bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2345: Amplification of mouse chromosome 4 in chemically induced and invasive mouse lung adenocarcinoma
Authors: Sargent Linda M. , Kashon Michael L. , Hubbs Ann F. , Lowry David T. , Ruppert Michael , Senft Jamie R. , McKinstry Kimberly T. , Tyson Tyson L. , Reynolds Steven H. 
Published: August 2012

Abstract
Lung cancer is the leading cause of cancer death in the United States and is ranked second only to bladder cancer in proportion of cases due to past occupational exposures. Though the genetic changes associated with lung cancer are not well understood, the pattern of mutations observed in lung adenocarcinoma from tobacco exposed patients is distinct from that of lung adenocarcinoma from unexposed patients. We used Spectral Karyotyping (SKY), mapping with fluorescently labeled genomic clones (FISH), comparative genomic hybridization (CGH), expression array, real time polymerase chain reaction and Western blot to analyze 15 primary adenocarcinoma and 9 pairs of high and low invasive cell cultures to detect molecular changes. The medial portion of chromosome 4 was deleted in 67% of all of the cell strains. Duplication of the proximal region of chromosome 4 occurred in 22% of the spontaneously-occurring high-invasive cells strains and 83% of the chemically-induced high-invasive cell cultures. Mouse chromosome 1 and 15 were amplified in 90% of the high-invasive cell strains. FISH mapping further narrowed the region of deletion of chromosome 4 to 39.6 centimorgans (cM) and the region of duplication to 10-35 cM. Expression array and real time PCR analysis demonstrated increased expression of the cell cycle inhibitory factor p16 and the apoptotic factor Cathepsin D in all of the tumor cell strains. The expression of cyclooxygenase 2 (COX-2), Kruppel like factor-4 (KLF4), Cyclin E and c-myc was significantly higher in the high-invasive cells strains compared to the low-invasive cell strains. Western blotting showed increased Cox-2, Cyclin E, KLF4 and c-myc proteins and decreased expression of Cathepsin D. In addition, the KLF4 protein was higher in the chemically-induced cell strains compared to the spontaneously-occurring cell strains while COX-2 was higher in the spontaneously-occurring cell strains. The KLF4 protein was identified in the tumor cell strains at the expected size of 55 KD as well as a smaller 45 KD form. Coordinated expression of KLF4 and c-myc is important in the induction of a stem cell phenotype and may be important in chemical carcinogenesis. The higher COX-2 in the spontaneous tumors indicates the importance of inflammation in spontaneous tumor induction. The homologous linkage groups on human chromosomes 9p21, 1p36, 9q and 8q are altered in asbestos-induced human lung adenocarcinoma. Alteration in copy number and expression of these genes may play a functional role in lung cancer development.
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 2345. doi:1538-7445.AM2012-2345
Abstract 235: Expression of DUSP4/MKP2 increases cell growth in colorectal cancer (CRC) cells and is associated with MSI-H phenotype in CRC
Authors: Dietmaier Wolfgang , Gröschl Benedikt , Bettstetter Marcus , Hofstädter Ferdinand 
Published: August 2012

Abstract
DUSP4, also termed MKP2 is a member of the mitogen-activated protein kinase phosphatase (MKP) family which negatively regulates the MAPKs (Mitogen-activated protein kinases) ERK, p38 and JNK. Using microarray analyses we found previously DUSP4 frequently overexpressed in high frequent microsatellite unstable (MSI-H) colorectal cancer CRC. Here we analysed DUSP4 expression on mRNA level in 38 CRC (19 MSI-H and 19 MSS) compared to matched normal tissue as well as in CRC cell lines by RT-qPCR. All 19 MSI-H tumors (100%) and 14/19 (73.7%) MSS tumors showed overexpressed DUSP4. However, median expression levels in MSI-H tumors were significantly higher than in MSS-tumors (p&lt;0.001). Likewise, MSI-H CRC cell lines showed 5.1-fold higher DUSP4 mRNA levels than MSS cell lines. Using quantitative methylation analysis (MethyQESD) we did not find DUSP4 expression regulated by promoter methylation in CRC cell lines as well as in tumor samples. DUSP4 overexpression in CRC cell lines through DUSP4 transfection caused increased expression of the MAPK targets CDC25A, CCND1, EGR1, MYC and CDKN1A in HCT116 cells as well as downregulation of the mismatch repair gene MSH2 in SW480 cells. Furthermore, DUSP4 overexpression caused increased proliferation in CRC cells using Real Time Cell Analysis (RTCA) system. Our findings suggest that DUSP4 plays as an important role in regulating cell growth within the MAPK pathway and causes enhanced cell growth in MSI-H colorectal 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 235. doi:1538-7445.AM2012-235
Abstract 2356: Establishment of HPV-positive and HPV-negative head and neck cancer tumorgrafts directly from patient biopsies
Authors: Torres Alexandra D. , Kimple Randall J. , Yang Robert Z. , Soriano Benjamin , Armstrong Eric A. , Harari Paul M. , Lambert Paul F. 
Published: August 2012

