bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3549: RUNX3 is a biomarker for determining sensitivity to pheophorbide a-photodynamic therapy in human oral squamous cell carcinoma.
Authors: Moon Sook , Bae Jung Yoon , Lee Doo Young , Park Gyeong Ju , Yoo Hyun , Ko Hyo jin , Kim Yong Chul , Kim Jin 
Published: August 2014

Abstract
Background & Objective: Photodynamic therapy (PDT) with photosensitizer is one of the promising modalities for cancer treatment. For clinical use of PDT, the screening process for sensitive cancers to PDT should be preceded. For this, we investigated a molecular biomarker to determine the sensitivity to Pa-PDT in immortalized human oral keratinocytes (IHOK) and OSCC cell lines.
Methods: For this study, two immortalized oral keratinocytes (IHOK-p, IHOK-s) and 8 oral squamous cell carcinoma (OSCC) cell lines were used. After cells were treated with Pa-PDT, phototoxicity and the level of reactive oxygen species (ROS) were measured. Apoptosis was measured using annexin V/PI staining and western blotting. mRNA and proteins of apoptotic genes were investigated by RT-PCR, real-time PCR, and western blotting. Transfection was performed using RUNX3-small interfering RNA.
Results: After Pa-PDT, cell viability was more than 50% reduced and ROS generated in IHOK and OSCC. In addition, apoptosis occurred in all cell lines. Among apoptosis-related genes, Bim expression was altered following Pa-PDT. Therefore, mRNA and protein expression of RUNX3, a gene upstream of Bim were examined by Pa-PDT. We found that RUNX3 was highly responsive to Pa-PDT. Furthermore, knockdown of RUNX3 expression reduced cytotoxicity by Pa-PDT. In addition, we found that the cytotoxicity by Pa-PDT was proportional to RUNX3 expression in OSCC cell lines.
Conclusion: This is the first study to find a new target molecule that enhances Pa-PDT effects in IHOK and OSCC cell lines. These results should be further proven by animal studies to apply to clinical trials. Nevertheless, the development of a PDT-dependent biomarker could provide a novel approach to improve the effects of PDT in oral precancerous and cancerous lesions.
Acknowledgments This study was supported by a grant of the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (No. A100490).
Citation Format: Sook Moon, Jung Yoon Bae, Doo Young Lee, Gyeong Ju Park, Hyun Yoo, Hyo jin Ko, Yong Chul Kim, Jin Kim. RUNX3 is a biomarker for determining sensitivity to pheophorbide a-photodynamic therapy in human oral squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3549. doi:10.1158/1538-7445.AM2013-3549
Abstract 3550: Benefits of follow-up screening for Epstein Barr virus DNA in patients with localized nasopharyngial carcinoma .
Authors: Hsu Cheng-Lung 
Published: August 2014

Abstract
Objective: In this study, we investigated whether detection of Epstein Barr virus (EBV)-DNA in plasma is a prognostic indicator of disease recurrence in patients who have been treated for localized nasopharyngeal carcinoma.
Methods: Study subjects comprised 389 patients who had received treatment for localized nasopharyngeal carcinoma in our outpatient department. Copy numbers of EBV-DNA in plasma were assessed by real-time quantitative PCR. Patients in whom disease recurrence was suspected underwent positron emission tomography (PET) imaging studies.
Results: Plasma EBV-DNA was detectable in 60 of 63 (95%) patients with metastatic disease and all had positive PET findings. In addition, of the 45 patients with localized recurrent disease, plasma EBV-DNA was detectable in 23 (51%) patients and positive PET scan results were obtained in 40 (89%) of the patients. Of the 284 patients who were disease free, plasma EBV-DNA was detected in 90 (32%) patients. Of the 19 patients in disease free group who were suspected disease recurrence with PET scanning, 7 positive PET images were found including 3 second primary malignancy and 4 non-cancer lesions. Two lymphoma cases with positive EBV-DNA value sequentially attacked before or after their NPC were diagnosed.
Conclusions: EBV-DNA is a good marker of localized disease recurrence/metastasis after treatment for NPC but needs to be combined with imaging studies such as PET to monitor disease status.
Citation Format: Cheng-Lung Hsu. Benefits of follow-up screening for Epstein Barr virus DNA in patients with localized nasopharyngial carcinoma . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3550. doi:10.1158/1538-7445.AM2013-3550
Abstract 3559: FKBP5 is an androgen-responsive gene in thyroid cancer cells.
Authors: MacEwan Melanie E. , Wong Ken , Swati Ismatun , Xie Suqing , Rasul Mohammad , Ardacheva Olena , Buchsbaum Joseph , Shin Edward , Moscatello Augustine , Schantz Stimson , Tiwari Raj K. , Geliebter Jan 
Published: August 2014

