bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2767: Identification of kinase fusion genes in bladder cancer through kinome-centered RNA sequencing
Authors: Groenendijk Floris , Rink Iris de , Mertens Laura , Broeks Annegien , Neuzillet Yann , Jong Jeroen de , Rhijn Bas van , Bernards Rene , Heijden Michiel van der 
Published: May 2015

Abstract
Urothelial carcinoma (UC) of the bladder is one of the most common cancers worldwide. The treatment of patients with metastatic or locally advanced UC consists of platinum-based chemotherapy. Unfortunately, a large number of patients will ultimately develop resistance. Therapeutic options at that point are very limited: the last FDA drug approval for the treatment of bladder cancer dates back more than 2 decades. Identification of activated signaling pathways in UC can provide new targets for treatment. Recent DNA and RNA sequencing projects in invasive UC have revealed somatic mutations in several cancer genes. Some of these mutated genes, such as FGFR3 and PIK3CA, could potentially guide therapy. However, our knowledge of gene rearrangements in bladder cancer remains limited. These fusion genes often involve multiple fusion partners, as was reported for FGFR3 fusions in bladder cancer, which represents a significant challenge for discovery and for subsequent diagnostic screening. Therefore, a global detection method is needed to fully understand the diversity of alterations driving this disease. We used a high-throughput platform to systematically profile kinase fusions through specific enrichment of kinase transcripts. Using this approach, we screened 80 muscle invasive UC specimens and identified a number of activating mutations and novel fusion transcripts. The fusion genes identified in this discovery set will be validated in a second cohort of UC specimens to determine their frequency. Functional validation will be presented for some of these fusion genes. These genetic alterations may provide new avenues for individualized molecular treatment of UC patients.
Citation Format: Floris Groenendijk, Iris de Rink, Laura Mertens, Annegien Broeks, Yann Neuzillet, Jeroen de Jong, Bas van Rhijn, Rene Bernards, Michiel van der Heijden. Identification of kinase fusion genes in bladder cancer through kinome-centered RNA sequencing. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2767. doi:10.1158/1538-7445.AM2014-2767
Abstract 2769: PKC/MARCKS pathway is a novel therapeutic target associated with breast cancer malignancy potential and paclitaxel resistance
Authors: Chen Ching-Hsien , Arif Muhammad , Chang Wen-Hsin , Yuan Yuan , Zhai Jing , Ann David K. , Wu Reen 
Published: May 2015

Abstract
Increasing evidence had suggested important roles of protein kinase C (PKC)-mediated phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) in modulating various cellular processes, including cancer cell growth and metastasis. However, there is a lack of information regarding to the roles of MARCKS and its pSer 159/163 phosphorylated product in breast cancer cells and tissues. To tackle this concern, we recently initiated both immunohistochemical and western blot analyses on a series of clinical specimens and several breast cancer cell lines. We have observed a significant elevation of phospho-MARCKS associated with advanced-stage breast cancer tissues as compared with benign ones, particularly in triple-negative breast cancer (TNBC) tissues and cell lines. Knockdown of MARCKS expression resulted in suppressions of lamellipodia/filopodia formation and migration/invasion as well as down-regulation of Src activity in these TNBC cell lines. Of note, MARCKS-silenced TNBC cells grew much more slowly and more sensitive to paclitaxel than the control and parental cells. Treatment with paclitaxel was shown to induce MARCKS phosphorylation in a dose-dependent manner, which may be related to an enhanced paclitaxel resistance in some of TNBC cells. However, PKC inhibitors were able to abrogate paclitaxel-induced MARCKS phosphorylation. Consistent with this potential, treatments of TNBC cells with a MARCKS N-terminus sequence peptide, namely MANS, to down regulate PKC/MARCKS pathway not only attenuated the associated aggressive phenotype but also synergistically enhanced paclitaxel-induced cytotoxicity in vitro and in vivo. These results demonstrate an association of PKC-mediated MARCKS phosphorylation with breast cancer malignancy potential and MARCKS phosphorylation as a predictor of paclitaxel resistance in TNBC cells. It is suggestive that an inhibition of PKC/MARCKS pathway may serve as an alternative therapeutic strategy for enhancing efficacy of chemotherapy.
Citation Format: Ching-Hsien Chen, Muhammad Arif, Wen-Hsin Chang, Yuan Yuan, Jing Zhai, David K. Ann, Reen Wu. PKC/MARCKS pathway is a novel therapeutic target associated with breast cancer malignancy potential and paclitaxel resistance. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2769. doi:10.1158/1538-7445.AM2014-2769
Abstract 2772: Ceramide analog sensitizes breast cancer cells to Fas-mediated apoptosis to suppress spontaneous lung metastasis
Authors: Li Xia , Paschall Amy V. , Bai Aiping , Bielawski Jacek , Bielawska Alicja , Liu Kebin 
Published: May 2015

