Purpose:The present study summarized cases of children(n=32)with medulloblastoma(MB)who were treated using stratified therapy based on risk grading and also discussed the factors affecting prognosis.Methods:According ...Purpose:The present study summarized cases of children(n=32)with medulloblastoma(MB)who were treated using stratified therapy based on risk grading and also discussed the factors affecting prognosis.Methods:According to the risk stratification criteria,the cases were divided into the following four risk groups:low,standard,high,and very high.The 5-year overall survival(OS)and progression-free survival(PFS)rates were summarized.Further,the effects on the prognosis of tumor size,tumor stage,degree of resection,treatment mode,metastatic recurrence,molecular typing,and risk stratification were analyzed.Results:In the present study,following surgery,3 cases abandoned radiotherapy(RT)and chemotherapy(CHT),7 cases(<3 years of age)received only CHT,and 22 cases received combined RT and CHT.Total and near-total tumor resections were performed in 29 cases(90.6%).Subtotal resections were performed in 3 cases,and there were no surgery-related deaths.The average follow-up duration was 47 months.The average 5-year PFS and OS rates were 57.3%±7.2%and 68.7%±8.6%,respectively.The OS and PFS rates were significantly correlated with tumor-risk stratification,molecular staging,tumor stage,treatment mode,and recurrence after surgery(p<0.01).The degree of tumor resection,pathological type,and the presence of preoperative implantation were secondary factors affecting the prognosis(p<0.05).Age was correlated with the PFS rate.There was no correlation between age/tumor location/tumor size and prognosis(p>0.05).Favorable prognostic factors in the low-and standard-risk groups were stage M0,wingless-type MB,postoperative RT combined with CHT,no postoperative recurrence,age≥3 years,and total tumor resection.Conclusions:Personalized treatment strategies based on the risk stratification of MB and postoperative stratified comprehensive treatment could help improve the prognosis for MB.展开更多
Medulloblastoma(MB)is considered the commonest malignant brain tumor in children.Multimodal treatments consisting of surgery,radiation,and chemotherapy have improved patients’survival.Nevertheless,the recurrence occu...Medulloblastoma(MB)is considered the commonest malignant brain tumor in children.Multimodal treatments consisting of surgery,radiation,and chemotherapy have improved patients’survival.Nevertheless,the recurrence occurs in 30%of cases.The persistent mortality rates,the failure of current therapies to extend life expectancy,and the serious complications of non-targeted cytotoxic treatment indicate the need for more refined therapeutic approaches.Most MBs originating from the neurons of external granular layer line the outer surface of neocerebellum and responsible for the afferent and efferent connections.Recently,MBs have been segregated into four molecular subgroups:Wingless-activated(WNT-MB)(Group 1);Sonichedgehog-activated(SHH-MB)(Group 2);Group 3 and 4 MBs.These molecular alterations follow specific gene mutations and disease-risk stratifications.The current treatment protocols and ongoing clinical trials against these molecular subgroups are still using common chemotherapeutic agents by which their efficacy have improved the progression-free survival but did not change the overall survival.However,the need to explore new therapies targeting specific receptors in MB microenvironment became essential.The immune microenvironment of MBs consists of distinctive cellular heterogeneities including immune cells and none-immune cells.Tumour associate macrophage and tumour infiltrating lymphocyte are considered the main principal cells in tumour microenvironment,and their role are still under investigation.In this review,we discuss the mechanism of interaction between MB cells and immune cells in the microenvironment,with an overview of the recent investigations and clinical trials.展开更多
This research work develops new and better prognostic markers for predicting Childhood MedulloBlastoma(CMB)using a well-defined deep learning architecture.A deep learning architecture could be designed using ideas fro...This research work develops new and better prognostic markers for predicting Childhood MedulloBlastoma(CMB)using a well-defined deep learning architecture.A deep learning architecture could be designed using ideas from image processing and neural networks to predict CMB using histopathological images.First,a convolution process transforms the histopathological image into deep features that uniquely describe it using different two-dimensional filters of various sizes.A 10-layer deep learning architecture is designed to extract deep features.The introduction of pooling layers in the architecture reduces the feature dimension.The extracted and dimension-reduced deep features from the arrangement of convolution layers and pooling layers are used to classify histopathological images using a neural network classifier.The performance of the CMB classification system is evaluated using 1414(10×magnification)and 1071(100×magnification)augmented histopathological images with five classes of CMB such as desmoplastic,nodular,large cell,classic,and normal.Experimental results show that the average classification accuracy of 99.38%(10×)and 99.07%(100×)is attained by the proposed CNB classification system.展开更多
Medulloblastoma(MB)is the most common childhood embryonal malignant tumour in the central nervous system.The diagnosis,prognosis and therapeutic targets of MB depend on the molecular characteristics of the tumor,and i...Medulloblastoma(MB)is the most common childhood embryonal malignant tumour in the central nervous system.The diagnosis,prognosis and therapeutic targets of MB depend on the molecular characteristics of the tumor,and it is a great challenge to obtain the tissue samples from the patients with brain tumor.Genomic changes found in cell-free DNA(cfDNA)of cerebrospinal fluid(CSF)can predict genomic changes present in tumor tissue,fluid biopsy of CSF can detect the genomic profile of tumor-associated cfDNA and evaluate cfDNA as a marker of measurable residual disease(MRD)in a relatively noninvasive manner,which provides the evidence of"individualized precision therapy"for MB patients.In this paper,we reviewed the recent studies in medulloblastoma based on cfDNA Liquid Biopsy of CSF.展开更多
