bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1944: Evaluation of the prognostic value of miRNA-181b and its target identification and validation in colorectal cancers.
Authors: Bovell Liselle , Putcha Balananda-Dhurjati K. , Devadasan Divya , Bae Sejong , Grizzle William E. , Manne Upender 
Published: August 2014

Abstract
Background: microRNAs (miRNAs) are 19 to 24 nucleotide sequences that regulate cell proliferation, differentiation, and apoptosis. miRNA-181b is involved in tumor initiation and progression of several human malignancies including colorectal cancers (CRCs). Thus, we sought to determine the prognostic value of miRNA-181b in CRCs.
Methods: Expression of miRNA-181b was quantified, by quantitative PCR (q-RT-PCR), in normal (benign colonic epithelia) tissues and in their corresponding CRC archival tissue samples collected from 345 patients. The expression levels were correlated with patient overall survival. Putative molecular targets of miRNA-181b were identified by in silico analysis. miRNA-181b mediated, post-transcriptional regulation of these targets was assessed in CRC cell lines (SW480, HCT116 p53-/- and HCT116 +/+) by transfection studies. The targets were validated by measuring their mRNA expression levels, by use of qRT-PCR, in CRC tissues that exhibited elevated levels of miRNA-181b as well as by cloning techniques to assess a direct interaction between miRNA-181b and 3’UTRs of its target genes using luciferase assays.
Results: Survival analysis indicated that increased expression of miRNA-181b was associated with poor prognosis for CRCs (log rank, p=0.004). Fourteen putative molecular targets of miRNA-181b were identified by in silico analysis, and miRNA-181b mediated post-transcriptional regulation of these targets was validated in CRC cell lines by q-RT-PCR. Integrin alpha-3 was up-regulated, and BCL2LII and TNFα were down-regulated upon overexpression of miRNA-181b in vitro. Also, these targets were validated in CRC tissues that exhibited elevated miRNA-181b levels. The direct interaction of miRNA-181b with the target gene 3’UTRs was validated with luciferase assays.
Conclusions: These findings demonstrate that miRNA-181b regulates expression of Integrin alpha-3, BCL2LII, and TNFα; and is a prognostic marker for colorectal cancers.
Citation Format: Liselle Bovell, Balananda-Dhurjati K. Putcha, Divya Devadasan, Sejong Bae, William E. Grizzle, Upender Manne. Evaluation of the prognostic value of miRNA-181b and its target identification and validation in colorectal cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1944. doi:10.1158/1538-7445.AM2013-1944
Abstract 1956: High-throughput screens identify microRNAs essential for HER2-positive breast cancer cell growth.
Authors: Leivonen Suvi-Katri , Kleivi Sahlberg Kristine , Makela Rami , Kallioniemi Olli , Borresen-Dale Anne-Lise , Perala Merja 
Published: August 2014

Abstract
MicroRNAs (miRNAs) are small non-coding RNAs regulating gene expression post-transcriptionally. Due to their capability to target multiple genes, often in a same pathway, miRNAs would be ideal candidates for therapeutic targeting. Here, our aim was to characterize the role of miRNAs in the regulation of HER2-signaling in breast cancer. HER2 is a receptor tyrosine kinase amplified in over 20% of human breast cancers and it regulates many important cellular processes, including cell growth and survival. HER2 mediates its signals by activating downstream pathways, such as phosphatidyl-inositol-3 kinase (PI3K)/AKT and the mitogen-activated protein kinases.
We performed miRNA gain-of-function assays by screening two HER2-positive cell lines (KPL-4 and JIMT-1) with a miRNA mimic library consisting of 810 human miRNAs. The levels of HER2, phospho-AKT, phospho-ERK1/2, cell proliferation (Ki67) and apoptosis (cleaved PARP) were detected with specific antibodies using protein lysate microarrays. In order to find the miRNAs most efficiently inhibiting HER2 signaling and proliferation as well as inducing apoptosis, we did rank product analyses through the whole data matrix. These analyses resulted in 38 miRNAs (q≤0.05). Among them were miR-491-5p, miR-342-5p and miR-744*, which were significantly (p≤0.05) down-regulated in HER2-positive breast tumors as compared to HER2-negative tumors. miR-342-5p appeared to specifically inhibit HER2-positive cell growth, as it had no effect on the growth of HER2-negative control cell line. Furthermore, higher expression of miR-342-5p was associated with better survival in breast cancer patients. We characterized also miRNAs directly targeting HER2 and identified eight novel miRNAs (miR-552, miR-541, miR-193a-5p, miR-453, miR-134, miR-498, miR-449b, and miR-449a) as direct regulators of the HER2 3’UTR.
Taken together, the miRNAs identified here are potent negative regulators of HER2 function and they may also play a role in vivo during breast cancer progression. These results suggest mechanistic insights in HER2 regulation in breast cancer and open potential new strategies towards prevention and therapeutic inhibition of HER2-positive breast cancer.
Citation Format: Suvi-Katri Leivonen, Kristine Kleivi Sahlberg, Rami Makela, Olli Kallioniemi, Anne-Lise Borresen-Dale, Merja Perala. High-throughput screens identify microRNAs essential for HER2-positive breast cancer cell growth. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1956. doi:10.1158/1538-7445.AM2013-1956
Abstract 1976: Targeting the PP2A tumor suppressor for the treatment of human pancreatic cancer.
Authors: Farrell Amy , Daniel Colin , Wang Zhiping , Allen-Petersen Brittany , Christensen Dale , Sheppard Brett , Lopez Charles D. , Sears Rosalie 
Published: August 2014

