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1.
Neuroophthalmology ; 45(6): 391-396, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34720270

RESUMO

A 60-year-old woman noted headaches, transient visual obscurations and pulsatile tinnitus. She had Frisén grade 4 papilloedema. Brain magnetic resonance imaging showed a large subfrontal cystic mass with ring enhancement. Tumour pathology was in-keeping with an intraparenchymal schwannoma. This uniquely rare tumour is discussed.

2.
Stem Cells ; 37(4): 453-462, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30629778

RESUMO

Tumorigenic and non-neoplastic tissue injury occurs via the ischemic microenvironment defined by low oxygen, pH, and nutrients due to blood supply malfunction. Ischemic conditions exist within regions of pseudopalisading necrosis, a pathological hallmark of glioblastoma (GBM), the most common primary malignant brain tumor in adults. To recapitulate the physiologic microenvironment found in GBM tumors and tissue injury, we developed an in vitro ischemic model and identified chromodomain helicase DNA-binding protein 7 (CHD7) as a novel ischemia-regulated gene. Point mutations in the CHD7 gene are causal in CHARGE syndrome (a developmental disorder causing coloboma, heart defects, atresia choanae, retardation of growth, and genital and ear anomalies) and interrupt the epigenetic functions of CHD7 in regulating neural stem cell maintenance and development. Using our ischemic system, we observed microenvironment-mediated decreases in CHD7 expression in brain tumor-initiating cells and neural stem cells. Validating our approach, CHD7 was suppressed in the perinecrotic niche of GBM patient and xenograft sections, and an interrogation of patient gene expression datasets determined correlations of low CHD7 with increasing glioma grade and worse patient outcomes. Segregation of GBM by molecular subtype revealed a novel observation that CHD7 expression is elevated in proneural versus mesenchymal GBM. Genetic targeting of CHD7 and subsequent gene ontology analysis of RNA sequencing data indicated angiogenesis as a primary biological function affected by CHD7 expression changes. We validated this finding in tube-formation assays and vessel formation in orthotopic GBM models. Together, our data provide further understanding of molecular responses to ischemia and a novel function of CHD7 in regulating angiogenesis in both neoplastic and non-neoplastic systems. Stem Cells 2019;37:453-462.


Assuntos
DNA Helicases/genética , Proteínas de Ligação a DNA/metabolismo , Células-Tronco Neoplásicas/metabolismo , Animais , Modelos Animais de Doenças , Glioblastoma , Humanos , Camundongos , Transfecção , Microambiente Tumoral
3.
J Neurooncol ; 141(2): 289-301, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30460631

RESUMO

INTRODUCTION: IDH1 mutation has been identified as an early genetic event driving low grade gliomas (LGGs) and it has been proven to exerts a powerful epigenetic effect. Cells containing IDH1 mutation are refractory to epigenetical reprogramming to iPSC induced by expression of Yamanaka transcription factors, a feature that we employed to study early genetic amplifications or deletions in gliomagenesis. METHODS: We made iPSC clones from freshly surgically resected IDH1 mutant LGGs by forced expression of Yamanaka transcription factors. We sequenced the IDH locus and analyzed the genetic composition of multiple iPSC clones by array-based comparative genomic hybridization (aCGH). RESULTS: We hypothesize that the primary cell pool isolated from LGG tumor contains a heterogeneous population consisting tumor cells at various stages of tumor progression including cells with early genetic lesions if any prior to acquisition of IDH1 mutation. Because cells containing IDH1 mutation are refractory to reprogramming, we predict that iPSC clones should originate only from LGG cells without IDH1 mutation, i.e. cells prior to acquisition of IDH1 mutation. As expected, we found that none of the iPSC clones contains IDH1 mutation. Further analysis by aCGH of the iPSC clones reveals that they contain regional chromosomal amplifications which are also present in the primary LGG cells. CONCLUSIONS: These results indicate that there exists a subpopulation of cells harboring gene amplification but without IDH1 mutation in the LGG primary cell pool. Further analysis of TCGA LGG database demonstrates that these regional chromosomal amplifications are also present in some cases of low grade gliomas indicating they are reoccurring lesions in glioma albeit at a low frequency. Taken together, these data suggest that regional chromosomal alterations may exist prior to the acquisition of IDH mutations in at least some cases of LGGs.


