bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3949: Microrna142 3p promotes tumorinitiating and radioresistant properties in malignant pediatric brain tumors
Authors: Chiou Shih-Hwa 
Published: May 2015

Abstract
Primary central nervous system (CNS) atypical teratoid/rhabdoid tumor (AT/RT) is an extremely malignant pediatric brain tumor in infancy and childhood. It has been reported that subpopulation of CD133+ cells isolated from ATRT tumors present cancer stem-like and radioresistant property. However, the exact biomolecular mechanism of ATRT or AT/RT-CD133+ is still unclear. In this study, we firstly showed that CD133-positive AT/RT cells (CD133+) have a pluripotent differentiation ability and the capability of malignant cells to be highly resistant to ionizing radiation (IR). Using microRNA array and quantitative RT-PCR, our data showed that expression of miR142-3p was lower in AT/RT-CD133+ than in AT/RT-CD133−. MiR142-3p overexpression significantly inhibited self-renewal and tumorigenicity of AT/RT-CD133+. On the contrary, silencing of endogenous miR142-3p dramatically increased tumor-initiating and stem-like cell capacities in ATRT or AT/RT-CD133− cells, and further promoted the mesenchymal-transitional and radioresistant properties of ATRT cells. Most importantly, therapeutic delivery of miR142-3p in ATRT effectively reduced its lethality by blocking tumor growth, repressing invasiveness, increasing radiosensitivity, and prolonging survival time in orthotropic-transplanted NOD-SCID mice. These results demonstrate the prospect of developing novel miRNA-based strategies to block the stem-like and radioresistant property of malignant pediatric brain cancer stem cells.
Citation Format: Shih-Hwa Chiou. Microrna142 3p promotes tumorinitiating and radioresistant properties in malignant pediatric brain tumors. [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 3949. doi:10.1158/1538-7445.AM2014-3949
Abstract 3961: Effectiveness of the combined treatment with hsp90 inhibitor and heavy ion irradiation
Authors: Okayasu Ryuichi , Masaoka Aya , Hirakawa Hirokazu , Fujisawa Hiroshi , Sunada Shigeaki , Hirayama Ryoichi , Noguchi Miho , Li Huizi , Fujimori Akira 
Published: May 2015

Abstract
Hsp90 inhibitors have been studied as effective sensitizers for radiation therapy. Some encouraging results have been observed and the mechanism of radio-sensitization has also been investigated mostly with X-or gamma-rays. There has not been any study for Hsp90 inhibitors with heavy ion radiation. In this report we show the data with the combined effect with hsp90 inhibitors including 17AAG and PU-H71 with high linear energy transfer (LET) heavy ion radiation. As in proton radiation treatment, heavy ions can be targeted to tumor tissues due to its physical properties, while significantly lower radiation doses are delivered in surrounding normal tissues. In addition, with heavy ions higher biological effectiveness, i.e, more tumor cell killing, can be attained than with proton or conventional photon radiation. We are finding that if tumor cells were pre-treated with an hsp90 inhibitor and then exposed to heavy ion (carbon) radiation, very effective cell killing were observed using SQ5 human lung tumor cells. Another interesting feature of hsp90 inhibitors is that normal cells are not much influenced by the drug. Our in vivo mouse xenograft studies using nude mice also indicate a better tumor control with the combination of hsp90 inhibitor and local carbon irradiation as compared with carbon irradiation alone. Further studies show that the mechanism behind this radio-sensitization may be attributed to inhibition of DNA double strand breaks (DSBs) by hsp90 inhibitors; particularly homologous recombination pathway of DSB repair might be affected. Our flow cytometry study also reveals some new aspect of tumor cell killing by this combination therapy. Our data suggest that hsp 90 inhibitors are good candidates for the combined cancer therapy using heavy ion irradiation.
Citation Format: Ryuichi Okayasu, Aya Masaoka, Hirokazu Hirakawa, Hiroshi Fujisawa, Shigeaki Sunada, Ryoichi Hirayama, Miho Noguchi, Huizi Li, Akira Fujimori. Effectiveness of the combined treatment with hsp90 inhibitor and heavy ion irradiation. [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 3961. doi:10.1158/1538-7445.AM2014-3961
Abstract 3963: MYCN-dependent expression of sulfatase2 regulates neuroblastoma cell survival
Authors: Solari Valeria , Borriello Lucia , Fernandez G. Esteban , Shimada Hiroyuki , Sposto Richard , Asgharzadeh Shahab , Yates Edwin A. , Turnbull Jeremy E. , Declerck Yves A. 
Published: May 2015

