bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2526: Regulation of angiogenic factors in glioblastoma progression
Authors: Larrain Carolina , Wesley Umadevi V. , Clark Paul , Kuo John S. , Dempsey Robert 
Published: July 2016

Abstract
Background & Purpose: Glioblastoma is the most malignant primary brain tumor in humans and has a very low survival rate. The aggressiveness of this cancer can be attributed to the presence of glioblastoma stem cells (GSC), which are highly invasive and therapy resistant. Increased aggressiveness of GSCs is attributed to the release of angiogenic factors, which promotes the formation of new blood vessels that enhances tumor cell survival and proliferation. The neovascularization also provides a scaffold for tumor cells to migrate, enabling metastasis. Therefore, identifying the altered expression of angiogenic factors is of clinical importance. In this study, we examined the changes in the expression of pro-angiogenic factors in GSCs as compared to the original tumor from which they were derived. We also determined if differentiation of GSC towards a less invasive phenotype decreased the levels of these pro-angiogenic factors. Methods: GBM tumor cells were grown in complete media containing 10% Fetal Calf Serum (FCS) and GSCs were grown in media containing B27, heparin, EGF, and FGF. GSCs were differentiated by growing them in media containing 10% FCS and B27 with vitamin A, for about one week. We examined the expression of a panel of pro-angiogenic factors in GSCs (33-GSC) and in the original tumor cells (33-T) from which GSCs were derived. We then examined if differentiation of 33-GSC decreased the levels of these pro-angiogenic factors. Changes in protein levels were evaluated by immunofluorescence staining. The mRNA levels were quantitated using real time Q-PCR. Results: Immunofluorescence staining showed that the GSCs express higher levels of pro-angiogenic factors examined (11 out of 16). GSCs were successfully differentiated into astrocytes as indicated by morphology and GFAP expression. The differentiation of GSCs into astrocytes was sufficient to cause decreased expression of VEGF and c-MYC. Our data showed 27 fold increase in VEGF mRNA levels, 63 fold increase in MMP2 mRNA levels, 11 fold increase in MMP9 mRNA levels, and 2 fold increase in c-MYC mRNA levels in GSCs compared to the tumor line, indicating the regulation of these pro-angiogenic factors at transcriptional level. Conclusions: Increased expression of pro-angiogenic factors in GSCs may render these cells to be more aggressive and invasive, and suggests that differential expression of angiogenic factors in GSC cells may play an important role in the GBM progression, and therapy resistance.
Citation Format: Carolina Larrain, Umadevi V. Wesley, Paul Clark, John S. Kuo, Robert Dempsey. Regulation of angiogenic factors in glioblastoma progression. [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 2526.
Abstract 2529: Expression of ABCF1 with stem cell markers CD133/GEP/beta-catenin in fetal liver and liver cancer cells
Authors: Fung Sze Wai , Cheung Phyllis Fung Yi , Yip Chi Wai , Tsao George Sai Wah , Cheung Siu Tim 
Published: July 2016

Abstract
Understanding stem cell biology in relation to cancer is of growing importance with the cancer stem cells (CSCs) notion and recurring deregulated stem cell pathways reported in cancers. ATP-binding cassette (ABC) transporter ABCB1 (also named P-glycoprotein and MDR1) has shown to be CSC marker, mediate multidrug-resistance in model systems though with controversial clinical relevance. We have systemically examined the expression profiles of ABC genes in hepatocellular carcinoma (HCC) clinical samples. ABCF1 was significantly over-expressed in HCCs compared to the adjacent non-tumor liver tissues (P&lt;0.001) and associated with recurrence-free survival after curative partial hepatectomy (log rank, P = 0.010). Recurrences have conventionally been attributed to aggressive