bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A09: A next generation sequencing based microsatellite instability assay suitable for routine risk stratification in colorectal cancer
Authors: Alhilal Ghanim , Redford Lisa , Alonso Angel , Moreno Sira , Arends Mark , Oniscu Anca , O'Brien Ottilia , Needham Stephanie , Burn John , Jackson Michael , Santibanez-Koref Mauro 
Published: May 2019

Abstract
3-5% of CRCs show microsatellite instability (MSI) caused by germline defects in mismatch repair genes (MMR) predisposing to Lynch syndrome. In addition, 12% of sporadic CRCs show MSI. Currently, MSI is tested using a fragment analysis based assay not suitable for high throughput testing with suboptimal sensitivity and specificity. Knowledge of microsatellite instability affects prognosis (MSI is a positive prognostic factor in stage II CRC), risk stratification (for the affected and at risk relatives in Lynch syndrome), prediction of lymph node involvement (lymph node metastasis is unlikely in stage I MSI positive CRC) and treatment of CRCs (MMR deficient tumours showed observable benefit from PD-1 blocking agent pembrolizumab). For all these important benefits, MSI testing is now recommended for all newly diagnosed CRCs. As a result, development of a high throughput approach is desirable. We have developed and validated a high throughput sequence based MSI assay.
In this study, we tested 17 short (7-12bp) mononucleotide markers (previously identified by our team via an in silico analyses of whole genome sequencing data). These 17 markers were able to discriminate between MSI-high (MSI-H) and microsatellite stable (MSS) cases. To define the optimal parameters to discriminate between MSI-H and MSS samples, we tested these 17 markers across a panel of 141 CRC samples. This allowed us to define a scoring scheme for the 17 markers using allelic imbalance based on a linked SNP (called weighted scoring scheme), which achieved 96% sensitivity and 100% specificity. This scoring scheme was then validated using an independent cohort of 70 CRCs without knowing their MSI status. The assay achieved a 100% sensitivity and specificity.
We provide here a high throughput tool to detect microsatellite instability that is less costly, uses short mononucleotide markers (eliminating the need to test matched normal tissue) and is validated on formalin fixed paraffin embedded (FFPE) samples (similar to routine samples). The ability to test the microsatellite instability status in all the newly diagnosed CRC cases would have a great clinical impact on prognosis, risk stratification and treatment of CRCs.
Citation Format: Ghanim Alhilal, Lisa Redford, Angel Alonso, Sira Moreno, Mark Arends, Anca Oniscu, Ottilia O'Brien, Stephanie Needham, John Burn, Michael Jackson, Mauro Santibanez-Koref. A next generation sequencing based microsatellite instability assay suitable for routine risk stratification in colorectal cancer. [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 A09.
Abstract B17: Comprehensive colorectal cancer risk prediction to inform personalized screening and intervention
Authors: Jeon Jihyoun , Berndt Sonja I. , Brenner Hermann , Campbell Peter T. , Chan Andrew T. , Chang-Claude Jenny , Du Mengmeng , Giles Graham , Gong Jian , Gruber Stephen B. , Harrison Tabitha A. , Hoffmeister Michael , LeMarchand Loic , Li Li , Potter John D. , Rennert Gad , Schoen Robert E. , Slattery Martha L. , White Emily , Woods Michael O. , Peters Ulrike , Hsu Li 
Published: May 2019

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR17) of the Conference Proceedings.
Citation Format: Jihyoun Jeon, Sonja I. Berndt, Hermann Brenner, Peter T. Campbell, Andrew T. Chan, Jenny Chang-Claude, Mengmeng Du, Graham Giles, Jian Gong, Stephen B. Gruber, Tabitha A. Harrison, Michael Hoffmeister, Loic LeMarchand, Li Li, John D. Potter, Gad Rennert, Robert E. Schoen, Martha L. Slattery, Emily White, Michael O. Woods, Ulrike Peters, Li Hsu. Comprehensive colorectal cancer risk prediction to inform personalized screening and intervention. [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 B17.
Abstract B19: Effect of cancer risk and patient preferences on net benefit of lung cancer screening: A Personalized Lung Cancer Screening Model
Authors: Cao Pianpian , Caverly Tanner , Hayward Rodney , Meza Rafael 
Published: May 2019

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR16) of the Conference Proceedings.
Citation Format: Pianpian Cao, Tanner Caverly, Rodney Hayward, Rafael Meza. Effect of cancer risk and patient preferences on net benefit of lung cancer screening: A Personalized Lung Cancer Screening Model. [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 B19.
Abstract A35: Somatic mutation profile of a panel of oncogenes and tumor suppressor genes in colorectal cancer in a Brazilian population
Authors: Santos Wellington , Evangelista Adriane Feijó , Durães Ronilson , Matsushita Marcus , Reis Rui Manuel , Guimarães Denise Peixoto 
Published: May 2019

