bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 81: Effect of HSP90 inhibition on the gene expression profile of MDM2 transfected LNCaP-MST prostate cancer cells
Authors: Venkatesan Thiagarajan , Alaseem Ali , Alhazzani Khalid , Rathinavelu Appu 
Published: August 2015

Abstract
The heat shock protein 90 (HSP90) is a major molecular chaperone of the cell that appears to be a master regulator of the stability and activity of multiple oncoproteins such as HER2, Akt, Bcr-Abl, c-Kit, EGFR and BRAF. Recent approaches have revealed that most of the target proteins of HSP90 are protein kinases or transcription factors which play important roles in the cellular carcinogenesis. The HSP90 also plays an important role in the regulation of cell cycle, proliferation, vascularization, invasion and metastasis of cancer cells, as well as in maintaining the stability and functions of several carcinogenic proteins involved in altering the signal transduction pathways of apoptosis. The 17-allylamino-17-demethoxygeldanamycin (17-AAG) is a well known inhibitor of HSP90 and it was speculated that, this inhibitor may have particular value in the antitumor and angiostatic therapies. Hence, we were trying to determine the expression profile of the genes in the angiogenesis pathway following treatment of MDM2 overexpressing LNCaP-MST prostate cancer cells with 17-AAG. In the LNCaP-MST cells, the expression of genes such as TNF-α, MMP9 and TGFB1 were found to be significantly up-regulated compared to the LNCaP cells. Hence, MDM2 overexpression was suspected as the primary cause of these increases. However, after treating the LNCaP-MST cells with 10 μm 17-AAG for 24 hrs, several of these genes were significantly altered compared to the untreated LNCaP-MST cells. In particular, the 17-AAG treatment significantly down-regulated the expression of TNF-α, TGFB1, ID1, IL8 and F3 which are involved in the regulation of angiogenesis and tumor growth. The heat map and scatterplot analysis clearly confirmed the alterations in the expression levels of these genes following 17-AAG treatment. Cluster analysis further indicated that the gene expression patterns are positively correlated with the anti-angiogenic effects of 17-AAG treatment in LNCaP-MST cells compared to untreated cells. Our results offer convincing evidence to suggest that the inhibition of HSP90 can control both pro-angiogenic and cell proliferative signals in LNCaP-MST cells. (The financial support from the Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida is gratefully acknowledged).
Citation Format: Thiagarajan Venkatesan, Ali Alaseem, Khalid Alhazzani, Appu Rathinavelu. Effect of HSP90 inhibition on the gene expression profile of MDM2 transfected LNCaP-MST prostate cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 81. doi:10.1158/1538-7445.AM2015-81
Abstract 824: A novel mechanism of areca nut-induced oral cancer is through the conversion of cancer stem cells to acquire malignant phenotypes
Authors: Li Yi-Chen , Cheng Ann-Joy 
Published: August 2015

Abstract
Areca nut is one of the most commonly used psychoactive substance worldwide. It is has been identified as a primary carcinogen of oral cancer in Southeast Asia. Previous studies to examine the effects of this carcinogen often used short-term and high-dose treatment of area nut extract (ANE) as a research model. To elucidate the molecular effects of areca nut and mimic patient chronic exposure situation, we established four areca nut extract (ANE)-trained oral cancer sublines by treating cells with low-dose of ANE (IC30, dose for 30% growth inhibition) for 2 months. Without evidence of cellular senescence, these sublines exhibited significant increases in invasive ability, along with the up-regulation of MMP1 and the reversed expression of epithelial-mesenchymal transition markers. These sublines also showed more resistant to chemotherapeutics and irradiation, which was associated with the over-expression of ABCG2 transporters, increased production of anti-oxidative enzymes, and insensitive to ROS induction. Furthermore, these chronically treated cells possessed characteristics of cancer stem cells, as indicated by enrichment of CD24-/CD44+ population, enhancing spheroid cell formation, and increasing expressions of stemness associated molecules, including Slug, Twist1, Sox9, and Grp78. Thus, we concluded that chronic areca nut exposure induces a pleotropic effect on stemness regulators that facilitates the conversion of cancer stem cells to acquire malignant transformation in oral cancer. This novel finding provides valuable knowledge on areca nut-induced oral carcinogenesis.
Citation Format: Yi-Chen Li, Ann-Joy Cheng. A novel mechanism of areca nut-induced oral cancer is through the conversion of cancer stem cells to acquire malignant phenotypes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 824. doi:10.1158/1538-7445.AM2015-824
Abstract 826: DNA adducts induced by in vitro activation of diesel and biodiesel exhaust extracts
Authors: Ross Jeffrey A. , Nelson Garret B. , Mutlu Esrta , Warren Sarah H. , Peggy Matthews P. , Gilmour M. Ian , DeMarini David M. 
Published: August 2015

