:10.1158/1538-7445.AM2014-3064
Abstract 3080: Comparison of CellSearch with polymeric microfluidic devices for CTC isolation using EpCAM-negative tumor cell lines of malignant pleural mesothelioma
Authors: Chikaishi Yasuhiro , So Tomoko , Takenaka Masaru , Oka Soichi , Hirai Ayako , Iwanami Takashi , Shimokawa Hidehiko , Yoneda Kazue , Nagata Yoshika , Uramoto Hidetaka , Ohnaga Takeshi , Tanaka Fumihiro 
Published: May 2015

Abstract
Background. The CellSearch system is the most commonly used technique approved by the FDA to isolate and quantify circulation tumor cells (CTCs). However, in this system, the efficiency of CTC isolation is influenced by the epithelial cell adhesion molecule (EpCAM). Therefore, it is difficult to isolate CTCs in the setting of the epithelial to mesenchymal transition (EMT), malignant pleural mesothelioma and so on. We developed polymeric microfluidic devices for CTC isolation (CTC-chip) and compared the efficacy of CellSearch with CTC-chip using EpCAM-negative tumor cell lines of malignant pleural mesothelioma.
Methods. In order to evaluate the accuracy of the number of CTCs, we used PBS samples and peripheral blood samples (blood samples) collected from healthy donors to which spiking the tumor cell lines ACC-MESO1 and ACC-MESO4. Both tumor cell lines (obtained from ATCC) were derived from malignant pleural mesothelioma, positive for mesothelin and podoplanin and negative for EpCAM. The recovery rate was evaluated using two methods. CellSearch was performed according to the normal method, while CTC-chip was performed using a two coating pattern with anti-mesothelin antibody (chip1) and anti-podoplanin antibody (chip2).
Results. In the PBS samples, the recovery rate of captured ACC-MESO1 was 8.6%/98%/99% (CellSearch/chip 1/chip 2), while those of ACC-MESO4 was 21.1%/97%/99%, respectively. In the blood samples, the recovery rate of captured ACC-MESO1 was 1.2%/6.2%/13.3% (CellSearch/chip 1/chip 2), while that of ACC-MESO4 was 6.0%/3.7%/11.6%, respectively.
Conclusions. Our experiments showed that the recovery rate of each sample was higher using CTC-chip than that obtained with CellSearch. Moreover, CTC-chip coated anti-podoplanin antibody exhibited a higher recovery rate than coated anti-mesothelin antibody. Future studies using experiments of CTC isolation in cancer patients with malignant pleural mesothelioma are thus required.
Citation Format: Yasuhiro Chikaishi, Tomoko So, Masaru Takenaka, Soichi Oka, Ayako Hirai, Takashi Iwanami, Hidehiko Shimokawa, Kazue Yoneda, Yoshika Nagata, Hidetaka Uramoto, Takeshi Ohnaga, Fumihiro Tanaka. Comparison of CellSearch with polymeric microfluidic devices for CTC isolation using EpCAM-negative tumor cell lines of malignant pleural mesothelioma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3080. doi:10.1158/1538-7445.AM2014-3080
Abstract 3951: Dual phosphoinositide 3-kinase/Mammalian target of rapamycin inhibitors, GSK2126458 and PKI-587, suppress tumor progression and increase radiosensitivity in nasopharyngeal carcinoma
Authors: Wang Wei , Li Qi , Liu Tongxin , Chen Longhua 
Published: May 2015

Abstract
Purpose
Although combined chemo-radiotherapy has provided considerable improvements for nasopharyngeal carcinoma (NPC), recurrence and metastasis are still frequent. The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway plays a critical role in tumor formation and tumor cell survival after radiation-induced DNA damage. In the present study, we evaluated whether inhibition of PI3K/mTOR by two novel dual inhibitors, GSK2126458 and PKI-587, could suppress tumor progression and sensitize NPC cells to radiation.
Experimental Design
Four NPC cell lines (CNE-1, CNE-2, 5-8F and 6-10B) were used to analyze the effects of GSK216458 and PKI-587 on cell proliferation, migration, invasion, clonogenic survival, amount of residual γ-H2AX foci, cell cycle and apoptosis after radiation. A 5-8F xenograft model was used to evaluate the in vivo effects of the two compounds in combination with ionizing radiation (IR).
Results
Both GSK216458 and PKI-587 effectively inhibited cell proliferation and motility in NPC cells and suppressed phosphorylation of Akt, mTOR, S6 and 4EBP1 proteins in a dose- and time-dependent manner. Moreover, both compounds sensitized NPC cells to ionizing radiation (IR) by increasing DNA damage, enhancing G2/M cell cycle delay and inducing apoptosis. In vivo, the combination of IR with GSK2126458 or PKI-587 significantly inhibited tumor growth. Tumor regression was correlated with induction of apoptosis and suppression of the phosphorylation of mTOR, Akt, and 4EBP1.
Conclusions
GSK2126458 and PKI-587 inhibit tumor progression and increase radiosensitivity by inhibiting PI3K/Akt/mTOR signaling in NPC. Combining IR with a dual PI3K/mTOR inhibitor, either GSK2126458 or PKI-587, might be a promising therapeutic strategy for NPC.
Citation Format: Wei Wang, Qi Li, Tongxin Liu, Longhua Chen. Dual phosphoinositide 3-kinase/Mammalian target of rapamycin inhibitors, GSK2126458 and PKI-587, suppress tumor progression and increase radiosensitivity in nasopharyngeal carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3951. doi:10.1158/1538-7445.AM2014-3951
Abstract 3986: Characterization of prostaglandin signaling in primary neuroblastoma
Authors: Kock Anna , Larsson Karin , Ljungblad Linda , Idborg Helena , Korotkova Marina , Elfman Lotta , Johnsen John-Inge , Jakobsson Per-Johan , Kogner Per 
Published: May 2015

