bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 561: Development of a highly specific Met antibody for screening Met overexpression in NSCLC
Authors: Chen Caiwei , Lu Hsiangmin Emily , Wei Haitao , Yuan Kehu , Ma Donghui , He Wei-Wu 
Published: August 2015

Abstract
Approximately 5%-22% of non-small cell lung cancer (NSCLC) patients with secondary resistance to EGFR TKIs had evidence of amplification of the Met oncogene. This dysregulation of Met signaling was implicated in the proliferation and eventual metastasis of NSCLC, and therefore represents an attractive target for anticancer drug development.
Currently, there are a number of clinical trials for Met targeted small molecule and monoclonal antibody therapies. Immunohistochemistry (IHC) analysis of the Met protein will be very important for these Met targeted therapies and requires a highly specific antibody to prevent false positives. To develop a highly specific monoclonal antibody against Met for IHC analysis in NSCLC, we generated 97 monoclonal antibodies. IHC evaluation showed that 8 of the antibodies had suitable performance in Met positive NSCLC patient tissues. The 8 Met monoclonal antibodies were further tested on a high density protein microarray chip containing 17,000 human proteins. The microarray analysis showed that clone 3G5 was highly specific as evidenced with it only reacting with Met on the microarray. This new 3G5 Met monoclonal antibody will be a promising candidate as a diagnostic reagent for detecting Met protein in NSCLC with minimal false positives.
Citation Format: Caiwei Chen, Hsiangmin Emily Lu, Haitao Wei, Kehu Yuan, Donghui Ma, Wei-Wu He. Development of a highly specific Met antibody for screening Met overexpression in NSCLC. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 561. doi:10.1158/1538-7445.AM2015-561
Abstract 562: Alterations in chromatin remodeling pathways as a predictive biomarker of cisplatin therapy in non-small cell lung cancer
Authors: Hlavin Bell Erica , Chakraborty Arup Ratan , Mo Xiaokui Molly , Carbone David , Chakravarti Arnab 
Published: August 2015

Abstract
BRG1 (SMARCA4) and BRM (SMARCA2) are two important catalytic (ATPase) components of the mammalian chromatin remodeling complex SWI/SNF. Alterations of these components have been implicated in many cancers including lung, prostate, pancreatic, breast, and colon. Several studies have reported that both BRG1 and BRM actively participate in DNA damage repair by inducing phosphorylation of γ-H2AX, stimulating nucleotide excision repair, and also regulating interstand cross-link repair. BRG1 is frequently deleted in many primary tumors and lung cancer cell lines. Therefore, we hypothesized that reduced DNA repair capacity due to loss of BRG1 may enhance the sensitivity to DNA-damaging agents and may serve as predictive biomarkers of sensitivity for these agents. The purpose of this study was to evaluate the association between BRG1 and/or BRM alterations and the outcome of platinum-based chemoradiation in resected non-small cell lung cancer (NSCLC). Using the gene profiling of the patient tumor samples from the North American Intergroup phase III trial of adjuvant cisplatin plus vinorelbine (JBR.10), we found that patients with low BRG1 (SMARCA4) or low BRM (SMARCA2) had significantly longer overall survival (OS) if they had adjuvant chemotherapy (both p&lt;0.05, vs no-adjuvant treatment patients). Interestingly, no significant differences in the OS were observed with high SMARCA4 or high SMARCA2 expression. Collectively, this study suggests that reduced expression of SMARCA4 and SMARCA2 may serve as putative predictive biomarkers of cisplatin therapy and warrants further investigation.
This study was supported by funds from the Lung Cancer Research Foundation (to EB), the Paul P. Carbone Memorial Foundation (to EB), The Ohio State University Comprehensive Cancer Center (to AC); NIH/NCI 1U10CA180850-01(to AC); NIH/NCI 1RC2CA148190 (to AC); NIH/NCI 2K12CA133250-06 (to AC); NIH/NCI/CTEP 1R01CA169368 (to AC); NIH/NCI 1R01CA11522358 (to AC), and RTOG (to AC).
Citation Format: Erica Hlavin Bell, Arup Ratan Chakraborty, Xiaokui Molly Mo, David Carbone, Arnab Chakravarti. Alterations in chromatin remodeling pathways as a predictive biomarker of cisplatin therapy in non-small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 562. doi:10.1158/1538-7445.AM2015-562
Abstract 564: The expression of fetal oncogene 5T4 in CTCs obtained from NSCLC patients is discordant with the expression measured in the primary tumor
Authors: Pirie-Shepherd Steven R. , Deng Shibing , Golas Jonathon , Vizcarra Pamela , Tucker Eric , Marrinuci Dena , Gerber Hans-Peter , Powell Eric L. 
Published: August 2015

