bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B53: Sonic Hedgehog inhibition in glioblastoma potentializes temozolomide effect?
Authors: Honorato Jessica , Lopes Giselle Pinto de Faria , Basile Gabriela , Moura-Neto Vivaldo , Spohr Tania 
Published: May 2019

Abstract
Gliomas are malignant intracranial tumors and may occur in any region of central nervous system (CNS). Among them, glioblastoma (GBM) is the most aggressive and frequent brain tumors. In GBM treatment, the alkylating agent temozolomide (TMZ) is the first-line chemotherapy used; however, the patients' prognosis remains limited. During tumorigenesis, several signaling pathways vital for embryonic development are activated or inhibited, such as transforming growth factor beta (TGFbeta), Wingless (Wnt), and Sonic hedgehog (Shh). Currently, it is known that Shh pathway is involved in the chemoresistance of GBMs, and most of them have this pathway constitutive activated, which is one of the factors responsible to resistance to TMZ treatment. The limitation of using TMZ treatment can be solved by the identification of cell type with stem cell-like properties, the cancer stem cells (CSCs). To overcome this problem, some selective inhibitory drugs of Shh pathway have been developed, such as GANT-61. In this work, we investigated if Shh inhibition potentiates the effects of TMZ and verified the mechanisms involved in this process. To achieve our goals, GBM11 and T98G cell lines were treated with TMZ (100, 200, and 400 μM) and GANT-61 (20 μM) at different times of incubation. Our results suggest that both cell lines are resistant to TMZ, and the combination of GANT-61 with TMZ during 72 h reduced the cell viability of T98G lineage by MTT assay. Also, our results suggest that among the mechanisms involved in the cell viability reduction observed by combination of TMZ+GANT, cell death occurs due to DNA fragmentation and loss of membrane integrity, as well as formation of acidic vesicles that are indicative of autophagy and reactive oxygen species (ROS) production. In short, our results suggest that selective inhibition of the Shh pathway by GANT-61 is potentiating the effect of TMZ, being a promising strategy for GBMs treatment.
Citation Format: Jessica Honorato, Giselle Pinto de Faria Lopes, Gabriela Basile, Vivaldo Moura-Neto, Tania Spohr. Sonic Hedgehog inhibition in glioblastoma potentializes temozolomide effect? [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 B53.
Abstract B55: Targeting indoleamine 2,3 dioxygenase to improve the efficacy of a therapeutic vaccine against human papillomaviruses-associated tumors
Authors: Moreno Ana Carolina Ramos , Porchia Bruna F. M. M. , Souza Patrícia da Cruz , Pagni Roberta Liberato , Pegoraro Rafael , Ferreira Luís Carlos de Souza 
Published: May 2019

Abstract
The activity of the enzyme indoleamine 2,3 dioxygenase-1 (IDO) has been associated with the maintenance of the immunosuppressive microenvironment in many types of cancers. IDO catalyzes the degradation of tryptophan via the kynurenine pathway, which impacts on the effector activity of immune cells. The role of IDO in immune tolerance observed in human papillomaviruses-associated tumors is poor understood. Here, we targeted IDO to improve the efficacy of a therapeutic protein vaccine against HPV-16-associated tumors. The combination of IDO inhibitors with immunotherapy showed evidence that can support a new antitumor therapeutic approach. In the murine model C57BL/6, different biologic parameters were evaluated in order to determine the activation of the protective immunity obtained by the combined immunotherapy. We observed that isoforms of 1-methyl tryptophan, combined with our therapeutic vaccine, led to an activation of cytotoxic CD8 (+) T cells in mice grafted with tumor cells expressing the HPV-16 oncoproteins. In addition, the combination of melatonin enhanced the efficacy of the immunotherapeutic approach, resulting in the complete eradication of tumor masses. Altogether, our results indicate that blocking the immunosuppressive mechanisms mediated by IDO may improve the antitumor response induced by immunotherapies.
Citation Format: Ana Carolina Ramos Moreno, Bruna F. M. M. Porchia, Patrícia da Cruz Souza, Roberta Liberato Pagni, Rafael Pegoraro, Luís Carlos de Souza Ferreira. Targeting indoleamine 2,3 dioxygenase to improve the efficacy of a therapeutic vaccine against human papillomaviruses-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 B55.
Abstract B70: Identification of reference genes for normalizing gene expression for RT-qPCR analysis in established cervical cancer cell lines and their derived cancer stem like cells
Authors: Campos Rafael Paschoal de , Schultz Iago Carvalho , Mello Paola de Andrade , Davies Samuel , Gasparin Manuela Sangalli , Bertoni Ana Paula Santin , Azevedo Jéssica Gonçalves , Buffon Andréia , Wink Márcia Rosângela 
Published: May 2019