Abstract
PURPOSE: To develop a clinically relevant model system to study head and neck squamous cell carcinoma (HNSCC), we have established a direct from patient, tumorgraft model of both Human Papillomavirus (HPV)-positive and HPV-negative cancers and have performed initial therapeutic response characterization. METHODS: Following IRB approval, patients with newly diagnosed or recurrent HNSCC were consented for donation of tumor at the time of surgical procedure. Tissue from either the primary site or a lymph node metastasis was obtained, washed in antibiotic rich media, manually disaggregated, and subcutaneously implanted into mice (NOD.Cg-Prkdc scid Il2rgtm1Wjl/SzJ) for initial tumorgraft establishment. Subsequent mouse-to-mouse passages were performed and formalin-fixed/paraffin embedded as well as flash frozen tissue was harvested for subsequent molecular analyses. On the basis of hematoxaylin/eosin staining, patient tumor and primary tumorgraft were compared by a pathologist. To assess tumor growth rates and response to therapy (radiation, cisplatin, cetuximab) tumors were implanted into athymic nude mice and tumor growth curves monitored with twice-weekly tumor measurement. RESULTS: Patient demographics demonstrate a diverse group of donors with significant variations in tobacco and alcohol history, age, HPV status, and prior therapy. To date, tumorgraft establishment has been successful in 60% of cases (18/30). Primary tumor and tumorgraft showed high pathology correlation for differentiation status (well, moderately or poorly differentiated, Fisher Exact probability test p&lt;0.0001). Significant variation in tumorgraft doubling time was observed with the most rapid of 4.9 days ranging up to 24.2 days. Increased tumor doubling time was noted following treatment with radiation (mean doubling time: 140% of control, range: 80% - 230%), cisplatin (mean: 150%, range: 91% - 180%), and cetuximab (mean: 240%, range: 81% - 390%). CONCLUSIONS: We have established a robust tumorgraft model system for investigating HPV-positive and HPV-negative HNSCC. Characterization to date shows significant heterogeneity of tumor types and therapeutic response paralleling that observed in clinical populations. These human tumorgrafts provide a powerful resource for investigating mechanisms of therapeutic response and preclinical testing of radiation and/or chemotherapy regimens.
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 2356. doi:1538-7445.AM2012-2356
Abstract 2359: Using the glycolytic inhibitor 2-fluorodeoxy-D-glucose, a novel glycolytic inhibitor approach to target the chemoresistant, hypoxic cell population in advanced LHBETATAG retinal tumors
Authors: Pina Yolanda , Decatur Christina L. , Houston Samuel , Murray Timothy G. , Shah Nikesh , Lampidis Theodore 
Published: August 2012

