bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3855: Refolded albumin inhibits IL-17B-driven pancreatic cancer migration
Authors: Liang Chi-Ming , Liao Ching-Chun , Liang Shu-Mei 
Published: July 2016

Abstract
Folding and refolding a protein may change its physical, chemical and biological properties. Here, we used a novel protein refolding protocol to convert globular albumin into another form, namely f-albumin, with melting point 10oC higher than albumin (83oC vs 72oC). f-albumin, unlike albumin, inhibited the migration/invasion of a variety of cancer cells. Recently, anti-IL-17RB antibodies have been shown to block the IL-17B-IL17RB signaling-mediated migration/metastasis of pancreatic cancer cells via silencing multiple chemokines, notably CCL20, CXCL1, IL-8 and TFF1. We thus examined whether f-albumin is effective in blocking the stimulatory effects of IL-17B. We found that f-albumin inhibited the migration of pancreatic cancer cells (BxPC3, MIA-paca2 and Panc1) with IC50 around 0.2 μM. Although IL-17B (50 ng/ml) increased the migration of pancreatic cells, this effect of IL-17B was abolished by f-albumin (0.2 μM). The inhibitory effect of f-albumin, however, was not necessarily correlated with its inhibition of CCL20, CXCL1, IL-8 or TFF1. Additional study revealed that IL-17B increased the phosphorylation of PI3K, Akt and MAPK in pancreatic cancer cells. f-albumin modulated not only the IL-17B-mediated phosphorylation of Akt but also the IL-17B-mediated phosphorylation of MAPK in an integrin-dependent manner. These findings demonstrated that f-albumin downregulates Akt/MAPK signaling via integrin to play a braking role in the IL-17B-driven pancreatic cancer migration.
Citation Format: Chi-Ming Liang, Ching-Chun Liao, Shu-Mei Liang. Refolded albumin inhibits IL-17B-driven pancreatic cancer migration. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3855.
Abstract 3873: Single cell cisplatin measurements by ICP-MS
Authors: Amable Lauren , Smith Stan , Stephan Chady 
Published: July 2016

Abstract
Cisplatin, carboplatin, and oxaliplatin are the most widely used class of cancer chemotherapy drugs in the Western world. Many cancers are initially sensitive to platinum treatment but drug resistance frequently occurs. Cellular uptake of cisplatin is related to tumor burden, thus lower intracellular cisplatin levels are associated with a decreased tumor response. Traditional methods to assess cisplatin uptake in cells involves digesting a cell population and measuring the total platinum content. This approach does not reflect the distribution and individual cellular variation of cisplatin uptake. Here, we present a new method, single cell inductively coupled plasma-mass spectrometry (SC-ICP-MS) to quantitate the platinum concentration within individual cells. Experiments were performed using the A2780 cisplatin-sensitive and the corresponding cisplatin-resistant A2780-CP70 ovarian cancer cell lines. Time course experiments were performed to measure the change of cisplatin uptake over time. Serum starvation experiments were also performed to examine if differences in cisplatin uptake were dependent on the cell cycle. SC-ICP-MS was performed by injecting cell suspensions and analyzing the platinum 195 isotope. Individual cellular cisplatin levels were collected and a histogram representing the cell population was generated using the instrument software (Syngistix Nano Application). Other metals, such as zinc, iron, and copper, were analyzed to measure the variation between cell lines after treatment. We observed a heterogeneous distribution of cisplatin concentrations within the sample reflecting that cisplatin uptake differs from cell to cell. Serum starvation affected the uptake of cisplatin within cells, changing the cisplatin distribution curve. SC-ICP-MS was also effective in measuring other metals within individual cells and differences were observed between the A2780 and A2780-CP70 cell lines. In conclusion, single cell ICP-MS analysis allows for the quantitation of cisplatin within individual cells. The heterogeneous distribution of cisplatin uptake more closely reflects what occurs within tumor cells. SC-ICP-MS allows for the development of strategies to increase cisplatin uptake, translating to better clinical responses.
Citation Format: Lauren Amable, Stan Smith, Chady Stephan. Single cell cisplatin measurements by ICP-MS. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3873.
Abstract 3877: A new frontier for molecular profiling of neoplastic bone tissue
Authors: Mueller Claudius , Liotta Lance A. , Chiechi Antonella , Picci Piero , Alberghini Marco , Memeo Lorenzo , Canzonieri Vincenzo , Espina Virginia 
Published: July 2016