cancer features and, recently, CSC features, as CSCs in small load could grow to tumor bulk. We therefore further explored the significance of ABCF1 in both fetal liver and liver cancer cells in respect to stem cell signaling. Expression of ABCF1 in fetal, neonatal and adult mouse livers were examined by immunohistochemistry, western blot and flow cytometry. Consistently, elevated ABCF1 expression was demonstrated in early embryonic stages [embryonic day 13 (E13): 42.4%; E15: 24.6%] but rarely in neonates and adult livers [1.5% and 1.2%, respectively]. Also, ABCF1 co-stained with stem cell-related marker β-catenin and hepatic CSC markers CD133 and GEP in fetal hepatocytes and in HCC cells (Table 1). ABCF1 suppression by siRNA enhanced chemo-sensitivity of the HCC cells Hep3B compared to control cells on cisplatin (cell apoptosis 7.5% vs 1.7%, P&lt;0.001) and 5-Fluorouracil (11.7% vs 4.7%, P&lt;0.001). Subcellular fractionation analysis on HCC cells showed that ABCF1 protein was present in both the cytoplasmic and membrane fractions. The current study highlighted the functional significance of ABCF1 in liver development and liver cancer as stem cell-related molecule regulating chemo-resistance. Table 1.Co-expression of ABCF1 and hepatic stem cell markers in mouse fetal livers and HCC cellsFetal liver cells (E15)Liver cancer cells (Hep3B)ABCF1+24.6%34.5%CD133+16.3%88.8%ABCF1+ CD133+20.9%34.3%GEP+45.7%65.7%ABCF1+ GEP+24.0%29.7%β-catenin+40.6%20.9%ABCF1+ β-catenin+13.5%17.5%
Citation Format: Sze Wai Fung, Phyllis Fung Yi Cheung, Chi Wai Yip, George Sai Wah Tsao, Siu Tim Cheung. Expression of ABCF1 with stem cell markers CD133/GEP/beta-catenin in fetal liver and liver 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 2529.
Abstract 2530: Live cell detection of intracellular biomarkers maintains cancer stem cells for further experimentation
Authors: Weldon Don , Williams Yuko , Patel Amish , McClellan Steven 
Published: July 2016

Abstract
Cancer stem cells are widely studied as a potential therapeutic target in cancer research. Their expression of cell surface biomarkers such as EpCAM, CD44, and CD133 have been well characterized as a method for identification and enrichment from heterogeneous populations. Additional biomarkers with more functional relevance to self-renewal such as the transcription factors Sox-2 and Nanog, are intracellular and traditionally require fixation and permeabilization of the sample. Here we describe a method for identification and enrichment of live cancer stem cells based on intracellular biomarker expression.
Live human head and neck squamous cell carcinoma (HNSCC) cell lines, UM-SCC-47 and UM-SCC-104 were used as a model for Cancer stem cells in a mixed population. They were assayed for their expression of EpCAM, CD44, and CD133 by flow cytometry. Additionally, Aldehyde dehydrogenase (ALDH) activity was also detected in a population of the HNSCC cell lines further corroborating the presence of a cancer stem cell population. Live cell probes specific to Nanog and Sox-2 were used to enrich for cells expressing the targets of interest through Fluorescent Activated Cell Sorting (FACS).
This live cell biomarker approach was also recently demonstrated on solid tumors which were digested and cultured as single cells where they were then incubated with the live cell probes. FACS sorting was utilized to enrich for a cancer stem cell population. More importantly after detection these cells remain live and intact allowing them to be returned to culture and further studied.
Citation Format: Don Weldon, Yuko Williams, Amish Patel, Steven McClellan. Live cell detection of intracellular biomarkers maintains cancer stem cells for further experimentation. [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 2530.
Abstract 2543: A family affair: Prostate cancer risk and family history of breast or prostate cancer
Authors: Barber Lauren E. , Gerke Travis A. , Markt Sarah C. , Parmigiani Giovanni , Mucci Lorelei A. 
