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PURPOSE: The systemic inflammation response index (SIRI) and systemic immune-inflammation index (SII) are based on neutrophil, monocyte, platelet, and lymphocyte counts. The SIRI and SII are used to predict the survival of patients with malignant tumors. It is well known that the inflammatory immune response is closely related to cancer occurrence and progression. In the present study, we evaluated the potential prognostic significance of SIRI and SII in patients with primary central nervous system lymphoma (PCNSL). METHODS: Fifty-eight consecutive patients were enrolled in this study between November 2006 and May 2022. Among the 58 patients, 47 patients with sufficient blood test data and follow-up were analyzed. The patients with steroid intake at the time point of the blood test and higher C-reactive protein were excluded. RESULTS: The median follow-up and survival times were 31 and 36 months, respectively. The optimal cutoff SIRI value was based on the receiver operating characteristic curve (ROC) for overall survival (OS) and stratified patients into low (< 1.43 × 109/L, n = 22) and high (≥ 1.43 × 109/L, n = 25) SIRI groups. The optimal cutoff SII value based on the ROC for OS stratified patients into low (< 694.9, n = 28) and high (≥ 694.9, n = 19) SII groups. A low SIRI value was associated with longer OS (p = 0.006). Furthermore, a low SII value was associated with longer OS (p = 0.044). The prognostic factors associated with prolonged survival in univariate analysis using the Cox proportional hazard model were age < 65 years, low SIRI, and low SII. The multivariate analysis demonstrated that age < 65 years and low SIRI independently predicted longer OS. CONCLUSION: Simple, less expensive, and routinely ordered preoperative blood count assessments such as SIRI and SII predict the OS of patients with PCNSL. This study demonstrated that PCNSL is associated with pre-treatment systemic immune-inflammation states.
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Neoplasias do Sistema Nervoso Central , Inflamação , Linfoma , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Neoplasias do Sistema Nervoso Central/imunologia , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/sangue , Adulto , Inflamação/imunologia , Inflamação/sangue , Linfoma/imunologia , Linfoma/mortalidade , Linfoma/sangue , Seguimentos , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem , Curva ROC , Neutrófilos/imunologiaRESUMO
Trigeminal neuralgia causes excruciating pain in patients. Microvascular decompression is indicated for drug-resistant s trigeminal neuralgia. Unlike facial spasms, any part of the nerve can be the culprit, not only the root entry zone. Intraoperative monitoring does not yet exist for trigeminal neuralgia. We successfully used intermittent stimulation of the superior cerebellar artery during surgery and confirmed the disappearance of the trigeminal nerve motor branch reaction after the release of the compression. Intermittent direct stimulation of the culprit blood vessel using the motor branch of the trigeminal nerve may assist in intraoperative monitoring of decompression during trigeminal nerve vascular decompression surgery.
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Cirurgia de Descompressão Microvascular , Neuralgia do Trigêmeo , Neuralgia do Trigêmeo/cirurgia , Humanos , Cirurgia de Descompressão Microvascular/métodos , Nervo Trigêmeo/cirurgia , Monitorização Intraoperatória/métodos , Masculino , Feminino , Idoso , Pessoa de Meia-IdadeRESUMO
Enhancing immune cell functions in tumors remains a major challenge in cancer immunotherapy. Natural killer cells (NK) are major innate effector cells with broad cytotoxicity against tumors. Accordingly, NK cells are ideal candidates for cancer immunotherapy, including glioblastoma (GBM). Hypoxia is a common feature of solid tumors, and tumor cells and normal cells adapt to the tumor microenvironment by upregulating the transcription factor hypoxia-inducible factor (HIF)-1α, which can be detrimental to anti-tumor effector immune cell function, including that of NK cells. We knocked out HIF-1α in human primary NK cells using clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9). Then, cellular characterizations were conducted in normoxic and hypoxic conditions. Electroporating two HIF-1α-targeting guide RNA-Cas9 protein complexes inhibited HIF-1α expression in expanded NK cells. HIF-1α knockout human NK cells, including populations in hypoxic conditions, enhanced the growth inhibition of allogeneic GBM cells and induced apoptosis in GBM-cell-derived spheroids. RNA-sequencing revealed that the cytotoxicity of HIF-1α knockout NK cells could be related to increased perforin and TNF expression. The results demonstrated that HIF-1α knockout human NK cells, including populations, enhanced cytotoxicity in an environment mimicking the hypoxic conditions of GBM. CRISPR-Cas9-mediated HIF-1α knockout NK cells, including populations, could be a promising immunotherapeutic alternative in patients with GBM.