Assuntos
Neoplasias Encefálicas/genética , Amplificação de Genes , Glioma/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , Isocitrato Desidrogenase/genética , Adulto , Neoplasias Encefálicas/metabolismo , Aberrações Cromossômicas , Células Clonais/fisiologia , Glioma/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/fisiologia , Isocitrato Desidrogenase/metabolismo , Masculino
4.
J Biol Chem ; 292(41): 16999-17010, 2017 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-28790173

RESUMO

Among primary brain cancers, gliomas are the most deadly and most refractory to current treatment modalities. Previous reports overwhelmingly support the role of the RNA-binding protein Hu antigen R (HuR) as a positive regulator of glioma disease progression. HuR expression is consistently elevated in tumor tissues, and a cytoplasmic localization appears essential for HuR-dependent oncogenic transformation. Here, we report HuR aggregation (multimerization) in glioma and the analysis of this tumor-specific HuR protein multimerization in clinical brain tumor samples. Using a split luciferase assay, a bioluminescence resonance energy transfer technique, and site-directed mutagenesis, we examined the domains involved in HuR multimerization. Results obtained with the combination of the split HuR luciferase assay with the bioluminescence resonance energy transfer technique suggested that multiple (at least three) HuR molecules come together during HuR multimerization in glioma cells. Using these data, we developed a model of HuR multimerization in glioma cells. We also demonstrate that exposing glioma cells to the HuR inhibitor tanshinone group compound 15,16-dihydrotanshinone-I or to the newly identified compound 5 disrupts HuR multimerization modules and reduces tumor cell survival and proliferation. In summary, our findings provide new insights into HuR multimerization in glioma and highlight possible pharmacological approaches for targeting HuR domains involved in cancer cell-specific multimerization.


Assuntos
Transformação Celular Neoplásica/metabolismo , Proteína Semelhante a ELAV 1/metabolismo , Glioma/metabolismo , Proteínas de Neoplasias/metabolismo , Agregação Patológica de Proteínas/metabolismo , Neoplasias Encefálicas , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Proteína Semelhante a ELAV 1/antagonistas & inibidores , Proteína Semelhante a ELAV 1/genética , Furanos , Glioma/tratamento farmacológico , Glioma/genética , Glioma/patologia , Humanos , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Fenantrenos/farmacologia , Agregação Patológica de Proteínas/tratamento farmacológico , Agregação Patológica de Proteínas/genética , Agregação Patológica de Proteínas/patologia , Domínios Proteicos , Quinonas
5.
J Neurooncol ; 133(2): 377-388, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28451993

RESUMO

Tumor progression to higher grade is a fundamental property of cancer. The malignant advancement of the pathological features may either develop during the later stages of cancer growth (natural evolution) or it may necessitate new mutations or molecular events that alter the rates of growth, dispersion, or neovascularization (transformation). Here, we model the pathological and radiological features of grades 2-4 gliomas at the times of diagnosis and death and study grade development and the progression to higher grades. We perform a retrospective review of clinical cases based on model predictions. Simulations uncover two unusual patterns of glioma progression, which are supported by clinical cases: (1) some grades 2 and 3 gliomas lack the ability of progression to higher grades, and (2) grade 3 glioma may evolve to GBM in a few weeks. All 13 gliomas that recurred at the same grade carry either the IDH1-R132H or the ATRX mutation. All (five of five) grade 3 tumors are 1p/19q co-deleted, IDH1-R132H mutated and ATRX wt. Furthermore, three of seven grade 2 gliomas are both IDH1-R132H mutated and ATRX mutated. Simulations replicate the good prognosis of secondary GBM. The results support the hypothesis that constant rates of dispersion, proliferation, and angiogenesis prescribe either a natural evolution or the inability to progress to higher grades. Furthermore, the accrual of molecular events that change a tumor's ability to infiltrate, proliferate or neovascularize may transform the glioma either into a more aggressive tumor at the same grade or elevate its grade.


