bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4882: Expression profiles of proinflammatory chemokines in prostate cancer cell supernatants
Authors: Reyes Niradiz , Correa Oscar , Bettin Alfonso , Tiwari Raj K. , Geliebter Jan 
Published: May 2015

Abstract
Background: Prostate cancer progression is a complex process in which chemokines and their receptors play an important role related to tumor survival, growth, and metastasis.
Objectives: 1) To determine the expression profiles of proinflammatory chemokines in prostate cancer cell line supernatants and their association with the metastatic phenotype, and 2) To determine whether these chemokines are present in the exosomes released from prostate cancer cell lines examined.
Methods: Prostate cancer lines investigated included PWR-1E (non-tumorigenic), LNCaP (low metastatic potential) and PC-3 (high metastatic potential). The Human Common Chemokines Multi-Analyte ELISArray Kit (Qiagen) was used to evaluate the expression profiles of several proinflammatory chemokines in the supernatant and in the exosomal fraction of prostate cancer cells in culture. Chemokine profiles were correlated with the metastatic abilities of the cell lines analyzed. Chemokines evaluated were CCL2, CCL3, CCL4, CCL5, CCL11, CCL17, CCL22, CXCL1, CXCL8, CXCL9, CXCL10 and CXCL11.
Results: Differential chemokine profiles in the cell lines were observed in the supernatant and in the exosomal fractions.
Conclusions: Prostate cancer cell lines with different phenotypes have different chemokine profiles, both in supernatant and in the exosomal fraction of these cells in culture. These results may be useful for the design of diagnostic, prognostic and/ or therapeutic strategies.
Financial support: Universidad de Cartagena Project Code: Res 04670 - 2012
Citation Format: Niradiz Reyes, Oscar Correa, Alfonso Bettin, Raj K. Tiwari, Jan Geliebter. Expression profiles of proinflammatory chemokines in prostate cancer cell supernatants. [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 4882. doi:10.1158/1538-7445.AM2014-4882
Abstract 4889: Oncolytic adenovirus coated with stimuli responsive block copolymer mPEG-b-poly(His) induces tumor microenvironment-specific antitumor efficacy
Authors: Yun Chae-Ok 
Published: May 2015

Abstract
Adenovirus (Ad) has shown great promise in cancer gene therapy. Ad coated with cationic polymers have already been shown to enhance transduction, but it showed nonspecific binding with cells, resulted in evoked side effect. To overcome these hurdles, in this study adenovirus coated with pH sensitive poly(His) polymer through ionic interaction for passive tumor targeting. We have characterized the effect of polymer concentration on particle size distribution, zeta potential, transduction efficiency, and structural properties. Remarkable enhanced transduction efficiency was observed in cells treated with Ad/poly(His) nanocomplex compared to naked Ad at low pH. In addition, cellular trafficking using time lapse total internal reflection fluorescence showed that the Ad/poly(His) nanocomplex was significantly enhanced cellular uptake at lower pH, in contrast to neutral pH. The biodistribution study confirmed that the Ad/poly(His) nanocomplex can effectively accumulate at the tumor site by the EPR effect and exhibited 3.3-fold higher luciferase expressions in tumor than the naked Ad. Additionally, MTT assay and cancer cell xenografts studies showed that polymer coated nanocomplex exhibited high cancer cell killing effect and also inhibited the tumor growth. Furthermore, poly(His)-coated Ad complex was not significantly inhibited by serum, in contrast to naked Ad. Moreover, Ad/poly(His) nanocomplex significantly reduced the innate immune response in contrast to naked Ad, as assessed by interleukin-6 cytokine release from macrophage cells in vivo. These results suggest that the stimuli-responsive Ad/poly(His) nanocomplex has potential to targeting tumors.
Note: This abstract was not presented at the meeting.
Citation Format: Chae-Ok Yun. Oncolytic adenovirus coated with stimuli responsive block copolymer mPEG-b-poly(His) induces tumor microenvironment-specific antitumor efficacy. [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 4889. doi:10.1158/1538-7445.AM2014-4889
Abstract 4893: USP7 modulates UV-induced PCNA monoubiquitylation by regulating DNA polymerase eta stability
Authors: Qian Jiang , Zhu Qianzhen , Pentz Kyle , He Jinshan , Wang Qien , Wani Altaf A. 
Published: May 2015

