bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 624: A case control study of benign breast disease and breast cancer among indigenous African women
Authors: ADEDOKUN BABATUNDE , Odedina Stella , Ojengbede Oladosu , Ademola Adeyinka , Ogundiran Temidayo , Huo Dezheng , Olopade Olufunmilayo , Agwai Imaria , Makumbi Timothy , Ndom Paul , Gakwaya Antony 
Published: August 2019

Abstract
Purpose: To determine the association between benign breast disease (BBD) and breast cancer and if BBD is a mediator of the association between established risk factors and breast cancer among native African women
Methods: We analysed data from 5154 women who participated in a case control study (2405 cases and 2749 controls) between March 1998 and December 2014 in three sub Saharan African countries: Nigeria (n= 4233), Uganda (n=477) and Cameroon (n=444). Breast cancer cases aged 18 years and older were enrolled in two tertiary hospitals in the two countries, unselected for age at diagnosis and family history. Controls who were free of breast cancer were enrolled in the same hospitals. Interviews were conducted to obtain data on potential epidemiological risk factors for breast cancer. We determined the association between breast cancer, history of BBD, age at diagnosis and types of BBD using logistic regression, while adjusting for socio-demographic characteristics and established risk factors. In addition, we estimated the proportion of the effects of other established risk factors mediated by BBD in the etiology of breast cancer.
Results: Less than a tenth (8.1%, 420) of the study participants reported having a history of BBD, 87 of the 420 reported a biopsy diagnosed BBD. Among breast cancer cases, the proportions of BBD and biopsy-confirmed BBD were 10.4% and 3.8%, respectively, compared to 6.3% and 1.3% among controls (both p&lt;0.001). Fibroadenoma (n=100, 45.2%) was the most commonly reported type of benign breast disease, followed by breast cyst (n=31, 15.2%) and fibrocystic diseases (n=19, 10.1%). Overall, the adjusted odds ratio of having breast cancer for those with benign breast disease relative to those without was 1.42 (95% CI 1.13-1.79). The odds ratios were also significantly higher among premenopausal (OR = 1.45, 95% CI: 1.07-1.95) and postmenopausal women (OR = 1.49, 95% CI 1.02-2.19). The proportion mediated by BBD in the association between age at menarche and breast cancer was 13.7%. Less than 1% of the effects of other risk factors that we examined was mediated by BBD.
Conclusions: Benign breast disease is a risk factor for breast cancer among women in SSA. The mediator role of BBD in the effects of established risk factors on breast cancer risk appears very minimal.
Citation Format: BABATUNDE ADEDOKUN, Stella Odedina, Oladosu Ojengbede, Adeyinka Ademola, Temidayo Ogundiran, Dezheng Huo, Olufunmilayo Olopade, Imaria Agwai, Timothy Makumbi, Paul Ndom, Antony Gakwaya. A case control study of benign breast disease and breast cancer among indigenous African women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 624.
Abstract 631: High BMI in relation to low risk of lung cancer among never smokers
Authors: Luu Hung N. , Wang Renwei , Adams-Haduch Jennifer , Jin Aizhen , Koh Woon-Puay , Yuan Jian-Min 
Published: August 2019

