bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B41: Transcriptome and proteome analyses of MCF7 cells with different expression profile of SPARC (secreted protein acidic in rich in cysteine) in the presence and absence of docetaxel
Authors: Pavanelli Ana Carolina , Barboza Luciana Pizzatti , Abdelhay Eliana Saul Furquim Werneck , Nagai Maria Aparecida 
Published: May 2019

Abstract
The SPARC (secreted protein, acidic, cysteine-rich) gene encodes a 32kDa protein that belongs to a family of matricellular proteins, which interact with cell-surface receptors, growth factors, and the ECM (extracellular matrix) components. SPARC plays a role in tissue remodeling, cell migration, angiogenesis, embryonic development, tumorigenesis, and chemosensitivity. Docetaxel is an effective chemotherapeutic drug for the treatment of advanced breast cancer. However, a considerable proportion of breast cancer patients do not respond positively to docetaxel. In a previous study, we identified SPARC as differentially expressed in mammary epithelial cells expressing different levels of HER-2. In the present study, we evaluate the effects of SPARC overexpression on the sensitivity of breast cancer cells to docetaxel. MCF7 cells were transfected with the expression vector pCMV6-SPARC or pCMV6-Neo. Real-time PCR, Western blot, and immunofluorescence were used to characterize the clones overexpressing SPARC. Using cDNA microarray and label-free approach for quantitative proteomic analysis, we evaluated the transcriptome and proteome changes in the comparison of the MCF7 cell control and overexpressing SPARC before and after docetaxel treatment. Several differentially expressed genes were identified as potentially involved in SPARC-mediated chemosensitivity to docetaxel. Among the molecular interaction networks from the differentially expressed proteins, extracellular matrix and cytoskeleton remodeling were the top pathway map observed in the comparison between MCF7 cells overexpressing SPARC and the control cells before docetaxel treatment. GTP metabolism pathway was the top pathway map observed in the comparison between MCF7 cells overexpressing SPARC and the control cells after docetaxel treatment. Transcriptome and proteome integrated data resulted in forty commonly up- and downregulated genes, with the WNT pathway represented among them. Our findings suggest that SPARC expression can influence docetaxel sensitivity in MCF7 cells by modulating genes involved in diverse biologic process that might be related to drug sensitivity. (Supported by Fapesp and CNPq.)
Citation Format: Ana Carolina Pavanelli, Luciana Pizzatti Barboza, Eliana Saul Furquim Werneck Abdelhay, Maria Aparecida Nagai. Transcriptome and proteome analyses of MCF7 cells with different expression profile of SPARC (secreted protein acidic in rich in cysteine) in the presence and absence of docetaxel [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 B41.
Abstract B59: Role of Dicer on human melanoma progression and resistance
Authors: Victo Nathalia Cruz de , Adjemian Sandy , Nunes Romulo dos Santos Sobreira , Volpini Rildo Aparecido , Giavina-Bianchi Mara Huffenbaecher , Neto Cyro Festa , Câmara Niels Olsen Saraiva , Amarante-Mendes Gustavo Pessini , Jacysyn Jacqueline de Fátima 
Published: May 2019