Abstract
Despite the well-demonstrated role of MYCN in the pathogenesis of neuroblastoma, the mechanisms underlying its oncogenic function are not entirely understood and there is evidence that its function is in part dependent on the tumor microenvironment (TME). Heparan sulfate proteoglycans (HSPG) play a critical role in the interaction between tumor cells and the TME in great part because of their ability to retain cytokines, chemokines and growth factors and to control their bioavailability. This function of HSPG is dependent on the sulfation pattern that itself is controlled by sulfotransferases that add sulfate groups to the repeating disaccharide units and sulfatases (SULF) that selectively remove 6-O-sulfates. An unbiased analysis of the expression of 12 of these enzymes by RT-PCR in 8 human neuroblastoma cell lines revealed higher levels of expression of SULF2 in cell lines with amplification of the MYCN oncogene (MYCN-A), an observation that was confirmed at the protein level by Western blot analysis. We then demonstrated that the knock down (KD) of SULF2 in MYCN-A cells by siRNA resulted in a significant decrease in cell viability caused by a decrease in cell cycle entry and in apoptosis as documented by increase in caspase 3/7 activity, PARP cleavage and annexin-V expression. Evidence was provided that SULF2 is a downstream target of MYCN by demonstrating that overexpression of MYCN in CHLA-255 neuroblastoma cells increased SULF2 expression whereas downregulation of MYCN expression in SHEP-21N cells was followed by a downregulation of SULF2. Underlying the importance of SULF2 in neuroblastoma cell survival independently of MYCN, we demonstrated that overexpression of SULF2 in MYCN-NA cells increased cell viability without increasing MYCN expression. Finally, an analysis of SULF2 protein expression in 65 primary human neuroblastoma tumors indicated a statistically significant higher level of expression in MYCN-A tumors along with an almost complete absence of expression in MYCN-non amplified (NA) tumors, whether they were of favorable or unfavorable histology. The data thus identify SULF2 as a new downstream target of MYCN and a key contributor to its oncogenic function in human neuroblastoma.
Citation Format: Valeria Solari, Lucia Borriello, G. Esteban Fernandez, Hiroyuki Shimada, Richard Sposto, Shahab Asgharzadeh, Edwin A. Yates, Jeremy E. Turnbull, Yves A. Declerck. MYCN-dependent expression of sulfatase2 regulates neuroblastoma cell survival. [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 3963. doi:10.1158/1538-7445.AM2014-3963
Abstract 3975: PID1, a new growth-inhibitory gene, sensitizes brain tumor cell lines to chemotherapy
Authors: Xu Jingying , Ren Xiuhai , Tran Anthony , Shackleford Gregory M. , Erdreich-Epstein Anat 
Published: May 2015

Abstract
BACKGROUND: Phosphotyrosine Interaction Domain containing protein-1 (PID1) is a gene discovered in 2006 in the context of obesity, which we recently showed inhibits growth of brain tumor cell lines and its mRNA level is directly correlated with survival of patients with gliomas and medulloblastomas (Erdreich-Epstein et al, Clin Cancer Res, In Press). PID1 mRNA was lower in more aggressive medulloblastomas and gliomas, and patients whose tumor had higher PID1 mRNA had longer survival. Moreover, overexpression of PID1 markedly decreased 2D colony formation in cell lines of medulloblastomas, GBM and atypical teratoid rhabdoid tumors (ATRT). The growth-inhibitory effect was due to both decreased proliferation and increased cell death.
METHODS/RESULTS: COSMIC showed no mutations of PID1 in brain tumors, suggesting that PID1 was not a formal tumor suppressor gene. Therefore, we hypothesized that PID1 may sensitize brain tumor cells to therapy, and thus account for the longer survival in patients with higher PID1 mRNA. Indeed, while both cisplatin (10µg/ml) or transient PID1 overexpression increased apoptosis of glioma and medulloblastoma cell lines (indicated by increased AnnexinV and mitochondrial depolarization), combining cisplatin with PID1 caused a markedly higher apoptosis. Moreover, knockdown of PID1 by siRNA inhibited the cisplatin-induced mitochondrial membrane depolarization and apoptosis (AnnexinV), suggesting that PID1 may be required for cisplatin-induced apoptosis. Taken together, this suggests a sensitizing effect of PID1 to chemotherapy in both glioma and medulloblastoma cell lines. Intriguingly, PID1 mRNA and protein both increased in response to etoposide (5µg/ml), vincristine (50ng/ml) or cisplatin (5µg/ml) in a time- and dose-dependent manner in the brain tumor cell lines. This chemotherapy-induced increase in PID1 mRNA was blocked by inhibitors of NFKB, suggesting that regulation of PID1 may be an NFKB-dependent mechanism. Ongoing work seeks to decipher the mechanism of these effects and test them in vivo in mouse models.
CONCLUSIONS: Our data suggest that PID1 acts to sensitize glioma and medulloblastoma cells to chemotherapy, possibly explaining the correlation between higher PID1 mRNA and survival in patients.
Citation Format: Jingying Xu, Xiuhai Ren, Anthony Tran, Gregory M. Shackleford, Anat Erdreich-Epstein. PID1, a new growth-inhibitory gene, sensitizes brain tumor cell lines to chemotherapy. [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 3975. doi:10.1158/1538-7445.AM2014-3975
Abstract 3979: NSC305787 inhibits specific protein–protein interactions involving ezrin in osteosarcoma cells
Authors: Celik Haydar , Han Jenny , Hong Sung-Hyeok , Bulut Gulay , Toretsky Jeffrey , Uren Aykut 
Published: May 2015

