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BACKGROUND: Brain metastases (BMs) are the most serious complication of lung cancer, affecting the prognosis of lung cancer patients, and pose distinct clinical challenges. This study was designed to explore the prognostic factors related to lung cancer BM and the value of surgical resection in BMs from lung cancer. METHODS: A retrospective analysis was performed on 714 patients with lung cancer BMs screened between January 2010 and January 2018 at the Sun Yat-sen University Cancer Center. A 1:1 propensity score matching analysis was performed to reduce the potential bias between the surgery and the nonsurgery group. In both the raw and the propensity-score matched dataset, univariate and multivariate Cox proportional hazards regression analyses were used to evaluate risk factors for survival. RESULTS: After matching, 258 patients (129 surgery, 129 no surgery) were analyzed. Multivariate analyses after propensity score matching demonstrated that surgical resection was an independent protective factor for overall survival (OS), and older age, lower Karnofsky Performance Scale (KPS) score, and extracranial metastases were independent risk factors for worse OS. Patients without extracranial metastases, without synchronous BM and with a single BM had a better prognosis. CONCLUSIONS: The findings showed that surgical resection, age, KPS score, and extracranial metastases are independent prognostic factors for predicting the OS of patients with lung cancer BMs, and surgical resection for brain metastatic lesions could significantly improve the OS. However, only certain groups of patients with BMs can benefit from intracranial lesion resection, such as no extracranial metastases and metachronous metastases.
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Neoplasias Encefálicas , Neoplasias Pulmonares , Neoplasias Encefálicas/secundário , Estudos de Coortes , Humanos , Neoplasias Pulmonares/patologia , Prognóstico , Estudos RetrospectivosRESUMO
INTRODUCTION: Surgical resection of medulloblastoma (MB) remains a challenge. At present, a variety of tracers have been used for intraoperative tumor visualization. However, there are few reports on the intraoperative visualization of MB. Hence, we reported our experience of applying fluorescein sodium (FS) in MB surgery. METHODS: We retrospectively analyzed the clinical information of patients with MB confirmed by surgery and pathology from January 2016 to December 2020 from Sun Yat-sen University Cancer Center. A total of 62 patients were enrolled, of which 27 received intraoperative FS and 35 did not. The intraoperative dose of FS was 3 mg/kg. RESULTS: Among the 62 patients, 42 were males, and twenty were females. The age of onset in the FS group was 9.588 ± 7.322, which in the non-fluorescein sodium group was 13.469 ± 10.968, p = 0.198. We did not find significant differences in tumor location, tumor size, tumor resection, tumor histology, and preoperative symptoms (hydrocephalus, headache, vomit, balance disorder) between the groups. There was no significant difference in the postoperative symptoms (hydrocephalus, headache, vomiting, balance disorder, and cerebellar mutism). However, patients in the FS group had a relatively low incidence of balance disorder and cerebellar mutism. There was definite fluorescence of tumor in all cases of the FS group, and even the tiny metastatic lesion was visible. No case had side effects related to the use of FS. CONCLUSIONS: FS is safe and effective in MB surgery. Whether the application of FS for surgery can reduce complications remains to be studied in the future.
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Neoplasias Cerebelares , Hidrocefalia , Meduloblastoma , Mutismo , Neoplasias Cerebelares/epidemiologia , Feminino , Fluoresceína , Cefaleia , Humanos , Hidrocefalia/complicações , Masculino , Meduloblastoma/complicações , Meduloblastoma/diagnóstico , Meduloblastoma/cirurgia , Mutismo/etiologia , Estudos Retrospectivos , SódioRESUMO
We aimed to develop a high-throughput deep DNA sequencing assay of cerebrospinal fluid (CSF) to identify clinically relevant oncogenic mutations that contribute to the development of glioblastoma (GBM) and serve as biomarkers to predict patients' responses to surgery. For this purpose, we recruited five patients diagnosed with highly suspicious GBM according to preoperative magnet resonance imaging. Subsequently, patients were histologically diagnosed with GBM. CSF was obtained through routine lumbar puncture, and plasma from peripheral blood was collected before surgery and 7 days after. Fresh tumor samples were collected using routine surgical procedures. Targeted deep sequencing was used to characterize the genomic landscape and identify mutational profile that differed between pre-surgical and post-surgical samples. Sequence analysis was designed to detect protein-coding exons, exon-intron boundaries, and the untranslated regions of 50 genes associated with cancers of the central nervous system. Circulating tumor DNAs (ctDNAs) were prepared from the CSF and plasma from peripheral blood. For comparison, DNA was isolated from fresh tumor tissues. Non-silent coding variants were detected in CSF and plasma ctDNAs, and the overall minor allele frequency (MAF) of the former corresponded to an earlier disease stage compared with that of plasma when the tumor burden was released (surgical removal). Gene mutation loads of GBMs significantly correlated with overall survival (OS, days) (Pearson correlationâ¯=â¯-0.95, Pâ¯=â¯0.01). We conclude that CSF ctDNAs better reflected the sequential mutational changes of driver genes compared with those of plasma ctDNAs. Deep sequencing of the CSF of patients with GBM may therefore serve as an alternative clinical assay to improve patients' outcomes.