Abstract
Pancreatic cancer is a disease with a high rate of mortality, as it is generally diagnosed in the advanced stages when few effective treatments are available. Given the clinical aggressivity of this disease and the lack of good treatment options, the development of new therapeutic agents for the treatment of pancreatic cancer is of the upmost importance. Recent reports have suggested that disruption of several key signal transduction pathways is important for the development of pancreatic cancer. Many of these pathways are negatively regulated by PP2A, a phosphatase that plays a role in many cellular processes, and whose inhibition is essential for cell transformation. PP2A inhibition can occur through inactivation by viral oncogenes, mutation of specific subunits, or by overexpression of endogenous inhibitors, including SET (also known as I2PP2A) and Cellular Inhibitor of PP2A (CIP2A). Here, we show that SET and CIP2A are frequently overexpressed in human pancreatic cancer cells and primary patient samples. This overexpression results in decreased PP2A activity, and overexpression and stabilization of a key PP2A target, c-Myc. Knockdown of SET or CIP2A increases PP2A activity and reduces tumorigenic potential. Furthermore, inhibition of SET using a peptide mimetic (OP449) in pancreatic cancer cell lines increases PP2A activity, reduces migration and invasion, and decreases tumorigenic potential. Thus, antagonizing SET and CIP2A could be an innovative approach for the treatment of human pancreatic cancer.
Citation Format: Amy Farrell, Colin Daniel, Zhiping Wang, Brittany Allen-Petersen, Dale Christensen, Brett Sheppard, Charles D. Lopez, Rosalie Sears. Targeting the PP2A tumor suppressor for the treatment of human pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1976. doi:10.1158/1538-7445.AM2013-1976
Abstract 1997: A gene expression profiling and molecular pathway analysis in early recurrence of patients with early stage lung adenocarcinoma.
Authors: Saji Hisashi , Tsuboi Masahiro , Shimada Yoshihisa , Kato Yasufumi , Hamanaka Wakako , Yoshida Koichi , Usuda Jitsuo , Ohira Tatsuo , Ikeda Norihiko 
Published: August 2014

