bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-133: A novel tumor suppressor role for sirt1 inhibiting mitophagy in prostate mouse tissue.
Authors: Sante Gabriele Di , Wang Liping , Wang Chenguang , Bisetto Sara , Casimiro Mathew C , Powell Michael , McBurney Michael , Pestell Richard 
Published: August 2014

Abstract
Introduction. Sirtuin family consists of NAD+-dependent class III histone deacetylases (HDACs). Sirtuin family members (SIRT1-SIRT7) were shown to regulate a variety of physiopathological process, including aging, cellular proliferation, metabolism, and autophagy. Prior studies report SIRT1 as either an oncogene or a tumor suppressor depending upon the cell type and system. However, a reduced expression of SIRT1 in prostate cancer has been reported, supporting the view of SIRT1 as a tumor suppressor. Deregulated intracellular reactive oxygen species (ROS) production induces oxidative stress and damage of nucleic acids, proteins and lipids and may contribute to tumorigenesis. Herein, we provide in vivo support for SIRT1 as a tumor suppressor in prostate cancer. The mechanism appears to involve SIRT1-mediated inhibition of A) mitochondrial ROS production and B) mitophagy.
Materials and methods. 7 month old Sirt1 transgenic mice were used. To investigate the molecular mechanisms through which SIRT1 regulate mitochondrial ROS production and mitophagy process, 3T3 cells wild type (Sirt1+/+) and SIRT1 knockout (Sirt1-/-) were used.
Results. Our clinical and experimental data show a decrease in both SIRT1 expression associated with reduced patient survival probability. A histological evaluation of the H&E performed on both Sirt1+/+ and Sirt1-/- mouse prostate tissues demonstrates that there is a focal atypical intraductal proliferation in prostatic glands of the Sirt1-/- mice, compatible with high grade prostatic intraductal neoplasia (HGPIN). The IHC and relative quantitation of the mouse prostate tissues with Ki67 and AMACR, which are a proliferative and PIN marker respectively, showed an increase of both markers in Sirt1-/- mouse prostate tissue. Preliminary data generated from Sirt1+/+ and Sirt1-/- 3T3 cells suggest that SIRT has a key role in maintaining the mitochondrial healthy status regulating ROS. Sirt1-/- cells undergo a higher oxidative stress, which can lead to cellular damage. We also found mitophagy markers; Beclin1, Bnip3l and LC3 to be overexpressed in Sirt1-/- mouse prostate tissues.
Conclusion and future prospects. These studies suggest SIRT1 inhibits PIN in vivo. The molecular mechanism through which SIRT1 works in a tumor suppressor way is still unknown. We propose a loss of SIRT1 expression may alter the oxidative environment, thereby promoting PIN.
Citation Format: Gabriele Di Sante, Liping Wang, Chenguang Wang, Sara Bisetto, Mathew C Casimiro, Michael Powell, Michael McBurney, Richard Pestell. A novel tumor suppressor role for sirt1 inhibiting mitophagy in prostate mouse tissue. [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 LB-133. doi:10.1158/1538-7445.AM2013-LB-133
Abstract LB-134: mTORC2 regulates the amount of cell surface receptors via its role in protein processing.
Authors: Navia Aixa , Wu Chang-chih , Oh Wonjun , Po-Chien Chou , DeStefano Michael A. , Werlen Guy , Jacinto Estela 
Published: August 2014

Abstract
Signals from cell surface receptors can become altered in cancer due to increased receptor levels. Little is known on how abnormal protein production and quality control may contribute to receptor amplification and tumorigenesis. The mammalian target of rapamycin (mTOR) complex 2 (mTORC2) associates with translating ribosomes and is involved in protein processing. Association of mTORC2 with ribosomes is increased in tumor cells with enhanced PI3K signaling. We found that inhibition of mTORC2 decreases the expression of ErbB1 and CD147 in breast cancer cells. Whereas upregulation of ErbB1 (EGFR1) expression and/or signaling is associated with increased proliferation in breast cancer, CD147 (basigin; EMMPRIN) is linked to tumor metastasis. In mTORC2-disrupted cells, ErbB1 and CD147 have defective expression and processing. Glucose-starved breast cancer cells undergo misprocessing of CD147 along with a decreased expression of mature receptors. Our findings suggest that mTORC2 plays a role in receptor processing and could therefore control cell proliferation via regulation of the amount of growth factor receptors in the cell surface.
Citation Format: Aixa Navia, Chang-chih Wu, Wonjun Oh, Chou Po-Chien, Michael A. DeStefano, Guy Werlen, Estela Jacinto. mTORC2 regulates the amount of cell surface receptors via its role in protein processing. [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 LB-134. doi:10.1158/1538-7445.AM2013-LB-134
Abstract LB-157: IL-12p70 producing dendritic cell vaccine elicits Tc1 polarized T cells and extends time to progression in metastatic melanoma.
Authors: Carreno Beatriz M. , Becker-Hapak Michelle , Huang Alexander , Chan Megan , Alyasiry Amer , Lie Wen-Rong , Aft Rebecca L. , Cornelius Lynn A. , Trinkaus Katherine M. , Linette Gerald P. 
Published: August 2014

