bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5027: Steadily improving survival in lung cancer
Authors: Dillman Robert O. , McClure Stephanie E. , Zusman Douglas R. , VanderMolen Louis A. , Mahdavi Khosrow , Hafer Russell A. , Cox Craig A. , Joyo Colin I. , Barth Neil M. 
Published: June 2012

Abstract
Background and Purpose: There have been many improvements in the diagnosis and management of lung cancer during the past 25 years, including better imaging and the potential for earlier diagnosis, better surgical staging and introduction of minimally invasive surgery, improved radiation technology, and introduction of several systemic cancer drugs, including targeted therapies, and acceptance of multidisciplinary approaches rather than focusing on single modalities of therapy. We examined how treatment has changed in successive eras and how this relates to survival. Patients and Methods: The Hoag Cancer Institute data base was used to identify patients with lung cancer diagnosed during 1986-2009, who were diagnosed and/or received some or all of their lung cancer treatment at Hoag Hospital within four months of diagnosis. For the four successive 5-year periods, data was summarized for patient demographics and treatment, and observed and relative 5-year survival rates were calculated. Results: Data is summarized in the table below.

Conclusion: Over time there have been steady increases in median age, and in the proportion that have adenocarcinoma, are female, have local stage disease, undergo surgery alone as therapy, and receive systemic therapy with surgery as initial treatment. These changes have been associated with a 13.3 percentage point absolute increase in observed survival and an 81% relative increase. Relative 5-year survival increased from 18% to 34%, which contrasts with national data showing an increase from only 14% to 16% in the U.S.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5027. doi:10.1158/1538-7445.AM2011-5027
Abstract 504: Epithelial-mesenchymal transition confers stem-like properties and migratory ability to lung tumor cells
Authors: Bertolini Giulia , Roz Luca , Tortoreto Monica , Boeri Mattia , Pastorino Ugo , Sozzi Gabriella 
Published: June 2012

Abstract
We previously demonstrated that lung cancer CD133+ cells are highly tumorigenic, display stem-like features and are spared by cisplatin treatment. Recent studies proposed that the process of EMT could generate cancer cells endowed with migratory and invasive abilities and with characteristics of cancer stem cells (CSCs)
To test this hypothesis in lung cancer we induced EMT by transforming growth factor β (TGFβ1) in a lung cancer cell line established from primary tumor (LT73). EMT program activation in LT73 cell line resulted in cellular morphological changes, repression of E-cadherin expression and up-regulation of EMT-related genes, as evaluated by Real Time PCR. We also demonstrated that EMT-induced cells expressed high levels of stemness genes, similarly to mesenchymal stem cells. We furthermore found that LT73 cells undergone EMT exhibited an enhanced migrating potential and an increased drug resistance to cisplatin treatment than parental cell line, indicating that EMT activation provided cells with mesenchymal traits as well as stem-like properties.
FASC analysis revealed an enrichment of CD133+ lung cancer initiating cells in EMT-induced LT73 cells. Interestingly in EMT-generated CD133+ cells we identified a fraction of CD133+ /ESA− cells, not detectable in parental cell line, that express high level of pro-metastatic chemokine receptor CXCR4.
To validate the results obtained in the in vitro model, we analyzed primary lung cancer and corresponding lymph nodes metastasis, as well as spontaneous lung metastasis generated from subcutaneous xenografts tumor of H460 cell line. Preliminary results confirmed the existence of CD133+/ESA− /CXCR4High cells also in some primary lung cancer. Interestingly we found that lymph node metastasis contained a higher amount of this subpopulation of cells compared to corresponding primary tumors. Moreover the phenotypic analysis of spontaneous lung metastasis, derived from subcutaneous H460 xenograft tumor, demonstrated an enrichment for CD133/CXCR4 double positive population compared to parental tumors.
In conclusion these data indicate that EMT process could generate a subpopulation of CD133+/ESA− /CXCR4High cells, endowed with the potential to initiate tumor and disseminate, that possibly may represent the migrating-CSC fraction, involved in metastatic process. The existence of EMT-generated cancer cells could provide new insights into the tumor metastatic progression and lead to novel approaches for selective targeting of CSC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 504. doi:10.1158/1538-7445.AM2011-504
Abstract 5045: AUY922, a heat shock protein 90 inhibitor, has antitumor effects in human hepatocellular carcinoma cells
Authors: Gao Ming , Yeh Pei Yen , Lu Yen-Shen , Yu Huei-Chieh , Lin Hsiu-Mei , Chen Jun-Wei , Lin Shiou-Der , Cheng Ann-Lii 
Published: June 2012

Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer and third leading cause of cancer death worldwide. Recently, molecular targeted therapy (MTT) agent, sorafenib, was shown efficacious in this dreadful cancer. However, HCC appears to be a cancer without single driver mutation, targeting multiple proteins in cancer cells might be an alternative strategy for better efficacy. Heat shock protein 90 (HSP90) is a ubiquitously expressed molecular chaperone regulating various important proteins associated with pivotal signal transduction and cancer progression of HCC. This study sought to explore whether HSP90 can be a potential target of HCC treatment. AUY922, a highly potent non-geldanamycin HSP90 inhibitor, suppressed cell growth of Huh7 and HepG2 cells with IC50 below 10nM. Flow cytometry analysis showed that G2/M arrest and sub G1 increase were induced after AUY922 treatment. AUY922 downregulated the expressions of Akt and cell cycle regulatory proteins, including Chk1, cdc2, Aurora B, and cyclin B1. Morphologic observation of AUY922-treated Huh7 cells demonstrated the formation of giant, micronucleated cells and multipolar mitosis, a picture compatible with mitotic cell death. Finally, treatment of BALB/c nude mice with 50mg/kg of AUY922 three times a week significantly suppressed the growth of Huh7 tumor xenografts. Our data provide the evidence that AUY922 inhibit HCC cells growth at least partially through mitotic cell death, and inhibiting HSP90 by AUY922 is a potentially useful therapeutic strategy for HCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5045. doi:10.1158/1538-7445.AM2011-5045
Abstract 5058: Effects of honokiol on UACC-62 malignant melanoma cell line
Authors: Guillermo Ruth F. , Stevens Jonathan , Kaushik Radhey S. , Young Alan , Dwivedi Chandradhar 
Published: June 2012

Abstract
Studies from our laboratory have indicated the chemopreventive effects of honokiol on UVB-induced squamous cell carcinoma in mouse skin. The purpose of this study is to investigate the effects of honokiol on UACC-62 malignant melanoma cell and elucidate the mechanisms of action. UACC-62 cells were grown in RPMI media in cell culture conditions. The effects of honokiol on cell viability and cell proliferation were studied by the MTT and BrdU assays. To investigate the effects of honokiol on cell cycle, UACC-62 cells were treated with honokiol, stained with propidium iodide and analyzed by flow cytometry. Cell lysates were prepared in similar conditions as the previous experiments to assess how honokiol affected the expressions of proteins involved in different pathways. The MTT assay showed a significant decrease in cell viability starting at 75 μM honokiol at 24 hours. The BrdU assay results indicated decreased cell proliferation as early as 12 hours and 50 μM honokiol. The cell cycle analysis indicated that honokiol caused G0/G1 phase arrest in melanoma cells (p &lt; 0.05) at 24h and 50 μM. Western blots of the cell lysates prepared showed that honokiol decreased the expressions of cyclin E, CDK4, cyclin D2, NF-kβ, and p-MEK starting at 50 μM honokiol at 24 hours. The expressions of apoptotic proteins cleaved caspase-3, cleaved caspase-9, caspase 8, and cleaved PARP were increased by honokiol treatments. This data indicated that honokiol decreases cell proliferation and induces apoptosis of UACC-62 cells thus could be a candidate for pre-clinical studies as an agent for treating or preventing melanoma skin cancer.
Supported by Translational Cancer Research Center funded as a 2010 Research Initiative Center by the State of South Dakota.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5058. doi:10.1158/1538-7445.AM2011-5058
Abstract 506: Mechanisms of microvesicle-mediated communication in cancer
Authors: Svensson Katrin J. , Christianson Helena C. , Wittrup Anders , Johansson Maria C. , Mörgelin Matthias , Belting Mattias 
Published: June 2012

