bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1698: ERG protein expression and genomic rearrangement status in primary and metastatic prostate cancer - A comparative study of two monoclonal antibodies
Authors: Tan Shyh-Han , Braun Martin , Goltz Diane , Shaikibrahim Zaki , Vogel Wenzel , Boehm Diana , Scheble Veit , Dobi Albert , Fend Falko , Wernert Nicolas , Kristiansen Glen , Perner Sven 
Published: August 2012

Abstract
Introduction and Objective: Overexpression of the ERG protein is highly prevalent in prostate cancer (PCa) and most commonly results from gene fusions involving the ERG gene. Recently, an N-terminal epitope targeted mouse and a C-terminal epitope targeted rabbit monoclonal anti-ERG antibody have been introduced for the detection of the ERG protein. Independent studies reported that immunohistochemical (IHC) stains with both monoclonal anti-ERG antibodies (ERG-MAbs) highly correlate with the underlying ERG gene rearrangement status. However, a comparative study of both antibodies has not been provided so far. Here, we are the first to compare the mouse ERG-MAb to the rabbit ERG-MAb for their concordance on the same PCa cohort. Furthermore, we assessed if the ERG protein expression is conserved in lymph node and distant PCa metastases, of which a subset underwent decalcification. Methods: We evaluated tissue microarrays of 278 specimens containing 265 localized PCa, 29 lymph node, 30 distant metastases, and 13 normal prostatic tissues. We correlated the ERG protein expression with the ERG rearrangement status using an ERG break-apart fluorescence in-situ hybridization (FISH) assay and IHC of both ERG antibodies. Results: ERG protein expression and ERG rearrangement status were highly concordant regardless of whether the mouse or rabbit ERG-MAb was used (97.8% versus 98.6%, respectively). Of interest, both ERG antibodies reliably detected the ERG expression in lymph node and distant PCa metastases, of which a subset underwent decalcification. If an ERG protein expression was present in localized PCa, we observed the same pattern in the corresponding lymph node metastases. Conclusions: This is the first study to comprehensively compare the two available ERG-MAbs. By demonstrating a broad applicability of IHC to study ERG protein expression using either antibody, this study adds an important step towards a facilitated routine clinical application. Further, we demonstrate that the clonal nature of the ERG rearrangement is not restricted to the genomic level, but proceeds in the proteome. Together, our results simplify future efforts to further elucidate the biological role of ERG in PCa.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1698. doi:1538-7445.AM2012-1698
Abstract 1700: The prognostic marker SHP-1 promoter 2 hypermethylation can detect lymph node micrometastases in early stage NSCLC
Authors: Vinayanuwattikun Chanida , Chantranuwatana Poonchavist , Mutirangura Apiwat , Sriuranpong Virote 
Published: August 2012

Abstract
Introduction; Despite adequate surgical management of stage I non-small cell lung cancer, many patients still relapse and die of their disease. Micrometastases within lymph nodes might not be detected by standard H&E method. The authors conducted the study of epithelial methylation marker, SHP-1 Promoter 2 (SHP1P2) methylation as a potential molecular marker to determine its association with a high risk of disease relapse in stage I resectable non-small cell lung cancer (NSCLC). Method; Lymph nodes from resectable NSCLC stage II-IIIA were examined as a test set. All study participants had stage I NSCLC and underwent curative resection during 2001-2007 and had follow-up at The King Chulalongkorn Memorial Hospital, Bangkok, Thailand. No adjuvant treatment was given. Recurrence of disease within 40 months after resection was defined as high risk. Results: In stage II-IIIA, 75 lymph nodes were analyzed. SHP1P2 methylation was significantly higher in lymph nodes containing H&E detectable metastasis compared with histologically negative nodes (p=0.008). One hundred and ninety-eight lymph nodes from 23 patients with stage I non-small cell lung cancer were analyzed in this study. Seven patients (30%) relapsed within 40 months. Median follow-up period from surgery to relapsed of disease or censored if no relapse of disease was 56 months (range 6-109 months). All clinical/pathologic features were similar except for a larger primary tumor size in the early relapse group. Median tumor size is 5 cms (range 2-11.5) vs 2.5 cms (range 1.5-5.7) in high and low risk group respectively. Multivariate logistic-regression analyses included demographic data (sex, age, staging, tumor grading, size, type of surgery and number of resected lymph node) and SHP1P2 methylation status were done. A high absolute level of SHP1P2 methylation (&gt;58%) in analyzed resected lymph node was associated with early relapse, sensitivity 71% and specificity 99% (HR 0.43-1.04; p=0.07 (univariate); p=.002 (multivariate) with an odds ratio of recurrent cancer of 32). Conclusion: SHP1P2 methylation of resected lymph node of stage I NSCLC treated with curative intent of surgery is associated with early relapsed of disease.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1700. doi:1538-7445.AM2012-1700
Abstract 1705: Diagnosis of chronic lymphoid leukemia on unstained blood smears using Raman microspectroscopy and supervised classification
Authors: Happillon Teddy 
Published: August 2012