Assuntos
Neoplasias Encefálicas/fisiopatologia , Transformação Celular Neoplásica , Progressão da Doença , Glioma/fisiopatologia , Modelos Biológicos , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Feminino , Proteína Glial Fibrilar Ácida , Glioma/diagnóstico por imagem , Glioma/genética , Humanos , Isocitrato Desidrogenase/genética , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Mutação , Estudos Retrospectivos , Índice de Gravidade de Doença , Proteína Nuclear Ligada ao X/genética
6.
J Neuroophthalmol ; 42(2): e527, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35483087
7.
Radiology ; 273(3): 940-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25420171

RESUMO

History A previously healthy 23-year-old white man presented to the emergency department of our hospital with a 2-month history of dysarthria, progressively worsening vertigo, and difficulty walking. A diagnosis of retinitis pigementosa was made in this patient's childhood. He did not have any history of congenital syphilis. He did not have a history of nausea or vomiting, fever, weight loss, headache, photophobia, seizure, extremity weakness, or sensory disturbance. Physical examination revealed dysarthria, dysmetria, and ataxia. Kernig and Brudzinski signs were absent, and pathergy test results were negative. Laboratory evaluation revealed normal complete and differential blood counts and normal serum chemistry, including a normal serum angiotensin-converting enzyme level. Analysis of his serum was negative for antinuclear antibody (or ANA), cytoplasmic antineutrophil cvtoplasmic antibody (or cANCA), Sjögren syndrome antigens A and B (SS-A and SS-B, respectively), antitissue transglutaminase and antiendomysial antibodies, and paraneoplastic profile. Serum analysis was also negative for human immunodeficiency virus type 1 and type 2 RNA, Venereal Disease Research Laboratory (VDRL) test, rapid plasma regain (RPR), and fluorescent treponemal antibody absorption. Cerebrospinal fluid (CSF) analysis revealed clear fluid, a normal glucose level (64 mg/dL [3.6 mmol/L]; normal range, 40-70 mg/dL [2.2-3.9 mmol/L]), an elevated protein level (97 mg/dL; normal range, 12-60 mg/dL), and an elevated white blood cell count (7/mm(3) [0.007 ×10(9)/L] in tube 1 and 17/mm(3) [0.017 × 10(9)/L] in tube 2) with 84% lymphocytes. CSF immunoglobulin G level was elevated (30.1 mg/dL; normal, <5.9 mg/dL); however, there were no oligoclonal bands. Gram staining, acid-fast staining, and lactic acid, cryptococcal antigen, histoplasma antigen, herpes simplex virus polymerase chain reaction, VDRL, and RPR test results for CSF were negative. CSF did not grow any bacteria, fungus, or acid-fast bacillus at culture. CSF flow cytometry did not reveal a monoclonal lymphoid population. Initial imaging included brain magnetic resonance (MR) imaging. Computed tomography (CT) images of the chest, abdomen, and pelvis were normal (not shown). The patient's clinical symptoms and imaging findings responded to treatment with a high dose of oral steroids. However, the patient's symptoms exhibited clinical and radiologic progression after several attempts to taper the steroid dose.


Assuntos
Encefalopatias/diagnóstico , Encefalopatias/tratamento farmacológico , Tronco Encefálico/patologia , Cerebelo/patologia , Imagem de Difusão por Ressonância Magnética , Glucocorticoides/uso terapêutico , Ponte/patologia , Biópsia , Encefalopatias/patologia , Doença Crônica , Diagnóstico Diferencial , Citometria de Fluxo , Humanos , Imuno-Histoquímica
8.
J Dance Med Sci ; 28(2): 125-131, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38385253

RESUMO

Purpose: The Backalast® compression jacket is intended to improve posture and proprioception of the trunk and shoulder girdle for dancers and dance students during dance training by way of elastic bands in the rear of the garment (which include bands enclosing the inferior thorax). This study was intended to investigate whether there is evidence to support those objectives. Materials and Methods: Fifteen dance students participated (4 male, mean age 19.9 ± 1.4 years old). The dependent variables of trunk-pelvis angle and proximity of trunk axis to global vertical for each participant were measured using optical motion capture before and after the completion of a series of trunk movements. The Helen Hayes model, which we used to represent the trunk, includes the shoulder girdles as part of the trunk. We compared the effect of the type of garment (Backalast® or control compression shirt) worn upon the 2 dependent variables, within-subject with paired t-tests. The order of whether Backalast® or control compression shirt was worn first was alternated between participants. Results: The pre/posttest difference in trunk proprioception as represented by the construct of ability to reproduce trunk-pelvis angle wearing the Backalast® was 0.8° ± 0.8°, but for the control shirt, the difference was 1.8° ± 1.4°, P = .03. The difference between garments in vertical trunk alignment, measured after the series of trunk movements, was not significant. Conclusion: Our findings suggest that the Backalast® can help enhance trunk proprioception when compared to the control compression shirt, although it did not change the angle at which the participants' held their trunks while standing erect (proximity to global vertical).