Medulloblastoma(MB)is a form of malignant brain tumor that predominantly arises in infants and children,of which approximately 25%is due to upregulation of canonical Wnt pathway with mainly mutations in CTNNB1.Therefo...Medulloblastoma(MB)is a form of malignant brain tumor that predominantly arises in infants and children,of which approximately 25%is due to upregulation of canonical Wnt pathway with mainly mutations in CTNNB1.Therefore,Wnt inhibitors could offer rational therapeutic strategies and chemoprevention for this malignant cancer.In our present study,we undertook a screening for antagonists of Wnt signaling from 600 natural compounds,and identified Ginkgetin,a biflavone isolated from Cephalotaxus fortunei var.alpina.Ginkgetin inhibited Wnt pathway with an IC50 value around 5.92 lM and structure–activity relationship analysis suggested the methoxy group in Ginkgetin as a functional group.Biflavone Ginkgetin showed obvious cytotoxicity in Daoy and D283 MB cells.Cell cycle analysis by flow cytometry showed that Ginkgetin induced efficiently G2/M phase arrest in Daoy cells.Further mechanism studies showed that Ginkgetin reduced the expression of Wnt target genes,including Axin2,cyclinD1 and survivin in MB cells.The phosphorylation level of b-catenin also decreased in a time-and concentration-dependent manner.Collectively,our data suggest that Ginkgetin is a novel inhibitor of Wnt signaling,and as such warrants further exploration as a promising antimedulloblastoma candidate.展开更多
Medulloblastoma (MB) is a malignant brain tumor with a usual potential for leptomeningeal spread. Intramedullary metastases of MB are rare and there are very few cases reported in the literature. Here, we report the c...Medulloblastoma (MB) is a malignant brain tumor with a usual potential for leptomeningeal spread. Intramedullary metastases of MB are rare and there are very few cases reported in the literature. Here, we report the case of an 18-year-old man with intramedullary spinal cord metastasis of MB occurring 9 years after the first diagnosis. The patient presented a 2-month history of progressive weakness in both lower limbs associated with urinary incontinence. Magnetic resonance imaging (MRI) demonstrated a large intramedullary spinal cord tumor extending from T10 to L1. The patient underwent surgical decompression and adjuvant therapy. Histological examination confirmed the diagnosis of classic MB metastasis. Postoperatively, the neurological status was stationary. Intramedullary metastasis of medulloblastoma is rare and difficult to manage with a poor prognosis. Comprehensive studies on the medulloblastoma dissemination mechanisms and clinical trials are needed to assess combined therapeutic approaches on metastases of MB.展开更多
PURPOSE:To review the efficacy and patterns of failure in average-risk medulloblastoma patients treated withconcurrent chemotherapy and reduced-dose cranial spinal irradiation and a conformal tumor bed boost.METH-ODS ...PURPOSE:To review the efficacy and patterns of failure in average-risk medulloblastoma patients treated withconcurrent chemotherapy and reduced-dose cranial spinal irradiation and a conformal tumor bed boost.METH-ODS AND MATERIALS:Thirty-three patients with average risk(defined as<==1.5 cm(2)of residual tumorafter resection,age>3 years,and no involvement of the cerebrospinal fluid or spine)medulloblastoma werediagnosed at our institution between January 1994 and December 2001.They were enrolled in an institutional展开更多
Medulloblastoma is the most common malignant pediatric brain tumor. In mice, Ptcl haploinsufficiency and disruption of DNA repair (DNA ligase IV inactivation) or cell cycle regulation (Kipl, Ink4d, or Inkd.c inactivat...Medulloblastoma is the most common malignant pediatric brain tumor. In mice, Ptcl haploinsufficiency and disruption of DNA repair (DNA ligase IV inactivation) or cell cycle regulation (Kipl, Ink4d, or Inkd.c inactivation), in conjunction with p53 dysfunction, predispose to medulloblastoma. To identify genes important for this tumor, we evaluated gene expression profiles in medulloblastomas from these mice. Unexpectedly, medulloblastoma展开更多
Medulloblastomas(MBs)are the most prevalent brain tumours in children.They are classified as grade IV,the highest in malignancy,with about 30%metastatic tumours at the time of diagnosis.Cancer stem cells(CSCs)are a sm...Medulloblastomas(MBs)are the most prevalent brain tumours in children.They are classified as grade IV,the highest in malignancy,with about 30%metastatic tumours at the time of diagnosis.Cancer stem cells(CSCs)are a small subset of tumour cells that can initiate and support tumour growth.In MB,CSCs contribute to tumour initiation,metastasis,and therapy resistance.Metabolic differences among the different MB groups have started to emerge.Sonic hedgehog tumours show enriched lipid and nucleic acid metabolism pathways,whereas Group 3 MBs upregulate glycolysis,gluconeogenesis,glutamine anabolism,and glutathione-mediated anti-oxidant pathways.Such differences impact the clinical behaviour of MB tumours and can be exploited therapeutically.In this review,we summarise the existing knowledge about metabolic rewiring in MB,with a particular focus on MB-CSCs.Finally,we highlight some of the emerging metabolism-based therapeutic strategies for MB.展开更多
Medulloblastoma (MB) is common tumor of the central nervous system in children. It’s reported that PI3K/AKT and Wnt signal pathway have important roles in MB. This study aims to investigate the expression of PI3K, AK...Medulloblastoma (MB) is common tumor of the central nervous system in children. It’s reported that PI3K/AKT and Wnt signal pathway have important roles in MB. This study aims to investigate the expression of PI3K, AKT, Β-catenin and VEGFR-2 in MB to find a new pathway for MB. A total of 33 MB and 17 control brain cases were retrospectively evaluate d for PI3K, AKT, β-catenin and VEGFR-2 expression by immunohistochemical staining, and the relationship with clinical feature were analyzed. The positive rate of PI3K, AKT, β-catenin and VEGFR-2 in 33 MB were significantly greater than those in control group展开更多
Medulloblastoma (MB) is one of the most common malignant tumors with poor survival in children. Nuclear factor erythroid 2-related factor2 (Nrf-2) and heme oxygenase-1 (HO-1) have been considered to play major roles i...Medulloblastoma (MB) is one of the most common malignant tumors with poor survival in children. Nuclear factor erythroid 2-related factor2 (Nrf-2) and heme oxygenase-1 (HO-1) have been considered to play major roles in the pathogenesis of many tumors. There is no report about clinicopathological significance of Nrf-2 and HO-1 expression in medulloblastoma. In the present study, to explore the expression and potential function of Nrf-2 and HO-1 in MBs, immunohistochemistry was used to examine the Nrf-2 and HO-1 expression in 41 MBs and 27 control tissues adjacent to the tumor. The results showed that in the cases of MB, the positive expression rates of Nrf-2 and HO-1 (82.9% and 78.0%) were significantly increased compared with that (37.0% and 29.6%) in peritumoral control brain tissues. The difference was statistically significant (P 0.05). The abnormal expression of Nrf-2 and HO-1 in MB suggest that the Nrf-2/HO-1 pathway plays an important role in the formation and development of MB and may be a potential therapeutic target for MB.展开更多