Abstract
Background. Lean smokers have increased oxidative DNA damage relative to their non-lean counterparts, indicating their heightened susceptibility to tobacco carcinogens-induced DNA damage. Epidemiological association between body mass index (BMI) and lung cancer is inconclusive. We have reported that BMI is a protective factor for smoking-related lung cancer and so did a recent meta-analysis. Knowledge about the association between BMI and non-smoking related lung cancer is limited as this is rare in Western population. We therefore sought to investigate the association between BMI and the risk of never-smoking related lung cancer in an on-going prospective cohort study, the Singapore Chinese Health Study.
Methods. The current analysis used data from the Singapore Chinese Health Study, a cohort of 63,257 middle-aged and older Chinese men and women enrolled between 1993 and 1998. As of December 31, 2015, 2,001 study participants who were free of lung cancer at baseline developed lung cancer of whom 621 were never smokers. Cox proportional hazard regression method was used to calculate hazard ratio (HR) and the corresponding 95% confidence interval (CI) for lung cancer associated with BMI in never-smokers.
Results. Our results shown that increasing BMI was a protective factor for never-smoking related lung cancer and there is no interaction by gender. The respective HRs and 95% CIs were 0.66 (0.45-0.95) for overall and 0.60 (0.39-0.93) in female for those with BMI&gt;27.5 compared to those with BMI&lt;18.5. Even after eliminating those with exposure to any second-hand smoke in childhood or adulthood, the inverse association between BMI and the risk of never-smoking related lung cancer was stronger and significant (HR=0.31, 95% CI: 0.13-0.75; Ptrend=0.01). There was no difference by histologic subtypes (i.e., adenocarcinomas vs. squamous cell).
Conclusion. There was an inverse association between BMI and the risk of never-smoking related lung cancer and there is no interaction by gender for this association. This association was also not different by histologic subtypes.
Citation Format: Hung N. Luu, Renwei Wang, Jennifer Adams-Haduch, Aizhen Jin, Woon-Puay Koh, Jian-Min Yuan. High BMI in relation to low risk of lung cancer among never smokers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 631.
Abstract 650: Gut microbiota population may be used to predict chemotherapeutic responsiveness in triple negative breast cancer
Authors: Bawaneh Alaa , Wilson Adam S. , Clear Kenysha YJ , Chiba Akiko , Cook Katherine L. 
Published: August 2019

Abstract
Triple negative breast cancer (TNBC) accounts for 15-20% of all breast cancers and predominately affects young and minority women. TNBC is characterized by a high recurrence rate, with about 34% of TNBC patients relapsing around 2.6 years. This type of breast cancer lacks targeted therapy options and is limited to chemotherapy treatment options. The purpose of our study was to determine whether gut microbiota populations correlate with chemotherapeutic responsiveness and may be a predictive biomarker of outcome. Moreover, we want to determine the impact of targeting the microbiome on chemotherapy efficacy. In this study, 8-week old female BALB/c mice were injected with TNBC 4T1-luciferase cells into their L4/5 mammary fat pad. Once tumors developed, mice were either untreated (control group), treated with 1 x weekly 2.5 mg/kg IV doxorubicin (DOX), or treated with doxorubicin + antibiotics (mixture of streptomycin, ampicillin, and colistin in the drinking water to ablate host bacterial populations). Tumors were collected at the end of the study. Fecal samples were collected at time point 0 weeks (T0; before therapy when tumors were approximately 100 mm3) and time point 4 weeks (T4; after treatment). We subdivided the doxorubicin treated group into DOX-responders (tumors stopped growing or shrank) or DOX-nonresponders (tumors continued to grow on treatment). Tumors from the DOX-responders and DOX + antibiotics groups were significantly smaller and mice from these groups displayed reduced lung weight, suggesting decreased lung metastatic burden. 16S-bacterial sequencing analysis was performed on breast tumor tissue and feces. We demonstrate that at T0, elevated fecal Ruminococcus correlates with DOX-nonresponsiveness. Furthermore, at T4, we show increased fecal abundance of Oscillospira and Bacteroidales are associated with better therapeutic outcome. Protein analysis of primary 4T1 breast tumor tissue indicate a significant elevation of apoptosis (cleaved caspase-3 protein levels) in DOX-responders and DOX + antibiotic treated mice. We also stained breast tumor tissue and lung tissue for bacteria to confirm presence of microbiota by immunohistochemistry. Taken together our data demonstrates that chemotherapy efficacy is modulated by the microbiome. Moreover, fecal microbiota populations could be used as a predictive biomarker of chemotherapeutic responsiveness and suggests that modulation of the gut microbiome through dietary or probiotic interventions may affect therapeutic outcomes.
Citation Format: Alaa Bawaneh, Adam S. Wilson, Kenysha YJ Clear, Akiko Chiba, Katherine L. Cook. Gut microbiota population may be used to predict chemotherapeutic responsiveness in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 650.
Abstract 652: Racial/ethnic differences in BRCA testing and test results among adult women
Authors: Guo Fangjian , Fuchs Erika L. , Berenson Abbey B. , Kuo Yong-Fang 
Published: August 2019

