bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1637: 22(S)-Hydroxycholesterol, an antagonist of LXR, inhibits breast cancer cell migration
Authors: Hwang Sewon , Na Tae Young , Na Hyelin , Lee Minho , Lee Mi-Ock 
Published: July 2016

Abstract
The Liver X Receptor (LXR) is a well-established ligand-regulated transcription factor involved in cholesterol homeostasis, lipid metabolism, and inflammation. Recent studies have reported a strong antiproliferative effect of LXRs in multiple types of cancer including prostate, colon, lung, and breast cancer. However, little is known about its association with cancer metastasis. Therefore we aimed to investigate the potential of LXR ligands in the context of breast cancer cell migration, and its underlying molecular mechanism. We first performed 2D-migration assay in 4T1 breast cancer cells. Treatment of an LXR antagonist significantly reduced the rate of 4T1 cell migration. However, LXR agonists such as T0901317, GW3965 did not have much effect. Next, we investigated the molecular mechanism of cell migration. Since the degree of invasion and metastasis of breast carcinoma is well correlated with elevated expression of metastasis-associated protein 1 (MTA1), we examined whether MTA1 expression could be regulated by LXR ligands. Interestingly, when LXR agonists were treated, increased protein expression of MTA1 and its downstream target protein HIF-1α was observed in MCF7, MDA-MB-231, and 4T1-Luc breast cancer cell lines. Transient expression of LXRα demonstrated the same results as well. Furthermore, the treat of 22(S)-HC down-regulated MTA1 and HIF-1α protein expressions. Together, our findings indicate that LXR influences migratory pattern of breast cancer cells, which may affect metastatic property of breast cancer cells via LXR-dependent regulation of MTA1 and HIF-1α expression.
Citation Format: Sewon Hwang, Tae Young Na, Hyelin Na, Minho Lee, Mi-Ock Lee. 22(S)-Hydroxycholesterol, an antagonist of LXR, inhibits breast cancer cell migration. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1637.
Abstract 1666: Biomarkers for early detection of radiation nephropathy
Authors: Song Feifei , Jacob Jidhin , Chakravarti Arnab , Jacob Naduparambil K. 
Published: July 2016

Abstract
Purpose/Background: Chronic kidney disease is among the common late effects detected in patients receiving chemotherapy and/or radiotherapy. Currently, there are no biomarkers that allow detection of normal tissue toxicity in late responding organs such as kidney. Developing predictive biomarkers could help identify individuals that are at high risk for close follow-up and prophylactic treatments. Our studies show that miRNAs detectable in cell-free body fluids can be developed as biomarkers of acute radiation syndromes. In the present study, we sought to investigate the potential of serum and urine miRNAs as indicators of radiation induced kidney damage in rodent models.
Methods and Results: An amplification-free hybridization based nCounter assay was optimized for evaluating the changes of miRNAs in body fluids. Comparison of cell-free miRNAs in urine as well as serum, collected from control versus irradiated mice, enabled us to identify candidate biomarkers that are potential indicators of radiation response. Over 40 miRNAs were detectable in urine samples collected from mice and over 80 miRNAs were detectable in serum. Molecules such as miR-1224, miR-804, miR-714 and miR-709 showed significant increase in their urine level after radiation, which peaked 6-8 hours after exposure to acute doses. On the other hand, markers such as miR-378 that are also abundant in urine did not show significant change after radiation, hence serving as an internal control. Comparison of urinary response in mice exposed to 2, 4, 6 and 8 Gy TBI revealed good dose response. Furthermore, the same markers exhibited a dose and time dependent changes following exposure to fractionated myeloablative regimen (6 × 2 Gy, bid) that is commonly used in leukaemia patients, prior to stem cell transplantation. Specifically, two of these biomarkers, miR-714 and miR-1224 exhibited a dose dependent increase in their serum level after fractionated or acute single dose exposure. In-situ hybridization displayed an overall increase in signals of miR-1224 and miR-714 at outer medulla after radiation. Increased signals detected in tubular epithelial cells indicate the possible tubular origin of the urinary miRNAs that are responsive to radiation.
Conclusion: We have developed a panel of miRNAs for non-/minimally invasive detection of radiation response in kidney. Several of the urinary miRNA biomarkers exhibited a dose and time dependent changes, suggesting their potential as biomarkers for non-invasive evaluation of radiation response in organs such as kidney for which early detection of damage is a major challenge.
Citation Format: Feifei Song, Jidhin Jacob, Arnab Chakravarti, Naduparambil K. Jacob. Biomarkers for early detection of radiation nephropathy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1666.
Abstract 1669: Inhibition of the Rac1/PAK pathway sensitizes pancreatic cancer cells to gamma-irradiation
Authors: Ouellette Michel M. , Batra Surinder K. , Yan Ying 
Published: July 2016