Abstract
Neuroblastoma (NB) is an embryonic childhood tumor of the sympathetic nervous system. Despite intensive treatment patients in the high-risk group of NB shows a poor prognosis.
We have shown the importance of inflammation in NB development and progression and that the pro-inflammatory lipid mediator prostaglandin E2 (PGE2) acts as a paracrine survival factor in NB. We have also shown that mPGES-1, essential for PGE2 synthesis, promotes growth and survival of several malignancies.
In this study we focus on the abundance of prostaglandins and their specific enzymes in primary NB of different biological and clinical subsets in the aim of finding a more specific and targeted NB treatment.
Levels of prostaglandins were assayed in 40 primary human NB tumors by mass spectrometry (MS) showing elevated levels of PGE2 in high risk 11q-deleted NB compared to low-risk NB whereas elevated levels of prostaglandin D2 (PGD2) could be coupled to NB with favorable clinical outcome.
The expression of COX-1, COX-2, mPGES-1, L-PGDS, H-PGDS and 15-PGDH were analyzed in tumors by immunohistochemistry (IHC). Expression of mPGES-1 and L-PGDS was found in all analyzed tumors.
Double stainings of mPGES-1 and the specific NB cell marker GD2 were performed on tumors with different biology using immunofluorescence. In low-risk tumors mPGES-1 is not expressed by the tumor cells whereas co-localization were found in 11q deleted high-risk tumors. To consider the level of inflammation and PGE2 signaling in these tumors we analyzed cell markers of both the innate and adaptive immune system together with mPGES-1. In all tumors mPGES-1 expressing cells are found in clusters closely together with T-cells, B-cells, dendritic cells and M1/M2 macrophages.
Together this suggests an involvement of inflammatory prostaglandins in neuroblastoma development and tumor progression opening up new strategies for targeted therapies.
Citation Format: Anna Kock, Karin Larsson, Linda Ljungblad, Helena Idborg, Marina Korotkova, Lotta Elfman, John-Inge Johnsen, Per-Johan Jakobsson, Per Kogner. Characterization of prostaglandin signaling in primary neuroblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3986. doi:10.1158/1538-7445.AM2014-3986
Abstract 3987: Evaluation of anti–malarial compounds as inhibitors of ezrin in osteosarcoma cells
Authors: Celik Haydar , Kallarakal Abraham , Colon-Lopez Daisy , Toretsky Jeffrey , Bosch Jurgen , Uren Aykut 
Published: May 2015

Abstract
Ezrin is a member of the ERM (Ezrin, Radixin, Moesin) family of proteins that functions as a cross-linker between the plasma membrane and actin cytoskeleton, thus allowing the cell to regulate cytoskeletal dynamics in response to external stimuli. Ezrin plays important roles in cell motility, membrane trafficking, morphogenesis, adhesion, survival and apoptosis. Ezrin also participates in crucial signal transduction pathways. Overexpression of ezrin contributes to the aggressive cancer behavior in various tumor types especially by enhancing the metastatic phenotype. Thus, ezrin represents a promising molecular target for cancer therapy. In our earlier studies, we have established that NSC305787 can directly bind to ezrin and inhibit its activity, which results in reduced metastasis. Since NSC305787 shares significant structural similarities with some anti-malarial drugs, we tested 400 anti-malarial compounds including 200 drug-like compounds and 200 probe-like compounds for their potential to directly bind to ezrin protein. We used surface plasmon resonance technology (Biacore) to screen direct binding. In this initial screen, 12 compounds demonstrated binding to ezrin over background values and selected as primary hits. Detailed SPR analysis of primary hits resulted in 7 compounds with comparable KD values to that obtained with our lead compound NSC305787. Primary hits were also evaluated for inhibition of the cell motility of murine osteosarcoma (OS) cells K7M2 and K12 that express high and low levels of ezrin, respectively. Cell motility and chemotaxis assays were conducted in parallel with viability assays to rule out general toxicity. Selected anti-malarial compounds were effective in inhibiting the motility of OS cells with high ezrin compared to cells with low ezrin. In conclusion, several anti-malarial drugs may have new indications in cancer therapy by inhibiting ezrin.
Citation Format: Haydar Celik, Abraham Kallarakal, Daisy Colon-Lopez, Jeffrey Toretsky, Jurgen Bosch, Aykut Uren. Evaluation of anti–malarial compounds as inhibitors of ezrin in osteosarcoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3987. doi:10.1158/1538-7445.AM2014-3987
Abstract 3988: The omega-3 fatty acids DHA and EPA inhibit medulloblastoma growth
Authors: Ljungblad Linda M. , Wickström Malin , Johnsen John-Inge , Kogner Per , Gleissman Helena 
Published: May 2015