Abstract
Fas is a member of the TNF death receptor superfamily. Despite other “non-apoptotic” cellular responses emanating from its signaling, the major and best known function of Fas is apoptosis. To avoid apoptosis, cancer cells, including breast cancer cells, tend to down-regulate Fas expression or alter the expression of key mediators of the Fas-mediated apoptosis signaling pathway to advance the disease. Therefore, therapeutic intervention of tumor cell resistance to Fas-mediated apoptosis potentially represents an effective approach to render tumor cell sensitivity to FasL+ cytotoxic T lymphocytes (CTL) of the host immunosurveillance system or to CTL-based adoptive cancer immunotherapy to suppress tumor progression. We report here that sublethal doses of ceramide analog LCL85 effectively overcome metastatic human breast cancer cells to FasL-induced apoptosis in vitro. Although it has been shown that ceramide targets the Bcl-2 family proteins to induce tumor cell apoptosis, we observed that LCL85 does not alter Bak, Bax, Bcl-2 and Bcl-xL protein levels in metastatic human breast cancer cells. Instead, we determined that LCL85 dramatically decreased cIAP1 and xIAP protein levels in the metastatic human breast cancer cells. Consistent with its apoptosis sensitization activity, subtoxic doses of LCL85 suppressed primary breast cancer growth. More importantly, subtoxic doses of LCL85 effectively suppressed spontaneous lung metastasis in an orthotopic breast cancer mouse model. Furthermore, LCL85 exhibited no significant liver toxicity in vivo at the effective doses. Our data thus suggest that LCL85, although effective as a single agent in suppression of tumor development at high doses, might be more valuable if used at a sublethal dose as a sensitizer for enhancing the efficacy of FasL-based cancer therapy, particularly CTL-based cancer immunotherapy.
Note: This abstract was not presented at the meeting.
Citation Format: Xia Li, Amy V. Paschall, Aiping Bai, Jacek Bielawski, Alicja Bielawska, Kebin Liu. Ceramide analog sensitizes breast cancer cells to Fas-mediated apoptosis to suppress spontaneous lung metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2772. doi:10.1158/1538-7445.AM2014-2772
Abstract 2783: Variability of HER2 expression between in vitro and in vivo models within gastric cancer cell lines
Authors: Gim Youme , Park Hee Seo , Jung Hae Rim , Chang Hae Ryung , Nam Seungyoon , Choi Yong Doo , Ku Ja-Lok , Kim Yon Hui 
Published: May 2015

Abstract
In the process of developing individualized cancer therapeutics, tumor derived cell line based preclinical (in vitro and in vivo) methods have been widely used. Patient derived genome analysis revealed significant cancer biomarkers for targeted drug development. Classic cancer biomarker, HER2, overexpression was discovered as a cancer biomarker and as a druggable target in breast cancer, which lead to the development of Trastuzumab. HER2 is overexpressed in 10-25% of gastric cancer, and treatment with Trastuzumab showed positive yet limited activity in advanced gastric cancer treatment in the ToGA study. These results present HER2 as an attractive target for gastric cancer. However, Gillet and colleagues reported the challenges in the use of in vitro and in vivo studies for drug validation and development. They reported variance in gene expression patterns between the in vitro and in vivo context within a single cancer cell line. In our study using gastric cancer derived cell lines, we observed differences in HER2 expression between in vitro and in vivo xenograft model. Also, we show the potential promising in vivo xenograft model in the development of HER2 targeting agents for gastric cancer.
Eleven out of 25 gastric cancer cell lines showed HER2 expression, which was demonstrated using the IHC assay on a cell microarray. Sixteen out of 25 cell lines successfully produced xenograft models. Gastric cancer cell lines (SNU-5, SNU-16, SNU-638, SNU-1967, MKN-1, MKN-28, and NUGC-3) that had no HER2 expression when cultured in vitro showed HER2 expression in vivo. Two cell lines (NCC-19 and NCI-N87) that had HER2 expression in vitro showed a decrease in HER2 expression in vivo. Three cell lines (SNU-484, SNU-668, and SNU-719) showed various levels of increase in HER2 expression. Two cell lines showed minor to no changes in HER2 expression. NUGC-4 had consistent significant HER2 expression levels in both assays, while MKN-45 had consistent insignificant to no HER2 expression. Our study demonstrates inconsistency in HER2 gene expression between in vitro and in vivo cancer cell line models for the first time in gastric cancer.
Citation Format: Youme Gim, Hee Seo Park, Hae Rim Jung, Hae Ryung Chang, Seungyoon Nam, Yong Doo Choi, Ja-Lok Ku, Yon Hui Kim. Variability of HER2 expression between in vitro and in vivo models within gastric cancer cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2783. doi:10.1158/1538-7445.AM2014-2783
Abstract 2799: Adoptive immunotherapy for pediatric solid tumors with CAR-T cells (chimeric antigen receptor bearing T cells) targeting ALK (anaplastic lymphoma kinase, CD246)
Authors: Walker Alec , Lopomo Paola , Babbitt William , Vigny Marc , Mackall Crystal L. , Orentas Rimas J. 
Published: May 2015