Abstract
Colorectal cancer (CRC) is the third most frequent cancer worldwide and the fourth leading cause of death due to cancer. The development of this disease usually occurs due to the progression of precursor lesions in the normal intestinal mucosa to tumor. Environment, age, lifestyle, and genetic background are considered risk factors for the development and progression of CRC. The molecular abnormalities involved in the progression of CRC have been well characterized, including mutations, microsatellite instability, and epigenetic changes. Although the molecular profile of colorectal cancer is well known in developed countries, in the Brazilian population information is still very limited. Therefore, in the present study we intended to characterize the mutation profile of a Brazilian population and associate this with their clinicopathologic features. A total of 61 colorectal cancer cases of different stages were included. DNA was extracted from frozen fresh tumors and sequenced using a panel of 298 genes by next-generation sequencing (NGS). The mean age of patients was 63 years old; 57.4% were male. Three patients had CRC in stage 0, 16 in stage I, 29 in stage II, 10 in stage III, and three in stage IV. Considering only nonsynonymous alterations, we found on average 7.24 mutations per patient. The majority were missense (61.8%), followed by nonsense (15.2%) and frameshift mutations (10.9%). The genes most frequently mutated were APC (78.7%), TP53 (72.1%), KRAS (60.7%), PIK3CA (14.8%), and FBXW7 (14.8%). Alterations in tumor suppressor genes such as APC and TP53 were found throughout the entire gene. On the other hand, oncogenes such as KRAS had alterations in hotspots of the gene. In conclusion, the frequency of alterations in genes sequenced in our population was similar to that found in the international literature for other populations.
Citation Format: Wellington Santos, Adriane Feijó Evangelista, Ronilson Durães, Marcus Matsushita, Rui Manuel Reis, Denise Peixoto Guimarães. Somatic mutation profile of a panel of oncogenes and tumor suppressor genes in colorectal cancer in a Brazilian population [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 A35.
Abstract A60: Full-length transcripts identification from deep transcriptomic analysis of Bothrops jararaca venom gland
Authors: Messias Elisa Alves , Eguchi Flavia Coltri , Sorroche Bruna Pereira , Oliveira Angela Das Neves , Arantes Lidia Maria Rebolho Batista , Carvalho Ana Carolina De , Azevedo Anita mitico tanaka , Grego Kathleen Fernandes , Melendez Matias Eliseo , Carvalho Andre Lopes 
Published: May 2019

Abstract
Introduction: Head and neck cancer is a collective term defined by topographic and anatomic features to describe malignant tumors of the upper aerodigestive tract. Despite the different strategies used in the treatment of head and neck squamous cell carcinoma (HNSCC), the overall survival rate is around 50% and the main reason for treatment failure is the frequent development of loco-regional recurrences, which affect around 30% of HNSCC patients. The increase in cancer diagnosis makes it necessary to search for alternative sources to inhibit tumor progression, as well as the development of more efficient drugs. Identification of natural resources as therapeutic potential may lead to the development of new antitumor treatments.
Objectives: The aim was to identify transcripts expressed in venom glands of the Bothrops jararaca snake with therapeutic potential for head and neck squamous cell carcinoma (HNSCC) tumors.
Materials and Methods: The mRNA library from B. jararaca was sequenced using Illumina NextSeq 500 platform (76 bp unpaired-end) and NextSeq 500/550 Mid Output v2 kit (150 cycles). Library was constructed using TruSeq Stranded mRNA LT Sample Prep Kit (Illumina). De novo assembly of the B. jararaca transcriptome was performed using Velvet software to assemble the transcriptome contigs.
Results: The RNA-seq of B. jararaca venom gland generated 4,401,692 raw reads. The de novo Velvet assembly produced 3,498,133 contigs, which matched against NCBI-Blastn transcripts. From these contigs were identified 3,638 full-length transcripts, from which were selected two potential therapeutic genes, Fosfolipases A2 1 and Fosfolipases A2 2.
Conclusions: In conclusion, this transcriptome sequencing identified two potential therapeutic transcripts, Fosfolipases A2 1 and Fosfolipases A2 2, which will be analyzed in HNSCC cell lines.
Citation Format: Elisa Alves Messias, Flavia Coltri Eguchi, Bruna Pereira Sorroche, Angela Das Neves Oliveira, Lidia Maria Rebolho Batista Arantes, Ana Carolina De Carvalho, Anita mitico tanaka Azevedo, Kathleen Fernandes Grego, Matias Eliseo Melendez, Andre Lopes Carvalho. Full-length transcripts identification from deep transcriptomic analysis of Bothrops jararaca venom gland [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 A60.
Abstract B09: Exploring IKKβ as an antiangiogenic therapeutic target in KRAS-induced lung cancer
Authors: Carneiro-Lobo Tatiana C. , Santos Edmilson Ozorio dos , Scalabrini Luiza Coimbra , Cardeal Laura B. , Baldwin Albert S. , Giordano Ricardo José , Basseres Daniela S. 
Published: May 2019

