bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 249: Dietary supplementation with methylseleninic acid reduces male mammary tumorigenesis in MMTV-PyMT mice
Authors: Sundaram Sneha 
Published: July 2017

Abstract
Male breast cancer makes up approximately 1% of all breast cancers and less than 1% of all cancers in men in the United States. However, it is an aggressive disease with poor prognosis and the incidence of male breast cancer is on the rise. The present study investigated the effects of dietary supplementation of selenium on male breast carcinogenesis in MMTV-PyMT mice (FVB/N background). Three-week-old male mice were weaned onto the AIN93G diet with or without supplementation of selenium in the form of methylseleninic acid (2.5 mg Se/kg). Mice were euthanized 10 weeks after the first palpable mammary tumor was detected. There were no differences in food intake and body weight between the groups. The median latency (the age at which the first palpable tumor was detected) was 14.1 and 13.9 weeks and the incidence of palpable mammary tumor was 71% and 70% for the control and the selenium group, respectively. Selenium supplementation compared to the control diet reduced mammary tumor progression by 258% and tumor weight by 84%, respectively. Tumor progression was defined as the change in tumor volume from detection of the first palpable mammary tumor to termination 10 weeks later. Incidence of lung metastasis was 74% and 50% in control and selenium group, respectively. In mice bearing lung metastases, selenium supplementation significantly reduced the number of metastases by 83% compared to the control group. In conclusion, dietary supplementation with selenium in the form of methylseleninic acid reduces male breast carcinogenesis and its metastasis in mice. It indicates that selenium may be useful in male breast cancer prevention.
Citation Format: Sneha Sundaram. Dietary supplementation with methylseleninic acid reduces male mammary tumorigenesis in MMTV-PyMT mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 249. doi:10.1158/1538-7445.AM2017-249
Abstract 2496: Targeting brain tumor stem cells by interfering with choline metabolism: Evidence for an EMT-choline oncometabolic network
Authors: Koch Katharina , Hartmann Rudolf , Suwala Abigail K. , Rios Dayana Herrera , Kahlert Ulf D. , Maciaczyk Jaroslaw 
Published: July 2017

Abstract
Glioblastoma (GBM) is the most lethal primary malignant brain tumor with a median survival of less than two years. High levels of therapy resistance, strong cellular invasiveness and rapid cell growth demand aggressive multimodal therapies involving resection as well as radio-chemotherapy. Recent evidence has pointed to the existence of brain tumor stem cells (BTSCs), a subpopulation of human brain tumors which is thought to be responsible for tumor dissemination, relapse and chemo resistance. BTSCs have been associated with the expression of mesenchymal features as a result of epithelial-mesenchymal transition (EMT). Using high resolution proton nuclear magnetic resonance spectroscopy (1H NMR) we compared the intracellular metabolic composition of GBM cells after induction vs. inhibition of EMT as well as under stem cell or differentiated conditions. We identified that both EMT and enrichment for stemness induces the cholinic phenotype which is characterized by high intracellular levels of phosphocholine and total choline derivatives. Furthermore, interference with choline metabolism by targeting choline kinase alpha (CHKα) reversed EMT in GBM cells as we observed reduced invasiveness, clonogenicity, and expression of EMT associated genes. Taken together, interfering with choline metabolism is a powerful strategy to suppress EMT and thus target BTSCs. Moreover, the newly identified BTSC-oncometabolic network could be used to non-invasively monitor the invasive properties of glioblastomas and the success of anti-BTSC therapy.
Citation Format: Katharina Koch, Rudolf Hartmann, Abigail K. Suwala, Dayana Herrera Rios, Ulf D. Kahlert, Jaroslaw Maciaczyk. Targeting brain tumor stem cells by interfering with choline metabolism: Evidence for an EMT-choline oncometabolic network [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2496. doi:10.1158/1538-7445.AM2017-2496
Abstract 2501: Assessing metabolic activity of patient-derived models of non-small cell lung cancer using stable isotope resolved metabolomics (SIRM)
Authors: Kinslow Connor J. , Tan Jinlian , Cai Yihua , Yan Jun , Higashi Richard M. , Lane Andrew N. , Fan Teresa W. 
Published: July 2017