Abstract
Osteosarcoma (OS) is the malignant tumor of bone that is most common in children and adolescents. OS is characterized by a high propensity for metastasis, especially to lungs, which is the main cause of death. The membrane-cytoskeleton cross-linker ezrin plays a key role in the metastatic progression of OS. In our earlier studies, we discovered that a small molecule, NSC305787, directly binds to ezrin and inhibits its function related to metastatic phenotype. In order to gain a better insight into the molecular mechanisms of NSC30787 action, an affinity pull-down coupled mass spectrometry was conducted to find the putative ezrin-interacting proteins whose interaction with ezrin is decreased or lost in the presence of NSC305787. Detailed mass spectrometry analysis identified 78 proteins after filtering for the potential background contaminants. Out of 78 proteins, 9 proteins were known ezrin-binding proteins including ezrin, radixin, moesin, polyadenylate-binding protein 1 (PABP-1), Na(+)/H(+) exchange regulatory cofactor (NHERF1/EPB-50), calpains, epidermal growth factor receptor kinase substrate 8 (EPS8), protein kinase C ioto (PKC-ioto) and focal adhesion kinase (FAK). For the remaining 69 proteins, we immunoprecipitated ezrin from K7M2 OS cells, and then western blotted for 8 selected functionally relevant proteins in order to test the validity of our approach. Of these 8 candidate proteins, Co-IP experiments verified binding of ezrin to 5 novel binding partners including DDX3 RNA helicase, caprin-1, AEG-1/MTDH/LYRIC, Rho guanine nucleotide exchange factor 2 (GEFH1) and catenin delta-1 (p120-catenin). NSC305787 effectively reduced the binding of DDX3 RNA helicase, AEG-1/MTDH/LYRIC and GEFH1 to ezrin in Co-IP experiments. Direct binding of ezrin to DDX3 RNA helicase was also demonstrated by surface plasmon resonance analysis using Biacore instrument. In conclusion, our results suggest that NSC305787 can modulate ezrin function through blocking its interaction with crucial proteins involved in adhesion, migration, invasion and survival. We also identified novel ezrin interactors that are involved in different levels of mRNA metabolism suggesting a completely new molecular function of ezrin that is independent from its classic role as a membrane cytoskeletal cross-linker at the plasma membrane. Thus, these results highlight novel molecular mechanisms for ezrin in cancer metastasis.
Citation Format: Haydar Celik, Jenny Han, Sung-Hyeok Hong, Gulay Bulut, Jeffrey Toretsky, Aykut Uren. NSC305787 inhibits specific protein–protein interactions involving 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 3979. doi:10.1158/1538-7445.AM2014-3979
Abstract 4001: Interaction of CD200 overexpression on tumor cells with CD200R1 overexpression on stromal cells: An escape from the host immune response in rectal cancer patients
Authors: Bisgin Atil , Meng Wen Jian , Adell Gunnar , Sun Xiao Feng 
Published: May 2015