Abstract
DNA polymerase eta (Polη), a product of the Xeroderma pigmentosum variant (XPV) gene, plays a unique role in translesion DNA synthesis (TLS). It is a short-lived proteasomally degraded protein and its steady-state level is tightly controlled by multiple pathways. In this study, we have identified the deubiquitylating enzyme ubiquitin-specific protease 7 (USP7) as a novel regulator of Polη stability. Polη and USP7 interact in vitro and in vivo. Overexpression of wild-type USP7, but not its interaction-defective and catalytic mutants, deubiquitylate Polη and increase its steady-state level. The data demonstrate that both physical interaction and catalytic activity of USP7 are necessary for Polη deubiquitylation and stability regulation. Interestingly, knockout of USP7 also increased the steady-state levels and slowed the turnover of both Polη and p53, which is likely caused by destabilizing MDM2, a targeting E3 ligase for ubiquitylation of both Polη and p53. Furthermore, ectopic expression of USP7 upregulated the UV-induced PCNA monoubiquitylation. In contrast, UV-induced PCNA monoubiquitylation was not observed in XPV cells ectopically expressing USP7. Taken together, our results demonstrated that USP7 facilitates UV-induced PCNA monoubiquitylation by directly and indirectly regulating Polη stability. (The work was supported by grants from NIH.)
Note: This abstract was not presented at the meeting.
Citation Format: Jiang Qian, Qianzhen Zhu, Kyle Pentz, Jinshan He, Qien Wang, Altaf A. Wani. USP7 modulates UV-induced PCNA monoubiquitylation by regulating DNA polymerase eta stability. [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 4893. doi:10.1158/1538-7445.AM2014-4893
Abstract 4899: Small proline rich protein 3 (SPRR3) is a potential mediator of radiation resistance in HPV negative head and neck squamous cell carcinoma
Authors: Martin Joshua A. , Gunderson Dana , Kimple Randall J. 
Published: May 2015

Abstract
Purpose: Head and neck cancers (HNCs) are caused by two major etiologies that have significant prognostic significance: tobacco and human papillomavirus (HPV). Patients with HPV-positive HNC have significantly better outcomes than those with HPV-negative HNC. We have previously shown that this difference may be due, in part, to increased sensitivity to radiation in HPV-positive HNCs. In order to identify additional factors that may underlie differences in radiation sensitivity, we sought to understand radiation-induced changes in global gene expression between HPV-positive and HPV-negative HNCs.
Methods: A panel of eight cell lines, four HPV positive (UD-SCC2, UM-SCC47, UPCI-SCC90, 93-VU-147T) and four HPV negative (SCC1, SCC6, SCC22B, SCC1483 were treated with radiation (4 Gy) or mock and total RNA isolated 4, 24, and 48 hrs after treatment. Global gene expression was analyzed using Affymetrix Gene 1.1 ST array chips. Comparisons between untreated, baseline control, and post-radiation expression were made using ArrayStar. Alterations in differentially expressed genes were validated by Real-Time quantitative PCR (RT-qPCR).
Results: Out of the top 15 hits, several members of the small proline rich repeat (SPRR) family were identified. SPRR1A, SPRR1B, and SPRR3 were significantly upregulated in HPV negative as compared to HPV-positive cell lines. Differences in expression were validated using RT-qPCR in a panel of HNC cell lines.
Conclusions: We identified changes in expression of SPRR3 in HPV negative cell lines. This gene is a member of a protein family known to scavenge reactive oxygen species. Its increased expression in HPV negative HNC may mediate resistance to radiation and contribute to the poor outcomes of patients in this cohort. SPRR3 is a potential novel molecular target that could improve the outcomes of patients with HPV negative HNC.
Citation Format: Joshua A. Martin, Dana Gunderson, Randall J. Kimple. Small proline rich protein 3 (SPRR3) is a potential mediator of radiation resistance in HPV negative head and neck squamous cell 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 4899. doi:10.1158/1538-7445.AM2014-4899
Abstract 4900: The role of Interleukin (IL)-22 on the UVB-induced proliferation and inflammation of human keratinocyte cell line, HaCaT
Authors: Kim Yejin , Kim Hyemin , Choi Jiwon , Jang Mirim , Choi Jiyea , Kang Jae Seung , Lee Wang Jae 
Published: May 2015

