bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 46: Loss of CADM1 expression is associated with poor prognosis and brain metastasis in breast cancer patients
Authors: Wikman Harriet , Westphal Laura , Schmid Felicitas , Glatzel Markus , Matschke Jakob , Westphal Manfred , Pollari Sirkku , Iljin Kristiina , Terracciani Luigi , Huhtala Heini , Kallioniemi Anne , Sauter Guido , Müller Volkmar , Witzel Isabell , Lamszus Katrin , Kemming Dirk , Pantel Klaus 
Published: May 2015

Abstract
Purpose: Breast cancer brain metastases (BCBM) are detected with increasing incidence. Therefore, identification of genes involved in BCBM formation is of great interest. Eperimental Design: In order to detect potential genes involved in BCBM, we first screened for genes down-regulated by methylation in cell lines with site-specific metastatic ability. The expression of five genes, CADM1, SPARC, RECK, TNFAIP3 and CXCL14, which were also found down-regulated in gene expression profiling analyses of BCBM tissue samples, were verified by qRT-PCR in a larger patient cohort. CADM1 was chosen for further down-stream analyses. Results: A higher incidence of CADM1 methylation, correlating with the expression levels, was found in BCBM as compared to non-matched primary BC. Similarly, loss of CADM1 protein expression was detected more commonly among BCBM samples as well as among primary breast tumors with subsequent brain relapse. The prognostic role of CADM1 expression was finally verified in two publicly available data sets (n=418) and in two large independent primary breast cancer TMA tumor cohorts (n=1718). The immunohistochemical analyses revealed an association between loss of CADM1 protein expression and risk factors such as disease stage, lymph node status, and tumor size in primary BC. Furthermore, all analyses revealed a significant association between CADM1 and shorter survival. In multivariate analyses, survival was significantly longer for patients with CADM1-positive primary tumors for both TMA data sets (p= 0.04 and p=0.01). Conclusions: Loss of CADM1 expression is an independent prognostic factor especially associated with the development of brain metastases in breast cancer patients.
Citation Format: Harriet Wikman, Laura Westphal, Felicitas Schmid, Markus Glatzel, Jakob Matschke, Manfred Westphal, Sirkku Pollari, Kristiina Iljin, Luigi Terracciani, Heini Huhtala, Anne Kallioniemi, Guido Sauter, Volkmar Müller, Isabell Witzel, Katrin Lamszus, Dirk Kemming, Klaus Pantel. Loss of CADM1 expression is associated with poor prognosis and brain metastasis in breast cancer patients. [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 46. doi:10.1158/1538-7445.AM2014-46
Abstract 4615: Influence of SF3B1 gene mutation is different from that of Sf3B1 inhibitor in colorectal cancer
Authors: Yamano Tomoki , Kubo Shuji , Matsubara Nagahide , Yano Aya , Tomita Naohiro 
Published: May 2015

Abstract
Purpose: We have reported that SF3B1 gene mutations are rare in colorectal cancer patients and SF3B1 gene mutations in codon 1074 are responsible for resistance to SF3B1 inhibitor (FR901464, FR) at the AACR annual meeting 2013. SF3B1 gene mutations in hematological malignancies are considered to be related to tumor progression. To elucidate the influence by SF3B1 gene mutation in colorectal cancer, we assessed the tumor growth of colorectal cancer cells bearing SF3B1 gene mutation in vitro and in vivo.
ExperimentalDesign: We assessed the tumor growth in vitro and in vivo using FR resistant clones (DLD/FR1, DLD/FR2, DLD/FR3, HCT/FR1, HCT/FR2, and LoVo/FR1) derived from DLD1, HCT116, and LoVo. We also performed microarray analysis of DLD1, DLD/FR1, HCT116, and HCT/FR1 with or without FR for 24 h to compare the change of gene expression by FR or SF3B1 gene mutation.
Results: Doubling time of growth in DLD/FR1, DLD/FR2, HCT/FR1, and HCT/FR2 in vitro was same as their parental cells. However, doubling time of growth in DLD/FR3 and LoVo/FR1 in vitro was longer than their parental cells. In mouse subcutaneous xenograft models, the tumor volume of DLD1/FR1, HCT/FR1, and HCT/FR2 were 61%, 32 %, and 25%, to compared to that of their parental DLD1 or HCT116 one month after inoculation, respectively. Microarray analysis showed the genes and pathways affected by SF3B1 inhibitor and SF3B1 gene mutation did not match at all. Though SF3B1 inhibitor strongly inhibited pathways related to cell cycle, Fanconi anemia, homologous recombination, ubiquitin mediated proteolysis, nucleotide excision repair, oocyte meiosis, basal transcription factors, and endocytosis, SF3B1 gene mutation did not influence these pathways. The genes influenced by SF3B1 gene mutations included MHC class I/II, MHC MYC, BCL2, IL2, and IL10.
Conclusion: Our data indicated SF3B1 gene mutation in colorectal cancer induced disadvantage in cancer progression by the different pathway from SF3B1 inhibitor.
Citation Format: Tomoki Yamano, Shuji Kubo, Nagahide Matsubara, Aya Yano, Naohiro Tomita. Influence of SF3B1 gene mutation is different from that of Sf3B1 inhibitor in colorectal 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 4615. doi:10.1158/1538-7445.AM2014-4615
Abstract 4616: Chemo-sensitisation in epithelial ovarian cancer cell lines by targeting Ankyrin Repeat Domain 1 (ANKRD1)
Authors: Lei Ying , Henderson Beric Ross , Emmanuel Catherine , Harnett Paul , Fazio Anna de 
Published: May 2015

