bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 460: Novel compound elicits anti-tumor macrophages associated with tumor regression in breast cancer
Authors: Ponichtera Holly E. , Guerriero Jennifer L. , Sotayo Alaba O. , Letai Anthony 
Published: August 2015

Abstract
Cancer immuno-therapies targeting components of the immune system have shown great promise for the treatment of various forms of cancer. Most of the immuno-therapies currently under trial intervene in adaptive immune cell pathways; however, the innate immune system has also recently been shown to play a potent immunomodulatory role in the tumor microenvironment. Tumor associated macrophages (TAMs) compose up to 50% of tumor volume. Presently, we demonstrate that administration of a novel compound stimulates rapid tumor regression that is associated with the infiltration of F4/80+ macrophages into tumors in the MMTV-PyMT murine model of breast cancer. A significant increase in tumor-infiltrating macrophages was visible by immunohistochemistry after five days of treatment and macrophages were necessary for tumor regression as demonstrated by cell depletion assays in vivo. Of note, macrophage infiltration correlated with an increase in tumor cell death as shown by elevated expression of the apoptotic protein cleaved-caspase-3 (CC3); conversely, cell proliferation factor Ki67 was decreased. Additionally, compound-treated animals exhibited striking changes in tumor vascularization, with a marked decrease in overall endothelial cell marker expression as displayed by immunohistochemistry. Taken together, these findings reveal a novel role for macrophages in breast tumor regression during treatment with a novel compound that alters the tumor microenvironment.
Citation Format: Holly E. Ponichtera, Jennifer L. Guerriero, Alaba O. Sotayo, Anthony Letai. Novel compound elicits anti-tumor macrophages associated with tumor regression in breast cancer. [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 460. doi:10.1158/1538-7445.AM2015-460
Abstract 4618: The risk prediction for esophageal cancer by drinking, smoking, and the polymorphisms of ALDH2 and ADH1B
Authors: Ito Hidemi , Oze Isao , Hosono Satoyo , Watanabe Miki , Tanaka Hideo , Matsuo Keitaro 
Published: August 2015

Abstract
Background: The impact of drinking and smoking on the risk of esophageal cancer has been established worldwide (IACR, 2012 updated). In our previous study, we found that the polymorphisms ofalcohol dehydrogenases 1B (ADH1B - rs1229984) and aldehyde dehydrogenases 2 (ALDH2 - rs671) were associated with esophageal cancer risk in a Japanese population (Matsuo K, 2001 & Oze I, 2009). However, the extent to which these environmental and genetic risk factors contribute as predictors of esophageal cancer among Japanese is unknown. The objective of our study was to evaluate the performance of a risk assessment model that incorporates both environmental and genetic risk factors in a Japanese population.
Methods: We conducted a case-control study with 265 cases and age- and sex- matched 530 controls within the framework of the Hospital-based Epidemiological Research Program at Aichi Cancer Center (HERPACC). We fit regression models with the risk factors. For discrimination assessment, we compared the area under the curves (AUC) in the receiver - operating curve (ROC) analysis of Environmental model (E-model), Genetic model (G-model), and Inclusive model. In addition, we evaluated contribution to risk prediction for each risk factor by calculating the integrated discrimination improvement (IDI) index.
Results: We created a risk prediction model for esophageal cancer by polymorphisms of ADH1B and ALDH2, drinking and smoking. The AUCs were 0.873 (0.847-0.898) for E-model and 0.747 (0.711-0.782) for G-model. The Inclusive model including all risk factors, with an AUC of 0.931 (0.912-0.949), showed promise for stratifying people into different risk groups. We found that each risk factor statistically significantly contributed to risk prediction for esophageal cancer (p&lt; 0.001, the IDI indexes of 0.064 for rs1229984, 0.066 for rs671, 0.220 for drinking and 0.101 for smoking).