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Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Glioblastoma/genética , Proteínas de Neoplasias/genética , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/líquido cefalorraquidiano , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/líquido cefalorraquidiano , Intervalo Livre de Doença , Feminino , Glioblastoma/sangue , Glioblastoma/líquido cefalorraquidiano , Glioblastoma/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/líquido cefalorraquidiano , Resultado do TratamentoRESUMO
BACKGROUND: Surgical procedures are critical in making a conclusive histopathological diagnosis of primary central nervous system lymphoma (PCNSL), which typically presents contrast-enhancing lesions in magnetic resonance imaging (MRI). The fluorescein sodium-guided technique could enhance tumor visibility. We reported a series of patients with PCNSL underwent fluorescein sodium-guided surgical procedures. PATIENTS AND METHODS: 12 patients clinically considered brain tumors underwent fluorescein sodium-guided surgery in Sun Yat-sen University Cancer Center from March 2016 to July 2017. The age of 4 female and 8 male patients ranges from 39 to 62 years. In 4 patients, corticosteroid had been prescribed before surgery due to intracranial hypertension. After injection of low dose of sodium fluorescein (3-5 mg/kg), the lesions with strong fluorescence staining were identified as the target area for biopsy or resection. RESULTS: Based on the targeted tissues with bright and homogenous fluorescence staining, all 12 patients were conclusively diagnosed as B cell non-Hodgkin's lymphoma (diffuse large cell). The specificity of the specimens sent for frozen section was 86.4% (19/22). No fluorescein sodium associated side effects were observed. CONCLUSION: Fluorescein sodium guided surgery is an effective and safe tool in biopsy or tumor resection in patients suspicious for PCNSL with preoperative MRI presented contrast-enhanced homogenous lesions. Such technique might still be considered in those patients who have been pretreated with corticosteroid.
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Neoplasias Encefálicas/cirurgia , Meios de Contraste , Fluoresceína , Biópsia Guiada por Imagem , Linfoma/cirurgia , Cirurgia Assistida por Computador , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Feminino , Humanos , Linfoma/diagnóstico por imagem , Linfoma/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Procedimentos NeurocirúrgicosRESUMO
Preoperative prognostic nutritional index (PNI) has been widely demonstrated to predict survival of patients with malignant tumors. Its utility in predicting outcomes in patients with high-grade gliomas (HGG) remains undefined. A retrospective study of 188 HGG patients was conducted. An optimal PNI cut-off value was applied to stratify patients into high PNI (≥52.55, n = 78) and low PNI (<52.55, n = 110) groups. Univariate and multivariate analysis was performed to identify prognostic factors associated with overall survival (OS) and progression free survival (PFS). The resulting prognostic models were externally validated using a demographic-matched cohort of 130 HGG patients. In the training set, PNI value was negatively correlated with age (p = 0.027) and tumor grade (p = 0.048). Both PFS (8.27 vs. 20.77 months, p < 0.001) and OS (13.57 vs. 33.23 months, p < 0.001) were significantly worse in the low PNI group. Strikingly, patients in high PNI group had a 52% decrease in the risk of tumor progression and 55% decrease of death relative to low PNI. Multivariate analysis further demonstrated PNI as an independent predictor for PFS (HR = 0.62, 95% CI 0.43-0.87) and OS (HR = 0.56, 95% CI 0.38-0.80). The PNI retained independent prognostic value in the validation set for both PFS (p = 0.013) and OS (p = 0.003). On subgroup analysis by tumor grade and treatment modalities, both PFS and OS were better for the patients with high PNI. The PNI is a potentially valuable preoperative marker for the survival of patients following HGG resection.