Abstract
Purpose: The aim of the current study is to assess the impact of 2-fluorodeoxy-D-glucose on tumor burden and hypoxia in the LHBETATAG retinal tumors. Methods: The study protocol was approved by the University of Miami Institutional Animal Care and Use Review Board Committee and the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. 17-week-old (n=54) LHBETATAG transgenic mice were treated with 2-fluorodeoxy-D-glucose or saline control. These animals received three different treatments. They were treated: (1) with one injection and sacrificed at one day post-treatment, (2) with one injection and sacrificed at one week post-treatment, or (3) twice a week for three weeks and sacrificed at one day post-last injection. At the time of enucleation, all eye samples were snap frozen and analyzed for tumor burden and hypoxia using immunohistochemical techniques. Average densities of the different groups were statistically analyzed using ANOVA. Results were considered significant if p≤ 0.05. Results: There was no apparent toxicity associated with 2-fluorodeoxy-D-glucose treatment. There was a significant reduction in tumor burden following treatment with 2-fluorodeoxy-D-glucose at 1 day (86%) and 3 weeks (63%) post-treatment (p≤0.05). There was no reduction of tumor burden observed when mice were treated with 1 injection and eyes harvested at 1 week post-treament (2%, p=0.0640). There was a significant reduction of hypoxia areas following treatment with 2-fluorodeoxy-D-glucose at 1 day (100%) and 3 weeks (75%) post-treatment (p≤0.05). There was an increase in hypoxia of 12% following treatment at 1 week post-injection, but this increase was not statistically significant. Conclusions: 2-FDG significantly reduces tumor burden and tumor hypoxia following a single injection, with continued efficacy following repeated injections for 3 weeks. 2-FDG treatment is efficacious in murine retinoblastoma tumors and may enhance tumor control when combined with other therapies. 2-FDG appears to target hypoxic cells, a population that has been resistant to chemotherapy and radiation. Additionally, 2-FDG is commonly used in medical imaging and does not pose significant toxicities.
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 2359. doi:1538-7445.AM2012-2359
Abstract 236: Characterizing cellular signal transduction cross-talk using in-cell kinase screen
Authors: Uzgare Rajneesh , Hundley Thomas , Tiruchinapalli Dhanrajan , Solomon Anna , Horton Cheryl , Chen Hao 
Published: August 2012

Abstract
Cancers are known to be heterogeneous diseases. Tumor cell proliferation and the development of metastatic disease involve the activation of multiple, sometime parallel and often compensatory signal transduction pathways. We have developed a cell-based assay platform that measures specific kinase activity within cells, thus allowing us to conduct pathway-based analyses. This platform can be used for 1) discovering new biomarkers and 2) guiding the design of new therapeutic strategies in personalzed medicine, specifically tailored to the patient's genotype. In the present study, we have used this platform to study the impact of G-protein coupled receptor (GPCR) mediation on IGF-1r (RTK) signal transduction cascades in the presence/absence of oestradiol (ER) using MCF-7 breast cancer cells. The results of these studies indicate that mediating neuroendocrine pathways may be an alternative approach that could enhance the efficacies of specific target therapeutics for the treatment of 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 236. doi:1538-7445.AM2012-236
Abstract 2377: New micro-fluidic devices with polymeric materials for isolation of circulating tumor cells
Authors: Shimada Yutaka , Onaga Takashi , Moriyama Makoto , Okumura Tomoyuki , Sekine Shinichi , Obata Tsutomu , Kishi Hiroyuki , Fukuoka Junya , Hori Takashi , Nagata Takuya , Tsukada Kazuhiro 
Published: August 2012

Abstract
Introduction: Circulating tumor cells (CTCs) have been isolated from peripheral blood of cancer patients using cell detection and capture system, however the machine itself and the running costs are expensive. Thus a low cost device has been desired. Recently, a micro-fluidic device has been introduced. In this study, we would like to present a new micro-fluidic device with polymeric materials for isolation of circulating tumor cells. The IRB approval number was #21-88. Materials & Methods: We prepared a micro-fluidic device with the structures imprinted using a mold on the resin followed by UV-light curing in a couple of minutes. The resin contained a monomer having an epoxy group which enabled the device surface to react with other functional groups for immobilization of antibodies. The antibodies were immobilized not directly but with polymers to the surface. Polyacrylic acid (Mw:5,000) was grafted to the device surface by the reaction of the carboxyl group and the surface epoxy group, then IgG antibodies were covalently bonded to the polymer with the condensation agent for amino and carboxyl groups. Finally, EpCAM antibodies were attached to the IgG antibodies in the polymer. Results: Esophageal cancer cells KYSE220 dispersed in phosphate buffered saline (PBS) at a concentration of 1000 cells/ml were flowed through the CTC capture device described above at a rate of 1ml/hour. After cells passed, we observed many cells captured on the microstructure of the device, whereas no cells were seen without EpCAM antibodies on the device surface. We could evaluate the trapped cells by a quick cell stain method or fluorescent staining. We also detected KYSE220 cells in the healthy whole blood or selected nuclear cell separation. We have just started to evaluate this for detection of CTC in cancer patients. The cost of the new device was 10 dollar for each chip excluding the cost of the antibody. Conclusion: We developed a new micro-fluidic device with polymeric materials for isolation of circulating tumor cells. This new chip may be useful for isolation of CTC at a low cost.
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 2377. doi:1538-7445.AM2012-2377
Abstract 2378: Detection of circulating tumors cells (CTCs) in mice, using cancer stem cell (CSC) markers and a novel cell surface marker, AnnexinA2
Authors: Kantara Carla , Sarkar Shubhashish , Maxwell Carrie , Ullrich Robert , Singh Pomila 
Published: August 2012

