bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3388: Progression of ductal carcinoma in situ to invasive breast cancer is associated with gene expression programs of EMT and myoepithelia
Authors: Witkiewicz Agnieszka , Ertel Adam , Knudsen Erik S. 
Published: August 2012

Abstract
Ductal carcinoma in situ (DCIS) is a precursor lesion that can give rise to invasive breast cancer (IBC). It has been proposed that both the nature of the lesion and the tumor microenvironment play key roles in progression to IBC. Here laser capture microdissected tissue from pure DCIS and pure IBC were employed to define key gene expression profiles in either the epithelial or stromal compartment associated with disease progression. Each tissue had distinct gene expression profiles, and a DCIS/IBC classifier accurately distinguished DCIS versus IBC in multiple independent data sets. However, contrary to other studies that profiled DCIS associated with IBC, we found that the most significant alterations in gene expression were observed in the epithelial compartment rather than in the stroma. In particular, genes associated with epithelial to mesenchymal transition (EMT) and myoepithelial cell specific genes were enriched in invasive cancer relative to pure DCIS. Such alterations in transcript levels were associated with all subtypes of breast cancer, but were particularly indicative of poor outcome in ER-negative breast cancer. Together, these studies indicate that lesion specific differences in gene expression associated with invasive phenotype are particularly relevant in the progression of DCIS to IBC.
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 3388. doi:1538-7445.AM2012-3388
Abstract 3393: Antibody-based array proteomics identify proteins differentially expressed in human metastatic and non-metastatic triple negative breast cancer cells
Authors: Roberti Maria P. , Arriaga Juan M. , Bianchini Michele , Quintá Héctor R. , Bravo Alicia I. , Levy Estrella M. , Mordoh José , Barrio María M. 
Published: August 2012

Abstract
Triple negative breast cancers (TNBC) lacking hormone receptors (ER, PR) and HER-2 amplification are very aggressive tumors. The IIB-BR-G cell line isolated from a primary TNBC, and its spontaneous metastatic variant, IIB-BR-G-MTS6 were compared using an antibody-based protein array to characterize their expression profile. We also analyzed their growth kinetics, migration, invasiveness, lymphangiogenesis and cytoskeleton structure. Doubling times in vitro were shorter for IIB-BR-G although in vivo IIB-BR-G-MTS6 tumors grew significantly faster than IIB-BR-G. IIB-BR-GMTS6 showed higher anchorage independent growth in a clonogenic assay. IIB-BR-G-MTS6 cells showed 100% incidence of lymph node metastasis at 5-6 weeks, although no metastasis was observed for IIB-BR-G even 19 weeks after inoculation. CCL3, IL1α, CXCL1, CSF2, CSF3, IGFBP1, IL1α, IL6, IL8, CCL20, PLAUR, PlGF and VEGF were strongly up-regulated in IIB-BR-G-MTS6 compared to IIB-BR-G, while CCL4, ICAM3, CXCL12, TNFRSF18, FIGF, were the more down-regulated proteins in the metastatic cell line. IIB-BR-G-MTS6 protein expression profile was compatible with higher NF-κB activation. In vitro, IIB-BR-G displayed higher migration but IIB-BR-G-MTS6 had a higher matrigel invasion. Accordingly, IIB-BR-G-MTS6 had an up-regulated expression of MMP1, MMP9, MMP13, PLAUR and HGF as compared to IIB-BR-G. IIB-BR-G-MTS6 tumors presented higher local lymphatic invasion than IIB-BR-G but similar lymphatic vessel densities. VEGFC and VEGFA/B expression were higher both in vitro and in vivo for IIB-BR-G-MTS6. Higher vimentin expression was mainly localized in the cellular extremities in IIB-BR-G-MTS6.Our results suggest that IIB-BR-G-MTS6 have acquired an epithelial-to-mesenchymal transition phenotype, modulating tumor stroma to favor tumor growth, increase angiogenesis and promote their metastatic dissemination.
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 3393. doi:1538-7445.AM2012-3393
Abstract 3396: Predictive value of metastatic lymph node ratio in diagnosis of recurrence after surgical resection of gastric cancer
Authors: Tanaka Hiroaki , Muguruma Kazuya , Yoshii Mami , Lee Tomohiro , Kimura Kenjiro , Nagahara HIsashi , Noda Eiji , Amano Ryosuke , Kubo Naoshi , Yashiro Masakazu , Yamada Nobuya , Maeda Kiyoshi , Sawada Tetsuji , Ohira Masaichi , Hirakawa Kosei 
Published: August 2012