Abstract
The fetal oncogene 5T4 is a cell surface protein, with over-expression observed in a variety of cancers as compared to normal adult tissue. Recent studies have shown that expression of 5T4 appears to be associated with the undifferentiated state and the epithelial-mesenchymal transition (EMT), and thus has been associated with a more invasive phenotype. We have developed assays to measure the expression of the fetal oncogene, 5T4, in both the primary tumor compartment and in the circulating tumor cell compartment. These assays were then used to investigate 5T4 expression in a small cohort of patients with NSCLC. We obtained matched primary tumor and blood samples, with the blood being obtained prior to resection of the primary tumor. The expression of 5T4 was found to be robust and measurable in both the primary and circulating tumor compartments. We observed expression of 5T4 in both adenocarcinoma and squamous cell carcinoma, in all stages and grades of tumor, with no specific correlation between expression and stage, grade or pathology. We further observed robust enumeration of CTCs in NSCLC samples. The expression of 5T4 was heterogeneous in the CTC compartment with no correlation to grade, stage or pathology. Finally, we observed no concordance between 5T4 expression in the primary tumor and the circulating tumor cell compartment. We discuss the current utility of target expression in predicting response to targeted therapy in the context of antibody based therapy, and the role that CTCs may have in the clinic.
Citation Format: Steven R. Pirie-Shepherd, Shibing Deng, Jonathon Golas, Pamela Vizcarra, Eric Tucker, Dena Marrinuci, Hans-Peter Gerber, Eric L. Powell. The expression of fetal oncogene 5T4 in CTCs obtained from NSCLC patients is discordant with the expression measured in the primary tumor. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 564. doi:10.1158/1538-7445.AM2015-564
Abstract 57: Substrates of protein kinase C drive cell rac1-dependent motility
Authors: Rotenberg Susan A. , Zhao Xin , De Shatarupa 
Published: August 2015

Abstract
This laboratory has identified and/or characterized substrates of PKC that upon phosphorylation give rise to motility, an aspect of metastasis. By use of the traceable kinase method, we discovered that alpha-tubulin and Cdc42 effector protein-4 (CEP4) are PKC substrates. Phosphorylation of alpha-tubulin stimulates its incorporation into microtubules (MTs), consequently increasing the stability and prolonged growth of MTs and leading to the activation of the small GTPase Rac1. CEP4 undergoes phosphorylation by PKC that results in its release from Cdc42, whereupon CEP4 binds a guanine nucleotide exchange factor (GEF) that in turn activates Rac1 GTPase. These results imply that Rac1 acts as a node in pathways driven by phosphorylated PKC substrates. Since translocation of IQGAP to the membrane is known to be promoted by Rac1, a role is explored in non-transformed human MCF-10A cells that express a specific phospho-mimetic mutant substrate. In addition, the phospho-mimetic mutant for each substrate expressed in human metastatic MDA-MB-231 cells produces different morphologies in 3-D growth assays. This research is being supported by NIH CA125632.
Citation Format: Susan A. Rotenberg, Xin Zhao, Shatarupa De. Substrates of protein kinase C drive cell rac1-dependent motility. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 57. doi:10.1158/1538-7445.AM2015-57
Abstract 574: CD133 and LGR5 characterize stem-cell like subtype of colorectal cancer
Authors: Stanisavljevic Luka , Myklebust Mette Pernille , Dahl Olav 
Published: August 2015

