bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3905: DBNL is a pro-survival adaptor in ErbB2+ breast cancer
Authors: Wixted Josephine F. , Robinson Matthew K. 
Published: August 2015

Abstract
DBNL, also known as mAbp1, Hip-55, or SH3P7, is a fairly novel, ubiquitously expressed, multidomain adapter protein consisting of an N-terminal F-actin binding domain, an internal proline-serine-and threonine-rich domain, and a C-terminal SH3-domain. The N-terminal and C-terminal domains of DBNL are highly conserved from mammal to yeast and are implicated in a multitude of cellular processes that include, endocytosis, migration, signaling, and viability. Recently, a proteomics analysis identified DBNL as a pro-survival signaling node in various cancers. Here we demonstrate that siRNA knockdown of DBNL reduces ErbB2+ breast cancer viability by arresting cell growth at the G1/S phase and by enhancing caspase-mediated apoptosis. Furthermore, knockdown of DBNL reduces cell surface levels of ErbB2 and decreases Akt phosphorylation. Elucidating the downstream signaling mechanisms that drive DBNL-mediated pro-survival will further aid in identifying new targets to ErbB2+ cancers as well as define additional roles of DBNL in cell biology.
Citation Format: Josephine F. Wixted, Matthew K. Robinson. DBNL is a pro-survival adaptor in ErbB2+ breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3905. doi:10.1158/1538-7445.AM2015-3905
Abstract 3906: Annexin A1 overexpression preferentially predicts poor prognosis of basal-like breast cancer patients by activating m TOR-S6 signaling
Authors: Tachibana Kazunoshin , Bhardwaj Anjana , Ganesan Nivetha , Rajapakshe Kimal , Albarracin Constance T. , Gunaratn Preethi H. , Coarfa Cristian , Bedrosian Isabelle 
Published: August 2015

Abstract
Introduction: Annexin A1 is an anti-inflammatory protein reported to play a role in cell proliferation, apoptosis and to be deregulated in breast cancer. The role and regulation of annexin A1 in the biology and prognosis of breast cancer remain unclear because most of the studies did not consider specific differences between the different subtypes of breast cancer. Thus, in this study, we hypothesize that annexin A1 plays subtype-specific role in basal like breast cancer progression and metastasis. Methods: By mining The Cancer Genome Atlas-Breast Cancer Dataset (TCGA-BRCA) and manipulating annexin A1 levels in breast cancer cell lines, we studied the role of annexin A1 in breast cancer and underlying signaling pathways. Results: Our in-silico analysis of TCGA-BRCA dataset demonstrated that annexin A1 mRNA expression is higher in basal subtype compared to luminal and HER2 subtypes. Within the basal subtype, patients show significantly poorer survival associated with higher expression of annexin A1. In both TCGA patient samples and cell lines, annexin A1 levels were significantly higher in basal-like breast cancer tumors than luminal and Her2/neu-positive breast cancer tumors. Stable annexin A1 knockdown in TNBC cell lines suppressed the mTOR-S6 pathway. Specifically, annexin A1 knockdown inhibited phosphorylation of mTOR and S6 (18-73% inhibition in pmTOR and 50-60% inhibition in pS6). But annexin A1 knockdown had no impact on the MAPK, c-Met, and EGFR pathways. In cell migration assays, annexin A1-depleted TNBC cells showed delayed migration as compared to wild-type cells which we found to be through suppression of MMP9. Conclusions: Our data suggest that annexin A1 is prognostic only in patients with basal like breast cancer. This appears to be due in part to the role of annexin A1 in activating mTOR-pS6 pathway.
Citation Format: Kazunoshin Tachibana, Anjana Bhardwaj, Nivetha Ganesan, Kimal Rajapakshe, Constance T. Albarracin, Preethi H. Gunaratn, Cristian Coarfa, Isabelle Bedrosian. Annexin A1 overexpression preferentially predicts poor prognosis of basal-like breast cancer patients by activating m TOR-S6 signaling. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3906. doi:10.1158/1538-7445.AM2015-3906
Abstract 391: Utility of circulating tumor cell (CTC) in advanced gastric cancer
Authors: Lee Won Suk , Kim Jeong Min , Kwon Woo Sun , Lim So Jung , Kim Tae Soo , Kim Ga Yun , Choi Sung Ho , Jeon Byung Hee , Jung Min Kyu , Ahn Joong Bae , Chung Hyun Cheol , Rha Sun Young 
Published: August 2015