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidade , Glioma/diagnóstico , Glioma/mortalidade , Avaliação Nutricional , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Neoplasias Encefálicas/cirurgia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Glioma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to build a convolutional neural network (CNN)-based prediction model of glioblastoma (GBM) molecular subtype diagnosis and prognosis with multimodal features. METHODS: In total, 222 GBM patients were included in the training set from Sun Yat-sen University Cancer Center (SYSUCC) and 107 GBM patients were included in the validation set from SYSUCC, Xuanwu Hospital Capital Medical University, and the First Hospital of Jilin University. The multimodal model was trained with MR images (pre- and postcontrast T1-weighted images and T2-weighted images), corresponding MRI impression, and clinical patient information. First, the original images were segmented using the Multimodal Brain Tumor Image Segmentation Benchmark toolkit. Convolutional features were extracted using 3D residual deep neural network (ResNet50) and convolutional 3D (C3D). Radiomic features were extracted using pyradiomics. Report texts were converted to word embedding using word2vec. These three types of features were then integrated to train neural networks. Accuracy, precision, recall, and F1-score were used to evaluate the model performance. RESULTS: The C3D-based model yielded the highest accuracy of 91.11% in the prediction of IDH1 mutation status. Importantly, the addition of semantics improved precision by 11.21% and recall in MGMT promoter methylation status prediction by 14.28%. The areas under the receiver operating characteristic curves of the C3D-based model in the IDH1, ATRX, MGMT, and 1-year prognosis groups were 0.976, 0.953, 0.955, and 0.976, respectively. In external validation, the C3D-based model showed significant improvement in accuracy in the IDH1, ATRX, MGMT, and 1-year prognosis groups, which were 88.30%, 76.67%, 85.71%, and 85.71%, respectively (compared with 3D ResNet50: 83.51%, 66.67%, 82.14%, and 70.79%, respectively). CONCLUSIONS: The authors propose a novel multimodal model integrating C3D, radiomics, and semantics, which had a great performance in predicting IDH1, ATRX, and MGMT molecular subtypes and the 1-year prognosis of GBM.
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Foxp3+ regulatory T cells (Treg) play an important part in the glioma immunosuppressive microenvironment. This study analyzed the effect of Foxsp3 on the immune microenvironment and constructed a Foxp3-related immune prognostic signature (IPS)for predicting prognosis in glioblastoma multiforme (GBM). Immunohistochemistry (IHC) staining for Foxp3 was performed in 72 high-grade glioma specimens. RNA-seq data from 152 GBM samples were obtained from The Cancer Genome Atlas database (TCGA) and divided into two groups, Foxp3 High (Foxp3_H) and Foxp3 Low (Foxp3_L), based on Foxp3 expression. We systematically analyzed the influence of Foxp3 on the immune microenvironment. Least Absolute Shrinkage and Selection Operator (LASSO) Cox analysis was conducted for immune-related genes that were differentially expressed between Foxp3_H and Foxp3_L GBM patients. We found a differential expression of Foxp3 in high-grade glioma tissues. The presence of Foxp3 was significantly associated with poor OS. From the four-gene IPS developed, GBM patients were stratified into low-risk and high-risk groups in both the training set and validation sets. Furthermore, we developed a novel nomogram to evaluate the overall survival in GBM patients. This study offers innovative insights into the GBM immune microenvironment and these findings contribute to individualized treatment and improvement in the prognosis for GBM patients.
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Neoplasias Encefálicas/genética , Fatores de Transcrição Forkhead/genética , Glioblastoma/genética , Microambiente Tumoral/genética , Neoplasias Encefálicas/imunologia , Feminino , Fatores de Transcrição Forkhead/imunologia , Perfilação da Expressão Gênica , Glioblastoma/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA-Seq , Taxa de Sobrevida , Transcriptoma , Microambiente Tumoral/imunologiaRESUMO
Enhancer RNAs, a type of long non-coding RNAs (lncRNAs), play a critical role in the occurrence and development of glioma. RNA-seq data from 161 glioblastoma multiforme (GBM) samples were acquired from The Cancer Genome Atlas database. Then, 70 eRNAs were identified as prognosis-related genes, which had significant relations with overall survival (log-rank test, p < 0.05). AC003092.1 was demonstrated as an immune-related eRNA by functional enrichment analysis. We divided samples into two groups based on AC003092.1 expression: AC003092.1 High (AC003092.1_H) and AC003092.1 Low (AC003092.1_L) and systematically analyzed the influence of AC003092.1 on the immune microenvironment by single-sample gene-set enrichment analysis and CIBERSORTx. We quantified AC003092.1 and TFPI2 levels in 11 high-grade gliomas, 5 low-grade gliomas, and 7 GBM cell lines. Our study indicates that AC003092.1 is related to glioma-immunosuppressive microenvironment, and these results offer innovative sights into GBM immune therapy.