Abstract
Peritoneal meatastasis is the most important pattern in postoperative recurrence of gastric cancer. The purpose of this study was to investigate the predictive factors of peritoneal recurrence in gastric cancer patients who underwent surgical resection. We retrospectively analyzed clinical data of 137 consecutive patients diagnosed with peritoneal recurrence after curative gastrectomy at Department of Osaka City University Hospital. We evaluated association of clinicopathological features with relapse free survival rate. Parameters analyzed in this study included age, sex, tumor diameter, histological type, tumor infiltration, number of lymph node metastasis, TNM stage, lymphatic invasion, venous invasion, and metastatic lymph node ratio (MLR). Median survival time of entire patients was 12 months and mean MLR was 34%. For statistical analysis, we divided patients into two groups based on relapse free survival time. 78 patients who had peritoneal recurrence within one year after gastrectomy were defined as early recurrence group. The remaining 59 patients were stratified to late recurrence group. In comparison of both groups, univariate analysis showed statistically significant predictive factors associated with recurrence, for example, peritoneal lavage cytology, lymphatic invasion, tumor diameter, number of lymph node metastasis, and MLR. In multivariate analysis, MLR was identified as an independent predictive factor. Also the patients with 20% or higher MLR had poorer prognosis in overall survival. We demonstrated that lymph node metastasis was associated with peritoneal recurrence. Our findings suggested that MLR should be considered for postoperative adjuvant therapy to impede progression of peritoneal metastasis for gastric 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 3396. doi:1538-7445.AM2012-3396
Abstract 3403: E-cadherin and vimentin patterns by immunohistochemistry identify epithelial and mesenchymal phenotypes in lung adenocarcinoma
Authors: Pool Mark D. , Kaiser Kelly A. , Basu Sanjib , Borgia Jeffrey A. , Fidler Mary J. , Bonomi Philip 
Published: August 2012

