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1.
Medicine (Baltimore) ; 100(4): e20426, 2021 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-33530151

RESUMEN

ABSTRACT: The present study aimed to investigate the association of A-kinase interacting protein 1 (AKIP1) with clinical characteristics, and further explore the prognostic value of AKIP1 in glioma patients.Totally 168 glioma patients who underwent tumor resection were analyzed, and their tumor tissue specimens were acquired for the detection of AKIP1 expression by immunohistochemistry (IHC), which was scored by a semi-quantitative method considering staining intensity and staining density.According to AKIP1 expression in tumor tissues of glioma patients, there were 65 (38.7%) patients with AKIP1 low expression (IHC score 0-3), 48 (28.6%) patients with AKIP1 high + expression (IHC score 4-6), 42 (25.0%) patients with AKIP1 high++ expression (IHC score 7-9) and 13 (7.7%) patients with AKIP1 high+++ expression (IHC score 10-12), respectively. AKIP1 expression was positively associated with World Health Organization grade. Overall survival (OS) was the lowest in the patients with AKIP1 high+++ expression, followed by those with AKIP1 high++ expression and those with AKIP1 high+ expression, and highest in those with AKIP1 low expression. Further subgroup analysis exhibited that AKIP1 expression was negatively associated with OS especially in high-grade glioma patients. In addition, AKIP1 expression was negatively associated with OS in all subgroups of patients with/without adjuvant radiotherapy, with/without adjuvant chemotherapy. Further multivariate Cox's regression exhibited that AKIP1 high expression was an independent predictive factor for worse OS.AKIP1 presents with the potential to be a novel biomarker for tumor management and prognosis surveillance in glioma patients.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidad , Glioma/genética , Glioma/mortalidad , Proteínas Nucleares/metabolismo , Adulto , Biomarcadores de Tumor/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor/métodos , Clasificación del Tumor/normas , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de Supervivencia , Organización Mundial de la Salud
2.
Nat Commun ; 12(1): 801, 2021 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-33547324

RESUMEN

Most trials do not release interim summaries on efficacy and toxicity of the experimental treatments being tested, with this information only released to the public after the trial has ended. While early release of clinical trial data to physicians and patients can inform enrollment decision making, it may also affect key operating characteristics of the trial, statistical validity and trial duration. We investigate the public release of early efficacy and toxicity results, during ongoing clinical studies, to better inform patients about their enrollment options. We use simulation models of phase II glioblastoma (GBM) clinical trials in which early efficacy and toxicity estimates are periodically released accordingly to a pre-specified protocol. Patients can use the reported interim efficacy and toxicity information, with the support of physicians, to decide which trial to enroll in. We describe potential effects on various operating characteristics, including the study duration, selection bias and power.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/psicología , Drogas en Investigación/uso terapéutico , Glioblastoma/psicología , Difusión de la Información/métodos , Modelación Específica para el Paciente , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Ensayos Clínicos como Asunto , Toma de Decisiones , Glioblastoma/tratamiento farmacológico , Glioblastoma/mortalidad , Glioblastoma/patología , Humanos , Difusión de la Información/ética , Seguridad del Paciente , Selección de Paciente/ética , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
3.
Anticancer Res ; 41(2): 1027-1034, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33517311

RESUMEN

BACKGROUND/AIM: This study aimed to evaluate the association of clinical characteristics with treatment outcomes to ascertain the appropriate treatment options for soft tissue sarcomas (STS) patients with brain metastasis (BM). PATIENTS AND METHODS: Medical records of STS patients with BM who were treated in our institutions were retrospectively reviewed, and analyzed to identify the factors associated with post-BM survival. RESULTS: Among the 509 STS patients, BM occurred in five patients (0.98%). The median survival after BM was 1.5 months. Histological subtypes of the primary lesions in the five BM patients were: two synovial sarcomas, one myxoid liposarcoma, one alveolar soft part sarcoma, and one rhabdomyosarcoma. Among the five BM patients, the post-BM survival of two patients, who underwent surgery and postoperative radiotherapy, was longer than that of the other patients (p<0.01). CONCLUSION: Combined surgery and postoperative radiotherapy effectively managed symptoms and prolonged survival in STS patients with BM.