Abstract
Introduction: CD200 imparts an immunoregulatory signal through its receptor - CD200R1, leading to the suppression of tumor specific immunity. The mechanism of CD200:CD200R1 signaling pathway is still uncertain.
The aim of this study was to investigate the expression pattern and localization of CD200 and its receptor CD200R1 in normal mucosa and rectal cancer patients.
Material and Methods: The immunohistochemical expressions and localizations of CD200 and CD200R1 were examined in 140 rectal cancer patients. Seventy nine of 140 underwent the preoperative radiotherapy treatment and the others were untreated prior to the surgery. In addition, 121 matched normal rectal mucosa samples from the same patients were evaluated.
Results: CD200 was expressed in normal mucosal epithelium and rectal cancer. Expression of CD200R1 was seen in normal mucosal epithelium and stromal cells of tumor samples. We found significant up-regulation of CD200 in rectal cancer tissues compared to the normal mucosa (P = 0.001). Interestingly, CD200R1 was overexpressed in stromal cells of rectal cancer patients presenting metastases compared to patients without metastases (P = 0.002). However, there is no difference in the expression levels between stromal cells and tumor cells. More than that, the up-regulation of CD2OO in tumor cells and CD200R1 overexpression in stromal cells was observed in 87 % of metastatic rectal cancer patients. These high expression levels of tumoral CD200 and stromal CD200R1 were significantly correlated with lymph node metastasis.
Conclusions: Interaction of CD200 and CD200R1 and their expression profile might be useful to follow-up disease progression in terms of carcinogenesis and metastasis.
Citation Format: Atil Bisgin, Wen Jian Meng, Gunnar Adell, Xiao Feng Sun. Interaction of CD200 overexpression on tumor cells with CD200R1 overexpression on stromal cells: An escape from the host immune response in rectal cancer patients. [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 4001. doi:10.1158/1538-7445.AM2014-4001
Abstract 4009: N-ras codon 61 mutation is associated with distant metastasis in patients with follicular thyroid carcinoma
Authors: Jeon MinJi , Jang Eun Kyung , Song Dong Eun , Sim So Young , Kim Eui Young , Choi Yun M. , Han Ji Min , Kim Won G. , Kim Tae Yong , Shong Young Kee , Kim Won Bae 
Published: May 2015

Abstract
Distant metastasis is a main cause of death in follicular thyroid carcinoma (FTC) patients. Factors related to distant metastasis in FTC had been known as age, primary tumor size, and invasiveness. Ras mutations were also supposed to be associated with poor clinical outcomes.
We analyzed Ras mutations in FTC with a distant metastasis (FTC M1, n=28), size matched-FTC without a distant metastasis (FTC M0, n=28), follicular adenoma (FA, n=17), and nodular hyperplasia (NH, n=12) to figure out the roles of Ras mutations in follicular thyroid carcinogenesis and metastasis. In addition, we assess the relationship between Ras mutations and clinical outcomes in FTC patients. NRAS, HRAS, and KRAS mutations were assessed using direct sequencing method.
Among 85 patients, 39 patients (46%) had Ras mutations. NRAS codon 61 mutation (n=21; 25%) was the most common point mutation. HRAS codon 61, KRAS codon 12/13, and KRAS codon 61 mutations were found in 7, 6, and 4 patients, respectively. NRAS codon 12/13 mutation was found in only 1 patient, and HRAS codon 12/13 mutation was not found. Ras mutations were significantly more common in the FTC than FA or NH groups. Especially, NRAS codon 61 mutation was associated with distant metastasis in patients with FTC. However, there was no significant difference in survival between the Ras mutation positive-FTC and Ras mutation negative-FTC patients.
Ras mutation, especially NRAS codon 61 mutation, was significantly associated with the presence of distant metastases. NRAS codon 61 mutation status might be a potential prognostic factor in FTC patients.
Citation Format: MinJi Jeon, Eun Kyung Jang, Dong Eun Song, So Young Sim, Eui Young Kim, Yun Mi Choi, Ji Min Han, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Won Bae Kim. N-ras codon 61 mutation is associated with distant metastasis in patients with follicular thyroid 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 4009. doi:10.1158/1538-7445.AM2014-4009
Abstract 4025: Combination strategy of endoscopic resection and telomerase-targeting oncolytic virus for eradicating lymph node metastasis of submucosal invasive colorectal cancer
Authors: Hori Naoto , Kikuchi Satoru , Kishimoto Hiroyuki , Tazawa Hiroshi , Hashimoto Yuuri , Kuroda Shinji , Kagawa Shunsuke , Urata Yasuo , Hoffman Robert M. , Fujiwara Toshiyoshi 
Published: May 2015