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Técnicas de Inativação de Genes , Glioblastoma , Subunidade alfa do Fator 1 Induzível por Hipóxia , Células Matadoras Naturais , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/imunologia , Glioblastoma/patologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Sistemas CRISPR-Cas , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Apoptose/genética , Citotoxicidade ImunológicaRESUMO
Despite standard multimodality treatment, containing maximum safety resection, temozolomide, radiotherapy, and a tumor-treating field, patients with glioblastoma (GBM) present with a dismal prognosis. Natural killer cell (NKC)-based immunotherapy would play a critical role in GBM treatment. We have previously reported highly activated and ex vivo expanded NK cells derived from human peripheral blood, which exhibited anti-tumor effect against GBM cells. Here, we performed preclinical evaluation of the NK cells using an in vivo orthotopic xenograft model, the U87MG cell-derived brain tumor in NOD/Shi-scid, IL-2RɤKO (NOG) mouse. In the orthotopic xenograft model, the retro-orbital venous injection of NK cells prolonged overall survival of the NOG mouse, indirectly indicating the growth-inhibition effect of NK cells. In addition, we comprehensively summarized the differentially expressed genes, especially focusing on the expression of the NKC-activating receptors' ligands, inhibitory receptors' ligands, chemokines, and chemokine receptors, between murine brain tumor treated with NKCs and with no agents, by using microarray. Furthermore, we also performed differentially expressed gene analysis between an internal and external brain tumor in the orthotopic xenograft model. Our findings could provide pivotal information for the NK-cell-based immunotherapy for patients with GBM.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Camundongos , Animais , Glioblastoma/terapia , Glioblastoma/tratamento farmacológico , Modelos Animais de Doenças , Transcriptoma , Xenoenxertos , Camundongos Endogâmicos NOD , Células Matadoras Naturais/metabolismo , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular TumoralRESUMO
Glioblastoma (GBM) is the leading malignant intracranial tumor, where prognosis for which has remained extremely poor for two decades. Immunotherapy has recently drawn attention as a cancer treatment, including for GBM. Natural killer (NK) cells are immune cells that attack cancer cells directly and produce antitumor immunity-related cytokines. The adoptive transfer of expanded and activated NK cells is expected to be a promising GBM immunotherapy. We previously established an efficient expansion method that produced highly purified, activated primary human NK cells, which we designated genuine induced NK cells (GiNKs). The GiNKs demonstrated antitumor effects in vitro and in vivo, which were less affected by blockade of the inhibitory checkpoint receptor programmed death 1 (PD-1). In the present study, we assessed the antitumor effects of GiNKs, both alone and combined with an antibody targeting killer Ig-like receptor 2DLs (KIR2DL1 and DL2/3, both inhibitory checkpoint receptors of NK cells) in vitro and in vivo with U87MG GBM-like cells and the T98G GBM cell line. Impedance-based real-time cell growth assays and apoptosis detection assays revealed that the GiNKs exhibited growth inhibitory effects on U87MG and T98G cells by inducing apoptosis. KIR2DL1 blockade attenuated the growth inhibition of the cell lines in vitro. The intracranial administration of GiNKs prolonged the overall survival of the U87MG-derived orthotopic xenograft brain tumor model. The KIR2DL1 blockade did not enhance the antitumor effects; rather, it attenuated it in the same manner as in the in vitro experiment. GiNK immunotherapy directly administered to the brain could be a promising immunotherapeutic alternative for patients with GBM. Furthermore, KIR2DL1 blockade appeared to require caution when used concomitantly with GiNKs.