Asunto(s)
Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/terapia , Sarcoma/terapia , Adulto , Anciano , Neoplasias Encefálicas/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioterapia Ayuvante , Estudios Retrospectivos , Sarcoma/mortalidad , Sarcoma/patología , Análisis de Supervivencia
4.
J Clin Neurosci ; 84: 1-7, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33485591

RESUMEN

BACKGROUND: We conducted a segmental volumetric analysis of pre-operative brain magnetic resonance images (MRIs) of glioblastoma patients to identify brain- and tumor-related features that are prognostic of survival. METHODS: Using a dataset of 210 single-institutional adult glioblastoma patients, total volumes of the following tumor- and brain-related features were quantified on pre-operative MRIs using a fully automated segmentation tool: tumor enhancement, tumor non-enhancement, tumor necrosis, peri-tumoral edema, grey matter, white matter, and cerebrospinal fluid (CSF). Their association with survival using Cox regression models, adjusting for the well-known predictors of glioblastoma survival. The findings were verified in a second dataset consisting of 96 glioblastoma patients from The Cancer Imaging Archive and The Cancer Genome Atlas (TCIA/TCGA). RESULTS: CSF volume and edema were independently and consistently associated with overall survival of glioblastoma patients in both datasets. Greater edema was associated with increased hazard or decreased survival [adjusted hazard ratio (aHR) with 95% confidence interval (CI): 1.34 [1.08-1.67], p = 0.008 (institutional dataset); and, 1.44 [1.08-1.93], p = 0.013 (TCIA/TCGA dataset)]. Greater CSF volume also correlated with increased hazard or decreased survival [aHR 1.27 [1.02-1.59], p = 0.035 (institutional dataset), and 1.42 [1.03-1.95], p = 0.032 (TCIA/TCGA dataset)]. CONCLUSIONS: Higher brain CSF volume and higher edema levels at diagnosis are independently associated with decreased survival in glioblastoma patients. These results highlight the importance of a broader, quantitative brain-wide radiological analyses and invite investigations to understand tumor-related causes of increased edema and possibly increased CSF volume.


Asunto(s)
Neoplasias Encefálicas/patología , Líquido Cefalorraquídeo , Edema/patología , Glioblastoma/patología , Adulto , Anciano , Neoplasias Encefálicas/líquido cefalorraquídeo , Neoplasias Encefálicas/mortalidad , Edema/etiología , Femenino , Glioblastoma/líquido cefalorraquídeo , Glioblastoma/mortalidad , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Pronóstico
5.
Anticancer Res ; 41(1): 341-345, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33419829

RESUMEN

BACKGROUND/AIM: The aim of this study was to identify patients at high risk of death from neurological cause because these patients may be appropriate candidates for intense brain-directed treatment, in contrast to patients with uncontrollable extracranial disease, inevitably leading to death. In this context, the LabBM score (endpoint: overall survival; five blood test results; often abnormal in patients with widespread disease) may be a relevant tool. PATIENTS AND METHODS: This was a retrospective single-institution analysis of 101 patients, managed with upfront brain irradiation. Associations between neurological death and different baseline and treatment parameters were assessed. RESULTS: A LabBM score of 0 (five normal blood test results) was present in 32% of patients. Neurological death was recorded in 27%. Seven parameters were associated with neurological death, including the LabBM score (univariate analyses). Three out of the seven were significantly associated with neurological death in the multi-nominal logistic regression analysis. The most important parameter was primary tumor type (colorectal or melanoma), with a hazard ratio of 14.3. Patients without liver metastases were also more likely to die from neurological causes. Finally, patients who did not receive additional systemic therapy were more likely to die from central nervous system progression. The median survival time was 3.9 months (entire cohort). When censoring patients who died from extracranial progression, the median time to neurological death was 17.4 months. CONCLUSION: The LabBM score was not suitable for prediction of neurological death, in contrast to three other parameters. Interestingly, additional systemic therapy reduced the risk of neurological death, possibly because several new agents have known antitumor activity in the brain.


Asunto(s)
Muerte Encefálica , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/secundario , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/radioterapia , Causas de Muerte , Terapia Combinada , Irradiación Craneana/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Radiocirugia/métodos , Radioterapia/métodos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
6.
Cancer Radiother ; 25(2): 182-190, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33436285

RESUMEN

PURPOSE: The efficacy of hypofractionated radiotherapy (HFRT) in glioblastoma (GBM) without age restrictions remains unclear. The aim of this meta-analysis is to access the survival outcomes of HFRT in these patients. METHODS: A comprehensive electronic literature search of PubMed, Web of Science and Cochrane Library was conducted up to June 1, 2020. The main evaluation data were the overall survival (OS) rate at 12 months and 24 months and the progression-free survival (PFS) rate at 6 and 12 months. The secondary evaluation data was the incidence of radionecrosis and adverse events. The study was performed using R "meta" package. RESULTS: Eleven studies met the inclusion criteria, which totally contained 484 participants. The 12-month OS and 24-month OS rate of HFRT in GBM were 71.3% and 34.8%, while the 6-month PFS and 12-month rate were 74.0% and 40.8%. Compared to low-BED (biological equivalent dose) schedules (<78Gy), high-BED schedules may increase survival benefit both in PFS-6 (P=0.003) and PFS-12 (P=0.011), while the difference did not show on OS. Different dose per fraction had no significant effect on both OS and PFS. Incidence of radionecrosis was 14.2%. Although the overall incidence of adverse reactions cannot be quantified, the toxicity of HFRT was acceptable. CONCLUSIONS: Compared with survival data for standard treatment, HFRT seemed to improve overall survival and progression-free survival, while high BED schedules may future increase benefit on PFS. Meanwhile, the toxicity of HFRT was tolerable. Further randomised controlled clinical studies are needed to confirm these findings.


Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/terapia , Quimioradioterapia/métodos , Glioblastoma/terapia , Hipofraccionamiento de la Dosis de Radiación , Temozolomida/uso terapéutico , Neoplasias Encefálicas/mortalidad , Quimioradioterapia/efectos adversos , Quimioterapia Adyuvante/métodos , Glioblastoma/mortalidad , Humanos , Incidencia , Necrosis , Supervivencia sin Progresión , Traumatismos por Radiación/epidemiología , Traumatismos por Radiación/patología , Tasa de Supervivencia , Factores de Tiempo
7.
J Clin Neurosci ; 84: 91-96, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33358093

RESUMEN

Central neurocytoma is a rare benign brain tumor that typically arises from the subependymal lining of the lateral ventricles in young adults and is generally associated with excellent survival following neurosurgical excision alone. This is a retrospective clinical audit of biopsy-proven neurocytoma registered between 2004 and 2019 at a single institution in India. All time-to event outcomes were analyzed using Kaplan-Meier method and compared with the log-rank test. Any p-value <0.05 was considered statistically significant. A total of 66 patients with neurocytoma were included in the descriptive analysis. Median age of study cohort was 31 years with equitable gender ratio. Majority (83%) of tumors were intraventricular, lateral ventricle being the commonest location. Following maximal safe resection, patients were generally kept on close clinico-radiological surveillance. Most patients (80%) had typical World Health Organization (WHO) grade II neurocytoma with remaining 20% showing histological atypia and/or high-grade features. Outcome analysis was restricted to 35 patients with relevant treatment details and adequate follow-up information. Six patients experienced recurrent/progressive disease with 2 documented deaths. At a median follow up of 52 months, 5-year Kaplan-Meier estimates of progression-free survival and overall survival were 93.3% and 96.8% respectively. Three patients developed delayed recurrence (>5-years after initial diagnosis) underscoring the importance of long-term follow-up. Atypical/high-grade histology was associated with inferior survival that may stand to benefit with upfront adjuvant radiotherapy. This represents the largest single-institution series of central neurocytoma and demonstrates excellent outcomes with adequate surgical resection alone, reserving radiotherapy for large residual tumor, recurrent disease, and/or atypical high-grade histology.


Asunto(s)
Neoplasias Encefálicas/patología , Neurocitoma/patología , Adulto , Biomarcadores de Tumor/análisis , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/cirugía , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , India , Masculino , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/radioterapia , Neurocitoma/mortalidad , Neurocitoma/cirugía , Radioterapia Ayuvante/métodos , Estudios Retrospectivos , Adulto Joven
8.
Am J Clin Oncol ; 44(2): 53-57, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33350680

RESUMEN

OBJECTIVES: The objective of this study were to improve the 3-tiered, purely biomarker-based LabBM score, which predicts the survival of patients with brain metastases, by adding the well-established prognostic factor performance status (PS), and to define its role in comparison with the recently proposed Extracranial-Graded Prognostic Assessment score, which is based on the well-known Diagnosis-specific Graded Prognostic Assessment and 2 of the same biomarkers. MATERIALS AND METHODS: This was a retrospective single-institution analysis of 212 patients, managed with upfront brain irradiation. Survival was stratified by LabBM and LabPS score. Each included serum hemoglobin, platelets, albumin, C-reactive protein, and lactate dehydrogenase (plus PS for the LabPS). Zero, 0.5, or 1 point was assigned and the final point sum calculated. A higher point sum indicates shorter survival. RESULTS: The new LabPS score predicted overall survival very well (median: 12.1 to 0.7 mo, 1-y rate: 52% to 0%), P=0.0001. However, the group with the poorest prognosis (3 or 3.5 points) was very small (4%). Most patients with comparably short survival had a lower point sum. The LabPS score failed to outperform the recently proposed Extracranial-Graded Prognostic Assessment score. CONCLUSIONS: Integration of blood biomarkers should be considered when attempting to develop improved scores. Additional research is needed to improve the tools which predict short survival, because many of these patients continue to go undetected with all available scores.


Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/secundario , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/terapia , Proteína C-Reactiva/análisis , Femenino , Humanos , Estimación de Kaplan-Meier , Lactato Deshidrogenasas/sangre , Masculino , Persona de Mediana Edad , Pronóstico , Radioterapia/métodos , Estudios Retrospectivos , Adulto Joven
9.
Int J Mol Sci ; 22(1)2020 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-33375517

RESUMEN

Despite advances in the diagnosis and treatment of the central nervous system malignancy glioma, overall survival remains poor. Cytoskeleton-associated protein 2-like (CKAP2L), which plays key roles in neural progenitor cell division, has also been linked to poor prognosis in lung cancer. In the present study, we investigated the role of CKAP2L in glioma. From bioinformatics analyses of datasets from The Cancer Gene Atlas and the Chinese Glioma Genome Atlas, we found that CKAP2L expression correlates with tumor grade and overall survival. Gene set enrichment analysis (GSEA) showed that MITOTIC_SPINDLE, G2M_CHECKPOINT, and E2F_TARGETS are crucially enriched phenotypes associated with high CKAP2L expression. Using U87MG, U118MG, and LNZ308 human glioma cells, we confirmed that CKAP2L knockdown with siCKAP2L inhibits glioma cell proliferation, migration, invasion, and epithelial-mesenchymal transition. Interestingly, CKAP2L knockdown also induced cell cycle arrest at G2/M phase, which is consistent with the GSEA finding. Finally, we observed that CKAP2L knockdown led to significant increases in miR-4496. Treating cells with exogenous miR-4496 mimicked the effect of CKAP2L knockdown, and the effects of CKAP2L knockdown could be suppressed by miR-4496 inhibition. These findings suggest that CKAP2L is a vital regulator of miR-4496 activity and that CKAP2L is a potentially useful prognostic marker in glioma.


Asunto(s)
Neoplasias Encefálicas/metabolismo , Proliferación Celular/genética , Proteínas del Citoesqueleto/metabolismo , Transición Epitelial-Mesenquimal/genética , Puntos de Control de la Fase G2 del Ciclo Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Glioblastoma/metabolismo , MicroARNs/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/metabolismo , Neoplasias del Sistema Nervioso Central/mortalidad , Neoplasias del Sistema Nervioso Central/patología , Proteínas del Citoesqueleto/genética , Bases de Datos Genéticas , Factores de Transcripción E2F/genética , Factores de Transcripción E2F/metabolismo , Femenino , Técnicas de Silenciamiento del Gen , Glioblastoma/genética , Glioma/genética , Glioma/metabolismo , Glioma/mortalidad , Glioma/patología , Humanos , Inmunohistoquímica , Masculino , MicroARNs/genética , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica/genética , Pronóstico , Análisis de Matrices Tisulares
10.
Nat Commun ; 11(1): 4997, 2020 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-33020472

RESUMEN

Despite a deeper molecular understanding, human glioblastoma remains one of the most treatment refractory and fatal cancers. It is known that the presence of macrophages and microglia impact glioblastoma tumorigenesis and prevent durable response. Herein we identify the dual function cytokine IL-33 as an orchestrator of the glioblastoma microenvironment that contributes to tumorigenesis. We find that IL-33 expression in a large subset of human glioma specimens and murine models correlates with increased tumor-associated macrophages/monocytes/microglia. In addition, nuclear and secreted functions of IL-33 regulate chemokines that collectively recruit and activate circulating and resident innate immune cells creating a pro-tumorigenic environment. Conversely, loss of nuclear IL-33 cripples recruitment, dramatically suppresses glioma growth, and increases survival. Our data supports the paradigm that recruitment and activation of immune cells, when instructed appropriately, offer a therapeutic strategy that switches the focus from the cancer cell alone to one that includes the normal host environment.


Asunto(s)
Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Glioma/metabolismo , Glioma/patología , Interleucina-33/metabolismo , Animales , Neoplasias Encefálicas/mortalidad , Carcinogénesis , Núcleo Celular/metabolismo , Citocinas/metabolismo , Glioblastoma/metabolismo , Glioblastoma/mortalidad , Glioblastoma/patología , Glioma/mortalidad , Humanos , Inflamación , Células Asesinas Naturales/metabolismo , Células Asesinas Naturales/patología , Macrófagos/metabolismo , Macrófagos/patología , Ratones , Ratones SCID , Microglía , Análisis de Supervivencia , Linfocitos T/metabolismo , Linfocitos T/patología , Microambiente Tumoral/inmunología
11.
Nat Commun ; 11(1): 4660, 2020 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-32938908

