bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 844: Tumor cell detection in autologous stem cell harvests in patients with high risk neuroblastoma
Authors: Stutterheim Janine , Vree Florentien M. , Zappeij-Kannegieter Lily , Caron Huib N. , van der Schoot C. Ellen , Tytgat Godelieve A.M. 
Published: February 2011

Abstract
Introduction
The presence of minimal residual disease (MRD) detected by real-time quantitative (RQ)-PCR in autologous stem cell harvests (ASCH) in children with high risk neuroblastoma (NBL) seems to be associated with an unfavourable outcome. However, to date only small studies have been performed, which suffered from lack of specificity of the assay due to background amplification in normal bone marrow (BM) and peripheral blood stem cells (PBSC). We previously developed a new panel of specific neuroblastoma RQ-PCR markers for MRD testing. The goal of this study was to determine the incidence of harvest contamination using this panel of markers and to investigate whether reinfusion of contaminated harvests was associated with poor outcome.
Methods
In this single center study, RQ-PCR was performed with six NBL-specific markers: homeobox2b (PHOX2B), tyrosine hydroxylase (TH), dopamine decarbohydroxylase (DDC), growth associated protein 43 (GAP43), cholinergic receptor3 (CHRNA3), and dopamine beta-hydroxylase (DBH) on 40 BM and 38 PBSC harvests of 70 high risk patients. The prognostic impact of MRD in reinfused autologous harvests (n=50) was assessed using Kaplan-Meier plots and log-rank tests.
Results
NBL mRNA was detected in 42% (18/40) of BM harvests and in 13% (5/38) of PBSC harvests of which in total 50 harvests were reinfused. In reinfused patients, 30% (15/50) received a MRD positive harvest, which was associated with poor outcome (5-y-OS 20±11.8 versus 62.3%±8.8;p=0.02). This association was more pronounced in patients reinfused with BM harvests than in patients reinfused with PBSC harvests, since more BM harvests were MRD positive. Remarkably, overall there was no difference in survival between patients reinfused with PBSC or BM harvest (p=0.7).
Conclusion
The presence of NBL mRNA in stem cell harvests, as reliably measured by a panel of NBL specific-PCR targets, is significantly associated with an unfavourable outcome. This could either mean that the amount of tumor cells reinfused in the graft influences relapse rate or that the stem cell graft reflects remission status.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 844.
Abstract 856: Blood transfusions and the subsequent risk of hematologic malignancies
Authors: Chang Cindy M. , Quinlen Scott , Warren Joan , Engels Eric 
Published: February 2011

Abstract
Background: Blood transfusions are associated with viral transmission and immunomodulation, perhaps increasing subsequent risk of hematologic malignancies (HMs). Prior studies of transfusion recipients have lacked details on specific HM subtypes. Methods: We evaluated HM risk following blood transfusion in a U.S. population-based case-control study using cancer registry data (77,488 HM cases, 154,509 controls). Transfusions were identified using linked Medicare hospitalization claims. We used polytomous logistic regression to calculate odds ratios (ORs) for associations between transfusion and HM subtypes according to features suggestive of a causal relationship. Results: A history of transfusion was present in 7.9% of HM cases vs. 5.9% of controls. Associations were present for almost all HM subtypes but mostly appeared non-specific and suggested reverse causality: ORs were elevated only during the shortest latency periods; ORs for unspecified anemia and gastrointestinal bleeding, which may be related to undiagnosed HM, were stronger than for surgeries, which are unlikely to be related to HM; and/or there was no dose-response. In contrast, risk for lymphoplasmacytic lymphoma (1,397 cases) was elevated overall (OR 1.59, 95% CI 1.32-1.92), at long latency (OR 1.56 at 10+ years following transfusion), following transfusions for surgeries (ORs 1.22-1.47), and in a strong dose-response relationship with number of transfusion-related hospitalizations (OR=1.53 with 1 hospitalization; OR=1.80 with 2+ hospitalizations, p-trend&lt;0.0001). Risk for marginal zone lymphoma (1,915 cases) was also elevated overall (OR 1.22, 95% CI 1.03-1.45) and at 10+ years following transfusion (OR 1.80). Discussion: Patterns of elevated risk for lymphoplasmacytic and marginal zone lymphomas suggest an etiologic role for transfusion. Both lymphoplasmacytic and marginal zone NHLs have previously been linked to infection with hepatitis C virus (HCV), a blood-borne virus, but HCV infection is too uncommon to explain the association that we observed. Other immunomodulatory effects of transfusion, including pro-inflammatory effects, may be responsible. Strengths of our study include the large number of subjects, population-based sampling of cases and controls, and detailed information on HM subtypes. The large number of cases with each HM subtype allowed us to assess subtype-specific associations with blood transfusions, particularly in terms of latency periods, medical diagnoses and procedures, and dose-response.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 856.
Abstract 878: Comorbidities in African American and Hispanic/Latina Breast Cancer Patients are associated with IGF-1 and IGFBP3-3 Gene Polymorphisms
Authors: Sarkissyan Marianna , Mishra Dhruva , Wu Yanyuan , Shang Xiying , Sarkissyan Suren , Vadgama Jaydutt V. 
Published: February 2011