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BACKGROUND: Cerebrospinal fluid (CSF) has been demonstrated as a better source of circulating tumor DNA (ctDNA) than plasma for brain tumors. However, it is unclear whether whole exome sequencing (WES) is qualified for detection of ctDNA in CSF. The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma. METHODS: CSFs of ten glioblastoma patients were collected pre-operatively at the Department of Neurosurgery, Sun Yat-sen University Cancer Center. ctDNA in CSF and genome DNA in the resected tumor were extracted and subjected to WES. The identified glioblastoma-associated mutations from ctDNA in CSF and genome DNA in the resected tumor were compared. RESULTS: Due to the ctDNA in CSF was unqualified for exome sequencing for one patient, nine patients were included into the final analysis. More glioblastoma-associated mutations tended to be detected in CSF compared with the corresponding tumor tissue samples (3.56â±â0.75 vs. 2.22â±â0.32, Pâ=â0.097), while the statistical significance was limited by the small sample size. The average mutation frequencies were similar in CSF and tumor tissue samples (74.1%â±â6.0% vs. 73.8%â±â6.0%, Pâ=â0.924). The R132H mutation of isocitrate dehydrogenase 1 and the G34V mutation of H3 histone, family 3A (H3F3A) which had been reported in the pathological diagnoses were also detected from ctDNA in CSF by WES. Patients who received temozolomide chemotherapy previously or those whose tumor involved subventricular zone tended to harbor more mutations in their CSF. CONCLUSION: Assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma, which may provide useful information for the decision of treatment strategy.
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DNA Tumoral Circulante , Glioblastoma , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Genômica , Glioblastoma/genética , Humanos , Mutação/genética , Sequenciamento do ExomaRESUMO
BACKGROUND: Skull base meningioma surgery is often difficult and complicated to perform. Therefore, this study aims to investigate the effectiveness of 3-dimensional (3D)-printed models of skull base meningioma in the representation of anatomical structures, the simulation of surgical plans, and patient education on surgical outcomes. METHODS: A retrospective study of 35 patients (3D group: 19 patients and non-3D group: 16 patients) with skull base meningioma was conducted. Mimics software was used to create 3D reconstructions (with the skull, blood vessels, nerves, and tumors set to different colors), and 3D solid models were printed to determine the surgical protocols and communication pathways with the patient. RESULTS: The 3D-printed model can visually display the relationship of different structures, including the skull, blood vessels, cranial nerves, and tumors. The surgeon should select the proper surgical approaches before surgery through the model and pay attention to protecting the important structures during the operation. According to the models, the surgeon should cut off the blood supply to the tumor to reduce intraoperative bleeding. For patients with skull base bone destruction, the skull base repair should be prepared in advance. Patients and their families should have a thorough understanding of the disease through the model, and there should be effective communication between doctors and patients. CONCLUSIONS: The 3D-printed model of a skull base meningioma can present the structures in a detailed manner and facilitate in helping the surgeon to develop a surgical plan. At the same time, it helps patients and their families to understand the condition and the surgical plan, which is conducive to better patient education.
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BACKGROUND: The present study explored the predictive value of systemic inflammatory indexes in diagnosing grade III gliomas of oligodendroglial origin. METHODS: A retrospective study of 154 patients with grade III gliomas was conducted. Systemic inflammatory indexes, including neutrophil-to-lymphocyte ratio (NLR), albumin-to-gamma-glutamyl transferase ratio (AGR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, prognostic nutritional index, and fibrinogen-to-albumin ratio, were reviewed. The resulting predictive model was externally validated using a demographic-matched cohort of 49 grade III glioma patients. RESULTS: In the training set, gliomas of oligodendroglial origin tended to have a lower NLR (P=0.018) and a higher AGR (P=0.036) than those with tumors of astrocytic origin. Moreover, both NLR and AGR had predictive value for oligodendroglial tumors, when compared with astrocytic tumors. The best diagnostic value was obtained using NLR + AGR (AUC =64.9%, 95% CI: 55.5-74.3%, P=0.005). In the validation set, NLR + AGR satisfactorily predicted the presence of oligodendroglial tumors (AUC =66.5%, 95% CI: 50.6-82.4%, P<0.05) and co-deletion of 1p/19q (AUC =73.7%, 95% CI: 59.2-88.1%, P=0.005). Multivariate analysis further demonstrated NLR + AGR as an independent predictor for overall survival. CONCLUSIONS: Pretreatment NLR and AGR aid in prognosis and diagnosing grade III oligodendroglial gliomas.
