bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA24: Developing and evaluating cancer risk assessment tools for primary care
Authors: Emery Jon 
Published: May 2019

Abstract
Numerous risk assessment tools have been developed which predict either current or future risk of a cancer diagnosis yet very few are used in routine clinical practice. These tools could be used for tailored disease prevention, more efficient use of cancer screening tests and to promote behavioural change to reduce cancer risk. We have a growing number of cancer risk-prediction models which incorporate phenotypic, behavioural and, increasingly, genomic variables; these models require simple-to-use risk assessment tools for their implementation into clinical practice, and in particular ones which can be incorporated into primary care. In this presentation I will present a recent systematic review of RCTs in primary care of cancer risk assessment tools. This will highlight some of the key issues which remain for successful implementation of these tools into primary care practice. Selecting which cancer risk prediction model to incorporate into a tool will depend not only the predictive utility of the model but also the feasibility of collecting more complex predictive variables in clinical practice. We should design tools that can be incorporated into the clinical consultation, and which present cancer risks in meaningful ways that are more likely to lead to appropriate behaviour change. I will present research on the development of the CRISP tool to demonstrate how we are applying these principles and trialing its effect on risk-stratified colorectal cancer screening in Australian primary care.
Citation Format: Jon Emery. Developing and evaluating cancer risk assessment tools for primary care. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr IA24.
Abstract PR06: Using frailty models to improve familial cancer risk prediction
Authors: Huang Theodore , Braun Danielle , Gorfine Malka , Parmigiani Giovanni 
Published: May 2019

Abstract
There are numerous statistical models used to identify individuals at high risk of cancer due to inherited mutations. We focus on models using Mendelian laws of inheritance to calculate the probability that a counselee is a mutation carrier and their future risk of cancer based on family history and known mutation prevalence and penetrance (the probability of having a disease at a certain age given the person's genotype). Mendelian risk prediction models for various cancers have previously been developed. These models include BRCAPRO, which identifies individuals at high risk for breast or ovarian cancer by calculating the probabilities of germline deleterious mutations in BRCA1 and BRCA2. These models do not account for the heterogeneity of risk across families due to sources such as environmental or unobserved genetic risk factors. We aim to improve breast cancer risk prediction in the BRCAPRO model by incorporating a frailty model that contains a family-specific variate to account for this heterogeneity. We apply our proposed model to data from the Cancer Genetics Network, and preliminary results show that model calibration (measured by the ratio of observed to expected number of events) improves, while discrimination (measured by the area under the receiver operating characteristic (ROC) curve) remains the same.
This abstract is also being presented as Poster A18.
Citation Format: Theodore Huang, Danielle Braun, Malka Gorfine, Giovanni Parmigiani. Using frailty models to improve familial cancer risk prediction. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr PR06.
Abstract PR13: External validation of a risk prediction model for lung cancer among smokers
Authors: Sakoda Lori C. , Habel Laurel A. , Thai Khanh K. , Quesenberry Charles P. 
Published: May 2019

