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3.
J Assoc Physicians India ; 69(2): 68-70, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33527818

RESUMO

Primary central nervous system lymphoma (PCNSL) is a rare, extranodal non- Hodgkin's lymphoma confined to craniospinal axis. PCNSL accounts for less than 5% of all primary CNS malignancies and 1 to 2% of all lymphomas. Amongst the causes of major cognitive dysfunction, primary brain tumor exists as a less frequent cause. We report a case of PCNSL as a rare and unusual presentation of rapidly progressive cognitive dysfunction which revealed clinicopathoradiological correlation. The patient revealed clinicoradiologically evident marked improvement after treatment, ascribing PCNSL as potentially reversible cause of major cognitive dysfunction.


Assuntos
Neoplasias do Sistema Nervoso Central , Disfunção Cognitiva , Linfoma não Hodgkin , Linfoma , Sistema Nervoso Central , Neoplasias do Sistema Nervoso Central/complicações , Neoplasias do Sistema Nervoso Central/diagnóstico , Disfunção Cognitiva/etiologia , Humanos , Linfoma/complicações , Linfoma/diagnóstico
4.
Turk Neurosurg ; 31(1): 99-106, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33491172

RESUMO

AIM: To determine the mitochondrial microsatellite instability (mtMSI) status in a series of Malaysian patients with brain tumors. Furthermore, we analyzed whether the mtMSI status is associated with the clinicopathological features of the patients. MATERIAL AND METHODS: Forty fresh frozen tumor tissues along with blood samples of brain tumor patients were analyzed for mtMSI by PCR amplification of genomic DNAs, and the amplicons were directly sequenced in both directions using Sanger sequencing. RESULTS: Microsatellite analysis revealed that 20% (8 out of 40) of the tumors were mtMSI positive with a total of 8 mtMSI changes. All mtMSI markers were detected in D310 and D16184 of the D-loop region. Additionally, no significant association was observed between mtMSI status and clinicopathological features. CONCLUSION: The variations, specifically the mtMSI, suggest that the mitochondrial DNA (mtDNA) can be targeted for genomic alteration in brain tumors. Therefore, the specific role of mtDNA alteration in brain tumor development and prognosis requires further investigation.


Assuntos
Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/genética , DNA Mitocondrial/genética , Instabilidade de Microssatélites , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/diagnóstico , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/epidemiologia , Neoplasias do Sistema Nervoso Central/genética , Criança , Pré-Escolar , Feminino , Humanos , Malásia/epidemiologia , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Mitocôndrias/genética , Reação em Cadeia da Polimerase/tendências , Adulto Jovem
5.
J Clin Neurosci ; 83: 49-55, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33339691

RESUMO

Primary CNS lymphomas (PCNSLs) are aggressive diffuse large B-cell lymphomas (DLBCLs) limited to the CNS that generally have a poor prognosis. Classification of DLBCL into germinal center B-cell (GCB) and activated B-cell (non-GCB) subtypes has prognostic value in systemic DLBCL, with GCB-type having a better prognosis. The aim of this study was to determine whether GCB versus non-GCB classification in PCNSLs has similar prognostic value. We analyzed clinical, radiological and histologic data from 24 patients with biopsy confirmed DLBCL of the CNS with classification into GCB versus non-GCB subtypes. We found that after a median follow-up of 15 months, only 39% of patients with non-GCB-type PCNS DLBCL were alive, whereas all patients with GCB-type were alive. Non-GCB-type had a median survival of 11 months, whereas all GCB-type patients were alive after a median follow-up of 22 months. As previously reported, we also found that patients younger than 70 years had longer survival (median 29 months) compared to older patients (median 8.8 months). There was no statistically significant difference between the ages, gender, focality, size or location of lesions, or treatment of non-GCB and GCB-type patients. Our findings suggest that classifying PCNSLs into GCB versus non-GCB subtype using the Hans algorithm may help stratify patients into two groups with different prognosis.