Abstract
Chronic Lymphoid Leukemia (CLL) is a blood cancerous disease characterized by the proliferation of lymphocytes (lymphocytosis). This is the most common leukemia, preferentially affecting people aged over 50 years old. It is incurable and in most cases shows no clinical signs. Thus, it is often discovered by chance during a blood test. If necessary, morphological and immunological studies are led by analyzing blood smears colored with May-Grünwald Giemsa, by making a complete blood count and by computing a Matutes scores. These studies are necessary because it is impossible to distinguish a healthy cell from a cancerous one only using a conventional microscope even if the cells are stained. In order to establish the diagnosis of the disease reliably and automatically, a new approach based on the Raman microspectroscopy is introduced in this study. Based on the interaction between matter and light, this technology acquires a real molecular and biochemical signature of the analyzed sample in a label-free manner (no staining or marking of the sample). Recently, Raman microspectroscopy has shown a promising potential to highlight the pathophysiological states in both human and animal since differences between different pathophysiological states occur at the molecular level. From unstained blood smears, obtained by spreading a drop of blood of CLL patients and healthy persons on standard glass slides, Raman spectra are acquired on the nucleus of white blood cells. Using a supervised classification algorithm such as the “Support Vector Machine” (SVM), a spectral model is established to distinguish spectra obtained from healthy or pathological cells. This model is computed using a population of spectra called “training set” and consists of 513 spectra from 6 CLL patients and 347 spectra from 4 healthy persons. Then, a classification of the “validation set” composed of 2820 spectra from 33 CLL patients and 1074 spectra from13 healthy individuals was achieved. A sensitivity of 84.84% and a specificity of 84.61% were obtained on the patient. Finally, a “blind set” composed of 721 spectra from 8 cases is classified. The sensitivity and specificity are respectively equal to 80% and 100%. The results obtained on the differentiation between healthy and pathological cells show the real potential of Raman spectroscopy coupled with supervised classification for the diagnosis of CLL. Future studies will concentrate on the prognosis, and if possible the prediction of CLL.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1705. doi:1538-7445.AM2012-1705
Abstract 1710: Quantitative 3D mapping of total choline in human breast cancer using high-speed MR spectroscopic imaging at 3T
Authors: Posse Stefan , Zhang Tongsheng , Royce Melanie , Dayao Zoneddy , Lopez Susan , Sillerud Laurel , Eberhardt Steven , Lomo Lesley , Lee Sang-Joon , Rajput Ashwani , Russell John , Casey Linda , Bolan Patrick 
Published: August 2012

