SUELY KAZUE NAGAHASHI MARIE
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Neurologia, Faculdade de Medicina - Docente
LIM/15 - Laboratório de Investigação em Neurologia, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/15 - Laboratório de Investigação em Neurologia, Hospital das Clínicas, Faculdade de Medicina - Líder
8 resultados
Resultados de Busca
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- Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies(2014) BETTEGOWDA, Chetan; SAUSEN, Mark; LEARY, Rebecca J.; KINDE, Isaac; WANG, Yuxuan; AGRAWAL, Nishant; BARTLETT, Bjarne R.; WANG, Hao; LUBER, Brandon; ALANI, Rhoda M.; ANTONARAKIS, Emmanuel S.; AZAD, Nilofer S.; BARDELLI, Alberto; BREM, Henry; CAMERON, John L.; LEE, Clarence C.; FECHER, Leslie A.; GALLIA, Gary L.; GIBBS, Peter; LE, Dung; GIUNTOLI, Robert L.; GOGGINS, Michael; HOGARTY, Michael D.; HOLDHOFF, Matthias; HONG, Seung-Mo; JIAO, Yuchen; JUHL, Hartmut H.; KIM, Jenny J.; SIRAVEGNA, Giulia; LAHERU, Daniel A.; LAURICELLA, Calogero; LIM, Michael; LIPSON, Evan J.; MARIE, Suely Kazue Nagahashi; NETTO, George J.; OLINER, Kelly S.; OLIVI, Alessandro; OLSSON, Louise; RIGGINS, Gregory J.; SARTORE-BIANCHI, Andrea; SCHMIDT, Kerstin; SHIH, Ie-Ming; OBA-SHINJO, Sueli Mieko; SIENA, Salvatore; THEODORESCU, Dan; TIE, Jeanne; HARKINS, Timothy T.; VERONESE, Silvio; WANG, Tian-Li; WEINGART, Jon D.; WOLFGANG, Christopher L.; WOOD, Laura D.; XING, Dongmei; HRUBAN, Ralph H.; WU, Jian; ALLEN, Peter J.; SCHMIDT, C. Max; CHOTI, Michael A.; VELCULESCU, Victor E.; KINZLER, Kenneth W.; VOGELSTEIN, Bert; PAPADOPOULOS, Nickolas; DIAZ JR., Luis A.The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in > 75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.
- Adult Neurogenesis and Glial Oncogenesis: When the Process Fails(2014) BATISTA, Chary Marquez; MARIANO, Eric Domingos; BARBOSA, Breno Jose Alencar Pires; MORGALLA, Matthias; MARIE, Suely Kazue Nagahashi; TEIXEIRA, Manoel Jacobsen; LEPSKI, GuilhermeMalignant brain tumors, including glioblastoma multiforme (GBM), are known for their high degree of invasiveness, aggressiveness, and lethality. These tumors are made up of heterogeneous cell populations and only a small part of these cells (known as cancer stem cells) is responsible for the initiation and recurrence of the tumor. The biology of cancer stem cells and their role in brain tumor growth and therapeutic resistance has been extensively investigated. Recent work suggests that glial tumors arise from neural stem cells that undergo a defective process of differentiation. The understanding of this process might permit the development of novel treatment strategies targeting cancer stem cells. In the present review, we address the mechanisms underlying glial tumor formation, paying special attention to cancer stem cells and the role of the microenvironment in preserving them and promoting tumor growth. Recent advancements in cancer stem cell biology, especially regarding tumor initiation and resistance to chemo-or radiotherapy, have led to the development of novel treatment strategies that focus on the niche of the stem cells that make up the tumor. Encouraging results from preclinical studies predict that these findings will be translated into the clinical field in the near future.