<b><span style="font-family:Verdana;">Aim:</span></b><span style="font-family:""><span style="font-family:Verdana;"> The aim of this study was to ...<b><span style="font-family:Verdana;">Aim:</span></b><span style="font-family:""><span style="font-family:Verdana;"> The aim of this study was to investigate whether magnetic resonance spectrum (MRS) and MR imaging features can be used for non-invasive medulloblastoma subgrouping, and analyse patient characteristics and prognosis of molecular subtypes of medulloblastoma. </span><b><span style="font-family:Verdana;">Material and Methods: </span></b><span style="font-family:Verdana;">32 patients with medulloblastoma underwent MRI prior to surgical resection, 16 of them underwent MRS. MR imaging features and metabolites measured by MRS were analysed to distinguish molecular subtypes of medulloblastoma. Patient demographics, histopathological types, and prognosis of different molecular subtypes were analysed and compared respectively. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">MRS and MR imaging features </span><span style="font-family:Verdana;">differed from different individuals, but without statistical significance that involves acquiring non-quantitative MR imaging features and NAA/Cr, Cho/Cr, Lip/Cr, Glu and Gln/Cr ratio, to be used to determine molecular subtypes. There was no significant difference of the three molecular subtypes in age, gender and pathological type. The 5-year event-free survival (EFS) of SHH, WNT and non SHH/WNT subtype respectively were 75%, 57.1%, 38.1%, with no significant difference (</span><i><span style="font-family:Verdana;">p</span></i><span style="font-family:Verdana;"> = 0.382). 5-year EFS of non SHH/WNT subtype was significantly higher in ≤3 years old group than >3 years old group (</span><i><span style="font-family:Verdana;">p </span></i><span style="font-family:Verdana;">= 0.047). </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> MRS and MR imaging features can’t be used to determine molecular subtypes based on our small sample study. There was no significant difference of the prognosis in the three molecular subtypes. The prognosis of ≤3 years old group of non SHH/WNT subtype is better than >3 years old group.展开更多
Microvesicles (MVs) or shedding membrane vesicles have recently been described as a novel model of intercellular communication. Previously, MVs were considered as unnecessary or secreted cellular debris, but MVs have ...Microvesicles (MVs) or shedding membrane vesicles have recently been described as a novel model of intercellular communication. Previously, MVs were considered as unnecessary or secreted cellular debris, but MVs have lately been described as having roles in a variety of biological functions, such as cell homeostasis and the cellular processes involved in the oncogenesis of many types of tumors. Carrying several key molecules that contribute to tumor development and progression, similar to mRNAs, microRNAs and other non-coding RNAs, DNA and even small proteins, MVs can be considered as a ubiquitous form of novel cell communication that is present in most somatic cells. Although tumor-derived MVs have been demonstrated in different types of cancers, the literature data on MVs in primary central nervous system (CNS) tumors are relatively scarce. In this review, we address the involvement of MVs in diffuse astrocytomas, particularly glioblastomas, as well as oligodendrogliomas and medulloblastomas. We placed particular focus on the cellular crosstalk between tumor and “normal” cells, the putative mechanisms how the tumor microenvironment is modulated and the spread of aggressive phenotypes. Additionally, a better understanding of the participation of tumor-derived MVs in the regulation of key cancer pathways will offer new insights into tumor pathogenesis and the mechanisms of multidrug resistance, and may help to develop new strategies for novel therapies against these infiltrative CNS tumors.展开更多
Purpose: To evaluate treatment outcomes and prognostic factors of pediatric Medulloblastoma (MB) patients treated by adjuvant post-operative riskadapted radiotherapy (RT) and chemotherapy (CT). Patients and Methods: A...Purpose: To evaluate treatment outcomes and prognostic factors of pediatric Medulloblastoma (MB) patients treated by adjuvant post-operative riskadapted radiotherapy (RT) and chemotherapy (CT). Patients and Methods: A retrospective analysis was conducted based on medical records of pediatric patients with pathologically confirmed MB treated between 2006 and 2013 at the National cancer Institute (NCI), Egypt. Various patients’ and disease characteristics, treatment details and outcome data were reviewed. Results: Fifty patients’ records were included in the analysis with a median age of 6 years at diagnosis (range 3 - 18). According to the Chang staging system;38%, 44%, 4%, and 14% were M0, M1, M2, and M3, respectively. All patients underwent primary surgery;gross total resection (with no residual) in 38%, near total resection (with residual ≤1.5 cm2) in 8%, subtotal resection (with residual > 1.5 cm2) in 34%, and 20% had only biopsy. All patients were treated by riskadapted craniospinal irradiation (CSI);high-risk patients were treated by CSI 36 Gy/20 fractions over 4 weeks followed by posterior fossa (PF) boost 18 Gy/10 fractions over 2 weeks (180 cGy per fraction), while standard-risk patients were treated by CSI 23.4 Gy/13 fractions over 2 and half weeks followed by PF boost 30.6 Gy/17 fractions over 3 and half weeks. Median overall treatment time (OTT) was 52 days. All patients received adjuvant CT;47 patients (94%) received concomitant chemo radiotherapy (CCRT), while 4 patients (8%) only received neoadjuvant CT (NB: only one patient received all neoadjuvant, concomitant and adjuvant CT). With a median follow up time of 32.5 months, ranging from 6 to 104 months, the whole group estimates of the overall survival (OS) at 1, 3, and 5 years were 83%, 70%, and 64%, respectively, while, the progression-free survival (PFS) rates at 1, 3, and 5 years were 79%, 62%, and 57% respectively. Four patients relapsed. Neural-axis was the commonest site of relapse (3 patients). Both risk groups were equally represented in relapsed patients (2 standard risk & 2 high risk patients) and relapse took place within 2 years. In univariate analysis, performance status,extent of surgery, and post-operative residual tumor size were significant prognostic factors for OS. On the other hand, factors which affected the PFS included gender, extent of surgery, and post-operative residual tumor. Conclusion: Neural-axis relapse was the commonest site of relapse for pediatric MB patients. Extent of surgical resection, post-operative residual tumor, and gender are powerful prognostic factors. Maximal safe resection is the standard surgical approach for MB patients to achieve cure.展开更多