Abstract
Early detection strategies for lung cancer may be improved by using valid risk prediction models to identify persons at highest risk for the disease. However, external validation of lung cancer risk prediction models has been limited. We sought to externally validate the PLCOM2012 model, which predicts the probability of lung cancer within six years on the basis of age, race, education, body mass index, chronic obstructive pulmonary disease, personal history of cancer, family history of lung cancer, and smoking status, quantity, duration, and quit years, in the Kaiser Permanente Northern California (KPNC) Research Program on Genes, Environment, and Health (RPGEH) cohort. To increase comparability to the populations of smokers used to initially develop and validate the PLCOM2012 model, we restricted our analysis to the 28,757 ever smokers ages 55 to 74 with no history of lung cancer, no history of other non-melanoma skin cancers in the prior five years, and complete data on all model predictors. For each person, the predicted probability of lung cancer risk was estimated with data ascertained from the RPGEH survey on all predictors except quit years, which was ascertained from electronic health records. Using KPNC Cancer Registry data, we identified 672 diagnosed with lung cancer within six years post-survey. Both calibration and discrimination were examined to assess model performance. Calibration was assessed by determining the mean absolute difference in observed and predicted probabilities of lung cancer for each decile of predicted risk. Discrimination was assessed by estimating the area under curve (AUC). The absolute difference in observed and predicted probabilities of lung cancer risk was generally small: &lt;0.010 and &lt;0.035 in half and 90% of the analytic cohort, respectively. Although the mean absolute difference in observed and predicted probabilities of lung cancer risk was smallest for the lowest decile (0.003; observed probability: 0.003) and largest for the highest decile (0.049; observed probability: 0.08), it did not increase monotonically with each increasing decile of predicted risk. Discrimination was modest with an AUC of 0.73 (95% confidence interval: 0.71, 0.75). In a large, independent population of smokers, we found the PLCOM2012 model did not perform as well as demonstrated previously.
Citation Format: Lori C. Sakoda, Laurel A. Habel, Khanh K. Thai, Charles P. Quesenberry, Jr. External validation of a risk prediction model for lung cancer among smokers. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr PR13.
Abstract A02: Potential role of SMC6 downregulation as an indicator of tumor genetic instability in breast cancer
Authors: Mangone Flavia Rotea , Krepischi Ana Cristina Victorino , Nonogaki Suely , Carraro Dirce Maria , Nagai Maria Aparecida 
Published: May 2019

Abstract
Genetic instability is a common feature of cancer. Homologous recombination (HR) is involved in one of the major mechanisms of DNA double strand break repair (DSB) and depends on the formation of Holliday junctions (HJ) that should be solved for the maintenance of genomic stability. Deregulation of HR control mechanisms results in DNA damage. Data from the literature has shown that SMC6 complexed with SMC5 is involved in DSB repair. Previous sequencing data from our group showed the occurrence of some SMC6 genetic variants in sporadic breast cancer. In the present study, we sought to investigate a possible association between SMC6 expression level and genomic instability in breast cancer. SMC6 mRNA expression pattern determined by qRT-PCR and Copy Number Variation (CNV) data obtained by using whole-genome comparative genomic hybridization on microarrays, were determined in a cohort of 33 breast cancer samples of women who did not carry BRCA1/BRCA2 mutations. SMC6 protein expression was carried out in a tissue micro-array containing breast cancers samples. Statistical analyses were performed by using SPSS Software 20. Data comparison revealed that tumors with higher SMC6 mRNA expression showed a trend toward lower median numbers of total CNVs per genome, corroborating the role of SMC6 genomic stability maintenance. SMC6 protein expression was tested in a panel of 74 breast cancer tumors, and cases were classified into two groups: SMC6 negative (negative to weak nuclear staining) and SMC6 positive (moderate to strong nuclear staining). No association among SMC6 staining and clinic-pathologic features was observed. However, patients with SMC6 negative tumors had a trend to a shorter disease-free survival (DFS) and overall survival (OS) than those with SMC6 positive tumors (median DFS 29.0 vs. 172.0 months, Log Rank = 0.123 and median OS 30.47 vs. 153.30 months, Log Rank = 0.117). Although preliminary, our findings point to a possible association between SMC6 downregulation and poor outcome of patients, suggesting theatSMC6 may serve as an indicator of tumor genetic instability for patients with breast cancer. Supported by Fapesp and CNPq.
Citation Format: Flavia Rotea Mangone, Ana Cristina Victorino Krepischi, Suely Nonogaki, Dirce Maria Carraro, Maria Aparecida Nagai. Potential role of SMC6 downregulation as an indicator of tumor genetic instability in breast cancer [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A02.
Abstract A14: Downregulation of desmin involves gene promoter hypermethylation in gallbladder cancer
Authors: Bhunia Shushruta , Barbhuiya Mustafa Ahmed , Gupta Sanjiv , Shrivastava Braj Raj , Tiwari Pramod Kumar 
Published: May 2019