Abstract
Radiation therapy is a staple treatment for pancreatic cancers. However, owing to the intrinsic radioresistance of pancreatic cancer cells, radiation therapy often fails to increase survival of pancreatic cancer patients. Radiation impedes cancer cells by inducing DNA damage, which can activate cell cycle checkpoints. Normal cells possess both G1/S and G2/M checkpoints. However, cancer cells are often defective in G1/S checkpoint due to mutations/alterations in the key regulators of this checkpoint. Accordingly, our results show that normal pancreatic ductal cells respond to ionizing radiation (IR) with activation of both checkpoints whereas pancreatic cancer cells respond to IR with G2/M arrest only. Overexpression/hyperactivation of Rac1 GTPase is detected in the majority of pancreatic cancers. Rac1 plays important roles in survival and Ras mediated transformation. Here, we show that Rac1 and its downstream effector, the PAK kinases, also plays a critical role in the response of pancreatic cancer cells to IR. Inhibition of Rac1/PAK pathway with pharmacological inhibitors (Ehop-016, AZA1, NSC23766, and FRAX597) or a dominant negative mutant of Rac1 (Rac1T17N) blocks activation of the ATM/Chk2 and ATR/Chk1 pathways, abrogates activation of the IR-induced G2/M checkpoint, delays the repair of IR-induced double-stranded DNA breaks, and increases the radiosensitivity of pancreatic cancer cells through induction of apoptosis. These results implicate Rac1 signaling in the survival of pancreatic cancer cells following IR, raising the possibility that this pathway contributes to the intrinsic radioresistance of pancreatic cancer.
Citation Format: Michel M. Ouellette, Surinder K. Batra, Ying Yan. Inhibition of the Rac1/PAK pathway sensitizes pancreatic cancer cells to gamma-irradiation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1669.
Abstract 1670: Radiosensitization of glioma cells by the ketone body β-hydroxybutyrate is associated with enhanced cell cycle arrest in the G2/M phase
Authors: Silva-Nichols Helena B. , Rossi Alex P. , Woolf Eric C. , Fairres Marshall J. , Deleyrolle Loic P. , Reynolds Brent A. , Scheck Adrienne C. 
Published: July 2016

Abstract
Glioblastoma multiforme (GBM) is an aggressive primary brain tumor with a 5 year survival rate of 25% in children and less than 10% in adults. Improvement in the prognosis of GBM patients requires the development of new therapeutic approaches. One emerging strategy is to target aberrant cell metabolism, a trait shared by virtually all tumor cells. The ketogenic diet (KD), a high fat, low carbohydrate and protein metabolic therapy has been shown to prolong survival in animal glioma models, and when used in conjunction with radiation cured 9 of 11 mice of their implanted tumors. We have also shown that the KD alters hypoxia, angiogenesis, and other hallmarks of glioma progression. To elucidate the underlying mechanisms through which ketones exert their effects on glioma, we are doing analyses of the effect of β-hydroxybutyrate (βHB), the most prevalent ketone body synthesized during ketosis, on glioma cells in vitro. We found that βHB both alone and in conjunction with radiation significantly inhibits proliferation of human and mouse glioma cells and human glioma stem cells (GSC). Alterations in passage through the cell cycle may affect proliferation, and cells are also more sensitive to radiation in the G2/M cell cycle phase. We therefore analyzed the effect of βHB on cell cycle distribution of cells treated with βHB and/or radiation. An analysis of cell cycle status by flow cytometry demonstrated that treating the GSC line L0 with 5mM βHB in combination with 4 Gy of radiation significantly increased the number of cells in G2/M cell cycle arrest. In GL261-Luc2 mouse glioma cells, 5mM βHB alone significantly enhanced G2/M cell cycle arrest, which could lead to radiosensitization. Currently we are analyzing proteins involved in cell cycle progression and apoptosis to better understand βHB mediated changes in growth and radioresistance. In summary, these data provide insight to the radiosensitization and anti-proliferative mechanisms of βHB and may hold implications for the use of the KD in the treatment of GBM.
Citation Format: Helena B. Silva-Nichols, Alex P. Rossi, Eric C. Woolf, Marshall J. Fairres, Loic P. Deleyrolle, Brent A. Reynolds, Adrienne C. Scheck. Radiosensitization of glioma cells by the ketone body β-hydroxybutyrate is associated with enhanced cell cycle arrest in the G2/M phase. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1670.
Abstract 1721: Desmoplasia stem and progenitor cells within the tumor microenvironment
Authors: Lannagan Tamsin , Woods Susan , Vrbanac Laura , Yang Miao , Ng Jia , Wang Tongtong , Tailor Yagnesh , Asfaha Samuel , Wang Timothy , Worthley Daniel L. 
Published: July 2016