Abstract
Background/Aim: Docosahexaenoic acid (DHA) and eicosapentaenic acid (EPA) are two essential omega-3 polyunsaturated fatty acid that have been shown to exert antitumoral effects in several cancer types, both in vitro and in vivo. DHA has also been shown to protect neural cells from apoptosis and is of importance in the maintenance of normal brain development and function.
Medulloblastoma (MB) is the most common malignant brain tumor in children with a poor 5-year survival of only 50-60%. It is a highly invasive embryonal neuroepithelial tumor that arises in the cerebellum and has a tendency to disseminate throughout the CNS early in its course. Multimodal treatment is always necessary in the form of surgery, radiotherapy and chemotherapy. However, treatment for this disease often results in significant endocrinological and intellectual sequelae. The neuroprotective and antitumoral properties of omega-3 fatty acids could therefore be of great benefit in this patient group. Here we aim to investigate the effect of DHA and EPA in medulloblastoma.
Methods: Cytotoxic activity of DHA and EPA was studied in cell viability assay in a panel of medulloblastoma cell lines. The molecular mechanisms were characterized using cell- and molecular biology techniques.
Results: By adding different concentrations of DHA and EPA we could demonstrate IC50s ranging between 1.9 and 46 µM for DHA and 3.8 and 68 µM for EPA in the six examined medulloblastoma cell lines. All cell lines showed greater sensitivity for DHA than EPA. Preliminary data showed that treatment with DHA inhibited the prostaglandin E2 production in medulloblastoma cells, indicating a possible mechanism of action.
Conclusions: Medulloblastoma cells are highly sensitive to omega-3 induced toxicity. Previous studies have showed that DHA can protect neurons from apoptosis. Therefore, omega-3 fatty acids are good candidates for improving medulloblastoma therapy by acting as both “sword and shield” by killing off cancer cells while protecting healthy neurons from therapy induced toxicity, thus possibly both inhibiting tumor growth and reducing the sequelae associated with other modes of brain tumor treatment.
Citation Format: Linda M. Ljungblad, Malin Wickström, John-Inge Johnsen, Per Kogner, Helena Gleissman. The omega-3 fatty acids DHA and EPA inhibit medulloblastoma growth. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3988. doi:10.1158/1538-7445.AM2014-3988
Abstract 3989: High throughput screening highlights NFkB signaling in Ewing sarcoma
Authors: Surdez Didier , Stoll Gautier , Tirode Franck , Laud Karine , Barillot Emmanuel , Delattre Olivier 
Published: May 2015

Abstract
Ewing sarcoma (ES) is the second most frequent pediatric bone tumor and still remains of poor prognosis especially for metastatic patients. Genetically, ES is characterized by a chromosomal translocation between EWSR1 and ETS family members (FLI1 in 85% of cases). This leads to the expression of EWS-FLI1 chimeric oncogene transcription factor. Aiming at identifying EWS-FLI1 regulated genes with potential therapeutic targets, a genome wide method was developed to rank these potential hits by combining Ewing sarcoma transcriptome and ChIPSeq data. Accordingly, 273 selected genes were further investigated using a siRNA approach for their impact on cell cycle phases and apoptosis using high throughput imaging methods. 133 of these genes displayed a phenotype and bioinformatics tools were used to connect these genes. NFkB turned out to be a major hub in this network and upstream activation pathways were further investigated. Interleukin-1 pathway may account for this observed effect and in vitro and in vivo experiments are currently on going to validate this hypothesis. Interestingly, preliminary results indicate that both tumor and tumor microenvironment are of prime importance for the activation of this pathway.
Citation Format: Didier Surdez, Gautier Stoll, Franck Tirode, Karine Laud, Emmanuel Barillot, Olivier Delattre. High throughput screening highlights NFkB signaling in Ewing sarcoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3989. doi:10.1158/1538-7445.AM2014-3989
Abstract 3990: Chemerin and chemerin receptors in neuroblastoma tumor microenvironment
Authors: Tuemmler Conny , Snapkov Igor , Moens Ugo L. , Sveinbjørnsson Baldur 
Published: May 2015