Abstract
Circulating tumor cells (CTCs), known as the “leukemic phase” of solid tumor, have been associated with poor prognosis and clinical outcome in various cancer including breast and colorectal. However, fewer studies reported characteristic and usefulness of CTC as an indicator in gastric cancer (GC). In this study, we evaluated utility of CTC in advanced GC cancer. First, we confirmed detection rate of GC cancer cell lines as a spiking test, and then defined CTC as DAPI+, EpCAM+ and CD45- cells through immunofluorescence stating. To determine a cut-off for CTC of GC, we assessed the number of CTCs in blood of 22 healthy volunteers, and observed 1 (3/22) to 2 (1/22) of CTCs. Based on these results, we determined CTC positivity of GC as more than 3 CTCs. When we evaluated CTC positive rate in Stage IV GC patients, 28 patients were
CTC positive (30.1%) with the median number of CTC 5 (range 3 to over 100). Interestingly, 3 out of 28 patients were showed more than 100 CTCs. While, in operable GC patients (Stage I to III), CTC positivity was 18.4% (7/38) and median number of CTC was 4 (range 3 to 9) in CTC positive patients. These results showed that Stage IV GC patients have high number of CTCs than operable GC patients. Tumor histology and Lauren classification did not affect to CTC positivity in Stage IV and operable GC patients. We also observed the potential use of CTC in serial follow-ups and one of the cases shows the decreasing CTCs followed by clinical response. In conclusion, this study demonstrates that detection of CTC may be useful prognostic indicator of GC cancer patients.
Citation Format: Won Suk Lee, Jeong Min Kim, Woo Sun Kwon, So Jung Lim, Tae Soo Kim, Ga Yun Kim, Sung Ho Choi, Byung Hee Jeon, Min Kyu Jung, Joong Bae Ahn, Hyun Cheol Chung, Sun Young Rha. Utility of circulating tumor cell (CTC) in advanced gastric cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 391. doi:10.1158/1538-7445.AM2015-391
Abstract 3917: PDGF induces cell growth and glycolysis in colon cancer
Authors: Moench Romana , Kannen Vinicius , Grimmig Tanja , Germer Christoph T. , Gasser Martin , Waaga-Gasser Ana Maria 
Published: August 2015

Abstract
The platelet derived growth factor (PDGF) plays an important role in several solid tumors. Involved in cell migration and proliferation primarily of stromal cells in cancers PDGF represents a key target in cancer therapy. The aim of this study was to analyze the specific role of PDGF on tumor cell proliferation and metabolism in colorectal cancer (CRC). The human colon cancer cell line HT-29 was cultured and stimulated time-dependently with PDGF. Additionally, inhibition of the PI3k/Akt/mTOR-pathway was performed simultaneously to PDGF stimulation. Whole cell and RNA extracts were analyzed by Western Blot and RT-q-PCR for the PI3k/Akt/mTOR-pathway and components of cellular metabolism. To investigate the effects of PDGF on proliferation MTS assays were performed. Additionally, mRNA levels of PDGF and metabolic factors in tumors from patients with CRC were analyzed by RT-qPCR. PDGF stimulation resulted in increased HT29 cell proliferation compared to untreated controls. Blocking of Akt resulted in inhibition of pS6, activation of Retinoblastoma (Rb) and reduced tumor cell growth. Additionally, under stimulation a higher glycolytic rate was observed while oxygen consumption remained unaltered. Investigated tumors from patients with CRC showed a stage-dependent increase in PDGF expression and a boosted glycolytic rate. The cytokine PDGF induced proliferation accompanied with an altered glycolysis in HT-29 colon cancer. An increased glycolysis and tumor cell proliferation support accelerated cell proliferation and tumor growth. The growth reducing effect of Akt inhibition indicates the PI3K/Akt/mTOR-pathway to play a crucial role in CRC progression and therefore could be an important target in cancer therapy.
Note: This abstract was not presented at the meeting.
Citation Format: Romana Moench, Vinicius Kannen, Tanja Grimmig, Christoph T. Germer, Martin Gasser, Ana Maria Waaga-Gasser. PDGF induces cell growth and glycolysis in colon cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3917. doi:10.1158/1538-7445.AM2015-3917
Abstract 3920: Identification of LASEP1 as a new serological and prognostic biomarker and a therapeutic target for lung cancer
Authors: Takano Atsushi , Nakamura Yusuke , Daigo Yataro 
Published: August 2015