Abstract
Petroleum diesel exhaust is a complex mixture containing many probable and known carcinogens. The development of biodiesel and biodiesel blends offers a renewable alternative to petroleum diesel, but few data are available concerning the carcinogenic potential of biodiesel exhausts. We compared the formation of covalent DNA adducts by the in vitro metabolic activation of organic extracts of diesel exhaust particles (DEP)from petroleum diesel and biodiesel. Two different petroleum diesel DEPs were examined (C-DEP and B0), as well as one biodiesel DEP (B100), and DEP resulting from combustion of a blend of 20% B100 and 80% B0 (B20), which is representative of commercially available biodiesel. Oxidative activation was performed in the presence of calf thymus DNA (ctDNA) using rat liver microsomal fractions with required cofactors (S9), and nitroreductive activation was performed using xanthine oxidase (XO) and hypoxanthine in the presence of ctDNA. The modified DNA was hydrolyzed and analyzed by 32P-postlabeling using either butanol extraction or nuclease P1 pre-enrichment. Multiple DNA adducts were produced with chromatographic mobilities consistent with polycyclic aromatic hydrocarbon (PAH) and nitro-PAH adducts. The types and quantities of DNA adducts produced from two independent petroleum diesel DEPs were similar, with evidence of formation of both PAH- and nitroPAH- derived adducts. In contrast, the biodiesel DEP B100 induced higher total levels of DNA adducts in both activation systems. The lowest levels of DNA adduct formation were observed with B20 DEP. These results suggest that the DEP from available biodiesel blends (B20) pose lower risk for induction of DNA damage than petroleum diesel.
This is an abstract or a proposed presentation and does not necessarily reflect EPA policy.
Citation Format: Jeffrey A. Ross, Garret B. Nelson, Esrta Mutlu, Sarah H. Warren, Matthews P. Peggy, M. Ian Gilmour, David M. DeMarini. DNA adducts induced by in vitro activation of diesel and biodiesel exhaust extracts. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 826. doi:10.1158/1538-7445.AM2015-826
Abstract 829: Circulating immune/inflammation markers in Chinese workers occupationally exposed to formaldehyde
Authors: Lan Qing , Seow Wei Jie , Zhang Luoping , Vermeulen Roel , Tang Xiaojiang , Hu Wei , Bassig Bryan A. , Ji Zhiying , Shiels Meredith S. , Kemp Troy J. , Shen Min , Qiu Chuangyi , Reiss Boris , Freeman Laura Beane , Blair Aaron , Kim Christopher , Guo Weihong , Wen Cuiju , Li Laiyu , Pinto Ligia A. , Huang Hanlin , Smith Martyn T. , Hildesheim Allan , Rothman Nathaniel 
Published: August 2015