Abstract
Purpose: To examine markers of epithelial-mesenchymal transition (EMT) in lung adenocarcinoma (ADC) defining epithelial-like (EPT) and mesenchymal-like (MES) phenotypes and correlate these with outcomes, in addition to other EMT markers. This study examined 33 patients with lung adenocarcinoma (ADC) who underwent surgical resection and later at disease progression received erlotinib. Experimental Design: All slides with tumor from resection specimens were reviewed (mean 4.8/case; range 1-9). Tumors were histologically subtyped according to recent IASLC classification. Tumor budding was graded per Ueno et al. (2002). A block containing the invasive front was selected for IHC staining with antibodies to e-cadherin (ECAD), vimentin (VIM), β-catenin (α-CAT), and SNAI1. Pattern-specific staining was evaluated at the invasive tumor front: E-cadherin-membranous, vimentin-cytoplasmic, α-CAT-membranous, SNAI1-nuclear, cytoplasmic. Complete circumferential membranous staining for e-cadherin was scored as present/absent; other markers were scored by the Allred system (0-8). PFS and OS were calculated from time of diagnosis to disease progression or death. Results: Two distinct phenotypes were identified with ECAD and VIM: EPT showing preserved membrane ECAD staining with low VIM (≥4) (N=19) and MES showing weak/absent membrane ECAD staining with high VIM (Δ5) (N=10). Median PFS for EPT group was 4.2 mo vs MES 1.6 mo; median OS for EPT group 15.5 mo vs 6.5 mo. These differences were not statistically significant. No association was found between high grade tumor budding and EPT vs MES phenotype p=0.221). Membranous α-CAT expression and nuclear SNAI1 expression showed a statistically significant correlation with EPT vs MES (β-catenin mean score 7.8 vs 6.1, p=0.0184) and (nuclear SNAI1 mean score 7.3 vs 6.1, p=0.0364). Conclusions: Epithelial and mesenchymal phenotypes can be identified by IHC for e-cadherin and vimentin. These phenotypes correlate with other EMT markers β-catenin and SNAI1 but not with tumor budding. Although differences in median PFS and OS were seen between the two groups, the number of cases is too small to identify a statistically significant difference. The results do support the rationale for defining EPT and MES groups for prognosis in a larger group of early-stage surgically resected patients.
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 3403. doi:1538-7445.AM2012-3403
Abstract 3405: MicroRNA expression characterizes oligometastasis(es)
Authors: Xing Rosie Hongmei , Lussier Yves A. , Salama Joseph K. , Khodarev Nikolai N. , Huang Yong , Zhang Qingbei , Khan Sajid A. , Yang Xinan , Hasselle Michael D. , Darga Thomas E. , Malik Renuka , Fan Hanli , Perakis Samantha , Filippo Matthew , Corbin Kimberly , Lee Younghee , Posner Mitchell C. , Chmura Steven J. , Hellman Samuel , Weichselbaum Ralph R. 
Published: August 2012

Abstract
Background: Cancer staging and treatment presumes a division into localized or metastatic disease. We proposed an intermediate state defined by β5 cumulative metastasis(es), termed oligometastases. In contrast to widespread polymetastases, oligometastatic patients may benefit from metastasis-directed local treatments. However, many patients who initially present with oligometastases progress to polymetastases. Predictors of progression could improve patient selection for metastasis-directed therapy. Methods: Here, we identified patterns of microRNA expression of tumor samples from oligometastatic patients treated with high-dose radiotherapy. Results: Patients who failed to develop polymetastases are characterized by unique prioritized features of a microRNA classifier that includes the microRNA-200 family. We created an oligometastatic-polymetastatic xenograft model in which the patient-derived microRNAs discriminated between the two metastatic outcomes. MicroRNA-200c enhancement in an oligometastatic cell line resulted in polymetastatic progression. Conclusions: These results demonstrate a biological basis for oligometastases and a potential for using microRNA expression to identify patients most likely to remain oligometastatic after metastasis-directed treatment.
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 3405. doi:1538-7445.AM2012-3405
Abstract 3432: HLJ1 serves as an inhibitor of epithelial-mesenchymal transition by inactivating β-catenin signaling
Authors: Chen Ching-Hsien , Lin Sheng-Yi , Chen Hsuan-Yu , Su Kang-Yi , Yuan Ang , Chen Huei-Wen , Yu Sung-Liang , Chen Jeremy 
Published: August 2012