- Uncovering the Role of N-Acetyl-Aspartyl-Glutamate as a Glutamate Reservoir in Cancer(2019) Tu Nguyen; KIRSCH, Brian James; ASAKA, Ryoichi; NABI, Karim; QUINONES, Addison; TAN, Jessica; ANTONIO, Marjorie Justine; CAMELO, Felipe; LI, Ting; NGUYEN, Stephanie; Giang Hoang; Kiet Nguyen; UDUPA, Sunag; SAZEIDES, Christos; SHEN, Yao-An; ELGOGARY, Amira; REYES, Juvenal; ZHAO, Liang; KLEENSANG, Andre; CHAICHANA, Kaisorn Lee; HARTUNG, Thomas; BETENBAUGH, Michael J.; MARIE, Suely K.; JUNG, Jin G.; WANG, Tian-Li; GABRIELSON, Edward; LE, AnneN-acetyl-aspartyl-glutamate (NAAG) is a peptide-based neurotransmitter that has been extensively studied in many neurological diseases. In this study, we show a specific role of NAAG in cancer. We found that NAAG is more abundant in higher grade cancers and is a source of glutamate in cancers expressing glutamate carboxypeptidase II (GCPII), the enzyme that hydrolyzes NAAG to glutamate and N-acetylaspartate (NAA). Knocking down GCPII expression through genetic alteration or pharmacological inhibition of GCPII results in a reduction of both glutamate concentrations and cancer growth. Moreover, targeting GCPII in combination with glutaminase inhibition accentuates these effects. These findings suggest thatNAAGserves as an important reservoir to provide glutamate to cancer cells through GCPII when glutamate production from other sources is limited. Thus, GCPII is a viable target for cancer therapy, either alone or in combination with glutaminase inhibition.
- Current perspectives in stem cell therapy for spinal cord repair in humans: a review of work from the past 10 years(2014) MARIANO, Eric Domingos; BATISTA, Chary Marquez; BARBOSA, Breno Jose Alencar Pires; MARIE, Suely Kazue Nagahashi; TEIXEIRA, Manoel Jacobsen; MORGALLA, Matthias; TATAGIBA, Marcos; LI, Jun; LEPSKI, GuilhermeSpinal cord injury (SCI) and amyotrophic laterals sclerosis (ALS) are devastating neurological conditions that affect individuals worldwide, significantly reducing quality of life, both for patients and their relatives. Objective: The present review aims to summarize the multiple restorative approaches being developed for spinal cord repair, the use of different stem cell types and the current knowledge regarding stem cell therapy. Method: Review of the literature from the past 10 years of human studies using stem cell transplantation as the main therapy, with or without adjuvant therapies. Conclusion: The current review offers an overview of the state of the art regarding spinal cord restoration, and serves as a starting point for future studies.
- Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis(2016) RAMASWAMY, Vijay; HIELSCHER, Thomas; MACK, Stephen C.; LASSALETTA, Alvaro; LIN, Tong; PAJTLER, Kristian W.; JONES, David T. W.; LUU, Betty; CAVALLI, Florence M. G.; ALDAPE, Kenneth; REMKE, Marc; MYNAREK, Martin; RUTKOWSKI, Stefan; GURURANGAN, Sridharan; MCLENDON, Roger E.; LIPP, Eric S.; DUNHAM, Christopher; HUKIN, Juliette; EISENSTAT, David D.; FULTON, Dorcas; LANDEGHEM, Frank K. H. van; SANTI, Mariarita; VEELEN, Marie-Lise C. van; MEIR, Erwin G. Van; OSUKA, Satoru; FAN, Xing; MURASZKO, Karin M.; TIRAPELLI, Daniela P. C.; OBA-SHINJO, Sueli M.; MARIE, Suely K. N.; CARLOTTI, Carlos G.; LEE, Ji Yeoun; RAO, Amulya A. Nageswara; GIANNINI, Caterina; FARIA, Claudia C.; NUNES, Sofia; MORA, Jaume; HAMILTON, Ronald L.; HAUSER, Peter; JABADO, Nada; PETRECCA, Kevin; JUNG, Shin; MASSIMI, Luca; ZOLLO, Massimo; CINALLI, Giuseppe; BOGNAR, Laszlo; KLEKNER, Almos; HORTOBAGYI, Tibor; LEARY, Sarah; ERMOIAN, Ralph