bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 340: Identification of p62/IMP2 novel targets in breast cancer metastasis
Authors: Li Yang , Peng Bo , Lei Ningjing , Qian Wei , Francia Giulio , Zhang Jianying 
Published: August 2015

Abstract
As one of the most common types of cancer in women, breast cancer is far from being well controlled, especially when the cancer spreads to other organs in the body. Therefore, it is important to understand the molecular and cellular mechanism of metastatic breast cancer, and to identify new proteins that regulate the metastatic process, as such proteins may be used as targets for possible therapeutic intervention. Our previous study showed that p62/IMP2 (IGF2 mRNA binding protein 2) is overexpressed in breast cancer tissues. In our present study, some variants were generated with stable overexpression of p62/IMP2 in MDA-MB-231 cells and LM2-4 cells, and we found that overexpression of p62/IMP2 can increase breast cancer cell migration and reduce cell adhesion. We also found that the p62/IMP2 can bind to c-myc mRNA and increase the expression of c-myc in the two cell lines. To identify new p62/IMP2 targets related with cell adhesion, we performed a Human Extracelluar Matrix & Adhesion Molecules PCR Array to see which gene expression changes in the p62/IMP2 overexpressed cells, compared to the control cells. Our results showed that 18 adhesion molecules are up-regulated with the overexpression of p62/IMP2 (Fold regulation&gt;2, p&lt;0.05) while 2 are down-regulated. We selected 7 up-regulated genes (such as CTGF, HTBS1 and COL15A1) and a down-regulated gene (ITGB4) as candidates for the further evaluation by real time PCR. All candidates genes were further verified byRNA immunoprecipitation (RIP). The data from RIP suggested that connective tissue growth factor (CTGF) may be a potential target of p62/IMP2. These results provided evidences for a better understanding of breast cancer metastasis and targets for future anti-metastatic drug design.
Note: This abstract was not presented at the meeting.
Citation Format: Yang Li, Bo Peng, Ningjing Lei, Wei Qian, Giulio Francia, Jianying Zhang. Identification of p62/IMP2 novel targets in breast cancer metastasis. [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 340. doi:10.1158/1538-7445.AM2015-340
Abstract 3429: Patient awareness of staging in cancer diagnosis: Helpful or hurtful
Authors: Schaap Ariel , Aggarwal Rashi , Domogauer Jason 
Published: August 2015

Abstract
Objective:
In this study we will examine if education levels of English-speaking patients in New Jersey Medical School's Outpatient Cancer Center is correlated with awareness of their disease. Next we will examine their level of depression, as well as explore if patients’ awareness of their disease is correlated with depression. Lastly we will explore if patients’ awareness of their disease is correlated with their level of self-perceived stigma regarding depression.
Methods:
This project is part of a larger questionnaire-based study examining depression prevalence and its associated stigma in cancer patients. Participants consisted of English-speaking oncology patients at New Jersey Medical Cancer Center outpatient oncology clinics. The parts of the questionnaire that I analyzed for this study:
1. What is your level of education?
2. What stage was your cancer in when you were diagnosed?
3. Currently is your cancer localized to a single area or has it metastasized to other areas?
4. Depression symptoms were assessed using the CES-D depression scale.
5. Self-stigma was assessed using Depression Stigma Scale.
Summary:
An increased level of education was associated with a significantly increased level of awareness of cancer staging, linear by linear association (1, N = 223) = 9.353 p = .002. 31% of patients did not know their cancer staging and/or whether or not it had metastasized. Out of the people who were aware of staging only 28.5% were depressed, whereas 34.8% of people who were unaware of staging and/or metastasis were depressed, Fisher Exact test p = .308. While this is not significant, the trend is an important one to be aware of and to examine in future research.
Patients who were aware of their staging and metastasis had a lower mean self-perceived stigma than patients who were unaware of staging and/or metastasis, 14.87 and 15.19 respectively, t(216) = .32, p = .031
Conclusion:
Doctors must recognize that patients in low educated demographic areas, such as Newark, require special attention and need to be evaluated on whether or not they understood what the doctor explained to them about their disease. Further research should focus on analyzing the exact reasons underlying this lack of patient knowledge. In addition, the correlation between lack of knowledge and depression should continue to be explored as patient control and autonomy can improve patient outcomes. Doctors should recognize that patients may have a high self-perceived stigma associated with depression, which can act as a barrier to treatment. Future studies should look at how to dispel that stigma.