Abstract
Increase in comorbidities such as diabetes and hypertension in cancer patients lead to poor disease free survival and overall survival. It is probable that risk factors associated with these comorbidities and cancer itself could be linked to alterations in gene polymorphisms associated with hormones and/or growth factors. In this study, we have investigated if (1) comorbidities were associated with our African American and Hispanic breast cancer subjects; and (2) if there was any association between Insulin-Like Growth Factor 1 (IGF-1), and IGF Binding Protein 3 (IGFBP3) gene polymorphisms with breast cancer and comorbidities. We studied 514 subjects (175 African Americans and 339 Hispanic/Latinas), which included 208 cases and 306 controls (no evidence of breast cancer) subjects. DNA was extracted from blood samples and IGF-1 and IGFBP-3 genotyping was performed by PCR-GeneScan and PCR-RFLP methods, respectively. Our results demonstrated that comorbidity is significantly correlated with breast cancer (OR = 2.12; 95% CI = 1.40-3.21; P-value &lt;0.01); especially the comorbidity of hypertension (OR= 2.27; 95% CI = 1.47-3.49; P-value &lt;0.01). Furthermore, there was a significant association between non-19/non-19 IGF-1 (CA)n polymorphisms and breast cancer (OR= 4.80; 95% CI = 1.87, 12.36; P-value &lt;0.01). This study also found a significant association between the non-19/non-19 IGF-1 (CA)n genotype, breast cancer, and comorbidity (OR= 4.65; 95% CI = 1.57, 13.82; P-value &lt;0.01). In summary, our study demonstrated a significant association of IGF-1 polymorphisms and breast cancer with a further link to comorbid diseases.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 878.
Abstract 88: Targeting Bcl-XL enhances arsenic-induced cell death in ovarian cancer cells
Authors: Tekedereli Ibrahim , Lopez-Berestein Gabriel , Ozpolat Bulent 
Published: February 2011

Abstract
Autophagy is an evolutionary conserved process in which long-lived proteins and damaged organelles are digested under physiological conditions including starvation. Autophagy has also been shown to act as a programmed cell death mechanism (type II PCD) and considered as caspase independent cell death. Several studies showed that autophagy has been triggered by anti-cancer treatments, such as chemo and hormonal therapy and radiotherapy and growth factor deprivation, function either as a protective survival pathway or cellular death mechanism.
Arsenic trioxide (ATO), which is a FDA approved drug and used as a treatment in acute promyelocytic leukemia, has been reported to induce autophagic and/or apoptotic cell death in leukemia, glioblastoma and also ovarian cancer cells, we have previously found that ATO induces autophagy in ovarian cancer cells. Here, we investigated the role of antiapoptotic protein Bcl-Xl, which inhibits autophagy by binding beclin-1, an essential autophagy promoting protein, in arsenic induced apoptosis and determined the effects of ATO/Bcl-XL RNA interference combination therapy in ovarian cancer. We found that ATO induces dose dependant growth inhibition in MTS proliferation assay. ATO treatment (2-4 uM) induced apoptosis in A2780 (40-50 %) and SKOV3 (20-25 %) cells, detected by annexin V staining and flow cytometric (FACS) analysis and by caspase 9 and PARP cleavage (Western blotting). ATO induced marked autophagy in A2780 (60-70 %) and in SKOV3 (15-20 %) as indicated by LC3-II, a marker for autophagy, formation autophagic vacuoles detected by acridine orange staining and FACS and by transmission electron microscopy. ATO induced Bcl-XL protein expression in ovarian cancer cells. We also found expression of high levels of Bcl-XL in all ovarian cancer cell lines including drug (i.e., cisplatin and paclitaxel) resistant cells. Inhibition of Bcl-XL expression by Bcl-XL siRNA induced growth inhibition (40-60 %), apoptosis (40-60 %) and autophagy (50-60% in A2780 and 15-25 % in SKOV3 ovarian cancer cell line). Furthermore, combination of ATO with Bcl-XL siRNA led to 90 % cell death and 70 % apoptosis in both A2780 and SKOV3 cells. Overall, our results suggest that combination of ATO and Bcl-XL induced predominantly apoptosis, although each of them induced autophagy. In conclusion we provided first evidence that inhibition of Bcl-XL induces autophagy in ovarian cancer cells and sensitizes them to ATO that may be a promising treatment regimen for ovarian cancer patients.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 88.
Abstract 887: Long-term prognostic role of functional limitations among women with breast cancer
Authors: Braithwaite Dejana , Satariano William , Hiatt Robert A. , Slattery Martha , Caan Bette 
Published: February 2011