Abstract
Lung cancer is the leading cause of cancer deaths in the world and the overall prognosis remains poor. The poor prognosis of lung cancer patients is largely a result of the occult metastatic dissemination. Thus, the development of early cancer detection biomarker and new treatment is required. This study aims to identify novel biomarkers or therapeutic targets for lung cancers. We used cDNA microarrays for screening genes encoding transmembrane/secretory proteins that are up-regulated in lung cancers. As a result of this process, we identified a secreted protein, LASEP1 (lung cancer-associated serum protein 1) as a candidate. Immunohistochemical staining of LASEP1 showed that LASEP1 expression was observed in 210 (56.1%) of 374 NSCLC (non-small cell lung cancer) that had undergone curative surgery. High level of LASEP1 expression was associated with poor prognosis for NSCLC patients (P&lt;0.0001 by log-rank test). Serum LASEP1 levels were higher in NSCLC patients than in healthy volunteers. The proportion of serum LASEP1-positive cases was 127 (38.6%) of 329 NSCLCs, while 4 (3.9%) of 102 healthy volunteers were falsely diagnosed. Furthermore, reduction of LASEP1 by siRNA significantly induced the apoptosis of lung cancer cells. Furthermore, the growth activity of the LASEP1-positive cells was neutralized by addition of originally developed anti-LASEP1 monoclonal antibodies into their culture media, and the systemic administration of the anti-LASEP1 antibody to tumor-implanted mice significantly suppressed tumor growth without any adverse events. By gene expression analysis using microarray and mRNAs from lung cancer cells transfected with siRNA for LASEP1, we identified WHSC1 gene that encodes an oncogenic histone methyltransferase as one of LASEP1-target genes. These data suggest that LASEP1 is a possible diagnostic and prognostic biomarker and therapeutic target for lung cancer.
Citation Format: Atsushi Takano, Yusuke Nakamura, Yataro Daigo. Identification of LASEP1 as a new serological and prognostic biomarker and a therapeutic target for lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3920. doi:10.1158/1538-7445.AM2015-3920
Abstract 3926: RhoB expression is upregulated by androgen in thyroid cancer cells
Authors: Gupta Anvita , Jones Melanie , Moscatello Augustine , Shin Edward , Tiwari Raj K. , Geliebter Jan 
Published: August 2015

Abstract
The incidence of thyroid cancer has increased three-fold over the last thirty years and the American Cancer Society estimates that there will be 62,980 new cases and 1,890 deaths due to the disease in the United States in 2014. Papillary Thyroid Cancer (PTC) is the most common endocrine malignancy and develops in premenopausal women, at a four-fold higher incidence, than in men. However, PTC exhibits increased aggressiveness with poor prognosis in men diagnosed with the disease. These observations led us to explore the role of androgen and androgen receptor in this disease. Preliminary data from our lab indicates that androgen receptor (AR) acts as a negative regulator of growth as evidenced by a statistically significant decrease in proliferation upon DHT addition to 8505c anaplastic/PTC cells stably transfected with AR. Transcriptional profiling using RNA-Seq and gene ontology analysis, on a 48 hour DHT treated 8505c-AR transfected clone, 84E7, revealed significant changes in the expression of genes associated with proliferation (474 genes, p = 2.4E-24), cell cycle progression (129 genes, p = 6.54E-6) and migration (301 genes, p = 3.77E-30). Amongst the genes which showed the highest significant differential expression was RhoB, a Rho GTPase, with an approximately 50-fold upregulation. Rho proteins are small molecules belonging to the Ras superfamily, known to regulate cell morphology, actin/microtubule cytoskeleton reorganization along with vesicle trafficking. While RhoA and RhoC promote cancer progression and metastasis, the functions of their structural homolog, RhoB, are largely context dependent. Evidence has emerged that RhoB expression may support malignancy in certain cancers, while exhibiting a tumor-suppressor gene function in others. In our system, addition of DHT to 84E7 cells for short time periods of 1, 3 and 6 hours resulted in rapid RhoB mRNA upregulation by 2.5, 8, and 17 fold, respectively, compared to untreated cells. This quick, time-dependent increase in androgen-responsive RhoB may play an integral protective and reparative role which is possibly lost during neoplasticity of thyrocytes. Investigations into various pathways linking RhoB and effector proteins with carcinogenesis would be crucial in assessing the potential of RhoB as a bio-marker for metastatic PTC and thence opening avenues for development of viable therapies for better management of the disease.
Citation Format: Anvita Gupta, Melanie Jones, Augustine Moscatello, Edward Shin, Raj K. Tiwari, Jan Geliebter. RhoB expression is upregulated by androgen in thyroid cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3926. doi:10.1158/1538-7445.AM2015-3926
Abstract 3933: The landscape and clonal architecture in lower grade glioma
Authors: Suzuki Hiromichi , Aoki Kosuke , Chiba Kenichi , Sato Yusuke , Shiozawa Yusuke , Shiraishi Yuichi , Niida Atsushi , Shimamura Teppei , Sanada Masashi , Miyano Satoru , Wakabayashi Toshihiko , Natsume Atsushi , Ogawa Seishi 
Published: August 2015