Medulloblastoma is a rare brain malignant lesion, reported more in children with less prevalence among adults and rarely seen during pregnancy. The diagnosis of Medulloblastoma is a challenging clinical situation in p...Medulloblastoma is a rare brain malignant lesion, reported more in children with less prevalence among adults and rarely seen during pregnancy. The diagnosis of Medulloblastoma is a challenging clinical situation in pregnancy as surgery;radiotherapy and chemotherapy are the choices of management.展开更多
Medulloblastoma (MDB) is an aggressive tumor of Central Nervous System (CNS). Radiotherapy after radical surgery has an important role in treatment of standard and high risk patients and is followed by intensive chemo...Medulloblastoma (MDB) is an aggressive tumor of Central Nervous System (CNS). Radiotherapy after radical surgery has an important role in treatment of standard and high risk patients and is followed by intensive chemotherapy. To explore modifications of protein expression induced by in vivo radiotherapy proteomic analysis was performed on a case of Anaplastic MDB. 2D-gel electrophoresis and MALDI-TOF mass spectrometry detected qualitative differences of protein expression in Anaplastic MDB at diagnosis and in relapse after radiotherapy. Relevant proteomic data were confirmed by western blot and Real-Time PCR analysis, validating the presence of Sthatmin 1 (STMN1), Heat shock protein 60 (HSP60), HSP27 and Disulfide Isomerase (ER60) among the six proteins present in both samples. The most relevant modification induced by radiotherapy was a drastic reduction of the total number of proteins (60.6%) and the appearance of few new proteins. The modifications and the striking simplification of proteins expressed by the tumor after radiotherapy may allow to tailor subsequent chemotherapy on a rational basis. A proteomic guided chemotherapy may be of great benefit to patients.展开更多
BACKGROUND: Medulloblastoma is a primitive neuro-ectodermal tumor. It is common in childhood, but rarely seen at adult age, comprising only 1% of primary brain tumors.METHODS: We treated a 31-year-old man presented to...BACKGROUND: Medulloblastoma is a primitive neuro-ectodermal tumor. It is common in childhood, but rarely seen at adult age, comprising only 1% of primary brain tumors.METHODS: We treated a 31-year-old man presented to the emergency department(ED) with a chief complaint of nausea and vomiting for one week duration. Immediate frozen section revealed a grade IV medulloblastoma. During the hospital course, the patient was given craniospinal irradiation with chemotherapy.RESULTS: The patient was eventually discharged from the hospital to an assisted living facility after an uneventful 15-day course with the aid of social work.CONCLUSIONS: Despite intracranial tumors generally being slow growing masses, this patient demonstrates how quickly one can decompensate, and how important it is to recognize these clinical signs and symptoms of an intracranial lesion. Although these symptoms(i.e. Cushing response) are extremely rare, the ED physician should be aware and appreciate their clinical signifi cance.展开更多
Lipomatous medulloblastoma is not a separate entity but apparently distinct variant of medulloblastoma. Since the first case report in 1978 by Bechtel et al. [1], few cases have been published. We report an additional...Lipomatous medulloblastoma is not a separate entity but apparently distinct variant of medulloblastoma. Since the first case report in 1978 by Bechtel et al. [1], few cases have been published. We report an additional case of a 52-year-old right-handed man presented to the emergency department with evaluation of progressive severe intracranial hypertension and ataxia. His past medical history was unremarkable. His physical examination showed cerebellar syndromes. He underwent magnetic resonance imaging (MRI) which revealed a unique mass in the posterior fossa, lying within a cerebellar hemisphere. The patient underwent a suboccipital craniotomy for with a complete resection and samples were sent for histologic examination, showing closely packed, and round to oval cells. The nuclei had an irregular shape with clumps of heterochromatin. Lipid accumulation was a prominent feature of neoplastic cells. Postoperatively the patient did not receive fractionated radiotherapy. He is alive without deficit and with no evidence of recurrence on neuroimaging.展开更多
Objective Medulloblastoma(MB)is the most common primary central nervous system malignancy in children.Nonetheless,there is no standard treatment for recurrent MB.The purpose of this study was to investigate the clinic...Objective Medulloblastoma(MB)is the most common primary central nervous system malignancy in children.Nonetheless,there is no standard treatment for recurrent MB.The purpose of this study was to investigate the clinical value and toxicity of recombinant human endostatin injection(Endostar~?)combined with craniospinal radiotherapy for the treatment of recurrent MB in children.Methods This study retrospectively analyzed 13 patients with recurrent MB aged 5–18 years.Endostar?7.5 mg/m~2/d was synchronized during craniospinal radiotherapy for 7 children with a portable micro uniform speed infusion pump.Endostar~?was applied 3 days prior to the initiation of radiotherapy.The drug was in continuous use for 7 days.Similarly,the withdrawal of the drug took place over 7 days.This represented a cycle.During radiotherapy,the application was repeated until the end of radiotherapy(experimental group).In the other 6 cases,only craniospinal radiotherapy was used(control group).Results The complete remission rate was 71.4%in the experimental group and 16.7%in the control group.The median progression-free survival(PFS)was 14 months(95%CI:0.0–29.60)and 19 months(95%CI:0.0–39.53)in the experimental and control groups,respectively.The median overall survival(OS)was 19 months(95%CI:0.0–38.20)and 23 months(95%CI:2.47–43.53)in the experimental and control groups,respectively.The most common adverse events included grade 1 thrombocytopenia(7.7%),grade 3 neutropenia(38.5%),and grade 1 anemia(30.8%).Conclusion Endostar~?synchronizing craniospinal radiotherapy significantly improved the complete response rate of children with recurrent MB.It did not increase the side effects of radiation therapy.However,it did not improve the PFS or OS.展开更多
基金funded by the Key Research and Development Project of the Science and Technology Department of Sichuan Province(No.2021YFS0010).
