bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2670: Decreased expression of miR-302 contributes radioresistance of breast cancer cells
Authors: Liang Zhongxing , Guo Donna , Votaw John R. , Wang Ya , Shim Hyunsuk 
Published: June 2012

Abstract
Radiotherapy is a common treatment strategy for many solid tumors, including breast cancer. Unfortunately, solid tumors can be resistant or develop resistance to radiotherapy. Though many studies have been conducted to further elucidate the mechanisms of radioresistance, they remain largely obscure due to the complex genetic cellular response to radiation and involvement of a large number of genes. MicroRNA, a recently discovered class of small, functional, non-coding RNA, is one of such class of potential regulators. A single microRNA can target a large number of genes and regulate several signal pathways simultaneously. Thus, miRNAs may be involved in the complex radioresistance of tumor cells. In the present study, we characterized miR-302 family members (miR-302s) pre-clinically as novel biomarkers for radiotherapy resistance. Our results showed that miR-302s were downregulated in irradiated breast cancer cells. Furthermore, we found, with a bioinformatic analysis, that AKT and RAD52, two critical regulators of radioresistance, are the predicted targets of miR-302s. Additionally, the expression levels of miR-302a were inversely consistently with those of AKT and RAD52. More promisingly, our data have demonstrated that miR-302a mimics sensitized breast cancer MDA-MB-231 cells to radiation therapy and reduced the expression of AKT and RAD52. Collectively, loss of miR-302s may be involved in the radioresistance of breast cancer cells, mainly through the release of repression of AKT and RAD52. Thus, our findings suggest that decreased expression of miR-302s contributes to radiotherapy-resistance and restoration of miR-302 baseline expression sensitizes breast cancer cells to radiotherapy. These data suggest that miR-302s may be potential sensitizers to radiotherapy and represent a novel strategy for radiotherapy of breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2670. doi:10.1158/1538-7445.AM2011-2670
Abstract 2674: Radio-sensitizer eluting nanoporous coatings on fiducials markers: Biological in-situ dose-painting for IGRT
Authors: Sridhar Srinivas , Nagesha Dattatri , Tada Dayane , Kumar Rajiv , Makrigiorgos G. Mike , Cormack Robert 
Published: June 2012

Abstract
Image-guided radiation treatments routinely utilize implantable devices, such as radio-opaque fiducials or brachytherapy spacers, for improved spatial accuracy. We study the hypothesis that the therapeutic efficiency of IGRT can be further enhanced by biological in-situ dose painting (BIS-IGRT) using local delivery of radiosensitizers embedded within nanoparticles and nanoporous polymer matrices coating gold fiducial markers. Biocompatible polymers loaded with model molecules were coated as a thin film on gold fiducials. The nanoporous morphology of the polymer coatings allowed the controlled release of the molecules and nanoparticles. Two experimental approaches were studied: (i) a free drug release system Doxorubicin, a hydrophilic drug in Poly(methyl methacrylate (PMMA) coating and (ii) Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles loaded with Coumarin-6, a model for a fluorescent hydrophobic drug, in a chitosan matrix applied as fiducial coating. Temporal release kinetics measurements in buffer were carried out using fluorescence spectroscopy. For flat gold films and gold fiducials coated with Doxorubicin in PMMA matrix, an initial release of Dox within the first few hours was followed by a sustained release over the course of next 3 months. Release of Dox from within PMMA matrix is dependent on the concentration of Dox, ratio of PMMA/Dox, thickness of PMMA/Dox coating on gold surface. The release profile of coumarin-6 loaded nanoparticles from chitosan film on gold fiducials showed a continuous release of NPs from the coating during forty days. (63±10)% of NPs were released in twenty days. After that, the release became slower and additional 37% of release was observed after twenty-days. Spatial release profiles in an agarose phantom were also measured and compared with release kinetics models. Results show that dosage and rate of release of these radiosensitizers can be precisely tailored to achieve the desired release profile for BIS-IGRT.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2674. doi:10.1158/1538-7445.AM2011-2674
Abstract 2715: Host genomic environment determines HTLV-1 clone size in vivo
Authors: Gillet Nicolas , Malani Nirav , Melamed Anat , Gormley Niall , Carter Richard , Bentley David , Berry Charles , Bushman Frederic , Taylor Graham , Bangham Charles 
Published: June 2012

