bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 126: The KISS1 metastasis suppressor appears to integrate glycolysis, mitochondrial biogenesis and metastasis via regulation of a PGC1α pathway
Authors: Liu Wen , Beck Benjamin , Vaidya Kedar S. , Nash Kevin T. , Ballinger Scott W. , Welch Danny R. 
Published: May 2015

Abstract
Considering the enormous energy requirements and stresses of the metastatic cascade, an interrelationship with aerobic glycolysis seems intuitive, but has not been definitively established. The purpose of these studies was to determine whether there is a relationship between KISS1 metastasis suppression and metabolism. Wild-type KISS1 expressed in human melanoma cells were metastasis suppressed and took up less glucose and produced less lactate, corresponding to higher pH[Ex]. Metabolism and metastasis changes did not occur when KISS1 was missing the secretion signal peptide (ΔSS). Changes in glucose transport and key glycolytic enzymes did not consistently correlate with metabolic changes; however, V-ATPase, which promotes extracellular acidification, invasion and metastasis, appears to be involved in KISS1-mediated metabolic changes. Also corresponding with the shift from glycolysis to oxidative phosphorylation, KISS1-expressing cells have 30-50% more mitochondrial mass accompanied increased higher expression of PPARγ co-activator 1α (PGC1α), a master regulator of mitochondrial biogenesis. PGC1α-mediated downstream pathways (i.e. fatty acid synthesis and β-oxidation) are differentially regulated by KISS1, apparently reliant upon direct KISS1 interaction with Nuclear Respiratory Factor 1 (NRF1), a major transcription factor involved in mitochondrial biogenesis. KISS1 does not affect PGC1α mRNA expression but stabilizes the protein through interaction with the ubiquitin-like protein, UBQLN1. To test whether a KISS1- PGC1α axis is critical for metastasis suppressor function, shRNA to KISS1 or PGC1α was introduced into KISS1-expressing cells. Metabolic changes and suppression of invasion and migration were reversed. Importantly, knock-down of PGC1α abolished KISS1-mediated metastasis suppression in vivo, strongly suggesting that PGC1α is an essential downstream mediator of KISS1 as a metastasis suppressor. Taken together, these data define a novel signaling pathway controlling metabolism and metastasis. Moreover, these data appear to directly connect changes in aerobic glycolysis, mitochondrial metabolism, and cancer metastasis.
Citation Format: Wen Liu, Benjamin Beck, Kedar S. Vaidya, Kevin T. Nash, Scott W. Ballinger, Danny R. Welch. The KISS1 metastasis suppressor appears to integrate glycolysis, mitochondrial biogenesis and metastasis via regulation of a PGC1α pathway. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 126. doi:10.1158/1538-7445.AM2014-126
Abstract 1268: High coffee consumption and different brewing methods in relation to postmenopausal endometrial cancer risk in the norwegian women and cancer study: A population-based prospective study
Authors: Gavrilyuk Oxana , Braaten Tonje , Skeie Guri , Weiderpass Elisabete , Dumeaux Vanessa , Lund Eiliv 
Published: May 2015