Abstract
Cervical cancer is the fourth most common cancer affecting women worldwide. Cancer stem cells are a subpopulation of tumor cells related to malignancy, resistance, and poor survival. Considering the importance of gene expression studies to understand cervical cancer stem cells (CCSC) biology and the need of proper validation of reference genes to normalize RT-qPCR data, this work identifies stable reference genes for the cervical cancer cell lines SiHa, HeLa, and ME180 as well as their respective derived cancer stem like cells. A literature review was performed to identify whether validation of reference genes was available for RT-qPCR assays in cervical cancer cell lines. Then cell lines were cultured in regular monolayer or in tumor sphere formation conditions. RT-PCR was carried out to validate cells grown as spheres as CCSC. RT-qPCR was performed using five commonly used reference genes: ACTB, B2M, GAPDH, HPRT1, and TBP. Stability was assessed through analysis of dispersion data and the Normfinder software to validate the selected genes as suitable reference genes. According to the literature review, no validation of reference genes for SiHa, HeLa, or ME180 cells in standard culture conditions or their CCSC subpopulations has been done so far. Our evaluation validated B2M, GAPDH, HPRT1, and TBP in these set conditions. Among them, GAPDH presented the lowest stability value (0.222), being therefore the most adequate gene to normalize the combination of all samples. Moreover, associating GAPDH and TBP led to a more stable value (0.184). These results suggest that B2M, GAPDH, HPRT1, and TBP are suitable reference genes to normalize RT-qPCR data of established cervical cancer cell lines SiHa, HeLa, and ME180 as well as their derived cancer stem like cells. Furthermore, GAPDH seems to be the most convenient choice for studying the combination of these cells.
Citation Format: Rafael Paschoal de Campos, Iago Carvalho Schultz, Paola de Andrade Mello, Samuel Davies, Manuela Sangalli Gasparin, Ana Paula Santin Bertoni, Jéssica Gonçalves Azevedo, Andréia Buffon, Márcia Rosângela Wink. Identification of reference genes for normalizing gene expression for RT-qPCR analysis in established cervical cancer cell lines and their derived cancer 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 B70.
Abstract B71: Stochastic model of contact inhibition and the proliferation of melanoma in situ
Authors: Morais Mauro Cesar C. , Stuhl Izabella , Sabino Alan U. , Lautenschlager Willian W. , Queiroga Alexandre S. , Tortelli Tharcisio C. , Chammas Roger , Suhov Yuri , Ramos Alexandre F. 
Published: May 2019

