bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3622: Predicting response to EC145 therapy using the folate receptor-specific radiodiagnostic imaging agent, 99mTc-EC20
Authors: Leamon Christopher P. , Reddy Joseph A. , Bloomfield Alicia , Dorton Ryan , Nelson Melissa , Klein Patrick J. , Vlahov Iontcho R. , Vetzel Marilynn 
Published: August 2012

Abstract
EC145 is a potent folate-targeted Vinca alkaloid conjugate that is currently being evaluated in a global phase 3 trial for the treatment of platinum-resistant ovarian cancer. By design, response to EC145 should be dependent on folate receptor (FR) expression. Therefore, characterizing the presence and functionality of the FR in real time is critical for the selection of patients for whom FR-targeted therapy may be beneficial. A promising method that's currently being co-developed with EC145 is to image patients prior to therapy using 99mTc-EC20, which is a small molecular weight folate-targeted companion imaging agent. Similar to EC145, 99mTc-EC20 binds to the FR with high affinity (Kd ∼ 3 nM) in a manner that is both saturable and independent of the cell type. 99mTc-EC20's binding specificity has been confirmed using validated preclinical models where it was found that i) binding of 99mTc-EC20 to cells or accumulation within solid tumors is dependent on FR expression (but independent of isoform), and ii) excess folic acid can competitively block 99mTc-EC20's cell/tissue binding. Furthermore, EC145 was also found to displace pre-bound 99mTc-EC20 from FR-positive tumors and kidneys in mice, strongly suggesting that EC145 and 99mTc-EC20 distribute similarly in vivo. Taken together, these findings indicate that the FR mediates tissue uptake of 99mTc-EC20. Since 99mTc-EC20 provides a non-invasive, real-time assessment of functionally active as well as anatomically-accessible FRs, this radiodiagnostic agent may predict what tissues will accumulate and potentially respond to folate-targeted drugs, such as EC145.
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 3622. doi:1538-7445.AM2012-3622
Abstract 3623: Clinical significance of serum tumor markers in patients with esophageal cancer
Authors: Hagiwara Nobutoshi , Miyashita Masao , Nomura Tsutomu , Makino Hiroshi , Matsutani Takeshi , Yamashita Naoyuki , Akagi Ichiro , Shinozuka Eriko , Kato Shunji , Fujita Itsuro , Kanazawa Yoshiichi , Sakurazawa Nobuyuki , Onodera Hiroyuki , Uchida Eiji 
Published: August 2012

Abstract
Background: Esophageal cancer is still a disease with a high degree of fatality despite resent advances in surgical techniques and various therapies. Several serum tumor markers have been applied to diagnose and to follow-up in patients with esophageal cancer in clinical practice in Japan. The aim of this study was to investigate the diagnostic and prognostic significance of various serum tumor markers in patients with esophageal cancer. Methods: Eighty one patients with esophageal cancer were recruited for this study. Serum level of tumor markers, squamous cell carcinoma antigen(SCC-Ag), p53 antibody(p53-Ab) carcinoembryonic antigen(CEA), and CYFRA 21-1, were measured in subjects before treatment. The results of these tumor markers were compared with the clinicopathological findings of the subjects. Results: The positive rates of SCC-Ag, p53-Ab, CEA and CYFRA 21-1 were 44%, 34%, 17%, and 16% patients with esophageal cancer, respectively. SCC-Ag and p53-Ab showed positive with a relatively high frequency in cases of early stage esophageal cancer or superficial invasion, while CEA and CYFRA 21-1 could rarely be detected in such cases. Positive for SCC-Ag was significantly higher in patients with tumor invading into or through the musclaris propria than the patients within the submucosal layer. Substantially, the positive rate of SCC-Ag was associated with an advanced stage of disease. Values of p53-Ab in serum virtually demonstrated gradual decrease after treatment, not rapid depletion. All negative cases for p53-Ab before treatment showed negative at any point of treatment or follow-up on a consistent basis. CYFRA 21-1 showed positive in cases with distant metastasis. Conclusion: Each tumor marker for esophageal cancer presented different features in a clinicopathological analysis. The use of several combination of serum tumor markers seems to be most important for the detection and follow-up for of esophageal cancer at present.
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 3623. doi:1538-7445.AM2012-3623
Abstract 3626: Quantitative analysis of microRNAs by in situ hybridization reveals prognostic value of miRNAs in melanoma and breast cancer
Authors: Hanna Jason A. , Wimberly Hallie , Kumar Salil , Agarwal Seema , Rimm David L. 
Published: August 2012