RESUMEN

Intratumor spatial heterogeneity facilitates therapeutic resistance in glioblastoma (GBM). Nonetheless, understanding of GBM heterogeneity is largely limited to the surgically resectable tumor core lesion while the seeds for recurrence reside in the unresectable tumor edge. In this study, stratification of GBM to core and edge demonstrates clinically relevant surgical sequelae. We establish regionally derived models of GBM edge and core that retain their spatial identity in a cell autonomous manner. Upon xenotransplantation, edge-derived cells show a higher capacity for infiltrative growth, while core cells demonstrate core lesions with greater therapy resistance. Investigation of intercellular signaling between these two tumor populations uncovers the paracrine crosstalk from tumor core that promotes malignancy and therapy resistance of edge cells. These phenotypic alterations are initiated by HDAC1 in GBM core cells which subsequently affect edge cells by secreting the soluble form of CD109 protein. Our data reveal the role of intracellular communication between regionally different populations of GBM cells in tumor recurrence.


Asunto(s)
Antígenos CD/metabolismo , Neoplasias Encefálicas/patología , Glioblastoma/patología , Histona Desacetilasa 1/metabolismo , Proteínas de Neoplasias/metabolismo , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidad , Femenino , Proteínas Ligadas a GPI/metabolismo , Regulación Neoplásica de la Expresión Génica , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/mortalidad , Histona Desacetilasa 1/antagonistas & inhibidores , Histona Desacetilasa 1/genética , Histona Desacetilasa 2/genética , Histona Desacetilasa 2/metabolismo , Humanos , Ratones SCID , Fenilbutiratos/farmacología , Transducción de Señal , Microambiente Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto
12.
BMC Bioinformatics ; 21(Suppl 13): 383, 2020 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-32938364

RESUMEN

BACKGROUND: Glioblastoma multiforme (GBM) is one of the most common malignant brain tumors and its average survival time is less than 1 year after diagnosis. RESULTS: Firstly, this study aims to develop the novel survival analysis algorithms to explore the key genes and proteins related to GBM. Then, we explore the significant correlation between AEBP1 upregulation and increased EGFR expression in primary glioma, and employ a glioma cell line LN229 to identify relevant proteins and molecular pathways through protein network analysis. Finally, we identify that AEBP1 exerts its tumor-promoting effects by mainly activating mTOR pathway in Glioma. CONCLUSIONS: We summarize the whole process of the experiment and discuss how to expand our experiment in the future.


Asunto(s)
Algoritmos , Neoplasias Encefálicas/genética , Biología Computacional/métodos , Glioblastoma/genética , Glioma/genética , Neoplasias Encefálicas/mortalidad , Glioblastoma/mortalidad , Glioma/mortalidad , Humanos , Análisis de Supervivencia
13.
Brain Tumor Pathol ; 37(4): 136-144, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32761533

RESUMEN

Oncogenic gene fusions have been reported in diffuse gliomas and may serve as potential therapeutic targets. Here, using next-generation sequencing analysis (Illumina TruSight Tumor 170 panel), we analyzed a total of 356 diffuse gliomas collected from 2017 to 2019 to evaluate clinical, pathological, and genetic features of gene fusion. We found 53 cases of glioblastomas harboring the following oncogenic gene fusions: MET (n = 18), EGFR (n = 14), FGFR (n = 12), NTRK (n = 5), RET (n = 2), AKT3 (n = 1), and PDGFRA fusions (n = 1). Gene fusions were consistently observed in both IDH-wildtype and IDH-mutant glioblastomas (8.8% and 9.4%, p = 1.000). PTPRZ1-MET fusion was the only fusion that genetically resembled secondary glioblastomas (i.e., high frequency of IDH mutation, ATRX loss, TP53 mutation, and absence of EGFR amplification), whereas other gene fusion types were similar to primary glioblastomas (i.e., high frequency of IDH-wildtype, TERT mutation, EGFR amplification, and PTEN mutation). In IDH-wildtype glioblastoma patients, multivariable analysis revealed that the PTPRZ1-MET fusion was associated with poor progression-free survival (HR [95% CI]: 5.42 (1.72-17.05), p = 0.004). Additionally, we described two novel cases of CCDC6-RET fusion in glioma. Collectively, our findings indicate that targetable gene fusions are associated with aggressive biological behavior and can aid the clinical treatment strategy for glioma patients.