Abstract
Detecting CTCs in plasma of patients with solid tumors has developed as a novel method for early detection of metastatic growths (Mets) and relapse of epithelial cancers. The current studies were undertaken to further improve sensitivity/specificity of CTC assays, based on recent developments. Accumulating evidence from many laboratories demonstrates that annexinA2 is increasingly translocated to cell-surface of tumor cells (labeled as CS-ANXA2), and is required for metastasis of cancer cells. We discovered that metastatic transformation of cells was associated with a significant increase in % CSCs co-expressing CS-ANXA2. We hypothesized that Circulating-CSCs (labeled as CTSCs) will likely be positive for CSC-Markers and CS-ANXA2, providing a more robust assay for identifying metastatic-CTCs or CTSCs, which may have the highest potential for seeding Mets; this novel possibility was examined in mice. Athymic nude mice were inoculated with either heat inactivated colon-cancer cells (HCT-116) (control, Gp1), or healthy sterile cells:- which were inoculated either subdermally (to grow primary xenografts) (Gp2) or intraspleenically (to grow liver/lung Mets) (Gp3). Mice were euthanized, when distinct sub-dermal tumors were present in Gp2 mice (wk3, post-inoculation) and blood plasma processed for depletion of WBC. Un-depleted samples had ∼ 109 RBC+WBC cells in all mice. Gp1 mice were negative for CTSCs or CTCs positive for CS-ANXA2. Gp2 mice had ∼40, 100 and 200 epithelial cells/ml blood, positive for CSC-Markers: DCAMKL-1, LGR5 and CD44, respectively, suggesting that DCAMKL-1 may be the most selective marker for CTSCs. Gp3 mice had significantly higher numbers of CTSCs/ml blood, in the order of CD44 (∼220), LGR5 (∼160) and DCAMKL-1 (∼60). CTCs, positive for CS-ANXA2, increased from 120 to 200/ml blood in Gp2 versus Gp3 mice, respectively, suggesting that high numbers of CTCs positive for CS-ANXA2 may be an independent selective marker for metastatic disease. Importantly, CTSCs in Gp3 mice, positive for either CD44 or DCAMKL-1 were also positive for CS-ANXA2. Therefore presence of circulating tumor stem cells (CTSCs) (positive for DCAMKL-1/CD44), co-expressing CS-ANXA2, may provide the most accurate approach for predicting presence of Mets or relapse of the cancer disease. Our studies so far, using fresh plasma samples from patients with colorectal growths (adenomas, adenocarcinomas ± Mets), supports this novel hypothesis. This work was supported by NIH grants CA97959 and CA114264 to PS; NASA NNX09AM08G and NNJ04HD83G to RU. CK and SS were equal contributors.
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 2378. doi:1538-7445.AM2012-2378
Abstract 2379: Expression of truncated HER2 receptor in circulating tumor cells (CTCs) of breast cancer patients
Authors: Kallergi Galaktia , Nasias Dimitris , Papadaki Maria A. , Mavroudis Dimitris , Georgoulias Vassilis , Agelaki Sophia 
Published: August 2012