Abstract
Background
Coffee and its compounds have been proposed to inhibit endometrial carcinogenesis. Studies in the Norwegian population can be especially interesting due to the high coffee consumption and increasing incidence of endometrial cancer in the country.
Methods
A total of 97 926 postmenopausal Norwegian women from the population-based prospective Norwegian Women and Cancer (NOWAC) Study, were included in the present analysis. We evaluated the general association between total coffee consumption and endometrial cancer risk as well as the possible impact of brewing method. Multivariate Cox regression analysis was used to estimate risks, and heterogeneity tests were performed to compare brewing methods.
Results
During an average of 10.9 years of follow-up, 462 incident endometrial cancer cases were identified. After multivariate adjustment, significant risk reduction was found among participants who drank ≥8 cups/day of coffee with a hazard ratio of 0.52 (95% confidence interval, CI 0.34-0.79). However, we did not observe a significant dose-response relationship. No significant heterogeneity in risk was found when comparing filtered and boiled coffee brewing methods. A reduction in endometrial cancer risk was observed in subgroup analyses among participants who drank ≥8 cups/day and had a body mass index ≥25 kg/m2, and in current smokers.
Conclusions
These data suggest that in this population with high coffee consumption, endometrial cancer risk decreases in women consuming ≥8 cups/day, independent of brewing method.
Citation Format: Oxana Gavrilyuk, Tonje Braaten, Guri Skeie, Elisabete Weiderpass, Vanessa Dumeaux, Eiliv Lund. High coffee consumption and different brewing methods in relation to postmenopausal endometrial cancer risk in the norwegian women and cancer study: A population-based prospective study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1268. doi:10.1158/1538-7445.AM2014-1268
Abstract 1271: Alcohol intake and breast cancer in the European Prospective investigation into Cancer and Nutrition (EPIC) study
Authors: Romieu Isabelle , Scoccianti Chiara , Chajes Veronique , Batlle Jordi De , Rinaldi Sabina 
Published: May 2015

Abstract
Context: Alcohol intake has been positively associated to breast cancer among both pre and postmenopausal women; however results are inconclusive with regards to tumor hormonal receptor status, and potential modifying factors such as age at start drinking, and dietary fiber.
Objective: To investigate the relation between alcohol intake and the risk of breast cancer using data from the European Prospective Investigation into Cancer and Nutrition (EPIC).
Design, Setting, and Participants: Prospective observational study of 334,850 women mostly aged 35-70 years at baseline enrolled in the ten countries of the EPIC study and followed up for 11.0 years on average. Information on alcohol intake at baseline and average lifetime alcohol intake were calculated from country-specific dietary and lifestyle questionnaires.
Main Outcome Measures: Hazard ratios (HR) of developing invasive breast cancer according to hormonal receptor status.
Results: During 3,670,439 person-years, 11,576 incident breast cancer cases were diagnosed. Increasing alcohol intake was significantly related to breast cancer risk, for each 10g/day increase in alcohol intake the HR increased by 4.2% (95% CI, 2.7% -5.8%). Taking 0 to 5g/day as reference, alcohol intake of &gt;5 to 15 g/day was related to a 5.9% increase of breast cancer risk (95% CI, 1% -11%). A significant increasing trend was observed between alcohol intake for ER+/PR+, ER-/PR-, HER2- and ER-/PR-/HER2-tumors. The risk of breast cancer appeared stronger among women who started drinking prior to first full-time pregnancy and among drinkers (&gt;15g/day) with low intake of fiber.
Conclusions: Our results confirm the association between alcohol intake and breast cancer risk, and suggest that some other risk factors such as fiber intake, may modulate this association. Women should be advised to control their alcohol intake, and increase their intake of fiber.
Citation Format: Isabelle Romieu, Chiara Scoccianti, Veronique Chajes, Jordi De Batlle, Sabina Rinaldi. Alcohol intake and breast cancer in the European Prospective investigation into Cancer and Nutrition (EPIC) study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1271. doi:10.1158/1538-7445.AM2014-1271
Abstract 1280: Germline PALB2 genetic variations of familial esophageal squamous cell carcinoma (ESCC) in Henan, a high risk ESCC region
Authors: Ko Josephine Mun Yee , Wang Li Dong , Lung Maria 
Published: May 2015