Abstract
The many functional roles of microvesicles (MVs) in tumor development and progression have lately become a subject of intense investigation. Cancer cell derived genetic material and signaling proteins residing in MVs can be transferred to recipient cells by as yet ill-defined mechanisms. We have found that heparan sulfate proteoglycans (HSPGs), which previously have been implicated as receptors of various macromolecular ligands, also can mediate the uptake of MVs. Our data suggest that MV uptake involves membrane raft, non-caveolin dependent endocytosis. These findings are consistent with recent data from our group on HSPG-mediated uptake of antibody-conjugated nanoparticles. Furthermore, MVs were found to be sorted to CD63-containing, vesicular compartments through intracellular transport that appeared highly dependent on an intact microtubule network. Intriguingly, preliminary findings support the concept of intracellular exchange of MV cargo, thus giving rise, in a single transporting vesicle, to a signal that integrates information from multiple cells. The presented results reveal a novel receptor that mediates MV uptake, and advance our general understanding of MV-dependent transfer of molecular information. Finally, the finding that MVs can potentially harbor molecules from multiple cells residing in the tumor environment opens up new, exciting roles of MVs as information carriers in cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 506. doi:10.1158/1538-7445.AM2011-506
Abstract 5075: An integrated in silico and proteomic approach towards the identification of novel cancer biomarkers based on tissue specificity
Authors: Prassas Ioannis , Makawita Shalini , Diamandis Eleftherios 
Published: June 2012

Abstract
Serological biomarkers represent a non-invasive and cost-effective means to aid in clinical management of cancer patients, particularly in areas of disease detection, prognosis, monitoring and therapeutic stratification. Several notable biomarkers currently in clinical use are proteins that demonstrate high tissue specificity to a single tissue, such as prostate specific antigen (PSA) for prostate cancer and human chorionic gonadotropin (hCG) for testicular cancer, the former being highly expressed only in the prostate and the latter in the placenta. Recent advances in high-throughput technologies (e.g. high-content microarray chips, serial analysis of gene expression platforms, thorough expressed sequence tag annotation) has enabled creation of publicly available gene and/or protein databases which describe the expression of thousands of genes (and/or proteins) in multiple tissues. Furthermore, over the past five years, our laboratory has characterized the proteomes of over 35 cell lines from numerous cancer sites as well as relevant biological fluids using a 2D-LC-MS/MS approach, identifying between 1000-4000 proteins per cancer site.
In this respect, the present study represents an integrative analysis of existing databases in combination with our in-house generated proteomic datasets, in pursuit of highly tissue specific proteins, which could be further explored as cancer biomarkers and/or therapeutic targets. Through stringent bioinformatic mining of the Human Protein Atlas, BioGPS, Unigene, TiGER, TiSGeD and other related databases, a list of proteins highly specific to normal lung, colon, prostate, testis and ovaries was generated. Interestingly, only a few proteins from each tissue were commonly reported as highly specific across all of these databases and these were selected for further analysis. Subsequent integration and comparison to our in-house generated proteomes: prostate cancer (PC3, LNCaP, 22Rv1 and seminal plasma from prostate cancer patients; 1958 proteins), lung cancer (H1688, H23, H460, and H520; 1856 proteins), ovarian cancer (HTB75, TOV-112D, TOV-21G and RMUG-S; 1123 proteins) and colon cancer (HCT116, LoVo, LS174T, LS180, SW1116, SW480 and SW620; 2124 proteins), helped to corroborate our candidate list.
Three, 4, 5, 10 and 7 highly specific proteins based on the applied criteria were prioritized for colon, testis, ovaries, prostate and lung, respectively. The identification of known biomarkers within these lists (e.g. PSA, KLK2, MSMB) warrants the analysis of the remaining proteins in serum, as potential cancer biomarkers and/or therapeutic targets.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5075. doi:10.1158/1538-7445.AM2011-5075
Abstract 5078: The NCI-NIST-FDA effort to develop fitness-for-purpose biospecimen assessment standards: Development of quality assessment metrics and standards for optimal biospecimen utilization
Authors: Aragon Richard , Dickherber Anthony , Litwack David , Vaught Jimmie , Compton Carolyn 
Published: June 2012