Citation Format: Ariel Schaap, Rashi Aggarwal, Jason Domogauer. Patient awareness of staging in cancer diagnosis: Helpful or hurtful. [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 3429. doi:10.1158/1538-7445.AM2015-3429
Abstract 3440: High-dose-rate brachytherapy as monotherapy for favorable-risk adenocarcinoma of the prostate delivered in a single 19 Gy fraction: Preliminary results of a prospective pilot study
Authors: Dahlbeck Scott , Hansen Chase C. , deRiese Werner , Kagan A. Robert , Torres Carlos , Chiriva-Internati Maurizio , Cobos Everardo , Figueroa Jose A. , Nguyen Diane , Tijani Lukman , Evans Jaden D. 
Published: August 2015

Abstract
INTRODUCTION: We evaluated the acute genitourinary (GU) and gastrointestinal (GI) toxicities, health-related quality of life (HRQOL) factors, biochemical control rates, and technical feasibility of high-dose-rate (HDR) brachytherapy as monotherapy for favorable-risk prostate cancer delivered in a single 19 Gy fraction.
METHODS: A single-institution, prospective pilot study was performed by evaluating 6 patients with low- and intermediate-risk prostate cancer treated with high-dose-rate (HDR) brachytherapy as monotherapy. Patients received a single 19 Gy fraction as HDR monotherapy without the use of a transperineal hyaluronic acid injection. Patients were assessed according to the Common Terminology Criteria for Adverse Events version 4.0 and Health-Related Quality of Life (HRQOL) questionnaires. Additionally, prostate specific antigen levels have been followed for evidence of biochemical failure.
RESULTS: All 6 patients tolerated the implant well and were all discharged home the same day. Median follow-up was 15 months with all subjects followed for at least 12 months. No grade 3, 4, or 5 toxicities were observed. Two of the 6 patients experienced grade 2 GU toxicity. One patient experienced grade 2 GI toxicity. HRQOL bowel and urinary assessments revealed peak complaints at 3 months which returned to baseline at 6 months. There have been no biochemical relapses.
CONCLUSION: This is the first study using HDR brachytherapy as monotherapy for favorable-risk prostate cancer using one implant delivered in a single 19 Gy dose in the United States. All patients demonstrated acceptable acute toxicities and were pleased with their cost-effective treatment choice.
Citation Format: Scott Dahlbeck, Chase C. Hansen, Werner deRiese, A. Robert Kagan, Carlos Torres, Maurizio Chiriva-Internati, Everardo Cobos, Jose A. Figueroa, Diane Nguyen, Lukman Tijani, Jaden D. Evans. High-dose-rate brachytherapy as monotherapy for favorable-risk adenocarcinoma of the prostate delivered in a single 19 Gy fraction: Preliminary results of a prospective pilot 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 3440. doi:10.1158/1538-7445.AM2015-3440
Abstract 3462: Proteomic profiling reveals novel targets for combination treatment with lanreotide in neuroendocrine tumors
Authors: Fotouhi Omid , Kjellin Hanna , Hashemi Jamileh , Lu Ming , Juhlin Christofer , Höög Anders , Zedenius Jan , Larsson Catharina , Lehtiö Janne , Kjellman Magnus 
Published: August 2015

Abstract
Somatostatin analogues (SSAs) are well established in the treatment of neuroendocrine tumors (NETs), including small intestinal NET (SI-NET) due to their tumor growth arrest and symptom relieving characteristics. Here we determined the direct effects of lanreotide treatment on NET cell lines and a primary SI-NET culture. The cell lines HC45 and H727 were treated with a pharmacological concentration of 10 nM lanreotide for different time periods and the proteome, analyzed by in-depth HiRIEF LC-MS/MS, was compared with the proteome of non-treated cells. We quantified 6 451 and 7 801 proteins in HC45 and H727. Differential expression of the candidate proteins APC, BIRC5/survivin, BMPER, C14orf142, FYN, INSM1 and SPAG16 was confirmed by Western blotting. The possible direct anti-proliferative effect of lanreotide was evaluated in the primary SI-NET culture and the HC45, H727 and BON1 cell lines, which showed only a slight inhibition of proliferation. However, based on proteomics driven pathway analysis a significant synergy in anti-proliferative effect of lanreotide was observed