bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3384: Cancer Core 125 Panel for quantitative expression and mutation profiling
Authors: Chenchik Alex , Makhanov Mikhail , Dolganov Gregory , Jeffrey Stefanie 
Published: August 2015

Abstract
Molecular profiling of heterogeneous circulating tumor cells (CTCs) and tumor biopsy samples at the single-cell level is critical for identifying different cancer cell subpopulations and understanding their value in predicting metastatic cancer progression and responses to treatment. Unfortunately, the isolation and comprehensive characterization of hundreds to thousands of individual cancer cells present formidable analytical and technical challenges.
To this end, we developed a high-throughput (HT) HiCellex technology to obtain the genome-wide expression and mutation profiles of hundreds to thousands of epithelial cancer cells at the single cell level. Importantly, HiCellex allows selective molecular profiling of a complete set of viable cells at the single-cell level in the presence of contaminating leukocytes without physical separation of individual cells. The genetic profiling technology uses unique cell-specific molecular barcodes to label mRNAs in individual viable cancer cells by a spliceosome-mediated trans-splicing mechanism. Barcoded trans-splicing constructs, necessary for the labeling of the entire population of pre-mRNAs, are delivered and expressed in a pool of target cancer cells with lentiviral vectors. Digital expression data are generated by HT sequencing of barcoded amplified cDNAs and easily cluster to each cell in silico using cell-specific barcodes.
This presentation will provide results of development and validation of genome-wide and multiplex RT-PCR profiling assay of the 500 most informative subtyping and metastatic signature genes (MGS) in model cancer cell lines, CTC and tumor samples. The developed HiCellex 500 MGS profiling assay is a cost-effective approach to effectively characterize, subtype and identify prognostic and diagnostic biomarkers in heterogeneous cancer cells at the single-cell level.
Citation Format: Alex Chenchik, Mikhail Makhanov, Gregory Dolganov, Stefanie Jeffrey. Cancer Core 125 Panel for quantitative expression and mutation profiling. [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 3384. doi:10.1158/1538-7445.AM2015-3384
Abstract 3386: The development of a highly specific monoclonal antibody against Ki67 useful for immunohistochemistry
Authors: Chen Caiwei , Yuan Kehu , Chu Boyang , Shu Youmin , Chen Jian , Stafford Joe , Fu Wei , He Wei-Wu , Chambers Ross , Ma Donghui 
Published: August 2015

Abstract
Ki-67 is a nuclear protein that is a useful marker of proliferation. Ki-67 antibodies are used to generate a Ki-67 labeling index, which is the percentage of cells with nuclear immunostaining in immunohistochemistry. The Ki-67 labeling index may be useful as a prognostic and predictive marker in cancer. The Ki-67 labeling index relies on the use of antibodies with a suitable level of sensitivity and specificity, and many Ki-67 antibodies have been developed over the last two decades. One of the most widely used Ki-67 antibodies is the mouse monoclonal MIB1. However, there have been many reports showing that in some cases MIB1 detects an unexpected membranous and cytoplasmic staining pattern in immunohistochemistry. Since Ki-67 is exclusively expressed in the nucleus this raises questions about the specificity of MIB1. We have created a nearly comprehensive microarray of about 17,000 human proteins to investigate the specificity of MIB1 and identify cross reacting proteins. The protein microarray was also used to screen new panels of mouse monoclonals against Ki-67. We have identified the antibody UMAB107 that in immunohistochemistry performs with similar sensitivity as MIB1, but unlike MIB1, UMAB107 is highly specific.
Citation Format: Caiwei Chen, Kehu Yuan, Boyang Chu, Youmin Shu, Jian Chen, Joe Stafford, Wei Fu, Wei-Wu He, Ross Chambers, Donghui Ma. The development of a highly specific monoclonal antibody against Ki67 useful for immunohistochemistry. [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 3386. doi:10.1158/1538-7445.AM2015-3386
Abstract 3397: ￼A novel clinical tool that provides quantitative and accurate measurement of Met protein
Authors: Cecchi Fabiola , Liao Wei-Li , Thyparambil Sheeno , Darfler Marlene , Krizman David , Hembrough Todd , Burrows Jon , Bottaro Don , Catenacci Daniel V.T. 
Published: August 2015