Abstract
Contact inhibition of proliferation can be described as the decrease of proliferation rates when the cell density increases. Its loss is a key feature of tumor development. Cell density of human metastatic melanoma cell line (SK-MEL-147) and immortalized keratinocyte cells (HaCaT) was evaluated daily in culture experiments. Keratinocytes reach lower cell density than melanoma cells at confluence, indicating that the population growth arrest is associated with contact inhibition (KHaCaT = 1779.6 ± 130.5 cells/mm2; KSK-MEL-147 = 5043.5 ± 316.5 cells/mm2). We performed a coculture experiment to assess the proliferation restriction between both cell lines. After 8 days a spatial pattern was detected, characterized by the formation of clusters of melanoma cells surrounded by keratinocytes constraining their proliferation. Despite showing approximately the same proliferation rates when data were fitted with a logistic model (ρHaCaT = 1.1 ± 0.1 days-1; ρSK-MEL-147 = 1.1 ± 0.3 days-1), the proportion of melanoma cells within the total population has increased from 1:10 to 1:4 approximately. To explain our results we propose a spatial stochastic model where we consider cell proliferation, death, migration, and cell-to-cell interaction through contact inhibition. The agreement between experimental results and numerical simulation indicates that loss of contact inhibition is important for the analysis of the development of melanoma in situ, and explains the increase in the proportion of tumor cells and generation of spatial patterns established in conducted experiments. In addition, the distribution of the distances between cells of the same line indicates the higher proximity of melanoma cells and allowed us to identify their clustering pattern. This work provides results of a quantitative study of the impact of contact inhibition upon formation and growth of tumor-like melanoma cell clusters in a coculture with keratinocytes.
Citation Format: Mauro Cesar C. Morais, Izabella Stuhl, Alan U. Sabino, Willian W. Lautenschlager, Alexandre S. Queiroga, Tharcisio C. Tortelli, Jr., Roger Chammas, Yuri Suhov, Alexandre F. Ramos. Stochastic model of contact inhibition and the proliferation of melanoma in situ [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 B71.
Abstract IA17: Liquid biopsies: Concepts and applications
Authors: Camargo Anamaria A. 
Published: May 2019

Abstract
The presence of cell-free DNA (cfDNA) in human blood was first described in 1948 by Mandel and Métais, but mutated KRAS DNA sequences derived from tumor cells were first reported in the plasma of patients with pancreatic cancer almost 50 years later. Since then, our ability to analyze cfDNA has significantly improved with the development of molecular technologies, such as digital PCR and next-generation sequencing, which enable the detection of circulating tumor DNA molecules (ctDNA) with high specificity and sensitivity. ctDNA is shed into the bloodstream by cells undergoing apoptosis or necrosis and genomic profiles of ctDNA have been shown to closely match those of the corresponding tumors. Recent studies have demonstrated the translational potential of ctDNA detection—commonly referred to as liquid biopsies—for diagnosis and prognosis, for treatment decision, and for monitoring residual disease, treatment response, and disease progression. This is an opportune time to discuss how liquid biopsies can be exploited to guide cancer patient care and ultimately be integrated into clinical practice.
Citation Format: Anamaria A. Camargo. Liquid biopsies: Concepts and applications [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 IA17.
Abstract IA18: Cancer evolution as a therapeutic target
Authors: Bardelli Alberto 
Published: May 2019

Abstract
When metastatic cancers are challenged with targeted agents, almost invariably a subset of cells insensitive to the drug emerges. As a result, in most instances, targeted therapies are only transiently effective in patients. Strategies to prevent or overcome resistance are therefore essential to design the next generation of clinical trials. How can we overcome the near-certainty of disease recurrence following treatment with targeted agents? Addressing this question means considering as a target not only individual oncogenes but also the evolving nature of human tumors.
We used colorectal cancer (CRC) as a model system to test the hypothesis that by understanding tumor's evolution, the emergence of drug resistance can be controlled. We find that clonal dynamics can be monitored in real time in the blood of patients, and liquid biopsies can be used to intercept the emergence of resistant clones before relapses are clinically manifest. We discovered that a multistep clonal evolution process driven by progressive increases in drug fitness underlies the development of resistance in cells and patient avatars.
To have long-term efficacy, the use of targeted therapies must take into account the continuous evolution of cancer cells, that is to say, therapies must adapt to tumor evolution. One possibility is to anticipate the changes the tumors will make. For example, by knowing in advance how CRC cells overcome resistance to EGFR blockade, we devised further rounds of therapy. Another approach is to unleash the ability of the immune system to recognize drug-resistant cells. We tested this possibility in syngeneic mouse models of CRC sensitive to targeted therapies. Our findings indicate that manipulation of the mutational loads can trigger prolonged therapeutic responses that are not observed when cancer cells are challenged with targeted drugs alone. We postulate that rationally combined targeted and immunotherapies can restrain tumor evolution and can limit the emergence of drug resistance, thus leading to long-term responses.
Citation Format: Alberto Bardelli. Cancer evolution as a therapeutic target [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 IA18.
Abstract A12: Vicoryx: A phase I/IIa clinical trial using a p16INK4a derived peptide as vaccine in patients with advanced human papillomavirus-associated cancer
Authors: Reuschenbach Miriam , Karbach Julia , Faulstich Franziska , Sauer Madeleine , Kloor Matthias , Rafiyan Mohammad-Reza , Pauligk Claudia , AlBatran Salah , Jaeger Elke , Doeberitz Magnus von Knebel 
Published: May 2019