Abstract
INTRODUCTION We report initial experience with 3D mapping of tCho to monitor treatment response in patients undergoing neoadjuvant chemotherapy to predict outcome [1]. METHOD Eleven patients aged: 28 - 77 years with biopsy-confirmed, infiltrating ductal carcinoma (IDC) were studied before and during neoadjuvant therapy. Data were collected on a 3T MR scanner equipped with 8- and 16-channel breast array using PRESS volume prelocalized 3D high-speed Proton-Echo-Planar-Spectroscopic-Imaging (PEPSI) [2] with MEGA lipid suppression (TR/TE=2000ms/135ms, matrix size up to 32×16×8, voxel size=1cc, scan time: 10 minutes including a water reference scan). Spectral quantification was performed using LCModel-based spectral fitting in reference to tissue water [3] using a customized basis set with empirically modeled Lorentzian singlet peaks to account for broad and irregular line shapes of residual lipid signals, relaxation correction and automated spectral quality thresholds. RESULTS Strongly elevated tCho with mean concentrations up to 5.1 mmol/kg was measured in 7 patients with single and multi-centric enhancing lesions (Table 1). Decreases in tCho concentration and number of voxels with detectable tCho were measured in 4 patients who underwent neoadjuvant therapy. DISCUSSION AND CONCLUSION This study demonstrates feasibility of quantitative 3D mapping of tCho in invasive breast carcinoma and assessment of regional tCho changes during neoadjuvent therapy. The long-term goal is to utilize 3D high-speed MRSI as an early predictor of treatment failure in women undergoing neoadjuvant therapy. REFERENCES [1] Danishad, A., et al. NMR Biomed. 2010; 23: 233-241. [2] Posse, S., et al., Magn Reson Med, 1997. 37(6): p. 858-65. [3] Provencher et al MRM 1993. GRANT SUPPORT: NIH, DoD, UNM Cancer Center.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1710. doi:1538-7445.AM2012-1710
Abstract 1712: Ki67 index is an independent prognostic factor in pleural mesothelioma
Authors: Ghanim Bahil , Torok Szilvia , Hoda Mir , Filipits Martin , Ostoros Gyula , Setinek Ulrike , Fillinger Janos , Dome Balazs , Klepetko Walter , Berger Walter , Hegedus Balazs 
Published: August 2012

Abstract
Aims: Malignant pleural mesothelioma is a devastating cancer with increasing incidence. Despite the fact that for establishing the diagnosis a number of immunohistochemical markers are needed, there is only one pathological prognosticator accepted and utilized, namely the histological subtype. Accordingly, we have investigated the prognostic significance of the Ki76 labeling index in malignant pleural mesothelioma. Patients and Methods: Ki67 index has been determined by assessing the labeled nuclei per high power field and correlated in a retrospective manner with patients’ clinical history and outcome. The prognostic power of the routine proliferation marker Ki67 was first determined in a test cohort (TC) of paraffin-embedded tissue samples from 55 patients. The independence of prognostic power against basic clinicopathological characteristics has been determined by multivariate analysis. Next, we measured the prognostic power in an independent validation cohort (VC) of 42 patients from another center. Results: Median Ki67 index was found to be 10 for both the test and validation. Patients whose tumor sample was categorized by low Ki67 index (≥ 10) had significantly longer survival times than those with higher Ki76 indices (in the test cohort: hazard ratio [HR] 2.49, 95% confidence interval [CI] 1.30-4.79, p&lt;0.01; in the validation cohort: HR 2.54, CI 1.26-5.13, p&lt;0.01). In the multivariate analyses of the test cohort (n=54), we could prove the prognostic power of Ki67, independent from gender, age, treatment, stage and histology. Treatment (HR 4.02, CI 1.82-8.90, p&lt;0.01) and Ki67 index (HR 2.19, CI 1.07-4.47, p=0.03) were the remaining independent significant prognosticators in the multivariate Cox regression model, whereas biphasic histology showed a clear tendency to worse prognosis when compared to the epitheloid subtype (HR 1.96, CI 0.94-4.07, p=0.07). Conclusion: Our study identifies Ki67 index as an independent, reproducible prognostic factor in malignant pleural mesothelioma and warrants its further investigation and clinical application in patients with this malignancy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1712. doi:1538-7445.AM2012-1712
Abstract 175: Atypical PKC knockdown alters TGFβ signaling potential
Authors: Gunaratne Adrian , Guglielmo Gianni Di 
Published: August 2012

