bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 508: Signal transduction and activator of transcription (STAT) 3 is necessary for environment-mediated drug resistance
Authors: Ara Tasnim , Nakata Rie , Shimada Hiroyuki , Buettner Ralf , Seeger Robert C. , Yu Hua , Jove Richard , DeClerck Yves A. 
Published: June 2012

Abstract
There is recent evidence that STAT3 plays a pivotal and central role in controlling inflammatory pathways that promote malignant transformation and progression, including the ability of tumor cells to escape drug-induced apoptosis. Using neuroblastoma as a model, our laboratory had previously demonstrated that bone marrow mesenchymal stem cells through their production of interleukin-6 are a source of environment-mediated drug resistance. Here we have examined the role of STAT3, a downstream target of IL-6, in this effect. We first demonstrate that in contrast to many other cancers, STAT3 is not constitutively active in most neuroblastoma cells. However, it is rapidly phosphorylated after 15 minutes of exposure to IL-6 and its soluble receptor (sIL6-R). Activation of STAT3 is associated with its nuclear translocation and DNA binding. Treatment of CHLA-255 and SK-N-SH neuroblastoma cells with IL-6 increases their resistance to Etoposide and Melphalan in a dose-dependent manner. IL-6 inhibits the release of cytochrome C from the mitochondria and upregulates several pro-survival factors like Bcl-XL, XIAP and survivin without affecting the expression of Bax and Bad. The protective effect of IL-6 on drug-induced apoptosis is significantly inhibited in the presence of the STAT3 inhibitor Stattic (2.5 μM) or upon downregulation of STAT3 by siRNA, indicating that STAT3 is necessary for drug resistance. We also show that sIL-6R, produced by monocytes, enhances STAT3 activation and promotes drug resistance. In vivo, IL-6 and sIL-6R increase STAT3 activation in CHLA-255 neuroblastoma cells and their proliferation. Finally we observed elevated expression of phosphoSTAT3 in bone marrow samples of patients with metastatic neuroblastoma cells. Altogether, the data demonstrate that in neuroblastoma STAT3 activation by IL-6 in the tumor microenvironment plays a key role in environment-mediated drug resistance.
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 508. doi:10.1158/1538-7445.AM2011-508
Abstract 5084: Investigation of expression of RAD51 in biopsied specimen as a predictive factor of chemo-radiation therapy for advanced rectal cancer
Authors: Iwata Takashi , Shimada Mitsuo , Kurita Nobuhiro , Nishioka Masanori , Morimoto Shinya , Yoshikawa Kozo , Higashijima Jun , Mikami Chie , Kashihara Hideya 
Published: June 2012

Abstract
BACKGROUND/AIMS: Chemo-radiation therapy (CRT) has been used to improve local control and survival in patients with advanced rectal carcinoma. However, a significant proportion of patients show poor response to adjuvant CRT. We thus investigated the usefulness of RAD51 expressions as a predictive maker of the CRT response.
METHODOLOGY: Twenty three biopsied specimens among forty two patients who were suffered from lower rectal cancer were investigated. All patients received preoperative CRT consisting of TS-1, concurrent with 40 Gy of pelvic irradiation before having curative radical resection. The relationship between pathological responses of the tumors after therapy and expression of RAD51 was evaluated by immunostaining of biopsied and resected specimen, and evaluated the expression of RAD51 as a predictive factor of CRT.
RESULTS: Positive expression of RAD51 was observed in 14 of 23 biopsied specimens (61%), and 24 of 42 patients (57.1%) in resected specimen. All RAD51 positive case which expressed in biopsied specimen expressed RAD51 positive in resected specimen. In biopsied specimen, RAD 51 positively expressed in 62.8% (10 of 14 cases) of SD, 44.4% (4 of 9 cases) of PR, and 0% (0 of 0 case) of CR, whereas in resected specimen, RAD 51 positively expressed in 68.2% (15 of 22 cases) of SD, and 42.2% (9 of 20 cases) of PR and CR. There is a tendency of reverse correlation between clinical response and expression of RAD51. Regarding the correlation between pathological response and RAD51 expression in biopsied specimen, positive expression of RAD51 was recognized in 90% (9 of 10 cases) of Grade 1, 50% (5 of 10 cases) of Grade 2, and 0% (0 of 3 cases) of Grade 3, and in resected specimen, positive expression of RAD51 was recognized in 75.0% (15 of 20 cases) of Grade 1, 47.1% (8 of 17 cases) of Grade 2 and 20.0% (1 of 5 cases) of Grade 3. A significant reverse correlation was recognized between RAD51 expression and pathological responses both in biopsied and resected specimen.CONCLUSIONS: RAD51 expression could be one of the most important predictive factors of preoperative CRT for advanced lower rectal 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 5084. doi:10.1158/1538-7445.AM2011-5084
Abstract 5089: Comparison of treatment results between two fractionation schedules of high-dose-rate intracavitary brachytherapy (HDR-ICBT) in patients with cervical cancer: A prospective cohort study
Authors: Huang Eng-Yen , Wang Chong-Jong 
Published: June 2012