Abstract
Background: Colorectal cancer (CRC) has recently been divided into six subtypes with cluster mRNA expression analysis. The subtype characterized as stem-like subtype exhibit the highest degree of stemness with poorest prognosis. Prominin-1 (CD133) and leucine-rich-repeat-containing G protein-coupled receptor (LGR5) mark cancer stem cells. High CD133 expression is associated with higher rate of metastases and disease progression. In mouse models, tumor cells expressing CD133 are enriched in chemotherapeutic-resistant colorectal cancer. LGR5+ cells characterize fast-cycling columnar-based stem cells of colon which are instrumental in neoplasia formation. Further, the LGR5+ cells are associated with metastasis formation.
Material and methods: A prospective randomized multicenter randomized trial in Norway recruited from December 1992 to October 1996. 412 colorectal cancer patients stage II and III were treated with surgery alone or 5-fluoruracil (5-FU) and levamisole (Lev) after surgical resection. The patients were followed up by routine clinical examination until five years after surgery. We constructed tissue microarrays from 409 patient samples. CD133 protein expression was assessed by mouse anti-CD133 ([clone AC133], Miltenyi Biotec, Bergisch Gladbach, Germany) at a dilution 1:10. LGR5 mRNA expression was assessed by RNAscope 2.0 HD Detection Kit-Brown (Advanced Cell Diagnostics, Hayward, CA, USA).
Results: Colon cancer stage III patients negative for CD133 had better five-year disease-free survival (DFS) when they received 5-FU/Lev (P = .016). In contrast, the patients did not respond to adjuvant therapy when CD133 was expressed (P = .500). LGR5 was a prognostic marker for colon cancer stage II (P = .045). In colon stage III, mRNA expression of LGR5 was associated with better DFS (P = .046) and patients with positive LGR5 responded to chemotherapy (P = .025). In stage II, LGR5 mRNA expression was associated with lower tumor diameter (P = .005), while in stage III there was no statistically significant association.
In conclusion, CD133 expression was associated with chemotherapy resistance in the colon stage III cohort. LGR5 was associated with a metastatic phenotype in CRC stage II and colon cancer stage III. In addition, LGR5 expression predicted response to chemotherapy in colon cancer stage III.
Citation Format: Luka Stanisavljevic, Mette Pernille Myklebust, Olav Dahl. CD133 and LGR5 characterize stem-cell like subtype of colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 574. doi:10.1158/1538-7445.AM2015-574
Abstract 575: Identification of response predictors to capecitabine/temozolomide in metastatic pancreatic neuroendocrine tumors
Authors: Strosberg Jonathan , Cives Mauro , Brelsford Marjorie , Black Michael , Meeker Alan , Ghayouri Masoumeh 
Published: August 2015

Abstract
Capecitabine and temozolomide are active in the treatment of metastatic pNETs, with response rates ranging from 30% to 70%. Several small retrospective series have suggested that MGMT deficiency may predict response to temozolomide, however expression of MGMT has not been validated as a predictive biomarker. Cytotoxic chemotherapy is thought to be most active in aggressive tumors, however the ki-67 index has not been formally evaluated as a predictive factor. It is unclear whether chromosomal instability (which correlates with alternate lengthening of telomeres) predicts response. 144 patients with pNET who underwent treatment with cape/tem were retrospectively evaluated for radiographic response. The predictive role of ki-67% and MGMT by IHC as well as ALT activation by FISH was assessed on up to 59 evaluable archival specimens. Frequently altered genes in pNETs were also sequenced and their status was correlated to the radiographic response. The ORR was 63%. Response to treatment was significantly higher in tumors with ki-67&gt;5% (n = 28) as compared to tumors with ki-67≤5% (n = 31) (ORR: 64% vs 29%; p = 0.006). MGMT status (p = 0.358) and ALT pathway activation (p = 0.174) were not predictive of response. pNETs with ki-67 &gt;5% are more likely to respond to cape/tem. MGMT status appears to have no correlation with response.
Citation Format: Jonathan Strosberg, Mauro Cives, Marjorie Brelsford, Michael Black, Alan Meeker, Masoumeh Ghayouri. Identification of response predictors to capecitabine/temozolomide in metastatic pancreatic neuroendocrine tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 575. doi:10.1158/1538-7445.AM2015-575
Abstract 577: The albumin to globulin ratio predicts chemotherapeutic outcomes in patients with unresectable metastatic CRC
Authors: Shibutani Masatsune , Maeda Kiyoshi , Nagahara Hisashi , Ohtani Hiroshi , Iseki Yasuhito , Ikeya Tetsuro , Sugano Kenji , Sakurai Katsunobu , Yamazoe Sadaaki , Kimura Kenjiro , Toyokawa Takahiro , Amano Ryosuke , Kubo Naoshi , Tanaka Hiroaki , Muguruma Kazuya , Ohira Masaichi , Hirakawa Kosei 
Published: August 2015