Abstract
Transforming growth factor beta (TGFβ) regulates many important cellular processes including growth control and cell migration. In epithelial tumor cells, TGFβ signaling is fundamentally altered and induces epithelial to mesenchymal transition (EMT) leading to increased migratory potential. We have recently reported that the inhibition of atypical PKC isoforms (aPKC) extends TGFβ induced Smad signaling by altering receptor trafficking. Here we report that siRNA targeting of aPKC in A549 lung adenocarcinoma cells extends temporal P-Smad2 signaling but does not alter the transcript levels of Snail and Slug, as assessed by qPCR analysis. Interestingly, TGFβ was not observed to have as robust an increase in MMP9 and PAI-1 levels in aPKC-silenced cells compared to cells transfected with control siRNA. To further analyze the functional consequences, we assessed EMT by immunofluorescence microscopy analysis as well as immunoblotting for epithelial and mesenchymal cell markers. We found that TGFβ-dependent EMT was significantly reduced in aPKC silenced cells. We also uncovered that in addition to increased P-Smad2 signaling, P38 MAPK phosphorylation was increased and extended in aPKC silenced cells. Finally, we discovered that aPKC phosphorylates Par6 on a conserved serine residue that has been shown to regulate EMT and metastasis in breast cancer. Taken together, we believe that aPKC regulates several aspects of TGFβ signaling, including P-Smad2, P-P38 and P-Par6 levels. Consequently, convergence of these signals in aPKC silenced cells leads to reduced EMT and migratory potential.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 175. doi:1538-7445.AM2012-175
Abstract 1751: A phase I study of lenalidomide in combination with bevacizumab, sorafenib, temsirolimus, or 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX) in patients with advanced cancers
Authors: Subbiah Ishwaria M. , Kurzrock Razelle , Naing Aung , Piha-Paul Sarina , Falchook Gerald S. , Hong David S. , Wheler Jennifer J. , Fu Siqing , Laday Shell , Tsimberidou Apostolia M. 
Published: August 2012

Abstract
Introduction: Patients with advanced cancer have limited therapeutic options. We conducted an investigator-initiated 4-arm phase I study of lenalidomide (len) combined with bevacizumab (bev), sorafenib (soraf), temsirolimus (tem), or 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX) in patients with advanced cancers. Patients and Methods: Patients were treated with escalating doses of len (5, 10, 20 mg daily) combined with bev (5, 7.5, 10 mg/m2 on days 1, 15); soraf (200, 400mg daily); tem (15, 20, 25mg on days 1, 8, 15, 22); or FOLFOX (oxaliplatin 65, 85 mg/m2 on day 1). The escalation phase (“3+3”) was followed by an expansion phase per arm. Response was assessed by RECIST v.1. Patients were to receive enoxaparin prophylaxis. Results: Overall, 101 patients were enrolled; and 59 were treated in the dose escalation phase (4 arms) and are included in this analysis (169 cycles to date). Diagnoses were colorectal cancer (n=19), sarcoma (n=5), ovarian (n=4), lung (n=3), hepatocellular carcinoma (n=3), melanoma (n=4), neuroendocrine (n=2), prostate (n=2) and other (n=17). The median number of cycles/patient was 2 (range, 1-10). Pretreatment characteristics and outcomes are shown in Table. Two DLTs were noted: Grade 3 transient ischemic attack (TIA) while on enoxaparin in the len + FOLFOX arm and Grade 3 acute renal failure (ARF) in the len + tem arm. Three pts (two on enoxaparin prophylaxis and one not) had venous thrombosis while on study. Fifteen of 59 (25%) pts had prolonged stable disease (SD) for &gt; 4 months, including 7 (12%) for &gt; 6 mos. The len+soraf and len+tem arms have reached the maximum dose level tested; currently, expansion phase). The lev+bev and len+FOLFOX arms are in the dose escalation phase. Conclusion: Lenalidomide combined with bev, soraf, tem or FOLFOX is well tolerated and it is associatd with antitumor activity in patients with advanced solid tumors. Anticoagulation phophylaxis is needed.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1751. doi:1538-7445.AM2012-1751
Abstract 1754: A pharmacokinetics/pharmacodynamics study of sequence specificity of the PARP inhibitor, olaparib (O) with carboplatin (C) in recurrent women's cancers NCT01237067
Authors: Lee Jung-min , Hays John , Annunziata Christina M. , Minasian Lori , Zujewski JoAnne , Squires Jennifer , Nielsen Deborah , Houston Nicole , Moorshead David , Cedillo Mario , Kohn Elise C. 
Published: August 2012