Abstract
Lower grade gliomas (LGGs, WHO grade II/III gliomas) account for approximately one third of all gliomas. Although LGGs are typically slowly progressive, their clinical course is invariably indolent and most patients ultimately succumb to death. In contrast to glioblastoma (GBM), our knowledge about the genetic lesions and clonal evolution in LGG is still incomplete. So, to obtain a complete registry of gene mutations involved in LGG pathogenesis and their role in clonal evolution, we performed whole exome sequencing (WES) and/or targeted sequencing of 335 LGG cases. Clonal evolution in LGG was investigated using paired primary/relapsed tumor specimens from 10 cases as well as multiple tumor specimens (median 5) from 4 cases.
Massive parallel sequencing revealed LGGs were clearly grouped into three subgroups with or without IDH1/2 mutation and 1p19q loss of heterozygous (LOH). Type I tumor with IDH1/2 mutation and 1p19q LOH had a most favorable survival and harbored mutations in TERT promoter, CIC, FUBP1 and NOTCH1. Type II tumor with IDH1/2 mutant/1p19q intact subtype represented TP53 bialleleic inactivation and/or ATRX mutations. Type III tumor with IDH1/2 intact showed GBM like mutation profile and poor prognosis.
Large scale samples allowed to obviously detect strong positive/negative correlations with each other driver genes. Extensive analysis of variant allele frequencies among co-existing mutations revealed temporal orders of gene mutations in each subtypes.
Multi regional/time-points sampling analysis suppoted mutational order and revealed regional and special heterogeneity with tumor evolution in LGGs. LGG contiguously developed and generated heterogeneity through acquiring new mutations in a complex but ordered fashion.
In conclusion, our findings delineated the landscape of gene mutations in LGG. LGG had mutually exclusive mutational patterns with hierarchical order in discrete subtypes. IDH1/2 and TERT promoter mutations and 1p19q LOH were thought to exist in the major clone and important role in tumor initiation. In contrast, common occurrence of parallel mutations found in TP53, ATRX, CIC, FUBP1 and NOTCH1 genes indicated central roles of these mutations in LGG development.
Citation Format: Hiromichi Suzuki, Kosuke Aoki, Kenichi Chiba, Yusuke Sato, Yusuke Shiozawa, Yuichi Shiraishi, Atsushi Niida, Teppei Shimamura, Masashi Sanada, Satoru Miyano, Toshihiko Wakabayashi, Atsushi Natsume, Seishi Ogawa. The landscape and clonal architecture in lower grade glioma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3933. doi:10.1158/1538-7445.AM2015-3933
Abstract 3945: PTEN loss is associated with aggressive behavior and poor prognosis in Middle Eastern Triple Negative Breast Cancer
Authors: Siraj Abdul K. , Beg Shaham , Prabhakaran Sarita , Jehan Zeenath , Ajarim Dahish , Al-Dayel Fouad , Tulbah Asma , Al-Kuraya Khawla 
Published: August 2015