Asunto(s)
Neoplasias Encefálicas/genética , Fusión Génica/genética , Estudios de Asociación Genética , Glioblastoma/genética , Glioma/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Proteínas Proto-Oncogénicas c-met/genética , Proteínas Tirosina Fosfatasas Clase 5 Similares a Receptores/genética , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Proteínas del Citoesqueleto/genética , Femenino , Glioblastoma/mortalidad , Glioblastoma/patología , Glioma/mortalidad , Glioma/patología , Humanos , Isocitrato Deshidrogenasa/genética , Masculino , Persona de Mediana Edad , Pronóstico , Proteínas Proto-Oncogénicas c-ret/genética , Tasa de Supervivencia
14.
Asia Pac J Clin Oncol ; 16(5): e223-e227, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32762134

RESUMEN

AIM: Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. In this study, we aimed to show the relationship between temporal muscle thickness (TMT) measurement and survival in newly diagnosed patients with GBM. METHODS: Forty-seven patients with newly diagnosed GBM were evaluated, retrospectively. TMT at diagnosis of GBM before any surgical procedure was measured on the contrast-enhanced axial longitudinal relaxation time (T1)-weighted magnetic resonance images. Overall survival (OS) was analyzed by the Kaplan-Meier method and log-rank test was used to determine the differences between the groups. The median TMT was used to determine the cutoff point. RESULTS: The median TMT was 4.7 mm (range, 2.8-6.6) in females and 5.4 mm (range, 2.9-8.1) in males. Median survival for TMT < 4.9 mm was 12.9 ± 3.5 (95% CI, 6.0-19.8) months, and 39.4 ± 11.9 (95% CI, 16.0-62.8) months for TMT ≥ 4.9 (P = .023). In the multivariate Cox regression model, the TMT group (Hazard ratio [HR] = 2.07, 95% CI, 0.92-4.61, P = .032) and age group (HR = 2.18, 95% CI, 1.01-4.67, P = .014) showed statistically significant difference. CONCLUSION: TMT is not an independent predictor of response but a predictor of sarcopenia and survival in newly diagnosed GBM. TMT measurement is an easy and practical method. Survival prediction will provide useful information in GBM patients having poor prognosis.


Asunto(s)
Neoplasias Encefálicas/fisiopatología , Glioblastoma/fisiopatología , Músculo Temporal/patología , Adolescente , Adulto , Anciano , Neoplasias Encefálicas/mortalidad , Femenino , Glioblastoma/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Adulto Joven
15.
Cancer Imaging ; 20(1): 55, 2020 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-32758279

RESUMEN

BACKGROUND: This study aims to identify robust radiomic features for Magnetic Resonance Imaging (MRI), assess feature selection and machine learning methods for overall survival classification of Glioblastoma multiforme patients, and to robustify models trained on single-center data when applied to multi-center data. METHODS: Tumor regions were automatically segmented on MRI data, and 8327 radiomic features extracted from these regions. Single-center data was perturbed to assess radiomic feature robustness, with over 16 million tests of typical perturbations. Robust features were selected based on the Intraclass Correlation Coefficient to measure agreement across perturbations. Feature selectors and machine learning methods were compared to classify overall survival. Models trained on single-center data (63 patients) were tested on multi-center data (76 patients). Priors using feature robustness and clinical knowledge were evaluated. RESULTS: We observed a very large performance drop when applying models trained on single-center on unseen multi-center data, e.g. a decrease of the area under the receiver operating curve (AUC) of 0.56 for the overall survival classification boundary at 1 year. By using robust features alongside priors for two overall survival classes, the AUC drop could be reduced by 21.2%. In contrast, sensitivity was 12.19% lower when applying a prior. CONCLUSIONS: Our experiments show that it is possible to attain improved levels of robustness and accuracy when models need to be applied to unseen multi-center data. The performance on multi-center data of models trained on single-center data can be increased by using robust features and introducing prior knowledge. For successful model robustification, tailoring perturbations for robustness testing to the target dataset is key.


Asunto(s)
Neoplasias Encefálicas/mortalidad , Glioblastoma/mortalidad , Aprendizaje Automático , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Neoplasias Encefálicas/diagnóstico por imagen , Glioblastoma/diagnóstico por imagen , Humanos , Persona de Mediana Edad , Análisis de Supervivencia
16.
Int J Nanomedicine ; 15: 5491-5501, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32848385