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Irradiated murine induced-pluripotent stem cells (iPSCs) elicit the antitumor response in vivo. However, it is unclear whether human iPSCs would elicit antitumor effects. In the present study, we investigated the capability of human iPSC lysate (iPSL)-pulsed dendritic cells (DCs) (iPSL/DCs) to induce cancer-responsive cytotoxic T lymphocytes (CTLs) in vitro. iPSCs and DCs were induced from peripheral blood mononuclear cells isolated from a human leukocyte antigen (HLA)-A33 homozygous donor. The iPSL was pulsed with immature DCs, which were then stimulated to allow full maturation. The activated DCs were co-cultured with autologous CTLs and their responses to SW48 colorectal carcinoma cells (HLA-A32/A33), T47D breast cancer cells (HLA-A33/A33), and T98G glioblastoma cells (HLA-A02/A02) were tested with enzyme-linked immunospot (ELISPOT) assays. Comprehensive gene expression analysis revealed that the established iPSCs shared numerous tumor-associated antigens with the SW48 and T47D cells. Immunofluorescent analysis demonstrated that the fluorescent-labeled iPSL was captured by the immature DCs within 2 h. iPSL/DCs induced sufficient CTL numbers in 3 weeks for ELISPOT assays, which revealed that the induced CTLs responded to SW48 and T47D cells. Human iPSL/DCs induced cancer-responsive CTLs on HLA-A33-matched cancer cells in vitro and could be a promising universal cancer vaccine for treating and preventing cancer.
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Células-Tronco Pluripotentes Induzidas , Neoplasias , Humanos , Camundongos , Animais , Linfócitos T Citotóxicos , Leucócitos Mononucleares/metabolismo , Células Dendríticas , Antígenos de Histocompatibilidade Classe II/metabolismo , Antígenos HLA/metabolismo , Neoplasias/metabolismoRESUMO
Laser speckle flowgraphy (LSFG) is a noninvasive technique that can measure relative blood flow velocity in the optic fundus contributed by the ophthalmic artery, the main first branch originating from the internal carotid artery (ICA). The aim of this study was to assess the feasibility of ocular blood flow measurement by LSFG to detect ischemic stress due to carotid clamping during carotid endarterectomy (CEA). Nineteen patients undergoing CEA with ocular blood flow measurement by LSFG and intraoperative monitoring (IOM) were prospectively enrolled between August 2016 and March 2019. The mean blur rate (MBR) of ocular blood flow by LSFG, representing relative blood flow of the branch of the retinal artery originating from the optic nerve head, was compared between before and after carotid clamping during CEA. The correlation between the reduction ratio of MBR and the regional saturation oxygen (rSO2) index by near infrared spectroscopy was investigated. Ocular blood flow measurement by LSFG could not be performed in one patient with a severe cataract. In the other 18 patients, LSFG could be performed in all 106 sessions during surgery. The MBR reduction ratio between before and after carotid clamping ranged from - 12 to 100%. The MBR reduction ratio was positively correlated with the rSO2 index (r = 0.694, 95% confidence interval: 0.336-0.877, p = 0.001). The MBR reduction ratio of ocular blood flow by LSFG after carotid clamping was significantly correlated with the rSO2 index. The ocular blood flow by LSFG could be considered an adjunct modality for evaluating cerebral ischemic tolerance during CEA.
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Isquemia Encefálica , Endarterectomia das Carótidas , Velocidade do Fluxo Sanguíneo , Humanos , Fluxometria por Laser-Doppler , Lasers , Fluxo Sanguíneo RegionalRESUMO
Balloon test occlusion (BTO) is a useful examination for evaluating ischemic tolerance to internal carotid artery (ICA) occlusion. The aim of this study was to investigate the relationships between intraoperative motor evoked potential (MEP) monitoring and the results of preoperative BTO. Between 2013 and 2017, 32 patients undergoing surgery under general anesthesia with intraoperative MEP monitoring, in whom preoperative BTO was performed, were identified. A receiver operator characteristic (ROC) analysis was performed to determine the appropriate cutoff value of MEP amplitude for BTO-positive. Furthermore, the accuracy of MEP monitoring for BTO-positive was compared with electroencephalogram (EEG) and somatosensory evoked potential (SEP) monitoring. Four of 32 (12.5%) patients were BTO-positive. The cutoff value of MEP amplitude for BTO-positive was a > 80% reduction from the baseline level, which showed sensitivity of 100% and specificity of 100%. Thus, the sensitivity and specificity for BTO-positive were significantly higher for MEP than for EEG (100% and 72.0%, p = 0.02) in 28 patients, but they were not significantly different compared with SEP (33.3% and 100%, p = 0.48) in 21 patients. MEP monitoring might be one of the alternatives for evaluating ischemic tolerance to ICA occlusion during surgery. The cutoff value of MEP amplitude was a > 80% reduction.