Abstract
The US Congress, through recent health care reform legislation, has directed the National Institutes of Health (NIH) to formulate a more aggressive strategy by which to translate scientific discoveries directly into the development of novel therapeutic and diagnostic capabilities. The National Cancer Institute (NCI) seeks to facilitate these efforts by targeting specific bottlenecks caused by the lack of standardization, quality metrics, and comparative benchmarks for research and clinical biospecimens used throughout the relevant discovery and validation pipelines. Many of the bottlenecks that currently impede routes to more effective biomarker discovery as well as drug, biologic and device development are impeded by a current lack of standards surrounding the research biospecimens used to advance this type of research.
The National Institutes of Standards and Technology (NIST), the Food and Drug Administration (FDA) and the NCI have engaged in an interagency effort to develop fitness-for-purpose quality assessment tools and metrics for the research biospecimens used by the clinical research, diagnostics, and technology development communities. An interagency workshop was convened consisting of biomedical and biospecimen scientists, standards/metrology scientists, commercial assay developers, experimental design and research methods experts, statisticians, and regulatory scientists that are among the leaders in their field. Subsequent to that workshop, a number of specimen quality assessment metric development projects were initiated to target metrics and standards that would have a significant impact on the development pipelines for diagnostics and therapeutics development, including the incorporation of certain regulatory efficiencies that could potentially accelerate development.
The NCI would like to present these ongoing projects and share ideas for future biospecimen quality assessment standards development projects for the cancer research, diagnostics, and technology development communities. Progress in designing such projects and preliminary results from experiments discussed in the October workshop will thus be described.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5078. doi:10.1158/1538-7445.AM2011-5078
Abstract 5081: Inhibiting DNA double strand break repair for alpha radioimmunotherapy
Authors: Song Hong , Hobbs Robert F. , Shao Chunbo , Sgouros George 
Published: June 2012

Abstract
Metastasis to distant organs is the major cause of mortality in breast cancer patients. Median overall survival remains poor (5 year survival 26.1%) despite recent advances in new targeted biological therapy. Radiolabeled antibody offers an effective approach to deliver cytotoxic radiation doses to eliminate micrometastatic tumors. Alpha particle emitters are promising against small micrometastases because of their high potency and specificity (high linear energy transfer, LET&gt;80 keV/µm, particle range ∼ 80 μm). Alpha particles typically cause DNA double strand breaks (DSBs) when they traverse the cell nucleus. Our experience with alpha particle emitter labeled antibody showed that it significantly prolonged survival in a mouse model of metastatic breast cancer with eventual recurrence at estimated micromet dose of 4.4 Gy. Understanding cellular repair of alpha radiation induced DNA DSBs could help us rationally design more effective strategy by inhibiting components of the DNA DSB repair pathways to sensitize cancer cells to alpha radiation. Under this hypothesis, we evaluated the role of DNA dependent protein kinase catalytic subunit (DNA-PKcs) inhibition on targeted alpha-emitter therapy. Inhibition, with small molecule inhibitor NU7441, of this key enzyme in the non-homologous end joining (NHEJ) pathway sensitizes triple negative breast cancer cells to alpha particle emitter 213Bi labeled anti-EGFR antibody. Immuno-fluorescent staining of γH2AX foci confirms a reduction in the DNA DSB repair rate in these cells. Using a cell-line deficient in the homologous recombination (HR) pathway (BRCA-1 deficient), we also have preliminary evidence suggesting that HR deficiency reduces the incremental effect of NHEJ inhibition but the combination increases overall cell kill. This data suggest inhibiting components of DNA double strand repair pathways is an effective approach to enhance the efficacy of alpha particle emitter labeled monoclonal antibody.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5081. doi:10.1158/1538-7445.AM2011-5081
Abstract 5082: c-Abl function in TPA- and radiation-induced apoptosis in human prostate cancer cells
Authors: Mino Akihisa , Penate-Medina Tuula , Truman Jean-Philip , Mesicek Judith , Lee Hyunmi , Kolesnick Richard , Fuks Zvi , Haimovitz-Friedman Adriana 
Published: June 2012