Abstract
HLJ1 (DnaJ-like heat shock protein), also known as DNAJB4, was classified as a tumor suppressor gene. The expression of HLJ1 inversely associates with invasive ability and can predict the clinical outcomes of non-small-cell lung cancer (NSCLC) patients. However, the role of HLJ1 in suppressing cancer metastasis is still unclear. Here, we identified HLJ1 as a novel inhibitor of epithelial-mesenchymal transition (EMT). Our functional assays in vitro and in vivo demonstrated that Knock-down of HLJ1 promotes invasion capabilities of lung cancer cells and causes liver macrometastasis; meanwhile, the crucial domain of HLJ1 in suppression of cancer invasion was also confirmed. We found that the HLJ1-overexpressing cells maintain the well-organized cell adhesion and polarity. Inversely, an increase in actin polymerization and the formation of actin stress fibers were observed in the HLJ1-silencing cells. HLJ1 down-regulates the transcriptional activities of slug promoter and facilitates E-cadherin transcription, leading to the inhibition of epithelial to mesenchymal transition. Further, we identified the Wnt/β-catenin signalling pathway in which HLJ1 involved by cDNA microarray and pathway analysis. The subcellular distribution of β-catenin is predominant in the nucleus and the tyrosine-phosphorylated levels of β-catenin are up-regulated in the HLJ1-silenced clones. Finally, we showed a decreased accumulation of β-catenin and an enhanced degradation of β-catenin in absence of HLJ1 expression. Taken together, our study reveals that HLJ1 has anti-metastatic activity by repressing β-catenin signaling and provides a molecular model for the development of new anticancer agents.
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 3432. doi:1538-7445.AM2012-3432
Abstract 3433: Molecular regulation of RKIP, a tumor metastasis suppressor in breast cancer
Authors: Lee Jiyoung , Yun Jieun , Yeung Kam C. , Rosner Marsha R. 
Published: August 2012

Abstract
Breast cancer mortality is primarily due to metastasis to organs including bone, lungs, liver and brain. Tumor metastasis suppressors are metastasis inhibitors but do not affect the ability of the transformed cells to produce a tumor at the primary sites. Raf kinase inhibitory protein (RKIP) has been identified as a metastasis suppressor for a number of cancers including breast, prostate, liver, colon, skin, and nasopharyngeal carcinoma. RKIP overexpression in hepatoma, melanoma, and prostate metastatic cell lines diminished their invasiveness and motility in vitro. The molecular mechanism by which RKIP transcription is regulated in breast cancer is largely unknown. Interestingly, RKIP expression was highly and positively correlated with patient's metastasis-free survival after radiotherapy. Likewise, when RKIP was reduced in human prostate cancer cells, radiation-induced apoptosis was reduced in xenograft tumors. Moreover, RKIP expression levels have been induced upon chemotherapeutic drug treatment in human breast cancer cells, sensitizing the tumor cells to apoptosis. These studies indicate that chemotherapy and radiotherapy are more effective when RKIP is present in the metastatic cancer cells. Therefore, high RKIP levels are desirable to prevent metastasis of breast tumor cells and to sensitize tumor cells for chemotherapy. Our goal is to understand the mechanism by which RKIP is regulated in order to restore its levels. Previously, we have observed that let-7 negatively regulates two target genes, BACH1 and HMGA2 that promote breast cancer metastasis in a xenograft mouse model. Here we demonstrate that BACH1 and HMGA2 are themselves negative regulators of RKIP. Specifically, we have delineated molecular mechanisms by which BACH1 and HMGA2 inhibit RKIP expression in breast cancer cell lines using both luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays. We are also analyzing whether BACH1 and HMGA2 are dysregulated by chemotherapy in highly metastatic breast cancer cells and whether suppression of these RKIP regulators can potentiate sensitivity of the breast cancer cells to chemotherapy. These studies provide valuable mechanistic insights for potentiating chemotherapeutic sensitivity as well as potential biomarkers for metastatic breast 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 3433. doi:1538-7445.AM2012-3433
Abstract 3447: Tetrac (tetraiidothyroacetic acid) decreases in vitro x-ray survival of a human medullary thyroid cancer cell line under oxic and hypoxic conditions
Authors: Hercbergs Aleck A. , Davis Faith B. , Davis Paul J. , Leith John T. 
Published: August 2012