Abstract
HTLV-1 persists by driving clonal proliferation of infected T-lymphocytes. A high proviral load predisposes to the inflammatory and malignant diseases associated with HTLV-1. Yet the reasons for the remarkable variation within and between individuals in the size of HTLV-1-infected clones remain unknown. We devised a high-throughput protocol to map the genomic location and quantify the abundance of &gt;91,000 distinct integration sites from 61 HTLV-1+ individuals and &gt;2,100 sites from in vitro infection. We show that a typical HTLV-1-infected host carries between 500 and 5000 distinct integrated proviral clones. We demonstrate that negative selection dominates during chronic infection, favouring survival of proviruses integrated in transcriptionally silenced DNA: this selection is significantly stronger in asymptomatic carriers. The high proviral load characteristic of HTLV-1-associated inflammatory disease results from a larger number of integrated proviruses and not as previously believed from a difference in clonality. The abundance of surviving integrated proviruses is determined by genomic features of the flanking DNA and the transcriptional orientation of the provirus relative to the nearest host gene. HTLV-1 clonal expansion in vivo is favoured by orientation of the provirus in the same sense as the nearest host gene.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2715. doi:10.1158/1538-7445.AM2011-2715
Abstract 2716: Overexpression of p16INK4a in Merkel cell carcinoma
Authors: Yu Dawen , Zhang Hong , Carrigg Alison , Wang-Rodriguez Jessica , Liu Yu-Tsueng 
Published: June 2012

Abstract
Merkel cell polyomavirus (MCV) is a recently discovered human oncogenic virus. The majority of Merkel cell carcinomas (MCC) have been found to be infected with MCV. The MCV large T antigen (LTA) consists of an Rb binding motif that is functionally analogous to the E7 protein of high-risk human papillomavirus (HPV) types (eg. 16 and 18). It has been well documented that inactivation of Rb leads to overexpression of p16INK4a. Clinically, immunohistochemistry for p16INK4a has proven useful in the diagnosis of HPV driven epithelial malignancies including cervical as well as head and neck cancers. The present study explores the relationship between MCV infection and p16INK4a expression using an in vitro cell culture system and 10 clinical specimens of MCC that have been diagnosed at the San Diego VA Hospital over a 21 year period. First, IMR-90 cells were transfected with MCV LTA plasmids, which carry either wild-type or mutant Rb binding motif for immunofluorescence analysis. Only cells transfected with wild-type, but not mutant LTA, were associated with p16INK4a up-regulation. Furthermore, a strong positive correlation was established between MCV LTA and p16INK4a expression in formalin-fixed, paraffin-embedded MCC samples by immunohistochemical staining using p16INK4a and MCV LTA specific monoclonal antibodies, and real-time PCR to detect MCV with two pairs of primers. In conclusion, strong association between p16INK4a expression and MCC suggests that the MCV and HPV related carcinomas share some common oncogenic pathways. In addition, p16INK4a positivity can be a useful diagnostic tool in differentiating MCC from other small blue cell tumors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2716. doi:10.1158/1538-7445.AM2011-2716
Abstract 2717: Detection of Merkel cell polyomavirus in chronic lymphocytic leukemia cells by fluorescence in situ hybridization (FISH)
Authors: Speel Ernst-Jan M. , Haugg Anke , Pantulu Naga Deepa , Pallasch Christian , Kurz Anna K. , Kassem Ahmad , Frenzel Lukas , Sodenkamp Sebastian , Kvasnicka Hans M. , Wendtner Clemens , Zur Hausen Axel 
Published: June 2012

Abstract
Background: Merkel cell polyomavirus (MCPyV) is detected in approximately 80% of Merkel cell carcinomas (MCC). A number of previous studies have shown that MCC patients are at a significantly increased risk to develop chronic lymphocytic leukemia (CLL) and vice versa. Until recently, clonal integration and truncating mutations of the Large T antigen (LTAg) of MCPyV were restricted to MCC. We have recently reported the presence of the MCPyV in highly purified tumor cells of CLL (n = 19/70, 27.1%) (Blood. 2010 Sep 3). Of these, six revealed a novel 246 bp deletion in the helicase gene of the LTAg. The presence of MCPyV was confirmed by immunohistochemistry.
Material and Method: Here we aimed to determine the presence of MCPyV by fluorescence in situ hybridization (FISH) analysis in CLL cells in order to evaluate whether MCPyV was integrated or episomal. For this purpose we performed FISH analysis as previously described (Int J Cancer. 2005, 115:419-428) using the MCPyV genome as FISH probe. We tested 2 of the previously reported MCPyV positive CLL cases (EDTA decalcified bone marrow trephines) and MCPyV-positive MCC (n = 5). In addition, we tested MCPyV-negative tumors, e.g. breast and colon cancers. All tissues were formalin-fixed and paraffin-embedded.
Results: Specific MCPyV DNA by FISH analysis was detected in the nuclei of MCPyV-positive CLL and MCC cells. In contrast to particularly punctate FISH signals in MCC indicating viral integration, the nuclear FISH signals of the CLL cases revealed especially granular signals, indicative for integrated MCPyV DNA together with transcribed viral RNA (Int J Cancer. 2008, 122:2656-2664). No signals were obtained by MCPyV FISH in breast or colon cancer specimens.
Conclusion: The specific detection of MCPyV in CLL cells further supports our previous report of a possible involvement of MCPyV in a significant subset of CLL. The specific but rather granular nuclear FISH signals in MCPyV positive CLL cells needs further study to evaluate if it is also generated by co-existing episomal virus copies, by viral RNA or by the decalcification process. In addition, more CLL cases will be analyzed for the presence of MCPyV.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2717. doi:10.1158/1538-7445.AM2011-2717
Abstract 2720: Cidofovir modulates HPV E6 and E7 as well as p53, Rb and MDM2 in HPV16 naturally transformed head and neck squamous cell carcinoma and enhances chemosensitivity to Cisplatin
Authors: Park Jung Je , Kommareddi Pavan K , Nair Thankam S. , Seo Ji Hyun , Jeon Sea-Yuong , Kim Sang Yoon , Prince Mark E. , Bradford Carol R. , Carey Thomas E. 
Published: June 2012

