bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 310: Enhanced stability of D-type cyclins correlates with glioblastoma resistance to ionizing radiation
Authors: Guessous Fadila , Benamar Mouadh , Zhong Hui , Abbas Tarek 
Published: July 2017

Abstract
Transition from G1 to S phase of the cell cycle is promoted by D-type cyclins (D1, D2 and D3), regulatory subunits critical for the activation of cyclin dependent kinases 4 and 6 (CDK4/6), which phosphorylate and inactivate the retinoblastoma protein (pRb) and activate the transcription factor E2F1 to promote the expression of genes essential for DNA synthesis. Deregulated expression of D-type cyclins is frequently observed in human malignancies and correlates with increased proliferation. Cyclin Ds overexpression is also associated with radioresistance, leading to radiotherapy failure and disease recurrence. Cyclin D1 undergoes ubiquitin-dependent degradation following the exposure of cancer cells to ionizing radiation (IR), and this has been shown to be critical for IR-induced G1 growth arrest and sensitivity of cancer cells to IR. While the role of cyclin D1 overexpression in drug resistance is already well documented, less is known about the role of cyclins D2 and D3 in radio-resistance in human cancer cells, particularly in brain neoplasms. In the present study, we investigated the effect of IR on different D-type cyclins (D1, D2, D3) in human glioblastoma cell lines as well as in tumor-derived mouse oligodendrocytes progenitor cells (OPCs). Here, we show that exposure of human astrocytes to increasing levels of IR led to a rapid proteasomal degradation of all three D-type cyclins. On the other hand, IR failed to induce significant cyclin Ds degradation in a number of human glioblastoma cells (U87, A172, U251, Snb19). Analysis of cell cycle profile of all glioblastoma cells tested and exposed to IR showed prominent cell cycle arrest in G1 starting at 24 hours following exposure. Furthermore, we show that the steady-state levels of D-type cyclin is higher in OPCs compared to mouse NIH3T3 cells and fail to undergo proteasomal degradation following IR exposure. Collectively, these results suggest that the degradation of D-type cyclins is not critical for IR-induced G1 cell cycle arrest in GMB and may underlie their resistance to IR. Understanding the role of cyclin Ds in promoting radioresistance may lead to a useful pharmacological strategy to enhance radiotherapy outcome and help implement a more effective treatment modality.
Citation Format: Fadila Guessous, Mouadh Benamar, Hui Zhong, Tarek Abbas. Enhanced stability of D-type cyclins correlates with glioblastoma resistance to ionizing radiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 310. doi:10.1158/1538-7445.AM2017-310
Abstract 3106: Targeted delivery via Elastin Like Polypeptide: Biodistribution of a doxorubicin derivative in MDA-MB231 human breast cancer xenografts in mice
Authors: Dragojevic Sonja , Ryu Jung Su , Kratz Felix , Raucher Drazen 
Published: July 2017