Abstract
Purpose: To compare the treatment results of two fractionation schedules for high-dose-rate intracavitary brachytherapy (HDR-ICBT) in patients with cervical cancer.
Materials and Methods: From June 2001 through December 2008, 321 patients with Stage IB-IVA cervical cancer were enrolled in the study. All patients underwent pelvic irradiation and HDR-ICBT. The median central dose and parametrial dose were 39.6 Gy and 45 Gy, respectively. Patient underwent either 6 Gy × 4 (HDR-4) (n=168) or 4.5 Gy × 6 (HDR-6) (n=153) to point A of ICBT twice per week. The biologically effective doses (BED) of point A were 38.4 and 39.15 Gy10 in HDR-4 and HDR-6 group, respectively. The rates of overall survival, local control, distant failure, proctitis, cystitis, and enterocolitis were compared between HDR-4 and HDR-6.
Results: There were no significant differences of demographic data between HDR-4 and HDR-6 except of total treatment time. The median follow-up time was 40.6 months (range 1.7-95.4). The 5-year proctitis rates were 21.7% and 22.3% in HDR-4 and HDR-6 (p = 0.417), respectively. The corresponding rates of Grade 2-4 proctitis were 15.9% and 9.7% (p = 0.120). The corresponding rates of Grade 3-4 proctitis were 4.3% and 3.1% (p = 0.804). Subgroup analysis in patients with age ≥ 63 years revealed that 5-year Grade 2-4 proctitis rates were 23.4% and 5.5% (p = 0.013) in HDR-4 and HDR-6, respectively. The corresponding rates in patients with age &lt; 63 years were 8.3% and 13.4% (p = 0.659). The rates of overall survival, local control, distant failure, cystitis, and enterocolitis were not significantly different between HDR-4 and HDR-6.
Conclusion: Small fraction size of HDR-ICBT decreases Grade 2-4 proctitis in elderly patients. The schedule is suggested in those patients who tolerate additional two applications of HDR-ICBT.
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 5089. doi:10.1158/1538-7445.AM2011-5089
Abstract 5098: Novel characteristic proteins of large cell neuroendocrine carcinoma of lung
Authors: Nomura Masaharu , Fukuda Tetsuya , Kawamura Takeshi , Tojo Hiromasa , Mikami Sayaka , Kihara Makoto , Bando Yasuhiko , Ohira Tatsuo , Tsuboi Masahiro , Kato Harubumi , Gazdar Adi F. , Varga Gyorgy Marko , Nishimura Toshihide , Ikeda Norihiko 
Published: June 2012