Abstract
Introduction: Most miRNA measurement methods require total RNA extraction which destroys spatial information and makes standardization a challenge. In situ hybridization (ISH) however, allows the direct assessment of miRNA expression levels in tissue and importantly allows for the evaluation of expression in malignant cells as well as stromal cells. We have developed and validated a novel method for the quantitative analysis of miRNA expression by ISH on formalin fixed paraffin embedded tissue microarrays (TMAs) using miR-21, miR-92a, miR-34a, miR-221, miR-205, and Let-7a. Methods: In order to quantitatively measure miRNA expression by ISH, DIG labeled LNA modified miRNA probes were employed and multiplexed with DAPI and cytokeratin or S100/GP100 immunofluorescence to apply the AQUA technology. This co-localization based, quantitative approach allows for the measurement of miRNA expression in subcellular compartments. The assay allows standardization of miRNA measurement and potential for rapid large cohort assessment. We also assessed protein targets of each miRNA by AQUA to investigate the hypothesized inverse relationship between miRNAs and target proteins. Results: In hundreds of tissue samples a broad dynamic range and a variable expression pattern specific to each miRNA was observed. Specificity of the assay was validated with anti-miR and miRNA mimic transfected cell lines, miR-21 knock out mouse tissue, and blocking oligo experiments. The assays were performed on near serial sections and were found to have high reproducibility with R*2&gt;0.8. miR-221 and miR-205 were found to be prognostic in breast cancer and melanoma respectively (p&lt;0.05). Finally, the inverse relationship between miRNAs and putative targets were not seen in the large population cohorts. Conclusions: This specific and reproducible method for the quantitative analysis of miRNA expression provides proof of concept for the use of miRNAs as tissue biomarkers using quantitative ISH. Future studies will further determine the prognostic value of miR-221 and miR-205, and the relationship between miRNAs and target protein expression.
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 3626. doi:1538-7445.AM2012-3626
Abstract 3630: Non-enrichment based method for analysis of androgen receptor expression in circulating tumor cells (CTCs) in patients with metastatic castrate resistant prostate cancer
Authors: Gross Mitchell E. , Lazar Daniel C. , Cho Edward H. , Luttgen Madelyn , Uson Maria L. , Kuhn Peter , Torrey Melissa L. 
Published: August 2012

Abstract
Background: We have established a fluid phase biopsy approach that identifies CTCs which preserves cytologic features in high-definition (HD) for diagnostic pathology without using immune or surface receptor-based enrichment. HD-CTCs identified with this approach can be used for enumeration and molecular characterization. Methods: Blood was collected from metastatic prostate cancer patients and normal donors in Cyto-Chex® tubes (Streck, Omaha, NE) as part of IRB approved protocols at each site. Following erythrocyte lysis, 3 million nucleated cells were deposited on a glass slide. Samples were incubated with a pan-cytokeratin (CK), CD45, and androgen receptor (AR) antibodies and counter-stained with DAPI. LNCaP cells were spiked into normal blood. Images were obtained with a fluorescent scanning microscope and analyzed with a computer algorithm. Candidate HD-CTCs were subsequently verified by expert readers. Slides were re-imaged for quantitative analysis using at a fixed exposure and gain. Results: A total of 227 CTCs from ten patients were compared to 20 LNCaP cells. The median (range) HD-CTCs in this cohort was: 9 (1-62) cells/ml. The mean ± standard deviation measurements in HD-CTCs were observed: CK intensity 60.4±154; total cell area 89.0 ± 53.8 μm2; nuclear area 61.1 ± 36.0 μm2. LNCaP cells spiked into normal blood gave the following values: CK intensity 1166+/−306; total cell area 143 ± 48.1 μm2; nuclear area 63.1 ± 18.6 μm2. CTCs were additionally classified as either AR positive (AR+) or AR negative (AR-). 37 of the 227 (16.3%) HD-CTCs were AR+. The average CK intensity was significantly higher in AR+ versus AR- cells at 174.23 and 39.86, respectively (p&lt;0.001). The AR expression intensity in AR+ HD-CTCs and LNCaP cells was comparable at 979.4 and 902.2, respectively (p=0.824). Conclusions: We find a positive association between AR and CK expression on a per cell basis. Further, we find AR is expressed at comparable levels in CTCs from patients and human prostate cancer cells in culture. The HD-CTC based approach may be used for enumeration and molecular interrogation of CTCs in patients with prostate cancer.
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 3630. doi:1538-7445.AM2012-3630
Abstract 3633: Prognostic value of chromogranin A and alkaline phosphatase in patients with advanced neuroendocrine tumor
Authors: Ter-Minassian Monica , Chan Jennifer A. , Hooshmand Susanne M. , Brais Lauren K. , Daskalova Anastassia , Heafield Rachel , Qian Zhiron , Lin Xihong , Christiani David C. , Kulke Matthew H. 
Published: August 2012