Abstract
Background and aims:
ESCC is often a deadly cancer diagnosed at late stage with a 5-year survival rate less than 10% in advanced cancers. It is important to elucidate the molecular genetic basis for this deadly cancer to achieve the ultimate goal of early cancer detection and improved clinical management. Our aim is to understand the genetic basis of inherited ESCC by deciphering PALB2 mutation status in high risk northern China. By investigation of PALB2 germline mutations and variants, as compared to healthy individuals, the genetic basis and genomic risk factor associations with inherited EC will be clarified.
Methods:
Blood was collected from high-risk Henan familial history-positive (FH+) individuals. Blood DNAs were extracted for Sanger sequencing analysis.
Results:
By Sanger sequencing with primers covering more than 90% of the PALB2 coding sequence, PALB2 variants were detected in exon 4 for 4% (2/50) FH+ ESCC patients from Henan, but no germline protein truncation variations were observed. Since mutations were only observed in exon 4, further mutation screening were confined to exon 4 of PALB2 with an additional 300 FH+ Henan ESCC, 283 FH- Henan ESCC, and 364 Henan non-ESCC control individuals. However, no mutations were detected in the validation samples.
Conclusions:
Infrequent PALB2 germline mutations were detected in Henan FH+ ESCC patients, suggesting PALB2 may be involved in a small proportion of familial ESCC in Henan. Further study is necessary to clarify if the identified mutations are pathogenic.
Citation Format: Josephine Mun Yee Ko, Li Dong Wang, Maria Lung. Germline PALB2 genetic variations of familial esophageal squamous cell carcinoma (ESCC) in Henan, a high risk ESCC region. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1280. doi:10.1158/1538-7445.AM2014-1280
Abstract 1289: Breast cancer predisposition in multiple endocrine neoplasia type 1
Authors: Dreijerink Koen , Conemans Elfi , Cornelissen Chantal , Blokland Marja Van , Mannstadt Michael , Pieterman Carla , Herder Wouter D. , Havekes Bas , Fliers Eric , Hermus Ad , Vriens Menno , Timmers Marc , Wall Elsken Van der , Brown Myles , Luijt Rob Van der , Diest Paul van , Valk Gerlof 
Published: May 2015

Abstract
Recent genetic and animal studies have suggested that the Multiple Endocrine Neoplasia type 1 (MEN1) gene is involved in breast carcinogenesis. In addition, the MEN1 gene product menin is a regulator of estrogen receptor alpha function in vitro.
In this retrospective study in two independent cohorts we aimed to investigate the prevalence of breast cancer in female MEN1 patients and to characterize MEN1-related breast tumors.
The Dutch MEN1 cohort contains data from 190 female MEN1 patients from 1990-2011. The second cohort from the U.S. has data from 68 female patients from 2004-2013. Observations were matched with demographic and cancer incidence and prevalence information from the general Dutch and U.S. populations. Breast cancer tissues from MEN1 patients were analyzed immunohistochemically and loss of heterozygosity (LOH) at the MEN1 gene locus was assessed.
Females with MEN1 were found to be at increased risk to develop breast cancer (relative risks 2.83 and 3.20). Eighty percent of MEN1-related breast tumors showed loss of expression of menin and in a subset also loss of heterozygosity at the MEN1 gene locus was found.
MEN1 is a breast cancer susceptibility syndrome. Further research will determine the relevance of the MEN1 gene for patients with non-familial breast cancer. Intensified breast cancer screening should be considered for female MEN1 patients.
Citation Format: Koen Dreijerink, Elfi Conemans, Chantal Cornelissen, Marja Van Blokland, Michael Mannstadt, Carla Pieterman, Wouter De Herder, Bas Havekes, Eric Fliers, Ad Hermus, Menno Vriens, Marc Timmers, Elsken Van der Wall, Myles Brown, Rob Van der Luijt, Paul van Diest, Gerlof Valk. Breast cancer predisposition in multiple endocrine neoplasia type 1. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1289. doi:10.1158/1538-7445.AM2014-1289
Abstract 1290: Survival in familial breast cancer: Novel findings based on a nationwide prospective cohort study
Authors: Kharazmi Elham , Försti Asta , Sundquist Kristina , Hemminki Kari 
Published: May 2015