Abstract
There has been a steady increase in the incidence thyroid cancer in the United States, with over 56,000 cases predicted for 2012. The increased aggressiveness of the disease and poorer clinical outcome in men and postmenopausal women may be due to androgen/androgen receptor (AR) related functions. FK506 binding protein 51 (FKBP5) is a member of the immunophilin family and plays a role in steroid receptor function. Further, FKBP5 regulates the NFkB and AKT pathways and is thought to be relevant to the neoplastic process. Immunohistochemical analysis of 38 papillary thyroid cancer (PTC) specimens indicated that androgen receptor is expressed in both normal and cancerous epithelial cells, in both men and women. Analysis of AR expression in thyroid cell lines indicated that the normal thyroid cell line, Nthy-ori 3-1 and PTC cell lines BCPAP and TPC-1 expressed very low levels of AR, as measured by qRT-PCR and western blotting (&gt;1000 fold less than the prostate cancer cell line, LNCaP). In contrast, PTC/anaplastic 8505C cells expressed higher levels of AR protein (approximately one third the level expressed in LNCaP cells). Upon addition of androgen, AR in 8505C translocated into the nucleus (as determined by immunocytochemistry) and upregulated transcription of both AR (∼1.7 fold) and FKBP5 (∼1.8 fold). To more fully understand the function of androgen/AR in thyroid cells, the AR cDNA from pSG5-AR was subcloned into the pcDNA3.1+ expression vector and stably transfected into thyroid cell lines. Primers for qRT-PCR of the endogenous or the transfected gene were designed. The 84E7 clone of transfected 8505C cells expressed 68 fold higher levels of AR mRNA than 8505C and 16 fold higher AR protein expression (∼5 fold higher AR protein expression than LNCaP). Upon addition of DHT to clone 84E7, AR translocated into the nucleus, and increased AR and FKBP5 mRNA expression (∼3 fold and ∼13 fold, respectively). The association between androgens/AR and upregulation of FKBP5 in thyroid cancer cells suggests that FKBP5 may play a role in thyroid cancer etiology and the different clinical presentation and outcomes between young women and men/postmenopausal women.
Citation Format: Melanie E. MacEwan, Ken Wong, Ismatun Swati, Suqing Xie, Mohammad Rasul, Olena Ardacheva, Joseph Buchsbaum, Edward Shin, Augustine Moscatello, Stimson Schantz, Raj K. Tiwari, Jan Geliebter. FKBP5 is an androgen-responsive gene in thyroid cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3559. doi:10.1158/1538-7445.AM2013-3559
Abstract 3564: ARID1A promotes endocrine resistance in ER+ breast cancer cells.
Authors: Chabot Catherine , Basik Mark 
Published: August 2014

Abstract
We recently identified the ARID1A gene as a new candidate tumor suppressor gene (TSG), mutated in the T47D cells, an ER+ breast cancer cell line. We have shown previously that re-expression of ARID1A in T47D cells inhibits both proliferation and anchorage-independent growth and also that nuclear expression of ARID1A is progressively decreased during the later stages of breast tumor progression. ARID1A encodes a member of the SWI/SNF family of proteins, which function to ‘remodel’ chromatin and thereby regulate gene expression programs. Most breast cancers express the estrogen receptor (ER), and are thus responsive to the mitogenic effects of the estrogen hormone as well as to the anti-proliferative effects of anti-estrogen therapies. To uncover the potential role of ARID1A in the regulation of estrogen signaling in ER+ breast cancer cells, we tested if re-expression of ARID1A may also affect estrogen-dependent growth. Surprisingly, we found that re-expression of ARID1A in T47D cells results in a decrease in the proliferative response of these cells to estrogen but also to a decrease in the viability of the cells in hormone-depleted conditions. Then, to further investigate if the loss of ARID1A may promote estrogen-independent growth, we silenced ARID1A expression by shRNA in MCF-7 cells that express moderate levels of ARID1A protein. We found that ARID1A-silencing increases the survival of MCF-7 cells in the absence of hormones. In addition, we also observed that phosphorylation of FAK and Src, whose activities have been suggested to be important in endocrine resistance, is highly increased in the absence of ARID1A. All together, these results suggest that loss of ARID1A can promote endocrine-resistance in ER-positive breast cancer cells.
Citation Format: Catherine Chabot, Mark Basik. ARID1A promotes endocrine resistance in ER+ breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3564. doi:10.1158/1538-7445.AM2013-3564
Abstract 3566: Altering the expression levels of CRABPII and FABP5 by curcumin sensitizes MDA-MB231 mammary carcinoma cells to retinoic acid mediated growth suppression.
Authors: Thulasiraman Padmamalini , McAndrews Daniel 
Published: August 2014