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Doenças das Artérias Carótidas , Potencial Evocado Motor , Artérias Carótidas , Doenças das Artérias Carótidas/cirurgia , Potenciais Somatossensoriais Evocados , Humanos , Monitorização IntraoperatóriaRESUMO
Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults. Natural Killer (NK) cells are potent cytotoxic effector cells against tumor cells inducing GBM cells; therefore, NK cell based- immunotherapy might be a promising target in GBM. T cell immunoglobulin mucin family member 3 (TIM3), a receptor expressed on NK cells, has been suggested as a marker of dysfunctional NK cells. We established TIM3 knockout in NK cells, using the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9). Electroporating of TIM3 exon 2- or exon 5-targeting guide RNA- Cas9 protein complexes (RNPs) inhibited TIM3 expression on NK cells with varying efficacy. T7 endonuclease I mutation detection assays showed that both RNPs disrupted the intended genome sites. The expression of other checkpoint receptors, i.e., programmed cell death 1 (PD1), Lymphocyte-activation gene 3 (LAG3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), and TACTILE (CD96) were unchanged on the TIM3 knockout NK cells. Real time cell growth assays revealed that TIM3 knockout enhanced NK cell-mediated growth inhibition of GBM cells. These results demonstrated that TIM3 knockout enhanced human NK cell mediated cytotoxicity on GBM cells. Future, CRISPR-Cas9 mediated TIM3 knockout in NK cells may prove to be a promising immunotherapeutic alternative in patient with GBM.
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Neoplasias Encefálicas/genética , Sistemas CRISPR-Cas , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Receptor Celular 2 do Vírus da Hepatite A/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/terapia , Linhagem Celular Tumoral , Técnicas de Inativação de Genes , Genoma Humano , Glioma/metabolismo , Glioma/terapia , Humanos , Imunoterapia/métodos , Estimativa de Kaplan-Meier , Células Matadoras Naturais/metabolismo , Ligantes , Análise de Sequência com Séries de Oligonucleotídeos , RNA Guia de Cinetoplastídeos/metabolismo , TransgenesRESUMO
Glioblastoma (GBM) is the leading malignant intracranial tumor and is associated with a poor prognosis. Highly purified, activated natural killer (NK) cells, designated as genuine induced NK cells (GiNKs), represent a promising immunotherapy for GBM. We evaluated the anti-tumor effect of GiNKs in association with the programmed death 1(PD-1)/PD-ligand 1 (PD-L1) immune checkpoint pathway. We determined the level of PD-1 expression, a receptor known to down-regulate the immune response against malignancy, on GiNKs. PD-L1 expression on glioma cell lines (GBM-like cell line U87MG, and GBM cell line T98G) was also determined. To evaluate the anti-tumor activity of GiNKs in vivo, we used a xenograft model of subcutaneously implanted U87MG cells in immunocompromised NOG mice. The GiNKs expressed very low levels of PD-1. Although PD-L1 was expressed on U87MG and T98G cells, the expression levels were highly variable. Our xenograft model revealed that the retro-orbital administration of GiNKs and interleukin-2 (IL-2) prolonged the survival of NOG mice bearing subcutaneous U87MG-derived tumors. PD-1 blocking antibodies did not have an additive effect with GiNKs for prolonging survival. GiNKs may represent a promising cell-based immunotherapy for patients with GBM and are minimally affected by the PD-1/PD-L1 immune evasion axis in GBM.