Abstract
Background:
Markers of the systemic inflammatory response have been recognized to correlate with prognosis in patients with various types of cancers. The pretreatment albumin to globulin ratio (AGR) has been reported to correlate with the long-term survival in patients with various cancers. However, there are no reports regarding the correlation between the pretreatment AGR and chemotherapeutic outcomes in patients with unresectable metastatic colorectal cancer. The aim of this study was to evaluate the prognostic significance of the pretreatment AGR in patients with unresectable metastatic colorectal cancer.
Methods:
A total of 66 patients with unresectable metastatic colorectal cancer who underwent palliative chemotherapy for metastatic tumors were enrolled. The AGR was calculated as follows: Albumin/(Total protein - Albumin).
Results:
The median pretreatment AGR was 1.254 (range: 0.849-1.840); we set 1.25 as the cut-off according to this value. Based on the cut-off value of 1.25, 34 patients were classified into the high-AGR group and 32 patients were classified into the low-AGR group. The high-AGR group had a significantly higher chemotherapeutic disease control rate (p = 0.040) and better progression-free survival (p = 0.0171) and overall survival (p = 0.0360) rates than the low-AGR group. Among the clinicopathological factors, the AGR was identified to be the only prognostic factor for progression-free survival (Hazard Ratio: 2.527, 95% Confidence Interval: 1.152-5.545, p = 0.021) and overall survival (Hazard Ratio: 1.946, 95% Confidence Interval: 1.033-3.668, p = 0.039).
Conclusions:
The pretreatment AGR is a useful prognostic marker in patients with unresectable metastatic colorectal cancer who receive palliative chemotherapy.
Citation Format: Masatsune Shibutani, Kiyoshi Maeda, Hisashi Nagahara, Hiroshi Ohtani, Yasuhito Iseki, Tetsuro Ikeya, Kenji Sugano, Katsunobu Sakurai, Sadaaki Yamazoe, Kenjiro Kimura, Takahiro Toyokawa, Ryosuke Amano, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira, Kosei Hirakawa. The albumin to globulin ratio predicts chemotherapeutic outcomes in patients with unresectable metastatic CRC. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 577. doi:10.1158/1538-7445.AM2015-577
Abstract 578: Molecular subgroup analysis of clinical outcomes in a phase 3 study of gemcitabine and oxaliplatin with or without erlotinib in advanced biliary tract cancer
Authors: Kim Seung T. , Park Joon 
Published: August 2015