Assuntos
Dança , Humanos , Masculino , Dança/fisiologia , Adulto Jovem , Feminino , Amplitude de Movimento Articular/fisiologia , Propriocepção/fisiologia , Tronco/fisiologia , Postura/fisiologia , Pelve/fisiologia , Vestuário , Fenômenos Biomecânicos
9.
J Dance Med Sci ; 27(2): 99-106, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37282353

RESUMO

INTRODUCTION: Research in court sports shows that factors which aid in extrinsic shock absorption, that is, flooring and footwear, can help reduce lower extremity injuries. However, since students and performers of ballet or most styles of contemporary dance cannot depend upon footwear, the only extrinsic factor to help them with shock absorption is flooring. METHODS: We investigated whether doing sauté on a low stiffness dance floor produced a difference in EMG output of the vastus lateralis, gastrocnemius, of soleus compared to a high stiffness floor. Average and average peak amplitude EMG output from 18 dance students or active dancers performing 8 repetitions of sauté on a low stiffness floor (Harlequin® Woodspring) was compared to a maple hardwood floor on concreted subflooring. RESULTS: The data showed a significant increase in average peak EMG muscle amplitude during jumping on the low stiffness floor compared to a high stiffness floor for the soleus muscle (P = .033) and a trend for increase average peak output for the medial gastrocnemius (P = .088). CONCLUSION: The difference in average peak amplitude of EMG output is explained through the difference in force absorption between floors. With the high stiffness floor, more force of the landing was returned to the dancers' legs, but the low stiffness floor absorbed some of the force of landing the jump, and therefore muscles needed to contribute more to maintain the same jump height. The force absorption characteristic of the low stiffness floor may decrease injury rates in dance through causing an adjustment in muscle velocity. Rapid eccentric muscle activity carries the greatest possibility of musculotendinous injury and is experienced in lower body muscles controlling all joints during impact absorption, which includes landing of jumps in dance. If a surface can decelerate the landing of a high velocity dance movement, it also decreases the musculotendinous demand for high velocity tension generation.


Assuntos
Tornozelo , Dança , Humanos , Dança/fisiologia , Articulação do Joelho/fisiologia , Perna (Membro)/fisiologia , Músculo Esquelético/fisiologia , Fenômenos Biomecânicos
10.
Neurooncol Adv ; 4(1): vdab186, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35088051

RESUMO

BACKGROUND: Glioblastoma (GBM) has a 5-year survival rate of 3%-5%. GBM treatment includes maximal resection followed by radiotherapy with concomitant and adjuvant temozolomide (TMZ). Cytochrome C oxidase (CcO) is a mitochondrial enzyme involved in the mechanism of resistance to TMZ. In a prior retrospective trial, CcO activity in GBMs inversely correlated with clinical outcome. The current Cyto-C study was designed to prospectively evaluate and validate the prognostic value of tumor CcO activity in patients with newly diagnosed primary GBM, and compared to the known prognostic value of MGMT promoter methylation status. METHODS: This multi-institutional, blinded, prospective biomarker study enrolled 152 patients with newly diagnosed GBM who were to undergo surgical resection and would be candidates for standard of care. The primary end point was overall survival (OS) time, and the secondary end point was progression-free survival (PFS) time. Tumor CcO activity and MGMT promoter methylation status were assayed in a centralized laboratory. RESULTS: OS and PFS did not differ by high or low tumor CcO activity, and the prognostic validity of MGMT promoter methylation was confirmed. Notably, a planned exploratory analysis suggested that the combination of low CcO activity and MGMT promoter methylation in tumors may be predictive of long-term survival. CONCLUSIONS: Tumor CcO activity alone was not confirmed as a prognostic marker in GBM patients. However, the combination of low CcO activity and methylated MGMT promoter may reveal a subgroup of GBM patients with improved long-term survival that warrants further evaluation. Our work also demonstrates the importance of performing large, multi-institutional, prospective studies to validate biomarkers. We also discuss lessons learned in assembling such studies.