Abstract
Activating mutations in KRAS are prevalent in cancer, but therapies targeted to oncogenic RAS have so far failed. An alternative route for blocking RAS-driven oncogenic pathways is to target downstream effectors of RAS involved in promoting the oncogenic phenotype. One of the critical characteristics required for tumors to grow and progress is the ability of tumor cells to drive angiogenesis. Interestingly, oncogenic RAS promotes angiogenesis by upregulating the proangiogenic IL-8 cytokine, an NF-κB target gene, and we have shown that NF-κB activation by KRAS requires the IKKβ kinase. Interestingly, IKKβ targeting only minimally affects KRAS-mutant cell growth in vitro, nonetheless it significantly reduces KRAS-induced lung tumor growth in situ. Therefore, we hypothesized that IKKβ inhibition would reduce KRAS-induced lung tumor growth by impairing angiogenesis. To test this hypothesis, we targeted IKKβ in KRAS-mutant lung cancer cell lines A549 and H358, both by RNAi and by treatment with Compound A (CmpdA), a highly specific IKKβ inhibitor. Both approaches reduced expression and secretion of IL-8 and VEGF, another NF-κB-regulated proangiogenic growth factor. Moreover, conditioned media from IKKβ-targeted lung cells reduced endothelial cell migration and tube formation in vitro. Furthermore, siRNA-mediated IKKβ inhibition reduced xenograft tumor growth and angiogenesis in vivo. Finally, we determined that IKKβ inhibition can affect endothelial cell function independently of cancer cells as well, as CmpdA treatment directly reduced endothelial cell migration and reduced pathologic retinal angiogenesis in a mouse model of neonatal retinopathy. Taken together, these results suggest that IKKβ inhibition therapy may be an important general antiangiogenic therapy and may reduce KRAS-induced lung tumor angiogenesis, thereby providing a clinical therapeutic benefit for lung cancer patients harboring KRAS mutations.
Citation Format: Tatiana C. Carneiro-Lobo, Edmilson Ozorio dos Santos, Luiza Coimbra Scalabrini, Laura B. Cardeal, Albert S. Baldwin, Ricardo José Giordano, Daniela S. Basseres. Exploring IKKβ as an antiangiogenic therapeutic target in KRAS-induced lung 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 B09.
Abstract B11: Prostate apoptosis response-4 (PAR4) secretion in breast tumor and normal cell lines cultured in hypoxic conditions
Authors: Garcia Simone Aparecida de Bessa , Brobovnitchaia Irina Gueroldovna , Mangone Flavia Rotea , Nagai Maria Aparecida 
Published: May 2019

Abstract
The prostate apoptosis response-4 (PAR4) gene encodes a 38kDa proapoptotic protein with tumor cell selective action and/or cell sensitization to an additional proapoptotic insult. This selective apoptotic ability is associated with PAR4 nuclear translocation and phosphorylation state. PAR-4 acts through intrinsic and extrinsic apoptotic pathways. PAR-4 can also be secreted by normal/immortalized and cancer cells via the classical ER stress pathway mediated by GRP78. The previous study from our group provided evidence that MCF10A cells cultured in three-dimensional conditions display an increased expression of PAR4 in the center of the acini, where the cells are dying to lumen formation and where the O2 levels are expected to be lower. In the present study, we sought to evaluate the effects of hypoxia on PAR4 secretion in mammary epithelial cells and breast cancer cells. MCF10A (immortalized mammary epithelial cells) and the breast cancer cells MCF7, MDA-MB-231, and SKBR3 were cultured in normoxic and hypoxic (1% O2) conditions. The conditioned medium (CM) was concentrated using Amicon Ultra 10kDA filters and resolved by SDS-PAGE gel electrophoresis in parallel to cell lysate analysis. Cells maintained under hypoxic conditions for 6 h, 24 h, and 48 h showed no alteration in intracellular PAR4 protein levels in relation to cells maintained in normoxia. After 72 h we observed a decrease in intracellular PAR4 protein expression. The GRP78 protein expression did not change in the same time periods. However, Caspase-7 activation could be seen in 24 h, 48 h, and 72 h. Furthermore, we observed an increase (2.7 fold) in PAR4 protein expression in the CM after 72 h under hypoxia. Our results demonstrated for the first time that PAR4 secretion is modulated by hypoxia in normal and tumor breast cells. Further experimental and clinical studies are needed to determine the mechanism and role played by PAR4 secretion in cells' sensitivity to standard chemotherapeutics agents.
Supported by FAPESP and CNPq.
Citation Format: Simone Aparecida de Bessa Garcia, Irina Gueroldovna Brobovnitchaia, Flavia Rotea Mangone, Maria Aparecida Nagai. Prostate apoptosis response-4 (PAR4) secretion in breast tumor and normal cell lines cultured in hypoxic conditions [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 B11.
Abstract B45: Rab5C enhances resistance to ionizing radiation in rectal cancer
Authors: Baptistella Antuani Rafael , Dias Marcos Vinicios Salles , Giudice Fernanda , Rodrigues Bruna Roz , Silva Petrus Paulo Combas Eufrazio , Cassinela Edson Kuatelela , Lacerda Tonielli , Marchi Fabio , Leme Adriana Franco Paes , Begnami Maria Dirlei , Junior Samuel Aguiar , Martins Vilma Regina 
Published: May 2019