Conclusion: The risk prediction model that includes these environmental and genetic factors could be useful to classify Japanese into relevant risk groups of esophageal cancer for personalized prevention programs.
Citation Format: Hidemi Ito, Isao Oze, Satoyo Hosono, Miki Watanabe, Hideo Tanaka, Keitaro Matsuo. The risk prediction for esophageal cancer by drinking, smoking, and the polymorphisms of ALDH2 and ADH1B. [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 4618. doi:10.1158/1538-7445.AM2015-4618
Abstract 462: Cytotoxic CD8+ T cells and immunosuppressive T regulatory cells are associated with aggressive breast cancer subtypes
Authors: Khramtsova Galina F. , Nanda Rita , Khramtsova Ekaterina A. , Sveen Lise , Olugbile Sope , Olopade Olufunmilayo I. 
Published: August 2015

Abstract
Background: An increase in tumor infiltrating lymphocytes (TILs) indicates an immune response to tumor antigens. CD8+ TILs play a vital role in cancer progression, and may have tumor suppressive effects. FoxP3+ T regulatory cells (Tregs), however, suppress a variety of immune cells - including CD4+ TILs, CD8+ TILs, dendritic cells, B cells, and macrophages - and thus may inhibit the beneficial effect these cells have on tumor suppression. Specifically, CD8+ TILs - which are a critical component of tumor-specific adaptive immunity - are a major target of Tregs. This study was aimed at understanding how these TILs correlate with breast cancer molecular subtypes in diverse population of breast cancer patients.
Methods: Tissue Microarrays (TMAs) of breast cancer cases from 1992-2010 were obtained from the University of Chicago breast cancer biospecimen bank under IRB approved protocols. Molecular subtype was assigned based on immunohistochemical (IHC) staining into the following groups: luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), HER2-like (ER/PR-, HER2+) and basal-like (ER/PR/HER2-, EGFR+ and/or CK5/6+). IHC for CD8 and FoxP3 was performed on TMAs using DAKO, cat # M7103 antibody, and Abcam antibody cat #ab20034. The amount of CD8+ and FoxP3+ cells presents within the neoplastic tissue were counted manually in two high-powered fields (x400) by two independent pathologists, and recalculated for 1 mm2. The ratio of FoxP3+/CD8+ was calculated and correlated with molecular subtype.
Results: Of the 292 cores evaluated, 268 were evaluable representing 134 individual cases. There were 28 basal-like (20.9%), 14 HER2 (10.4%), 78 luminal A (58.3%), and 14 luminal B (10.4%). Basal-like tumors showed the highest infiltration of both Tregs and CD8+ TILs when compared to other breast cancer subtypes, and the ratio of FoxP3+: CD8+ TILs in basal-like tumors were 1.7, 2.5, and 4.5-fold higher than in HER2, Luminal A, and Luminal B tumors respectively (p&lt;0.05 for all correlations).
Summary: FoxP3+ and CD8+ TIL infiltration density were significantly different among molecular subtypes of breast cancer. Future studies will examine the genomic determinants and prognostic significance of TILs in aggressive breast cancer subtypes, especially basal-like breast cancers.