Abstract
Primary and acquired chemotherapy resistance remains a major challenge in the treatment of epithelial ovarian cancer and there are currently few targeted treatments that improve clinical outcome. We screened for genes that could potentially be targeted to sensitise, or re-sensitise, ovarian cancer cells to chemotherapy and identified a novel candidate, Ankyrin Repeat Domain 1 (ANKRD1), not previously described in ovarian cancer. ANKRD1 is a putative transcription factor with roles in muscle development, inflammation and response to cell stress. ANKRD1 is a target of TGF-β/Wnt signalling, and is also a binding partner of Titin (TTN) which been identified as a candidate with a high probability of carrying ‘driver’ mutations in ovarian cancer. ANKRD1 was expressed in serous ovarian cancer samples and higher tumor levels were found in patients with worse outcome (overall survival, p=0.013), (Scurr et al, Clin Cancer Res 2008; 14: 6924-32). In this study we showed that ANKRD1 levels decrease in response to cisplatin, in concert with induction of PARP cleavage and apoptosis in human ovarian cancer cell lines, COLO316, PEO14 and OAW42. We showed that decreasing ANKRD1 expression using siRNA (ON-TARGETplus Human ANKRD1 siRNA) increased cisplatin-induced apoptosis. Increased cisplatin sensitivity was associated with endoplasmic reticulum (ER) stress, evidenced by induction of GRP78, GADD153 and increased intracellular Ca2+ release. We have screened drug libraries (Prestwick library) for agents that sensitise ovarian cancer cell lines to platins, via an ANKRD1 related mechanism, and have identified several potential candidate molecules. Taken together, these results suggest that ANKRD1 plays a significant role in the regulation of apoptosis in human ovarian cancer cells, and is a potential molecular target to enhance sensitivity of ovarian cancer to chemotherapy.
Citation Format: Ying Lei, Beric Ross Henderson, Catherine Emmanuel, Paul Harnett, Anna de Fazio. Chemo-sensitisation in epithelial ovarian cancer cell lines by targeting Ankyrin Repeat Domain 1 (ANKRD1). [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 4616. doi:10.1158/1538-7445.AM2014-4616
Abstract 4638: NVP-CGM097: a novel p53-Mdm2 inhibitor exhibiting potent antitumor activity in mouse models of human cancer
Authors: Ferretti Stéphane , Berger Marjorie , Rebmann Ramona , Santacroce Francesca , Sterker Dario , Jensen Michael , Masuya Keiichi , Jeay Sébastien 
Published: May 2015