Abstract
Stable Isotope-Resolved Metabolomics (SIRM) has been a useful tool in interrogating metabolic reprogramming in cancer. We have recently published several protocols using SIRM in patient-derived models of non-small cell lung cancer (NSCLC)1. In this case study, we compared central metabolic activity in three different model systems, all derived from the same patient. Slices from the human tumor (Warburg slices 2,3), slices from an NSG mouse bearing the human tumor 4, and the patient-derived cell culture were incubated in [U-13C]-glucose or [U-13C,15N]-glutamine for 24 hours. Samples were then harvested and analyzed by gas-chromatography-mass spectrometry and NMR. All three models displayed similar levels of fractional enrichment after 24 hours, making metabolic comparison possible, despite their very different 3D architectures. Glucose metabolism in particular, showed consistent labeling patterns of metabolites in glycolysis and the Krebs cycle. Glutamine metabolism, however, was distinct in the cell culture, with a pattern that indicated upregulation of anaplerotic glutaminolysis. Activation of glutaminolysis may be an important transformative step in the establishment of a viable cell culture. We are also in the process of validating the present finding by comparing multiple patient-derived models of NSCLC and tracking the evolution of their metabolic activity.
1 Lane, A. N., Higashi, R. M. & Fan, T. W.-M. Preclinical models for interrogating drug action in human cancers using Stable Isotope Resolved Metabolomics (SIRM) Metabolomics 12, 1-15 (2016).
2 Fan, T. W.-M. et al. Distinctly perturbed metabolic networks underlie differential tumor tissue damages induced by immune modulator β-glucan in a two-case ex vivo non-small cell lung cancer study. CSH Molec. Case Studies J. 2, a00083, (2016).
3 Fan, T. W.-M., Lane, A. N. & Higashi, R. M. Stable Isotope Resolved Metabolomics Studies in ex vivo Tissue Slices. Bio-protocol 6, e1730 (2016).
4 Lane, A. N., Yan, J. & Fan, T. W.-M. 13C Tracer Studies of Metabolism in Mouse Tumor Xenografts. Bio-protocol 5, e1650 (2015).
Citation Format: Connor J. Kinslow, Jinlian Tan, Yihua Cai, Jun Yan, Richard M. Higashi, Andrew N. Lane, Teresa W. Fan. Assessing metabolic activity of patient-derived models of non-small cell lung cancer using stable isotope resolved metabolomics (SIRM) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2501. doi:10.1158/1538-7445.AM2017-2501
Abstract 2502: Liquid diet introduction of tracers into mice for stable isotope-resolved metabolomics (SIRM) investigations
Authors: Sun Ramon C. , Warmoes Marc O. , Yang Ye , Deng Pan , Sun Qiushi , Lane Andrew N. , Higashi Richard M. , Fan Teresa W-M 
Published: July 2017

Abstract
Tracer-based mapping of metabolic networks in vivo is a powerful approach for revealing metabolic reprogramming in human cancer. However, current in vivo labeling techniques for model animals face important challenges including insufficient depth of pathway coverage (e.g. inability to detect labeled nucleotides, proteins, and lipids) and stress-related artifacts. Here, we report stress-free administration of 13C6-glucose via liquid diet into mice. 13C enrichment was observed in metabolites of glycolysis, the Krebs cycle, the pentose phosphate pathway, nucleobases, UDP-sugars, as well as macromolecules glycogen, lipids, and proteins from major organs in NSG mice. We have applied the liquid diet method to map the glucose metabolic networks in NSCLC tumors in a patient-derived xenograft (PDX) model. We observed a high enrichment in the metabolites of glycolysis, Krebs cycle, and PPP as well as de novo synthesized nucleotides and amino acids by IC-UHR-FTMS analysis. Lung PDX displayed unexpected metabolic complexity, such as the use of pyruvate to fuel anaplerosis as well as gluconeogenesis. We also found high 13C enrichment in both tumor and plasma glutamine, which implies that glutamine in the PDX tumors largely came from other organs via the blood rather than being synthesized in situ. Our data showed that liquid diet is an effective and noninvasive means for comprehensive analysis of glucose-associated metabolic networks in human tumor xenografts, which can also be extended to SIRM studies with other fuel sources.
Acknowledgements: This work was supported in part by grants: 1R01ES022191-01 (to TWMF and RMH), 1P01CA163223-01A1 (to ANL and TWMF), and 1U24DK097215-01A1 (to RMH, TWMF, and ANL)
R.C. Sun was supported by a T32 training grant to M. Vore (5T32ES007266-25)
Citation Format: Ramon C. Sun, Marc O. Warmoes, Ye Yang, Pan Deng, Qiushi Sun, Andrew N. Lane, Richard M. Higashi, Teresa W-M Fan. Liquid diet introduction of tracers into mice for stable isotope-resolved metabolomics (SIRM) investigations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2502. doi:10.1158/1538-7445.AM2017-2502
Abstract 2507: Using 1H NMR metabolomics to study breast cancer and endothelial cell metabolic interactions
Authors: Acevedo-Acevedo Suehelay , Palecek Sean P. 
Published: July 2017