Abstract
Interleukin 22 (IL-22), a member of IL-10 family, is a potent mediator of inflammatory responses. It is produced by activated CD4+ T cells and natural killer (NK) cells, but IL-22Rα expression is restricted to nonhematopoietic cells in the skin, pancreas, intestine, liver, lung and kidney. IL-22 suppresses IL-4 production from Th2 cells and induces acute phase proteins in liver and pancreas. It is recently found that IL-22 plays a critical role in the maintenance of epidermal homeostasis by controlling cell cycle of keratinocytes. Therefore, we investigated that role of IL-22 on the proliferation and inflammation of ultraviolet B (UVB)-irradiated human keratinocytes, HaCaT. First, we found the expression of IL-22Rα mRNA and protein level was increased in HaCaT by UVB (100 J/m2) irradiation. Interestingly, the translocation of IL-22Rα from cytosol to membrane was increased by UVB irradiation. When UVB-irradiated HaCaT was cultured in the presence of recombinant IL-22 (rIL-22), the suppressed proliferation of HaCaT by UVB was rescued. In addition, we found that the production of UVB-induced pro-inflammatory cytokines, such as IL-1α, IL-6 and IL-18, was increased by the treatment of rIL-22. Taken together, IL-22 plays a critical role in inflammation by UVB irradiation. And it suggests that UVB-induced skin inflammation could effectively be controlled by the regulation of IL-22 production and its action on keratinocytes.
Note: This abstract was not presented at the meeting.
Citation Format: Yejin Kim, Hyemin Kim, Jiwon Choi, Mirim Jang, Jiyea Choi, Jae Seung Kang, Wang Jae Lee. The role of Interleukin (IL)-22 on the UVB-induced proliferation and inflammation of human keratinocyte cell line, HaCaT. [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 4900. doi:10.1158/1538-7445.AM2014-4900
Abstract 4901: Clostridium cluster XIVa species an early biomarker in radiation injury
Authors: Ahmed Ishfaq , McLauglin William , Anant Shrikant , Umar Shahid , Papineni Rao V. 
Published: May 2015

Abstract
Radiation therapy is being used in the treatment of nearly 60% of the current cancer patients. In spite of the best efforts to provide special care in minimizing radiation exposure, significant radiation injury remains a common side-effect particularly to the gastro intestinal tract. Severe injury to GI tract may lead to multiple organ dysfunction syndrome. The status of fecal microbiota has been proposed as a rapid diagnostic platform in radiation injury. Gut microbes play a role in immunity, health, and disease. Imbalances in gut microbiota are related to numerous disorders, such as inflammatory bowel disease, colorectal cancer (CRC), and atopy. In patients with immune suppression due to high-dose chemotherapy or that undergoing radiation therapy, disruption of the microbiota through antibiotics and impairment of host immunity gives rise to perturbations favoring intestinal domination by pathogenic species, resulting in increased bacterial translocation and susceptibility to systemic infection. Here, using real-time PCR assays, we assessed the immediate changes and quantitative alterations to fecal microbiota in response to radiation injury. Swiss-albino Mice were subjected to 10 Gy X-ray whole body irradiation doses using commercially available X-RAD 320 irradiator (1Gy/min; F2 beam hardening filter 1.5mm Al, 0.25mm Cu, 0.75mm Sn; Precision X-ray inc, USA). Fecal samples collected immediately after the radiation exposure were analyzed. We show that Clostridium cluster XIVa that accounts for almost 60% of the mucin-adhered microbiota is significantly increased (11.71 +/- 0.29 fold n=6) in the fecal samples, compared to the total bacteria and other bacteria that tend to enrich in the luminal region. Along with the Bacteroidetes and Proteobacteria from the luminal region, minimal changes in the levels of Firmicutes that colonize the mucin layer were observed. Further, these changes varied considerably between the subjects and were inconsistent compared to the Clostridium cluster species. Clostridium cluster XIVa has been proposed to be the mucosal butyrate producers producing butyrate close to the epithelium. This enhances butyrate bioavailability required in treating diseases such as inflammatory bowel disease. These findings provide opportunities to evaluate the potential use of intestinal microbiota as biomarkers in radiation injury. Also, provides insights into the microbial changes tantamount to the radiation induced GI injury.
Citation Format: Ishfaq Ahmed, William McLauglin, Shrikant Anant, Shahid Umar, Rao V. Papineni. Clostridium cluster XIVa species an early biomarker in radiation injury. [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 4901. doi:10.1158/1538-7445.AM2014-4901
Abstract 4906: mTOR kinase inhibition enhances radiosensitivity in glioblastoma
Authors: Tandle Anita T. , Tofilon Philip , Camphausen Kevin 
Published: May 2015