Abstract
Although functional inactivation of the tumor suppressor p53 is a frequent genetic event, half of all human tumors express wild-type p53. Stabilization of p53 by antagonizing its negative regulator mouse double minute 2 (Mdm2) leads to selective induction of the p53 pathway, thus offering a promising therapeutic opportunity.
NVP-CGM097 binds in the p53 pocket on the surface of Mdm2 and effectively disrupts the interaction between p53 and Mdm2. The aim of this study was to determine the pharmacokinetic (PK), pharmacodynamic (PD) and efficacy profile of this novel p53-Mdm2 inhibitor in mouse models of human cancer. During the medicinal chemistry discovery efforts, the compound series was optimized for oral administration. The selected compound, NVP-CGM097, was well absorbed in mice where the maximum plasma concentration (Tmax) was observed about 3 hours post dose followed by a prolonged absorption phase. PD effects were determined by measuring the expression levels of p53 target genes including p21, PUMA and Mdm2 in tumors. The expression levels of p53 target genes correlated with the concentrations of NVP-CGM097 demonstrating a good PK/PD relationship.
Optimal treatment schedules were investigated in the Mdm2-amplified, p53 wild-type osteosarcoma xenograft model SJSA-1. Interestingly, various schedules were highly efficacious at well-tolerated dose levels. Tumor regression was observed when NVP-CGM097 was administered in schedules ranging from daily to twice per week with no adverse effects. Following dose optimization studies, potent anti-tumor efficacy was observed in a range of p53 wild-type expressing xenograft models including Mdm2 non-amplified orthotopic AML as well as well-differentiated (WDLPS) and dedifferentiated (DDLPS) liposarcomas.
Overall, we demonstrate that the novel p53-Mdm2 inhibitor NVP-CGM097 has a good PK profile and affects PD markers in human tumors leading to tumor regression at well-tolerated dose levels. These data strongly support clinical development of NVP-CGM097.
Citation Format: Stéphane Ferretti, Marjorie Berger, Ramona Rebmann, Francesca Santacroce, Dario Sterker, Michael Jensen, Keiichi Masuya, Sébastien Jeay. NVP-CGM097: a novel p53-Mdm2 inhibitor exhibiting potent antitumor activity in mouse models of human 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 4638. doi:10.1158/1538-7445.AM2014-4638
Abstract 4661: The regulatory mechanism of fibronectin in EGFR and/or HER2 positive breast cancer
Authors: Jeon Myeongjin 
Published: May 2015

Abstract
Fibronectin (FN) is a glycoprotein of the extracellular matrix and plays a major role in cell adhesion, migration and oncogenic transformation. Aberrant FN expression is associated with poor prognosis in a variety of cancers including breast cancer. However, the regulatory mechanism between FN and HER2 is not fully elucidated in breast cancer.
Our clinical data showed that both disease free survival (DFS) and overall survival (OS) was lower in EGFR (+) and HER2 (+) breast cancer patients than in EGFR (+) breast cancer patients. To verify the causing of poor prognosis, we analyzed secreted proteins in EGFR and/or HER2 overexpressed MDA-MB231 cells. Our results showed that the level of FN expression was significantly increased in HER2 overexpressed MDA-MB231 cells. On the other hand, the induction of FN by HER2 overexpression was decreased by trastuzumab (HER2 monoclonal antibody) and AG825 (HER2 inhibitor), respectively. In addition, we observed that the expression of FN was dose-dependently increased by EGFR ligands in SKBR3 cells which are expressed endogenous EGFR and HER2. EGF ligands-induced FN expression also decreased through the suppression of HER2 in SKBR3 cell. However, these effects did not detect in trastuzumab-resistant breast cancer cell line, JIMT-1. Taken together, we demonstrated that the induction of FN by HER2 correlates poor clinical outcome in breast cancer patients.
Citation Format: Myeongjin Jeon. The regulatory mechanism of fibronectin in EGFR and/or HER2 positive breast 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 4661. doi:10.1158/1538-7445.AM2014-4661
Abstract 4662: Prognostic value of total lesion glycolysis from 18F-fluorodeoxyglucose positron emission tomography patients with gastric neuroendocrine carcinoma
Authors: Jung Minkyu , Kang Beodeul , Park Ji Soo , Lim Sun Min , Kim Hyo Song , Rha Sun Young , Ahn Joong Bae , Chung Hyun Cheol , Yun Mijin , Cho Arthur 
Published: May 2015