Assuntos
Linfócitos B/patologia , Neoplasias do Sistema Nervoso Central/diagnóstico , Centro Germinativo/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma não Hodgkin/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/patologia , Feminino , Humanos , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
7.
PLoS One ; 15(12): e0243839, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33315914

RESUMO

The preoperative imaging-based differentiation of primary central nervous system lymphomas (PCNSLs) and glioblastomas (GBs) is of high importance since the therapeutic strategies differ substantially between these tumors. In this study, we investigate whether the gamma distribution (GD) model is useful in this differentiation of PNCSLs and GBs. Twenty-seven patients with PCNSLs and 57 patients with GBs were imaged with diffusion-weighted imaging using 13 b-values ranging from 0 to 1000 sec/mm2. The shape parameter (κ) and scale parameter (θ) were obtained with the GD model. Fractions of three different areas under the probability density function curve (f1, f2, f3) were defined as follows: f1, diffusion coefficient (D) <1.0×10-3 mm2/sec; f2, D >1.0×10-3 and <3.0×10-3 mm2/sec; f3, D >3.0 × 10-3 mm2/sec. The GD model-derived parameters were compared between PCNSLs and GBs. Receiver operating characteristic (ROC) curve analyses were performed to assess diagnostic performance. The correlations with intravoxel incoherent motion (IVIM)-derived parameters were evaluated. The PCNSL group's κ (2.26 ± 1.00) was significantly smaller than the GB group's (3.62 ± 2.01, p = 0.0004). The PCNSL group's f1 (0.542 ± 0.107) was significantly larger than the GB group's (0.348 ± 0.132, p<0.0001). The PCNSL group's f2 (0.372 ± 0.098) was significantly smaller than the GB group's (0.508 ± 0.127, p<0.0001). The PCNSL group's f3 (0.086 ± 0.043) was significantly smaller than the GB group's (0.144 ± 0.062, p<0.0001). The combination of κ, f1, and f3 showed excellent diagnostic performance (area under the curve, 0.909). The f1 had an almost perfect inverse correlation with D. The f2 and f3 had very strong positive correlations with D and f, respectively. The GD model is useful for the differentiation of GBs and PCNSLs.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/diagnóstico , Glioblastoma/diagnóstico por imagem , Glioblastoma/diagnóstico , Linfoma/diagnóstico por imagem , Linfoma/diagnóstico , Imagem por Ressonância Magnética , Modelos Biológicos , Idoso , Diagnóstico Diferencial , Feminino , Gadolínio/química , Humanos , Masculino , Pessoa de Meia-Idade , Movimento (Física) , Curva ROC
8.
Medicine (Baltimore) ; 99(38): e22062, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957327

RESUMO

RATIONALE: Primary central nervous system lymphoma (PCNSL) involving the choroid plexus is exceedingly rare. The differential diagnosis for choroid plexus enhancing lesions in addition to lymphoma includes infections, sarcoidosis, tuberculosis, papilloma, meningioma, subependymoma, and metastatic lesions. PATIENT CONCERNS: A 71-year-old man presented with 3 days of episodic memory loss and gait disturbance. Brain magnetic resonance imaging showed homogenously enhancing lesions with mildly restricted diffusion and T2 hypointensity in the lateral ventricles, as well as T2 hyperintensity and enhancement in the right hippocampus. His episodic memory loss was thought to be secondary to subclinical focal seizures, supported by EEG revealing right temporal lobe epileptiform discharges. DIAGNOSES: Large B-cell lymphoma, nongerminal center type was revealed on pathological examination. INTERVENTIONS: Stereotactic biopsy of his right thalamic lesion was performed. OUTCOMES: The patient underwent induction therapy with high-dose methotrexate, temozolomide, and rituximab, which resulted in complete resolution of the enhancing lesions. He then underwent conditioning chemotherapy with carmustine and thiotepa, followed by autologous stem cell transplantation. His PCNSL remains in remission 42 weeks after the onset of symptoms. LESSONS: We report a patient with multifocal PCNSL involving the choroid plexus, who presented with abnormal gait and episodic confusion and memory loss. PCNSL should be considered in the differential diagnosis of acute encephalopathy among immunocompetent older individuals who have choroid plexus enhancing lesions.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Linfoma não Hodgkin/diagnóstico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Neoplasias do Sistema Nervoso Central/terapia , Diagnóstico Diferencial , Eletroencefalografia , Transplante de Células-Tronco Hematopoéticas , Humanos , Linfoma não Hodgkin/terapia , Imagem por Ressonância Magnética , Masculino
9.
Medicine (Baltimore) ; 99(33): e21196, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871983