Abstract
Purpose: The increasing incidence of oropharyngeal head and neck squamous cell carcinoma (HNSCC) is largely associated with sexually transmitted infection with high risk human papillomavirus (HPV), particularly HPV16. Cidofovir is an acyclic nucleoside phosphate that has broad antiviral activity against DNA viruses and is used clinically in recurrent respiratory papillomatosis. It is not known whether Cidofovir has any therapeutic effects on naturally transformed and non-transformed HNSCC cell lines.
Experimental Design: We investigated the effects of Cidofovir on naturally HPV16 transformed HNSCC cell lines, and compared these with the effects on non-transformed HNSCC cell lines from similar tumor sites. We performed RT-PCR in HPV16 transformed cell lines to evaluate the effect of Cidofovir on HPV16 E6 and E7 gene transcription. Modulation of p53, Rb, MDM2, p21(WAF1), and p16 protein levels were studied by Western blot analysis. To evaluate chemosensitivity in the cells, we pretreated the tumor cell with Cidofovir followed by Cisplatin and then assessed cell cycle by FACS analysis, and survival by clonogenic, cell viability, and MTT assays.
Results: HPV16 transformed cell lines exhibited decreased E6 and E7 expression after treatment with Cidofovir. This treatment also increased p53 and Rb as well as MDM2, and p21(WAF1) in HPV16 transformed cell lines. We demonstrated that the combination of Cidofovir and Cisplatin treatment enhanced chemosensitivity in HPV16 transformed cell lines, but the effect in HPV negative tumor cells was less pronounced.
Conclusion: Our results suggest that Cidofovir may have a role in senisitizing HPV16 naturally transformed HNSCC to conventional treatment and could reduce unwanted toxicity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2720. doi:10.1158/1538-7445.AM2011-2720
Abstract 2721: Comparative responses of HPV-positive vs HPV-negative head and neck cancer cells to radiation and/or chemotherapeutic drugs
Authors: Kimple Randall J. , Yang Robert Z. , Armstrong Eric A. , Lambert Paul F. , Harari Paul M. 
Published: June 2012

Abstract
Purpose: HPV is associated with a growing proportion of head and neck squamous cell carcinomas (HNSCCs), which show improved clinical outcome compared with non-HPV associated HNSCC. Whether this improved outcome reflects enhanced responsiveness to radiation and/or chemotherapy remains unclear. There is little data available regarding the radio- and chemo-sensitivity of HPV-associated HNSCC. We provide detailed analysis of radiation response profiles in verified HPV-positive HNSCC lines.
Methods: Degenerate PCR and Southern blot were used to confirm HPV status in HNSCC human tumor cell lines. Clonogenic survival assays were used to assess radiation sensitivity. Proliferation assays were used to assess sensitivity to chemotherapy. Western blot was used to assess EGFR expression, activity, and the effect of EGFR inhibitor treatment.
Results: Clonal expansion of existing HPV-positive HNSCC cell lines was performed to confirm the presence of a homogeneous population of cells and HPV-integration status confirmed by Southern Blot. HPV-positive cells were more sensitive to radiation-induced cell death compared to HPV-negative cells using single dose and fractionated radiation exposure regimens. Of the HPV+ cells tested to date, we have seen further radiosensitization with exposure to EGFR inhibitors (e.g., enhancement ratio 1.27 for UM-SCC47 with erlotinib) despite similar response to the EGFR inhibitor alone. HPV+ tumor xenografts have been raised in immunocompromised mice for in vivo radiation and chemotherapy response assessment.
Conclusions: Consistent with clinical reports, HPV-associated HNSCC cells exhibit increased sensitivity to radiation. The in vitro sensitivity of HPV-positive HNSCC to chemotherapy is in progress, as is the response evaluation of HPV+ xenografts to radiation and chemotherapy. Underlying molecular mechanisms for altered response profiles in HPV+ HNSCC are considered as they pertain to future clinical trial designs.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2721. doi:10.1158/1538-7445.AM2011-2721
Abstract 273: Protein kinase C-iota self regulates its expression by regulating the activity of the transcription factor Elk-1
Authors: Pillai Prajit Pillai P. , Acevedo-Duncan Mildred 
Published: June 2012