Abstract
We previously reported that 12-O-tetradecanoylphorbol 13-acetate (TPA) decreased transcription and protein levels of Ataxia-Telangiectasia Mutated (ATM) in human prostate cancer cell lines LNCaP and CWR22-Rv1, de-repressing the enzyme ceramide synthase (CerS) to promote apoptosis. Here we analyzed the expression and subcellular distribution of the six mammalian CerS isoforms and their specific ceramide species generated within mitochondrial-associated membranes (MAM) and within the mitochondria in these cells before and after TPA±radiation treatments. This analysis revealed that TPA±radiation induces de novo synthesis of ceramide by specifically activating CerS isoforms 5 and/or 6 generating pro-apoptotic C16-ceramide species in mitochondrial membranes. In addition we demonstrate that LNCaP cells transfected with a c-Abl kinase dead (KD) mutant showed a significant decrease in both TPA and TPA + radiation-induced apoptosis compared with c-Abl (WT) transfected LNCaP cells. Thus, this result indicates that the kinase activity of c-Abl is necessary for TPA±radiation-induced apoptosis in LNCaP cells. In LNCaP cells transfected with WT-c-Abl, ceramide elevation was observed in response to TPA coupled to a synergistic increase of ceramide after TPA+radiation treatment. However, ceramide elevation was abolished in LNCaP transfected with the KD-c-Abl, for both TPA and TPA+radiation treatments. These findings identify kinase active c-Abl as a pro-apoptotic factor in these cells, which utilizes the activation of the CerS pathway to transduce this apoptotic response. Whether c-Abl directly or indirectly activates CerS5 and/or 6 activities, responsible for the generation of the pro-apoptotic ceramide species in response to TPA±radiation, remains to be elucidated.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5082. doi:10.1158/1538-7445.AM2011-5082
Abstract 5083: Nanoaerosol delivery of beclin1 combined with radiation suppressed tumor growth in the lungs of K-rasLA1 mice
Authors: Shin Ji Young , Cho Myung Haing 
Published: June 2012

Abstract
As incidence and mortality due to lung cancer increase, great effort has been put into developing feasible therapeutics in medical field. Radiation, together with surgery and chemotherapy, is the must in treating lung cancer, however, side effects have to be taken into consideration.
To minimize the side effect of radiotherapy, repeated exposures (5 times, 24 hours interval) with low dose (2Gy) of radiation to restricted area (thorax, 2cm) were attempted. After sensitizing lungs of K-rasLA1 mice with radiation, beclin1, known to be a tumor suppressor, involved in autophagy, complexed with nano-sized biodegradable poly(ester amine), was prepared and delivered into K-rasLA1 mice via aerosol 3 times for 4 weeks. Seventeen weeks old K-rasLA1 lung cancer model mice (n=20, 5 mice/group) were sacrificed and collected samples were analysed.
K-rasLA1 mice treated with beclin1 and radiation showed significant tumor regression with low progression to adenocarcinoma and increment in number of autophagic vacuoles. Precedent event of beclin1-bcl2 dissociation stimulated synergistic anti-tumor effect via inhibition of protein translation and angiogenesis.
Taken together, non-invasive treatment, radiation with PEA-beclin1 aerosol delivery, can be a feasible candidate for developing novel therapeutics in lung cancer treatment.
This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (MEST) (NRF-2010-0000784).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5083. doi:10.1158/1538-7445.AM2011-5083