11.
Med Probl Perform Art ; 26(4): 195-9, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22211195

RESUMO

Our objective in this study was to compare stiffness of bilateral lower extremities (LEs) in ballet dancers performing sauté on a low-stiffness "sprung floor" to that during the same movement on a high-stiffness floor (wood on concrete). LE stiffness was calculated as the ratio of vertical ground reaction force (in kN) to compression of the lower limb (in meters). Seven female dancers were measured for five repetitions each at the point of maximum leg compression while performing sauté on both of the surfaces, such that 43 ms of data were represented for each trial. The stiffness of bilateral LEs at the point of maximum compression was higher by a mean difference score of 2.48 ± 2.20 kN/m on the low-stiffness floor compared to a high-stiffness floor. Paired t-test analysis of the difference scores yielded a one-tailed probability of 0.012. This effect was seen in six out of seven participants (one participant showed no difference between floor conditions). The finding of increased stiffness of the LEs in the sprung floor condition suggests that some of the force of landing the jump was absorbed by the surface, and therefore did not need to be absorbed by the participants' LEs themselves. This in turn implies that a sprung dance floor may help to prevent dance-related injuries.


Assuntos
Dança/fisiologia , Pisos e Cobertura de Pisos , Traumatismos do Joelho/prevenção & controle , Articulação do Joelho/fisiologia , Locomoção/fisiologia , Fenômenos Biomecânicos , Dança/lesões , Feminino , Humanos , Equilíbrio Postural , Amplitude de Movimento Articular , Adulto Jovem
12.
Neurosurgery ; 88(6): E537-E542, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33611519

RESUMO

BACKGROUND AND IMPORTANCE: Ameloblastic carcinoma (AC) is a malignant neoplasm of epithelial origin that typically arises from the mandible or maxilla. It represents approximately 2% of all odontogenic tumors. Gross total resection is the surgical goal given AC's aggressiveness and propensity for recurrence. We present the first reported AC metastasis to the cervical spine. CLINICAL PRESENTATION: A 61-yr-old African American female with a history of AC of bilateral mandibles and lung metastases presented with neck pain and right arm weakness progressive over several months. Cervical spine imaging demonstrated a cervical 3 pathological fracture with severe anterior vertebral body compression and resultant cervical 2-3 kyphotic deformity and bony retropulsion causing severe cord compression. The patient underwent a cervical 3 corpectomy and cervical 2-4 anterior fixation followed by a cervical 3 laminectomy and cervical 2-5 dorsal internal fixation and fusion. Postoperatively, the patient's neurological exam remained stable and imaging showed improved spinal alignment and appropriate anterior and posterior instrumentation. Unfortunately, the patient thereafter suffered a decline in performance status and progression of lung metastatic disease. Her oncology team is considering chemotherapy and stereotactic radiosurgery, but her prognosis remains grim. CONCLUSION: AC is a rare and aggressive pathology with a poor prognosis despite multimodal therapy. We present the first case of AC metastatic spread to the spine. We aim to bring this pathology to the attention of our worldwide neurosurgical colleagues and share our surgical approach and multidisciplinary management to assist those who may encounter this pathology in the future.


Assuntos
Vértebras Cervicais/patologia , Vértebras Cervicais/cirurgia , Tumores Odontogênicos/patologia , Compressão da Medula Espinal/patologia , Neoplasias da Coluna Vertebral/secundário , Neoplasias da Coluna Vertebral/cirurgia , Feminino , Fixação Interna de Fraturas/efeitos adversos , Humanos , Laminectomia , Pessoa de Meia-Idade , Tumores Odontogênicos/cirurgia , Compressão da Medula Espinal/etiologia , Fusão Vertebral/métodos
13.
Surg Neurol Int ; 12: 2, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33500817

RESUMO

BACKGROUND: Intravenous (IV) methamphetamine abuse is associated with a variety of short- and long-term effects on the nervous system, some of which have yet to be fully elucidated. One known systemic complication that has not been described in nervous system tissues is the deposition of substrate crystals contained in injectable drugs. CASE DESCRIPTION: An unusual case is presented of a 35-year-old active IV methamphetamine abuser with posterior reversible encephalopathy syndrome (PRES) who subsequently developed multifocal bilateral cerebellar enhancing lesions and leptomeningeal enhancement due to biopsy-proven crystalline deposits. CONCLUSION: Although large crystalline substances will not normally penetrate the blood-brain barrier (BBB), during a state of BBB compromise such as with PRES, talc deposition may occur in the central nervous system.