Abstract
Although great progress has been made in the treatment of breast cancer, drug resistance is a major problem in breast cancer patients, promoting the need to understand the molecular mechanisms involved in the disease and identify future targeted therapy. Curcumin, a hydrophobic polyphenol extracted from the plant, Curcuma Longa, has been reported to possess anti-tumorigenic properties in several different cancers. Curcumin has been widely used in combination with other therapies to enhance apoptosis and promote anti-carcinogenic activities. In this study, we explore the effect of curcumin on retinoic acid binding proteins, cellular retinoic acid binding protein II (CRABPII) and fatty acid binding protein 5 (FABP5). Retinoic acid (RA) can inhibit carcinoma cell growth by activating nuclear retinoic acid receptors (RAR) but enhances cell proliferation and survival by activating a different nuclear receptor, namely PPARβ/δ (peroxisome proliferator activated-protein β/δ). The hormone is either targeted to RAR by CRABPII, or delivered to PPARβ/δ by FABP5. Hence, RA exerts anticarcinogenic activities in cells that express a high CRABPII/FABP5 ratio but facilitates the growth of carcinoma cells in which this ratio is low. We investigated whether curcumin can alter the ratio of CRABPII/FABP5 and promote retinoic acid mediated growth suppression in RA resistant MDA-MB231 mammary carcinoma cells. Using quantititive real-time PCR, we report that 30 μM curcumin suppresses the mRNA level of FABP5 and PPARβ/δ, while concomitantly enhances CRABPII mRNA expression by 3-fold. Additionally, we performed western blot analysis and demonstrated that in addition to the downregulation of FABP5 mRNA,curcumin downregulates the protein expression of FABP5 by approximately 50%. Interestingly, we have observed that curcumin sensitizes MDA-MB231 cells to retinoic acid mediated growth suppression by using MTT assay. The combination of curcumin with RA suppresses mammary carcinoma growth of MDA-MB231 cells by 30-40% in comparison to curcumin alone. Thus, altering the expression level of CRABPII and FABP5 by curcumin diverts the RA signalling from the proliferative FABP5/PPARβ/δ pathway to the growth inhibitory CRABPII/RAR path and sensitizes MDA-MB231 cells to RA-mediated growth suppression.
Citation Format: Padmamalini Thulasiraman, Daniel McAndrews. Altering the expression levels of CRABPII and FABP5 by curcumin sensitizes MDA-MB231 mammary carcinoma cells to retinoic acid mediated growth suppression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3566. doi:10.1158/1538-7445.AM2013-3566
Abstract 357: A glial origin for medulloblastoma and inhibition of MYCN stabilization.
Authors: Bolin Sara , Lau Jasmine , Savov Vasil , Chen Justin , Persson Anders I. , Hede Sanna-Maria , Weiss William A. , Swartling Fredrik J. 
Published: August 2014

Abstract
The origin of MYCN-driven medulloblastoma, a poor-prognosis childhood brain tumor is not known. We recently showed that MYCN could generate tumors with high penetrance from a glutamate transporter (GLT1) promoter in a transgenic model (GTML) of medulloblastoma. By using Rosa26-lsl-LacZ reporters we also showed that GLT1-positive neural stem cells (NSCs) from normal brain represent putative cells of tumor origin.
GTML mice generate aggressive MYCN-driven medulloblastoma 2-3 months after birth. BrdU-labeling of 3-week-old GTML mice detected significantly more proliferation in thalamic forebrain cells and of BrdU/BLBP-double positive Bergmann glia in the cerebellum as compared to corresponding normal brain. Retroviral tagging with the RCAS/tv-a system marked BLBP- or GFAP-positive tumor initiating cells and expression analysis could further determine genetic profiles of tumor origin.
Interestingly, MYCN levels and early proliferation of brain tumors could be reduced by specific inhibition of CDK2 or by using the bromodomain inhibitor JQ1. Both treatment strategies induced tumor cell senescence as seen by SA-beta-gal activity and by downregulated Lamin B1. Our results propose a radial glial or a Bergmann glial origin for MYCN-driven medulloblastoma and further suggest ways to inhibit tumor growth by repressing MYCN stabilization.
Citation Format: Sara Bolin, Jasmine Lau, Vasil Savov, Justin Chen, Anders I. Persson, Sanna-Maria Hede, William A. Weiss, Fredrik J. Swartling. A glial origin for medulloblastoma and inhibition of MYCN stabilization. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 357. doi:10.1158/1538-7445.AM2013-357
Abstract 3574: Studies of castrate resistant 22Rv1 cells identifies AR regulated interrelated networks of transcription factors, co-regulators, chromatin, and nuclear scaffolding proteins.
Authors: Mudryj Maria , Libertini Stephen J. , Lombard Alan P. 
Published: August 2014