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To date the management of glioma remains a great challenge in cancer therapy worldwide. The identification of novel diagnostic and therapeutic methods is required. Although there is data indicating that matrix metalloproteinase (MMP)-26 serves an important role in many human cancer types, its clinical significance in glioma remains uncertain. The present study aimed to evaluate MMP-26 expression in human astrocytic glioma specimens, and investigate its role and significance in the progression of astrocytic glioma. Immunohistochemistry was performed to assess MMP-26 expression in astrocytic glioma tissues. The levels of MMP-26 expression and its relevance to the clinicopathological features and prognostic factors in patients with astrocytic glioma patients were then investigated. The results demonstrated that MMP-26 expression was significantly assocaited with the World Health Organization grade (P<0.05). Additionally, it was identified that MMP-26 expression was an effective predictor of the overall survival of patients with astrocytic glioma (P<0.05). Analyses of univariate and multivariate Cox regression confirmed that MMP-26 expression was an independent factor for evaluating the prognosis of astrocytic glioma patients (P<0.05). The current results support that MMP-26 may be a novel indicator of diagnosis and an independent factor for evaluating prognosis in patients with glioma.
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OBJECTIVE: The aim of this single-institution cohort study is to describe clinical characteristics of patients with breast cancer brain metastases (BCBM), to investigate survival after diagnosis of brain metastases (BM), and to assess the aggressive treatments to BCBM. PATIENTS AND METHODS: We identified 134 consecutive patients diagnosed with operable breast cancer and then who developed BM at the Sun Yat-sen University Cancer Center from 2000 to 2015, and analyzed the therapeutic methods for primary breast cancer and BM to evaluate whether they were associated with longer survival after the development of BM. The median age at breast cancer diagnosis was 47 years (range 21-73 years). RESULTS: The median survival after BM was 16.2 months (range 12.1-20.3 months), and the survival rates were 62% and 37% at 1 and 2 years, respectively. Multivariate analysis showed that craniotomy (pâ¯=â¯0.034) and targeted therapy (pâ¯<â¯0.001) for BCBM were positively correlated with survival after diagnosis of BM; radiotherapy (pâ¯=â¯0.024) after surgery for primary breast cancer was beneficial to BM. CONCLUSIONS: Surgical resection and targeted therapy are effective treatment for BCBM. Radiotherapy after surgery for the management of primary breast cancer is necessary in patients with brain progression later.
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Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/mortalidade , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/mortalidade , Adulto , Idoso , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Neoplasias da Mama/cirurgia , Estudos de Coortes , Craniotomia/mortalidade , Craniotomia/tendências , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida/tendências , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: The presence of brain metastasis (BM) in patients with colorectal cancer (CRC) is usually associated with terminal-stage illness; however, a subgroup of patients receiving aggressive treatment can have a satisfactory prognosis. This study was designed to investigate the profile of prognostic factors in CRC patients with BM treated aggressively. PATIENTS AND METHODS: CRC patients with BM were retrospectively reviewed. Survival analysis was performed to identify potential prognostic factors in the entire cohort of patients and a subgroup of patients treated aggressively. Aggressive treatments included surgical resection, radiotherapy, and/or chemotherapy. Overall survival was defined as the time between the diagnosis of BM and death or until the date of the last follow-up visit. RESULTS: A total of 78 CRC patients were confirmed as having BM. Sixty-eight of them had extracranial metastases at the time of their BM diagnosis. The most common sites of extracranial metastases were lung (n=51, 65.4%), followed by liver (n=25, 32.1%) and bone (n=12, 15.4%). Fifty-one patients who were treated aggressively had significantly longer overall survival than those who accepted palliative care (14.1 months vs 2.0 months, P<0.0001). Multivariate analysis was applied, and the results showed that aggressive treatment (n=51), recursive partitioning analysis class I/II (hazard ratio [HR]=0.27, 95% CI: 0.12-0.6, P=0.001), and fewer BM (HR=0.4, 95% CI: 0.21-0.78, P=0.07) predicted longer survival. In contrast, the presence of bone metastasis, rather than lung or liver metastasis, at the time of diagnosis of BM (HR=2.38, 95% CI: 1.08-5.28, P=0.032) predicted a poor prognosis. CONCLUSIONS: Although the prognosis of CRC patients having BM is frequently very poor, those with good performance status and few brain lesions responded to aggressive treatment, while those with bone metastasis at the time of diagnosis of BM had relatively dismal survival rates, even when treated aggressively.