Abstract
Objectives: The tumor suppressor p16INK4a is strongly overexpressed in HPV-associated neoplasia, whereas in normal tissues barely any p16INK4a expression is detectable. Targeting this HPV type-independent antigen by vaccination could represent an interesting complementary therapeutic approach to recently developed HPV-E6/E7-based therapeutic or secondary preventive vaccines. We performed a phase I/IIa peptide vaccination trial to monitor toxicity and immunogenicity of p16INK4a vaccination in patients with advanced HPV-associated cancers.
Patients and Methods: 21 patients with p16INK4a-overexpressing, HPV DNA-positive advanced cancers (16 cervical, 5 head and neck) were included. The protocol comprised 12 applications of a synthetic 27mer p16INK4a peptide mixed with Montanide® ISA-51 VG over a six months period. Objectives of the study were clinical safety and changes of humoral and cellular immune responses against the p16INK4a peptide. T cell responses were monitored by interferon-gamma ELISpot and antibodies by ELISA.
Conclusions: No vaccine-related toxicity was observed in any of the patients. One patient (head and neck cancer) completed the entire study protocol with stable disease for now 18 months after the last vaccination.11 patients had progressing disease and were excluded from the study after 4 to 12 weeks. 9 patients continue to be vaccinated. While at baseline only one patient had pre-existing T cell responses (CD4) against the p16INK4a peptide, p16INK4a-reactive T cells (CD4) were successfully induced in at least four patients after 4 to 12 vaccine doses. None of the patients had pre-existing p16INK4a antibodies, but 3 patients developed increasing p16INK4a peptide-specific antibody titers after the 5th dose.
This is the first study demonstrating that p16INK4a peptide vaccination is safe and well tolerated. The results show that spontaneous immune responses against p16INK4a are rare, but can be induced by p16INK4a peptide vaccination. Further studies are needed to assess clinical efficacy of the approach. Please refer to the protocol of this trial under http://clinicaltrials.gov/show/NCT01462838.
Citation Format: Miriam Reuschenbach, Julia Karbach, Franziska Faulstich, Madeleine Sauer, Matthias Kloor, Mohammad-Reza Rafiyan, Claudia Pauligk, Salah AlBatran, Elke Jaeger, Magnus von Knebel Doeberitz. Vicoryx: A phase I/IIa clinical trial using a p16INK4a derived peptide as vaccine in patients with advanced human papillomavirus-associated cancer. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A12.
Abstract A23: Metformin as a potent antiangiogenic factor: From diabetes to cancer angioprevention
Authors: Dallaglio Katiuscia , Bruno Antonino , Cantelmo Anna Rita , Pfeffer Ulrich , Bertolini Francesco , Noonan Douglas M. , Albini Adriana 
Published: May 2019