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Neoplasias Encefálicas/imunologia , Glioblastoma/imunologia , Células Matadoras Naturais/citologia , Ativação Linfocitária/imunologia , Animais , Apoptose , Antígeno B7-H1/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Citocinas/metabolismo , Glioblastoma/patologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Receptor 1 Desencadeador da Citotoxicidade Natural/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Tela Subcutânea/patologia , Análise de SobrevidaRESUMO
BACKGROUND: Visual evoked potential (VEP) is used as a means of intraoperative visual function monitoring. It remains unclear, however, whether intraoperative VEP monitoring is a means of real-time visual function monitoring that has satisfactory effectiveness and sensitivity. To evaluate this, the relationships between VEP waveform changes in endoscopic transsphenoidal surgery and postoperative visual function were analyzed retrospectively. MATERIALS AND METHODS: Intraoperative VEP monitoring was carried out during 82 endoscopic transnasal transsphenoidal surgeries for 164 eyes at Nara Medical University Hospital, Nara, Japan under total intravenous anesthesia. Red light flash stimulation was provided to each eye independently. The VEP recording and postoperative visual function were then analyzed. RESULTS: In 160 of 164 eyes (98%), steady VEP monitoring was performed. Stable VEP was acquired from eyes with a corrected visual acuity >0.1. VEP was not recorded in four eyes that had a corrected visual acuity under 0.05. A transient VEP decrease was observed in 26 eyes, 8 of which had improved visual acuity and 18 of which had no change in visual acuity. A permanent gradual VEP decrease occurred in eight eyes; this finding did not correspond to a change in visual function. The visual acuity of the patients who underwent the transsphenoidal operation in our study did not worsen. CONCLUSION: Intraoperative monitoring of VEP predicts postoperative visual function, and a reversible change in VEP indicates that visual function will be preserved. Intraoperative VEP monitoring will be mandatory for surgeries harboring a risk of visual impairment.
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Potenciais Evocados Visuais/fisiologia , Monitorização Neurofisiológica Intraoperatória/métodos , Procedimentos Neurocirúrgicos/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Fusiform aneurysms in the posterior inferior cerebellar artery (PICA) are rare and challenging to treat. Surgical treatment options for a fusiform aneurysm in the PICA include trapping with/without bypass and wrap-clipping, when elimination of the pathological wall from the systemic circulation and prevention of perforator injury are important. In addition, lower cranial nerve impairment due to surgical manipulation should also be avoided. METHOD: A fusiform-shaped aneurysm was found in a proximal part of the PICA by magnetic resonance angiography undertaken for evaluation of repeated vertigo in a 36-year-old man. The patient underwent direct surgery via a lateral suboccipital transcondylar fossa approach. The entrance of the pseudolumen was the only part to be wrapped and obstructed by clip application, through the corridor between the acoustic and glossopharyngeal nerves to avoid lower cranial nerve injury. RESULTS: Indocyanine green (ICG) videoangiography demonstrated obliteration of pseudolumen and patency of peripheral PICA and perforator contributing to the medulla oblongata. The postoperative course was uneventful without periprocedural complications, including dysphagia and hoarseness. CONCLUSIONS: Partial wrap-clipping technique for obstruction of the entrance into a pseudolumen is one of alternatives for dissecting fusiform-shaped aneurysm in the PICA. ICG videoangiography was helpful to confirm the obliteration of the pseudolumen and patency of parent vessel and perforators.
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Dissecção Aórtica/cirurgia , Cerebelo/irrigação sanguínea , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adulto , Dissecção Aórtica/diagnóstico por imagem , Artérias/patologia , Artérias/cirurgia , Cerebelo/diagnóstico por imagem , Angiografia Cerebral/métodos , Transtornos de Deglutição/etiologia , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/instrumentação , Complicações Pós-Operatórias/etiologia , Instrumentos CirúrgicosRESUMO
Nitrogen-containing bisphosphonates (N-BPs), which prevent bone resorption, exert direct and γδT cell (GDT)-mediated antitumor effects against several tumor cell types, including glioblastoma (GBM). However, limited information is available regarding the antitumor effects of N-BPs in GBM. Specifically, the antitumor effects of minodronate (MDA), a third-generation N-BP, in GBM are yet unclear. This study aimed to investigate the antitumor effects of MDA in GBM in vitro and in vivo. We performed growth inhibition and apoptosis detection assays using the GBM cell lines U87MG and U138MG. Apoptosis inhibition assays were also conducted. In vivo xenograft assays were performed in highly immunodeficient NOD.Cg-Prkdc(scid) Il2rg(tm1Sug)/Jic mice subcutaneously implanted with U87MG and U138MG cells. Growth inhibition and apoptosis detection assays demonstrated that MDA inhibited GBM cell growth via apoptosis, which was markedly enhanced by ex vivo expanded GDT. A pan-caspase inhibitor, z-VAD-fmk, inhibited MDA-induced U138MG apoptosis and MDA/GDT-induced U87MG and U138MG apoptosis. But z-VAD-fmk increased MDA-induced U87MG apoptosis. MDA/GDT-mediated apoptosis was blocked by the anti-T cell receptor (TCR) Vγ9, mevalonate pathway inhibitor, granzyme B inhibitor, and antitumor necrosis factor (TNF)-α. In vivo xenograft assays showed that combined intraperitoneal administration of MDA/GDT induced antitumor effects on unestablished U87MG-derived subcutaneous tumors. MDA exerted direct and GDT-mediated anti-GBM apoptotic effects in a caspase-dependent manner. GDT recognized MDA-exposed GBM cells via TCRVγ9 and induced apoptosis via granzyme B and TNF-α release. Because MDA elicited anti-GBM effects in synergy with GDT in vivo, a combination of MDA and ex vivo-generated GDT could be an effective treatment in patients with GBM.