Abstract
Introduction: HER2 receptor is overexpressed in 15-25% of patients with breast cancer. In HER2 positive breast cancer the administration of trastuzumab has changed the outcome of disease. However, most patients will eventually develop resistance to trastuzumab. The presence of a truncated receptor with loss of the extracellular portion of HER2 (p95HER2) has been proposed as a potential mechanism of resistance. Preclinical and clinical data suggest that the expression of p95HER2 is associated with poor overall prognosis, resistance to trastuzumab and sensitivity to lapatinib, a dual EGFR and HER2 tyrosine kinase inhibitor. We have recently shown that approximately 50% of breast cancer patients express HER2 in their CTCs (Kallergi et al., 2007; Kallergi et al., 2008). The aim of the present study was to characterize, for the first time, the expression of p95HER2 in CTCs of breast cancer patients. Methods: Triple staining immunofluorescent (IF) experiments were performed in peripheral blood mononuclear cells (PBMC) cytospins of patients with early (n=24) and metastatic (n=33) breast cancer who were CK-19 mRNA-positive by real time PCR. Pancytokeratin A45-B/B3 antibody (as a marker of CK-positive cells) was coupled with antibodies against the extracellular and the intracellular domains of HER2. Slides were analysed with either confocal laser scanning microscopy or with the Ariol system. Results: Cytokeratin positive cells were identified in 17 (71%) out of 24 early and in 20 (61%) out of 33 metastatic patients. HER2 positive CTCs were identified in 53% of early and 50% of metastatic CTC-positive breast cancer patients. HER2-positive CTCs lacking the extracellular domain of the receptor (p95HER positive CTCs) were identified in 35% of metastatic and 12% of early breast cancer patients. Exclusively p95HER2 positive CTCs were detected in 12% of patients with metastatic but not in patients with early disease. Conclusions: These data suggest that the truncated p95HER2 receptor is expressed in CTCs of both early and metastatic breast cancer patients. This finding has important therapeutic implications and may explain the observed increased efficacy of the trastuzumab plus lapatinib combination in HER2 positive 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 2379. doi:1538-7445.AM2012-2379
Abstract 2388: Dendrimer-mediated multivalent binding strongly captures tumor cells
Authors: Myung Ja Hye , Gajjar Khyati A. , Saric Jelena , Eddington David T. , Hong Seungpyo 
Published: August 2012

Abstract
Multivalent interactions, simultaneous binding of multiple ligands toward their multiple receptors, commonly occur in physiological and pathological events, which have been utilized to enhance targeting efficacy. The multivalent binding can be leveraged to develop an extremely sensitive device for detection of rare cells such as circulating tumor cell (CTC). Accurate enumeration of CTCs is of clinical importance in diagnosis and prognosis of cancer metastasis; however the rareness of CTCs, comprising as few as one tumor cell in the background of one million-one billion of normal blood cells, has made the effective detection of the cells extremely difficult. Here we report a novel surface chemistry that utilizes the multivalent effect for a highly stable cancer cell capture. Poly(amidoamine) (PAMAM) dendrimers have been reported as an excellent multivalent binding mediator due to their deformability and multiple functional groups. PAMAM dendrimers were conjugated with anti-epithelial cell adhesion molecules (aEpCAM), a commonly used antibody for CTC detection. A direct, quantitative analysis using surface plasmon resonance (SPR) revealed that the aEpCAM-dendrimer conjugates exhibited a dramatically enhanced binding avidity by a million-fold, compared to free aEpCAM. Dendrimers and aEpCAM were successfully immobilized on the surfaces, as confirmed by x-ray photoelectron spectroscopy and fluorescence microscopy. The surfaces were tested using in vitro cell lines (MDA-MB-361, MCF-7, and MDA-MB-231 cells as a CTC model). Surface immobilization of the dendrimer-aEpCAM conjugates resulted in a significantly enhanced tumor cell detection than the surfaces with the linear PEG-aEpCAM conjugates by ∼1.9 fold with higher binding stability over agitation (up to 69.1-fold). The enhancement through dendrimer-mediated multivalent binding effect was further increased up to 7-fold with addition of E-selectin that recruits the cancer cells onto the surface and induces their rolling under flow. This study demonstrates a novel surface engineering approach to exploiting the strong multivalent binding for sensitive detection of tumor cells, which has great potential for clinically significant detection of CTCs.
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 2388. doi:1538-7445.AM2012-2388