Abstract
The anticancer agent doxorubicin has been widely used in the treatment of a variety of hematological malignancies and solid tumors. Despite doxorubicin’s efficiency in eradicating tumor cells, severe damage to healthy tissues, along with cardiotoxicity, limits its use in clinics. To overcome adverse side effects, improve patient safety, and enhance therapeutic efficacy, we have designed a thermally responsive biopolymer doxorubicin carrier that can be specifically targeted to tumor tissue by locally applying mild hyperthermia (41 degrees C).
The developed drug vehicle is composed of: a cell penetrating peptide (SynB1) to promote tumor and cellular uptake; thermally responsive Elastin like polypeptide (ELP); and the (6-maleimidocaproyl) hydrazone derivative of doxorubicin (DOXO-EMCH) containing a pH-sensitive hydrazine linker that releases dox in the acidic tumor environment. We used the in vivo imaging system, IVIS, to determine the biodistribution of doxorubicin-delivered ELP in MDA-MB231 triple negative human breast cancer cell line xenografts in nude mice. Tumor bearing mice were treated with a single IV injection of 10 mg/kg doxorubicin equivalent dose with free doxorubicin, thermally responsive SynB1 ELP 1-DOXO, and a thermally nonresponsive control biopolymer, SynB1 ELP 2-DOXO. Following a 2 hour treatment with hyperthermia, tumors showed a 2-fold higher uptake when treated with SynB1 ELP 1-DOXO compared to free doxorubicin. Accumulation of the thermally non-responsive control SynB1 ELP2 -DOXO was comparable to free doxorubicin, indicating that an increase in dox accumulation with ELP is due to aggregation in response to thermal targeting. Higher levels of SynB1 ELP1 -DOXO and SynB1 ELP2 -DOXO with respect to free doxorubicin were observed in kidneys. Fluorescence intensity from hearts of animals treated with SynB1 ELP1 - DOXO show a 5-fold lower accumulation of doxorubicin than the same dose of free doxorubicin. SynB1-ELP1-DOXO biopolymers demonstrated a 6-fold increase in tumor/heart ratio in comparison to free doxorubicin, indicating preferential accumulation of the drug carrier in tumors.
Overall, thermally targeted polymers are a promising therapy to enhance tumor targeting and uptake of anticancer drugs and to minimize free drug toxicity in healthy tissues, representing a great potential for clinical application.
Citation Format: Sonja Dragojevic, Jung Su Ryu, Felix Kratz, Drazen Raucher. Targeted delivery via Elastin Like Polypeptide: Biodistribution of a doxorubicin derivative in MDA-MB231 human breast cancer xenografts in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3106. doi:10.1158/1538-7445.AM2017-3106
Abstract 3111: Validated antibody Database: A curated database of antibodies cited in formal publications
Authors: Xie Hanqing 
Published: July 2017

Abstract
Currently research antibodies have a serious quality problem, which is one of the major contributing factors to the irreproducibility of published reports. Labome organizes antibody applications cited in formal publications and has developed Validated Antibody Database (VAD). VAD, a manually curated database, compiles commercial and non-commercial antibodies whose specificities and applications have been independently reported in published results from formal articles. Labome prioritizes the curation of articles with knockout studies and monoclonal antibodies. One of the benefits of our curation effort is the identification of cross-reactive species and novel applications for antibodies, which are often developed for human/mouse proteins and tested by suppliers for a limited number of applications. Labome registers many antibodies having cross-reactivities with model organisms such as flies, worms, zebrafish, and frogs and with novel applications from the literature. The current version released in September 2016 is based on over 50000 formal publications and is freely accessible for online browsing.
Citation Format: Hanqing Xie. Validated antibody Database: A curated database of antibodies cited in formal publications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3111. doi:10.1158/1538-7445.AM2017-3111
Abstract 3114: The role of prostaglandin signaling in human glioblastoma cell activities and growth in vitro and in vivo
Authors: Qiu Jiange , Du Yifeng , Li Qianqian , Shi Zhi , Jiang Jianxiong 
Published: July 2017

Abstract
Glioblastoma multiforme (GBM) constitutes the most frequent and aggressive form of malignant brain primary tumors. Despite current combined treatment involving surgery, chemotherapy and radiation therapy, the median survival of GBM patients is only about one year, with less than 3-5% of patients surviving over 5 years. Cyclooxygenase-2 (COX-2) is overexpressed in glioblastoma, and its expression level is highly positively correlated with the tumor grade. As a major enzymatic product of COX-2, prostaglandin E2 (PGE2) mediates inflammatory processes within the brain and facilitates progression of many chronic inflammation-associated neurological diseases via its four downstream receptors - EP1-EP4. We hypothesize that selectively targeting these receptors might provide an alternative therapeutic strategy for GBM with more specificity than generic blockade of the entire COX-2 cascade. In this study, two engineered human GBM cells with or without activated COX-2 were used to explore the PGE2 signaling involved in the development and progression of GBM. COX-2 activation by LPS or its overexpression facilitated migration, invasion, and transformation of these GBM cells in vitro. Moreover, the COX-2-mediated GBM cell activities were substantially suppressed by selective antagonists of PGE2 receptors that are highly expressed in these cells. Furthermore, the tested PGE2 receptor selective antagonists also suppressed the growth of GBM cells in vivo. In sum, our results suggested the inflammatory PGE2 signaling is involved in human GBM cell inflammation, migration, invasion and transformation through its downstream receptors, and should be explored as alternative molecular targets for novel GBM therapies.
Citation Format: Jiange Qiu, Yifeng Du, Qianqian Li, Zhi Shi, Jianxiong Jiang. The role of prostaglandin signaling in human glioblastoma cell activities and growth in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3114. doi:10.1158/1538-7445.AM2017-3114
Abstract 312: Anti-proliferative effects of cinnamon extract in colon cancer
Authors: Carriere Patrick P. , Mir Hina , Kapur Neeraj , Clark Clarence E. , Singh Shailesh 
Published: July 2017