Abstract
BACKGROUND:
Overexpression of Met tyrosine kinase receptor is associated with poor prognosis. Overexpression, and particularly MET amplification, are predictive of response to Met-specific therapy in preclinical models. Immunohistochemistry (IHC) of formalin-fixed paraffin-embedded (FFPE) tissues is currently used to select for ‘high Met’ expressing tumors for Met inhibitor trials. IHC suffers from antibody non-specificity, lack of quantitative resolution, and, when quantifying multiple proteins, inefficient use of scarce tissue.
METHODS:
After describing the development of the Liquid-Tissue-Selected Reaction Monitoring-mass spectrometry (LT-SRM-MS) Met assay, we evaluated the expression level of Met in 130 FFPE gastroesophageal cancer (GEC) tissues. We assessed the correlation of SRM Met expression to IHC and mean MET gene copy number (GCN)/nucleus or MET/CEP7 ratio by fluorescence in situ hybridization (FISH).
RESULTS:
Proteomic mapping of recombinant Met identified 418TEFTTALQR426 as the optimal SRM peptide. Limits of detection (LOD) and quantitation (LOQ) for this peptide were 150 and 200 amol/μg tumor protein, respectively. The assay demonstrated excellent precision and temporal stability of measurements in serial sections analyzed one year apart. Expression levels of 130 GEC tissues ranged (&lt;150 amol/μg to 4669.5 amol/μg. High correlation was observed between SRM Met expression and both MET GCN and MET/CEP7 ratio as determined by FISH (n = 30; R2 = 0.898). IHC did not correlate well with SRM (n = 44; R2 = 0.537) nor FISH GCN (n = 31; R2 = 0.509). A Met SRM level of &gt;1500 amol/μg was 100% sensitive (95% CI 0.69-1) and 100% specific (95% CI 0.92-1) for MET amplification.
CONCLUSIONS:
The Met SRM assay measured the absolute Met levels in clinical tissues with high precision. Compared to IHC, SRM provided a quantitative and linear measurement of Met expression, reliably distinguishing between non-amplified and amplified MET tumors. These results demonstrate a novel clinical tool for efficient tumor expression profiling, potentially leading to better informed therapeutic decisions for patients with GEC.
Citation Format: Fabiola Cecchi, Wei-Li Liao, Sheeno Thyparambil, Marlene Darfler, David Krizman, Todd Hembrough, Jon Burrows, Don Bottaro, Daniel V.T. Catenacci. ￼A novel clinical tool that provides quantitative and accurate measurement of Met protein. [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 3397. doi:10.1158/1538-7445.AM2015-3397
Abstract 3415: PAICS is the prognostic marker in colorectal cancer patients with stage III
Authors: Kobayashi Yusuke , Kumamoto Kensuke , Matsumoto Yoshiko , Saito Motonobu , Shimura Tatsuo , Takenoshita Seiichi 
Published: August 2015