Abstract
All developing and adult organs are supported by connective tissues. We recently demonstrated that Gremlin 1 expressing cells in the bone (osteochondroreticular stem cells) and the bowel (intestinal reticular stem cells) are connective tissue stem cells, during development and healing. The contribution of these stem cells to the desmoplasia surrounding gastrointestinal and skeletal cancers, however, is unknown. In this study we first established that typical markers of bone marrow skeletal stem cells, also identify colony forming unit-fibroblasts (CFU-Fs) in the tumour microenvironment (identified by CD45-Ter-119-CD31-CD1040a+CD105+). Next we tested the local origins of alpha-smooth muscle actin (Acta2) expressing cancer-associated fibroblasts in orthotopic (colonoscopically delivered MC38 and carcinogenesis AOM/DSS) mouse models of colorectal cancer. Using transgenic mouse models to lineage trace and report the connective tissues in the bone and bowel, including Grem1-creERT;R26-LSL-ZsGreen; Acta2-RFP and our Acta2-CreERT line, we found that normal Grem1-expressing and Acta2-expressing cells each contribute to some, but not all, of the reactive cancer-associated fibroblasts surrounding our mouse models of cancer. Whilst, neoplastic cells appear to make a significant contribution to cancer-associated fibroblasts in some other cancers, using an epithelial specific Cre (K19-cre) there was no contribution of epithelium to Acta2-expressing cells in our AOM-DSS colorectal cancer models. We investigated Grem1 and Acta2 derived cells from the tumor microenvironment and found that these cells were clonagenic. Finally, we compared their capacity to support the in vitro growth of colorectal normal and neoplastic organoids compared to other colonic mesenchymal cell types. We are currently examining the role of these cells on expanding intestinal stem cells in normal and neoplastic gastrointestinal glands and examining the secreted factors from these cells that are relevant to tumor initiation and spread.
Citation Format: Tamsin Lannagan, Susan Woods, Laura Vrbanac, Miao Yang, Jia Ng, Tongtong Wang, Yagnesh Tailor, Samuel Asfaha, Timothy Wang, Daniel L. Worthley. Desmoplasia stem and progenitor cells within the tumor microenvironment. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1721.
Abstract 1787A: Puerto Rico BioBank: The first cancer tissue biobank at a US Hispanic-serving institution
Authors: Casbas-Hernandez Patricia , Flores Idhaliz , Seijo Edward , Coppola Domenico , Eschrich Steve , Carvajal-Pelaez Rodrigo , Abac Sonia , Correa Dagmar , Gordian Edna , Munoz-Antonia Teresita 
Published: July 2016