RESUMO

INTRODUCTION: Circulating tumor DNA (ctDNA) has provided a minimally invasive approach for the detection of genetic mutations in glioma. However, the diagnostic value of ctDNA in glioma remains unclear. This meta-analysis was designed to investigate the diagnostic value of ctDNA, compared with the current "criterion standard" tumor tissues. MATERIALS AND METHODS: The included studies were collected by searching PubMed, Web of Science, Cochrane Library, and Embase databases. All statistical analyses were performed using the STATA12.0 and Meta-DiSc1.4 software. RESULT: A total of 11 studies comprising 522 glioma patients met our inclusion criteria. The pooled sensitivity and specificity were 0.69 (95% confidence interval [CI] 0.66-0.73) and 0.98 (95% CI 0.96-0.99), respectively. The pooled diagnostic odds ratio was 23.27 (95% CI 13.69-39.53) and the area under the curve of the summary receiver operating characteristics curve was 0.90 (95% CI 0.89-0.92). CONCLUSIONS: ctDNA analysis is an effective method to detect the genetic mutation status in glioma patients with high specificity and relatively moderate sensitivity. The application of high-throughput technologies, the detection of patients with high-grade glioma, and sampling from cerebrospinal fluid could have higher diagnostic accuracy. The improvement of detection methods and more large-sample case-control studies are required in the future.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , DNA Tumoral Circulante , Glioma/diagnóstico , Glioma/genética , Biomarcadores Tumorais/análise , DNA Tumoral Circulante/análise , Humanos
10.
J Clin Neurosci ; 78: 444-445, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32741568

RESUMO

Sarcoidosis is uncommon multiple organ granulomatous disease of unknown etiology. Neurosarcoidosis occurs in about 5% of cases and most frequently follows systemic disease. We present a case of 52-years-old woman with a progressive hemifacial paresthesia and multiple enhancing dural based lesions. Resection of the right frontal mass allowed for the diagnosis to be made. The patient had no other features of sarcoidosis. Therefore, the diagnosis of neurosarcoidosis, especially when unaccompanied by systemic features can be challenging but should be considered in the differential diagnosis of multiple enhancing dural based tumours.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Hipestesia/diagnóstico , Doenças do Sistema Nervoso Central/etiologia , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Hipestesia/diagnóstico por imagem , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Sarcoidose/etiologia
11.
Brain Tumor Pathol ; 37(4): 127-135, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32627089