Abstract
Breast cancer is the second most commonly diagnosed cancer among women worldwide. Patient death is typically caused by metastasis development rather than the primary tumor. Metastasis in breast cancer has been shown to occur via blood and lymphatic vessels. Research shows that breast cancer cells ‘educate’ lymphatic and blood endothelial cells to support tumor growth by stimulating growth factor secretion; specifically VEGF, PDGF-BB and EGF secretion. In addition, cell metabolism is altered during malignant transformation. Cancer cells have increased energy and macromolecule biosynthesis requirements to sustain rapid proliferation. Increased angiogenesis observed in tumors points to a need for an increased nutrient supply. However, it remains unclear how tumor endothelial cell metabolism is altered and how metabolism regulates tumor angiogenesis. Therefore, this study aims to use 1H NMR metabolomics to identify breast cancer-endothelial cell metabolic interactions in a high-throughput manner. Firstly, we studied if in vitro co-culture with breast cancer altered endothelial cell metabolism. We identified distinct metabolic profiles for HUVECs grown in monoculture or co-culture with three different breast cancer cell lines. Metabolism of HUVECs co-cultured with MCF7 and SKBR3 breast cancer cell lines was significantly altered compared to mono-culture control. The most impacted metabolic pathways by co-culture were amino acid metabolism, energy metabolism and lipid biosynthesis pathways. Culturing HUVECs with MDA-MB-231 triple negative breast cancer cells did not have a significant impact on HUVEC metabolism, however. Together, these results indicate that culturing HUVECs with certain breast cancer lines causes significant changes in endothelial metabolism. Alterations in endothelial cell metabolism in response to breast cancer co-culture can further our understanding of tumor-vascular interactions and may lead to identification of metabolic biomarkers or therapeutic targets that can disrupt tumor angiogenesis.
Citation Format: Suehelay Acevedo-Acevedo, Sean P. Palecek. Using 1H NMR metabolomics to study breast cancer and endothelial cell metabolic interactions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2507. doi:10.1158/1538-7445.AM2017-2507
Abstract 2511: The role of lipids metabolism in bladder cancer
Authors: Wang Gang , Cao Rui , Ge Qiangqiang , Xiao Yu , Wang Xinghuan 
Published: July 2017

Abstract
Bladder cancer (BCa) is one of the most common malignancy of the urinary tract. Many risk factors for BCa has been demonstrated, including aging, smoking, exposure to chemicals, dietary total cholesterol intake, dietary fatty acids intake, etc. In order to investigate the role of lipids metabolism in bladder cancer, we collected several human BCa tissues and normal bladder tissues to generate an affected pathway network by microarray analysis, and it revealed that glycerolipid metabolism, fatty acid degradation and fatty acid biosynthesis have a close correlation with bladder cancer. Therefore, Simvastatin, one of the 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors, have been well-known regarding its effects on rate-limiting step in cholesterol synthesis, was used to treat with BCa cells. We observed that simvastatin could reduce BCa cell proliferation, induce cell cycle arrest at G0/G1 phase and inhibit cell metastasis. Then, the potential alterations of lipids metabolism in bladder cancer cells after simvastatin treatment was investigate by lipidomics analysis. These foundings demonstrate that lipids metabolism plays important role in bladder cancer and some lipids or related enzymes may be the novel targets for bladder cancer treatment.
Note: This abstract was not presented at the meeting.
Citation Format: Gang Wang, Rui Cao, Qiangqiang Ge, Yu Xiao, Xinghuan Wang. The role of lipids metabolism in bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2511. doi:10.1158/1538-7445.AM2017-2511
Abstract 2514: Tetra-O-methyl nordihydroguaiaretic acid (M4N) broadly suppresses cancer metabolism and synergistically induces strong anticancer activity in combination with etoposide, rapamycin and UCN-01
Authors: Kimura Kotohiko , Huang Ru Chih C. 
Published: July 2017