Abstract
Neuroblastoma is the most common non-CNS tumor in children. High-risk disease has a dire prognosis and new treatment strategies are need. The identification of unique cell-surface proteins expressed on tumor cells, yet not expressed on normal tissues, has been challenging for pediatric malignancies. However, identification of such antigens allows for the development of new immune-based therapies featuring Ig-like binding motifs. The cell surface tyrosine kinase ALK (CD246, anaplastic lymphoma kinase) is a promising target for neuroblastoma in that it is expressed in either native, mutated, or over-expressed forms on the plasma membrane surface of the tumor cell and may contribute to disease progression or severity. We identified antibodies that bind to extracellular domains of ALK, sequenced their variable regions, and used this sequence information to construct chimeric antigen receptors (CARs). Primary human T lymphocytes were then transduced with retroviral gene vectors expressing a series of ALK-specific CAR. We tested CARs that incorporated both different structural and signaling motifs. Transduced T cells demonstrated ALK-specific cytolytic activity against ALK-expressing tumors and produced Th1 cytokines upon culture in the presence of tumor. In exploring different iterations of CAR domain structure we found that the scFv domains created from the heavy and light variable domains of ALK-specific immunoglobulin could be interchanged with respect to their orientation in the context of CAR tertiary protein structure. Moreover, ALK-specific scFv functioned whether expressed in a short format, that is as a single domain proximal to the T cell membrane, or in a long format, that is extended away from the plasma membrane using an IgG1-derived spacer domain composed of CH2 and CH3. Using a xenogeneic NSG mouse model for neuroblastoma, human ALK-specific CAR-expressing T cells were found to eradicate ALK-positive tumor, when IL-7 was included to support T cell persistence. These data argue for the continued evaluation of ALK-specific CARs in pre-clinical studies.
Citation Format: Alec Walker, Paola Lopomo, William Babbitt, Marc Vigny, Crystal L. Mackall, Rimas J. Orentas. Adoptive immunotherapy for pediatric solid tumors with CAR-T cells (chimeric antigen receptor bearing T cells) targeting ALK (anaplastic lymphoma kinase, CD246). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2799. doi:10.1158/1538-7445.AM2014-2799
Abstract 280: Cancer risk in World Trade Center rescue and recovery workers
Authors: Boffetta Paolo , Solan Samara , Wallenstein Sylvan , Lucchini Roberto , Landrigan Philip 
Published: May 2015