Citation Format: Galina F. Khramtsova, Rita Nanda, Ekaterina A. Khramtsova, Lise Sveen, Sope Olugbile, Olufunmilayo I. Olopade. Cytotoxic CD8+ T cells and immunosuppressive T regulatory cells are associated with aggressive breast cancer subtypes. [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 462. doi:10.1158/1538-7445.AM2015-462
Abstract 4620: Somatic mutation profile of gastric cancer cases from the Hispanic population
Authors: Prieto-Sanchez Rodrigo , Sahasrabudhe Ruta Madhusudan , Lott Paul , Bohorquez Mabel , Jairo Suarez Jhon , Mateus Gilbert , Torres Javier , Echeverry Magdalena , Carvajal-Carmona Luis 
Published: August 2015

Abstract
Gastric cancer contributes to a significant health care burden, being the third most common cause of cancer related deaths worldwide. In the US, gastric cancer incidence and mortality in the Hispanic population is more than double compared to Non-Hispanic whites (NHW). However, a majority of the large-scale gastric cancer genome characterization studies that have been carried so far have been largely limited to non-Hispanic (NH) populations, predominantly Non-Hispanic Whites (NHW). This “mono-ethnic” approach is likely to miss driver mutations that are unique or common in Hispanics but rare in NHWs and can lead to future genomic-driven cancer health disparities. Identification of driver mutations is important to understand the molecular basis of tumorigenesis and to develop better preventive and therapeutic strategies in minority groups like Hispanics. Therefore, the purpose of this study was to characterize gastric cancer somatic changes in the understudied Hispanic population. Somatic mutations were identified using whole exome sequencing (WES) of 36 tumor-normal pairs from Hispanic gastric cancer patients. Microsatellite stability tasting was also performed on all the samples and samples were divided into 27 microsatellite stable (MSS) and 9 microsatellite instable (MSI) cases. Interestingly, preliminary analysis of exome sequencing data delineates differences in mutational profile in our study population compared to publish studies in NH. For example, we found that the frequency of TP53, the most commonly mutated gastric cancer driver in NHs, had a significantly lower frequency in our Hispanic sample (33% in MSS tumors and 11% in MSI tumors compared to 50% in MSS and 35% in MSI tumors reported in TCGA dataset). Similar differences were also found in other frequently mutated gastric cancer genes, which suggest that the genetic pathways leading to gastric cancer in Hispanics are likely to be different to the ones involved in NHW tumors. In summary, our sequencing study of Hispanic gastric cancer cases have identified important differences with other populations, are likely to identify novel cancer drivers in this tumor type and would help bridge the gap in heath care disparities
Citation Format: Rodrigo Prieto-Sanchez, Ruta Madhusudan Sahasrabudhe, Paul Lott, Mabel Bohorquez, Jhon Jairo Suarez, Gilbert Mateus, Javier Torres, Magdalena Echeverry, Luis Carvajal-Carmona. Somatic mutation profile of gastric cancer cases from the Hispanic population. [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 4620. doi:10.1158/1538-7445.AM2015-4620
Abstract 464: Hypoxia-induced miR-210 potentiates MDSC function through regulation of Arg1, Il-16 and Cxcl12, and promotes tumor growth
Authors: Noman Muhammad Zaeem , Chouaib Salem 
Published: August 2015

Abstract
Myeloid Derived Suppressor Cells (MDSCs) are an integral component of the hypoxic tumor microenvironment. We demonstrated that hypoxia selectively induced miR-210 via HIF-1α in splenic MDSCs from tumor-bearing mice. Overexpression of miR-210 enhanced MDSC-mediated T cell suppression under normoxia, while targeting of hypoxic miR-210 decreased MDSC function. Our data show that miR-210 modulated MDSCs function by increasing arginase activity and NO production, although it had no effect on ROS or cytokine (IL-6 and IL-10) production and PD-L1 expression. A comprehensive approach using microRNA target predictions tool, transcriptome analysis, and luciferase reporter assay strongly pointed to the regulation of Arg1, Cxcl12 and Il16 at both mRNA and protein levels by miR-210 in splenic MDSCs. In mediating the immunosuppressive effects of miR-210, targeting of Arg1, and blockade of IL-16 and CXCL12, in splenic MDSCs from tumor-bearing mice under normoxia dramatically decreased MDSC-mediated T cell proliferative response and IFN-gamma production. Interestingly, miR-210 overexpressing MDSCs enhanced in vivo their immune suppressive activity resulting in an increase in 4T1 tumor growth. Therefore, the potential therapeutic use of miR-210 inhibitor oligonucleotide alone, or along with HIF-1α inhibitors as adjuvant tool combined to immunotherapeutic approaches, may be beneficial for boosting the immune system in cancer patients.