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This retrospective study was designed to determine the prognostic value of a cumulative score (FA score) based on pretreatment plasma fibrinogen and serum albumin levels for 326 patients newly diagnosed high-grade glioma (HGG). Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off values. Univariate and multivariate analysis were performed to evaluate the independent prognostic value of the FA scores associated with overall survival (OS) and progression-free survival (PFS). The optimal cut-off values were 2.815 g/L for fibrinogen and 43.65 g/L for albumin. PFS and OS were significantly worse for patients with higher FA scores. Patients with elevated fibrinogen level and decreased albumin levels had 3.00-fold higher risk of tumor progression and had a 3.23-fold higher risk of death compared with those with normal values. Multivariate analysis demonstrated FA score was an independent predictive factor for PFS and OS. Moreover, PFS and OS were better for the patients with lower FA score, either in patients with grade III or IV gliomas. These findings indicated that the pretreatment FA score could serve as a simple and noninvasive marker to predict the prognosis of patients with HGG.
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Fibrinogênio , Glioma/sangue , Glioma/diagnóstico , Albumina Sérica , Adolescente , Adulto , Idoso , Biomarcadores Tumorais , Criança , Pré-Escolar , Feminino , Glioma/mortalidade , Glioma/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Adulto JovemRESUMO
Currently, immunotherapy by blocking the immune checkpoint inhibitors, such as anti-PD-1, has been carried out in many clinical studies on recurrent glioma, and the preliminary results are satisfactory, which provides a rationale for the exploration of immune checkpoint inhibitors in glioma. B7-H6 is a newly discovered member of the B7 family, which triggers antitumor of natural killer cell cytotoxicity and cytokine secretion by binding the NKp30 receptor. B7-H6 mRNA and protein expressions, which are not detected in normal tissues, are expressed mainly on the cell surface of various primary tumors and cell lines. However, up until now, there is no data about the clinical significance of B7-H6 expression in astrocytoma patients. The present study provides an investigation on the relationship between prognostic and clinical value of B7-H6 protein in astrocytoma tissues. All the astrocytic glioma tissues were stained for B7-H6. Immunohistochemistry stain of 122 astrocytoma samples showed that immunoreactivity of B7-H6 was seen predominantly in the cytoplasm. The B7-H6 expression did not show significant relevance with patient age, sex distribution, Karnofsky performance status score, extent of resection, and tumor location in astrocytoma patients, but B7-H6 positive expression is significantly associated with World Health Organization grade (P=0.046). However, the survival rate after operation presented no significant difference of B7-H6 expression in astrocytoma patients. Kaplan-Meier analysis and the log-rank test revealed that B7-H6 expression cannot predict the overall survival. In all, it seems that the B7-H6 expression might be a marker to differentiate the World Health Organization grade level of astrocytoma, but the prognosis value of B7-H6 in astrocytoma should be studied in detail.
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Zoledronic acid (ZA) has been tested in clinical trials as an additive therapy for early-stage breast cancer. However, the mechanism by which ZA exerts its antitumor activity is still unclear. The aim of this study is to investigate whether the prevention of tumor growth by ZA is through regulating the mesenchymal stem cells (MSC)-monocyte chemotactic protein 1 (MCP-1)-macrophages axis in the tumor microenvironment. To address this issue, MDA-MB-231-FLUC human breast cancer cells were cultured and injected either alone, or coupled with MSC into the mammary fat pads of nude mice. MSC were treated with either ZA or untreated. Tumor growth was determined by using an in vivo bioluminescence imaging (BLI) and the tumor-associated macrophages (TAMs) in tumor tissues were immunohistochemically analyzed by using CD206 antibody. The effects of ZA on the cytokine related gene expression of MSC were assessed by using real-time PCR. In this study, we found that ZA-treated mice showed a significant delay in tumor growth. In addition, our data revealed that ZA weakened the ability of MSC to promote tumor growth by impairing TAMs recruitment and tumor vascularization. Furthermore, it was found that ZA decreased MCP-1 expression of MSC, and therefore reduced the recruitment of TAMs to the tumor sites and hence inhibited the tumor growth. Altogether, our study demonstrated ZA can prevent the tumor-promoting effects of MSC. The antitumor effects of ZA were caused by decreasing the MCP-1 expression of MSC, which further decreased the infiltration of TAMs into tumor sites, and therefore inhibited the tumor growth.