文摘Purpose:The present study summarized cases of children(n=32)with medulloblastoma(MB)who were treated using stratified therapy based on risk grading and also discussed the factors affecting prognosis.Methods:According to the risk stratification criteria,the cases were divided into the following four risk groups:low,standard,high,and very high.The 5-year overall survival(OS)and progression-free survival(PFS)rates were summarized.Further,the effects on the prognosis of tumor size,tumor stage,degree of resection,treatment mode,metastatic recurrence,molecular typing,and risk stratification were analyzed.Results:In the present study,following surgery,3 cases abandoned radiotherapy(RT)and chemotherapy(CHT),7 cases(<3 years of age)received only CHT,and 22 cases received combined RT and CHT.Total and near-total tumor resections were performed in 29 cases(90.6%).Subtotal resections were performed in 3 cases,and there were no surgery-related deaths.The average follow-up duration was 47 months.The average 5-year PFS and OS rates were 57.3%±7.2%and 68.7%±8.6%,respectively.The OS and PFS rates were significantly correlated with tumor-risk stratification,molecular staging,tumor stage,treatment mode,and recurrence after surgery(p<0.01).The degree of tumor resection,pathological type,and the presence of preoperative implantation were secondary factors affecting the prognosis(p<0.05).Age was correlated with the PFS rate.There was no correlation between age/tumor location/tumor size and prognosis(p>0.05).Favorable prognostic factors in the low-and standard-risk groups were stage M0,wingless-type MB,postoperative RT combined with CHT,no postoperative recurrence,age≥3 years,and total tumor resection.Conclusions:Personalized treatment strategies based on the risk stratification of MB and postoperative stratified comprehensive treatment could help improve the prognosis for MB.
文摘Medulloblastoma(MB)is considered the commonest malignant brain tumor in children.Multimodal treatments consisting of surgery,radiation,and chemotherapy have improved patients’survival.Nevertheless,the recurrence occurs in 30%of cases.The persistent mortality rates,the failure of current therapies to extend life expectancy,and the serious complications of non-targeted cytotoxic treatment indicate the need for more refined therapeutic approaches.Most MBs originating from the neurons of external granular layer line the outer surface of neocerebellum and responsible for the afferent and efferent connections.Recently,MBs have been segregated into four molecular subgroups:Wingless-activated(WNT-MB)(Group 1);Sonichedgehog-activated(SHH-MB)(Group 2);Group 3 and 4 MBs.These molecular alterations follow specific gene mutations and disease-risk stratifications.The current treatment protocols and ongoing clinical trials against these molecular subgroups are still using common chemotherapeutic agents by which their efficacy have improved the progression-free survival but did not change the overall survival.However,the need to explore new therapies targeting specific receptors in MB microenvironment became essential.The immune microenvironment of MBs consists of distinctive cellular heterogeneities including immune cells and none-immune cells.Tumour associate macrophage and tumour infiltrating lymphocyte are considered the main principal cells in tumour microenvironment,and their role are still under investigation.In this review,we discuss the mechanism of interaction between MB cells and immune cells in the microenvironment,with an overview of the recent investigations and clinical trials.
文摘This research work develops new and better prognostic markers for predicting Childhood MedulloBlastoma(CMB)using a well-defined deep learning architecture.A deep learning architecture could be designed using ideas from image processing and neural networks to predict CMB using histopathological images.First,a convolution process transforms the histopathological image into deep features that uniquely describe it using different two-dimensional filters of various sizes.A 10-layer deep learning architecture is designed to extract deep features.The introduction of pooling layers in the architecture reduces the feature dimension.The extracted and dimension-reduced deep features from the arrangement of convolution layers and pooling layers are used to classify histopathological images using a neural network classifier.The performance of the CMB classification system is evaluated using 1414(10×magnification)and 1071(100×magnification)augmented histopathological images with five classes of CMB such as desmoplastic,nodular,large cell,classic,and normal.Experimental results show that the average classification accuracy of 99.38%(10×)and 99.07%(100×)is attained by the proposed CNB classification system.