Abstract
Background: Functional limitations have been associated with poor survival among women with breast cancer within the first year of diagnosis. The long-term prognostic role of these difficulties in the completion of tasks of everyday life remains unknown. Methods: We studied a cohort of 2270 women diagnosed with breast cancer between 1997 and 2000, who provided information on functional limitations of body functions involving endurance, strength, muscular range of motion and small muscle dexterity at enrollment. The median follow up was 8.7 years (range 0-10 years). We investigated the association of functional limitations with survival from all causes, breast cancer and competing (non-breast cancer) causes in delayed entry Cox regression models. All statistical tests were two-sided. Results: Proportionately more patients with limitations were older, less educated and obese (p&lt;.0001 for each) versus those without these difficulties. The age-adjusted hazard ratio for functional limitations as a 13-level variable of 1.08 (95%CI 1.05-1.14) suggests that there was an 8% increase in risk of death with each additional limitation. In multivariate models, functional limitations were associated with a statistically significant risk of death from all causes [hazard ratio (HR)=1.40, 95% confidence interval (CI) 1.03-1.92] and from competing causes (HR=2.60, 95%CI 1.69-3.98) but not breast cancer (HR=.90, 95%CI .64 −1.26). Conclusion: Women with breast cancer and functional limitations present after initial breast cancer treatment have a greater likelihood of dying of competing causes than breast cancer. Intervening to improve physical function among women with breast cancer may lead to improvements in life expectancy.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 887.
Abstract 898: Glucose metabolism Gene Polymorphisms and Clinical Outcome in Pancreatic Cancer
Authors: Dong Xiaoqun , Tang Hongwei , Hess Kenneth R. , Abbruzzese James L. , Li Donghui 
Published: February 2011

Abstract
Background Altered glucose-metabolism is the most common metabolic hallmark of malignancies. The ‘Warburg effect’ (aerobic glycolysis, a persistently high rate of glucose conversion into lactate even under normoxic condition), is a distinctive metabolic characteristic of malignancies that distinguishes them from normal cells. Glucose-metabolism plays a crucial role in determining the cell fate (survival or death), has become a therapeutic target for cancer treatment. We explored weather glucose-metabolism gene variations correlate with clinical outcome in pancreatic cancer.
Methods We retrospectively genotyped 26 single nucleotide polymorphisms (SNPs) from 5 glucose-metabolism genes (Hexokinase 2,HK2; glucokinase, GCK; glutamine-fructose-6-phosphate transaminase, GFPT1; glucose phosphate isomerase, GPI; O-linked N-acetylglucosamine (GlcNAc) transferase, OGT) in 154 patients with localized disease enrolled in clinical trials of preoperative gemcitabine-based chemoradiation and validated the findings in 552 patients with different stages of pancreatic adenocarcinoma recruited in a case-control study conducted at The University of Texas M. D. Anderson Cancer Center from February 1999 to May 2007, with follow-up to August 2009. Association between genotypes and overall survival (OS) or tumor characteristics was evaluated using multivariable Cox proportional hazard regression or logistic regression models with adjustment of clinical predictors. Findings GCK IVS1+9652C&gt;T and HK2 N692N homozygous variants were significantly associated with reduced OS in the training set of 154 patients (P &lt; 0.001). These associations were confirmed in the validation set of 552 patients and in the combined dataset of all 706 patients (Ps ≤ 0.001). In addition, HK2 R844K variant K allele was associated with a better survival in the validation set and the combined dataset (Ps ≤ 0.001). When data was further analyzed by disease stage, GFPT1 IVS14-3094T&gt;C, HK2 N692N and R844K in patients with localized disease, and GCK IVS1+9652C&gt;T in patients with advanced disease were significant independent predictors for OS (Ps ≤ 0.001). Haplotype CGG of GPI and GCTATGG of HK2 were associated with better OS, respectively, with a P value of 0.004 and 0.007. HK2 N692N CC, R844K GG genotype correlated with poorer tumor response to therapy, advanced tumor stage and lower rate of tumor resectability.
Interpretation We demonstrated that glucose-metabolism gene polymorphisms correlated with clinical outcome in pancreatic cancer. If confirmed, the genotype marker may be useful in identifying patients for glucose-metabolism-targeted therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 898.
Abstract 904: Obesity is an independent prognostic variable in colon cancer survivors
Authors: Sinicrope Frank A. , Foster Nathan R. , Sargent Daniel J. , O'Connell Michael J. , Rankin Cathyrn 
Published: February 2011