Abstract
Melanoma is a serious public health problem that affects the population of Latin America and is increasing rapidly compared to other types of tumors. The growth or change in this type of tumor is progressive and is in the horizontal and/or vertical direction. Breslow thickness (vertical staging) is the tumor thickness in the dermis where patients with lesion thickness less than 0.75 mm have good prognosis, unlike lesion thickness larger than 3 mm. This stage is classified into T (primary tumor): T0 (with no evidence of primary tumor); Tis (in situ melanoma); T1 (1 mm); T2 (1.01 to 2 mm); T3 (2.01 to 4 mm); and T4 (above 4 mm). Knowing some molecular markers of melanoma is essential for the identification of genetically predisposed individuals, as well as early detection of the disease. Recent works has demonstrated that microRNAs may be involved in modulation of melanoma. Dicer is an essential member of the RNase III family which controls maturation of miRNAs in the cytoplasm from microRNA precursors (pre-miRNAs). The upregulation of Dicer is associated with aggressive features and proliferation of melanoma and no other skin tumors such as carcinomas and sarcoma. In our present study, we found that the knockdown expression of Dicer using the CRISPR/CAS9 in melanoma cell line induced more chemosensitivity to cisplatin and these changes correlated with the downregulation of Dicer. We examined the consequence of Dicer knockdown on melanoma cell proliferation, clonogenic assays, and overall survival. We also compared Dicer in tissue from patients diagnosed with melanoma in different stages with the prognosis of these patients, suggesting that the reduction in Dicer expression is associated with melanoma progression. Considering the fundamental and multiple biologic roles of Dicer in various cellular processes, our results suggest that modulation of Dicer in melanoma should become a promising therapeutic candidate for further clinical application.
Note: This abstract was not presented at the conference.
Citation Format: Nathalia Cruz de Victo, Sandy Adjemian, Romulo dos Santos Sobreira Nunes, Rildo Aparecido Volpini, Mara Huffenbaecher Giavina-Bianchi, Cyro Festa Neto, Niels Olsen Saraiva Câmara, Gustavo Pessini Amarante-Mendes, Jacqueline de Fátima Jacysyn. Role of Dicer on human melanoma progression and resistance [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 B59.
Abstract B66: P53 expression and survivin subcellular localization contribute to the diagnosis and prognosis of patients with astrocytomas
Authors: Faccion Roberta Soares , Bernardo Paula Sabbo , Lopes Giselle Pinto de Faria , Bastos Leonardo Soares , Teixeira Cristina Lordello , Oliveira José Antonio de , Fernades Priscila Valverde , Dubois Luiz Gustavo , Chimelli Leila Maria , Maia Raquel Ciuvalschi 
Published: May 2019

Abstract
Astrocytomas are the most frequent subtype of primary central nervous system (CNS) tumors. Diffuse astrocytoma (grade II), anaplastic astrocytoma (grade III) and glioblastoma (GB–grade IV) are diffuse infiltrating astrocytomas derived from glial cells or precursors. Despite continuous efforts from the scientific community, these tumors still have a poor prognosis. Histologic grading is still challenging, and prognostic factors are still limited to age and tumor grade. Biomarkers that could improve histologic grading, especially that could help differentiate grade III from the other subtypes, and/or serve as prognostic factors are much needed. Furthermore, the relationship between survivin and p53 in astrocytoma progression and survival is still controversial. The present study aims to investigate the role of these proteins in the accuracy of histologic grading of diffuse astrocytic tumors and treatment response. One hundred thirty-five formalin-fixed, paraffin-embedded astrocytoma samples were obtained from patients. Tumor samples were reviewed and stained for survivin and p53 by immunohistochemistry, and the staining levels and survivin subcellular localization were correlated with histologic grading and patient outcomes. Age and histologic grade were the only clinical features that had a prognostic impact. High nuclear survivin and p53 correlated with grade III astrocytomas. High cytoplasmic survivin correlated with GB. Furthermore, patients whose tumors expressed high cytoplasmic survivin, high nuclear surviving, or high p53 and did not receive radiotherapy had worse short-term and long-term survival. Our results suggest that survivin subcellular localization and p53 expression improve the accuracy of histologic grading. Patients whose tumors overexpress these proteins benefit from radiotherapy regardless of age and histologic grade. Furthermore, patients whose tumors overexpress survivin may benefit from novel targeted antisurvivin treatment.
Citation Format: Roberta Soares Faccion*, Paula Sabbo Bernardo*, Giselle Pinto de Faria Lopes*, Leonardo Soares Bastos, Cristina Lordello Teixeira, José Antonio de Oliveira, Priscila Valverde Fernades, Luiz Gustavo Dubois, Leila Maria Chimelli, Raquel Ciuvalschi Maia. P53 expression and survivin subcellular localization contribute to the diagnosis and prognosis of patients with astrocytomas [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 B66.
Abstract B81: SUMO and ubiquitin post-transcriptional modifications regulate the stability of the IRF2BP2 transcriptional cofactor
Authors: Ramalho-Oliveira Renata , Rajão Matheus , Souza Vilenia , Viola João P. B. 
Published: May 2019