基金Key Social Development Project in Hainan Province(No.ZDYF2019173)。
文摘Medulloblastoma(MB)is the most common childhood embryonal malignant tumour in the central nervous system.The diagnosis,prognosis and therapeutic targets of MB depend on the molecular characteristics of the tumor,and it is a great challenge to obtain the tissue samples from the patients with brain tumor.Genomic changes found in cell-free DNA(cfDNA)of cerebrospinal fluid(CSF)can predict genomic changes present in tumor tissue,fluid biopsy of CSF can detect the genomic profile of tumor-associated cfDNA and evaluate cfDNA as a marker of measurable residual disease(MRD)in a relatively noninvasive manner,which provides the evidence of"individualized precision therapy"for MB patients.In this paper,we reviewed the recent studies in medulloblastoma based on cfDNA Liquid Biopsy of CSF.
基金the hundreds top talents program from Chinese Academy of Sciences,the NSFC(Nos.81173076,81403050)the projects of science and technology of Yunnan Province(2009C1120,2013FA047).
文摘Medulloblastoma(MB)is a form of malignant brain tumor that predominantly arises in infants and children,of which approximately 25%is due to upregulation of canonical Wnt pathway with mainly mutations in CTNNB1.Therefore,Wnt inhibitors could offer rational therapeutic strategies and chemoprevention for this malignant cancer.In our present study,we undertook a screening for antagonists of Wnt signaling from 600 natural compounds,and identified Ginkgetin,a biflavone isolated from Cephalotaxus fortunei var.alpina.Ginkgetin inhibited Wnt pathway with an IC50 value around 5.92 lM and structure–activity relationship analysis suggested the methoxy group in Ginkgetin as a functional group.Biflavone Ginkgetin showed obvious cytotoxicity in Daoy and D283 MB cells.Cell cycle analysis by flow cytometry showed that Ginkgetin induced efficiently G2/M phase arrest in Daoy cells.Further mechanism studies showed that Ginkgetin reduced the expression of Wnt target genes,including Axin2,cyclinD1 and survivin in MB cells.The phosphorylation level of b-catenin also decreased in a time-and concentration-dependent manner.Collectively,our data suggest that Ginkgetin is a novel inhibitor of Wnt signaling,and as such warrants further exploration as a promising antimedulloblastoma candidate.
文摘Medulloblastoma (MB) is a malignant brain tumor with a usual potential for leptomeningeal spread. Intramedullary metastases of MB are rare and there are very few cases reported in the literature. Here, we report the case of an 18-year-old man with intramedullary spinal cord metastasis of MB occurring 9 years after the first diagnosis. The patient presented a 2-month history of progressive weakness in both lower limbs associated with urinary incontinence. Magnetic resonance imaging (MRI) demonstrated a large intramedullary spinal cord tumor extending from T10 to L1. The patient underwent surgical decompression and adjuvant therapy. Histological examination confirmed the diagnosis of classic MB metastasis. Postoperatively, the neurological status was stationary. Intramedullary metastasis of medulloblastoma is rare and difficult to manage with a poor prognosis. Comprehensive studies on the medulloblastoma dissemination mechanisms and clinical trials are needed to assess combined therapeutic approaches on metastases of MB.
文摘PURPOSE:To review the efficacy and patterns of failure in average-risk medulloblastoma patients treated withconcurrent chemotherapy and reduced-dose cranial spinal irradiation and a conformal tumor bed boost.METH-ODS AND MATERIALS:Thirty-three patients with average risk(defined as<==1.5 cm(2)of residual tumorafter resection,age>3 years,and no involvement of the cerebrospinal fluid or spine)medulloblastoma werediagnosed at our institution between January 1994 and December 2001.They were enrolled in an institutional
文摘Medulloblastoma is the most common malignant pediatric brain tumor. In mice, Ptcl haploinsufficiency and disruption of DNA repair (DNA ligase IV inactivation) or cell cycle regulation (Kipl, Ink4d, or Inkd.c inactivation), in conjunction with p53 dysfunction, predispose to medulloblastoma. To identify genes important for this tumor, we evaluated gene expression profiles in medulloblastomas from these mice. Unexpectedly, medulloblastoma
基金Supported by the Miguel Servet and pFIS fellowships,No.CP16/00121(P.S.) and No.FI21/00031(P.E-R.) from the Instituto de Salud Carlos Ⅲ and cofinanced by European funds(FSE:“el FSE invierte en tu futuro”)Magnus Bergvalls Stiftelse,No.2021-04284(L.C.)the Ⅳ Grant for Childhood Cancer Research from Asociación de Padres de Niños con Cáncer de Aragón(ASPANOA,P.S.).
文摘Medulloblastomas(MBs)are the most prevalent brain tumours in children.They are classified as grade IV,the highest in malignancy,with about 30%metastatic tumours at the time of diagnosis.Cancer stem cells(CSCs)are a small subset of tumour cells that can initiate and support tumour growth.In MB,CSCs contribute to tumour initiation,metastasis,and therapy resistance.Metabolic differences among the different MB groups have started to emerge.Sonic hedgehog tumours show enriched lipid and nucleic acid metabolism pathways,whereas Group 3 MBs upregulate glycolysis,gluconeogenesis,glutamine anabolism,and glutathione-mediated anti-oxidant pathways.Such differences impact the clinical behaviour of MB tumours and can be exploited therapeutically.In this review,we summarise the existing knowledge about metabolic rewiring in MB,with a particular focus on MB-CSCs.Finally,we highlight some of the emerging metabolism-based therapeutic strategies for MB.