RESUMO

In recent years, the features of lymphomas associated with chronic inflammation, referred to as diffuse large B-cell lymphoma (DLBCL) associated with chronic inflammation (DLBCL-CI), have been elucidated. DLBCL-CI is an aggressive lymphoma occurring in the context of long-standing chronic inflammation and showing an association with Epstein-Barr virus. Fibrin-associated diffuse large B-cell lymphoma (F-DLBCL) was suggested as a new and unusual form of DLBCL-CI in the most recent version of the World Health Organization classification. From the perspective of genetics, DLBCL-CI was associated with frequent TP53 mutation, MYC amplification and complex karyotypes, but cases of F-DLBCL behaved indolently and showed a relatively lower genetic complexity. In the central nervous system (CNS), several examples of DLBCL-CI and F-DLBCL have been reported. As with DLBCL-CI outside the CNS, DLBCL-CI in the CNS is an aggressive lymphoma. However, the clinical outcome of F-DLBCL in the CNS is good. Immunohistochemistry for p53 and c-Myc in DLBCL-CI and F-DLBCL in the CNS showed similar findings of those outside the CNS. However, one aggressive case showed transitional genetics and morphology between F-DLBCL and DLBCL-CI. These findings suggest that some cases of F-DLBCL in the CNS might have the potential to progress to DLBCL-CI.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Progressão da Doença , Fibrina , Humanos , Inflamação , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Mutação , Proteínas Proto-Oncogênicas c-myc/genética , Proteína Supressora de Tumor p53/genética
12.
Int J Clin Oncol ; 25(6): 997-1003, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32468200

RESUMO

The updated 2016 World Health Organization (WHO) Classification of Tumours of the Central Nervous System (CNS) has incorporated molecular parameters into pathological diagnosis, for the first time in the molecular era. While it has led to the more precise diagnoses of well-understood entities and the better comprehension of less-understood entities, its practical application has also created some concerns whether or not genotypes predominate over phenotypes in tumor diagnostics. In response to these concerns, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official WHO (cIMAPCT-NOW) was established under the sponsorship of the International Society of Neuropathology to provide a forum to evaluate and recommend proposed changes to future CNS tumor classifications. cIMPACT has thus far published five updates on the proposal and clarification of existing and new terms and entities. Also, recent studies have shown that WHO grading based on histology has lost its prognostic relevance, which necessitates novel, improved grading criteria. We herein highlight the current status of clinical application of WHO 2016 classification and cIMPACT proposals, and the future endeavor to incorporate DNA methylation profiling of the CNS tumors for better clinical decision-making to achieve a goal of precision medicine for each patient with brain tumors.


Assuntos
Neoplasias do Sistema Nervoso Central/classificação , Neoplasias do Sistema Nervoso Central/diagnóstico , Glioma/classificação , Glioma/diagnóstico , Neuropatologia/normas , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Genótipo , Glioma/genética , Glioma/patologia , Humanos , Neuropatologia/organização & administração , Fenótipo , Prognóstico , Organização Mundial da Saúde
13.
Medicine (Baltimore) ; 99(14): e19598, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32243381

RESUMO

INTRODUCTION: Primary Central Nervous System Lymphoma (PCNSL) remains a diagnostic challenge due to the variable clinical manifestations. Liquid biopsies, particularly those involving cell-free DNA (cfDNA) from plasma, are rapidly emerging as important and minimally invasive adjuncts to traditional biopsies. However, conventional pathology may be still essential to obtain a diagnosis. PATIENT CONCERNS: A 56-year-old woman presented with a progressive headache, dizziness, blurred vision, and lower limbs weakness with dysesthesia. Atypical clinical and radiological presentations, previous empirical treatment in another hospital, together with the patient's refusal to stereotactic brain biopsy made it challenging to diagnose. Her status deteriorated continuously during hospitalization. DIAGNOSIS: Lumber punctual was performed, and CSF cytological analysis revealed malignancy cells with a high nuclear-cytoplasmic ratio. However, these cells were too loose to perform immunohistochemical stains. Genetic aberrations detections with CSF and peripheral blood sample were also inconclusive. We made a "cell-block" using the sedimentary cells collected from CSF collected through multiple aspirations via an Omaya reservoir. We further performed cytopathological and immunohistochemical analysis using this "cell-block," which finally confirmed the diagnosis of diffuse large-B cell PCNSL. INTERVENTIONS: Intracranial chemotherapy began afterwards (MTX 15 mg and dexamethasone 5 mg, twice per weeks). OUTCOMES: Unfortunately, this patient was dead 2 weeks later due to severe myelosuppression and secondary septic shock. CONCLUSION: We provided "cell-block" method, which collects cell components from large amount of CSF for cytology and immunohistochemical analysis. "Cell-block" cytology can be an alternative diagnostic method in diagnosis of PCNSL.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Citodiagnóstico/métodos , Linfoma Difuso de Grandes Células B/diagnóstico , Diagnóstico Diferencial , Evolução Fatal , Feminino , Humanos , Biópsia Líquida , Pessoa de Meia-Idade
14.
Jpn J Clin Oncol ; 50(5): 512-518, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32129443