Abstract
IRF2BP2 (Interferon Regulatory Factor 2 Binding Protein 2) protein is a gene expression regulator, acting as transcriptional cofactor. IRF2BP2 acts in different cellular process including DNA damage repair, apoptosis, and immune response. Even though a few targets are known, there are several putative IRF2BP2-regulated genes. Novel evidence suggests that IRF2BP2 plays central functions in gene expression regulation. Recently, our group characterized the IRF2BP2 as an NFAT1 transcriptional repressor. To further understand the IRF2BP2 role in cellular functions, this work aims to clarify mechanisms involved in IRF2BP2 regulation. Initially, we performed a yeast two-hybrid screening to identify IRF2BP2-interacting proteins using IRF2BP2 as a bait. Among others, the UBE2I SUMO-conjugating enzyme and SUMO1 were identified as possible IRF2BP2 partners. Confocal microscopy demonstrated that these proteins colocalized in the nucleus. Furthermore, analysis by His-pull down and FRET confirmed the interaction between IRF2BP2 and UBE2I. Moreover, yeast two-hybrid assays showed that the interaction occurs independently of N-terminus C4-zinc finger of IRF2BP2. Subsequently, we observed that IRF2BP2 protein is SUMO1-modified in vivo. Our results indicated that three SUMO-1 molecules are added at three lysine residues. Finally, we demonstrated that the SUMO-modification favors disperse nuclear IRF2BP2 distribution and does not affect its repressor activity on NFAT1 transcription factor. Nevertheless, different assays showed that IRF2BP2 has a long half-life and that SUMO-1 conjugation increases IRF2BP2 protein stability. On the other hand, we showed that IRF2BP2 protein is also poliubiquitinated. Interestingly, the modifications observed were mainly Lys6- and Lys11-linked ubiquitin chains. Moreover, our data suggest that IRF2BP2 is not degraded by the proteasome and that Lys11-linked chain may constitute a signal for lysosome degradation. In conclusion, SUMO-modification upregulates IRF2BP2 protein stability. However, the consequences of Lys6 and Lys11 atypical ubiquitin chains linkage remain to be elucidated.
Citation Format: Renata Ramalho-Oliveira, Matheus Rajão, Vilenia Souza, João P. B. Viola. SUMO and ubiquitin post-transcriptional modifications regulate the stability of the IRF2BP2 transcriptional cofactor [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 B81.
Abstract IA04: Opportunities for translational and discovery research: Next-Gen genomics
Authors: Hahn William C. 
Published: May 2019

Abstract
Recent advances in genomics now make it possible to consider enumerating all of the genetic lesions in specific cancers. These approaches will yield critical information regarding the identification, number, and types of alterations found in human tumors and are increasingly being applied prospectively to patient samples in the clinic. We have deployed an enterprise level cancer genotyping test, PROFILE, for all cancer patients at the Brigham and Women's Hospital and the Dana-Farber Cancer Institute. This initial approach has already provided insight into how to integrate such efforts into clinical care. New technologies now also allow the interrogation of tumors from circulating nucleic acids. At the same time, complementary efforts to identify new targets and therapeutics are being used to increase the repertoire of agents to operationalize precision cancer medicine.
Citation Format: William C. Hahn. Opportunities for translational and discovery research: Next-Gen genomics [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 IA04.
Abstract IA07: ER stress responses as new immune checkpoints in cancer
Authors: Cubillos-Ruiz Juan R. 
Published: May 2019