文摘Medulloblastoma (MB) is common tumor of the central nervous system in children. It’s reported that PI3K/AKT and Wnt signal pathway have important roles in MB. This study aims to investigate the expression of PI3K, AKT, Β-catenin and VEGFR-2 in MB to find a new pathway for MB. A total of 33 MB and 17 control brain cases were retrospectively evaluate d for PI3K, AKT, β-catenin and VEGFR-2 expression by immunohistochemical staining, and the relationship with clinical feature were analyzed. The positive rate of PI3K, AKT, β-catenin and VEGFR-2 in 33 MB were significantly greater than those in control group
文摘Medulloblastoma (MB) is one of the most common malignant tumors with poor survival in children. Nuclear factor erythroid 2-related factor2 (Nrf-2) and heme oxygenase-1 (HO-1) have been considered to play major roles in the pathogenesis of many tumors. There is no report about clinicopathological significance of Nrf-2 and HO-1 expression in medulloblastoma. In the present study, to explore the expression and potential function of Nrf-2 and HO-1 in MBs, immunohistochemistry was used to examine the Nrf-2 and HO-1 expression in 41 MBs and 27 control tissues adjacent to the tumor. The results showed that in the cases of MB, the positive expression rates of Nrf-2 and HO-1 (82.9% and 78.0%) were significantly increased compared with that (37.0% and 29.6%) in peritumoral control brain tissues. The difference was statistically significant (P 0.05). The abnormal expression of Nrf-2 and HO-1 in MB suggest that the Nrf-2/HO-1 pathway plays an important role in the formation and development of MB and may be a potential therapeutic target for MB.
文摘<b><span style="font-family:Verdana;">Aim:</span></b><span style="font-family:""><span style="font-family:Verdana;"> The aim of this study was to investigate whether magnetic resonance spectrum (MRS) and MR imaging features can be used for non-invasive medulloblastoma subgrouping, and analyse patient characteristics and prognosis of molecular subtypes of medulloblastoma. </span><b><span style="font-family:Verdana;">Material and Methods: </span></b><span style="font-family:Verdana;">32 patients with medulloblastoma underwent MRI prior to surgical resection, 16 of them underwent MRS. MR imaging features and metabolites measured by MRS were analysed to distinguish molecular subtypes of medulloblastoma. Patient demographics, histopathological types, and prognosis of different molecular subtypes were analysed and compared respectively. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">MRS and MR imaging features </span><span style="font-family:Verdana;">differed from different individuals, but without statistical significance that involves acquiring non-quantitative MR imaging features and NAA/Cr, Cho/Cr, Lip/Cr, Glu and Gln/Cr ratio, to be used to determine molecular subtypes. There was no significant difference of the three molecular subtypes in age, gender and pathological type. The 5-year event-free survival (EFS) of SHH, WNT and non SHH/WNT subtype respectively were 75%, 57.1%, 38.1%, with no significant difference (</span><i><span style="font-family:Verdana;">p</span></i><span style="font-family:Verdana;"> = 0.382). 5-year EFS of non SHH/WNT subtype was significantly higher in ≤3 years old group than >3 years old group (</span><i><span style="font-family:Verdana;">p </span></i><span style="font-family:Verdana;">= 0.047). </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> MRS and MR imaging features can’t be used to determine molecular subtypes based on our small sample study. There was no significant difference of the prognosis in the three molecular subtypes. The prognosis of ≤3 years old group of non SHH/WNT subtype is better than >3 years old group.
文摘Microvesicles (MVs) or shedding membrane vesicles have recently been described as a novel model of intercellular communication. Previously, MVs were considered as unnecessary or secreted cellular debris, but MVs have lately been described as having roles in a variety of biological functions, such as cell homeostasis and the cellular processes involved in the oncogenesis of many types of tumors. Carrying several key molecules that contribute to tumor development and progression, similar to mRNAs, microRNAs and other non-coding RNAs, DNA and even small proteins, MVs can be considered as a ubiquitous form of novel cell communication that is present in most somatic cells. Although tumor-derived MVs have been demonstrated in different types of cancers, the literature data on MVs in primary central nervous system (CNS) tumors are relatively scarce. In this review, we address the involvement of MVs in diffuse astrocytomas, particularly glioblastomas, as well as oligodendrogliomas and medulloblastomas. We placed particular focus on the cellular crosstalk between tumor and “normal” cells, the putative mechanisms how the tumor microenvironment is modulated and the spread of aggressive phenotypes. Additionally, a better understanding of the participation of tumor-derived MVs in the regulation of key cancer pathways will offer new insights into tumor pathogenesis and the mechanisms of multidrug resistance, and may help to develop new strategies for novel therapies against these infiltrative CNS tumors.
文摘Purpose: To evaluate treatment outcomes and prognostic factors of pediatric Medulloblastoma (MB) patients treated by adjuvant post-operative riskadapted radiotherapy (RT) and chemotherapy (CT). Patients and Methods: A retrospective analysis was conducted based on medical records of pediatric patients with pathologically confirmed MB treated between 2006 and 2013 at the National cancer Institute (NCI), Egypt. Various patients’ and disease characteristics, treatment details and outcome data were reviewed. Results: Fifty patients’ records were included in the analysis with a median age of 6 years at diagnosis (range 3 - 18). According to the Chang staging system;38%, 44%, 4%, and 14% were M0, M1, M2, and M3, respectively. All patients underwent primary surgery;gross total resection (with no residual) in 38%, near total resection (with residual ≤1.5 cm2) in 8%, subtotal resection (with residual > 1.5 cm2) in 34%, and 20% had only biopsy. All patients were treated by riskadapted craniospinal irradiation (CSI);high-risk patients were treated by CSI 36 Gy/20 fractions over 4 weeks followed by posterior fossa (PF) boost 18 Gy/10 fractions over 2 weeks (180 cGy per fraction), while standard-risk patients were treated by CSI 23.4 Gy/13 fractions over 2 and half weeks followed by PF boost 30.6 Gy/17 fractions over 3 and half weeks. Median overall treatment time (OTT) was 52 days. All patients received adjuvant CT;47 patients (94%) received concomitant chemo radiotherapy (CCRT), while 4 patients (8%) only received neoadjuvant CT (NB: only one patient received all neoadjuvant, concomitant and adjuvant CT). With a median follow up time of 32.5 months, ranging from 6 to 104 months, the whole group estimates of the overall survival (OS) at 1, 3, and 5 years were 83%, 70%, and 64%, respectively, while, the progression-free survival (PFS) rates at 1, 3, and 5 years were 79%, 62%, and 57% respectively. Four patients relapsed. Neural-axis was the commonest site of relapse (3 patients). Both risk groups were equally represented in relapsed patients (2 standard risk & 2 high risk patients) and relapse took place within 2 years. In univariate analysis, performance status,extent of surgery, and post-operative residual tumor size were significant prognostic factors for OS. On the other hand, factors which affected the PFS included gender, extent of surgery, and post-operative residual tumor. Conclusion: Neural-axis relapse was the commonest site of relapse for pediatric MB patients. Extent of surgical resection, post-operative residual tumor, and gender are powerful prognostic factors. Maximal safe resection is the standard surgical approach for MB patients to achieve cure.