RESUMO

BACKGROUND: Primary central nervous system lymphoma (PCNSL) responds relatively quickly to chemotherapy or radiotherapy. However, determination of a complete response after treatment is often difficult because of extremely light residual contrast enhancement on magnetic resonance images due to the effects of microhemorrhages and scar tissue formation. These small enhancing lesions define an unconfirmed complete response. The aim of this study was to investigate the usefulness of carbon-11-labeled methionine (11C-Met) positron-emission tomography (PET) for determining the treatment response of PCNSL. METHODS: Data for 36 patients who were treated for PCNSL between 2011 and 2015 and underwent magnetic resonance imaging and 11C-Met PET were reviewed. Magnetic resonance imaging findings were classified as complete response, unconfirmed complete response, and tumor mass (a composite of partial response, stable disease and progressive disease). PET images were evaluated, standardized uptake values were quantified, and the tumor-to-normal tissue count ratio (TNR) was calculated. Receiver operating characteristic curves were generated to determine the optimal cutoff TNRs. RESULTS: The optimal TNRs for differentiating complete response and unconfirmed complete response from tumor mass were 1.83 (area under the curve, 0.951) and 1.80 (area under the curve, 0.932), respectively. The corresponding sensitivity and specificity values for the diagnosis of tumor mass were 82.4 and 100%, respectively, in the complete response group and 85.3 and 85%, respectively, in the unconfirmed complete response group. CONCLUSIONS: A TNR of ≥1.80 can aid in the detection of active PCNSL using 11C-Met PET. Thus, 11C-Met-PET may be a useful tool for accurate evaluation of the treatment efficacy in PCNSL.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/terapia , Metionina/química , Tomografia por Emissão de Pósitrons , Adulto , Idoso , Neoplasias do Sistema Nervoso Central/diagnóstico , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Curva ROC , Resultado do Tratamento
15.
Cancer Genet ; 243: 19-47, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32203924

RESUMO

The period from the 1990s to the 2010s has witnessed a burgeoning sea change in the practice of surgical neuropathology due to the incorporation of genomic data into the assessment of a range of central nervous system (CNS) neoplasms. This change has since matured into the adoption of genomic information into the definition of several World Health Organization (WHO)-established diagnostic entities. The data needed to accomplish the modern diagnosis of CNS neoplasia includes DNA copy number aberrations that may be assessed through a variety of mechanisms. Through a review of the relevant literature and professional practice guidelines, here we provide a condensed and scored overview of the most critical DNA copy number aberrations to assess for a selection of primary CNS neoplasms.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Variações do Número de Cópias de DNA , Genômica/normas , Oncologia/normas , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/terapia , Tomada de Decisão Clínica , Humanos , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Prognóstico , Intervalo Livre de Progressão , Medição de Risco/métodos , Medição de Risco/normas
16.
J Pathol ; 250(5): 510-517, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32057098