Abstract
Introduction: BRCA mutation testing has been recommended for targeted, individualized cancer prevention and treatment among women whose family histories or ethnic backgrounds are associated with increased risks for BRCA mutations. This study was to assess BRCA testing in different racial/ethnic groups in the US.
Methods: We used data from ClinformaticsTM Data Mart (CDM) Electronic Health Records. We included 134,827 women 18-65 years old with BRCA testing results from 1/1/2015-9/1/2017. BRCA testing rates and test result positive rates were calculated by race/ethnicity. Women with positive test results had a high risk for developing susceptible cancers - breast or ovarian cancer. As we only had data through 9/1/2017, we calculated annual test rates based on data in 2016.
Results: The BRCA mutation test rate in 2016 was highest among non-Hispanic Whites (582 per 100,000), while it was 313 per 100,000 in non-Hispanic Black women, 310 per 100,000 in Hispanic Women, and 281 per 100,000 in women of other races/ethnicities. Percentage of positive results was lowest among non-Hispanic White women tested (75.7%), and highest among non-Hispanic Black test takes (85.1%). After adjusting for age, region of residence, education, income, and family history of breast or ovarian cancer, adjusted odds ratio for having a positive test among non-Hispanic Black women tested vs. non-Hispanic White women tested was 1.71, 95% confidence interval 1.61-1.82, and adjusted odds ratio for Hispanics vs non-Hispanic Whites was 1.21, 95% confidence interval 1.13-1.31.
Conclusions: There are significant differences in test utilization and test results. Test utilization was highest in non-Hispanic Whites, who were also less likely to have a positive test result. Non-Hispanic Black women tested were more likely to have a positive test result, suggesting a more stringent test selection criteria for this underserved population.
Citation Format: Fangjian Guo, Erika L. Fuchs, Abbey B. Berenson, Yong-Fang Kuo. Racial/ethnic differences in BRCA testing and test results among adult women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 652.
Abstract 658: Antiproliferative effects of type II diabetes agents in Fanconi derived oral squamous carcinoma
Authors: Miller Kim , Wuertz Beverly , Potter David , Ondrey Frank G. 
Published: August 2019

Abstract
Fanconi anemia is a rare disease characterized by bone marrow failure requiring transplantation at a young age. Patients with Fanconi Anemia are at risk for the development of squamous cell carcinomas of the skin and mucosal surfaces at risks several hundred fold higher than control populations and these malignancies can pursue an aggressive, often fatal, course. Our group has been interested in repurposing Type 2 diabetes agents for oral cancer prevention and treatment. Presently, we examined the effects of the thiazolidinedione drug, pioglitazone, and an experimental biguanide, N1-hexyl-N5-benzyl-biguanide (HBB), on the proliferation of Fanconi-derived oral carcinoma cells. We incubated MOP FA1,a, VU-1131, and VU-1365 b, and C squamous cell carcinoma cell lines with vehicle controls or the thiazolidinedione pioglitazone or biguanide (HBB). We found dose-dependent decreases in cellular proliferation in all three Fanconi-derived cell lines at physiologically relevant concentrations (10 - 50 µM) after 1 to 3 days in several experiments. The effects were not due to simple cytotoxicity as judged by trypan blue staining. In other non-squamous cell lines of cervical and oral cavity origins we have previously discovered similar effects. These agents affect PPAR gamma associated pathways (pioglitazone) or mTOR and mitochondrial glucose metaboliscm pathways (HBB). Since Fanconi anemia patients are highly susceptible to DNA damaging effects of cytotoxic chemotherapy, these classes of agents might be attractive in Fanconi Anemia oral cancer treatment or prevention. Metformin, another biguanide, is currently postulated to delay bone marrow failure in the Fanconi population and is currently in use in an early phase clinical trial. Our results may, therefore, be attratciveattractive for oral cancer prevention and treatment in this population, as they are well tolerated. Further examination of molecular mechanisms will likely generate putative pharmacodynamics markers for future clinical trials.
Citation Format: Kim Miller, Beverly Wuertz, David Potter, Frank G. Ondrey. Antiproliferative effects of type II diabetes agents in Fanconi derived oral squamous carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 658.
Abstract 661: Adipose specific monocyte chemotactic protein-1 knockdown reduces pulmonary metastasis of Lewis lung carcinoma in mice
Authors: Sundaram Sneha , Yan Lin 
Published: August 2019