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Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/terapia , Difosfonatos/uso terapêutico , Glioblastoma/terapia , Imidazóis/uso terapêutico , Linfócitos Intraepiteliais/fisiologia , Linfócitos Intraepiteliais/transplante , Clorometilcetonas de Aminoácidos/farmacologia , Animais , Anexina A5/metabolismo , Apoptose/efeitos dos fármacos , Inibidores de Caspase/farmacologia , Contagem de Células , Linhagem Celular Tumoral , Proliferação de Células , Difosfonatos/farmacologia , Feminino , Humanos , Masculino , Camundongos Endogâmicos NOD , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Intracerebral hemorrhage (ICH) remains a serious condition for which early aggressive care is warranted. Japanese evidence-based stroke guidelines were published in 2015 to present the current and comprehensive recommendations for the diagnosis and treatment of stroke. In the spontaneous ICH, topics focused on prevention, management in the acute and chronic stage, complications, management of coagulopathy and blood pressure, prevention and control of secondary brain injury and intracranial pressure, the role of surgery, and other pathologies of ICH. The management of ICH in pregnancy and the puerperium was newly added. These guidelines provide a framework for goal-directed treatment of the patient with ICH.
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Hemorragia Cerebral/etiologia , Hemorragia Cerebral/terapia , Guias de Prática Clínica como Assunto , Doença Aguda , Anti-Hipertensivos/administração & dosagem , Neoplasias Encefálicas/complicações , Malformações Vasculares do Sistema Nervoso Central/complicações , Hemorragia Cerebral/prevenção & controle , Fator VIIa/administração & dosagem , Feminino , Hemangioma Cavernoso/complicações , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Malformações Arteriovenosas Intracranianas/complicações , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos , Procedimentos Neurocirúrgicos , Inibidores da Agregação Plaquetária/efeitos adversos , Gravidez , Complicações na Gravidez , Embolia Pulmonar/prevenção & controle , Proteínas Recombinantes/administração & dosagem , Recidiva , Respiração Artificial , Trombose Venosa/prevenção & controleAssuntos
Linfócitos B/imunologia , Citidina Desaminase/genética , Switching de Imunoglobulina/genética , Hipermutação Somática de Imunoglobulina/genética , Animais , Linfócitos B/citologia , Linhagem Celular , Genes de Imunoglobulinas/genética , Genes de Imunoglobulinas/imunologia , História do Século XX , História do Século XXI , Humanos , Síndrome de Imunodeficiência com Hiper-IgM/genética , Imunoglobulina A/genética , Switching de Imunoglobulina/imunologia , Imunoglobulina M/genética , Camundongos , Camundongos Knockout , Edição de RNA/genética , Hipermutação Somática de Imunoglobulina/imunologiaRESUMO
Glioblastoma (GBM) is a highly aggressive brain tumor for which novel therapeutic approaches, such as immunotherapy, are urgently needed. Zoledronate (ZOL), an inhibitor of osteoclastic activity, is known to stimulate peripheral blood-derived γδT cells and sensitize tumors to γδT cell-mediated killing. To investigate the feasibility of γδT cell-based immunotherapy for patients with GBM, we focused on the killing of GBM cell lines by γδT cells and the molecular mechanisms involved in these cell-cell interactions. Peripheral blood mononuclear cells were expanded in ZOL and interleukin (IL)-2 for 14 days, and γδT cells were enriched in the expanded cells by the immunomagnetic depletion of αßT cells. Gliomas are resistant to NK cells but susceptible to lymphokine-activated killer cells and some cytotoxic T lymphocytes. When the γδT cell-mediated killing of three GBM cell lines (U87MG, U138MG and A172 cells) and an NK-sensitive leukemia cell line (K562 cells) were tested, 32% U87MG, 15% U138MG, 1% A172, and 50% K562 cells were killed at an effector:target ratio of 5:1. The γδT cell-mediated killing of all three GBM cell lines was significantly enhanced by ZOL and this ZOL-enhanced killing was blocked by an anti-T cell receptor (TcR) antibody. These results indicated that TcR γδ is crucial for the recognition of ZOL-treated GBM cells by γδT cells. Since the low level killing of GBM cells by the γδT cells was enhanced by ZOL, γδT cell-targeting therapy in combination with ZOL treatment could be effective for patients with GBM.