Abstract
Systemic administration of IL-12p70 has demonstrated clinical activity in cancer patients but dose-limiting toxicities have hindered its incorporation in vaccine formulations. In this proof-of-concept phase I clinical trial (NCT00683670), we report on the immunological and clinical outcomes upon vaccination of newly diagnosed stage IV melanoma patients with CD40L/IFN-γ matured IL-12p70 producing dendritic cells (mDC). HLA-A*0201+ individuals with treatment naïve metastatic melanoma were vaccinated with mDC pulsed with melanoma gp100-derived peptides, every 3 weeks by intravenous infusion for six doses, after a single dose of cyclophosphamide (300 mg/m2 iv). CT imaging was performed at baseline, week 9 and 18 for clinical assessment using RECIST. PBMC were taken weekly for immune monitoring by tetramer analysis and functional assays. Six of seven treated patients develop sustained T cell immunity to all three melanoma gp100 antigen-derived (G154, G209-2M and G280-9V) peptides, while one patient had transient immunity only to the G209-2M peptide. Three of the six immunological responders developed a radiographic response by RECIST criteria and all three individuals had a time to progression (TTP) &gt;11.5 mo. A Cox regression analysis followed by likelihood-ratio test revealed a positive correlation (p=0.0198) between DC derived IL-12p70 and TTP. Moreover, among clinical responders, vaccine-induced gp100-specific T cells displayed a Tc1 phenotype. In contrast, a selective defect in IL-12p35 transcription was identified in clinical non-responder patient DC and gp100-specific T cells from these patients displayed the Tc2 phenotype. Incorporation of TLR3 and TLR8 agonists into the CD40L/IFN-γ maturation protocol corrected the IL-12p70 production defect in DC derived from clinical non-responder patients. These findings underscore the essential role of IL-12p70 in the development of type-1 immunity in humans with cancer and provide evidence-based rationale for incorporating IL-12p70 into the next generation of cancer vaccine formulations.
Citation Format: Beatriz M. Carreno, Michelle Becker-Hapak, Alexander Huang, Megan Chan, Amer Alyasiry, Wen-Rong Lie, Rebecca L. Aft, Lynn A. Cornelius, Katherine M. Trinkaus, Gerald P. Linette. IL-12p70 producing dendritic cell vaccine elicits Tc1 polarized T cells and extends time to progression in metastatic melanoma. [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 LB-157. doi:10.1158/1538-7445.AM2013-LB-157
Abstract LB-16: Breast cancer risk in association with occupational exposure to organic solvents.
Authors: Ekenga Christine , Parks Christine G. , D'Aloisio Aimee A. , DeRoo Lisa A. , Sandler Dale P. 
Published: August 2014