Abstract
Gallbladder cancer (GBC) is a fatal malignancy with widespread geographical variations in incidence worldwide. There are limited studies on systematic molecular profiling of gallbladder cancer in literature. Previously, we carried out differential proteomic and methylome-based analysis in gallbladder tumors and adjacent non-tumors to identify differentially expressed proteins and global methylation status of genes involved in gallbladder cancer. Quantitative tissue proteomics analysis using Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) based Liquid Chromatography-Mass Spectrometry (LC-MS/MS) showed that desmin protein was significantly downregulated (~3 folds) in tumors. Global methylation profiling using Illumina's Infinium Human Methylation 450 BeadChip array revealed hypermethylation in desmin in gallbladder tumors compared to non-tumor tissue. These findings lead us to further investigate the epigenetic regulation of desmin gene expression in gallbladder cancer. Real-time PCR analysis revealed significant downregulation of desmin (p=0.001) expression in tumors (n=12) as compared to the non-tumor tissue (n=12). Immunohistochemical analysis also showed significantly (p&lt;0.0001) decreased level of desmin in 95% (26/27) of tumor cells in comparison to non-tumors 35.71% (5/14). This was again validated by Western blotting, showing downregulation of desmin (p=0.0081) at protein level in tumor tissues compared to the non-tumors. Methylation specific polymerase chain reaction analysis showed 86.67% methylation of desmin in corresponding gallbladder tumors compared to non-tumor tissue (p=0.004). Taken together, our observations showing decreased expression and hypermethylation of desmin gene suggest desmin as a potential epigenetically controlled biomarker for GBC. However, further studies are warranted to explore its role in tumorogenesis of gallbladder cancer.
Citation Format: Shushruta Bhunia, Mustafa Ahmed Barbhuiya, Sanjiv Gupta, Braj Raj Shrivastava, Pramod Kumar Tiwari. Downregulation of desmin involves gene promoter hypermethylation in gallbladder cancer [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A14.
Abstract A15: Oncomirs expression profiling in uterine leiomyosarcoma cells
Authors: Almeida Bruna Cristine De , Garcia Natalia , Baracat Edmund Chada , Carvalho Kátia Candido 
Published: May 2019

Abstract
miRNAs act as regulators of gene expression at the post-transcriptional level, playing a key role in several biologic processes; their abnormal expression may to lead a cellular transformation and tumorigenesis. miRNAs are considered as oncomirs when regulated oncogenes or tumor suppressor genes. Here, we aimed to evaluate the expression profile of 84 oncomirs sequences in immortalized cells of myometrium (MM), uterine leiomyoma (ULM), and uterine leiomyosarcoma (ULMS), seeking specific signatures for these cells. MM (PCS-460-011), LM (T HESCs CRL-4003) and ULMS (SK-UT-1 HTB-114) cells line were cultured in specific medium and conditions (ATCC recommendations). Quantitative Real Time - PCR was performed using the MIHS-109ZA-Qiagen 96 wells plate; all data were normalized and analyzed by ΔΔCt method in the pcrdataanalysis.sabiosciences.com/mirna software. Data analysis showed nine miRNAs with significant differential expression in ULM and fifteen in ULMS, using MM cells as reference. Six miRNAs were overexpressed in ULM;among them two had a high fold regulation (miR-205-5p and miR-328-3p). In ULMS six miRNAs exhibited a significant overexpression, with greater fold regulation in miR-148a-3p, miR-202-3p, and miR-203a-3p. We found nine downregulated miRNAs in ULMS and four in ULM. A reverse expression was observed in miR-21-5p and miR-27b-3p in ULM and ULMS; in addition, these miRNAs showed a downregulation in ULMS with high fold regulation. miR-495-3p, miR-27b-3p, and miR-152-3p had a significant downregulated expression in ULMS. Only two miRNAs (miR-31-5p and miR-210-3p) showed downregulated expression in ULM than ULMS. In conclusion, our preliminary approach identified 17 oncomirs with a significantly deregulated expression profile in ULM and ULMS that might lead to alterations in their mRNA-target. Their role in ULM and ULMS may be further investigated.
Citation Format: Bruna Cristine De Almeida, Natalia Garcia, Edmund Chada Baracat, Kátia Candido Carvalho. Oncomirs expression profiling in uterine leiomyosarcoma cells [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A15.
Abstract A26: Analysis of alternative splicing events in high- and low-grade bladder tumors
Authors: Sávio André Luiz Ventura , Piuco Ricardo , Leite Katia Ramos Moreira , Salvadori Daisy Maria Favero , Galante Pedro Alexandre Favoretto , Penalva Luiz Otavio Ferraz 
Published: May 2019