Abstract
Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor and predicts a poor prognosis despite current treatment modalities. Aberrant activation of the phosphatidyl-inositol-3-kinase (PI3K) pathway is observed in nearly 90% of GBMs making the downstream effector, mammalian target of rapamycin (mTOR), a potential drug target. mTOR is a serine/threonine kinase that regulates cell growth, proliferation, survival, protein translation and metabolism by integrating signals received from the PI3 K/Akt signaling pathway. The allosteric mTOR inhibitor rapamycin has failed in the clinic as a treatment for GBM patients. Therefore, in the current study, we examined the potential benefit of MLN0128, a novel potent mTOR ATP competitive inhibitor, as a therapeutic strategy for GBM. We assessed in vitro antiproliferative activity of MLN0128 in a panel of GBM tumor and stem cell lines. MLN0128 significantly inhibited cell proliferation of both GBM tumor and stem cells. It decreased the phosphorylation of mTOR, Akt, S6, 4E-BP1, and NDRG1, inhibiting both mTORC1 and mTORC2 signaling in GBM. Thus, MLN0128 appears to be superior in blocking mTORC1/2 signaling in contrast to rapamycin. It inhibited migration and invasion of GBM cells in a matrigel coated chamber assay. On clonogenic survival assay MLN0128 decreased GBM cell survival and increased radiosensitivity. To investigate the mechanism of radiosensitization, the induction and repair of DNA double-strand breaks were evaluated by γH2AX foci formation. MLN0128 exposure significantly delayed the dispersal of radiation induced γH2AX foci formation in both tumor and stem cells. These results indicate that MLN0128 enhances tumor cell radiosensitivity by inhibiting DNA repair. Next we combined MLN0128 with temozolomide (TMZ), a FDA approved radiosensitizer for GBM therapy. Although, we did not observe any synergy in inhibition, addition of TMZ did not adversely affect MLN0128 inhibitory effects. These findings support the rationale for clinical testing of MLN0128 in patients with GBM to provide insight towards optimizing therapeutic efficacy of mTOR kinase inhibitors with standard care.
Note: This abstract was not presented at the meeting.
Citation Format: Anita T. Tandle, Philip Tofilon, Kevin Camphausen. mTOR kinase inhibition enhances radiosensitivity in glioblastoma. [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 4906. doi:10.1158/1538-7445.AM2014-4906
Abstract 4912: Hyperthermia induced NO repressed NFκB regulates IR-induced EMT, CSC self-renewal and pluripotency
Authors: Dinges Corinne , Natarajan Mohan , Aravindan Sheeja , Herman Terence S. , Aravindan Natarajan 
Published: May 2015