Abstract
Background: Organic solvents are widely used in occupational settings as adhesives, degreasing agents and cleaning products, and in the production of plastics and textiles. Several solvents have been recognized as human carcinogens; however, there is limited data on solvent exposure and the risk of breast cancer. The objective of this study was to examine the relationship between occupational exposure to organic solvents and breast cancer among women enrolled in the Sister Study.
Methods: The Sister Study is a prospective cohort of over 50,000 US and Puerto Rican women aged 35-74 with a family history of breast cancer; enrollment and completion of baseline questionnaires occurred between 2004 and 2009. This analysis includes 47,763 women who reported working outside the home. We categorized occupational solvent exposure using baseline data on self-reported use of solvents on each job held for 12 months or longer. Women were followed for breast cancer incidence through 2012. Cox regression analyses were performed, adjusting for established breast cancer risk factors, including parity and age at first birth.
Preliminary Results: A total of 1,596 women were diagnosed with invasive or in situ breast cancer during follow-up. Overall, there was no increased risk of breast cancer associated with lifetime use or duration of exposure to solvents (HR: 0.93, 95%CI: 0.79-1.09, p trend = 0.26). Among parous women, those who worked with solvents for five or more years prior to their first birth had an increased risk of breast cancer compared to women who never worked with solvents (HR: 2.12, 95%CI: 0.94-4.80, p trend = 0.02). Among all women, an increased risk was seen for solvent-exposed assemblers and fabricators (HR: 2.28, 95%CI: 1.13-4.57), and non-significantly elevated risks were noted among solvent-exposed cooks and nurses.
Conclusions: These findings suggest that occupational exposure to organic solvents prior to first birth, a critical period of breast tissue differentiation, may result in increased vulnerability for breast cancer. Our results also give some indication of increased risks for solvent-exposed women in production, service and healthcare occupations. Future studies on solvent-related breast cancer risk should focus on exposure time window and types of organic solvents used across different occupational settings.
Citation Format: Christine Ekenga, Christine G. Parks, Aimee A. D'Aloisio, Lisa A. DeRoo, Dale P. Sandler. Breast cancer risk in association with occupational exposure to organic solvents. [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 LB-16. doi:10.1158/1538-7445.AM2013-LB-16
Abstract LB-208: Small interfering RNA library screen to identify therapeutic transcription factor.
Authors: Hu Zhi , Gu Shenda , Gray Joe , Rantala Juha 
Published: August 2014

Abstract
Post-genomic analyses of major transcription factor families, in both malignant and non-malignant cell types, have resulted in a broader revision of understanding the biology of transcription factor families. A number of oncogenic transcription factors, such as activator protein (AP)-1, estrogen receptor(ER) and signal transducer and activator of transcription (STAT)-3/STAT-5, are overactivated in human carcinomas. Up to now, three main groups of transcription factors are known to be important in human cancer. Transcription factor-directed anticancer drug development has focused on membrane or cytosolic targeting of molecules acting as ligand receptors. Recent technologies, such as small interfering RNA (siRNA), have shifted transcription factor targeting toward a more sophisticated rationale to elucidate the mechanisms that govern gene expression by analyzing the functions of proteins commonly over-expressed in transformed and malignant cells. In this study, we've applied a cell spot microarray (CSMA) method which provides reproducible multi-parametric phenotypic readouts for large-scale gene knockdown genetic screens. A human transcription factor siRNA library including 350 transcription factor genes which were significantly overexpressed in human breast cancer was screened against 6 breast cancer cell lines including (Triple negative breast cancer, HER2 positive ER positive) SUM149, BT20, HCC1569, SKBR3, MDAMB361 and MCF7 for measuring cell proliferation using EdU incorporation, cell apoptosis with c-PARP staining. We ranked the candidate gene list by the change of the rate of EdU or level of c-PARP or the combination of both. Our data showed that the silencing of LHX1, BCL6, GABPA or SMAD1 increased the c-PARP levels in most of cell lines. The Knockdown of ZNF215, NFATC1, HOXD4 or ZNF169 reduced the levels of EdU staining. Selected siRNAs were then tested on more different breast cancer cell lines to confirm the spectrum of activity. In the near future, based on this pilot screen, a complete siRNA library of transcription factors including 1000 gene list will be tested on our panel of 50 breast cancer cell lines. Our screen will provide comprehensive information on the central role of transcription factor in breast cancer, and will lead to the identity of novel therapeutics selectively against transcription factors.
Citation Format: Zhi Hu, Shenda Gu, Joe Gray, Juha Rantala. Small interfering RNA library screen to identify therapeutic transcription factor. [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 LB-208. doi:10.1158/1538-7445.AM2013-LB-208
Abstract LB-221: Inhibition of rapamycin-induced feedback activation of AKT with dasatinib induces complete tumor regression in a preclinical model of breast cancer.
Authors: Yori Jennifer L. , Lozada Kristen , Seachrist Darcie D. , Mosley Jonathan , Abdul-Karim Fadi W. , Booth Christine N. , Flask Chris A. , Keri Ruth A. 
Published: August 2014