Abstract
Background: Clinico-histopathological staging is insufficient to predict disease progression and clinical outcome in lung carcinoma. Here, we show that gene expression profiles and molecular pathways based on microarray and functional analysis can be used to predict early relapse in patients with early-stage lung adenocarcinoma.
Methods and Results: Based on the results of principal component analysis of a series of 24 samples of early-stage lung adenocarcinoma, there were two subgroups within the early-relapse group. The histological classification of all of group A was poorly differentiated, whereas only one of three cases in group B was classified as such. DAVID functional annotation analysis revealed 16 and 17 enriched pathways in groups A and B, respectively. Clusters of genes related to oncological or immunological functional signaling were found enriched in group A as were pathways such as cell adhesion molecules (CAMs), cell cycle, and antigen processing and presentation, whereas in group B the pathways were CAMs, T cell receptor signaling, cytokine-cytokine receptor interaction, toll-like receptor signaling, chemokine signaling, primary immunodeficiency, and natural killer cell mediated cytotoxicity. The CAMs pathway was found to be enriched in both groups.Conclusions: In this study, we present a comprehensive gene expression analysis and functional pathway analysis of early-stage lung adenocarcinoma, wherein we identified a distinct molecular pathway category, CAMs that correlated with early relapse of early-stage lung adenocarcinoma subclasses. This prognostic signature could be used to identify patients with early-stage high-risk NSCLC who might benefit from adjuvant therapy following surgery.
Citation Format: Hisashi Saji, Masahiro Tsuboi, Yoshihisa Shimada, Yasufumi Kato, Wakako Hamanaka, Koichi Yoshida, Jitsuo Usuda, Tatsuo Ohira, Norihiko Ikeda. A gene expression profiling and molecular pathway analysis in early recurrence of patients with early stage lung adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1997. doi:10.1158/1538-7445.AM2013-1997
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 20: GIST-specific markers identified by comprehensive gene expression profiles.
Authors: Iwadate Manabu , Miyamoto Kohtaro , Ito Emi , Imai Jun-ichi , Sawada Naoki , Nakamura Izumi , Ohki Shinji , Watanabe Shinya , Waguri Satoshi , Takenoshita Seiichi 
Published: August 2014

Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract and highly express c-kit. Although surgical removal and molecularly targeted therapy are known to be effective, specific markers other than c-kit would be beneficial for histopathological classification, risk assessment, and treatment decision. To this end, we conducted a DNA-microarry analysis using approximately 900 tumor tissues obtained in Fukushima Medical University Hospital from 2007 to present. The database contained more than 30 kinds of tumors including 10 cases of GIST. We searched ∼32,000 genes on the array that showed expression ratio of &gt;2.0 in GIST samples compared to others, and finally extracted 54 GIST-specific genes. In this study, we identified that cathepsin L mRNA is highly expressed in GISTs. Moreover, immunohistochemical analysis of 43 GIST specimens revealed that 86.0% (n = 37) were cathepsin-L positive, and this positivity was significantly correlated with c-kit positivity. From these results, we conclude that cathepsin L is highly expressed in GISTs.
Citation Format: Manabu Iwadate, Kohtaro Miyamoto, Emi Ito, Jun-ichi Imai, Naoki Sawada, Izumi Nakamura, Shinji Ohki, Shinya Watanabe, Satoshi Waguri, Seiichi Takenoshita. GIST-specific markers identified by comprehensive gene expression profiles. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 20. doi:10.1158/1538-7445.AM2013-20
Abstract 2002: Genomic landscape of copy number aberrations enables the identification of oncogenic drivers in hepatocellular carcinoma.
Authors: Wang Kai , Lim Ho Yeong , Shi Stephanie , Lee Jeeyun , Deng Shibing , Xie Tao , Zhu Zhou , Wang Yuli , Pocalyko David , Yang Wei J. , Rejto Paul A. , Mao Mao , Park Cheol-Keun , Xu Jiangchun 
Published: August 2014

Abstract
Cancer is a genetic disease with frequent somatic alterations in DNA. Study of recurrent copy number aberrations (CNAs) in human cancers would enable the elucidation of disease mechanisms and the identification of key oncogenic drivers with causal roles in oncogenesis. We have comprehensively and systematically characterized CNAs and accompanied gene expression changes in the tumors and their matched non-tumor liver tissues from 286 hepatocellular carcinoma (HCC) patients. Our analysis identified 29 recurrently amplified regions and 22 deleted regions with a high level of copy number changes, harboring established oncogenes and tumor suppressors, including CCND1, MET, CDKN2A and CDKN2B, as well as many other genes not previously reported to be involved in liver carcinogenesis. Pathway analysis of cis-acting genes in the amplification and deletion peaks suggests the alterations of core cancer pathways, including cell cycle, p53, PI3K, MAPK, Wnt and TGFβ signaling, in large proportions of HCC patients. We further credentialed two candidate driver genes, BCL9 and MTDH, from the recurrent focal amplification peaks and showed that they play a significant role in HCC growth and survival. In summary, we have demonstrated that characterizing the CNA landscape in HCC will facilitate the understanding of disease mechanisms and the identification of oncogenic drivers that may serve as potential therapeutic targets for the treatment of this devastating disease.
Citation Format: Kai Wang, Ho Yeong Lim, Stephanie Shi, Jeeyun Lee, Shibing Deng, Tao Xie, Zhou Zhu, Yuli Wang, David Pocalyko, Wei J. Yang, Paul A. Rejto, Mao Mao, Cheol-Keun Park, Jiangchun Xu. Genomic landscape of copy number aberrations enables the identification of oncogenic drivers in hepatocellular carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2002. doi:10.1158/1538-7445.AM2013-2002
Abstract 203: Dynamic biochemical tissue analysis provides a unique method to detect functional in situ L-selectin ligands and unveils intercellular heterogeneity in colon cancer tissues.
Authors: Carlson Grady E. , Shirure Venktesh S. , Resto Vicente A. , Malgor Ramiro , Goetz Douglas J. , Burdick Monica M. 
Published: August 2014