when the small molecule IGF1R inhibitor, NVP-AEW541, was combined with lanreotide .This effective combination also represents an indirect model of suppressed IGF1 activity in the NET patients treated with SSA. Targeting of survivin with the small molecule YM155 dramatically reduced the proliferation of HC45. We also studied the effect of lanreotide alone or in combination with IGF-1R inhibitor on signaling pathways PI3K/Akt, Erk1/2 and P38. P38, Erk1/2 and GSK3β phosphorylation was equally increased by lanreotide and/or NVP-AEW541, however, lanreotide-induced AktS473 dephosphorylation was reversed after6 hours, unlike consistent AktS473 dephosphorylation after treating with NVP-AEW451 alone or in combination. In conclusion, we report growth inhibitory and potential feedback pro-growth signaling of the SSA lanreotide on NET cells, highlighting the role of SSAs in modulation of IGF1 in NET cell growth arrest and propose combination treatment candidate targets for improved efficacy of this agent.
Citation Format: Omid Fotouhi, Hanna Kjellin, Jamileh Hashemi, Ming Lu, Christofer Juhlin, Anders Höög, Jan Zedenius, Catharina Larsson, Janne Lehtiö, Magnus Kjellman. Proteomic profiling reveals novel targets for combination treatment with lanreotide in neuroendocrine tumors. [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 3462. doi:10.1158/1538-7445.AM2015-3462
Abstract 3485: Uncertainty envelope to evaluate drug interactivity with statistical analysis
Authors: Zhao Liang , Au Jessie L.-s. , Wientjes M. Guill 
Published: August 2015

Abstract
Introduction. Development of new therapies for cancer and infections frequently involves combinations of two or more drugs. Existing methods to quantify drug interactivity are suitable for analyzing drugs with parallel concentration-effect curves and similar maximum drug effects. This study established a method for the remaining situations.
Methods. Equations describing zero-interactivity effects of combination therapy were developed based on the principle that a drug cannot interact with itself (i.e., additivity only). These equations were used to convert the concentration-effect (C-E) curve of the combination to C-E curve for each of the two drugs in the combination as if they were used as single agents (single agent-equivalent curves). Confidence intervals (CI) of these curves were generated using the error propagation method. Effect data of drug combinations were analyzed by the new and existing methods.
Results. The calculated single agent-equivalent curves plus 95% CI defined the boundaries of an envelope for additive drug effects (Uncertainty Envelope). The Envelope shape and size were determined by differences in the shapes of single agent C-E curves. The nature of drug interactivity is indicated by the location of experimental data points of the combination; data points located within the Envelope indicate additivity, whereas points above and below the Envelope respectively indicate statistically significant synergy and antagonism. In comparison with the existing methods, the Envelope method yielded more conservative results (additivity vs. synergy or antagonism).
Conclusion. Uncertainty Envelope method enables the interactivity analysis between drugs with nonparallel C-E curves and unequal maximal effect, with statistical confidence.
Citation Format: Liang Zhao, Jessie L.-s. Au, M. Guill Wientjes. Uncertainty envelope to evaluate drug interactivity with statistical analysis. [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 3485. doi:10.1158/1538-7445.AM2015-3485
Abstract 3493: Disulfiram a dual mgmt and aldehyde dehydrogenase inhibitor sensitizes pancreatic cancer to gemcitabine and abraxane
Authors: Bobustuc George C. , Holmuhamedov Alisher , Srivenugopal Kalkunte S. , Frick Jacob C. , WEESE JAMES L. , Konduri Santhi D. 
Published: August 2015

Abstract
Background: O6 methylguanine DNA methyltransferase (MGMT) is overexpressed in a majority of cancers, including pancreatic cancer. MGMT has been the focus of significant research for its role in the repair of DNA damage caused by chemotherapeutic agents. Aldehyde Dehydrogenase as a progenitor/stem cell marker has been linked to chemotherapy and radiation resistance.