Abstract
Harnessing the intrinsic ability of our immune system to eliminate malignant cells represents the most promising anticancer strategy since the development of chemotherapy. However, cancer cells employ diverse strategies that enable them to thrive under adverse conditions while simultaneously inhibiting antitumor immune responses. Diverse microenvironmental conditions within tumor masses, such as hypoxia and nutrient deprivation, disturb the protein-folding capacity of the endoplasmic reticulum (ER) and provoke a cellular state of “ER stress.” Sustained activation of ER stress sensors endows malignant cells with greater tumorigenic, metastatic, and drug-resistant capacity. Interestingly, recent studies demonstrate that tumor-infiltrating immune cells also experience ER stress, and that this process causes severe immune cell dysfunction and immunosuppression in cancer hosts. Aggressive ovarian cancers, for instance, cripple protective immunity by inducing excessive activation of the IRE1-XBP1 arm of the ER stress in tumor-associated dendritic cells. These recent findings uncover a new immunoregulatory role for ER stress in the tumor microenvironment and suggest that targeting aberrant ER stress responses may represent a new strategy to control tumor-induced immunosuppression and enhance the effectiveness of emerging immunotherapies.
Citation Format: Juan R. Cubillos-Ruiz. ER stress responses as new immune checkpoints in 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 IA07.
Abstract IA09: The dynamics of cancer cell heterogeneity
Authors: Lenz Guido , Onzi Giovana R. , Pereira Luiza C. , Breitenbach Karen , Lenz Luana s. , Leonardo Brunnet G. , Dalsin Eloisa 
Published: May 2019

Abstract
Cancer cells behave heterogeneously regarding proliferation and survival to therapy. This heterogeneity is not static, fluctuating over time with different frequencies and amplitudes. Here we set out to measure the dynamics of the proliferative and tolerant phenotype of untreated and glioma cell lines treated with temozolomide (TMZ) and/or cisplatin. For this, we followed single clones of glioma cells and measured the number of cells in each clone for three consecutive time points. The larger the clone, the more similar is their proliferation rate among clones of the same size, indicating that division shuffled the proliferation phenotypes of the cells. The response to TMZ or cisplatin is highly variable in small clones, but this response becomes more homogeneous with the increase in colony size, due to small heritability of the phenotype that controls the response to these drugs. The reduction in variance in relation to colony size is twice as high for the response to TMZ or cisplatin when compared to untreated colonies. Inhibition of HDAC prior to treatment freezes the variability of the response to TMZ, but not cisplatin, so that small and large colonies respond with the same variance. This indicates that the response to TMZ is phenocopied over generations of cells in the presence of HDAC inhibition, but rapidly fluctuates in its absence. With the aid of a computational model of the mother-daughter and sister-sister differences in proliferation and survival in the presence of the chemotherapeutic drugs, we described the dynamics of these phenotypes in response to TMZ, cisplatin, and their combination. We conclude that the proliferative and response to chemotherapeutic phenotypes fluctuate with time and can be stabilized with inhibition of HDACs, with important insights into drug combination to improve therapeutic potential.
Citation Format: Guido Lenz, Giovana R. Onzi, Luiza C. Pereira, Karen Breitenbach, Luana s. Lenz, Brunnet G. Leonardo, Eloisa Dalsin. The dynamics of cancer cell heterogeneity [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 IA09.
Abstract IA20: Targeting DNA repair in cancer therapy
Authors: D'Andrea Alan D. 
Published: May 2019