Abstract
Purpose: Obesity is associated with an increased risk of colon cancer. However, the influence of body mass index (BMI) upon the prognosis of colon cancer survivors and its relationship to gender remains unknown.
Experimental Design: BMI (kg/m2) was categorized in patients with TNM stage II and III colon carcinomas (n= 4,381) enrolled in 7 randomized trials of 5-fluorouracil-based adjuvant chemotherapy. Cox proportional hazards models were used to determine the association of BMI with disease-free (DFS) and overall survival (OS).
Results: Among colon cancer patients, 868 (20%) were obese (BMI &gt;30 kg/m2) of which 606 were class 1 (BMI 30-34 kg/m2) and 262 were class 2,3 (BMI &gt;35 kg/m2). Obese versus normal-weight patients were more likely to be younger (p=0.038), have distal tumors (0.058), show intact DNA mismatch repair (MMR) (p=0.035), and have more lymph node metastases (p=0.017). In a multivariate analysis, BMI was significantly associated with both DFS (p=0.030) and OS (p=0.0017). Men with class 2,3 obesity showed reduced OS compared to normal weight men [HR 1.35 (1.02, 1.79); p=0.039]. Women with class I obesity had reduced OS [HR 1.24 (1.01, 1.53), p=0.045] compared to normal weight women. Overweight status was associated with improved OS in men (p= 0.006) and underweight women had significantly worse OS (p= 0.019). BMI was not predictive of therapeutic benefit.
Conclusions: Obesity is an independent prognostic variable in colon cancer survivors and shows gender-related differences. These data suggest that obesity-related biological factors can influence clinical outcome.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 904.
Abstract 91: Advanced computational algorithms for deep interrogation of microbial communities using pyrosequencing
Authors: Sun Yijun , Cai Yunpeng , Goodison Steven 
Published: February 2011

Abstract
The microbial community within the human gastrointestinal tract plays an important role in the balance of health and disease in the individual host. The advent of molecular techniques now facilitates the deep interrogation of the components of the gut microbiota, but the immense amount of data obtained requires the parallel development of advanced computational algorithms in order to maximize information extraction. In this study, we applied a novel computational strategy to analyze a microbial 16S rRNA sequence dataset consisting of more than one million sequences obtained from the fecal material of 154 individuals of known weight status. A large-scale taxonomy independent analysis revealed that collectively the human gut harbors more than 150,000 microbial species, at least one order magnitude larger than previously estimated. Furthermore, discriminant and topology analyses showed that despite the fact that each individual has diverse gut microbial compositions, there exist distinct microbial signatures associated with obese and lean physiological states. The analytic methods we developed for this study have never been used before in the interrogation of microbial communities. The combination of deep sequencing techniques with the computational approach described here will facilitate our understanding of the role the gut microbiota plays in health and disease and may lead to novel interventional strategies to prevent or ameliorate diseases of the gastrointestinal tract.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 91.
Abstract 92: dbCPCO: The database of genetic predictive and prognostic factors in colorectal cancer
Authors: Savas Sevtap , Younghusband Ban 
Published: February 2011

Abstract
Introduction: Colorectal cancer is the third most common cancer in the North America with a 5-year survival rate of ∼65%. A portion of the inter-patient variability in disease outcome in colorectal cancer patients is attributed to inherited and somatic genetic factors. Identification of these genetic factors helps implementing personalized medicare to improve the chances of cure in patients. While numerous research articles have investigated the genetic basis of clinical outcome in colorectal cancer, there has not been a central resource, such as a public database, that compiles these findings in a systematic, comprehensive and concise way.
Here we describe the dbCPCO, a database of genetic factors investigated in relation to clinicopathological characteristics and clinical outcome (i.e. treatment response and toxicity, prognosis and survival) in colorectal cancer.
Methods: Literature reports were retrieved from PUBMED. The data that met the inclusion criteria were compiled in a relational database and posted in a dedicated website.
Results: The genetic factors included the inherited genetic polymorphisms, somatic and germline mutations in both nuclear and mitochondrial DNA. As of November 2009, the dbCPCO website posts 610 scientific findings on &gt;300 polymorphisms, somatic and germline mutations from 146 genes tested for correlation with clinicopathological and/or clinical outcome in colorectal cancer.
Conclusion: The dbCPCO is a unique and comprehensive database that compiles literature findings on the genetic basis of disease phenotype and clinical outcome in colorectal cancer and will be instrumental in expediting personalized medicine and further research in this disease. The dbCPCO is updated periodically and is freely available for the scientific and medical community at http://www.med.mun.ca/cpco/Default.aspx.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 92.