bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A42: Prenatal role of medical radiation in children diagnosed with a blood cancer: Single-institution study, 2006-2016
Authors: Rohrer Robin L. 
Published: May 2019

Abstract
Background: Prenatal exposure to medical radiation is an identified risk for childhood cancers, but is difficult to document. The author developed a family questionnaire and interview form to identify possible exposures in children diagnosed from 2006-2016 with a blood cancer at a single institution. The Children's Hospital of Pittsburgh historically in this ten-year period has seen 180-200 new cases of a pediatric cancer each year with approximately 35-40% of these cancers being a blood cancer, notably an acute leukemia, chronic leukemia, Hodgkins's lymphoma, or a non-Hodgkin's lymphoma.
Method: Each converted family (approximately 30% of the cohort) has been interviewed at hospital, clinic, or through phone conversation who were diagnosed with a type of acute or chronic leukemia or lymphoma. All children were diagnosed/treated at the Children's Hospital of Pittsburgh (CHP). CHP is the tristate regional referral center which sees about 180-200 new cases of a pediatric cancer each year. Medical staff and psychosocial staff referred patient families for interview with the author.
Results: Among the families interviewed, at least one medical radiation prenatally has been identified in over one-third of families. These exposures prominently included sinus, chest or abdominal x-rays, or CT in either patient.
Conclusion: Exposures to medical radiation for a child later diagnosed with cancer may occur pre-conception, in utero, or in early childhood. These exposures may be part of the “perfect storm” which eventually results in a blood or other cancer in children. Documenting these exposures may possibly in future lead to more preventive measures pre-conception similar to the “image gently” initiative to limit the number of diagnostic procedures and radiation doses in CT imaging of children today.
Citation Format: Robin L. Rohrer. Prenatal role of medical radiation in children diagnosed with a blood cancer: Single-institution study, 2006-2016 [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 A42.
Abstract A53: Akt inhibitior MK2206 combination to neoadjuvant radiotherapy: Improving the rectal cancer treatment
Authors: Koyama Fernanda C. , Ramos Camila M. Lopes , Fernandes Jennifer M. , Ledesma Fernanda C. , Alves Venancio A F , Vailati Fernanda C. , Habr-Gama Angelita , Perez Rodrigo O. , Camargo Anamaria A. 
Published: May 2019

Abstract
Resistance to therapy is the major obstacle to a favorable outcome in cancer treatment. Neoadjuvant chemoradiotherapy (nCRT) can lead to complete tumor regression in a significant proportion of patients with rectal cancer (up to 40%). The possibility of avoiding radical surgery and its associated functional consequences for those who present complete response has become increasingly attractive, but approximately 60% of patients have only partial or no tumor remission after nCRT. In order to identify molecular mechanisms determining poor response to nCRT and to uncover optimized treatment strategies, we have conducted global gene expression analysis followed by pathway enrichment analysis in pretreatment biopsies from patients showing complete or poor clinical response to nCRT. We show that mitochondrial oxidative phosphorylation and phosphatidylinositol signaling pathways are consistently altered in rectal tumors comparatively. Both pathways have already been associated with resistance to radiation and chemotherapy in solid tumors and appear to converge on the activation of the Akt pathway in nonresponding tumors. To further address the role of Akt activation in response to nCRT, we evaluated by immunohistochemistry, Akt activation in an independent set of pretreatment biopsies from rectal cancer patients and observed not only high pAkt levels in those presenting poor response to nCRT but also that nuclear pAkt can also discriminate resistant tumors. We also evaluated the combination of an allosteric Akt-inhibitor MK2206 to chemoradiation in a radioresistant colorectal cancer cell line SW480 either in vitro and in vivo and observed an improvement of 50% of tumoricidal effect. Altogether, our results indicate that activation of the Akt pathway is a key event affecting response to nCRT and that combining chemoradiotherapy and Akt inhibitors such as MK2206 may significantly improve response rates to neoadjuvant therapy in rectal cancer.
Citation Format: Fernanda C. Koyama, Camila M. Lopes Ramos, Jennifer M. Fernandes, Fernanda C. Ledesma, Venancio A F Alves, Fernanda C. Vailati, Angelita Habr-Gama, Rodrigo O. Perez, Anamaria A. Camargo. Akt inhibitior MK2206 combination to neoadjuvant radiotherapy: Improving the rectal cancer treatment [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 A53.
Abstract A61: Identification of therapeutic proteins in venom gland of Ectatomma opaciventre for head and neck tumor therapy
Authors: Oliveira Ângela das Neves , Correia Lucas Ian Veloso , Arantes Lídia Maria Rebolho Batista , Carvalho Ana Carolina de , Messias Elisa Alves , Sorroche Bruna Pereira , Eguchi Flávia Coltri , Rodrigues Renata Santos , Melendez Matias Eliseo , Carvalho André Lopes 
Published: May 2019