Abstract
Objective: To find out whether breast cancer (BC) patients with positive family history of concordant cancer are diagnosed at earlier TNM stages and to explore the survival in familial breast cancer compared to sporadic cases who were diagnosed at identical TNM status and staging.
Design: Nationwide prospective cohort study.
Setting and method: The nationwide Swedish Family-Cancer Database including all Swedes born after 1931 and their biological parents, totaling &gt;14.7 million individuals. Hazard ratios (HR) were calculated for 4,709 women with BC in a first-degree relative (FDR) versus 25,366 BC women without such a family history.
Results: Familial BC cases were not diagnosed at earlier stages compared to sporadic cases. There was no difference in survival of familial BC patients who were diagnosed at high TNM staging (T2-T4, N1-N3, M1) compared to sporadic cases diagnosed at the same late stage. Young BC patients (age&lt;40) in early stages (T0-T1, N0, M0, Stage 0-I) had the worst survival when their FDR were diagnosed with single (HR: 2-3.7) or multiple (HR: 2.4-7.1) BC at any age.
Conclusion: Young BC patients (age&lt;40), diagnosed at early stages (T0-T1, N0, M0, stage 0-I), whose FDR were diagnosed with BC at any age had the higher risk of mortality compared to sporadic cases at the same stages. Our results offer novel information for personalized genetic counseling and treatment modalities and urge the need for identifying the underling genetic component for such a difference in survival of familial breast cancer.
Citation Format: Elham Kharazmi, Asta Försti, Kristina Sundquist, Kari Hemminki. Survival in familial breast cancer: Novel findings based on a nationwide prospective cohort study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1290. doi:10.1158/1538-7445.AM2014-1290
Abstract 1294: A pilot study of FBRSL1 and melanoma: What's the connection
Authors: Lilyquist Jenna Marie , Lee Pedro , Berwick Marianne , Reinberg Danny 
Published: May 2015

Abstract
FBRSL1 is a novel protein and a member of a heterogeneous group of proteins that form polycomb repressive complex 1 (PRC1). The canonical function of PRC1 is monoubiquitination of H2A at lysine 119 which has been associated with nucleotide excision repair of UV-induced DNA lesions; however, the role FBRSL1 plays in the PRC1 complex is unknown. Additionally, single nucleotide polymorphisms residing in FBRSL1 have been shown to modify melanoma risk following indoor tanning. Since very little is known about the function of FBRSL1, the connection between FBRSL1 and melanoma is unclear. To investigate FBRSL1 expression in relationship to melanoma, we performed an immunohistochemistry (IHC) pilot study, using antibodies against both the long and short forms of murine FBRSL1, on a small set of melanoma tumor and benign patient tissues. Our results indicate that both murine antibodies recognize FBRSL1 in human skin. The FBRSL1 amino acid sequence is highly conserved between mice and humans, but only the long isoform has been validated in humans indicating that further characterization of the human isoforms of FBRSL1 is needed. Additionally, we found FBRSL1 expression only in melanoma tissues, and not in benign tissues. Future directions include validating these results in a larger group of patients using both melanoma and benign tissues to confirm the relationship between FBRSL1 expression and melanoma. Ultimately, we will investigate the association between FBRSL1 and patient characteristics that modify melanoma risk and prognosis. We expect that these results will inform experiments to elucidate the role of FBRSL1 in melanoma.
Citation Format: Jenna Marie Lilyquist, Pedro Lee, Marianne Berwick, Danny Reinberg. A pilot study of FBRSL1 and melanoma: What's the connection. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1294. doi:10.1158/1538-7445.AM2014-1294
Abstract 130: Deadly KISS, Kisspeptin10 interaction with osteoblasts and breast cancer metastastic cells
Authors: Leahey Kaitlyn E. , Welch Danny R. , Chen Yu-Chi , Bussard Karen M. , Mastro Andrea M. 
Published: May 2015