Abstract
BACKGROUND. We previously reported that the addition of erlotinib to gemcitabine and oxaliplatin (GEMOX) resulted in greater antitumor activity and might be a treatment option for patients with biliary tract cancers. Molecular subgroup analysis of treatment outcomes in patients who had specimens available for analysis was undertaken.
METHODS. EGFR, KRAS, and PIK3CA mutations were evaluated using peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp reactions. Survival and response rates were analyzed according to the mutational status. 64 patients (48.1%) were available for mutational analysis in the chemotherapy alone group and 61 (45.1%) in the chemotherapy plus erlotinib group.
RESULTS. 1.6% (2/116) harboured an EGFR mutation (2 patients; exon 20), 9.6% (12/121) harboured a KRAS mutation (12 patients; exon 2), and 9.6% (12/118) a PIK3CA mutation (10 patients; exon 9 and 2 patients; exon 20). The addition of erlotinib to GEMOX in patients with KRAS wild type disease (n = 109) resulted in significant improvements in overall response compared with GEMOX alone (30.2% vs. 12.5%, P = 0.024). In 95 patients with both wild type KRAS and PIK3CA, there was evidence of a benefit associated with the addition of erlotinib to GEMOX with respect to response rate (RR) as compared with GEMOX alone (P = 0.04).
CONCLUSION. This study demonstrates that KRAS mutational status might be considered a predictive biomarker for the response to erlotinib in biliary tract cancers (BTCs). Additionally, the mutation status of PIK3CA may be a determinant for adding erlotinib to chemotherapy in KRAS wild type BTCs.
Keywords: KRAS, PIK3CA, Erlotinib
Citation Format: Seung T. Kim, Joon Park. Molecular subgroup analysis of clinical outcomes in a phase 3 study of gemcitabine and oxaliplatin with or without erlotinib in advanced biliary tract cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 578. doi:10.1158/1538-7445.AM2015-578
Abstract 580: hENT1 testing in pancreatic ductal adenocarcinoma: Are we ready yet? A comparative analysis of the murine and the rabbit antibodies
Authors: Cros Jerome , Marechal Raphael , Bachet Jean Baptiste , Laurent-Puig Pierre , Flejou Jean Francois , Demetter Pieter , Svrcek Magali 
Published: August 2015

Abstract
Introduction
Human equilibrative nucleoside transporter 1 (hENT1) level of expression in pancreatic adenocarcinoma (PAC) may predict survival in gemcitabine-treated patients after resection. These results have been obtained with a murine anti-hENT1 antibody (10D7G2), which is not commercially available. Another antibody, rabbit-derived (SP120), appears to have no predictive value in local, advanced or metastatic PAC. This raises the question of the equivalence of the antibodies.
Patients and Methods
Murine (10D7G2) and rabbit (SP120) monoclonal anti-hENT1 antibodies were applied on the same tissue microarrays of resected PAC. Two sets of patients from 2 separate institutions (n = 147 each) were used to compared hENT1 expression with both antibodies on two different immunochemistry automates. An additional amplification technique was performed on the second set. hENT1 expression was scored as previously reported. Results were correlated with overall survival (OS) following gemcitabine treatment.
Results
The rate of “hENT1 high” cases was lower with the SP120 clone (set 1: 7 versus 48%, set 2:11 versus 38%). With the amplification technique, the rate of “hENT1 high” cases was globally similar between both antibodies. However, the concordance between the antibodies was found in only 50% of cases. High hENT1 expression was predictive of OS with the 10D7G2 antibody (HR = 0.49; 95% CI: 0.24-0.98; P = 0.045) but not with the SP120 (HR = 1.61; 95% CI: 0.80-3.21; P = 0.18).
Conclusion
Our data suggest that the two antibodies are not equivalent. Further studies are ongoing and will be presented at the meeting: 1/ Comparative analysis of the rabbit antibody on a larger series (n = 471) with staining performed by Ventana® (Roche®), 2/ Comparative analysis of 3 additional anti-hENT1 antibody together with mRNA level correlation, 3/ Comparative expression of hENT1 in a series of matched primary tumors-metastases.
Citation Format: Jerome Cros, Raphael Marechal, Jean Baptiste Bachet, Pierre Laurent-Puig, Jean Francois Flejou, Pieter Demetter, Magali Svrcek. hENT1 testing in pancreatic ductal adenocarcinoma: Are we ready yet? A comparative analysis of the murine and the rabbit antibodies. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 580. doi:10.1158/1538-7445.AM2015-580