Abstract
Resistance to receptor tyrosine kinase (RTK) blockade in breast cancer treatment is commonly mediated by activation of bypass pathways that sustain growth. We propose moving away from the individual targeting of RTKs to inhibit multiple commonly activated, overlapping, and essential downstream pathways. The mammalian Target of Rapamycin (mTOR) and the non-receptor tyrosine kinase, Src, are two intrinsic targets that intersect downstream of most RTKs. To date, limited clinical efficacy has been shown with either mTOR or Src inhibitors as single agents. Here we show that dasatinib, a dual Src/c-abl inhibitor, is able to block the well-established de-repression of AKT that occurs with rapamycin inhibition of mTOR. Furthermore, dual inhibition of these distinct, but compensatory arms of RTK signaling results in rapid and complete regression in over 80% of MMTV-PyMT-induced mammary tumors, with only moderate effects on tumor inhibition as single agents. Importantly, Src and mTOR pathway co-activation occurs in nearly half of human breast cancers, independent of tumor sub-type. These studies support the evaluation of combined mTOR and Src inhibitors in breast cancer patients. Such inhibitors are currently FDA approved, expediting the transition to clinical safety and efficacy trials. We expect this approach will prevent molecular evolution of bypass pathways and induce tumor regression.
Citation Format: Jennifer L. Yori, Kristen Lozada, Darcie D. Seachrist, Jonathan Mosley, Fadi W. Abdul-Karim, Christine N. Booth, Chris A. Flask, Ruth A. Keri. Inhibition of rapamycin-induced feedback activation of AKT with dasatinib induces complete tumor regression in a preclinical model of breast cancer. [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 LB-221. doi:10.1158/1538-7445.AM2013-LB-221
Abstract LB-230: Multiple omics profiling reveals the evolutionary history of metastatic renal cell carcinoma.
Authors: Gao Shengjie , Yi Huang , Wu Song , Yu Yuan , Song Pengfei , Guo Guangwu , Hu Xueda 
Published: August 2014

Abstract
About 50% of renal cell carcinomas (RCCs) progress to the metastatic stage, and become fatal and incurable. Whether such a dismal prognosis is due to early dissemination or late diagnosis of the disease remains unknown. To explore the evolutionary history of metastatic RCC (mRCC), we characterized the genetic, epigenetic and expression profiles of multiple tumors from a mRCC patient, including primary RCC (pRCC), local metastasis in vena cava (MVC) and distant metastasis in brain (MB). Although the multi-omics profiles of bulk tumor tissues differed substantially from each other, quantitative analysis of the multi-level data suggested mRCCs to be resulted from clonal expansion of the rare advantageous subclone developed within the heterogeneous pRCC. Moreover, from the genetic distances between mRCCs and their parental subclone, we estimated that about two and eight years were required for the parental subclone to evolve into progeny subclones that give rise to MVC and MB, respectively. Thus, distant metastasis occurred late during RCC progression and there was a broad window period for early detection of the circulating tumor cells before pRCC acquired full metastatic potential. These findings proved that early detection, followed by early intervention, is possible and necessary for controlling the spread of RCC.
Citation Format: Shengjie Gao, Huang Yi, Song Wu, Yuan Yu, Pengfei Song, Guangwu Guo, Xueda Hu. Multiple omics profiling reveals the evolutionary history of metastatic renal 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 LB-230. doi:10.1158/1538-7445.AM2013-LB-230
Abstract LB-243: microRNA mimics: siRNA lessons apply. miRNA mimics exhibit a significant off-target effect that is cell-line, length and dose dependent.
Authors: Goldgraben Mae A. , Git Anna , Rueda Oscar , Caldas Carlos 
Published: August 2014