Abstract
BACKGROUND: Serum chromogranin A (CgA) or alkaline phosphatase (ALP) are often assessed in patients with advanced neuroendocrine tumor (NET) patients but their prognostic significance continues to be debated. We evaluated whether elevated CgA or ALP levels were associated with shorter survival in a large, prospectively collected cohort of NET patients. METHODS: We identified patients with metastatic NET enrolled in an institutional database between 2003-10. We used the single measurement of serum CgA or ALP levels collected with shortest time after metastatic diagnosis and classified them as binary variables (elevated/normal) based on clinical laboratory specification of elevated value. Elevated biomarker levels were correlated with overall survival using the log-rank test. Hazard ratios for each biomarker were calculated using multivariate Cox regression, adjusting for baseline characteristics of age, gender, tumor histology, and tumor subtype. Each biomarker was modeled as a time-varying covariate to account for variability in time from initial metastatic diagnosis to time of biomarker test. RESULTS: We identified 526 patients who presented at our institution with metastatic NET. Of these, 349 had available CgA values and 350 had available ALP values. There were 146 and 153 deaths among those tested for CgA and ALP, respectively. The median survival time from time of metastatic diagnosis (yrs, (95%CI)) for patients with elevated CgA was 5.98 (5.04, 7.3), as compared to 13.27 (9.51, -) for those at normal CgA limits (p&lt;0.0001). The median survival time from time of metastatic diagnosis (yrs, (95%CI)) for patients with elevated ALP was 4.51 (3.27, 5.93), as compared to 8.87 (7.07, 9.64) for those at normal ALP levels (p=0.0001). Using the adjusted time-varying model, either elevated CgA (aHR 3.97 (2.73, 5.75) p=3.15E-13) or elevated ALP (aHR 2.4 (1.7, 3.4) p=7.96E-07) were adverse prognostic factors for patients with advanced NET. Elevated CgA was significantly associated with shorter survival in all NET subgroups (pancreatic NET, carcinoid, other NET). Elevated ALP was also a predictor of shorter survival in advanced NET patients, with the exception of those with advanced pancreatic NET. CONCLUSION: Elevated serum CgA or elevated ALP is an independent adverse prognostic factor in patients with advanced NET.
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 3633. doi:1538-7445.AM2012-3633
Abstract 3641: The predictive and prognostic roles of DNA damage response genes in epithelial ovarian cancer
Authors: Alkema Nicolette G. , Everts Marieke , van der Zee Ate G.J. , Hoor Klaske A. ten , Hollema Harry , de Jong Steven , van Vugt Marcel A.T.M. , Wisman Bea G.B.A. 
Published: August 2012