Citation Format: Muhammad Zaeem Noman, Salem Chouaib. Hypoxia-induced miR-210 potentiates MDSC function through regulation of Arg1, Il-16 and Cxcl12, and promotes tumor growth. [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 464. doi:10.1158/1538-7445.AM2015-464
Abstract 4640: Andrographolide modulates cell cycle, cell migration and tumor growth in prostate cancer
Authors: Forestier-Roman Ingrid , Sánchez Maria , Casillas Joseph , Rohena Krizia , Martínez-Ferrer Magaly 
Published: August 2015

Abstract
Prostate cancer is the most frequently diagnosed non-cutaneous cancer and is the second leading cause of cancer death in American men. Chemopreventive strategies have been tested to prevent the development of different types of cancer including prostate cancer. Andrographolide, a labdane diterpenoid that is the main bioactive component of the medicinal plant Andrographis paniculata, has been reported to have a wide range of biological activities including anticarcinogenic properties. In this study we aim to determine the role of Andrographolide in the progression of prostate cancer using in vitro and in vivo models. Andrographolide significantly inhibited PC3 cell growth at a concentration of 10μM after 24 h of treatment (P &lt; 0.001), and inhibited LNCaP cell growth at a concentration of 15 μM after 24 h of treatment (P &lt; 0.001). Wound healing assays and boyden chamber experiments showed that PC3 prostate cancer cells treated with Andrographolide (25uM) significantly reduced (P&lt;0.001) their migration and invasion. Flow cytometry assays for Annexin V, cell cycle and cell count and viability were performed. Andrographolide (25uM) significantly increased apoptosis, decreased cell population in G1 phase, and reduced count and viability of PC3 cells treated for 48 hours. Immunofluorescence analysis showed that MMP-11 expression levels were significantly decreased and ZO-1 expression was significantly increased in PC3 cells treated with Andrographolide (25uM). Tumor progression was evaluated using a xenograft model in which the anterior prostate lobes of SCID mice were injected with 250,000 22RV1 cells or 500,000 PC3 cells. Andrographolide was administered bi-weekly at concentrations of 10uM and 25uM intraperitoneal injections during 4 weeks (22RV1) or 8 weeks (PC3). Tumor tissue was collected for gross examination, immunohistochemical analysis and gene expression analysis. In vivo results demonstrated that Andrographolide treatment significantly decreased tumor volume when compared with tumors generated in mice treated with vehicle. Our results suggest that the anti-migration and anti-invasion effects of andrographolide may be associated with alterations in the expression of ZO-1 and MMP-11.
Citation Format: Ingrid Forestier-Roman, Maria Sánchez, Joseph Casillas, Krizia Rohena, Magaly Martínez-Ferrer. Andrographolide modulates cell cycle, cell migration and tumor growth in prostate cancer. [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 4640. doi:10.1158/1538-7445.AM2015-4640
Abstract 4642: Quercetin inhibits prostate cancer by modulating molecules involved in apoptosis and cell proliferation
Authors: Ward Ashely B. , Mir Hina , Kapur Neeraj , Singh Shailesh 
Published: August 2015

Abstract
Prostate cancer (PCa) remains the second leading cause of death in men, despite the multimodal options offered in the clinics. Long latency and indolent nature of PCa provides window of opportunity for preventive interventions using natural and synthetic agents. Quercetin, a bioflavonoid abundant in fruits and vegetables, has been reported to inhibit growth in cancer and reduce inflammation in conditions like prostatitis. Considering this, we investigated the chemo-preventive effects of Quercetin on PCa. The effects of Quercetin on apoptosis and associated proteins on both RNA and protein levels were determined using apoptosis assay, real-time qPCR and western blot, respectively. Furthermore, an antibody microarray was performed to observe changes induced by Quercetin on signaling molecules and possible mechanism of cell survival/apoptosis in PCa. PCa cells treated with Quercetin showed decreased cell proliferation in a time and dose dependent manner, while no significant effect was seen on normal prostate cells. Quercetin treatment also significantly induced apoptosis in PCa cells, as compared with untreated controls. Different phosphorylation status of key molecules (Bcl-2, Akt-1 and NF-k B) was observed following Quercetin treatment in PCa cell lines, as compared with untreated controls, which are known to be involved in supporting PCa progression. These results suggest that Quercetin could be a potential chemo-preventative agent capable of slowing down the progression of PCa, by increasing apoptosis and decreasing cell proliferation.