Abstract
In light of the great success of siRNA reagents in modern research, similar reagents have also become increasingly popular to study miRNAs in cancer biology. To explore the endogenous function of a particular miRNA in fine-tuning target protein translation, synthetic mimics are transfected into host cells either to examine the effect of a candidate target 3′UTR on the expression of a reporter, or to identify new targets using microarray technology. Such studies typically employ a proprietary commercial universal negative control, whose suitability is taken for granted.
Methods: We transfected commercial miRNA mimics into a large panel of breast cancer cell lines (BT549, Cama1, HCC1500, MCF7, MDAMB134, MDAMB231 MDAMB436, MFM223, SUM159, ZR75-1) to identify endogenous targets of miR-155 using microarray analysis. ‘Seed’ and passenger-strand mutants were integrated into the study as additional controls.
Results: The resulting list of differentially-expressed genes often reflects a saturation of transcripts pertaining to a strong immune response to the transfected double-stranded RNA (dsRNA). Different cell lines exhibit variable sensitivity to dsRNA mimics, evident as the induction of the interferon pathway and apoptosis. Using custom variants of the mimics we show that this sequence-independent response is predominantly length-dependent and dose-dependent. Moreover, a substantial part of the remaining, seemingly sequence-specific response could be attributed to the passenger strand, assumed to be inert.
Conclusions and future work: Commercial miRNA mimics may have significant off-target effects that require careful controls to account for the phenotypes under study. In particular, ‘seed’ mutants rather than universal negative controls are of essence. Additionally, alternative methods of transient miRNA over-expression are currently under investigation to validate targets identified to date. Taken together, these lessons have significant implications for all areas of cancer biology where synthetic mimic transfections are a means for investigating the functional role of miRNAs in the cell.
Citation Format: Mae A. Goldgraben, Anna Git, Oscar Rueda, Carlos Caldas. microRNA mimics: siRNA lessons apply. miRNA mimics exhibit a significant off-target effect that is cell-line, length and dose dependent. [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 LB-243. doi:10.1158/1538-7445.AM2013-LB-243
Abstract LB-251: Comparison of MicroRNA deep sequencing of matched formalin-fixed paraffin-embedded and fresh frozen cancer tissues.
Authors: Meng Wei , McElroy Joseph , Volinia Stefano , Palatini Jeff , Warner Sarah , Ayers Leona , Palanichamy Kamalakannan , Chakravarti Arnab , Lautenschlaeger Tim 
Published: August 2014

Abstract
Purpose/Objective(s): MicroRNAs regulate several aspects of tumorigenesis and cancer progression. Most cancer tissues are archived formalin-fixed and paraffin-embedded (FFPE). While microRNAs are a more stable form of RNA thought to withstand FFPE-processing and degradation there is only limited evidence for the latter assumption. We examined whether microRNA profiling can be successfully conducted on FFPE cancer tissues using SOLiD ligation based sequencing.
Materials/Methods: Nine paired human malignant tissue samples were received. Remnant surgical tissues were taken after diagnostic samples were secured from patients (five males and four females; median age 58 years, range 39-78 years) with breast invasive ductal carcinoma (2), renal clear cell carcinoma (2), lung squamous cell carcinoma (1) and adenocarcinoma (1), prostate adenocarcinoma (1), metastatic melanoma (1), and sarcoma of thigh (1). RNA from FFPE samples were extracted using Recover All Total Nucleic Acid Isolation Kit (Life Technologies Corporation, Carlsbad, CA). Small RNAs from FFPE and fresh frozen samples were prepared for SOLiD (Version 4) system, and reads data were analyzed by using the SOLiD™ small RNA Analysis pipeline (Life Technologies), then normalized as reads per million (RPM).
Results: Tissue storage times (2-9 years) appeared to not affect the number of detected microRNAs in FFPE samples compared to matched frozen samples (paired t-test p&gt;0.7). Correlations of microRNA expression values were very high across microRNAs in a given sample (Pearson's r=0.74-0.94). Higher variance of expression values among samples was associated with higher correlation coefficients between FFPE and frozen tissues. One of the FFPE samples in this study was degraded for unknown reasons with a peak read length of 17 nucleotides compared to 21 in all other samples. The number of detected microRNAs in this sample was within the range of microRNAs detected in all other samples.
Conclusion: Ligation-based microRNA deep sequencing on FFPE cancer tissues is feasible and RNA degradation to the degree observed in our study appears to not affect the number of microRNAs that can be quantified.
Citation Format: Wei Meng, Joseph McElroy, Stefano Volinia, Jeff Palatini, Sarah Warner, Leona Ayers, Kamalakannan Palanichamy, Arnab Chakravarti, Tim Lautenschlaeger. Comparison of MicroRNA deep sequencing of matched formalin-fixed paraffin-embedded and fresh frozen cancer tissues. [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 LB-251. doi:10.1158/1538-7445.AM2013-LB-251