Abstract
Large cell neuroendocrine carcinoma (LCNEC) is a subtype of large cell carcinoma (LCC), which has a neuroendocrine feature like small cell lung carcinoma (SCLC). We applied a novel emerging proteomic method using tissues to identify characteristic proteins of LCNEC. Proteins from cancer cells, which collected from formalin fixed paraffin-embedded (FFPE) tissues by laser microdissection were extracted and subjected to liquid chromatography / mass spectrometry. Proteins identified by database search were semi-quantified and subjected further to statistical evaluation. We identified three characteristic proteins of LCNEC, aldehyde dehydrogenase 1 family, member A1 (AL1A1), aldo-keto reductase family 1, member C1 (AK1C1) and C3 (AK1C3) that have been considered as some of cancer stem cell markers. Immunohistochemical verification showed those proteins correlated well with the frequency of immunopositive cells with AL1A1 the greatest. These results suggest that candidate biomarkers of LCNEC are related to cancer stem cells, consistent with its undifferentiated and aggressive nature.
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 5098. doi:10.1158/1538-7445.AM2011-5098
Abstract 5100: Secretome proteomics to identify indicators for lung cancer treatment response prediction and monitoring
Authors: Schaaij-Visser Tieneke B.M , Proost Natalie , Nagel Remco , Piersma Sander R. , Pham Thang V. , Brakenhoff Ruud H. , Berns Anton , Jimenez Connie R. 
Published: June 2012

Abstract
Lung cancer is currently the number one cause of cancer-related deaths worldwide. Five-year survival rates for both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) are still less than twenty percent due to late stage of presentation, treatment failure and lack of biomarkers for personalized therapy. Aim of this study is to identify protein biomarkers that can be used for treatment response prediction and therapy monitoring.
Rather than following a broad strategy by analyzing the proteome of whole cell or tissue lysates, we chose to use a more specific approach based on the assumption that the best tumor markers are shed or secreted by the tumor and can be detected in blood. Secretome (i.e. all proteins shed from or secreted by a cell or tissue) proteomics (Piersma SR et al. J Proteome Res. 2010 Apr 5;9(4):1913-22.) was performed on a set of tumors from conditional mouse models for SCLC and NSCLC (Meuwissen R et al. Oncogene. 2001 Oct 4;20(45):6551-8; Meuwissen R et al. Cancer Cell. 2003 Sep;4(3):181-9.), a set of human and mouse SCLC and NSCLC cell lines and a series of human NSCLC cell lines with a range of IC50-values for cisplatin (1.5 – 15 µM). Secretomes were obtained by collecting serum-free media from the cell lines or collecting PBS in which a tumor tissue piece had been incubated.
In the secretome samples, up to 2,000 proteins can be identified with 80% reproducibility by label-free, shotgun nanoLC tandem mass spectrometry and quantified by spectral counting. The beta-binomial test (Pham TV et al. Bioinformatics. 2010 Feb 1;26(3):363-9.) is used to find significant differences in protein expression between the different secretomes and network analysis is performed to provide insight into the underlying cellular mechanisms. The secretomes from the mouse models are used to find proteins specifically secreted by either NSCLC or SCLC, while the comparison between the secretomes of the several human and mouse cell lines allows extrapolation of the results from the mouse models to the human situation. Furthermore, the analysis of the cell lines with various cisplatin IC50-values permits selection of the protein markers that are indicative of sensitivity or resistance. The results of the different proteomics analyses will be presented along with the most promising biomarker candidates and an overview of the functional network analysis.
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 5100. doi:10.1158/1538-7445.AM2011-5100
Abstract 5101: Biomarker identification in non-small cell lung cancer (NSCLC) with activity-based proteomics
Authors: Wiedl Thomas , Arni Stephan , Roschitzki Bernd , Grossmann Jonas , Soltermann Alex , Hillinger Sven , Aebersold Rudolf , Weder Walter 
Published: June 2012