Published: July 2016

Abstract
Background - There is suggestive evidence of familial clustering of breast and prostate cancer in first-degree relatives; women with a family history of prostate cancer are at increased risk of breast cancer. Few studies have investigated joint family history of breast and prostate cancer and prostate cancer risk, and no study to date has examined lethal prostate cancer.
Methods - We studied 42,672 from the Health Professionals Follow-up Study between 1996 to 2012. During follow-up, 4,258 prostate cancer cases were diagnosed, of whom 380 were lethal disease. Men self-reported family history of breast and prostate cancer, including in siblings or parents. Using cause-specific hazards regression, we estimated hazard ratios (HR) and 95% confidence intervals (CI) of the association between family history and prostate cancer risk and progression.
Results - About 8% of men had a family history of prostate cancer, 8.7% had a family history of breast cancer, and 1.4% of men had a family history of both breast and prostate cancer. A family history of prostate cancer was significantly associated with an increased risk of prostate cancer (HR: 1.69; 95% CI: 1.54-1.85). Increased risk was higher for men with a father diagnosed with prostate cancer (HR: 1.64 95% CI: 1.49-1.80) than for men with a diagnosis in a brother(s) (HR: 1.51 95% CI: 1.27-1.80). A positive family history of breast cancer was associated with a small, but significant 22% increased risk (HR: 1.22; 95% CI: 1.11-1.35). Familial breast cancer in a sister (HR: 1.22 95% CI: 1.06-1.41) increased risk more than familial breast cancer in a mother (HR: 1.12; 95% CI: 0.99-1.25). Men with a family history of both prostate and breast cancer had a 52% (HR: 1.52; 95%CI: 1.23-1.88) increased risk of prostate cancer compared to men with no family history of either cancer. Risk of lethal prostate cancer was also significantly increased for men with a positive family history of prostate cancer (HR: 1.64; 95% CI: 1.20-2.24), as well as for men with a family history of breast cancer (HR: 1.47; 95% CI: 1.07-2.01).
Conclusions - These results support the findings of familial aggregation of breast and prostate cancer, and for the first time suggest an association between familial breast cancer and lethal prostate cancer. Data from this prospective study have translational relevance for family counseling of cancer patients.
Citation Format: Lauren E. Barber, Travis A. Gerke, Sarah C. Markt, Giovanni Parmigiani, Lorelei A. Mucci. A family affair: Prostate cancer risk and family history of breast or prostate cancer. [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 2543.
Abstract 2546: With increasing age at tumor diagnosis in families with cancer, cancer is limited to fewer organs
Authors: Olsson Hakan L. 
Published: July 2016

Abstract
Hereditary cancer that has monogenic inheritance affects every tenth patient, on average, who is diagnosed with cancer, and it has been suggested based on twin studies, that approximately 30% of all cancer patients have a genetic predisposition to developing cancer. The author posited that familial syndromes become more organ specific with increasing age at tumour presentation to the point that very late in life, only a few organs are affected by tumours disease. The reason for this could be that the tumour originates from a more differentiated, organ-specific progenitor/stem cell later in life, while the progenitor/stem cell might be involved in organogenesis in different organs earlier in life. Examples are given for skin cancer and breast cancer.
Summary: Patients with familial cancer who present with cancer at an older age at tumour presentation have a more organ restricted disease. This could be because the tumor has a more differentiated progenitor/stem cell origin. Examples are given for families with breast cancer, melanoma, and non- melanoma skin cancer.
References: Olsson H. A hypothesis about tumour development and the clinical features of hereditary cancer. European Journal of Cancer 2001 2023-2029.