Abstract
Objective: The purpose of this investigation was to evaluate cancer incidence in responders during the first 7 years after 11 September 2001.
Methods: Cancers among 20,984 consented participants in the WTC Health Program were identified through linkage to state tumor registries in New York, New Jersey, Connecticut, and Pennsylvania. The follow-up lasted until 2008. Standardized incidence ratios (SIRs) were calculated to compare cancers diagnosed in responders to predicted numbers for the general population. Multivariate regression models were used to estimate associations with degree of exposure.
Results: A total of 575 cancers were diagnosed in 552 individuals. Increases above registry-based expectations were noted for all cancer sites combined (SIR = 1.15; 95% CI: 1.06, 1.25), thyroid cancer (SIR = 2.39; 95% CI: 1.70, 3.27), prostate cancer (SIR = 1.21; 95% CI: 1.01, 1.44), combined hematopoietic and lymphoid cancers (SIR = 1.36; 95% CI: 1.07, 1.71), and soft tissue cancers (SIR = 2.26; 95% CI: 1.13, 4.05). When restricted to 302 cancers diagnosed ≥ 6 months after enrollment, the SIR for all cancers decreased to 1.06 (95% CI: 0.94, 1.18), but thyroid and prostate cancer diagnoses remained greater than expected. All cancers combined were increased in very highly exposed responders and among those exposed to significant amounts of dust, compared with responders who reported lower levels of exposure.
Conclusion: Estimates should be interpreted with caution given the short follow-up and long latency period for most cancers, the intensive medical surveillance of this cohort, and the small numbers of cancers at specific sites. However, our findings highlight the need for continued follow-up and surveillance of WTC responders. The follow-up of the cohort is currently being updated and efforts are being made to improve the assessment of exposure to carcinogens related to WTC experience.
Citation Format: Paolo Boffetta, Samara Solan, Sylvan Wallenstein, Roberto Lucchini, Philip Landrigan. Cancer risk in World Trade Center rescue and recovery workers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 280. doi:10.1158/1538-7445.AM2014-280
Abstract 2824: Circulating tumor cells (CTCs) can predict survival and response to treatment in non-metastatic colorectal cancer (CRC): Correlation between flowcytometry, quantitative real-time pcr (qPCR) and cytomorphology
Authors: Bahnassy Abeer , Zekri Abdel-Rahman N. , Salem Salem E. , Mohamad Marwa , Mohanad Marwa 
Published: May 2015

Abstract
Background: Circulating tumor cells (CTCs) were detected in patients with metastatic epithelial malignancies using different methodologies. The number of CTCs before and during treatment of advanced CRC is an independent predictor of poor response to treatment, progression-free (PFS) and overall survival (OS). We investigated 1) whether CTC count can predict outcome in patients with CRC and 2) the utility of FCM supplemented with PCR and/or cyto-morphology (CM) in enumerating CTCs.
Methodology: CTCs were enumerated in 56 CRC cases and 20 normal controls (NC) by flowcytometry (FCM), and quantitative real time PCR (qPCR) using CK19, MUC, CD44, CD133 and ALDH1after immune-magnetic separation. Results were correlated to cytomorphology, standard prognostic factors, overall and progression free survival (OS&PFS).
Results: CTCs &lt; 3 were detected in 45% of the cases compared to 55% with ≥3 CTCs. CK19, MUC1, CD44, CD133 and ALDH1-RNA expression was detected in (55.4%, 44.6%, 53.6%, 43.6%, 46.4%; respectively). The concordance between FCM& qPCR, FCM&CM, qPCR& CM ranged from 82% to 96%. Significant correlations were reported between CTCs and tumor stage and grade (p&lt;0.01). OS was significantly associated with pathological tumor type, T stage, lymph nodes involvement, CTC, CK, MUC1, CD44 and CD133. PFS was significantly associated with pathological tumor type, disease stage, N stage, CTC, CK, MUC1, CD44 and CD133 (p=).
Conclusions:1)enumeration of CTCs, pre- and after initial treatment, can predict outcome in CRC patients, 2)FCM is a sensitive, rapid and easy technique for enumeration of CTCs, especially if supplemented with qPCR for detection of CRC cells biomarkers (CK19), MUC, CD44, CD133 and ALDH1).
Citation Format: Abeer Bahnassy, Abdel-Rahman N. Zekri, Salem E. Salem, Marwa Mohamad, Marwa Mohanad. Circulating tumor cells (CTCs) can predict survival and response to treatment in non-metastatic colorectal cancer (CRC): Correlation between flowcytometry, quantitative real-time pcr (qPCR) and cytomorphology. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2824. doi:10.1158/1538-7445.AM2014-2824
Abstract 2848: Urinary prostaglandin E metabolite as a biomarker predicting response to EGFR therapy in patients with head and neck cancer
Authors: Kekatpure Vikram D. , Suresh Amritha , Rangarajan Bharath , Siddappa Gangotri , Kuriakose Moni Abraham 
Published: May 2015