Abstract
Background: Gastric neuroendocrine carcinomas (NET) are very rare, aggressive tumors of the stomach. The objective of this study was to examine the predictive role of pretreatment fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET)-assessed metabolic parameter of the whole-body and primary tumors in patients with gastric NET
Method: We conducted a retrospective review of the 25 patients with histopathologically confirmed poorly differentiated NETs of the stomach at our hospital between January 2005 and December 2012. All of the patients underwent 18F-FDG-PET examination at diagnosis. Metabolic parameters [SUVmax, SUVmean, and total lesion glycolysis (TLG)] on pretreatment 18F-FDG-PET were analyzed for survival.
Results: Median follow up duration was 39.4 months (95% CI, 20.0-58.1 months) and median overall survival (OS) was 25.7 months (95% CI, 14.1-37.2 months). When subjects were divided into two groups according to TLG with a cutoff value of 500, the high TLG group showed significantly shorter OS compared to the low TLG group (p=0.006). However, SUVmean and SUVmax had no significant association OS (p = 0.258, and p = 0.52, respectively).
Conclusions: Our findings suggest that TLG may be more useful than SUVmean and SUVmax for predicting OS in patient with NET. The TLG measurement on 18F-FDG-PET imaging could be routinely recommended to advanced gastric cancer with neuroendocrine carcinoma
Citation Format: Minkyu Jung, Beodeul Kang, Ji Soo Park, Sun Min Lim, Hyo Song Kim, Sun Young Rha, Joong Bae Ahn, Hyun Cheol Chung, Mijin Yun, Arthur Cho. Prognostic value of total lesion glycolysis from 18F-fluorodeoxyglucose positron emission tomography patients with gastric neuroendocrine carcinoma. [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 4662. doi:10.1158/1538-7445.AM2014-4662
Abstract 4670: Characterization of Met signaling in urothelial cancer of the bladder
Authors: Lee Young H. , Apolo Andrea , Agarwal Piyush K. , Bottaro Donald P. 
Published: May 2015

Abstract
Background: Mounting evidence supports Met as a target in urothelial cancer (UC). Activated Met can promote angiogenesis and tumor growth by upregulating VEGF and may play a role in UC pathogenesis. Cabozantinib inhibits both VEGFR2 and Met pathways. In this study, we assessed cabozantinib's effects on HGF-driven UC cell growth and invasion.
Methods: sMet levels in serum and urine samples from 31 patients with UC (23 metastatic, 8 muscle-invasive) were correlated with stage, presence of visceral metastases and urinary source. The effects of cabozantinib on 6 human UC-derived cell lines were studied in vitro. Intact RT4, TCC-SUP, T24M2, T24M3, J82 and SW780 cells at 80% confluence were serum deprived 16 h, then left untreated or treated with hepatocyte growth factor (HGF) and/or cabozantinib prior to analysis of Met, phospho- (p)Met, pAkt, Akt, pErk and ErK by immunoassay or immunoblotting. Cabozantinib effects on basal and HGF-induced UC cell invasion, proliferation and soft agar growth were measured.
Results: Median serum Met levels were modestly higher in patients with metastatic versus muscle-invasive disease. Urinary Met levels were clearly higher in patients with visceral metastasis (p=0.0111) and in urine from ileal conduits and neobladders compared to normally voided urine, regardless of stage (p=0.0489). Met content in UC cell lines was low in RT4 and higher in T24M2, T24M3, TCC-SUP, J82 and SW780. Basal pMet content was universally low, increased significantly by HGF and this was reversed by cabozantinib. HGF-driven increases in pAkt/Akt and pErK/ErK in all 6 cell lines were reversed by cabozantinib, as were HGF-enhanced UC cell invasion, proliferation and anchorage independent growth.
Conclusions: Median urinary sMet is significantly higher in patients with visceral metastasis and in specimens from ileal conduits and neobladders relative to normally voided urine. UC cell Met content in culture increased with disease grade; HGF stimulated activation of Met and known effectors, and enhanced invasion, growth rate and anchorage-independent grow¬¬¬th; cabozantinib effectively reversed these HGF-driven effects.
Citation Format: Young H. Lee, Andrea Apolo, Piyush K. Agarwal, Donald P. Bottaro. Characterization of Met signaling in urothelial cancer of the bladder. [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 4670. doi:10.1158/1538-7445.AM2014-4670
Abstract 4674: Finding cancer biomarkers in platelets
Authors: Tjon-Kon-Fat Lee-Ann , Lundholm Marie , Wurdinger Thomas , Thellenberg Camilla , Widmark Anders , Wikström Pernilla , Nilsson Jonas 
Published: May 2015