Abstract
Current cancer research focuses on blockading metastasis with the hope of increasing patient survival and prognoses. This research has spurred an interest in metastasis suppressor genes, such as KISS-1, whose role in breast cancer remains controversial. This study focuses on the interactions among one of the proteolytic processing products of the Kiss1 protein (kisspeptin10, KP10), its receptor, KISS1R (GPR54, AXOR12), osteoblasts (bone forming cells), and bone-metastatic breast cancer cells, MDA-MB-231. Previous research suggests that treatment with KP10 reduces the ability of the cancer cells to invade a reconstituted basement membrane (Matrigel) and to migrate in response to osteosarcoma cells. The aim of this present study was to determine if KP10 affected the interaction of MC3T3-E1 osteoblasts and bone-metastatic breast cancer cells.
Our laboratory had previously determined that osteoblasts exhibit an inflammatory response when treated with conditioned medium from breast cancer cells. This inflammatory response may contribute to cancer cell proliferation in the bone. This response has not yet been characterized in the presence of KP10. I hypothesized that KP10 would down regulate the inflammatory response of osteoblasts to breast cancer cells. MDA-MB-231 breast cancer cells express theKISS1R; therefore, these cells were treated with KP10 (10-100 nM, 2hr), the medium was collected, and the osteoblasts were treated with it. KP10 significantly decreased the inflammatory response of osteoblasts to breast cancer conditioned media indicated by decreased levels of IL-6 as determined by ELISA. This research has important implications because it provides insight into how KP10 may be acting on either the breast cancer cells or the bone cells. In my future research, I will continue to characterize how KP10 can be used to prevent proliferation or activation of breast cancer metastases in the bone.
This work was supported by an undergraduate research grant from the Eberly College of Science of Penn State University.
Citation Format: Kaitlyn E. Leahey, Danny R. Welch, Yu-Chi Chen, Karen M. Bussard, Andrea M. Mastro. Deadly KISS, Kisspeptin10 interaction with osteoblasts and breast cancer metastastic cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 130. doi:10.1158/1538-7445.AM2014-130
Abstract 1300: Exploration of rare variants from exome sequencing in families with Waldenstrom macroglobulinemia (WM)
Authors: McMaster Mary L. , Goldin Lynn R. , Rotunno Melissa , He Ji , Burdette Laurie , Hutchinson Amy , Boland Joseph , Yeager Meredith , Tucker Margaret A. , Chanock Stephen J. , Caporaso Neil E. 
Published: May 2015

Abstract
In spite of progress in the identification of the somatic events associated with Waldenström macroglobulinemia (WM), the genetic determinants of WM susceptibility have not been identified. We have conducted exome sequencing in 32 individuals from 9 well-characterized families at high risk for WM. We sequenced 3 or more patients or obligate carriers from each family. We used Nimblegen v2.0 and v3.0 for exome capture followed by sequencing on the Illumina HiSeq2000. Among quality control measures, we required 80% of coding sequences to achieve 15x coverage. To eliminate other possible sequencing artifacts, variants found in more than 1% of samples sequenced in our laboratory from other studies were excluded. Novoalign v.2.07.14 was used for alignment and GATK was used for local re-alignment and variant calling. A large number of rare (&lt;1% frequency in European populations) non-synonymous variants were shared among patients in each family. To prioritize variants for further validation and follow-up, we first searched for variants shared in more than one family; variants in highly conserved regions; those predicted to be damaging by one or more in silico functional models; and variants in genes known to be related to B-cell function and/or disease. We used Ingenuity Variant Analysis to facilitate annotation. We then applied a semi-quantitative scoring algorithm based on these variables to prioritize genes for further evaluation. Although no single gene met all criteria when analyzed across families using this method, we are currently conducting targeted sequencing of 17 highest-scoring genes in an additional 2 WM patients and 92 relatives from these families and 272 other subjects (95 familial WM, 28 nonfamilial WM and 149 informative relatives). Susceptibility gene discovery in this complex disease remains challenging.
Citation Format: Mary L. McMaster, Lynn R. Goldin, Melissa Rotunno, Ji He, Laurie Burdette, Amy Hutchinson, Joseph Boland, Meredith Yeager, Margaret A. Tucker, Stephen J. Chanock, Neil E. Caporaso. Exploration of rare variants from exome sequencing in families with Waldenstrom macroglobulinemia (WM). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1300. doi:10.1158/1538-7445.AM2014-1300