14.
Motor Control ; 24(1): 39-56, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31323640

RESUMO

Most studies of high-speed lower body movements include practice repetitions for facilitating consistency between the trials. We investigated whether 20 repetitions of drop landing (from a 30.5-cm platform onto a force plate) could improve consistency in maximum ground reaction force, linear lower body stiffness, depth of landing, and jump height in 20 healthy, young adults. Coefficient of variation was the construct for variability used to compare the first to the last five repetitions for each variable. We found that the practice had the greatest effect on maximum ground reaction force (p = .017), and had smaller and similar effects on lower body stiffness and depth of landing (p values = .074 and .044, respectively), and no measurable effect on jump height. These findings suggest that the effect of practice on drop landing differs depending upon the variable measure and that 20 repetitions significantly improve consistency in ground reaction force.


Assuntos
Fenômenos Biomecânicos/fisiologia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Adulto Jovem
15.
Clin Breast Cancer ; 20(5): e569-e575, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32381383

RESUMO

BACKGROUND: Receptor activator of nuclear factor κB (RANK) and its ligand, RANKL, are essential for mammary gland development and play a vital role in breast carcinogenesis. RANKL-RANK signaling also drives thermoregulation and modulates inflammatory activation in the brain. The expression of RANKL in primary breast cancer (BC) has been negatively associated with brain metastases, while significantly higher levels of RANK are seen in BC with brain metastases. We examined the expression of RANK and RANKL in BC metastasis to the brain. PATIENTS AND METHODS: We examined the expression of RANK and RANKL in 40 cases of BC metastasis to the brain. RESULTS: RANK was variably expressed in BC cells but minimally expressed in the adjacent brain parenchyma. In contrast, the expression of RANKL was minimal in metastatic BC but highly variable in tumoral stroma. RANKL expression in normal brain stroma obtained during autopsy was negligible. Histologic grade and BC subtypes were not significantly associated with RANK expression in metastatic BC. A significant negative correlation between RANK in metastatic BC and RANKL in tumoral stroma was identified (P < .001). CONCLUSION: RANK expressed by primary BC and RANKL detected in the tumor microenvironment together participate in cancer development, while the same principle may operate at distant sites. Further investigation is necessary to provide additional insight into the role of the RANKL-RANK pathway in BC progression and to investigate the potential efficacy of therapeutic strategies targeting these molecules in BC metastasis to the brain.


Assuntos
Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundário , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Transdução de Sinais , Microambiente Tumoral
16.
Neurohospitalist ; 10(4): 314-317, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32983354

RESUMO

No clear guidelines exist for the appropriate diagnostic workup of an intracranial mass suspected to be a metastasis from unknown primary origin. Dural metastasis from prostatic origin is very rare. Patients with a known history of metastatic prostate cancer who present with a newly discovered lesion on brain imaging require neurosurgical biopsy to confirm diagnosis prior to initiating treatment. Intracranial metastasis from prostate cancer is rare, and dural metastasis is rarer than intraparenchymal metastasis. Current consensus guidelines support immunohistochemical staining with classic markers such as prostate-specific antigen (PSA) to identify prostatic origin. However, PSA detection of prostate metastases declines with higher Gleason scores and in patients undergoing androgen deprivation therapy. NKX3.1 is another stain that is highly sensitive and specific for prostate. Our patient was a 54-year-old man with a history of metastatic prostate cancer who presented with new-onset seizures. Brain imaging revealed a dural-based lesion with surrounding vasogenic edema and midline shift. The patient underwent resection of the lesion, which was stained with multiple cancer markers. Prostate-specific antigen was negative, but NKX3.1 was positive indicating a prostatic origin for the mass. He underwent a craniectomy to remove the lesion and was given steroids. However, he succumbed to his illness several months later. Here, we document the first report to our knowledge of a patient with prostate metastasis to the dura that is PSA negative, but NKX3.1 positive.