Abstract
Background: Formaldehyde has been proposed to be a human myeloid leukemogen. However, the exact mechanism for the basis for this link is still debated. We aimed to evaluate whether circulating immune/inflammation markers were different in workers occupationally exposed to formaldehyde.
Methods: Using a multiplexed bead-based assay, we measured serum levels of 38 immune/inflammation markers in a cross-sectional study of 43 formaldehyde-exposed and 51 unexposed factory workers in Guangdong, China. Linear regression models adjusting for potential confounders were used to compare marker levels in exposed and unexposed workers.
Results: We found significantly lower circulating levels of four markers among exposed factory workers compared to unexposed controls that remained significant after adjusting for multiple comparisons, including thymus and activation regulated chemokine (TARC;52pg/ml in exposed versus 75pg/ml in controls,P = 0.0015), TNF-related apoptosis-inducing ligand (TRAIL;11.7pg/ml in exposed versus 22.1pg/ml in controls,P = 0.011), C-reactive protein (CRP;797.3ng/ml in exposed versus 3269.1ng/ml in controls,P = 0.013) and chemokine (C-X-C motif) ligand 11 (CXCL11;36.2pg/ml in exposed versus 48.4pg/ml in controls,P = 0.017), suggesting immunosuppression among formaldehyde-exposed workers.
Conclusions: Our findings are consistent with recently emerging understanding that immunosuppression might be associated with myeloid diseases. These findings, if replicated in a larger study, may provide insights into the mechanism by which formaldehyde promotes leukemogenesis.
Citation Format: Qing Lan, Wei Jie Seow, Luoping Zhang, Roel Vermeulen, Xiaojiang Tang, Wei Hu, Bryan A. Bassig, Zhiying Ji, Meredith S. Shiels, Troy J. Kemp, Min Shen, Chuangyi Qiu, Boris Reiss, Laura Beane Freeman, Aaron Blair, Christopher Kim, Weihong Guo, Cuiju Wen, Laiyu Li, Ligia A. Pinto, Hanlin Huang, Martyn T. Smith, Allan Hildesheim, Nathaniel Rothman. Circulating immune/inflammation markers in Chinese workers occupationally exposed to formaldehyde. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 829. doi:10.1158/1538-7445.AM2015-829
Abstract 858: Periodontal bone loss and risk of epithelial ovarian cancer in the Nurses’ Health Study
Authors: Babic Ana , Poole Elizabeth M. , Terry Kathryn L. , Cramer Daniel W. , Teles Ricardo P. , Tworoger Shelley S. 
Published: August 2015

Abstract
Periodontitis, a chronic inflammatory reaction to dysbiotic oral microbiota, is common in the adult population in the United States. It is associated with increased risk of several medical conditions, including cardiovascular diseases, and potentially with lung, oral and pancreatic cancer. One of the proposed mechanisms behind these associations is systemic inflammation, which has also been implied in ovarian cancer etiology. We investigated association between periodontal bone loss, a marker of periodontitis, and risk of epithelial ovarian cancer among 60,560 participants of the Nurses’ Health Study. We did not observe an increased risk of ovarian cancer among participants suffering from periodontal bone loss (HR = 0.86, 95% CI: 0.64-1.15). Association was unchanged after adjusting for numerous factors including smoking. Among women younger than 69 years periodontal bone loss was associated with a 40% (HR = 0.60, 95% CI: 0.36-0.98) decreased ovarian cancer risk, while there was no association in those older than 69 (HR = 1.09, 95% CI: 0.75-1.58), although this difference did not reach a statistical significance (p-heterogeneity = 0.06). There also was a suggestive decreased risk for serous tumors (HR = 0.76, 95% CI: 0.53-1.09). The number of natural teeth and number of root canals, which are other metrics of oral health, were not associated with ovarian cancer risk. Our results do not support an increased risk of ovarian cancer for women with periodontal bone loss; however, given the unexpected associations in younger women, further research is warranted.
Note: This abstract was not presented at the meeting.
Citation Format: Ana Babic, Elizabeth M. Poole, Kathryn L. Terry, Daniel W. Cramer, Ricardo P. Teles, Shelley S. Tworoger. Periodontal bone loss and risk of epithelial ovarian cancer in the Nurses’ Health Study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 858. doi:10.1158/1538-7445.AM2015-858
Abstract 889: Mouse model for chemotherapy-induced alopecia with transplantation of human hair follicles onto immune deficient mouse
Authors: Kwon Ohsang , Yoon Ji-Seon , Choi Mira , Shin Chang Yup , Kim Kyu Han 
Published: August 2015