Abstract
Functioning primarily in the rearrangement of identical pre-mRNA into different molecules, the alternative splicing (AS) contributes to the organism proteomic diversity. There are still unknown AS events, especially the aberrant splicing events that are associated to nonfunctional final products or tumorigenesis. For instance, hallmarks, such as apoptosis, metastasis, and angiogenesis, of certain types of cancer are known to be affected by some kind of aberrant splicing event. As examples, for BCLX gene, antiapoptotic and proapoptotic isoforms have been discovered, and, for the VEGFA gene, changes between proangiogenic and antiangiogenic isoforms expression have been detected in tumors and normal-matched samples, as well as among several distinct tissues. We hypothesize that AS events can also be associated and contribute to the origin and maintenance of specific tumor types and sub-types. We characterized the AS events in 35 samples of primary bladder tumors, classified as 20 high-grade (cells poorly differentiated, invasive and metastatic tumor), 11 low-grade (cell differentiated, noninvasive tumor), and 5 normal tissues. To access the AS events, we generated in total 2.5 billion of reads using RNAseq. The next step was mapping these reads against the human reference genome, using a set of in-house and publicly available pipelines to detect AS events in high-/low-grade bladder samples and normal tissues. As result, we observed 992 significant splicing events on high-grade tumors as compared to normal samples, 796 significant events on low-grade versus normal samples, and 871 significant events on low-grade versus high-grade tumors. After looking for some of these events in combinations of tumor grades and control, we found a tumor-specific isoform for RPS24 gene and five splicing events of genes RPL13A, RPL3, RPL37A, RPS27A, and RPL34 that are unique to high-grade tumors. We believe that these low-/high-grade AS specific events should be further studied in order to contribute to the understanding and to the development of new drugs for bladder tumors presenting low- or high-grade.
Citation Format: André Luiz Ventura Sávio, Ricardo Piuco, Katia Ramos Moreira Leite, Daisy Maria Favero Salvadori, Pedro Alexandre Favoretto Galante, Luiz Otavio Ferraz Penalva. Analysis of alternative splicing events in high- and low-grade bladder tumors [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A26.
Abstract A57: Glutathione depletion overcomes chemotherapy resistance in aggressive medulloblastoma stem-like cells
Authors: Barbieri Beatriz Dias , Marçola Marina , Rocha Clarissa , Okamoto Oswaldo Keith 
Published: May 2019