Abstract
Background: Tissue is alive and reacting to ex vivo stress during “cold ischemia time”. Tumor cells react to the absence of vascular perfusion, hypoxia, acidosis, and accumulation of cellular waste, which can critically mask cancer related signaling network data. Standard formalin fixation of calcified tissue requires decalcification with formic/nitric acid solution, which greatly interferes with downstream molecular analysis. We developed a non-formalin fixative (TheraLin) for preserving biomarker molecules and tissue histomorphology in one step, which greatly facilitates the analysis of phosphoprotein signaling pathways in calcified tumor samples.
Methods: Fifty specimens of neoplastic bone were collected at the Istituto Ortopedico Rizzoli (Bologna, Italy). Matched 0.5 cm samples were fixed in TheraLin preservative; or fixed in 4% buffered formalin and decalcified with formic/nitric acid solution. Specimens were processed into paraffin blocks and 5 μm tissue sections cut onto glass slides. Enriched tumor cell populations were procured using Laser Capture Microdissection. Reverse Phase Protein Microarrays were constructed with the microdissected tumor cells and probed with &gt;40 antibodies to unmodified or phosphorylated proteins. Immunohistochemistry (&gt;200 stains in total) was performed on routine clinical protein targets and a subset of phosphorylated proteins.
Results: TheraLin fixation greatly facilitated molecular profiling of bony tissues by eliminating the need for decalcification (18.5 hour average reduction in processing time) while maintaining or improving histomorphology (&gt;85% of cases) and immunohistology (&gt;75% of cases). In addition, we were able to demonstrate full compatibility with laser capture microdissection, reverse phase protein microarrays and downstream analysis of cell signal protein activation. Protein extractability from microdissected material was significantly increased (&gt;2.5 fold, p&lt;0.01) compared to formalin fixed, decalcified bone tissue.
Conclusion: TheraLin obviates the need for decalcification of bone tissue while simultaneously preserving histomophology and immunohistochemistry. TheraLin enables reliable quantification of phosphorylated signal transduction proteins, the substrates of kinase drug targets, and greatly facilitates tumor cell enrichment compared to standard formalin fixation and decalcification.
Citation Format: Claudius Mueller, Lance A. Liotta, Antonella Chiechi, Piero Picci, Marco Alberghini, Lorenzo Memeo, Vincenzo Canzonieri, Virginia Espina. A new frontier for molecular profiling of neoplastic bone tissue. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3877.
Abstract 3879: Comprehensive delineation of stromal proteins implicated in the multistage carcinogenesis and identification of Tenascin-C as stromal marker for metastasis of colon carcinoma
Authors: Chen Yongheng , Li Maoyu 
Published: July 2016

Abstract
Colon carcinoma (CC) is one of the most common malignancies threatening the human health. Early diagnosis or effective biomarker for intervention is still a challenge in clinical application for CC. The stroma in human cancer provides the microenvironment for cancer initiation and development, and furthermore, the stroma has been regarded as a therapeutic target for cancer. However, little is known about the dynamics of proteins within the stroma during the carcinogenic process. To discover the involvement of stroma in carcinogenesis and identify the biomarker candidates, the stromal components at the various stages of colonic carcinogenesis were purified by laser capture microdissection (LCM) and iTRAQ-based quantitative proteomic analysis was used for identifying the differentially expressed stromal proteins at different stages. In total, 222 differentially expressed proteins were identified. The expression of two of the top ranked proteins, extracellular matrix protein TNC and S100 family protein S100A9, was further confirmed by immunohistochemical analysis. Further analysis revealed that TNC was highly expressed in the stroma of metastasis and also abundantly secreted by the high metastatic cells. These results suggested that TNC was potential stromal marker for metastasis of colon carcinoma. Our results will contribute to investigating the role of stroma in the colonic carcinogenesis and might provide clues for pathogenesis, early diagnosis, and clinical therapy of CC.
Citation Format: Yongheng Chen, Maoyu Li. Comprehensive delineation of stromal proteins implicated in the multistage carcinogenesis and identification of Tenascin-C as stromal marker for metastasis of colon carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3879.
Abstract 3890: NCI's Clinical Proteomic Tumor Analysis Consortium
Authors: Mesri Mehdi , Boja Emily , Hiltke Tara , Kinsinger Chris , Lee Jerry , Rodriguez Henry 
Published: July 2016