Abstract
Background: Cross talk between the epidermal growth factor receptor (EGFR) and prostaglandin E2 pathways (PGE2) is well established. Activation of EGFR signaling can induce PGE2. Urinary PGE-M is a stable end metabolite of PGE2. The purpose of this study was to evaluate the role of urinary PGE-M as a biomarker predicting response to anti-EGFR monoclonal antibody therapy in patients with head and neck squamous cell carcinoma (HNSCC).
Patients and Methods: Ten HNSCC patients with recurrent and/or metastatic disease received Nimotuzumab, a humanized monoclonal antibody against EGFR. The response to Nimotuzumab was assessed 2 weeks following the fourth cycle using PERCIST criteria. Urine samples were collected before treatment and 2 weeks after the fourth cycle of therapy.
Results: Seven patients had progressive disease (PD) while two patients had stable disease (SD) and one patient had a partial response (PR) to therapy. The mean pretreatment value of urinary PGE-M in patients with SD or PR was 63 ng/mg Cr (range 48-78 ng/mg Cr). By comparison, patients with progressive disease had lower baseline levels of urinary PGE-M with mean pretreatment value of 37ng/mg Cr (range 15- 54ng/mg Cr). More than a 20% reduction in post treatment vs. pretreatment urinary PGE-M values was seen in patients with SD and PR. By comparison, patients with progressive disease had either a minimal reduction or an increase in the post treatment levels of urinary PGE-M.
Conclusion: Elevated pretreatment levels of urinary PGE-M may predict response to anti-EGFR therapy in patients with HNSCC. These findings need further validation.
Citation Format: Vikram D. Kekatpure, Amritha Suresh, Bharath Rangarajan, Gangotri Siddappa, Moni Abraham Kuriakose. Urinary prostaglandin E metabolite as a biomarker predicting response to EGFR therapy in patients with head and neck cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2848. doi:10.1158/1538-7445.AM2014-2848
Abstract 2857: S100A14 plays an important role in cell growth and metastasis of epithelial ovarian cancer through PI3K-AKT pathway
Authors: Cho Hanbyoul , Lee Maria , Shin Ha-Yeon , Yang Wookyeom , Lee Eun-ju , Kwon Hyunja , Kim Sol , Kim Jae-Hoon 
Published: May 2015

Abstract
Background: S100A14 is an EF-hand containing calcium protein of the S100 protein family that exerts its biological effects on different types of cancers. The roles of S100A14 in tumorigenesis and its underlying mechanism have not been fully understood. This study aims to investigate the clinical significance and possible mechanisms of action of S100A14 in the growth and metastasis of epithelial ovarian cancer (EOC).
Method: S100A14 expression in ovarian cancer was studied using a total of 104 ovarian tissue specimens (13 normal ovarian tissues, 10 benign ovarian tumors, 10 borderline ovarian tumors, and 71 EOC tissues) via immunohistochemistry. We investigated the possible functions of S100A14 in EOC stable cell by lentivirus-mediated overexpression and short hairpin RNA (shRNA).
Results: S100A14 protein was significantly over-expressed in EOC cells and tissues. S100A14 expression was significantly associated with advanced stage (P&lt;0.001), serous type (P=0.004), and poor tumor grade (P&lt;0.001). Patients with S100A14 overexpression had shorter overall (Hazard Ratio = 4.53 [1.16-17.69], P=0.029) and disease-free survival (Hazard Ratio = 3.10 [1.22-7.89], P=0.017) in multivariate analysis. In vitro analysis of cell function revealed that cell proliferation, migration and invasion were regulated by S100A14. We investigated the underlying mechanism and found that the phosphorylation levels of AKT have increased after S100A14 overexpression. Inhibition of AKT by a specific AKT inhibitor (MK-2206) and PI3K inhibitor (wortmannin) at least partly reversed the AKT-phosphorylation events in S100A14-overexpressed cells.
Conclusions: The data revealed the aberrant expression of S100A14 in ovarian cancer, suggesting a potentially important role of S100A14 in ovarian carcinogenesis; S100A14 regulated AKT via phosphorylation of its ser473 site also implies that S100A14 could be used as a novel therapeutic target for ovarian cancer treatment.
Citation Format: Hanbyoul Cho, Maria Lee, Ha-Yeon Shin, Wookyeom Yang, Eun-ju Lee, Hyunja Kwon, Sol Kim, Jae-Hoon Kim. S100A14 plays an important role in cell growth and metastasis of epithelial ovarian cancer through PI3K-AKT pathway. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2857. doi:10.1158/1538-7445.AM2014-2857