bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4622: PAM4-antigen levels in the serum of patients with pancreatic carcinoma: Early detection of disease and correlation with responses to radioimmunotherapy
Authors: Gold David V. , Newsome Guy , Modrak David E. , Horne Heather , Wegener William A. , Goldenberg David M. 
Published: February 2011

Abstract
Background: A serum-based enzyme immunoassay (EIA) employing MAb-PAM4 demonstrates high specificity and sensitivity for detection of advanced pancreatic carcinoma (PC). We are currently exploring use of the immunoassay as a means to detect early-stage PC, as well as detection of nascent disease progression or relapse during routine post-treatment follow-up. We now also report initial results that provide correlation of serum PAM4-antigen levels with responses to radiolabeled PAM4 therapy.
Methods: The PAM4-based EIA was employed for detection and quantitation of antigen in the serum of pancreatic carcinoma patients with known stage of disease (N=68). An additional 11 patients with stage-4 disease who participated in an ongoing phase-1b clinical trial to evaluate the combination of 90Y-hPAM4 IgG, (clivatuzumab tetrexate) radioimmunotherapy with low-dose, radiosensitizing, gemcitabine (Gem) were also examined. Serum specimens from this latter group were collected at baseline prior to treatment, at the end of the 4-week treatment cycle, and again at 4 weeks post-treatment (week 8 from baseline), when a CT scan was performed to determine tumor response.
Results: Overall, the sensitivity of the immunoassay for detection of PC was 81%, with a 5% false-positive rate for the healthy volunteers (N=19). When examined by stage of disease, sensitivity rates were 91%, 86% and 62% for stages 3/4 advanced disease, stage-2, and stage-1 PC, respectively. For those patients who had treatment with 90Y-hPAM4 + Gem, a decrease in antigen levels greater than 40%, observed at the end of the treatment cycle (4 weeks), with sustained decline in the antigen levels at the 8-week post-treatment evaluation, provided presumptive evidence of tumor response, either stable disease (SD, N=2) or partial response (PR, N=5) by CT RECIST criteria. None of the patients with progressive disease (N=4) had a sustainable decrease in serum levels of PAM4-antigen, whereas all of the responders did. The median decrease in serum PAM4-mucin levels at the 8-week follow-up evaluation timepoint was 54% (range: 47% - 98% decrease), with a median tumor response (only SD and PR responders) being a decrease in tumor size of 37% (range: 46% decrease to 4% increase), from a baseline median primary tumor size of 10.0 cm (range 2.6 - 12.1 cm).
Conclusions: These results suggest that the PAM4-based immunoassay should be further evaluated for use in the detection of early pancreatic carcinoma, as well as to evaluate tumor response to therapy. (Supported in part by grant CA096924 from the NIH.)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4622.
Abstract 4624: Differentiation of female donors classified as “normal”, with benign disease and with breast cancer based on blood RNA signature
Authors: Somiari Richard I. , Russell Stephen , Bharathan Seema , Lyons-Weiler James , Somiari Stella A. 
Published: February 2011

Abstract
Breast cancer still imposes significant healthcare burden on women worldwide. Mammography is currently the benchmark for screening, but mammography may not; a) detect all early stage breast cancers especially in young women with dense breast, b) unequivocally distinguish between benign disease and cancer and c) be beneficial to people in remote and underserved areas without mammograms. Biomarkers could complement mammography because of the potential to enable earlier detection, accurate differentiation between non-cancerous and cancerous breast lesions, and allow screening of a specimen like blood collected from a remote site. As a step towards developing a biomarker-based blood test for early detection of breast disease, we have used the branched-DNA multiplex technology to measure the levels of 24 candidate biomarkers in blood of fully informed and consented female donors classified into three broad categories; normal, with breast cancer (BC), and with benign breast disease (BD). To determine if the groups can be identified using the levels of the 24 candidate biomarkers we trained prediction models based on the data without background subtraction and applied the same training process on background subtracted data. Next we used an in-house developed software, to identify the optimal transformation and normalization methods. Due to the small sample size available for the current study, we generated 1,000 cases and 1,000 controls by simulating the original data via a distributional sampling model, and used the simulated data as the test validation set (TVS). Three prediction models were then applied to the original data and simulated TVS, namely: in-house GA optimized k of m, Random Forest (Salford System), Logistic Regression (SAS). Random Forest proved to be the best model for group prediction displaying sensitivities and specificities above 90%. This presentation will discuss the extent to which the levels of the biomarkers in blood allowed the identification of donors classified as “normal” and with “breast disease”.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4624.
Abstract 4635: FK506 binding protein 51 is a possible novel tumoral marker
Authors: Romano Maria Fiammetta , Romano Simona , D'Angelillo Anna , Luna Elvira De , Staibano Stefania , Mascolo Massimo , Bisogni Rita 
Published: February 2011