Abstract
Colon cancer is the third most lethal cancer worldwide, and is estimated to cause 49,190 cancer-related deaths in the U.S. in 2016 alone. Current treatments for colon cancer are limited in their capacity to target tumor cells employing adaptive mechanisms necessary for survival and proliferation, often resulting in poor prognosis. Therefore, it is critical to develop novel target-specific therapeutic approaches with minimal cytotoxicity to normal cells, in order to mitigate potential side effects. Proanthocyanidins represent a subclass of flavonoids, which have been widely investigated for their chemopreventive and therapeutic potential. Cinnamtannin B-1 (CTB-1) is a proanthocyanidin shown to have anti-cancer effects in several cancers, but its anti-cancer potential in colon cancer has not been tested. Hence, the focus of this study was to determine the anticancer effects of CTB-1 in colon cancer. Our results show that CTB-1 treatment significantly decreases the cell viability and proliferation of DLD-1 and COLO 201 human colon cancer cells in a time and dose-dependent manner. In addition, CTB-1 treatment modulated the cell cycle progression of colon cancer cells via G2/M arrest, coupled with a reduction of cells in the S phase. The expression and/or phosphorylation of key molecules involved in apoptosis and cell cycle progression were also modulated in response to CTB-1 treatment. Collectively, these findings, for the first time, shed light on the anti-proliferative effects of CTB-1 in colon cancer, and further demonstrate its potential as a novel therapeutic/preventive agent.
Citation Format: Patrick P. Carriere, Hina Mir, Neeraj Kapur, Clarence E. Clark, Shailesh Singh. Anti-proliferative effects of cinnamon extract in colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 312. doi:10.1158/1538-7445.AM2017-312
Abstract 3123: Identification of TIFA as a novel therapeutic target in acute myeloid leukemia
Authors: Wu Pei-Yu , Wei Tong-You Wade , Wu Ting-Jung , Tsai Ming-Daw 
Published: July 2017

Abstract
Aurora A-dependent NF-κB signaling portends poor prognosis of cancers including acute myeloid leukemia (AML). Our previous study demonstrated that phosphorylation-dependent oligomerization of TRAF-interacting protein with FHA domain (TIFA) triggers the activation of NF-κB. The present study identifies that Aurora A is an essential kinase for the Thr9 phosphorylation of TIFA, and that TIFA functionally mediates the Aurora A-driven NF-κB survival pathway in AML. Overexpression of TIFA occurred concurrently with Aurora A and NF-κB signaling factors in de novo AML patients but not healthy individuals, and also correlated with poor prognosis. Silencing of TIFA specifically attenuated leukemic cell growth and enhanced chemosensitivity of AML cells via down-regulation of pro-survival factors Bcl-2 and Bcl-XL that support NF-κB-dependent anti-apoptotic events. In addition, molecular targeting of TIFA perturbed leukemic cytokine secretion and significantly lowered the IC50 of chemotherapeutic drugs to treat AML cells. Furthermore, in vivo delivery of TIFA-inhibitory fragments potentiates the clearance of leukemic myeloblasts in the bone marrow of xenograft-recipient mice via enhanced chemotoxicity, similar to the effect of anti-inflammatory drug treatments. Collectively, we proposed that TIFA functionally supports the positive feedback between TNF-α, Aurora A, and NF-κB to facilitate AML survival signaling, and impairment in this pathway can enhance the efficacy of AML treatments.
Citation Format: Pei-Yu Wu, Tong-You Wade Wei, Ting-Jung Wu, Ming-Daw Tsai. Identification of TIFA as a novel therapeutic target in acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3123. doi:10.1158/1538-7445.AM2017-3123
Abstract 3125: Therapeutic implications of mTORC1 and mTORC2 inhibitors in genetically heterogeneous glioblastoma
Authors: Amin Anubhav G. , Wang Arthur , Braun Alex , Tobias Michael , Murali Raj , Jhanwar-Uniyal Meena 
Published: July 2017