Abstract
Adipose accumulation is a strong indicator of detrimental health outcomes because adipose tissue produces pro-inflammatory adipokines that participate in many pathological processes including cancer. Monocyte chemotactic protein-1 (MCP-1) is a potent adipokine and body adiposity is positively correlated with adipose MCP-1 expression. This study tested the hypothesis that adipose-produced MCP-1 contributes to metastasis. In a metastasis model of Lewis lung carcinoma (LLC), male adipose MCP-1 knockdown (MCP-1-/-) and wild-type (WT) mice were fed the standard AIN93G diet or a high-fat diet (HFD) containing 16% or 45% of energy from soybean oil. The duration of experimental feeding was 11 weeks. The expression of MCP-1 in epididymal adipose tissue was analyzed by quantitative real-time PCR and ELISA. Pulmonary metastases from a primary tumor, established by subcutaneous injection of LLC cells, were the primary endpoints. There was no significant difference in fat body mass between MCP-1-/- and WT mice fed the same diet. There were no differences in energy intake among the four groups. The HFD increased and adipose MCP-1 knockdown decreased MCP-1 mRNA and protein in adipose tissue compared to their respective controls. The HFD increased the number of metastases formed in the lungs in WT mice. The number of metastasis was lower in MCP-1-/- mice fed the HFD than in WT mice fed the HFD but was higher compared to WT mice fed the AIN93G diet. The volume of metastases was smaller in MCP-1-/- mice than in WT mice, regardless of diet. Adipose MCP-1-/- mice, compared to WT mice, exhibited lower concentrations of insulin, pro-inflammatory adipokines (leptin, plasminogen activator inhibitor-1, and resistin), and angiogenic markers (vascular endothelial growth factor, hepatic growth factor, and angiopoietin-2) in plasma. These results indicate that adipose MCP-1 knockdown may lead to the down-regulation of inflammatory and angiogenic pathways during malignant spread. We conclude that adipose MCP-1 deficiency attenuates HFD-enhanced pulmonary metastasis of LLC and supports our hypothesis that adipose-produced MCP-1 contributes to malignant spread.
Citation Format: Sneha Sundaram, Lin Yan. Adipose specific monocyte chemotactic protein-1 knockdown reduces pulmonary metastasis of Lewis lung carcinoma in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 661.
Abstract 665: Cancer neoantigen and autoantibody discovery with PEP functional proteomics platform
Authors: Wang Xing , Landon Trevor 
Published: August 2019

Abstract
Proteins play essential roles in numerous biological processes and being able to pinpoint functional differences between cell or tissue samples can greatly aid in understanding disease processes and metabolic changes. The PEP technology allows systematic analysis of protein functions within a proteome. Hundreds of functional proteins can be separated and functionally assayed to generate a comprehensive three-dimensional landscape of protein families such as protein kinases, phosphatases, proteinases and oxido-reductases. This information can then be integrated into other genomic and proteomic knowledge bases to provide further insight of important biological processes such as cancer development and aging. Array Bridge has developed a 2-Dimensional separation technology called PEP (Protein Elution Plate) that can separate proteins into two-dimensional display and efficiently recover all the separated proteins into 384-microplates that can be probed in a standard ELISA format with high throughput. Our initial studies using breast cancer cell line proteins indicated that the PEP technology can be used to separate the proteins efficiently and probed with plasma from cancer patient for autoantibody discovery. Using the autoantibodies exist in the cancer patient, strong signals can be detected from a subset of proteins from the breast cancer cell line. We also use this platform to separate proteins from the cancer cell lines and probed with the plasma from the same cancer patient to identify the neoantigen candidates with mass spectrometry identification, the identified neoantigens can be used for the development of personalized immunotherapy such as CAR-T and other treatments.
Note: This abstract was not presented at the meeting.
Citation Format: Xing Wang, Trevor Landon. Cancer neoantigen and autoantibody discovery with PEP functional proteomics platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 665.
Abstract 669: Dynamic modeling of responses to PDL-1 inhibitors in non-small cell lung cancer: implications for precision combination therapy
Authors: Tavassoly Iman 
Published: August 2019