Abstract
The ability of Tetra-O-methyl nordihydroguaiaretic acid (M4N) to induce rapid cell death in combination with Etoposide, Rapamycin, or UCN-01 was examined in LNCaP cells, both in cell culture and animal experiments. Mice treated with M4N drug combinations with either Etoposide or Rapamycin showed no evidence of tumor and had a 100% survival rate 100 days after tumor implantation. By comparison all other vehicles or single drug treated mice failed to survive longer than 30 days after implantation. This synergistic improvement of anticancer effect was also confirmed in more than 20 cancer cell lines. In LNCaP cells, M4N was found to reduce cellular ATP content, and suppress NDUFS1 expression while inducing hyperpolarization of mitochondrial membrane potential. M4N-treated cells lacked autophagy with reduced expression of BNIP3 and ATG5. To understand the mechanisms of this anticancer activity of M4N, the effect of this drug on three cancer cell lines (LNCaP, AsPC-1, and L428 cells) was further examined via transcriptome and metabolomics analyses. Metabolomic results showed that there were reductions of 26 metabolites essential for energy generation and/or production of cellular components in common with these three cell lines following 8 hours of M4N treatment. For instance, among the amino acids, the content of aspartate, a key metabolite in electron transport system in the mitochondria, was specifically suppressed by M4N. Deep RNA sequencing analysis demonstrated that there were sixteen genes whose expressions were found to be modulated following 6 hours of M4N treatment similarly in these three cell lines. Six out of these 16 genes were functionally related to the 26 metabolites described above. One of these up-regulated genes encodes for CHAC1, a key enzyme affecting the stress pathways through its degradation of glutathione. In fact M4N was found to suppress glutathione content and induce reactive oxygen species production. The data overall indicate that M4N has profound specific negative impacts on a wide range of cancer metabolisms supporting the use of M4N combination for cancer treatments.
Citation Format: Kotohiko Kimura, Ru Chih C. Huang. Tetra-O-methyl nordihydroguaiaretic acid (M4N) broadly suppresses cancer metabolism and synergistically induces strong anticancer activity in combination with etoposide, rapamycin and UCN-01 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2514. doi:10.1158/1538-7445.AM2017-2514
Abstract 2516: Pokemon functions as a metabolic oncoprotein integrating glucose & lipid metabolism in hepatocellular carcinoma
Authors: Jin Yibao , Li Shangfu , Cao Deliang , Gao Dan , Liu Hongxia , Liu Feng , Wang Tiejie , Jiang Yuyang 
Published: July 2017

Abstract
Pokemon (also known as FBI-1 or LRF) is a proto-oncogene encoded by ZBTB7A gene. It functions as a transcription factor, playing important roles in embryonic development, cell differentiation and neoplasia. Pokemon is abnormally expressed in hepatocellular carcinoma (HCC) and may contribute to the metabolic homeostasis of HCC cells, but the mechanism of action remains to be fully understood. This study demonstrated that Pokemon may integrate glycolysis and lipid metabolism in hepatocellular carcinogenesis. Our data showed that Pokemon was upregulated in HCC cell lines and clinical samples. Ectopic expression of Pokemon stimulated HCC cell growth and proliferation in culture and tumorigenesis in nude mice. Lipid metabolomic analysis by LC/MS exhibited that in HCC cells lipogenesis was positively correlated with Pokemon expression levels, and targeted expression of Pokemon in HCC cells promoted the flux of radiolabeled glucose to lipids, including membrane phospholipids, through the aerobic glycolysis-acetyl-CoA metabolic stream. Mechanistic studies revealed that Pokemon stimulated glycolysis through activation of PKA and its mediated Raf/c-Myc pathway. In the tested HCC cells, Pokemon activated fatty acid synthase (FASN) and suppressed AMPK, an inhibitor of acetyl-CoA carboxylase α (ACC-α), stimulating fatty acid and lipid synthesis. Together our results suggest that Pokemon correlates glycolysis and lipid synthesis and thus promotes lipogenesis and hepatocellular tumorigenesis.
Note: This abstract was not presented at the meeting.
Citation Format: Yibao Jin, Shangfu Li, Deliang Cao, Dan Gao, Hongxia Liu, Feng Liu, Tiejie Wang, Yuyang Jiang. Pokemon functions as a metabolic oncoprotein integrating glucose & lipid metabolism in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2516. doi:10.1158/1538-7445.AM2017-2516
Abstract 253: Mammary tumorigenesis causes bone loss and dietary selenium supplementation does not affect such bone loss in male MMTV-PyMT mice
Authors: Yan Lin 
Published: July 2017