RESUMEN

Purpose: Currently, the treatment of brain metastases from non-small cell lung cancer (NSCLC) is rather difficult in the clinic. A combination of small molecule-targeted drug and chemo-drug is a promising therapeutic strategy for the treatment of NSCLC brain metastases. But the efficacy of this combination therapy is not satisfactory due to the blood-brain barrier (BBB). Therefore, it is urgent to develop a drug delivery system to enhance the synergistic therapeutic effects of small molecule-targeted drug and chemo-drug for the treatment of NSCLC brain metastases. Methods: T7 peptide installed and osimertinib (AZD9291) loaded intracellular glutathione (GSH) responsive doxorubicin prodrug self-assembly nanocarriers (T7-DSNPs/9291) have been developed as a targeted co-delivery system to enhance the combined therapeutic effect on brain metastases from NSCLC. In vitro cell experiments, including intracellular uptake assay, in vitro BBB transportation, and MTT assay were used to demonstrate the efficacy of T7-DSNPs/9291 in NSCLC brain metastasis in vitro. Real-time fluorescence imaging analysis, magnetic resonance imaging analysis, and Kaplan-Meier survival curves were used to study the effect of T7-DSNPs/9291 on an animal model in vivo. Results: T7-DSNPs/9291 could significantly enhance BBB penetration of AZD9291 and doxorubicin via transferrin receptor-mediated transcytosis. Moreover, T7-DSNPs/9291 showed significant anti-NSCLC brain metastasis effect and prolonged median survival of an intracranial NSCLC brain metastasis animal model. Conclusion: T7-DSNPs/9291 is a potential drug delivery system for the combined therapy of brain metastasis from NSCLC.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Portadores de Fármacos/administración & dosificación , Neoplasias Pulmonares/patología , Acrilamidas/administración & dosificación , Compuestos de Anilina/administración & dosificación , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Barrera Hematoencefálica/efectos de los fármacos , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Colágeno Tipo IV/química , Doxorrubicina/administración & dosificación , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Ratones Endogámicos BALB C , Nanoestructuras/administración & dosificación , Nanoestructuras/química , Fragmentos de Péptidos/química , Profármacos/administración & dosificación , Profármacos/química , Receptores de Transferrina/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
17.
Cancer Invest ; 38(7): 394-405, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32643440

RESUMEN

The study investigated the human cytomegalovirus (HCMV) and human papillomavirus (HPV) in gliomas. A retrospective study was conducted on 112 samples. HCMV was investigated by PCR, in situ hybridization (ISH) and immunohistochemistry. HPV was tested by PCR and DNA ISH. HCMV was identified in 60 gliomas, including 55 GBM. However, RNA ISH and immunohistochemistry failed to detect HCMV positivity. HPV was identified in 44 GBM. No significant relationship was identified between HCMV and HPV and tumour characteristics (p > 0.05). Our findings support the HCMV and HPV presence in gliomas. Further assays are required to more explore the potential efficient antiviral management.


Asunto(s)
Neoplasias Encefálicas/virología , Citomegalovirus/aislamiento & purificación , Glioma/virología , Papillomaviridae/aislamiento & purificación , Adulto , Anciano , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Citomegalovirus/genética , Infecciones por Citomegalovirus/virología , Femenino , Glioma/mortalidad , Glioma/patología , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Estudios Retrospectivos , Túnez , Adulto Joven
18.
Medicine (Baltimore) ; 99(28): e21147, 2020 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-32664146

RESUMEN

High-grade gliomas (HGGs) are a rapidly progressive and highly recurrent group of primary brain tumors. Despite aggressive surgical resection with chemoradiotherapy, prognoses remained poor. Valproic acid (VPA), a histone deacetylase inhibitor has shown the potential to inhibit glioma cell growth in vitro through several diverse mechanisms. However clinical studies regarding the effect of VPA on HGGs are limited. This study aimed to investigate whether using VPA in patients with HGGs under temozolomide (TMZ) would lead to a better overall survival (OS).We used the Taiwan National Health Insurance Research database to conduct this population-based cohort study. A total of 2379 patients with HGGs under TMZ treatment were included and were further classified into VPA (n = 1212, VPA ≥ 84 defined daily dose [DDD]) and non-VPA (n = 1167, VPA < 84 DDD) groups. Each patient was followed from 1998 to 2013 or until death. A Cox proportional hazard regression was performed to evaluate the effect of VPA and OS.The VPA group had a longer mean OS time compared with the non-VPA group (OS: 50.3 ±â€Š41.0 vs 42.0 ±â€Š37.2 months, P < .001). In patients between 18 and 40 years old, the difference is most significant (OS: 70.5 ±â€Š48.7 vs 55.1 ±â€Š46.0, P = .001). The adjusted hazard ratio is 0.81 (95% confidence interval, 0.72-0.91) for the VPA group relative to the non-VPA group.VPA at over 84 DDD improved OS in HGGs TMZ treatment.


Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Estadificación de Neoplasias , Vigilancia de la Población/métodos , Temozolomida/uso terapéutico , Ácido Valproico/uso terapéutico , Adolescente , Adulto , Anciano , Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidad , Inhibidores Enzimáticos/uso terapéutico , Femenino , Estudios de Seguimiento , Glioma/diagnóstico , Glioma/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Taiwán/epidemiología , Adulto Joven
19.
Pediatr Blood Cancer ; 67(9): e28426, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32614133

RESUMEN

BACKGROUND: Relapse occurs in 50% of pediatric ependymoma cases and has poor prognosis. Few studies have investigated the clinical progress of relapsed disease, and treatment lacks a standardized approach. METHODS AND MATERIALS: We analyzed 302 pediatric ependymoma cases. Tumor, demographic, and treatment variables were investigated for association with relapse risk, time to recurrence, and survival after relapse. DNA methylation profiling was performed for 135/302 cases, and predominant subgroups were EPN_PFA (n = 95) and EPN_RELA (n = 24). Chromosome 1q status was ascertained for 185/302 cases by fluorescent in-situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), and DNA methylation profiles. RESULTS: Sixty-two percent of cases relapsed, with a median of two recurrences with no difference between posterior fossa and supratentorial locations (66% vs 55% relapse rate). One hundred seventeen (38%) cases relapsed within two years and five (2%) beyond 10 years. The late relapses were clinically heterogeneous. Tumor grade and treatment affected risk and time to relapse variably across subgroups. After relapse, surgery and irradiation delayed disease progression with a minimal impact on survival across the entire cohort. In the EPN_PFA and EPN_RELA groups, 1q gain was independently associated with relapse risk (subhazard ratio [SHR] 4.307, P = 0.027 and SHR 1.982, P = 0.010, respectively) while EPN_PFA had increased relapse risk compared with EPN_RELA (SHR = 0.394, P = 0.018). CONCLUSIONS: Recurrent pediatric ependymoma is an aggressive disease with poor outcomes, for which current treatments are inadequate. We report that chromosome 1q gain increases relapse risk in common molecular subgroups in children but a deeper understanding of the underlying biology at relapse and novel therapeutic approaches are urgently needed.


Asunto(s)
Neoplasias Encefálicas , Cromosomas Humanos Par 1 , Metilación de ADN , ADN de Neoplasias , Ependimoma , Recurrencia Local de Neoplasia , Adolescente , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/terapia , Niño , Preescolar , Cromosomas Humanos Par 1/genética , Cromosomas Humanos Par 1/metabolismo , ADN de Neoplasias/genética , ADN de Neoplasias/metabolismo , Ependimoma/genética , Ependimoma/metabolismo , Ependimoma/mortalidad , Ependimoma/terapia , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/terapia , Estudios Retrospectivos , Factores de Riesgo
20.
BMC Neurol ; 20(1): 259, 2020 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-32600353

RESUMEN

BACKGROUND: To investigate associations between lower-grade glioma (LGG) mRNA-based subtypes (R1-R4) and MR features. METHODS: mRNA-based subtyping was obtained from the LGG dataset in The Cancer Genome Atlas (TCGA). We identified matching patients (n = 145) in The Cancer Imaging Archive (TCIA) who underwent MR imaging. The associations between mRNA-based subtypes and MR features were assessed. RESULTS: In the TCGA-LGG dataset, patients with the R2 subtype had the shortest median OS months (P < 0.05). The time-dependent ROC for the R2 subtype was 0.78 for survival at 12 months, 0.76 for survival at 24 months, and 0.76 for survival at 36 months. In the TCIA-LGG dataset, 41 (23.7%) R1 subtype, 40 (23.1%) R2 subtype, 19 (11.0%) R3 subtype and 45 (26.0%) R4 subtype cases were identified. Multivariate analysis revealed that enhancing margin (ill-defined, OR: 9.985; P = 0.003) and T1 + C/T2 mismatch (yes, OR: 0.091; P = 0.023) were associated with the R1 subtype (AUC: 0.708). The average accuracy of the ten-fold cross validation was 71%. Proportion of contrast-enhanced (CE) tumour (> 5%, OR: 14.733; P < 0.001) and necrosis/cystic changes (yes, OR: 0.252; P = 0.009) were associated with the R2 subtype (AUC: 0.832). The average accuracy of the ten-fold cross validation was 82%. Haemorrhage (yes, OR: 8.55; P < 0.001) was positively associated with the R3 subtype (AUC: 0.689). The average accuracy of the ten-fold cross validation was 87%. Proportion of CE tumour (> 5%, OR: 0.14; P < 0.001) was negatively associated with the R4 subtype (AUC: 0.672). The average accuracy of the ten-fold cross validation was 71%. For the prediction of the R2 subtype, the nomogram showed good discrimination and calibration. Decision curve analysis demonstrated that prediction with the R2 model was clinically useful. CONCLUSIONS: Patients with the R2 subtype had the worst prognosis. We demonstrated that MRI features can identify distinct LGG mRNA-based molecular subtypes.


Asunto(s)
Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Glioma/diagnóstico por imagen , Glioma/genética , ARN Mensajero/genética , Adolescente , Adulto , Anciano , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Femenino , Genómica/métodos , Glioma/mortalidad , Glioma/patología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Adulto Joven
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