Abstract
Background: Head and neck cancer is the sixth most common cancer site worldwide and is associated with low survival and high mortality rates, when diagnosed in advanced stages. The pursuit for potential therapeutic targets in natural resources may lead to the development of new antineoplastic agents. Several compounds coming from venomous animals are being tested in clinical trials due to their high selectivity and different physiologic activities. In this way, ant-venom glands are composed of bioactive molecules, such as peptides/proteins and allergens, which may be considered as potential therapeutic agents for oncology.
Objectives: The aim was to identify potential therapeutic proteins expressed in venomous glands of Ectatomma opaciventre ants, for the treatment of head and neck squamous cell carcinoma (HNSCC) tumors.
Materials and Methods: The mRNA library of Ectatomma opaciventre was sequenced using Illumina NextSeq 500 platform (76 bp unpaired-end) and NextSeq 500/550 Mid Output v2 kit (150 cycles). Libraries were constructed using TruSeq Stranded mRNA LT Sample Prep Kit (Illumina). A de novo assembly of the Ectatomma opaciventre transcriptome was performed using Velvet software.
Results: The RNA-seq of E. opaciventre venom gland generated 55,131,904 raw reads. The de novo Velvet assembly produced 23,254 contigs, which matched against 12,061 NCBI-Blastn transcripts. From these contigs, 437 full-length transcripts were identified, from which two potential therapeutic genes were selected: SPARC and Phospholipase B. Both SPARC and Phospholipase B genes have been previously described as having antitumor properties.
Conclusions: In conclusion, this deep transcriptome sequencing may have identified two potential therapeutic proteins, which are being analyzed in HNSCC cell lines.
Citation Format: Ângela das Neves Oliveira, Lucas Ian Veloso Correia, Lídia Maria Rebolho Batista Arantes, Ana Carolina de Carvalho, Elisa Alves Messias, Bruna Pereira Sorroche, Flávia Coltri Eguchi, Renata Santos Rodrigues, Matias Eliseo Melendez, André Lopes Carvalho. Identification of therapeutic proteins in venom gland of Ectatomma opaciventre for head and neck tumor therapy [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 A61.
Abstract A62: In vivo electroporation improves the immune responses induced by a DNA vaccine and confers complete antitumor protection against HPV-associated tumors
Authors: Sales Natiely Silva , Diniz Mariana de Oliveira , Silva Jamile Ramos , Silva Mariângela de Oliveira , Porchia Bruna F. M. M. , Aps Luana R. M. M. , Ferreira Luis Carlos Souza 
Published: May 2019