Abstract
Very recently, we have identified FK506 binding protein 51 (FKBP51), an immunophilin phisiologically expressed in lymphocytes, as a protein associated with malignant melanoma. Its expression correlates with tumor aggressiveness and is maximal in metastatic lesions. We have also demonstrated that FKBP51 is a factor of resistance to genotoxic agents, including anthracyclins and ionizing radiations, because it promotes NF-kB activation. Aim of the present study was to investigate FKBP51 expression in solid tumors. Overall 60 samples, stored in our Patology section, of the following tumors: breast, colon, lung, pancreas, ovary and prostate (10 for each tumor), and a comparable number of normal tissue samples, were analysed for FKBP51 expression by immunohistochemistry. An intense signal was observed in all prostatic and ovarian adenocarcinomas analyzed, but only in a proportion of pancreatic cancer samples analyzed (mostly, esocrine pancreas tumors). Furthermore, an intense nuclear signal was observed in colon and lung adenocarcinomas. Immunohistochemistry was negative in breast cancer. Normal tissues of the same histotype showed very low or undetectable levels of FKBP51. We also measured FKBP51 mRNA levels in deparaffinized tissues from breast, pancreas, prostate and lung samples, both normal and tumoral, by Realtime PCR. All normal tissues analyzed, except for prostate, displayed mRNA levels lower than those of peripheral blood mononuclear cells (PBL). FKBP51 levels in prostate and PBL were similar. Increases in mRNA levels, from 3 to 30 folds, were found in prostate, esocrine pancreas and lung cancers, compared to normal tissue of the same histotype. Very low FKBP51 mRNA levels were found in breast cancer. In conclusion, our preliminary results show that FKBP51 expression increases in different solid tumors, including ovary, prostate, lung, colon, and esocrine pancreas, in comparison with the normal tissue counterpart. This study support the conclusion that deregulated FKBP51 can play a role in malignant transformation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4635.
Abstract 4638: Over-expression of p19 protein in human gastric carcinoma and its clinicopathological significance
Authors: Tsai Ming-Ming , Wang Chia-Siu , Lin Kwang-Huei 
Published: February 2011

Abstract
Gastric cancer is the fifth leading cause of cancer-related death in Taiwan. Identification of gastric cancer related factor is essential to increase patient survival. P19 protein was identified using two-dimensional electrophoresis (2-DE) combined with Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometer (MALDI-TOF MS) and isobaric tag for relative and absolute quantitation (iTRAQ). We evaluated the p19 protein expression as a potential biomarker of gastric cancer since it aberrantly expressed in gastric cancer and associated with metastasis. Tumor tissue and matching noncancerous mucosa were obtained from 60 patients immediately after gastric resection. P19 protein expression levels were determined by quantitative reverse transcriptase-polymerase chain reaction (Q-RT-PCR) and Western blot. The expression of p19 was up-regulated 76.3% of 55 patients, or 45% of 60 patients with gastric cancer in tumor tissues (compared with adjacent non-tumor tissues) at mRNA or protein levels, respectively. Paraffin-fixed tumor tissues were used for immunohistochemistry (IHC) study in 110 patients with gastric cancer. The p19 protein was up-regulated in about 58% tumor tissues, however, not in plasma. The clinic-pathological correlation of p19 protein was also valuated. The higher p19 expressions were significantly associated with lymph node metastasis, and were significantly higher in the stages of III and IV than those in the stages I and II. The depth of wall invasion was significantly greater in the stage of (T3 and T4) compared to the (T1 and T2). Five-year survival of patients with lower p19 expression was significantly better than those patients with a higher expression. To better understand the function of p19 protein in human gastric cancer cells, the isogenic p19 protein overexpressing cell lines (AZ521, SC-M1) were prepared. The proliferative, migratory and invasive abilities were increased in the p19 overexpressing cell lines. The results indicate the p19 protein is a potential prognostic marker for gastric cancer and its function associates with cell invasion.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4638.
Abstract 464: Hypoxia-regulated Delta-like 1 homologue (DLK1) enhances cancer cell stemness and tumorigenicity
Authors: Kim Yuri , Lin Qun , Zelterman Daniel , Yun Zhong 
Published: February 2011