Abstract
Rectal cancer is currently the second most common cancer in the large intestine, and represents one-third of the colorectal cancers that are diagnosed. Neoadjuvant chemoradiation is a well-established protocol for rectal cancer treatment and it reduces the risk of local recurrence. However, a pathologic complete response is only achieved in 10–40% of cases and the mechanisms associated with chemoradiation resistance are poorly understood. To identify potential targets for preventing therapy resistance, a proteomic analysis of biopsy specimens collected from stage II and III rectal adenocarcinoma patients before neoadjuvant treatment was performed. These results were then compared with a proteomic analysis of residual rectal adenocarcinoma tissues that were removed by surgery after neoadjuvant therapy. Three proteins, Ku70, Ku80, and Rab5C, exhibited a significant increase in expression after chemoradiation treatment. To better understand the possible role of these proteins in therapy resistance, a rectal adenocarcinoma cell line was irradiated to generate a radiotherapy-resistant lineage. These cells overexpressed the same three proteins that were identified in the tissue samples. Furthermore, radiotherapy resistance in this in vitro model was found to involve modulation of epidermal growth factor receptor (EGFR) internalization by Rab5C in response to irradiation, and this affected expression of the DNA repair proteins, Ku70 and Ku80. Taken together, these findings indicate that EGFR and Rab5C are potential targets for the sensitization of rectal cancer cells to neoadjuvant treatment and they should be further investigated.
Supported by FAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulo.
Note: This abstract was not presented at the conference.
Citation Format: Antuani Rafael Baptistella, Marcos Vinicios Salles Dias, Fernanda Giudice, Bruna Roz Rodrigues, Petrus Paulo Combas Eufrazio Silva, Edson Kuatelela Cassinela, Tonielli Lacerda, Fabio Marchi, Adriana Franco Paes Leme, Maria Dirlei Begnami, Samuel Aguiar Junior, Vilma Regina Martins. Rab5C enhances resistance to ionizing radiation in rectal 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 B45.
Abstract B49: Perillyl alcohol: Dynamic interactions with the lipid bilayer and implications for long-term inhalational chemotherapy for gliomas
Authors: Fonseca Clovis 
Published: May 2019

Abstract
Gliomas display a high degree of intratumor heterogeneity, including changes in physiologic parameters and lipid composition of the plasma membrane, which may contribute to the development of drug resistance. Biophysical interactions between therapeutic agents and the lipid components at the outer plasma membrane interface are critical for effective drug uptake. Amphipathic molecules such as perillyl alcohol (POH) have a high partition coefficient and generally lead to altered lipid acyl tail dynamics near the lipid-water interface, impacting the lipid bilayer structure and transport dynamics. We therefore hypothesized that glioma cells may display enhanced sensitivity to POH-induced apoptosis due to plasma membrane alterations, while in nontransformed cells, POH may be expelled through thermal agitation. Interactions between POH and the plasma membrane was studied using molecular dynamics simulations. In this phase I/II trial, we set up to evaluate the clinical effectiveness of long-term (up to 5 years) daily intranasal administration of POH in a cohort of 19 patients with low-grade glioma (LGG). Importantly, in a series of clinical studies previously published by our group, we have successfully established that intranasal delivery of POH to patients with malignant gliomas is a viable and effective therapeutic strategy. POH altered the plasma membrane potential of the lipid bilayer of gliomas and prolonged intranasal administration of POH in a cohort of patients with LGG halted disease progression with virtually no toxicity. Altogether, the results suggest that POH-induced alterations of the plasma membrane might be contributing to its therapeutic efficacy in preventing LGG progression.
Citation Format: Clovis Fonseca. Perillyl alcohol: Dynamic interactions with the lipid bilayer and implications for long-term inhalational chemotherapy for gliomas [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 B49.