Abstract
Glioblastoma (GB) is the most common malignant primary brain tumor, which is characterized by marked intra-tumor genetic heterogeneity in receptor tyrosine kinases (RTK) genes. Aberrations in the RTK/PI3K/Akt pathways in GB leads to an abnormal signaling pathway of mechanistic target of Rapamycin (mTOR). mTOR exists in two distinct complexes, namely, mTORC1 and mTORC2, which are involved in regulation of cell survival, growth, and motility. In this investigation, we test the hypothesis that the genetic heterogeneity of GBM cells and its stem cells with respect to the expression of EGFR and/or PDGFRα may define the treatment efficacy of RTK inhibitors with or without PI3K/ mTOR inhibitors. We demonstrated that GB tumors over-expressed PDGFRα and EGFR at range of 80% and 30%, respectively, with varying degree of overlap. Combined treatment with the inhibitors of PDGFRα (AC 710) or EGFR (gefitinib), with or without inhibitors of mTORC1 (rapamycin) or mTORC1/2 (Torin1 and Torin 2), led to suppression of cell proliferation, cell cycle, cell migration and drug resistance in GB cells to varying degrees that correlated with EGFR or PDGFRα expression. Downstream signaling pathway substrates of mTORC 1 and 2, namely pS6k and pAkt, respectively, were suppressed by combined treatments of RTK and mTORC1/2 inhibitors. Furthermore, GB stem cell self-renewal and growth was also suppressed with combined treatments. The combination of AC710 plus mTORC1/2 inhibitor, Torin2, was the most effective. These findings underscore the usefulness of determining PDGFRα and EGFR status when considering viable PI3K/mTOR inhibitors for targeted treatment of GB.
Citation Format: Anubhav G. Amin, Arthur Wang, Alex Braun, Michael Tobias, Raj Murali, Meena Jhanwar-Uniyal. Therapeutic implications of mTORC1 and mTORC2 inhibitors in genetically heterogeneous glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3125. doi:10.1158/1538-7445.AM2017-3125
Abstract 313: Tbata induces G2/M cell cycle arrest and sensitizes osteosarcoma cells to etoposide in a p53-independent manner
Authors: Miljkovic Milos D. , Flomerfelt Francis A. , Gress Ronald E. 
Published: July 2017