Abstract
A growing body of evidence suggests that E-,P-, and L-selectin, a family of cell adhesion molecules, engage their ligands on colon cancer cells to initiate adhesion with the blood vessel wall at the secondary site during metastasis. This initial adhesion is a “rolling” adhesion in which selectin/selectin ligand bonds break and reform under forces in hemodynamic flow. Current standards for tissue analyses, such as immunostaining, do not assay for functional in situ selectin ligands, i.e., those that promote rolling. Recently, our lab developed a novel tissue analysis, termed dynamic biochemical tissue analysis (DBTA), which detects functional selectin ligands in situ by probing pathological tissues with selectin-coated microspheres. Due to the application of hydrodynamic flow in the assay, the selectin coated microspheres “roll” on tissue sections presenting functional selectin ligands. When colon cancer tissue sections of diverse histological classifications were probed with L-selectin-coated microspheres in DBTA, functional L-selectin ligands were detected (i.e., L-selectin microspheres rolled on the surface of the tissue sections). Rolling velocities were a function of hemodynamic shear stress, illustrating the unique kinetic and tensile properties of force-dependent L-selectin/L-selectin ligand bonds. More specifically, DBTA preserved the catch-slip behavior of selectin/selectin ligand bonds. That is, rolling became stabilized at physiologic shear stresses between 0.5-0.75 dyne/cm2, but outside this range microsphere rolling was increasingly erratic as bond breakage exceeded bond formation necessary to preserve adhesion. Differences in microsphere rolling velocities varied with position on the tissue surface and thereby demonstrated the heterogeneous expression of functional L-selectin ligands on colon cancer tissues. In summary, DBTA provides a unique method to detect functional in situ L-selectin ligands and unveils intercellular heterogeneity such that, with further development, DBTA may promote potential diagnostics and prognostics for cancer characterization.
Citation Format: Grady E. Carlson, Venktesh S. Shirure, Vicente A. Resto, Ramiro Malgor, Douglas J. Goetz, Monica M. Burdick. Dynamic biochemical tissue analysis provides a unique method to detect functional in situ L-selectin ligands and unveils intercellular heterogeneity in colon cancer tissues. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 203. doi:10.1158/1538-7445.AM2013-203
Abstract 2033: Identification of a novel genetic abnormality, the amplification of rictor (rapamycin-insensitive companion of mTOR), in a patient with non-small cell lung cancer.
Authors: Cheng Haiying , Piperdi Bilal , Schwartz Edward L. , Zhu Changcheng , Zhang Zhenfeng , Halmos Balazs , Miller Vincent , Perez-Soler Roman 
Published: August 2014