Abstract
Optimized research models of chemotherapy-induced alopecia (CIA) require for further understanding the pathogenesis and protection of CIA. The present study was aimed to develop a new mouse model for CIA by follicular unit transplantation of human hair follicles onto the immune-deficient mice. At 22 weeks after transplantation, single dose of cyclophosphamide (Cph) was treated in mice of Cph100 (100mg/kg) and Cph150 (150mg/kg) groups. On day 6 of treatment, hair follicles showed dystrophic anagen representing with swollen dermal papilla and ectopic melanin clumping in the hair bulb. In addition, up-regulated P53 expression and apoptotic matrix keratinocytes, and down-regulated expression of Ki67 and melanogenic protein in the hair bulb were also noted in both groupsin Cph100 and Cph150. Subsequently, hair follicles in Cph100 appeared to recover as anagen hair follicles after 9 days. Ki67 and melanogenic protein expression returned as the levels analogous to the control. On the other hands, hair follicles of Cph150 prematurely entered dystrophic catagen-telogen phase after 9 days of treatment. Ki67 and melanogenic protein expression in immunofluorescence staining were barely visible. Those findings indicate that this model represented two pathways of dystrophic anagen pathway in Cph100 and dystrophic catagen pathway in Cph150. Our model will be a useful tool for the further understanding of the impact of chemotherapy on the human hair follicle.
Citation Format: Ohsang Kwon, Ji-Seon Yoon, Mira Choi, Chang Yup Shin, Kyu Han Kim. Mouse model for chemotherapy-induced alopecia with transplantation of human hair follicles onto immune deficient mouse. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 889. doi:10.1158/1538-7445.AM2015-889
Abstract 925: Helicobacter pylori induces phosphorylation of STAT3 at Ser727 to promote mitophagy in gastric cancer cells
Authors: Piao Juan-Yu , Lee Hee Geum , Kim Su-Jung , Kim Do-Hee , Na Hye-Kyung , Surh Young-Joon 
Published: August 2015

Abstract
Chronic Helicobacter pylori (H. pylori) infection has been considered to be one of the high risk factors of gastric cancer, but the exact mechanism underlying H. pylori-mediated carcinogenesis has not been completely elucidated. Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) is implicated in inflammation-associated carcinogenesis. In a canonical STAT3 pathway, phosphorylation of STAT3 at Tyr705 is a major event of STAT3 activation. In the present study, we found that H. pylori induced phosphorylation of STAT3 at not only Tyr705 but also Ser727. Notably, STAT3 Ser727 phosphorylation occurred at late time independently of Tyr705 phosphorylation followed by migration to mitochondrion. It has been reported that mitophagy is a specialized form of autophagy that removes damaged mitochondria to maintain efficient cellular metabolism and reduces cellular stress. In our study, H. pylori infection induced mitophagy with upregulation of LC3 (microtubule-associated chain3), which is an autophagy marker, in mitochondria. H. pylori-induced Ser727 phosphorylation appears to regulate expression of LC3 based on the experiment utilizing the STAT3 mutant vector in which Ser727 is replaced by alanine, suggesting a potential link between mitophagy and STAT3 phosphorylation at Ser727. Furthermore, we found that STAT3 phosphorylated at Ser727 bound to Grim19 which is a component of complex I and heat shock protein 90 in mitochondria. How this binding contributes to mitopagy is under investigation. In conclusion, H. pylori induced STAT3 phosphorylation at Ser727 to promote mitophagy
Citation Format: Juan-Yu Piao, Hee Geum Lee, Su-Jung Kim, Do-Hee Kim, Hye-Kyung Na, Young-Joon Surh. Helicobacter pylori induces phosphorylation of STAT3 at Ser727 to promote mitophagy in gastric cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 925. doi:10.1158/1538-7445.AM2015-925
Abstract 947: An antibody drug conjugate (ADC) directed to lymphocyte antigen 6 complex, locus E (LY6E) delivers targeted chemotherapy to a wide range of solid tumor malignancies
Authors: Asundi Jyoti , Crocker Lisa , Tremayne Jarrod , Polakis Paul , Firestein Ron 
Published: August 2015

Abstract
Chemotherapies are limited by a narrow therapeutic index resulting in suboptimal exposure of the tumor to the drug and acquired tumor resistance. One approach to overcome this is through Antibody Drug Conjugates (ADCs); that facilitate greater potency via target specific chemotherapy delivery. In this study, we used a bioinformatics approach to identify Lymphocyte antigen 6, locus E, (LY6E), an interferon-inducible glycosylphosphatidylinositol (GPI)-linked cell membrane protein, as a promising ADC target. Immunohistochemical analysis revealed LY6E was overexpressed in a number of tumor types, such as, breast, including triple negative breast cancer, lung, gastric, ovarian, pancreatic and head/neck carcinomas. Characterization of the endocytic pathways for LY6E revealed rapid uptake of the LY6E specific antibody into cells leading to lysosomal accumulation. Consistent with this, a LY6E specific ADC inhibited in vitro cell proliferation and produced durable tumor regression in vivo in high LY6E expressing cancers. Our results identify LY6E as a highly promising molecular ADC target for a variety of solid tumor types with current unmet medical need.
Citation Format: Jyoti Asundi, Lisa Crocker, Jarrod Tremayne, Paul Polakis, Ron Firestein. An antibody drug conjugate (ADC) directed to lymphocyte antigen 6 complex, locus E (LY6E) delivers targeted chemotherapy to a wide range of solid tumor malignancies. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 947. doi:10.1158/1538-7445.AM2015-947
Abstract 965: Identification of KJ-Pyr-9 as a potent MYC inhibitor
Authors: Hart Jonathan R. , Bister Klaus , Janda Kim D. , Vogt Peter K. 
Published: August 2015