Abstract
The NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC) constitutes a network of Proteome Characterization Centers (PCCs), which coordinate and conduct research and data sharing activities to comprehensively interrogate genomically characterized cancer biospecimens. Such integrated proteogenomics approach brings key insights into genomic abnormalities manifested at the protein network and pathway level. Established in late 2011, CPTAC works closely with genomics initiatives such as The Cancer Genome Atlas (TCGA) to systematically identify proteins that derive from alterations in cancer genomes and related biological processes, and provide this data with accompanying assays and protocols to the public. CPTAC investigators conducted the first in-depth comprehensive proteome (global, phosphoproteome and N-glycoproteome) study on understanding the impact of cold ischemia that has resulted in the development of an ischemic signature database and best practice procedures for biospecimen (tissue) sample collection/processing. The PCCs have deeply characterized three cancer types (colorectal, ovarian and breast tumors) previously analyzed by TCGA and additional tissue collections, all of which are accompanied by genomic datasets. Scientific findings examining 95 TCGA colon and rectal tumors using deep proteomic analysis include: a) five proteomic subtypes were identified, with the TCGA MSI/CIMP transcriptomic subtype separated into distinct proteomic subtypes including one subtype (subtype C) that displayed protein network features characteristic of epithelial-mesenchymal transition (EMT); b) copy number alterations (CNAs) on mRNA abundance analysis showed strong cis- and trans-effects; but few extending to the protein level; and c) chromosome 20q amplicon was shown to contain the largest global changes in both mRNA and protein levels, allowing for prioritizing driver genes. In addition to the publicly available proteomic datasets (https://cptac-data-portal.georgetown.edu/cptacPublic), proteomic targeted assays developed by the consortium are available at CPTAC's Assay Portal (http://assays.cancer.gov). This is a public resource of mass spectrometry-based quantitative targeted proteomic assays for measuring proteins of interest from the program. Lastly, monoclonal antibodies targeting cancer specific proteins and peptides are made available at CPTAC's Antibody Portal (http://antibodies.cancer.gov).
Citation Format: Mehdi Mesri, Emily Boja, Tara Hiltke, Chris Kinsinger, Jerry Lee, Henry Rodriguez. NCI's Clinical Proteomic Tumor Analysis Consortium. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3890.
Abstract 3894: A xenograft mouse model coupled with in-depth cell surface proteome analysis facilitates further elucidation of K-Ras driven tumorigenesis in lung carcinoma
Authors: Ye Xiaoying , Whiteley Gordon , Nissley Dwight , McCormick Frank , Blonder Josip 
Published: July 2016