Abstract
Despite recent advances, clinically-relevant oncogenic drivers have not been identified in about half of lung adenocarcinormas. Here, we report rictor (rapamycin-insensitive companion of mTOR) amplification as a novel genetic abnormality in a young patient with non-small cell lung cancer. This male patient was a never smoker and was diagnosed with lung adenocarcinorma at the age of 18. He initially presented with refractory cough and persistent left lung lesions. Pathology was consistent with lung adenocarcinorma, poorly differentiated. Extensive molecular testing was negative for common genetic alterations in K-RAS, EGFR, ALK, HER2, RET, AKT, PIK3CA, BRAF and ROS1. His tumor was subsequently subjected to next generation DNA sequencing (FoundationOne, Foundation Medicine, Cambridge, MA) targeting a cohort of more than 180 cancer-related genes. This analysis identified rictor amplification of at least 6 copies as the sole DNA abnormality. Immunohistochemistry further documented rictor overexpression in the patient's lung tumor. The neoplastic lung tissue exhibited diffuse and strong cytoplasmic staining for rictor, compared to surrounding non-neoplastic tissues. Furthermore, the tumor tissue showed diffuse overexpression of phospho-S473 Akt, an essential downstream target of rictor.
Rictor is a key component of mTORC2 complex, where it modifies actin cytoskeleton organization, cell proliferation and survival. Activation of rictor signaling has been suggested to play critical roles in regulating cancer cell migration, invasion and metastasis in breast, ovarian, and colorectal cancers and gliomas. To our knowledge, this is the first report of rictor amplification in lung cancer. Moreover, we found that blockade of the rictor-mTORC2 pathway by siRNA-mediated rictor knockdown or with pharmacological inhibitors led to decreased phosphorylation of S473-AKT and growth inhibition in lung cancer cell lines. Thus, rictor amplification may represent a potential novel target in lung cancer. We will perform further studies to determine whether rictor amplification is a unique molecular subtype of lung cancer. Further, we hope to identify which targeted drugs are active against tumors with rictor amplification and overexpression.
Citation Format: Haiying Cheng, Bilal Piperdi, Edward L. Schwartz, Changcheng Zhu, Zhenfeng Zhang, Balazs Halmos, Vincent Miller, Roman Perez-Soler. Identification of a novel genetic abnormality, the amplification of rictor (rapamycin-insensitive companion of mTOR), in a patient with non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2033. doi:10.1158/1538-7445.AM2013-2033
Abstract 2062: The effects of a cell cycle inhibitory peptide fused to elastin-like polypeptide on pancreatic cancer cells with hyperthermia and its combination with gemcitabine.
Authors: Ryu Jung Su , Mikecin Ana-Matea , Raucher Drazen 
Published: August 2014

Abstract
Pancreatic cancer is the fourth most common cause of death in United States. Gemcitabine, a pyrimidine nucleoside analogue similar to cytarabine, has been used as a first line treatment for pancreatic cancer since 1997. However, its use has been limited by the side effects such as myelosuppression. So far, many efforts have been made to combine gemcitabine with other drugs, but have failed to prove superior to gemcitabine alone. This work describes the effects of genetically engineered elastin - like polypeptide (ELP) with the p21 Waf1/Cip1 - derived cell cycle inhibitory peptide (p21) on pancreatic tumor cells with or without gemcitabine. ELP is a thermally responsive polypeptide carrier that are soluble in aqueous solutions at physiological temperature (37 °C), but aggregate when the temperature is raised above its transition temperature (Tt, 42 °C). This allows it to be a promising thermally responsive therapeutic carrier that may be actively targeted to solid tumors by application of focused hyperthermia. For this study, we designed p21-ELP conjugates modified with the cell penetrating peptide, Bac, on the C-terminus of ELP. The anti-proliferative activity of p21-ELP-Bac was greater in with the presence of hyperthermia, and the combination therapy with gemcitabine showed the synergism on three pancreatic cancer cells - S2013, Panc-1, and Mia PaCa-2 in vitro. The reduced phosphorylated Rb level and the decrease of S- phase population in tumor cells treated with p21-ELP-Bac conjugates proves that the cytotoxicity which is based on cell cycle inhibition. In the S2013 pancreatic xenograft model, p21-ELP-Bac showed significant tumor growth inhibition in the presence of local hyperthermia; and this tumor growth inhibition was further enhanced upon co-treatment with gemcitabine. This combinatorial effect is expected to alleviate the toxicity of gemcitabine by reducing the dose in the clinics. Overall, our data suggest that thermal targeting of ELP-based therapeutic peptides to the pancreatic cancer cells is an effective and promising treatment strategy, especially in combination with gemcitabine.
Citation Format: Jung Su Ryu, Ana-Matea Mikecin, Drazen Raucher. The effects of a cell cycle inhibitory peptide fused to elastin-like polypeptide on pancreatic cancer cells with hyperthermia and its combination with gemcitabine. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2062. doi:10.1158/1538-7445.AM2013-2062