Abstract
Prostate cancer development, progression and acquisition of castrate resistance are reliant on the activity of the androgen receptor (AR), a transcription factor that governs the proliferation of prostate cancer cells. Multiple studies have focused on the principle components that are critical for cell cycle transversal and these studies have identified members of the E2F/RB family, c-Myc, cyclins and cyclin dependent kinase inhibitors as key proteins that are instrumental in prostate cell proliferation and development of castrate resistance. But the mechanism by which the AR dominates this process is unclear. To identify the link between the AR and cell cycle control we used 22Rv1 cells which are castrate resistant due to the expression of low molecular weight AR forms that are missing the ligand binding domain. However, a siRNA mediated decrease in AR expression induces a growth arrest confirming that proliferation is AR dependent. RNA-seq analysis of gene expression at castrate levels of androgen and following AR ablation identified transcripts that were AR dependent. This methodology reduced the number of AR regulated transcripts, by excluding transcripts regulated by super-physiological levels of androgens. The AR regulated transcripts included previously identified genes (PMEPA1, C1orf116, PCDH7, APP) including NFAT a gene shown to be regulated by a low molecular weight AR isoform. The analysis also revealed that interrelated networks of transcription factors and co-factors were AR transactivated or repressed. These included proteins such as the LBR, LMNB, TMPO and SATB1 that do not directly promote transcription, but rather link chromatin to the nuclear membrane or scaffolding, suggesting that the AR may modulate gene expression through epigenetics mechanisms. Network analysis showed connections between these proteins and cell cycle components including E2Fs and Myc where a number of the regulated transcripts are known E2F or Myc targets. In addition, this analysis identified a number of non-coding RNAs; some that have been previously described and some that have yet to be annotated. qPCR studies found that a number of the transcripts regulated in 22Rv1 cells are also AR regulated in LNCaP cells. Coupled with ChIP-seq data, the study characterizes the link between the AR and the cell cycle machinery and chromatin modulating proteins.
Citation Format: Maria Mudryj, Stephen J. Libertini, Alan P. Lombard. Studies of castrate resistant 22Rv1 cells identifies AR regulated interrelated networks of transcription factors, co-regulators, chromatin, and nuclear scaffolding proteins. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3574. doi:10.1158/1538-7445.AM2013-3574
Abstract 3576: USP22 modulates AR activity to critically regulate prostate cancer progression.
Authors: Schrecengost Randy , Dean Jeffry , Stanek Tim , Birbe Ruth , Hicks Jessica , Visakorpi Tapio , DeMarzo Angelo , McMahon Steve , Knudsen Karen 
Published: August 2014