Abstract
Thymus, brain, and testes-associated (Tbata) is a negative control cell-cycle gene highly expressed in murine thymic epithelial cells (TECs). Tbata protein binds to Uba3, inhibiting formation of Nedd8 E1 and subsequent target degradation via neddylation of several cell cycle control proteins needed for G2/M transition, which may be a major mechanism of TEC growth arrest during thymic involution. Etoposide is a cytotoxic drug which targets the enzyme toposimerase II — increased 2-3 fold during the G2 phase. To further characterize effect of Tbata on the cell cycle, we modified p53 wild-type U2OS cells derived from human osteosarcoma to express a Tbata/mCherry fusion protein when mifepristone is added to culture media. Tbata-expressing cells identified on flow cytometry did exhibit growth arrest, with quantitative assessment of DNA content in U2OS cells by flow cytometry establishing that 32% of Tbata/mCherry-expressing cells were in the G2 phase when exposed to mifepristone for 24 hours, compared to 11% of mCherry-expressing cells. Gene expression studies were consistent with these results. Cells expressing Tbata/mCherry were also more sensitive to etoposide at 0.5, 1, and 5 times the IC50 dose. To test whether p53 function was required, we further modified the cells to overexpress a dominant negative p53 mutant along with Tbata/mCherry. Similar G2 arrest and increased sensitivity to etoposide were observed, indicating that the effects of Tbata did not require normal p53 function. Potential Tbata analogues or mimetics may therefore be used as an adjunct to G2-targeted chemotherapy.
Citation Format: Milos D. Miljkovic, Francis A. Flomerfelt, Ronald E. Gress. Tbata induces G2/M cell cycle arrest and sensitizes osteosarcoma cells to etoposide in a p53-independent manner [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 313. doi:10.1158/1538-7445.AM2017-313
Abstract 3135: Benzaldehyde suppresses the binding activity of overexpressed 14-3-3ζ to multiple signaling proteins in cancer cells
Authors: Saitoh Jun , Saya Hideyuki 
Published: July 2017

Abstract
Benzaldehyde is the simplest aromatic aldehyde constituent of almonds and many fruits. Anticancer effect of Benzaldehyde was first reported in 1980, and multi-institutional clinical trials were performed in those days in Japan. However, trial was over without determination of effectiveness, only its’ safety was confirmed. The underlying mechanism why Benzaldehyde specifically suppresses growth of some particular cancer cells but not that of normal cells has not been elucidated. Therefore, we attempted to clarify the mechanism of anticancer effect of Benzaldehyde. We have previously reported that, in pancreatic cancer cell BxPC3 and in non-small cell lung cancer cell A549, Benzaldehyde inhibits PI3K/AKT/mTOR, STAT3, NFκB and ERK pathways, those are major signaling pathways activated in cancer cells. Effects of Benzaldehyde on multiple signaling pathways are found to be derived from regulation of 14-3-3 family proteins which interact with phosphorylation sites of various proteins of multiple signals. In BxPC3 cells, Benzaldehyde treatment reduced the phosphorylation levels of 14-3-3-binding sites. Moreover, we ectopically expressed seven isoforms of 14-3-3 in HEK293T cells and found that Benzaldehyde treatment significantly suppressed association of 14-3-3ζ with client proteins such as mTOR, Rictor, cRaf, STAT3 and FOXOs. The interaction of other isoforms of 14-3-3 with their client proteins was also partially reduced. But, the expression levels of those seven 14-3-3 isoforms were not significantly changed. Here we further analysis the Benzaldehyde-mediated 14-3-3ζ regulation, in HEK293 cells overexpressing 14-3-3ζ. Benzaldehyde significantly suppressed mTOR pathway while it was not observed in parental HEK293 cells. Furthermore, we performed pull down assay by using 14-3-3ζ GST tagged recombinant proteins and lysates of HEK293T and BxPC3 and found that Benzaldehyde treatment suppressed the interaction of 14-3-3ζ with cRaf, TSC2 and other 14-3-3ζ client proteins. From these data, we confirmed that Benzaldehyde is an inhibitor of the overexpressed 14-3-3ζ. Recent reports have shown that 14-3-3ζ is overexpressed in many cancers and acts as a signaling hub controlling the network of oncogenic pathways, suggesting that overexpressed 14-3-3ζ associates with carcinogenesis, metastasis and resistance for chemotherapy and radiation. Hence, Benzaldehyde is considered to be a new molecular target agent of 14-3-3ζ which promote and maintain cancer signals.
Citation Format: Jun Saitoh, Hideyuki Saya. Benzaldehyde suppresses the binding activity of overexpressed 14-3-3ζ to multiple signaling proteins in cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3135. doi:10.1158/1538-7445.AM2017-3135