Note: This abstract was not presented at the meeting.
Citation Format: Ashely B. Ward, Hina Mir, Neeraj Kapur, Shailesh Singh. Quercetin inhibits prostate cancer by modulating molecules involved in apoptosis and cell proliferation. [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 4642. doi:10.1158/1538-7445.AM2015-4642
Abstract 4645: Decursin, a coumarin compound, inhibits the growth of human hepatoma cells involving cell cycle arrest, apoptosis, and autophagy
Authors: Kujur Praveen K. , Yim Dongsool , Singh Rana P. 
Published: August 2015

Abstract
Although recent advances have been made for the treatment of liver cancer, it still remains the sixth most diagnosed cancer worldwide and second most cause of mortality related to cancer. Decursin, a naturally occurring coumarin compound isolated from Angelica gigas Nakai is known for its hepatoprotective activity. For the first time we show that decursin has strong cytotoxic and growth inhibitory effects against liver cancer cells. Decursin (1-25 μM) resulted in a dose-dependent inhibition of Hep3B cell proliferation by upto 65-85% (p&lt;0.005-0.001) in 24-48 h. Similarly in HepG2 cells, decursin (25-100 μM) decreased cell number by upto 61-74% (p&lt;0.005-0.001) at 24-48 h. Growth inhibition was not due to the cell death in HepG2 cells, whereas, Hep3B cells showed an increased cell death (9-45%; p&lt;0.001). Decursin enhanced sub-G1 population of cells in Hep3B but not in HepG2. Further, decursin induced G1 arrest at lower doses, however, at the higher doses cell death prevailed over cell cycle arrest. A consistent G2/M phase arrest in HepG2 cells at all the time points, however, at 100 μM, there was an induction of S-phase arrest. Decursin strongly decreased the colony forming efficiency of Hep3B cells. Decursin induced both apoptotic and autophagic cell death. In flow cytometry analyses, an increase in the acidic vesicular organelle development was observed at 24 and 48 h in Hep3B cells. Interestingly, in decursin treated HepG2 cells, autophagic induction occurred much later (48 h). This was further validated by MDC staining. Mechanistic studies for cell cycle regulators showed that decursin mediated G1 arrest could be via an increase in p21/cip1. Concomitantly, we observed reduced levels of Cyclin A and B1 and their respective kinases. PCNA, a marker of proliferation showed decreased in expression. Decursin mediated induction of apoptosis involved cleavage of caspase-3 and PARP and reduction in survivin level. This was accompanied by an enhanced Bax/Bcl-2 ratio. Additionally, a potent decrease in the phosphorylation of IGF-IR and its downstream effector Akt, was observed. Decursin increased Erk1/2 phosphorylation, however, it was not associated with cell growth or survival. Collectively, these findings suggest that decursin strongly inhibits liver cancer growth and proliferation involving induction of cell cycle arrest, apoptosis and autophagy and could be further explored and developed as novel treatment option for the hepatic malignancies.
Citation Format: Praveen K. Kujur, Dongsool Yim, Rana P. Singh. Decursin, a coumarin compound, inhibits the growth of human hepatoma cells involving cell cycle arrest, apoptosis, and autophagy. [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 4645. doi:10.1158/1538-7445.AM2015-4645