SUELI MIEKO OBA SHINJO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Neurologia, Faculdade de Medicina
LIM/15 - Laboratório de Investigação em Neurologia, Hospital das Clínicas, Faculdade de Medicina
LIM/15 - Laboratório de Investigação em Neurologia, Hospital das Clínicas, Faculdade de Medicina
3 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.
- 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.
- 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.