Abstract
Metformin, an anti-diabetic drug commonly used for type 2 diabetes therapy, is associated with a decreased risk for certain cancer. Due to extensive reports of its in vitro and in vivo anti-tumor activity, we and others have focused on the anti-angiogenic potential as a possible mechanism through which metformin could affect tumor progression, and to propose its use as an angiopreventive drug. Metformin was able to interfere with endothelial cell proliferation, apoptosis and invasion in vitro. Gene arrays analyses were performed to verify the effect of metformin on endothelial gene expression profiles and the matrigel sponge assay to test its effect in vivo.
We show that metformin inhibited endothelial cell proliferation by effecting cell cycle regulation rather than inducing apoptosis. In vitro, metformin reduces endothelial cell invasion and represses their ability to organize into capillary-like networks. These effects are partially reverted by compound C, a specific inhibitor of AMPK, confirming that metformin could interfere with angiogenesis responses by activating AMPK signaling. Gene expression profiles of endothelial cells treated with metformin showed down-regulation of several angiogenesis-related genes but up-regulation of chemokine pathways. In vivo, metformin inhibited angiogenesis induced by VEGF. Considering the strict correlation between type II diabetes and obesity, we evaluated the ability of Metformin to modulate endothelial precursor cells in an obese murine model and we reported that Metformin decreases the number of adipose tissue progenitor endothelial cells in vivo only in obese mice.
These data suggest that metformin has anti-angiogenic effect associated with down-regulation of specific molecule although it also induces some inflammatory mediators, and that it may be most effective in the context of obesity.
Citation Format: Katiuscia Dallaglio, Antonino Bruno, Anna Rita Cantelmo, Ulrich Pfeffer, Francesco Bertolini, Douglas M. Noonan, Adriana Albini. Metformin as a potent antiangiogenic factor: From diabetes to cancer angioprevention. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A23.
Abstract A51: The heritability of colorectal cancer in the Nordic Twin Study of Cancer (NorTwinCan)
Authors: Graff Rebecca E. , Skytthe Axel , Adami Hans-Olov , Czene Kamila , Harris Jennifer R. , Kaprio Jaakko , Giovannucci Edward , Mucci Lorelei A. , Hjelmborg Jacob B. 
Published: May 2019

Abstract
Background: Family history is a strong risk factor for colorectal cancer, but the extent to which familial risk can be attributed to heritability versus shared environment remains obscure. Whether familial risk is distinct for colon versus rectal cancer also remains unclear and is important to examine given accumulating evidence that their etiologies are distinct.
Methods: We estimated the concordance and heritability of colorectal, colon and rectal cancer using information from 40,634 monozygotic and 111,897 dizygotic twin pairs from the Nordic Twin Study of Cancer. Time-to-event analyses accounted for left-censoring due to variable initiation of cancer registration and right-censoring resulting from end of follow-up or competing risk of death.
Results: From earliest cancer registration in 1943 through 2009, 2,286 twins were diagnosed with colon cancer and 1,493 were diagnosed with rectal cancer. The cumulative risk of colorectal cancer overall was 4.5%, while the cumulative risk for twins whose co-twins had colorectal cancer was 15.7% for monozygotic and 11.0% for dizygotic twins. The heritability of colon cancer was 16.2% (95% CI: 2.3%-61.8%), with shared environment accounting for 14.2% (95% CI: 2.7%-49.1%) of the variation in disease liability. For rectal cancer, a model including only environmental effects best fit the data; heritability was not statistically important. Shared environment accounted for 16.6% (95% CI: 8.8%-28.8%) of the variation in liability.
Conclusions: These results suggest a greater genetic contribution to the risk of colon cancer than the risk of rectal cancer. The contribution of shared environment to both cancers may be larger than previously thought.
Citation Format: Rebecca E. Graff, Axel Skytthe, Hans-Olov Adami, Kamila Czene, Jennifer R. Harris, Jaakko Kaprio, Edward Giovannucci, Lorelei A. Mucci, Jacob B. Hjelmborg. The heritability of colorectal cancer in the Nordic Twin Study of Cancer (NorTwinCan). [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A51.