Abstract
Background: Lung cancer is the leading cause of all cancer related deaths and treatment is still suboptimal. Novel biomarkers with a reliable predictive significance which may additionally represent therapeutic targets are therefore of utmost importance. In biomarker discovery studies transcript or protein abundances are typically compared in normal versus disease states. However, crucial changes in enzymatic activities remain undetected. Based on the work of Prof. Cravatt and others, activity-based proteomics has become a promising option to circumvent this limitation. This study aims to establish a robust and high throughput activity-based proteomics platform and to investigate the role of serine hydrolase activity profiles as prognostic biomarkers in lung cancer.
Methods: A fluorophosphate derivate (CAS-Number: 353754-93-5) was used to covalently target serine hydrolases in proteomes derived from human lung adenocarcinoma biopsies and corresponding normal lung tissues (tumor cell content: &gt;50%, TNM-stage: I-IV). Tagged proteins were subsequently affinity purified and analyzed using a directed mass spectrometry based approach (LTQ-FTMS, Thermo Finnigan). Data were qualitatively analyzed using the Mascot 2.2 search engine and Progenesis LC-MS version 2.5 (Nonlinear Dynamics) was employed for relative quantification.
Results: The strategy described above results in the simultaneous qualitative and quantitative analysis of serine hydrolase activities in complex proteomes, thereby representing a valid alternative to activity-based proteomics approaches described so far. The analysis of 40 pairs of fresh frozen malignant and corresponding normal lung tissues in combination with clinical follow-up data led to the identification of two biomarker candidates that have previously not been associated with lung cancer.
Conclusion & Outlook: Based on the results obtained in this study we conclude that activity-based proteomics represents a powerful strategy in the seek for novel biomarker candidates in human lung adenocarcinoma. Future research will involve data validation with additional samples from our tumor bank using advanced quantitative Multiple Reaction Monitoring (MRM) technology.
Liu, Y., Patricelli, M.P. & Cravatt, B.F. Activity-based protein profiling: the serine hydrolases. Proceedings of the National Academy of Sciences of the United States of America 96, 14694-14699 (1999).
Jessani, N., et al. A streamlined platform for high-content functional proteomics of primary human specimens. Nature methods 2, 691-697 (2005).
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 5101. doi:10.1158/1538-7445.AM2011-5101
Abstract 5106: Development of plasma biomarkers for pancreatic cancer diagnosis
Authors: Pan Sheng , Chen Ru , Crispin David A. , May Damon , McIntosh Martin , Anton-Culver Hoda , Cao Brian , Stevens Tyler K. , Bronner Mary P. , Brentnall Teresa A. 
Published: June 2012

Abstract
Pancreatic cancer is the fourth leading cause of cancer deaths in the United States. It has the worst five year survival rate (1 to 4%) among all the cancers. This cancer is deadly because the diagnosis occurs at a late stage when the disease is inoperable and because there is a lack of effective therapy. The current pancreatic cancer biomarker CA19-9 does not provide the high sensitivity and specificity required to screen an asymptomatic population for diagnosis. Therefore, biomarkers that can improve current pancreatic cancer diagnosis would have great value to improve the patient management and survival rate of this deadly disease. In this study, we perform a large scale quantitative proteomics profiling to identify differential plasma proteins that are associated with pancreatic cancer. The proteome of plasma samples from patients with pancreatic ductal adenocarcinoma were quantitatively compared with that of non-pancreatic disease controls and patients of chronic pancreatitis, a pancreas disease that shares many molecular features with pancreatic cancer. To tackle the challenge presented by the enormous complexity and heterogeneity of plasma proteome, we applied an integrated proteomics strategy, including immunodepletion, multi-dimensional fractionations at both protein and peptide level, to enhance the detection of low abundance proteins, especially those derived from tumor cells. With stringent criteria, 1340 proteins were identified in plasma across 8-order of magnitude in protein concentration. A group of differential proteins that are associated with pancreatic cancer was identified, and their relationship with the previous studies in pancreatic tissue and pancreatic juice was investigated. A pilot study was performed to confirm a subgroup of differential proteins with ELISA using independent cohort of blood samples from well-diagnosed patients of pancreatic cancer, pancreatitis and non-pancreatic disease control. The performance of the selected protein candidates were benchmarked against CA19-9. Among the nine protein candidates tested, two demonstrated better specificity and sensitivity than CA19-9 in distinguishing pancreatic cancer from the controls; and one protein candidate was verified as a biomarker candidate for chronic pancreatitis. The protein candidates identified in this study provide a biomarker candidate pool for future development of blood-based assays for pancreatic cancer diagnosis. The discovery and technical strategy presented by this study may be pertinent to biomarker development for other cancers.
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 5106. doi:10.1158/1538-7445.AM2011-5106
Abstract 5110: RNA helicase p68 is a new marker for breast cancer heterogeneity
Authors: Wang Daojing 
Published: June 2012