Olsson H. With increasing age at tumor diagnosis in families with cancer, cancer is limited to fewer organs. Journal of Cancer and Therapy (in press). Examples of the median age at diagnosis for melanoma (*) and breast cancer (**) in familial settingsFamilies with melanoma. CDKN2A positive melanoma cases. (melanoma, pancreas, smoking associated cancer)39*Families with melanoma. CDKN2A negative melanoma cases. (melanoma and skin cancer)48*Four or more tumors in the cancer registry, at least one of which is a melanoma. Multiple melanoma cases with other tumors and CDKN2A mutations.60*Four or more tumors in the cancer registry, at least one of which isa melanoma. Melanoma, other tumours and adenocarcinomas.67*Four or more tumors in the cancer registry, at least one of which is a melanoma. Melanoma and skin cancer.78*Li Fraumeni's syndrome&lt;40**BRCA144**BRCA245**BRCAX (majority breast only families)48**Vertical inheritance52**Horizontal inheritance (possible recessive inheritance, breast cancer only families).63**
Citation Format: Hakan L. Olsson. With increasing age at tumor diagnosis in families with cancer, cancer is limited to fewer organs. [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 2546.
Abstract 2549: Familial risk of upper gastrointestinal cancers by tumor location
Authors: Kharazmi Elham , Babaei Masoud , Fallah Mahdi , Chen Thianhui , Sundquist Kristina , Hemminki Kari 
Published: July 2016

Abstract
Background: Upper gastrointestinal (UGI) cancers are within the most common malignancies worldwide. Familial clustering of UGI cancers and the significance of family history have been addressed in the past. We aimed to further elucidate the familial risk based on specified tumor locations.
Methods: Using the Swedish Family-Cancer Database, we determined the familial risk of UGI cancer patients diagnosed between 1958 and 2012. Standardized incidence ratio (SIR) was used for calculating concordant and discordant familial cancers risks, stratified by tumor locations. All results were adjusted for sex, age group, period, and socioeconomic status.
Results: Risk of esophageal cancer in first-degree relatives (FDRs) of esophageal cancer patients was 2•4-fold higher than that in those without such a family history. Familial risk for concordant cancer in upper and middle third of esophagus was 3•2- and 5•6-fold, respectively. Family history of esophageal cancer in lower part was associated with increased risk of gastric cardia cancer in FDRs and vice versa. Family history of both adenocarcinoma and SCC of esophageal cancer increased the familial risk of concordant (similar) and discordant subtypes. Occurrence of gastric cancer in the body and the antrum of stomach in a FDR were associated with an increased risk of gastric cancer 6- to 7-fold in the same location in family members, respectively.
Conclusion: Family history of UGI cancers in some specific locations like upper and middle third of esophagus, body and antrum of stomach can be considered as an important predictive evidence for the same cancers in relatives.
Citation Format: Elham Kharazmi, Masoud Babaei, Mahdi Fallah, Thianhui Chen, Kristina Sundquist, Kari Hemminki. Familial risk of upper gastrointestinal cancers by tumor location. [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 2549.
Abstract 2565: Prostate cancer GWAS from more than 89,000 men identifies more than 30 novel prostate cancer susceptibility loci
Authors: Schumacher Fredrick R. , Al Olama Ali A. , Berndt Sonja I. , Wiklund Fredrik , Conti David V. , Ahmed Mahbubl , Benlloch Sarah , Easton Douglas F. , Kraft Peter , Chanock Stephen J. , Henderson Brian E. , Kote-Jarai Zsofia , Haiman Christopher A. , Eeles Rosalind A. 