Abstract
Background: Despite platinum-based chemotherapy, 5-year survival of advanced stage ovarian cancer patients is only 15-30%. Exposure to platinum-based chemotherapeutics induces double strand DNA breaks (DSBs) and subsequently leads to activation of the DNA damage response (DDR). Therefore inhibition of components of the DDR may lead to better response to therapy. Aim of this study was to investigate in a large series of ovarian cancer patients the predictive and prognostic role of the activation status of four DDR-proteins- ATM, a key controller in the DDR, and three ATM substrates, including Chk2, 53BP1 and γ-H2AX, of which the latter is a direct readout for DNA damage. Methods: Expression of phospho-ATM, Chk2, phospho-Chk2, 53BP1, phospho-53BP1 and γ-H2AX was immunohistochemically assessed in 309 patients with chemo-naive ovarian cancer. Expression levels were related to clinicopathological characteristics and survival. Response to platinum-based chemotherapy was analyzed by defining two populations with either an optimal therapy response or a very poor therapy response. Both groups consisted of patients with advanced stage ovarian cancer, &gt;2 cm residual disease after primary surgery and were all treated with platinum-based chemotherapy. The responder group had a well-defined PFS of more than 18 months while the non-responder group had a PFS of less than 6 months. Results: In the two well-defined groups with the largest contrast regarding response to treatment, positive γ-H2AX expression (OR=0.193; p=0.036) and positive Chk2 expression (OR=0.149; p=0.011) were related to a good response to platinum-based chemotherapy. In advanced stage patients, phospho-53BP1 expression was independently related to a worse disease-specific survival (HR=1.905; p= 0.044). Conclusion: High DDR protein expression in advanced stage ovarian cancers suggests a high degree of genomic instability, while the negative prognostic impact of phospho-53BP1 may be due to enhanced repair capacity of chemotherapy-induced DSBs on the long term.
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 3641. doi:1538-7445.AM2012-3641
Abstract 3644: The PSP94αprostasin pathway and early detection of ovarian cancer
Authors: Guo Yi , Yan Bingxue , Mueller Michael D. , Yu Jing Jie 
Published: August 2012

Abstract
Objective: Our long-term goal is to better understand the mechanism of tumor development in human epithelial ovarian cancer. The short-term goal is to identify a biomarker for early detection of this malignancy. Methods: qPCR was performed for PSP94 expression using SYBR® Green reagents kit in 3 pairs of tumor and normal samples of ovarian cancer patients and 4 ovarian cancer cell lines on ABI 7500 Fast Real-Time PCR System. Overexpression of PSP94 or prostasin by cDNA transfection was performed in ovarian cancer cell lines. The expression levels of PSP94 and prostasin after cDNA transfection were determined by western blot analysis. Results: In gene expression analysis by qPCR, we found that PSP94 expresses in tumor tissues of ovarian cancer patients and cancer cell lines but not in normal ovarian specimens. Our investigation of the relationship between PSP94 and prostasin by cDNA transfection assay demonstrated that expression of prostasin was increased in the PSP94 overexpressed cells. In contrast, PSP94 expression did not change in the prostasin-forced-expression cells. This suggests that the two genes most likely share part of a regulation network and that PSP94 appears to be an upstream regulator of prostasin. Conclusions: We conclude that PSP94 expression occurs only in tumor samples and PSP94 and prostasin share a signaling pathway. We hypothesize that alteration of PSP94-prostasin pathway may be an early event in the development of epithelial ovarian cancer; PSP94 appears to be an upstream regulator that modulates prostasin expression. Thus, PSP94 seems to play an important role in tumorigenesis and may hold great promise as a biomarker for early detection of human epithelial ovarian cancer.
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 3644. doi:1538-7445.AM2012-3644
Abstract 3647: Integrin β5 as a new target in ovarian cancer treatment
Authors: Ohyagi Chifumi , Sawada Kenjiro , Kinose Yasuto , Tomita Yasuhiko , Morishige Ken-ichirou , Kamiura Shoji , Kimura Tadashi 
Published: August 2012