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Glioblastoma/patologia , Leucócitos Mononucleares/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Subpopulações de Linfócitos T/imunologia , Análise de Variância , Antígenos CD/metabolismo , Conservadores da Densidade Óssea/farmacologia , Linhagem Celular Tumoral , Difosfonatos/farmacologia , Citometria de Fluxo , Fluoresceínas/metabolismo , Glioblastoma/imunologia , Humanos , Imidazóis/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Subpopulações de Linfócitos T/efeitos dos fármacos , Fatores de Tempo , Ácido ZoledrônicoRESUMO
BACKGROUND: Ventriculoperitoneal (VP) shunt tube migration is recognized as an occasional complication; however, migration into the cardiac system is rare. The authors report a case of VP shunt tube migration into the heart and pulmonary artery and the safe removal of the tube. OBSERVATIONS: The patient had a VP shunt implanted for hydrocephalus after a subarachnoid hemorrhage. The screening chest radiograph taken a few months later showed the migration of the abdominal tube into the heart. Examinations revealed that the abdominal tube had migrated from the left subclavian vein, passed through the superior vena cava, right atrium and ventricle, and looped into the pulmonary artery. The patient had no symptoms; however, there were some risks, such as damage to the valves or fatal arrhythmia. The authors therefore decided to remove the tube. To avoid various intraoperative risks, in particular tube knot formation, the tube was removed under fluoroscopy with a guidewire inserted, which was 0.035 inches for the angiography catheter. The tube was successfully removed without any complications. LESSONS: Knot formation can be one of the fatal complications of shunt tube removal. The authors' technique is an effective method for safe removal. https://thejns.org/doi/10.3171/CASE24127.
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OBJECTIVE: The prognosis for patients with cancer with brain metastasis (BM) requiring surgical removal is quite limited. Preoperative prognostic factors can provide meaningful information to surgeons, oncologists, and patients. This study evaluated the preoperative blood counts in patients with BM who were treated with surgical removal. METHODS: Between January 2011 and November 2021, 221 consecutive surgeries were conducted on 198 patients with BM. Among the 198 patients, 188 patients with sufficient blood test data and follow-up were analyzed in this study. The tumors originated from the lungs (n = 102, 54.3%), colon (n = 26, 13.3%), breast (n = 13, 6.9%), kidney (n = 8, 4.3%), stomach (n = 6, 3.2%), and others (n = 33, 17.6%). The blood test data included neutrophils, lymphocytes, monocytes, eosinophils, basophils, red blood cell count, hemoglobin, and albumin. RESULTS: The median follow-up and median survival times were both 11 months (range: 0-139 months). Higher neutrophil-lymphocyte ratio ≥ 3.17, platelet-lymphocyte ratio ≥112.7, systemic immune-inflammation index ≥594.4, systemic inflammation response index ≥1.25 were unfavorable predictors of prognosis for the patients treated with surgical removal for BM (P < 0.001). Furthermore, lower lymphocyte-monocyte ratio < 2.33 and prognostic nutritional index < 48.5 were unfavorable predictors. CONCLUSIONS: Simple, less expensive, routinely ordered preoperative blood count assessments, such as the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio, systemic immune-inflammation index, systemic inflammation response index, and prognostic nutritional index, can predict the overall survival of patients treated with surgical removal for BM.