Abstract
We have identified a novel small-molecule inhibitor of MYC, KJ-Pyr-9, from a Kröhnke pyridine library. KJ-Pyr-9 functions as an inhibitor of MYC in biochemical assays, in cells and in xenograft experiments. In vitro, KJ-Pyr-9 binds to MYC as well as MYC-MAX dimers and can disrupt binding of MYC-MAX dimers with E-box DNA. In cells, MYC-MAX dimerization can be disrupted in cells as demonstrated by protein fragment complementation assays. KJ-PYR-9 disrupts the transcriptional targets of MYC. The P493-6 cell line has tetracycline regulatable MYC expression. For this cell line, the transcriptional targets of MYC can be readily observed upon the addition of 0.1 ug/mL doxycycline. Both doxycycline and KJ-PYR-9 negatively regulate MYC transcriptional signatures as determined by GSEA. The growth of a variety of different MYC-dependent cell lines are inhibited, including MYC translocated Burkitt's lymphoma cell lines expressing high levels of MYC as well as solid tumor cell lines expressing moderate amounts of MYC. In vivo, KJ-Pyr-9 effectively blocks the growth of a xenotransplant of MYC-amplified human cancer cells.
Citation Format: Jonathan R. Hart, Klaus Bister, Kim D. Janda, Peter K. Vogt. Identification of KJ-Pyr-9 as a potent MYC inhibitor. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 965. doi:10.1158/1538-7445.AM2015-965
Abstract 975: Monoclonal antibody targeting of ADAM17 is an effective treatment for metastatic colorectal cancer resulting in tumor growth control and reductions of cancer stem cells
Authors: Dosch Joseph , Ziemke Elizabeth , Welling Theodore , Hardiman Karin , Sebolt-Leopold Juidth , Michelotti Emil , Hollingsworth Robert , Hurt Elaine 
Published: August 2015

Abstract
ADAM17/TACE (TNFα converting enzyme) has been implicated to play a role in the drug resistance of colorectal cancers. The present study addresses the hypothesis that MEDI3622, a specific ADAM17 monoclonal antibody known to possess both human and mouse cross reactivity, represents a viable therapeutic strategy to improve outcome in the treatment of metastatic colorectal cancer (mCRC). We have generated both in vitro and in vivo data in patient-derived CRC models to provide compelling support for further exploration of this treatment strategy. A heterogeneous panel of low passage colorectal patient-derived xenografts (PDX) has been established from biospecimens procured during patient surgeries conducted at University of Michigan. All xenograft models have been genomically profiled and their histologies mimicked those observed in the original samples. As anticipated, approximately half of these models harbor an oncogenic KRAS mutation and exhibit widely differing histologies, consistent with the heterogeneity encountered in the clinic. Efficacy testing of MEDI3622 has shown that this agent significantly impaired tumor growth in 3 of the 5 PDX models examined, including one model that is KRASMT. Furthermore, cancer stem cell function in these CRC models is negatively impacted by MEDI3622, reducing tumor initiation frequencies in tumor re-implantation studies at the conclusion of treatment. Therefore our results suggest that a monoclonal antibody approach that targets ADAM17 may provide an attractive therapeutic strategy for the treatment of metastatic colorectal cancer both by reducing tumor growth and inhibiting cancer stem cells.
Citation Format: Joseph Dosch, Elizabeth Ziemke, Theodore Welling, Karin Hardiman, Juidth Sebolt-Leopold, Emil Michelotti, Robert Hollingsworth, Elaine Hurt. Monoclonal antibody targeting of ADAM17 is an effective treatment for metastatic colorectal cancer resulting in tumor growth control and reductions of cancer stem cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 975. doi:10.1158/1538-7445.AM2015-975