P.; OLSON, James M.; LEONARD, Jeffrey R.; GARDNER, Corrine; GRAJKOWSKA, Wieslawa A.; CHAMBLESS, Lola B.; CAIN, Jason; EBERHART, Charles G.; AHSAN, Sama; MASSIMINO, Maura; GIANGASPERO, Felice; BUTTARELLI, Francesca R.; PACKER, Roger J.; EMERY, Lyndsey; YONG, William H.; SOTO, Horacio; LIAU, Linda M.; EVERSON, Richard; GROSSBACH, Andrew; SHALABY, Tarek; GROTZER, Michael; KARAJANNIS, Matthias A.; ZAGZAG, David; WHEELER, Helen; HOFF, Katja von; ALONSO, Marta M.; TUON, Teresa; SCHUELLER, Ulrich; ZITTERBART, Karel; STERBA, Jaroslav; CHAN, Jennifer A.; GUZMAN, Miguel; ELBABAA, Samer K.; COLMAN, Howard; DHALL, Girish; FISHER, Paul G.; FOULADI, Maryam; GAJJAR, Amar; GOLDMAN, Stewart; HWANG, Eugene; KOOL, Marcel; LADHA, Harshad; VERA-BOLANOS, Elizabeth; WANI, Khalida; LIEBERMAN, Frank; MIKKELSEN, Tom; OMURO, Antonio M.; POLLACK, Ian F.; PRADOS, Michael; ROBINS, H. Ian; SOFFIETTI, Riccardo; WU, Jing; METELLUS, Phillipe; TABORI, Uri; BARTELS, Ute; BOUFFET, Eric; HAWKINS, Cynthia E.; RUTKA, James T.; DIRKS, Peter; PFISTER, Stefan M.; MERCHANT, Thomas E.; GILBERT, Mark R.; ARMSTRONG, Terri S.; KORSHUNOV, Andrey; ELLISON, David W.; TAYLOR, Michael D.PurposePosterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known.MethodsFour independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses.ResultsMolecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation.ConclusionThe most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence.
- Intraoperative assistive technologies and extent of resection in glioma surgery: a systematic review of prospective controlled studies(2015) BARBOSA, Breno Jose Alencar Pires; MARIANO, Eric Domingos; BATISTA, Chary Marquez; MARIE, Suely Kazue Nagahashi; TEIXEIRA, Manoel Jacobsen; PEREIRA, Carlos Umberto; TATAGIBA, Marcos Soares; LEPSKI, Guilherme AlvesSeveral studies published to date about glioma surgery have addressed the validity of using novel technologies for intraoperative guidance and potentially improved outcomes. However, most of these reports are limited by questionable methods and/or by their retrospective nature. In this work, we performed a systematic review of the literature to address the impact of intraoperative assistive technologies on the extent of resection (EOR) in glioma surgery, compared to conventional unaided surgery. We were also interested in two secondary outcome variables: functional status and progression-free survival. We primarily used PubMed to search for relevant articles. Studies were deemed eligible for our analysis if they (1) were prospective controlled studies; (2) used EOR as their primary target outcome, assessed by MRI volumetric analysis; and (3) had a homogeneous study population with clear inclusion criteria. Out of 493 publications identified in our initial search, only six matched all selection criteria for qualitative synthesis. Currently, the evidence points to 5-ALA, DTI functional neuronavigation, neurophysiological monitoring, and intraoperative MRI as the best tools for improving EOR in glioma surgery. Our sample and conclusions were limited by the fact that studies varied in terms of population characteristics and in their use of different volumetric analyses. We were also limited by the low number of prospective controlled trials available in the literature. Additional evidence-based high-quality studies assessing cost-effectiveness should be conducted to better determine the benefits of intraoperative assistive technologies in glioma surgery.