Abstract
Drug resistance is one of the main limiting steps for the successful treatment of most cancers. Additionally, the presence of cancer cells with stem cell traits favors the process of treatment resistance, tumor recurrence, and spreading. Glutathione (GSH) is a major antioxidant intracellular molecule and has been positively correlated with the development of drug resistance. The purpose of this study was to verify whether GSH depletion potentiates the effect of chemotherapy in stem-like cells from the medulloblastoma cell line Daoy. Cells expressing normal (control tumor cells) or high levels of the pluripotency factor OCT4A (stem-like cells) were treated with a combination of BSO (glutathione inhibitor), cisplatin, and temozolomide (TMZ). Cell viability was assessed through MTT and apoptosis assays. Initially, the concentration of BSO required to deplete the GSH in both Daoy and Daoy-OCT4A cells was established (50 and 58 μM, respectively), as well as the IC50 of each chemotherapeutic drug. Both cells were sensitive to cisplatin (IC50 = 0.494 μM for Daoy and 0.215 μM for Daoy-OCT4A), but resistant to TMZ. The highest dose of TMZ used (500 μM) reduced the viability of Daoy cells to 56%, but only to 80% in Daoy-OCT4A cells, denoting the chemoresistant phenotype of these cancer stem-like cells. Next, the ideal combination of the three compounds was defined. For Daoy cells, it was BSO 50 μM + cisplatin 0.8 μM + TMZ 0.8 μM. As for Daoy-OCT4A cells, it was BSO 58 μM + cisplatin 0.215 μM + TMZ 500 μM. Daoy-OCT4A cells required a higher dose of TMZ than control Daoy cells to attain similar death rates; however, the combined treatment was effective for both cells. When combining these three drugs, a synergistic effect was observed for Daoy-OCT4A cells, reducing cell viability to ~17%, in comparison with treatment of cisplatin+TMZ alone. As for Daoy cells, an additive effect was observed and viability was reduced to ~15%, in comparison with cisplatin+TMZ alone. This indicates that the use of a glutathione inhibitor in combination with cisplatin and TMZ may be useful in the treatment of medulloblastoma, even in the case of aggressive tumors. Similarly, this approach may also be useful in the development of therapeutic strategies for other chemoresistant tumors.
Citation Format: Beatriz Dias Barbieri, Marina Marçola, Clarissa Rocha, Oswaldo Keith Okamoto. Glutathione depletion overcomes chemotherapy resistance in aggressive medulloblastoma stem-like cells [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A57.
Abstract A66: Anticancer activity of selective TrkB inhibition in medulloblastoma cells
Authors: Thomaz Amanda , Pinheiro Kelly V. , Silva Camila A. da , Farias Caroline B. de , Roesler Rafael 
Published: May 2019

Abstract
Medulloblastomas (MB) occur in the central nervous system and are the most common pediatric intracranial tumors. Despite the knowledge regarding the molecular biology of these tumors, patients still suffer long-term side effects in consequence of the current treatments. Several advances have collaborated to the identification of new therapeutic targets for cancer treatment, including the characterization of BDNF/TrkB signalling in cell fate. This pathway has been associated with increased proliferative capabilities, invasiveness, and chemotherapy resistance in many types of cancer. We have previously shown that the selective TrkB inhibitor, ANA-12, markedly reduced the viability and survival of MB cell lines. These findings provided a rationale to further investigations relating TrkB inhibition as a potential novel strategy for MB treatment. We investigated the effects of ANA-12 in apoptosis and the effects of combined treatment with cisplatin in MB cell viability. Human MB cell lines D283 and UW-228 were treated with increasing concentrations of ANA-12 (5, 20, or 30 μM) or BDNF (50 ng/ml) for 24 or 48 hours. Cells were also treated with different combinations of ANA-12 and cisplatin for 48 hours. Cell viability was assessed by trypan blue cell counting. Cell apoptosis was analyzed by flow cytometry to annexin-V and propidium iodide staining. Data represent at least three independent experiments performed in triplicates. Statistical analyses: two-way ANOVA followed by followed by Tukey for multiple comparisons. We found that ANA-12 leads to a dose- and time-dependent reduction of D283 and UW-228 MB cell viability. ANA-12 at 30 μM increased the population of apoptotic cells in both MB cell lines. In D283 29.9% and 61.9% of the cells were apoptotic after 24 and 48 hours of treatment, respectively. In UW-228 apoptosis rates were 49.1% after 24 hours and 80.7% after 48 hours. When used in combination, ANA-12 enhanced cisplatin cytotoxic effects in UW-228 cells. Cell viability in the presence of 5 μM of cisplatin alone was 37.48% (UW-228) and 49.8% (D283), but decreased with the combination of 20 μM of ANA-12, 18.4% (UW-228) and 23.4% (D283). Here we present the evidence that in human MB, ANA-12 decreases viability, induces apoptosis, and acts synergistically with cisplatin in suppressing MB cell viability.
Citation Format: Amanda Thomaz, Kelly V. Pinheiro, Camila A. da Silva, Caroline B. de Farias, Rafael Roesler. Anticancer activity of selective TrkB inhibition in medulloblastoma cells [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A66.