Abstract
There are currently 580 million people worldwide considered to be of Hispanic origin. In the US Hispanics represent 17% of the population and its largest ethnic minority. Funded by NIH, Moffitt Cancer Center (Florida) and Ponce School of Medicine (Puerto Rico) initiated a partnership that conducts high-quality research, training, and community outreach focusing on cancer health disparities among Hispanics. A central component to this partnership is the establishment of the first cancer-focused biobank in the island, the Puerto Rico BioBank (PRBB). The PRBB has actively recruited cancer patients since 2009; over these years we have established essential collaborations and a functional infrastructure. Eligible cancer patients provide informed consent and agree to donate blood samples (for DNA) and solid tissue(fresh-frozen & paraffin embedded). Additionally, patients complete a comprehensive questionnaire related to clinical and lifestyle factors. Biospecimen collection at the PHSU follow standard operating procedures that mirror and often exceed NCI biobaking best practices for biospecimens and ensuring patient data confidentiality. Currently, the PRBB has over 1,100 consented patients (65.8% females, 34.2% males) all of Hispanic origin. The most common banked tumors are Breast, Prostate, Lung and Endometrium, although other tumors are represented. All the information and data are entered into a biospecimen management system (BMS) developed by the partnership, which allows for real-time biospecimen inventory management and reporting functionality. In conclusion, the Puerto Rican patient samples banked in the PRBB are a unique resource that can support multiple molecular and population studies. Also, a Hispanic-specific biobank can foster collaborations among local and international researchers that may facilitate the application of novel molecular techniques to solving cancer health disparities among Hispanics.
Citation Format: Patricia Casbas-Hernandez, Idhaliz Flores, Edward Seijo, Domenico Coppola, Steve Eschrich, Rodrigo Carvajal-Pelaez, Sonia Abac, Dagmar Correa, Edna Gordian, Teresita Munoz-Antonia. Puerto Rico BioBank: The first cancer tissue biobank at a US Hispanic-serving institution. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1787A.
Abstract 1796A: Race and gender differences in lung cancer: examining the effect of smoking history and depression on hospitalization costs
Authors: Husaini Baqar A. , Cain Van A. , Levine Robert S. 
Published: July 2016

Abstract
Objective: Incidence rates of lung cancer (LC) are reported to have declined in the nation. However, the role of depression and tobacco history relative to hospitalization cost for LC remains unknown. Tennessee, being a tobacco producing State, provides an opportunity to examine two issues: (i) Prevalence of LC, depression, and history of tobacco use among LC patients by race and gender; (ii) Effect of depression and smoking history on hospitalization costs by sub-groups of LC patients.
Methods: We extracted data pertaining to depression, smoking history, and demographics on patients discharged with all lung cancer (adenocarcinoma, ICD-9 codes 160-165) from the 2008 Tennessee Hospital Discharge Data System (HDDS). The sample (n = 6,665) had patients that were mostly white (86%) and male (57%), with an average age of 67 years. We computed age-adjusted LC rates for race and gender (per CDC methodology), and compared the costs for LC patients with depression/ smoking history with LC patients without depression/smoking history.
Results: LC rates (per 100K) were higher among blacks than whites (146.6 vs. 131.6, p&lt;.000), and higher among male than female patients (174.9 vs. 118.0, p&lt;.00). While nearly 40% of LC patients had a smoking history (more males than females had a history with no racial variation), 25% had depression (more females and whites were depressed). Further, the total hospitalization cost for 2008 was 50% higher for LC patients with depression plus smoking history compared to peers without depression/smoking history ($122,500 vs. 80,522, p&lt;.000).
Conclusion: LC rates are higher among blacks and males who also have more smoking history. Depression is higher among females and whites with LC. Further, both depression and smoking history adds significantly to the hospitalization costs. These results point to: (i) costs savings might be realized by treating depression first among the LC patients, and (ii) population-based smoking cessation programs need to be vigorously implemented to reduce lung cancer and associated co-morbidities.
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This presentation at the Eight AACR annual Conference, New Orleans, April 16-20, 2016, was partially supported by grants from CDC #U58CCU422782, a sub-contract #ED-07-20811-09, and a NCI/NIH grant (5U54CA163066) to Tennessee State University, B. Husaini, PI.
Citation Format: Baqar A. Husaini, Van A. Cain, Robert S. Levine. Race and gender differences in lung cancer: examining the effect of smoking history and depression on hospitalization costs. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1796A.
Abstract 1816: Alpha lipoic acid inhibits proliferation and epithelial mesenchymal transition of thyroid cancer cells
Authors: Kwon Hyemi , Jeon Min Ji , Kim Won Gu , Lim Seonhee , Sim Soyoung , Kim Tae Yong , Shong Young Kee , Kim Won Bae 
Published: July 2016