Abstract
PAICS (Phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase) is an important bifunctional enzyme in de novo purine biosynthesis. It could be an attractive target for anticancer drug design, since rapidly dividing cancer cells rely on the purine through de novo pathway for synthesis of adenine and guanine, whereas normal cells favor the salvage pathway.
Previous reports demonstrated that PAICS expression was up-regulated in ALL, lung cancer, and glioblastoma. In the present study, we first performed the comparison of PAICS mRNA expression between cancer tissue and normal colonic mucosa in 83 colorectal cancer (CRC) patients by realtime RT-PCR. We further investigated PAICS expression by immunohistochemical staining in 258 CRC patients and analyzed the association between PAICS expression and clinicopathological factors and prognosis. To understand the biological significance of PAICS expresssion, knockdown experiments of PAICS expression were performed by a siRNA method using the colon cancer cell line, HCT116. We analyzed the relationship between PAICS mRNA expression and genetic status and prognosis using several databases.
PAICS mRNA expression in CRC tissue was significantly enhanced when compared to that in normal tissue. In immunohistochemical examination, PAICS expression was observed in cytoplasm of cancer cells. PAICS expression was detected in 55% cases of colorectal cancer patients. There were significant association between PAICS expression and histology (p = 0.049). There was not significant correlation between PAICS expression and overall survival in CRC patients. Regarding CRC patients with stage III, patients with positive expression of PAICS had significantly good prognosis as compared to those with negative expression (p = 0.015). Knockdown of PAICS expression acquired the ability of cellular invasion using colon cancer cell lines, HCT116 and SW480. In all CRC databases we analyzed, stage III patients with high expression of PAICS had good prognosis as compared to those with low expression of PAICS.
We concluded that PAICS expression was up-regulated in approximately 55% CRC, and higher level of PAICS expression might serve as a good prognostic marker in advanced CRC patients.
Citation Format: Yusuke Kobayashi, Kensuke Kumamoto, Yoshiko Matsumoto, Motonobu Saito, Tatsuo Shimura, Seiichi Takenoshita. PAICS is the prognostic marker in colorectal cancer patients with stage III. [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 3415. doi:10.1158/1538-7445.AM2015-3415
Abstract 3417: Snail and serpinA1 promote tumor progression and predict prognosis in colorectal cancer
Authors: Kwon Chae Hwa , Park Hye Ji , Lee Ja Rang , Kim Hye Kyung , Park Do Youn 
Published: August 2015

Abstract
Purpose: Snail and serpin peptidase inhibitor clade A member 1 (serpinA1) are involved in tumor progression. In this study, we investigated the role of Snail and serpinA1 in colorectal cancer (CRC) and examined the mechanisms through which these proteins mediate CRC progression.
Experimental Design: Tumors from 528 patients with CRC were examined to determine the clinicopathological significance of Snail and serpinA1 expression. Cell migration and invasion were assessed to determine the functional roles of Snail and serpinA1. Snail binding to the serpinA1 promoter was analyzed by chromatin immunoprecipitation (ChIP) assays.
Results: Immunohistochemical analysis of 528 samples from patients with CRC showed that elevated expression of Snail or serpinA1 was correlated with advanced stage, lymph node metastasis, and poor prognosis. Moreover, we detected a correlation between Snail and serpinA1 expression. Functional studies performed using the CRC cell lines DLD-1 and SW-480 showed that overexpression of Snail or serpinA1 significantly increased CRC cell invasion and migration. Conversely, knockdown of Snail or serpinA1 expression suppressed CRC cell invasion and migration. ChIP analysis revealed that Snail regulated serpinA1 by binding to its promoter. In addition, fibronectin mediated Snail and serpinA1 signaling and was involved in CRC cell invasion and migration.
Conclusion: Taken together, our data showed that Snail and serpinA1 promoted CRC progression through fibronectin. These findings suggested that Snail and serpinA1 were novel prognostic biomarkers and candidate therapeutic targets in CRC.
Note: This abstract was not presented at the meeting.
Citation Format: Chae Hwa Kwon, Hye Ji Park, Ja Rang Lee, Hye Kyung Kim, Do Youn Park. Snail and serpinA1 promote tumor progression and predict prognosis in colorectal 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 3417. doi:10.1158/1538-7445.AM2015-3417
Abstract 3424: The efficacy of Gasdermin gene family for tumor marker in colorectal cancer
Authors: Orita Hajime , Tanaka Shigekazu , Watanabe Shunsuke , Matsuzawa Hirokazu , Mizuguchi Konomi , Ito Tomoaki , Senuma Koji , Kushida Tomoyuki , Sakurada Mutsumi , Maekawa Hiroshi , Wada Ryo , Sato Koichi 
Published: August 2015