Assuntos
Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/mortalidade , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Contagem de Células Sanguíneas , Prognóstico , Idoso de 80 Anos ou mais , Adulto Jovem , Estudos Retrospectivos , Adolescente , Seguimentos , Procedimentos Neurocirúrgicos , Neutrófilos/patologiaRESUMO
BACKGROUND: Accurately evaluating plaque characteristics is essential because lesions with lipid-rich plaque put patients at risk of thromboembolic complications from carotid artery stenting. Near-infrared spectroscopy (NIRS) is a diagnostic imaging modality that identifies lipid components from the near-infrared absorption pattern but does not reveal the distribution of calcification. The purpose of this study was to investigate the calcification characteristics of unstable carotid plaques, focusing on relationships between the calcification characteristics revealed by computed tomography angiography and the lipid core distribution derived from NIRS. METHODS: Participants in this retrospective analysis comprised 35 patients (29 men, 6 women; mean age, 76.0 years; range, 52-89 years) who underwent carotid artery stenting in our institute between January 2021 and December 2022. We evaluated the thickness and length of carotid calcifications at the minimal lumen level from preoperative computed tomography angiography and analyzed the relationship with maximum lipid core burden index (max-LCBI) from NIRS. RESULTS: Strong negative linear correlations were observed between the thickness of calcification and max-LCBI at Area (any segment in a target lesion) (r = -0.795, P < 0.001), max-LCBI at minimal lumen area (r = -0.795, P < 0.001) and lipid core burden index (LCBI) at lesion (rate of LCBI in entire plaque lesion) (r = -0.788, P < 0.001), respectively. Significant negative linear correlations were observed between distribution of calcification length and max-LCBI at area (r = -0.429, P = 0.01), max-LCBI at minimal lumen area (r = -0.373, P = 0.027), and LCBI at lesion (r = -0.443, P = 0.008). CONCLUSIONS: Thin and ubiquitous carotid calcification was associated with LCBI values derived from NIRS indicative of carotid lipid plaque distribution, implying the possibility of predicting lesion instability.
Assuntos
Estenose das Carótidas , Doença da Artéria Coronariana , Placa Aterosclerótica , Masculino , Humanos , Feminino , Idoso , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Estenose das Carótidas/complicações , Estudos Retrospectivos , Stents , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/complicações , Artérias Carótidas/patologia , Lipídeos/análise , Doença da Artéria Coronariana/complicações , Ultrassonografia de Intervenção , Valor Preditivo dos TestesRESUMO
Objective: To evaluate the effect of ventricular opening (VO) on recurrence patterns in patients with newly diagnosed glioblastoma (GBM) treated with bis-chloroethyl-nitrosourea (BCNU) wafer implantation. Methods: This single-center retrospective study included 40 patients with newly diagnosed GBM who received BCNU wafer implantation after tumor resection between March 2013 and February 2022. The patients were categorized into two groups based on whether VO occurred during the GBM resection. While 18 patients had VO, 22 did not have VO. In cases with VO, the ventricular wall defect is closed with gelatin or oxidized regenerated cellulose and fibrin glue before BCNU wafer implantation. Recurrence patterns-classified as local, diffuse, distant, or multifocal-and time to recurrence were compared between patients with and without VO. Results: The median follow-up period for the entire cohort was 32.2 months (interquartile range, 16.7-38 months). Median survival time was comparable between patients with VO and patients without VO (38 vs. 26 months, p=0.53). Recurrence occurred in 31/40 patients (77.5%) in entire cohort. The incidence of recurrence was comparable between patients with VO and patients without VO (14 [77.8%] vs. 17 [77.3%], p=1.0). No significant differences were seen between the two groups in time to recurrence (p=0.59) or recurrence patterns (p=0.35). Conclusion: Ventricular opening during surgery with BCNU wafer implantation does not seem to influence the recurrence patterns. Ventricular opening does not induce distant recurrence if appropriate ventricular closure is performed.