Abstract
Based on clinical evidence, hyperthermia treatment (HT) in combination with radiation (IR) achieves superior local control for recurrent chest wall breast cancer (BCa). The effect of HT combined with IR is due partly to its independent cytotoxic effects, and partly to its radiosensitizing effect. Recently, we have shown that apoptosis upon hyperthermia of BCa cells is regulated by NO-mediated suppression of NFκB. Also, we have demonstrated that tumor cells that survive a course of IR are instrumental in tumor relapse and progression. Accordingly, we investigated whether HT exerts NO-NFκB axis dependent regulation of IR-induced alterations in factors that drive the EMT, CSCs self-renewal capacity and pluripotency maintenance in surviving BCa Cells. Human breast adenocarcinoma (MCF-7) cells either mock-irradiated or exposed IR (2Gy) with or without HT (43°C for 1h) were analyzed for transcriptional regulation of 93 stem cell related molecules using QPCR profiling. NFκB (p50/p65) overexpression, muting by ΔIκBα (with IR) and NO induction by SNP (with HT) approach were used to delineate the role of HT-induced NO and the selective targeting of IR-induced NFκB. Nanog, Sox-2, ABCG-2, N-Cadherin and Myc expressions were examined with immunoblotting. IR profoundly increased the transactivation of 80 stem-cell related molecules. Interestingly, HT reverted the activation of 79 IR-induced genes. Attenuation of all 80 IR-induced genes observed after blocking NFκB with ΔIκBα and by increasing intracellular NO with SNP demonstrated the significant role of NO dependent NFκB suppression in HT-induced inhibition of IR modulated stem-cell related transcriptome. Expression levels of Nanog, Sox-2, ABCG-2, N-Cadherin and Myc validates the potential of HT in mitigating IR-induced stemness. Together this data demonstrates that HT attenuates IR-induced stemness in BCa cells and further imply that HT induced increase in NO may alleviate stemness by selectively targeting IR-induced NFκB.
Citation Format: Corinne Dinges, Mohan Natarajan, Sheeja Aravindan, Terence S. Herman, Natarajan Aravindan. Hyperthermia induced NO repressed NFκB regulates IR-induced EMT, CSC self-renewal and pluripotency. [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 4912. doi:10.1158/1538-7445.AM2014-4912
Abstract 4924: Mucolytic drug N-Acetylcystein improves 89Zr-trastuzumab HER2-immunoPET imaging by restoring accessibility to HER2 hampered by membrane mucin overexpression in a HER2 positive MUC4 overexpressing xenograft mouse model
Authors: Wimana Zena , Gebhart Geraldine , Morandini Renato , Flamen Patrick , Ghanem Ghanem 
Published: May 2015

Abstract
89Zr-trastuzumab, a 89-Zirconium radiolabeled anti-HER2 monoclonal antibody, has been shown appropriate to enable positron emission tomography (PET) imaging of HER2 positive lesions in breast cancer (BC) patients. Binding of 89Zr-trastuzumab to the HER2 receptor, a prerequisite could be undermined by one of the postulated resistance mechanisms to trastuzumab, i.e. the interference of cell membrane glycoproteins mucins. This study aimed to assess whether mucolytic drug N-Acetylcystein (NAC) could enhance the uptake of 89Zr-trastuzumab in a HER2 positive and MUC4 overexpressing xenograft mouse model.
Materials & Methods: Trastuzumab was first coupled with the chelate N-succinyl-desferal ester, subsequently N-SucDF-trastuzumab was radiolabelled with 89Zr-oxalate in a HEPES buffered solution and purified by size exclusion chromatography. The impact of NAC on 89Zr-trastuzumab PET was studied in a dual model xenograft generated by s.c. inoculation of HER2+/MUC4- SKBr3 and JIMT1 HER2+/MUC4- BC cell lines, with the latter overexpressing MUC4. Mice were treated with NAC p.o. during 6 days. Body distribution and uptake of the tracer were measured 1) by in vivo PET/CT imaging and by 2)ex vivo tissue analysis.
Results: In mice treated with NAC, there was a significant increase of the Standardized Uptake Value (SUV) mean, SUVmax and SUV Volume Histogram (SVH) in the MUC4 overexpressing tumors compared to the control group. This was not the case for MUC4 negative SKBR3 tumors. Furthermore, ex vivo body distribution data supported these results with a significant increase of radioactivity uptake in the MUC4 positive tumors and no change in non-tumoral tissues
Conclusion: N-Acetylcysteine may be an interesting drug to improve the accessibility of trastuzumab to its receptors, HER2, by affecting mucin masking.
Note: This abstract was not presented at the meeting.
Citation Format: Zena Wimana, Geraldine Gebhart, Renato Morandini, Patrick Flamen, Ghanem Ghanem. Mucolytic drug N-Acetylcystein improves 89Zr-trastuzumab HER2-immunoPET imaging by restoring accessibility to HER2 hampered by membrane mucin overexpression in a HER2 positive MUC4 overexpressing xenograft mouse model. [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 4924. doi:10.1158/1538-7445.AM2014-4924