Abstract
In 2009 we showed that 2 µM tetrac given for 1 hour at 37oC prior to 250 kVP x-irradiation sensitized GL261 murine brain tumor cells. Radiosensitization was accomplished by increasing the alpha component in the linear-quadratic equation of cell survival (Cell Cycle, 8:2586-91). In 2011, we showed that tetrac also sensitized U87MG human brain tumor cells to 250 kVp x-rays (Cell Cycle, 10: 352-57). Again radiosensitization was accomplished by an increase in the αx-ray component. Tetrac also inhibited the repair of DNA double strand breaks in U87MG cells. However, tetrac which binds to the αvβ3 integrin receptor and inhibitssignaling from the αvβ3 receptor, penetrates the cell and has a thyromimetic effect which offsets radiosensitization. In this regard, we synthesized a nanoparticle tetrac formulation termed Nano-T. Nano-T also binds to the αvβ3 receptor but does notpenetrate the cell. Nano-T causes radiosensitization in vitro in H522 lung cancer cells, producing an added benefit compared to tetrac. We have also shown that daily treatment of in vivo human-MTC (h-MTC) solid tumors in mice with Nano-T for 20 days produced significant growth inhibition. It is our intent to combine Nano-T with ionizing radiation in vivo, and we have begun by studying the effects of tetrac on h-MTC cells in vitro. These h-MTC cells are show an in vitro cell culture doubling time of 96.2 hours and a clonogenicity of 3.16%. We irradiated cells in exponential growth with 250 kVp X-rays. Below we give the LQ survival parameters, and the surviving fraction at 2 Gy (SF2). Table 1. Initial Results of 250 kVp Single Dose X-irradiation on h-MTC CellsIn Vitro without and with Tetrac ≤ α SF2 Tetrac Oxygen (Gy-1 x 10-1) (Gy-2 x 10-2) Enhancment Enhancement Factor Factor Without Tetrac Oxic Cells - 0.033 0.0256 0.901 2.55 Hypoxic Cells 0.030 0.0023 0.922 With Tetrac Oxic Cells 0.472 0.0495 0.330 2.84 2.60 Hypoxic Cells 0.013 0.0256 0.803 2.84 First, h-MTC cells irradiated as oxic or hypoxic, exponentially growing cells are very radioresistant suggesting a large capacity to repair radiation damage. Second, tetrac sensitized both oxic and hypoxic h-MTC cells. These characteristics speak to our proposed Nano-T in treatment of h-MTC tumors in vivo. Nano-T should increase the radiosensitivity of both oxic and hypoxic cells and should also decrease the repair of radiation damage in conventional fractionated radiation therapy.
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 3447. doi:1538-7445.AM2012-3447
Abstract 3452: The role of CX3CR1 in resistance of ovarian carcinoma cells to radiation therapy
Authors: Xie Jia , Barbolina Maria 
Published: August 2012

Abstract
Ovarian carcinoma is a leading cause of death from gynecologic malignancies. The current standard of care, a combination of chemotherapy and radiation, fails to keep patients in remission. Thus, modifications of the therapy and the combinations with the new molecular biological technologies are crucial for the development of the modernized approaches to combat this disease. Previous attempts to use radiotherapy as an additional treatment was not successful mainly due to the dose-related side effects, as well as radioresistance. Therefore, mechanistical understanding of the biology of ovarian carcinoma could offer ways to overcome current problems. Fractalkine receptor (CX3CR1) belongs to a chemokine family of G protein-coupled receptors, the most frequently and successfully drug-targeted group of proteins. Interaction of chemokines with their receptors plays a pivotal role in homing distant metastasis, as well as promoting migration, adhesion, and proliferation in many types of cancer. This project is aimed at understanding the role of CX3CR1 in sensitization of epithelial ovarian cancer cells to radiotherapy. Our data indicate that downregulation of CX3CR1 in ovarian carcinoma cells leads to approximately 50% sensitization to x-ray radiation, as determined by the clonogenic ability assay. Our Western blotting and immunofluorescence analysis data also show that downregulation of CX3CR1 results in accumulation of DNA damage at lower doses. Thus, our data indicate that disruption of the CX3CR1 signaling could sensitize ovarian carcinoma to radiation therapy.
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 3452. doi:1538-7445.AM2012-3452