Abstract
Immunotherapy by immune checkpoint blockade has had a promising impact on the treatment of Non-Small Cell Lung Cancer (NSCLC). Although single and combination therapy with checkpoint inhibitors such as PDL-1 inhibitors have been proved to be effective in making the survival of patients with NSCLC longer, but there is always a population of patients which shows resistance to these therapeutic modalities. The source of resistance emerges from signaling pathways and regulatory systems in tumors and the immune system, but the dynamics among tumor components, T cells, and tumor microenvironment contribute in this process as well. To understand the complex system of these interactions, a mathematical model of these pathways and interactions are presented using Ordinary Differential Equations (ODEs). The specific characteristics of NSCLC tumors including metabolic reprogramming have been considered in this model. The model is capable of decoding patient-to-patient variabilities regarding responses to PDL-1 inhibitors, and parameter-sensitivity analysis shows the vulnerable biomarkers to be targeted by combination therapy to give better results in killing the tumor cells. The model can be integrated with PK/PD models to provide an in-silico platform for investigating the therapeutic responses in NSCLC for precision oncology.
Note: This abstract was not presented at the meeting.
Citation Format: Iman Tavassoly. Dynamic modeling of responses to PDL-1 inhibitors in non-small cell lung cancer: implications for precision combination therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 669.
Abstract 675: Network modeling of drug resistance mechanisms and drug combinations in breast cancer
Authors: Zañudo Jorge Gómez Tejeda , Mao Pingping , Montero Joan , Xu Guotai , Kowalski Kailey J. , Johnson Gabriela N. , Baselga José , Scaltriti Maurizio , Letai Anthony G. , Wagle Nikhil , Albert Reka 
Published: August 2019

Abstract
Durable control of invasive solid tumors is thwarted by the lack of knowledge of effective drug combinations and of the acquired and intrinsic resistance mechanisms of drugs. In an effort to tackle this problem, the SU2C-NSF-TVF Drug Combination Convergence Team is using mechanistic models of cancer cell signaling based on therapeutic and cell line data in order to identify elements within cancer cells that might eventually be exploited through therapeutic combinations.
Here we present a comprehensive mechanistic network model of signal transduction in ER+ PIK3CA-mutant breast cancer. Focusing on PI3K inhibitors, the model recapitulates known resistance mechanisms and predicts other possibilities for resistance: loss of RB1, FOXO3, P27, or PRAS40. To test these predictions, we analyzed genome-wide CRISPR screens of two breast cell lines in the presence of PI3K inhibitors (BYL719 and GDC0032) and found that the predicted genes (RB1, FOXO3, P27, and PRAS40) were significantly enriched in the screens. Some of these resistance genes (e.g. loss of RB1) were found to be cell-line specific and follow-up experiments in RB1-KO cells confirmed the cell-line-specific nature of PI3K-inhibitor resistance. The model also reveals known and novel combinatorial interventions that are more effective than PI3K inhibition alone. For example, the model predicts that the combination of PI3K inhibitors with inhibitors of anti-apoptotic protein MCL1 would be effective. Follow up experiments in cell lines using cell viability assays, cell death analyses, and dynamic BH3 profiling experiments to determine increases in apoptotic priming upon treatment confirmed that MCL1 inhibitors (S63845) enhance the effect of PI3K inhibitors (BYL719) and that this combinatorial effect is cell-line-specific, similarly to what was found in the resistance genes case.
In conclusion, the model predicted drug resistance mechanisms and effective drug combinations, some of which were verified experimentally and found to be cell-line-specific. Next iterations of the model will incorporate the identified discrepancies and newly identified resistance mechanisms to drugs of clinical interest.
Citation Format: Jorge Gómez Tejeda Zañudo, Pingping Mao, Joan Montero, Guotai Xu, Kailey J. Kowalski, Gabriela N. Johnson, José Baselga, Maurizio Scaltriti, Anthony G. Letai, Nikhil Wagle, Reka Albert. Network modeling of drug resistance mechanisms and drug combinations in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 675.