Abstract
Endoscopic resection is now one of the options as minimally invasive therapy for early colorectal cancer, However, surgical resection has been still standard for submucosal invasive colorectal cancer, because about 10% of that have LN metastasis. To secure endoscopic resection for submucosal invasive colorectal cancer, an alternative, innovational strategy to purge potential LN metastasis is required. We previously reported that a telomerase-dependent oncolytic adenovirus (OBP-301) spreads to the regional LNs, selectively replicates, and eradicates metastatic cancer cells in LNs, when administered into the orthotopically xenotransplanted rectal tumor in mouse model. In this study we evaluated whether OBP-301 could inhibit LN metastasis after the local resection mimicking endoscopic resection in a submucosal invasive rectal tumor mouse model. Human colon cancer HCT-116 cells expressing green fluorescent protein (GFP) were orthotopically implanted into the submucosal layer of the rectum in nude mouse, to develop resultant rectal tumor mimicking submucosal invasive one. LN metastasis was observed in 78.5% of mice as early as 7 days after cancer cell inoculation. The rectal tumor was injected with OBP-301 peritumorally, and then got locally excised mimicking Endoscopic submucosal dissection (ESD) technique. Seven days after tumor resection, the treatment with OBP-301 showed a significant inhibition in LN metastasis, whereas the other control treatment did not. Moreover, LN metastatic recurrence was not detected in OBP-301-treated group even 4 weeks after tumor resection. Similar results were also observed in another model with human colon cancer Colo-205-GFP cells. These results suggest that a novel combination of ESD and OBP-301 might have potential to take place of the conventional surgical approach in treating submucosal invasive colorectal cancer.
Citation Format: Naoto Hori, Satoru Kikuchi, Hiroyuki Kishimoto, Hiroshi Tazawa, Yuuri Hashimoto, Shinji Kuroda, Shunsuke Kagawa, Yasuo Urata, Robert M. Hoffman, Toshiyoshi Fujiwara. Combination strategy of endoscopic resection and telomerase-targeting oncolytic virus for eradicating lymph node metastasis of submucosal invasive 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 4025. doi:10.1158/1538-7445.AM2014-4025
Abstract 4041: Involvement of Notch1 signaling pathway in medulloblastoma metastasis
Authors: Kahn Suzana A. , Gholamin Sharareh , Zhang Michael , Nitta Ryan , Weissman Irving , Mitra Siddhartha , Cheshier Samuel 
Published: May 2015

Abstract
Medulloblastoma (MB) is a malignant brain tumor that originates in the cerebellum in children and spreads via the cerebrospinal fluid to the leptomeningeal spaces of the brain and of the spinal cord. MB is stratified into four distinct groups, according to genetic and clinical features, and patients from group 3 (also known as c-Myc-amplified group) have the highest risk of developing metastatic disease and, consequently, a poor prognosis. Treatment protocols involve surgery, craniospinal radiation, and high-dose chemotherapy, which frequently cause disabling neurotoxic effects in long-term survivors. We used MB cell lines and primary cells isolated from patients from the c-Myc-amplified group to develop a spontaneous spinal metastasis orthotopic xenograft model as a tool to understand the cellular determinants of leptomeningeal and spinal dissemination. Human cells isolated from the primary site tumors expressed 10 fold higher NICD1 (Notch1 Intracellular Domain), the active form of Notch1, than cells isolated from spinal metastatic sites (as quantified by western blot and imunohistochemistry), suggesting the downregulation of canonical Notch1 signaling pathway in MB metastasis. Moreover, flow cytometry analyses revealed that a higher percentage of cells isolated from metastatic sites expressed full-length surface Notch1 as compared to the primary site tumor. These differences cannot be explained by enrichment in the stem cell population at primary tumor sites, as we observed that MB cells isolated from primary tumors and metastatic sites exhibit equivalent self-renewal potential and express equivalent levels of CD133 and CD15. Our goal is to understand the role of notch in regulating medulloblastoma metastasis.
Citation Format: Suzana A. Kahn, Sharareh Gholamin, Michael Zhang, Ryan Nitta, Irving Weissman, Siddhartha Mitra, Samuel Cheshier. Involvement of Notch1 signaling pathway in medulloblastoma metastasis. [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 4041. doi:10.1158/1538-7445.AM2014-4041