Abstract
[Background] Ovarian cancer is a highly metastatic characterized by widespread peritoneal dissemination andascites, and is the leading cause of death from gynecological malignancies. Previously, we identified integrin β5 as a key molecule for peritoneal dissemination. In this study, we aimed to determine the predictivevalue of integrin β5 in Japanese ovarian cancer patients.[Methods] Ovarian carcinoma samples were collected from 148 patients who were treated at Osaka Medical Center for Cancer and Cardiovascular Disease (Osaka, Japan) between 2000 and 2005 and were subject to the tissue microarray (TMA) slides. Satisfactory spots and clinical data were obtained from 114patients. The slides were stained with an antibody against human integrin β5 and each sample was scored based on the percentage of positive cells (0, α10%;1, 10-25%; 2, 25-50%; 3, Δ50%) and the intensity of the staining (0, none; 1, very weak; 2, weak; 3, strong). Overexpression was defined if the total scoreof density and intensity is Δ5. “Low” expression was defined if the total score of density and intensity scores was α4. Survivalestimates were computed using the Kaplan-Meier method, and comparisons between groups were analyzed using the log-rank test.[Results] Of 114 patients, 33(29.8%) had integrin β5 overexpression, including 6 of 30 serous (20.0%), 1 of 12 mucinous (8.3%), 1of 13 endometrioid (7.7%), 13 of 17 clear cell (75.6%), 7 of 26 low potential malignant (26.9%) and 5 of 18 others (27.8%) ovarian carcinomas. Among patients with advanced stages (stage lll/lV), those who had integrin β5 overexpression showed significantly worse overall survival than those who had low expression (11.2 months vs 40.0months, P=0.05).[Conclusion] Integrin β5 overexpression was seen in most of clear cell carcinoma, which is extremely resistantto the current chemotherapies. Besides, in advanced ovarian cancer patients, integrin β5 was an independent prognostic maker. These datasuggested that targeting this integrin could be a promising treatment option, at least, for a subset of ovarian cancer such as clear cell carcinoma and needs to be explored for future clinical application.
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 3647. doi:1538-7445.AM2012-3647
Abstract 3653: Cancerous inhibitor of PP2A (CIP2A) expression for bladder cancer diagnostics
Authors: Huang Lisa P. , Adelson Martin , Mordechai Eli , Trama Jason 
Published: August 2012

Abstract
Bladder cancer is one of the most common cancers in the United States. In 2011, the National Cancer Institute estimates approximately 70,000 cases of bladder cancer will be diagnosed; of those, more than 15,000 are expected to die. According to the American Cancer Society, the five-year survival rate for patients diagnosed with bladder cancer is 98% (at stage 0), 88% (at stage I), 63% (at stage II), 46% (at stage III), and 15% (at stage IV). These statistics highlight the fact that early detection of bladder cancer is critical for improving prognosis and long-term survival. Numerous markers have been tested for bladder cancer detection and surveillance. These markers include complement factor H (BTA-Stat/TRAK), nuclear matrix proteins (NMP22), mucin-like antigens, hyaluronic acid, hyaluronidase, survivin, soluble Fas, telomerase and detection of chromosomal aneuploidy and deletion using fluorescence in situ hybridization (UroVysion®). However, none of them are accepted as a routine tool for bladder cancer diagnostics and surveillance. There exists a continuing need for an assay that detects the presence of bladder cancer in humans. It would be advantageous to develop an assay with a protein that is associated with the development of bladder cancer. We sought to identify cancerous inhibitor of PP2A (CIP2A) as a novel bladder cancer biomarker. In this study, Western blot and ELISA were used to access the level of CIP2A protein and other known bladder cancer protein biomarkers (i.e., survivin) in bladder cancer cell lines, bladder cancer patient tissues, and bladder cancer patient urines. Our studies indicate CIP2A protein was abundantly expressed in bladder cancer cell lines and it was not expressed in non-tumor epithelial cell lines. CIP2A protein was specifically expressed in bladder tumor tissue at different cancer stages, and not in adjacent non-tumor bladder tissue. Our data showed that CIP2A protein detection in bladder cancer tissues had a sensitivity of 75% and specificity of 100%. Our study also suggests there was no detectable level of CIP2A protein in bladder cancer patient urine, in contrast to that of other bladder cancer biomarkers such as survivin. In conclusion, our studies suggest that CIP2A protein is specifically expressed in human bladder cancer tissue and not in adjacent tissue. It will be important to extend this finding and to develop non-invasive assays for early detection or for surveillance of bladder cancer in humans.
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 3653. doi:1538-7445.AM2012-3653