Abstract
The purpose of this study was to develop a proteomic approach for analysis of cell surface proteins in tissue specimens and applied it on a K-Ras driven mouse model of metastatic lung carcinoma. Metastatic disease is the leading cause of lung cancer-related mortality in the United States. In spite of continuous efforts, effective treatments targeting oncogenic K-Ras in lung and other K-Ras driven malignancies are slow to develop. To expand the treatment options for lung cancer and facilitate better understanding of metastasis new targets need to be identified and characterized at the surface of cancer cells, preferably in their native tissue microenvironment. Towards this goal we developed a mass-spectrometry (MS)-based glyco-proteomic approach targeting specifically cell surface proteins in tissue specimens and applied it on a xenograft lung cancer mouse model. We used A549 cells expressing endogenous K-RasG12S to induce lung tumor xenografts in BALB/c mice via tail vein injection. A comparative surface glyco-proteomics of cultured A549 cells, dissected tumor tissue (TT), adjacent tumor (AT) tissue and normal mouse lung tissue (NT) obtained from saline-injected age-matched littermates yielded high enrichment (i.e., ≥80%) of surface proteins. It resulted in extensive catalogue/map of more than 400 glycoproteins identified on tumor cell surface. More than 50% of proteins identified on the surface of A549 cultured cells were unambiguously identified in mouse TT, featuring proteins and pathways implicated in metastasis, invadopodia formation and cancer cell migration. These markers also provide insight regarding species determination of tissue origin (i.e., human vs. mouse) differentiation of tumor parenchyma from stroma, and regulation of tumor immune response.
Citation Format: Xiaoying Ye, Gordon Whiteley, Dwight Nissley, Frank McCormick, Josip Blonder. A xenograft mouse model coupled with in-depth cell surface proteome analysis facilitates further elucidation of K-Ras driven tumorigenesis in lung carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3894.
Abstract 3914: Repurposing disulfiram for use as an anticancer drug: a story about metabolism and metal binding
Authors: Wehbe Moe , Anantha Malathi , Backstrom Ian , Leung Ada , Chen Kent , Shi Minghan , Malhotra Armaan , Edwards Katarina , Sanche Léon , Bally Marcel B. 
Published: July 2016

Abstract
Disulfiram (DSF) is an FDA approved agent for the treatment of alcoholism with over 60 years of clinical use. It was identified in several high-throughput screen to be effective against glioma tumor initiating cells; this activity is amplified more than 100-fold in the presence of copper (Cu2+). DSF is metabolized to diethyldithiocarbamate (DDC), an established copper chelating agent. One mechanism attributed to the copper DDC (Cu(DDC)2) complex is proteosome inhibition. Cu(DDC)2 is very poorly soluble in aqueous solution; making it difficult to purse development for any cancer indication. A novel liposomal formulation of Cu(DDC)2 is described here; which represents the first iv injectable Cu(DDC)2. 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol (CHOL) (55:45 molar ratio) liposomes were prepared by extrusion methods in the presence of 300 mM unbuffered CuSO4 to ∼100 nm in size. DDC was added to these pre-formed liposomes at room temperature, unentrapped drug was removed using column chromatography. The therapeutic activity of this formulation was determined in vitro against a variety of cancer cell lines. The toxicity and pharmacokinetic (PK) behaviour of this formulation was determined in CD-1 mice. DDC was tested in the presence and absence of Cu2+ in vitro with U251, U87, MDA231-BR and A549 cell lines giving IC50 values greater than &gt;10 μM in the absence and from 300- 900 nM in the presence of Cu2+. The liposomal Cu(DDC)2 formulation was as active as unencapsulated Cu(DDC)2 when tested in vitro. The maximum tolerated dose of liposomal Cu(DDC)2 was determined to be 8mg/kg given iv using a Q2D schedule for two weeks. The PK studies suggested that Cu(DDC)2 was rapidly released from circulating liposomes. Initial efficacy studies were completed using convection enhanced delivery of liposomal Cu(DDC)2 in the F98 rat glioma model. Treatment resulted in a statistically significant delay in tumour growth upon injection of 10 μL of 0.5 mg Cu(DDC)2 /mL solution. Further anti-tumor efficacy studies are being conducted in a subcutaneous leukemia xenograft model (MV-4-11). This work describes a novel formulation of Cu(DDC)2, the active agent generated when administering DSF and Cu to treat cancer.
Citation Format: Moe Wehbe, Malathi Anantha, Ian Backstrom, Ada Leung, Kent Chen, Minghan Shi, Armaan Malhotra, Katarina Edwards, Léon Sanche, Marcel B. Bally. Repurposing disulfiram for use as an anticancer drug: a story about metabolism and metal binding. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3914.
Abstract 3915: PBA2, a dual BCR-ABL and GSK3βkinases inhibitor, represses a wide array of Imatinib resistant cell lines in chronic myeloid leukemia
Authors: Yang Ke , Fu li-Wu 
Published: July 2016