RESUMO

Brain tumours are the most common tumour-related cause of death in young people. Survivors are at risk of significant disability, at least in part related to the effects of treatment. Therefore, there is a need for a precise diagnosis that stratifies patients for the most suitable treatment, matched to the underlying biology of their tumour. Although traditional histopathology has been accurate in predicting treatment responses in many cases, molecular profiling has revealed a remarkable, previously unappreciated, level of biological complexity in the classification of these tumours. Among different molecular technologies, DNA methylation profiling has had the most pronounced impact on brain tumour classification. Furthermore, using machine learning-based algorithms, DNA methylation profiling is changing diagnostic practice. This can be regarded as an exemplar for how molecular pathology can influence diagnostic practice and illustrates some of the unanticipated benefits and risks. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , Metilação de DNA/genética , Regulação Neoplásica da Expressão Gênica/genética , Patologia Molecular , Algoritmos , Biomarcadores Tumorais/genética , Neoplasias do Sistema Nervoso Central/patologia , Humanos , Patologia Molecular/métodos
17.
BMC Cancer ; 20(1): 120, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054467

RESUMO

BACKGROUND: The interaction of programmed death-1 protein (PD-1) and programmed death-1 ligand (PD-L1) produces immunosuppressive activity, protecting tumor cells from anti-tumor immunity and possibly releasing soluble PD-L1 (sPD-L1) from PD-L1 expressing tumor cells. Therefore, we measured serum levels of sPD-L1 in patients with primary central nervous system lymphoma (PCNSL) and explored its clinical implications. METHODS: Sixty-eight patients with newly diagnosed PCNSL had diffuse large B-cell lymphoma and were treated with high-dose methotrexate-containing chemotherapy. The measurement of sPD-L1 and cytokines was performed using serum samples archived at diagnosis, and the tissue expression of PD-L1 was also analyzed from archived paraffin-embedded tissue blocks. Disease relapse, progression-free survival (PFS), and overall survival (OS) were analyzed according to the extent of sPD-L1 in serum and PD-L1 in tissue. RESULTS: The median level of serum sPD-L1 (0.429 ng/mL) was higher than in healthy control patients (0.364 ng/mL). The occurrence of relapse was more frequent in the high sPD-L1 (78%) than the low sPD-L1 group (50%), though the groups did not have different clinical or pathological characteristics at diagnosis. As a result, the OS and PFS for the high sPD-L1 group were significantly lower than those in the low group. PD-L1-positive tumor cells were found in 35 patients (67%), and the extent of PD-L1-postive tumor cells was positively associated with serum sPD-L1 levels (r = 0.299, P = 0.031). Among the 34 cytokines analyzed, only the serum level of IL-7 correlated with the serum level of sPD-L1 (r = 0.521, P < 0.001). CONCLUSIONS: Serum levels of sPD-L1 could reflect the expression of PD-L1 in PCNSL tumor cells and predict patient survival outcomes. Therefore, sPD-L1 in serum could be a feasible biomarker for determining a risk-adapted treatment strategy for PCNSL patients. TRIAL REGISTRATION: The study population was patients who were diagnosed with PCNSL between January 2009 and February 2017 and registered for our prospective cohort studies after providing written informed consent (ClinicalTrials.gov: NCT00822731 [date of registration - January 14, 2009] and NCT01877109 [date of registration - June 13, 2013]).


Assuntos
Antígeno B7-H1/sangue , Biomarcadores Tumorais , Neoplasias do Sistema Nervoso Central/sangue , Linfoma Difuso de Grandes Células B/sangue , Adulto , Idoso , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/terapia , Citocinas/sangue , Feminino , Humanos , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Adulto Jovem
18.
Int J Mol Sci ; 21(3)2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32033160