Methods: We tested the administration of Antabuse (disulfiram, DSF) at nontoxic doses in combination with gemcitabine (GEM) and Abraxane (ABX) on pancreatic cancer cells.
Results: DSF at very low doses (achievable in human serum with standard DSF clinical dosing) decreases pancreatic cancer cell growth in a dose-dependent manner. DSF further sensitizes pancreatic cancer cells to GEM and ABX and significantly inhibits pancreatic cancer growth without causing unwanted side effects to the normal pancreatic cells. Dose effect and isobologram studies confirm synergistic activity of DSF and ABX combination and moderate synergism for DSF and GEM combination. DSF, either alone or in combination with GEM (DSF ± GEM) and/or ABX (DSF ± ABX), significantly inhibits expression of MGMT, aldehyde dehydrogenase, antigen Ki-67 and BIRC5 gene (survivin) - all involved in pancreatic cancer tumorigenesis. DSF+/-GEM+/-ABX induces the expression of p21Cip1, a cell cycle inhibitor. We show an inverse correlation between aldehyde dehydrogenase activity and MGMT expression, where MGMT expression is high, aldehyde dehydrogenase activity is low and where aldehyde dehydrogenase activity is high, MGMT levels were low. The ALDH3A1 expression is significantly higher in highly metastatic cancer cells (L3.6pl) compared to other metastatic cancer cells (PANC1, Mia PaCa2, ASPC1). We further report that in our model DSF at very low doses (achievable in human serum with standard DSF clinical dosing) effectively inhibits both aldehyde dehydrogenase and MGMT in pancreatic cancer cells. DSF also induces caspase activation indicative of mitochondrial induced apoptosis in these cells.
Conclusions: Our findings suggest that DSF as dual inhibitor of MGMT and aldehyde dehydrogenase potentially provides a novel therapeutic approach to inhibiting pancreatic cancer growth/metastasis and synergistically enhances GEM and ABX activity.
Citation Format: George C. Bobustuc, Alisher Holmuhamedov, Kalkunte S. Srivenugopal, Jacob C. Frick, JAMES L. WEESE, Santhi D. Konduri. Disulfiram a dual mgmt and aldehyde dehydrogenase inhibitor sensitizes pancreatic cancer to gemcitabine and abraxane. [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 3493. doi:10.1158/1538-7445.AM2015-3493
Abstract 35: Diacylglycerol kinase zeta-mediated regulation of mTOR and SREBP-1 offers new opportunities for cancer management
Authors: Torres-Ayuso PEDRO , Jones David , Tello-Lafoz Maria , Avila-Flores Antonia , Merida Isabel 
Published: August 2015

Abstract
Diacylglycerol (DAG) and phosphatidic acid (PA) are two lipids that lie at the core of several metabolic and signaling pathways, which allows integrated control of cell growth and nutrient sensing with cell metabolism. Diacylglycerol kinases (DGK) are a family of enzymes that balance the levels of both lipids. Some DGK isoforms, mainly DGKα, have been recently suggested as potential targets for cancer treatment (Dominguez et al, 2013; Torres-Ayuso et al, 2014). Previous observations from us indicate that the DGKζ isoform contributes the most to DGK activity in cancer cells, and DGKζ-derived PA is required for mTOR activation, a master regulator of cell growth and metabolism (Avila-Flores et al, 2005).
To address the potential of DGKζ as new therapeutic target for cancer treatment, we used several breast and colon cancer cell lines, and analyzed the effect of its pharmacological inhibition or siRNA-mediated knock down in the proliferation, survival and metabolism of these cells.
We found that DGKζ protein levels where higher in malignant cells compared to their non-transformed counterparts, and its depletion abrogated cancer cell growth in colony assays. DGKζ was prominent over other PA sources to activate mTOR, and its activity was induced by rapamycin. We also investigated whether DGKζ-derived PA functions were coordinated with DAG metabolism and signaling. We observed that DGKζ-dependent DAG consumption was crucial for cell homeostasis via control of the SREBP-1 transcription factor, which was negatively regulated by DAG. Our data provide new evidence of the crosstalk between mTOR and lipid metabolism, and suggest that DGKζ represents an effective target for cancer control.