Abstract
Tumor hypoxia, i.e. O2 deficiency, is a common feature of solid tumors and predicts poor clinical outcomes. Tumor hypoxia is associated with increased aggressiveness and resistance to cancer therapies. Hypoxic tumors appear to be poorly differentiated and express stem/progenitor cell genes. It remains unclear, however, whether and how hypoxia regulates cancer cell differentiation and maintains cancer cell stemness. In this study, we demonstrate that hypoxia increases the expression of delta-like 1 homolog (DLK1), a transmembrane protein mainly expressed in stem/progenitor cells. Both HIF-1α and HIF-2α can bind to the DLK1 promoter. Using neuroblastoma (NB) cells as a model, we have found that DLK1 is highly expressed in undifferentiated, but not in differentiated, NB tumor cells. Downregulation of DLK1 expression by siRNA interference results in spontaneous differentiation, whereas overexpression of DLK1 inhibits retinoic acid-induced differentiation. We have further found that DLK1 is required for maintaining tumor sphere growth, a key feature reflecting the cancer stem cell-like characteristics. Importantly, we have demonstrated that loss of DLK1 expression leads to significantly reduced clonogenic growth in vitro, suppressed tumor take and growth of tumor xenografts in vivo. Furthermore, we have found that the intracellular domain of DLK1, especially its two conserved putative phosphorylation sites (Tyrosine 339 and Serine 355), is required for its biological functions. In summary, our results clearly demonstrate that DLK1 has the ability to regulate all the key aspects of cancer stem cell-like characteristics, i.e. tumor cell differentiation, self-renewal (tumor sphere growth), clonogenicity, and tumorigenicity. Because elevated DLK1 expression is also found in many tumor types, our observations suggest that hypoxia and DLK1 may constitute an important stem cell pathway for the regulation of cancer stem cell-like functionality and tumorigenicity by the tumor microenvironment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 464.
Abstract 4642: Risk stratification of bladder cancer patients using a panel of 5 prognostic protein markers
Authors: Fristrup Niels , Ulhøi Benedicte P. , Borre Michael , Hartmann Arndt , Ørntoft Torben F. , Dyrskjøt Lars 
Published: February 2011

Abstract
The majority of patients with bladder cancer are initially diagnosed with noninvasive or superficially invasive urothelial tumors. These tumors form a heterogeneous group, spanning from benign low grade Ta tumors that rarely progress to high grade T1 tumors with concomitant CIS that progress in up to 60% of cases. No biomarkers have yet been accepted in clinical routine for predicting the individual disease courses of these patients. Previously, we have identified gene expression signatures for prediction disease outcome for patients with non-muscle invasive bladder cancer. The aim of the present study was to validate key candidate markers from these signatures on the protein level. Five genes were selected for investigation: CTSE, BIRC5, TRIM29, PLK1 and SERPINB5.
A total of 289 primary non-muscle invasive urothelial tumors (182 pTa, 101 pT1 and 6 CIS) were chosen for tissue microarray construction. 118 patients showed later disease progression to pT2-4 bladder cancer with a median time to progression of 22 months. None of the remaining 171 patients showed later disease progression within the follow-up period with a median follow-up of 93 months. Protein expression was investigated using immunohistochemistry.
We found that high expression of BIRC5 and PLK1 identified patients with an increased risk of progression; (HR=2.47 (1.57-3.87), P&lt;0.001 and HR=1.52 (1.00-2.29), P=0.048 respectively). Whereas high expression of CTSE, SERPINB5 and TRIM29 identified patients with a reduced risk of progression; (HR=0.60 (0.39-0.93), P=0.02), (HR=0.58 (0.38-0.89), P=0.01) and (HR=0.38 (0.20-0.73), P=0.003 respectively).
We found all five proteins to be independent prognostic variables for predicting disease progression to muscle invasive bladder cancer when stratifying for other known clinical and histopathological risk factors. Consequently, we successfully transferred key markers from the gene expression signatures to the protein level. This marker panel is currently being validated in a new series of pT1 bladder tumors and the results from this independent validation set will also be presented at the meeting.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4642.
Abstract 4662: Genetic variations in the cell-cycle pathway and survival of patients with advanced non-small cell lung cancer receiving platinum-based chemotherapy
Authors: Yin Jikai , Wu Xifeng , Lu Charles , Chang Joe , Hildebrandt Michelle , Stewart David , Spitz Margaret R. , Gu Jian 
Published: February 2011