Abstract
Cervical cancer associated with persistent papilloma virus infections (HPV) is a public health problem and represents the third most frequent type of cancer in women. Our group developed a DNA vaccine against HPV-induced tumors based on the expression of the HPV-16 E7 oncoprotein genetically fused to the HSV-1 glycoprotein D (gD) (pgDE7h). This vaccine is capable of promoting antitumoral effects against tumor cells expressing HPV-16 E6 and E7 proteins (TC-1 cells) and induces specific cellular immune responses. In view of the low success rate of DNA vaccines in clinical trials, in vivo electroporation (EP) is a promising strategy for plasmid delivery, leading to increased cellular transfection and enhanced immune responses. In this study, C57BL/6 mice were inoculated with TC-1 cells subcutaneously and immunized 3 days later with pgDE7h intramuscularly, associated or not with EP. Immune responses were analyzed 14 days after vaccination and tumor growth was monitored for 60 days. Similar antitumor effects were obtained with 10-fold less DNA associated with EP when compared to the group that was inoculated only with DNA, reaching around 20% of tumor-free mice. Dose-response curves indicated that maximum protective immunity was achieved with 50 ug of vaccine inoculated with EP, promoting 100% of antitumor protection. This group also had enhanced frequencies of cytotoxic lymphocytes expressing the degranulation marker CD107a and high in vivo cytotoxic activities. Besides that, a delayed vaccination performed 10 days after the TC-1 injection led to 70% of tumor-free mice until the end of the observed period. Collectively, these data confirmed that EP can be used as an efficient method of DNA vaccine delivery and should be further studied to improve the chances of cancer vaccine success in clinical trials.
Citation Format: Natiely Silva Sales, Mariana de Oliveira Diniz, Jamile Ramos Silva, Mariângela de Oliveira Silva, Bruna F. M. M. Porchia, Luana R. M. M. Aps, Luis Carlos Souza Ferreira. In vivo electroporation improves the immune responses induced by a DNA vaccine and confers complete antitumor protection against HPV-associated 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 A62.
Abstract B17: Gene therapy and chemotherapy cooperate to inhibit prostate cancer progression in an animal model
Authors: Tamura Rodrigo Esaki , Strauss Bryan Eric 
Published: May 2019

Abstract
Patients with localized prostate carcinoma have a 5 year-survival rate of almost 100%; however, for patients with metastatic disease the rate is 31%, and mortality in 90% of these cases is the result of metastases. Clearly, there is a need for novel therapies and room for improving existing modalities. We propose that gene therapy and chemotherapy, when combined, may provide superior tumor cell killing. Our laboratory has developed a novel adenoviral vector expressing p53 under the control of a p53 responsive promoter; thus a positive feedback mechanism is established, providing high levels of p53, resulting in cell death of prostate cancer cells in vitro and in vivo. In previous assays, we have shown that our vector (AdRGDPGp53) is more effective than typical gene therapy approaches which employ a constitutive promoter (CMV) to control expression of p53. Here, we evaluate whether the union of gene therapy and chemotherapy applied to prostate cancer cell lines would promote a synergistic response in the induction of programmed cell death and reduction of tumor progression in an animal model. We combined AdRGDPGp53 along with the chemotherapy drugs used in the clinical treatment of prostate carcinoma, mitoxantrone, docetaxel, or cabazitaxel. Our results indicate that all drugs increase phosphorylation of p53, leading to improved induction of p53 targets. In vitro experiments indicate that AdRGDPGp53 sensitizes prostate cancer cells to each of the drugs tested, conferring increased levels of cell death. In a xenograft mouse model of in situ gene therapy, AdRGDPGp53 treatment, when combined with cabazitaxel, drastically reduced tumor progression and increased survival rates to 100%. Strikingly, we used a sub-therapeutic dose of cabazitaxel, thus avoiding leukopenia, yet still showed potent antitumor effects when combined with AdRGDPGp53 in this mouse model. The AdRGDPGp53 approach warrants further development for its application in gene therapy of prostate carcinoma.
Citation Format: Rodrigo Esaki Tamura, Bryan Eric Strauss. Gene therapy and chemotherapy cooperate to inhibit prostate cancer progression in an animal model [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 B17.
Abstract B24: Role of Dermcidin in growth and survival of melanoma tumor cells
Authors: Montoya Jennifer N. , Perez-Sosa Marcela N. , Sangiuliano Beatriz A. , Belizario Jose E. 
Published: May 2019