Abstract
Background: C, O, and C+O have documented activity in BRCA1/2mut+ or BRCA-like breast and ovarian cancers (Br/OvCa). The effect of drug sequence on DNA damage and cell death is unknown. Our in vitro modeling suggests that exposure to O prior to C (O&gt;C) reduced double stranded DNA damage and cell loss. Our trial tests the hypothesis that C&gt;O causes more cellular injury. Methods: Eligible pts have recurrent women's cancers, good end organ function, and evaluable disease. A 3+3 dose escalation run-in defined the O tablet dose in combination with C (AUC 4). The study will now randomize pts to schedule A or B (below), allowing intra-pt and inter-cohort analysis of PK/PD endpoints. PBMCs will be collected C1/2 for measurement of platination and DNA damage/repair; DNA repair protein integrity will be assessed on archival tissues. Clinical benefit, response frequency and duration, and toxicity will be ascertained. Mutation carriers will undergo progression biopsy for analysis of BRCA1/2 re-expression mutations. Results: The phase I portion is complete. 12 women (8Ov/3Br/1Endometrial[En]) have been accrued on 3 dose levels (DLs). Median prior number of regimens was 5. No DLT have been seen in 5 evaluable pts on DL3 (O tablet 200mg q12h/C AUC4 [1 pt pending]). Gr3 AEs included neutropenia (44%), and gr2 were anemia (56%), fatigue (22 %), C hypersensitivity (22%), thrombocytopenia (11%), and nausea (11%). 1 pt (DL2; stable disease) died of unrelated bleeding during C4. Clinical benefit has been observed in 8 evaluable pts with PR in 2 BRCA1mut+ OvCa (9+, 11+ mo), stabilization &gt; 4mo in 6 pts (4OvCa,1BrCa, 1EnCa), and 3 are TETE. Conclusions: O in tablet formulation at 200mg q12h x 7d with C AUC4 q21d is active and tolerable, with observed interactive marrow suppression. Subsequent women will be randomized to examine schedule dependence of activity and toxicity.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1754. doi:1538-7445.AM2012-1754
Abstract 176: Kinase activity of tumor-derived exosomes as a potential biomarker for response to treatment
Authors: van der Mijn Johannes C. , Jimenez Connie R. , Piersma Sander R. , Dekker Henk , Labots Mariette , Schutte Lisette M. , Smit Egbert F. , Broxterman Henk J. , Tannous Bakhous , Wurdinger Tom , Verheul Henk M.W. 
Published: August 2012

Abstract
Introduction Exosomes are nanometer-sized vesicles secreted by tumor cells after fusion of multivesicular bodies with the plasma membrane that reflect tumor cell biology. Exosomes contain distinct classes of molecules including mRNA, miRNA and proteins. Because they can be isolated from blood they are promising candidate biomarkers. Diagnostic biomarkers for selection of patients for treatment with tyrosine kinase inhibitors are urgently warranted. We hypothesize that exosomes contain tumor derived kinases that may serve as biomarkers for treatment with kinase inhibitors. Methods The U87 glioma cell line with or without EGFRvIII (U87ΔEGFR) was used as an in vitro model in this study. Cell viability was studied with the MTT-assay. Exosomes were isolated from 32h conditioned media either serum-free or containing 10% exosome-deprived serum and from 5-9mL of fresh human serum from 3 cancer patients. The isolation procedure consisted of subsequent centrifugation at 500G, 2000G, 10.000G and 100.000G. The exosome pellet was treated with proteases for 1h at 37°C to digest soluble proteins, washed in PBS and lysed. Western blots for phospho-EGFR (y1068), EGFR, phospho-AKT, AKT, phospho-ERK, ERK, Alpha-Tubulin and exosome markers CD63, ALIX and CD81 were performed. Results The sensitivity of U87ΔEGFR to erlotinib (ERL) was significantly higher compared to parental U87 cells with IC50s of 1µM and 5.4µM (p&lt;0.001), respectively. Treatment with 1 μM ERL resulted in reduced phosphorylation of EGFR, AKT and ERK in U87ΔEGFR, but not in U87 cells. The overexpression of constitutively active EGFRvIII mutant increased the phosphorylation of EGFR and downstream AKT and ERK in cells as well as in exosomes. Trypsin treatment only affected membrane proteins, where AKT and ERK levels were not altered. Exosomes from U87ΔEGFR cells treated with 0, 1 and 10µM ERL reflected the phosphorylation patterns of the cells with dose-dependent effects on AKT and ERK. Phosphorylated AKT and ERK could also be detected in exosomes from the cancer patients. Conclusion We here show that kinase activity and treatment response are reflected by exosomes derived from tumor cells in vitro. In addition we found that phosphorylated proteins can be detected in exosomes derived from blood of patients with cancer. Our aim is to further develop exosomal kinase activity analysis as an early biomarker for treatment response.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 176. doi:1538-7445.AM2012-176