Abstract
Recently, the deubiquitylase Ubiquitin-specific protease 22 (USP22) was identified as a member of the 11 gene ‘death-from-cancer’ signature, which can predict poor response to therapy and/or propensity toward metastasis of multiple tumor types, including breast and prostate. However, the mechanism for how USP22 impacts cancer is currently unknown. Our new data implicate a specific role for USP22 in hormone-dependent cancers, especially prostate cancer (PCa) where USP22 expression is elevated in primary and metastatic PCa. USP22 has an established role in regulating oncogenic c-Myc activity as it is recruited by c-Myc for transcriptional activation through deubiquitylation of histones, and is necessary for c-Myc-mediated cell transformation. Similarly, our data in PCa cells demonstrates that USP22 controls c-Myc activity but does not affect expression levels.
Additional data has also identified USP22 as a critical effector of androgen receptor (AR) levels and output. This is of great clinical relevance since PCa is intricately dependent on AR signaling for disease initiation and progression to castrate resistant disease (CRPC). First, USP22 overexpression in hormone-dependent and CRPC cell lines increased AR protein expression and activity, but did not perturb transcript. Second, in the absence of ligand, USP22 upregulation resulted in enhanced AR recruitment to target genes, as determined by chromatin immunoprecipitation, which corresponded with significant enhancement of cell proliferation and BrdU incorporation. Third, USP22 depletion resulted in attenuated AR activity and caused a significant reduction in AR protein levels that could be attributed to protein stability. Importantly, in the CRPC setting, USP22 depletion dramatically inhibited in vivo tumor growth while expression correlated with decreased time for tumor regression.
In sum, the data suggest that USP22 upregulation is sufficient for aberrant c-Myc activity, altered AR expression and activity, and establishment of a CRPC phenotype. We propose that modulation of UPS22 expression and/or activity may present a novel platform to achieve combinatorial suppression of AR and c-Myc function, and therefore could be potentially developed as a novel approach for treatment of PCa.
Citation Format: Randy Schrecengost, Jeffry Dean, Tim Stanek, Ruth Birbe, Jessica Hicks, Tapio Visakorpi, Angelo DeMarzo, Steve McMahon, Karen Knudsen. USP22 modulates AR activity to critically regulate prostate cancer progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3576. doi:10.1158/1538-7445.AM2013-3576
Abstract 3579: Mechanistic roles of cytochrome P4501A1 and 1A2 in lung carcinogenesis mediated by polycyclyc aromatic hydrocarbons: Implications for lung cancer in humans .
Authors: Moorthy Bhagavatula , Zhou Guodong , Wang Lihua , Jiang Weiwu 
Published: August 2014

Abstract
Humans are frequently exposed to polycyclic aromatic hydrocarbons (PAHs). Cytochrome P4501A (CYP1A) enzymes play important roles in the activation of PAHs such as 3-methylcholanthrene (MC) to DNA-binding metabolites, which in turn mediate carcinogenesis in target organs such as lung, breast, and skin. In this study, we tested the hypothesis that CYP1A1 and 1A2 play mechanistic roles in PAH-mediated carcinogenesis and tumorigenesis. Eight week-old female wild type (WT) (A/J) mice or mice lacking the gene for CYP1A1 or CYP1A2 on the A/J background were treated with a single dose of MC (40 μmol/kg), benzo[a]pyrene (BP), or vehicle (corn oil), and liver and lung tumors were studied after 28 weeks. While 100% of WT or Cyp1a2-null mice exposed to MC showed lung tumors after 28 weeks, about 80% of the Cyp1a1-null mice showed lung tumors. However, there were striking differences in the Cyp1a1-null and Cyp1a2-null mice in regard to lung tumor multiplicities. The WT mice treated with MC had about 15 lung tumors/animal. On the other hand, the Cyp1a2-null mice displayed about 40 lung tumors/animal, while the Cyp1a1-null mice showed about 2-3 tumors/mouse. Although BP was less potent in inducing lung tumors in the WT mice compared to MC, it was similar to MC In that tumors were suppressed in the Cyp1a1-null mice and augmented in the Cyp1a2-null mice. DNA adduct studies at early time points showed increased MC or BP adducts in lungs of Cyp1a2-null mice compared to WT mice, and decreased adduct formation in the Cyp1a1-null mice, supporting the hypothesis that DNA adducts are early biomarkers of PAH-mediated carcinogenesis. Immunohistochemical studies showed that CYP1A1 was overexpressed in the tumorous portions of the lung in the Cyp1a2-null or WT mice, compared to non-tumorous regions. These results suggest that CYP1A1 contributes to the formation of tumorigenesis by PAHs, while CYP1A2 protects against carcinogenesis mediated by PAHs, presumably through it role in PAH detoxification. In conclusion, our results strongly suggest that CYP1A1 and 1A2 could be novel candidates for cancer prevention and therapy though either inhibition of CYP1A1 or induction of CYP1A2. (Supported by NIH grant ES009132.)
Citation Format: Bhagavatula Moorthy, Guodong Zhou, Lihua Wang, Weiwu Jiang. Mechanistic roles of cytochrome P4501A1 and 1A2 in lung carcinogenesis mediated by polycyclyc aromatic hydrocarbons: Implications for lung cancer in humans . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3579. doi:10.1158/1538-7445.AM2013-3579