Abstract
Dermcidin (DCD) is a candidate oncogene localized at 12q13.1 which is normally expressed in the skin sweat gland and brain and overexpressed in various tumor cells. We have established the role of DCD in melanoma growth and survival by silencing DCD via shRNA expression in human melanoma G361 cell line. Biologic and biochemical assays showed that DCD gene knockdown decreased significantly melanoma cell growth in culture and tumor formation in NUDE mice. A DNA microarray-based study identified a total of 162 upregulated and 212 downregulated genes, in a G-361 control clone (pLKO) and clones expressing shRNA to DCD mRNA (IBC-I). We found, notably, genes involved in the nucleosome organization and signaling pathway to APRIL/BAFF receptor. Additionally, we examined DCD expression by immunohistochemistry in TMA (tissue microarray) of 101 patients and found that DCD-negative tumor had a 65.54% survival rate and DCD-positive tumor 43.33% survival rate in 5 years. We found an association with BRAF V600E and ERBB4 mutation in DCD-positive tumor with most frequent E43K mutation. Finally, we have screened clones resistant to Vemurafenib after long-term treatment in vitro and in xenografts in nude mice. Overall, these studies provide further support for DCD as oncogene to melanomas.
Financial support: FAPESP, CNPq and CAPES.
Citation Format: Jennifer N. Montoya, Marcela N. Perez-Sosa, Beatriz A. Sangiuliano, Jose E. Belizario. Role of Dermcidin in growth and survival of melanoma tumor 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 B24.
Abstract B48: Proteomic analysis of extracellular vesicles from resistant gastric cancer cell line
Authors: Cassinela Edson Kuatelela , Oliveira Grabriela Pintar , Landemberger Michele Christine , Martins Vilma Regina 
Published: May 2019

Abstract
Background: Gastric cancer is the fourth most common cause of cancer death worldwide and one of the tumors with higher mortality rates in Brazil. Chemotherapy is one of the major treatments for gastric cancer, but drug resistance limits the effectiveness, resulting in treatment failure. The mechanisms of gastric cancer pathogenesis are largely unknown, as is what causes limitations in the personalized treatment. Neoadjuvant therapy has been largely applied in these tumors because it can improve tumor resectability and survival of patients. However, tumors can develop resistance during chemotherapy, or this resistance can be present intrinsically before chemotherapy. Indeed, mechanisms associated to chemotherapy resistance in gastric cancer are complex and multifactorial; understanding the variety of these factors that are involved in chemoresistance is of great relevance.
Materials and Methods: Gastric adenocarcinoma cell line (AGS) was treated with increased concentration of 5-fluorouracil to generate a resistant cell (rAGS_FU). Extracellular vesicles (EVs) secreted from AGS and rAGS_FU cell lines were isolated by ultracentrifugation, quantified, and evaluated regarding their aggressiveness through invasion and colony assays. Proteomics analysis of EVs and secreting cells were performed to identify potential markers for chemotherapy resistance in gastric cancer cell lines.
Results: We found proteins involved in resistance to chemotherapy upregulated in EVs derived from resistant cells; parental cells treated with EVs derived from resistant cells were able to promote high colony formation and increased invasion potential. Thus, cells resistant to chemotherapy have a more aggressive phenotype and are able to transfer these acquired characteristics to the nonresistant ones using EVs. We compared the proteomes of EVs derived from the two cell lines and revealed important pathways that can be associated with chemoresistance in gastric cancers.
Conclusion: It is crucial to understand these chemoresistance mechanisms and develop efficient treatment strategies to overcome them. A deep investigation of these data is needed to understand and create new opportunities for the discovery of new biomarkers of response to chemotherapy in gastric cancers and contribute to the better understanding of the biologic role of molecules shuttled by EVs.
Citation Format: Edson Kuatelela Cassinela, Grabriela Pintar Oliveira, Michele Christine Landemberger, Vilma Regina Martins. Proteomic analysis of extracellular vesicles from resistant gastric cancer cell line [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 B48.
Abstract B62: Intratumoral genetic heterogeneity in rectal cancer and response to neoadjuvant chemoradiotherapy
Authors: Masotti Cibele , Bettoni Fabiana , Correa Bruna R. , Habr-Gama Angelita , Gama-Rodrigues Joaquim , Viana Maria , Vailati Bruna B. , Juliao Guilherme P. Sao , Fernandez Laura M. , Galante Pedro A. F. , Perez Rodrigo O. , Camargo Anamaria A. 
Published: May 2019