Abstract
The short-chain fatty acid, α-lipoic acid (ALA) is a powerful antioxidant used for treatment of diabetic neuropathy. Recent studies suggested the possibility of ALA as a potential anti-cancer agent, because it could activate adenosine monophosphate activated protein kinase (AMPK) and inhibit transforming growth factor-β (TGFβ) pathway. We evaluate the effects of ALA on thyroid cancer cell proliferation, migration, and invasion. We performed in vitro cell proliferation analysis with BCPAP, HTH-83, CAL-62, and FTC-133 cells. ALA suppressed cell proliferation through activation of AMPK and subsequent down-regulation of mammalian target of rapamycin (mTOR)-S6 signaling pathway. Low-dose ALA, which had minimal effects on cell proliferation, also decreased cell migration and invasion of BCPAP, CAL-62, and HTH-83 cells. ALA inhibited epithelial mesenchymal transition (EMT) evidently by increase of E-cadherin and decreases of activated β-catenin, vimentin, snail, and twist in these cells. ALA suppressed TGFβ production and inhibited induction of p-Smad2, and twist by TGFβ1 or TGFβ2. These findings indicate that ALA reduces thyroid cancer cell migration and invasion through suppression of TGFβ production and inhibition of TGFβ signaling pathways. ALA also significantly suppressed tumor growth in mouse xenograft model using BCPAP and FTC-133 cells. This is the first study to show anti-cancer effect of ALA on thyroid cancer cells. ALA could be a potential therapeutic agent for advanced thyroid cancer, as an adjuvant therapy with other systemic therapeutic agents.
Citation Format: Hyemi Kwon, Min Ji Jeon, Won Gu Kim, Seonhee Lim, Soyoung Sim, Tae Yong Kim, Young Kee Shong, Won Bae Kim. Alpha lipoic acid inhibits proliferation and epithelial mesenchymal transition of thyroid cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1816.
Abstract 1834: Semaphorin 3C is an androgen receptor-regulated gene
Authors: Tam Kevin J. , Dalal Kush , Hsing Michael , Cheng Chi Wing , Chiang Yan Ting , Sharma Aishwariya , Peacock James W. , Cherkasov Artem , Wang Yuzhuo , Gleave Martin E. , Rennie Paul S. , Ong Christopher J. 
Published: July 2016

Abstract
Prostate cancer (PCa) is the second leading cause of cancer-related deaths in North America. The androgen receptor (AR) is a member of the nuclear receptor superfamily of transcription factors and is heavily implicated in PCa progression. First-line therapies frequently target the AR axis and are initially met with favourable response but restored and aberrant AR signaling fuel disease progression to stages for which treatment is palliative. Transcriptional targets of the AR include genes involved in cell growth and cell fate but are not completely described. The semaphorin family of signaling proteins is a large grouping of cell-surface or secreted signaling proteins that function in neurogenesis and development. The roles of semaphorins in cancer are becoming increasingly evident however mechanistic details surrounding their involvement in cancer are poorly defined. One member of the class 3 semaphorins, SEMA3C, has been shown to confer invasive phenotypes in prostate cancer cells. Using the AR-positive LNCaP cell line we show that SEMA3C is an androgen-responsive gene. Additionally, using RSAT DNA analysis software we identify an androgen response element (ARE) in intron 2 of SEMA3C and show that AR is recruited to this genomic region in an androgen-dependent manner in chromatin immunoprecipitation assays. Furthermore, the isolated ARE binds to the AR-DNA binding domain in gel shift assays and can be transactivated by AR in reporter gene assays. Finally we show that the pioneering factor, GATA2, is necessary for AR-mediated expression of SEMA3C. Collectively, our work identifies SEMA3C as a direct transcriptional target of AR in support of our hypothesis that dysregulated AR signaling drives inadvertent upregulation of SEMA3C and PCa disease progression. Deregulated AR signaling underpins prostate cancer progression and underscores the need to elucidate transcriptional targets of AR. Identification of SEMA3C as a novel target of AR provides the rationale for targeted therapies directed against SEMA3C.
Citation Format: Kevin J. Tam, Kush Dalal, Michael Hsing, Chi Wing Cheng, Yan Ting Chiang, Aishwariya Sharma, James W. Peacock, Artem Cherkasov, Yuzhuo Wang, Martin E. Gleave, Paul S. Rennie, Christopher J. Ong. Semaphorin 3C is an androgen receptor-regulated gene. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1834.