Published: July 2016

Abstract
Genome-wide association studies (GWAS) and fine-mapping efforts have identified over 100 loci associated with prostate cancer susceptibility. Combined multiplicatively, these loci capture 33% of the familial risk for prostate cancer among European-ancestral populations. In order to identify novel prostate cancer susceptibility loci we conducted a GWAS involving over 53,000 prostate cancer cases and 36,000 controls using the OncoArray that includes a 260K GWAS backbone and a custom portion of 310K SNPs developed from previous GWAS and fine-mapping studies of multiple cancer types (http://epi.grants.cancer.gov/oncoarray/). Following standard quality control procedures, the prostate cancer OncoArray genotyped data were imputed using the October 2014 release of the 1000 genomes project data as a reference and analyzed by participating study for overall and advanced prostate cancer using logistic regression. The study-specific results were combined using inverse variance fixed effect meta-analysis. Regions surrounding previously associated variants (+/- 500kb of the reported index variant) were excluded to identify novel associations. In the OncoArray meta-analysis, we identified more than 30 novel loci significantly associated (P&lt;5.0×10-8) with overall, advanced (Gleason ≥8, death from PrCa, PSA&gt;100, or disease stage “Distant”), or early-onset (≤55 years of age) prostate cancer. Previous GWAS of prostate cancer are being imputed to the latest release of the 1000 genomes project to enhance our statistical power for novel discovery. In total our overall meta-analysis will incorporate over 176,000 individuals of European ancestry - more than 95,000 prostate cancer cases and 79,000 controls. The current results, as well as the larger ongoing meta-analysis, provide further insight into the underlying mechanisms of prostate cancer carcinogenesis and will improve the utility of genetic risk scores for targeted screening and prostate cancer prevention.
Citation Format: Fredrick R. Schumacher, Ali A. Al Olama, Sonja I. Berndt, Fredrik Wiklund, David V. Conti, Mahbubl Ahmed, Sarah Benlloch, Douglas F. Easton, Peter Kraft, Stephen J. Chanock, Brian E. Henderson, Zsofia Kote-Jarai, Christopher A. Haiman, Rosalind A. Eeles. Prostate cancer GWAS from more than 89,000 men identifies more than 30 novel prostate cancer susceptibility loci. [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 2565.
Abstract 2566: Comprehensive analysis to identify functional basis of prostate cancer risk SNPs
Authors: Middha Mridu , Xu Xing , Vaananen Riina-Minna , Hayes James , Taimen Pekka , Gao Xiaoni , Lilja Hans G. , Pettersson Kim , Klein Robert J. 
Published: July 2016

Abstract
Introduction:
Genome-wide association studies (GWAS) have identified numerous common single nucleotide polymorphisms (SNPs) associated with the risk of developing prostate cancer. Many of these prostate cancer GWAS hits occur in intergenic regions, distant from any annotated gene. Little is yet known about how these SNPs function to alter an individual's risk of prostate cancer. Here we test the hypothesis that many of these SNPs, or SNPs with which they are correlated, alter regulatory regions and thus gene expression in the prostate.
Materials and Methods:
To test if prostate cancer risk SNPs are correlated with gene expression changes, we conducted expression quantitative trait locus (eQTL) association analysis. Using genome-wide high-density genotypes and gene expression data from 56 tumor and 58 adjacent normal prostate tissues we asked if any of the prostate cancer risk SNPs correlate with expression changes in nearby genes using linear regression, adjusting gene expression levels for principal components of ancestry and different batches. We also asked if individuals who have a higher genetic risk of prostate cancer based on the genotype of all of their risk SNPs show different gene expression patterns in the prostate than those at lower risk of prostate cancer.
Results:
We have identified several novel cis-eQTLs in prostate tissue for prostate cancer risk SNPs including rs1933488 with RGS17. We have also replicated several previously known cis-eQTLs, including those for IRX4, PPP1R14A, and FOXP4. Individuals at higher genetic risk of developing prostate cancer have altered expression of 37 genes (p&lt;0.001) in their tumor tissue compared to individuals at lower genetic risk.
Conclusions:
These data demonstrate that several prostate cancer risk SNPs are associated with expression changes in nearby genes in both pathologically malignant and pathologically benign prostate tissue from patients who underwent radical prostatectomy. Additional genes, including HMOX1, CSGALNACT1, and WDR36 show altered expression in patients with different levels of genetic risk of prostate cancer.
Citation Format: Mridu Middha, Xing Xu, Riina-Minna Vaananen, James Hayes, Pekka Taimen, Xiaoni Gao, Hans G. Lilja, Kim Pettersson, Robert J. Klein. Comprehensive analysis to identify functional basis of prostate cancer risk SNPs. [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 2566.