文摘Medulloblastoma is a rare brain malignant lesion, reported more in children with less prevalence among adults and rarely seen during pregnancy. The diagnosis of Medulloblastoma is a challenging clinical situation in pregnancy as surgery;radiotherapy and chemotherapy are the choices of management.
文摘Medulloblastoma (MDB) is an aggressive tumor of Central Nervous System (CNS). Radiotherapy after radical surgery has an important role in treatment of standard and high risk patients and is followed by intensive chemotherapy. To explore modifications of protein expression induced by in vivo radiotherapy proteomic analysis was performed on a case of Anaplastic MDB. 2D-gel electrophoresis and MALDI-TOF mass spectrometry detected qualitative differences of protein expression in Anaplastic MDB at diagnosis and in relapse after radiotherapy. Relevant proteomic data were confirmed by western blot and Real-Time PCR analysis, validating the presence of Sthatmin 1 (STMN1), Heat shock protein 60 (HSP60), HSP27 and Disulfide Isomerase (ER60) among the six proteins present in both samples. The most relevant modification induced by radiotherapy was a drastic reduction of the total number of proteins (60.6%) and the appearance of few new proteins. The modifications and the striking simplification of proteins expressed by the tumor after radiotherapy may allow to tailor subsequent chemotherapy on a rational basis. A proteomic guided chemotherapy may be of great benefit to patients.
文摘BACKGROUND: Medulloblastoma is a primitive neuro-ectodermal tumor. It is common in childhood, but rarely seen at adult age, comprising only 1% of primary brain tumors.METHODS: We treated a 31-year-old man presented to the emergency department(ED) with a chief complaint of nausea and vomiting for one week duration. Immediate frozen section revealed a grade IV medulloblastoma. During the hospital course, the patient was given craniospinal irradiation with chemotherapy.RESULTS: The patient was eventually discharged from the hospital to an assisted living facility after an uneventful 15-day course with the aid of social work.CONCLUSIONS: Despite intracranial tumors generally being slow growing masses, this patient demonstrates how quickly one can decompensate, and how important it is to recognize these clinical signs and symptoms of an intracranial lesion. Although these symptoms(i.e. Cushing response) are extremely rare, the ED physician should be aware and appreciate their clinical signifi cance.
文摘Lipomatous medulloblastoma is not a separate entity but apparently distinct variant of medulloblastoma. Since the first case report in 1978 by Bechtel et al. [1], few cases have been published. We report an additional case of a 52-year-old right-handed man presented to the emergency department with evaluation of progressive severe intracranial hypertension and ataxia. His past medical history was unremarkable. His physical examination showed cerebellar syndromes. He underwent magnetic resonance imaging (MRI) which revealed a unique mass in the posterior fossa, lying within a cerebellar hemisphere. The patient underwent a suboccipital craniotomy for with a complete resection and samples were sent for histologic examination, showing closely packed, and round to oval cells. The nuclei had an irregular shape with clumps of heterochromatin. Lipid accumulation was a prominent feature of neoplastic cells. Postoperatively the patient did not receive fractionated radiotherapy. He is alive without deficit and with no evidence of recurrence on neuroimaging.
基金Supported by a grant from the Chongqing Science and Health Joint Medical Research Foundation of China(No.2019MSXM079)。
文摘Objective Medulloblastoma(MB)is the most common primary central nervous system malignancy in children.Nonetheless,there is no standard treatment for recurrent MB.The purpose of this study was to investigate the clinical value and toxicity of recombinant human endostatin injection(Endostar~?)combined with craniospinal radiotherapy for the treatment of recurrent MB in children.Methods This study retrospectively analyzed 13 patients with recurrent MB aged 5–18 years.Endostar?7.5 mg/m~2/d was synchronized during craniospinal radiotherapy for 7 children with a portable micro uniform speed infusion pump.Endostar~?was applied 3 days prior to the initiation of radiotherapy.The drug was in continuous use for 7 days.Similarly,the withdrawal of the drug took place over 7 days.This represented a cycle.During radiotherapy,the application was repeated until the end of radiotherapy(experimental group).In the other 6 cases,only craniospinal radiotherapy was used(control group).Results The complete remission rate was 71.4%in the experimental group and 16.7%in the control group.The median progression-free survival(PFS)was 14 months(95%CI:0.0–29.60)and 19 months(95%CI:0.0–39.53)in the experimental and control groups,respectively.The median overall survival(OS)was 19 months(95%CI:0.0–38.20)and 23 months(95%CI:2.47–43.53)in the experimental and control groups,respectively.The most common adverse events included grade 1 thrombocytopenia(7.7%),grade 3 neutropenia(38.5%),and grade 1 anemia(30.8%).Conclusion Endostar~?synchronizing craniospinal radiotherapy significantly improved the complete response rate of children with recurrent MB.It did not increase the side effects of radiation therapy.However,it did not improve the PFS or OS.