Abstract
Gasdermin (GSDM/Gsdm) family was originally identified as a candidate causative gene for a mouse skin mutation, recombination induced mutation 3 (Rim3). It has four human homologs, GSDMA, GSDMB, GSDMC, and GSDMD. All GSDM family members are located in amplicons, genomic regions often amplified during cancer development, and are considered to be involved in the regulation of epithelial apoptosis. GSDMA is mainly expressed in the upper gastrointestinal tract. In contract, GSDMD is expressed in the colorectal tract.
In this study, we researched those expressions in colorectal cancer and evaluated them for tumor marker, comparing between those expressions and clinical pathological status.
We immunohistologically analyzed both expressions of GSDMA and GSDMD, using thirty colorectal cancer cases which were surgically treated at our institution 2013-2014 (Stage1 10 cases, Stage2 10 cases, Stage3a 10cases). Thenretrospectively analyzed the connection, between GSDM expression and clinicopathological data.
GSDMA was no expressed in normal colorectal epithelium, but was overexpressed gradually rising in carcinoma.
However, GSDMD showed the opposite results compared with GSDMA.
The results of the expression analysis suggested that GSDMA and GSDMD act antagonictically with each other in the clinical stage of colorectal cancer.
Citation Format: Hajime Orita, Shigekazu Tanaka, Shunsuke Watanabe, Hirokazu Matsuzawa, Konomi Mizuguchi, Tomoaki Ito, Koji Senuma, Tomoyuki Kushida, Mutsumi Sakurada, Hiroshi Maekawa, Ryo Wada, Koichi Sato. The efficacy of Gasdermin gene family for tumor marker in colorectal 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 3424. doi:10.1158/1538-7445.AM2015-3424
Abstract 343: The homeobox gene DLX4 promotes inflammatory signaling and peritoneal metastasis of ovarian cancer
Authors: Haria Dhwani , Trinh Bon Q. , Ko Song Yi , Barengo Nicolas , Naora Honami 
Published: August 2015

Abstract
The lethality of ovarian cancer stems from the propensity of the disease to involve the peritoneal cavity. However, the mechanisms that drive peritoneal metastasis of ovarian cancer are poorly understood. We previously identified that high expression of the homeobox gene DLX4 in ovarian cancer is strongly associated with advanced disease stage and reduced survival. In this study, we identified that DLX4 stimulates the attachment of ovarian cancer cells to mesothelial cells that line the peritoneal cavity. DLX4 induced expression of the cell adhesion molecule CD44 which interacts with hyaluronic acid, a glycosaminoglycan that is produced by peritoneal mesothelial cells. Neutralization of CD44 abrogated the ability of DLX4 to stimulate tumor-mesothelial cell interactions. The induction of CD44 expression by DLX4 was found to be largely due to the ability of DLX4 to transcriptionally activate the gene encoding the pro-inflammatory cytokine interleukin-1beta (IL-1beta) which in turn stimulated the nuclear factor kappa B (NF-kB) signaling pathway. Furthermore, inhibition of IL-1beta or of NF-kB activity abrogated the stimulatory effect of DLX4 on tumor-mesothelial cell interactions. This study provides insights into the mechanisms of inflammatory signaling and peritoneal metastasis of ovarian cancer, and raises the possibility that targeting inflammatory signaling might be a strategy for treatment of advanced-stage ovarian cancer.
Citation Format: Dhwani Haria, Bon Q. Trinh, Song Yi Ko, Nicolas Barengo, Honami Naora. The homeobox gene DLX4 promotes inflammatory signaling and peritoneal metastasis of ovarian 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 343. doi:10.1158/1538-7445.AM2015-343
Abstract 3459: A new promising drug through abating endoplasmic reticulum stress response in treating endometrial cancer
Authors: Wang Chao , Guo Wei , Mills Gordon B. , Lu Yiling 
Published: August 2015