Abstract
Despite the clinical efficacy of the BCR-ABL (Tyrosine Kinase Inhibitors) TKIs for the treatment of Chronic Myeloid Leukemia (CML), BCR-ABL-T315I mutation still confers higher-level resistance to imatinib and the second generation BCR-ABL TKIs. Ponatinib, as the third generation BCR-ABL TKIs, has the potential activity against CML with T315I mutant BCR-ABL whereas high frequency of serious adverse events limits its clinical use. Through a compound library screen, we identified a novel compound PBA2, a dual kinases inhibitor of GSK3β and BCR-ABL, as a promising agent for the treatment of imatinib-resistant CML. Not only can PBA2 inhibit cell growth but also induce terminal cell differentiation in a series of kinase mutant CML cell lines as well as T315I mutation. Remarkably, the mechanism of action of this compound involved the simultaneous inhibition effect of BCR-ABL and GSK3β, which could be a fruitful approach to suppress the β-catenin/CBP signal pathway that promoted the interaction of β-catenin/p300, leading to growth inhibition and subsequent terminal differentiation. More importantly, we found a novel molecular link between CBP and BCR-ABL. We showed that CBP could regulate BCR-ABL expression through activating CREB which binds to the BCR-ABL promoter in CML cells to start transcription, and the BCR-ABL in turns affect the expression level of CBP. This positive feedback pathway between CBP and BCR-ABL represents a novel way for the treatment of CML, and the novel compound PBA2 targeting at this loop deserves further investigation in clinical trial.
Citation Format: Ke Yang, li-Wu Fu. PBA2, a dual BCR-ABL and GSK3βkinases inhibitor, represses a wide array of Imatinib resistant cell lines in chronic myeloid leukemia. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3915.
Abstract 3933: CETSA as a diagnostic tool to guide personalized breast cancer therapy
Authors: Öberg Anette , Laursen Henriette , Packham Sylvia , Martinez Molina Daniel , Seki Takahiro , Cao Yihai , Hartman Johan , Bergh Jonas , Nordlund Pär , Lööf. Sara 
Published: July 2016

Abstract
The increased knowledge of fundamental cancer biology has translated into the development of a large number of targeted drugs. However, the potential for breakthroughs in cancer therapy is hampered by the lack of knowledge regarding which patients would benefit from a specific drug. Therefore, there is a need of diagnostic tools that can predict if the individual patient will respond or develop resistance to a specific treatment plan.
In the present project we aim to meet this challenge by developing stringent clinical diagnostic assays for assessing target engagement (TE; i.e. drug binding to its target protein in situ) of current and emerging drugs in breast cancer treatment. The key to develop these clinical TE assays is our novel technology Cellular Thermal Shift Assay (CETSA). This method allow for the first time direct monitoring of biophysical drug TE in cells, animals and patient samples. The main aim of the project is to correlate the results obtained by CETSA on breast cancer biopsies to the treatment outcome for the biopsied patient, with the goal of creating a diagnostic tool for guiding personalized breast cancer treatment. We also aim to identify new biomarkers of efficacy and resistance for specific drugs, by implementing proteome wide CETSA based on a quantitative mass spectrometry read out.
Our recent data demonstrates that CETSA can assess TE in intact cells of drugs commonly used in breast cancer treatment, such as microtubule inhibitors, anthracyclins and CDK4/6 inhibitors. Further we show that CETSA can be applied in vivo on human breast cancer Xenografts and breast cancer patient samples. These data further strengthens the potential of CETSA to become a valuable clinical tool and complement other diagnostic methods to improve efficacy and minimize adverse effects of cancer drugs.
Citation Format: Anette Öberg, Henriette Laursen, Sylvia Packham, Daniel Martinez Molina, Takahiro Seki, Yihai Cao, Johan Hartman, Jonas Bergh, Pär Nordlund, Sara Lööf. CETSA as a diagnostic tool to guide personalized breast cancer therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3933.