Abstract
Tumor promoting inflammatory cells as well as inflammatory mediators such as chemokines are important contributors to the tumor microenvironment as they can support tumor progression, angiogenesis and metastasis. Chemerin (also known as TIG-2 or RARRES2) is a chemoattractant factor for macrophages, immature DCs and NK-cells and a known adipokine involved in inflammation, metabolism and adipogenesis. Synthesized as a 163aa preproprotein, chemerin is N-terminally cleaved and secreted as inactive prochemerin. Following secretion, chemerin can be cleaved at the C-terminus by a variety of extracellular proteases resulting in several isoforms with varying length and biological activity. During inflammation initiation, maintenance and resolution the different chemerin isoforms may function pro- and/ or anti- inflammatory. Chemerin is a natural ligand for the G protein- coupled receptors CMKLR1 (Chem23) and GPR1. The role of chemerin and CMKLR1 in the tumor microenvironment has not been extensively studied.
The aim of this work is to study the function of chemerin and its receptors in neuroblastoma (NB). Screening of mRNA expression arrays showed a correlation between high expression of CMKLR1 and GPR1 and a worsened prognosis in NB. Chemerin, CMKLR1 and GPR1 expression was detected in different neuroblastoma cell lines by RT-PCR, immunocytochemistry and Western Blot. Stimulation with chemerin resulted in rapid and transient ERK1/2 and Akt phosphorylation.
TNF-α and IL-1β treatment increased chemerin and CMKLR1 protein levels. The functional significance of chemerin/ CMKLR1 in NB will be assessed by the use of NB animal models using cell clones silenced for chemerin/ CMKLR1.
Citation Format: Conny Tuemmler, Igor Snapkov, Ugo L. Moens, Baldur Sveinbjørnsson. Chemerin and chemerin receptors in neuroblastoma tumor microenvironment. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3990. doi:10.1158/1538-7445.AM2014-3990
Abstract 3992: Modes of metastasis evolution in human and murine cancer revealed by whole exome sequencing
Authors: Carter Scott L. , Brastianos Priscilla K. , McFadden David G. , Papagiannakopoulos Thales , Taylor-Weiner Amaro , Cibulskis Kristian , Jacks Tyler , Hahn William , Getz Gad 
Published: May 2015

Abstract
Despite that fact that 90% of cancer deaths are due to metastasis, relatively little is known about how metastases evolve from primary cancers. We subjected 101 trios consisting of primary tumor, brain metastasis, and normal reference tissue to whole exome sequencing (WES). To analyze the data, we developed novel computational tools to derive high quality allelic copy-number profiles directly from the WES data. These were used to perform an integrative analysis of somatic copy-number alterations (SCNAs) and somatic single nucleotide variants (SSNVs). This analysis allowed us to estimate the clonal architecture of the primary and metastatic samples from each patient, and to reconstruct a single phylogenetic tree relating all of the subclones detected in both samples.
We determined that all of the matched metastases analyzed likely formed from a single clone. In all cases, we observed a sibling relationship between the metastasis and primary tumor samples, indicating that they share a common ancestor, but ongoing evolution in the primary tumor resulted in fully clonal mutations in the primary biopsy that were not present in the metastasis sample. An important corollary of this is that in no case was a metastasis-founding subclone detected in a primary tumor sample. Using mutational spectra associated with tobacco exposure in lung cancers, we determined that most of the evolution leading up to the brain metastasis like occurred within the lung.
In contrast with these findings, analysis of related primary tumor and metastasis families in a mouse model of small cell lung cancer using identical methodology revealed evidence of more variable patterns of metastatic spread. Analysis of draining lymph nodes revealed that multiple subclones of the primary contributed to these metastases. In addition, we uncovered evidence for the sequential spread of metastases, consistent with multiregion sequencing of primary and metastatic human pancreatic cancer. The extension of this finding to a mouse cancer model suggests this may be a more frequent feature of cancer metastasis, and raises the possibility of genetically dissecting these processes in this experimental system.
Citation Format: Scott L. Carter, Priscilla K. Brastianos, David G. McFadden, Thales Papagiannakopoulos, Amaro Taylor-Weiner, Kristian Cibulskis, Tyler Jacks, William Hahn, Gad Getz. Modes of metastasis evolution in human and murine cancer revealed by whole exome sequencing. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3992. doi:10.1158/1538-7445.AM2014-3992