RESUMO

This review highlights the added value of PET imaging in Central Nervous System (CNS) tumors, which is a tool that has rapidly evolved from a merely diagnostic setting to multimodal molecular diagnostics and the guidance of targeted therapy. PET is the method of choice for studying target expression and target binding behind the assumedly intact blood-brain barrier. Today, a variety of diagnostic PET tracers can be used for the primary staging of CNS tumors and to determine the effect of therapy. Additionally, theranostic PET tracers are increasingly used in the context of pharmaceutical and radiopharmaceutical drug development and application. In this approach, a single targeted drug is used for PET diagnosis, upon the coupling of a PET radionuclide, as well as for targeted (nuclide) therapy. Theranostic PET tracers have the potential to serve as a non-invasive whole body navigator in the selection of the most effective drug candidates and their most optimal dose and administration route, together with the potential to serve as a predictive biomarker in the selection of patients who are most likely to benefit from treatment. PET imaging supports the transition from trial and error medicine to predictive, preventive, and personalized medicine, hopefully leading to improved quality of life for patients and more cost-effective care.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/terapia , Tomografia por Emissão de Pósitrons/métodos , Nanomedicina Teranóstica/métodos , Animais , Biomarcadores/metabolismo , Neoplasias do Sistema Nervoso Central/metabolismo , Humanos , Medicina de Precisão/métodos , Compostos Radiofarmacêuticos/uso terapêutico
19.
Future Oncol ; 16(7): 269-279, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32043375

RESUMO

Aim: Trastuzumab prolongs progression-free and overall survival in HER2+ breast cancer (BC), but these are associated with increased distant recurrences and central nervous system metastases (CNSm). We retrospectively evaluated outcome and prognostic factors in CNSm and non-CNSm patients. Methods: Records of HER2+ BC treated in 2000-2017 were reviewed. Results: 283/1171 (24%) HER2+ BC patients developed metastatic disease. 109/283 patients (39%) have CNSm associated with worse prognosis and increased risk of death (hazard ratio: 4.7; 95% CI: 3.5-6.4). Prognostic factors were: number of CNSm (single vs multiple lesions; 3-year overall survival 39 vs 18%; p = 0.003); brain radiation (30 vs 14%; p < 0.001); new HER2-targeting therapies (30.6 vs 22.5%; p = 0.025). Conclusion: Prognosis of BC patients with CNSm has improved using HER2-targeting therapies but remains poor.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/secundário , Receptor ErbB-2/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/terapia , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/terapia , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Avaliação de Resultados da Assistência ao Paciente , Prognóstico , Receptor ErbB-2/genética , Resultado do Tratamento
20.
Int J Mol Sci ; 21(3)2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31979374

RESUMO

The neurotrophic tropomyosin receptor kinase (NTRK) genes (NTRK1, NTRK2, and NTRK3) code for three transmembrane high-affinity tyrosine-kinase receptors for nerve growth factors (TRK-A, TRK-B, and TRK-C) which are mainly involved in nervous system development. Loss of function alterations in these genes can lead to nervous system development problems; conversely, activating alterations harbor oncogenic potential, promoting cell proliferation/survival and tumorigenesis. Chromosomal rearrangements are the most clinically relevant alterations of pathological NTRK activation, leading to constitutionally active chimeric receptors. NTRK fusions have been detected with extremely variable frequencies in many pediatric and adult cancer types, including central nervous system (CNS) tumors. These alterations can be detected by different laboratory assays (e.g., immunohistochemistry, FISH, sequencing), but each of these approaches has specific advantages and limitations which must be taken into account for an appropriate use in diagnostics or research. Moreover, therapeutic targeting of this molecular marker recently showed extreme efficacy. Considering the overall lack of effective treatments for brain neoplasms, it is expected that detection of NTRK fusions will soon become a mainstay in the diagnostic assessment of CNS tumors, and thus in-depth knowledge regarding this topic is warranted.


Assuntos
Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/metabolismo , Fusão Gênica , Glicoproteínas de Membrana/genética , Inibidores de Proteínas Quinases/uso terapêutico , Receptor trkA/genética , Receptor trkB/genética , Receptor trkC/genética , Animais , Biomarcadores Tumorais/genética , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Humanos , Glicoproteínas de Membrana/metabolismo , Medicina de Precisão , Receptor trkA/metabolismo , Receptor trkB/metabolismo , Receptor trkC/metabolismo , Transdução de Sinais/genética
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