- A simplified approach using Taqman low-density array for medulloblastoma subgrouping(2019) CRUZEIRO, Gustavo Alencastro Veiga; SALOMAO, Karina Bezerra; BIAGI JR., Carlos Alberto Oliveira de; BAUMGARTNER, Martin; STURM, Dominik; LIRA, Regia Caroline Peixoto; MAGALHAES, Taciani de Almeida; MILAN, Mirella Baroni; SILVEIRA, Vanessa da Silva; SAGGIORO, Fabiano Pinto; OLIVEIRA, Ricardo Santos de; KLINGER, Paulo Henrique dos Santos; SEIDINGER, Ana Luiza; YUNES, Jose Andres; QUEIROZ, Rosane Gomes de Paula; OBA-SHINJO, Sueli Mieko; SCRIDELI, Carlos Alberto; NAGAHASHI, Suely Marie Kazue; TONE, Luiz Gonzaga; VALERA, Elvis TerciNext-generation sequencing platforms are routinely used for molecular assignment due to their high impact for risk stratification and prognosis in medulloblastomas. Yet, low and middle-income countries still lack an accurate cost-effective platform to perform this allocation. TaqMan Low Density array (TLDA) assay was performed using a set of 20 genes in 92 medulloblastoma samples. The same methodology was assessed in silico using microarray data for 763 medulloblastoma samples from the GSE85217 study, which performed MB classification by a robust integrative method (Transcriptional, Methylation and cytogenetic profile). Furthermore, we validated in 11 MBs samples our proposed method by Methylation Array 450K to assess methylation profile along with 390MB samples (GSE109381) and copy number variations. TLDA with only 20 genes accurately assigned MB samples into WNT, SHH, Group 3 and Group 4 using Pearson distance with the average-linkage algorithm and showed concordance with molecular assignment provided by Methylation Array 450k. Similarly, we tested this simplified set of gene signatures in 763MB samples and wewere able to recapitulate molecular assignment with an accuracy of 99.1% (SHH), 94.29% (WNT), 92.36% (Group 3) and 95.40% (Group 4), against 97.31, 97.14, 88.89 and 97.24% (respectively) with the Ward.D2 algorithm. t-SNE analysis revealed a high level of concordance (k=4) with minor overlapping features between Group 3 and Group 4. Finally, we condensed the number of genes to 6 without significantly losing accuracy in classifying samples into SHH, WNT and non-SHH/non-WNT subgroups. Additionally, we found a relatively high frequency of WNT subgroup in our cohort, which requires further epidemiological studies. TLDA is a rapid, simple and cost-effective assay for classifying MB in low/middle income countries. A simplified method using six genes and restricting the final stratification into SHH, WNT and non-SHH/non-WNT appears to be a very interesting approach for rapid clinical decision-making.
- Stem cells in neurology - current perspectives(2014) BATISTA, Chary Ely Marquez; MARIANO, Eric Domingos; MARIE, Suely Kazue Nagahashi; TEIXEIRA, Manoel Jacobsen; MORGALLA, Matthias; TATAGIBA, Marcos; LI, Jun; LEPSKI, GuilhermeCentral nervous system (CNS) restoration is an important clinical challenge and stem cell transplantation has been considered a promising therapeutic option for many neurological diseases. Objective: The present review aims to briefly describe stem cell biology, as well as to outline the clinical application of stem cells in the treatment of diseases of the CNS. Method: Literature review of animal and human clinical experimental trials, using the following key words: ""stem cell"", neurogenesis"", ""Parkinson"", ""Huntington"", ""amyotrophic lateral sclerosis"", ""traumatic brain injury"", ""spinal cord injury"", ""ischemic stroke"", and ""demyelinating diseases"". Conclusion: Major recent advances in stem cell research have brought us several steps closer to their effective clinical application, which aims to develop efficient ways of regenerating the damaged CNS.