17.
Cancers (Basel) ; 12(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31906320

RESUMO

Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome that affects children and adults. Individuals with NF1 are at high risk for central nervous system neoplasms including gliomas. The purpose of this review is to discuss the spectrum of intracranial gliomas arising in individuals with NF1 with a focus on recent preclinical and clinical data. In this review, possible mechanisms of gliomagenesis are discussed, including the contribution of different signaling pathways and tumor microenvironment. Furthermore, we discuss the recent notable advances in the developing therapeutic landscape for NF1-associated gliomas including clinical trials and collaborative efforts.

18.
Clin Case Rep ; 8(9): 1757-1764, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32983491

RESUMO

Intraventricular melanoma is a very rare and highly malignant disease. Safe resection is the mainstay of treatment, but no standard guidelines exist for adjuvant therapy. Early histologic and molecular diagnosis is key for improved survival.

19.
World Neurosurg ; 134: 25-32, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31629928

RESUMO

BACKGROUND: Arteriovenous malformations (AVMs) can occur in all regions of the brain and spinal cord, with clinical consequences and risks varying by location. Delayed AVM rupture despite digital subtraction angiography-confirmed obliteration post-radiation is exceedingly rare. CASE DESCRIPTION: To our knowledge, we present the first documented case of delayed hemorrhage associated with a cerebellar AVM 5 years after linear accelerator-based radiation in a man aged 31 years despite apparent angiographic obliteration. CONCLUSIONS: Intracranial hemorrhage after radiosurgery in digital subtraction angiography-confirmed obliterated AVMs is rare, with limited understanding of risk factors, appropriate preventative management, and mechanisms of occurrence. This case serves to demonstrate the need for greater awareness of this rare complication, as well as the need for appropriate surveillance and management strategies.


Assuntos
Doenças Cerebelares/radioterapia , Malformações Arteriovenosas Intracranianas/radioterapia , Hemorragias Intracranianas/prevenção & controle , Ruptura Espontânea/prevenção & controle , Adulto , Angiografia Digital , Doenças Cerebelares/diagnóstico por imagem , Doenças Cerebelares/patologia , Angiografia Cerebral , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/patologia , Hemorragias Intracranianas/diagnóstico por imagem , Hemorragias Intracranianas/patologia , Hemorragias Intracranianas/cirurgia , Masculino , Radiocirurgia , Ruptura Espontânea/diagnóstico por imagem , Ruptura Espontânea/patologia , Ruptura Espontânea/cirurgia , Falha de Tratamento
20.
J Neurosurg ; 134(3): 721-732, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059178

RESUMO

OBJECTIVE: Despite an aggressive multimodal therapeutic regimen, glioblastoma (GBM) continues to portend a grave prognosis, which is driven in part by tumor heterogeneity at both the molecular and cellular levels. Accordingly, herein the authors sought to identify metabolic differences between GBM tumor core cells and edge cells and, in so doing, elucidate novel actionable therapeutic targets centered on tumor metabolism. METHODS: Comprehensive metabolic analyses were performed on 20 high-grade glioma (HGG) tissues and 30 glioma-initiating cell (GIC) sphere culture models. The results of the metabolic analyses were combined with the Ivy GBM data set. Differences in tumor metabolism between GBM tumor tissue derived from within the contrast-enhancing region (i.e., tumor core) and that from the peritumoral brain lesions (i.e., tumor edge) were sought and explored. Such changes were ultimately confirmed at the protein level via immunohistochemistry. RESULTS: Metabolic heterogeneity in both HGG tumor tissues and GBM sphere culture models was identified, and analyses suggested that tyrosine metabolism may serve as a possible therapeutic target in GBM, particularly in the tumor core. Furthermore, activation of the enzyme tyrosine aminotransferase (TAT) within the tyrosine metabolic pathway influenced the noted therapeutic resistance of the GBM core. CONCLUSIONS: Selective inhibition of the tyrosine metabolism pathway may prove highly beneficial as an adjuvant to multimodal GBM therapies.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Glioma/tratamento farmacológico , Glioma/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , Tirosina/metabolismo , Sequência de Bases , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Células Cultivadas , Quimioterapia Adjuvante , Sistemas de Liberação de Medicamentos , Glioma/patologia , Humanos , Imuno-Histoquímica , Metabolômica , Nitrogênio/metabolismo , Tirosina Transaminase/metabolismo
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