Abstract
Protein kinase C-iota (PKC-ι), a member of the atypical PKC family of Ser/Thr kinases has been recognized as an oncogene. PKC-ι manifests its effect by targeting various aspects of cancer cells such as growth, invasion and survival. Bcr-Abl has been shown to regulate the activation of the transcription factor ELK-1 which in turn regulates the expression of PKC-ι. Alternatively, we hypothesize that PKC-ι self regulates its expression by directly regulating the activity of ELK-1. Our preliminary data from immunoprecipitation studies show that PKC-ι directly associates with Elk-1 in neuroblastoma and glioma cells. PKC-ι directly phosphorylated cytoplasmic Elk-1 at Ser 383 in these cells. It has been reported that phosphorylation of cytoplasmic Elk-1 at Ser 383 results in conformational change that promotes the nuclear translocation of Elk-1, increased DNA binding and upregulation of its transcriptional activity. Furthermore, our data from cell cycle analysis showed that the nuclear translocation of Elk-1 coincided with the phosphorylation of cytoplasmic Elk-1 by PKC-ι. Robust phosphorylation of cytoplasmic Elk-1 was observed in the G1/S cell cycle phases, however, as the cells entered the M-phase, no phosphorylation of ELK-1 was observed. Similarly, the cytoplasmic to nuclear ratio of Elk-1 decreased as the cells entered the M-phase suggesting the role of PKC-ι in the promoting the nuclear translocation of Elk-1. Thus, our data supports our hypothesis that PKC-ι self regulates its expression by regulating the transcriptional activity of Elk-1.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 273. doi:10.1158/1538-7445.AM2011-273
Abstract 274: PGC-1α over-expression is related to increased cell proliferation and tumorigenesis
Authors: Park Joo-In , Shin Sung-Won , Park Eun-Seon , Yun Seong-Hoon , Lee Seon-A , Jeong Jin-Sook , Kwak Jong-Young 
Published: June 2012

Abstract
Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) is a coactivator interacting with multiple transcription factors and regulates several metabolic processes. Recent studies have focused on the role of several coactivators in cancer. Especially, a role of PGC-1α in cancer has been controversial. Some studies show that the expression level of PGC-1α decreased in certain cancer tissues and PGC-1α over-expression induces apoptosis in ovarian cancer cells. On the contrary, it has been found that PGC-1α promotes cell growth in prostate cancer cells, suggesting that PGC-1α may be involved in the pathogenesis of cancer. However, the molecular mechanism for it has not been clarified. Thus, the role of PGC-1α in the cell proliferation and tumorigenesis was evaluated using human embryonic kidney HEK293 cells that stably over-expressed PGC-1α. Forced expression of PGC-1α in HEK293 cells resulted in increased cell proliferation and anchorage-independent growth in soft agar. In addition, HEK293 cells that highly expressed PGC-1α enhanced tumor formation when these cells are subcutaneously injected into the bilateral flanks of immunodeficient Balb/c mice. To find out the molecular targets for increased proliferation and tumorigenesis by PGC-1α, GeneFishing DEG screening system was employed. As a result, one up-regulated gene (acyl-CoA binding protein; ACBP) was identified. Up-regulated ACBP expression was confirmed by Western blot and immunofluorescence microscopy. The expression of ACBP was decreased by PGC-1α siRNA transfection. These data suggest that the expression of ACBP may be related to the expression of PGC-1α. In addition, down-regulation of ACBP and PGC-1α by siRNA transfections resulted in the decreased cell proliferation. Taken together, these findings suggest that PGC-1α may promote cell proliferation and tumorigenesis. Thus, PGC-1α can be a good candidate for a molecular therapeutic target for cancers. However, the detailed molecular mechanisms for up-regulation of ACBP by PGC-1α are remained unresolved. Thus, further studies on the clarification of molecular interactions of ACBP and PGC-1α are needed.
This study was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) through the Medical Research Center for Cancer Molecular Therapy at Dong-A University (R13-2002-044-05002-0).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 274. doi:10.1158/1538-7445.AM2011-274