Abstract
Response to neoadjuvant chemoradiotherapy (nCRT) varies substantially among patients with locally advanced rectal cancer, but key determinants of treatment response are not fully understood. Intratumoral genetic heterogeneity (ITGH) is a common feature of solid tumors and has been proposed to drive disease progression and treatment response. Others and we have recently demonstrated that primary nontreated rectal tumors exhibit significant ITGH, but the effect of nCRT in shaping the clonal architecture of rectal cancer has not yet been addressed. In the present work, we further expanded the analysis of ITGH in rectal cancer by analyzing whole-exome sequencing (WES) and clinical data from 79 primary nontreated rectal cancers obtained from The Cancer Genome Atlas. We show that primary rectal tumors exhibit a remarkable variability in the degree of ITH. We also analyzed the effect of nCRT on ITGH and monitored tumor cell subpopulation dynamics after treatment through WES of paired tumor samples collected at diagnosis (pretreatment) and at surgery following nCRT (post-treatment) from seven patients. We show that treatment exposure does not introduce novel somatic mutations or significantly alter tissue genetic heterogeneity. Instead, nCRT acts as a potent selective pressure, shaping the mutational landscape of rectal tumors and allowing the selection and expansion of tumor cell subpopulations, which are more prone to resist nCRT. Our results shed light on the highly heterogeneous and dynamic mutational landscape of rectal tumors and indicate that ITGH may directly affect response to nCRT.
Citation Format: Cibele Masotti, Fabiana Bettoni, Bruna R. Correa, Angelita Habr-Gama, Joaquim Gama-Rodrigues, Maria Viana, Bruna B. Vailati, Guilherme P. Sao Juliao, Laura M. Fernandez, Pedro A. F. Galante, Rodrigo O. Perez, Anamaria A. Camargo. Intratumoral genetic heterogeneity in rectal cancer and response to neoadjuvant chemoradiotherapy [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 B62.
Abstract B64: The role of deubiquitinating enzyme USP17, hyaluronan synthase 2, and hyaluronan in non-small-cell lung cancer oncogenic transformation
Authors: Mehic Merima , Sá Vanessa Karen de , Hebestreit Sandra , Heldin Paraskevi , Heldin Carl Henrik 
Published: May 2019

Abstract
Introduction: Lung cancer is the result of a multistep accumulation of genetic and/or epigenetic alterations; therefore, a better understanding of the molecular mechanism by which these alterations affect lung cancer pathogenesis would provide new diagnostic procedures and prognostic factors for early detection of recurrence. The remarkable qualitative and quantitative modifications of extracellular matrix components as the deubiquitinating enzyme (USP17), hyaluronan (HA), and hyaluronan synthases 2 (HAS 2) may favor invasion, cellular motility, and proliferation in several cancers including lung.
Results: The silencing of USP17 led to decreased hyaluronan production, whereas the suppression of USP4 increased hyaluronan synthesis. Importantly, high levels of USP17 and HAS2 were detected in a panel of cancer cell lines compared to normal cells, and immunohistochemical stainings revealed higher expression of USP17 and HAS2 in tissues of lung cancer patients compared to normal tissue. Numerous epithelial cells expressed USP17 and HAS2 in dysplasia compared to squamous cell carcinoma (SqCC) (p=0.001). USP17 and HAS2 were prominently expressed in adenocarcinoma (ADC) (p≤0.005). HA immunostaining indexes were increased in ADC and SqCC compared to normal and dysplasia cells (p=0.05). Consistent with the immunohistochemical analyses, low amounts of hyaluronan and USP17 were observed in SqCC by confocal analysis, coincident with less colocalization as determined by confocal microscopy. In contrast, a high expression of hyaluronan (48% of positive index) and high USP17 expression (78% of positive index) in ADC was consistent with a higher degree of colocalization.
Conclusions: HAS2, hyaluronan and USP17 were expressed at higher levels in particular in preneoplastic lesions and ADC, suggesting a role in NSCLC oncogenic transformation, possibly by promoting cellular division by USP17-mediated. Elucidation of the mechanism of how USP17 and HAS2 cooperate in the regulation of the cell cycle might be of therapeutic importance.
Citation Format: Merima Mehic, Sr., Vanessa Karen de Sá, Sr., Sandra Hebestreit, Sr., Paraskevi Heldin, Sr., Carl Henrik Heldin, Sr.. The role of deubiquitinating enzyme USP17, hyaluronan synthase 2, and hyaluronan in non-small-cell lung cancer oncogenic transformation [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 B64.