Abstract
PTEN is a tumor suppressor that negatively regulates the PI3K-AKT signaling pathway which is involved in the pathogenesis of many different tumor types and serves as a prognostic marker in breast cancer. However, the significance of the role of PTEN in Middle Eastern ethnic breast cancer has not been explored especially with the fact that breast cancer originating from this ethnic population tend to behave more aggressively than breast cancer in the west. In order to learn more on the prevalence and clinical significance of PTEN protein expression and PTEN gene deletions, a tissue microarray containing more than 1000 primary breast cancers with clinical follow up data was used. Tissue Microarray sections were analyzed for protein expression and copy number change using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Loss of PTEN immunostaining was observed in 77% of the cases. PTEN loss was significantly associated with large tumor size (p = 0.0030), high grade (p = 0.0281), tumor recurrence (p = 0.0333) and Triple negative breast cancers (p = 0.0086). PTEN loss in Triple negative breast cancers was significantly associated with rapid tumor cell proliferation (p = 0.0396) and poor prognosis (p = 0.0408). PTEN deletion was found only in 60 cases (6.4%) of cases. It was concluded that loss of PTEN protein expression occurs at high frequency in Middle Eastern breast cancer. PTEN inactivation may potentially lead to an aggressive behavior of tumor cells through stimulation of tumor cell proliferation. Furthermore PTEN signaling pathway might be used as potential therapeutic target in Triple negative breast cancers since loss of its expression is shown to be significantly associated with this aggressive subtype of breast cancer.
Citation Format: Abdul K. Siraj, Shaham Beg, Sarita Prabhakaran, Zeenath Jehan, Dahish Ajarim, Fouad Al-Dayel, Asma Tulbah, Khawla Al-Kuraya. PTEN loss is associated with aggressive behavior and poor prognosis in Middle Eastern Triple Negative Breast Cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3945. doi:10.1158/1538-7445.AM2015-3945
Abstract 3970: Development of novel form of mimic microRNA for lung cancer therapy
Authors: Ohno Shinichiro , Itano Karen , Harada Yuichirou , Asada Koutaro , Oikawa Keiki , Kashiwazako Mikie , Takanashi Masakatsu , Sudo Katsuko , Ikeda Norihiko , Kuroda Masahiko 
Published: August 2015

Abstract
Exogenously supplied tumor suppressor miR-34a induces apoptosis and cell cycle arrest in lung cancer cell lines. It is suggested that miRNA replacement therapy of miR-34a is a promising approach for the treatment of lung cancer. On the one hand, the immunological response to nucleic acid via Toll like receptors (TLRs) and RIG-I like receptors (RLRs) that restrict the practical use of nucleic acid drugs in the clinical setting. It is known that the immunological response to the nucleic acid is strongly depends the length of nucleic acid. Therefore, we have tried to develop a shorter nucleic acid drugs that can escape immune surveillance. The deletion of nucleotide with maintenance of the secondary structure of short miR-34a keeps the activity and the target specificity of miR-34a. Finally, miR-34a can be shortened from 44 to 30 nucleobase. The shortened 30 nucleotides miR-34a was named “Guide hairpin RNA (ghR) -34a” and analyzed in detail. The inhibitory activity against miR-34a targets genes such as AXL, MET and CDK6 were comparable between ghR-34a and physiological form of miR-34a at both the mRNA and protein levels. Similarly, there is no difference in the antiproliferative activity against lung cancer cell line between ghR-34a and miR-34a. On the other hand, the ghR-34a does not induce inflammatory response and unwanted gene inhibition by passenger strand. These data indicated that ghR-34a can inhibits lung cancer with low side effects. Furthermore, the shortening methods can be broadly applied to the other miRNAs. Thus, the shortening methods of miRNA developed in the study may be provide a novel, safe and effective nucleic acid drug platform and promote the clinical usefulness of nucleic acid therapy.
Note: This abstract was not presented at the meeting.
Citation Format: Shinichiro Ohno, Karen Itano, Yuichirou Harada, Koutaro Asada, Keiki Oikawa, Mikie Kashiwazako, Masakatsu Takanashi, Katsuko Sudo, Norihiko Ikeda, Masahiko Kuroda. Development of novel form of mimic microRNA for lung cancer therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3970. doi:10.1158/1538-7445.AM2015-3970