Abstract
Two major challenges in diagnosis and therapy of breast cancer lie in its heterogeneity and drug resistance. RNA helicase p68 (DDX5) has been shown to be involved in all aspects of RNA metabolism and serves as a transcriptional co-regulator. However, its functional role in breast cancer remains elusive. We utilized an integrative biology approach strategy to further define the role of p68 in breast cancer. Specifically, we determined the expression pattern of p68 at both mRNA and protein levels for a panel of ∼50 breast cancer cell lines. We performed immunohistochemistry of p68 using tissue microarrays containing a total of over 200 cases of primary human malignant breast cancer (various grades and stages). We knocked down p68 in a panel of representative breast cancer cell lines (e.g., SKBR3 and MDA-MB-231) and investigated the functional consequences such as their proliferation and responses to Lapatinib after the p68 knockdown. Finally, we carried out SILAC-based proteomic profiling of these breast cancer cells after p68 knockdown and identified p68-targeted proteins and networks contributing to the drug responses. We found that p68 expression pattern is distinct among different subtypes of breast cancers. More aggressive basal subtypes have predominantly high p68 protein expression while low p68 expression is predominantly associated with the luminal subtype. Knockdown of p68 inhibits the proliferation of breast cancer cells and sensitizes them to cancer drugs such as Lapatinib. We demonstrated that p68 is a new marker for breast cancer heterogeneity in addition to ER, PR, and Her2. Importantly, we identified p68-regualted cytoskeletal reorganization as a new mechanism in controlling breast cancer proliferation and drug resistance. In summary, RNA helicase p68 may serve as a new marker for breast cancer heterogeneity, as a predictor for drug resistance, and as a target for a combinational therapy to circumvent drug resistance of aggressive tumors.
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 5110. doi:10.1158/1538-7445.AM2011-5110
Abstract 512: Reprogramming of the tumor microenvironment by stromal Pten-regulated miR-320
Authors: Bronisz Agnieszka M. , Godlewski Jakub , Wallace Julie , Merchant Anand , Leone Gustavo , Ostrowski Michael C. 
Published: June 2012

Abstract
The tumor microenvironment is increasingly recognized as an essential collaborator for tumor cell growth and dissemination. However, our understanding of how the dialogue between stroma and tumor occurs at the molecular level is rudimentary. Recently, we showed that the genetic inactivation of Phosphatase and tensin homolog deleted on chromosome ten (Pten) in mouse mammary fibroblasts (MMFs) accelerates the initiation, progression and malignant transformation of mammary epithelial tumors and that this was associated with the activation of the transcription factor v-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2). In order to provide a molecular framework that defines how Pten deletion in MMFs, reprograms expression of other cells in the tumor microenvironment we carried out global miR profiling of Pten-/- MMFs. Among several significant changes in the miR expression profile compared with wild type MMFs, a novel and highly significant down-regulation of miR-320 was detected. We found that miR-320 in Pten-/- MMFs acted as a tumor suppressor to inhibit epithelial tumor growth in vivo, providing the first evidence for tumor suppressive functions of miRs outside the confines of the tumor cell. Proteomic analysis of the extracellular matrix showed that down-regulation of miR-320 in stromal fibroblasts induces a tumor-promoting secretome that incites profound changes in endothelial and epithelial cell phenotypes typical of malignant tumors. We found ETS2 as a direct target of miR-320 that was largely responsible for regulating the expression of the fibroblast-specific secretome. Multispectral imaging of human invasive breast carcinoma samples revealed a positive correlation between PTEN and miR-320 downregulation and negative correlation between miR-320 and ETS2 expression. Importantly, we show that expression of the miR-320/ETS2 regulated secretome can distinguish tumor stroma form normal breast stroma in breast cancer patients and can retrospectively predict patient outcome in multiple breast cancer gene expression data sets.These results extend the concept of miR function beyond the tumor cell boundary and define a network of communication between tumor fibroblasts and tumor cells that can potentially be targeted in human cancer. This work reveals miR-320 as a critical component of the Pten tumor suppressor axis that acts in stromal fibroblasts to reprogram the tumor microenvironment and curtail tumor progression.
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 512. doi:10.1158/1538-7445.AM2011-512