References
Avila-Flores A, Santos T, Rincon E, Merida I (2005) Modulation of the mammalian target of rapamycin pathway by diacylglycerol kinase-produced phosphatidic acid. The Journal of biological chemistry 280: 10091-10099
Dominguez CL, Floyd DH, Xiao A, Mullins GR, Kefas BA, Xin W, Yacur MN, Abounader R, Lee JK, Wilson GM, Harris TE, Purow BW (2013) Diacylglycerol kinase alpha is a critical signaling node and novel therapeutic target in glioblastoma and other cancers. Cancer discovery 3: 782-797
Torres-Ayuso P, Daza-Martin M, Martin-Perez J, Avila-Flores A, Merida I (2014) Diacylglycerol kinase alpha promotes 3D cancer cell growth and limits drug sensitivity through functional interaction with Src. Oncotarget 5: 9710-9726
Citation Format: PEDRO Torres-Ayuso, David Jones, Maria Tello-Lafoz, Antonia Avila-Flores, Isabel Merida. Diacylglycerol kinase zeta-mediated regulation of mTOR and SREBP-1 offers new opportunities for cancer management. [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 35. doi:10.1158/1538-7445.AM2015-35
Abstract 3522: BET and BRAF inhibitors act synergistically against BRAF mutant melanoma
Authors: Paoluzzi Luca , Hanniford Douglas , Sokolova Elena , Osman Iman , Darvishian Farbod , Wang Jinhua , Bradner James E. , Hernando Eva 
Published: August 2015

Abstract
Purpose: Despite major advances in the treatment of metastatic melanoma, treatment failure is still inevitable in most cases. Manipulation of key epigenetic regulators, including inhibition of Bromodomain and extra-terminal domain (BET) family members impairs cell proliferation in vitro and tumor growth in vivo in different cancers, including melanoma. BET inhibition is thought to impair downstream transcriptional activity of the MAPK (MAPK) pathway and other key oncogenic signaling pathways, suggesting complementarity with MAPK inhibition. Here, we investigated the effect of combining the BET inhibitor JQ1 with the BRAF inhibitor Vemurafenib in in vitro and in vivo models of BRAF-mutant melanoma. We additionally screened potential synergism of JQ-1 with 27 additional compounds including inhibitors of the proteasome, histone deacetylases (HDACi) and MEK.
Methods: We performed cytotoxicity and apoptosis assays, and a xenograft mouse model to determine the in vitro and in vivo efficacy of JQ1 in combination with Vemurafenib against BRAF-mutant melanoma cell lines. Further, to investigate the molecular mechanisms underlying the effects of this combined treatment, we conducted antibody arrays of in vitro drug-treated cell lines and RNA sequencing of drug-treated xenograft tumors. Synergism between JQ1 and other targeted compounds was examined by in vitro cytotoxicity assays.
Results: The combination of JQ1 and Vemurafenib acted synergistically in BRAF-mutant cell lines. Additional combinations that were found synergistic included JQ-1 plus proteasome inhibitors (carfilzomib and marizomib, HDAC inhibitors (romidepsin and panobinostat), or anti-Bcl2 small molecules (Obatoclax and TW-37). The combination of JQ-1 and Vemurafenib resulted in marked apoptosis in vitro, with up-regulation of several pro-apoptotic proteins involved in both the intrinsic and extrinsic pathways of apoptosis. In vivo, this combination treatment suppressed tumor growth and significantly improved survival compared to either drug alone. RNA sequencing of tumor tissues revealed almost four thousand genes that were uniquely modulated by the combination. Furthermore, several anti-apoptotic genes such as MCL-1, BCL-XL and BCL-2 were significantly down-regulated.
Conclusions: Collectively, our data provide a rationale for combinations of BET inhibitors with additional compounds including BRAF inhibitors, as a novel strategy for the treatment of melanoma.
Citation Format: Luca Paoluzzi, Douglas Hanniford, Elena Sokolova, Iman Osman, Farbod Darvishian, Jinhua Wang, James E. Bradner, Eva Hernando. BET and BRAF inhibitors act synergistically against BRAF mutant melanoma. [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 3522. doi:10.1158/1538-7445.AM2015-3522