Abstract
Introduction: In the development of personalized medicine we need a window in to the tumor; it should be minimal invasive, being able to find the disease and follow how the tumor alters its behaviour to circumvent the treatment. Platelets could be one such window, with its ability to sequester tumor-derived material during its passage through the circulation. Material & Methods: With conventional quantitative PCR and microarray techniques “potential” biomarkers were analysed from WTA (whole transcriptome amplified) platelet-derived RNA isolated from cancer patients and healthy controls. Results: We demonstrate that platelets contain several cancer-associated RNA biomarkers. In addition, there was a distinct biomarker signature in platelets from cancer patients of different grades as compared to normal control subjects. Conclusion: These findings are preliminary, and need to be validated in a larger patient cohort. However, they support our earlier findings in gliomas that platelets may carry the needle from the haystack that will give us a window into the cancer biology of individual patients.
Citation Format: Lee-Ann Tjon-Kon-Fat, Marie Lundholm, Thomas Wurdinger, Camilla Thellenberg, Anders Widmark, Pernilla Wikström, Jonas Nilsson. Finding cancer biomarkers in platelets. [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 4674. doi:10.1158/1538-7445.AM2014-4674
Abstract 4677: Niclosamide analogs for treatment of ovarian cancer
Authors: Haygood Christen L. Walters , Arend Rebecca C. , Li Pui-Kai , Li Yonghe , Kurpad Chandrika , Gangrade Abhishek , Straughn John M. , Buchsbaum Donald 
Published: May 2015

Abstract
Objective: Niclosamide has shown promising activity against ovarian cancer in vitro;, however, it has low bioavailability in vivo. Thus, we investigated the cytotoxicity of niclosamide analogs in combination with carboplatin in ovarian cancer cell lines and against ovarian cancer patient ascites cells.
Methods: Tumorspheres were isolated from ascites collected from 8 patients undergoing ovarian cancer surgery at UAB. Tumorspheres were plated at 10,000 cells per 50 µL into low attachment plates. Eight patient samples were treated concurrently with niclosamide analog 11 (0.1 µM - 5 µM) and carboplatin (5 - 150 μM), while four 4 patient samples were treated with analog 32 (0.1 µM - 5 µM) and carboplatin (5 - 100 μM). After 48 hours, cells were analyzed for viability using the ATPlite assay. Analogs 11 and 32 were also assayed in combination with carboplatin against ovarian cancer cell lines, A2780, A2780.cp20, SKOV3ip2, and SKOV3ip2.TR.
Results: IC50 values for analog 11 ranged from 0.5 - 1 μM in the 8 patient ascites samples. With 150 μM carboplatin alone, patient samples had 40-80% cytotoxicity. In combination with analog 11 at 1 μM, 100% of cells were killed with 100 μM carboplatin in the 8 patient ascites samples. In the established ovarian cancer cell lines, cytotoxicity approached 100% at a dose of 3 - 5 μM of analog 11. In the 4 patient samples treated with analog 32, IC50 values ranged from 0.4 μM - 3 μM. With 100 μM carboplatin alone, patient samples had 40-80% cytotoxicity. In combination with 100 μM carboplatin, nearly 100% of cells were killed at a dose of 1 μM of analog 32. In the cell lines, IC50 values for analog 32 ranged from 0.9 - 2.5 μM. With combination treatment, there was increased cytotoxicity in the chemoresistant cells, A2780.cp20 and SKOV3ip2, compared to carboplatin alone.
Conclusion: These niclosamide analogs produced cytotoxicity both alone and in combination with carboplatin against ovarian cancer cells and tumorspheres from patient ascites. Future studies will evaluate the PK/PD of the analogs.
Citation Format: Christen L. Walters Haygood, Rebecca C. Arend, Pui-Kai Li, Yonghe Li, Chandrika Kurpad, Abhishek Gangrade, John M. Straughn, Donald Buchsbaum. Niclosamide analogs for treatment of ovarian 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 4677. doi:10.1158/1538-7445.AM2014-4677