Abstract
Cancer progression is accompanied by wasting that eventually results in cachexia characterized by significant weight loss and multi-organ functional failures. Limited clinical trials indicate that bone is adversely affected by cancer-associated wasting. To determine the effects of breast cancer on skeletal health, we performed micro-computed tomographic analysis of femurs and vertebrae collected from a recently completed study showing that dietary supplementation with selenium (methylseleninic acid, 2.5 mg Se/kg) reduced male mammary tumorigenesis in MMTV-PyMT mice. Compared to age-matched non-tumor-bearing mice (MMTV-PyMT negative), the presence of mammary tumors significantly reduced bone volume fraction, trabecular thickness and bone mineral density and increased the structure model index (an indicator of the plate- and rod-like geometry of trabecular structure) in femoral trabecular bone. Mammary tumor development did not affect vertebral trabeculae nor femoral and vertebral cortical bone, except it significantly reduced cortical bone thickness of vertebrae. There were no differences in aforementioned measurements between groups with or without selenium supplementation. In conclusion, mammary tumorigenesis causes bone loss and dietary selenium supplementation at 2.5 mg Se/kg, which is antitumorigenic, does not affect mammary tumor-associated bone loss in this male MMTV-PyMT breast cancer model.
Citation Format: Lin Yan. Mammary tumorigenesis causes bone loss and dietary selenium supplementation does not affect such bone loss in male MMTV-PyMT mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 253. doi:10.1158/1538-7445.AM2017-253
Abstract 2531: Regulation of androgen signaling axis and tumor suppressive function of miR-149-5p in prostate cancer
Authors: Singh Savita , Ebron Jey Sabith , Shankar Eswar , Gupta Sanjay , Lindner Daniel , Shukla Girish 
Published: July 2017

Abstract
Prostate cancer growth and proliferation depends on androgen signaling mediated by transactivation of Androgen Receptor (AR). Androgen ablation remains the mainstay therapy for treatment of the disease. However, despite androgen ablation, the disease relapses to more aggressive form known as castration-resistant prostate cancer (CRPC). Androgen Signaling Inhibitor such as Abiraterone Acetate and Enzalutamide are the most effective treatment methods currently being used to treat CRPC. However, more than one-third of CRPC patients develop resistance to these treatments, mostly due to the gain of function in the AR protein and increase in intratumoral dihydrotestosterone (DHT) synthesis. Intratumoral DHT synthesis from steroid precursors in tumors is augmented by up-regulation of enzymes of cholestrogenesis and steroidogenesis, such as HMG-CoA reductase, SCARB1, and 17βHSD respectively. Tumor-specific downregulation of microRNAs which regulate the AR and steroid biosynthesis has been implicated in tumor growth and resistance to therapeutics in CRPC. We are focusing on tumor suppressive role of miR-149-5p in PCa. We discovered that miR-149-5p expression was significantly lower in prostate cancer tissues compared to normal tissues. The mechanistic investigation revealed that miR-149-5p downregulates wild type and alternatively spliced variant of AR. It also down regulates the expression of SCARB1, HMGCS and HMG-CoA reductase, the proteins known to facilitate intratumoral DHT synthesis. Ectopic expression of miR-149-5p negatively regulated the expression of prostate-specific antigen, a downstream target of androgen signaling and it also inhibited invasion and proliferation of CRPC cells. Our findings indicate a significant role of miR-149-5p in regulating androgen signaling and possibly DHT synthesis in CRPC. This provides a strong rationale for further investigating the significance of miR-149-5p for generation of new therapeutic for CRPC.
Citation Format: Savita Singh, Jey Sabith Ebron, Eswar Shankar, Sanjay Gupta, Daniel Lindner, Girish Shukla. Regulation of androgen signaling axis and tumor suppressive function of miR-149-5p in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2531. doi:10.1158/1538-7445.AM2017-2531