Abstract
Human cancer cells have genomic instability resulting from germline or acquired defects in DNA repair. One DNA repair pathway—the Fanconi anemia/BRCA pathway (D'Andrea A. N Engl J Med 2010;362:1909)—is defective in many human cancers, including breast, ovarian, and pancreatic neoplasms. Disruption of the FA/BRCA pathway results in the characteristic chromosome instability and radiation/crosslinker hypersensitivity of these tumors. In general, loss of one DNA repair pathway often leads to hyperdependence on another pathway for tumor cell survival. This hyperdependence offers a unique opportunity for the development of anticancer therapeutics. For instance, FA/BRCA pathway-deficient tumors are hyperdependent on base excision repair (BER) and, accordingly, these tumors are hypersensitive to single-agent treatment with PARP1 inhibitors, which block BER, or with ATM inhibitors. Our research program is focused on profiling the FA/BRCA pathway and the other five major DNA repair pathways in tumor cells (Kennedy RD, D'Andrea A. J Clin Oncol 2006;24:3799, 2006). Each DNA repair pathway has a characteristic biomarker and repairs a specific type of DNA lesion. By profiling these pathways in primary tumor samples with activation-specific antibodies to DNA repair proteins, we have been able (1) to predict the sensitivity of tumors to conventional chemotherapy and radiation; (2) to subset tumors for their sensitivity to novel classes of DNA repair inhibitors, (i.e., PARP1, Chk1, ATM, and proteasome inhibitors); and (3) to screen for new small-molecule inhibitors of other DNA repair pathways. This combination of novel DNA repair inhibitors, conventional DNA-damaging agents, and DNA repair biomarkers offers new opportunities for developing more effective anticancer therapy. In my presentation, I will also discuss novel approaches to sensitizing triple negative breast cancers (TNBCs) and ovarian tumors (OCs) to PARP1 inhibitors. We have previously shown that exposure of these tumors to either a CDK inhibitor or a proteasome inhibitor can block homologous recombination (HR) repair and thereby sensitize the tumor cells to PARP1 inhibitor. The CDK inhibitor/PARP1 inhibitor combination has been examined in orthotopic primary TNBC and OC xenograft models. Finally, we have identified an additional PARP1-dependent DNA repair mechanism in TNBCs and OCs. This pathway is driven by a novel alternative end-joining polymerase, POLθ. These tumors are hypersensitive to inhibitors of this new pathway, suggesting a new target for DNA repair therapies.
Citation Format: Alan D. D'Andrea. Targeting DNA repair in cancer 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 IA20.
Abstract IA24: Targeting DNA repair dysfunction in advanced prostate cancer
Authors: Knudsen Karen E. 
Published: May 2019

Abstract
Prostatic adenocarcinoma (PCa) is the 2nd leading cause of cancer death in US men. Organ-confined PCa can be effectively managed, but there is no durable treatment for advanced disease. Advanced PCa is treated through androgen deprivation therapy, often coupled with direct AR antagonists, as PCa is exquisitely dependent on androgen receptor (AR) activity for survival. Furthermore, recent studies identified AR as a major effector of DNA repair, manifest through the ability of the receptor to regulate DNAPK expression and activity. While AR-directed therapeutics effectively suppress the proproliferative, prosurvival, and pro-DNA repair functions of AR and result in tumor remission, relapse is common. Recurrent disease arises largely due to resurgent AR activity with 2-3 years, and there is no cure for this castration-resistant phase (CRPC, castration-resistant PCa). Thus, there is a significant need to develop new means for targeting recurrent AR activity or develop adjuvant therapies in advanced PCa.
Emerging data from our laboratory and others strongly support the concept that alterations in DNA damage repair (DDR) pathways are more common than previously thought in sporadic PCa, and that alterations in these pathways may accord new, more effective means of therapeutic intervention. New studies to be discussed will address underlying mechanisms of action with regard to the pathway, and identify clinically actionable ramifications of DNA repair dysfunction. Major concepts to be considered include new discoveries regarding PARP1 function and activity in lethal disease, and that a newly identified gene signature of PARP1-regulated networks is associated with poor outcome. Further, mechanistic investigation revealed new insight into the means by which PARP1 inhibitors likely function as single agents in advanced prostate cancer, manifest through both DNA repair and transcriptional regulatory functions. Other major concepts to be considered include the differential roles of DNAPK in controlling PCa progression. Findings to be discussed strongly support a model wherein selected DDR pathways can be developed as therapeutic targets to tailor treatment for prostate cancer and improve outcome for advanced disease.
Citation Format: Karen E. Knudsen. Targeting DNA repair dysfunction in advanced prostate 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 IA24.