Abstract
Background: In order to survive under ER stress conditions, cells have a self-protective mechanism against ER stress, which has been termed the ER stress response. BIP/HSPA5 is a well-known marker of ER stress. In multiple tumors, BIP expressed highly, which even confers resistance to of chemotherapeutic agents. Some methods targeting to BIP have been studied to enhance chemotherapy efficacy. CBIO showed the most relative proteins with BIP is YAP-pS127. Objects: try to understand what roles YAP plays in ER stress and to explore a new drug for endometrial cancer taking advantage of ER stress. Methods: to analyze the YAP and YAP-pS127 level as well as HSPA5 mRNA level of EC patients. Then, overexpression of YAP, proteasome inhibitors and YAP inhibitor were employed to explore the relationship between YAP and BIP by immunoprecipitate (IP), western blot (WB) and SRB techniques and to investigate the most effective combination of drugs cell. Results: 1. 322 EC patients with G3 had higher HSPA5 level and lower YAP-pS127 level compared with G1-2, patients with higher HSPA5 level had lower YAP-pS127 level. 12 EC patients had higher HSPA5 level than 12 normal women. 2. MG132 and Bortezomib induced ER stress successfully with the increase of BIP, CHOP,PERK, IRE-1a. 3. Overexpression YAP also increased the BIP, CHOP and IRE-1a level. However, Verteporfin(VP) as a YAP inhibitor decreased IRE-1a level, moreover offset the effect of MG132 on increasing IRE-1a. 4. VP induced the death of EC cells in a dose and time course manner. The sequential method of VP- Carboplatin or VP-Taxol is most effective than the simultaneous method of VP+ Carboplatin or VP+ Taxol. Conclusion: BIP impacted the grade of EC and correlated with YAP-pS127 negatively in EC. The YAP could contribute to the occurrence of ER stress. VP destroyed the capacity of ER stress response of EC cell so that it induced cell to die effectively. Making failure of ER stress response before chemotherapy will enhance the effectiveness of chemotherapeutic drugs.
Citation Format: Chao Wang, Wei Guo, Gordon B. Mills, Yiling Lu. A new promising drug through abating endoplasmic reticulum stress response in treating endometrial 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 3459. doi:10.1158/1538-7445.AM2015-3459
Abstract 3461: RSK2 is a driver of estrogen receptor positive breast cancer
Authors: Ludwik Katarzyna , Lannigan Deborah 
Published: August 2015

Abstract
For unknown reasons, high levels of active Ser/Thr protein kinase RSK in estrogen receptor α (ERα)-positive (ER+) breast cancer patients correlate with better responsiveness to anti-estrogen therapies. Investigation of these surprising observations led us to discover an unanticipated mechanism in which ERα controls RSK2 nuclear accumulation. RSK2 is retained in the nucleus by physical association with ERα and this interaction is disrupted by anti-estrogen treatment. Consistent with these findings, in primary human ER+ breast tissue organoids, 4-hydroxy-tamoxifen (4-OHT) drove export of RSK2 to the cytoplasm. Importantly, RSK2 nuclear accumulation is critical for the expression of the oncogene, cyclin D1. This conclusion is supported by the observations that a RSK2 mutant, which cannot accumulate in the nucleus, does not rescue cyclin D1 in cells silenced for endogenous RSK2. Analysis of RNAseq data shows that ERα and RSK2 cooperatively regulate a transcriptional program, which includes cyclin D1. The physiological relevance of these conclusions is supported by our observations that in ∼60% of ER+ breast cancer patients, active nuclear RSK correlates with ERα and cyclin D1 levels. Taken together, these findings suggest that responsiveness to endocrine-based therapy is driven by reduced RSK2 nuclear accumulation, which in turn reduces expression of cyclin D1 and of other tumor-promoting effectors. Based on these observations we hypothesized that nuclear RSK2 cooperates with ERα and is a physiologically relevant driver of ER+ breast cancer. To test this hypothesis we generated a transgenic mouse model in which the MMTV promoter controls expression of RSK2 fused with the nuclear localization signal (NLS) of SV40. Strikingly, in ∼50% of transgenic mice forced nuclear accumulation of RSK2 in the mammary gland caused hyperplasia and ductal carcinoma in situ (DCIS). These results are the first demonstration that RSK2 can drive proliferation and transformation in vivo. Transgenic animals had a 4-fold increase in the number of cyclin D1 expressing cells and a 6-fold increase in Ki67 levels. Surprisingly, in vivo expression of nuclear RSK2 expanded the population of ER+ cells. These results demonstrate, for the first time, that nuclear RSK2 drives the amplification of the cell population relevant to ER+ breast cancer. In agreement with these observations we found that overexpression of ERα in the mouse mammary gland expands exclusively, by ∼3 fold, the cell population that co-expresses ERα and active nuclear RSK. These results further support our hypothesis that RSK2 cooperates with ERα and is an important drug target for ER+ breast cancer.
Citation Format: Katarzyna Ludwik, Deborah Lannigan. RSK2 is a driver of estrogen receptor positive 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 3461. doi:10.1158/1538-7445.AM2015-3461