Abstract
Background: Platinum-based chemotherapy is the main choice of treatment for patients with advanced Non-small cell lung cancer (NSCLC). Platinum agents target DNA preferentially for cytotoxicity, which will lead to DNA damage and cell-cycle arrest. We hypothesize that genetic variations in cell cycle pathway may modulate response to platinum-based chemotherapy. In this study, we utilized a comprehensive pathway-based approach to identify genetic variations in the cell-cycle pathway as predictors of overall survival in NSCLC patients treated with platinum-based chemotherapy. Material and Methods: We genotyped 633 polymorphisms from 105 cell cycle-related genes in 598 advanced NSCLC cases who received first-line platinum-based chemotherapy. All genotypes were analyzed for association with overall survival and evaluated for potential cumulative and gene-gene interactions that further modulated overall survival. Multiple statistic analyses were applied, including individual SNP analysis, cumulative genotype analysis, haplotype analysis, survival tree analysis and Kaplan-Meier survival analysis. Results: 65 SNPs from 40 cell-cycle genes were identified that were significantly associated with NSCLC overall survival (p&lt;0.05) individually. We found that increasing numbers of potential high-risk alleles in any cell-cycle checkpoint would lead to increased risk of death. Compared with other checkpoints, G1/S checkpoint showed more significant associations with patients’ survival. For the combined analysis of unfavorable genotypes in G1/S checkpoint, compared with the referent group (≤20 unfavorable genotypes), the HRs for patients carrying 21-23 and 24-32 unfavorable genotypes were 1.94(95%CI 1.47-2.56) and 3.00(95%CI 2.33-3.85), respectively (p for trend &lt; 0.0001), and also a significant reduction of median survival time from 24.05 to 9.18 months (log-rank p &lt; 0.0001). Heplotype analysis revealed that a TP73 haplotype (GTGTTA) was significantly associated with increased risk of death (p=0.00026). Survival tree analysis of overall cell-cycle pathway indicated G1/S checkpoint genes categorized patients into subgroups with different survival pattern. Conclusions: These results suggest that G1 and G1/S checkpoint genetic variations affect survival of advanced NSCLC patients treated with platinum-based chemotherapy and that there are gene-dosage effect and gene-gene interactions in modulating clinical outcomes.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4662.
Abstract 4664: Fast analysis and quantification of collagen fibril alignment in the tumor microenvironment in an MNU-induced model of mammary carcinogenesis
Authors: Ericson Marna E. , Gallus Nathan , Grubbs Clinton J. , Bode Ann , Lubet Ronald 
Published: February 2011

Abstract
We have developed a one-day imaging acquisition and analysis protocol to quantify orientation of the collagen fibrils at the boundary of a mammary tumor lobule in a tissue biopsy. We reported that the degree of radially-aligned collagen fibrils in the tumor-stromal interface of rodent mammary tumor tissue is an indicator of chemotherapeutic potential of the EGFr inhibitor, gefitinib (Ericson et al. 2009 In: Proc Annu Meet AACR; Abstract nr 5002).
The MNU-induced model of mammary carcinogenesis was used to develop image capture and analysis protocols. Small, 1-mm punch biopsies, were acquired from female rats with palpable (app. 250 mm2) tumor masses. Biopsy tissues were fixed and cut into 150-micron thick sections. No staining was necessary as fibrillar collagen, a hyperpolarizable structural protein, is readily detected using second harmonic generation imaging (SHG). Using this technique, the collagen fibrils can be imaged using fresh ex vivo, fixed, or paraffin-embedded tissue.
Multiple SHG images of adjacent fields of view (FOV) were acquired at 200X magnification over the entire 1-mm biopsy section. Each FOV image is a stack of 14 five-micron optical sections, acquired in the Z-plane of the sample. This is an automated process using a programmable stage allowing for fast 3D data acquisition over the entire section. We developed Photoshop and Image J plug-ins to automate the projection of the individual optical Z-stacks and subsequent image stitching of all the projections. Tumor/stromal boundaries were then identified by the operator. The angle of divergence to the tangent at the tumor interface for all fibrils was quantified. Collagen fibrils running parallel to the tangent are at zero degrees while fibrils perpendicular to the tangent are at 90 degrees. This analysis can be completed in a single day.
More perpendicular collagen orientation at the tumor/stromal interface may be indicative of a fast-growing aggressive tumor or enhanced ability of the tumor to invade surrounding tissue whereas predominant parallel collagen orientation could reflect increased encapsulation of the tumor mass which would then discourage further tumor growth or as our work has shown, the collagen orientation may serve as an indicator of responsiveness to chemotherapy. The development of an indicator/test for chemotherapeutic efficacy would be a useful tool for drug design or in creation of an individualized patient treatment plan.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4664.